bluuebunny/crossref_metadata_2025 huggingface dataset:
Goodness-of-Fit Tests and Descriptive Measures in Fuzzy-Set Analysis
Authors: Eliason Scott R. , Stryker Robin
Published: September 2009

In this article the authors develop goodness-of-fit tests for fuzzy-set analyses to formally assess the fit between empirical information and various causal hypotheses while accounting for measurement error in membership scores. These goodness-of-fit tests, and the accompanying logic, provide a sound inferential foundation for fuzzy-set methodology. The authors also develop descriptive measures to complement these tests. Examples from Stryker and Eliason (2003) and Mahoney (2003) show how goodness-of-fit tests and descriptive measures may be used to assess individual causal factors as well as conjunctions of factors. The authors show how these tools provide more information in a fuzzy-set analysis than do tests currently in use. In providing this inferential foundation, the authors also show that fuzzy-set methods (a) are no less amenable to falsificationist methods of the Neyman-Pearson type than are standard statistical techniques and (b) may be usefully applied in either an exploratory/inductive or a confirmatory/deductive research design.
Hypersensitivity Syndrome Induced by Anticonvulsants: Possible Cross‐Reactivity Between Carbamazepine and Lamotrigine
Authors: Aouam Karim , Romdhane Foued Ben , Loussaief Chaouki , Salem Randa , Toumi Adnène , Belhadjali Hichem , Chaabane Amel , Boughattas Naceur A. , Chakroun Mohamed
Published: September 2009

A 14‐year‐old male presents with erythroderma and fever 44 days after carbamazepine intake. Laboratory exams show eosinophilia and elevated liver enzymes, and thoracic imaging reveals interstitial pneumonitis. All symptoms disappear after carbamazepine withdrawal. A patch test to carbamazepine performed 6 weeks after recovery is positive. About 8 months later, the patient exhibits the same clinical and biological picture 52 days after lamotrigine intake. Lamotrigine is stopped and all symptoms disappear. A patch test to LMG is positive. This case illustrates a possible cross‐reactivity between carbamazepine and lamotrigine, which are aromatic and nonaromatic anticonvulsants, respectively.
Compatibilizing Effect of Fluororubber Grafted by γ-Methacryloxypropyltrimethoxysliane in Fluororubber/Silicone Rubber Blends
Authors: Guo Jianhua , Zeng Xingrong , Luo Quankun
Published: September 2009

The fluororubber/silicone rubber blends were prepared by using fluororubber grafted by γ-methacryloxypropyltrimethoxysliane as a compatibilizer. Fourier transform infrared Spectra revealed that γ-methacryloxypropyltrimethoxysliane has been grafted onto fluororubber backbone. The effect of the compatibilizer content on curing characteristics, stress—strain behavior, mechanical properties, heat aging properties, and oil resistance was investigated. The results showed that the mechanical properties and oil resistance of the blends were improved with increasing of the compatibilizer up to 11.8 wt%. The compatibility of fluororubber and silicone rubber phase was characterized by dynamic mechanical analysis.
Food or Fuel? An Analysis of Systems in Conflict
Authors: Burkink Tim J. , Marquardt Raymond
Published: September 2009

Ethanol, a petroleum-alternative fuel produced in the United States primarily from corn, is being heralded as a remedy for global warming, geopolitical instability, and rural economic malaise. However, there are potential negative repercussions from increasing ethanol production, including pressure on the world food supply. Stakeholder performance and interconnections among stake-holders are explored in this examination of the sustainability of the corn-based ethanol system at a critical juncture. The most likely winners and losers from a growing ethanol industry and directions for future research are identified.
The Effect of Early Hyaluronic Acid Delivery on the Development of an Acute Articular Cartilage Lesion in a Sheep Model
Authors: Kaplan Lee D. , Lu Yan , Snitzer Jonathan , Nemke Brett , Hao Zhengling , Biro Steven , Albiero William , Stampfli Herman F. , Markel Mark , Popkin Charles , Baum Samuel Z.
Published: September 2009

Background

Partial-thickness articular cartilage lesions occur with knee trauma and may progress to osteoarthritis. This study evaluates the effectiveness of hyaluronic acid on cartilage healing after acute knee injury in sheep.

Hypothesis

Early administration of hyaluronic acid to an acute cartilage injury will prevent chondrocyte death and improve cartilage metabolism.

Study Design

Controlled laboratory study.

Methods

A 10 × 10 mm partial-thickness articular cartilage lesion was created on the medial condyle of 16 adult sheep stifles (hindlimbs). Eight sheep received intra-articular hyaluronic acid injections at days 0, 8, and 15, and 8 controls received saline. Contralateral stifles were nonoperated controls. All sheep were sacrificed at 12 weeks after surgery. Synovial fluid was drawn before surgery and after euthanasia for collagen II, nitric oxide, and interleukin-1 beta analysis. The medial condyle was analyzed by gross appearance, confocal laser microscopy for cell viability, histologic analysis for cartilage morphology, and dimethylmethylene blue assay for proteoglycan.

Results

At 12 weeks, histologic analysis revealed that the hyaluronic acid group had significantly better scores than the saline group ( P = .001). The hyaluronic acid group had significantly greater glycosaminoglycan content than the saline group ( P = .011), and showed a trend of reduced chondrocyte death compared with the saline group ( P = .07). Synovial fluid showed no significant differences between the groups in collagen II, nitric oxide, and interleukin-1 beta levels.

Conclusion

The results demonstrated that early administration of hyaluronic acid shows a significant improvement in cartilage histologic analysis and increased glycosaminoglycan content after acute traumatic cartilage injury.

Clinical Relevance

Early hyaluronic acid treatment for acute partial-thickness articular cartilage lesions may decrease or delay articular degeneration.
Islamic Alternatives to Purely Capitalist Modes of Finance: A Study of Malaysian Banks from 1999 to 2006
Authors: ElGindi Tamer , Said Mona , Salevurakis John William
Published: September 2009

Like Western financial markets, Islamic modes of finance offer services characterized by profit-and-loss sharing while also providing certain debt-based instruments. Unlike traditional capitalist modes of finance, however, Islamic finance places a unique emphasis upon the former, thus prompting many comparisons between the performance of Islamic banks and conventional ones. Given the mixed results of these studies, our paper analyzes eight banks in Malaysia offering both conventional and Islamic banking operations. Our comparison is conducted via discussions of profitability, liquidity, and asset quality. It is illustrated via this micro-level analysis that Islamic modes of finance may generally equal or surpass the quantitative measures of performance describing traditional capitalist finance systems and simultaneously encourage higher levels of social equity and economic stability in the era of financialization.

JEL classification: B25, D33, D63, E44, N25
Officer Safety Trumps Passenger Privacy
Authors: Ross Darrell L. , Myers Jill Joline
Published: September 2009

In a unanimous 2009 opinion, the Supreme Court of the United States ruled that the Fourth Amendment authorizes officers to frisk vehicle occupants during a traffic stop if there is reasonable suspicion to believe that the person is armed and dangerous. Situations reasonably suggesting the possible presence of weapons by any or all seized persons during legitimate traffic stops now affirmatively allow an immediate show of authority to neutralize the potential danger. The decision resulted from the court’s balancing interests under the Reasonableness Clause of the Fourth Amendment. The nature and extent of the passenger’s privacy interest in bodily integrity was weighed against the government’s interest in officer safety. Officer safety trumped passenger privacy. Although there are those who would claim that the current decision is but another step toward dissipating the Bill of Rights provision as it relates to matters involving the automobile, the decision is more of an evolution than an outright abandonment (Coolidge v. New Hampshire, 1971). The Fourth Amendment mandates that all searches and seizure be reasonable. This article discusses the evolution of Fourth Amendment law as it relates to frisks involving vehicles and its occupants. This research traces the evolution of these frisks from its earliest roots under Carroll v. United States (1925), to its inception under Terry v. Ohio (1968) and finally, to the most recent decision, Arizona v. Johnson (2009). Society’s privacy interests and police officers’ safety interests are explored from a practical and workable context such that an appropriate balance of conduct may result when conducting legitimate traffic encounters.
Mercury recovery from cold cathode fluorescent lamps using thermal desorption technology
Authors: Chang T.C. , Chen C.M. , Lee Y.F. , You S.J.
Published: September 2009

Cold cathode fluorescent lamps (CCFLs) are globally used components of high technology products. A large amount of mercury in waste CCFLs is being recovered by thermal desorption technology in Taiwan. However, the complexity of the samples affects the thermal desorption efficiency and increases costs. This study identifies the mercury release behaviour of amalgam, phosphor and mercury-containing components as well as waste CCFLs by bench scale thermal desorption test. The results show that the mercury was released from amalgam and mercury/fluorescent powder from a real treatment plant at temperatures between 550°C to 850°C, which is much higher than from cinnabar at 300°C to 380°C and that of pure mercury, high pressure mercury lamps, and fluorescent tubes containing mercury/fluorescent-powder at 50°C to 250°C. In addition, the experiment also showed the mercury release peak of the mercury/fluorescent powders from a real treatment plant occurs at much higher temperatures than that of commercial phosphor at 50°C to 200°C. Thus, complete separation of the cracked CCFLs is necessary to effectively recover phosphor and mercury at low financial and energy cost.
Problems of solid waste management on Mount Kilimanjaro: A challenge to tourism
Authors: Kaseva Mengiseny E. , Moirana Josia L.
Published: September 2009

We report on the findings of a study on the problems of solid waste management (SWM) on Mountain Kilimanjaro (MK) which is located within Kilimanjaro National Park (KINAPA) in Northern Tanzania. The study was prompted by the fact that flourishing tourism on the mountain over the years has resulted in an increase in the tonnage of solid waste (SW) generated, posing serious challenges in its collection and disposal. The methodology employed in this study included physical observations and questionnaire surveys, as well as waste sorting and weighing to quantify and characterize waste loads collected from each tourist route station covered in this study. On the basis of the established SW generation rate (0.6 kg ca—1 day—1) a total amount of SW generated was estimated to range from about 87 tonnes (in 2003) to 125 tonnes (in 2006). An improvement in SW collection from 64% in 2003 to 94% in 2006 was also noted. This improvement can be attributed to the trash-in-trash-out (TITO) system of SW collection which is currently practiced by the management of KINAPA for SWM on MK. The study also highlights potential environmental pollution including air pollution from open burning and pit disposal of SW. Based on average percentage values of waste components and the estimated quantity of waste generated, it was established that the total waste quantum contains about 34% of recyclables. The study recommends that resource recovery and conservation measures through waste recycling and re-use be instituted as one of the options for sustainable SWM on MK.
Yield and chemical composition of fractions from fermented shrimp biowaste
Authors: Narayan Bhaskar , Velappan Suresh Puthanveetil , Zituji Sakhare Patiram , Manjabhatta Sachindra Nakkerike , Gowda Lalitha Ramakrishna
Published: September 2009

Chemical composition of chitinous residue and fermentation liquor fractions, obtained from fermented shrimp biowaste, was evaluated in order to explore their potential for further utilization. Lyophilization of the liquor fraction obtained after fermentation resulted in a powder rich in both protein (30%) and carotenoids (217.18 ± 2.89 µg/g). The yield of chitinous residue was 44% (w/w) whereas the yield of lyophilized powder was >25% (w/v). About 69% of total carotenoids were recovered by fermentation. Fermentation resulted in the removal of both protein as well as ash content from the shrimp biowaste, as indicated by ~92% deproteination and >76% demineralization, respectively. Post fermentation, the residue had a chitin content of >90%. The lyophilized liquor fraction had all the essential amino acids (except threonine) in quantities comparable to Food & Agriculture Organization/World Health Organization reference protein. The composition of fermentation liquor is indicative of its potential for application as an amino acid supplement in aquaculture feed formulations.
Accumulating care
Authors: Maher JaneMaree
Published: September 2009

Women who mother and undertake paid work are often represented as moving between separate spheres of caring and paid labour whilst facing intractable temporal conflicts. Despite this conflict, often represented as a ‘care time deficit’, mothers in western societies have continued their movement into the paid workforce. I examine the different temporal modes of paid work and caring labour that women undertake and argue that there are temporal commonalities as well as conflicts in paid work and care. I propose that women’s diverse labours across these spheres are directed towards accumulating care, and suggest women may be generating a new temporal framework for work and care beyond conflicting schedules. I argue that women’s practices do occur across complex and potentially conflictive temporalities but are unified by a focus on the accumulation of care. Recognizing women’s capacity to draw together and synthesize work across diverse temporal orders may allow for greater understanding of how women create and use time to give care.
The re-enchantment of time
Authors: Lee Raymond L.M.
Published: September 2009

Rationalization of time is generally taken as part of the human effort to break free from the vicissitudes of nature and to actualize greater stability in social life through structured routines predicated on temporal measurements. As a result, abstract notions of time allow the conceptualization of the future to be framed as calculable alternative possibilities related to decisions and actions made in the here and now. However, the problem of reflexivity in modernity as well as the question of fragmentation in postmodernism introduced deep scepticism to the idea of calculable and predictable futures. Variable risks and yawning uncertainties accompany the endeavour to see and plan the future. Rationalization has ironically increased the inexactitude of the means to perceive the future. Here, a parallel can be drawn with the fear of death as the delimitation of the life space where the means to perceive the future are not conceived as applicable beyond the point of death. In the modern world of hard-nosed empiricism and hard-driving technology, death is reckoned as the final frontier in which the future is simply unknowable, and so it comes to present a source of consternation for any individual inquiring into the possibility of existence beyond the life space. Yet re-enchantment of this life space is providing new means for perceiving alternative time and reviving ideas about the afterlife. In a sense, the uncertainty of what the future holds for individuals living in late modernity is compensated by alternative beliefs in transcendental futures.
Working status and leisure
Authors: Kraaykamp Gerbert , van Gils Wouter , van der Lippe Tanja
Published: September 2009

Paid labour is often said to come at a price. Using time-budget information on 9063 Dutch respondents and their partners, we investigated whether couples working full time economize on their solitary and social time budget. Results show that individuals who are part of a full-time working couple spend a smaller share of their available time budget on social interaction with relatives and friends than individuals from single-earner families or combination households. Instead, in full-time working couples, partners prefer to spend a relatively large share of their leisure time on institutionalized social interaction, such as volunteering, cultural participation and attending sports events.
Chemotherapy-Related Side Effects in Childhood Acute Lymphoblastic Leukemia in Indonesia: Parental Perceptions
Authors: Sitaresmi Mei Neni , Mostert Saskia , Purwanto Ignatius , Gundy Chad M. , Sutaryo  , Veerman Anjo J. P.
Published: September 2009

Noncompliance with prescribed medication has been associated with increased chance of relapse and poor outcome. Side effects may be an important cause of noncompliance. Fifty-one parents of children with acute lymphoblastic leukemia in a tertiary care hospital in Indonesia were interviewed about their perception of side effects and their impact on treatment noncompliance and daily activities. A symptom checklist assessing 13 common symptoms was used to examine side effects. During chemotherapy, childhood acute lymphoblastic leukemia patients suffered from psychological as well as physical side effects. The most frequent side effect reported by parents was behavior alteration (92%). Second and third in frequency were increased appetite and infections, reported by 88% and 83% of parents, respectively. The most severe side effects were leg weakness, increased appetite, and behavior alteration. The overall frequency of side effects was weakly correlated to noncompliance. Reducing the impact of side effects may increase compliance with the treatment.
A Comparison of Disabled Veteran and Nonveteran Income
Authors: Fulton Lawrence V. , Belote Janna M. , Brooks Matthew S. , Coppola M. Nicholas
Published: September 2009

This study evaluates disabled veteran compensation law against its stated objective, equalizing the pay differential associated with disability. The significance of this study is that it provides insight into the efficacy of disabled veteran compensation policy, which derives from tables listed in the Code of Federal Regulations (38 CFR 4). In some cases, these tables have not been updated since 1945. Through regression analysis, personal income (appropriately transformed) is modeled as a function of four variable blocks (demographics, education, geographical, and veteran-related) using secondary data from the 2007 American Community Survey. The population includes working-age adults ages 18 to 64 ( n = 1.8 million, representing N = 190 million U.S. citizens). Regression captured 37.2% of the variance in personal income. Veteran-related variables (entered last into the model) accounted for 2.2% of the unique variance. The sample size guaranteed statistical significance, but the analysis proved practically relevant. Disabled veteran status had a large and negative effect, especially as the number of disabilities increased. The results suggest that disabled veterans who have multiple categories of disabilities do not receive income on par with society or with disabled nonveterans reporting the same number of disabilities. This finding provides evidence that 38 CFR 4 is ineffective.
2D Adaptive FE Simulations in Finite Thermo-Elasto-Viscoplasticity with Ductile Damage: Application to Orthogonal Metal Cutting by Chip Formation and Breaking
Authors: Saanouni Khemais , Lestriez Philippe , Labergère Carl
Published: September 2009

Fully coupled thermo-elasto-visco-plastic-damage constitutive equations based on the state variables under large plastic deformation are developed for metal forming simulation. Relevant numerical aspects concerning both the global resolution strategy as well as the local integration scheme are discussed. The model is implemented into ABAQUS/Explicit using the Vumat user subroutine and used in connection with a 2D adaptive mesh facility. Application is made to the orthogonal metal cutting resulting in chip formation and segmentation or breaking. This example is studied in order to examine the ability of this adaptive fully coupled approach to predict qualitatively the formation and the segmentation of the chip compared to the classical procedure, which neglects the damage effect.
Prevalence of Platelet Dysfunction and Abnormal Coagulation: Results of a Population-Based Study
Authors: Marxsen Jan H. , Forchheim Sonja , Zuske-Matthäus Alexandra , Wagner Thomas
Published: September 2009

The prevalence of impairments in the hemostatic process is unknown in acutely ill people. Data on hemostasis (PFA 100®) and the coagulation cascade of 1015 people are presented here, establishing a cohort of unselected emergency patients in a population-based approach. A high prevalence of reduced platelet function (38%) was found, which was more frequent than expected. In contrast, there was a lower prevalence (20%) of abnormal plasmatic coagulation, which was almost always explained by medication, whereas medication could not predict abnormal platelet function. Moreover, a history of disproportionate bleeding did not correlate well with abnormal platelet or coagulation factor function and could not substitute for a screening in this setting. The effect of acetylsalicylic acid (ASA) on PFA-closure time was frequently missing (34%), indicating a considerable prevalence of ASA nonresponse among the study population. These data should be applicable in similar settings. The high prevalence of unexpectedly abnormal platelet function in acute illness as well as the high prevalence of possible ASA nonresponders suggests a functional platelet assay to be effective in screening certain subpopulations of emergency patients.
Road lighting and energy saving
Authors: Boyce PR , Fotios S , Richards M
Published: September 2009

This paper examines how the lighting of roads in the UK might be changed so as to preserve the benefits while minimising energy consumption. It is divided into four sections, these being changes in technology, changes in patterns of use, changes in standards and contracts and changes in the basis of design. Useful changes in technology and patterns of use are available now, but their use will raise the question as to whether or not environmental considerations can override conventional financial constraints. Changes in standards and the basis of design are much more long term. Comparisons of road lighting standards used in different countries show significant differences that deserve examination. As for the basis of design, consideration of the importance of light to fatal and personal injury accidents of different types suggests that road lighting should be concentrated where pedestrians are common, not where speeds are highest. Ultimately, considering carefully what problem road lighting is intended to solve and whether or not road lighting is the best answer is the key to minimising the energy consumption of road lighting without diminishing road safety.
Lamps for improving the energy efficiency of domestic lighting
Authors: Jacob B
Published: September 2009

Change is coming to the domestic lighting market. The light source that has dominated domestic lighting since the birth of electric lighting is going to be squeezed out and others with different characteristics will replace it. Some of these are already on the market, some are entering the market now and some have yet to make an entrance. The householder is certainly going to have plenty of lamp types to choose from, all of them claiming to be ‘low energy’. Alternative domestic light sources include compact fluorescents which produce enormous energy savings over the incandescent lamp, but do not have its visual appearance, colour quality or instantaneous full light output. Tungsten halogen lamps do possess the light qualities of the incandescent lamp and are available in the traditional light bulb shape, but do not provide the same energy savings as compact fluorescents. LED’s are potentially the ideal replacement for incandescent lamps having a long life with a discrete appearance, but improvements to efficacy for the warm white version are required to meet Building Regulations. Research on OLEDs continues, but current usage is limited to display applications, a situation which may not change for some years.
Reply to: Differences in the Success of NFL Coaches by Race
Authors: Madden Janice Fanning , Ruther Matthew
Published: September 2009

Malone, Couch, and Barrett argue that a broader analysis of fired coaches, including adding in partial season fires, considering a wider range of causes of firing, and analyzing rehiring makes the results reported by Madden ‘‘disappear.’’ We show that Malone et al. have analyzed inaccurate data. When the data used by Malone et al. are corrected and their speculations tested empirically, Madden’s conclusion that analyses of all employment decisions involving head coaches between 1990 and 2002 are consistent with discrimination against African Americans is supported.
Characterization of the specific O-polysaccharide structure and biosynthetic gene cluster of Yersinia pseudotuberculosis serotype O:15
Authors: De Castro Cristina , Skurnik Mikael , Molinaro Antonio , Holst Otto
Published: September 2009

Yersinia pseudotuberculosis serotyping scheme contains 21 serotypes based on the distribution of about 30 different O-factors within the species. The chemical structures of LPSs and the genetic basis of their biosynthesis has been determined for a number of Y. pseudotuberculosis strains representing different serotypes; thus, an overall picture of the relationship between genetics and structures is emerging. In this work, we have performed a structural and genetic analysis of the Y. pseudotuberculosis serotype O:15 O-specific polysaccharide. Our results showed that the set-up of the Y. pseudotuberculosis O:15 gene cluster is a hybrid between those of Y. pseudotuberculosis serotypes O:1b and O:5a, possibly due to a single recombination event. The hybrid nature could also be seen in the structure of the O-specific polysaccharide repeating unit pentasaccharide. It contains a tetrameric backbone identical to that of O:5a while the branching paratofuranose residue is identical to that of O:1b.
Low dietary sodium intake is associated with enhanced vascular endothelial function in middle-aged and older adults with elevated systolic blood pressure
Authors: Jablonski Kristen L. , Gates Phillip E. , Pierce Gary L. , Seals Douglas R.
Published: September 2009

Background: Age and increasing systolic blood pressure (BP) are associated with vascular endothelial dysfunction, but the factors involved are incompletely understood. We tested the hypothesis that vascular endothelial function is related to dietary sodium intake among middle-aged and older adults (MA and O) with elevated systolic BP.

Methods: Data were analyzed on 25 otherwise healthy adults aged 48—73 years with high normal systolic BP or stage I systolic hypertension (130—159 mmHg). Self-reported sodium intake was <100 mmol/d in 12 (7 M) subjects (low sodium, 73±6 mmol/d) and between 100 and 200 mmol/d in 13 (9 M) subjects (normal sodium, 144±6 mmol/d).

Results: Groups did not differ in other dietary factors, age, body weight and composition, BP, metabolic risk factors, physical activity and maximal aerobic capacity. Plasma concentrations of norepinephrine, endothelin-1, oxidized low-density lipoproteins (LDL), antioxidant status and inflammatory markers did not differ between groups. Brachial artery flow-mediated dilation (FMD) was 42% (mm Δ) to 52% (% Δ) higher in the low versus normal sodium group ( p < 0.05). In all subjects, brachial artery FMD was inversely related to dietary sodium intake (FMD mm Δr =—0.40, p < 0.05; %Δr =—0.53, p < 0.01). Brachial artery FMD was not related to any other variable. In contrast, endothelium-independent dilation did not differ between groups ( p ≥ 0.24) and was not related to sodium intake in the overall group ( p ≥ 0.29).

Conclusions: Low sodium intake is associated with enhanced brachial artery FMD in MA and O with elevated systolic BP. These results suggest that dietary sodium restriction may be an effective intervention for improving vascular endothelial function in this high-risk group.
Depletion of endogenous tumor-associated regulatory T cells improves the efficacy of adoptive cytotoxic T-cell immunotherapy in murine acute myeloid leukemia
Authors: Zhou Qing , Bucher Christoph , Munger Meghan E. , Highfill Steven L. , Tolar Jakub , Munn David H. , Levine Bruce L. , Riddle Megan , June Carl H. , Vallera Daniel A. , Weigel Brenda J. , Blazar Bruce R.
Published: September 2009

Tumor-induced immune suppression can permit tumor cells to escape host immune resistance. To elucidate host factors contributing to the poor response of adoptively transferred tumor-reactive cytotoxic T lymphocytes (CTLs), we used a systemic model of murine acute myeloid leukemia (AML). AML progression resulted in a progressive regulatory T-cell (Treg) accumulation in disease sites. The adoptive transfer of in vitro–generated, potently lytic anti–AML-reactive CTLs failed to reduce disease burden or extend survival. Compared with non–AML-bearing hosts, transferred CTLs had reduced proliferation in AML sites of metastases. Treg depletion by a brief course of interleukin-2 diphtheria toxin (IL-2DT) transiently reduced AML disease burden but did not permit long-term survival. In contrast, IL-2DT prevented anti-AML CTL hypoproliferation, increased the number of transferred CTLs at AML disease sites, reduced AML tumor burden, and resulted in long-term survivors that sustained an anti-AML memory response. These data demonstrated that Tregs present at AML disease sites suppress adoptively transferred CTL proliferation, limiting their in vivo expansion, and Treg depletion before CTL transfer can result in therapeutic efficacy in settings of substantial pre-existing tumor burden in which antitumor reactive CTL infusion alone has proven ineffective.
Relationship of erythropoietin, fetal hemoglobin, and hydroxyurea treatment to tricuspid regurgitation velocity in children with sickle cell disease
Authors: Gordeuk Victor R. , Campbell Andrew , Rana Sohail , Nouraie Mehdi , Niu Xiaomei , Minniti Caterina P. , Sable Craig , Darbari Deepika , Dham Niti , Onyekwere Onyinye , Ammosova Tatiana , Nekhai Sergei , Kato Gregory J. , Gladwin Mark T. , Castro Oswaldo L.
Published: September 2009

Hydroxyurea and higher hemoglobin F improve the clinical course and survival in sickle cell disease, but their roles in protecting from pulmonary hypertension are not clear. We studied 399 children and adolescents with sickle cell disease at steady state; 38% were being treated with hydroxyurea. Patients on hydroxyurea had higher hemoglobin concentration and lower values for a hemolytic component derived from 4 markers of hemolysis (P ≤ .002) but no difference in tricuspid regurgitation velocity compared with those not receiving hydroxyurea; they also had higher hemoglobin F (P < .001) and erythropoietin (P = .012) levels. Hemoglobin F correlated positively with erythropoietin even after adjustment for hemoglobin concentration (P < .001). Greater hemoglobin F and erythropoietin each independently predicted higher regurgitation velocity in addition to the hemolytic component (P ≤ .023). In conclusion, increase in hemoglobin F in sickle cell disease may be associated with relatively lower tissue oxygen delivery as reflected in higher erythropoietin concentration. Greater levels of erythropoietin or hemoglobin F were independently associated with higher tricuspid regurgitation velocity after adjustment for degree of hemolysis, suggesting an independent relationship of hypoxia with higher systolic pulmonary artery pressure. The hemolysis-lowering and hemoglobin F–augmenting effects of hydroxyurea may exert countervailing influences on pulmonary blood pressure in sickle cell disease.
How I treat EBV lymphoproliferation
Authors: Heslop Helen E.
Published: September 2009

Epstein-Barr virus (EBV)–associated B-cell lymphoproliferation is a life-threatening complication after hematopoietic stem cell or solid organ transplantation resulting from outgrowth of EBV-infected B cells that would normally be controlled by EBV-cytotoxic T cells. During the past decade, early detection strategies, such as serial measurement of EBV-DNA load in peripheral blood samples, have helped to identify high-risk patients and to diagnose early lymphoproliferation. Treatment options include manipulation of the balance between outgrowing EBV-infected B cells and the EBV cytotoxic T lymphocyte response and targeting the B cells with monoclonal antibodies or chemotherapy. Major challenges remain for defining indications for preemptive therapies and integrating novel and conventional therapies.
Increased ATP generation in the host cell is required for efficient vaccinia virus production
Authors: Chang Chia-Wei , Li Hui-Chun , Hsu Che-Fang , Chang Chiao-Yen , Lo Shih-Yen
Published: September 2009

To search for cellular genes up-regulated by vaccinia virus (VV) infection, differential display-reverse transcription-polymerase chain reaction (ddRT-PCR) assays were used to examine the expression of mRNAs from mock-infected and VV-infected HeLa cells. Two mitochondrial genes for proteins that are part of the electron transport chain that generates ATP, ND4 and CO II, were up-regulated after VV infection. Up-regulation of ND4 level by VV infection was confirmed by Western blotting analysis. Up-regulation of ND4 was reduced by the MAPK inhibitor, apigenin, which has been demonstrated elsewhere to inhibit VV replication. The induction of ND4 expression occurred after viral DNA replication since ara C, an inhibitor of poxviral DNA replication, could block this induction. ATP production was increased in the host cells after VV infection. Moreover, 4.5 μM oligomycin, an inhibitor of ATP production, reduced the ATP level 13 hr after virus infection to that of mock-infected cells and inhibited viral protein expression and virus production, suggesting that increased ATP production is required for efficient VV production. Our results further suggest that induction of ND4 expression is through a Bcl-2 independent pathway.
Comparative study of gene set enrichment methods
Authors: Abatangelo Luca , Maglietta Rosalia , Distaso Angela , D'Addabbo Annarita , Creanza Teresa Maria , Mukherjee Sayan , Ancona Nicola
Published: September 2009

Background

The analysis of high-throughput gene expression data with respect to sets of genes rather than individual genes has many advantages. A variety of methods have been developed for assessing the enrichment of sets of genes with respect to differential expression. In this paper we provide a comparative study of four of these methods: Fisher's exact test, Gene Set Enrichment Analysis (GSEA), Random-Sets (RS), and Gene List Analysis with Prediction Accuracy (GLAPA). The first three methods use associative statistics, while the fourth uses predictive statistics. We first compare all four methods on simulated data sets to verify that Fisher's exact test is markedly worse than the other three approaches. We then validate the other three methods on seven real data sets with known genetic perturbations and then compare the methods on two cancer data sets where our a priori knowledge is limited.

Results

The simulation study highlights that none of the three method outperforms all others consistently. GSEA and RS are able to detect weak signals of deregulation and they perform differently when genes in a gene set are both differentially up and down regulated. GLAPA is more conservative and large differences between the two phenotypes are required to allow the method to detect differential deregulation in gene sets. This is due to the fact that the enrichment statistic in GLAPA is prediction error which is a stronger criteria than classical two sample statistic as used in RS and GSEA. This was reflected in the analysis on real data sets as GSEA and RS were seen to be significant for particular gene sets while GLAPA was not, suggesting a small effect size. We find that the rank of gene set enrichment induced by GLAPA is more similar to RS than GSEA. More importantly, the rankings of the three methods share significant overlap.

Conclusion

The three methods considered in our study recover relevant gene sets known to be deregulated in the experimental conditions and pathologies analyzed. There are differences between the three methods and GSEA seems to be more consistent in finding enriched gene sets, although no method uniformly dominates over all data sets. Our analysis highlights the deep difference existing between associative and predictive methods for detecting enrichment and the use of both to better interpret results of pathway analysis. We close with suggestions for users of gene set methods.
Weighted gene co-expression network analysis of the peripheral blood from Amyotrophic Lateral Sclerosis patients
Authors: Saris Christiaan GJ , Horvath Steve , van Vught Paul WJ , van Es Michael A , Blauw Hylke M , Fuller Tova F , Langfelder Peter , DeYoung Joseph , Wokke John HJ , Veldink Jan H , van den Berg Leonard H , Ophoff Roel A
Published: September 2009

Background

Amyotrophic Lateral Sclerosis (ALS) is a lethal disorder characterized by progressive degeneration of motor neurons in the brain and spinal cord. Diagnosis is mainly based on clinical symptoms, and there is currently no therapy to stop the disease or slow its progression. Since access to spinal cord tissue is not possible at disease onset, we investigated changes in gene expression profiles in whole blood of ALS patients.

Results

Our transcriptional study showed dramatic changes in blood of ALS patients; 2,300 probes (9.4%) showed significant differential expression in a discovery dataset consisting of 30 ALS patients and 30 healthy controls. Weighted gene co-expression network analysis (WGCNA) was used to find disease-related networks (modules) and disease related hub genes. Two large co-expression modules were found to be associated with ALS. Our findings were replicated in a second (30 patients and 30 controls) and third dataset (63 patients and 63 controls), thereby demonstrating a highly significant and consistent association of two large co-expression modules with ALS disease status. Ingenuity Pathway Analysis of the ALS related module genes implicates enrichment of functional categories related to genetic disorders, neurodegeneration of the nervous system and inflammatory disease. The ALS related modules contain a number of candidate genes possibly involved in pathogenesis of ALS.

Conclusion

This first large-scale blood gene expression study in ALS observed distinct patterns between cases and controls which may provide opportunities for biomarker development as well as new insights into the molecular mechanisms of the disease.
Characterization of a salt-induced DhAHP, a gene coding for alkyl hydroperoxide reductase, from the extremely halophilic yeast Debaryomyces hansenii
Authors: Chao Hsiu-fung , Yen Yung-fu , Ku Maurice SB
Published: September 2009

Background

Debaryomyces hansenii is one of the most salt tolerant species of yeast and has become a model organism for the study of tolerance mechanisms against salinity. The goal of this study was to identify key upregulated genes that are involved in its adaptation to high salinity.

Results

By using forward subtractive hybridization we have cloned and sequenced DhAHP from D. hansenii that is significantly upregulated during salinity stress. DhAHP is orthologous to the alkly hydroperoxide reductase of the peroxiredoxin gene family, which catalyzes the reduction of peroxides at the expense of thiol compounds. The full-lengthed cDNA of DhAHP has 674 bp of nucleotide and contains a 516 bp open reading frame (ORF) encoding a deduced protein of 172 amino acid residues (18.3 kDa). D. hansenii Ahp is a cytosolic protein that belongs to the Ahp of the 1-Cys type peroxiredoxins. Phylogentically, the DhAhp and Candida albicans Ahp11 (Swiss-Prot: Q5AF44) share a common ancestry but show divergent evolution. Silence of its expression in D. hansenii by RNAi resulted in decreased tolerance to salt whereas overexpression of DhAHP in D. hansenii and the salt-sensitive yeasts Saccharomyces cereviasiae and Pichia methanolica conferred a higher tolerance with a reduced level of reactive oxygen species.

Conclusion

In conclusion, for the first time our study has identified alkly hydroperoxide reductase as a key protein involved in the salt tolerance of the extremely halophilic D. hansenii. Apparently, this enzyme plays a multi-functional role in the yeast's adaptation to salinity; it serves as a peroxidase in scavenging reactive oxygen species, as a molecular chaperone in protecting essential proteins from denaturation, and as a redox sensor in regulating H2O2-mediated cell defense signaling.
Optimal strategy to identify incidence of diagnostic of diabetes using administrative data
Authors: Asghari Shabnam , Courteau Josiane , Carpentier André C , Vanasse Alain
Published: September 2009

Background

Accurate estimates of incidence and prevalence of the disease is a vital step toward appropriate interventions for chronic disease like diabetes. A growing body of scientific literature is now available on producing accurate information from administrative data. Advantages of use of administrative data to determine disease incidence include feasibility, accessibility and low cost, but straightforward use of administrative data can produce biased information on incident cases of chronic disease like diabetes. The present study aimed to compare criteria for the selection of diabetes incident cases in a medical administrative database.

Methods

An exhaustive retrospective cohort of diabetes cases was constructed for 2002 using the Canadian National Diabetes Surveillance System case definition (one hospitalization or two physician claims with a diagnosis of diabetes over a 2-year period) with the Quebec health service database. To identify previous occurrence of diabetes in the database, a five-year observation period was evaluated using retrograde survival function and kappa agreement. The use of NDSS case definition to identify incident cases was compared to a single occurrence of an ICD-9 code 250 in the records using the McNemar test.

Results

Retrograde survival function showed that the probability of being a true incident case after a 5-year diabetes-free observation period was almost constant and near 0.14. Agreement between 10 years (maximum period) and 5 years and more diabetes-free observation periods were excellent (kappa > 0.9). Respectively 41,261 and 37,473 incident cases were identified using a 5-year diabetes-free observation period with NDSS definition and using a single ICD-9 code 250.

Conclusion

A 5-year diabetes-free observation period was a conservative time to identify incident cases in an administrative database using one ICD-9 code 250 record.
Microsatellites and SNPs linkage analysis in a Sardinian genetic isolate confirms several essential hypertension loci previously identified in different populations
Authors: Mocci Evelina , Concas Maria P , Fanciulli Manuela , Pirastu Nicola , Adamo Mauro , Cabras Valentina , Fraumene Cristina , Persico Ivana , Sassu Alessandro , Picciau Andrea , Prodi Dionigio A , Serra Donatella , Biino Ginevra , Pirastu Mario , Angius Andrea
Published: September 2009

Background

A multiplicity of study designs such as gene candidate analysis, genome wide search (GWS) and, recently, whole genome association studies have been employed for the identification of the genetic components of essential hypertension (EH). Several genome-wide linkage studies of EH and blood pressure-related phenotypes demonstrate that there is no single locus with a major effect while several genomic regions likely to contain EH-susceptibility loci were validated by multiple studies.

Methods

We carried out the clinical assessment of the entire adult population in a Sardinian village (Talana) and we analyzed 16 selected families with 62 hypertensive subjects out of 267 individuals. We carried out a double GWS using a set of 902 uniformly spaced microsatellites and a high-density SNPs map on the same group of families.

Results

Three loci were identified by both microsatellites and SNP scans and the obtained linkage results showed a remarkable degree of similarity. These loci were identified on chromosome 2q24, 11q23.1–25 and 13q14.11–21.33. Further support to these findings is their broad description present in literature associated to EH or related phenotypes. Bioinformatic investigation of these loci shows several potential EH candidate genes, several of whom already associated to blood pressure regulation pathways.

Conclusion

Our search for major susceptibility EH genetic factors evidences that EH in the genetic isolate of Talana is due to the contribution of several genes contained in loci identified and replicated by earlier findings in different human populations.
Frequency of single nucleotide polymorphisms in NOD1gene of ulcerative colitis patients: a case-control study in the Indian population
Authors: Verma Ravi , Ahuja Vineet , Paul Jaishree
Published: September 2009

Background

Epidemiological studies have provided enough evidence that genetic factors have an important role in determining susceptibility to IBD. The most significant finding in the IBD research has been identification of mutations in the gene that encodes Nod2 (nucleotide-binding oligomerization domain 2) protein in a subgroup of patients with Crohn's disease. However, a very similar gene encoding Nod1 protein still has not been well documented for its association with Ulcerative colitis patients. Detection of polymorphism in NOD1 gene using SNP analysis has been attempted in the present study. We evaluated frequency and significance of mutations present in the nucleotide-binding domain (NBD) of NOD1 gene in context to Indian population.

Methods

A total of 95 patients with ulcerative colitis and 102 controls enrolled in the Gastroenterology department of All India Institute of Medical Sciences, New Delhi were screened for SNPs by DHPLC and RFLP techniques. Exon 6 locus in the NBD domain of NOD1 gene was amplified and sequenced. Genotype and allele frequencies of the patients and controls were calculated by the Pearson's χ2 test, Fisher's exact test and ANOVA with Bonferroni's correction using SPSS software version 12.

Results

We have demonstrated DHPLC screening technique to show the presence of SNPs in Exon 6 locus of NBD domain of NOD1 gene. The DHPLC analysis has proven suitable for rapid detection of base pair changes. The data was validated by sequencing of clones and subsequently by RFLP analysis. Analyses of SNP data revealed 3 significant mutations (W219R, p = 0.002; L349P, p = 0.002 and L370R, p = 0.039) out of 5 in the Exon 6 locus of NBD domain of the gene that encompasses ATP and Mg2+binding sites. No significant association was observed within different sub phenotypes.

Conclusion

We propose that the location of mutations in the Exon 6 spanning the ATP and Mg2+ binding site of NBD in NOD1 gene may affect the process of oligomerization and subsequent function of the LRR domain. Further studies are been conducted at the protein level to prove this possibility.