bluuebunny/crossref_metadata_2025 huggingface dataset:
EFFECT ON PLANTAR PRESSURE DISTRIBUTION WITH WEARING DIFFERENT BASE SIZE OF HIGH-HEEL SHOES DURING WALKING AND SLOW RUNNING
Authors: GUO LAN-YUEN , LIN CHIEN-FEN , YANG CHICH-HAUNG , HOU YI-YOU , LIU HUNG-LIN , WU WEN-LAN , LIN HWAI-TING
Published: September 2011

High heeled shoes may alter the regular loading pattern of the plantar pressure, especially increased in the forefoot area. Walking with narrow base of high heeled shoes may induce the brisk acceleration of the supported leg due to instability that increases the force on the plantar area. Particularly, this phenomenon may be amplified while slow running, but never been investigated. Materials and Methods: Plantar pressures were measured for different specific area of foot using the Pedar-X system. The effects on plantar pressure with different sized bases (1.2× 1.2 cm2 and 2.2 × 3.5 cm2) of high-heeled shoe (7.8 cm in height) were examined while walking in thirteen healthy female subjects and during slow running in nine healthy female subjects. Results: The plantar pressures of the hallux and toe while wearing narrow base high heel were significantly (p < 0.05) greater than those when walking with wearing wide base one. For both narrow and wide base heels, significantly increased (p < 0.05) plantar pressure were found in the medial forefoot while slow running at 2.0 m/s as compared with walking at 1.0 m/s and 1.5 m/s. While slow running with wearing narrow base high heel indicated significantly (p < 0.05) increased plantar pressures in the medial, central and lateral forefoot and toes regions compared with those with wearing wide base one. Conclusion: The findings suggest that if individuals have to wear high heeled shoes, it would be better to select one with a wide based heel to avoid running in at any circumstance.
DAMAGE INITIATION AND PROPAGATION UNTIL FAILURE OF CEMENT–BONE INTERFACE BY THE ELEMENT-FAILURE METHOD
Authors: GUEDES RUI M. , NABAIS CLÁUDIA , SIMÕES JOSÉ A.
Published: September 2011

Aseptic loosening of cemented hip implants frequently indicates failure by shear or tension of the cement–bone interface. An element-failure algorithm is proposed for the simulation of the mechanical behavior of the cement–bone interface until failure, under tensile and shear loading. To validate the model proposed, analysis on the cement–bone interface properties (elastic modulus, strength and thickness) and failure criteria, as well as mesh convergence analysis, were performed. Numerical results showed that the proposed element-failure method is able to determine the initiation and progression of interface failure in cemented hip replacements.
NUMERICAL ANALYSIS OF AN AXIAL BLOOD PUMP WITH DIFFERENT IMPELLER BLADE HEIGHTS
Authors: QI JIAXING , ZHOU YANHONG , WANG DONGFANG , ZHONG LIANG
Published: September 2011

Computational fluid dynamics (CFD) simulations of the flow in an axial blood pump with different blade heights (BH150, BH200 and BH250) were performed in the present study. The flow in the pump was assumed as steady and turbulent, and blood was treated as incompressible and Newtonian fluid. The flow rate increased with the rise in blade heights. At the impeller rotating speed of 20,000 rpm and a pressure of 100 mm Hg, the pump produces a flow rate up to 5 L/min in BH200 and BH250 models. The reverse flow and vortices have been identified in the BH150 and BH200 models in the outlet regions, but not for BH250 model. The high shear stress of the flow in the pump mainly occurred at the blade tips. The BH200 model achieved an expected flow rate up to 5 L/min with 90% of the shear stresses less than 500 Pa and the exposure time less than 22 ms, which has the acceptable shear stress level in the literature.
SENSITIVITY ANALYSIS OF COMPUTATIONAL STRUCTURAL DYNAMICS IN A CEREBRAL ANEURYSM MODEL TO WALL THICKNESS AND MODEL
Authors: VALENCIA ALVARO , ROJO MAXIMILIANO , RIVERA RODRIGO , BRAVO EDUARDO
Published: September 2011

Intracranial saccular aneurysms tend to be thin walled and stiffer compared with a normal artery. The current work describes computational structural dynamics (CSD) in an anatomically realistic model of a cerebral aneurysm located in the ophthalmic region, using different wall thickness, model data for the artery and aneurysm, and geometry size. The model was obtained from three-dimensional rotational angiography image data. The wall was assumed three-dimensional hyperelastic solid with different thickness in the artery and in the aneurysm regions. The effects of carotid siphon length are reported. The CSD was solved with the finite elements package ADINA. The predictions of stress and strain on the aneurysm wall were compared.
MATHEMATICAL MODELING OF OSCILLATORY MAGNETO-CONVECTION OF A COUPLE-STRESS BIOFLUID IN AN INCLINED ROTATING CHANNEL
Authors: BÉG O. ANWAR , GHOSH S. K. , AHMED S. , BÉG TASVEER
Published: September 2011

A mathematical study is conducted of the oscillatory hydromagnetic flow of a viscous, incompressible, electrically conducting, non-Newtonian bio-fluid in an inclined, rotating channel with nonconducting walls, incorporating couple stress effects. The constitutive equations for a couple-stress fluid and the Maxwell electromagnetic field equations are presented and then reduced to a set of coupled partial differential equations for the primary and secondary flow. The model is then nondimensionalized with appropriate variables and shown to be controlled by the inverse Ekman number (K2= 1/Ek), the hydromagnetic body force parameter (M), channel inclination (α), Grashof number (Gr), Prandtl number (Pr), oscillation frequency (ω), and time variable (ωT). Analytical solutions are derived using complex variables. The influence of the governing parameters on the primary velocity (u), secondary velocity (w), temperature (θ), primary and secondary flow discharges per unit depth in the channel (Qx, Qz), and frictional shear stresses due to primary and secondary flow (τx, τz), are studied graphically and using tables. Applications of the study arise in the simulation of the manufacture of electrically conducting bio-polymeric liquids and magneto-physiological flow devices.
HEAT TRANSFER ANALYSIS FOR THE PERISTALTIC FLOW OF CHYME IN SMALL INTESTINE: A THEORETICAL STUDY
Authors: AKBAR NOREEN SHER , NADEEM S. , HAYAT T. , ALSAEDI A.
Published: September 2011

In this article, we considered the peristaltic flow of Newtonian incompressible fluid of chyme in small intestine. The analysis has been performed using an endoscope. The peristaltic flow of chyme is modeled by assuming that the peristaltic wave is formed in non-periodic mode comprising two sinusoidal waves of different wave lengths propagating with same speed along the outer wall of the tube. Heat transfer mechanisms have been taken into account, such that the constant temperature [Formula: see text] and [Formula: see text] are assigned to inner and outer tubes, respectively. A complex system of equations has been simplified using long wavelength and low Reynolds number approximation because such assumptions exist in small intestine. Exact solutions have been carried out for velocity temperature and pressure gradient. Graphical results have been discussed for pressure rise, frictional forces, temperature, and velocity profile. Comparison of present results with the results of the existing literature have been presented through figures. Trapping phenomena have been presented at the conclusion of the article.
A MATHEMATICAL MODEL FOR BLOOD FLOW THROUGH INCLINED ARTERIES UNDER THE INFLUENCE OF INCLINED MAGNETIC FIELD
Authors: TRIPATHI DHARMENDRA
Published: September 2011

A mathematical model is developed to study the characteristics of blood flow through flexible inclined arteries under the influence of an inclined magnetic field. The blood is supposed to be couple stress fluid and the geometry of wall surface of inclined arteries is taken as peristaltic wave. The expressions for axial velocity, volume flow rate, pressure gradient and stream function are obtained under the assumptions of long wavelength and low Reynolds number. The effects of different physical parameters reflecting couple stress parameter, Hartmann number, Reynolds number, Froude number, inclination of channel and inclination of magnetic field on velocity profile, pressure and frictional force are discussed. The stream lines are drawn for various values of emerging parameters and the trapping phenomenon is discussed. The significant features of the blood flow characteristics are analyzed by plotting graphs and discussed numerically in detail.
Remodeling of calcium handling in skeletal muscle through PGC-1α: impact on force, fatigability, and fiber type
Authors: Summermatter Serge , Thurnheer Raphael , Santos Gesa , Mosca Barbara , Baum Oliver , Treves Susan , Hoppeler Hans , Zorzato Francesco , Handschin Christoph
Published: September 2011

Regular endurance exercise remodels skeletal muscle, largely through the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). PGC-1α promotes fiber type switching and resistance to fatigue. Intracellular calcium levels might play a role in both adaptive phenomena, yet a role for PGC-1α in the adaptation of calcium handling in skeletal muscle remains unknown. Using mice with transgenic overexpression of PGC-1α, we now investigated the effect of PGC-1α on calcium handling in skeletal muscle. We demonstrate that PGC-1α induces a quantitative reduction in calcium release from the sarcoplasmic reticulum by diminishing the expression of calcium-releasing molecules. Concomitantly, maximal muscle force is reduced in vivo and ex vivo. In addition, PGC-1α overexpression delays calcium clearance from the myoplasm by interfering with multiple mechanisms involved in calcium removal, leading to higher myoplasmic calcium levels following contraction. During prolonged muscle activity, the delayed calcium clearance might facilitate force production in mice overexpressing PGC-1α. Our results reveal a novel role of PGC-1α in altering the contractile properties of skeletal muscle by modulating calcium handling. Importantly, our findings indicate PGC-1α to be both down- as well as upstream of calcium signaling in this tissue. Overall, our findings suggest that in the adaptation to chronic exercise, PGC-1α reduces maximal force, increases resistance to fatigue, and drives fiber type switching partly through remodeling of calcium transients, in addition to promoting slow-type myofibrillar protein expression and adequate energy supply.
Collecting duct-specific endothelin B receptor knockout increases ENaC activity
Authors: Bugaj Vladislav , Mironova Elena , Kohan Donald E. , Stockand James D.
Published: September 2011

Collecting duct (CD)-derived endothelin-1 (ET-1) acting via endothelin B (ETB) receptors promotes Na+ excretion. Compromise of ET-1 signaling or ETB receptors in the CD cause sodium retention and increase blood pressure. Activity of the epithelial Na+ channel (ENaC) is limiting for Na+ reabsorption in the CD. To test for ETB receptor regulation of ENaC, we combined patch-clamp electrophysiology with CD-specific knockout (KO) of endothelin receptors. We also tested how ET-1 signaling via specific endothelin receptors influences ENaC activity under differing dietary Na+ regimens. ET-1 significantly decreased ENaC open probability in CD isolated from wild-type (WT) and CD ETA KO mice but not CD ETB KO and CD ETA/B KO mice. ENaC activity in WT and CD ETA but not CD ETB and CD ETA/B KO mice was inversely related to dietary Na+ intake. ENaC activity in CD ETB and CD ETA/B KO mice tended to be elevated under all dietary Na+ regimens compared with WT and CD ETA KO mice, reaching significance with high (2%) Na+ feeding. These results show that the bulk of ET-1 inhibition of ENaC activity is mediated by the ETB receptor. In addition, they could explain the Na+ retention and elevated blood pressure observed in CD ET-1 KO, CD ETB KO, and CD ETA/B KO mice consistent with ENaC regulation by ET-1 via ETB receptors contributing to the antihypertensive and natriuretic effects of the local endothelin system in the mammalian CD.
Effects of weight loss and leptin on skeletal muscle in human subjects
Authors: Baldwin Kenneth M. , Joanisse Denis R. , Haddad Fadia , Goldsmith Rochelle L. , Gallagher Dympna , Pavlovich Katherine H. , Shamoon Elisabeth L. , Leibel Rudolph L. , Rosenbaum Michael
Published: September 2011

Maintenance of a 10% or greater reduced body weight results in decreases in the energy cost of low levels of physical activity beyond those attributable to the altered body weight. These changes in nonresting energy expenditure are due mainly to increased skeletal muscle work efficiency following weight loss and are reversed by the administration of the adipocyte-derived hormone leptin. We have also shown previously that the maintenance of a reduced weight is accompanied by a decrease in ratio of glycolytic (phosphofructokinase) to oxidative (cytochrome c oxidase) activity in vastus lateralis muscle that would suggest an increase in the relative expression of the myosin heavy chain I (MHC I) isoform. We performed analyses of vastus lateralis muscle needle biopsy samples to determine whether maintenance of an altered body weight was associated with changes in skeletal muscle metabolic properties as well as mRNA expression of different isoforms of the MHC and sarcoplasmic endoplasmic reticular Ca2+-dependent ATPase (SERCA) in subjects studied before weight loss and then again after losing 10% of their initial weight and receiving twice daily injections of either placebo or replacement leptin in a single blind crossover design. We found that the maintenance of a reduced body weight was associated with significant increases in the relative gene expression of MHC I mRNA that was reversed by the administration of leptin as well as an increase in the expression of SERCA2 that was not significantly affected by leptin. Leptin administration also resulted in a significant increase in the expression of the less MHC IIx isoform compared with subjects receiving placebo. These findings are consistent with the leptin-reversible increase in skeletal muscle chemomechanical work efficiency and decrease in the ratio of glycolytic/oxidative enzyme activities observed in subjects following dietary weight loss.
Angiotensin II acts through the angiotensin 1a receptor to upregulate pendrin
Authors: Verlander Jill W. , Hong Seongun , Pech Vladimir , Bailey James L. , Agazatian Diana , Matthews Sharon W. , Coffman Thomas M. , Le Thu , Inagami Tadashi , Whitehill Florence M. , Weiner I. David , Farley Donna B. , Kim Young Hee , Wall Susan M.
Published: September 2011

Pendrin is an anion exchanger expressed in the apical regions of B and non-A, non-B intercalated cells. Since angiotensin II increases pendrin-mediated Cl− absorption in vitro, we asked whether angiotensin II increases pendrin expression in vivo and whether angiotensin-induced hypertension is pendrin dependent. While blood pressure was similar in pendrin null and wild-type mice under basal conditions, following 2 wk of angiotensin II administration blood pressure was 31 mmHg lower in pendrin null than in wild-type mice. Thus pendrin null mice have a blunted pressor response to angiotensin II. Further experiments explored the effect of angiotensin on pendrin expression. Angiotensin II administration shifted pendrin label from the subapical space to the apical plasma membrane, independent of aldosterone. To explore the role of the angiotensin receptors in this response, pendrin abundance and subcellular distribution were examined in wild-type, angiotensin type 1a (Agtr1a) and type 2 receptor (Agtr2) null mice given 7 days of a NaCl-restricted diet (< 0.02% NaCl). Some mice received an Agtr1 inhibitor (candesartan) or vehicle. Both Agtr1a gene ablation and Agtr1 inhibitors shifted pendrin label from the apical plasma membrane to the subapical space, independent of the Agtr2 or nitric oxide (NO). However, Agtr1 ablation reduced pendrin protein abundance through the Agtr2 and NO. Thus angiotensin II-induced hypertension is pendrin dependent. Angiotensin II acts through the Agtr1a to shift pendrin from the subapical space to the apical plasma membrane. This Agtr1 action may be blunted by the Agtr2, which acts through NO to reduce pendrin protein abundance.
Urine-concentrating defects exacerbate with age in male offspring with a low-nephron endowment
Authors: Singh Reetu R. , Denton Kate M. , Bertram John F. , Dowling John , Moritz Karen M.
Published: September 2011

Fetal uninephrectomy (uni-x) in male sheep at 100 days of gestation (term = 150 days) reduces overall nephron endowment without affecting birth weight. Offspring have a lower glomerular filtration rate (GFR) and elevated mean arterial pressure (MAP) at 6 mo of age. This study investigated whether this reduction in renal function was associated with impaired urine-concentrating ability at 6 mo of age and exacerbated with ageing (4 yr) and examined response to 1) nonpressor dose of exogenous arginine vasopressin (AVP; 0.2 μg·kg−1·h−1iv) and 2) 30 h of water deprivation. Basal MAP was higher in uni-x animals at both ages, and became further elevated with age compared with the sham group (elevation in MAP with age; sham: ∼4 mmHg, uni-x: 9 mmHg, Pgroup × age< 0.01). GFR declined with ageing in both groups with the decrease being greater with age in the uni-x group (further 26%, Pgroup × age< 0.001). In response to AVP infusion, urine osmolality increased in both treatment groups; this response was significantly lower in the uni-x animals and became further reduced with ageing. Uni-x animals had reduced renal expression of vasopressin-2 receptor and aquaporin-2 at both ages ( P < 0.01). The increase in plasma AVP levels in response to dehydration was similar between the treatment groups, suggesting the urine-concentrating defect was associated with these renal gene changes rather than defects in AVP secretion. Renal insufficiency due to a low-nephron endowment increases the risk of hypertension and chronic renal disease and may incur greater vulnerability to physiological challenges such as water deprivation as observed in the uni-x animals.
Duration tuning in the inferior colliculus of the mustached bat
Authors: Macías Silvio , Mora Emanuel C. , Hechavarría Julio C. , Kössl Manfred
Published: September 2011

We studied duration tuning in neurons of the inferior colliculus (IC) of the mustached bat. Duration-tuned neurons in the IC of the mustached bat fall into three main types: short (16 of 136), band (34 of 136), and long (29 of 136) pass. The remaining 51 neurons showed no selectivity for the duration of sounds. The distribution of best durations was double peaked with maxima around 3 and 17 ms, which correlate with the duration of the short frequency-modulated (FM) and the long constant-frequency (CF) signals emitted by Pteronotus parnellii. Since there are no individual neurons with a double-peaked duration response profile, both types of temporal processing seem to be well segregated in the IC. Most short- and band-pass units with best frequency in the CF2 range responded to best durations > 9 ms (66%, 18 of 27 units). However, there is no evidence for a bias toward longer durations as there is for neurons tuned to the frequency range of the FM component of the third harmonic, where 83% (10 of 12 neurons) showed best durations longer than 9 ms. In most duration-tuned neurons, response areas as a function of stimulus duration and intensity showed either V or U shape, with duration tuning retained across the range of sound levels tested. Duration tuning was affected by changes in sound pressure level in only six neurons. In all duration-tuned neurons, latencies measured at the best duration were longer than best durations, suggesting that behavioral decisions based on analysis of the duration of the pulses would not be expected to be complete until well after the stimulus has occurred.
Modeling the contribution of neuron-astrocyte cross talk to slow blood oxygenation level-dependent signal oscillations
Authors: DiNuzzo Mauro , Gili Tommaso , Maraviglia Bruno , Giove Federico
Published: September 2011

A consistent and prominent feature of brain functional magnetic resonance imaging (fMRI) data is the presence of low-frequency (<0.1 Hz) fluctuations of the blood oxygenation level-dependent (BOLD) signal that are thought to reflect spontaneous neuronal activity. In this report we provide modeling evidence that cyclic physiological activation of astroglial cells produces similar BOLD oscillations through a mechanism mediated by intracellular Ca2+ signaling. Specifically, neurotransmission induces pulses of Ca2+ concentration in astrocytes, resulting in increased cerebral perfusion and neuroactive transmitter release by these cells (i.e., gliotransmission), which in turn stimulates neuronal activity. Noticeably, the level of neuron-astrocyte cross talk regulates the periodic behavior of the Ca2+ wave-induced BOLD fluctuations. Our results suggest that the spontaneous ongoing activity of neuroglial networks is a potential source of the observed slow fMRI signal oscillations.
Biological Effects of Osteoblast-Like Cells on Nanohydroxyapatite Particles at a Low Concentration Range
Authors: Liu Xiaochen , Wei Jie , Wei Shicheng
Published: September 2011

The biological effects of osteoblast-like MG-63 cells on nanohydroxyapatite (n-HA) at the low concentration range (5–25 g/mL) for 5 days was investigated. The results showed the viability and actin cytoskeleton of the cells descended with the increase of the concentration of n-HA, and the actin cytoskeleton of cells was depolymerised and became more disordered. Apoptotic rate of cells (1.85%, 1.99%, and 2.29%) increased with the increase of n-HA concentration (5, 15, and 25 g/mL) and become significantly higher than the control. Total intracellular protein content decreased with n-HA concentration increase, showing significant difference between 25 g/mL and the control, and no significant change of ALP activity was observed at the 5th day. The results revealed that the cell growth was inhibited by n-HA in a concentration-dependent manner, and the obvious biological effects of MG-63 cells on n-HA existed at the low concentration range from 5 to 25 g/mL.
Spontaneous Severe Haemoperitoneum in the Third Trimester Leading to Intrauterine Death: Case Report
Authors: Williamson Harriet , Indusekhar Radha , Clark Alexander , Hassan Ismail M.
Published: September 2011

Spontaneous haemoperitoneum during pregnancy is a rare but potentially catastrophic cause of acute abdominal pain. A healthy 37-year-old primigravida presented with acute abdominal pain and hypovolaemic shock at 37-weeks gestation. An emergency caesarean section was indicated on the clinical suspicion of placental abruption. However, an ultrasound scan confirmed the absence of a fetal heartbeat, and, in light of the mother’s haemodynamic stability, a vaginal delivery was deemed most appropriate. Subsequent imaging, due to deterioration over the following 24-hours, revealed a large heterogenous haematoma within the pelvic cavity, which was later found to be caused by severe pelvic endometriosis. Despite fertility problems associated with severe endometriosis, advanced assisted reproductive technology enables more of these patients to become pregnant, highlighting the need to be aware of this rare complication in pregnancy.
Synthesis of Gold Nanoanisotrops UsingDioscorea bulbiferaTuber Extract
Authors: Ghosh Sougata , Patil Sumersing , Ahire Mehul , Kitture Rohini , Jabgunde Amit , Kale Sangeeta , Pardesi Karishma , Bellare Jayesh , Dhavale Dilip D. , Chopade Balu A.
Published: September 2011

Biosynthesis of metal nanoparticles employing plant extracts and thereby development of an environmentally benign process is an important branch of nanotechnology. Here, the synthesis of gold nanoparticles usingDioscorea bulbiferatuber extract (DBTE) as the reducing agent is reported. Field emission scanning electron microscopy (FESEM), energy-dispersive spectroscopy (EDX), X-ray diffraction (XRD), and UV-visible absorption spectroscopy confirmed the reduction of gold ions to AuNPs. The anisotropic nanoparticles consist of a mixture of gold nanotriangles, nanoprisms, nanotrapezoid, and spheres. The kinetics of particle formation was time dependent and was enhanced by the increase of temperature from 6°C to 50°C, the optimum being 50°C. The optimum concentration of chloroauric acid was found to be 1 mM. Complete reduction of the metal ions within 5 hours by DBTE highlights the development of a novel ecofriendly route of biological synthesis of gold nanoparticles. This is the first paper on synthesis of gold nanoparticles using DBTE.
Malliavin Calculus of Bismut Type for Fractional Powers of Laplacians in Semi‐Group Theory
Authors: Léandre Rémi
Published: September 2011

We translate into the language of semi‐group theory Bismut′s Calculus on boundary processes (Bismut (1983), Lèandre (1989)) which gives regularity result on the heat kernel associated with fractional powers of degenerated Laplacian. We translate into the language of semi‐group theory the marriage of Bismut (1983) between the Malliavin Calculus of Bismut type on the underlying diffusion process and the Malliavin Calculus of Bismut type on the subordinator which is a jump process.
Coexistence of Vulvar Dowling-Degos Disease and Seborrhoeic Keratosis
Authors: Guedes R. , Leite Luiz
Published: September 2011

Dowling-Degos disease is a rare autosomal dominant inherited pigmentary disorder, mostly confined to the flexures. Diagnosis is established based on the clinical and histopathological correlation. The authors describe the clinical case of a female patient with vulvar involvement and multiple seborrhoeic keratoses on her face, neck, and upper trunk. Major and minor clinical manifestations of Dowling-Degos disease are discussed, with particular emphasis on the genital location of the lesions, which is a rare finding. Also the presence of seborrhoeic keratosis is discussed as a coincidence or a true-associated phenomenon.
Cytokines and Oxidative Stress Status Following a Handball Game in Elite Male Players
Authors: Marin Douglas Popp , Macedo dos Santos Rita de Cassia , Bolin Anaysa Paola , Guerra Beatriz Alves , Hatanaka Elaine , Otton Rosemari
Published: September 2011

Background. Handball is considered an intermittent sport that places an important stress on a player's aerobic and anaerobic metabolism. However, the oxidative stress responses following a handball game remain unknown. We investigated the responses of plasma and erythrocyte antioxidant system and oxidative stress biomarkers following a single handball game.Methods. Fourteen male elite Brazilian handball athletes were recruited in the present study. Blood samples were taken before, immediately, and 24 hours after the game.Results. After the game and during 24 hours of recovery, the concentration of all oxidative stress indices changed significantly in a way indicating increased oxidative stress in the blood (thiol groups and reduced glutathione decreased, whereas TBARS and plasma antioxidant capacity was increased) as well as in erythrocyte (increased levels of TBARS and protein carbonyls). Erythrocyte antioxidant enzyme activities were also significantly changed by handball. Muscle damage indices (creatine kinase and lactate dehydrogenase) increased significantly after exercise. In addition, IL-6 increased after the game, whereas TNF-αdecreased during recovery.Conclusion. This study demonstrates that a single handball game in elite athletes induces a marked state of oxidative stress evidenced by the oxidative modification in plasma and erythrocyte macromolecules, as well as by changes in the enzymatic and nonenzymatic antioxidant system.
The Role of BCL2 Family of Apoptosis Regulator Proteins in Acute and Chronic Leukemias
Authors: Tzifi Flora , Economopoulou Christina , Gourgiotis Dimitrios , Ardavanis Alexandros , Papageorgiou Sotirios , Scorilas Andreas
Published: September 2011

The disturbance of apoptosis molecular signaling pathways is involved in carcinogenesis. BCL2 family of proteins is the hallmark of apoptosis regulation. In the last decade, new members ofBCL2gene family were discovered and cloned and were found to be differentially expressed in many types of cancer. BCL2 protein family, through its role in regulation of apoptotic pathways, is possibly related to cancer pathophysiology and resistance to conventional chemotherapy. It is well known that leukemias are haematopoietic malignancies characterized by biological diversity, varied cytogenetics, different immunophenotype profiles, and diverse outcome. Current research focuses on the prognostic impact and specific role of these proteins in the pathogenesis of leukemias. The understanding of the molecular pathways that participate in the biology of leukemias may lead to the design of new therapies which may improve patients' survival. In the present paper, we describe current knowledge on the role of BCL2 apoptosis regulator proteins in acute and chronic leukemias.
A Case of Definitive Therapy for Localised Prostate Cancer: Report of a Urological Nightmare
Authors: Sommerhuber Andreas , Traxlmayr Verena , Loidl Wolfgang
Published: September 2011

Radical prostatectomy, external beam radiotherapy and permanent brachytherapy are the most common treatment options for nonmetastatic localised adenocarcinoma of the prostate (PCa). Accurate pretherapeutic clinical staging is difficult, the number of positive cores after biopsy does not imperatively represent the extension of the cancer. Furthermore postoperative upgrading in Gleason score is frequently observed. Even in a localised setting a certain amount of patients with organ-confined PCa will develop biochemical progression. In case of a rise in PSA level after radiation the majority of patients will receive androgen deprivation therapy what must be considered as palliative. If local or systemic progressive disease is associated with evolving neuroendocrine differentiation hormonal manipulation is increasingly ineffective; radiotherapy and systemic chemotherapy with a platinum agent and etoposide are recommended. In case of local progression complications such as pelvic pain, gross haematuria, infravesical obstruction and rectal invasion with obstruction and consecutive ileus can possibly occur. In this situation palliative radical surgery is a therapy option especially in the absence of distant metastases. A case with local and later systemic progression after permanent brachytherapy is presented here.
Population Pharmacokinetics of Busulfan in Children: Increased Evidence for Body Surface Area and Allometric Body Weight Dosing of Busulfan in Children
Authors: Trame Mirjam N. , Bergstrand Martin , Karlsson Mats O. , Boos Joachim , Hempel Georg
Published: September 2011

Purpose: To evaluate the best method for dosing busulfan in children, we retrospectively analyzed two different data sets from three different dosing regimens by means of population pharmacokinetics using NONMEM.

Experimental Design: The development data set consisted of plasma samples from 94 children, in the age range of 0.4 to 18.8 years, receiving either oral or intravenous busulfan. The external model evaluation data set comprised 24 children, in the age range of 0.1 to 18.9 years, who belonged to the once-daily intravenous busulfan dosing regimen. A one-compartment model with first-order absorption using body surface area (BSA) or allometric body weight (BW) as covariate on clearance (CL) and BW as covariate on volume of distribution (V) were used to describe the results sufficiently. In addition to interindividual variability on all pharmacokinetic parameters, interoccasion variability was included for CL and V.

Results: CL values in the present study did not reflect the shape of the CL versus weight curve reported in previous investigations. By external model evaluation, we were able to confirm these findings. Furthermore, bioavailability was calculated to be between 93% and 99% for the development data set. On the basis of the final models, we simulated two dosing schemes according to allometric BW and BSA showing that we estimated to include about 30% more patients into the proposed therapeutic area under the curve (AUC) range of 900 to 1,500 μM*min and could, furthermore, achieve a reduction in the AUC variability when dosed according to the labeled European Medicines Agency (EMA) dosing recommendation.

Conclusion: We recommend a BSA or an allometric BW dosing regimen for individualizing busulfan therapy in children to reduce variability in busulfan exposure and to improve safety and efficacy of busulfan treatment. Clin Cancer Res; 17(21); 6867–77. ©2011 AACR.
A Novel Anti-Human HB-EGF Monoclonal Antibody with Multiple Antitumor Mechanisms against Ovarian Cancer Cells
Authors: Miyamoto Shingo , Iwamoto Ryo , Furuya Akiko , Takahashi Kumiko , Sasaki Yuka , Ando Hiroshi , Yotsumoto Fusanori , Yoneda Tomoko , Hamaoka Miki , Yagi Hiroshi , Murakami Takuya , Hori Sayaka , Shitara Kenya , Mekada Eisuke
Published: September 2011

Purpose: Heparin-binding epidermal growth factor (EGF)–like growth factor (HB-EGF) is a member of the EGF family and plays a pivotal role in tumor progression in ovarian cancer. We developed an anti-HB-EGF monoclonal antibody (mAb) and investigated its antitumor activities in vitro and in vivo to evaluate its potential as a therapeutic antibody against ovarian cancer.

Experimental Design: We prepared mAbs from HB-EGF null mice immunized with recombinant human soluble HB-EGF and evaluated their binding and neutralizing activity against HB-EGF. Next, we generated a mouse–human chimeric antibody and examined its in vitro and in vivo antitumor activities.

Results: Two murine anti-HB-EGF mAbs were developed, and one of them, KM3566, was revealed to have a high binding reactivity for membrane-anchored HB-EGF (pro-HB-EGF) expressed on the cell surface, as well as neutralizing activity against growth promoting activity of soluble HB-EGF. The mouse–human chimeric counterpart for KM3566 (cKM3566) induced dose-dependent antibody-dependent cellular cytotoxicity (ADCC) against cancer cells expressing HB-EGF in vitro, and significantly inhibited tumor growth in severe combined immunodeficient mice inoculated with MCAS or ES-2 human ovarian cancer cells.

Conclusions: A novel anti-HB-EGF chimeric antibody, cKM3566, with two antitumor mechanisms, neutralization and ADCC, exhibits potent in vivo antitumor activity. These results indicate that cKM3566 is a promising antiovarian cancer therapeutic antibody. Clin Cancer Res; 17(21); 6733–41. ©2011 AACR.
Potential Health Economic Impact of Intravenous Iron Supplementation to Erythropoiesis-Stimulating Agent Treatment in Patients with Cancer- or Chemotherapy-Induced Anemia
Authors: Szucs T.D. , Blank P.R. , Schwenkglenks M. , Aapro M.
Published: September 2011

Background: Intravenous (i.v.) iron supplementation significantly improves the response to erythropoiesis-stimulating agent (ESA)-based therapies in patients with cancer- or chemotherapy-induced anemia. The economic implications of adding i.v. iron to ESA treatment are less well investigated. Published randomized controlled trials do not provide sufficient data for a comprehensive cost-effectiveness analysis. Methods: Preliminary cost calculations from the Swiss health care system perspective based on a meta-analysis and published results of eight randomized controlled trials without correction for decreased ESA need provide a conservative cost-effectiveness estimate. Results: The additional total cost of i.v. iron supplementation ranged from EUR 417 to EUR 901 per patient depending on the evaluated iron-carbohydrate complex. Considering a 24% absolute increase in the proportion of ESA responders, the incremental cost-effectiveness ratios per additional responder are EUR 1,704–3,686. In routine practice, better values may be achieved due to ESA dose savings. Conclusion: Supplementation of ESAs with i.v. iron appears to be an economically viable treatment option in anemic cancer patients. Additional research on ESA dose savings and cost-effectiveness is required.
Assessment of Diffuse Myocardial Fibrosis in Rats Using Small-Animal Look-Locker Inversion Recovery T1 Mapping
Authors: Messroghli Daniel R. , Nordmeyer Sarah , Dietrich Thore , Dirsch Olaf , Kaschina Elena , Savvatis Kostas , O h-Ici Darach , Klein Christoph , Berger Felix , Kuehne Titus
Published: September 2011

Background—

The concentration of gadopentetate dimeglumine in myocardium and blood can be assessed from T1 measurements and can be used to calculate the extracellular volume (ECV) of the myocardium. We hypothesized that diffuse myocardial fibrosis in a small-animal model could be quantitatively assessed by measuring myocardial ECV using small-animal Look-Locker inversion recovery T1 mapping.

Methods and Results—

Sprague-Dawley rats (n=10) were subjected to continuous angiotensin-2 (AT2) infusion for 2 weeks via a subcutaneously implanted minipump system. Magnetic resonance imaging (MRI) was performed both before and after AT2 infusion. The MRI protocol included multislice cine imaging and before-and-after contrast small-animal Look-Locker inversion recovery T1 mapping and late gadolinium enhancement imaging. Myocardial ECV was calculated from hematocrit and T1 values of blood and myocardium. During the course of AT2 infusion, the mean±SD systolic blood pressure increased from 122±10.9 to 152±27.5 mm Hg (
P
=0.003). Normalized heart weight was significantly higher in AT2-treated animals than in control littermates (
P
=0.033). Cine MRI documented concentric left ventricular hypertrophy. Postcontrast myocardial T1 times were shortened after treatment (median [interquartile range], 712 [63] versus 820 [131] ms;
P
=0.002). Myocardial ECV increased from 17.2% (4.3%) before to 23.0% (6.2%) after AT2 treatment (
P
=0.031), which was accompanied by perivascular fibrosis and microscarring on myocardial histological analysis. There was a moderate level of correlation between ECV and collagen volume fraction, as assessed by histological analysis (
r
=0.69,
P
=0.013).

Conclusions—

In a small-animal model of left ventricular hypertrophy, contrast-enhanced T1 mapping can be used to detect diffuse myocardial fibrosis by quantification of myocardial ECV.
Large-Scale Rossby Normal Modes during Some Recent Northern Hemisphere Winters
Authors: Sassi F. , Garcia R. R. , Hoppel K. W.
Published: September 2011

Large-scale Rossby normal modes are studied for the Northern Hemisphere winters of 2005, 2006, 2008, and 2009 using global observational meteorological analyses spanning the 0–92-km altitude range. Spectral analysis of geopotential height fields shows pronounced peaks at westward-propagating zonal wavenumber 1 near the theoretical locations of the free Rossby waves at 25, 16, 10, and 5 days that, in some cases, have amplitudes significantly larger than the estimated background spectrum. Evidence is also found for a wavenumber-2 free mode near 4 days. A coherence analysis is used to extract the amplitude and phase of the waves, and to isolate those regions of the latitude/altitude plane where the signals are statistically significant. Although the spectral location, temporal evolution, and vertical structure of several of these waves are suggestive of the presence of Rossby normal modes, this study shows that in the real atmosphere the waves only occasionally have the global properties of classical normal modes. Moreover, no evidence is found that the amplitudes of these modes are enhanced during stratospheric sudden warmings.
Effects of Sea-Salt Aerosols on Precipitation in Simulations of Shallow Cumulus
Authors: Kogan Yefim L. , Mechem David B. , Choi Kityan
Published: September 2011

A suite of large-eddy simulations with size-resolving microphysical processes was performed in order to assess effects of sea-salt aerosols on precipitation process in trade cumulus. Simulations based on observations from the Rain in Cumulus over the Ocean (RICO) field campaign explored the effects of adding sea-salt nuclei in different size ranges by following the evolution of 369 cloud cells over the 24-h simulation period. The addition of large (small) sea-salt nuclei tends to accelerate (suppress) precipitation formation; however, in marine environments the sea-salt spectra always include a combination of both small (film) and large (jet) nuclei. When realistic sea-salt spectra are specified as a function of surface wind, the effect of the larger nuclei to enhance the precipitation predominates, and accumulated precipitation increases with wind speed. This effect, however, is strongly influenced by the choice of background CCN spectrum. Adding the same sea-salt specification to an environment with a higher background aerosol load results in a decrease in accumulated precipitation with increasing surface wind speed.

Results also suggest that the slope of the relationship between vertical velocity W and the concentration of embryonic precipitation particles at cloud base Nr may indicate the role of sea-salt nuclei. A negative slope (Nr decreasing with increasing W) points to the predominance of small sea-salt nuclei, in which larger updrafts activate a greater number of smaller cloud drops with smaller coalescence efficiencies, resulting in fewer embryonic rain drops. A positive slope, on the other hand, indicates the presence of large sea-salt nuclei, which are the source of embryonic rain drops.
Numerical Prediction of Submesoscale Flow in the Nocturnal Stable Boundary Layer over Complex Terrain
Authors: Seaman Nelson L. , Gaudet Brian J. , Stauffer David R. , Mahrt Larry , Richardson Scott J. , Zielonka Jeffrey R. , Wyngaard John C.
Published: September 2011

Numerical weather prediction models often perform poorly for weakly forced, highly variable winds in nocturnal stable boundary layers (SBLs). When used as input to air-quality and dispersion models, these wind errors can lead to large errors in subsequent plume forecasts. Finer grid resolution and improved model numerics and physics can help reduce these errors. The Advanced Research Weather Research and Forecasting model (ARW-WRF) has higher-order numerics that may improve predictions of finescale winds (scales <~20 km) in nocturnal SBLs. However, better understanding of the physics controlling SBL flow is needed to take optimal advantage of advanced modeling capabilities.

To facilitate ARW-WRF evaluations, a small network of instrumented towers was deployed in the ridge-and-valley topography of central Pennsylvania (PA). Time series of local observations and model forecasts on 1.333- and 0.444-km grids were filtered to isolate deterministic lower-frequency wind components. The time-filtered SBL winds have substantially reduced root-mean-square errors and biases, compared to raw data. Subkilometer horizontal and very fine vertical resolutions are found to be important for reducing model speed and direction errors. Nonturbulent fluctuations in unfiltered, very finescale winds, parts of which may be resolvable by ARW-WRF, are shown to generate horizontal meandering in stable weakly forced conditions. These submesoscale motions include gravity waves, primarily horizontal 2D motions, and other complex signatures. Vertical structure and low-level biases of SBL variables are shown to be sensitive to parameter settings defining minimum “background” mixing in very stable conditions in two representative turbulence schemes.
Determinants of child immunization in Nepal: The role of women’s empowerment
Authors: Pandey Shanta , Lee Hae nim
Published: September 2011

Background:

Approximately 1.4 million or 13% of all children who die each year could be prevented with widely-available vaccines.

Objective:

We examined if women’s empowerment improved child immunization using data on 1,056 mothers with young children from Nepal.

Methods:

The study utilized the 2006 Nepal Demographic and Health Survey, a nationally-representative sample of 10,793 women from 8,707 households across Nepal. We selected all mothers with first child between the ages of 12 and 23 months at the time of interview. This resulted in a sample of 1,056 mothers.

Results:

Among the measures of women’s empowerment, mothers’ education was significantly associated with child immunization. The odds of being fully immunized for children of mothers with secondary education were 5.91 times the odds for children of mothers without any formal education. Other measures of women’s empowerment – women’s age at birth of first child, gap in age between spouses, women’s knowledge about sexually-transmitted diseases, their role in intra-household financial, health and mobility decisions, and their perceptions toward wife beating – were not associated with child immunization. Among control variables, mothers who received antenatal care were 3.31 times as likely to immunize their children as mothers who did not receive any antenatal care. Other such barriers to health service use such as cost of care, distance to health services, and quality of health services were not significant.

Conclusions:

To improve child immunization, Nepal should strengthen its antenatal care services. Additionally, over 56% of mothers in Nepal had no formal education; to improve child health in the long run, the country should focus on education of women and girls.
Procedural Instructions, Principles, and Examples
Authors: Eiriksdottir Elsa , Catrambone Richard
Published: September 2011

Objective: The goal of this article is to investigate how instructions can be constructed to enhance performance and learning of procedural tasks.

Background: Important determinants of the effectiveness of instructions are type of instructions (procedural information, principles, and examples) and pedagogical goal (initial performance, learning, and transfer).

Method: Procedural instructions describe how to complete tasks in a stepwise manner, principles describe rules governing the tasks, and examples demonstrate how instances of the task are carried out. The authors review the research literature associated with each type of instruction to identify factors determining effectiveness for different pedagogical goals.

Results: The results suggest a trade-off between usability and learnability. Specific instructions help initial performance, whereas more general instructions, requiring problem solving, help learning and transfer. Learning from instructions takes cognitive effort, and research suggests that learners typically opt for low effort. However, it is possible to meet both goals of good initial performance and learning with methods such as fading and by combining different types of instructions.

Conclusion: How instructions are constructed influences their effectiveness for the goals of good initial performance, learning, and transfer, and it is therefore important for researchers and practitioners alike to define the pedagogical goal of instructions.

Application: If the goal is good initial performance, then instructions should highly resemble the task at hand (e.g., in the form of detailed procedural instructions and examples), but if the goal is good learning and transfer, then instructions should be more abstract, inducing learners to expend the necessary cognitive effort for learning.