bluuebunny/crossref_metadata_2025 huggingface dataset:
Vehicle Optimal Velocity Curves for Minimum-Time Maneuver
Authors: Zhang Li-xia , Pan Fu-quan , Chen Xiao-yuan , Wang Feng-yuan , Lu Jun , Tong Qi-ming
Published: February 2014

A problem in vehicle minimum-time maneuver is the assumption that a vehicle passes through a given path in a minimal amount of time without deviating from the boundary of the given path. Vehicle handling inverse dynamics provides a new perspective to solve such problem. Based on inverse dynamics, this paper transformed the problem of optimal vehicle velocity for minimum-time maneuver into that of optimal control with the objective function of minimum time. The path for minimum vehicle travel time and the optimal control model were established. The optimal velocity curves for three types of paths, namely, monotonically increasing path, monotonically decreasing path, and constant radius path, were analyzed. On this basis, the optimal velocity curves were solved for two kinds of concrete paths: a path of decreasing curvature radius followed by a path of increasing curvature radius and another path of increasing curvature radius followed by a path of decreasing curvature radius. Nine cases of possible optimal velocity curves were acquired. The optimal velocity curve of the given path, that is, a parabola followed by a semicircle, was obtained. Optimal velocity curves can be used as reference for vehicle minimum-time maneuver, which is an important issue for driver safety in fast-moving vehicles.
Measurement of SUVs-Maximum for Normal Region Using VOI in PET/MRI and PET/CT
Authors: Park Jeong Kyu , Kim Sung Kyu , Cho Ihn Ho , Kong Eun Jung
Published: February 2014

The purpose of this research is to establish an overall data set associated with the VOI (Volume of Interest), which is available for simultaneous assessment of PET/MRI and PET/CT regardless of the use of contrast media. The participants as objects of this investigation are 26 healthy examinees in Korea, SUV (standardized-uptake-value)s-maximum evaluation for whole-body F-18 FDG (fluorodeoxyglucose) PET/MRI image using VOI of normal region has exhibited very significant difference to that for whole-body F-18 FDG PET/CT image (significant probability value(P)<0.0001). However, there appeared high correlation between them in view of statistics (R-square(R)>0.8). It is shown that one needs to decide SUVs-maximum for PET/MRI with the reduction of 25.0~26.4% from their evaluated value and needs to decide with the reduction of 28.8~29.4% in the same situation but with the use of contrast media. The use ofSUVLBM-maximum (SUVLean Body Mass-maximum) is very advantageous in reading overall image of PET/CT and PET/MRI to medical doctors and researchers, if we consider its convenience and efficiency. We expect that this research enhances the level of the early stage accurate diagnosis with whole-body images of PET/MRI and PET/CT.
Mutations in the H, F, or M Proteins Can Facilitate Resistance of Measles Virus to Neutralizing Human Anti-MV Sera
Authors: Kweder Hasan , Ainouze Michelle , Cosby Sara Louise , Muller Claude P. , Lévy Camille , Verhoeyen Els , Cosset François-Loïc , Manet Evelyne , Buckland Robin
Published: February 2014

Although there is currently no evidence of emerging strains of measles virus (MV) that can resist neutralization by the anti-MV antibodies present in vaccinees, certain mutations in circulating wt MV strains appear to reduce the efficacy of these antibodies. Moreover, it has been hypothesized that resistance to neutralization by such antibodies could allow MV to persist. In this study, we use a novelin vitrosystem to determine the molecular basis of MV’s resistance to neutralization. We find that both wild-type and laboratory strain MV variants that escape neutralization by anti-MV polyclonal sera possess multiple mutations in their H, F, and M proteins. Cytometric analysis of cells expressing viral escape mutants possessing minimal mutations and their plasmid-expressed H, F, and M proteins indicates that immune resistance is due to particular mutations that can occur in any of these three proteins that affect at distance, rather than directly, the native conformation of the MV-H globular head and hence its epitopes. A high percentage of the escape mutants contain mutations found in cases of Subacute Sclerosing Panencephalitis (SSPE) and our results could potentially shed light on the pathogenesis of this rare fatal disease.
Total Lip Reconstruction with Tendinofasciocutaneous Radial Forearm Flap
Authors: Silberstein Eldad , Krieger Yuval , Shoham Yaron , Arnon Ofer , Sagi Amiram , Bogdanov-Berezovsky Alexander
Published: February 2014

Introduction.Squamous cell carcinoma is a common tumour of lower lip. Small defects created by surgical resection may be readily reconstructed by linear closure or with local flaps. However, large tumours resection often results with microstomia and oral incompetence, drooling, and speech incomprehension. The goal of this study is to describe our experience with composite free radial forearm-palmaris longus tendon flap for total or near total lower lip reconstruction.Patients and Methods.This procedure was used in 5 patients with 80–100% lip defect resulting from Squamous cell carcinoma. Patients’ age ranged from 46 to 82 years. They are three male patients and two female. In 3 cases chin skin was reconstructed as well and in one case a 5 cm segment of mandible was reconstructed using radius bone. In one case where palmaris longus was missing hemi-flexor carpi radialis tendon was used instead. All patients tolerated the procedure well.Results.All flaps totally survived. No patient suffered from drooling. All patients regained normal diet and normal speech. Cosmetic result was fair to good in all patients accept one.Conclusion.We conclude that tendino-fasciocutaneous radial forearm flap for total lower lip reconstruction is safe. Functional and aesthetic result approaches reconstructive goals.
PhoneProtector: Protecting User Privacy on the Android-Based Mobile Platform
Authors: Zhang Weizhe , He Hui , Zhang Qizhen , Kim Tai-hoon
Published: February 2014

With the popularity of Android platform based mobile phones, privacy protection of Android platform becomes a focus area. Now protection for Android based smart phone has many shortages, and also most phone protection systems are based on C/S model. In this paper, we propose a browser-free multilevel smart phone privacy protection system, which is based on the Android sensor platform. In this system, protection is ensured by means of SMS, which turns out to be easy, quick, and convenient. Users can send SMS to phones remotely as operating instructions; then the sensors on remote phones execute the instructions and return useful information. Second, the sensors based on the daemon process mechanism are used to prevent the sensors from being maliciously closed and uninstalled. Third, our system adopts SIM detecting mechanism to judge whether the SIM card is removed or changed. If exception is detected, the phone will be locked automatically by its inside sensors. The three points ensure full protection of phone privacy. Test results show that our system has good robustness and low resource consumption.
Effect of Hydroalcoholic Extract ofCydonia oblongaMiller (Quince) on Sexual Behaviour of Wistar Rats
Authors: Aslam Muhammad , Sial Ali Akbar
Published: February 2014

Cydonia oblongaMiller (quince) is regarded as a potent libido invigorator in Tib-e-Nabvi and Unani System of Medicine. This study was carried out to evaluate the aphrodisiac activity of the hydroalcoholic extract of the fruits ofCydonia oblongaMiller (quince) in Wistar rats. The extract was administered orally by gavage in the dose of 500 mg/kg and 800 mg/kg body weight per day as a single dose for 28 days. The observed parameters were mounting frequency, assessment of mating performance, and orientation activities towards females, towards the environment, and towards self. The results showed that after administration of the extract mounting frequency and the mating performance of the rats increased highly significantlyP<0.01. The extract also influenced the behaviour of treated animals in comparison to nontreated rats in a remarkable manner, making them more attracted to females. These effects were observed in sexually active male Wistar rats.
ROS, Notch, and Wnt Signaling Pathways: Crosstalk between Three Major Regulators of Cardiovascular Biology
Authors: Caliceti C. , Nigro P. , Rizzo P. , Ferrari R.
Published: February 2014

Reactive oxygen species (ROS), traditionally viewed as toxic by-products that cause damage to biomolecules, now are clearly recognized as key modulators in a variety of biological processes and pathological states. The development and regulation of the cardiovascular system require orchestrated activities; Notch and Wnt/β-catenin signaling pathways are implicated in many aspects of them, including cardiomyocytes and smooth muscle cells survival, angiogenesis, progenitor cells recruitment and differentiation, arteriovenous specification, vascular cell migration, and cardiac remodelling. Several novel findings regarding the role of ROS in Notch and Wnt/β-catenin modulation prompted us to review their emerging function in the cardiovascular system during embryogenesis and postnatally.
Constraint Violations in Stochastically Generated Data: Detection and Correction Strategies
Authors: Fadlalla Adam , Munakata Toshinori
Published: February 2014

We consider the generation of stochastic data under constraints where the constraints can be expressed in terms of different parameter sets. Obviously, the constraints and the generated data must remain the same over each parameter set. Otherwise, the parameters and/or the generated data would be inconsistent. We consider how to avoid or detect and then correct such inconsistencies under three proposed classifications: (1) data versus characteristic parameters, (2) macro- versus microconstraint scopes, and (3) intra- versus intervariable relationships. We propose several strategies and a heuristic for generating consistent stochastic data. Experimental results show that these strategies and heuristic generate more consistent data than the traditional discard-and-replace methods. Since generating stochastic data under constraints is a very common practice in many areas, the proposed strategies may have wide-ranging applicability.
Neutralization by Insulin of the Hypertensive Effect of Dermcidin Isoform 2: An Environmentally Induced Diabetogenic and Hypertensive Protein
Authors: Ghosh Rajeshwary , Bank Sarbashri , Bhattacharya Rabindra , Khan Nighat N. , Sinha A. Kumar
Published: February 2014

The effect of dermcidin isoform 2 (dermcidin), an environmentally induced stress protein, was investigated on the genesis of diabetes mellitus and hypertension, the two major atherosclerotic risk factors. The role of dermcidin as an atherosclerotic risk factor related to the impaired systemic insulin level was investigated. Dermcidin was prepared by electrophoresis using plasma from the subjects with acute ischemic heart disease. Injection of 0.2 μM dermcidin in mice increased the blood glucose level from98±2.45 mg/dL to350 ±10.2 mg/dL which was normalized by the oral administration of acetyl salicylic acid (aspirin) after 24 h. Hypertensive subjects with systolic and diastolic blood pressure of 165 mm and 95 mm of Hg, respectively, had plasma dermcidin level of 95 nM. Ingestion of acetyl salicylic acid (aspirin) (150 mg/70 kg body weight) decreased the systolic and diastolic pressures to 125 mm and 80 mm of Hg, respectively, with decrease of dermcidin level to 15 nM. Incubation of kidney cortex cells with 0.2 μM dermcidin-inhibited synthesis of (r)-cortexin, an antihypertensive protein, and the basal (r)-cortexin level was reduced from 33 nM to 15 nM. Addition of 25 μunits of insulin/mL was found to reverse the inhibition of cortexin synthesis. The effect of dermcidin as a diabetogenic and a hypertensive agent could be controlled either by aspirin or by insulin.
Esthetic Root Coverage with Double Papillary Subepithelial Connective Tissue Graft: A Case Report
Authors: Mutthineni Ramesh Babu , Dudala Ram Babu , Ramisetty Arpita
Published: February 2014

Patients today have become excessively concerned about esthetics. These esthetic concerns of patients have become an integral part of periodontal practice. Gingival recession is an esthetic problem that can be successfully treated by means of several mucogingival surgical approaches, any of which can be used, provided that the biologic conditions for accomplishing root coverage are satisfied with no loss of soft and hard tissue height interdentally. There are currently different techniques for root coverage which include pedicle grafts, free gingival grafts, connective tissue grafts, and guided tissue regeneration (GTR). This paper reports a case in which a new double papillary connective tissue graft technique has been used in the treatment of gingival recession.
Experiments in Computing: A Survey
Authors: Tedre Matti , Moisseinen Nella
Published: February 2014

Experiments play a central role in science. The role of experiments in computing is, however, unclear. Questions about the relevance of experiments in computing attracted little attention until the 1980s. As the discipline then saw a push towards experimental computer science, a variety of technically, theoretically, and empirically oriented views on experiments emerged. As a consequence of those debates, today's computing fields use experiments and experiment terminology in a variety of ways. This paper analyzes experimentation debates in computing. It presents five ways in which debaters have conceptualized experiments in computing: feasibility experiment, trial experiment, field experiment, comparison experiment, and controlled experiment. This paper has three aims: to clarify experiment terminology in computing; to contribute to disciplinary self-understanding of computing; and, due to computing’s centrality in other fields, to promote understanding of experiments in modern science in general.
Mass Spectrometric Screening of Ovarian Cancer with Serum Glycans
Authors: Kim Jae-Han , Park Chang Won , Um Dalho , Baek Ki Hwang , Jo Yohahn , An Hyunjoo , Kim Yangsun , Kim Tae Jin
Published: February 2014

Changes of glycosylation pattern in serum proteins have been linked to various diseases including cancer, suggesting possible development of novel biomarkers based on the glycomic analysis. In this study, N-linked glycans from human serum were quantitatively profiled by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) and compared between healthy controls and ovarian cancer patients. A training set consisting of 40 healthy controls and 40 ovarian cancer cases demonstrated an inverse correlation betweenPvalue of ANOVA and area under the curve (AUC) of each candidate biomarker peak from MALDI-TOF MS, providing standards for the classification. A multibiomarker panel composed of 15 MALDI-TOF MS peaks resulted in AUC of 0.89, 80~90% sensitivity, and 70~83% specificity in the training set. The performance of the biomarker panel was validated in a separate blind test set composed of 23 healthy controls and 37 ovarian cancer patients, leading to 81~84% sensitivity and 83% specificity with cut-off values determined by the training set. Sensitivity of CA-125, the most widely used ovarian cancer marker, was 74% in the training set and 78% in the test set, respectively. These results indicate that MALDI-TOF MS-mediated serum N-glycan analysis could provide critical information for the screening of ovarian cancer.
Dyschromatosis Symmetrica Hereditaria of Late Onset?
Authors: Gaiewski Caroline Balvedi , Zuneda Serafini Sergio , Werner Betina , Deonizio Janyana M. D.
Published: February 2014

Dyschromatosis symmetrica hereditaria (DSH), also known as reticulated acropigmentation of Dohi, is an autosomal dominant disease with high penetrance, characterized by hypo- and hyperpigmented macules of varying sizes on the dorsal of the extremities with reticulated pattern. This paper presents a female patient with typical dermatological lesions, but only diagnosed in adulthood. It is necessary to perform differential diagnosis with other pigmentary disorders. This entity is not very common in South America, and the vast majority of cases were described in Japanese population. Since it is a benign disease, it is important to be aware of this diagnosis in order to establish the correct conduct for these patients.
An Ultrastructural and Fluorescent Study of the Teratocytes ofMicroctonus aethiopoidesLoan (Hymenoptera: Braconidae) from the Hemocoel of Host Alfalfa Weevil,Hypera postica(Gyllenhal) (Coleoptera: Curculionidae)
Authors: Shelby Kent S. , Habibi Javad , Puttler Benjamin
Published: February 2014

The braconid waspMicroctonus aethiopoidesLoan is an idiobiont endoparasitoid of alfalfa weevil adultsHypera postica(Gyllenhal). After oviposition and subsequent egg maturation, large trophic cells called teratocytes dissociate from the serosa and are released into the host hemocoel. These teratocytes are present in large numbers and are visible to the naked eye. It is thought that they accumulate host hemocoelic metabolites for later consumption by the parasitoid larvae. We have undertaken a microscopic study of these gargantuan and complex cells at approximately seven months after parasitization. Parasitized adult weevils were dissected into medium and teratocytes were fixed, embedded, and sectioned at 1 μm. Teratocytes were stained with various specific fluorescent dyes for plasma membrane, Golgi, nuclei, lysosomes, mitochondria, and endoplasmic reticulum (ER). The surface of each cell is covered with a dense microvillar layer. Analysis of fluorescent images showed that these cells do not have condensed nuclei. ER was abundant around the nuclear envelope. Lysosomes were positioned around the periphery of the nucleus and the Golgi apparatus was significantly enlarged, being located around the nuclear envelope.
An Improved FCM Medical Image Segmentation Algorithm Based on MMTD
Authors: Zhou Ningning , Yang Tingting , Zhang Shaobai
Published: February 2014

Image segmentation plays an important role in medical image processing. Fuzzy c-means (FCM) is one of the popular clustering algorithms for medical image segmentation. But FCM is highly vulnerable to noise due to not considering the spatial information in image segmentation. This paper introduces medium mathematics system which is employed to process fuzzy information for image segmentation. It establishes the medium similarity measure based on the measure of medium truth degree (MMTD) and uses the correlation of the pixel and its neighbors to define the medium membership function. An improved FCM medical image segmentation algorithm based on MMTD which takes some spatial features into account is proposed in this paper. The experimental results show that the proposed algorithm is more antinoise than the standard FCM, with more certainty and less fuzziness. This will lead to its practicable and effective applications in medical image segmentation.
Emerging Stent and Balloon Technologies in the Femoropopliteal Arteries
Authors: Pastromas Georgios , Katsanos Konstantinos , Krokidis Miltiadis , Karnabatidis Dimitrios , Spiliopoulos Stavros
Published: February 2014

Endovascular procedures for the management of the superficial femoral (SFA) and popliteal artery disease are increasingly common. Over the past decade, several stent technologies have been established which may offer new options for improved clinical outcomes. This paper reviews the current evidence for SFA and popliteal artery angioplasty and stenting, with a focus on randomized trials and registries of nitinol self-expanding stents, drug-eluting stents, dug-coated balloons, and covered stent-grafts. We also highlight the limitations of the currently available data and the future routes in peripheral arterial disease (PAD) stent and balloon technology.
Ultrasound Guided Core Biopsy versus Fine Needle Aspiration for Evaluation of Axillary Lymphadenopathy in Patients with Breast Cancer
Authors: Ganott Marie A. , Zuley Margarita L. , Abrams Gordon S. , Lu Amy H. , Kelly Amy E. , Sumkin Jules H. , Chivukula Mamatha , Carter Gloria , Austin R. Marshall , Bandos Andriy I.
Published: February 2014

Rationale and Objectives. To compare the sensitivities of ultrasound guided core biopsy and fine needle aspiration (FNA) for detection of axillary lymph node metastases in patients with a current diagnosis of ipsilateral breast cancer. Materials and Methods. From December 2008 to December 2010, 105 patients with breast cancer and abnormal appearing lymph nodes in the ipsilateral axilla consented to undergo FNA of an axillary node immediately followed by core biopsy of the same node, both with ultrasound guidance. Experienced pathologists evaluated the aspirate cytology without knowledge of the core histology. Cytology and core biopsy results were compared to sentinel node excision or axillary dissection pathology. Sensitivities were compared using McNemar’s test. Results. Of 70 patients with axillary node metastases, FNA was positive in 55/70 (78.6%) and core was positive in 61/70 (87.1%) (P = 0.18). The FNA and core results were discordant in 14/70 (20%) patients. Ten cases were FNA negative/core positive. Four cases were FNA positive/core negative. Conclusion. Core biopsy detected six (8.6%) more cases of metastatic lymphadenopathy than FNA but the difference in sensitivities was not statistically significant. Core biopsy should be considered if the node is clearly imaged and readily accessible. FNA is a good alternative when a smaller needle is desired due to node location or other patient factors. This trial is registered with NCT01920139.
Nonlinear Fault Separation for Redundancy Process Variables Based on FNN in MKFDA Subspace
Authors: Su Ying-ying , Liang Shan , Li Jing-zhe , Deng Xiao-gang , Li Tai-fu , Zeng Cheng
Published: February 2014

Nonlinear faults are difficultly separated for amounts of redundancy process variables in process industry. This paper introduces an improved kernel fisher distinguish analysis method (KFDA). All the original process variables with faults are firstly optimally classified in multi-KFDA (MKFDA) subspace to obtain fisher criterion values. Multikernel is used to consider different distributions for variables. Then each variable is eliminated once from original sets, and new projection is computed with the same MKFDA direction. From this, differences between new Fisher criterion values and the original ones are tested. If it changed obviously, the effect of eliminated variable should be much important on faults called false nearest neighbors (FNN). The same test is applied to the remaining variables in turn. Two nonlinear faults crossed in Tennessee Eastman process are separated with lower observation variables for further study. Results show that the method in the paper can eliminate redundant and irrelevant nonlinear process variables as well as enhancing the accuracy of classification.
Theoretical Investigations of Structural Phase Transitions and Magnetic, Electronic and Thermal Properties of DyNi: Under High Pressures and Temperatures
Authors: Rana Pooja , Verma U. P.
Published: February 2014

Present work is influenced by the requirement of investigation of rare earth intermetallics due to the nonavailability of theoretical details and least information from experimental results. An attempt has been made to analyse the structural, electronic, magnetic and thermal properties of DyNi using full potential linear augmented plane wave method based on density functional theory. DyNi differs from other members of lanthanides nickelates as in ground state it crystallizes in FeB phase rather than orthorhombic CrB structure. The equilibrium lattice constant, bulk modulus, and pressure derivative of bulk modulus are presented in four polymorphs (FeB, CrB, CsCl and NaCl) of DyNi. At equilibrium the cell volume of DyNi for FeB structure has been calculated as 1098.16 Bohr3 which is comparable well with the experimental value 1074.75 Bohr3. The electronic band structure has been presented for FeB phase. The results for thermal properties, namely, thermal expansion coefficient, Gruneisen parameter, specific heat and Debye temperature at higher pressure and temperatures have been reported. The magnetic moments at equilibrium lattice constants have also been tabulated as the rare earth ions associated with large magnetic moments increase their utility in industrial field for the fabrication of electronic devices due to their magnetocaloric effect used in magnetic refrigeration.
SPDEs with α-Stable Lévy Noise: A Random Field Approach
Authors: Balan Raluca M.
Published: February 2014

This paper is dedicated to the study of a nonlinear SPDE on a bounded domain in Rd, with zero initial conditions and Dirichlet boundary, driven by an α-stable Lévy noise Z with α∈(0,2), α≠1, and possibly nonsymmetric tails. To give a meaning to the concept of solution, we develop a theory of stochastic integration with respect to this noise. The idea is to first solve the equation with “truncated” noise (obtained by removing from Z the jumps which exceed a fixed value K), yielding a solution uK, and then show that the solutions uL,L>K coincide on the event t≤τK, for some stopping times τK converging to infinity. A similar idea was used in the setting of Hilbert-space valued processes. A major step is to show that the stochastic integral with respect to ZK satisfies a pth moment inequality. This inequality plays the same role as the Burkholder-Davis-Gundy inequality in the theory of integration with respect to continuous martingales.
Annealing Heat Treatment of ZnO Nanoparticles Grown on Porous Si Substrate Using Spin-Coating Method
Authors: Eswar K. A. , Rouhi J. , Husairi H. F. , Rusop M. , Abdullah S.
Published: February 2014

ZnO nanoparticles were successfully deposited on porous silicon (PSi) substrate using spin-coating method. In order to prepare PSi, electrochemical etching was employed to modify the Si surface. Zinc acetate dihydrate was used as a starting material in ZnO sol-gel solution preparation. The postannealing treatments were investigated on morphologies and photoluminescence (PL) properties of the ZnO thin films. Field emission scanning electron microscopy (FESEM) results indicate that the thin films composed by ZnO nanoparticles were distributed uniformly on PSi. The average sizes of ZnO nanoparticle increase with increasing annealing temperature. Atomic force microscopic (AFM) analysis reveals that ZnO thin films annealed at 500°C had the smoothest surface. PL spectra show two peaks that completely correspond to nanostructured ZnO and PSi. These findings indicate that the ZnO nanostructures grown on PSi are promising for application as light emitting devices.
Characterization of the Existence of anN0-Completion of a PartialN0-Matrix with an Associated Directed Cycle
Authors: Jordán Cristina , Torregrosa Juan R.
Published: February 2014

Ann×nmatrix is called anN0-matrix if all its specified principal minors are nonpositive. In the context of partial matrices, a partial matrix is called a partialN0-matrix if all its specified principal minors are nonpositive. In this paper we characterize the existence of anN0-matrix completion of a partialN0-matrix whose associated graph is a directed cycle.
Phase Transformation of VO2Nanoparticles Assisted by Microwave Heating
Authors: Phoempoon Phatcharee , Sikong Lek.
Published: February 2014

The microwave assisted synthesis nowadays attracts a great deal of attention. Monoclinic phase VO2(M) was prepared from NH4VO3andH2C2O4·2H2Oby a rapid microwave assisted technique. The synthesis parameters, microwave irradiation time, microwave power, and calcinations temperature were systematically varied and their influences on the structure and morphology were evaluated. The microwave power level has been carried out in range 180–600 W. TEM analysis demonstrated nanosized samples. The structural and morphological properties were measured using XRD, TEM, and thermal analyses. The variations of vanadium phase led to thermochromic properties.
A Kernel Based Neighborhood Discriminant Submanifold Learning for Pattern Classification
Authors: Zhao Xu
Published: February 2014

We propose a novel method, called Kernel Neighborhood Discriminant Analysis (KNDA), which can be regarded as a supervised kernel extension of Locality Preserving Projection (LPP). KNDA nonlinearly maps the original data into a kernel space in which two graphs are constructed to depict the within-class submanifold and the between-class submanifold. Then a criterion function which minimizes the quotient between the within-class representation and the between-class representation of the submanifolds is designed to separate each submanifold constructed by each class. The real contribution of this paper is that we bring and extend the submanifold based algorithm to a general model and by some derivation a simple result is given by which we can classify a given object to a predefined class effectively. Experiments on the MNIST Handwritten Digits database, the Binary Alphadigits database, the ORL face database, the Extended Yale Face Database B, and a downloaded documents dataset demonstrate the effectiveness and robustness of the proposed method.
PP2A-B55β Antagonizes Cyclin E1 Proteolysis and Promotes Its Dysregulation in Cancer
Authors: Tan YingMeei , Sun Dahui , Jiang Weijian , Klotz-Noack Kathleen , Vashisht Ajay A. , Wohlschlegel James , Widschwendter Martin , Spruck Charles
Published: February 2014

Cyclin E1 regulates the initiation of S-phase in cellular division. However, in many cancers, cyclin E1 is aberrantly overexpressed and this molecular phenotype correlates with increased tumor aggressiveness and poor patient survival. The molecular cause(s) of cyclin E1 abnormalities in cancers is poorly understood. Here, we show that cyclin E1 overexpression in cancer is promoted by dysregulation of the protein phosphatase PP2A-B55β. PP2A-B55β targets the N- and C-terminal phosphodegrons of cyclin E1 for dephosphorylation, thus protecting it from degradation mediated by the SCFFbxw7 ubiquitin ligase. Augmented B55β expression stabilizes cyclin E1 and promotes its overexpression in cancer-derived cell lines and breast tumors. Conversely, B55β ablation enforces the degradation of cyclin E1 and inhibits cancer cell proliferation in vitro and tumor formation in vivo. Therefore, PP2A-B55β promotes cyclin E1 overexpression by antagonizing its degradation and its inhibition could represent a therapeutic mechanism for abrogating cyclin E1 function in cancers. Cancer Res; 74(7); 2006–14. ©2014 AACR.
Apoptosis Imaging for Monitoring DR5 Antibody Accumulation and Pharmacodynamics in Brain Tumors Noninvasively
Authors: Weber Thomas G. , Osl Franz , Renner Anja , Pöschinger Thomas , Galbán Stefanie , Rehemtulla Alnawaz , Scheuer Werner
Published: February 2014

High-grade gliomas often possess an impaired blood–brain barrier (BBB), which allows delivery of large molecules to brain tumors. However, achieving optimal drug concentrations in brain tumors remains a significant hurdle for treating patients successfully. Thus, detailed investigations of drug activities in gliomas are needed. To investigate BBB penetration, pharmacodynamics, and tumor retention kinetics of an agonistic DR5 antibody in a brain tumor xenograft model, we utilized a noninvasive imaging method for longitudinal monitoring of apoptosis induction. Brain tumors were induced by intracranial (i.c.) implantation of a luciferase-expressing tumor cell line as a reporter. To quantify accumulation of anti-DR5 in brain tumors, we generated a dosage–response curve for apoptosis induction after i.c. delivery of fluorescence-labeled anti-DR5 at different dosages. Assuming 100% drug delivery after i.c. application, the amount of accumulated antibody after i.v. application was calculated relative to its apoptosis induction. We found that up to 0.20% to 0.97% of antibody delivered i.v. reached the brain tumor, but that apoptosis induction declined quickly within 24 hours. These results were confirmed by three-dimensional fluorescence microscopy of antibody accumulation in explanted brains. Nonetheless, significant antitumor efficacy was documented after anti-DR5 delivery. We further demonstrated that antibody penetration was facilitated by an impaired BBB in brain tumors. These imaging methods enable the quantification of antibody accumulation and pharmacodynamics in brain tumors, offering a holistic approach for assessment of central nervous system–targeting drugs. Cancer Res; 74(7); 1913–23. ©2014 AACR.
Cofilin Drives Cell-Invasive and Metastatic Responses to TGF-β in Prostate Cancer
Authors: Collazo Joanne , Zhu Beibei , Larkin Spencer , Martin Sarah K. , Pu Hong , Horbinski Craig , Koochekpour Shahriar , Kyprianou Natasha
Published: February 2014

Cofilin (CFL) is an F-actin–severing protein required for the cytoskeleton reorganization and filopodia formation, which drives cell migration. CFL binding and severing of F-actin is controlled by Ser3 phosphorylation, but the contributions of this step to cell migration during invasion and metastasis of cancer cells are unclear. In this study, we addressed the question in prostate cancer cells, including the response to TGF-β, a critical regulator of migration. In cells expressing wild-type CFL, TGF-β treatment increased LIMK-2 activity and cofilin phosphorylation, decreasing filopodia formation. Conversely, constitutively active CFL (SerAla) promoted filipodia formation and cell migration mediated by TGF-β. Notably, in cocultures of prostate cancer epithelial cells and cancer-associated fibroblasts, active CFL promoted invasive migration in response to TGF-β in the microenvironment. Further, constitutively active CFL elevated the metastatic ability of prostate cancer cells in vivo. We found that levels of active CFL correlated with metastasis in a mouse model of prostate tumor and that in human prostate cancer, CFL expression was increased significantly in metastatic tumors. Our findings show that the actin-severing protein CFL coordinates responses to TGF-β that are needed for invasive cancer migration and metastasis. Cancer Res; 74(8); 2362–73. ©2014 AACR.
Urinary Levels of Melatonin and Risk of Postmenopausal Breast Cancer: Women's Health Initiative Observational Cohort
Authors: Sturgeon Susan R. , Doherty Ashley , Reeves Katherine W. , Bigelow Carol , Stanczyk Frank Z. , Ockene Judith K. , Liu Simin , Manson JoAnn E. , Neuhouser Marian L.
Published: February 2014

Background: Results from prospective studies on the association between urinary levels of melatonin and risk of postmenopausal breast cancer have been mixed. Several although not all studies have found lower urinary levels of melatonin in women who developed breast cancer compared with cancer-free women.

Methods: We examined the association between urinary levels of melatonin and breast cancer risk in postmenopausal women in a case–control study nested in the Women's Health Initiative Observational Cohort. Levels of 6-sulfatoxymelatonin were measured in first morning voids from 258 women who later developed breast cancer and from 515 matched controls. Multivariable conditional logistic regression was used to calculate ORs and 95% confidence intervals (CI).

Results: Fully adjusted risk estimates of breast cancer, relative to the lowest quartile level of creatinine-adjusted melatonin, were 1.07 (95% CI, 0.67–1.71), 1.26 (95% CI, 0.79–2.01), and 1.25 (95% CI, 0.78–2.02) for women in the second, third, and highest quartile (Ptrend = 0.27). Comparable results for cases diagnosed less than four years after urinary collection and matched controls were 1.0, 1.25 (95% CI, 0.51–3.06), 1.85 (95% CI, 0.75–4.57), and 1.94 (95% CI, 0.75–5.03; Ptrend = 0.11). Melatonin levels and breast cancer were not associated in cases diagnosed four or more years after urinary collection and matched controls (Ptrend = 0.89).

Conclusions: We found no evidence that higher urinary levels of melatonin are inversely associated with breast cancer risk in postmenopausal women.

Impact: Accumulating discrepancies in results across studies warrant further exploration. Cancer Epidemiol Biomarkers Prev; 23(4); 629–37. ©2014 AACR.
Novel Target for Peptide-Based Imaging and Treatment of Brain Tumors
Authors: Hyvönen Maija , Enbäck Juulia , Huhtala Tuulia , Lammi Johanna , Sihto Harri , Weisell Janne , Joensuu Heikki , Rosenthal-Aizman Katri , El-Andaloussi Samir , Langel Ulo , Närvänen Ale , Bergers Gabriele , Laakkonen Pirjo
Published: February 2014

Malignant gliomas are associated with high mortality due to infiltrative growth, recurrence, and malignant progression. Even with the most efficient therapy combinations, median survival of the glioblastoma multiforme (grade 4) patients is less than 15 months. Therefore, new treatment approaches are urgently needed. We describe here identification of a novel homing peptide that recognizes tumor vessels and invasive tumor satellites in glioblastomas. We demonstrate successful brain tumor imaging using radiolabeled peptide in whole-body SPECT/CT imaging. Peptide-targeted delivery of chemotherapeutics prolonged the lifespan of mice bearing invasive brain tumors and significantly reduced the number of tumor satellites compared with the free drug. Moreover, we identified mammary-derived growth inhibitor (MDGI/H-FABP/FABP3) as the interacting partner for our peptide on brain tumor tissue. MDGI was expressed in human brain tumor specimens in a grade-dependent manner and its expression positively correlated with the histologic grade of the tumor, suggesting MDGI as a novel marker for malignant gliomas. Mol Cancer Ther; 13(4); 996–1007. ©2014 AACR.
CD4 T-cell Subsets and Tumor Immunity: The Helpful and the Not-so-Helpful
Authors: Kim Hye-Jung , Cantor Harvey
Published: February 2014

Research over the past decade has revealed the increasingly complex biologic features of the CD4+ T-cell lineage. This T-cell subset, which was originally defined on the basis of helper activity in antibody responses, expresses receptors that recognize peptides that have been processed and presented by specialized antigen-presenting cells. At the core of the adaptive immune response, CD4 T cells display a large degree of plasticity and the ability to differentiate into multiple sublineages in response to developmental and environmental cues. These differentiated sublineages can orchestrate a broad range of effector activities during the initiation, expansion, and memory phase of an immune response. The contribution of CD4 cells to host defense against pathogenic invasion and regulation of autoimmunity is now well established. Emerging evidence suggests that CD4 cells also actively participate in shaping antitumor immunity. Here, we outline the biologic properties of CD4 T-cell subsets with an emphasis on their contribution to the antitumor response. Cancer Immunol Res; 2(2); 91–98. ©2014 AACR.
Killer Immunoglobulin-like Receptors and Tumor Immunity
Authors: Benson Don M. , Caligiuri Michael A.
Published: February 2014

Natural killer (NK) cells, large granular lymphocytes comprising a key cellular subset of innate immunity, were originally named for their capacity to elicit potent cytotoxicity against tumor cells independent of prior sensitization or gene rearrangement. This process is facilitated through the expression of activating and inhibitory receptors that provide for NK cell “education” and a subsequent ability to survey, recognize, and lyse infected or transformed cells, especially those lacking or possessing mutated MHC class I expression. Since these original observations were made, how NK cells recognize candidate target cells continues to be the topic of ongoing investigation. It is now appreciated that NK cells express a diverse repertoire of activating and inhibitory receptors of which killer immunoglobulin-like receptors (KIR) appear to play a critical role in mediating self-tolerance as well as facilitating cytotoxicity against infected or transformed cells. In addition, in the presence of an activating signal, the absence or mismatch of MHC class I molecules on such targets (which serve as inhibitory KIR ligands) promotes NK cell–mediated lysis. An increasing understanding of the complexities of KIR biology has provided recent opportunities to leverage the NK cell versus tumor effect as a novel avenue of immunotherapy for cancer. The present review summarizes the current understanding of KIR expression and function and highlights ongoing efforts to translate these discoveries into novel NK cell–mediated immunotherapies for cancer. Cancer Immunol Res; 2(2); 99–104. ©2014 AACR.
Noninvasive Assessment of Hypoxia in Rabbit Advanced Atherosclerosis Using
18
F-fluoromisonidazole Positron Emission Tomographic Imaging
Authors: Mateo Jesus , Izquierdo-Garcia David , Badimon Juan J. , Fayad Zahi A. , Fuster Valentin
Published: February 2014

Background—

Hypoxia is an important microenvironmental factor influencing atherosclerosis progression by inducing foam-cell formation, metabolic adaptation of infiltrated macrophages, and plaque neovascularization. Therefore, imaging plaque hypoxia could serve as a marker of lesions at risk.

Methods and Results—

Advanced aortic atherosclerosis was induced in 18 rabbits by atherogenic diet and double balloon endothelial denudation. Animals underwent
18
F-fluoromisonidazole positron emission tomographic and
18
F-fluorodeoxyglucose positron emission tomographic imaging after 6 to 8 months (atherosclerosis induction) and 12 to 16 months (progression) of diet initiation. Four rabbits fed standard chow served as controls. Radiotracer uptake of the abdominal aorta was measured using standardized uptake values. After imaging, plaque hypoxia (pimonidazole), macrophages (RAM-11), neovessels (CD31), and hypoxia-inducible factor-1α were assessed by immunohistochemistry.
18
F-fluoromisonidazole uptake increased with time on diet (standardized uptake value mean, 0.10±0.01 in nonatherosclerotic animals versus 0.20±0.03 [
P
=0.002] at induction and 0.25±0.03 [
P
<0.001] at progression). Ex vivo positron emission tomographic imaging corroborated the
18
F-fluoromisonidazole uptake by the aorta of atherosclerotic rabbits.
18
F-fluorodeoxyglucose uptake also augmented in atherosclerotic animals, with an standardized uptake value mean of 0.43±0.02 at induction versus 0.35±0.02 in nonatherosclerotic animals (
P
=0.031) and no further increase at progression. By immunohistochemistry, hypoxia was mainly located in the macrophage-rich areas within the atheromatous core, whereas the macrophages close to the lumen were hypoxia-negative. Intraplaque neovessels were found predominantly in macrophage-rich hypoxic regions (pimonidazole
+
/hypoxia-inducible factor-1α
+
/RAM-11
+
).

Conclusions—

Plaque hypoxia increases with disease progression and is present in macrophage-rich areas associated with neovascularization.
18
F-fluoromisonidazole positron emission tomographic imaging emerges as a new tool for the detection of atherosclerotic lesions.
Predictors of Long-Term Recurrent Vascular Events After Ischemic Stroke at Young Age
Authors: Pezzini Alessandro , Grassi Mario , Lodigiani Corrado , Patella Rosalba , Gandolfo Carlo , Zini Andrea , DeLodovici Maria Luisa , Paciaroni Maurizio , Del Sette Massimo , Toriello Antonella , Musolino Rossella , Calabrò Rocco Salvatore , Bovi Paolo , Adami Alessandro , Silvestrelli Giorgio , Sessa Maria , Cavallini Anna , Marcheselli Simona , Bonifati Domenico Marco , Checcarelli Nicoletta , Tancredi Lucia , Chiti Alberto , Del Zotto Elisabetta , Spalloni Alessandra , Giossi Alessia , Volonghi Irene , Costa Paolo , Giacalone Giacomo , Ferrazzi Paola , Poli Loris , Morotti Andrea , Rasura Maurizia , Simone Anna Maria , Gamba Massimo , Cerrato Paolo , Micieli Giuseppe , Melis Maurizio , Massucco Davide , De Giuli Valeria , Iacoviello Licia , Padovani Alessandro
Published: February 2014

Background—

Data on long-term risk and predictors of recurrent thrombotic events after ischemic stroke at a young age are limited.

Methods and Results—

We followed 1867 patients with first-ever ischemic stroke who were 18 to 45 years of age (mean age, 36.8±7.1 years; women, 49.0%), as part of the Italian Project on Stroke in Young Adults (IPSYS). Median follow-up was 40 months (25th to 75th percentile, 53). The primary end point was a composite of ischemic stroke, transient ischemic attack, myocardial infarction, or other arterial events. One hundred sixty-three patients had recurrent thrombotic events (average rate, 2.26 per 100 person-years at risk). At 10 years, cumulative risk was 14.7% (95% confidence interval, 12.2%–17.9%) for primary end point, 14.0% (95% confidence interval, 11.4%–17.1%) for brain ischemia, and 0.7% (95% confidence interval, 0.4%–1.3%) for myocardial infarction or other arterial events. Familial history of stroke, migraine with aura, circulating antiphospholipid antibodies, discontinuation of antiplatelet and antihypertensive medications, and any increase of 1 traditional vascular risk factor were independent predictors of the composite end point in multivariable Cox proportional hazards analysis. A point-scoring system for each variable was generated by their β-coefficients, and a predictive score (IPSYS score) was calculated as the sum of the weighted scores. The area under the receiver operating characteristic curve of the 0- to 5-year score was 0.66 (95% confidence interval, 0.61–0.71; mean, 10-fold internally cross-validated area under the receiver operating characteristic curve, 0.65).

Conclusions—

Among patients with ischemic stroke aged 18 to 45 years, the long-term risk of recurrent thrombotic events is associated with modifiable, age-specific risk factors. The IPSYS score may serve as a simple tool for risk estimation.
Racial and Regional Differences in Venous Thromboembolism in the United States in 3 Cohorts
Authors: Zakai Neil A. , McClure Leslie A. , Judd Suzanne E. , Safford Monika M. , Folsom Aaron R. , Lutsey Pamela L. , Cushman Mary
Published: February 2014

Background—

Blacks are thought to have a higher risk of venous thromboembolism (VTE) than whites. However, prior studies are limited to administrative databases that lack specific information on VTE risk factors or have limited geographic scope.

Methods and Results—

We ascertained VTE from 3 prospective studies: the Atherosclerosis Risk in Communities Study (ARIC), the Cardiovascular Health Study (CHS), and the Reasons for Geographic and Racial Differences in Stroke study (REGARDS). We tested the association of race with VTE using Cox proportional hazard models adjusted for VTE risk factors. Over 438 090 person-years, 916 incident VTE events (302 in blacks) occurred in 51 149 individuals (17 318 blacks) who were followed up. In risk factor–adjusted models, blacks had a higher rate of VTE than whites in the CHS (hazard ratio, 1.81; 95% confidence interval, 1.20–2.73) but not ARIC (hazard ratio, 1.21; 95% confidence interval, 0.96–1.54). In REGARDS, there was a significant region-by-race interaction (
P
=0.01): Blacks in the Southeast had a significantly higher rate of VTE than blacks in the rest of the United States (hazard ratio, 1.63; 95% confidence interval, 1.08–2.48) that was not seen in whites (hazard ratio, 0.83; 95% confidence interval, 0.61–1.14).

Conclusions—

The association of race with VTE differed in each cohort, which may reflect the different time periods of the studies or different regional rates of VTE. Further studies of environmental and genetic risk factors for VTE are needed to determine which underlie racial and perhaps regional differences in VTE.