bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiology of Diabetic Foot and Management of Foot Problems in India
Authors: Viswanathan Vijay
Published: August 2010

Diabetes the global epidemic is rapidly increasing at an alarming rate. Developing countries like India harbor the majority of diabetic people and by the year 2030 AD India will have the largest number of diabetic patients. Diabetic foot is one of the common diabetic complications found in India. Both aerobic and anaerobic pathogens form the etiology for diabetic foot infection. Members of the Enterobacteriaceae family were the most prominent among the aerobes while members of the Genus Peptostreptococcus and Clostridium were most prominent among the anaerobes. Ulcers infected with anaerobic pathogens showed a longer healing time than ulcers infected with aerobic pathogens. Oxidative stress is one of the major markers of inflammatory response and oxidative stress markers such as lipid peroxidation, thiobarbituric acid reactive substance (TBARS), Superoxide Dismutase (SOD), Catalase, G Peroxidase, G-S Peroxidase and plasma total antioxidant play a major role in the nonhealing of diabetic foot ulcers. Growth factors such as platelet-derived growth factor (PDGF), transforming growth factor (VEGF), and epidermal growth factor (EGF) are needed for normal wound repair, while proteases such as matrix metalloproteinase (MMP) and serine proteases found in chronic wounds delay the healing process.
The Etiopathogenesis of the Diabetic Foot: An Unrelenting Epidemic
Authors: Sanjeev Kumar Gupta  , Panda Satyajit , Surya Kumar Singh
Published: August 2010

Diabetes mellitus is a metabolic disease that is associated with hyperglycemia affecting various organ systems of the body. One of the most dreaded complications of this disease is the diabetic foot. The diabetic foot is the end result of multiple causal pathways, which include peripheral neuropathy and vascular disease. The problem is compounded by the increased incidence of infection. This article deals with the various pathogenic pathways associated with the development of the diabetic foot.
Alstonia scholaris Linn R Br in the Treatment and Prevention of Cancer: Past, Present, and Future
Authors: Manjeshwar Shrinath Baliga
Published: August 2010

Alstonia scholaris, commonly known as devil’s tree is an important medicinal plant in the various folk and traditional systems of medicine in Asia, Australia, and Africa. The decoction, mostly prepared from the bark, is used to treat a variety of diseases of which the most important is malaria. Furthermore, ethnomedicinal practices also suggest it to be of use in treating cancer, and preclinical studies performed with cultured neoplastic cells and tumor-bearing animals having validated these observations. Additionally, the phytochemicals like echitamine, alstonine, pleiocarpamine, O-methylmacralstonine, macralstonine, and lupeol are also reported to possess antineoplastic effects. In addition to the cytotoxic effects, A scholaris is also observed to possess radiomodulatory, chemomodulatory, and chemopreventive effects and free-radical scavenging, antioxidant, anti-inflammatory, antimutagenic, and immunomodulatory activities, all of which are properties efficacious in the treatment and prevention of cancer. The current review for the first time summarizes the results related to these properties. An attempt is also made to address the lacunae in these published studies and emphasize aspects that need further investigations for it to be of use in clinics in the future.
Regulation of p21, MMP-1, and MDR-1 Expression in Human Colon Carcinoma HT29 Cells by Tian Xian Liquid, a Chinese Medicinal Formula, In Vitro and In Vivo
Authors: Sze Stephen C. W. , Wong Kam L. , Liu Wing K. , Ng Tzi B. , Wong Jack H. , Cheung Ho P. , Yow Christine M. L. , Chu Ellie S. M. , Qing Liu  , Hu Yong M. , Tsang Kam W. , Lee Wai S. , Yao Tong
Published: August 2010

Ethnopharmacological relevance. Tian-Xian liquid (TXL), a commercially available Chinese medicine decoction, has been used as an anticancer dietary agent for more than 10 years without reported side effects. Aim of the study. The safety and quality consistency of TXL and its mechanisms of action on antiproliferation, antimetastasis, and reversion of multidrug resistance (MDR) regimens were explored. Materials and methods. In this study, an atomic absorption spectrophotometer and reversed phase high performance liquid chromatography with photodiode array detection (HPLC-DAD) were used to evaluate the main toxic elements and the quality consistency among different batches of TXL extracts, respectively. HT29 human colon cancer cell line and tumor-bearing nude mice were used. TXL was provided by China-Japan Feida Union Company Limited. The effect of TXL on in vitro proliferation of HT29 human colon cancer cell line was examined. The percentages of treated cells distributed in different phases of the cell cycles were analyzed by flow cytometry. Antiproliferative effect after treatment with TXL was assessed by determination of the protein levels of p21, cyclinD1, PCNA, and cdk-2, which are the key regulators for cell cycle progression. Meanwhile, the protein levels of MMP-1 and MDR-1 (multidrug resistance protein-1) were also determined to assess the effect of TXL on antimetastasis and reversion of MDR regimen, respectively. Results. The contents of main toxic elements were lower in TXL extract compared with the standard set by the Department of Health of the Government of Hong Kong Special Administrative Region (SAR). Our HPLC results showed that the relative standard deviations of the amount of the 5 standards were less than 5% in different batches of TXL. Immunoblotting analysis revealed a dramatic induction of cyclin kinase inhibitor p21 as well as an inhibition of cyclinD1, PCNA, and cdk-2 in the TXL-treated in vitro models, thereby, impeding cell progression from G1/S phase. Results obtained from the in vivo study also demonstrated that TXL upregulated the protein level of p21 and downregulated the protein levels of MMP-1 and MDR-1. Conclusions. Results obtained from the present investigation not only demonstrate the safety and quality of TXL extract but also demonstrate that TXL possesses antiproliferative and antimetastatic activities and brings about reversion of MDR on HT29 cell and on xenografted tissue in tumor-implanted nude mice.
Hematoporphyrin Monomethyl Ether Enhances the Killing of Ultrasound on Osteosarcoma Cells Involving Intracellular Reactive Oxygen Species and Calcium Ion Elevation
Authors: Zedan Tian  , Xuemou Quan  , Wingnang Leung Albert , Junyan Xiang  , Chuanshan Xu
Published: August 2010

Objective: The present study aims to investigate the possible mechanisms of hematoporphyrin monomethyl ether (HMME) enhancing the cytotoxicity of ultrasound in osteosarcoma cells. Methods: Osteosarcoma cell line UMR-106 was treated by HMME and ultrasound radiation, with the HMME concentration kept at 20 μg/mL and ultrasound radiation for 10 seconds at the intensity of 0.5 W/cm2. Cell proliferation was investigated at 12, 24, 36, and 48 hours using MTT assay after ultrasound and HMME treatment. Ultrastructural morphology was observed using transmission electron microscopy (TEM). Intracellular reactive oxygen species (ROS) was measured using a flow cytometry with DCFH-DA staining and intracellular free calcium ion (Ca2+) with Fluo-3-AM staining. Results: The UMR-106 cells proliferated rapidly in the sham radiation and HMME treatment alone group, but ultrasound-treated cells and HMME-ultrasound-treated cells proliferated slowly. There was a significant difference between HMME-ultrasound treatment and the controls, including ultrasound radiation, HMME treatment alone, and sham radiation ( P < .05). TEM showed endoplasmic reticulum and mitochondrial swelling in the ultrasound-treated cells, and more cells presented apoptosis and necrosis after treatment with ultrasound and HMME together. Intracellular ROS and Ca2+ in the cells increased more significantly after both ultrasound and HMME treatment than after ultrasound treatment alone. Conclusions: HMME could effectively enhance the inhibition effect of ultrasound on osteosarcoma cells. Intracellular ROS and Ca2+ in the UMR-106 cells increased more significantly after the treatment of HMME and ultrasound together, indicating that the enhancement of HMME on ultrasound cytotoxicity to osteosarcoma cells possibly involves both intracellular ROS and Ca2+ elevation.
Trait Approach Motivation Relates to Dissonance Reduction
Authors: Harmon-Jones Cindy , Schmeichel Brandon J. , Inzlicht Michael , Harmon-Jones Eddie
Published: August 2010

Over 50 years of work on cognitive dissonance theory has suggested that dissonance reduction is a motivated process. However, no research has unambiguously demonstrated the direction of this motivation—whether it is approach or avoidance oriented. The action-based model of dissonance proposes that dissonance reduction is an approach-related process that assists in the implementation of decisions. It follows from the action-based model that approach-related personality traits should be related to greater dissonance reduction. The current research tested this idea. Study 1 found that trait behavioral approach sensitivity (BAS) related to more spreading of alternatives (more liking for the chosen over the rejected decision alternative) following a difficult decision. Study 2 found that BAS related to attitudes being more consistent with recent induced compliance behavior. This research therefore suggests that dissonance reduction is an approach-motivated process.
Violent Video Games Cause an Increase in Aggression Long After the Game Has Been Turned Off
Authors: Bushman Brad J. , Gibson Bryan
Published: August 2010

Experimental studies show that violent video games cause people to behave more aggressively, but how long does the effect last? In most experiments, aggression is measured immediately after gameplay. The present experiment is the first to test the long-term causal effects of violent video games on aggression. By the flip of a coin, participants played a violent or nonviolent game for 20 min. Within each group, half ruminated about the game. The next day, participants competed with an ostensible opponent on a competitive task in which the winner could punish the loser with painful noise blasts through headphones. Results showed that violent video games increased aggression 24 hr later, but only among men who ruminated about the game. Rumination keeps aggressive thoughts, feelings, and behavioral tendencies active. If players ruminate about the violence in a game, the aggression-stimulating effects of the game persist long after it has been turned off.
Review: Role of metformin in the management of polycystic ovary syndrome
Authors: Lashen Hany
Published: August 2010

Polycystic ovary syndrome is the most common endocrinological disorder affecting 4-12% of women and also the most controversial. Metformin was logically introduced to establish the extent to which hyperinsulinaemia influences the pathogenesis of the condition. Early studies were very encouraging. Randomized controlled studies and several meta-analyses have changed the picture and put the drug that was once heralded as magic in a much contracted place. More work is needed to establish its right place in particular with regards to the prevention of many gestational and long-term complications.
Conventional and pretargeted radioimmunotherapy using bismuth-213 to target and treat non-Hodgkin lymphomas expressing CD20: a preclinical model toward optimal consolidation therapy to eradicate minimal residual disease
Authors: Park Steven I. , Shenoi Jaideep , Pagel John M. , Hamlin Don K. , Wilbur D. Scott , Orgun Nural , Kenoyer Aimee L. , Frayo Shani , Axtman Amanda , Bäck Tom , Lin Yukang , Fisher Darrell R. , Gopal Ajay K. , Green Damian J. , Press Oliver W.
Published: August 2010

Radioimmunotherapy (RIT) with α-emitting radionuclides is an attractive approach for the treatment of minimal residual disease because the short path lengths and high energies of α-particles produce optimal cytotoxicity at small target sites while minimizing damage to surrounding normal tissues. Pretargeted RIT (PRIT) using antibody-streptavidin (Ab-SA) constructs and radiolabeled biotin allows rapid, specific localization of radioactivity at tumor sites, making it an optimal method to target α-emitters with short half-lives, such as bismuth-213 (213Bi). Athymic mice bearing Ramos lymphoma xenografts received anti-CD20 1F5(scFv)4SA fusion protein (FP), followed by a dendrimeric clearing agent and [213Bi]DOTA-biotin. After 90 minutes, tumor uptake for 1F5(scFv)4SA was 16.5% ± 7.0% injected dose per gram compared with 2.3% ± .9% injected dose per gram for the control FP. Mice treated with anti-CD20 PRIT and 600 μCi [213Bi]DOTA-biotin exhibited marked tumor growth delays compared with controls (mean tumor volume .01 ± .02 vs. 203.38 ± 83.03 mm3 after 19 days, respectively). The median survival for the 1F5(scFv)4SA group was 90 days compared with 23 days for the control FP (P < .0001). Treatment was well tolerated, with no treatment-related mortalities. This study demonstrates the favorable biodistribution profile and excellent therapeutic efficacy attainable with 213Bi-labeled anti-CD20 PRIT.
Proteomic characterization of an isolated fraction of synthetic proteasome inhibitor (PSI)-induced inclusions in PC12 cells might offer clues to aggresomes as a cellular defensive response against proteasome inhibition by PSI
Authors: Li Xing'an , Zhang Yingjiu , Xie Peng , Piao Jinhua , Hu Yihong , Chang Ming , Liu Tao , Hu Linsen
Published: August 2010

Background

Cooperation of constituents of the ubiquitin proteasome system (UPS) with chaperone proteins in degrading proteins mediate a wide range of cellular processes, such as synaptic function and neurotransmission, gene transcription, protein trafficking, mitochondrial function and metabolism, antioxidant defence mechanisms, and apoptotic signal transduction. It is supposed that constituents of the UPS and chaperone proteins are recruited into aggresomes where aberrant and potentially cytotoxic proteins may be sequestered in an inactive form.

Results

To determinate the proteomic pattern of synthetic proteasome inhibitor (PSI)-induced inclusions in PC12 cells after proteasome inhibition by PSI, we analyzed a fraction of PSI-induced inclusions. A proteomic feature of the isolated fraction was characterized by identification of fifty six proteins including twenty previously reported protein components of Lewy bodies, twenty eight newly identified proteins and eight unknown proteins. These proteins, most of which were recognized as a profile of proteins within cellular processes mediated by the UPS, a profile of constituents of the UPS and a profile of chaperone proteins, are classed into at least nine accepted categories. In addition, prolyl-4-hydroxylase beta polypeptide, an endoplasmic reticulum member of the protein disulfide isomerase family, was validated in the developmental process of PSI-induced inclusions in the cells.

Conclusions

It is speculated that proteomic characterization of an isolated fraction of PSI-induced inclusions in PC12 cells might offer clues to appearance of aggresomes serving as a cellular defensive response against proteasome inhibition.
Malaria risk in Corsica, former hot spot of malaria in France
Authors: Toty Céline , Barré Hélène , Le Goff Gilbert , Larget-Thiéry Isabelle , Rahola Nil , Couret Daniel , Fontenille Didier
Published: August 2010

Background

The prevalence ofPlasmodium falciparumandPlasmodium vivaxmalaria was very high in Corsica just before the Second World War. The last outbreak was in 1972 and the most recent indigenous case was in 2006.

Results

Analysis of historical data shows that anopheline vectors were abundant. Recent surveys demonstrated that potential vectors are still present in Corsica, despite the likely disappearance ofAnopheles sacharovi. Moreover,P. falciparumcan develop experimentally into these mosquitoes, notablyAnopheles labranchiae, which is locally abundant, and parasites are regularly introduced into the island.

Discussion, Conclusions

The presence of vectors, the introduction of parasites and the conducive climate raise questions about the possibility of malaria re-emerging and becoming re-established in Corsica. Analysis of historic and current parasitological and entomological data shows that the current theoretical risk of indigenous cases or malaria foci is negligible, particularly since there is very little contact between humans andAnophelesmosquitoes,Plasmodiumcarriers are reliably treated and there is a widespread vector control on the island.
Local Induction of Adiponectin Reduces Lipopolysaccharide-Triggered Skeletal Muscle Damage
Authors: Jortay Julie , Senou Maximin , Delaigle Aurélie , Noel Laurence , Funahashi Tohru , Maeda Norikazu , Many Marie C. , Brichard Sonia M.
Published: August 2010

Adiponectin (ApN) exhibits metabolic and antiinflammatory properties. This hormone is exclusively secreted by adipocytes under normal conditions. We have shown that ApN was induced in tibialis anterior muscle of mice injected with lipopolysaccharide (LPS) and in C2C12 myotubes cultured with proinflammatory cytokines. We hypothesized that muscle ApN could be a local protective mechanism to counteract excessive inflammatory reaction and oxidative damage. To test this paradigm, we examined whether muscles of ApN-knockout (KO) mice exhibit a higher degree of oxidative stress and apoptosis than wild-type mice when challenged by ip LPS and whether these abnormalities may be corrected by local administration of ApN. Eventually we investigated the effects of ApN in vitro. When compared with wild-type mice, ApN-KO mice exhibited myocyte degenerescence, especially after LPS. Myocytes of ApN-KO mice also displayed much stronger immunolabeling for markers of oxidative stress (peroxiredoxin-3/5 and heme oxygenase-1) as well as for a lipid peroxidation product (hydroxynonenal). Expression of TNF-α, caspase-6, a marker of apoptosis, and nuclear factor-κB was enhanced as well. Eventually muscle electrotransfer of the ApN gene, which did not induce any rise of systemic ApN, corrected all these abnormalities in LPS-injected ApN-KO mice. Likewise, ApN attenuated LPS-induced production of proinflammatory cytokines and activation of nuclear factor-κB in C2C12 cells. Thus, induction of ApN into skeletal muscle in response to an inflammatory aggression appears to be a crucial mechanism to counteract in an autocrine or paracrine fashion excessive inflammatory damage, oxidative stress, and subsequent apoptosis.
Fast Feedback Inhibition of the HPA Axis by Glucocorticoids Is Mediated by Endocannabinoid Signaling
Authors: Evanson Nathan K. , Tasker Jeffrey G. , Hill Matthew N. , Hillard Cecilia J. , Herman James P.
Published: August 2010

Glucocorticoid hormones are secreted in response to stimuli that activate the hypothalamo-pituitary-adrenocortical (HPA) axis and self-regulate through negative feedback. Negative feedback that occurs on a rapid time scale is thought to act through nongenomic mechanisms. In these studies, we investigated fast feedback inhibition of HPA axis stress responses by direct glucocorticoid action at the paraventricular nucleus of the hypothalamus (PVN). Local infusion of dexamethasone or a membrane-impermeant dexamethasone-BSA conjugate into the PVN rapidly inhibits restraint-induced ACTH and corticosterone release in a manner consistent with feedback actions at the cell membrane. The dexamethasone fast feedback response is blocked by the cannabinoid CB1 receptor antagonist AM-251, suggesting that fast feedback requires local release of endocannabinoids. Hypothalamic tissue content of the endocannabinoid 2-arachidonoyl glycerol is elevated by restraint stress, consistent with endocannabinoid action on feedback processes. These data support the hypothesis that glucocorticoid-induced fast feedback inhibition of the HPA axis is mediated by a nongenomic signaling mechanism that involves endocannabinoid signaling at the level of the PVN.
Endogenous Activation of Glucokinase by 6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase Is Glucose Dependent
Authors: Langer Sara , Kaminski Martin T. , Lenzen Sigurd , Baltrusch Simone
Published: August 2010

Glucokinase (GK) plays a crucial role as glucose sensor in glucose-induced insulin secretion in pancreatic β-cells. The bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2) acts as an endogenous GK activator. Therefore, the goal of this study was the analysis of GK-PFK-2/FBPase-2 complex formation and its effect on metabolic stimulus-secretion coupling in β-cells in dependence upon glucose. The interaction between GK and PFK-2/FBPase-2 was analyzed in insulin-secreting MIN6 cells with a new fluorescence-based mammalian two-hybrid system. In contrast to the commonly used mammalian two-hybrid systems that require sampling before detection, the system used allows monitoring of the effects of environmental changes on protein-protein interactions on the single-cell level. Increasing the glucose concentration in the cell culture medium from 3 to 10 and 25 mmol/liter amplified the interaction between the enzymes stepwise. Importantly, in line with these results, overexpression of PFK-2/FBPase-2 in MIN6 cells evoked only at 10 and 25 mmol/liter, an increase in insulin secretion. Furthermore, a PFK-2/FBPase-2 mutant with an abolished GK-binding motif neither showed a glucose-dependent GK binding nor was able to increase insulin secretion. The results obtained with the mammalian two-hybrid system could be confirmed by fluorescence resonance energy transfer experiments in COS cells. Furthermore, the established interaction between GK and the liver GRP served in all experiments as a control. Thus, this study clearly showed that binding and activation of GK by PFK-2/FBPase-2 in β-cells is promoted by glucose, resulting in an enhancement of insulin secretion at stimulatory glucose concentrations, without affecting basal insulin secretion.
The iron exporter ferroportin 1 is essential for development of the mouse embryo, forebrain patterning and neural tube closure
Authors: Mao Jinzhe , McKean David M. , Warrier Sunita , Corbin Joshua G. , Niswander Lee , Zohn Irene E.
Published: August 2010

Neural tube defects (NTDs) are some of the most common birth defects observed in humans. The incidence of NTDs can be reduced by peri-conceptional folic acid supplementation alone and reduced even further by supplementation with folic acid plus a multivitamin. Here, we present evidence that iron maybe an important nutrient necessary for normal development of the neural tube. Following implantation of the mouse embryo, ferroportin 1 (Fpn1) is essential for the transport of iron from the mother to the fetus and is expressed in the visceral endoderm, yolk sac and placenta. The flatiron (ffe) mutant mouse line harbors a hypomorphic mutation in Fpn1 and we have created an allelic series of Fpn1 mutations that result in graded developmental defects. A null mutation in the Fpn1 gene is embryonic lethal before gastrulation, hypomorphic Fpn1ffe/ffe mutants exhibit NTDs consisting of exencephaly, spina bifida and forebrain truncations, while Fpn1ffe/KI mutants exhibit even more severe NTDs. We show that Fpn1 is not required in the embryo proper but rather in the extra-embryonic visceral endoderm. Our data indicate that loss of Fpn1 results in abnormal morphogenesis of the anterior visceral endoderm (AVE). Defects in the development of the forebrain in Fpn1 mutants are compounded by defects in multiple signaling centers required for maintenance of the forebrain, including the anterior definitive endoderm (ADE), anterior mesendoderm (AME) and anterior neural ridge (ANR). Finally, we demonstrate that this loss of forebrain maintenance is due in part to the iron deficiency that results from the absence of fully functional Fpn1.
Forecasting the stochastic demand for inpatient care: the case of the Greek national health system
Authors: Boutsioli Zoe
Published: August 2010

The aim of this study is to estimate the unexpected demand of Greek public hospitals. A multivariate model with four explanatory variables is used. These are as follows: the weekend effect, the duty effect, the summer holiday and the official holiday. The method of the ordinary least squares is used to estimate the impact of these variables on the daily hospital emergency admissions series. The forecasted residuals of hospital regressions for each year give the estimated stochastic demand. Daily emergency admissions decline during weekends, summer months and official holidays, and increase on duty hospital days. Stochastic hospital demand varies both among hospitals and over the five-year time period under investigation. Variations among hospitals are larger than time variations. Hospital managers and health policy-makers can be availed by forecasting the future flows of emergent patients. The benefit can be both at managerial and economical level. More advanced models including additional daily variables such as the weather forecasts could provide more accurate estimations.
Customer-Base Analysis in a Discrete-Time Noncontractual Setting
Authors: Fader Peter S. , Hardie Bruce G. S. , Shang Jen
Published: August 2010

Many businesses track repeat transactions on a discrete-time basis. These include (1) companies for whom transactions can only occur at fixed regular intervals, (2) firms that frequently associate transactions with specific events (e.g., a charity that records whether supporters respond to a particular appeal), and (3) organizations that choose to utilize discrete reporting periods even though the transactions can occur at any time. Furthermore, many of these businesses operate in a noncontractual setting, so they have a difficult time differentiating between those customers who have ended their relationship with the firm versus those who are in the midst of a long hiatus between transactions. We develop a model to predict future purchasing patterns for a customer base that can be described by these structural characteristics. Our beta-geometric/beta-Bernoulli (BG/BB) model captures both of the underlying behavioral processes (i.e., customers' purchasing while “alive” and time until each customer permanently “dies”). The model is easy to implement in a standard spreadsheet environment and yields relatively simple closed-form expressions for the expected number of future transactions conditional on past observed behavior (and other quantities of managerial interest). We apply this discrete-time analog of the well-known Pareto/NBD model to a data set on donations made by the supporters of a nonprofit organization located in the midwestern United States. Our analysis demonstrates the excellent ability of the BG/BB model to describe and predict the future behavior of a customer base.
Commentary—Bidders' Experience and Learning in Online Auctions: Issues and Implications
Authors: Srinivasan Kannan , Wang Xin
Published: August 2010

This study explores the implications of rejecting the sealed-bid abstraction proposed by Zeithammer and Adams [Zeithammer, R., C. Adams. 2010. The sealed-bid abstraction in online auctions. Marketing Sci. 29(6) 964–987]. Using a conditional order statistic model that relies on the joint distribution of the top two proxy bids of an auction, Zeithammer and Adams show that inexperienced bidders' reactive bidding is the main cause of the rejection of the sealed-bid abstraction. Their empirical study suggests that a large percentage of bidders reactively bid, and there is weak evolutionary pressure for bidders to converge to sealed bidding. We discuss theoretical implications of this rejection and the role of bidder experience, as well as inferences about bidder learning. Tracking an inexperienced bidder's bidding behavior over time, we show that bidders learn and their bidding strategy gravitates toward rational bidding. Potential biases in bidder experience measurement and bidder learning can be assessed using a cross-sectional, time-series data set that tracks a random sample of new eBay bidders. Learning speed is faster with their complete bidding history rather than feedback ratings or winning observations only. We highlight the importance of proper measures of bidder experience and its effect on bidding strategy evolutions, both of which play important roles in clarifying bidding behavior in online auctions.
Calcium Homeostasis and Skeletal Integrity in Individuals with Familial Hypercholesterolemia and Aortic Calcification
Authors: Awan Zuhier , Alwaili Khalid , AlShahrani Ali , Langsetmo Lisa , Goltzman David , Genest Jacques
Published: August 2010

BACKGROUND

Familial hypercholesterolemia (FH) due to mutations in the low-density lipoprotein receptor (LDLR) gene exhibit severe, premature aortic calcification in a gene-dosage, age-dependent fashion. We sought to determine potential associations with mineral and skeletal indices.

METHODS

We obtained computed tomography (CT) scan aortic calcium scores (AoCSs) in 19 (age 49 [SD 14] years) FH patients heterozygous for the 15-kb deletion at the LDLR gene and examined associations with various indices of mineral and skeletal homeostasis.

RESULTS

We found that mean bone mineral density (BMD) at the femoral neck in these patients did not differ from age-, sex-, and province-matched mean BMD, and we observed no association of AoCS with any marker of bone resorption. However, there were negative correlations between AoCS and serum concentrations of osteocalcin, a marker of bone formation (r = −0.64, P = 0.0034), urinary calcium (r = −0.59, P = 0.0085), and estimated glomerular filtration rate (r = −0.67, P = 0.0019).

CONCLUSIONS

We found that LDLR-deficient FH was not associated with obvious bone loss or a major disturbance in calcium homeostasis. The lack of LDLR, however, may modify osteoblast function or extracellular calcium distribution, manifesting as lower bone formation, and reduced calcium excretion, resulting in increased deposition in calcifying vascular tissue.
A Consolidation and Contaminant Transport Device for Assessing Reactive Mat Effectiveness for Subaqueous Sediment Remediation
Authors: Meric Dogus , Sheahan Thomas C. , Alshawabkeh Akram , Shine James
Published: August 2010

This paper describes the design and fabrication of a new laboratory testing column to assess the effectiveness of a permeable reactive mat for in situ sediment remediation. After the composite mat, which consists of top and bottom filtering geotextile layers and a middle reactive core, is placed on the sediment surface, hydrodynamic dispersion and pore fluid flow carry contaminants through the mat. In the reactive layer, the contaminants react with one or more amendments. A thin cap of new sediment material can be placed on top of the geocomposite to promote a new, healthy benthic community. The processes controlling these geocomposites have not been physically modeled to assess their effectiveness. The new device is fundamentally a sediment column, but with the capability to apply a constant, overlying stress to the sediment-reactive mat column to cause its consolidation. Pressure-volume controllers at the top and bottom of the sediment column allow in situ pressure conditions to be imposed and allow for chemical sampling of inflow/outflow fluids.
Guided Side-Bend: An Alternative Qualification Method for Butt Fusion Joining of Polyethylene Pipe and Fittings
Authors: Sandstrum Steve , Burwell Dudley , McGriff Steve , Craig Jim , Svetlik Harvey
Published: August 2010

Historically, the procedure for butt fusion joining of polyethylene pipe has been qualified on the basis of two fundamental tests that are widely recognized within the industry. These are the tensile-impact (T-I) test method found in ASTM F2634-07 and the reverse-bend (RB) or bend-back test as described in ASTM F2620-06. Both of these test methods have been extensively utilized within the industry, and both have some specific limitations as it relates to qualification of butt fusion joining conducted in the field. ASTM F2634-07 is a highly sophisticated testing method involving precision instrumented laboratory equipment. This makes it impractical for an on-site qualification for butt fusion procedures in the field. The bend-back test, on the other hand, lends itself to field implementation, but as the method is applied to a larger diameter, heavy-walled pipe, the practicality of performing the test and safety considerations become a limiting factor. This paper will examine an alternative test method referred to as guided side-bend or full-face testing that appears very promising as an alternative to the RB test as described in ASTM F2620-06. The test method will be fully described, and data will be presented comparing T-I results and traditional bend-back results to those obtained using the side-bend test method. The discussion of the test results and safety considerations of the proposed test method will be addressed, and conclusions will be drawn regarding its future applicability.
Identification of several novel non-p.R132 IDH1 variants in thyroid carcinomas
Authors: Hemerly Jefferson Pessoa , Bastos André Uchimura , Cerutti Janete M
Published: August 2010

Context

Somatic mutations at residue R132 of isocitrate dehydrogenase 1 (IDH1) were recently discovered in gliomas and leukaemia at a high frequency. IDH1 is a metabolic gene, and the R132 mutations create a new enzymatic activity.

Objectives

To determine whether IDH1 had somatically acquired mutations in thyroid carcinomas.

Design

Exons 4 and 6 of IDH1 were sequenced in a large panel of thyroid tumours (n=138) and compared with the patients normal DNA (n=26). We also correlated IDH1 mutations with clinical–pathological data and BRAF and RAS mutational status.

Results

We identified four novel and two previously described non-synonymous variants in thyroid carcinomas, which were absent in benign tumours and paired normal thyroid. Although IDH1 variants occurred at higher frequency in follicular thyroid carcinomas, follicular variant of papillary thyroid carcinoma (PTC) and undifferentiated thyroid carcinomas than the observed variants in classical PTC (15/72 vs 3/37), it was not significant (P=0.1). Sequence alignment across several species shows that all IDH1 genetic alterations occurred at evolutionarily conserved residues located within the active site, and therefore, are likely to affect protein function. Unlike other tumours, IDH1 and BRAF or RAS mutations are not mutually exclusive. There was no association between IDH1 mutational status and clinical characteristics.

Conclusion

IDH1-acquired genetic alterations are highly prevalent in thyroid carcinomas (16%). Our findings not only extend our understanding of the molecular mechanism underlying pathogenesis of thyroid tumours, but also emphasize the biological differences between tumour types. Those tumours with IDH1 mutations might benefit from therapies that exploit this alteration.
SDHB loss predicts malignancy in pheochromocytomas/sympathethic paragangliomas, but not through hypoxia signalling
Authors: Blank Annika , Schmitt Anja M , Korpershoek Esther , van Nederveen Francien , Rudolph Thomas , Weber Nicole , Strebel Räto Thomas , de Krijger Ronald , Komminoth Paul , Perren Aurel
Published: August 2010

Prediction of malignant behaviour of pheochromocytomas/sympathetic paragangliomas (PCCs/PGLs) is very difficult if not impossible on a histopathological basis. In a familial setting, it is well known that succinate dehydrogenase subunit B (SDHB)-associated PCC/PGL very often metastasise. Recently, absence of SDHB expression as measured through immunohistochemistry was shown to be an excellent indicator of the presence of an SDH germline mutation in PCC/PGL. SDHB loss is believed to lead to tumour formation by activation of hypoxia signals. To clarify the potential use of SDHB immunohistochemistry as a marker of malignancy in PCC/PGL and its association with classic hypoxia signalling we examined SDHB, hypoxia inducible factor-1α (Hif-1α) and its targets CA-9 and GLUT-1 expression on protein level using immunohistochemistry on a tissue micro array on a series of familial and sporadic tumours of 115 patients. Survival data was available for 66 patients. SDHB protein expression was lost in the tumour tissue of 12 of 99 patients. Of those 12 patients, 5 had an SDHB germline mutation, in 4 patients no germline mutation was detected and mutational status remained unknown in parts in 3 patients. Loss of SDHB expression was not associated with increased classic hypoxia signalling as detected by Hif-1α, CA-9 or GLUT-1 staining. Loss of SDHB expression was associated with an adverse outcome. The lack of correlation of SDHB loss with classic hypoxia signals argues against the current hypoxia hypothesis in malignant PCC/PGL. We suggest SDHB protein loss as a marker of adverse outcome both in sporadic and in familial PCC/PGL.
The chemokine CXCL1 induces proliferation in epithelial ovarian cancer cells by transactivation of the epidermal growth factor receptor
Authors: Bolitho Christine , Hahn Michael A , Baxter Robert C , Marsh Deborah J
Published: August 2010

The chemokine CXCL1 is elevated in plasma and ascites from patients with ovarian cancer. We have previously shown that CXCL1 is a marker of phosphatidylinositol 3-kinase signalling in epithelial ovarian cancer (EOC) cell lines, a pathway that is commonly activated in ovarian tumours. To investigate whether CXCL1 also has functional significance in ovarian cancer, this chemokine was either down-regulated using siRNAs or overexpressed by transfection of CXCL1 into the EOC cell lines SKOV3 and OVCAR-3 and proliferation assessed over 7 days. Overexpression of CXCL1 increased proliferation of ovarian cancer cells over 7 days, while down-regulation was inhibitory. Treatment of cells with recombinant CXCL1 induced epidermal growth factor receptor (EGFR) phosphorylation at Y1068, indicating crosstalk between the CXCL1 G-protein-coupled receptor CXCR2 and the EGFR. CXCL1-induced proliferation was also decreased by inhibition of EGFR kinase activity and was dependent on extracellular matrix metalloproteinase-mediated release of heparin-binding EGF (HB-EGF). Involvement of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1/2 (ERK1/2) signalling was also evident since inhibition of both Ras and MEK activity decreased CXCL1-induced proliferation. CXCL1-induced ERK1/2 phosphorylation was inhibited by the MEK1 inhibitor PD98059; however, EGFR phosphorylation was unaffected, indicating that CXCL1 activation of MAPK signalling is downstream of the EGFR. Taken together, these data show that CXCL1 functions through CXCR2 to transactivate the EGFR by proteolytic cleavage of HB-EGF, leading to activation of MAPK signalling and increased proliferation of EOC cells.
Real-Time Fiber-Optic Casing Imager
Authors: Rambow F. H. , Dria D. E. , Childers B. A. , Appel M.. , Freeman J. J. , Shuck M. Y. , Poland S. H. , Dominique T..
Published: August 2010

During the last several years, significant progress has been made in the use of fiber-optic technology for well and reservoir surveillance. While most effort in this field appears to be concentrated on the development of fiber-optic-based meters for temperature, pressure, and flow, comparably few publications have been made to date about the use of fiber-optic technology for monitoring deformations of well tubulars and casings.

In this article, we report on recent advances in our development of a real-time fiber-optic-based casing imager. This device is designed for continuous, high-resolution monitoring of the shape of casings or well tubulars and, therefore, enables the determination of strain imposed on the well. Small-scale and full-casing-sized laboratory tests have demonstrated that the latest generation of this system is sufficiently sensitive to detect casing deformations of less than 10°/100 ft and covers compressive and tensile axial-strain ranges from less than 0.1 to 10%. We will discuss the background technology, measurement sensitivity and strain-response characterization, as well as the scaleup work that has been performed to date. Our article also includes an overview of field-test results and illustrates how real-time deformation monitoring could form a significant component of reservoir-surveillance strategies.
Sand Cleanouts With Coiled Tubing: Choice of Process, Tools and Fluids
Authors: Li Jeff , Misselbrook John , Sach Manfend
Published: August 2010

Cleaning fill from wellbores is the most common coiled tubing (CT) application. The process is a function of multiple variables including fluid properties, flow velocities, wellbore geometry and deviation, pipe eccentricity, particle properties, fill penetration rate and wiper trip speed. Removing fill from wells with low bottom hole pressures (BHP) can be challenging especially if wells are completed with smaller diameter production tubulars which significantly reduce circulation flow cross-section and choke flow(1). Such challenges are further compounded by high deviation or horizontal well trajectories especially in large diameter wellbores.

A variety of cleanout methods have been developed in the past, often incorporating high circulation rates, special fluids, wiper trips, or reverse circulation to remove solids. Many of these conventional sand cleanout methods often apply excess hydrostatic pressure on the formation, resulting in lost circulation in pressure depleted reservoirs. The conventional solution to overcome excess hydrostatic pressure has been to include nitrogen to reduce fluid density and thus lessen the hydrostatic head; however, sand vacuuming technology using a concentric coiled tubing (CCT) with a downhole jet pump is an alternative technique for removing fill without placing a hydrostatic load on the reservoir.

This paper reviews the individual sand cleanout systems and discusses the advantages and limitations related to each method. In recent years, cleaning sand using the wiper trip method has become the preferred technique. However, an appropriate pump rate and reservoir pressure are needed to maintain a proper return flow rate to carry the sands to the surface. For pressure-depleted reservoirs completed with horizontal wells, a sand vacuuming system can be used to efficiently remove the debris without circulating nitrogen and without high pump rates. When the fill cannot be removed from large-diameter deviated wellbores using conventional low-cost cleanout fluids, then fluids with high solids suspension capability (under shear conditions) in conjunction with wiper tripping may be an economical option. The main application for the reverse circulation technique is cleaning sand from large diameter wellbores when the necessary pump rates for conventional "forward" circulation are not achievable. A venturi junk bailer is often used to retrieve larger or heavier material which cannot be circulated out by traditional methods. Field cases are provided, demonstrating how to select the proper cleaning method and how to efficiently remove sand from a wellbore based on both operational and logistical conditions.
Determining Wax Type: Paraffin or Naphthene?
Authors: Bacon Mark M. , Romero-Zerón Laura B. , Chong Ken K.
Published: August 2010

Paraffin-wax deposits are known to be a worldwide problem in the upstream petroleum industry. Considerable resources are expended on inhibiting or removing wax deposits every year. Paraffin wax is not the only type of crude-oil-based wax. Microcrystalline waxes, composed of naphthene and iso-paraffin molecules, also exist but are not well studied. The predominance of paraffin (also called macrocrystalline) wax and paraffin-wax-inhibition techniques will likely lead to paraffin-wax treatments being applied to naphthene- based reservoirs. It is unclear how well a paraffin-based treatment will apply to naphthene-based oil.

The current study investigates the use of cross-polarized microscopy (CPM) to determine if a crude oil contains macrocrystalline or microcrystalline waxes. The type of wax present in the crude oil can be determined using crystal morphology and size. This study demonstrates that paraffin-wax crystals are elongated structures with statistically larger sizes than the microcrystals. Microcrystalline waxes are shown to be statistically smaller and rounded structures.
Significant Improvement in the Accuracy of Pressure-Transient Analysis Using Total Least Squares
Authors: Dastan Aysegul , Horne Roland N.
Published: August 2010

In this study, we show significant improvements over conventional pressure-transient analysis on the basis of nonlinear regression by using total least squares (TLS), which minimizes errors in both pressure and time simultaneously. To our knowledge, TLS has not been applied to pressure-transient analysis before in this sense.

TLS regression is not an easy problem to solve mathematically, especially for nonlinear pressure-transient-model functions. In this work, we compare four different versions of TLS. We formulate a robust approximation of the TLS solution, which can handle a variety of tests and reservoir models yet does not compromise the performance of the analysis. We show that our technique reduces ambiguity in the estimation of parameters to a large extent, especially in the presence of noise in time. Using our TLS algorithm, we obtain much narrower confidence intervals on the parameter estimates of a variety of real data sets, compared to the conventional least squares (LS) approach. For synthetic data sets, we observe that the TLS estimates are often closer to the true values than estimates made with LS, especially for poorly determined problems. When the deviation is in pressure only, TLS and LS results are comparable. However, in the presence of deviations in time in addition to pressure, the performance of TLS algorithms is substantially better. We, therefore, expect that our technique will provide more accurate estimation of reservoir parameters, allowing for better forecasting of reservoir performance.
A Fully Coupled Three-Phase Model for Capillary Pressure and Relative Permeability for Implicit Compositional Reservoir Simulation
Authors: Hustad Odd Steve , Browning David John
Published: August 2010

A coupled formulation for three-phase capillary pressure and relative permeability for implicit compositional reservoir simulation is presented. The formulation incorporates primary, secondary, and tertiary saturation functions. Hysteresis and miscibility are applied simultaneously to both capillary pressure and relative permeability. Two alternative three-phase capillary pressure formulations are presented: the first as described by Hustad (2002) and the second that incorporates six representative two-phase capillary pressures in a saturation-weighting scheme. Consistency is ensured for all three two-phase boundary conditions through the application of two-phase data and normalized saturations.

Simulation examples of water-alternating-gas (WAG) injection are presented for water-wet and mixed-wet saturation functions. 1D homogeneous and 2D and 3D heterogeneous examples are employed to demonstrate some model features and performance.