bluuebunny/crossref_metadata_2025 huggingface dataset:
Caveolar Endocytosis Is Critical for BK Virus Infection of Human Renal Proximal Tubular Epithelial Cells
Authors: Moriyama Takahito , Marquez J. Pablo , Wakatsuki Tetsuro , Sorokin Andrey
Published: June 2007

In recent years, BK virus (BKV) nephritis after renal transplantation has become a severe problem. The exact mechanisms of BKV cell entry and subsequent intracellular trafficking remain unknown. Since human renal proximal tubular epithelial cells (HRPTEC) represent a main natural target of BKV nephritis, analysis of BKV infection of HRPTEC is necessary to obtain additional insights into BKV biology and to develop novel strategies for the treatment of BKV nephritis. We coincubated HRPTEC with BKV and the cholesterol-depleting agents methyl beta cyclodextrin (MBCD) and nystatin (Nys), drugs inhibiting caveolar endocytosis. The percentage of infected cells (detected by immunofluorescence) and the cellular levels of BKV large T antigen expression (detected by Western blot analysis) were significantly decreased in both MBCD- and Nys-treated HPRTEC compared to the level in HRPTEC incubated with BKV alone. HRPTEC infection by BKV was also tested after small interfering RNA (siRNA)-dependent depletion of either the caveolar structural protein caveolin-1 (Cav-1) or clathrin, the major structural protein of clathrin-coated pits. BKV infection was inhibited in HRPTEC transfected with Cav-1 siRNA but not in HRPTEC transfected with clathrin siRNA. The colocalization of labeled BKV particles with either Cav-1 or clathrin was investigated by using fluorescent microscopy and image cross-correlation spectroscopy. The rate of colocalization of BKV with Cav-1 peaked at 4 h after incubation. Colocalization with clathrin was insignificant at all time points. These results suggest that BKV entered into HRPTEC via caveolae, not clathrin-coated pits, and that BKV is maximally associated with caveolae at 4 h after infection, prior to relocation to a different intracellular compartment.
Proline 35 of Human Immunodeficiency Virus Type 1 (HIV-1) Vpr Regulates the Integrity of the N-Terminal Helix and the Incorporation of Vpr into Virus Particles and Supports the Replication of R5-Tropic HIV-1 in Human Lymphoid Tissue Ex Vivo
Authors: Votteler Jörg , Studtrucker Nicole , Sörgel Stefan , Münch Jan , Rücker Elke , Kirchhoff Frank , Schick Bernhard , Henklein Peter , Fossen Torgils , Bruns Karsten , Sharma Alok , Wray Victor , Schubert Ulrich
Published: June 2007

Mutational analysis of the four conserved proline residues in human immunodeficiency virus type 1 (HIV-1) Vpr reveals that only Pro-35 is required for efficient replication of R5-tropic, but not of X4-tropic, viruses in human lymphoid tissue (HLT) cultivated ex vivo. While Vpr-mediated apoptosis and G
2
cell cycle arrest, as well as the expression and subcellular localization of Vpr, were independent, the capacity for encapsidation of Vpr into budding virions was dependent on Pro-35.
1
H nuclear magnetic resonance data suggest that mutation of Pro-35 causes a conformational change in the hydrophobic core of the molecule, whose integrity is required for the encapsidation of Vpr, and thus, Pro-35 supports the replication of R5-tropic HIV-1 in HLT.
High turnover of ezrin T567 phosphorylation: conformation, activity, and cellular function
Authors: Zhu Lixin , Zhou Rihong , Mettler Shelley , Wu Tim , Abbas Aennes , Delaney Joseph , Forte John G.
Published: June 2007

In its dormant state, the membrane cytoskeletal linker protein ezrin takes on a NH2 terminal-to-COOH terminal (N-C) binding conformation. In vitro evidence suggests that eliminating the N-C binding conformation by Thr567 phosphorylation leads to ezrin activation. Here, we found for resting gastric parietal cells that the levels of ezrin phosphorylation on Thr567 are low and can be increased to a small extent (∼40%) by stimulating secretion via the cAMP pathway. Treatment of cells with protein phosphatase inhibitors led to a rapid, dramatic increase in Thr567 phosphorylation by 400% over resting levels, prompting the hypothesis that ezrin activity is regulated by turnover of phosphorylation on Thr567. In vitro and in vivo fluorescence resonance energy transfer analysis demonstrated that Thr567 phosphorylation opens the N-C interaction. However, even in the closed conformation, ezrin localizes to membranes by an exposed NH2 terminal binding site. Importantly, the opened phosphorylated form of ezrin more readily cosediments with F-actin and binds more tightly to membrane than the closed forms. Furthermore, fluorescence recovery after photobleaching analysis in live cells showed that the Thr567Asp mutant had longer recovery times than the wild type or the Thr567Ala mutant, indicating the Thr567-phosphorylated form of ezrin is tightly associated with F-actin and the membrane, restricting normal activity. These data demonstrate and emphasize the functional importance of reversible phosphorylation of ezrin on F-actin binding. A novel model is proposed whereby ezrin and closely associated kinase and phosphatase proteins represent a motor complex to maintain a dynamic relationship between the varying membrane surface area and filamentous actin length.
Distension during gastroesophageal reflux: effects of acid inhibition and correlation with symptoms
Authors: Tipnis Neelesh A. , Rhee Poong-Lyul , Mittal Ravinder K.
Published: June 2007

We studied spontaneous gastroesophageal reflux (GER)-induced esophageal distension using ultrasound imaging and its role in the genesis of esophageal symptoms before and during esomeprazole therapy. Ten controls and 10 GER disease (GERD) patients were studied by combined impedance, esophageal pH, manometry, and ultrasonography before and during esomeprazole therapy. Physiological data and symptoms were recorded for 2 h following a standardized meal. From ultrasound images, the esophageal cross-sectional area (CSA) at the peak of GER-induced distension was determined and compared between controls vs. patients, symptomatic vs. asymptomatic GER episodes, and before vs. during esomeprazole in GERD patients. The mean lumen CSA is greater in the patients than controls (271 ± 71 mm2 vs. 163 ± 56 mm2, P = 0.001) but not different among asymptomatic reflux episodes, and those associated with regurgitation (290 ± 110 mm2) or heartburn (271 ± 67 mm2). Eight chest pain episodes associated with reflux revealed a tendency toward larger mean esophageal distension (459 ± 40 mm2) compared with asymptomatic reflux (268 ± 70 mm2, P = 0.058). Following esomeprazole treatment, most GER episodes were nonacidic and asymptomatic except in two patients in whom cyclical reflux was associated with large esophageal distensions. Esomeprazole did not alter the lumen CSA during GER. Esophageal distension is greater in the GERD subjects compared with controls; however, it is unlikely that the GER-induced distension of the esophagus plays a significant role in the genesis of heartburn sensation. Esomeprazole therapy does not alter the GER-induced distension of the esophagus.
Long-term consequences of maternal high-fat feeding on hypothalamic leptin sensitivity and diet-induced obesity in the offspring
Authors: Férézou-Viala Jacqueline , Roy Anne-France , Sérougne Colette , Gripois Daniel , Parquet Michel , Bailleux Virginie , Gertler Arieh , Delplanque Bernadette , Djiane Jean , Riottot Michel , Taouis Mohammed
Published: June 2007

Epidemiological and animal studies suggest that the alteration of hormonal and metabolic environment during fetal and neonatal development can contribute to development of metabolic syndrome in adulthood. In this paper, we investigated the impact of maternal high-fat (HF) diet on hypothalamic leptin sensitivity and body weight gain of offspring. Adult Wistar female rats received a HF or a control normal-fat (C) diet for 6 wk before gestation until the end of the suckling period. After weaning, pups received either C or HF diet during 6 wk. Body weight gain and metabolic and endocrine parameters were measured in the eight groups of rats formed according to a postweaning diet, maternal diet, and gender. To evaluate hypothalamic leptin sensitivity in each group, STAT-3 phosphorylation was measured in response to leptin or saline intraperitoneal bolus. Pups exhibited similar body weights at birth, but at weaning, those born to HF dams weighed significantly less (−12%) than those born to C dams. When given the HF diet, males and females born to HF dams exhibited smaller body weight and feed efficiency than those born to C dams, suggesting increased energy expenditure programmed by the maternal HF diet. Thus, maternal HF feeding could be protective against adverse effects of the HF diet as observed in male offspring of control dams: overweight (+17%) with hyperleptinemia and hyperinsulinemia. Furthermore, offspring of HF dams fed either C or HF diet exhibited an alteration in hypothalamic leptin-dependent STAT-3 phosphorylation. We conclude that maternal high-fat diet programs a hypothalamic leptin resistance in offspring, which, however, fails to increase the body weight gain until adulthood.
α-Catalytic subunits of 5′AMP-activated protein kinase display fiber-specific expression and are upregulated by chronic low-frequency stimulation in rat muscle
Authors: Putman Charles T. , Martins Karen J. B. , Gallo Maria E. , Lopaschuk Gary D. , Pearcey Jean A. , MacLean Ian M. , Saranchuk Ryan J. , Pette Dirk
Published: June 2007

5′-AMP-activated protein kinase (AMPK) signaling initiates adaptive changes in skeletal muscle fibers that restore homeostatic energy balance. The purpose of this investigation was to examine, in rats, the fiber-type protein expression patterns of the α-catalytic subunit isoforms in various skeletal muscles, and changes in their respective contents within the tibialis anterior (TA) after chronic low-frequency electrical stimulation (CLFS; 10 Hz, 10 h daily), applied for 4 ± 1.2 or 25 ± 4.8 days. Immunocytochemical staining of soleus (SOL) and medial gastrocnemius (MG) showed that 86 ± 4.1 to 97 ± 1.4% of type IIA fibers stained for both the α1- and α2-isoforms progressively decreased to 63 ± 12.2% of type IID/X and 9 ± 2.4% of IIB fibers. 39 ± 11.4% of IID/X and 83 ± 7.9% of IIB fibers expressed only the α2 isoform in the MG, much of which was localized within nuclei. α1 and α2 contents, assessed by immunoblot, were lowest in the white gastrocnemius [WG; 80% myosin heavy chain (MHC) IIb; 20% MHCIId/x]. Compared with the WG, α1 content was 1.6 ± 0.08 ( P < 0.001) and 1.8 ± 0.04 ( P < 0.0001)-fold greater in the red gastrocnemius (RG: 13%, MHCIIa) and SOL (21%, MHCIIa), respectively, and increased in proportion to MHCIIa content. Similarly, α2 content was 1.4 ± 0.10 ( P < 0.02) and 1.5 ± 0.07 ( P < 0.001)-fold greater in RG and SOL compared with WG. CLFS induced 1.43 ± 0.13 ( P < 0.007) and 1.33 ± 0.08 ( P < 0.009)-fold increases in the α1 and α2 contents of the TA and coincided with the transition of faster type IIB and IID/X fibers toward IIA fibers. These findings indicate that fiber types differ with regard to their capacity for AMPK signaling and that this potential is increased by CLFS.
Effects on neurite outgrowth and cell survival of a secreted fibroblast growth factor binding protein upregulated during spinal cord injury
Authors: Tassi Elena , Walter Sharon , Aigner Achim , Cabal-Manzano Rafael H. , Ray Ranjan , Reier Paul J. , Wellstein Anton
Published: June 2007

The fibroblast growth factor binding protein (FGF-BP; GenBank accession no. NP_005121 ) is a secreted protein that mobilizes FGFs from the extracellular matrix, protects them from degradation, and enhances their biological activity. Several previous studies reported that FGF-BP is an early response gene upregulated during tissue repair processes including wound healing and atherogenesis. In this study we analyzed whether FGF-BP expression was impacted by spinal cord injury and could have an effect on neuronal cell viability. Immunohistochemical and in situ hybridization studies revealed a dramatic upregulation of FGF-BP protein and mRNA levels following unilateral hemisection and contusion injury of adult rat spinal cord. In spinal cord sections of laminectomized rats, increased FGF-BP expression was observed in the fibers and cell bodies ipsilateral to the lesion site but was absent in the uninjured spinal cord tissue contralateral to the lesion. Increased expression of FGF-BP was observed at all postinjury time points, examined with peak levels occurring at day 4, a time when injury-induced increased levels of FGF2 have also been reported to be maximal. Moreover, using PC12 cells as a neuronal model, we observed that exogenous FGF-BP increased the capacity of FGF2 to stimulate neurite outgrowth and to increase cell survival. At the molecular level, FGF-BP enhanced FGF2-induced protein tyrosine phosphorylation and AKT/PKB activation. Collectively, these results suggest that FGF-BP is an early response gene after spinal cord injury and that its upregulation in regenerating spinal cord tissue may provide a molecular mechanism for enhancing the initial FGF2-mediated neurotrophic effects occurring after such tissue damage.
Linear acceleration-evoked cardiovascular responses in awake rats
Authors: Zhu Hong , Jordan James R. , Hardy Steven P. G. , Fulcher Beverly , Childress Curtis , Varner Cheryl , Windham Byron , Jeffcoat Ben , Rockhold Robin W. , Zhou Wu
Published: June 2007

It has been well documented that vestibular-mediated cardiovascular regulation plays an important role in maintaining stable blood pressure (BP) during postural changes. But the underlying neural mechanisms remain to be elucidated. In particular, because the vestibular stimulation employed in previous animal studies activated both semicircular canals and otolith organs, the contributions of the otolith system has not been studied selectively. The goal of the present study was to characterize cardiovascular responses to natural otolith stimulation in awake rats that were subjected to pure linear motion. In any of the four directions tested, transient linear motion produced a short-latency (∼520 ms) increase in mean BP with a peak of 8.27 ± 0.66 mmHg and was followed by a decrease in BP. There was an initial small biphasic response in heart rate (HR) that was followed by a longer duration increase. The short-latency increase in BP was absent in rats that were pentobarbital sodium anesthetized or that were labyrinthectomized bilaterally, but it was unaffected by baroreceptor denervation, indicating that it was of otolith origin. The increase in BP was linear acceleration intensity dependent and was not affected by absence of visual cues. Furthermore, the BP response was attenuated by inactivation of the medial and inferior vestibular nuclei by microinjections of muscimol, indicating that the otolith-driven cardiovascular responses are mediated by the neurons in these areas. These results not only demonstrate the otolith specific influences on the cardiovascular system but also they establish the first rodent model for examining the neural mechanisms underlying the otolith-mediated cardiovascular regulation.
Simultaneous determination of the accuracy and precision of closed-circuit cardiac output rebreathing techniques
Authors: Jarvis S. S. , Levine B. D. , Prisk G. K. , Shykoff B. E. , Elliott A. R. , Rosow E. , Blomqvist C. G. , Pawelczyk J. A.
Published: June 2007

Foreign and soluble gas rebreathing methods are attractive for determining cardiac output (Q̇c) because they incur less risk than traditional invasive methods such as direct Fick and thermodilution. We compared simultaneously obtained Q̇c measurements during rest and exercise to assess the accuracy and precision of several rebreathing methods. Q̇c measurements were obtained during rest (supine and standing) and stationary cycling (submaximal and maximal) in 13 men and 1 woman (age: 24 ± 7 yr; height: 178 ± 5 cm; weight: 78 ± 13 kg; V̇o2max: 45.1 ± 9.4 ml·kg−1·min−1; mean ± SD) using one-N2O, four-C2H2, one-CO2 (single-step) rebreathing technique, and two criterion methods (direct Fick and thermodilution). CO2 rebreathing overestimated Q̇c compared with the criterion methods (supine: 8.1 ± 2.0 vs. 6.4 ± 1.6 and 7.2 ± 1.2 l/min, respectively; maximal exercise: 27.0 ± 6.0 vs. 24.0 ± 3.9 and 23.3 ± 3.8 l/min). C2H2 and N2O rebreathing techniques tended to underestimate Q̇c (range: 6.6–7.3 l/min for supine rest; range: 16.0–19.1 l/min for maximal exercise). Bartlett's test indicated variance heterogeneity among the methods ( P < 0.05), where CO2 rebreathing consistently demonstrated larger variance. At rest, most means from the noninvasive techniques were ±10% of direct Fick and thermodilution. During exercise, all methods fell outside the ±10% range, except for CO2 rebreathing. Thus the CO2 rebreathing method was accurate over a wider range (rest through maximal exercise), but was less precise. We conclude that foreign gas rebreathing can provide reasonable Q̇c estimates with fewer repeat trials during resting conditions. During exercise, these methods remain precise but tend to underestimate Q̇c. Single-step CO2 rebreathing may be successfully employed over a wider range but with more measurements needed to overcome the larger variability.
Target Acceleration Can Be Extracted and Represented Within the Predictive Drive to Ocular Pursuit
Authors: Bennett Simon J. , de Xivry Jean-Jacques Orban , Barnes Graham R. , Lefèvre Philippe
Published: June 2007

Given sufficient exposure to stimulus presentation, the oculomotor system generates a representation of the stimulus characteristics, which is then used to predict the upcoming target motion. In addition to compensating for the perceptual-motor delay, these predictive processes perpetuate eye motion during a transient occlusion and compensate for the loss of visual input. At present, however, it is not well understood whether and how the oculomotor system extracts and represents target acceleration for subsequent predictive control. To this end, we used a target occlusion paradigm where both position and velocity of the target during the occlusion and at reappearance could not be predicted without extracting target acceleration before target disappearance. We found that the oculomotor response during the blanking period was not influenced by target acceleration when the initial exposure was 200 ms. However, smooth and saccadic eye movements did discriminate between the different levels of acceleration after an initial 500- or 800-ms exposure. In the event that the smooth response during the occlusion did not match well the target trajectory and thus eliminate a developing displacement error, there was an increased saccadic displacement. Still, the combined response during the blanking period did not eliminate retinal slip and position error at target reappearance. These results indicate that information on target acceleration can be extracted on-line, during pursuit of a visible ramp, and then used to drive a predictive oculomotor response in the absence of visual input.
Aging Effects on the Limits and Stability of Long-Term Synaptic Potentiation and Depression in Rat Hippocampal Area CA1
Authors: Kumar Ashok , Thinschmidt Jeffrey S. , Foster Thomas C. , King Michael A.
Published: June 2007

Altered hippocampal synaptic plasticity may underlie age-related memory impairment. In acute hippocampal slices from aged (22–24 mo) and young adult (1–12 mo) male Brown Norway rats, extracellular excitatory postsynaptic field potentials were recorded in CA1 stratum radiatum evoked by Schaffer collateral stimulation. We used enhanced Ca2+to Mg2+ratio and paired-pulse stimulation protocol to induce maximum changes in the synaptic plasticity. Six episodes of theta-burst stimulation (TBS) or nine episodes of paired low-frequency stimulation (pLFS) were used to generate asymptotic long-term potentiation (LTP) and long-term depression (LTD), respectively. In addition, long-term depotentiation (LTdeP) or de-depression (LTdeD) from maximal LTP and LTD were examined using two episodes of pLFS or TBS. Multiple episodes of TBS or pLFS produced significant LTP or LTD in aged and young adult rats; this was not different between age groups. Moreover, there was no significant difference in the amount of LTdeP or LTdeD between aged and young adult rats. Our results show no age differences in the asymptotic magnitude of LTP or LTD, rate of synaptic modifications, development rates, reversal, or decay after postconditioning. Thus impairment of the basic synaptic mechanisms responsible for expression of these forms of plasticity is not likely to account for decline in memory function within this age range.
Convergence of Solutions of Certain Fourth-Order Nonlinear Differential Equations
Authors: Ogundare B. S. , Okecha G. E.
Published: June 2007

We give sufficient criteria for the existence of convergence of solutions for a certain class of fourth-order nonlinear differential equations using Lyapunov's second method. A complete Lyapunov function is employed in this work which makes the results to include and improve some existing results in literature.
Upregulation of Neurotrophic Factors Selectively in Frontal Cortex in Response to Olfactory Discrimination Learning
Authors: Naimark Ari , Barkai Edi , Matar Michael A. , Kaplan Zeev , Kozlovsky Nitzan , Cohen Hagit
Published: June 2007

We have previously shown that olfactory discrimination learning is accompanied by several forms of long-term enhancement in synaptic connections between layer II pyramidal neurons selectively in the piriform cortex. This study sought to examine whether the previously demonstrated olfactory-learning-task-induced modifications are preceded by suitable changes in the expression of mRNA for neurotrophic factors and in which brain areas this occurs. Rats were trained to discriminate positive cues in pair of odors for a water reward. The relationship between the learning task and local levels of mRNA for brain-derived neurotrophic factor, tyrosine kinase B, nerve growth factor, and neurotrophin-3 in the frontal cortex, hippocampal subregions, and other regions were assessed 24 hours post olfactory learning. The olfactory discrimination learning activated production of endogenous neurotrophic factors and induced their signal transduction in the frontal cortex, but not in other brain areas. These findings suggest that different brain areas may be preferentially involved in different learning/memory tasks.
Maximizing Banking Profit on a Random Time Interval
Authors: Mukuddem-Petersen J. , Petersen M. A. , Schoeman I. M. , Tau B. A.
Published: June 2007

We study the stochastic dynamics of banking items such as assets, capital, liabilities and profit. A consideration of these items leads to the formulation of a maximization problem that involves endogenous variables such as depository consumption, the value of the bank's investment in loans, and provisions for loan losses as control variates. A solution to the aforementioned problem enables us to maximize the expected utility of discounted depository consumption over a random time interval,[t,τ], and profit at terminal timeτ. Here, the term depository consumption refers to the consumption of the bank's profits by the taking and holding of deposits. In particular, we determine an analytic solution for the associated Hamilton-Jacobi-Bellman (HJB) equation in the case where the utility functions are either of power, logarithmic, or exponential type. Furthermore, we analyze certain aspects of the banking model and optimization against the regulatory backdrop offered by the latest banking regulation in the form of the Basel II capital accord. In keeping with the main theme of our contribution, we simulate the financial indices return on equity and return on assets that are two measures of bank profitability.
Existence Results for Polyharmonic Boundary Value Problems in the Unit Ball
Authors: Ben Othman Sonia , Mâagli Habib , Zribi Malek
Published: June 2007

Here we study the polyharmonic nonlinear elliptic boundary value problem on the unit ballBinℝn(n≥2)(−△)mu+g(⋅,u)=0, inB(in the sense of distributions)limx→ξ∈∂B(u(x)/(1−|x|2)m−1)=0(ξ). Under appropriate conditions related to a Kato class on the nonlinearityg(x,t), we give some existence results. Our approach is based on estimates for the polyharmonic Green function onBwith zero Dirichlet boundary conditions, including a 3G-theorem, which leeds to some useful properties on functions belonging to the Kato class.
A Unified Approach to Mapping and Routing on a Network-on-Chip for Both Best-Effort and Guaranteed Service Traffic
Authors: Hansson Andreas , Goossens Kees , Rădulescu Andrei
Published: June 2007

One of the key steps in Network-on-Chip-based design is spatial mapping of cores
and routing of the communication between those cores. Known solutions to the mapping and
routing problems first map cores onto a topology and then route communication, using separate
and possibly conflicting objective functions. In this paper, we present a unified single-objective
algorithm, called Unified MApping, Routing, and Slot allocation (UMARS+). As the main
contribution, we show how to couple path selection, mapping of cores, and
channel time-slot allocation to minimize the network required to meet the constraints of
the application. The time-complexity of UMARS+ is low and experimental results indicate
a run-time only 20% higher than that of path selection alone. We apply the algorithm to an MPEG
decoder System-on-Chip, reducing area by 33%, power dissipation by 35%, and worst-case latency by a factor four over a traditional waterfall approach.
Nonlinear Mean Ergodic Theorems for Semigroups in Hilbert Spaces
Authors: Temir Seyit , Gul Ozlem
Published: June 2007

Let "Equation missing" be a nonempty subset (not necessarily closed and convex) of a Hilbert space and let "Equation missing" be a semigroup on "Equation missing" and let "Equation missing" be an almost orbit of "Equation missing". In this paper, we prove that every almost orbit of "Equation missing" is almost weakly and strongly convergent to its asymptotic center.
Experimental and Theoretical Investigations of Mouldability for Feedstocks Used in Powder Injection Moulding
Authors: Karatas Çetin , Sözen Adnan , Arcaklioglu Erol , Erguney Sami
Published: June 2007

Experimental and theoretical analyses of mouldability for feedstocks used in powder injection moulding are performed. This study covers two main analyses. (i)The experimental analysis: the barrel temperature, injection pressure, and flow rate are factors for powder injection moulding (PIM). Powder-binder mixture used as feedstock in PIM requires a little more attention and sensitivity. Obtaining the balance among pressure, temperature, and especially flow rate is the most important aspect of undesirable conclusions such as powder-binder separation, sink marks, and cracks in moulded party structure. In this study, available feedstocks used in PIM were injected in three different cavities which consist of zigzag form, constant cross-section, and stair form (in five different thicknesses) and their mouldability is measured. Because of the difference between material and binder, measured lengths were different. These were measured as 533 mm, 268 mm, 211 mm, and 150 mm in advanced materials trade marks Fe–2Ni, BASF firm Catamould A0-F, FN02, and 316L stainless steel, respectively. (ii)The theoretical analysis: the use of artificial neural network (ANN) has been proposed to determine the mouldability for feedstocks used in powder injection moulding using results of experimental analysis. The back-propagation learning algorithm with two different variants and logistic sigmoid transfer function were used in the network. In order to train the neural network, limited experimental measurements were used as training and test data. The best fitting training data set was obtained with three and four neurons in the hidden layer, which made it possible to predict yield length with accuracy at least as good as that of the experimental error, over the whole experimental range. After training, it was found that theR2values are 0.999463, 0.999445, 0.999574, and 0.999593 for Fe–2Ni, BASF firm Catamould A0-F, FN02, and 316L stainless steel, respectively. Similarly, these values for testing data are 0.999129, 0.999666, 0.998612, and 0.997512, respectively. As seen from the results of mathematical modeling, the calculated yield lengths are obviously within acceptable uncertainties.
Prostate Cancer Associated with p53 and Rb Deficiency Arises from the Stem/Progenitor Cell–Enriched Proximal Region of Prostatic Ducts
Authors: Zhou Zongxiang , Flesken-Nikitin Andrea , Nikitin Alexander Yu.
Published: June 2007

Recently, we have shown that prostate epithelium–specific deficiency for p53 and Rb tumor suppressors leads to metastatic cancer, exhibiting features of both luminal and neuroendocrine differentiation. Using stage-by-stage evaluation of carcinogenesis in this model, we report that all malignant neoplasms arise from the proximal region of the prostatic ducts, the compartment highly enriched for prostatic stem/progenitor cells. In close similarity to reported properties of prostatic stem cells, the cells of the earliest neoplastic lesions express stem cell marker stem cell antigen 1 and are not sensitive to androgen withdrawal. Like a subset of normal cells located in the proximal region of prostatic ducts, the early neoplastic cells coexpress luminal epithelium markers cytokeratin 8, androgen receptor, and neuroendocrine markers synaptophysin and chromogranin A. Inactivation of p53 and Rb also takes place in the lineage-committed transit-amplifying and/or differentiated cells of the distal region of the prostatic ducts. However, the resulting prostatic intraepithelial neoplasms never progress to carcinoma by the time of mouse death. Interestingly, in an ectopic transplantation assay, early mutant cells derived from either region of the prostatic ducts are capable of forming neoplasms within 3 months. These findings indicate that p53 and Rb are critically important for the regulation of the prostatic stem cell compartment, the transformation in which may lead to particularly aggressive cancers in the context of microenvironment. [Cancer Res 2007;67(12):5683–90]
Cellular and Molecular Mechanisms of Proteinuria in Diabetic Nephropathy
Authors: Wolf Gunter , Ziyadeh Fuad N.
Published: June 2007

One of the earliest clinically detectable abnormalities in diabetic nephropathy is microalbuminuria that eventually progresses to proteinuria. The degree of proteinuria correlates with the progression of glomerulosclerosis and tubulointerstitial fibrosis. In the glomerulus, a typical podocytopathy develops that participates in the initiation of glomerulosclerosis and the accelerated plasma protein leakage across the glomerular basement membrane (GBM) into Bowman’s space. Downstream into the tubular compartment, the proteinuria induces proinflammatory and profibrogenetic injury in tubular cells which can facilitate the development of interstitial fibrosis and tubular atrophy. It has long been held that hemodynamic changes and the loss of negatively charged proteoglycans in the GBM are important mediators of proteinuria. More recently, biopsy studies in humans with diabetic kidney disease have provided strong evidence that podocytes are injured very early in the course of nephropathy. This podocytopathy – which is characterized by decreased podocyte number and/or density, GBM thickening and altered matrix composition, and foot process effacement – correlates closely with the development and progression of albuminuria. Components of the diabetic milieu (high glucose, accumulation of glycated proteins, high intrarenal angiotensin II (ANG II), and hypertension-induced mechanical stress) result in activation of cytokine systems, the most important of which are transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor-A (VEGF-A). ANG II-stimulated podocyte-derived VEGF, through a novel autocrine signaling loop, appears to be a major cause of nephrin downregulation and the development of proteinuria. Nephrin is an important protein of the slit diaphragm with anti-apoptotic signaling properties. TGF-β1 causes podocyte apoptosis and an increase in extracellular matrix deposition. As a consequence, the denuded GBM adheres to Bowman’s capsule initiating the development of glomerulosclerosis. Good control of hyperglycemia and hypertension and maximal inhibition of ANG II are essential steps in preventing the development and progression of diabetic nephropathy.
Role of the VEGF-A Signaling Pathway in the Glomerulus: Evidence for Crosstalk between Components of the Glomerular Filtration Barrier
Authors: Eremina Vera , Baelde Hans J. , Quaggin Susan E.
Published: June 2007

Background/Aims: Vascular endothelial growth factor is a major regulator of angiogenesis and vascular permeability [Carmeliet et al.: Nature 1996;380:435–439]. The podocyte, the outermost layer of the glomerular filtration barrier, produces large amounts of VEGF-A. The observation that levels of VEGF-A are altered in glomerular diseases, the identification of a link between pre-eclampsia and elevated levels of a circulating soluble VEGF receptor, and the entry of anti-VEGF therapies into the clinical arena have generated intense interest in the functional role of VEGF-A in the glomerulus. Methods: A variety of studies have been performed to address the role of VEGF-A signaling in the glomerulus. These include descriptions of expression patterns in human renal biopsies, cell culture studies to dissect paracrine versus autocrine signaling roles, and manipulation of VEGF-A expression in animal models using pharmacologic, biologic or genetic approaches. Results: Exquisite dosage sensitivity to VEGF-A exists in the developing glomerulus as small reductions in the expression of VEGF-A lead to profound changes in glomerular structure and function in mice. The use of VEGF inhibitors is associated with damage to the glomerular endothelium in animal models and proteinuria in patients, suggesting that local VEGF-A production is also required for maintenance of this specialized vascular bed. Conclusions: Tight regulation of VEGF-A signaling is required for development and maintenance of the glomerular filtration barrier (GFB) and emphasizes the role of podocyte-endothelial crosstalk in the glomerulus. The relative contributions of various VEGF-A isoforms, the role of autocrine signaling in vivo and identification of factors and mechanisms that regulate constitutive expression, storage and delivery of VEGF-A in the glomerulus are still under investigation.
Root Surface Caries in Older Individuals from Sri Lanka
Authors: Kularatne S. , Ekanayake L.
Published: June 2007

The aim of the present study was to assess the prevalence and factors associated with root surface caries in older individuals from Sri Lanka. A total of 600 urban subjects aged 60 years and above was selected using a two-stage cluster sampling combined with probability-proportionate-to-size technique. The data were collected by means of an interviewer-administered questionnaire and an oral examination. The mean number of teeth present was 13.4 ± 8.7. The prevalence of root surface caries was 89.7%. The mean number of root surfaces with decay or fillings and the mean root caries index (RCI) per subject were 3.8 and 25.0%, respectively. In both arches, the molars were the most affected by root caries. A multiple logistic regression analysis showed that betel chewing (OR = 0.36; 95% CI 0.20, 0.65), being >80 years of age (OR = 0.24; CI 0.09, 0.57), number of retained teeth (OR = 0.88; CI 0.83, 0.93) and number of root surfaces with recession (OR = 1.03; CI 1.01, 1.07) were significantly associated with the presence of root surface caries. In conclusion, it was evident from the study that the prevalence of root surface caries was high in this group of older individuals. Chewing betel, age, number of retained teeth and the number of root surfaces with recession emerged as significant predictors of root caries.
In vitro Evaluation of the Effectiveness of Acidic Fluoride Dentifrices
Authors: Alves K.M.R.P. , Pessan J.P. , Brighenti F.L. , Franco K.S. , Oliveira F.A.L. , Buzalaf M.A.R. , Sassaki K.T. , Delbem A.C.B.
Published: June 2007

This study evaluated the effectiveness of acidic low-fluoride dentifrices compared to conventional neutral dentifrices. Enamel blocks were submitted to pH cycling and treatment with slurries of dentifrices containing 0, 275, 412, 550 and 1,100 µg F/g (pH 4.5 or 7.0), and also a commercial dentifrice (1,100 µg F/g) and a commercial children’s dentifrice (500 µg F/g). Variations in surface microhardness and in the mineral content in enamel after pH cycling were calculated. Enamel blocks treated with acidic dentifrices exhibited less mineral loss compared to neutral dentifrices (ANOVA; p < 0.05). The acidic dentifrices with 412 and 550 µg F/g had the same effectiveness as the neutral 1,100-µg F/g dentifrice and commercial 1,100-µg F/g dentifrice.
Successful Intrauterine Therapy for Congenital Cystic Adenomatoid Malformation of the Lung
Authors: Isnard M. , Kohler A. , Kohler M. , Vayssière C. , Favre R.
Published: June 2007

Congenital cystic adenomatoid malformation (CCAM) of the lung is a rare abnormality which is amenable to be diagnosed by prenatal ultrasonography. In general, CCAM associated with non-immune hydrops has a poor prognosis unless a fetal intervention is performed. In some series almost 100% of either prenatal or early neonatal deaths are observed without intervention. Recently the cystic adenomatoid malformation volume ratio (CVR) has been proposed as an index to predict the development of hydrops in this condition. If the CVR is >1.6, the risk of hydrops is approximately 75%. We report a case of CCAM (macrocystic type) of the left lung referred to our center at 21 weeks of gestation. Fetal therapy was considered owing to enlargement of the CCAM volume, severe mediastinal shift, right lung compression, polyhydramnios and ascites from 21 to 26 weeks. Thoracoamniotic shunting was performed successfully at 26 weeks with resolution of the cystic mass. At 37 weeks a male infant was born vaginally weighing 3,210 g with Apgar scores of 5 and 10. Resection of the mass was performed uneventfully on day 3. The infant is currently 22 months of age, asymptomatic and in good condition.
Umbilical Cord Insertion to the Lower Uterine Segment Is a Risk Factor for Vasa Previa
Authors: Hasegawa Junichi , Matsuoka Ryu , Ichizuka Kiyotake , Fujikawa Hiroshi , Sekizawa Akihiko , Okai Takashi
Published: June 2007

The perinatal mortality rate of vasa previa is high if it is not prenatally diagnosed. Systematic strategies for vasa previa screening have been recommended. In this paper, three cases of vasa previa diagnosed prenatally, with umbilical cord inserted to the lower segment of the uterus, are presented. It should be considered that umbilical cord insertion to the lower uterine segment is a high risk for vasa previa. Ultrasound screening for cord insertion will make it possible to do efficient and certain detection of vasa previa.
Brain-Derived Neurotrophic Factor and Its Intracellular Signaling Pathways in Cocaine Addiction
Authors: Corominas M. , Roncero C. , Ribases M. , Castells X. , Casas M.
Published: June 2007

Cocaine addiction is one of the severest health problems faced by western countries, where there is an increasing prevalence of lifelong abuse. The most challenging aspects in the treatment of cocaine addiction are craving and relapse, especially in view of the fact that, at present, there is a lack of effective pharmacological treatment for the disorder. What is required are new pharmacological approaches based on our current understanding of the neurobiological bases of drug addiction. Within the context of the behavioral and neurochemical actions of cocaine, this paper considers the contribution of brain-derived neurotrophic factor (BDNF) and its main intracellular signaling mechanisms, including mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MAPK/ERK) and phosphatidylinositol 3-kinase (PI3K), in psychostimulant addiction. Repeated cocaine administration leads to an increase in BDNF levels and enhanced activity in the intracellular pathways (PI3K and MAPK/ERK) in the reward-related brain areas, which applies especially several days following withdrawal. It has been hypothesized that these neurochemical changes contribute to the enduring synaptic plasticity that underlies sensitized responses to psychostimulants and drug-conditioned memories leading to compulsive drug use and frequent relapse after withdrawal. Nevertheless, increased BDNF levels could also have a role as a protection factor in addiction. The inhibition of the intracellular pathways, ERK and PI3K, leads to a disruption in sensitized responses and conditioned memories associated with cocaine addiction and suggests new, potential therapeutic strategies to explore in the dependence on psychostimulants.
Melanopsin in Lower Vertebrates: The Race Is On to Show that It Is Really There
Authors: Meyer-Rochow V. Benno
Published: June 2007

The retina of the Antarctic teleost Trematomus bernacchii was examined immunocytochemically, using antisera against bovine rhodopsin (1:1,000) and visinin (1:250). There were no surprises with regard to rhodopsin, but positive visinin reactions occurred not only in the cones (visinin has a broad range of sensitivity to opsins), but also in some cells of the ganglion and bipolar cell layers. The reactions could be due to the presence of melanopsin or another opsin-like photopigment, but since experimental work on Antarctic fish is difficult, more accessible fish species should be examined under summer and winter conditions and different light/dark regimens. Furthermore, the search for melanopsin or similar proteins should also involve the pineal organs of lower vertebrates.
Predicting Pertussis in a Pediatric Emergency Department Population
Authors: Mackey Jennifer E. , Wojcik Susan , Long Ray , Callahan James M. , Grant William D.
Published: June 2007

Cases of pertussis, a potentially life-threatening illness in infants younger than 6 months of age, are at a 40-year high. Children frequently present to emergency departments for initial evaluation. Quick recognition of the illness allows rapid triage, isolation, and prevention of nosocomial transmission. A retrospective, case−control chart review was conducted of pediatric emergency department patients (0 to 18 years of age) presenting between January 1, 2003, and December 31, 2004. Analysis focused on the exploration of medical history and physical examination variables as predictors using laboratory verification of the presence of pertussis as a binary outcome variable. Infants younger than 2 months who have a cough or choking associated with cyanosis, as well as a cough and rhonchi on physical examination, have a high likelihood of pertussis and should be identified in triage, isolated immediately, and tested for pertussis. This may lead to appropriate therapy for this population and decrease the transmission of pertussis to other patients and staff in the pediatric emergency department.
Resident Continuity Clinic: A Modest Proposal
Authors: Barton Leslie L. , Ball Thomas , Villar Rodrigo , Duncan Burris
Published: June 2007

Resident continuity clinics are an integral and mandated component of the pediatric core curriculum. Hospital-based and community-based settings have been traditionally used, with varied success. This article proposes the use and testing of an additional site, the primary care clinic housed at the Children's Clinic for Rehabilitative Services. This site provides concomitant continuity, and community and advocacy experiences for children with complex chronic conditions. Further study of the educational efficiency of this site is warranted.
Evaluation of the Potential for Pharmacodynamic and Pharmacokinetic Drug Interactions Between Selegiline Transdermal System and Two Sympathomimetic Agents (Pseudoephedrine and Phenylpropanolamine) in Healthy Volunteers
Authors: Azzaro Albert J. , VanDenBerg Chad M. , Ziemniak John , Kemper Eva M. , Blob Lawrence F. , Campbell Bryan J.
Published: June 2007

Selegiline transdermal system is a recently approved monoamine oxidase inhibitor antidepressant. Medications that inhibit monoamine oxidase type A can augment the pressor effects of sympathomimetic amines, increasing the potential for hypertensive crisis. This study examined the potential for drug‐drug interactions during treatment with selegiline transdermal system and pseudoephedrine or phenylpropanolamine. Two studies were conducted with 25 healthy volunteers to assess changes in blood pressure and heart rate during administration of pseudoephedrine or phenylpropanolamine alone or together with selegiline transdermal system. No significant differences in mean maximum changes in vital signs occurred with pseudoephedrine. No significant differences were found in mean maximum changes in systolic heart rate with phenylpropanolamine; however, 4 of 12 subjects each experienced 1 isolated protocol‐defined minimal pressor response without concurrent adverse effects (1 with phenylpropanolamine alone; 3 with phenylpropanolamine + selegiline transdermal system). Pharmacokinetic parameters obtained following selegiline transdermal system and pseudoephedrine or phenylpropanolamine were unremarkable. The results suggest that selegiline transdermal system 6 mg/24 h does not significantly alter the pharmacodynamics or pharmacokinetics of either pseudoephedrine or phenylpropanolamine when administered to healthy volunteers; however, it is prudent to avoid coadministration of selegiline transdermal system and sympathomimetics.
Photocopiers and Water-coolers: The Affordances of Informal Interaction
Authors: Fayard Anne-Laure , Weeks John
Published: June 2007

There has been increasing recognition of the importance of informal interactions in organizations, but research examining the effects of the physical environment on informal interaction has produced contradictory results and practical attempts to control the level of informal interaction by design have been marked by unintended consequences. Drawing on a qualitative study of informal interactions observed in photocopier rooms in three organizations, this paper builds on the work of ecological psychologist James Gibson to develop a theory of the affordances of informal interaction. The affordances of an environment are the possibilities for action called forth by it to a perceiving subject. Research on affordances has typically focused on the affordances of individual behavior. We introduce the notion of social affordances and identify the social and physical characteristics that produce the propinquity, privacy, and social designation necessary for an environment to afford informal interactions. The theory of social affordances provides a lens through which to reinterpret the conflicting results of previous studies and to reexamine the seemingly simple water-cooler around which the organization gathers.
Towards a Dynamic Resource-based View: Insights from Austrian Capital and Entrepreneurship Theory
Authors: Foss Nicolai J. , Ishikawa Ibuki
Published: June 2007

Over the last two decades, the resource-based view (RBV) has become dominant in the strategic management field. It has often been observed that the RBV is lacking in the dynamic dimension. For example, processes of building competitive advantages by means of combining existing complementary resources in novel ways are not inquired into. We argue that the RBV may profitably draw on insights in entrepreneurship and capital theory, drawn from Austrian economists as well as Frank Knight, in order to strengthen its dynamic dimension. We link the RBV and Austrian ideas in the context of the theory of complex systems pioneered by Herbert Simon. We draw a number of implications for strategic management from this synthesis, notably into resource value and sustainability of competitive advantage.