bluuebunny/crossref_metadata_2025 huggingface dataset:
A NOTE ON THE HILBERT SCHEME OF POINTS ON A CUSP CURVE
Authors: LEE HWAYOUNG
Published: January 2012

We study the Hilbert scheme of points on a cusp curve, mostly the punctual Hilbert scheme [Formula: see text] which parameterizes m points supported at a cusp. We show that the reduced punctual scheme [Formula: see text] is isomorphic to ℙ1 and the Hilbert scheme has one singularity along [Formula: see text].
Selective estrogen receptor modulator promotes weight loss in ovariectomized female rhesus monkeys (Macaca mulatta) by decreasing food intake and increasing activity
Authors: Sullivan Elinor L. , Shearin Jean , Koegler Frank H. , Cameron Judy L.
Published: January 2012

The effect of hormone replacement therapy (HRT) on body weight in postmenopausal women is controversial, with studies reporting an increase, a decrease, and no change in body weight. To examine estrogen receptor actions on body weight, we investigated the effects of treatment with a selective estrogen receptor modulator (SERM) on body weight, food intake, and activity and metabolic rate in a nonhuman primate model. Eighteen ovariectomized female rhesus monkeys were treated with a nonsteroidal SERM (GSK232802A, 5 mg/kg po) for 3 mo. GSK232802A decreased lutenizing hormone ( P < 0.0001) and follicle-stimulating hormone levels ( P < 0.0001), consistent with the estrogenic action of the compound. GSK232802A treatment produced a small but sustained weight loss (4.6 ± 1.0%, P < 0.0001) and reduced adiposity ( P < 0.0001), which was due at least in part to a suppression of food intake (3.6 ± 3.7%, P < 0.0001). Physical activity increased during the 3rd mo of treatment ( P = 0.04). Baseline activity level and the change in activity due to treatment were correlated, with the most sedentary individuals exhibiting increased physical activity during the 1st mo of treatment ( P = 0.02). Metabolic rate did not change ( P = 0.58). These results indicate that GSK232802A treatment reduces body weight and adiposity in ovariectomized nonhuman primates by suppressing food intake and increasing activity, particularly in the most sedentary individuals. These findings suggest that SERM treatment may counteract weight gain in postmenopausal women.
Higher ghrelin and lower leptin secretion are associated with lower LH secretion in young amenorrheic athletes compared with eumenorrheic athletes and controls
Authors: Ackerman Kathryn E. , Slusarz Katherine , Guereca Gabriela , Pierce Lisa , Slattery Meghan , Mendes Nara , Herzog David B. , Misra Madhusmita
Published: January 2012

Amenorrhea is common in young athletes and is associated with low fat mass. However, hormonal factors that link decreased fat mass with altered gonadotropin pulsatility and amenorrhea are unclear. Low levels of leptin (an adipokine) and increased ghrelin (an orexigenic hormone that increases as fat mass decreases) impact gonadotropin pulsatility. Studies have not examined luteinizing hormone (LH) secretory dynamics in relation to leptin or ghrelin secretory dynamics in adolescent and young adult athletes. We hypothesized that 1) young amenorrheic athletes (AA) would have lower LH and leptin and higher ghrelin secretion than eumenorrheic athletes (EA) and nonathletes and 2) higher ghrelin and lower leptin would be associated with lower LH secretion. This was a cross-sectional study. We examined ghrelin and leptin secretory patterns (over 8 h, from 11 PM to 7 AM) in relation to LH secretory patterns in AA, EA, and nonathletes aged 14–21 yr. Ghrelin and leptin were assessed every 20 min and LH every 10 min. Groups did not differ for age, bone age, or BMI. However, fat mass was lower in AA than in EA and nonathletes. AA had lower LH and higher ghrelin pulsatile secretion and AUC than nonathletes and lower leptin pulsatile secretion and AUC than EA and nonathletes. Percent body fat was associated positively with LH and leptin secretion and inversely with ghrelin. In a regression model, ghrelin and leptin secretory parameters were associated independently with LH secretory parameters. We conclude that higher ghrelin and lower leptin secretion in AA related to lower fat mass may contribute to altered LH pulsatility and amenorrhea.
Guidelines for Managing Sensors in Cyber Physical Systems with Multiple Sensors
Authors: Ashok Pradeepkumar , Krishnamoorthy Ganesh , Tesar Delbert
Published: January 2012

Cyber physical systems (CPSs) typically have numerous sensors monitoring the various physical processes involved. Some sensor failures are inevitable and may have catastrophic effects. The relational nature of the diverse measurands can be very useful in detecting faulty sensors, monitoring the health of the system, and reducing false alarms. This paper provides procedures on how one may integrate data from the various sensors, by careful design of a sensor relationship network. Once such a network has been adopted, choices become available in real time for enhancing the reliability, safety, and performance of the overall system.
Failure to Diagnose Phaeochromocytoma Preoperatively: A Case Report and Review of Diagnostic Criteria
Authors: Antonopoulou Ileana , Heining Mark
Published: January 2012

We present a case in which phaeochromocytoma was not diagnosed preoperatively despite extensive investigation. There was significant haemodynamic instability during surgery. We review current diagnostic criteria with a view to reducing such a risk in future.
Rapid Evolution of Assortative Fertilization between Recently Allopatric Species ofDrosophila
Authors: Ahmed-Braimah Yasir H. , McAllister Bryant F.
Published: January 2012

The virilis group ofDrosophilarepresents a relatively unexplored but potentially useful model to investigate the genetics of speciation. Good resolution of phylogenetic relationships and the ability to obtain fertile hybrid offspring make the group especially promising for analysis of genetic changes underlying reproductive isolation separate from hybrid sterility and inviability. Phylogenetic analyses reveal a close relationship between the sister species,Drosophila americanaandD. novamexicana, yet excepting their contemporary allopatric distributions, factors that contribute to reproductive isolation between this species pair remain uncharacterized. A previous report has shown reduced progeny numbers in laboratory crosses between the two species, especially when femaleD. novamexicanaare crossed with maleD. americana. We show that the hatch rate of eggs produced from heterospecific matings is reduced relative to conspecific matings. Failure of eggs to hatch, and consequent reduction in hybrid progeny number, is caused by low fertilization success of heterospecific sperm, thus representing a postmating, prezygotic incompatibility. Following insemination, storage and motility of heterospecific sperm is visibly compromised in femaleD. novamexicana. Our results provide evidence for a mechanism of reproductive isolation that is seldom reported forDrosophilaspecies, and indicate the rapid evolution of postmating, prezygotic reproductive barriers in allopatry.
Malignant Adenomyoepithelioma of the Breast with Lymph Node Metastasis: A Detailed Immunohistochemical Study
Authors: Awamleh Ahlam A. , Gudi Mihir , Shousha Sami
Published: January 2012

Malignant adenomyoepithelioma of the breast is a rare tumour with around 30 cases reported in the literature. Metastases associated with these tumours are usually haematogenous. Axillary lymph node metastases are thought to be unusual, and it has been recently suggested that axillary node dissection is not indicated unless clinically palpable. We here present a case of a 63-year-old woman, who developed a malignant adenomyoepithelioma with axillary lymph node metastasis, that included epithelial and myoepithelial elements, in spite of the absence of clinically enlarged nodes. We suggest that histological examination of axillary sentinel node(s) or node sampling may be worthwhile in this condition.
Unexpected Precipitation of a Re-Rich Phase in Single Crystal Superalloy CMSX-4 during Thermal Exposure
Authors: Cheng Kuiyu , Jo ChangYong , Kim DooHyun , Jin Tao , Hu Zhuangqi
Published: January 2012

A Re-rich phase (up to 85.40% wt.Re) was occasionally found in a single crystal superalloy during thermal exposure. Interestingly, this phase is located in front of the dendrite periphery in the interdendritic region, while the Re is segregated in the dendrite core. Formation of this phase was suggested to relate to the unusual accumulation of the Re resulting from the uneven diffusion process of Re. Appearance of this phase may imply the preference of forming Re-Re atomic bond in the superalloys.
An Application of Classifier Combination Methods in Hand Gesture Recognition
Authors: Wang Guan-Wei , Zhang Chunxia , Zhuang Jian
Published: January 2012

Hand gesture recognition is a topic in artificial intelligence and computer vision with the goal to
automatically interpret human hand gestures via some algorithms. Notice that it is a difficult classification
task for which only one simple classifier cannot achieve satisfactory performance; several classifier
combination techniques are employed in this paper to handle this specific problem. Based on some related
data at hand, AdaBoost and rotation forest are seen to behave significantly better than all the other
considered algorithms, especially a classification tree. By investigating the bias‐variance decompositions
of error for all the compared algorithms, the success of AdaBoost and rotation forest can be attributed
to the fact that each of them simultaneously reduces the bias and variance terms of a SingleTree′s error
to a large extent. Meanwhile, kappa‐error diagrams are utilized to study the diversity‐accuracy patterns
of the constructed ensemble classifiers in a visual manner.
Laser Control of Self-Organization Process in Microscopic Region and Fabrication of Fine Microporous Structure
Authors: Matsumura Yukimasa , Inami Wataru , Kawata Yoshimasa
Published: January 2012

We present a controlling technique of microporous structure by laser irradiation during self-organization process. Self-organization process is fabrication method of microstructure. Polymer solution was dropped on the substrate at high humid condition. Water in air appears dropping air temperature below the dew point. The honeycomb structure with regularly aligned pores on the film was fabricated by attaching water droplets onto the solution surface. We demonstrate that it was possible to prevent forming pores at the region of laser irradiation and flat surface was fabricated. We also demonstrated that a combination structure with two pore sizes and flat surface was produced by a single laser-pulse irradiation. Our method is a unique microfabrication processing technique that combines the advantages of bottom-up and top-down techniques. This method is a promising technique that can be applied to produce for photonic crystals, biological cell culturing, surface science and electronics fields, and so forth.
A Case of Persistent Foot Pain in a Neurofibromatosis Type I Patient
Authors: Stavrinides Vasilis , Nasra Salim
Published: January 2012

Introduction. This is the case of a young male patient who presented to his family physician with atypical left foot pain, which was extremely resistant to analgesia and caused significant disability. Despite extensive investigations, the cause of his pain was not identified until 18 months after his initial symptoms, when the official diagnosis of malignant peripheral nerve sheath tumour (MPNST) was made. Detailed review of the patient’s past history established the diagnosis of type I neurofibromatosis (NF-1), previously undetected.Discussion. NF-1 is an autosomal dominant genetic disorder caused by loss of function mutations of theNF1gene in chromosome 17. Patients with this condition are at increased risk for developing MPNSTs which, however, are treatable only in early stages.Conclusion. Although monitoring NF-1 patients for the development of MPNSTs is common practice, the index of clinical suspicion in patients without an established NF-1 diagnosis is low. Any atypical pain in young adults should raise the possibility of this malignancy, and this case illustrates the fact that MPNSTs can be the first manifestation of NF-1 in patients previously undiagnosed with the disease.
The Liapunov Center Theorem for a Class of Equivariant Hamiltonian Systems
Authors: Li Jia , Shi Yanling
Published: January 2012

We consider the existence of the periodic solutions in the
neighbourhood of equilibria for C∞ equivariant Hamiltonian vector fields. If the equivariant symmetry S acts antisymplectically and S2 = I, we prove that generically
purely imaginary eigenvalues are doubly degenerate and the equilibrium is contained
in a local two‐dimensional flow‐invariant manifold, consisting of a one‐parameter family of symmetric periodic solutions and two two‐dimensional flow‐invariant manifolds
each containing a one‐parameter family of nonsymmetric periodic solutions. The result is a version of Liapunov Center theorem for a class of equivariant Hamiltonian
systems.
WAVE2 Protein Complex Coupled to Membrane and Microtubules
Authors: Takahashi Kazuhide
Published: January 2012

E-cadherin is one of the key molecules in the formation of cell-cell adhesion and interacts intracellularly with a group of proteins collectively named catenins, through which the E-cadherin-catenin complex is anchored to actin-based cytoskeletal components. Although cell-cell adhesion is often disrupted in cancer cells by either genetic or epigenetic alterations in cell adhesion molecules, disruption of cell-cell adhesion alone seems to be insufficient for the induction of cancer cell migration and invasion. A small GTP-binding protein, Rac1, induces the specific cellular protrusions lamellipodia via WAVE2, a member of WASP/WAVE family of the actin cytoskeletal regulatory proteins. Biochemical and pharmacological investigations have revealed that WAVE2 interacts with many proteins that regulate microtubule growth, actin assembly, and membrane targeting of proteins, all of which are necessary for directional cell migration through lamellipodia formation. These findings might have important implications for the development of effective therapeutic agents against cancer cell migration and invasion.
The Effects of Maternal Supplementation of Polyunsaturated Fatty Acids on Visual, Neurobehavioural, and Developmental Outcomes of the Child: A Systematic Review of the Randomized Trials
Authors: Lo Andrea , Sienna Julianna , Mamak Eva , Djokanovic Nada , Westall Carol , Koren Gideon
Published: January 2012

Polyunsaturated fatty acid (PUFA) use in pregnancy has been promoted as beneficial for visual and neurobehavioural development in the fetus. However, no systematic review of the randomized trials has been conducted. The objective of this review was to evaluate potential advantages of this regiment by reviewing all randomized trials in pregnancy.Methods. Systematic review of randomized controlled studies comparing cognitive and visual achievements among infants whose mothers were treated and untreated with PUFA during gestation.Results. Nine studies met the inclusion criteria, three focusing on visual and six on neurobehavioural development. Due to differing outcome measurements in the infants, the studies could not be combined into a formal meta-analysis. Synthesizing the existing data, for both visual and neurobehavioural development, most studies could not show sustained benefits to infant cognition or visual development.Conclusion. At the present time a recommendation to change practice and supplement all expecting mothers with PUFA to improve offspring vision or neurobehavioural function is not supported by existing evidence.
Existence and Multiplicity of Solutions for Some Fractional Boundary Value Problem via Critical Point Theory
Authors: Chen Jing , Tang X. H.
Published: January 2012

We study the existence and multiplicity of solutions for the following fractional boundary value problem: , where F(t, ·) are superquadratic, asymptotically quadratic, and subquadratic, respectively. Several examples are presented to illustrate our results.
Efficient Model Predictive Algorithms for Tracking of Periodic Signals
Authors: Chu Yun-Chung , Chen Michael Z. Q.
Published: January 2012

This paper studies the design of efficient model predictive controllers for fast-sampling linear time-invariant systems subject to input constraints to track a set of periodic references. The problem is decomposed into a steady-state subproblem that determines the optimal asymptotic operating point and a transient subproblem that drives the given plant to this operating point. While the transient subproblem is a small-sized quadratic program, the steady-state subproblem can easily involve hundreds of variables and constraints. The decomposition allows these two subproblems of very different computational complexities to be solved in parallel with different sampling rates. Moreover, a receding horizon approach is adopted for the steady-state subproblem to spread the optimization over time in an efficient manner, making its solution possible for fast-sampling systems. Besides the conventional formulation based on the control inputs as variables, a parameterization using a dynamic policy on the inputs is introduced, which further reduces the online computational requirements. Both proposed algorithms possess nice convergence properties, which are also verified with computer simulations.
Biologically Based Restorative Management of Tooth Wear
Authors: Kelleher Martin G. D. , Bomfim Deborah I. , Austin Rupert S.
Published: January 2012

The prevalence and severity of tooth wear is increasing in industrialised nations. Yet, there is no high-level evidence to support or refute any therapeutic intervention. In the absence of such evidence, many currently prevailing management strategies for tooth wear may be failing in their duty of care to first and foremost improve the oral health of patients with this disease. This paper promotes biologically sound approaches to the management of tooth wear on the basis of current best evidence of the aetiology and clinical features of this disease. The relative risks and benefits of the varying approaches to managing tooth wear are discussed with reference to long-term follow-up studies. Using reference to ethical standards such as “The Daughter Test”, this paper presents case reports of patients with moderate-to-severe levels of tooth wear managed in line with these biologically sound principles.
Hermite-Hadamard and Simpson-Like Type Inequalities for Differentiable ()-Convex Mappings
Authors: Park Jaekeun
Published: January 2012

The author establish several Hermite-Hadamard and Simpson-like type inequalities for mappings whose first derivative in absolute value aroused to the th () power are ()-convex. Some applications to special means of positive real numbers are also given.
Synthesis of Hyperbranched Polymer Using Slow Monomer Addition Method
Authors: Satoh Toshifumi
Published: January 2012

This paper details the synthesis of a well-defined hyperbranched polymer using a slow monomer addition method. The polymerization under slow monomer addition conditions results in a very low monomer concentration actually present in the reaction mixture, and the exclusive reaction of the monomer with the growing polyfunctional macromolecules occurs, resulting in a high molecular weight and a high degree of branching value. Thus, the slow monomer addition is a versatile and preferential method for the controlled synthesis of a well-defined hyperbranched polymer with both a high molecular weight and a high degree of branching value.
Role of Macrophage Migration Inhibitory Factor in the Proliferation of Smooth Muscle Cell in Pulmonary Hypertension
Authors: Zhang Bo , Shen Min , Xu Min , Liu Li-Li , Luo Ying , Xu Dun-Quan , Wang Yan-Xia , Liu Man-Ling , Liu Yi , Dong Hai-Ying , Zhao Peng-Tao , Li Zhi-Chao
Published: January 2012

Pulmonary hypertension (PH) contributes to the mortality of patients with lung and heart diseases. However, the underlying mechanism has not been completely elucidated. Accumulating evidence suggests that inflammatory response may be involved in the pathogenesis of PH. Macrophage migration inhibitory factor (MIF) is a critical upstream inflammatory mediator which promotes a broad range of pathophysiological processes. The aim of the study was to investigate the role of MIF in the pulmonary vascular remodeling of hypoxia-induced PH. We found that MIF mRNA and protein expression was increased in the lung tissues from hypoxic pulmonary hypertensive rats. Intensive immunoreactivity for MIF was observed in smooth muscle cells of large pulmonary arteries (PAs), endothelial cells of small PAs, and inflammatory cells of hypoxic lungs. MIF participated in the hypoxia-induced PASMCs proliferation, and it could directly stimulate proliferation of these cells. MIF-induced enhanced growth of PASMCs was attenuated by MEK and JNK inhibitor. Besides, MIF antagonist ISO-1 suppressed the ERK1/2 and JNK phosphorylation induced by MIF. In conclusion, the current finding suggested that MIF may act on the proliferation of PASMCs through the activation of the ERK1/2 and JNK pathways, which contributes to hypoxic pulmonary hypertension.
Studies on the Feeding Habits ofLutzomyia (Lutzomyia) longipalpis(Lutz & Neiva, 1912) (Diptera: Psychodidae: Phlebotominae) Populations from Endemic Areas of American Visceral Leishmaniasis in Northeastern Brazil
Authors: Afonso Margarete Martins dos Santos , Duarte Rosemere , Miranda José Carlos , Caranha Lindenbergh , Rangel Elizabeth Ferreira
Published: January 2012

The aim of this study was to identify potential blood feeding sources ofL. (L.) longipalpisspecimens from populations in Northeastern Brazil, endemic areas of American Visceral Leishmaniasis (AVL) and its correlation with the transmission ofL. (L.) i. chagasi. The ELISA technique was applied using bird, dog, goat, opossum, equine, feline, human, sheep, and rodent antisera to analyze 609 females, resulting in an overall positivity of 60%. In all municipalities, females showed higher positivity for bird followed by dog antiserum and sand fly specimens were also positive for equine, feline, human, sheep, goat, opossum, and rodent antisera. The finding for 17 combinations of two or three types of blood in some females corroborates the opportunistic habit of this sand fly species. The results demonstrating the association betweenL. (L.) longipalpisand opossum suggest the need for further evaluation of the real role of this synanthropic mammal in the eco-epidemiology of AVL.
Association between Depressive Symptoms and Metabolic Syndrome in Police Officers: Results from Two Cross-Sectional Studies
Authors: Hartley Tara A. , Knox Sarah S. , Fekedulegn Desta , Barbosa-Leiker Celestina , Violanti John M. , Andrew Michael E. , Burchfiel Cecil M.
Published: January 2012

Policing is one of the most dangerous and stressful occupations and such stress can have deleterious effects on health. The purpose of this study was to examine the association between depressive symptoms and metabolic syndrome (MetSyn) in male and female police officers from two study populations, Buffalo, NY and Spokane, WA. Depressive symptoms were measured using the Center for Epidemiologic Studies-Depression (CES-D) scale. MetSyn was defined using the 2005 AHA/NHBLI guidelines. Analysis of covariance was used to describe differences in number of MetSyn components across depressive symptom categories. The number of MetSyn components increased significantly across categories of CES-D for Spokane men only (p-trend = 0.003). For each 5-unit increase in CES-D score, odds increased by 47.6% for having hypertriglyceridemia, by 51.8% for having hypertension, and by 56.7% for having glucose intolerance. Exploring this association is important since both are predictors of future chronic health problems and the results could be helpful in developing future gender-specific prevention and intervention efforts among police officers.
Functional Exercise and Physical Fitness Post Stroke: The Importance of Exercise Maintenance for Motor Control and Physical Fitness after Stroke
Authors: Langhammer Birgitta , Lindmark Birgitta
Published: January 2012

It is argued that all stroke patients, indifferent of disability, have the same possibility to improve with training. The aim of the study was to follow and register functional improvements in two groups with different functional capacities at baseline for a period of 36 months. Stroke patients were recruited and divided into groups related to their functional status at baseline. During the acute rehabilitation, both groups received functional task-oriented training, followed by regular self- or therapeutic driven training the first year after stroke and varied exercise patterns the following 24 months. The participants were tested on admission, and at three, six, twelve, and thirty-six months after the onset of stroke. Both groups improved functional activity up to six months which then stabilized up to twelve months to decline somewhat at thirty-six months after stroke. Change scores indicate a greater potential for rehabilitation in the MAS ≤35 in relation to group MAS >35 although the functional capacity was higher in the latter. This indicates the importance of maintaining exercise and training for all persons after stroke.
Hand Recognition Using Thermal Image and Extension Neural Network
Authors: Wang Meng-Hui
Published: January 2012

Hand recognition is one of the popular biometry methods for access control systems. In this paper, a new scheme for personal recognition using thermal images of the hand and an extension neural network (ENN) is presented. The features of the recognition system are extracted from gray level hand images, which are taken by an infrared camera. The main advantage of the thermal image is that it can reduce errors and noise in the features extracted stage, which is most important to increase the accuracy of recognition systems. Moreover, a new recognition method based on the ENN is proposed to perform the core functions of the hand recognition system. The proposed ENN‐based recognition method also permits rapid adaptive processing for a new pattern, as it only tunes the boundaries of classified features or adds a new neural node. It is feasible to implement the proposed method on a Microcomputer for a portable personal recognition device. From the tested examples, the proposed method has a significantly high degree of recognition accuracy and shows good tolerance to errors added.
Treatment of Anterior Cruciate Ligament Injury in Skeletally Immature Patients
Authors: Hudgens Joshua L. , Dahm Diane L.
Published: January 2012

The incidence of ACL tears is rising in the pediatric and adolescent populations as these individuals succumb to traumatic and nontraumatic athletic injuries. Management of this condition in the skeletally immature patient poses a challenge and is controversial. Operative reconstruction carries the concern for damage to the physis with resultant limb length inequality and angular joint deformity but provides stability to the knee and allows return of function in most patients. On the other hand, nonoperative treatment has been shown to carry an increased risk of meniscal and articular cartilage damage and is difficult from a compliance standpoint in this demographic. For the majority of skeletally immature patients, operative treatment is recommended as it has shown good clinical and functional results with minimal risk of growth disturbance. This paper aims to address the natural course of ACL injuries in the skeletally immature patient, treatment options with associated complications, and current preventative strategies.
Study on the Combustion Process and Emissions of a Turbocharged Diesel Engine with EGR
Authors: Deqing Mei , Junnan Qian , Ping Sun , Yan Miao , Shuang Zhang , Yongjun Cai
Published: January 2012

A high pressure EGR system was adopted to a turbocharged inter-cooled diesel engine, to analyze its combustion and emission characteristics under the condition of different loads and constant speed. Under the same steady operating mode, with the increase of EGR rate, the temperature of compressed gas ascended, the ignition delay was shortened, the pressure and temperature of the burned gas descended, and the combustion process was prolonged. According to the experimental data, it was found that, at the same EGR rate, lower the load of engine was, lower the temperature in cylinder, and higher the increase rate of CO was. However, the increase rate of HC present a falling trend. The decrease rate of the specific emission of NOxlinearly varied with EGR rate with a slope of 1.651. The increase rate of smoke opacity behaved a second-order polynomial uprising trend, and the higher the load was, the sharpener the smoke opacity deteriorated, with the increase of EGR rate. From the point of emission view, the engine with EGR system can achieve the lesser exhaust emissions in some operations by adjusting the engine parameters.
Inverse Source Identification by the Modified Regularization Method on Poisson Equation
Authors: Li Xiao-Xiao , Guo Heng Zhen , Wan Shi Min , Yang Fan
Published: January 2012

This paper deals with an inverse problem for identifying an unknown source which depends only on one variable in two‐dimensional Poisson equation, with the aid of an extra measurement at an internal point. Since this problem is illposed, we obtain the regularization solution by the modified regularization method. Furthermore, we obtain the Hölder‐type error estimate between the regularization solution and the exact solution. The numerical results show that the proposed method is stable and the unknown source is recovered very well.
p53 Inhibits Angiogenesis by Inducing the Production of Arresten
Authors: Assadian Sarah , El-Assaad Wissal , Wang Xue Q.D. , Gannon Phillipe O. , Barrès Véronique , Latour Mathieu , Mes-Masson Anne-Marie , Saad Fred , Sado Yoshikazu , Dostie Josée , Teodoro Jose G.
Published: January 2012

Several types of collagen contain cryptic antiangiogenic noncollagenous domains that are released upon proteolysis of extracellular matrix (ECM). Among those is Arresten, a collagen-derived antiangiogenic factor (CDAF) that is processed from α1 collagen IV. However, the conditions under which Arresten is released from collagen IV in vivo or whether the protein functions in tumor suppressor pathways remain unknown. Here, we show that p53 induces the expression of α1 collagen IV and release of Arresten-containing fragments from the ECM. Comparison of the transcriptional activation of COL4A1 with other CDAF-containing genes revealed that COL4A1 is a major antiangiogenic gene induced by p53 in human adenocarinoma cells. p53 directly activated transcription of the COL4A1 gene by binding to an enhancer region 26 kbp downstream of its 3′ end. p53 also stabilized the expression of full-length α1 collagen IV by upregulation of α(II) prolyl-hydroxylase and increased the release of Arresten in the ECM through a matrix metalloproteinase (MMP)-dependent mechanism. The resulting upregulation of α1 collagen IV and production of Arresten by the tumor cells significantly inhibited angiogenesis and limited tumor growth in vivo. Furthermore, we show that immunostaining of Arresten correlated with p53 status in human prostate cancer specimens. Our findings, therefore, link the production of Arresten to the p53 tumor suppressor pathway and show a novel mechanism through which p53 can inhibit angiogenesis. Cancer Res; 72(5); 1270–9. ©2012 AACR.
KR-POK Interacts with p53 and Represses Its Ability to Activate Transcription of p21WAF1/CDKN1A
Authors: Jeon Bu-Nam , Kim Min-Kyeong , Choi Won-Il , Koh Dong-In , Hong Sung-Yi , Kim Kyung-Sup , Kim Minjung , Yun Chae-Ok , Yoon Juyong , Choi Kang-Yell , Lee Kyung-Ryul , Nephew Kenneth P. , Hur Man-Wook
Published: January 2012

Transcriptional regulation by p53 is thought to play a role in its ability to suppress tumorigenesis. However, there remain gaps in understanding about how p53 regulates transcription and how disrupting this function may promote cancer. Here we report a role in these processes for the kidney cancer–related gene KR-POK (ZBTB7C), a POZ domain and Krüppel-like zinc finger transcription factor that we found to physically interact with p53. Murine embryonic fibroblasts isolated from genetically deficient mice (Kr-pok−/− MEFs) exhibited a proliferative defect relative to wild-type mouse embryonic fibroblasts (MEF). The zinc finger domain of Kr-pok interacted directly with the DNA binding and oligomerization domains of p53. This interaction was essential for Kr-pok to bind the distal promoter region of the CDKN1A gene, an important p53 target gene encoding the cell-cycle regulator p21WAF1, and to inhibit p53-mediated transcriptional activation of CDKN1A. Kr-pok also interacted with the transcriptional corepressors NCoR and BCoR, acting to repress histone H3 and H4 deacetylation at the proximal promoter region of the CDKN1A gene. Importantly, Kr-pok−/− MEFs displayed an enhancement in CDKN1A transactivation by p53 during the DNA damage response, without any parallel changes in transcription of either the p53 or Kr-pok genes themselves. Furthermore, Kr-pok promoted cell proliferation in vitro and in vivo, and its expression was increased in more than 50% of the malignant human kidney cancer cases analyzed. Together, our findings define KR-POK as a transcriptional repressor with a pro-oncogenic role that relies upon binding to p53 and inhibition of its transactivation function. Cancer Res; 72(5); 1137–48. ©2012 AACR.
Human TH17 Immune Cells Specific for the Tumor Antigen MAGE-A3 Convert to IFN-γ–Secreting Cells as They Differentiate into Effector T Cells In Vivo
Authors: Hamaï Ahmed , Pignon Pascale , Raimbaud Isabelle , Duperrier-Amouriaux Karine , Senellart Hélène , Hiret Sandrine , Douillard Jean-Yves , Bennouna Jaafar , Ayyoub Maha , Valmori Danila
Published: January 2012

The role of TH17 cells in cancer is being investigated, but the existence of tumor antigen–specific TH17 cells has yet to be ascertained. Here, we report the first description of a spontaneous TH17 (IL-17+) response to the important tumor antigen MAGE-A3, which occurred concurrently with a TH1 (IFN-γ+) response in a lung cancer patient. MAGE-A3–specific interleukin (IL)-17+ T cells were mainly CCR7+ central memory T cells, whereas IFN-γ+ cells were enriched for CCR7− effector memory T cells. An assessment of the fine specificity of antigen recognition by these T cells indicated that the CCR6+CCR4+ and CCR6+CXCR3+ fractions contained the same TH17/TH1 population at early and late differentiation stages, respectively, whereas the CCR6−CXCR3+ fraction contained a distinct TH1 population. These findings are important because they suggest a differentiation model in which tumor antigen–specific CD4+ T cells that are primed under TH17 polarizing conditions will progressively convert into IFN-γ–secreting cells in vivo as they differentiate into effector T cells that can effectively attack tumors. Cancer Res; 72(5); 1059–63. ©2012 AACR.
Reduced DICER1 Elicits an Interferon Response in Endometrial Cancer Cells
Authors: Chiappinelli Katherine B. , Haynes Brian C. , Brent Michael R. , Goodfellow Paul J.
Published: January 2012

DICER1 is essential for the generation of mature miRNAs and other short noncoding RNAs. Several lines of investigation implicate DICER1 as a tumor suppressor. Reduced DICER1 levels and changes in miRNA abundance have been associated with aggressive tumor phenotypes. The global effects of reduced DICER1 on mRNA transcript abundance in tumor cells remain largely unknown. We used short hairpin RNA to stably knock down DICER1 in endometrial cancer cell lines to begin to determine how reduced DICER1 activity contributes to tumor phenotypes. DICER1 knockdown did not affect cell proliferation but caused enhanced cell migration and growth in soft agar. miRNA and mRNA profiling in KLE cells revealed overall decreases in miRNA levels and changes in the relative abundance of many mRNAs. One of the most striking changes in mRNA levels was the upregulation of IFN-stimulated genes (ISG), the majority of which lack known miRNA target sequences. IFNβ, a key upstream regulator of the IFN response, was significantly increased in DICER1 knockdowns in the AN3CA, Ishikawa, and KLE endometrial cancer cell lines and in the normal endometrial cell line EM-E6/E7/TERT. IFNβ secreted in media from KLE and EM-E6/E7/TERT shDcr cells was sufficient to activate an IFN response in HT29 cells. The reduced miRNA processing in DICER1 knockdowns was associated with increases in pre-miRNAs in the cytoplasm. Our findings suggest that elevated pre-miRNA levels trigger the IFN response to double-stranded RNA. We thus report a novel effect of reduced DICER1 function in cancer cells. Mol Cancer Res; 10(3); 316–25. ©2012 AACR.
Effects of Neurointermediate Pituitary Lobectomy and Desmopressin on Acute Experimental Autoimmune Encephalomyelitis in Lewis Rats
Authors: Quintanar-Stephano Andrés , Organista-Esparza Alejandro , Chavira-Ramírez Roberto , Kovacs Kalman , Berczi Istvan
Published: January 2012

Objective: The role of arginine vasopressin (AVP) as a direct immune regulator has not yet been clarified, and more work is needed to assess its involvement in the immunoneuroendocrine network. In the present study, the effects of neurointermediate pituitary lobectomy (NIL) and desmopressin (DP), an agonist of AVP, on acute experimental autoimmune encephalomyelitis (EAE) in female Lewis rats were evaluated. The activity of the hypothalamic-pituitary-adrenocortical (HPA) axis was also assessed. Methods: Five groups of rats were used, as follows: (1) sham-operated (SHAM) rats, (2) SHAM + DP rats, (3) NIL rats, (4) NIL + DP rats and (5) untreated normal control rats. DP treatment started 2 weeks after surgery, and immunization to induce EAE was carried out 1 week later. Results: SHAM rats developed full-blown clinical and histological signs of EAE and activation of the HPA axis. SHAM + DP animals had mild clinical signs of EAE, inflammatory infiltrations in the spinal cord and an activated HPA axis. NIL animals developed minimal EAE, scanty spinal cord inflammation and no changes in HPA axis activity. NIL + DP rats developed severe clinical signs of EAE, extensive spinal cord inflammatory infiltrations and marked activation of the HPA axis. Conclusions: NIL decreased the cell-mediated immune response, while DP in NIL animals restored the immune response. AVP is directly involved in the maintenance of immune competence.
Cervicocranial Fibromuscular Dysplasia in Taiwanese Ischemic Stroke Patients
Authors: Liu Chi-Hung , Wu Dean , Chin Shy-Chyi , Fu Ser-Chen , Wu Tai-Cheng , Chang Chien-Hung , Peng Tsung-I , Chang Yeu-Jhy , Lee Tsong-Hai
Published: January 2012

Introduction: Clinical research of cervicocranial fibromuscular dysplasia (FMD) is rare in Asian populations. Our study reviewed Taiwanese ischemic stroke patients with cervicocranial FMD and compared them with previous reports. Methods: Between 2000 and 2011, we collected 19 consecutive cervicocranial FMD patients who received demographic registration, a blood test for excluding vasculitis, and comprehensive angiography. Cerebral ultrasound, vascular images and clinical outcomes (Barthel index, modified Rankin scale, recurrent stroke, or death) were monitored during follow-up. Results: Of the 19 patients, 16 (84%) had carotid FMD, while 7 (37%) had vertebral FMD. Only 2 investigated patients (13%) had renal FMD and 1 (5%) had cerebral aneurysm. 14 (74%) presented acute arterial dissection. All patients received medical treatment and had neither recurrent stroke nor dissection during follow-up. In the literature review of 225 FMD patients, 3.6% had recurrent stroke during follow-up, and some reported surgical procedure or angioplasty could give a good clinical outcome in progressing ischemia irrelevant to the cause of stenosis. Conclusion: In Taiwanese cervicocranial FMD patients, arterial dissection was one of the most common clinical presentations. Most of our patients had isolated involvement of the cervicocranial artery and carried a favorable outcome under medical treatment.
Inhibition of Protein Kinase C β2 Prevents Tumor Necrosis Factor-α-Induced Apoptosis and Oxidative Stress in Endothelial Cells: The Role of NADPH Oxidase Subunits
Authors: Deng Bingqing , Xie Shuanglun , Wang Jingfeng , Xia Zhengyuan , Nie Ruqiong
Published: January 2012

We investigate the cell signal transduction pathway protein kinase C (PKC) and the role of NADPH subunits in the process of TNF-α-induced endothelial apoptosis. Human umbilical vein endothelial cells (HUVEC) were treated with one of these: 1 mM PKC β2 inhibitor CGP53353, 10 mM PKC δ inhibitor rottlerin, combination CGP53353 with rottlerin, 3 ×10–4M NADPH oxidase inhibitor apocynin, 5 × 10–6M NADPH oxidase peptide inhibitor gp91ds-tat. The apoptosis process was assessed by Hoechst 33342 stain, flow cytometry and Western blot analysis, while intracellular reactive oxygen species (ROS) production was detected by 2,7’-dichlorodihydrofluorescein diacetate (DCFH-DA). The NADPH oxidase subunit gene and protein expression were assessed by quantitative real-time PCR and Western blot analysis, respectively. TNF-α significantly induced HUVEC apoptosis and ROS production, accompanying with dramatic upregulation of NADPH oxidase subunits: NOX2/gp91phox, NOX4, p47phox and p67phox, whereas these enhancements were abolished by the treatment with PKC inhibitors. High TNF-α level exposure induces HUVEC apoptosis, as well as a ROS generation increase via the PKC β2-dependent activation of NADPH oxidase. Although the PKC δ pathway may enhance TNF-α-induced HUVEC apoptosis, it does not involve the ROS pathway. Upregulation of expression of NADPH subunits is important in this process, which leads to a new target in antioxidative therapy for vascular disease prevention.
Maternal Serum Vitamin D at 11–13 Weeks in Pregnancies Delivering Small for Gestational Age Neonates
Authors: Ertl Rebecca , Yu Christina K.H. , Samaha Robert , Akolekar Ranjit , Nicolaides Kypros H.
Published: January 2012

Objectives: To determine if maternal serum levels of 25(OH)D at 11–13 weeks’ gestation are altered in pregnancies that subsequently deliver small for gestational age (SGA) neonates and whether the levels are related to placental function reflected in serum concentration of pregnancy-associated plasma protein-A (PAPP-A). Methods: Serum 25(OH)D and PAPP-A were measured at 11–13 weeks in 150 singleton pregnancies that delivered SGA neonates and 1,000 appropriate for gestational age (AGA) controls. The median 25(OH)D and PAPP-A multiple of the unaffected median (MoM) in the outcome groups were compared. Results: In the SGA, the median serum 25(OH)D and PAPP-A were significantly decreased (0.78 vs. 1.00 MoM, p < 0.0001 and 0.78 vs. 1.00 MoM, p < 0.0001, respectively). The incidence of 25(OH)D levels below the 10th percentile was significantly higher in the SGA than the AGA group in Caucasian women (p = 0.002) but not in those of African racial origin (p = 0.183). There was no significant association between 25(OH)D MoM and PAPPA MoM in either the SGA or the AGA groups. Conclusion: Serum 25(OH)D levels at 11–13 weeks are decreased in pregnancies of Caucasian women that deliver SGA neonates but not in those of African racial origin. The decrease in 25(OH)D levels is unrelated to placental function.
Phenotypic Variation of Autosomal-Dominant Corticobasal Degeneration
Authors: Jung Hans H. , Bremer Juliane , Streffer Johannes , Virdee Kanwar , Spillantini Maria Grazia , Crowther R. Anthony , Brugger Peter , Van Broeckhoven Christine , Aguzzi Adriano , Tolnay Markus
Published: January 2012

Neurodegenerative tauopathies may be inherited as autosomal-dominant disorders with variable clinicopathological phenotypes, and causative mutations in the microtubule-associated protein tau (MAPT) gene are not regularly seen. Herein, we describe a patient with clinically typical and autopsy-proven corticobasal degeneration (CBD). Her mother was diagnosed to have Parkinson’s disease, but autopsy showed CBD pathology as in the index patient. The sister of the index patient had the clinical symptoms of primary progressive aphasia (PPA), but no pathology was available to date. Molecular analysis did not reveal any mutation in the MAPT or progranulin (GRN) genes. Our findings illustrate that CBD, progressive supranuclear palsy and PPA may be overlapping diseases with a common pathological basis rather than distinct entities. Clinical presentation and course might be determined by additional, yet unknown, genetic modifying factors.
A Combined Functional Annotation Score for Non-Synonymous Variants
Authors: Lopes Margarida C. , Joyce Chris , Ritchie Graham R.S. , John Sally L. , Cunningham Fiona , Asimit Jennifer , Zeggini Eleftheria
Published: January 2012

Aims: Next-generation sequencing has opened the possibility of large-scale sequence-based disease association studies. A major challenge in interpreting whole-exome data is predicting which of the discovered variants are deleterious or neutral. To address this question in silico, we have developed a score called Combined Annotation scoRing toOL (CAROL), which combines information from 2 bioinformatics tools: PolyPhen-2 and SIFT, in order to improve the prediction of the effect of non-synonymous coding variants. Methods: We used a weighted Z method that combines the probabilistic scores of PolyPhen-2 and SIFT. We defined 2 dataset pairs to train and test CAROL using information from the dbSNP: ‘HGMD-PUBLIC’ and 1000 Genomes Project databases. The training pair comprises a total of 980 positive control (disease-causing) and 4,845 negative control (non-disease-causing) variants. The test pair consists of 1,959 positive and 9,691 negative controls. Results: CAROL has higher predictive power and accuracy for the effect of non-synonymous variants than each individual annotation tool (PolyPhen-2 and SIFT) and benefits from higher coverage. Conclusion: The combination of annotation tools can help improve automated prediction of whole-genome/exome non-synonymous variant functional consequences.
Healthy Aging: Is Smaller Better? – A Mini-Review
Authors: Bartke Andrzej
Published: January 2012

A recent report of virtually complete protection from diabetes and cancer in a population of people with hereditary dwarfism revived interest in elucidating the relationships between growth, adult body size, age-related disease and longevity. In many species, smaller individuals outlive those that are larger and a similar relationship was shown in studies of various human populations. Adult body size is strongly dependent on the actions of growth hormone (GH) and the absence of GH or GH receptor in mice leads to a remarkable extension of longevity. Many mechanisms that may account for, or contribute to, this association have been identified. It is suggested that modest modifications of the diet at different ages may extend human healthspan and lifespan by reducing levels of hormones that stimulate growth.