bluuebunny/crossref_metadata_2025 huggingface dataset:
An aggressive course of Xp11 translocation renal cell carcinoma in a 28‐year‐old man
Authors: Koie Takuya , Yoneyama Takahiro , Hashimoto Yasuhiro , Kamimura Noritaka , Kusumi Tomomi , Kijima Hiroshi , Ohyama Chikara
Published: March 2009

Abstract:  Cases of renal cell carcinoma (RCC) associated with Xp11 translocations are rare and are reported predominantly in children. We report a case of a young man who developed an aggressive Xp11 translocation RCC. A 28‐year‐old man presented with back pain, fever and macroscopic hematuria. Computed tomography of the abdomen showed a heterogeneous mass in the left kidney. Left radical nephrectomy was performed. Hematoxylin–eosin staining revealed nested and papillary architecture, clear and eosinophilic cytoplasm and vesicles with prominent nucleoli. Immunohistochemical evaluation revealed that the tumor cells showed nuclear labeling for TFE3 protein. On the basis of these findings, the case was diagnosed as Xp11 translocation RCC. This tumor massively recurred and led to the patient's death 2 years after the initial diagnosis. The utility of immunohistochemistry using antibodies against TFE3 in RCC occurring in young adults may be necessary for accurate diagnosis.
Symptom severity and patient perceptions in overactive bladder: how are they related?
Authors: Homma Yukio , Gotoh Momokazu
Published: March 2009

OBJECTIVE

To assess the relationship between symptom severity and patient perceptions in patients with overactive bladder (OAB), as estimated by OAB Symptom Score (OABSS) and patient‐reported outcome measures, respectively.

PATIENTS AND METHODS

Post‐hoc analyses were conducted on the existing data from patients with OAB. In addition to the OABSS, patients completed three patient‐reported outcome measures, the OAB questionnaire (OAB‐q), Patient Perception of Bladder Condition (PPBC) and Medical Outcomes Study Short‐Form 36 (SF‐36). Relationships of the OABSS were assessed through correlations with the OAB‐q, PPBC and SF‐36; all analyses were exploratory.

RESULTS

In all, 194 participants were analysed; the OABSS correlated relatively closely with the PPBC and OAB‐q subscales of health‐related quality of life (r = 0.36–0.57). There was a particularly good correlation with the OAB‐q symptom bother (r = 0.73). However, the OABSS correlated somewhat less with the SF‐36 subscales (r = 0.16–0.27). There were fairly close correlations between the OABSS and the OAB‐q items; for daytime frequency with ‘frequency of urination during daytime hours’ (r = 0.44); night‐time frequency with ‘night‐time urination’ (r = 0.44), ‘waking up at night because you had to urinate’ (r = 0.51) and ‘awakening from sleep’ (r = 0.44); urgency with ‘a sudden urge to urinate with little or no warning’ (r = 0.65) and ‘an uncontrollable urge to urinate’ (r = 0.69), urgency incontinence with ‘accidental loss of small amounts of urine’ (r = 0.74) and ‘urine loss associated with a strong desire to urinate’ (r = 0.79). All the items except ‘awakening from sleep’ belonged to the OAB‐q symptom bother domain.

CONCLUSIONS

It is possible to roughly but sufficiently infer patient perceptions of bladder condition and symptom bother by measuring symptom severity, as estimated by the OABSS.
Rational Choice and Interpretive Evidence: Caught between a Rock and a Hard Place?
Authors: Hampsher-Monk Iain , Hindmoor Andrew
Published: March 2009

Following Green and Shapiro's critique, debate about the value of rational choice theory has focused upon the question of its relationship to what we call ‘external’, largely quantitative, empirical evidence. We argue that what is most striking about rational choice theory is, however, its neglect of interpretive evidence. Our survey of 570 articles, published in the American Political Science Review and the American Journal of Political Science between 1984 and 2005 employing rational choice theory, revealed that only 139 made even the most cursory use of interpretive evidence. Does this matter? We argue that the absence of interpretive evidence undermines rational choice's explanatory credentials. However, we also argue that the admission of interpretive evidence risks rendering redundant the rational choice element of any explanation. This is the rock and the hard place between which rational choice is caught. In the final part of the article we distinguish those cases where rational choice may prove useful, namely those circumstances in which interpretive evidence either cannot be relied upon or does not subsume that which an explanation is intended to achieve.
OPTIMAL CONSUMPTION AND PORTFOLIO DECISIONS WITH PARTIALLY OBSERVED REAL PRICES
Authors: Bensoussan Alain , Keppo Jussi , Sethi Suresh P.
Published: March 2009

We consider optimal consumption and portfolio investment problems of an investor who is interested in maximizing his utilities from consumption and terminal wealth subject to a random inflation in the consumption basket price over time. We consider two cases: (i) when the investor observes the basket price and (ii) when he receives only noisy observations on the basket price. We derive the optimal policies and show that a modified Mutual Fund Theorem consisting of three funds holds in both cases. The compositions of the funds in the two cases are the same, but in general the investor's allocations of his wealth into these funds will differ. However, in the particular case when the investor has constant relative risk‐aversion (CRRA) utility, his optimal investment allocations into these funds are also the same in both cases.
ESTIMATION OF VALUE AT RISK AND RUIN PROBABILITY FOR DIFFUSION PROCESSES WITH JUMPS
Authors: Denis Laurent , Fernández Begoña , Meda Ana
Published: March 2009

In this paper we give upper bounds for both the Value at Risk VaRα,  0 < α < 1, and for ruin probabilities associated with the supremum of a process driven by a Brownian motion and a compound Poisson process. We obtain lower bounds for the same Value at Risk, and for different cases we discuss the behavior of the bounds for small α. We prove our bounds are “asymptotically” optimal, as α tends to zero. The ruin probabilities obtained are related to other bounds found in recent literature.
IMPLIED VOLATILITY IN THE HULL–WHITE MODEL
Authors: Gulisashvili Archil , Stein Elias M.
Published: March 2009

We study the implied volatility K↦I(K) in the Hull–White model of option pricing, and obtain asymptotic formulas for this function as the strike price K tends to infinity or zero. We also prove that the function I is convex near zero and concave near infinity, and characterize the behavior of the first two derivatives of this function.
Schools and Obesity Prevention: Creating School Environments and Policies to Promote Healthy Eating and Physical Activity
Authors: STORY MARY , NANNEY MARILYN S. , SCHWARTZ MARLENE B.
Published: March 2009

Context: Research consistently shows that the majority of American children do not consume diets that meet the recommendations of the Dietary Guidelines for Americans, nor do they achieve adequate levels of daily physical activity. As a result, more children are overweight today than at any other time in U.S. history. Schools offer many opportunities to develop strategies to prevent obesity by creating environments in which children eat healthfully and engage regularly in physical activity.

Methods: This article discusses the role of schools in obesity prevention efforts. Current issues in schools' food and physical activity environments are examined, as well as federal, state, and local policies related to food and physical activity standards in schools. The article is organized around four key areas: (1) school food environments and policies, (2) school physical activity environments and policies, (3) school body mass index measurements, and (4) school wellness policies. Recommendations for accelerating change also are addressed.

Findings: The article found that (1) competitive foods (foods sold outside of federally reimbursed school meals) are widely available in schools, especially secondary schools. Studies have related the availability of snacks and drinks sold in schools to students' high intake of total calories, soft drinks, total fat and saturated fat, and lower intake of fruits and vegetables; (2) physical activity can be added to the school curriculum without academic consequences and also can offer physical, emotional, and social benefits. Policy leadership has come predominantly from the districts, then the states, and, to a much lesser extent, the federal government; (3) few studies have examined the effectiveness or impact of school‐based BMI measurement programs; and (4) early comparative analyses of local school wellness policies suggest that the strongest policies are found in larger school districts and districts with a greater number of students eligible for a free or reduced‐price lunch.

Conclusions: Studies show that schools have been making some progress in improving the school food and physical activity environments but that much more work is needed. Stronger policies are needed to provide healthier meals to students at schools; limit their access to low‐nutrient, energy‐dense foods during the school day; and increase the frequency, intensity, and duration of physical activity at school.
Cardiac magnetic resonance imaging in valvular heart disease
Authors: Koskenvuo Juha W. , Järvinen Vesa , Pärkkä Jussi P. , Kiviniemi Tuomas O. , Hartiala Jaakko J.
Published: March 2009

Cardiac magnetic resonance imaging (CMR) has rapidly gained acceptance as an accurate, reproducible and non‐invasive imaging method for assessment of a wide range of cardiovascular diseases. However, CMR has not been used widely for diagnostic purposes in valvular heart disease (VHD). Unlike echocardiography it has no body habitus‐related limitations and can thus be used to complement echocardiography. It is an especially good alternative for clinical follow‐up in patients with VHD, as it allows accurate measurement of valvular dysfunction and related ventricular burden. Additionally, CMR is an ideal method for evaluating complex congenital heart disease and determining the significance of its components. It can also be used to study the physiological course of valvular dysfunction and response to therapeutic interventions. In this review, we present a basic introduction to CMR methodology, including its advantages and potential problems, and the physiology and quantification in VHD. We also discuss clinical applications of CMR in VHD. Furthermore, we describe how a CMR study statement should be structured in order to increase clinical use of this valuable methodology in cardiology.
Assessment of hepatic steatosis: comparison of quantitative and semiquantitative methods in 108 liver biopsies
Authors: Turlin Bruno , Ramm Grant A. , Purdie David M. , Lainé Fabrice , Perrin Michelle , Deugnier Yves , Macdonald Graeme A.
Published: March 2009

Background: There is growing interest in the role of hepatic steatosis in liver injury. The current standard for steatosis assessment is histological grading, although there is variability in the scoring systems used.

Aims: The aim of this study was to compare steatosis assessment by image analysis and histological grading.

Methods: Three methods were used to measure steatosis: histological grading (from 0 to 4); estimation of the percentage of hepatocytes (to nearest 5%) with steatosis; and computer‐assisted image analysis. Image analysis was performed on multiple fields for each biopsy with image pro plus 4.5, with steatotic droplets identified on the basis of shape, colour and size. Computer‐selected objects were reviewed to ensure that these were steatotic droplets. The predictive accuracy of the three techniques was assessed using measures of obesity and insulin resistance (homeostasis model assessment) as the outcome variables.

Results: There was a strong correlation between the results of image analysis and histological grade (rs=0.89, P<0.01), and estimated per cent steatosis (rs=0.93, P<0.01). The variability in the area of steatosis calculated by image analysis in different fields of a biopsy correlated with the total steatosis area (rs=0.93, P<0.01).

Conclusions: Image analysis did not offer any additional predictive value when the association between degree of obesity or insulin resistance was correlated with the different methods of assessing steatosis. Image analysis allows measurement of area of steatosis in liver biopsy material and generates a continuous variable that facilitates statistical analysis. These aspects may prove beneficial in research settings.
Hepatitis B virus with the rtL80V/I mutation is associated with a poor response to adefovir dipivoxil therapy
Authors: Lee Yoon‐Seon , Chung Young‐Hwa , Kim Jeong A. , Kim Sung Eun , Shin Jung Woo , Kim Kang Mo , Lim Young‐Suk , Park Neung Hwa , Lee Han Chu , Lee Yung Sang , Suh Dong Jin
Published: March 2009

Background/Aims: Lamivudine (LAM) resistance is frequently associated with various types of genomic changes in hepatitis B virus (HBV)‐DNA including YMDD mutations (rtM204V/I). We intended to examine the effects of these genotypic variants on the antiviral efficacy of adefovir dipivoxil (ADV) therapy.

Methods: A total of 97 chronic hepatitis B (CHB) patients with YMDD mutants who had been treated with ADV for >12 months were analysed. Mutations of the entire polymerase domain of HBV were determined by direct sequencing.

Results: All the 97 patients had genotype C HBV associated with rtM204V/I mutations; 63 (65%) rtM204I, 27 (28%) rtM204V and seven (7%) both. The rtL80V/I and rtL180M variants were identified in 66 (68%) and 67 (69%) patients respectively. The rtM204I and rtM204V variants were strongly associated with rtL80V/I and rtL180M respectively (P<0.01). There was no difference in antiviral response at 12 months after ADV therapy between patients in relation to the type of YMDD mutation or the presence of rtL180M. However, interestingly, after ADV therapy for 12 months, patients with rtL80V/I achieved a much smaller reduction in serum HBV‐DNA titre than those without it (mean, −3.43 vs. −4.43 log10 copies/ml; P=0.018). In addition, patients with rtL80V/I had lower rates of undetectable HBV‐DNA (20 vs. 26%), alanine aminotransferase normalization (70 vs. 81%) and HBeAg loss (16 vs. 26%) than those without it, although none of these differences was statistically significant.

Conclusions: These results provide evidence that rtL80V/I variants of HBV may be associated with a poor antiviral response to ADV in CHB patients with YMDD mutants.
Microsomal triglyceride transfer protein polymorphism (−493G/T) is associated with hepatic steatosis in patients with chronic hepatitis C
Authors: Mirandola Silvia , Österreicher Christoph H. , Marcolongo Moira , Datz Christian , Aigner Elmar , Schlabrakowski Anne , Realdon Stefano , Gerotto Martina , Alberti Alfredo , Stickel Felix
Published: March 2009

Background: Hepatic steatosis may promote progression of chronic hepatitis C (CHC). Microsomal triglyceride transfer protein (MTP) is required for assembly and secretion of ApoB lipoprotein and is implicated in hepatitis C virus (HCV)‐related steatosis. The MTP −493G/T polymorphism may promote liver fat accumulation, but its role in HCV‐related steatosis is still unclear.

Methods: Two hundred ninety‐eight CHC patients were studied and genotyped for MTP −493G/T variants. Hepatic MTP mRNA expression and activity were determined in a subgroup.

Results: Patients with grades 2/3 steatosis were older, had a higher body mass index (BMI), more advanced fibrosis and lower MTP mRNA expression and carried more often HCV genotype 3 and the MTP T allele. Age, BMI, HCV‐3 and MTP T allele [odds ratio (OR) 2.05; 95% confidence interval (CI) 1.2–3.53; P=0.009] were independent risk factors for steatosis grades 2/3, and in HCV genotype non‐3 patients, the MTP T allele was the strongest predictor for steatosis grade 2/3 (OR 2.17; 95% CI 1.22–3.86; P=0.008). Moreover, TT carriers had higher high‐density lipoprotein (65.6±14.6 vs 56.1±16.2 mg/dl; P=0.003) and apolipoprotein AI (1.80±0.3 vs 1.60±0.3 g/L; P=0.005) levels than G allele carriers.

Conclusions: Chronic hepatitis C patients with the MTP −493T allele reveal higher grades of steatosis, indicating a relevant contribution to liver fat accumulation, particularly in HCV non‐3 patients.
Meta‐Analysis: The Effect of Supplementation with Lactoferrin on Eradication Rates and Adverse Events During Helicobacter pylori Eradication Therapy
Authors: Zou Jian , Dong Jie , Yu Xiao Feng
Published: March 2009

Abstracts

Background: Recent evidence shown that lactoferrin could exert an antimicrobial effect against Helicobacter pylori both in vitro and in vivo models. To systematically evaluate whether adding lactoferrin to H. pylori eradication regimens could improve eradication rates and reduce side‐effects during anti‐H. pylori treatment.

Materials and Methods:  Eligible articles were identified by searches of electronic databases. We included all randomized trials comparing lactoferrin supplementation to placebo or no treatment during anti‐H. pylori regimens. Statistical analysis was performed with Review Manager 5.0.10. Subanalysis/Sensitivity analysis was also performed.

Results: We identified nine randomized trials (n = 1343). Pooled H. pylori eradication rates were 86.57% (95% confidence interval (CI) = 83.99–89.15%) and 74.44% (95% CI = 71.14–77.74%) for patients with or without lactoferrin by intention‐to‐treat analysis, respectively, the odds ratio (OR) was 2.26 (95% CI = 1.70–3.00); the occurrence of total side‐effects was 9.05% (95% CI = 6.83–11.27%) and 16.28% (95% CI = 13.43%–19.13%) for groups with or without lactoferrin, especially for nausea, the summary OR was 0.15 (95% CI = 0.04–0.54).

Conclusions: Our review suggests that supplementation with lactoferrin could be effective in increasing eradication rates of anti‐H. pylori therapy, and could be considered helpful for patients with eradication failure. Furthermore, lactoferrin shows a positive impact on H. pylori therapy‐related side‐effects.
Prevalence of Helicobacter pylori Infection and Identification of Risk Factors in Rural and Urban Beijing, China
Authors: Cheng Hong , Hu Fulian , Zhang Lian , Yang Guibin , Ma Junling , Hu Jichun , Wang Weihong , Gao Wen , Dong Xinhong
Published: March 2009

Background:  The prevalence of Helicobacter pylori is higher in developing countries such as China. The aim of this study was to investigate the prevalence of H. pylori in one rural and one urban region of Beijing, China.

Materials and Methods:  Healthy individuals in rural Pinggu and urban Haidian voluntarily participated in this study. The diagnosis of H. pylori infection was reached using the 13C‐urea breath test. Associations between H. pylori and sex, age, living area (i.e. rural vs urban), education level, smoking, and alcohol consumption were evaluated.

Results:  Of the 1232 included subjects, 54.7% of tested individuals residing in Pinggu and 41.3% in Haidian were positive for H. pylori. In urban region, more individuals were negative for H. pylori (429 of 731), whereas in the rural region, more individuals were positive for H. pylori (p < .05). Univariate analysis identified geographic area and lower education and annual income as significant factors associated with H. pylori. Men in rural areas were more likely than women in rural areas to be infected, and both men and women in the rural area were more likely to be positive for H. pylori than men and women in the urban area (all p < .05).

Conclusions:  H. pylori infection is common in both rural and urban regions of Beijing. Residing in a rural area, having a lower family income, and lower education level are significant risk factors associated with infection.
Meta‐analysis: Four‐Drug, Three‐Antibiotic, Non‐bismuth‐Containing “Concomitant Therapy” Versus Triple Therapy for Helicobacter pylori Eradication
Authors: Essa Abdallah Said , Kramer Jennifer Rosenthal , Graham David Y. , Treiber Gerhard
Published: March 2009

Background: Low success rates with triple therapy for Helicobacter pylori infections have prompted search for alternatives. In one, a proton‐pump inhibitor (PPI) and amoxicillin was followed by the PPI plus clarithromycin and a nitroimidazole (sequential therapy); in another, these four drugs were given concomitantly (concomitant therapy).

Aim: To compare concomitant therapy with standard triple therapy for H. pylori infection.

Methods: By searching PubMed, EMBASE, the Cochrane Central Register of Controlled Trials and abstracts of major gastrointestinal meeting, two independent reviewers systemically identified randomized controlled trials (RCT) comparing concomitant quadruple to standard triple therapies as well as studies reporting eradication rates of concomitant quadruple therapy in treatment of H. pylori. Pooled eradication rates and odds ratios (OR) with 95% confidence intervals (CI) were calculated, and univariable metaregression analysis for all extracted variables was conducted.

Results: We identified nine studies (10 treatment arms) including five qualifying RCTs (576 subjects) comparing concomitant (293 subjects, duration 3 to 5 days) and triple therapy (283 subjects, duration 5 to 10 days) and four other studies evaluating concomitant therapy (478 subjects, duration 3 to 7 days). Pooled estimates of the five RCTs showed superiority of concomitant therapy over triple therapy; with intention‐to‐treat) pooled OR of 2.86 (95% CI: 1.73–4.73) and per‐protocol (PP) pooled OR of 3.52 (95% CI: 1.95–6.38). Considering all 10 treatment arms, the ITT eradication rate was 89.7% (95% CI: 86.8–92.1%) and PP was 92.9% (95% CI: 90.2–94.8%).

Conclusion: Concomitant therapy appears to be an effective alternative to triple therapy and is less complex than sequential therapy.
Treatment of Juvenile Pemphigus Vulgaris with Intravenous Immunoglobulin Therapy
Authors: Asarch Adam , Razzaque Ahmed A.
Published: March 2009

Abstract:  We report the clinical response and follow‐up on eight patients with juvenile pemphigus vulgaris treated with intravenous immunoglobulin. Six Caucasian females and two Caucasian males ages 15 to 18 (mean 15.5) were treated with intravenous immunoglobulin based on a published protocol. The indications were lack of response and development of serious side‐effects to conventional therapy in four, lack of response to dapsone in two, and parental choice in two patients. In seven patients, a prolonged clinical remission was achieved. They received a mean of 28.5 cycles of intravenous immunoglobulin in a mean of 43.4 months and were followed for a mean of 29.8 months after discontinuing treatment. The remaining patient responded, but was lost to follow‐up. Mean follow‐up was 71.7 months. Six patients experienced mild headache, but no serious side‐effects were observed in any patient. Intravenous immunoglobulin is a safe biological agent to use in the treatment of juvenile pemphigus vulgaris. It can be used as monotherapy and has the potential to induce and sustain long‐term clinical remissions. In these eight patients, it appears that intravenous immunoglobulin is a safe biological agent without serious, immediate, or long‐term side effects. Intravenous immunoglobulin is a valuable agent in the treatment of certain cases of juvenile pemphigus vulgaris.
Political Challenges of Innovation in the Developing World1
Authors: Doner Richard F. , Hicken Allen , Ritchie Bryan K.
Published: March 2009

In this article, we seek to rectify the absence of political analysis characterizing most literature on innovation and development. Although existing research is careful to note the lack of any single recipe or model of innovation, most scholars identify a range of institutions and policies influencing innovative performance. But such explanations beg the question of where institutions, so critical to policy implementation, actually come from. We argue that the answer lies in (1) the desire of political leaders to promote innovation and related institutions, and (2) the structure of political arrangements—especially the number of actors with the power and interest to block or promote reform—through which leaders must operate. We argue that both of these variables are strongly influenced by the threats facing leaders and the resources available to address such threats.
Morality and Personal Experience: The Moral Conceptions of a Muscovite Man
Authors: Zigon Jarrett
Published: March 2009

Abstract
Use of the concept of morality allows anthropologists to avoid the difficulties of their traditional concepts of culture, society, and power, and provides an intimate perspective on the everyday lives of subjects and interlocutors. Yet the very concept of morality remains undertheorized by anthropologists. As a result there is little agreement or coherence among those anthropologists who study moralities regarding what it is they are attempting to study and how to do so. In this article I contribute to the current debate by presenting a moral portrait of a Moscow man, in which I hope to show that life‐historical methods and hermeneutic analysis of narratives allow for a deep and rich description of individuals' moral conceptions as emergent within their social milieu. This is so because the narratives reveal the ways in which personal experiences play a significant role in shaping personal morality. This methodological approach is supported by an anthropological theory of morality that posits a distinction between morality and ethics, and focuses on moral breakdowns as the primary context that makes possible the experiences that shape personal morality. [morality, ethics, experience, narrative, life history, Russia]
The RAB Family GTPase Rab1A from Plasmodium falciparum Defines a Unique Paralog Shared by Chromalveolates and Rhizaria
Authors: ELIAS MAREK , PATRON NICOLA J. , KEELING PATRICK J.
Published: March 2009

ABSTRACT. The RAB GTPases, which are involved in regulation of endomembrane trafficking, exhibit a complex but incompletely understood evolutionary history. We elucidated the evolution of the RAB1 subfamily ancestrally implicated in the endoplasmic reticulum‐to‐Golgi traffic. We found that RAB1 paralogs have been generated over the course of eukaryotic evolution, with some duplications coinciding with the advent of major eukaryotic lineages (e.g. Metazoa, haptophytes). We also identified a unique, derived RAB1 paralog, orthologous to the Plasmodium Rab1A, that occurs in stramenopiles, alveolates, and Rhizaria, represented by the chlorarachniophyte Gymnochlora stellata. This finding is consistent with the recently documented existence of a major eukaryotic clade (“SAR”) comprising these three lineages. We further found a Rab1A‐like protein in the cryptophyte Guillardia theta, but it exhibits unusual features among RAB proteins: absence of a C‐terminal prenylation motif and an N‐terminal extension with two MSP domains; and its phylogenetic relationships could not be established convincingly due to its divergent nature. Our results nevertheless point to a unique membrane trafficking pathway shared by at least some lineages of chromalveolates and Rhizaria, an insight that has implications towards interpreting the early evolution of eukaryotes and the endomembrane system.
Inborn errors of interferon (IFN)‐mediated immunity in humans: insights into the respective roles of IFN‐α/β, IFN‐γ, and IFN‐λ in host defense
Authors: Zhang Shen‐Ying , Boisson‐Dupuis Stéphanie , Chapgier Ariane , Yang Kun , Bustamante Jacinta , Puel Anne , Picard Capucine , Abel Laurent , Jouanguy Emmanuelle , Casanova Jean‐Laurent
Published: March 2009

Summary: Interferon (IFN) was originally identified as a substance ‘interfering’ with viral replication in vitro. The first IFNs to be identified were classified as type I IFNs (IFN‐α/β and related molecules), two other types have since been identified: type II IFN (IFN‐γ) and type III IFNs (IFN‐λ). Each IFN binds to one of three type‐specific receptors. In the mouse model of experimental infections in vivo, IFN‐α/β are essential for immunity to most viruses tested, whereas IFN‐γ is important for immunity to a smaller number of viruses, together with bacteria, fungi, and parasites, consistent with IFN‐γ acting as the ‘macrophage activating factor.’ The precise role of IFN‐λ remains unclear. In recent years, inborn errors affecting the production of, or the response to, IFNs have been reported in human patients, shedding light onto the function of IFNs in natura. Disorders of IFN‐γ production, caused by IL12B, IL12RB1, and specific NEMO mutations, or of IFN‐γ responses, caused by IFNGR1, IFNGR2, and dominant STAT1 mutations, confer predisposition to mycobacterial disease in patients resistant to most viruses. By contrast, disorders of IFN‐α/β and IFN‐λ production, caused by UNC93B1 and TLR3 mutations, confer predisposition to herpes simplex encephalitis (HSE) in otherwise healthy patients. Consistently, patients with impaired responses to IFN‐α/β, IFN‐γ, and presumably IFN‐λ (carrying recessive mutations in STAT1), or with impaired responses to IFN‐α/β and impaired IFN‐γ production (carrying mutations in TYK2), or with impaired production of IFN‐α/β, IFN‐γ, and IFN‐λ (carrying specific mutations in NEMO), are vulnerable to mycobacterial and viral infections, including HSE. These experiments of nature suggest that the three types of IFNs play at least two different roles in host defense. IFN‐γ is essential for anti‐mycobacterial immunity, whereas IFN‐α/β and IFN‐λ are essential for anti‐viral immunity. Future studies in humans aim to define the specific roles of IFN‐α/β and IFN‐λ types and individual molecules in host defense in natura.
Welcome to the neighborhood: epithelial cell‐derived cytokines license innate and adaptive immune responses at mucosal sites
Authors: Saenz Steven A. , Taylor Betsy C. , Artis David
Published: March 2009

Summary: There is compelling evidence that epithelial cells (ECs) at mucosal surfaces, beyond their role in creating a physical barrier, are integral components of innate and adaptive immunity. The capacity of these cells to license the functions of specific immune cell populations in the airway and gastrointestinal tract offers the prospect of novel therapeutic strategies to target multiple inflammatory diseases in which barrier immunity is dysregulated. In this review, we discuss the critical functions of EC‐derived thymic stromal lymphopoietin (TSLP), interleukin‐25 (IL‐25), and IL‐33 in the development and regulation of T‐helper 2 (Th2) cytokine‐dependent immune responses. We first highlight recent data that have provided new insights into the factors that control expression of this triad of cytokines and their receptors. In addition, we review their proinflammatory and immunoregulatory functions in models of mucosal infection and inflammation. Lastly, we discuss new findings indicating that despite their diverse structural features and differential expression of their receptors, TSLP, IL‐25, and IL‐33 cross‐regulate one another and share overlapping properties that influence Th2 cytokine‐dependent responses at mucosal sites.
From interleukin‐23 to T‐helper 17 cells: human T‐helper cell differentiation revisited
Authors: Boniface Katia , Blom Bianca , Liu Yong‐Jun , De Waal Malefyt René
Published: March 2009

Summary: Protracted inflammation leading to dysregulation of effector T‐cell responses represents a common feature of a wide range of autoimmune diseases. The interleukin‐12 (IL‐12)/T‐helper 1 (Th1) pathway was thought to be responsible for the pathogenesis of multiple chronic inflammatory diseases, including psoriasis, inflammatory bowel disease, arthritis, or multiple sclerosis, mainly through their production of interferon‐γ and its effects on macrophage activation and chemokine production. However, this initial concept of T‐cell‐mediated chronic inflammation required an adjustment with the discovery of an IL‐12‐related cytokine, designated IL‐23. IL‐23 was rapidly recognized for its involvement in the establishment of chronic inflammation and in the development of a Th cell subset producing IL‐17, designated Th17, which is distinct from the previously reported Th1 and Th2 populations. This review aims to describe the characterization of IL‐23 and its receptor, its biological activities, as well as its involvement in the development of human Th17 cells and autoimmunity.
Are overweight adolescents at higher risk of engaging in unhealthy weight‐control behaviours?
Authors: Fonseca Helena , Matos Margarida G , Guerra António , Pedro J Gomes
Published: March 2009

Aim: To examine correlates of unhealthy weight‐control behaviours (UNWCB), and to explore possible associated variables.

Methods: Sample included 3762, 8th and 10th grade public school Portuguese students who participated in the 2002 Health Behaviour in School‐Aged Children (HBSC)/World Health Organization (WHO) survey of adolescent health. Factor analysis was used, and two scales were identified as ‘healthy weight‐control behaviours’ (HWCB) and ‘UNWCB’ through Kaiser criteria analysis. Frequency scores were developed and used in analysis of variance (ANOVAs) test as dependent variables, according to gender and age. Pearson correlations and post‐hoc analysis were performed to identify potential associations.

Results: UNWCB were significantly higher among those who were dieting or not dieting, but considering they should, and were significantly and progressively increasing from those perceiving themselves as thin, to those perceiving themselves as being the right size and those perceiving themselves as fat. Overweight reported more frequently than non‐overweight, both HWCB and UNWCB. Finally, there were significant differences concerning alcohol use, with UNWCB increasing progressively from reporting ‘drinking rarely or never’ to ‘drinking every week’ and ‘everyday’.

Conclusion: Because UNWCB are associated with both medical and psychological health risks, routine screening is warranted. Special attention needs to be directed towards youth at greatest risk for disordered eating, including overweight youth.
DRYING EFFECTS OF TWO AIR‐DRYING SHELTERS IN A PILOT TEST ON SULTANA GRAPES
Authors: LI LINGLING , WANG ZHENGFU , HU XIAOSONG , WU JIHONG , LIAO XIAOJUN , CHEN FANG , ZHAO GUANGHUA
Published: March 2009

The drying effects of sultana grapes in two different air‐drying shelters were tested and analyzed. Ten different thin‐layer drying mathematical models were compared according to their coefficients of determination andχ2test. The Wang and Singh model was found to be the most suitable for describing the air‐drying curves of sultana grapes. As compared with the local traditional shelter, the reformed shelter with a greenhouse can reduce about 12–18% of air‐drying time, increase about 23% in green‐grade rate of raisins and increase 33% in the effective moisture diffusivity of sultana grapes.

PRACTICAL APPLICATIONS

Grapes are one of the most popular and palatable fruits in the world. The preservation of grapes by drying is a major industry in many parts of the world where grapes are grown. Drying grapes, either by open sun drying, shade drying or mechanical drying, produces raisins. Air‐drying of solar energy has been demonstrated to be cost‐effective and could be an effective alternative to traditional and mechanical drying systems, especially in locations with good sunshine during the harvest season. The traditional air‐drying shelter of grapes has been used for thousands of years in Asia and other places around the world. However, less investigation was done about the drying characteristics and the optimization of the shelter. The work of this manuscript provides interesting information that is useful for design of the drying shelter of raisins and for the improvement of raisin quality, especially using air‐drying of solar energy.
Dynamic Model and Numerical Simulation for Synchronal Rotary Compressor
Authors: Zhou Hui , Qu Zongchang , Yang Hua , Yu Bingfeng
Published: March 2009

The synchronal rotary compressor (SRC) has been developed to resolve high friction and severe wear that usually occur in conventional rotary compressors due to the high relative velocity between the key tribo-pairs. In this study, the working principle and structural characteristics of the SRC are presented first. Then, the kinematic and force models are established for the key components—cylinder, sliding vane, and rotor. The velocity, acceleration, and force equations with shaft rotation angle are derived for each component. Based on the established models, numerical simulations are performed for a SRC prototype. Moreover, experiments are conducted to verify the established models. The simulated results show that the average relative velocity between the rotor and the cylinder of the present compressor decreases by 80–82% compared with that of the conventional rotary compressors with the same size and operating parameters. Moreover, the average relative velocity between the sliding contact tribo-pairs of the SRC decreases by 93–94.3% compared with that of the conventional rotary compressors. In addition, the simulated results show that the stresses on the sliding vane are greater than those on the other components. The experimental results indicate that the wear of the side surface of the sliding vane is more severe than that of the other components. Therefore, special treatments are needed for the sliding vane in order to improve its reliability. These findings confirm that the new SRC has lower frictional losses and higher mechanical efficiency for its advanced structure and working principle.
Meclofenamic Acid Blocks Electrical Synapses of Retinal AII Amacrine and on-Cone Bipolar Cells
Authors: Veruki Margaret Lin , Hartveit Espen
Published: March 2009

Gap junction channels constitute specialized intercellular contacts that can serve as electrical synapses. In the rod pathway of the retina, electrical synapses between AII amacrine cells express connexin 36 (Cx36) and electrical synapses between AII amacrines and on-cone bipolar cells express Cx36 on the amacrine side and Cx36 or Cx45 on the bipolar side. For physiological investigations of the properties and functions of these electrical synapses, it is highly desirable to have access to potent pharmacological blockers with selective and reversible action. Here we use dual whole cell voltage-clamp recordings of pairs of AII amacrine cells and pairs of AII amacrine and on-cone bipolar cells in rat retinal slices to directly measure the junctional conductance ( Gj) between electrically coupled cells and to study the effect of the drug meclofenamic acid (MFA) on Gj. Consistent with previous tracer coupling studies, we found that MFA reversibly blocked the electrical synapse currents in a concentration-dependent manner, with complete block at 100 μM. Whereas MFA evoked a detectable decrease in Gj within minutes of application, the time to complete block of Gj was considerably longer, typically 20–40 min. After washout, Gj recovered to 20–90% of the control level, but the time to maximum recovery was typically >1 h. These results suggest that MFA can be a useful drug to investigate the physiological functions of electrical synapses in the rod pathway, but that the slow kinetics of block and reversal might compromise interpretation of the results and that explicit monitoring of Gj is desirable.
The Estimation of Product Standard Time by Artificial Neural Networks in the Molding Industry
Authors: Eraslan Ergün
Published: March 2009

Determination of exact standard time with direct measurement procedures is particularly difficult in companies which do not have an adequate environment suitable for time measurement studies or which produce goods requiring complex production schedules. For these companies new and special measurement procedures need to be developed. In this study, a new time estimation method based on different robust algorithms of artificial neural networks (ANNs) is developed. For the proposed method, the products that have similar production processes were chosen from among the whole product range within the cleansing department of a molding company. While using ANNs, to train the network, some of the chosen products′ standard time that had been previously measured is used to estimate the standard time of the remaining products. The different ANN algorithms are trained and four of them, which are converged the data, are stated and compared in different architectures. In this way, it is concluded that this estimation method could be applied accurately in many similar processes using the relevant algorithms.
ADP-Ribosylation Factor 6 Regulates Tumorigenic and Invasive Properties In vivo
Authors: Muralidharan-Chari Vandhana , Hoover Holly , Clancy James , Schweitzer Jill , Suckow Mark A. , Schroeder Valerie , Castellino Francis J. , Schorey Jeffrey S. , D'Souza-Schorey Crislyn
Published: March 2009

This study shows that the small GTP-binding protein ADP-ribosylation factor 6 (ARF6) is an important regulator of tumor growth and metastasis. Using spontaneous melanoma tumor growth assays and experimental metastasis assays in nude mice, we show that sustained activation of ARF6 reduces tumor mass growth but significantly enhances the invasive capacity of tumor cells. In contrast, mice injected with tumor cells expressing a dominantly inhibitory ARF6 mutant exhibited a lower incidence and degree of invasion and lung metastasis compared with control animals. Effects on tumor growth correlate with reduced cell proliferation capacity and are linked at least in part to alterations in mitotic progression induced by defective ARF6 cycling. Furthermore, phospho-ERK levels in subcultured cells from ARF6(GTP) and ARF6(GDP) tumor explants correlate with invasive capacity. ARF6-induced extracellular signal-regulated kinase (ERK) signaling leads to Rac1 activation to promote invadopodia formation and cell invasion. These findings document an intricate role for ARF6 and the regulation of ERK activation in orchestrating mechanisms underlying melanoma growth, invasion, and metastases. [Cancer Res 2009;69(6):2201–9]
Common Polymorphisms in the Prostaglandin Pathway Genes and Their Association with Breast Cancer Susceptibility and Survival
Authors: Abraham Jean E. , Harrington Patricia , Driver Kristy E. , Tyrer Jonathan , Easton Douglas F. , Dunning Alison M. , Pharoah Paul D.P.
Published: March 2009

Purpose: There is evidence that genetic variation in the prostaglandin pathway affects cancer susceptibility and progression. Conflicting data from several studies exist for the association of PTGS2 (cyclooxygenase 2) polymorphisms with breast cancer risk. We investigated associations between common germ-line variations in seven genes in the prostaglandin pathway and breast cancer susceptibility and survival among women with invasive breast cancer in the SEARCH study.

Experimental Design: DNA samples from 9,030 cases and controls were genotyped for 64 single nucleotide polymorphisms tagging known common variants (minor allele frequency > 0.05) in PTGS1, PTGS2, TBXAS1, PTGIS, PTGES, PTGDS, and PGDS with a two-stage case-control study design.

Results: Four tagging single nucleotide polymorphisms showed modest association with breast cancer susceptibility. All four fit a recessive genetic model. Minor allele homozygotes for PTGISrs5602 [odds ratio (OR), 1.15; 95% confidence interval (95% CI), 1.04-1.27; P = 0.005], PTGISrs8183919 (OR, 1.22; 95% CI, 1.06-1.41; P = 0.006), and TBXASrs41727 (OR, 1.83; 95% CI, 1.22-2.73; P = 0.003) are associated with an increased risk compared with common allele carriers. For PTGISrs44627 minor allele homozygotes (OR, 0.66; 95% CI, 0.5-0.86; P = 0.002), a protective effect was observed.

Conclusion: Specific PTGIS and TBXAS1 variants may affect breast cancer susceptibility, but common variants in PTGS1, PTGS2, PTGES, PTGDS, and PGDS have no major role in breast cancer susceptibility. None of the variants in the seven genes studied appear to affect survival. Further larger studies correlating clinical and genotypic data are required to establish if the clinical utility of prostaglandin-targeted therapies, as chemoprevention agents, is influenced by an individual's profile of genetic variants in key prostaglandin pathway genes.
Sperm-Derived SPANX-B Is a Clinically Relevant Tumor Antigen That Is Expressed in Human Tumors and Readily Recognized by Human CD4+ and CD8+ T Cells
Authors: Almanzar Giovanni , Olkhanud Purevdorj B. , Bodogai Monica , Dell'Agnola Chiara , Baatar Dolgor , Hewitt Stephen M. , Ghimenton Claudio , Tummala Mohan K. , Weeraratna Ashani T. , Hoek Keith Sean , Kouprina Natalay , Larionov Vladimir , Biragyn Arya
Published: March 2009

Purpose: The sperm-derived SPANX family proteins can be found expressed in human tumors. Here, we aimed to perform a comprehensive study to evaluate immunotherapeutic relevance of one of its members, SPANX-B. We wanted to test its expression pattern in human tumors and to evaluate CD4+ and CD8+ T-cell responses in healthy humans after in vitro immunizations.

Experimental Design: Expression of SPANX-B in human malignancies, including a multitumor tissue array of 145 primary tumors, was assessed using reverse transcription-PCR, Western blotting, and immunohistochemical analysis. T-cell immunogenicity and immunodominant epitopes of SPANX-B were studied using in vitro immunizations of healthy human donor-derived leukocytes.

Results: SPANX-B was abundantly expressed in melanoma and carcinomas of lung, ovary, colon, and breast. In melanoma, tissue array data indicated that it was expressed in advanced and metastatic disease. Unlike most tumor-associated antigens, SPANX-B was an immunogenic antigen that was recognized by circulating T-cell precursors in healthy humans. Importantly, these T cells were readily expanded to generate SPANX-B-specific helper CD4+ and cytolytic CD8+ T cells that recognized unique immunodominant epitopes: at least one HLA-DR-restricted Pep-9 epitope (SPANX-B12-23) and two HLA-A2-restricted Pep-2 and Pep-4 epitopes (SPANX-B23-31 and SPANX-B57-65, respectively). CD8+ T cells were fully functional to recognize and lyse HLA-A2-expressing tumors, including primary human melanomas.

Conclusions: SPANX-B is an immunogenic sperm-derived antigen that is expressed in several human tumors. SPANX-B is also efficiently recognized by the human T-cell immune arm, indicating its significant value for the development of protective and therapeutic cancer vaccines.
Sunitinib Mediates Reversal of Myeloid-Derived Suppressor Cell Accumulation in Renal Cell Carcinoma Patients
Authors: Ko Jennifer S. , Zea Arnold H. , Rini Brian I. , Ireland Joanna L. , Elson Paul , Cohen Peter , Golshayan Ali , Rayman Patricia A. , Wood Laura , Garcia Jorge , Dreicer Robert , Bukowski Ronald , Finke James H.
Published: March 2009

Purpose: Immune dysfunction reported in renal cell carcinoma (RCC) patients may contribute to tumor progression. Myeloid-derived suppressor cells (MDSC) represent one mechanism by which tumors induce T-cell suppression. Several factors pivotal to the accumulation of MDSC are targeted by the tyrosine kinase inhibitor, sunitinib. The effect of sunitinib on MDSC-mediated immunosuppression in RCC patients has been investigated.

Experimental Design: Patient peripheral blood levels of MDSC and regulatory T-cell (Treg) and T-cell production of IFN-γ were evaluated before and after sunitinib treatment. Correlations between MDSC and Treg normalization as well as T-cell production of IFN-γ were examined. The in vitro effect of sunitinib on patient MDSC was evaluated.

Results: Metastatic RCC patients had elevated levels of CD33+HLA-DR− and CD15+CD14− MDSC, and these were partially overlapping populations. Treatment with sunitinib resulted in significant reduction in MDSC measured by several criteria. Sunitinib-mediated reduction in MDSC was correlated with reversal of type 1 T-cell suppression, an effect that could be reproduced by the depletion of MDSC in vitro. MDSC reduction in response to sunitinib correlated with a reversal of CD3+CD4+CD25hiFoxp3+ Treg cell elevation. No correlation existed between a change in tumor burden and a change in MDSC, Treg, or T-cell production of IFN-γ. In vitro addition of sunitinib reduced MDSC viability and suppressive effect when used at ≥1.0 μg/mL. Sunitinib did not induce MDSC maturation in vitro.

Conclusions: Sunitinib-based therapy has the potential to modulate antitumor immunity by reversing MDSC-mediated tumor-induced immunosuppression.