bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermal monitoring mechanisms for chip multiprocessors
Authors: Long Jieyi , Memik Seda Ogrenci , Memik Gokhan , Mukherjee Rajarshi
Published: September 2008

With large-scale integration and increasing power densities, thermal management has become an important tool to maintain performance and reliability in modern process technologies. In the core of dynamic thermal management schemes lies accurate reading of on-die temperatures. Therefore, careful planning and embedding of thermal monitoring mechanisms into high-performance systems becomes crucial. In this paper, we propose three techniques to create sensor infrastructures for monitoring the maximum temperature on a multicore system. Initially, we extend a nonuniform sensor placement methodology proposed in the literature to handle chip multiprocessors (CMPs) and show its limitations. We then analyze a grid-based approach where the sensors are placed on a static grid covering each core and show that the sensor readings can differ from the actual maximum core temperature by as much as 12.6°C when using 16 sensors per core. Also, as large as 10.6% of the thermal emergencies are not captured using the same number of sensors. Based on this observation, we first develop an interpolation scheme, which estimates the maximum core temperature through interpolation of the readings collected at the static grid points. We show that the interpolation scheme improves the measurement accuracy and emergency coverage compared to grid-based placement when using the same number of sensors. Second, we present a dynamic scheme where only a subset of the sensor readings is collected to predict the maximum temperature of each core. Our results indicate that, we can reduce the number of active sensors by as much as 50%, while maintaining similar measurement accuracy and emergency coverage compared to the case where the entire sensor set on the grid is sampled at all times.
Reducing complexity of multiobjective design space exploration in VLIW-based embedded systems
Authors: Catania Vincenzo , Palesi Maurizio , Patti Davide
Published: September 2008

Architectures based on very-long instruction word (VLIW) have found fertile ground in multimedia electronic appliances thanks to their ability to exploit high degrees of instruction level parallelism (ILP) with a reasonable trade-off in complexity and silicon cost. Specialization of such architectures involves the configuration of both hardware-related aspects (e.g., register files, functional units, memory subsystem) and software-related issues (e.g., the compilation strategy). The complex interactions between the components of such systems will force a human designer to rely on judgment and experience in designing them, possibly eliminating interesting configurations, and making tuning of the system, for either power, energy, or performance, difficult. In this paper we propose tools and methodologies to efficiently cope with this complexity from a multiobjective perspective. We first analyze the impact of ILP-oriented code transformations using two alternative compilation profiles to quantitatively show the effect of such transformations on typical design objectives like performance, power dissipation, and energy consumption. Next, by means of statistical analysis, we collect useful data to predict the effectiveness of a given compilation profiles for a specific application. Information gathered from such analysis can be exploited to drastically reduce the computational effort needed to perform the design space exploration.
A method for passing data between C and Opaque Fortran 90 pointers
Authors: Decyk Viktor K.
Published: September 2008

This paper discusses a portable, standard conforming method for passing data arrays between C and Fortran 90.
The new features of Fortran 2008
Authors: Reid John
Published: September 2008

The aim of this paper is to summarize the new features of the draft Fortran 2008 standard (ISO/IEC 2008). We take as our starting point Fortran 2003 (ISO/IEC 2008). An official extension for enhanced module facilities (ISO/IEC 2005) that has been published as a Type 2 Technical Report (TR), and WG5 is committed to include this in Fortran 2008. For an informal description of Fortran 2003 and Enhanced Module Facilities see Metcalf, Reid, and Cohen (2004). The major proposed extension consists of coarrays for parallel computing. Since the author has already summarised coarrays in another WG5 paper (Reid 2008), we refer the reader to this for further details.

This is not an official document and has not been approved by either of the Fortran committees WG5 or J3.
Compiler support for the Fortran 2003 standard
Authors: Chivers Ian D. , Sleightholme Jane
Published: September 2008

This is a repeating article in Fortran Forum. The first version appeared in Fortran Forum in April 2007. The basis for the entries in the list of features was a report by John Reid. An electronic version can be found at: ftp://ftp.nag.co.uk/sc22wg5/N1601-N1650/N1648.pdf

The next edition of the article will include support for the Fortran 2008 standard, and again the basis for the entries will be a John Reid article!

If you are a compiler vendor and would like to be included in future versions of this table please email one of us with details and they will be added to the table and published in Fortran Forum.
A Mechanistic View of Genomic Imprinting
Authors: Sha Ky
Published: September 2008

Genomic imprinting results in the expression of genes in a parent-of-origin-dependent manner. The mechanism and developmental consequences of genomic imprinting are most well characterized in mammals, plants, and certain insect species (e.g., sciarid flies and coccid insects). However, researchers have observed imprinting phenomena in species in which imprinting of endogenous genes is not known to exist or to be developmentally essential. In this review, I survey the known mechanisms of imprinting, focusing primarily on examples from mammals, where imprinting is relatively well characterized. Where appropriate, I draw attention to imprinting mechanisms in other organisms to compare and contrast how diverse organisms employ different strategies to perform the same process. I discuss how the various mechanisms come into play in the context of the imprint life cycle. Finally, I speculate why imprinting may be more widely prevalent than previously thought.
Hypoxia, Nitrogen, and Fisheries: Integrating Effects Across Local and Global Landscapes
Authors: Breitburg Denise L. , Hondorp Darryl W. , Davias Lori A. , Diaz Robert J.
Published: September 2008

Anthropogenic nutrient enrichment and physical characteristics result in low dissolved oxygen concentrations (hypoxia) in estuaries and semienclosed seas throughout the world. Published research indicates that within and near oxygen-depleted waters, finfish and mobile macroinvertebrates experience negative effects that range from mortality to altered trophic interactions. Chronic exposure to hypoxia and fluctuating oxygen concentrations impair reproduction, immune responses, and growth. We present an analysis of hypoxia, nitrogen loadings, and fisheries landings in 30 estuaries and semienclosed seas worldwide. Our results suggest that hypoxia does not typically reduce systemwide fisheries landings below what would be predicted from nitrogen loadings, except where raw sewage is released or particularly sensitive species lose critical habitat. A number of compensatory mechanisms limit the translation of local-scale effects of hypoxia to the scale of the whole system. Hypoxia is, however, a serious environmental challenge that should be considered in fisheries management strategies and be a direct target of environmental restoration.
GATA-6 mediates transcriptional activation of aquaporin-5 through interactions with Sp1
Authors: Zhou Beiyun , Francis Tricia A. , Yang Hui , Tseng Wanru , Zhong Qian , Frenkel Baruch , Morrisey Edward. E. , Ann David. K. , Minoo Parviz , Crandall Edward D. , Borok Zea
Published: September 2008

We investigated mechanisms underlying GATA-6-mediated transcriptional activation of the alveolar epithelial type I cell-enriched gene aquaporin-5 (AQP5). GATA-6 expression increases in alveolar epithelial cells in primary culture, concurrent with upregulation of AQP5 and transition to a type I cell-like phenotype. Cotransfections in MLE-15 and NIH 3T3 cells demonstrated trans-activation by GATA-6 of a rat 1,716-bp-AQP5-luciferase (−1716-AQP5-Luc) reporter. Electrophoretic mobility shift assay and chromatin immunoprecipitation identified an interaction between GATA-6 and putative binding sites in the AQP5 promoter. However, mutation of these sites did not reduce GATA-6-mediated activation, implicating mechanisms in addition to direct binding of GATA-6 to DNA. A 5′-deletion construct, −358-AQP5-Luc, that does not encompass GATA motifs was still activated by GATA-6 by as much as 50% relative to −1716-AQP5-Luc. Internal deletion of the −358/−173 GC-rich domain, which includes several putative Sp1 consensus sites, reduced trans-activation by ∼60%, suggesting importance of this region for GATA-mediated activity. −358-AQP5-Luc was similarly activated by both GATA-6 and a GATA DNA-binding defective mutant, whereas cotransfections in Schneider S2 cells demonstrated dose-dependent trans-activation of −358-AQP5-Luc by Sp1. Activation of −358-AQP5-Luc by GATA-6 was dramatically reduced by Sp1 small-interfering RNA, and −358-AQP5-Luc was activated synergistically by GATA-6 and Sp1 in NIH 3T3 cells. Furthermore, association between endogenous GATA-6 and Sp1 was demonstrated by coimmunoprecipitation. These results suggest that transcriptional activation of AQP5 by GATA-6 is mediated at least in part through cooperative interactions with Sp1 occurring at the proximal promoter.
MAP kinase/phosphatase pathway mediates the regulation of ACE2 by angiotensin peptides
Authors: Gallagher Patricia E. , Ferrario Carlos M. , Tallant E. Ann
Published: September 2008

Angiotensin-converting enzyme 2 (ACE2) catalyzes the conversion of the vasoconstrictor angiotensin II (ANG II) to the vasodilatory peptide angiotensin-(1-7) [ANG-(1-7)]. We showed that treatment of hypertensive rats with the AT1 receptor antagonist olmesartan increased ACE2 mRNA and protein in the thoracic aorta, suggesting that endogenous ANG II tonically reduces the enzyme. We now report that ANG II downregulates ACE2 activity and mRNA in rat aortic vascular smooth muscle cells (VSMCs) to reduce the conversion of ANG II to ANG-(1-7). Although ANG-(1-7) alone had no effect on the regulation of ACE2 mRNA, the heptapeptide prevented the ANG II-mediated reduction in ACE2 mRNA, an effect blocked by the selective ANG-(1-7) receptor antagonist [d-Ala7]-ANG-(1-7). The reduction in ACE2 mRNA by ANG II was also prevented by the mitogen-activated protein (MAP) kinase kinase inhibitor PD98059. Treatment of VSMCs with ANG II increased ERK1/ERK2 activity, which was significantly reduced by pretreatment with ANG-(1-7). Blockade of the ANG II-mediated reduction in ACE2 mRNA and increase in MAP kinase activity by ANG-(1-7) was prevented by pretreatment with sodium vanadate, a tyrosine phosphatase inhibitor, or okadaic acid, a serine-threonine phosphatase inhibitor, suggesting that the heptapeptide activates a MAP kinase phosphatase. This study is the first to show that the MAP kinase-phosphatase pathway is a primary molecular mechanism for regulating ACE2 to maintain the balance between ANG II and ANG-(1-7). The modulatory role of ANG-(1-7) in the regulation of ACE2 by ANG II suggests a complex interplay between the two peptides that is mediated by specific receptors to activate distinct signaling pathways.
Distinct phospho-forms of cortactin differentially regulate actin polymerization and focal adhesions
Authors: Kruchten Anne E. , Krueger Eugene W. , Wang Yu , McNiven Mark A.
Published: September 2008

Cortactin is an actin-binding protein that is overexpressed in many cancers and is a substrate for both tyrosine and serine/threonine kinases. Tyrosine phosphorylation of cortactin has been observed to increase cell motility and invasion in vivo, although it has been reported to have both positive and negative effects on actin polymerization in vitro. In contrast, serine phosphorylation of cortactin has been shown to stimulate actin assembly in vitro. Currently, the effects of cortactin serine phosphorylation on cell migration are unclear, and furthermore, how the distinct phospho-forms of cortactin may differentially contribute to cell migration has not been directly compared. Therefore, we tested the effects of different tyrosine and serine phospho-mutants of cortactin on lamellipodial protrusion, actin assembly within cells, and focal adhesion dynamics. Interestingly, while expression of either tyrosine or serine phospho-mimetic cortactin mutants resulted in increased lamellipodial protrusion and cell migration, these effects appeared to be via distinct processes. Cortactin mutants mimicking serine phosphorylation appeared to predominantly affect actin polymerization, whereas mutation of cortactin tyrosine residues resulted in alterations in focal adhesion turnover. Thus these findings provide novel insights into how distinct phospho-forms of cortactin may differentially contribute to actin and focal adhesion dynamics to control cell migration.
Ankyrin facilitates intracellular trafficking of α1-Na+-K+-ATPase in polarized cells
Authors: Stabach Paul R. , Devarajan Prasad , Stankewich Michael C. , Bannykh Serguei , Morrow Jon S.
Published: September 2008

Defects in ankyrin underlie many hereditary disorders involving the mislocalization of membrane proteins. Such phenotypes are usually attributed to ankyrin's role in stabilizing a plasma membrane scaffold, but this assumption may not be accurate. We found in Madin-Darby canine kidney cells and in other cultured cells that the 25-residue ankyrin-binding sequence of α1-Na+-K+-ATPase facilitates the entry of α1,β1-Na+-K+-ATPase into the secretory pathway and that replacement of the cytoplasmic domain of vesicular stomatitis virus G protein (VSV-G) with this ankyrin-binding sequence bestows ankyrin dependency on the endoplasmic reticulum (ER) to Golgi trafficking of VSV-G. Expression of the ankyrin-binding sequence of α1-Na+-K+-ATPase alone as a soluble cytosolic peptide acts in trans to selectively block ER to Golgi transport of both wild-type α1-Na+-K+-ATPase and a VSV-G fusion protein that includes the ankyrin-binding sequence, whereas the trafficking of other proteins remains unaffected. Similar phenotypes are also generated by small hairpin RNA-mediated knockdown of ankyrin R or the depletion of ankyrin in semipermeabilized cells. These data indicate that the adapter protein ankyrin acts not only at the plasma membrane but also early in the secretory pathway to facilitate the intracellular trafficking of α1-Na+-K+-ATPase and presumably other selected proteins. This novel ankyrin-dependent assembly pathway suggests a mechanism whereby hereditary disorders of ankyrin may be manifested as diseases of membrane protein ER retention or mislocalization.
Krüppel-like factor 4, Elk-1, and histone deacetylases cooperatively suppress smooth muscle cell differentiation markers in response to oxidized phospholipids
Authors: Yoshida Tadashi , Gan Qiong , Owens Gary K.
Published: September 2008

Phenotypic switching of vascular smooth muscle cells (SMCs), such as increased proliferation, enhanced migration, and downregulation of SMC differentiation marker genes, is known to play a key role in the development of atherosclerosis. However, the factors and mechanisms controlling this process are not fully understood. We recently showed that oxidized phospholipids, including 1-palmitoyl-2-(5-oxovaleroyl)- sn-glycero-3-phosphocholine (POVPC), which accumulate in atherosclerotic lesions, are potent repressors of expression of SMC differentiation marker genes in cultured SMCs as well as in rat carotid arteries in vivo. Here, we examined the molecular mechanisms whereby POVPC induces suppression of SMC differentiation marker genes in cultured SMCs. Results showed that POVPC induced phosphorylation of ERK1/2 and Elk-1. The MEK inhibitors U-0126 and PD-98059 attenuated POVPC-induced suppression of smooth muscle ( SM) α-actin and SM-myosin heavy chain. POVPC also induced expression of Krüppel-like factor 4 (Klf4). Chromatin immunoprecipitation assays revealed that POVPC caused simultaneous binding of Elk-1 and Klf4 to the promoter region of the SM α-actin gene. Moreover, coimmunoprecipitation assays showed a physical interaction between Elk-1 and Klf4. Results in Klf4-null SMCs showed that blockade of both Klf4 induction and Elk-1 phosphorylation completely abolished POVPC-induced suppression of SMC differentiation marker genes. POVPC-induced suppression of SMC differentiation marker genes was also accompanied by hypoacetylation of histone H4 at the SM α-actin promoter, which was mediated by the recruitment of histone deacetylases (HDACs), HDAC2 and HDAC5. Coimmunoprecipitation assays showed that Klf4 interacted with HDAC5. Results provide evidence that Klf4, Elk-1, and HDACs coordinately mediate POVPC-induced suppression of SMC differentiation marker genes.
The extreme COOH terminus of the retinoblastoma tumor suppressor protein pRb is required for phosphorylation on Thr-373 and activation of E2F
Authors: Gorges Laura L. , Lents Nathan H. , Baldassare Joseph J.
Published: September 2008

The retinoblastoma protein pRb plays a pivotal role in G1- to S-phase cell cycle progression and is among the most frequently mutated gene products in human cancer. Although much focus has been placed on understanding how the A/B pocket and COOH-terminal domain of pRb cooperate to relieve transcriptional repression of E2F-responsive genes, comparatively little emphasis has been placed on the function of the NH2-terminal region of pRb and the interaction of the multiple domains of pRb in the full-length context. Using “reverse mutational analysis” of RbΔCDK (a dominantly active repressive allele of Rb), we have previously shown that restoration of Thr-373 is sufficient to render RbΔCDK sensitive to inactivation via cyclin-CDK phosphorylation. This suggests that the NH2-terminal region plays a more critical role in pRb regulation than previously thought. In the present study, we have expanded this analysis to include additional residues in the NH2-terminal region of pRb and further establish that the mechanism of pRb inactivation by Thr-373 phosphorylation is through the dissociation of E2F. Most surprisingly, we further have found that removal of the COOH-terminal domain of either RbΔCDK+T373 or wild-type pRb yields a functional allele that cannot be inactivated by phosphorylation and is repressive of E2F activation and S-phase entry. Our data demonstrate a novel function for the NH2-terminal domain of pRb and the necessity for cooperation of multiple domains for proper pRb regulation.
Rapamycin does not improve insulin sensitivity despite elevated mammalian target of rapamycin complex 1 activity in muscles ofob/obmice
Authors: Miller Andrew M. , Brestoff Jonathan R. , Phelps Charles B. , Berk E. Zachary , Reynolds Thomas H.
Published: September 2008

Studies of cultured cells have indicated that the mammalian target of rapamycin complex 1 (mTORC1) mediates the development of insulin resistance. Because a role for mTORC1 in the development of skeletal muscle insulin resistance has not been established, we studied mTORC1 activity in skeletal muscles of ob/ob (OB) mice and wild-type (WT) mice. In vivo insulin action was assessed in muscles of mice 15 min following an intraperitoneal injection of insulin or an equivalent volume of saline. In the basal state, the phosphorylation of S6K on Thr389, mTOR on Ser2448, and PRAS40 on Thr246were increased significantly in muscles from OB mice compared with WT mice. The increase in basal mTORC1 signaling was associated with an increase in basal PKB phosphorylation on Thr308and Ser473. In the insulin-stimulated state, no differences existed in the phosphorylation of S6K on Thr389, but PKB phosphorylation on Thr308and Ser473was significantly reduced in muscles of OB compared with WT mice. Despite elevated mTORC1 activity in OB mice, rapamycin treatment did not improve either glucose tolerance or insulin tolerance. These results indicate that the insulin resistance of OB mice is mediated, in part, by factors other than mTORC1.
Thermal tolerance of contractile function in oxidative skeletal muscle: no protection by antioxidants and reduced tolerance with eicosanoid enzyme inhibition
Authors: Oliver S. Ryan , Wright Valerie P. , Parinandi Narasimham , Clanton Thomas L.
Published: September 2008

Mechanisms for the loss of muscle contractile function in hyperthermia are poorly understood. This study identified the critical temperature, resulting in a loss of contractile function in isolated diaphragm (thermal tolerance), and then tested the hypotheses 1) that increased reactive oxygen species (ROS) production contributes to the loss of contractile function at this temperature, and 2) eicosanoid metabolism plays an important role in preservation of contractile function in hyperthermia. Contractile function and passive force were measured in rat diaphragm bundles during and after 30 min of exposure to 40, 41, 42 or 43°C. Between 40 and 42°C, there were no effects of hyperthermia, but at 43°C, a significant loss of active force and an increase in passive force were observed. Inhibition of ROS with the antioxidants, Tiron or Trolox, did not inhibit the loss of contractile force at 43°C. Furthermore, treatment with dithiothreitol, a thiol (-SH) reducing agent, did not reverse the effects of hyperthermia. A variety of global lipoxygenase (LOX) inhibitors further depressed force during 43°C and caused a significant loss of thermal tolerance at 42°C. Cyclooxygenase (COX) inhibitors also caused a loss of thermal tolerance at 42°C. Blockage of phospholipase with phospholipase A2inhibitors, bromoenol lactone or arachidonyltrifluoromethyl ketone failed to significantly prevent the loss of force at 43°C. Overall, these data suggest that ROS do not play an apparent role in the loss of contractile function during severe hyperthermia in diaphragm. However, functional LOX and COX enzyme activities appear to be necessary for maintaining normal force production in hyperthermia.
Photoperiod alters phase difference between activity onset in vivo and mPer2::luc peak in vitro
Authors: Mickman Carl T. , Stubblefield Jeremy S. , Harrington Mary E. , Nelson Dwight E.
Published: September 2008

Photoperiod is a significant modulator of behavior and physiology for many organisms. In rodents changes in photoperiod are associated with changes in circadian period and photic resetting of circadian pacemakers. Utilizing rhythms of in vivo behavior and in vitro mPer2::luc expression, we investigated whether different entrainment photoperiods [light:dark (L:D) 16:8 and L:D 8:16] alter the period or phase relationships between these rhythms and the entraining light cycle in Per2::luc C57BL/6J mice. We also tested whether mPer2::luc rhythms differs in anterior and posterior suprachiasmatic nucleus (SCN) slices. Our results demonstrate that photoperiod significantly changes the timing of the mPer2::luc peak relative to the time of light offset and the activity onset in vivo. In both L:D 8:16 and L:D 16:8 the mPer2::luc peak maintained a more stable phase relationship to activity offset, while altering the phase relationship to activity onset. After the initial cycle in culture, the period, phase, and peaks per cycle were not significantly different for anterior vs. posterior SCN slices taken from animals within one photoperiod. After short-photoperiod treatment, anterior SCN slices showed increased-amplitude Per2::luc waveforms and posterior SCN slices showed shorter-duration peak width. Finally, the SCN tissue in vitro did not demonstrate differences in period attributable to photoperiod pretreatment, indicating that period aftereffects observed in behavioral rhythms after long- and short-day photoperiods are not sustained in Per2::luc rhythms in vitro. The change in phase relationship to activity onset suggests that Per2::luc rhythms in the SCN may track activity offset rather than activity onset. The reduced amplitude rhythms following long-photoperiod treatment may represent a loss of coupling of component oscillators.
WNK3 positively regulates epithelial calcium channels TRPV5 and TRPV6 via a kinase-dependent pathway
Authors: Zhang Wei , Na Tao , Peng Ji-Bin
Published: September 2008

WNK3, a member of the With No Lysine (K) family of protein serine/threonine kinases, was shown to regulate members of the SLC12A family of cation-chloride cotransporters and the renal outer medullary K+ channel ROMK and Cl− channel SLC26A9. To evaluate the effect of WNK3 on TRPV5, a renal epithelial Ca2+ channel that serves as a gatekeeper for active Ca2+ reabsorption, WNK3 and TRPV5 were coexpressed in Xenopus laevis oocytes and the function and expression of TRPV5 were subsequently examined. An 82.7 ± 7.1% increase in TRPV5-mediated Ca2+ uptake was observed when WNK3 was coexpressed. A similar increase in TRPV5-mediated Na+ current was observed with the voltage-clamp technique. WNK3 also enhanced Ca2+ influx and Na+ current mediated by TRPV6, which is the closest homolog of TRPV5 that mediates active intestinal Ca2+ absorption. The kinase domain of WNK3 alone was sufficient to increase TRPV5-mediated Ca2+ transport, and the positive regulatory effect was abolished by the kinase-inactive D294A mutation in WNK3, indicating a kinase-dependent mechanism. The complexly glycosylated TRPV5 that appears at the plasma membrane was increased by WNK3. The exocytosis of TRPV5 was increased by WNK3, and the effect of WNK3 on TRPV5 was abolished by the microtubule inhibitor colchicine. The increased plasma membrane expression of TRPV5 was likely due to the enhanced delivery of mature TRPV5 to the plasma membrane from its intracellular pool via the secretory pathway. These results indicate that WNK3 is a positive regulator of the transcellular Ca2+ transport pathway.
Accelerated senescence in the kidneys of patients with type 2 diabetic nephropathy
Authors: Verzola Daniela , Gandolfo Maria Teresa , Gaetani Gianfranco , Ferraris Annamaria , Mangerini Rosa , Ferrario Franco , Villaggio Barbara , Gianiorio Fabio , Tosetti Fanny , Weiss Ursula , Traverso Paolo , Mji Mariano , Deferrari Giacomo , Garibotto Giacomo
Published: September 2008

We examined the hypothesis that senescence represents a proximate mechanism by which the kidney is damaged in type 2 diabetic nephropathy (DN). As a first step, we studied whether the senescence-associated β-galactosidase (SA-β-Gal) and the cell cycle inhibitor p16INK4Aare induced in renal biopsies from patients with type 2 DN. SA-β-Gal staining was approximately threefold higher ( P < 0.05) than in controls in the tubular compartment of diabetic kidneys and correlated directly with body mass index and blood glucose. P16INK4Aexpression was significantly increased in tubules ( P < 0.005) and in podocytes ( P = 0.04). Nuclear p16INK4Ain glomeruli was associated with proteinuria ( P < 0.002), while tubular p16INK4Awas directly associated with body mass index, LDL cholesterol, and HbA1c ( P < 0.001–0.05). In a parallel set of experiments, proximal tubule cells passaged under high glucose presented a limited life span and an approximately twofold increase in SA-β-Gal and p16INK4Aprotein. Mean telomere lengths decreased ∼20% as an effect of replicative senescence. In addition, mean telomere decreased further by ∼30% in cells cultivated under high glucose. Our results show that the kidney with type 2 diabetic nephropathy displays an accelerated senescent phenotype in defined renal cell types, mainly tubule cells and, to a lesser extent, podocytes. A similar senescent pattern was observed when proximal tubule cell cultures where incubated under high-glucose media. These changes are associated with shortening tubular telomere length in vitro. These findings indicate that diabetes may boost common pathways involving kidney cell senescence, thus reinforcing the role of the metabolic syndrome on biological aging of tissues.
Hand Interactions in Rapid Grip Force Adjustments Are Independent of Object Dynamics
Authors: White Olivier , Dowling Noreen , Bracewell R. Martyn , Diedrichsen Jörn
Published: September 2008

Object manipulation requires rapid increase in grip force to prevent slippage when the load force of the object suddenly increases. Previous experiments have shown that grip force reactions interact between the hands when holding a single object. Here we test whether this interaction is modulated by the object dynamics experienced before the perturbation of the load force. We hypothesized that coupling of grip forces should be stronger when holding a single object than when holding separate objects. We measured the grip force reactions elicited by unpredictable load perturbations when participants were instructed to hold one single or two separate objects. We simulated these objects both visually and dynamically using a virtual environment consisting of two robotic devices and a calibrated stereo display. In contrast to previous studies, the load forces arising from a single object could be uncoupled at the moment of perturbation, allowing for a pure measurement of grip force coupling. Participants increased grip forces rapidly (onset ∼70 ms) in response to perturbations. Grip force increases were stronger when the load force on the other hand also increased. No such coupling was present in the reaction of the arms to the load force increase. Surprisingly, however, the grip force interaction did not depend on the nature of the manipulated object. These results show fast obligatory coupling of bimanual grip force responses. Although this coupling may play a functional role for providing stability in bimanual object manipulation, it seems to constitute a relatively hard-wired modulation of a reflex.
Theoretical Analysis of Thermodynamic Effect of Cavitation in Cryogenic Inducer Using Singularity Method
Authors: Watanabe S. , Furukawa A. , Yoshida Y.
Published: September 2008

Vapor production in cavitation extracts the latent heat of
evaporation from the surrounding liquid, which decreases the local temperature, and
hence the local vapor pressure in the vicinity of cavity. This is called thermodynamic/thermal
effect of cavitation and leads to the good suction performance of cryogenic turbopumps.
We have already established the simple analysis of partially cavitating flow with the
thermodynamic effect, where the latent heat extraction and the heat transfer between
the cavity and the ambient fluid are taken into account. In the present study, we carry
out the analysis for cavitating inducer and compare it with the experimental data available
from literatures using Freon R‐114 and liquid nitrogen. It is found that the present analysis
can simulate fairly well the thermodynamic effect of cavitation and some modification of the
analysis considering the real fluid properties, that is, saturation characteristic, is favorable for
more qualitative agreement.
On the Optimality of (s, S) Inventory Policies: A Quasivariational Approach
Authors: Benkherouf Lakdere
Published: September 2008

This paper revisits the classical discrete‐time stationary inventory model. A new proof, based on the theory of
quasivariational inequality (QVI), of the optimality of (s, S) policy
is presented. This proof reveals a number of interesting properties of the optimal cost function. Further, the proof could be used as a tutorial for applications of QVI to inventory control.
Potential of Peroxisome Proliferator‐Activated Receptor Gamma Antagonist Compounds as Therapeutic Agents for a Wide Range of Cancer Types
Authors: Burton Jack D. , Goldenberg David M. , Blumenthal Rosalyn D.
Published: September 2008

PPARγ is a therapeutic target that has been exploited for
treatment of type II diabetes mellitus (T2DM) with agonist drugs.
Since PPARγ is expressed by many hematopoietic, mesodermal and
epithelial cancers, agonist drugs were tested and shown to have
both preclinical and clinical anticancer activities. While
preclinical activity has been observed in many cancer types,
clinical activity has been observed only in pilot and phase II
trials in liposarcoma and prostate cancer. Most studies address
agonist compounds, with substantially fewer reports on anticancer
effects of PPARγ antagonists. In cancer model systems, some
effects of PPARγ agonists were not inhibited by PPARγ antagonists,
suggesting noncanonical or PPARγ‐independent mechanisms. In
addition, PPARγ antagonists, such as T0070907 and GW9662, have
exhibited antiproliferative effects on a broad range of
hematopoietic and epithelial cell lines, usually with greater
potency than agonists. Also, additive antiproliferative effects
of combinations of agonist plus antagonist drugs were observed.
Finally, there are preclinical in vivo data showing that
antagonist compounds can be administered safely, with favorable
metabolic effects as well as antitumor effects. Since PPARγ
antagonists represent a new drug class that holds promise as a
broadly applicable therapeutic approach for cancer treatment, it
is the subject of this review.
Fast Track Open Partial Nephrectomy: Reduced Postoperative Length of Stay with a Goal-Directed Pathway Does Not Compromise Outcome
Authors: Chughtai Bilal , Abraham Christa , Finn Daniel , Rosenberg Stuart , Yarlagadda Bharat , Perrotti Michael
Published: September 2008

Introduction. The aim of this study is to examine the feasibility of reducing postoperative hospital stay following open partial nephrectomy through the implementation of a goal directed clinical management pathway.Materials and Methods. A fast track clinical pathway for open partial nephrectomy was introduced in July 2006 at our institution. The pathway has daily goals and targets discharge for all patients on the 3rd postoperative day (POD). Defined goals are (1) ambulation and liquid diet on the evening of the operative day; (2) out of bed (OOB) at least 4 times on POD 1; (3) removal of Foley catheter on the morning of POD 2; (4) removal of Jackson Pratt drain on the afternoon of POD 2; (4) discharge to home on POD 3. Patients and family are instructed in the fast track protocol preoperatively. Demographic data, tumor size, length of stay, and complications were captured in a prospective database, and compared to a control group managed consecutively immediately preceding the institution of the fast track clinical pathway.Results. Data on 33 consecutive patients managed on the fast track clinical pathway was compared to that of 25 control patients. Twenty two (61%) out of 36 fast track patients and 4 (16%) out of 25 control patients achieved discharge on POD 3. Overall, fast track patients had a shorter hospital stay than controls (median, 3 versus 4 days;P= .012). Age (median, 55 versus 57 years), tumor size (median, 2.5 versus 2.5 cm), readmission within 30 days (5.5% versus 5.1%), and complications (10.2% versus 13.8%) were similar in the fast track patients and control, respectively.Conclusions. In the present series, a fast track clinical pathway after open partial nephrectomy reduced the postoperative length of hospital stay and did not appear to increase the postoperative complication rate.
Suppression of Performance Curve Instability of an Axial‐Flow Pump by Using a Double‐Inlet‐Nozzle
Authors: Pérez Flores P. , Kosyna G. , Wulff D.
Published: September 2008

It has been shown that the sudden decrease of pump head in an axial flow pump caused by stall can be overcome by means of casing treatment. Flat axial grooves in front of the impeller break the swirl of the near‐casing backflow. The disadvantage of this method is strong cavitation at the inlet of the grooves for flow rates below the stall point. In this paper another improved method to stabilize the performance curve will be presented, using a double‐inlet‐nozzle. At the onset of stall the initial near‐casing backflow with its high swirl is lead off into the gap between both nozzles. At design conditions this double‐inlet‐nozzle is working as an injector, supporting the near‐casing‐inflow. The function of the double‐inlet‐nozzle is demonstrated by PIV‐measurements.
Reinduction of Bevacizumab in Combination with Pegylated Liposomal Doxorubicin in a Patient with Recurrent Glioblastoma Multiforme Who Progressed on Bevacizumab/Irinotecan
Authors: Almubarak Mohammed , Newton Michael , Altaha Ramin
Published: September 2008

Glioblastoma multiforme (GBM) carries a dismal prognosis despite the current standard of multimodality treatments. Recent studies showed promising results to a regimen consisting of a VEGF inhibitor, (bevacizumab) and a topoisomerase I inhibitor (irinotecan) [BI] in recurrent GBM. However, those patients with GBM who progress on BI will succumb to their disease generally in a very short period of time. We report a case of a 56-year-old male patient with GBM who declined surgical resection and received chemoradiation with temozolomide. This treatment was withheld secondary to significant thrombocytopenia. Subsequently, he achieved stable disease for 10 months with a regimen consisting of thalidomide and tamoxifen before progressing. This was followed by bevacizumab with irinotecan [BI], for which he had a significant partial response for 8 months with subsequent progression. Reinducing the patient with bevacizumab in combination with a pegylated liposomal doxorubicin [PLD] (a topoisomerase II inhibitor) demonstrated antitumor activity with significant shrinkage of contrast enhancing mass and peritumoral edema.
A Simple Scheme for Belief Propagation Decoding of BCH and RS Codes in Multimedia Transmissions
Authors: Baldi Marco , Chiaraluce Franco
Published: September 2008

Classic linear block codes, like Bose-Chaudhuri-Hocquenghem (BCH) and Reed-Solomon (RS) codes, are widely used in multimedia transmissions, but their soft-decision decoding still represents an open issue. Among the several approaches proposed for this purpose, an important role is played by the iterative belief propagation principle, whose application to low-density parity-check (LDPC) codes permits to approach the channel capacity. In this paper, we elaborate a new technique for decoding classic binary and nonbinary codes through the belief propagation algorithm. We focus on RS codes included in the recent CDMA2000 standard, and compare the proposed technique with the adaptive belief propagation approach, that is able to ensure very good performance but with higher complexity. Moreover, we consider the case of long BCH codes included in the DVB-S2 standard, for which we show that the usage of “pure” LDPC codes would provide better performance.
A New Instability Result to Nonlinear Vector Differential Equations of Fifth Order
Authors: Tunç Cemil , Karta Melike
Published: September 2008

By constructing a Lyapunov function, a new instability result is established,
which guarantees that the trivial solution of a certain nonlinear vector differential equation of
the fifth order is unstable. An example is also given to illustrate the importance of the result
obtained. By this way, our findings improve an instability result related to a scalar differential
equation in the literature to instability of the trivial solution to the afore‐mentioned differential
equation.
Reproductive Biology in Egg-Laying Mammals
Authors: Grützner F. , Nixon B. , Jones R.C.
Published: September 2008

The duck-billed platypus and short-beaked echidna are iconic species in Australia. Their morphology and physiology have puzzled scientists all over the world for more than 200 years. Recent genetic studies, particularly the platypus whole-genome sequencing project, have revealed the molecular basis of some of the extraordinary characteristics of monotremes. This and other works demonstrate the great value of research on our most distantly related mammalian relatives for comparative genomics and developmental biology. In this review we focus on the reproductive biology of monotremes and discuss works that unravel genes involved in lactation, testicular descent, gamete biology and fertilization, and early development. In addition we discuss works on the evolution of the complex sex chromosome system in platypus and echidna, which has also significant impact on our general understanding of mammalian sex chromosomes and sex determination.
Peritubular Myoid Cells Are Not the Migrating Population Required for Testis Cord Formation in the XY Gonad
Authors: Cool J. , Carmona F.D. , Szucsik J.C. , Capel B.
Published: September 2008

Cell migration is one of the earliest events required for development of the testis. Migration occurs only in XY gonads downstream of Sry expression and is required for the subsequent epithelialization of testis cords. Using organ culture experiments and tissue recombination, we and others speculated that peritubular myoid (PTM) cells were among the migratory cells and were likely the cell type required for cord formation. However, because no unique marker was found for PTM cells, their positive identification during or after migration remained unclear. α-Smooth Muscle Actin (αSma; approved gene symbol Acta2), a classic marker of adult PTM cells,is expressed broadly in testis interstitial cells at E12.5, and becomes highly enriched in PTM cells by E15.5–16.5. We used a novel transgenic line expressingEYFP under the control of an αSma promoter to determine whether αSma-EYFP positive cellsmigrate into the gonad. Surprisingly, mesonephroi expressing αSma-EYFP do not contribute any EYFP positive cells to XY gonads when used as donors in recombination cultures. These results indicate that αSma-EYFP cells do not migrate into the gonad during the critical window of sex determination and cannot be the migrating cell type required for testis cord formation. Our results suggest that PTM cells, and most other interstitial lineages, with the exception of endothelial cells, are induced within the gonad. These experiments suggest that endothelial cells are the migrating cell type required for epithelialization of testis cords.
Attempt to Rescue Sex-Reversal by Transgenic Expression of the PISRT1 Gene in XX PIS–/– Goats
Authors: Boulanger L. , Kocer A. , Daniel N. , Pannetier M. , Chesné P. , Heyman Y. , Renault L. , Mandon-Pépin B. , Chavatte-Palmer P. , Vignon X. , Vilotte J.-L. , Cotinot C. , Renard J.-P. , Pailhoux E.
Published: September 2008

The Polled Intersex Syndrome (PIS mutation) in goats leads to an absence of horn and to an early sex-reversal of the XX gonads. This mutation is a deletion of an 11.7-kb DNA fragment showing a tissue-specific regulatory activity. Indeed, in XX PIS–/– gonads the deletion of PIS leads to the transcriptional extinction of at least 3 neighboring genes, FOXL2, PFOXic and PISRT1. Among them, only FOXL2 is a ‘classical’ gene, encoding a highly conserved transcription factor. On the other hand, knock-out of Foxl2 in mice results in an early blocking of follicle formation without sex-reversal. This phenotype discrepancy leads to two hypotheses, either FOXL2 is responsible for XX sex-reversal in goat assuming distinct functions of its protein during ovarian differentiation in different mammals, or other PIS-regulated genes are involved. To assess the second possibility, PISRT1 expression was constitutively restored in XX PIS–/– gonads. Six transgenic fetuses were obtained by nuclear transfer and studied at 2 developmental stages, 41 and 46 days post-reconstruction. The gonads of these fetuses appear phenotypically identical to those of cloned non-transgenic controls. Conclusively, this result argues for FOXL2 being responsible for the PIS gonad-associated phenotype. Its invalidation in goat will help to better understand this complex syndrome.
Expression Profiles of SRY and SOX9 in Rabbit Gonads: The Classical Model of Mammalian Sex Differentiation
Authors: Díaz-Hernández V. , León del Río A. , Zamora M. , Merchant-Larios H.
Published: September 2008

Sex determination in mammalian gonads depends on the concerted action of SRY and SOX at the genital ridge. Although most research on the mechanisms involved in sex determination has been done in mice, the study of non-model organisms may indicate the extent of the generalizations currently based on model systems. The present study investigated the correlation between SRY/SOX9 expression patterns and the process of morphogenesis in the developing gonad of the rabbit. In males, the onset of SRY/SOX9 expression closely followed the establishment of undifferentiated genital ridges at 13 to 14 dpc. In contrast to mouse, real-time PCR in the rabbit revealed that levels of SRY/ SOX9 peak after the onset of seminiferous cord formation, while in mouse this occurs before. Furthermore, rabbit gonads maintain low levels of SRY and SOX9 expression in male and female gonads, respectively. In situ hybridization suggests that cells of the mesonephric Bowman capsules, which do not express SRY, may become SOX9-expressing pre-Sertoli cells during the long period of seminiferous cord formation in the rabbit. In contrast to mouse, current results indicate that the patterns of SRY/SOX9 expression associated with the process of gonadal morphogenesis in rabbit appear similar to those of other mammals, including humans.
Fetal Cardiac Diagnosis and Its Influence on the Pregnancy and Newborn – A Tertiary Centre Experience
Authors: Yeu B.K. , Chalmers R. , Shekleton P. , Grimwade J. , Menahem S.
Published: September 2008

Objectives: To evaluate the impact of an abnormal fetal cardiac scan on the management of the pregnancy and the outcome of the newborn. Methods: We reviewed all pregnancies that were referred to the Fetal Cardiac Unit for assessment to determine if the finding of a cardiac abnormality influenced the pregnancy and fetus, timing and mode of delivery, the treatment and outcome of the newborn. Diagnoses were confirmed by echocardiography following the baby’s delivery. Results: Between January 2005 and July 2006, there were 251 detailed fetal cardiac scans carried out on at risk pregnancies or those with suspected abnormal scans in 127 fetuses. Seven of the 92 mothers with abnormal fetal cardiac scans opted for termination. Two were successfully treated during the pregnancy for hydrops fetalis arising from a tachyarrhythmia. One was induced early because of deterioration of fetal well-being and increasing cardiac size. Twenty-six infants required a prostaglandin infusion prior to surgery. Two required intensive care for associated malformations. There were 24 survivors following complex surgery, and 2 deaths. Two infants with severe tricuspid valve incompetence from a dysplastic valve died, one associated with a septicaemia and the other where surgery was delayed because of prematurity and low birth weight. There was no maternal morbidity or mortality. Conclusions: Early detection of fetal cardiac malformation allows for careful counselling of the parents, ongoing antenatal review with a planned site and timing of delivery, and anticipatory postnatal care for optimum outcomes. The importance of careful screening is emphasized to allow for referral of mothers with potentially abnormal scans to an appropriate tertiary centre for confirmation and management.