bluuebunny/crossref_metadata_2025 huggingface dataset:
The mode of ovulation in the Namaqua rock mouse, Micaelamys namaquensis
Authors: Relton C.E. , Bennett N.C. , Medger K.
Published: October 2013

The pattern of ovulation in mammals is generally considered to be either spontaneous or induced by copulation, with environmental and social factors playing a key role in determining the specific mode of ovulation that would maximize the reproductive potential of the species. This study aims to determine whether the Namaqua rock mouse (Micaelamys namaquensis (A. Smith, 1834)) is a spontaneous or induced ovulator. Females were divided into three treatments differing in the degree of contact with a male. Namely, seven control females had no contact with a male; a further seven separated females had only chemical, auditory, and visual contact with a male; whereas six females had intermittent periods of full contact with a vasectomized male. Ovarian size, follicular development, and plasma progesterone concentrations were compared between the three treatments. Penile morphology was also investigated. Corpora lutea were found in all three treatments and the penis was smooth without any ridges or spikes, indicating that M. namaquensis is a spontaneous ovulator. Interestingly, however, the presence of a male (physical as well as just visual and olfactory) positively affected ovarian size, ovulation, and plasma progesterone concentrations. This signifies that although M. namaquensis ovulates spontaneously, male contact significantly influences ovulation rate and ultimately reproductive success.
PARALLEL ALGORITHM FOR SECOND–ORDER RESTRICTED WEAK INTEGER COMPOSITION GENERATION FOR SHARED MEMORY MACHINES
Authors: PAGE DANIEL R.
Published: October 2013

In 2012, Page presented a sequential combinatorial generation algorithm for generalized types of restricted weak integer compositions called second–order restricted weak integer compositions. Second–order restricted weak integer compositions cover various types of restricted weak integer compositions of n parts such as integer compositions, bounded compositions, and part–wise integer compositions. In this paper, we present a parallel algorithm that derives from our parallelization of Page's sequential algorithm with a focus on load balancing for shared memory machines.
SUPERIORITY OF GENERALIZED BOND-MOVING RENORMALIZATION IN STUDYING PHASE TRANSITION OF COMPLEX SPIN SYSTEMS
Authors: WANG CHUN-YANG , YANG WEN-XIAN , DU HONG
Published: October 2013

The superiority of the generalized Migdal–Kadanoff bond-moving renormalization (GMKBR) method in studying phase transition of complex spin systems is revealed by a sampled application on the classical S4model. In three different cases of nearest-neighbor, next-nearest neighbor and external field, we obtain the critical points and further calculate the critical exponents according to the scaling theory. In all the cases, it is shown that the method is of great convenience in obtaining results which are in good conformity with the previous ones.
EMERGENCE OF THE LORENTZIAN STRUCTURE IN CLASSICAL FIELD THEORY
Authors: MUKOYAMA SHINJI , UZAN JEAN-PHILIPPE
Published: October 2013

The Lorentzian metric structure allows one to implement the relativistic notion of causality in any field theory and to define a notion of time dimension. We propose that at the microscopic level the metric is Riemannian and that the Lorentzian structure, usually thought as fundamental, is in fact an effective property, that emerges in some regions of a 4-dimensional space with a positive definite metric. We argue that a decent classical field theory for scalars, vectors and spinors in flat spacetime can be constructed, and that gravity can be included under the form of a covariant Galileon theory instead of general relativity.
ENTANGLEMENT ENTROPY FROM SURFACE TERMS IN GENERAL RELATIVITY
Authors: BHATTACHARYYA ARPAN , SINHA ANINDA
Published: October 2013

Entanglement entropy in local quantum field theories is typically ultraviolet divergent due to short distance effects in the neighborhood of the entangling region. In the context of gauge/gravity duality, we show that surface terms in general relativity are able to capture this entanglement entropy. In particular, we demonstrate that for 1 + 1-dimensional (1 + 1d) conformal field theories (CFTs) at finite temperature whose gravity dual is Banados–Teitelboim–Zanelli (BTZ) black hole, the Gibbons–Hawking–York term precisely reproduces the entanglement entropy which can be computed independently in the field theory.
NEW METHODS IN FATIGUE OF STRUCTURES
Authors: KY DANG VAN
Published: October 2013

Combining the application of the shakedown theory and a multiscale approach to analysis of fatigue allows interpreting all types of fatigue problems in an efficient manner. The description of the stabilized mechanical state after shakedown at the engineering macroscopic scale and at the mesoscopic scale of grains gives access to the engineering values which will drive the fatigue damage of the structure. The evolution of stress and strain tensors thus obtained for a cycle of fatigue allows predicting the fatigue strength of structures. At high cycle fatigue (HCF), when elastic shakedown takes place, the fatigue strength can be described by a simple combination of mesoscopic shear amplitude and hydrostatic tension at any point of the calculated structure, irrespective of the complexity of the structure and the loading. Two new developments incorporating spectral or modal approaches allow analyzing the fatigue resistance of structures undergoing vibrations in a very efficient manner. At low cycle fatigue (LCF), from the stabilized state of stress and strain, the fatigue strength is derived from a combination of the inelastic strain energy and the hydrostatic pressure. Numerous examples of fatigue analysis are presented.
Advancements and challenges in generating accurate animal models of gestational diabetes mellitus
Authors: Pasek Raymond C. , Gannon Maureen
Published: October 2013

The maintenance of glucose homeostasis during pregnancy is critical to the health and well-being of both the mother and the developing fetus. Strikingly, approximately 7% of human pregnancies are characterized by insufficient insulin production or signaling, resulting in gestational diabetes mellitus (GDM). In addition to the acute health concerns of hyperglycemia, women diagnosed with GDM during pregnancy have an increased incidence of complications during pregnancy as well as an increased risk of developing type 2 diabetes (T2D) later in life. Furthermore, children born to mothers diagnosed with GDM have increased incidence of perinatal complications, including hypoglycemia, respiratory distress syndrome, and macrosomia, as well as an increased risk of being obese or developing T2D as adults. No single environmental or genetic factor is solely responsible for the disease; instead, a variety of risk factors, including weight, ethnicity, genetics, and family history, contribute to the likelihood of developing GDM, making the generation of animal models that fully recapitulate the disease difficult. Here, we discuss and critique the various animal models that have been generated to better understand the etiology of diabetes during pregnancy and its physiological impacts on both the mother and the fetus. Strategies utilized are diverse in nature and include the use of surgical manipulation, pharmacological treatment, nutritional manipulation, and genetic approaches in a variety of animal models. Continued development of animal models of GDM is essential for understanding the consequences of this disease as well as providing insights into potential treatments and preventative measures.
Influence of abnormally high leptin levels during pregnancy on metabolic phenotypes in progeny mice
Authors: Makarova Elena N. , Chepeleva Elena V. , Panchenko Polina E. , Bazhan Nadezhda M.
Published: October 2013

Maternal obesity increases the risk of obesity in offspring, and obesity is accompanied by an increase in blood leptin levels. The “yellow” mutation at the mouse agouti locus ( A y) increases blood leptin levels in C57BL preobese pregnant mice without affecting other metabolic characteristics. We investigated the influence of the A y mutation or leptin injection at the end of pregnancy in C57BL mice on metabolic phenotypes and the susceptibility to diet-induced obesity (DIO) in offspring. In both C57BL- A y and leptin-treated mice, the maternal effect was more pronounced in male offspring. Compared with males born to control mothers, males born to A y mothers displayed equal food intake (FI) but decreased body weight (BW) gain after weaning, equal glucose tolerance, and enhanced FI-to-BW ratios on the standard diet but the same FI and BW on the high-fat diet. Males born to A y mothers were less responsive to the anorectic effect of exogenous leptin and less resistant to fasting (were not hyperphagic and gained less weight during refeeding after food deprivation) compared with males born to control mothers. However, all progeny displayed equal hypothalamic expression of Agouti gene-related protein (AgRP), neuropeptide Y (NPY), and proopiomelanocortin (POMC) and equal plasma leptin and glucose levels after food deprivation. Leptin injections in C57BL mice on day 17 of pregnancy decreased BW in both male and female offspring but inhibited FI and DIO only in male offspring. Our results show that hyperleptinemia during pregnancy has sex-specific long-term effects on energy balance regulation in progeny and does not predispose offspring to developing obesity.
Joint tuning for direction of motion and binocular disparity in macaque MT is largely separable
Authors: Smolyanskaya Alexandra , Ruff Douglas A. , Born Richard T.
Published: October 2013

Neurons in sensory cortical areas are tuned to multiple dimensions, or features, of their sensory space. Understanding how single neurons represent multiple features is of great interest for determining the informative dimensions of the neurons' response, the decoding algorithms appropriate for extracting this information from the neuronal population, and for determining where specific transformations occur along the visual hierarchy. Despite the established role of cortical area MT in judgments of motion and depth, it is not known how individual neurons jointly encode the two dimensions. We investigated the joint tuning of individual MT neurons for two visual features: direction of motion and binocular disparity, an important depth cue. We found that a separable, multiplicative combination of tuning for the two features can account for more than 90% of the variance in the joint tuning function for over 91% of MT neurons. These results suggest 1) that each feature can be read out independently from MT by simply averaging across the population without regard to the other feature and 2) that the inseparable representations seen in subsequent areas, such as MST, must be computed beyond MT. Intriguingly, we found that the remaining nonseparable component of the joint tuning function often manifested as small but systematic changes in the neurons' preferences for one feature as the other one was varied. We believe this reflects the local columnar organization of tuning for direction and binocular disparity in MT, indicating that joint tuning may provide a new tool with which to probe functional architecture.
Suprasellar Mature Cystic Teratoma: An Unusual Location for an Uncommon Tumor
Authors: Sweiss Raed B. , Shweikeh Faris , Sweiss Fadi B. , Zyck Stephanie , Dalvin Lauren , Siddiqi Javed
Published: October 2013

Intracranial germ cell tumors are uncommon and account for only 0.3–3.4% of all intracranial tumors. Teratomas are a subset of these neoplasms, and their finding in brain structures is exceptionally rare, and occurrence within the skull base is quite novel. The authors report the case of a 57-year-old male patient who presented with vision changes, incontinence, ataxia, and altered mental status of 1 week’s duration. Imaging revealed a large intrasellar mass with suprasellar extension, involvement of the ventricular system, and marked hydrocephalus with the enlargement of the lateral and third ventricles. The patient underwent a pterional craniotomy/transsylvian approach for resection of the mass. Postoperative histological examination of the resected mass was confirmatory for a mature cystic teratoma. This was followed by radiotherapy, stereotactic radiosurgery, and adjuvant radiotherapy. At the most recent followup, approximately 4 years later, the patient is doing well with improved vision since the operation. This report highlights our experience with a teratoma in a very unusual location, and we review the relevant literature.
Equivalency Relations between Continuous g-Frames and Stability of Alternate Duals of Continuous g-Frames in Hilbert -Modules
Authors: Xiang Zhong-Qi
Published: October 2013

We introduce the modular continuous g-Riesz basis to improve one existing result for continuous g-Riesz basis in Hilbert -modules, and then we study the equivalency relations between continuous g-frames in Hilbert -modules, and, in particular, we obtain two necessary and sufficient conditions under which two continuous g-frames are similar. Finally, we generalize a stability result for alternate duals of g-frames in Hilbert spaces to alternate duals of continuous g-frames in Hilbert -modules.
Cooperative Search by Combining Simulated and Real Robots in a Swarm under the View of Multibody System Dynamics
Authors: Tang Qirong , Eberhard Peter
Published: October 2013

This paper presents a new approach for cooperative search of a robot swarm. After modeling the robot, the mechanical Particle Swarm Optimization method is conducted based on physical robot properties. Benefiting from the effective localization and navigation by sensor data fusion, a mixed robot swarm which contains both simulated and real robots is then successfully used for searching a target cooperatively. With the promising results from experiments based on different scenarios, the feasibility, the interaction of real and simulated robots, the fault tolerance, and also the scalability of the proposed method are investigated.
Preparation and Characterization of Chitosan Binder-Based Electrode for Dye-Sensitized Solar Cells
Authors: Jin En Mei , Park Kyung-Hee , Park Ju-Young , Lee Jae-Wook , Yim Soon-Ho , Zhao Xing Guan , Gu Hal-Bon , Cho Sung-Young , Fisher John Gerard , Kim Tae-Young
Published: October 2013

A chitosan binder-based TiO2photoelectrode is used in dye-sensitized solar cells (DSSCs). Field-emission scanning electron microscope (FE-SEM) images revealed that the grain size, thickness, and distribution of TiO2films are affected by the chitosan content. With addition of 2.0 wt% chitosan to the TiO2film (D2), the surface pore size became the smallest, and the pores were fairly evenly distributed. The electron transit time, electron recombination lifetime, diffusion coefficient, and diffusion length were analyzed by IMVS and IMPS. The best DSSC, with 2.0 wt% chitosan addition to the TiO2film, had a shorter electron transit time, longer electron recombination lifetime, and larger diffusion coefficient and diffusion length than the other samples. The results of 2.0 wt% chitosan-added TiO2DSSCs are an electron transit time of  s, electron recombination lifetime of  s, diffusion coefficient of  cm2s−1, diffusion length of 14.81 μm, and a solar conversion efficiency of 4.18%.
Uniform Dispersion of Multiwalled Carbon Nanotubes in Copper Matrix Nanocomposites Using Metal Injection Molding Technique
Authors: Muhsan Ali Samer , Ahmad Faiz , Mohamed Norani M. , Megat Yusoff Puteri Sri Melor , Rafi Raza Muhammad
Published: October 2013

This work presents a novel fabrication approach of multiwalled carbon nanotubes (MWNTs) reinforced copper (Cu) matrix nanocomposites. A combination of nanoscale dispersion of functionalized MWNTs in low viscose media of dissolved paraffin wax under sonication treatment followed by metal injection molding (MIM) technique was adopted. MWNTs contents were varied from 0 to 10 vol.%. Information about the degree of purification and functionalization processes, evidences on the existence of the functional groups, effect of sonication time on the treated MWNTs, and microstructural analysis of the fabricated Cu/MWNTs nanocomposites were determined using TEM, EDX, FESEM, and Raman spectroscopy analysis. The results showed that the impurities of the pristine MWNTs such as Fe, Ni catalyst, and the amorphous carbon have been significantly removed after purification process. Meanwhile, FESEM and TEM observations showed high stability of MWNTs at elevated temperatures and uniform dispersion of MWNTs in Cu matrix at different volume fractions and sintering temperatures (950, 1000 & 1050°C). The experimentally measured thermal conductivities of Cu/MWNTs nanocomposites showed remarkable increase (11.25% higher than sintered pure Cu) with addition of 1 vol.% MWNTs, and slight decrease below the value of sintered Cu at 5 and 10 vol.% MWNTs.
Thyroid Hemiagenesis Associated with Hashimoto’s Thyroiditis
Authors: Nsame D. , Chadli A. , Hallab L. , El Aziz S. , El Ghomari H. , Farouqi A.
Published: October 2013

Thyroid hemiagenesis is a rare congenital anomaly resulting from failure of one thyroid lobe development. We report a 23-year-old female presented with Hashimoto’s thyroiditis in left lobe, associated with hemiagenesis of right lobe and isthmus which was previously diagnosed as Graves’ hyperthyroidism, but developed further into Hashimoto’s thyroiditis after being treated with antithyroid drugs. The symptoms of hyperthyroidism in the current case led to the diagnostic confirmation by scintiscanning of an absent lobe. The antithyroid pharmacotherapy by thiamazole was used. However, due to symptoms of hypothyroidism, it was discontinued two months later, so thyroid hormone substitution was reintroduced. Antithyroid antibody studies and ultrasonography documented the presence of Hashimoto’s thyroiditis.
Combined Treatment with Myo-Inositol and Selenium Ensures Euthyroidism in Subclinical Hypothyroidism Patients with Autoimmune Thyroiditis
Authors: Nordio Maurizio , Pajalich Raffaella
Published: October 2013

Background. Hashimoto's thyroiditis (HT), also known as chronic lymphocytic thyroiditis or chronic autoimmune thyroiditis, is the most common form of thyroiditis affecting more than 10% of females and 2% of males. The present study aims to evaluate the beneficial effect of a combined treatment, Myo-Inositol plus selenomethionine, on subclinical hypothyroidism.Methods. The study was designed as a double-blind randomized controlled trial. Eligible patients were women diagnosed with subclinical hypothyroidism having Tg antibodies (TgAb) titer higher than 350 IU/mL. Outcome measures were Thyroid Stimulating Hormone (TSH) levels, thyroid peroxidase antibodies (TPOAb) and TgAb titer, selenium, and Myo-Inositol plasma concentration.Results. In the present paper, we demonstrated that the beneficial effects obtained by selenomethionine treatment on patients affected by subclinical hypothyroidism, likely due to the presence of autoantibody (TPOAb and TgAb), are further improved by cotreatment with Myo-Inositol.Conclusions. Indeed, due to its action as TSH second messenger, Myo-Inositol treatment reduces TSH levels closer to physiological concentrations.
The Role of Mannose-Binding Lectin in Severe Sepsis and Septic Shock
Authors: De Pascale Gennaro , Cutuli Salvatore Lucio , Pennisi Mariano Alberto , Antonelli Massimo
Published: October 2013

Severe sepsis and septic shock are a primary cause of death in patients in intensive care unit (ICU). Investigations upon genetic susceptibility profile to systemic complications during severe infections are a field of increasing scientific interest. Particularly when adaptive immune system is compromised or immature, innate immunity plays a key role in the immediate defense against invasive pathogens. Mannose-binding lectin (MBL) is a serum protein that recognizes a wide range of pathogenic microorganisms and activates complement cascade via the antibody-independent pathway. More than 30% of humans harbor mutations in MBL gene (MBL2) resulting in reduced plasmatic levels and activity. Increased risk of infection acquisition has been largely documented in MBL-deficient patients, but the real impact of this form of innate immunosuppression upon clinical outcome is not clear. In critically ill patients higher incidence and worse prognosis of severe sepsis/septic shock appear to be associated with low-producers haplotypes. However an excess of MBL activation might be also harmful due to the possibility of an unbalanced proinflammatory response and an additional host injury. Strategies of replacement therapies in critically ill patients with severe infections are under investigation but still far to be applied in clinical practice.
Global Analysis of a Model of Viral Infection with Latent Stage and Two Types of Target Cells
Authors: Liu Shuo , Ma Lina , Li Jianquan , Zhao Qingbo
Published: October 2013

By introducing the probability function describing latency of infected cells, we unify some models of viral infection with latent stage. For the case that the probability function is a step function, which implies that the latency period of the infected cells is constant, the corresponding model is a delay differential system. The model with delay of latency and two types of target cells is investigated, and the obtained results show that when the basic reproduction number is less than or equal to unity, the infection-free equilibrium is globally stable, that is, the in-host free virus will be cleared out finally; when the basic reproduction number is greater than unity, the infection equilibrium is globally stable, that is, the viral infection will be chronic and persist in-host. And by comparing the basic reproduction numbers of ordinary differential system and the associated delayed differential system, we think that it is necessary to elect an appropriate type of probability function for predicting the final outcome of viral infection in-host.
Preparation and Properties of Clay-Reinforced Epoxy Nanocomposites
Authors: Kusmono  , Wildan M. W. , Mohd Ishak Z. A.
Published: October 2013

The clay-reinforced epoxy nanocomposite was prepared by the polymerization method. The effect of clay addition on the mechanical properties of epoxy/clay nanocomposites was studied through tensile, flexural, impact strength, and fracture toughness tests. The morphology and tribology behavior of epoxy/clay nanocomposites were determined by X-ray diffraction (XRD) and wear test, respectively. The wear test was performed to determine the specific abrasion of the nanocomposites. In addition, the water absorption characteristic of the nanocomposites was also investigated in this study. XRD analysis indicated that the exfoliation structure was observed in the epoxy nanocomposites with 3 wt% of clay, while the intercalated structure was shown at 6 wt% of clay. It was found that the addition of clay up to 3 wt% increased the tensile strength, flexural strength, impact strength, and the fracture toughness. On the contrary, the presence of above 3 wt% of clay produced a reverse effect. It could be concluded that the best properties in mechanical, wear resistance, and water resistance were obtained for the epoxy nanocomposites containing 3 wt% of clay.
A Novel Fusion Scheme for Vision Aided Inertial Navigation of Aerial Vehicles
Authors: Xiao Ming , Pan Liang , Hu Tianjiang , Shen Lincheng
Published: October 2013

Vision-aided inertial navigation is an important and practical mode of integrated navigation for aerial vehicles. In this paper, a novel fusion scheme is proposed and developed by using the information from inertial navigation system (INS) and vision matching subsystem. This scheme is different from the conventional Kalman filter (CKF); CKF treats these two information sources equally even though vision-aided navigation is linked to uncertainty and inaccuracy. Eventually, by concentrating on reliability of vision matching, the fusion scheme of integrated navigation is upgraded. Not only matching positions are used, but also their reliable extents are considered. Moreover, a fusion algorithm is designed and proved to be the optimal as it minimizes the variance in terms of mean square error estimation. Simulations are carried out to validate the effectiveness of this novel navigation fusion scheme. Results show the new fusion scheme outperforms CKF and adaptive Kalman filter (AKF) in vision/INS estimation under given scenarios and specifications.
Microstructural Evolution during DPRM Process of Semisolid Ledeburitic D2 Tool Steel
Authors: Mohammed M. N. , Omar M. Z. , Syarif J. , Sajuri Z. , Salleh M. S. , Alhawari K. S.
Published: October 2013

Semisolid metal processing is a relatively new technology that offers several advantages over liquid processing and solid processing because of the unique behaviour and characteristic microstructure of metals in this state. With the aim of finding a minimum process chain for the manufacture of high‐quality production at minimal cost for forming, the microstructural evolution of the ledeburitic AISI D2 tool steel in the semisolid state was studied experimentally. The potential of the direct partial remelting (DPRM) process for the production of AISI D2 with a uniform globular microstructure was revealed. The liquid fraction was determined using differential scanning calorimetry. The microstructures of the samples were investigated using an optical microscope and a scanning electron microscope equipped with an energy dispersive spectroscopy analyser, while X‐ray phase analysis was performed to identify the phase evolution and the type of carbides. Mechanical characterisation was completed by hardness measurements. The typical microstructure after DPRM consists of metastable austenite which was located particularly in the globular grains (average grain size about 50 μm), while the remaining interspaces were filled by precipitated eutectic carbides on the grain boundaries and lamellar network.
Copper Corrosion by Atmospheric Pollutants in the Electronics Industry
Authors: Valdez Salas Benjamin , Schorr Wiener Michael , Zlatev Koytchev Roumen , López Badilla Gustavo , Ramos Irigoyen Rogelio , Carrillo Beltrán Monica , Radnev Nedev Nicola , Curiel Alvarez Mario , Rosas Gonzalez Navor , Bastidas Rull Jose María
Published: October 2013

Hydrogen sulphide (H2S) is considered one of the most corrosive atmospheric pollutants. It is a weak, diprotic, reducing acid, readily soluble in water and dispersed into the air by winds when emitted from natural, industrial, and anthropogenic sources. It is a pollutant with a high level of toxicity impairing human health and the environment quality. It attacks copper forming thin films of metallic sulphides or dendrite whiskers, which are cathodic to the metal substrate, enhancing corrosion. H2S is actively involved in microbially influenced corrosion (MIC) which develops in water, involving sulphur based bacteria, in oxidizing and reducing chemical reactions. H2S is found in concentrated geothermal brines, in the atmosphere of geothermal fields, and in municipal sewage systems. Other active atmospheric pollutants include SOX, NOX, and CO. This investigation reports on the effects of H2S on copper in microelectronic components of equipment and devices, with the formation of nonconductive films that lead to electrical failures.
Risk Factors for High-Titer Inhibitor Development in Children with Hemophilia A: Results of a Cohort Study
Authors: Halimeh Susan , Bidlingmaier Christoph , Heller Christine , Gutsche Sven , Holzhauer Susanne , Kenet Gili , Kurnik Karin , Manner Daniela , Iorio Alfonso , Nowak-Göttl Ulrike
Published: October 2013

Among the discussed risk factors for high-titre inhibitor (HRI) development in patients with hemophilia A (HA) are high dose FVIII replacement therapy and use of recombinant FVIII concentrates (rFVIII). The aim of this study was to evaluate the aforementioned risk factors for HRI development in children with hemophilia A ≤2%. About 288 ascertained PUPs (Israel and Germany) were followed after initial HA diagnosis over 200 exposure days. Inhibitor-free survival, hazard ratios (HR), and 95% confidence intervals (CIs) were calculated. Adjustment was performed for factor VIII concentrates, median single dose over the first three months of treatment, first FVIII administration before the age of three months, presence of risk HA gene mutations, “intensive treatment moments” and “year of birth” (proxy for different treatment periods). HRI occurred in 71/288 children (24.7%). In multivariate analysis adjusted for “year of birth”, underlying risk gene mutations (HR/CI: 2.37/1.40–3.99), FVIII dose, measured per one IU increase per kgbw (HR/CI: 1.05/1.04–1.07), and first FVIII administration before the age of three months showed a significant impact on HR development. The risk of HRI development was similar for recombinant or plasmatic FVIII products. Children at risk should be treated with carefully calculated lower dose regimens, adapted to individual bleeding situations.
Partial Regularity for Nonlinear Subelliptic Systems with Dini Continuous Coefficients in Heisenberg Groups
Authors: Wang Jialin , Hong Pingzhou , Liao Dongni , Yu Zefeng
Published: October 2013

This paper is concerned with partial regularity to nonlinear subelliptic systems with Dini continuous coefficients under quadratic controllable growth conditions in the Heisenberg groupℍn. Based on a generalization of the technique of𝒜-harmonic approximation introduced by Duzaar and Steffen, partial regularity to the sub-elliptic system is established in the Heisenberg group. Our result is optimal in the sense that in the case of Hölder continuous coefficients we establish the optimal Hölder exponent for the horizontal gradients of the weak solution on its regular set.
The Diagonally Dominant Degree and Disc Separation for the Schur Complement of Ostrowski Matrix
Authors: Zhao Jianxing , Wang Feng , Li Yaotang
Published: October 2013

By applying the properties of Schur complement and some inequality techniques, some new estimates of diagonally and doubly diagonally dominant degree of the Schur complement of Ostrowski matrix are obtained, which improve the main results of Liu and Zhang (2005) and Liu et al. (2012). As an application, we present new inclusion regions for eigenvalues of the Schur complement of Ostrowski matrix. In addition, a new upper bound for the infinity norm on the inverse of the Schur complement of Ostrowski matrix is given. Finally, we give numerical examples to illustrate the theory results.
Factors Associated with Women’s Chronic Disease Management: Associations of Healthcare Frustrations, Physician Support, and Self-Care Needs
Authors: Smith Matthew Lee , Ory Marcia G. , Ahn SangNam , Miles Toni P.
Published: October 2013

Previous research emphasizes the importance of reducing healthcare frustrations and enhancing physician supports to help patients engage in recommended healthcare regimens. However, less is known about how these factors are associated with aging women’s knowledge about self-care behavior. This study examined the sociodemographics, health indicators, healthcare-related frustrations, and perceptions of physician support associated with middle-aged and older adult females’ self-reported need for help to learn how to take better care of their health. Data were analyzed from 287 females with one or more chronic conditions who completed The National Council on Aging (NCOA) Chronic Care Survey. A logistic regression model was developed. Women who were non-White (OR=2.26,P=0.049) were more likely to need help learning how to better manage their health. Those who had some college education or more (OR=0.55,P=0.044) and lower healthcare-related frustrations (OR=0.44,P=0.017) and perceived to have more physician support (OR=0.49,P=0.033) were less likely to need help learning how to better manage their health. Findings can inform the planning, implementation, assessment, and dissemination of evidence-based self-management programs for middle-aged and older women within and outside of clinical settings.
Morphology and Optical Property of ZnO Nanostructures Grown by Solvothermal Method: Effect of the Solution Pretreatment
Authors: Zhang Wenhui , Chen Xiahui , Xu Ning , Xiang Rong , Zhu Yuan , Tang Zikang
Published: October 2013

Zinc oxide (ZnO) nanostructures with different morphologies such as nanopyramids, nanosheets, and nanoparticles have been grown by a simple solvothermal method. The influence of solution pretreatmentt on the morphology and optical properties of ZnO nanostructures has been studied. The experimental results revealed the morphology of ZnO transformed from nanopyramids or nanosheets to nanoparticles after solution pretreatment. Raman and photoluminescence spectra are recorded to examine the crystallinity and optical property of the samples.
Intestinal GUCY2C Prevents TGF-β Secretion Coordinating Desmoplasia and Hyperproliferation in Colorectal Cancer
Authors: Gibbons Ahmara V. , Lin Jieru E. , Kim Gilbert W. , Marszalowicz Glen P. , Li Peng , Stoecker Brian A. , Blomain Erik S. , Rattan Satish , Snook Adam E. , Schulz Stephanie , Waldman Scott A.
Published: October 2013

Tumorigenesis is a multistep process that reflects intimate reciprocal interactions between epithelia and underlying stroma. However, tumor-initiating mechanisms coordinating transformation of both epithelial and stromal components are not defined. In humans and mice, initiation of colorectal cancer is universally associated with loss of guanylin and uroguanylin, the endogenous ligands for the tumor suppressor guanylyl cyclase C (GUCY2C), disrupting a network of homeostatic mechanisms along the crypt-surface axis. Here, we reveal that silencing GUCY2C in human colon cancer cells increases Akt-dependent TGF-β secretion, activating fibroblasts through TGF-β type I receptors and Smad3 phosphorylation. In turn, activating TGF-β signaling induces fibroblasts to secrete hepatocyte growth factor (HGF), reciprocally driving colon cancer cell proliferation through cMET-dependent signaling. Elimination of GUCY2C signaling in mice (Gucy2c−/−) produces intestinal desmoplasia, with increased reactive myofibroblasts, which is suppressed by anti-TGF-β antibodies or genetic silencing of Akt. Thus, GUCY2C coordinates intestinal epithelial–mesenchymal homeostasis through reciprocal paracrine circuits mediated by TGF-β and HGF. In that context, GUCY2C signaling constitutes a direct link between the initiation of colorectal cancer and the induction of its associated desmoplastic stromal niche. The recent regulatory approval of oral GUCY2C ligands to treat chronic gastrointestinal disorders underscores the potential therapeutic opportunity for oral GUCY2C hormone replacement to prevent remodeling of the microenvironment essential for colorectal tumorigenesis. Cancer Res; 73(22); 6654–66. ©2013 AACR.
CTLA-4 and PD-1/PD-L1 Blockade: New Immunotherapeutic Modalities with Durable Clinical Benefit in Melanoma Patients
Authors: Ott Patrick A. , Hodi F. Stephen , Robert Caroline
Published: October 2013

Immune checkpoint blockade with monoclonal antibodies directed at the inhibitory immune receptors CTLA-4, PD-1, and PD-L1 has emerged as a successful treatment approach for patients with advanced melanoma. Ipilimumab is the first agent associated with a documented improved overall survival benefit in this patient population. A striking attribute of CTLA-4 blockade is the durability of objective responses, leading to speculation of a possible cure for some patients. Many tumor responses achieved with PD-1 and PD-L1 inhibition were durable in the phase I trials and were seen in a higher proportion of patients with melanoma than typically observed with ipilimumab. Biomarker development to identify the subset of patients with melanoma who will achieve durable clinical benefit with checkpoint blockade is critical; tumor PD-L1 expression has been promising in early studies. The contrast between unprecedented response rates but limited durability of responses achieved with BRAF and MEK inhibition in BRAFV600-mutated melanoma and the impressive durability but relatively low rate of response achieved with immune checkpoint blockade is striking. Preclinical data on potential synergies between CTLA-4/PD-1/PD-L1 inhibition and MAPK-targeted therapy is emerging, and combined immune checkpoint blockade and MAPK inhibition are being explored in clinical trials. Other promising approaches to increase the number of patients with melanoma who benefit from durable responses with immune checkpoint blockade include concurrent or sequenced CTLA-4 and PD-1/PD-L1 inhibition and combination with other immunotherapeutic strategies. Clin Cancer Res; 19(19); 5300–9. ©2013 AACR.
Adoptive T-cell Transfer Therapy and Oncogene-Targeted Therapy for Melanoma: The Search for Synergy
Authors: Kwong Mei Li M. , Neyns Bart , Yang James C.
Published: October 2013

The clinical strengths of immunotherapy and small-molecule inhibitors targeting the mitogen-activated protein kinase (MAPK) pathway appear to be largely complementary for the treatment of advanced melanoma. In current practice, most patients with BRAF V600 mutant melanomas will see both modalities. Several in vitro and in vivo studies suggest that combining immunotherapy with MAPK inhibition may have synergistic effects. First, mouse models show that adoptive cell therapy (ACT) can be enhanced by vaccination. Rapid tumor destruction by vemurafenib could provide a vaccine-like stimulus to adoptively transferred T cells. Second, both in mice and in early clinical trials, melanoma metastases treated with MAPK inhibitors seem to display increased T-cell infiltrates. Third, MAPK inhibition upregulates the expression of some melanoma antigens and, therefore, may enhance T-cell recognition of vemurafenib-treated melanomas. Fourth, vemurafenib may sensitize tumor cells to immune destruction. Finally, some investigators have found that an optimal antitumor effect from MAPK inhibition is dependent on an intact host immune response. Currently, the Surgery Branch of the National Cancer Institute has initiated a phase II trial combining the BRAF inhibitor vemurafenib with ACT using tumor-infiltrating lymphocytes in patients with BRAF-mutant tumors to investigate the safety and efficacy of this combination. The proposed mechanisms for synergy between these two modalities can be complex, and their optimal combination may require testing a variety of sequences and schedules. Clin Cancer Res; 19(19); 5292–9. ©2013 AACR.
New Strategies in Endometrial Cancer: Targeting the PI3K/mTOR Pathway—The Devil Is in the Details
Authors: Myers Andrea P.
Published: October 2013

Endometrial cancer is the most common gynecologic malignancy in the developed world and affects approximately 40,000 women in the United States each year. The phosphoinositide 3-kinase (PI3K) signaling pathway regulates key aspects of cancer biology including glucose uptake and metabolism, cellular growth, and survival. Endometrial cancers harbor the highest rates of PI3K pathway alterations reported to date. The PI3K pathway is highly druggable and several classes of agents are in clinical development including rapalogs, pan-PI3K inhibitors, PI3K isoform-specific inhibitors, dual PI3K/mTOR catalytic inhibitors, mTOR-specific catalytic inhibitors, and AKT inhibitors. It has been 10 years since the initiation of the first studies of rapalogs as anticancer agents. There are more than 20 registered clinical trials of PI3K/mTOR inhibitors as single agents or in therapeutic combinations for the treatment of endometrial cancers. What have we learned from the completed studies? What can we expect to learn from ongoing studies? What should we anticipate moving forward? Clin Cancer Res; 19(19); 5264–74. ©2013 AACR.
Lycopene Metabolite, Apo-10′-Lycopenoic Acid, Inhibits Diethylnitrosamine-Initiated, High Fat Diet–Promoted Hepatic Inflammation and Tumorigenesis in Mice
Authors: Ip Blanche C. , Hu Kang-Quan , Liu Chun , Smith Donald E. , Obin Martin S. , Ausman Lynne M. , Wang Xiang-Dong
Published: October 2013

Obesity is associated with increased risk in hepatocellular carcinoma (HCC) development and mortality. An important disease control strategy is the prevention of obesity-related hepatic inflammation and tumorigenesis by dietary means. Here, we report that apo-10′-lycopenoic acid (APO10LA), a cleavage metabolite of lycopene at its 9′,10′-double bond by carotene-9′,10′-oxygenase, functions as an effective chemopreventative agent against hepatic tumorigenesis and inflammation. APO10LA treatment on human liver THLE-2 and HuH7 cells dose dependently inhibited cell growth and upregulated sirtuin 1 (SIRT1), a NAD+-dependent protein deacetylase that may suppress hepatic carcinogenesis. This observed SIRT1 induction was associated with decreased cyclin D1 protein, increased cyclin-dependent kinase inhibitor p21 protein expression, and induced apoptosis. APO10LA supplementation (10 mg/kg diet) for 24 weeks significantly reduced diethylnitrosamine-initiated, high fat diet (HFD)–promoted hepatic tumorigenesis (50% reduction in tumor multiplicity; 65% in volume) and lung tumor incidence (85% reduction) in C57Bl/6J mice. The chemopreventative effects of APO10LA were associated with increased hepatic SIRT1 protein and deacetylation of SIRT1 targets, as well as with decreased caspase-1 activation and SIRT1 protein cleavage. APO10LA supplementation in diet improved glucose intolerance and reduced hepatic inflammation [decreased inflammatory foci, TNFα, interleukin (IL)-6, NF-κB p65 protein expression, and STAT3 activation] in HFD-fed mice. Furthermore, APO10LA suppressed Akt activation, cyclin D1 gene, and protein expression and promoted PARP protein cleavage in transformed cells within liver tumors. Taken together, these data indicate that APO10LA can effectively inhibit HFD-promoted hepatic tumorigenesis by stimulating SIRT1 signaling while reducing hepatic inflammation. Cancer Prev Res; 6(12); 1304–16. ©2013 AACR.
Initiating a Pediatric Spasticity Program with Multispecialty and Multi-Institutional Support: A Preliminary Report
Authors: James Hector E. , Hofrichter Paul B. , Spierre Louise Z. , Aldana Philipp R.
Published: October 2013

We describe the initiation and development of a comprehensive multidisciplinary and multi-institutional program for the evaluation and management of youth with spasticity. A descriptive step-by-step process of the administrative and organizational sequence of the development of the program is delineated. The Spasticity Clinic now meets regularly, and multiple diagnostic and treatment modalities are performed. This experience may assist those that wish to initiate a similar venue for youth with spasticity.
Nutrition and Epigenetics
Authors: Tokunaga Miki , Takahashi Toru , Singh Ram B. , De Meester Fabien , Wilson Douglas W.
Published: October 2013

Cardiovascular diseases (CVDs), diabetes, obesity and cancer are polygenic in nature and their prevalences and mortality vary depending upon genetic susceptibility and the presence of phenotype risk factors. The heritability of variant phenotypes may depend on the intake of proinflammatory or anti-inflammatory nutrients, for their expression as phenotypes or their suppression. Genes are important for the determination of enzymes, receptors, cofactors, structural components involved in the regulation of blood pressure, the metabolism of lipids, lipoproteins and inflammatory and coagulation factors that help discover individual risks for CVDs. An interaction of specific nutrients with the genetic code possessed by all nucleated cells can be recognized. Further studies indicate that methylation of the chromatins appears to be most important in epigenetics leading to an increased risk of obesity and metabolic syndrome. The new field of epigenetics has emerged with more impact on cellular transgeneration profiles primarily dealing with health perspectives. It is not a change in the sequence of the DNA itself, but in how genes are expressed because some of them may get ‘shut off' as a result of environmental trauma and others are expressed due to a favorable environment.
Impact of age on the efficacy and safety of extended-duration thromboprophylaxis in medical patients
Authors: Hull Russell D. , Schellong Sebastian M. , Tapson Victor F. , Monreal Manuel , Samama Meyer-Michel , Chen Min , Deslandes Bruno , Turpie Alexander G. G. , Yusen Roger D.
Published: October 2013

The EXCLAIM study enrolled hospitalised acutely ill medical patients with age >40 years and recently-reduced mobility into a trial of extended-duration anticoagulant thromboprophylaxis. This post-hoc analysis evaluated the impact of age on patient outcomes. After completion of open-label therapy with enoxaparin 40 mg once-daily (10 ± 4 days), eligible patients underwent randomisation to receive double-blind therapy of enoxaparin (n=2,975) or placebo (n=2,988) for 28 ± 4 days. During follow-up, the venous thromboembolism (VTE) risk increased with age in both treatment groups. In patients with age >75 years, those who received extended-duration enoxaparin had lower incidence of VTE (2.5% vs 6.7%; absolute difference [AD] [95% confidence interval]: −4.2% [−6.5, −2.0]), proximal deep-vein thrombosis (2.5% vs 6.6%; AD −4.1 % [−6.2, −2.0]), and symptomatic VTE (0.3% vs 1.5%; AD −1.2% [−2.2, −0.3]), in comparison to those who received placebo. In patients with age ≤75 years, those who received enoxaparin had reduced VTE (2.4% vs 2.8%; AD −0.4% [−1.5, 0.7]) and symptomatic VTE (0.2% vs 0.7%; AD −0.6% [−1.0, −0.1]) in comparison to those who received placebo. In both age subgroups, patients who received enoxaparin had increased rates of major bleeding versus those who received placebo: age >75 years (0.6% vs 0.2%; AD +0.3% [−0.2, 0.9], respectively); age ≤75 years (0.7% vs 0.2%; AD +0.5% [0.1, 0.9]). Patients in both age subgroups that received enoxaparin had similar low bleeding rates (0.6% and 0.7%, respectively). VTE risk increased with age, though the bleeding risk did not. Patients with age >75 years had a more favourable benefit-to-harm profile than younger patients.
Prognostic significance of free-floating right heart thromboemboli in acute pulmonary embolism
Authors: Becattini Cecilia , Guglielmelli Emanuele , Floriani Irene , Morrone Vincenzo , Caponi Carla , Pizzorno Luigi , Masotti Luca , Bongarzoni Amedeo , Pignataro Luigi , Casazza Franco
Published: October 2013

The exact prevalence of mobile right heart thromboemboli (RHTh) in patients with pulmonary embolism (PE) is unknown, depending upon PE severity and the use of early echocardiography. Similarly, the mortality rate is variable, though RHTh detection appears to substantially increase the risk of death in patients with PE. The aim of this study was to assess the prevalence of RHTh in different risk categories in a wide series of patients with PE, and to analyse the effect of RHTh on in-hospital mortality. Among 1,716 patients enrolled in the Italian Pulmonary Embolism Registry, 1,275 (13.3% at high risk, 59.3% at intermediate risk and 27.4% at low risk) had echocardiography within 48 hours from hospital admission and entered the study. Overall, RHTh were detected in 57 patients (4.5%, at admission echocardiography in 88%): in 27/169 (16%) high-risk, in 29/756 (3.8%) intermediate-risk and 1/350 (0.3%) low-risk patients, respectively. At multivariate analysis, only advanced age (odds ratio [OR] 1.61, 95% confidence [CI] 1.27–2.03, p<0.0001), high-risk category (OR vs low-risk category 37.82, 95% CI 11.26–127.06, p<0.0001) and recurrent PE (OR 45.92, 95%CI 15.19–139.96, p<0.0001) showed a statistically significant effect on mortality. The presence of RHTh significantly increased the risk of dying (OR 3.89, 95%CI 1.98–7.67, p=0.0001) at univariate analysis, but this result was not mantained in the multivariate model (OR 1.64, 95%CI 0.75–3.60, p=0.216). In conclusion, though patients with RHTh had a more severe presentation of PE, this study did not detect an association between RHTh and prognosis.