bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficiency Improvement of Centrifugal Reverse Pumps
Authors: Derakhshan Shahram , Mohammadi Bijan , Nourbakhsh Ahmad
Published: January 2009

Pumps as turbines have been successfully applied in a wide range of small hydrosites in the world. Since the overall efficiency of these machines is lower than the overall efficiency of conventional turbines, their application in larger hydrosites is not economical. Therefore, the efficiency improvement of reverse pumps is essential. In this study, by focusing on a pump impeller, the shape of blades was redesigned to reach a higher efficiency in turbine mode using a gradient based optimization algorithm coupled by a 3D Navier–Stokes flow solver. Also, another modification was done by rounding the blades’ leading edges and hub/shroud interface in turbine mode. After each modification, a new impeller was manufactured and tested in the test rig. The efficiency was improved in all measured points by the optimal design of the blade and additional modification as the rounding of the blade’s profile in the impeller inlet and hub/shroud inlet edges in turbine mode. Experimental results confirmed the numerical efficiency improvement in all measured points. This study illustrated that the efficiency of the pump in reverse operation can be improved just by impeller modification.
Incubation Time and Cavitation Erosion Rate of Work-Hardening Materials
Authors: Franc Jean-Pierre
Published: January 2009

A phenomenological analysis of the cavitation erosion process of ductile materials is proposed. On the material side, the main parameters are the thickness of the hardened layer together with the conventional yield strength and ultimate strength. On the fluid side, the erosive potential of the cavitating flow is described in a simplified way using three integral parameters: rate, mean amplitude, and mean size of hydrodynamic impact loads. Explicit equations are derived for the computation of the incubation time and the steady-state erosion rate. They point out two characteristic scales. The time scale, which is relevant to the erosion phenomenon, is the covering time—the time necessary for the impacts to cover the material surface—whereas the pertinent length scale for ductile materials is the thickness of the hardened layer. The incubation time is proportional to the covering time with a multiplicative factor, which strongly depends on flow aggressiveness in terms of the mean amplitude of impact loads. As for the erosion rate under steady-state conditions, it is scaled by the ratio of the thickness of hardened layers to the covering time with an additional dependence on flow aggressiveness, too. The approach is supported by erosion tests conducted in a cavitation tunnel at a velocity of 65 m/s on stainless steel 316 L. Flow aggressiveness is inferred from pitting tests. The same model of material response that was used for mass loss prediction is applied to derive the original hydrodynamic impact loads due to bubble collapses from the geometric features of the pits. Long duration tests are performed in order to determine experimentally the incubation time and the mean depth of penetration rate and to validate the theoretical approach.
Strong Release of Methane on Mars in Northern Summer 2003
Authors: Mumma Michael J. , Villanueva Geronimo L. , Novak Robert E. , Hewagama Tilak , Bonev Boncho P. , DiSanti Michael A. , Mandell Avi M. , Smith Michael D.
Published: January 2009

Living systems produce more than 90% of Earth's atmospheric methane; the balance is of geochemical origin. On Mars, methane could be a signature of either origin. Using high-dispersion infrared spectrometers at three ground-based telescopes, we measured methane and water vapor simultaneously on Mars over several longitude intervals in northern early and late summer in 2003 and near the vernal equinox in 2006. When present, methane occurred in extended plumes, and the maxima of latitudinal profiles imply that the methane was released from discrete regions. In northern midsummer, the principal plume contained ∼19,000 metric tons of methane, and the estimated source strength (≥0.6 kilogram per second) was comparable to that of the massive hydrocarbon seep at Coal Oil Point in Santa Barbara, California.
Effects of Genetic Perturbation on Seasonal Life History Plasticity
Authors: Wilczek Amity M. , Roe Judith L. , Knapp Mary C. , Cooper Martha D. , Lopez-Gallego Cristina , Martin Laura J. , Muir Christopher D. , Sim Sheina , Walker Alexis , Anderson Jillian , Egan J. Franklin , Moyers Brook T. , Petipas Renee , Giakountis Antonis , Charbit Erika , Coupland George , Welch Stephen M. , Schmitt Johanna
Published: January 2009

Like many species, the model plant
Arabidopsis thaliana
exhibits multiple different life histories in natural environments. We grew mutants impaired in different signaling pathways in field experiments across the species' native European range in order to dissect the mechanisms underlying this variation. Unexpectedly, mutational loss at loci implicated in the cold requirement for flowering had little effect on life history except in late-summer cohorts. A genetically informed photothermal model of progression toward flowering explained most of the observed variation and predicted an abrupt transition from autumn flowering to spring flowering in late-summer germinants. Environmental signals control the timing of this transition, creating a critical window of acute sensitivity to genetic and climatic change that may be common for seasonally regulated life history traits.
The Formation of Massive Star Systems by Accretion
Authors: Krumholz Mark R. , Klein Richard I. , McKee Christopher F. , Offner Stella S. R. , Cunningham Andrew J.
Published: January 2009

Massive stars produce so much light that the radiation pressure they exert on the gas and dust around them is stronger than their gravitational attraction, a condition that has long been expected to prevent them from growing by accretion. We present three-dimensional radiation-hydrodynamic simulations of the collapse of a massive prestellar core and find that radiation pressure does not halt accretion. Instead, gravitational and Rayleigh-Taylor instabilities channel gas onto the star system through nonaxisymmetric disks and filaments that self-shield against radiation while allowing radiation to escape through optically thin bubbles. Gravitational instabilities cause the disk to fragment and form a massive companion to the primary star. Radiation pressure does not limit stellar masses, but the instabilities that allow accretion to continue lead to small multiple systems.
Sensing Chromosome Bi-Orientation by Spatial Separation of Aurora B Kinase from Kinetochore Substrates
Authors: Liu Dan , Vader Gerben , Vromans Martijn J. M. , Lampson Michael A. , Lens Susanne M. A.
Published: January 2009

Successful cell division requires that chromosomes attach to opposite poles of the mitotic spindle (bi-orientation). Aurora B kinase regulates chromosome-spindle attachments by phosphorylating kinetochore substrates that bind microtubules. Centromere tension stabilizes bi-oriented attachments, but how physical forces are translated into signaling at individual centromeres is unknown. Using fluorescence resonance energy transfer–based biosensors to measure localized phosphorylation dynamics in living cells, we found that phosphorylation of an Aurora B substrate at the kinetochore depended on its distance from the kinase at the inner centromere. Furthermore, repositioning Aurora B closer to the kinetochore prevented stabilization of bi-oriented attachments and activated the spindle checkpoint. Thus, centromere tension can be sensed by increased spatial separation of Aurora B from kinetochore substrates, which reduces phosphorylation and stabilizes kinetochore microtubules.
An incidental enterocolic lymphocytic phlebitis pattern is seen commonly in the rectal stump of patients with diversion colitis superimposed on inflammatory bowel disease
Authors: Chetty R , Hafezi S , Montgomery E
Published: January 2009

Aims:

Enterocolic lymphocytic phlebitis (ELP) is an uncommon cause of bowel pathology and most frequently results in ischaemia. It is characterised by an artery-sparing, venulocentric lymphoid infiltrate that causes a phlebitis and vascular compromise. Rare cases of ELP have been encountered with lymphocytic colitis in the absence of ischaemic bowel change. The present study examined the occurrence of ELP in the setting of diversion colitis and inflammatory bowel disease, as well as in random colectomy specimens.

Methods:

The study cohort comprised the following: 26 completion proctectomy specimens for ulcerative colitis with superimposed diversion colitis in the rectal stump; 3 colectomy specimens for Crohn disease with diversion colitis; 6 colectomy specimens for adenocarcinoma and/or diverticular disease with diversion colitis; 34 resection specimens with ulcerative colitis only; 19 with Crohn disease only; and 100 random colon resection specimens for adenocarcinoma, adenoma, diverticular disease and ischaemia.

Results:

ELP was present in 18 of the 26 ulcerative colitis cases with diversion colitis, 3/3 Crohn disease cases with diversion colitis, 1/6 cases of diverticular disease with diversion colitis, 6/34 cases of ulcerative colitis without diversion, 2/19 Crohn disease cases without diversion colitis, and only 1 of 100 colectomy cases without inflammatory bowel disease or diversion colitis.

Conclusion:

ELP occurs most frequently in cases that have been diverted for inflammatory bowel disease. Fewer cases of ELP were noted in cases of inflammatory bowel disease in the absence of diversion colitis. It is postulated that altered bowel flora and immune dysregulation may be pivotal in the causation of this association.
Repeated respiratory hospital encounters among children with asthma and residential proximity to traffic
Authors: Chang J , Delfino R J , Gillen D , Tjoa T , Nickerson B , Cooper D
Published: January 2009

Objective:

The prevalence of adverse respiratory outcomes among children has been frequently associated with measurements of traffic-related exposures, and other data suggest asthma severity is worsened with residence near heavy traffic. We examined the association between neighbourhood traffic burden and repeated acute respiratory illnesses that required emergency department visits and/or hospitalisation for children with a primary or secondary diagnosis of asthma (89% acute bronchitis or pneumonia).

Methods:

This is a hospital-based longitudinal study of a southern California urban catchment area around two adjacent children’s hospitals. Subjects’ home addresses were geocoded and linked to nearby traffic data. Recurrent event proportional hazard analysis was used to estimate the hazard of repeated hospital encounters.

Results:

We found living within 300 metres of arterial roads or freeways increased risk of repeated hospital encounters in 3297 children age 18 years or less. At highest risk were children in the top quintile of traffic density (HR = 1.21; 95% CL 0.99 to 1.49) and those who had 750 metres or more of arterial road and freeway length within 300 metres of their residence (HR = 1.18; 95% CL 0.99 to 1.41). Associations between repeated hospital encounters and residence near heavy traffic were stronger in females than males and in children without insurance or who required government sponsored insurance than children with private insurance. The gender disparity was most notable among infants (age 0) and children ages 6–18 years.

Conclusions:

Results suggest exposure to traffic-related air pollution increases asthma severity as indicated by hospital utilisation. The finding in infants suggests this is an especially vulnerable population, although the validity of asthma diagnosis at this age is unknown. Females and children who do not have private insurance may also be more vulnerable to air pollution from traffic.
Mobile phone base stations and adverse health effects: phase 2 of a cross-sectional study with measured radio frequency electromagnetic fields
Authors: Berg-Beckhoff G , Blettner M , Kowall B , Breckenkamp J , Schlehofer B , Schmiedel S , Bornkessel C , Reis U , Potthoff P , Schüz J
Published: January 2009

Objective:

The aim of the cross-sectional study was to test the hypothesis that exposure to continuous low-level radio frequency electromagnetic fields (RF-EMFs) emitted from mobile phone base stations was related to various health disturbances.

Methods:

For the investigation people living mainly in urban regions were selected from a nationwide study in 2006. In total, 3526 persons responded to a questionnaire (response rate 85%). For the exposure assessment a dosimeter measuring different RF-EMF frequencies was used. Participants answered a postal questionnaire on how mobile phone base stations affected their health and they gave information on sleep disturbances, headaches, health complaints and mental and physical health using standardised health questionnaires. Information on stress was also collected. Multiple linear regression models were used with health outcomes as dependent variables (n = 1326).

Results:

For the five health scores used, no differences in their medians were observed for exposed versus non-exposed participants. People who attributed adverse health effects to mobile phone base stations reported significantly more sleep disturbances and health complaints, but they did not report more headaches or less mental and physical health. Individuals concerned about mobile phone base stations did not have different well-being scores compared with those who were not concerned.

Conclusions:

In this large population-based study, measured RF-EMFs emitted from mobile phone base stations were not associated with adverse health effects.
Isotopic homogeneity of breath CO2 from fasting and berry-eating polar bears: implications for tracing reliance on terrestrial foods in a changing Arctic
Authors: Hobson K. A. , Stirling I. , Andriashek D. S.
Published: January 2009

With a changing Arctic climate, it is important to know whether polar bears ( Ursus maritimus Phipps, 1774) can supplement their stored fat reserves by intake of terrestrial berries. Although polar bears are known to consume berries while on land, it has been difficult to quantify their relative dependence on stored adipose tissue and berry carbohydrates to meet their energy needs. We sampled breath CO2 from 300 bears fasting on land in western Hudson Bay during the open-water seasons of 1997 and 1998 and analyzed this breath for stable carbon isotope (δ13C) values. We found no difference in the bear breath δ13C values for bears known to have recently fed on berries and those that had not. The distribution of δ13C values was remarkably tight with average values ranging from –24.2‰ to –24.8‰ with no effect of age, sex, or year of capture. This result was counter to our simple isotopic discrimination model that predicted bears metabolizing adipose tissue derived from seals would have breath δ13C values close to –24.7‰ and those metabolizing berries exclusively would have values close to –32.6‰. If correct, our results suggests that the bears which had fed on berries while fasting on land received an insignificant amount of energetic benefit.
GAUSSIAN TYPE INTERACTING FOCK SPACES
Authors: LU YUN GANG
Published: January 2009

We prove in this paper that the vacuum expectation of any product of field operator of an interacting Fock space with the interactions λn's is driven by pair partitions if and only if each interaction λn is a linear combination of permutation operators.
Expression and subcellular localization of BNIP3 in hypoxic hepatocytes and liver stress
Authors: Metukuri Mallikarjuna R. , Beer-Stolz Donna , Namas Rajaie A. , Dhupar Rajeev , Torres Andres , Loughran Patricia A. , Jefferson Bahiyyah S. , Tsung Allan , Billiar Timothy R. , Vodovotz Yoram , Zamora Ruben
Published: January 2009

We have previously demonstrated that the Bcl-2/adenovirus EIB 19-kDa interacting protein 3 (BNIP3), a cell death-related member of the Bcl-2 family, is upregulated in vitro and in vivo in both experimental and clinical settings of redox stress and that nitric oxide (NO) downregulates its expression. In this study we sought to examine the expression and localization of BNIP3 in murine hepatocytes and in a murine model of hemorrhagic shock (HS) and ischemia-reperfusion (I/R). Freshly isolated mouse hepatocytes were exposed to 1% hypoxia for 6 h followed by reoxygenation for 18 h, and protein was isolated for Western blot analysis. Hepatocytes grown on coverslips were fixed for localization studies. Similarly, livers from surgically cannulated C57Bl/6 mice and from mice cannulated and subjected to 1–4 h of HS were processed for protein isolation and Western blot analysis. In hepatocytes, BNIP3 was expressed constitutively but was upregulated under hypoxic conditions, and this upregulation was countered by treatment with a NO donor. Surprisingly, BNIP3 was localized in the nucleus of normoxic hepatocytes, in the cytoplasm following hypoxia, and again in the nucleus following reoxygenation. Upregulation of BNIP3 partially required p38 MAPK activation. BNIP3 contributed to hypoxic injury in hepatocytes, since this injury was diminished by knockdown of BNIP3 mRNA. Hepatic BNIP3 was also upregulated in two different models of liver stress in vivo, suggesting that a multitude of inflammatory stresses can lead to the modulation of BNIP3. In turn, the upregulation of BNIP3 appears to be one mechanism of hepatocyte cell death and liver damage in these settings.
Mitochondrial DNA and gastrointestinal motor and sensory functions in health and functional gastrointestinal disorders
Authors: Camilleri Michael , Carlson Paula , Zinsmeister Alan R. , McKinzie Sanna , Busciglio Irene , Burton Duane , Zaki Essam A. , Boles Richard G.
Published: January 2009

Nerve, muscle, and inflammatory cells involved in gastrointestinal (GI) function have high-energy requirements and are affected in mitochondrial disorders. Familial aggregation of irritable bowel syndrome (IBS) frequently involves mothers and their children. Since mitochondrial DNA (mtDNA) is maternally inherited, mtDNA single nucleotide polymorphisms (SNPs) could confer risk to the development of IBS. The mtDNA SNPs, 16519C>T and 3010G>A, are associated with migraine and childhood cyclic vomiting syndrome. Our hypothesis is that these mtDNA SNPs are associated with functional GI disorders (FGIDs) and GI functions. The mt genome was first tested for the 7028C polymorphism (defining haplogroup H) in 699 patients or controls, and those with 7028C were further genotyped at 16519 and 3010. Phenotypes were based on symptoms (validated questionnaires and criteria) and GI physiology using validated motor and sensory studies. Constipation-predominant IBS and alternating constipation and diarrhea IBS are less prevalent in individuals with the 7028C mtDNA polymorphism than in individuals with 7028T. Conversely, 7028C is associated with higher maximum tolerated volume (lower satiation) compared with 7028T. Among those with 7028C, nonspecific abdominal pain (chronic abdominal pain or dyspepsia) was significantly associated with 3010A compared with 3010G (odds ratio 3.3, P = 0.02), and slower gastric emptying was statistically associated with 3010G. There were no significant associations of mtDNA genotypes tested and stomach volumes, small bowel or colonic transit, rectal compliance, and motor or sensory functions. Thus variation in mtDNA may be associated with satiation, gastric emptying, and possibly pain; further studies of mtDNA in appetite regulation and larger numbers of patients with FGIDs are warranted.
PPAR-α activation protects the type 2 diabetic myocardium against ischemia-reperfusion injury: involvement of the PI3-Kinase/Akt and NO pathway
Authors: Bulhak Aliaksandr A. , Jung Christian , Östenson Claes-Göran , Lundberg Jon O. , Sjöquist Per-Ove , Pernow John
Published: January 2009

Several clinical studies have shown the beneficial cardiovascular effects of fibrates in patients with diabetes and insulin resistance. The ligands of peroxisome proliferator-activated receptor-α (PPAR-α) reduce ischemia-reperfusion injury in nondiabetic animals. We hypothesized that the activation of PPAR-α would exert cardioprotection in type 2 diabetic Goto-Kakizaki (GK) rats, involving mechanisms related to nitric oxide (NO) production via the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. GK rats and age-matched Wistar rats (n ≥ 7) were given either 1) the PPAR-α agonist WY-14643 (WY), 2) dimethyl sulfoxide (DMSO), 3) WY and the NO synthase inhibitor NG-nitro-l-arginine (l-NNA), 4) l-NNA, 5) WY and the PI3K inhibitor wortmannin, or 6) wortmannin alone intravenously before a 35-min period of coronary artery occlusion followed by 2 h of reperfusion. Infarct size (IS), expression of endothelial NO synthase (eNOS), inducible NO synthase, and Akt as well as nitrite/nitrate were determined. The IS was 75 ± 3% and 72 ± 4% of the area at risk in the Wistar and GK DMSO groups, respectively. WY reduced IS to 56 ± 3% in Wistar ( P < 0.05) and to 46 ± 5% in GK rats ( P < 0.001). The addition of either l-NNA or wortmannin reversed the cardioprotective effect of WY in both Wistar (IS, 70 ± 5% and 65 ± 5%, respectively) and GK (IS, 66 ± 4% and 64 ± 4%, P < 0.05, respectively) rats. The expression of eNOS and eNOS Ser1177 in the ischemic myocardium from both strains was increased after WY. The expression of Akt, Akt Ser473, and Akt Thr308 was also increased in the ischemic myocardium from GK rats following WY. Myocardial nitrite/nitrate levels were reduced in GK rats ( P < 0.05). The results suggest that PPAR-α activation protects the type 2 diabetic rat myocardium against ischemia-reperfusion injury via the activation of the PI3K/Akt and NO pathway.
Suppressed hindlimb perfusion in Rac2−/− and Nox2−/− mice does not result from impaired collateral growth
Authors: Distasi Matthew R. , Case Jamie , Ziegler Matthew A. , Dinauer Mary C. , Yoder Mervin C. , Haneline Laura S. , Dalsing Michael C. , Miller Steven J. , Labarrere Carlos A. , Murphy Michael P. , Ingram David A. , Unthank Joseph L.
Published: January 2009

While tissue perfusion and angiogenesis subsequent to acute femoral artery occlusion are suppressed in NADPH oxidase 2 ( Nox2)-null ( Nox2−/−) mice, studies have not established the role of Nox2 in collateral artery enlargement. Rac2 is a small GTPase that binds Nox2 and activates Nox2-based NAD(P)H oxidase but, unlike Nox2, is primarily restricted to bone marrow-derived cells. In this study, we used Rac2-null ( Rac2−/−) and Nox2−/− mice with a novel method of identifying primary hindlimb collaterals to investigate the hypothesis that collateral growth requires these molecules. When initial experiments performed with femoral ligation demonstrated similar perfusion and collateral growth in Rac2−/− and wild-type C57BL/6J (BL6) mice, subsequent experiments were performed with a more severe ischemia model, femoral artery excision. After femoral excision, tissue perfusion was suppressed in Rac2−/− mice relative to BL6 mice. Histological assessment of ischemic injury including necrotic and regenerated muscle fibers and lipid and collagen deposition demonstrated greater injury in Rac2−/− mice. The diameters of primary collaterals identified during Microfil injection with intravital microscopy were enlarged to a similar extent in BL6 and Rac2−/− mice. Intimal cells in collateral cross sections were increased in number in both strains and were CD31 positive and CD45 negative. Circulating leukocytes and CD11b+ cells were increased more in Rac2−/− than BL6 animals. Experiments performed in Nox2−/− mice to verify that the unexpected results related to collateral growth were not unique to Rac2−/− mice gave equivalent results. The data demonstrate that, subsequent to acute femoral artery excision, perfusion recovery is impaired in Rac2−/− and Nox2−/− mice but that collateral luminal expansion and intimal cell recruitment/proliferation are normal. These novel results indicate that collateral luminal expansion and intimal cell recruitment/proliferation are not mediated by Rac2 and Nox2.
Effects of fatiguing jumping exercise on mRNA expression of titin-complex proteins and calpains
Authors: Lehti Maarit , Kivelä Riikka , Komi Paavo , Komulainen Jyrki , Kainulainen Heikki , Kyröläinen Heikki
Published: January 2009

Eccentric exercise induced by electrostimulation increases mRNA expression of titin-complex proteins in rodent skeletal muscle. In this study, mRNA expression of titin, muscle LIM protein (MLP), cardiac ankyrin repeat protein (CARP), ankyrin repeat domain protein 2 (Ankrd2), diabetes-related ankyrin repeat protein (DARP), and calcium-activated proteinases, calpains, were investigated in human skeletal muscle after fatiguing jumping exercise. Fatiguing jumping exercise did not change mRNA expression of titin, DARP, calpain 1, or calpain 3. MLP, Ankrd2 and calpain 2 mRNA levels were increased 2 days postexercise. CARP mRNA level was already elevated 30 min and remained elevated 2 days postexercise. Increased mRNA expression of MLP, CARP, and Ankrd2, observed for the first time in human skeletal muscle, may be part of the signaling activated by physical exercise. The rapid increase in the level of CARP mRNA nominates CARP as one of the first genes to respond to exercise. The increase in the mRNA level of calpain 2 suggests its involvement in myofiber remodeling after strenuous jumping exercise.
Nutritional and contractile regulation of human skeletal muscle protein synthesis and mTORC1 signaling
Authors: Drummond Micah J. , Dreyer Hans C. , Fry Christopher S. , Glynn Erin L. , Rasmussen Blake B.
Published: January 2009

In this review we discuss current findings in the human skeletal muscle literature describing the acute influence of nutrients (leucine-enriched essential amino acids in particular) and resistance exercise on muscle protein synthesis and mammalian target of rapamycin complex 1 (mTORC1) signaling. We show that essential amino acids and an acute bout of resistance exercise independently stimulate human skeletal muscle protein synthesis. It also appears that ingestion of essential amino acids following resistance exercise leads to an even larger increase in the rate of muscle protein synthesis compared with the independent effects of nutrients or muscle contraction. Until recently the cellular mechanisms responsible for controlling the rate of muscle protein synthesis in humans were unknown. In this review, we highlight new studies in humans that have clearly shown the mTORC1 signaling pathway is playing an important regulatory role in controlling muscle protein synthesis in response to nutrients and/or muscle contraction. We propose that essential amino acid ingestion shortly following a bout of resistance exercise is beneficial in promoting skeletal muscle growth and may be useful in counteracting muscle wasting in a variety of conditions such as aging, cancer cachexia, physical inactivity, and perhaps during rehabilitation following trauma or surgery.
Mechanisms of Vascular Smooth Muscle NADPH Oxidase 1 (Nox1) Contribution to Injury-Induced Neointimal Formation
Authors: Lee Moo Yeol , Martin Alejandra San , Mehta Puja K. , Dikalova Anna E. , Garrido Abel Martin , Datla S. Raju , Lyons Erin , Krause Karl-Heinz , Banfi Botond , Lambeth J. David , Lassègue Bernard , Griendling Kathy K.
Published: January 2009

Objective—

Vascular NADPH oxidases (Noxes) have been implicated in cardiovascular diseases; however, the importance of individual Nox homologues remains unclear. Here, the role of the vascular smooth muscle cell (VSMC) Nox1 in neointima formation was studied using genetically modified animal models.

Methods and Results—

Wire injury–induced neointima formation in the femoral artery, along with proliferation and apoptosis, was reduced in Nox1
y/−
mice, but there was little difference in Tg
SMCnox1
mice compared with wild-type (WT) mice. Proliferation and migration were reduced in cultured Nox1
y/−
VSMCs and increased in Tg
SMCnox1
cells. Tg
SMCnox1
cells exhibited increased fibronectin secretion, but neither collagen I production nor cell adhesion was affected by alteration of Nox1. Using antibody microarray and Western blotting analysis, increased cofilin phosphorylation and mDia1 expression and decreased PAK1 expression were detected in Nox1
y/−
cells. Overexpression of S3A, a constitutively active cofilin mutant, partially recovered reduced migration of Nox1
y/−
cells, suggesting that reduction in cofilin activity contributes to impaired migration of Nox1
y/−
VSMCs.

Conclusions—

These results indicate that Nox1 plays a critical role in neointima formation by mediating VSMC migration, proliferation, and extracellular matrix production, and that cofilin is a major effector of Nox1-mediated migration. Inhibition of Nox1 may be an efficient strategy to suppress neointimal formation.
FXR Promotes Endothelial Cell Motility Through Coordinated Regulation of FAK and MMP-9
Authors: Das Amitava , Yaqoob Usman , Mehta Dolly , Shah Vijay H.
Published: January 2009

Objective—

Farnesoid X Receptor (FXR) mediates important signaling functions of bile acids in diverse cell types including those residing in the vascular wall. Indeed, recent work has identified FXR as a potential regulator of vascular structure and function in part through transcriptional activation of MMP-9. However, the signal transduction pathways linking bile acids to changes in actin cytoskeleton that are responsible for bile acid-induced vascular cell migration remain unexplored.

Methods and Results—

The FXR agonist and prototypical bile acid, chenodeoxycholic acid (CDCA), significantly increased endothelial cell (EC) motility, as analyzed by time lapse video microscopy, and tube formation, an in vitro correlate for angiogenesis. Increased cell motility was associated with prominent increases in focal adhesion (FA) plaques and was inhibited by FXR or MMP-9 siRNA, indicating a FXR-MMP-9-dependency of this signaling pathway. Mechanistically, incubation of cells with CDCA was associated with phosphorylation of a key FA protein, Focal Adhesion Kinase (FAK) at Y397 but not at Y576/577, or Y925. Studies using a site-specific phosphorylation mutant (phosphodeficient) of FAK revealed that FAK phosphorylation at tyrosine residue −397 was required for CDCA induced activation of the downstream FA assembly protein, paxillin. Lastly, siRNA-based silencing of FAK as well as phosphodeficient FAK mutant inhibited CDCA induced upregulation of MMP-9, cell motility, and vascular tube formation.

Conclusion—

Thus, this study demonstrates a pivotal role for FAK in the process of FXR-induced and MMP-9-dependent EC motility and vascular tube formation.
NOTCH3 Expression Is Induced in Mural Cells Through an Autoregulatory Loop That Requires Endothelial-Expressed JAGGED1
Authors: Liu Hua , Kennard Simone , Lilly Brenda
Published: January 2009

Endothelial cells and mural cells (smooth muscle cells, pericytes, or fibroblasts) are known to communicate with one another. Their interactions not only serve to support fully functional blood vessels but also can regulate vessel assembly and differentiation or maturation. In an effort to better understand the molecular components of this heterotypic interaction, we used a 3D model of angiogenesis and screened for genes, which were modulated by coculturing of these 2 different cell types. In doing so, we discovered that NOTCH3 is one gene whose expression is robustly induced in mural cells by coculturing with endothelial cells. Knockdown by small interfering RNA revealed that NOTCH3 is necessary for endothelial-dependent mural cell differentiation, whereas overexpression of NOTCH3 is sufficient to promote smooth muscle gene expression. Moreover, NOTCH3 contributes to the proangiogenic abilities of mural cells cocultured with endothelial cells. Interestingly, we found that the expression of NOTCH3 is dependent on Notch signaling, because the γ-secretase inhibitor DAPT blocked its upregulation. Furthermore, in mural cells, a dominant-negative Mastermind-like1 construct inhibited NOTCH3 expression, and endothelial-expressed JAGGED1 was required for its induction. Additionally, we demonstrated that NOTCH3 could promote its own expression and that of JAGGED1 in mural cells. Taken together, these data provide a mechanism by which endothelial cells induce the differentiation of mural cells through activation and induction of NOTCH3. These findings also suggest that NOTCH3 has the capacity to maintain a differentiated phenotype through a positive-feedback loop that includes both autoregulation and JAGGED1 expression.
Mediation of Electronegative Low-Density Lipoprotein Signaling by LOX-1
Authors: Lu Jonathan , Yang Jun-Hai , Burns Alan R. , Chen Hsin-Hung , Tang Daming , Walterscheid Jeffrey P. , Suzuki Shinichi , Yang Chao-Yuh , Sawamura Tatsuya , Chen Chu-Huang
Published: January 2009

The lectin-like oxidized LDL receptor LOX-1 mediates endothelial cell (EC) uptake of experimentally prepared copper-oxidized LDL (oxLDL). To confirm the atherogenic role of this receptor cloned against copper-oxLDL, we examined whether it mediates EC uptake of L5, an electronegative LDL abundant in dyslipidemic but not normolipidemic human plasma. Hypercholesterolemic (LDL-cholesterol, >160 mg/dL) human LDL was fractionated into L1–L5, increasingly electronegative, by ion-exchange chromatography. In cultured bovine aortic ECs (BAECs), L5 upregulated LOX-1 and induced apoptosis. Transfection of BAECs with LOX-1–specific small interfering RNAs (siLOX-1) minimized baseline LOX-1 production and restrained L5-induced LOX-1 upregulation. Internalization of labeled L1–L5 was monitored in BAECs and human umbilical venous ECs by fluorescence microscopy. LOX-1 knockdown with siLOX-1 impeded the endocytosis of L5 but not L1–L4. In contrast, blocking LDL receptor with RAP (LDL receptor–associated protein) stopped the internalization of L1–L4 but not L5. Although chemically different, L5 and oxLDL competed for EC entry through LOX-1. Via LOX-1, L5 signaling hampered Akt phosphorylation and suppressed EC expression of fibroblast growth factor-2 and Bcl-2. L5 also selectively inhibited Bcl-xL expression and endothelial nitric oxide synthase phosphorylation but increased synthesis of Bax, Bad, and tumor necrosis factor-α. Blocking Akt phosphorylation with wortmannin increased LOX-1 expression, suggesting a modulatory role of Akt in LOX-1 synthesis; L5 upregulated LOX-1 by dephosphorylating Akt. Because endothelial nitric oxide synthase and Bcl-2 activities are Akt-dependent, L5 impairs Akt-mediated growth and survival signals in vascular ECs by way of LOX-1. Thus, the L5/LOX-1 complex may play a critical role in atherogenesis and illuminate important targets for disease intervention.
Dynamic Cerebral Autoregulation in Homozygous Sickle Cell Disease
Authors: Kim Yu-Sok , Nur Erfan , van Beers Eduard J. , Truijen Jasper , Davis Shyrin C.A.T. , Biemond Bart J. , van Lieshout Johannes J.
Published: January 2009

Background and Purpose—

Sickle cell disease (SCD) is associated with cerebral hyperperfusion and an increased risk of stroke. Also, both recurrent microvascular obstruction and chronic hemolysis affect endothelial function, potentially interfering with systemic and cerebral blood flow control. We addressed the question whether cerebrovascular control in patients with SCD is affected and related to hemolysis.

Methods—

Systemic and cerebrovascular control were studied in 18 patients with SCD and 10 healthy subjects. Dynamic cerebral autoregulation was evaluated by transfer function analysis assessing the relationship between mean cerebral blood flow velocity and mean arterial pressure.

Results—

Normal baroreflex sensitivity and postural cardiovascular reflex responses indicated integrity of systemic cardiovascular control. In the low- (0.07 to 0.15 Hz) frequency region, mean arterial pressure variability was comparable for both groups, but a larger mean cerebral blood flow velocity variability in SCD (6.1 [4.6 to 7.0] versus 4.2 [2.6 to 5.2] [cm·s
−1
]
2
·Hz
−1
;
P
<0.05) indicated a reduced capacity to buffer the transfer of blood pressure surges to the cerebral tissue. Impairment of dynamic cerebrovascular control was confirmed by a reduced mean arterial pressure-to-mean cerebral blood flow velocity transfer function phase lead in SCD versus healthy subjects (32±17° versus 50±19°,
P
<0.05) that was unrelated to the severity of hemolysis.

Conclusions—

In patients with SCD, dynamic cerebral autoregulation is impaired but appears unrelated to hemolysis.
Effects of Pravastatin on Serum Osteoprotegerin Levels in Patients With Hypercholesterolemia and Type 2 Diabetes
Authors: Mori Katsuhito , Jono Shuichi , Emoto Masanori , Kawagishi Takahiko , Yasumoto Hideo , Konishi Toshiaki , Furumitsu Yutaka , Shioi Atsushi , Shoji Tetsuo , Inaba Masaaki , Nishizawa Yoshiki
Published: January 2009

Osteoprotegerin is a secretory glycoprotein. Recent experimental findings have suggested that osteoprotegerin may protect against vascular calcification and/or atherosclerosis. In humans, osteoprotegerin levels are positively correlated with the presence and severity of coronary artery disease and the progression of atherosclerosis. However, it is unclear how osteoprotegerin levels are regulated. Statins are known to have beneficial pleiotropic effects against atherosclerosis beyond their lipid-lowering effects. In this study, we examined whether treatment with pravastatin can alter osteoprotegerin levels in patients with hypercholesterolemia and type 2 diabetes. Osteoprotegerin levels were significantly increased from 6.64 ± 2.18 pmol/L at baseline to 7.08 ± 2.29 pmol/L (P = .024) after 3-month treatment with pravastatin. These increases in osteoprotegerin levels remained after 6 months of treatment (7.05 ± 2.22 pmol/L, P = .026). These findings suggest that pravastatin may exert its pleiotropic effects in part through alteration of osteoprotegerin levels.
Causation in the Social Sciences
Authors: Reiss Julian
Published: January 2009

All univocal analyses of causation face counterexamples. An attractive response to this situation is to become a pluralist about causal relationships. “Causal pluralism” is itself, however, a pluralistic notion. In this article, I argue in favor of pluralism about concepts of cause in the social sciences. The article will show that evidence for, inference from, and the purpose of causal claims are very closely linked.
Beliefs About What Works in Juvenile Rehabilitation
Authors: Perelman Abigayl M. , Clements Carl B.
Published: January 2009

Throughout the past half century, public sentiment about sentencing of offenders has vacillated between rehabilitative and punitive goals. Whether these shifting positions are influenced by actual knowledge regarding program effectiveness or merely reflect underlying attitudes is unknown. The current study used an online survey to examine college students' ( N = 130) judgments about the effectiveness of different interventions for juvenile offenders. Results indicated that participants rated three popular but empirically unsupported (get tough) programs as being equally effective as four empirically validated treatments. However, personal attitudes were a strong moderator of program effectiveness ratings. For example, those endorsing rehabilitative goals were more likely to rate empirically supported interventions as effective. A punishment orientation was associated with endorsement of get tough programs. Possible follow-up studies include evaluating the connection between attitudes and program effectiveness knowledge, examining the impact of educational interventions, and conducting replications with justice professionals and community leaders.
Long-Term Cost-Effectiveness of Disease Management in Systolic Heart Failure
Authors: Miller George , Randolph Stephen , Forkner Emma , Smith Brad , Galbreath Autumn Dawn
Published: January 2009

Background. Although congestive heart failure (CHF) is a primary target for disease management programs, previous studies have generated mixed results regarding the effectiveness and cost savings of disease management when applied to CHF. Objective. We estimated the long-term impact of systolic heart failure disease management from the results of an 18-month clinical trial. Methods. We used data generated from the trial (starting population distributions, resource utilization, mortality rates, and transition probabilities) in a Markov model to project results of continuing the disease management program for the patients' lifetimes. Outputs included distribution of illness severity, mortality, resource consumption, and the cost of resources consumed. Both cost and effectiveness were discounted at a rate of 3% per year. Cost-effectiveness was computed as cost per quality-adjusted life year (QALY) gained. Results. Model results were validated against trial data and indicated that, over their lifetimes, patients experienced a lifespan extension of 51 days. Combined discounted lifetime program and medical costs were $4850 higher in the disease management group than the control group, but the program had a favorable long-term discounted cost-effectiveness of $43,650/QALY. These results are robust to assumptions regarding mortality rates, the impact of aging on the cost of care, the discount rate, utility values, and the targeted population. Conclusions. Estimation of the clinical benefits and financial burden of disease management can be enhanced by model-based analyses to project costs and effectiveness. Our results suggest that disease management of heart failure patients can be cost-effective over the long term.
Women, Dowries, and Patrimonial Law in Old Regime Romania (c. 1750—1830)
Authors: Jianu Angela
Published: January 2009

This study explores the legal aspects of dowry provision in the Romanian Principalities of Wallachia and Moldavia in the period 1750—1830. Drawing on the period's law codes, dowry papers, testaments, and court records, it highlights the legal and emotional difficulties created by the affective/patrimonial nexus within couples, families, and stepfamilies in a society where divorce and up to three remarriages were allowed by both church and state. A growing body of research into the history of the Romanian family is suggesting that the prescriptions governing dowry provision in the late eighteenth and early nineteenth centuries and the consequent exclusion of dowered girls from the family inheritance led to increased cohesion within the nuclear family and to the legal empowerment of women, while providing economic security to divorced women, widows, and children.
Alterations in Regional Brain Volume and Individual MRI-Guided Perfusion in Normal Control, Stable Mild Cognitive Impairment, and MCI-AD Converter
Authors: Huali Wang  , Golob Edward , Bert Alberto , Ke Nie  , Yong Chu  , Dick Malcolm B. , Mandelkern Mark , Su Min-Ying
Published: January 2009

Regional differences in tissue volume and perfusion in brains of individuals with mild cognitive impairment (MCI) versus normal healthy age-matched controls (NC), and the differences between MCI-AD converters and stable MCI patients were investigated. MRI and SPECT scans were performed on 13 MCI (74+6 years) and 12 NC (75+4 years). Of the MCI patients, 10 were followed for up to three years and 4 subsequently converted to Alzheimer's disease (AD). Episodic memory function was assessed using tests of delayed recall for word lists and stories. The volume reductions and hypoperfusion were mainly confined to the medial temporal lobe (MTL) of MCI patients and associated with worse scores on memory tests. Perfusion in the corpus callosum and the gray matter of frontal, lateral temporal, parietal or occipital lobe was not significantly affected in MCI. The 4 MCI-AD converters had relatively low MTL structural volume and perfusion compared to their stable peers.
Anti-RNP neonatal lupus in a female newborn
Authors: McGeachy C , Lam J
Published: January 2009

We describe a case of neonatal lupus erythematosus in a term female infant who presented at birth with mild, scattered facial erythema and ice-pick lesions at lateral and superior borders of her face. These lesions then progressed to an erythematous raccoon-like mask following exposure to the sun. Initial blood work performed at four-months-old showed speckled anti-nuclear antibody titers of 1:320, with negative anti-Ro/SSA and La/SSB negative and a positive anti-RNP. The infant had no evidence of cardiac, haematological or hepatobilary involvement initially or throughout her course of evaluation. The patient’s mother was asymptomatic throughout the investigation of the infant but through blood work and evolvement of symptoms, she was diagnosed with mixed connective tissue disease.
The clinical characterisation of systemic lupus erythematosus in a Far North Queensland Indigenous kindred
Authors: Mason JA , Bossingham D
Published: January 2009

The aetiology of systemic lupus erythematosus (SLE) is thought to involve both genetic and environmental factors. In other complex diseases, analysis of large multi-case families has resulted in insights into biological mechanisms. We have sought to characterise the members of an extended Indigenous family, five of whom have been diagnosed with SLE. Pedigree members were evaluated using the Lupus Screening Questionnaire, clinical interviews and medical records. Participants contributed blood and urine samples for laboratory analysis. A Mendelian pattern of inheritance was not observed. The five affected members (all female) shared two American College of Rheumatology criteria (positive ANA and arthritis) but showed a wide variety of other SLE manifestations. Disease onset, severity and progression were discordant. Including the five individuals with SLE, 15 blood relatives and two non-consanguineous spouses had autoimmune manifestations. Autoimmune haemolytic anaemia (one case), idiopathic thrombocytopenic purpura (ITP) (one case) and hypothyroidism (two cases) were observed in non-SLE affected individuals. Anti-nuclear antibodies were present in 12 blood relatives and one non-consanguineous spouse. Infections (especially of the skin) were observed to be common in the kindred. The lack of clear Mendelian inheritance or phenotypic concordance makes a rare monogenic explanation for SLE unlikely in this family. The finding of familial autoimmunity associated with SLE further supports the hypothesis that a common genetic pathway can precipitate autoimmunity, with further genes and possible environmental factors interacting to produce the eventual phenotype. Future genetic linkage studies may reveal a rare ‘autoimmune gene’ variant in this kindred.
Acute Chlamydia pneumoniae infection in the pathogenesis of autoimmune diseases
Authors: Fujita M , Hatachi S , Yagita M
Published: January 2009

Autoimmune diseases have several etiologies. Acute Chlamydia pneumoniae ( C. pneumoniae) infection may be involved in the pathogenesis of several autoimmune diseases. In this study, 82 patients with several autoimmune diseases and 70 controls were enrolled, and acute C. pneumoniae infection has been evaluated by monitoring the levels of IgM antibody. Chlamydia pneumoniae IgM positive results were observed in 29% ( P < 0.05) of the patients with several autoimmune diseases and in 10% of the controls. Chlamydia pneumoniae IgM positive cases were more frequent among the patients with rheumatoid arthritis (RA; 30%, P < 0.05), systemic lupus erythematosus (SLE; 28.0%, P < 0.05), dermatomyositis/polymyositis (23%, NS), myeloperoxidase-antineutrophil cytoplasmic autoantibody (MPO-ANCA)-associated vasculitis (33%, NS), adult onset of Still’s disease (29%, NS) and giant cell arteritis/Takayasu arteritis (50%, NS) than among the controls. This positive frequency was statistically significant in RA and SLE. These results suggest that acute C. pneumoniae infection is probably involved in the pathogenesis of autoimmune diseases.