bluuebunny/crossref_metadata_2025 huggingface dataset:
Worldwide impact of economic cycles on suicide trends over 3 decades: differences according to level of development. A mixed effect model study
Authors: Blasco-Fontecilla Hilario , Perez-Rodriguez M Mercedes , Garcia-Nieto Rebeca , Fernandez-Navarro Pablo , Galfalvy Hanga , de Leon Jose , Baca-Garcia Enrique
Published: May 2012

Objectives

To investigate the trends and correlations of gross domestic product (GDP) adjusted for purchasing power parity (PPP) per capita on suicide rates in 10 WHO regions during the past 30 years.

Design

Analyses of databases of PPP-adjusted GDP per capita and suicide rates. Countries were grouped according to the Global Burden of Disease regional classification system.

Data sources

World Bank's official website and WHO's mortality database.

Statistical analyses

After graphically displaying PPP-adjusted GDP per capita and suicide rates, mixed effect models were used for representing and analysing clustered data.

Results

Three different groups of countries, based on the correlation between the PPP-adjusted GDP per capita and suicide rates, are reported: (1) positive correlation: developing (lower middle and upper middle income) Latin-American and Caribbean countries, developing countries in the South East Asian Region including India, some countries in the Western Pacific Region (such as China and South Korea) and high-income Asian countries, including Japan; (2) negative correlation: high-income and developing European countries, Canada, Australia and New Zealand and (3) no correlation was found in an African country.

Conclusions

PPP-adjusted GDP per capita may offer a simple measure for designing the type of preventive interventions aimed at lowering suicide rates that can be used across countries. Public health interventions might be more suitable for developing countries. In high-income countries, however, preventive measures based on the medical model might prove more useful.
An Aqueous Extract ofPortulaca oleraceaAmeliorates Diabetic Nephropathy Through Suppression of Renal Fibrosis and Inflammation in Diabetic db/db Mice
Authors: Lee An Sook , Lee Yun Jung , Lee So Min , Yoon Jung Joo , Kim Jin Sook , Kang Dae Gill , Lee Ho Sub
Published: May 2012

Diabetic nephropathy is one of the most common microvascular complications of diabetes and the leading cause of end-stage renal disease. In the present study, we investigated the renoprotective effect of the aqueous extract of Portulaca oleracea (AP) on diabetic nephropathy accelerated by renal fibrosis and inflammation in type 2 diabetic db/db mice. The mice were treated with AP (300 mg/kg/day, p.o.) for ten weeks to examine the long-term effects on diabetic nephropathy and renal dysfunction. We found that AP treatment markedly lowered blood glucose to 412 ± 11.4 mg/dl and plasma creatinine level to 2.3 ± 0.8 mg/dl compared to db/db mice (p < 0.05, p < 0.01, respectively). This study also showed that treatment with AP significantly decreased water intake and urine volume in diabetic db/db mice (p < 0.05). In immunohistological study, the renal expression of transforming growth factor-β1 (TGF-β1), advanced glycation end products (AGE), and intercellular adhesion molecule (ICAM)-1 markedly increased in the renal cortex of untreated db/db mice (p < 0.01). In contrast, AP treatment significantly reduced these expressions to 50 ± 2.1%, 48 ± 2.8%, 61 ± 1.1%, respectively (p < 0.01). Furthermore, NF-κB p65 activation in renal tissues markedly increased in untreated db/db mice, which was significantly suppressed by AP treatment. Taken together, these findings suggest that AP attenuates diabetic nephropathy through inhibition of renal fibrosis and inflammation in db/db mice.
Effect of the Best Compatibility of Components in Corni Fructus on WT1 Expression in Glomerular Podocytes of Type 2 Diabetic Rats with Early Nephropathy
Authors: Liu Hong , Xu Huiqing , Shen Cunsi , Wu Chen
Published: May 2012

Our previous studies have shown that the best compatibility of components in Corni Fructus (PC) had a protective effect on vascular endothelial cells. In this study, the effect of PC on WT1 expression in glomerular podocytes and the mechanism of PC on early nephropathy in type 2 diabetic rats have been investigated. Type 2 diabetic rats were generated by high-fat diet combined with intraperitoneal injection of 30 mg/kg streptozotocin (STZ), then fed aminoguanidine (100 mg/kg), glimepiride (0.4 mg/kg), low-dose (60 mg/kg) or high-dose (120 mg/kg) of PC once a day for 12 weeks. Fasting blood glucose (FBG) was examined regularly. Insulin (INS) was measured by a radioimmunoassay. Microalbuminuria (mALB) was measured by an ELISA assay. Urinary creatinine (UCr), blood urea nitrogen (BUN) and N-acetyl-β-D-glucosaminidase (NAG) were measured by colorimetric assays. Renal morphological changes were observed by optical microscopy. The expression index of Wilms tumor 1 (WT1EI) in glomeruli was examined by immunohistochemistry. The results showed that PC led to a decrease in FBG (p < 0.01), NAG (p < 0.05) and mALB (p < 0.05) and an increase in INS (p < 0.01) and WT1EI (p < 0.05) compared to the diabetic group. PC could improve renal damage and greatly reduce the renal morphology score (p < 0.05). These results suggested that PC had the protective effect on early nephropathy in type 2 diabetic rats, which was closely related to the regulation of podocytes.
The Aqueous Extract of Prunella vulgaris Suppresses Cell Invasion and Migration in Human Liver Cancer Cells by Attenuating Matrix Metalloproteinases
Authors: Kim Seung-Hum , Huang Chung-Yueh , Tsai Cheng-Yu , Lu Shu-Yi , Chiu Chien-Chih , Fang Kang
Published: May 2012

The mechanism of action of Prunella vulgaris L. (PV) affecting cell migration and invasion of human liver cancer cells remains unknown. In this work we showed that the aqueous extract of PV affected migration and invasion of human liver carcinoma cells by inhibiting activities of metalloproteases, MMP-2 and MMP-9, without affecting cell viabilities. We further showed that PV suppressed migration through attenuation of enzymatic activities of MMP-9 and MMP-2 at transcriptional levels and the effects can be correlated with the status of p53 in hepatocarcinoma cells. This work provides a new dimension of understanding on Prunella vulgaris in restraining migration and invasion in human liver cancer cells.
COLLECTIVE PROPERTIES OF STABLE EVEN–EVEN Cd ISOTOPES
Authors: PRÓCHNIAK LESZEK , QUENTIN PHILIPPE , IMADALOU MOURAD
Published: May 2012

We analyze collective properties of the 110-116 Cd isotopes in the framework of the general Bohr Hamiltonian which is obtained from the ATDHFB theory with the Skyrme interaction. Calculated energies and B(E2) transition probabilities and experimental data are in good agreement.
SOME SUBCLASSES OF MEROMORPHICALLY MULTIVALENT FUNCTIONS ASSOCIATED WITH THE GENERALIZED MULTIPLIER TRANSFORMATIONS
Authors: Aouf M. K. , Shamandy A. , El-Ashwah R. M. , Ali E. E.
Published: May 2012

In this present paper, we introduce and investigate each of the following new subclasses [Formula: see text] and hp(λ, ℓ;φ) as well as [Formula: see text] and [Formula: see text] of meromorphically p-valent functions, which is defined by means of a certain meromorphically p-modified version of the multiplier transformation. Such results as inclusion relationships, integral representations and convolution properties for these function classes are proved.
SYMMETRY ANALYSIS AND SIMILARITY REDUCTION OF THE KORTEWEG–DE VRIES–ZAKHAROV–KUZNETSOV EQUATION
Authors: Nadjafikhah Mehdi , Ahangari Fatemeh
Published: May 2012

In this paper, the problem of determining the largest possible set of symmetries for an important nonlinear dynamical system in mathematical physics, the Korteweg–de Vries–Zakharov–Kuznetsov (KdV–ZK) equation, is studied. By applying the basic Lie symmetry method for the KdV–ZK equation, the classical Lie point symmetry operators are obtained. Also, the structure of the Lie algebra of symmetries is discussed and the optimal system of subalgebras of the equation is constructed. The Lie invariants as well as similarity reduced equations corresponding to infinitesimal symmetries are obtained. The non-classical symmetries of the KdV–ZK equation are also investigated.
Causal ACTH-Depot Therapy during Pregnancies following Infertility Treatment
Authors: Klimek Rudolf , Klimek Marek , Gralek Peter , Jasiczek Dariusz
Published: May 2012

The aim of this paper was to confirm the efficacy of adrenocorticotropin depot (ACTH-depot) therapy in pregnancies with threatened miscarriage and preterm delivery through the desired stimulation of the adrenal glands controlled by the rest of organism. The activity of hypothalamic-pituitary-adrenal axis plays a key role in pregnancy. Such naturally stimulated endogenous corticosteroid hormones are free from unwanted side effects of their synthetics analogs. Low level of maternal blood ACTH and insufficient increase of induced by hypothalamic hormones oxytocinases (cystine-β-aminopeptidases) were indication to ACTH-depot therapy (0.5 mg/week) in our consecutive prospective studies. Contrary to antenatal use of synthetic corticosteroids, there are no temporal limits of this therapy, which has to be more often recommended into clinical prevention of fetal morbidity, treatment of premature delivery, and finally elimination of the newborn's mortality caused by the neuroendocrinological gestoses.
The Multiplication Operator fromF(p,q,s)Spaces tonth Weighted-Type Spaces on the Unit Disk
Authors: Liu Yongmin , Yu Yanyan
Published: May 2012

LetH(𝔻)be the space of analytic functions on𝔻andu∈H(𝔻). The boundedness and compactness of the multiplication operatorMufromF(p,q,s),(or  F0(p,q,s))spaces tonth weighted-type spaces on the unit disk are investigated in this paper.
Risk and Protective Factors for Breast Cancer in Midwest of Brazil
Authors: Inumaru Lívia Emi , Irineu Gomes Duarte Quintanilha Maíra , Aparecida da Silveira Érika , Veloso Naves Maria Margareth
Published: May 2012

Patterns of physical activity, body composition, and breastfeeding are closely related to health and are influenced by environmental, economic, and social factors. With the increase of sedentary lifestyle and overweight, many chronic diseases have also increased, including cancer. Breast cancer is the most common cancer in women worldwide, and the knowledge of its risk and protective factors is important to the adoption of primary prevention strategies. We aimed to investigate some risk and protective factors for breast cancer among women from Midwest Brazil. It is a case-control study of outpatient basis, carried out with 93 breast cancer cases and 186 controls. Socioeconomic, gynecological, anthropometric, and lifestyle variables were collected, and odds ratios (ORs) values were estimated (significance level, 5%; confidence interval (CI), 95%). Per capita income equal to or lower than 1/2 Brazilian minimum wage (OR=1.88;CI=1.06–3.29), residence in rural area (OR=4.93;CI=1.65–14.73), and presence of family history of breast cancer (OR=5.38;CI=1.46–19.93) are risk factors for breast cancer. In turn, physical activity (past 6 months) (OR=0.23;CI=0.10–0.55) and leisure physical activity at 20 years old (OR=0.13;CI=0.03–0.54) are protective factors for the disease in women who live in Midwest of Brazil.
H∞Filtering over Networks for a Class of Discrete-Time Stochastic System with Randomly Occurred Sensor Nonlinearity
Authors: Sun Tao , Su Hongye , Wu Zhengguang , Duan Qihui
Published: May 2012

TheH∞filtering problem for a class of discrete-time stochastic system with randomly occurred nonlinearity (RON) suffering from network packet loss is considered. Based on the Lyapunov-Krasovskii functional method, the asymptotical mean-square stability condition of the filtering system with a prescribedH∞level is derived. Besides, the filter parameters can be obtained simultaneously by solving the matrix inequalities we achieve. It is worth noting that no slack variable is introduced in the proposed conditions. The effectiveness of the theory developed is verified through a numerical example.
Combination of LC-MS2 and GC-MS as a Tool to Differentiate Oxidative Metabolites of Zearalenone with Different Chemical Structures
Authors: Hildebrand Andreas A. , Pfeiffer Erika , Damm Georg , Metzler Manfred
Published: May 2012

Recent studies on the mammalian and fungal metabolism of the mycotoxin zearalenone (ZEN) have disclosed the formation of six regioisomers of monohydroxy-ZEN and its reductive metabolite zearalenol (ZEL). Hydroxylation occurs at the aromatic ring or at one of four positions of the aliphatic macrocycle. In addition, an aliphatic ZEN epoxide, its hydrolysis product, and other products were identified in fungal cultures. In this paper, we report the product ion spectra of the [M-H]− ions of 22 oxidative metabolites of ZEN and ZEL, obtained by LC-MS2 analysis using a linear ion trap mass spectrometer with negative electrospray ionization. The MS2 spectra exhibit qualitative and quantitative differences which allow a clear distinction of most metabolites. Moreover, GC-MS analysis of the trimethylsilylated metabolites yields electron impact mass spectra with numerous fragment ions which can be used as fingerprint to confirm the chemical structure derived by LC-MS2 analysis.
High-Gain Textile Antenna Array System for Off-Body Communication
Authors: Scarpello Maria Lucia , Vallozzi Luigi , Rogier Hendrik , Vande Ginste Dries
Published: May 2012

A novel high-gain textile antenna array system, fully integrated into a rescue-worker’s vest and operating in the Industrial, Scientific, and Medical wireless band (2.4–2.4835 GHz), is presented. The system comprises an array consisting of four tip-truncated equilateral triangular microstrip patch antennas (ETMPAs), a power divider, line stretchers, and coaxial cables. The array is vertically positioned on the human torso to produce a narrow beam in elevation, as such reducing fading and allowing to steer the maximum gain in a small angular sector centered around the broadside direction. To allow simple low-cost beam steering, we specifically minimize mutual coupling by using a relative large distance between the patches and by selecting the ETMPA element as the most suited topology from three potential patch geometries. Moreover, we investigate the stability of return loss and mutual coupling characteristics under different relative humidity conditions, when bending the array, when placing the system on-body, and when covering it by different textile layers. Reflection coefficient and gain patterns are simulated and measured for the antenna system in free space and placed on the human body.
Examination of Far-Field Mathematical Absorber Reflection Suppression through Computational Electromagnetic Simulation
Authors: Gregson S. F. , Newell A. C. , Hindman G. E.
Published: May 2012

The mathematical absorber reflection suppression (MARS) technique has been used to identify and then suppress the effects of spurious scattering within spherical, cylindrical, and planar near-field antenna measurement systems, compact antenna test ranges (CATRs), and far-field measurement facilities for some time now. The recent development of a general-purpose three-dimensional computational electromagnetic model of a spherical antenna test system has enabled the MARS measurement and postprocessing technique to be further investigated. This paper provides an overview of the far-field MARS technique and presents an introduction to the computational electromagnetic range model. Preliminary results of computational electromagnetic range simulations that replicate typical MARS measurement configurations are presented and discussed which, for the first time, confirm through simulation many of the observations that have previously been noted using purely empirical techniques.
Characteristics of Suppressor Macrophages Induced by Mycobacterial and Protozoal Infections in relation to Alternatively Activated M2 Macrophages
Authors: Tomioka Haruaki , Tatano Yutaka , Maw Win Win , Sano Chiaki , Kanehiro Yuichi , Shimizu Toshiaki
Published: May 2012

In the advanced stages of mycobacterial infections, host immune systems tend to change from a Th1-type to Th2-type immune response, resulting in the abrogation of Th1 cell- and macrophage-mediated antimicrobial host protective immunity. Notably, this type of immune conversion is occasionally associated with the generation of certain types of suppressor macrophage populations. During the course ofMycobacterium tuberculosis(MTB) andMycobacterium avium-intracellularecomplex (MAC) infections, the generation of macrophages which possess strong suppressor activity against host T- and B-cell functions is frequently encountered. This paper describes the immunological properties of M1- and M2-type macrophages generated in tumor-bearing animals and those generated in hosts with certain microbial infections. In addition, this paper highlights the immunological and molecular biological characteristics of suppressor macrophages generated in hosts with mycobacterial infections, especially MAC infection.
Role of Functional MRI in Presurgical Evaluation of Memory Function in Temporal Lobe Epilepsy
Authors: Limotai Chusak , Mirsattari Seyed M.
Published: May 2012

Many diagnostic tools have been employed to predict the likelihood of a postoperative memory decline after a standard temporal lobectomy, including the intracarotid amobarbital testing (IAT) or Wada, regarded as the gold standard test for over the past half a century. Functional MRI (fMRI) is also a promising tool in that regard. Its routine use to predict the postoperative memory decline has been limited because of the varied study paradigms, discrepancies in analysis, and interpretation of the results. Based on the existing literatures, fMRI cannot replace IAT for the routine presurgical evaluation of the patients with temporal lobe epilepsy (TLE) yet. Large multicentre studies with a panel of memory test are required to determine the full potential of fMRI and use it reliably to replace IAT in the routine clinical practice. In this paper, we review various aspects of memory fMRI, including the experimental designs, data analysis, and findings.
Guaranteed Cost Control Design of 4D Lorenz‐Stenflo Chaotic System via T‐S Fuzzy Approach
Authors: Hou Yi-You , Hung Meei-Ling , Lin Jui-Sheng
Published: May 2012

This paper investigates the guaranteed cost control of chaos problem in 4D Lorenz‐Stenflo (LS) system via Takagi‐Sugeno (T‐S) fuzzy method approach. Based on Lyapunov stability theory and linear matrix inequality (LMI) technique, a state feedback controller is proposed to stabilize the 4D Lorenz‐Stenflo chaotic system. An illustrative example is provided to verify the validity of the results developed in this paper.
Closely Mounted Compact Wideband Diversity Antenna for Mobile Phone Applications
Authors: Yu Bunggil , Jung Chang Won , Lee Haechun , Park Myun-Joo , Kim Byeongkwan , Wi Hyunho , Choi Yonggyu , Kim Deokyun , Lee Byungje
Published: May 2012

Here a compact wideband diversity antenna covering the PCS/UMTS/WiMAX bands with high isolation and low enveloped correlation coefficient (ECC) is proposed. To widen the bandwidth, the proposed antenna uses a structure with a gap-coupled feed and an inductively shorted line that has capacitive compensation between the radiator and the ground plane. Also, a suspended line with a parasitic element is used to enhance the isolation between the two antennas.
Anticancer Activity of Green Tea Polyphenols in Prostate Gland
Authors: Davalli Pierpaola , Rizzi Federica , Caporali Andrea , Pellacani Davide , Davoli Serena , Bettuzzi Saverio , Brausi Maurizio , D’Arca Domenico
Published: May 2012

Numerous evidences from prevention studies in humans, support the existence of an association between green tea polyphenols consumption and a reduced cancer risk. Prostate cancer is one of the most frequently diagnosed male neoplasia in the Western countries, which is in agreement with this gland being particularly vulnerable to oxidative stress processes, often associated with tumorigenesis. Tea polyphenols have been extensively studied in cell culture and animal models where they inhibited tumor onset and progression. Prostate cancer appears a suitable target for primary prevention care, since it grows slowly, before symptoms arise, thus offering a relatively long time period for therapeutic interventions. It is, in fact, usually diagnosed in men 50-year-old or older, when even a modest delay in progression of the disease could significantly improve the patients quality of life. Although epidemiological studies have not yet yielded conclusive results on the chemopreventive and anticancer effect of tea polyphenols, there is an increasing trend to employ these substances as conservative management for patients diagnosed with less advanced prostate cancer. Here, we intend to review the most recent observations relating tea polyphenols to human prostate cancer risk, in an attempt to outline better their potential employment for preventing prostate cancer.
Mitochondrial Bcl-2 Family Dynamics Define Therapy Response and Resistance in Neuroblastoma
Authors: Goldsmith Kelly C. , Gross Michelle , Peirce Susan , Luyindula Dema , Liu Xueyuan , Vu Annette , Sliozberg Michael , Guo Rong , Zhao Huaqing , Reynolds C. Patrick , Hogarty Michael D.
Published: May 2012

Neuroblastoma is a childhood tumor in which transient therapeutic responses are typically followed by recurrence with lethal chemoresistant disease. In this study, we characterized the apoptotic responses in diverse neuroblastomas using an unbiased mitochondrial functional assay. We defined the apoptotic set point of neuroblastomas using responses to distinct BH3 death domains providing a BH3 response profile and directly confirmed survival dependencies. We found that viable neuroblastoma cells and primary tumors are primed for death with tonic sequestration of Bim, a direct activator of apoptosis, by either Bcl-2 or Mcl-1, providing a survival dependency that predicts the activity of Bcl-2 antagonists. The Bcl-2/Bcl-xL/Bcl-w inhibitor ABT-737 showed single-agent activity against only Bim:Bcl-2 primed tumor xenografts. Durable complete regressions were achieved in combination with noncurative chemotherapy even for highest risk molecular subtypes with MYCN amplification and activating ALK mutations. Furthermore, the use of unique isogenic cell lines from patients at diagnosis and at the time of relapse showed that therapy resistance was not mediated by upregulation of Bcl-2 homologues or loss of Bim priming, but by repressed Bak/Bax activation. Together, our findings provide a classification system that identifies tumors with clinical responses to Bcl-2 antagonists, defines Mcl-1 as the principal mediator of Bcl-2 antagonist resistance at diagnosis, and isolates the therapy resistant phenotype to the mitochondria. Cancer Res; 72(10); 2565–77. ©2012 AACR.
Advances in the Genetics of High-Risk Childhood B-Progenitor Acute Lymphoblastic Leukemia and Juvenile Myelomonocytic Leukemia: Implications for Therapy
Authors: Loh Mignon L. , Mullighan Charles G.
Published: May 2012

Hematologic malignancies of childhood comprise the most common childhood cancers. These neoplasms derive from the pathologic clonal expansion of an abnormal cancer-initiating cell and span a diverse spectrum of phenotypes, including acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN), and myelodysplastic syndromes (MDS). Expansion of immature lymphoid or myeloid blasts with suppression of normal hematopoiesis is the hallmark of ALL and AML, whereas MPN is associated with proliferation of 1 or more lineages that retain the ability to differentiate, and MDS is characterized by abnormal hematopoiesis and cytopenias. The outcomes for children with the most common childhood cancer, B-progenitor ALL (B-ALL), in general, is quite favorable, in contrast to children affected by myeloid malignancies. The advent of highly sensitive genomic technologies reveals the remarkable genetic complexity of multiple subsets of high-risk B-progenitor ALL, in contrast to a somewhat simpler model of myeloid neoplasms, although a number of recently discovered alterations displayed by both types of malignancies may lead to common therapeutic approaches. This review outlines recent advances in our understanding of the genetic underpinnings of high-risk B-ALL and juvenile myelomonocytic leukemia, an overlap MPN/MDS found exclusively in children, and we also discuss novel therapeutic approaches that are currently being tested in clinical trials. Recent insights into the clonal heterogeneity of leukemic samples and the implications for diagnostic and therapeutic approaches are also discussed. Clin Cancer Res; 18(10); 2754–67. ©2012 AACR.
Genetically InFormed Therapies—A “GIFT” for Children with Cancer
Authors: Thiele Carol J. , Cohn Susan L.
Published: May 2012

The national investment that was made in oncology research with the passage of the National Cancer Act in 1971 is now coming to fruition. Nowhere is this more apparent than in the exciting prospects for genetically informed precision medicine as applied to the treatment of children with cancer. The wealth of information gleaned from intensive genetic analyses and NexGen sequencing studies has identified a number of viable targets in leukemias and solid tumors. Our rapidly evolving understanding of the enzymatic controls that regulate chromatin dynamics during normal differentiation of stem cells and their mutation or dysregulation in tumor cells is leading to a new library of therapeutically tractable tumor targets. The recent identification of germline variants associated with toxicity and/or response to therapy has further enhanced our ability to deliver individualized treatments for pediatric cancer patients. Our challenge today is to determine how best to use genomic data and integrate it into evolving clinical protocols to provide more efficacious therapies and a better quality of life for children with cancer. Clin Cancer Res; 18(10); 2735–9. ©2012 AACR.
SAR131675, a Potent and Selective VEGFR-3–TK Inhibitor with Antilymphangiogenic, Antitumoral, and Antimetastatic Activities
Authors: Alam Antoine , Blanc Isabelle , Gueguen-Dorbes Geneviève , Duclos Olivier , Bonnin Jacques , Barron Pauline , Laplace Marie-Claude , Morin Gaelle , Gaujarengues Florence , Dol Frédérique , Hérault Jean-Pascal , Schaeffer Paul , Savi Pierre , Bono Françoise
Published: May 2012

SAR131675 is a potent and selective VEGFR-3 inhibitor. It inhibited VEGFR-3 tyrosine kinase activity and VEGFR-3 autophosphorylation in HEK cells with IC50 values of 20 and 45 nmol/L, respectively. SAR131675 dose dependently inhibited the proliferation of primary human lymphatic cells, induced by the VEGFR-3 ligands VEGFC and VEGFD, with an IC50 of about 20 nmol/L. SAR131675 was found to be highly selective for VEGFR-3 versus 107 receptors, enzymes, ion channels, and 65 kinases. However, it was moderately active on VEGFR-2 with a VEGFR-3/VEGFR-2 ratio of about 10. SAR131675 had no antiproliferative activity on a panel of 30 tumors and primary cells, further showing its high specificity and indicating that SAR131675 is not a cytotoxic or cytostatic agent. SAR131675 was very well tolerated in mice and showed a potent antitumoral effect in several orthotopic and syngenic models, including mammary 4T1 carcinoma and RIP1.Tag2 tumors. Interestingly, it significantly reduced lymph node invasion and lung metastasis, showing its antilymphangiogenic activity in vivo. Moreover, treatment of mice before resection of 4T1 primary tumors was sufficient to prevent metastasis. Tumor-associated macrophages (TAM) play an important role in tumor growth and metastasis. The expression of VEGFR-3 on TAMs has been recently described. F4/80 immunostaining clearly showed that SAR131675 significantly reduced TAM infiltration and aggregation in 4T1 tumors. Taken together, SAR131675 is the first highly specific VEGFR-3-TK inhibitor described to date, displaying significant antitumoral and antimetastatic activities in vivo through inhibition of lymphangiogenesis and TAM invasion. Mol Cancer Ther; 11(8); 1637–49. ©2012 AACR.
How to Make a Gonad: Cellular Mechanisms Governing Formation of the Testes and Ovaries
Authors: Ungewitter E.K. , Yao H.H.-C.
Published: May 2012

Sex determination of the gonad is an extraordinary process by which a single organ anlage is directed to form one of two different structures, a testis or an ovary. Morphogenesis of these two organs utilizes many common cellular events; differences in the timing and execution of these events must combine to generate sexually dimorphic structures. In this chapter, we review recent research on the cellular processes of gonad morphogenesis, focusing on data from mouse models. We highlight the shared cellular mechanisms in testis and ovary morphogenesis and examine the differences that enable formation of the two organs responsible for the perpetuation of all sexually reproducing species.
Day-Night Dip and Early-Morning Surge in Blood Pressure in Hypertension
Authors: Verdecchia Paolo , Angeli Fabio , Mazzotta Giovanni , Garofoli Marta , Ramundo Elisa , Gentile Giorgio , Ambrosio Giuseppe , Reboldi Gianpaolo
Published: May 2012

We investigated the relationship between the day-night blood pressure (BP) dip and the early morning BP surge in an cohort of 3012 initially untreated subjects with essential hypertension. The day-night reduction in systolic BP showed a direct association with the sleep trough (
r
=0.564;
P
<0.0001) and the preawakening (
r
=0.554;
P
<0.0001) systolic BP surge. Over a mean follow-up period of 8.44 years, 268 subjects developed a major cardiovascular event (composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and heart failure requiring hospitalization) and 220 subjects died. In a Cox model, after adjustment for predictive covariates, including age, sex, diabetes mellitus, cigarette smoking, total cholesterol, left ventricular hypertrophy on ECG, estimated glomerular filtration rate, and average 24-hour systolic BP, a blunted sleep trough (≤19.5 mm Hg; quartile 1) and preawakening (≤9.5 mm Hg; quartile 1) BP surge was associated with an excess risk of events (hazard ratio, 1.66 [95% CI, 1.14–2.42];
P
=0.009; hazard ratio, 1.71 [95% CI, 1.12–2.71];
P
=0.013). After adjustment for the same covariates, neither the dipping pattern nor the measures of early morning BP surge were independent predictors of mortality. In conclusion, in initially untreated subjects with hypertension, a blunted day-night BP dip was associated with a blunted morning BP surge and vice versa. In these subjects, a blunted morning BP surge was an independent predictor of cardiovascular events, whereas an excessive BP surge did not portend an increased risk of events.
Wave Reflections, Assessed With a Novel Method for Pulse Wave Separation, Are Associated With End-Organ Damage and Clinical Outcomes
Authors: Weber Thomas , Wassertheurer Siegfried , Rammer Martin , Haiden Anton , Hametner Bernhard , Eber Bernd
Published: May 2012

We recently developed a novel method for assessment of arterial wave reflections (ARCSolver method): based on adopted Windkessel methods, flow curves are estimated from pressure waveforms, and wave separation analysis is performed, yielding the amplitudes of the forward and backward waves. The aim of this study was to investigate their clinical correlates and prognostic impact. In 725 patients (417 men; mean age, 64 years) undergoing coronary angiography, we determined wave reflections from radial tonometry and transfer function-derived aortic waveforms using pulse wave analysis, as well as wave separation analysis. Measures of pulsatile arterial function were statistically significant, although moderately associated with markers of cardiac load and subclinic cardiac, renal, and aortic end-organ damage. After a median follow-up duration of 1399 days, 139 patients reached the combined cardiovascular end point (death, myocardial infarction, stroke, coronary, cerebrovascular, and peripheral revascularization). In univariate analysis, the relative risk of the combined end point increased with increasing levels of incident pressure wave height, augmented pressure, and forward and backward wave amplitude (hazard ratio for 1 SD was 1.302, 1.236, 1.226, and 1.276;
P
<0.01 for all, respectively). In multivariate analysis, backward wave amplitude was the most consistent predictor of the combined end point. Of note, its predictive value was independent of brachial systolic, diastolic, and mean blood pressures and was superior to brachial pulse pressure. In conclusion, the amplitude of the reflected wave, as assessed with a novel method for wave separation, is associated with hypertensive end organ damage and is an independent predictor of cardiovascular events in high-risk patients.
From Baghdad to London: Unraveling Urban Development in Europe, the Middle East, and North Africa, 800–1800
Authors: Bosker Maarten , Buringh Eltjo , van Zanden Jan Luiten
Published: May 2012

This paper empirically investigates why, between 800 and 1800, the urban center of gravity moved from the Islamic world to Europe. Using a large new city-specific data set covering Europe, the Middle East, and North Africa, we unravel the role of geography and institutions in determining long-run city development in the two regions. We find that the main reasons for the Islamic world's stagnation and Europe's long-term success are specific to each region: any significant positive interaction between cities in the two regions hampered by their different main religious orientation. Together, the long-term consequences of a different choice of main transport mode (camel versus ship) and the development of forms of local participative government in Europe that made cities less dependent on the state explain why Europe's urban development eventually outpaced that in the Islamic world.
Compliance of Middle School–Aged Babysitters in Central Pennsylvania With National Recommendations for Emergency Preparedness and Safety Practices
Authors: Hackman Nicole M. , Cass Katie , Olympia Robert P.
Published: May 2012

Objective. To determine the compliance of middle school–aged babysitters with national recommendations for emergency preparedness and safety practices. Patients and methods. A prospective, self-administered questionnaire-based study was conducted at 3 middle schools in central Pennsylvania. Results. A total of 1364 questionnaires were available for analysis. Responding babysitters (n = 890) reported previous training that included babysitter (21%), first aid (64%), and cardiopulmonary resuscitation (59%) training. Reported unsafe babysitter practices were leaving a child unattended (36%) and opening the door to a stranger (24%). The most common emergency experience encountered by responding babysitters included cut or scrape (83%), burns (28%), and choking (14%). Ten percent of responding babysitters have activated the 911 system. Conclusions. Middle school–aged babysitters will likely encounter common household emergencies and therefore benefit from first aid training; however, very little difference in safety knowledge was found between trained and untrained babysitters, suggesting modifications in babysitter training programs may be required.
Feminist Social Justice Orientation
Authors: Moradi Bonnie
Published: May 2012

This article underscores several themes evident in Yoder, Snell, and Tobias’s research; these include the conceptualization of feminism and social justice as inextricably linked, the conceptualization and operationalization of optimal functioning at intrapersonal, interpersonal, and collective levels, and potential connections and disconnections between empowerment and liberation from oppression. In addition, selected patterns of findings from Yoder et al.’s study are elaborated on in the context of prior research on feminism in order to probe potential connections and disconnections among empowerment, oppression consciousness, and optimal functioning. This analysis culminates in the following question: Is feminist social justice orientation, with its potential accompanying sense of discontent, itself a form of optimal functioning? This question is posed, with an invitation to critically evaluate it and its implications, and with the hope of informing future scholarship, practice, and training in feminist social justice orientation and optimal functioning.
‘To Fall Short’ or ‘To Lack’? Reconsidering the Meaning and Translation of ‘ΥΣΤΕΡΕΩ in Romans 3:23
Authors: Cirafesi Wally V.
Published: May 2012

This article challenges the common English translation of ὑτεροῦνται in Rom. 3:23 as ‘to fall/come short’, and suggests that this rendering is due to the over-influence of the 1611 King James Version. In the light of the verb’s sense and grammatical relations with other words found in Romans, as well as its typical usage in Paul and the New Testament in general, the article contends that ‘to lack’ is a more helpful translation.
Non-linear composite control with applications to 3-DOF planar motor
Authors: Xin Li , Kai-ming Yang , Yu Zhu , Dong-dong Yu
Published: May 2012

A 3-DOF (degree of freedom) planar motion motor using multiple linear motors as actuators is widely implemented in ultra-precision positioning systems. It is a multi-input multi-output (MIMO) system and requires an accurate decoupled model for controller design. In practice, there are modelling errors between the nominal model and the actual model, such as the force ripple, inhomogeneous air-gap thickness, measurement noise and uncertain disturbances. Due to the modelling errors, this MIMO system cannot be decoupled and the desired tracking performance specifications will not be achieved. In order to improve the servo performance of the planar motor with uncertainties, a non-linear composite controller consisting of u1 and u2 terms is proposed. u1 is designed to compensate for the modelling errors; therefore the coupling effects between multi-degrees of freedom are reduced and the robustness is improved. In order to reduce the large servo error amplitudes, which are caused by the low-frequency disturbances and high-frequency noise, an amplitude-based variable-gain function is applied in u2; thus the control action benefits from this operation by suppressing the low-frequency contribution and no extra control effect, to avoid the high-frequency noise. The convergence and stability of the control law are guaranteed by Lyapunov stability theory. The trajectory tracking experimental results show that the proposed control method has superior tracking performance and positioning ability compared with the well-known inverse dynamics controller. This indicates that the non-linear composite controller is an attractive approach to improve the servo performance of a system with uncertainties.
Regulatory Forum Opinion Piece
Authors: Long Gerald G. , Hardisty Jerry F.
Published: May 2012

The definition of diagnostic thresholds is an important aspect of identification and recording of histopathologic lesions in toxicology studies. Although the primary goal of the pathology examination is to identify and interpret lesions associated with the administration of the test article, the toxicologic pathologist will encounter many changes in the tissues that are variations in tissue morphology, tissue artifacts, and spontaneous background findings. The pathologist must establish appropriate thresholds to produce a comprehensive record of the findings so that potentially treatment-related lesions may be identified. However, the findings should not be so detailed as to create overly complex data with the appearance of differences when none exist. Care must be taken to be consistent in the identification and recording of background lesions, since they are important for historical control data, which is often used as a reference when interpreting findings in current studies. Insufficient or inconsistent recording of findings may result in a deficiency in the historical control data for the identification and interpretation of a finding in the future.
Regulatory Forum Opinion Piece: The Role of the Toxicologic Pathologist in the Postgenomic Era
Authors: Maronpot Robert R.
Published: May 2012

The “omics,” high-throughput screening, computational modeling, and database mining revolutions have each arrived with euphoric expectations, considerable hand waving, and promises to set toxicity testing priorities and reduce reliance on conventional animal toxicity and carcinogenicity testing. Reflecting back on prior experience with other predictive approaches and alternatives, what follows the rush to endorse a promising new technology or different approach to toxicity/carcinogenicity testing is years of grinding out data for validation and optimization. Much of what has driven the enthusiasm for each new emerging technology and approach is the costly, labor-intensive, and sometimes irrelevant and inefficient rodent bioassay-testing paradigm. However, no one should expect abandonment of all animal testing for the foreseeable future, especially for agrochemicals and environmental xenobiotic exposures. It is reasonable to anticipate the future will bring still new approaches to safety testing and human risk assessment. In the past, each new approach has not achieved the inflated expectations for safety testing and human risk assessment but often has become a useful research tool with tangible contributions to basic biology and clinical medicine. The toxicologic pathologist is embedded in the matrix of a mixed disciplinary milieu and is faced with some critical challenges and important opportunities in the postgenomic decades ahead. So what advice do we give to the journeyman toxicologic pathologist who will hopefully function effectively in the postgenomic decades ahead? And what advice do we also give to the experienced bench pathologist confronted with emerging technologies each accompanied by a bewildering array of techno-jargon so that he or she can remain effective as a toxicologic pathology practitioner?
Nation Branding
Authors: Kerrigan Finola , Shivanandan Jyotsna , Hede Anne-Marie
Published: May 2012

India is a vast, diverse country, which attracts much attention as a political and economic entity as well as a major tourism destination. This commentary explores the Incredible India Campaign, a Nation Branding campaign which has been running in India for approximately ten years. In doing so, we consider nation branding as a mechanism for communicating between a nation and the rest of the world. We draw on a published account of the campaign by one of its architects, a series of images utilized in the campaign as well as a series of interviews with members of the pubic regarding their reaction to the images used. We argue that national branding campaigns can tell us much about imagined identities of those “being branded.” In doing so, we illustrate the difficultly of representing a vast and diverse population within a fast developing economy as well as the benefits of placing the target of the campaign among “the other” rather than orientalizing the citizen at the heart of the nation branding campaign.
Learning to place new objects in a scene
Authors: Jiang Yun , Lim Marcus , Zheng Changxi , Saxena Ashutosh
Published: May 2012

Placing is a necessary skill for a personal robot to have in order to perform tasks such as arranging objects in a disorganized room. The object placements should not only be stable but also be in their semantically preferred placing areas and orientations. This is challenging because an environment can have a large variety of objects and placing areas that may not have been seen by the robot before. In this paper, we propose a learning approach for placing multiple objects in different placing areas in a scene. Given point-clouds of the objects and the scene, we design appropriate features and use a graphical model to encode various properties, such as the stacking of objects, stability, object–area relationship and common placing constraints. The inference in our model is an integer linear program, which we solve efficiently via an linear programming relaxation. We extensively evaluate our approach on 98 objects from 16 categories being placed into 40 areas. Our robotic experiments show a success rate of 98% in placing known objects and 82% in placing new objects stably. We use our method on our robots for performing tasks such as loading several dish-racks, a bookshelf and a fridge with multiple items.
The Rising ‭תורהנ‬ of Psalm 93: Chaotic Order
Authors: Sylva Dennis
Published: May 2012

The relation between Yahweh and the sea in Psalm 93 has usually been considered to be an adversarial one. Particularly stressed in this regard are the three references to the rising ‭תורהנ‬ in v. 3. There are, however, several features of the psalm that are unamenable to this view. In addition, proponents of this line of thought have attempted to modify an element in v. 4b so as to make this perspective more probable. The style of this psalm argues against such emendations. The new thesis advanced in this article is that the chaotic waters manifest, rather than oppose, the power of Yahweh. This proposal is grounded both in stylistic and terminological considerations and in the function of similar imagery both in other ‭ךלמהוהי‬ (‘Yahweh reigns’) psalms and in other throne visions in the books of Isaiah and Ezekiel. Psalm 93 imbues Yahweh with the hue of a sea god and in the process provides a different modulation on the theme of Yahweh and the primeval chaos than is found elsewhere in the Old Testament.
Proleptic Fulfillment of the Prophetic Word: Ezekiel's Dirges over Tyre and Its Ruler
Authors: Goering Greg Schmidt
Published: May 2012

Debates about Ezek. 28.1–19 have long centered on textual difficulties and cryptic mythological language. While these issues remain intractable, the overall structure and rhetorical strategy of the oracles concerning Tyre's ruler can be perceived by analyzing Ezek. 26.1–28.19 as a whole. Specifically, the larger passage evinces a repeated pattern of judgment oracle followed by funeral dirge. The dirges, which contain elements of parody, proleptically eulogize Tyre and its ruler before they have perished. In this way, they communicate the irreversibility of Yhwh's judgments against Tyre. Such a study suggests that rhetorical considerations ought to be considered when examining the redactional artistry of larger literary units.