bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of zwitterionic N-alkylaminomethanesulfonic acids to related compounds in the Good buffer series
Authors: Long Robert D , Hilliard Newton P , Chhatre Suneel A , Timofeeva Tatiana V , Yakovenko Andrey A , Dei Daniel K , Mensah Enoch A
Published: April 2010

Several N-alkyl and N,N-dialkylaminomethanesulfonic acids were synthesized (as zwitterions and/or sodium salts) to be tested for utility as biological buffers at lower pH levels than existing Good buffer compounds (aminoalkanesulfonates with a minimum of two carbons between amine and sulfonic acid groups as originally described by Norman Good, and in common use as biological buffers). Our hypothesis was that a shorter carbon chain (one carbon) between the amino and sulfonic acid groups should lower the ammonium ion pKa values. The alkylaminomethanesulfonate compounds were synthesized in aqueous solution by reaction of primary or secondary amines with formaldehyde/sodium hydrogensulfite addition compound. The pKa values of the ammonium ions of this series of compounds (compared to existing Good buffers) was found to correlate well with the length of the carbon chain between the amino and sulfonate moeties, with a significant decrease in amine basicity in the aminomethanesulfonate compounds (pKa decrease of 2 units or more compared to existing Good buffers). An exception was found for the 2-hydroxypiperazine series which shows only a small pKa decrease, probably due to the site of protonation in this compound (as confirmed by X-ray crystal structure). X-ray crystallographic structures of two members of the series are reported. Several of these compounds have pKa values that would indicate potential utility for buffering at pH levels below the normal physiological range (pKa values in the range of 3 to 6 without aqueous solubility problems) – a range that is problematic for currently available Good buffers. Unfortunately, the alkylaminomethanesulfonates were found to degrade (with loss of their buffering ability) at pH levels below the pKa value and were unstable at elevated temperature (as when autoclaving) – thus limiting their utility.
Cost-effectiveness analysis of roadmap models in chronic hepatitis B using tenofovir as the rescue therapy
Authors: Lui Yanni Yan-Ni , Tsoi Kelvin Kam-Fai , Wong Vincent Wai-Sun , Kao Jia-Horng , Hou Jin-Lin , Teo Eng-Kiong , Mohamed Rosmawati , Piratvisuth Teerha , Han Kwang-Hyub , Mihm Ulrike , Wong Grace Lai-Hung , Chan Henry Lik-Yuen
Published: April 2010

Background

The roadmap approach is recommended to guide chronic hepatitis B treatment. We evaluated the cost- effectiveness of various treatment strategies in the global market.

Methods

Lamivudine and telbivudine were tested in roadmap models with switch-to tenofovir if HBV was detectable at week 24 or add-on tenofovir if resistance developed at year 1. Tenofovir and entecavir were tested as continuous monotherapy. In the reference arm, lamivudine was used with add-on tenofovir if resistance developed at year 1. The primary measure of effectiveness was undetectable HBV DNA at year 2. Cost-effectiveness was measured by incremental cost-effectiveness ratio (ICER) in US dollars against the reference arm.

Results

In the US and Germany, costs of the reference arms were US $14,486 and US $9,998 for hepatitis B e antigen (HBeAg)-positive and US $11,398 and US $7,531 for HBeAg-negative patients, respectively. In HBeAg-positive patients, the lamivudine roadmap was most cost-effective (ICER US $15,260 in the US and US $29,113 in Germany) with comparable effectiveness (75.1%) to other strategies. In HBeAg-negative patients, tenofovir and entecavir monotherapies were most effective (91–96%) and cost- effective (ICER US $31,297–43,387 in the US and US $53,976–59,822 in Germany). In Asia, where telbivudine cost was lower, both telbivudine and lamivudine roadmaps were cost-effective in HBeAg-positive patients. Tenofovir would be most cost-effective in HBeAg-negative patients if its cost equaled that of telbivudine in Asia.

Conclusions

In HBeAg-positive patients, lamivudine roadmap was most cost-effective; in Asia, telbivudine roadmap had comparable cost-effectiveness to lamivudine roadmap because of the relatively low price of telbivudine. In HBeAg-negative patients, entecavir and tenofovir monotherapies were more cost-effective than the roadmap models.
Differential effects of interferon and lamivudine on serum HBV RNA inhibition in patients with chronic hepatitis B
Authors: Huang Yi-Wen , Chayama Kazuaki , Tsuge Masataka , Takahashi Shoichi , Hatakeyama Tsuyoshi , Abe Hiromi , Hu Jui-Ting , Liu Chun-Jen , Lai Ming-Yang , Chen Ding-Shinn , Yang Sien-Sing , Kao Jia-Horng
Published: April 2010

Background

Lamivudine and interferon have been widely used for the treatment of patients with chronic HBV infection. Serum HBV RNA is detected during lamivudine therapy as a consequence of interrupted reverse transcription and because RNA replicative intermediates are unaffected by the drug. In this study, we aimed to determine the detectability of serum HBV RNA during sequential combination therapy of interferon and lamivudine.

Methods

HBV DNA and RNA in serum samples were quantified by reverse transcription of HBV nucleic acid extract and real-time PCR. Samples were analysed every 2 weeks to 3 months from three groups of patients: 10 male patients treated with nucleoside analogue mono-therapy for 44–48 weeks (5 with lamivudine and 5 with entecavir), 6 males on sequential interferon and lamivudine combination therapy, and 3 males on lamivudine monotherapy for 20–24 weeks.

Results

HBV RNA was not detectable in any patients before treatment, but became detectable in 15 during antiviral treatment. Among the three groups, pre-treatment HBV DNA (8.1 ±2.4 versus 7.7 ±1.4 versus 5.1 ±0.3 log10copies/ml; P=0.06), treatment and follow-up durations (45.5 ±2.0 versus 49.7 ±5.6 versus 48.7 ±6.4 weeks; P=0.32) were comparable. HBV RNA was detectable at the end of treatment or follow-up in all patients with monotherapy, but in none of those with sequential combination therapy (100% versus 0%; P<0.001).

Conclusions

Compared with lamivudine therapy with detectable serum HBV RNA in patients with chronic HBV infection, interferon treatment might reduce HBV DNA replication through the inhibition of HBV RNA replicative intermediates, resulting in the loss of serum HBV RNA.
The Protease Inhibitors Ritonavir and Saquinavir Influence Lipid Metabolism: A Pig Model for the Rapid Evaluation of New Drugs
Authors: Petersen Eskild , Mu Huiling , Porsgaard Trine , Bertelsen Lone S
Published: April 2010

Background

Studies of the effects of antiretroviral drugs on lipid metabolism are limited by the availability of suitable models. We have thus developed an animal model utilising Göttingen mini-pigs. The normal lipid metabolism of mini-pigs closely reflects that of humans and they are expected to have similar reactions to antiretroviral drugs.

Methods

The pigs were treated orally with high doses of the protease inhibitors ritonavir and saquinavir for 4 weeks. The model allows repeated concomitant biopsies from liver, muscle, adipose tissue and plasma samples.

Results

The study showed a general decrease in poly-unsaturated fatty acids; changes in both saturated and monounsaturated fatty acids were also apparent after antiretroviral treatment. The changes were observed after 4 weeks of treatment. At 4 weeks post-treatment, the levels of all fatty acids were lower compared with pre-treatment levels, suggesting a prolonged effect of the antiretroviral drug treatment lasting beyond the 4 week post-treatment observation period.

Conclusions

The Göttingen mini-pig model is a promising animal model for rapid screening of the metabolic effects induced by antiretroviral drugs.
Long-term adefovir dipivoxil monotherapy for up to 5 years in lamivudine-resistant chronic hepatitis B
Authors: Lee Jung Min , Park Jun Yong , Kim Do Young , Nguyen Tin , Hong Sun Pyo , Kim Soo Ok , Chon Chae Yoon , Han Kwang-Hyub , Ahn Sang Hoon
Published: April 2010

Background

Large clinical studies assessing long-term adefovir dipivoxil salvage monotherapy in patients with lamivudine-resistant chronic hepatitis B (CHB) are lacking, particularly in patients positive for hepatitis B e antigen (HBeAg). We assessed the efficacy and resistance profile of adefovir dipivoxil monotherapy for up to 5 years in a large cohort of Korean patients with lamivudine-resistant CHB.

Methods

A total of 320 patients (81.3% HBeAg-positive; 100% genotype C) with confirmed genotypic lamivudine-resistant CHB were switched to adefovir dipivoxil 10 mg once daily. Liver function tests and HBV DNA were monitored every 3 months. Genotypic resistance to adefovir dipivoxil was performed in patients with detectable HBV DNA.

Results

The overall cumulative virological response rate at 5 years of adefovir dipivoxil therapy was 48.8%. The virological response rate was significantly higher in HBeAg-negative patients (62.0% versus 45.9%; P=0.010). Most cases of virological response (131/134, 97.8%) occurred within the first 36 months of therapy. The 5-year cumulative probability of genotypic resistance and virological breakthrough was 65.6% and 61.8%, respectively. Predictive factors for a virological response included baseline HBeAg seronegativity, HBV DNA≤8 log10 copies/ml and achievement of an on-treatment initial virological response.

Conclusions

Adefovir dipivoxil salvage monotherapy for lamivudine-resistant CHB resulted in a modest cumulative virological response rate at 5 years, which was associated with progressive antiviral resistance. Consequently, adefovir monotherapy is not preferable as a first-line strategy for lamivudine resistance where combination lamivudine plus adefovir dipivoxil therapy is available.
Positive and Negative drug Selection Pressures on the N348I Connection Domain Mutation: New Insights from in vivo Data
Authors:   UK Collaborative Group on HIV Drug Resistance,   UK Collaborative HIV Cohort Study, Price Huw , Asboe David , Pozniak Anton , Gazzard Brian , Fearnhill Esther , Pillay Deenan , Dunn David
Published: April 2010

Background

There is conflicting evidence on specific reverse transcriptase inhibitors to which the N348I mutation in the connection domain of HIV type-1 reverse transcriptase confers resistance. Here, we examined associations between the emergence of N348I and anti-retroviral history in a large clinical database.

Methods

We analysed 5,353 resistance tests (that were sequenced beyond codon 348) among 2,266 antiretroviral-experienced patients. Associations between N348I and individual antiretroviral drug exposure were estimated using a matched case-control approach. Cases were defined as the first resistance test where N348I was detected; for each case, the 10 closest (in calendar time) N348N tests were selected as controls. Odds ratios (ORs) adjusted for effects of all other drugs were estimated by conditional logistic regression.

Results

N348I was detected in 198 (8.7%) cases. Drugs that were statistically significantly positively associated with N348I were efavirenz (OR 1.55, 95% confidence interval [CI] 1.08–2.23; P=0.017) and nevirapine (OR 2.06, 95% CI 1.49–2.85; P<0.001). Tenofovir disoproxil fumarate (TDF) was significantly negatively associated (OR 0.27, 95% CI 0.15–0.48; P<0.001) with N348I. Similar findings were observed when the analysis was repeated to include only those tests within 2 years of the resistance test. Effects for zidovudine and stavudine were evident only in an additional analysis, which considered exposure to both drugs jointly within 2 years prior to the resistance test: exposure to zidovudine alone (OR 4.61, 95% CI 1.83–11.61; P<0.001) and exposure to stavudine alone (OR 3.39, 95% CI 1.32–8.71; P=0.011).

Conclusions

This is the first clinical evidence to suggest that efavirenz might select for N348I in addition to nevirapine, that stavudine might select for N348I in addition to zidovudine and that TDF might protect against the mutation.
Predicting the magnitude of short-term CD4+ T-cell recovery in HIV-infected patients during first-line highly active antiretroviral therapy
Authors: Castagna Antonella , Galli Laura , Torti Carlo , Monforte Antonella D'Arminio , Mussini Cristina , Antinori Andrea , Cozzi-Lepri Alessandro , Ladisa Nicoletta , De Luca Andrea , Seminari Elena , Gianotti Nicola , Lazzarin Adriano
Published: April 2010

Background

The extent of short-term CD4+ T-cell recovery in patients tolerating first-line highly active antiretroviral therapy (HAART) and attaining undetectable HIV RNA levels is inadequately defined.

Methods

We retrospectively analysed patients in four Italian cohorts who started HAART between January 1996 and September 2006. All patients had known HCV coinfection status, did not modify the regimen for 6 months and had <50 HIV RNA copies/ml at the end of the sixth month.

Results

The analysis involved 1,488 patients (1,096 males, 73.7%) with a median age of 43 years (interquartile range [IQR] 39–49); 435 (29.2%) were positive for HCV, 71 (4.8%) were positive for hepatitis B surface antigen (HBsAg) and 76 (5.1%) had experienced a previous AIDS-defining event. At baseline, patient CD4+ T-cell counts were 226 cells/μl (IQR 99–332), CD4+ T-cell percentages were 14.7% (IQR 8.7–21.2) and HIV RNA levels were 4.91 log10 copies/ml (IQR 4.38–5.34). Overall, 24-week CD4+ T-cell recovery was 144 cells/μl (IQR 70–240). At multivariable analysis, T-cell recovery was positively related to the use of a boosted protease inhibitor ( P<0.0001) or thymidine analogues ( P<0.0001), baseline HIV RNA levels ( P<0.0001), the baseline percentage of CD4+ T-cells ( P<0.0001) and the absence of HCV coinfection ( P=0.006). Age, gender, baseline CD4+/CD8+ T-cell ratio and a history of AIDS-defining events had no independent effect on CD4+ T-cell recovery.

Conclusions

Among HIV-infected patients tolerating first-line HAART and with undetectable HIV RNA after 6 months, CD4+ T-cell recovery is significantly greater in those without HCV coinfection, with a high baseline viral load, a high baseline percentage of CD4+ T-cells and in those treated with a boosted protease inhibitor.
Intravenous immunoglobulin therapy for patients with idiopathic cardiomyopathy and endomyocardial biopsy-proven high PVB19 viral load
Authors: Dennert Robert , Velthuis Sebastiaan , Schalla Simon , Eurlings Luc , van Suylen Robert-Jan , van Paassen Pieter , Tervaert Jan William Cohen , Wolffs Petra , Goossens Valère J , Bruggeman Catrien , Waltenberger Johannes , Crijns Harry J , Heymans Stephane
Published: April 2010

Background

Parvovirus B19 (PVB19) persistence in the heart has been associated with progressive cardiac dysfunction and evolution to dilated cardiomyopathy. In the present study, we investigated whether immunomodulation with intravenous immunoglobulin (IVIg) in addition to conventional heart failure therapy is safe and achieves virus reduction. Such therapy might improve cardiac function in patients with chronic dilated cardiomyopathy (DCM) and a significant PVB19 viral load in the heart.

Methods

PVB19 viral load was studied in 25 post-mortem cardiac samples of patients with a normal heart. Then, 17 consecutive patients (mean age 53 ±3 years) with DCM and symptomatic heart failure for >1 year with a PVB19 viral load in endomyocardial biopsies of >250 copies/μg DNA were treated with a high dose of IVIg (2 g/kg).

Results

The post-mortem cardiac samples revealed a PVB19 presence in 80% with a mean load of 131 ±40 copies/μg DNA. In the treated patients, IVIg resulted in a significant decrease of PVB19 viral load from 1,420 ±216 to 619 ±200 copies/μg DNA ( P=0.004) and significantly improved the ejection fraction from 33 ±3% 6 months before treatment and 34 ±3% at baseline to 41 ±3% 6 months ( P=0.001) after IVIg therapy. The New York Heart Association classification significantly improved from 2.5 ±0.1 at baseline to 2.1 ±0.1 at follow-up ( P=0.004). No therapy-related complications were noted.

Conclusion

The present pilot study demonstrates that IVIg significantly reduces viral load and improves cardiac function in patients with DCM related to increased PVB19 viral load in the heart.
The effect of tenofovir disoproxil fumarate on whole-body insulin sensitivity, lipids and adipokines in healthy volunteers
Authors: Randell Paul A , Jackson Akil G , Zhong Lijie , Yale Kitty , Moyle Graeme J
Published: April 2010

Background

Certain antiretrovirals are known to affect lipid and glucose homeostasis. The aim of this study was to assess the effect on insulin sensitivity (determined by peripheral glucose uptake using a hyperinsulinaemic euglycaemic clamp) of tenofovir disoproxil fumarate (TDF) administration compared with placebo for 2 weeks in HIV-1-seronegative healthy male volunteers. Changes in lipids, adiponectin, leptin, plasminogen activator inhibitor 1 (PAI-1) and the adhesion molecules E-selectin and P-selectin were also assessed.

Methods

This was a single-centre, randomized, double-blinded, placebo-controlled study that used a two-sequence, two-period cross-over design. A total of 19 HIV-negative males were recruited to the study and randomized 1:1 to receive either 2 weeks of TDF (300 mg once daily) followed by 2 weeks of placebo or placebo initially followed by tenofovir. Clamps were performed at baseline, after 2 weeks and after 4 weeks.

Results

All three clamps were completed by 16 participants. During the euglycaemic clamp, there were no significant changes in insulin sensitivity after 2 weeks of TDF administration compared with placebo or baseline. There was a significant reduction in the mean total cholesterol (9.4%) and low-density lipoprotein (LDL; 8.1%) cholesterol following 2 weeks of TDF compared with placebo. Levels of adiponectin, leptin, PAI-1, P-selectin and E-selectin were not significantly altered.

Conclusions

TDF use for 2 weeks does not affect insulin sensitivity, as assessed by the hyperinsulinaemic euglycaemic clamp in HIV-negative male volunteers. TDF use resulted in modest, but statistically significant, reductions in total and LDL cholesterol.
Treatment simplification to once daily darunavir/ ritonavir guided by the darunavir inhibitory quotient in heavily pretreated HIV-infected patients
Authors: Moltó José , Valle Marta , Santos José Ramón , Mothe Beatriz , Miranda Cristina , Cedeño Samandhy , Negredo Eugenia , Yritia Mercedes , Videla Sebastián , Barbanoj Manuel José , Clotet Bonaventura
Published: April 2010

Background

We explored a treatment simplification strategy to darunavir/ritonavir 900/100 mg once daily guided by the darunavir virtual inhibitory quotient (vIQ) in patients receiving salvage therapy with darunavir/ ritonavir 600/100 mg twice daily.

Methods

Open-label, randomized pilot study in HIV-infected patients on darunavir/ritonavir 600/100 mg twice daily (viral load <50 copies/ml; darunavir vIQ >2). Thirty patients were randomized to darunavir/ritonavir 900/100 mg once daily (once-daily group, n=15) or 600/100 mg twice daily (twice-daily group, n=15). Viral load, blood chemistry, and darunavir and ritonavir trough plasma concentrations (Ctrough) were determined up to 48 weeks. If the darunavir vIQ fell to <1.5, the dosage was switched to 600/100 mg twice daily. The primary end point was the percentage of 48-week treatment failure.

Results

Patients had taken a mean 11.6 (sd ±3.9) antiretro-viral regimens before darunavir/ritonavir administration. The proportion of patients without 48-week treatment failure was 86.7% in both groups. The median (interquartile range [IQR]) darunavir Ctrough decreased from 3.09 mg/l (IQR 2.43–3.93) at baseline to 1.60 mg/l (IQR 1.25–2.04) at week 48 ( P=0.001) in the once-daily group. Three once-daily group patients switched to darunavir/ritonavir 600/100 mg twice daily. Fewer patients had triglyceride levels >200 mg/ dl at week 48 in the once-daily group (20.0%) than in the twice-daily group (20.0% versus 57.1%; P=0.046).

Conclusions

Treatment simplification to darunavir/ ritonavir 900/100 mg once daily guided by the darunavir vIQ in treatment-experienced HIV-infected patients receiving darunavir/ritonavir 600/100 mg twice-daily seems to be safe enough to be tested in adequately powered clinical trials.
Estimating Indirect Costs in Primary Sjögren’s Syndrome
Authors: BOWMAN SIMON J. , ST. PIERRE YVAN , SUTCLIFFE NURHAN , ISENBERG DAVID A. , GOLDBLATT FIONA , PRICE ELIZABETH , HAMBURGER JOHN , RICHARDS ANDREA , RAUZ SAAEHA , REGAN MARIAN , RIGBY SHIRLEY , JONES ADRIAN , MULHERIN DIARMUID , CLARKE ANN E.
Published: April 2010

Objective.

To estimate the indirect costs associated with primary Sjögren’s syndrome (pSS) compared with rheumatoid arthritis (RA) and community controls.

Methods.

Data were obtained from 84 women patients with pSS as part of a study to develop a systemic activity measure, from 87 consecutive women patients with RA attending a hospital clinic, and from 96 women community controls on a general practice list. A modified economic component of the Stanford Health Assessment Questionnaire was used to assess lost productivity.

Results.

Using a conservative model, the estimated total annual indirect costs (95% CI) were £7677 (£5560, £9794) for pSS, £10,444 (£8206, £12,681) for RA, and £892 (£307, £1478) for controls. Using a model that maximizes the estimates, the equivalent figures were £13,502 (£9542, £17,463), £17,070 (£13,112, £21,028), and £3382 (£2187, £4578), respectively. These were all significantly greater at p < 0.001 for patient groups than for the control group.

Conclusion.

pSS is associated with significantly increased indirect costs equivalent to 69%–83% of that for patients with RA. This needs to be taken into account when evaluating the overall economic consequences of pSS.
Education, Zip Code-based Annualized Household Income, and Health Outcomes in Patients with Systemic Lupus Erythematosus
Authors: JOLLY MEENAKSHI , MIKOLAITIS RACHEL A. , SHAKOOR NAJIA , FOGG LOUIS F. , BLOCK JOEL A.
Published: April 2010

Objective.

To determine the association of socioeconomic status [SES; education and zip code-based annual household income (Z-AHI)] and ethnicity with health-related quality of life (HRQOL) among patients with systemic lupus erythematosus (SLE).

Methods.

Data on 211 subjects from a cross-sectional study (LupusPRO©) using the Medical Outcomes Study Short Form-36 questionnaire to evaluate physical health scores (PCS) and mental health scores were used to obtain education and zip code. The 2000 US Census was used to obtain each zip code’s median annual household income.

Results.

Education and Z-AHI correlated with PCS (education standardized β = 0.17, 95% CI 0.47, 3.65, p = 0.01, r2 = 0.03; Z-AHI standardized β = 0.15, 95% CI 0.57, 8.30, p = 0.02, r2 = 0.02) on regression analysis. Z-AHI was linked to PCS, independent of education. Ethnicity was associated with PCS through disease activity and SES.

Conclusion.

SES is associated with HRQOL in SLE. Z-AHI and education are equally predictive surrogates of SES; however, Z-AHI, independent of education, was predictive of HRQOL. Z-AHI has less subject bias and is easily obtainable, therefore its use for future HRQOL studies is suggested.
Information Search Patterns in E-Commerce Product Comparison Services
Authors: Nah Fiona Fui-Hoon , Hong Weiyin , Chen Liqiang , Lee Hong-Hee
Published: April 2010

To facilitate product selection and purchase decisions on e-commerce Web sites, the presentation of product information is very important. In this research, the authors study how disposition styles influence users’ search patterns in product comparison services of e-commerce Web sites. The results show that people use relatively more feature paths and less product paths in vertical disposition style than horizontal disposition style. The findings also indicate that there are relatively more feature paths and less product paths in the first half than second half of the information search paths. This is consistent with Gensch’s two-stage choice model which suggests that people use attribute processing to derive a consideration set before they apply alternative processing to arrive at a final choice in product comparison services.
Antecedents of the Closeness of Human-Avatar Relationships in a Virtual World
Authors: Zhao Yi , Wang Weiquan , Zhu Yan
Published: April 2010

Virtual worlds (e.g., Second Life), where users interact and form relationships with other users’ virtual identities represented by avatars (i.e., human-avatar relationships), are increasingly influential in today’s businesses and society. Nevertheless, the sustainability and impact of virtual worlds depend largely on the closeness of human-avatar relationships. This study investigates the antecedents of the closeness of such relationships. The authors conceptualize human-avatar relationship closeness as composed of interaction frequency, activity diversity, and relational influence. They identify its antecedents (perceived needs fulfillment, relationship irreplaceableness, and resource investment) by extending Rusbult’s investment model of interpersonal relationship commitment to the domain of human-computer interaction. The authors test the hypotheses through an online survey of Second Life users and find that (1) resource investment is positively associated with all three human-avatar relationship closeness dimensions; (2) needs fulfillment is positively associated with interaction frequency and relational influence; and (3) relationship irreplaceableness is positively associated with relational influence.
To Bid or to Buy?
Authors: Tseng Fan-Chen
Published: April 2010

Online retailing is a rapidly expanding business. There are three major purchasing channels for online shoppers to choose when they conduct online purchasing: (1) shopping in online stores, (2) bidding in online auctions, and (3) direct purchasing in online auctions. Each channel has its strengths and weaknesses, and suits different kinds of online shoppers. This article explores the relationships between online shoppers’ lifestyles and their preferences for online purchasing channels. Knowledge about online shoppers’ preferences for online purchasing channels helps online retailers place right products in the right channel for the right customers and consequently generate stable revenues. Major findings are: (1) the online shoppers with extravert lifestyle prefer online auctions, (2) the online shoppers with indulgent lifestyle prefer online stores, and (3) the online shoppers with shrewd lifestyle have a more balanced preference for all three purchasing channels. Theoretical and practical implications are discussed.
Overcoming Visibility Issues in a Small-to-Medium Retailer Using Automatic Identification and Data Capture Technology
Authors: Hamilton Dane , Michael Katina , Wamba Samuel Fosso
Published: April 2010

In this paper, the authors the inventory control practices of a small-to-medium retailer to identify common challenges this type of organization experiences with respect to automated data capture (ADC) and the implementation of an enterprise wide information system. The study explores a single case of a hardware store in a regional town in New South Wales, Australia. Four semi-structured interviews were conducted with employees, focusing on issues related to inventory control including delivery discrepancies, checking and sorting of orders, locating stock and goods, loss prevention, customer purchasing and point of sale processing and replenishment. Flowcharts illustrate the current processes of the retailer with an understanding of how ADC technologies like bar code and radio-frequency identification (RFID) impact the retailer. The findings promote an evolutionary approach toward the use of automated data capture technology by adopting barcode technology and subsequently introducing the complementary RFID technology.
The Role of Skin-Derived Dendritic Cells in CD8+ T Cell Priming Following Immunization with Lentivectors
Authors: Furmanov Karina , Elnekave Mazal , Lehmann Dan , Clausen Bjorn E. , Kotton Darrell N. , Hovav Avi-Hai
Published: April 2010

Although skin dendritic cells (DCs) have been shown to directly present Ag to CD8+ T cells after intradermal immunization with lentivectors, the contribution of the different skin DC subsets to this process remains unclear. Using langerin-diphtheria toxin receptor transgenic mice we demonstrated that ablation of langerhans cells and langerin-expressing positive dermal DCs (Ln+dDCs) did not interfere with the generation of CD8+ T cells by lentiviral vectors. Consistent with these findings, the absence of langerhans cells and Ln+dDCs did not hamper the presentation level of lentiviral-derived Ag by skin DCs in vitro. We further demonstrated that only dDCs and Ln+dDCs were capable of presenting Ag, however, the number of dDCs migrating to the draining lymph nodes was 6-fold higher than that of Ln+dDCs. To study how the duration of DC migration influences CD8+ T cell responses, we analyzed the kinetics of Ag expression at the injection site and manipulated DC migration by excising the injected skin at various times after immunization. A low level of Ag expression was seen 1 wk after the immunization; peaked during week 2, and was considerably cleared by week 3 via a perforin-dependent fas-independent mechanism. Removing the injection site 3 or 5 d, but not 10 d, after the immunization, resulted in a reduced CD8+ T cell response. These findings suggest that dDCs are the main APCs active after intradermal lentiviral-mediated immunization, and migration of dDCs in the initial 10-d period postimmunization is required for optimal CD8+ T cell induction.
TLR4 Promotes B Cell Maturation: Independence and Cooperation with B Lymphocyte-Activating Factor
Authors: Hayashi Elize A. , Granato Alessandra , Paiva Luciana S. , Bertho Álvaro L. , Bellio Maria , Nobrega Alberto
Published: April 2010

We have previously shown that TLR4 triggering promotes the generation of CD23+CD93+ transitional T2-like cells in vitro from mouse B cell precursors, suggesting a possible role for this receptor in B cell maturation. In this study, we perform an extensive study of cell surface markers and functional properties of B cells matured in vitro with LPS, comparatively with the well-known B cell maturation factor B lymphocyte-activating factor (BAFF). LPS increased generation of CD23+ transitional B cells in a TLR4-dependent way, upregulating IgD and CD21 and downregulating CD93, without inducing cell proliferation, in a manner essentially equivalent to BAFF. For both BAFF and LPS, functional maturation of the IgM+CD23+CD93+ cells was confirmed by their higher proliferative response to anti-CD40 plus IL-4 compared with IgM+CD23negCD93+ cells. BAFF-R-Fc–mediated neutralization experiments showed that TLR4-induced B cell maturation was independent of BAFF. Distinct from BAFF, maturation by LPS relied on the activation of canonical NF-κB pathway, and the two factors together had complementary effects, leading to higher numbers of IgM+CD23+CD93+ cells with their simultaneous addition. Importantly, BCR cross-linking abrogated the generation of CD23+ B cells by LPS or BAFF, indicating that signals mimicking central tolerance act on both systems. Addition of cyclosporin A reverted BCR-mediated inhibition, both for BAFF and LPS, suggesting similar regulation of signaling pathways by calcineurin. Finally, LPS-injected mice showed a rapid increase of mature B cells in the bone marrow, suggesting that TLR4 signaling may effectively stimulate B cell maturation in vivo, acting as an accessory stimulus in B cell development, complementary to the BAFF physiological pathway.
Intron-Containing Type I and Type III IFN Coexist in Amphibians: Refuting the Concept That a Retroposition Event Gave Rise to Type I IFNs
Authors: Qi Zhitao , Nie Pin , Secombes Chris J. , Zou Jun
Published: April 2010

Type I and III IFNs are structurally related cytokines with similar antiviral functions. They have different genomic organizations and bind to distinct receptor complexes. It has been vigorously debated whether the recently identified intron containing IFN genes in fish and amphibians belong to the type I or III IFN family or diverged from a common ancestral gene, that subsequently gave rise to both types. In this report, we have identified intron containing type III IFN genes that are tandemly linked in the Xenopus tropicalis genome and hence demonstrate for the first time that intron containing type I and III genes diverged relatively early in vertebrate evolution, and at least by the appearance of early tetrapods, a transition period when vertebrates migrated from an aquatic environment to land. Our data also suggest that the intronless type I IFN genes seen in reptiles, birds, and mammals have originated from a type I IFN transcript via a retroposition event that led to the disappearance of intron-containing type I IFN genes in modern vertebrates. In vivo and in vitro studies in this paper show that the Xenopus type III IFNs and their cognate receptor are ubiquitously expressed in tissues and primary splenocytes and can be upregulated by stimulation with synthetic double-stranded RNA, suggesting they are involved in antiviral defense in amphibians.
An Imbalance of Two Functionally and Phenotypically Different Subsets of Plasmacytoid Dendritic Cells Characterizes the Dysfunctional Immune Regulation in Multiple Sclerosis
Authors: Schwab Nicholas , Zozulya Alla L. , Kieseier Bernd C. , Toyka Klaus V. , Wiendl Heinz
Published: April 2010

Plasmacytoid dendritic cells (pDCs) are instrumental in peripheral T cell tolerance and innate immunity. How pDCs control peripheral immunetolerance and local parenchymal immune response and contribute to the altered immunoregulation in autoimmune disorders in humans is poorly understood. Based on their surface markers, cytokine production, and ability to prime naive allogenic T cells, we found that purified BDCA-2+BDCA-4+ pDCs consist of at least two separate populations, which differed in their response to oligodeoxynucleotides and IFNs (IFN-β), and differently induced IL-17– or IL-10–producing T cells. To evaluate the potential immunoregulatory role of these two types of pDCs in multiple sclerosis (MS) and other human autoimmune disorders (myasthenia gravis), we studied the phenotype and regulatory function of pDCs isolated from clinically stable, untreated patients with MS (n = 16). Patients with MS showed a reversed ratio of pDC1/pDC2 in peripheral blood (4.4:1 in healthy controls, 0.69:1 in MS), a phenomenon not observed in the other autoimmune disorders. As a consequence, MS pDCs had an overall propensity to prime IL-17–secreting cells over IL-10–secreting CD4+ T cells. Immunomodulatory therapy with IFN-β induced an increase of the pDC1 population in vivo (n = 5). Our data offer a plausible explanation for the disturbed immune tolerance in MS patients and provide evidence that immunomodulatory therapy acts at the level of reconstituting homeostasis of pDC, thus reconstituting the disturbed balance.
Cutting Edge: Granulocyte-Macrophage Colony-Stimulating Factor Is the Major CD8+ T Cell-Derived Licensing Factor for Dendritic Cell Activation
Authors: Min Lin , Mohammad Isa Siti Aminah Bte , Shuai Wang , Piang Cher Boon , Nih Fam Wee , Kotaka Masayo , Ruedl Christiane
Published: April 2010

During priming, CD8+ T lymphocytes can induce robust maturation of dendritic cells (DCs) in a CD40-independent manner by secreting licensing factor(s). In this study, we isolate this so-far elusive licensing factor and identify it, surprisingly, as GM-CSF. This provides a new face for an old factor with a well-known supporting role in DC development and recruitment. Signaling through the GM-CSFR in ex vivo-purified DCs upregulated the expression of costimulatory molecules more efficiently than did any tested TLR agonist and provided a positive feedback loop in the stimulation of CD8+ T cell proliferation. Combined with a variety of microbial stimuli, GM-CSF supports the formation of potent “effector” DCs capable of secreting a variety of proinflammatory cytokines that guide the differentiation of T cells during the immune response.
CD4+CD25+Foxp3+ Regulatory T Cells Optimize Diversity of the Conventional T Cell Repertoire during Reconstitution from Lymphopenia
Authors: Winstead Colleen J. , Reilly Cavan S. , Moon James J. , Jenkins Marc K. , Hamilton Sara E. , Jameson Stephen C. , Way Sing Sing , Khoruts Alexander
Published: April 2010

The functional capacity of the adaptive immune system is dependent on the size and the diversity of the T cell population. In states of lymphopenia, T cells are driven to proliferate to restore the T cell population size. However, different T cell clones proliferate at different rates, and some T cells experience burst-like expansion called spontaneous lymphopenia-induced proliferation (LIP). These T cells are likely receiving stimulation from cognate Ags and are most responsible for inflammatory pathology that can emerge in lymphopenic states. Foxp3+ regulatory T cells (Tregs) selectively inhibit spontaneous LIP, which may contribute to their ability to prevent lymphopenia-associated autoimmunity. We hypothesized that another potential negative consequence of unrestrained spontaneous LIP is constriction of the total T cell repertoire. We demonstrate that the absence of Foxp3+ Tregs during the period of immune reconstitution results in the development of TCR repertoire “holes” and the loss of Ag-specific responsiveness to infectious microorganisms. In contrast, the presence of Tregs during the period of immune reconstitution preserves optimal TCR diversity and foreign Ag responsiveness. This finding contrasts with the generally accepted immunosuppressive role of Tregs and provides another example of Treg activity that actually enhances immune function.
Collagen‐Induced Arthritis
Authors: Rosloniec Edward F. , Cremer Michael , Kang Andrew H. , Myers Linda K. , Brand David D.
Published: April 2010

The mouse model collagen‐induced arthritis (CIA) is a widely studied autoimmune model of rheumatoid arthritis. In this model, autoimmune arthritis is induced by immunization with type II collagen (CII) emulsified in complete Freund's adjuvant. This unit describes the steps necessary for the acquisition, handling, and preparation of CII, in addition to the selection of mouse strains, proper immunization technique, and methods for evaluation of the incidence and severity of arthritis. In this model, the first signs of arthritis appear approximately 21 to 28 days after immunization. The protocols in this unit should provide the investigator with all the necessary information required to reproducibly induce a high incidence of CIA in genetically susceptible strains of mice, and to critically evaluate the pathology of the disease. Curr. Protoc. Immunol. 89:15.5.1‐15.5.25. © 2010 by John Wiley & Sons, Inc.
Oxidation Resistance of Multilayer SiC for Space Vehicle Thermal Protection Systems
Authors: Vega Bolivar Claudia Milena , Antonini Andrea , Biamino Sara , Pavese Matteo , Fino Paolo , Badini Claudio
Published: April 2010

The oxidation resistances of different kinds of SiC‐based laminates are compared. The materials under investigation are produced by tape casting of green ceramic sheets, followed by stacking of the sheets in a multilayer structure and laminate consolidation by de‐binding and sintering. Three kinds of specimens are tested: multilayer SiC with fully dense layers, multilayer SiC integrating porous layers and multilayer composites made by stacking SiC/Cf composite layers. Two kinds of chopped carbon fibres (polyamide coated and uncoated) are used for the manufacture of the composite sheets. The oxidation behaviour is investigated by simultaneous TGA–DTA–MS analysis. Specimens are also submitted to a long‐term oxidation treatment (30 h at 1 600 °C in flowing air) and their microstructure and mechanical behaviour compared before and after oxidation. This assessment shows that the integration of porous or composite layers in the multilayer architecture does not worsen the oxidation resistance. In every case the formation of a surface passivating layer prevents major degradation phenomena, so that only small changes in the mechanical features are found after oxidation.
Plasticity and Grain Boundary Diffusion at Small Grain Sizes
Authors: Wilde Gerhard , Ribbe Jens , Reglitz Gerrit , Wegner Matthias , Rösner Harald , Estrin Yuri , Zehetbauer Michael , Setman Daria , Divinski Sergiy
Published: April 2010

Bulk nanostructured—or ultrafine‐grained materials are often fabricated by severe plastic deformation to break down the grain size by dislocation accumulation. Underlying the often spectacular property enhancement that forms the basis for a wide range of potential applications is a modification of the volume fraction of the grain boundaries. Yet, along with the property enhancements, several important questions arise concerning the accommodation of external stresses if dislocation‐based processes are not longer dominant at small grain sizes. One question concerns so‐called “non‐equilibrium” grain boundaries that have been postulated to form during severe deformation and that might be of importance not only for the property enhancement known already today, but also for spectacular applications in the context of, e.g., gas permeation or fast matter transport for self‐repairing structures. This contribution addresses the underlying issues by combining quantitative microstructure analysis at high resolution with grain boundary diffusion measurements.
The 1,3‐Diaminobenzene‐Derived Aminophosphine Palladium Pincer Complex {C6H3[NHP(piperidinyl)2]2Pd(Cl)} – A Highly Active Suzuki–Miyaura Catalyst with Excellent Functional Group Tolerance
Authors: Bolliger Jeanne L. , Frech Christian M.
Published: April 2010

The rapidly prepared 1,3‐diaminobenzene‐derived aminophosphine pincer complex {C6H3[NHP(piperidinyl)2]2Pd(Cl)} (1) is an effective Suzuki catalyst with excellent functional group tolerance. Side‐product formations, such as homocoupling, debromation or protodeboration have only rarely been detected and if so, were in all cases below the 5% level. The presented reaction protocol is universally applicable. Experimental observations indicate that palladium nanoparticles are the catalytically active form of 1.
Highly Enantioselective Hydrogenation of Quinoline and Pyridine Derivatives with Iridium‐(P‐Phos) Catalyst
Authors: Tang Wei‐Jun , Tan Jing , Xu Li‐Jin , Lam Kim‐Hung , Fan Qing‐Hua , Chan Albert S. C.
Published: April 2010

The use of a chiral iridium catalyst generated in situ from the (cyclooctadiene)iridium chloride dimer, [Ir(COD)Cl]2, the P‐Phos ligand [4,4′‐bis(diphenylphosphino)‐2,2′,6,6′‐tetramethoxy‐3,3′‐bipyridine] and iodine (I2) for the asymmetric hydrogenation of 2,6‐substituted quinolines and trisubstituted pyridines [2‐substituted 7,8‐dihydroquinolin‐5(6H)‐one derivatives] is reported. The catalyst worked efficiently to hydrogenate a series of quinoline derivatives to provide chiral 1,2,3,4‐tetrahydroquinolines in high yields and up to 96% ee. The hydrogenation was carried out at high S/C (substrate to catalyst) ratios of 2000–50000, reaching up to 4000 h−1 TOF (turnover frequency) and up to 43000 TON (turnover number). The catalytic activity is found to be additive‐controlled. At low catalyst loadings, decreasing the amount of additive I2 was necessary to maintain the good conversion. The same catalyst system could also enantioselectively hydrogenate trisubstituted pyridines, affording the chiral hexahydroquinolinone derivatives in nearly quantitative yields and up to 99% ee. Interestingly, increasing the amount of I2 favored high reactivity and enantioselectivity in this case. The high efficacy and enantioselectivity enable the present catalyst system of high practical potential.
A Simple Copper‐Catalyzed Cascade Synthesis of 2‐Amino‐1H‐indole‐3‐carboxylate Derivatives
Authors: Yang Xiaobo , Fu Hua , Qiao Renzhong , Jiang Yuyang , Zhao Yufen
Published: April 2010

We have developed a simple and efficient copper‐catalyzed method for the synthesis of 2‐amino‐1H‐indole‐3‐carboxylate derivatives via cascade reactions of substituted N‐(2‐halophenyl)‐2,2,2‐trifluoroacetamide with alkyl 2‐cyanoacetate or malononitrile under mild conditions, and the method is of wide practical application.
Deracemisation of Mandelic Acid to Optically Pure Non‐Natural L‐Phenylglycine via a Redox‐Neutral Biocatalytic Cascade
Authors: Resch Verena , Fabian Walter M. F. , Kroutil Wolfgang
Published: April 2010

A biocatalytic redox‐neutral reaction cascade was designed for the deracemisation of racemic mandelic acid to yield optically pure L‐phenylglycine employing three enzymes. The cascade consisted of three steps: a racemisation, an enantioselective oxidation and a stereoselective reductive amination. The enantioselective oxidation of D‐mandelic acid to the corresponding oxo acid was coupled with the stereoselective reductive amination of the latter; thus the oxidation as well as the reduction reactions were performed simultaneously. The formal hydrogen abstracted in the first step – the oxidation – was consumed in the reductive amination allowing a redox‐neutral cascade due to a cascade‐internal cofactor recycling. The enantiomers of the starting material were interconverted by a racemase (mandelate racemase) ensuring that in theory 100% of the starting material can be transformed. Using this set‐up racemic mandelic acid was transformed to optically pure L‐phenylglycine (ee >97%) at 94% conversion without the requirement of any additional redox reagents in stoichiometric amounts.
Deletions of NRXN1 (neurexin‐1) predispose to a wide spectrum of developmental disorders
Authors: Ching Michael S.L. , Shen Yiping , Tan Wen‐Hann , Jeste Shafali S. , Morrow Eric M. , Chen Xiaoli , Mukaddes Nahit M. , Yoo Seung‐Yun , Hanson Ellen , Hundley Rachel , Austin Christina , Becker Ronald E. , Berry Gerard T. , Driscoll Katherine , Engle Elizabeth C. , Friedman Sandra , Gusella James F. , Hisama Fuki M. , Irons Mira B. , Lafiosca Tina , LeClair Elaine , Miller David T. , Neessen Michael , Picker Jonathan D. , Rappaport Leonard , Rooney Cynthia M. , Sarco Dean P. , Stoler Joan M. , Walsh Christopher A. , Wolff Robert R. , Zhang Ting , Nasir Ramzi H. , Wu Bai‐Lin ,   on behalf of the Children's Hospital Boston Genotype Phenotype Study Group
Published: April 2010

Research has implicated mutations in the gene for neurexin‐1 (NRXN1) in a variety of conditions including autism, schizophrenia, and nicotine dependence. To our knowledge, there have been no published reports describing the breadth of the phenotype associated with mutations in NRXN1. We present a medical record review of subjects with deletions involving exonic sequences of NRXN1. We ascertained cases from 3,540 individuals referred clinically for comparative genomic hybridization testing from March 2007 to January 2009. Twelve subjects were identified with exonic deletions. The phenotype of individuals with NRXN1 deletion is variable and includes autism spectrum disorders, mental retardation, language delays, and hypotonia. There was a statistically significant increase in NRXN1 deletion in our clinical sample compared to control populations described in the literature (P = 8.9 × 10−7). Three additional subjects with NRXN1 deletions and autism were identified through the Homozygosity Mapping Collaborative for Autism, and this deletion segregated with the phenotype. Our study indicates that deletions of NRXN1 predispose to a wide spectrum of developmental disorders. © 2010 Wiley‐Liss, Inc.