bluuebunny/crossref_metadata_2025 huggingface dataset:
Facial and Periorbital Cellulitis due to Skin Peeling with Jet Stream by an Unauthorized Person
Authors: Kaptanoglu Asli Feride , Mullaaziz Didem , Suer Kaya
Published: April 2014

Technologies and devices for cosmetic procedures are developing with each passing day. However, increased and unauthorized use of such emerging technologies may also lead to increases in unexpected results and complications as well. Here, we report a case of facial cellulitis after a “beauty parlor” session of skin cleaning with jet stream peeling device in 19-year old female patient for the first time. Complications due to improper and unauthorized use of jet stream peeling devices may also cause doubts about the safety and impair the reputation of the technology as well. In order to avoid irreversible complications, local authorities should follow the technology and update the regulations where the dermatologists should take an active role.
Investigation of a New Flux-Modulated Permanent Magnet Brushless Motor for EVs
Authors: Fan Ying , Gu Lingling , Luo Yong , Han Xuedong , Cheng Ming
Published: April 2014

This paper presents a flux-modulated direct drive (FMDD) motor. The key is to integrate the magnetic gear with the PM motor while removing the gear inner-rotor. Hence, the proposed FMDD motor can achieve the low-speed high-torque output and high-speed compact design requirements as well as high-torque density with a simple structure. The output power equation is analytically derived. By using finite element analysis (FEA), the static characteristics of the proposed motor are obtained. Based on these characteristics, the system mathematical model can be established. Hence, the evaluation of system performances is conducted by computer simulation using the Matlab/Simulink. A prototype is designed and built for experimentation. Experimental results are given to verify the theoretical analysis and simulation.
Baseband Transceiver Design of a High Definition Radio FM System Using Joint Theoretical Analysis and FPGA Implementation
Authors: Chen Chien-Sheng , Lu Chyuan-Der , Shou Ho-Nien , Lin Le-Wei
Published: April 2014

Advances in wireless communications have enabled various technologies for wireless digital communication. In the field of digital radio broadcasting, several specifications have been proposed, such as Eureka-147 and digital radio mondiale (DRM). These systems require a new spectrum assignment, which incurs heavy cost due to the depletion of the available spectrum. Therefore, the in-band on-channel (IBOC) system has been developed to work in the same band with the conventional analog radio and to provide digital broadcasting services. This paper discusses the function and algorithm of the high definition (HD) radio frequency modulation (FM) digital radio broadcasting system. Content includes data format allocation, constellation mapping, orthogonal frequency division multiplexing (OFDM) modulation of the transmitter, timing synchronization, OFDM demodulation, integer and fraction carrier frequency (integer carrier frequency offset (ICFO) and fractional CFO (FCFO)) estimation, and channel estimation of the receiver. When we implement this system to the field programmable gate array (FPGA) based on a hardware platform, both theoretical and practical aspects have been considered to accommodate the available hardware resources.
On the Analyticity for the Generalized Quadratic Derivative Complex Ginzburg-Landau Equation
Authors: Huang Chunyan
Published: April 2014

We study the analytic property of the (generalized) quadratic derivative Ginzburg-Landau equation(1/2⩽α⩽1)in any spatial dimensionn⩾1with rough initial data. For1/2<α⩽1, we prove the analyticity of local solutions to the (generalized) quadratic derivative Ginzburg-Landau equation with large rough initial data in modulation spacesMp,11-2α(1⩽p⩽∞). Forα=1/2, we obtain the analytic regularity of global solutions to the fractional quadratic derivative Ginzburg-Landau equation with small initial data inB˙∞,10(ℝn)∩M∞,10(ℝn). The strategy is to develop uniform and dyadic exponential decay estimates for the generalized Ginzburg-Landau semigroupe-a+it-Δαto overcome the derivative in the nonlinear term.
A Mathematical Model for the Transmission and Spread of Drug Sensitive and Resistant Malaria Strains within a Human Population
Authors: Tumwiine Julius , Hove-Musekwa Senelani D. , Nyabadza Farai
Published: April 2014

Malaria remains by far the world's most important tropical disease, killing more people than any other communicable disease. A number of preventive and control measures have been put in place and most importantly drug treatment. The emergence of drug resistance against the most common and affordable antimalarials is widespread and poses a key obstacle to malaria control. A mathematical model that incorporates evolution of drug resistance and treatment as a preventive strategy is formulated and analyzed. The qualitative analysis of the model is given in terms of the effective reproduction number, Re. The existence and stability of the disease-free and endemic equilibria of the model are studied. We establish the threshold parameters below which the burden due to malaria can be brought under control. Numerical simulations are done to determine the role played by key parameters in the model. The public health implications of the results are twofold; firstly every effort should be taken to minimize the evolution of drug resistance due to treatment failure and secondly high levels of treatment and development of immunity are essential in reducing the malaria burden.
Statistical Summability through de la Vallée-Poussin Mean in Probabilistic Normed Spaces
Authors: Esi Ayhan
Published: April 2014

Two concepts—one of statistical convergence and the other of de la Vallée-Poussin mean—play an important role in recent research on summability theory. In this work we define a new type of summability methods and statistical completeness involving the ideas of de la Vallée-Poussin mean and statistical convergence in the framework of probabilistic normed spaces.
Effect of Three Colostrum Diets on Passive Transfer of Immunity and Preweaning Health in Calves on a California Dairy following Colostrum Management Training
Authors: Williams Deniece R. , Pithua Patrick , Garcia Angel , Champagne John , Haines Deborah M. , Aly Sharif S.
Published: April 2014

Following colostrum management training, a randomized field trial was conducted on a California dairy to determine the effect of supplementing pooled colostrum with either colostrum-derived replacer (CDR) or second-milking colostrum (transition milk) on failure of passive transfer (FPT) and preweaning morbidity risks. A total of 166 calves were randomly assigned to 4L first-milking pooled colostrum (treatment 1), 2L first-milking pooled colostrum and 2L of CDR (treatment 2), or 2L first-milking pooled colostrum and 2L second-milking pooled colostrum (treatment 3). Mean 24-hour serum TP and IgG for treatments 2 (TP 5.2 g/dL, IgG 15.9 g/L) and 3 (TP 5.4 g/dL, IgG 18.3 g/L) did not statistically differ but were significantly lower than for treatment 1 (TP 5.9 g/dL, IgG 24.6 g/L). Risk of FPT did not differ for treatments 1, 2, and 3 (0.0%, 9.3%, and 1.9%, resp.). Similarly, the preweaning risk of diarrhea (81.0%, 92.5%, and 87.0%, resp.) or pneumonia (6.9%, 13.2%, and 18.5%, resp.) did not differ between treatments. Feeding 4L first-milking pooled colostrum resulted in adequate passive transfer. When first-milking pooled colostrum quantity is inadequate, CDR or second-milking pooled colostrum can be used to supplement the required colostrum volume and IgG mass without adversely affecting the risks of FPT or preweaning diarrhea and pneumonia.
Bifurcations of Nontwisted Heteroclinic Loop with Resonant Eigenvalues
Authors: Jin Yinlai , Zhu Xiaowei , Guo Zheng , Xu Han , Zhang Liqun , Ding Benyan
Published: April 2014

By using the foundational solutions of the linear variational equation of the unperturbed system along the heteroclinic orbits to establish the local coordinate systems in the small tubular neighborhoods of the heteroclinic orbits, we study the bifurcation problems of nontwisted heteroclinic loop with resonant eigenvalues. The existence, numbers, and existence regions of 1-heteroclinic loop, 1-homoclinic loop, 1-periodic orbit, 2-fold 1-periodic orbit, and two 1-periodic orbits are obtained. Meanwhile, we give the corresponding bifurcation surfaces.
Bifurcations of Tumor-Immune Competition Systems with Delay
Authors: Bi Ping , Xiao Heying
Published: April 2014

A tumor-immune competition model with delay is considered, which consists of two-dimensional nonlinear differential equation. The conditions for the linear stability of the equilibria are obtained by analyzing the distribution of eigenvalues. General formulas for the direction, period, and stability of the bifurcated periodic solutions are given for codimension one and codimension two bifurcations, including Hopf bifurcation, steady-state bifurcation, and B-T bifurcation. Numerical examples and simulations are given to illustrate the bifurcations analysis and obtained results.
Global Bifurcation of a Novel Computer Virus Propagation Model
Authors: Ren Jianguo , Xu Yonghong , Liu Jiming
Published: April 2014

In a recent paper by J. Ren et al. (2012), a novel computer virus propagation model under the effect of the antivirus ability in a real network is established. The analysis there only partially uncovers the dynamics behaviors of virus spread over the network in the case where around bifurcation is local. In the present paper, by mathematical analysis, it is further shown that, under appropriate parameter values, the model may undergo a global B-T bifurcation, and the curves of saddle-node bifurcation, Hopf bifurcation, and homoclinic bifurcation are obtained to illustrate the qualitative behaviors of virus propagation. On this basis, a collection of policies is recommended to prohibit the virus prevalence. To our knowledge, this is the first time the global bifurcation has been explored for the computer virus propagation. Theoretical results and corresponding suggestions may help us suppress or eliminate virus propagation in the network.
Using the Sadakane Compressed Suffix Tree to Solve the All-Pairs Suffix-Prefix Problem
Authors: Haj Rachid Maan , Malluhi Qutaibah , Abouelhoda Mohamed
Published: April 2014

The all-pairs suffix-prefix matching problem is a basic problem in string processing. It has an application in the de novo genome assembly task, which is one of the major bioinformatics problems. Due to the large size of the input data, it is crucial to use fast and space efficient solutions. In this paper, we present a space-economical solution to this problem using the generalized Sadakane compressed suffix tree. Furthermore, we present a parallel algorithm to provide more speed for shared memory computers. Our sequential and parallel algorithms are optimized by exploiting features of the Sadakane compressed index data structure. Experimental results show that our solution based on the Sadakane’s compressed index consumes significantly less space than the ones based on noncompressed data structures like the suffix tree and the enhanced suffix array. Our experimental results show that our parallel algorithm is efficient and scales well with increasing number of processors.
Concomitant Intake of Quercetin with a Grain-Based Diet Acutely Lowers Postprandial Plasma Glucose and Lipid Concentrations in Pigs
Authors: Wein Silvia , Wolffram Siegfried
Published: April 2014

Treatment goals of diabetes mellitus type 2 (DMT2) include glycemic control and reduction of nonglycemic risk factors, for example, dyslipidemia. Quercetin, a plant-derived polyphenol, often discussed for possible antidiabetic effects, was investigated for acute postprandial glucose- and lipid-lowering effects in healthy growing pigs. Male pigs (n = 16, body weight = BW 25–30 kg) were fed flavonoid-poor grain-based meals without (GBM) or with quercetin (GBMQ). In a first experiment, postprandial plasma concentrations of glucose, nonesterified fatty acids (NEFA), and triacylglycerols were analyzed in 8 pigs receiving 500 g of either GBM or GBMQ (10 mg/kg BW) in a cross-over design. Blood samples were collected before, and up to 5 h every 30 min, as well as 6 and 8 h after the feeding. In the second experiment, 2 h after ingestions of 1000 g of either GBM or GBMQ (50 mg/kg BW) animals were sacrificed; gastric content was collected and analyzed for dry matter content. Quercetin ingestion reduced postprandial glucose, NEFA, and TG concentration, but two hours after ingestion of the meal no effect on gastric emptying was observed. Our results point to inhibitory effects of quercetin on nutrient absorption, which appear not to be attributable to delayed gastric emptying.
Korean Red Ginseng Saponin Fraction Rich in Ginsenoside-Rb1, Rc and Rb2 Attenuates the Severity of Mouse Collagen-Induced Arthritis
Authors: Endale Mehari , Im Eun Ju , Lee Joo Young , Kim Sung Dae , Yayeh Taddesse , Song Yong-Bum , Kwak Yi-Seong , Kim Chaekyun , Kim Seung-Hyung , Roh Seong-Soo , Cho Jae Youl , Rhee Man Hee
Published: April 2014

Despite a multitude of reports on anti-inflammatory properties of ginseng extracts or individual ginsenosides, data on antiarthritic effect of ginseng saponin preparation with mixed ginsenosides is limited. On the other hand, a combined therapy of safe and inexpensive plant-derived natural products such as ginsenosides can be considered as an alternative to treat arthritis. Our previousin vitrodata displayed a strong anti-inflammatory action of red ginseng saponin fraction-A (RGSF-A). We, herein, report a marked antiarthritic property of RGSF-A rich in ginsenoside Rb1, Rc, and Rb2. Collagen-induced arthritic (CIA) mice were treated with RGSF-A or methotrexate (MTX) for 5 weeks. Joint pathology, serum antibody production and leukocye activation, cytokine production in the circulation, lymph nodes, and joints were examined. RGSF-A markedly reduced severity of arthritis, cellular infiltration, and cartilage damage. It suppressed CD3+/CD69+, CD4+/CD25+, CD8+T-cell, CD19+, B220/CD23+B-cell, MHCII+/CD11c+, and Gr-1+/CD11b+cell activations. It further suppressed anti-CII- or anti-RF-IgG/IgM, TNF-α, IL-1β, IL-17, and IL-6 secretions but stimulated IL-10 levels in the serum, joint, or splenocyte. RGSF-A attenuated arthritis severity, modified leukocyte activations, and restored cytokine imbalances, suggesting that it can be considered as an antiarthritic agent with the capacity to ameliorate the immune and inflammatory responses in CIA mice.
Copper(II) Complexes of 2-(Methylthiomethyl)anilines: Spectral and Structural Properties and In Vitro Antimicrobial Activity
Authors: Olalekan Temitope E. , Beukes Denzil R. , Van Brecht Bernardus , Watkins Gareth M.
Published: April 2014

Copper(II) complexes of 2-(methylthiomethyl)anilines (1a–1f) have been obtained and characterized by elemental analyses, IR, electronic spectra, conductivity, and X-ray crystallography. The complexes (2a–2f) have the structural formula [CuCl2L] with the bidentate ligand coordinating through sulfur and nitrogen. The single crystal X-ray diffraction data reveal that the copper complex (2f) has a tetragonally distorted octahedral structure with long Cu–Cl equatorial bonds. Magnetic susceptibility measurements indicate the availability of one unpaired electron in the complexes and the conductivity measurements in DMF show their behaviour as nonelectrolytes. The solid reflectance spectra and the electronic spectra of the complexes in DMSO were determined. The ligands and their copper complexes were screened for in vitro antimicrobial activity against S. aureus, B. subtilis, E. coli, and C. albicans. The methoxysubstituted complex (2c) showed more promising antibacterial activity against S. aureus and B. subtilis than other compounds at the concentration tested.
Transforming Pain into Beauty: On Art, Healing, and Care for the Spirit
Authors: Ettun Rachel , Schultz Michael , Bar-Sela Gil
Published: April 2014

From drawing to sculpture, poetry to journaling, and dance to music and song, the arts can have a major impact on patients’ spiritual well‐being and health. The arts empower patients to fulfill the basic human drive to create and give patients a sense of possibility. Through creative expression, patients regain a feeling of wholeness, individually and as part of the larger world. Although spiritual caregivers have made occasional use of the arts, it would be better for the arts to be seen as a pillar of spiritual care provision. This paper provides a model for arts‐based spiritual care (chaplaincy) in oncology/hematology and elsewhere. We discuss how to match the art form intervention to the individual patient and give examples of many kinds of uniquely spiritual arts‐based interventions.
In life, there are occasional “caseuras,” or ruptures. Using a theoretical foundation drawn from theologian Michael Fishbane, our model of arts‐based spiritual care bridges the experience of the caesura to a renewed sense of meaning, or spiritual reorientation, that can be discovered within the reality of illness. Additionally, the ambiguity and playfulness inherent to creative expression strengthen the patient’s flexibility and resilience.
Antitumor and Antiangiogenic Activities of Curcumin in Cervical Cancer Xenografts in Nude Mice
Authors: Yoysungnoen-Chintana Pornphrom , Bhattarakosol Parvapan , Patumraj Suthiluk
Published: April 2014

To evaluate the effects of curcumin (CUR) on tumor progression and angiogenesis in cervical cancer- (CaSki-) implanted nude mice and on the angiogenic biomarkers: vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), and epidermal growth factor receptor (EGFR). CaSki cells were subcutaneously injected in nude mice to establish subcutaneous tumors. One month after injection, mice were orally administered vehicle or 500, 1,000, and 1,500 mg/kg of CUR daily × 30 consecutive days. Tumor volume was measured every 3-4 days. At the end of the study, tumor microvasculature was observed under confocal microscope, and immunohistochemical analyses were performed to detect CD31, VEGF, COX-2, and EGFR. CUR at the doses of 1,000 and 1,500 mg/kg showed significant tumor growth retardation (21.03% and 35.57%) versus CaSki + vehicle group. The microvascular density (MVD) in CaSki + vehicle group was significantly increased versus Control + vehicle group and significantly reduced by CUR (1,000 and 1,500 mg/kg). VEGF, COX-2, and EGFR expressions were upregulated in CaSki + vehicle group and attenuated significantly by CUR (1,000 and 1,500 mg/kg). In conclusion, high dose CUR inhibited tumor growth and angiogenesis in CaSki-implanted mice probably mediated by the downregulation of VEGF, COX-2 and EGFR. CUR may have a role in treating human cervical cancer and should be explored further.
Performance Study of CdS/Co‐Doped‐CdSe Quantum Dot Sensitized Solar Cells
Authors: Zou Xiaoping , He Sheng , Teng Gongqing , Zhao Chuan
Published: April 2014

In order to optimize the charge transfer path in quantum dot sensitized solar cells (QDSCs), we employed successive ionic layer adsorption and reaction method to dope CdSe with Co for fabricating CdS/Co‐doped‐CdSe QDSCs constructed with CdS/Co‐doped‐CdSe deposited on mesoscopic TiO2 film as photoanode, Pt counter electrode, and sulfide/polysulfide electrolyte. After Co doping, the bandgap of CdSe quantum dot decreases, and the conduction band and valence band all improve, forming a cascade energy level which is more conducive to charge transport inside the solar cell and reducing the recombination of electron‐hole thus improving the photocurrent and ultimately improving the power conversion efficiency. This work has not been found in the literature.
Stability of a Class of Coupled Systems
Authors: Jin Kun-Peng
Published: April 2014

We consider a class of coupled systems with damping terms. By using multiplier method and the estimation techniques of the energy, we show that even if the kernel function is nonincreasing and integrable without additional conditions, the energy of the system decays also to zero in a good rate.
Spatial Analysis on Future Housing Markets: Economic Development and Housing Implications
Authors: Liu Xin , Wang Lizhe
Published: April 2014

A coupled projection method combining formal modelling and other statistical techniques was developed to delineate the relationship between economic and social drivers for net new housing allocations. Using the example of employment growth in Tyne and Wear, UK, until 2016, the empirical analysis yields housing projections at the macro- and microspatial levels (e.g., region to subregion to elected ward levels). The results have important implications for the strategic planning of locations for housing and employment, demonstrating both intuitively and quantitatively how local economic developments affect housing demand.
Focusing Modeling of OPFC Linear Array Transducer by Using Distributed Point Source Method
Authors: Wang Ziping , Luo Ying
Published: April 2014

The improvement of ultrasonic phased array detection technology is a major concern of engineering community. Orthotropic piezoelectric fiber composite (OPFC) can be constructed to multielement linear array which may be applied conveniently to actuators and sensors. The phased array transducers can generate special directional strong actuator power and high sensitivity for its orthotropic performance. Focusing beam of the linear phased array transducer is obtained simply only by adjusting a parabolic time delay. In this work, the distributed point source method (DPSM) is used to model the ultrasonic field. DPSM is a newly developed mesh-free numerical technique that has been developed for solving a variety of engineering problems. This work gives the basic theory of this method and solves the problems from the application of new OPFC phased array transducer. Compared with traditional transducer, the interaction effect of two OPFC linear phased array transducers is also modeled in the same medium, which shows that the pressure beam produced by the new transducer is narrower or more collimated than that produced by the conventional transducer at different angles. DPSM can be used to analyze and optimally design the OPFC linear phased array transducer.
In Vitro and In Vivo Leishmanicidal Activity ofAstronium fraxinifolium(Schott) andPlectranthus amboinicus(Lour.) Spreng againstLeishmania (Viannia) braziliensis
Authors: de Lima Silvio César Gomes , Teixeira Maria Jania , Lopes Júnior José Evaldo Gonçalves , de Morais Selene Maia , Torres Alba Fabiola , Braga Milena Aguiar , Rodrigues Raphael Oliveira , Santiago Gilvandete Maria Pinheiro , Martins Alice Costa , Nagao-Dias Aparecida Tiemi
Published: April 2014

The aim of the present work was to evaluate antileishmanial activity ofAstronium fraxinifoliumandPlectranthus amboinicus. For the in vitro tests, essential oil ofP. amboinicus(OEPA) and ethanolic extracts fromA. fraxinifolium(EEAF) were incubated with 106  promastigotes ofL. (Viannia) braziliensis. The OEPA was able to reduce the parasite growth after 48 h; nonetheless, all the EEAFs could totally abolish the parasite growth. For the in vivo studies, BALB/c mice were infected subcutaneously (s.c.) with 107  L. braziliensispromastigotes. Treatment was done by administering OEPA intralesionally (i.l.) for 14 days. No difference was found in lesion thickness when those animals were compared with the untreated animals. Further, golden hamsters were infected s.c. with 106  L. braziliensispromastigotes. The first protocol of treatment consisted of ethanolic leaf extract fromA. fraxinifolium(ELEAF) administered i.l. for 4 days and a booster dose at the 7th day. The animals showed a significant reduction of lesion thickness in the 6th week, but it was not comparable to the animals treated with Glucantime. The second protocol consisted of 15 daily intralesional injections. The profiles of lesion thickness were similar to the standard treatment. In conclusion, in vivo studies showed a high efficacy when the infected animals were intralesionally treated with leaf ethanolic extract fromA. fraxinifolium.
Combustion and Emission Characteristics of Variable Compression Ignition Engine Fueled withJatropha curcasEthyl Ester Blends at Different Compression Ratio
Authors: Kumar Rajneesh , Dixit Anoop Kumar
Published: April 2014

Engine performance and emission characteristics of unmodified biodiesel fueled diesel engines are highly influenced by their ignition and combustion behavior. In this study, emission and combustion characteristics were studied when the engine operated using the different blends (B10, B20, B30, and B40) and normal diesel fuel (B0) as well as when varying the compression ratio from 16.5 : 1 to 17.5 : 1 to 18.5 : 1. The change of compression ratio from 16.5 : 1 to 18.5 : 1 resulted in 27.1%, 27.29%, 26.38%, 28.48%, and 34.68% increase in cylinder pressure for the blends B0, B10, B20, B30, and B40, respectively, at 75% of rated load conditions. Higher peak heat release rate increased by 23.19%, 14.03%, 26.32%, 21.87%, and 25.53% for the blends B0, B10, B20, B30, and B40, respectively, at 75% of rated load conditions, when compression ratio was increased from16.5 : 1 to 18.5 : 1. The delay period decreased by 21.26%, CO emission reduced by 14.28%, andNOxemission increased by 22.84% for B40 blends at 75% of rated load conditions, when compression ratio was increased from 16.5 : 1 to 18.5 : 1. It is concluded that Jatropha oil ester can be used as fuel in diesel engine by blending it with diesel fuel.
Elementary Flux Mode Analysis of Acetyl-CoA Pathway in Carboxydothermus hydrogenoformans Z-2901
Authors: Chinnasamy Perumal Rajadurai , Selvaraj Ashok , Ramesh Kumar Gopal
Published: April 2014

Carboxydothermus hydrogenoformans is a carboxydotrophic hydrogenogenic bacterium species that produces hydrogen molecule by utilizing carbon monoxide (CO) or pyruvate as a carbon source. To investigate the underlying biochemical mechanism of hydrogen production, an elementary mode analysis of acetyl-CoA pathway was performed to determine the intermediate fluxes by combining linear programming (LP) method available in CellNetAnalyzer software. We hypothesized that addition of enzymes necessary for carbon monoxide fixation and pyruvate dissimilation would enhance the theoretical yield of hydrogen. An in silico gene knockout of pyk, pykC, and mdh genes of modeled acetyl-CoA pathway allows the maximum theoretical hydrogen yield of 47.62 mmol/gCDW/h for 1 mole of carbon monoxide (CO) uptake. The obtained hydrogen yield is comparatively two times greater than the previous experimental data. Therefore, it could be concluded that this elementary flux mode analysis is a crucial way to achieve efficient hydrogen production through acetyl-CoA pathway and act as a model for strain improvement.
A Network Map of FGF-1/FGFR Signaling System
Authors: Raju Rajesh , Palapetta Shyam Mohan , Sandhya Varot K. , Sahu Apeksha , Alipoor Abbas , Balakrishnan Lavanya , Advani Jayshree , George Bijesh , Kini K. Ramachandra , Geetha N. P. , Prakash H. S. , Prasad T. S. Keshava , Chang Yu-Jung , Chen Linyi , Pandey Akhilesh , Gowda Harsha
Published: April 2014

Fibroblast growth factor-1 (FGF-1) is a well characterized growth factor among the 22 members of the FGF superfamily in humans. It binds to all the four known FGF receptors and regulates a plethora of functions including cell growth, proliferation, migration, differentiation, and survival in different cell types. FGF-1 is involved in the regulation of diverse physiological processes such as development, angiogenesis, wound healing, adipogenesis, and neurogenesis. Deregulation of FGF-1 signaling is not only implicated in tumorigenesis but also is associated with tumor invasion and metastasis. Given the biomedical significance of FGFs and the fact that individual FGFs have different roles in diverse physiological processes, the analysis of signaling pathways induced by the binding of specific FGFs to their cognate receptors demands more focused efforts. Currently, there are no resources in the public domain that facilitate the analysis of signaling pathways induced by individual FGFs in the FGF/FGFR signaling system. Towards this, we have developed a resource of signaling reactions triggered by FGF-1/FGFR system in various cell types/tissues. The pathway data and the reaction map are made available for download in different community standard data exchange formats through NetPath and NetSlim signaling pathway resources.
A New System of Multivalued Mixed Variational Inequality Problem
Authors: Li Xi , Li Xue-song
Published: April 2014

We consider a new system of multivalued mixed variational inequality problem, which includes some known systems of variational inequalities as special cases. Under suitable conditions, the existence of solutions for the system of multivalued mixed variational inequality problem and the convergence of iterative sequences generated by the generalizedf-projection algorithm are proved. A perturbational algorithm for solving a special case of multivalued mixed variational inequality problem is formally constructed. The results concerned with the existence of solutions and the convergence of iterative sequences generated by the perturbational algorithm are also given. Some known results are improved and generalized.
Immune-Based Antitumor Effects of BRAF Inhibitors Rely on Signaling by CD40L and IFNγ
Authors: Ho Ping-Chih , Meeth Katrina M. , Tsui Yao-Chen , Srivastava Bhaskar , Bosenberg Marcus W. , Kaech Susan M.
Published: April 2014

B-RafV600E inhibitors have been suggested to promote tumor regression with the help of host immunity, but this hypothesis has not been examined directly in detail. In this study, we profiled immunologic changes in the tumor microenvironment and tumor-infiltrating lymphocytes (TIL) in a B-RafV600E/Pten-driven murine model of melanoma after administration of the B-RafV600E small molecule inhibitor PLX4720. In this model, we found that as tumors developed, they gradually acquired immunosuppressive features, including accumulation of regulatory T cells (Treg) and CD11b+/Gr-1+ myeloid cells and loss of Th1 effector functions on CD4+ TILs, such as CD40L and IFNγ expression. PLX4720 administration promoted development of a more immune stimulatory microenvironment associated with a relative increase in CD40L and IFNγ expression on intratumoral CD4+ TILs and a reduced accumulation of Tregs and CD11b+/Gr-1+ myeloid cells. Strikingly, CD40L or IFNγ blockade compromised the ability of PLX4720 to inhibit melanoma growth. Supporting this result, agonistic CD40 antibody was sufficient to evoke antitumor immunity and suppress tumor growth in tumor-bearing mice. Taken together, our results establish the critical role of immune-related changes, with key contributions for CD40L and IFNγ signaling in the antitumor responses triggered in vivo by B-RafV600E inhibitors. Cancer Res; 74(12); 3205–17. ©2014 AACR.
Noninvasive Urinary Metabolomic Profiling Identifies Diagnostic and Prognostic Markers in Lung Cancer
Authors: Mathé Ewy A. , Patterson Andrew D. , Haznadar Majda , Manna Soumen K. , Krausz Kristopher W. , Bowman Elise D. , Shields Peter G. , Idle Jeffrey R. , Smith Philip B. , Anami Katsuhiro , Kazandjian Dickran G. , Hatzakis Emmanuel , Gonzalez Frank J. , Harris Curtis C.
Published: April 2014

Lung cancer remains the most common cause of cancer deaths worldwide, yet there is currently a lack of diagnostic noninvasive biomarkers that could guide treatment decisions. Small molecules (<1,500 Da) were measured in urine collected from 469 patients with lung cancer and 536 population controls using unbiased liquid chromatography/mass spectrometry. Clinical putative diagnostic and prognostic biomarkers were validated by quantitation and normalized to creatinine levels at two different time points and further confirmed in an independent sample set, which comprises 80 cases and 78 population controls, with similar demographic and clinical characteristics when compared with the training set. Creatine riboside (IUPAC name: 2-{2-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)-oxolan-2-yl]-1-methylcarbamimidamido}acetic acid), a novel molecule identified in this study, and N-acetylneuraminic acid (NANA) were each significantly (P < 0.00001) elevated in non–small cell lung cancer and associated with worse prognosis [HR = 1.81 (P = 0.0002), and 1.54 (P = 0.025), respectively]. Creatine riboside was the strongest classifier of lung cancer status in all and stage I-II cases, important for early detection, and also associated with worse prognosis in stage I-II lung cancer (HR = 1.71, P = 0.048). All measurements were highly reproducible with intraclass correlation coefficients ranging from 0.82 to 0.99. Both metabolites were significantly (P < 0.03) enriched in tumor tissue compared with adjacent nontumor tissue (N = 48), thus revealing their direct association with tumor metabolism. Creatine riboside and NANA may be robust urinary clinical metabolomic markers that are elevated in tumor tissue and associated with early lung cancer diagnosis and worse prognosis. Cancer Res; 74(12); 3259–70. ©2014 AACR.
GM-CSF Production by Tumor Cells Is Associated with Improved Survival in Colorectal Cancer
Authors: Nebiker Christian A. , Han Junyi , Eppenberger-Castori Serenella , Iezzi Giandomenica , Hirt Christian , Amicarella Francesca , Cremonesi Eleonora , Huber Xaver , Padovan Elisabetta , Angrisani Basilio , Droeser Raoul A. , Rosso Raffaele , Bolli Martin , Oertli Daniel , von Holzen Urs , Adamina Michel , Muraro Manuele G. , Mengus Chantal , Zajac Paul , Sconocchia Giuseppe , Zuber Markus , Tornillo Luigi , Terracciano Luigi , Spagnoli Giulio C.
Published: April 2014

Purpose: Colorectal cancer infiltration by CD16+ myeloid cells correlates with improved prognosis. We addressed mechanistic clues and gene and protein expression of cytokines potentially associated with macrophage polarization.

Experimental Design: GM-CSF or M-CSF–stimulated peripheral blood CD14+ cells from healthy donors were cocultured with colorectal cancer cells. Tumor cell proliferation was assessed by 3H-thymidine incorporation. Expression of cytokine genes in colorectal cancer and autologous healthy mucosa was tested by quantitative, real-time PCR. A tumor microarray (TMA) including >1,200 colorectal cancer specimens was stained with GM-CSF- and M-CSF–specific antibodies. Clinicopathological features and overall survival were analyzed.

Results: GM-CSF induced CD16 expression in 66% ± 8% of monocytes, as compared with 28% ± 1% in cells stimulated by M-CSF (P = 0.011). GM-CSF but not M-CSF–stimulated macrophages significantly (P < 0.02) inhibited colorectal cancer cell proliferation. GM-CSF gene was expressed to significantly (n = 45, P < 0.0001) higher extents in colorectal cancer than in healthy mucosa, whereas M-CSF gene expression was similar in healthy mucosa and colorectal cancer. Accordingly, IL1β and IL23 genes, typically expressed by M1 macrophages, were expressed to significantly (P < 0.001) higher extents in colorectal cancer than in healthy mucosa. TMA staining revealed that GM-CSF production by tumor cells is associated with lower T stage (P = 0.02), “pushing” growth pattern (P = 0.004) and significantly (P = 0.0002) longer survival in mismatch-repair proficient colorectal cancer. Favorable prognostic effect of GM-CSF production by colorectal cancer cells was confirmed by multivariate analysis and was independent from CD16+ and CD8+ cell colorectal cancer infiltration. M-CSF expression had no significant prognostic relevance.

Conclusions: GM-CSF production by tumor cells is an independent favorable prognostic factor in colorectal cancer. Clin Cancer Res; 20(12); 3094–106. ©2014 AACR.
Genetic Variations Associated with Postoperative Recurrence in Stage I Non–Small Cell Lung Cancer
Authors: Yoon Kyong-Ah , Jung Mee Kyung , Lee Donghoon , Bae Kieun , Joo Jung Nam , Lee Geon Kook , Lee Hyun-Sung , Lee Jin Soo
Published: April 2014

Purpose: Postoperative recurrence in stage I non–small cell lung cancer (NSCLC) is the major cause of a poor prognosis. This study aims to identify genetic variants that are associated with the prognosis of early-stage NSCLCs.

Experimental Design: A genome-wide association study (GWAS) was conducted in 250 patients in stage I NSCLCs and the results were replicated in additional 308 patients.

Results: Results from an Affymetrix Genome-wide Human SNP array in 250 patients identified 94 SNPs with significant associations (P < 2 × 10−4), which were selected for replication in 308 additional patients. Pooled analysis of the 558 patients determined that rs1454694 in chromosome 4q34 was the most significant marker of lung cancer prognosis in the stage I patients (adjusted HR = 2.81; P = 5.91 × 10−8). After the candidate loci were mapped, an additional four markers at chromosome 4q34.3 were significantly associated with recurrence-free survival (RFS; P < 5 × 10−5). A haplotype of five SNPs in 4q34 also showed significant association with RFS (P = 4.29 × 10−6).

Conclusions: A genetic polymorphism rs1454694 was identified as a novel genetic risk factor for RFS of stage I NSCLCs. This genome-wide study suggests that genetic markers in 4q34.3 contribute to predict the prognosis of Korean patients with stage I NSCLCs. Clin Cancer Res; 20(12); 3272–9. ©2014 AACR.
U.S. Food and Drug Administration Inspections of Clinical Investigators: Overview of Results from 1977 to 2009
Authors: Morgan-Linnell Sonia K. , Stewart David J. , Kurzrock Razelle
Published: April 2014

The U.S. Food and Drug Administration (FDA) Center for Drug Evaluation and Research is responsible for evaluating drug safety and efficacy, including oversight of clinical trials and principal investigators. The FDA Clinical Investigator Inspection List (CIIL) contains online, detailed, relevant information of all FDA inspections. We reviewed FDA inspections of clinical investigators to ascertain their outcome and included all inspections on the list (July 1977 through December 31, 2009; n = 9,481 inspections). Eighty-eight percent of inspections were “data audit” (primary purpose = verification of data), and the rest (12%) were “for cause.” The number of inspections each year significantly increased over time (P < 0.0001) and averaged 350 per year in the past decade. No deficiencies were found in only 11.2% of all “data audit” and 5% of all “for cause” inspections. Only 31% of inspections resulted in “no action indicated.” About two thirds of inspections resulted in some finding, requiring either voluntary investigator action (61.3% of inspections) or official FDA action (3.9%). The most frequently cited deficiencies were failure to follow investigational plan (34%), inadequate informed consent form (28%), and inadequate/inaccurate records (27%). In conclusion, over the past decade, the FDA has performed approximately 350 inspections per year, with the number increasing over time. The vast majority of FDA inspections yield deficiency findings and, as a result, only about one third of inspections have an outcome of “no action indicated.” Clin Cancer Res; 20(13); 3364–70. ©2014 AACR.
Geranylgeranylacetone Blocks Doxorubicin-Induced Cardiac Toxicity and Reduces Cancer Cell Growth and Invasion through RHO Pathway Inhibition
Authors: Sysa-Shah Polina , Xu Yi , Guo Xin , Pin Scott , Bedja Djahida , Bartock Rachel , Tsao Allison , Hsieh Angela , Wolin Michael S. , Moens An , Raman Venu , Orita Hajime , Gabrielson Kathleen L.
Published: April 2014

Doxorubicin is a widely used chemotherapy for solid tumors and hematologic malignancies, but its use is limited due to cardiotoxicity. Geranylgeranylacetone (GGA), an antiulcer agent used in Japan for 30 years, has no significant adverse effects, and unexpectedly reduces ovarian cancer progression in mice. Because GGA reduces oxidative stress in brain and heart, we hypothesized that GGA would prevent oxidative stress of doxorubicin cardiac toxicity and improve doxorubicin's chemotherapeutic effects. Nude mice implanted with MDA-MB-231 breast cancer cells were studied after chronic treatment with doxorubicin, doxorubicin/GGA, GGA, or saline. Transthoracic echocardiography was used to monitor systolic heart function and xenografts evaluated. Mice were euthanized and cardiac tissue evaluated for reactive oxygen species generation, TUNEL assay, and RHO/ROCK pathway analysis. Tumor metastases were evaluated in lung sections. In vitro studies using Boyden chambers were performed to evaluate GGA effects on RHO pathway activator lysophosphatidic acid (LPA)–induced motility and invasion. We found that GGA reduced doxorubicin cardiac toxicity, preserved cardiac function, prevented TUNEL-positive cardiac cell death, and reduced doxorubicin-induced oxidant production in a nitric oxide synthase–dependent and independent manner. GGA also reduced heart doxorubicin-induced ROCK1 cleavage. Remarkably, in xenograft-implanted mice, combined GGA/doxorubicin treatment decreased tumor growth more effectively than doxorubicin treatment alone. As evidence of antitumor effect, GGA inhibited LPA-induced motility and invasion by MDA-MB-231 cells. These anti-invasive effects of GGA were suppressed by geranylgeraniol suggesting GGA inhibits RHO pathway through blocking geranylation. Thus, GGA protects the heart from doxorubicin chemotherapy-induced injury and improves anticancer efficacy of doxorubicin in breast cancer. Mol Cancer Ther; 13(7); 1717–28. ©2014 AACR.
A Case of Metastatic Gastric Neuroendocrine Tumor: Therapeutic Considerations
Authors: Kim Shin Young , Woo In Sook , Yang Ji Hyun , Han Chi Wha , Roh Sang Young , Jung Yun Hwa
Published: April 2014

Despite remarkable progression in the treatment and classification system of neuroendocrine tumor (NET), some questions have remained unanswered. The lack of an established treatment strategy for gastric NET is one of the problems. Because of its paucity, gastric NET is not discussed in independent, large-scaled prospective studies and tends to be excluded from clinical trials. Moreover, a separate classification system and some distinguished clinical features render the treatment of gastric NET more complicated. Here, we present a case of a female gastric NET patient with G2 proliferation index and multiple liver metastases. Based on the histologic grade and a high serum gastrin level, we initially treated her with somatostatin analogue. However, the patient did not respond. After that, cytotoxic chemotherapy with the etoposide plus cisplatin regimen only showed response in the short-term period. However, combination therapy with octreotide and interferon brought about significant regression of the tumor. Herein, we present our case together with a literature review of the treatment of metastatic gastric NET.
Improved Hemodynamic Parameters in Middle Cerebral Artery Infarction After Decompressive Craniectomy
Authors: Amorim Robson Luis , de Andrade Almir Ferreira , Gattás Gabriel S. , Paiva Wellingson Silva , Menezes Marcos , Teixeira Manoel Jacobsen , Bor-Seng-Shu Edson
Published: April 2014

Background and Purpose—

Decompressive craniectomy (DC) reduces mortality and improves functional outcome in patients with malignant middle cerebral artery infarction. However, little is known regarding the impact of DC on cerebral hemodynamics. Therefore, our goal was to study the hemodynamic changes that may occur in patients with malignant middle cerebral artery infarction after DC and to assess their relationship with outcomes.

Methods—

Twenty-seven patients with malignant middle cerebral artery infarction who were treated with DC were studied. The perfusion CT hemodynamic parameters, mean transit time, cerebral blood flow, and cerebral blood volume were evaluated preoperatively and within the first 24 hours after DC.

Results—

There was a global trend toward improved cerebral hemodynamics after DC. Preoperative and postoperative absolute mean transit times were associated with mortality at 6 months, and the ratio of post- and preoperative cerebral blood flow was significantly higher in patients with favorable outcomes than those with unfavorable outcomes. Patients who underwent surgery 48 hours after stroke, those with midline brain shift >10 mm, and those who were >55 years showed no significant improvement in any perfusion CT parameters.

Conclusions—

DC improves cerebral hemodynamics in patients with malignant middle cerebral artery infarction, and the level of improvement is related to outcome. However, some patients did not seem to experience any additional hemodynamic benefit, suggesting that perfusion CT may play a role as a prognostic tool in patients undergoing DC after ischemic stroke.
Sex Differences in Trends of Incidence and Mortality of First-Ever Stroke in Rural Tianjin, China, From 1992 to 2012
Authors: Wang Jinghua , Ning Xianjia , Yang Li , Tu Jun , Gu Hongfei , Zhan Changqing , Zhang Wenjuan , Su Ta-Chen
Published: April 2014

Background and Purpose—

Sex differences in secular trends of stroke incidence are rarely reported. We aimed to explore sex differences in incidence and mortality of stroke in rural China from 1992 to 2012.

Methods—

In 1992, 14 920 residents were recruited to participate in the Tianjin Brain Study, a population-based study on stroke surveillance. Stroke events and all deaths were annually registered.

Results—

We observed 908 incident strokes (366 in women) from 1992 to 2012. Women were significantly younger than men (64±12 versus 68±11 years) in 1992 to 1998 (
P
=0.024). The incidence of first-ever stroke per 100 000 person-years for men was 166 in 1992 to 1998, 227 in 1999 to 2005, and 376 in 2006 to 2012; for women, the rates were 86 (1992–1998), 148 (1999–2005), and 264 (2006–2012). From 1992 to 2012, the incidence grew annually by 5.8% in men and 8.0% in women. The male/female incidence ratio declined significantly: 1.9 in 1992 to 1998, 1.5 in 1999 to 2005, and 1.4 in 2006 to 2012. There were no significant sex differences in mortality. The prevalence of obesity and diabetes mellitus, the levels of total cholesterol and triglycerides, and the age of menopause and reproductive years in women concurrently increased in 2011.

Conclusions—

There was a significant increase in the incidence of first-ever stroke in women annually and a declining trend in the male/female rate ratio in rural China during the past 21 years. These results suggest that stroke will become one of the major diseases affecting women in future decades in China.