bluuebunny/crossref_metadata_2025 huggingface dataset:
Enantioselective, Organocatalytic Morita-Baylis-Hillman and Aza-Morita-Baylis-Hillman Reactions: Stereochemical Issues
Authors: Mansilla Javier , Saá José M.
Published: February 2010

Conscious of the importance that stereochemical issues may have on the design of efficient organocatalyts for both Morita-Baylis-Hillman and aza-Morita-Baylis-Hillman reaction we have analyzed them in this minireview. The so-called standard reactions involve “naked” enolates which therefore should lead to the syn adducts as the major products, irrespective of the E, Z stereochemistry of the enolate. Accordingly, provided the second step is rate determining step, the design of successful bifunctional or polyfunctional catalysts has to consider the geometrical requirements imposed by the transition structures of the second step of these reactions. On the other hand, MBH and aza-MBH reactions co-catalyzed by (S)-proline and a secondary or tertiary amine (co-catalyst) involve the aldol-type condensation of either a 3-amino-substituted enamine, dienamine, or both, depending on the cases. A Zimmerman-Traxler mechanism defines the stereochemical issues regarding these co-catalyzed condensations which parallel those of the well established (S)-proline catalyzed aldol-like reactions.
Radiometric Calibration for AgCam
Authors: Olsen Doug , Dou Changyong , Zhang Xiaodong , Hu Lianbo , Kim Hojin , Hildum Edward
Published: February 2010

The student-built Agricultural Camera (AgCam) now onboard the International Space Station observes the Earth surface through two linescan cameras with Charge-Coupled Device (CCD) arrays sensitive to visible and near-infrared wavelengths, respectively. The electro-optical components of the AgCam were characterized using precision calibration equipment; a method for modeling and applying these measurements was derived. Correction coefficients to minimize effects of optical vignetting, CCD non-uniform quantum efficiency, and CCD dark current are separately determined using a least squares fit approach. Application of correction coefficients yields significant variability reduction in flat-field images; comparable results are obtained when applied to ground test images.
System Interface for an Integrated Intelligent Safety System (ISS) for Vehicle Applications
Authors: Hannan Mahammad  A. , Hussain Aini , Samad Salina  A.
Published: February 2010

This paper deals with the interface-relevant activity of a vehicle integrated intelligent safety system (ISS) that includes an airbag deployment decision system (ADDS) and a tire pressure monitoring system (TPMS). A program is developed in LabWindows/CVI, using C for prototype implementation. The prototype is primarily concerned with the interconnection between hardware objects such as a load cell, web camera, accelerometer, TPM tire module and receiver module, DAQ card, CPU card and a touch screen. Several safety subsystems, including image processing, weight sensing and crash detection systems, are integrated, and their outputs are combined to yield intelligent decisions regarding airbag deployment. The integrated safety system also monitors tire pressure and temperature. Testing and experimentation with this ISS suggests that the system is unique, robust, intelligent, and appropriate for in-vehicle applications.
Cooperative Anchor-Free Position Estimation for Hierarchical Wireless Sensor Networks
Authors: Wen Chih-Yu , Hsiao Yu-Cheng , Chan Fu-Kai
Published: February 2010

This paper proposes a distributed algorithm for establishing connectivity and location estimation in cluster-based wireless sensor networks. The algorithm exploits the information flow while coping with distributed signal processing and the requirements of network scalability. Once the estimation procedure and communication protocol are performed, sensor clusters can be merged to establish a single global coordinate system without GPS sensors using only distance information. In order to adjust the sensor positions, the refinement schemes and cooperative fusion approaches are applied to reduce the estimation error and improve the measurement accuracy. This paper outlines the technical foundations of the localization techniques and presents the tradeoffs in algorithm design. The feasibility of the proposed schemes is shown to be effective under certain assumptions and the analysis is supported by simulation and numerical studies.
ZnO-Based Amperometric Enzyme Biosensors
Authors: Zhao Zhiwei , Lei Wei , Zhang Xiaobing , Wang Baoping , Jiang Helong
Published: February 2010

Nanostructured ZnO with its unique properties could provide a suitable microenvironment for immobilization of enzymes while retaining their biological activity, and thus lead to an expanded use of this nanomaterial for the construction of electrochemical biosensors with enhanced analytical performance. ZnO-based enzyme electrochemical biosensors are summarized in several tables for an easy overview according to the target biosensing analyte (glucose, hydrogen peroxide, phenol and cholesterol), respectively. Moreover, recent developments in enzyme electrochemical biosensors based on ZnO nanomaterials are reviewed with an emphasis on the fabrications and features of ZnO, approaches for biosensor construction (e.g., modified electrodes and enzyme immobilization) and biosensor performances.
Reducing Energy Subsidies in China, India and Russia: Dilemmas for Decision Makers
Authors: Dansie Grant , Lanteigne Marc , Overland Indra
Published: February 2010

This article examines and compares efforts to reduce energy subsidies in China, India and Russia. Despite dissimilarities in forms of governance, these three states have followed surprisingly similar patterns in reducing energy subsidies, characterised by two steps forward, one step back. Non-democratic governments and energy importers might be expected to be more likely to halt subsidies. In fact, the degree of democracy and status as net energy exporters or importers does not seem to significantly affect these countries’ capacity to reduce subsidies, as far as can be judged from the data in this article. Politicians in all three fear that taking unpopular decisions may provoke social unrest.
Developing Vaccines to Combat Pandemic Influenza
Authors: Robertson James S. , Engelhardt Othmar G.
Published: February 2010

Influenza vaccine manufacturers require antigenically relevant vaccine viruses that have good manufacturing properties and are safe to use. In developing pandemic vaccine viruses, reverse genetics has been employed as a rational approach that can also be used effectively to attenuate the highly virulent H5N1 virus and at the same time place the H5 HA and N1 NA on a background of PR8, a virus that has been used over many decades to provide high yielding vaccine viruses. Reverse genetics has also been used successfully alongside classical reassorting techniques in the development of (swine flu) pandemic A(H1N1)v vaccine viruses.
Sonochemical Treatment of Water Polluted by Chlorinated Organocompounds. A Review
Authors: González-García José , Sáez Verónica , Tudela Ignacio , Díez-Garcia María Isabel , Deseada Esclapez María , Louisnard Olivier
Published: February 2010

As one of several types of pollutants in water, chlorinated compounds have been routinely subjected to sonochemical analysis to check the environmental applications of this technology. In this review, an extensive study of the influence of the initial concentration, ultrasonic intensity and frequency on the kinetics, degradation efficiency and mechanism has been analyzed. The sonochemical degradation follows a radical mechanism which yields a very wide range of chlorinated compounds in very low concentrations. Special attention has been paid to the mass balance comparing the results from several analytical techniques. As a conclusion, sonochemical degradation alone is not an efficient treatment to reduce the organic pollutant level in waste water.
Supporting Mobility: Evaluating Mobile Technology Advances in Tourism
Authors: Clarke Alan , Raffay Ágnes , Beritelli Pietro , Wittmer Andreas
Published: February 2010

This is a product of the work undertaken by the Aladdin consortium to develop mobile support systems for tourists and tour guides to meet the demands for relevant, up-to-date information and problem-solving options in real time in the destination. There are many approaches advocated
to evaluation and this article considers the implications of hard and soft approaches, over and under evaluating projects, and the issues of inclusion and exclusion of key actors from the evaluation. A framework for the review of the evaluations undertaken within seven completed projects,
critically assessing the methods used, is presented leading to a model of best practice, advocating greater clarity in evaluation, emphasizing the importance of transparency, traceability, and triangulation. The process has been informed by the need to be reflexively critical (taking our own
processes through a process of critical examination, evaluation, and reflection) and we have been concerned to ensure that Aladdin learns from and builds on those experiences and that our own development processes are transparent, reflexive, and self-critical.
Cultural Mobility and Acceptance: The Case of Japanese Tourists in Alpine Destinations
Authors: Mueller Sabine , Peters Mike , Weiermair Klaus
Published: February 2010

The purpose of this article is to identify and evaluate determinants of cultural acceptance among tourists. Specifically the question to be answered is: which variables influence travelers' cultural mobility and which clusters of cultural interest can be identified among specific groups
of Japanese long-haul distance travelers to alpine destinations? While the first part of the article provides a literature review focusing on tourists' cultural mobility, the second part of the article presents a case study in form of a survey that was carried out in the winter of 2005/2006
in the Alpine region of St. Anton, Austria and Zermatt, Switzerland. The two winter sport destinations differ appreciably in terms of their characteristics of cultural supply vis-à-vis Japanese long-haul visitors. Japanese tourists had been asked to indicate their travel motives as
well as their satisfaction with the supplied tourism products and services offered. In addition, the questionnaire assessed their overall destination activities and their participation in cultural/local events. The authors were able to cluster Japanese long-haul tourists into two groups. To
do so, their participation in local cultural events was analyzed and interpreted. The authors present this case study in order to demonstrate the relevance for continued research in the area of cultural and spiritual mobility. Tourism policy implications as well as suggestions for the design
of destination authenticity will be presented in the final part of the article.
Motivation Segmentation of Chinese Tourists Visiting the US
Authors: Li Xiangping , Xu Yueying , Weaver Pamela A.
Published: February 2010

This study attempts to segment Chinese tourists visiting the US based on items representing motivations. A factor-cluster approach was used to analyze the data. Factor analysis resulted in six underlying motivation factors: Relaxation/Escape, Prestige, Knowledge, Job Fulfillment, Entertainment,
and Novelty. Based on the six motivation factors, cluster analysis identified three homogeneous groups of respondents. The distinct groups were identified as High Brow Traveler, Enthusiastic Traveler, and Reluctant Traveler. Marketing implications were provided based on the findings.
Time-Dependent Reasons for Peritoneal Dialysis Technique Failure and Mortality
Authors: Kolesnyk Inna , Dekker Friedo W. , Boeschoten Elisabeth W. , Krediet Raymond T.
Published: February 2010

Background

Peritoneal dialysis (PD) technique failure is high compared to hemodialysis (HD). There is a lack of data on the impact of duration of PD treatment on technique survival and on whether there is a difference in risk factors with respect to early and late failure. The aim of this study was to clarify these issues by performing a time-dependent analysis of PD technique and patient survival in a large cohort of incident PD patients.

Methods

We analyzed 709 incident PD patients participating in the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD), who started their treatment between 1997 and 2007. We compared technique and patient survival on PD in 4 periods of follow-up: within the first 3 months, and after 3 – 12 months, 12 – 24 months, and 24 – 36 months of treatment. Cox proportional hazards model was used to analyze survival on PD and technique failure. Risk factors were also identified by comparing patients that were transferred to HD with those that remained on PD. Incidence rates for every cause of dropout for each period of follow-up were calculated to establish their trends with respect to PD treatment duration.

Results

There was a significant increase in transplantation rate after the first year of treatment. The rate of switching to HD was highest during the first 3 months and decreased afterward. One-, 2- and 3-year technique survival was 87%, 76%, and 66%, respectively. Age, diabetes, and cardiovascular disease appeared to be risk factors for death on PD or switch to HD: a 1-year increase in age was associated with a relative risk (RR) of PD failure of 1.04 [95% confidence interval (CI) 1.003 – 1.06]; for diabetes, RR of stopping PD after 3 months of treatment increased from 1.8 (95% CI 1.1 – 3) during the first year to 2.2 (95% CI 1.3 – 4) after the second year; cardiovascular disease had a major impact in the earliest period (RR 2.5, 95% CI 1.2 – 5) and had a stable influence further on (RR 2, 95% CI 1.1 – 3.5). Loss of 1 mL/minute residual glomerular filtration rate (rGFR) appeared to be a significant predictor of PD failure after 3 months of treatment, but within the first 2 years, RR was 1.1 (95% CI 1.04 – 1.25).

Conclusions

In The Netherlands, transplantation is a main reason to stop PD treatment. The incidence of PD technique failure is at its highest during the earliest months after treatment initiation and decreases later due to fewer catheter and abdominal complications as well as less influence of psychosocial factors. Risk factors for PD discontinuation are those responsible for patient survival: age, cardiovascular disease, diabetes, and rGFR.
Early Diagnostic Markers for Encapsulating Peritoneal Sclerosis: A Case-Control Study
Authors: Sampimon Denise E. , Korte Mario R. , Barreto Deirisa Lopes , Vlijm Anniek , de Waart Rudy , Struijk Dirk G. , Krediet Raymond T.
Published: February 2010

Objective

Encapsulating peritoneal sclerosis (EPS) is a severe complication of long-term peritoneal dialysis (PD). The aim of this study was to investigate whether dialysate levels of cancer antigen-125 (CA125), K+, interleukin (IL)-6, and vascular endothelial growth factor (VEGF) are early diagnostic markers of EPS. Therefore, we analyzed the time courses of the above described dialysate markers in EPS patients and controls.

Methods

Dialysate and serum samples of 11 EPS patients and 31 control patients, all treated with PD for at least 57 months, were longitudinally collected during standard peritoneal permeability analyses. CA125 and IL-6 were measured in dialysate only, K+ and VEGF were measured in both dialysate and serum. CA125 and IL-6 are expressed as appearance rates (AR). The linear mixed model was used to analyze the time courses. Sensitivity and specificity were calculated based on the results of the last 2 time points.

Results

No differences in the time courses of the different markers were present between the groups. For K+ and VEGF attributed to local production, no differences between the groups were found. However, AR-CA125 was lower during the last 3 years prior to EPS ( p < 0.05) and AR-IL-6 tended to be higher 2 years prior to EPS ( p = 0.09). The combination of AR-CA125 < 33 U/min and AR-IL-6 > 350 pg/min had a sensitivity of 70% and a specificity of 89% for the development of EPS.

Conclusions

Compared to controls, AR-CA125 showed lower values and AR-IL-6 tended to be higher during the last years prior to the diagnosis of EPS. The sensitivity and specificity of the combination of CA125 and IL-6 indicate their potential use for an early diagnosis of EPS.
Performance over Time on Adults with Simultaneous Bilateral Cochlear Implants
Authors: Chang Son-A , Tyler Richard S. , Dunn Camille C. , Ji Haihong , Witt Shelley A. , Gantz Bruce , Hansen Marlan
Published: February 2010

Background:Maximum performance and long-term stability of bilateral cochlear implants has become an important topic because there has been increasing numbers of recipients of bilateral cochlear implants.Purpose:To determine the performance over time (up to 6 yr)
of subjects with simultaneous bilateral cochlear implants (CI+CI) on word recognition and localization.Research Design:Over-time investigation of word recognition in quiet (CNC) and sound localization in quiet (Everyday Sounds Localization Test).Study Sample:The subjects
were 48 adults who simultaneously received their cochlear implants at the University of Iowa.Results:For word recognition, percent correct scores continuously improved up to 1 yr postimplantation with the most benefit occurring within the first month of implantation. In observing
up to 72 mo, the averaged scores reached to the plateau of about 63% correct in CNC after 2 yr (N = 31). But, when we followed 17 subjects who have complete data set between 12 mo and 48+ months, word recognition scores were significantly different
from 12 mo to 48+ months, which implies binaural advantages need more time to be developed. Localization test results suggested that the root mean square (RMS) error scores continuously improved up to 1 yr postimplantation with most benefits occurring within the first
3 mo. After 2 yr, the averaged scores reached to the plateau of about 20° RMS error (N = 27). When we followed 10 subjects who have complete data set between 12 mo and 48+ months, localization scores were not improved from 12 mo to 48+ months.
There were large individual differences in performance over time.Conclusions:In general, substantial benefits in both word recognition and localization were found over the first 1‐12 mo postimplantation for subjects who received simultaneous bilateral cochlear implants.
These benefits were maintained over time up to 6 yr postimplantation.
Benefits of Localization and Speech Perception with Multiple Noise Sources in Listeners with a Short-Electrode Cochlear Implant
Authors: Dunn Camille C. , Perreau Ann , Gantz Bruce , Tyler Richard S.
Published: February 2010

Background:Research suggests that for individuals with significant low-frequency hearing, implantation of a short-electrode cochlear implant may provide benefits of improved speech perception abilities. Because this strategy combines acoustic and electrical hearing within the
same ear while at the same time preserving low-frequency residual acoustic hearing in both ears, localization abilities may also be improved. However, very little research has focused on the localization and spatial hearing abilities of users with a short-electrode cochlear implant.Purpose:The
purpose of this study was to evaluate localization abilities for listeners with a short-electrode cochlear implant who continue to wear hearing aids in both ears. A secondary purpose was to document speech perception abilities using a speech-in-noise test with spatially separate noise sources.Research
Design:Eleven subjects that utilized a short-electrode cochlear implant and bilateral hearing aids were tested on localization and speech perception with multiple noise locations using an eight-loudspeaker array. Performance was assessed across four listening conditions using various combinations
of cochlear implant and/or hearing aid use.Results:Results for localization showed no significant difference between using bilateral hearing aids and bilateral hearing aids plus the cochlear implant. However, there was a significant difference between the bilateral hearing aid condition
and the implant plus use of a contralateral hearing aid for all 11 subjects.Results for speech perception showed a significant benefit when using bilateral hearing aids plus the cochlear implant over use of the implant plus only one hearing aid.Conclusion:Combined use of both
hearing aids and the cochlear implant show significant benefits for both localization and speech perception in noise for users with a short-electrode cochlear implant. These results emphasize the importance of low-frequency information in two ears for the purpose of localization and speech
perception in noise.
Structural and antigenic variance between novel influenza A/H1N1/2009 and influenza A/H1N1/2008 viruses
Authors: Saxena Shailendra K , Mishra Niraj , Saxena Rakhi , Swamy ML Arvinda , Sahgal Pranshu , Saxena Shailja , Tiwari Shrish , Mathur Asha , Nair Madhavan P
Published: February 2010

Background: The emergence of influenza A/H1N1/2009 is alarming. The severity of previous epidemics suggests that the susceptibility of the human population to H1N1 is directly proportional to the degree of changes in hemagglutinin/HA and neuraminidase/NA; therefore, H1N1/2009 and H1N1/2008 were analyzed for their sequence as well as structural divergence. Methodology: The structural and sequence divergence of H1N1/2009 and H1N1/2008 strains were analyzed by aligning HA and NA amino acid sequences by using ClustalW and ESyPred3D software. To determine the variations in sites of viral attachment to host cells, a comparison between amino acid sequences of HA and NA glycosylation sites was performed with NetNGlyc software. The antigenic divergence was executed by CTL epitope prediction method.  Results: The amino acid homology levels of H1N1/2009 were 20.32% and 18.73% compared to H1N1/2008 for HA and NA genes, respectively.  In spite of the high variation in HA and NA amino acid composition, there was no significant difference in their structures. Antigenic analysis proposes that great antigenic differences exist between both the viral strains, but no addition of a new site of glycosylation was observed. Conclusions: To our knowledge, this is the first report suggesting that the circulating novel influenza virus A/H1N1/2009 attaches to the same glycosylation receptor sites as its predecessor influenza A/H1N1/2008 virus, but is antigenically different and may have the potential for initiating a significant pandemic. Our study may facilitate the development of better therapeutics and preventive strategies, as well as impart clues for novel H1N1 diagnostic and vaccine development.
Neonatal septicemia isolates and resistance patterns in a tertiary care hospital of North India
Authors: Kaistha Neelam , Mehta Manjula , Singla Nidhi , Garg Ritu , Chander Jagdish
Published: February 2010

Background: Septicemia continues to be a major cause of neonatal mortality and morbidity worldwide. Methodology: To know the rate of neonatal septicemia in our tertiary care centre, a retrospective analysis of 2,247 blood samples was done over a period of four years and three months (July 2003 to October 2007). Results: During that period, a total of 296 (13.17%) blood samples were found to be positive for bacterial isolates. Gram-negative septicemia (80.40%) was identified in more cases than Gram-positive septicemia (20.60%) with Klebsiella species 84 (28.3%) being the most common isolate. Maximum resistance among Gram-negative organisms was seen in amoxycillin/ampicillin and third-generation cephalosporins. Amikacin, cefoperazone/sulbactam and imipenem were found to be good alternative drugs.  Among Gram-positive organisms, all strains were sensitive to Vancomycin. Conclusion: Continued surveillance for various pathogens and their susceptibility profile should be done to effectively and timely treat the patients of neonatal septicaemia.
A Novel HLA (HLA-A*0201) Transgenic Rabbit Model for Preclinical Evaluation of Human CD8+ T Cell Epitope-Based Vaccines against Ocular Herpes
Authors: Chentoufi Aziz A. , Dasgupta Gargi , Christensen Neil D. , Hu Jiafen , Choudhury Zareen S. , Azeem Arfan , Jester James V. , Nesburn Anthony B. , Wechsler Steven L. , BenMohamed Lbachir
Published: February 2010

We introduced a novel humanized HLA-A*0201 transgenic (HLA Tg) rabbit model to assess the protective efficacy of a human CD8+ T cell epitope-based vaccine against primary ocular herpes infection and disease. Each of the three immunodominant human CD8+ T cell peptide epitopes from HSV-1 glycoprotein D (gD53–61, gD70–78, and gD278–286) were joined with a promiscuous human CD4+ T cell peptide epitope (gD49–82) to construct three separate pairs of CD4–CD8 peptides. Each CD4–CD8 peptide pair was then covalently linked to an Nε-palmitoyl–lysine residue via a functional base lysine amino group to construct CD4–CD8 lipopeptides. HLA Tg rabbits were immunized s.c. with a mixture of the three CD4–CD8 HSV-1 gD lipopeptides. The HSV-gD–specific T cell responses induced by the mixture of CD4–CD8 lipopeptide vaccine and the protective efficacy against acute virus replication and ocular disease were determined. Immunization induced HSV-gD49–82–specific CD4+ T cells in draining lymph node (DLN); induced HLA-restricted HSV-gD53–61, gD70–78, and gD278–286–specific CD8+ T cells in DLN, conjunctiva, and trigeminal ganglia and reduced HSV-1 replication in tears and corneal eye disease after ocular HSV-1 challenge. In addition, the HSV-1 epitope-specific CD8+ T cells induced in DLNs, conjunctiva, and the trigeminal ganglia were inversely proportional with corneal disease. The humanized HLA Tg rabbits appeared to be a useful preclinical animal model for investigating the immunogenicity and protective efficacy of human CD8+ T cell epitope-based prophylactic vaccines against ocular herpes. The relevance of HLA Tg rabbits for future investigation of human CD4–CD8 epitope-based therapeutic vaccines against recurrent HSV-1 is discussed.
TLR Activation Pathways in HIV-1–Exposed Seronegative Individuals
Authors: Biasin Mara , Piacentini Luca , Lo Caputo Sergio , Naddeo Valentina , Pierotti Piera , Borelli Manuela , Trabattoni Daria , Mazzotta Francesco , Shearer Gene M. , Clerici Mario
Published: February 2010

TLRs trigger innate immunity that recognizes conserved motifs of invading pathogens, resulting in cellular activation and release of inflammatory factors. The influence of TLR activation on resistance to HIV-1 infection has not been investigated in HIV-1 exposed seronegative (ESN) individuals. PBMCs isolated from heterosexually ESN individuals were stimulated with agonists specific for TLR3 (poly I:C), TLR4 (LPS), TLR7 (imiquimod), and TLR7/8 (ssRNA40). We evaluated expression of factors involved in TLR signaling cascades, production of downstream effector immune mediators, and TLR-expression in CD4+ and CD14+ cells. Results were compared with those obtained in healthy controls (HCs). ESN individuals showed: 1) comparable percentages of CD14+/TLR4+ and CD4+/TLR8+ CD14+/TLR8+ cells; 2) higher responsiveness to poly I:C, LPS, imiquimod, and ssRNA40 stimulation, associated with significantly increased production of IL-1β, IL-6, TNF-α, and CCL3; 3) augmented expression of mRNA specific for other targets (CCL2, CSF3, CSF2, IL-1α, IL-8, IL-10, IL-12, cyclooxygenase 2) demonstrated by broader TLRs pathway expression analyses; and 4) increased MyD88/MyD88s(short) ratio, mainly following TLR7/8 stimulation. We also compared TLR–agonist-stimulated cytokine/chemokine production in CD14+ PBMCs and observed decreased IFN-β production in ESN individuals compared with HCs upon TLR7/8-agonist stimulation. These data suggest that TLR stimulation in ESN individuals results in a more robust release of immunologic factors that can influence the induction of stronger adaptive antiviral immune responses and might represent a virus-exposure–induced innate immune protective phenotype against HIV-1.
Dendritic Cell (DC)-Specific Targeting Reveals Stat3 as a Negative Regulator of DC Function
Authors: Melillo Jessica A. , Song Li , Bhagat Govind , Blazquez Ana Belen , Plumlee Courtney R. , Lee Carolyn , Berin Cecilia , Reizis Boris , Schindler Christian
Published: February 2010

Dendritic cells (DCs) must achieve a critical balance between activation and tolerance, a process influenced by cytokines and growth factors. IL-10, which transduces signals through Stat3, has emerged as one important negative regulator of DC activation. To directly examine the role Stat3 plays in regulating DC activity, the Stat3 gene was targeted for deletion with a CD11c-cre transgene. Stat3 CKO mice developed cervical lymphadenopathy as well as a mild ileocolitis that persisted throughout life and was associated with impaired weight gain. Consistent with this, Stat3-deficient DCs demonstrated enhanced immune activity, including increased cytokine production, Ag-dependent T-cell activation and resistance to IL-10–mediated suppression. These results reveal a cell-intrinsic negative regulatory role of Stat3 in DCs and link increased DC activation with perturbed immune homeostasis and chronic mucosal inflammation.
Nod1 and Nod2 Are Expressed in Human and Murine Renal Tubular Epithelial Cells and Participate in Renal Ischemia Reperfusion Injury
Authors: Shigeoka Alana A. , Kambo Amanpreet , Mathison John C. , King Andrew J. , Hall Wesley F. , da Silva Correia Jean , Ulevitch Richard J. , McKay Dianne B.
Published: February 2010

Nucleotide-binding oligomerization domain (Nod) 1 and Nod2 are members of a family of intracellular innate sensors that participate in innate immune responses to pathogens and molecules released during the course of tissue injury, including injury induced by ischemia. Ischemic injury to the kidney is characterized by renal tubular epithelial apoptosis and inflammation. Among the best studied intracellular innate immune receptors known to contribute to apoptosis and inflammation are Nod1 and Nod2. Our study compared and contrasted the effects of renal ischemia in wild-type mice and mice deficient in Nod1, Nod2, Nod(1 × 2), and in their downstream signaling molecule receptor-interacting protein 2. We found that Nod1 and Nod2 were present in renal tubular epithelial cells in both mouse and human kidneys and that the absence of these receptors in mice resulted in protection from kidney ischemia reperfusion injury. Significant protection from kidney injury was seen with a deficiency of Nod2 and receptor-interacting protein 2, and the simultaneous deficiency of Nod1 and Nod2 provided even greater protection. We conclude that the intracellular sensors Nod1 and Nod2 play an important role in the pathogenesis of acute ischemic injury of the kidney, although possibly through different mechanisms.
Sexually dimorphic interaction between the DRD1 and COMT genes in schizophrenia
Authors: Hoenicka Janet , Garrido Elena , Ponce Guillermo , Rodríguez‐Jiménez Roberto , Martínez Isabel , Rubio Gabriel , Jiménez‐Arriero Miguel Ángel , Palomo Tomás
Published: February 2010

Dopaminergic dysfunction in the prefrontal cortex (PFC) is involved in the pathophysiology of schizophrenia. In the PFC, dopamine signalling largely depends on the D1 receptors, which are coded by the DRD1 gene, and on the regulation of dopamine levels by the enzyme catechol‐O‐methyltransferase (COMT). Here, we investigate the role of DRD1 and its interaction with the COMT gene in schizophrenic patients. In two gender‐limited independent patient and control samples, we genotype five Tag single nucleotide polymorphisms (tagSNPs) of DRD1. The DRD1 SNP and haplotype associations, as well as interaction effects with the Val158Met COMT SNP were analyzed. In the male sample, we found the rs11746641 and rs11749676 DRD1 SNPs were associated with schizophrenia. Haplotype analyses identified the T‐A‐T‐C‐T variant related to a protective effect (P = 0.008) and the G‐G‐T‐C‐C variant that showed a tendency to be a risk factor for the disorder (P = 0.012). A logistic regression analysis revealed a significant pattern of interaction between DRD1 and COMT for both the rs11746641 (P = 0.002) and rs11749676 (P = 4.5 × 10−5) SNPs. DRD1‐associated haplotypes were exclusively related to schizophrenia in the Val homozygous subgroup of patients (T‐A‐T‐C‐T: P = 0.003; G‐G‐T‐C‐C: P = 0.006). In females, none of the DRD1 SNPs were linked to the disorder. Our genetic data suggest that DRD1 and COMT are epistatically associated with protection against and the risk of developing schizophrenia in a gender‐dependent fashion, and support the role of dopamine dysfunction at the PFC in the pathophysiology of this disorder. © 2010 Wiley‐Liss, Inc.
Numerical Simulation of Particle Segregation in Bubbling Gas‐Fluidized Beds
Authors: Azizi S. , Hossein Hosseini S. , Ahmadi G. , Moraveji M.
Published: February 2010

A multi‐fluid Eulerian model incorporating the kinetic theory of granular flow is used for the simulation of bubbling fluidized beds containing a binary mixture of Geldart B particles at low gas velocities. The cases of density, size and combined density/size segregation are investigated using computational fluid dynamic simulations. Various expressions for the drag force are evaluated for predicting different segregations. The simulation results show that summation of the particle‐particle drag force, i.e., the “hindrance effect” term, and the Stokes drag of particles, which is modified based on the Wen‐Yu drag model can be used for accurate simulation of a binary mixture of particles differing in size, density, or both. Bed expansion and dimensionless axial segregation profiles of CFD results are compared with the experimental data and good agreement is found.
Rheological Behavior and Structure of a Commercial Esterquat Surfactant Aqueous System
Authors: Calero N. , Alfaro M. C. , Lluch M. Á. , Berjano M. , Muñoz J.
Published: February 2010

Aqueous dispersions of a commercial esterquat‐type surfactant widely used in fabric softeners were rheologically characterized. While at 4 wt % esterquat concentration, a Newtonian response was observed; non‐Newtonian (Sisko) flow behavior and viscoelastic properties were found at 12 wt % and higher concentrations. The onset of nonlinear viscoelasticity in oscillatory shear provided interesting information on the strength of quiescent surfactant aggregates. Mechanical spectra corresponded to the plateau zone and the onset of the transition zone. The plateau modulus and the characteristic slopes of the relaxation spectra depended on the strength of the interactions among the aggregates. Start‐up at the inception of the shear experiments were carried out to obtain information on the time‐dependent shear behavior. Cryo‐SEM micrographs demonstrated the occurrence of a dispersion of vesicles embedded into a bilayer matrix.
Prevention of Contrast‐induced Nephropathy: A Single Center Randomized Study
Authors: Castini Diego , Lucreziotti Stefano , Bosotti Laura , Salerno Uriarte Diego , Sponzilli Carlo , Verzoni Alessandro , Lombardi Federico
Published: February 2010

Background

Contrast‐induced nephropathy (CIN) is the third cause of acute deterioration of renal function in hospitalized patients.

Hypothesis

The purpose of the study was to compare the efficacy of saline infusion, saline infusion plus N‐acetylcysteine (NAC), and sodium bicarbonate (SB) infusion to prevent CIN in patients undergoing coronary angiography and/or percutaneous coronary intervention.

Methods

We prospectively studied 156 patients with a baseline creatinine level ≥ 1.2 mg/dL. The primary endpoint was the development of CIN, defined as an increase in serum creatinine concentration ≥ 25% over the baseline value within 5 days from contrast exposure.

Results

Contrast‐induced nephropathy developed in 23 patients (14.7%). Incidence of the primary endpoint was similar in the 3 groups of treatment, occurring in 7 patients (14%) in the saline infusion group, in 9 (17%) in the saline infusion plus NAC group, and in 7 (14%) in the SB infusion group.

Conclusions

Our findings suggest that neither the addition of NAC nor the administration of SB add further benefit in CIN prevention, compared to standard hydration with isotonic saline infusion. Copyright © 2009 Wiley Periodicals, Inc.
Experienced Clinicians Improve Detection of Third and Fourth Heart Sounds by Viewing Acoustic Cardiography
Authors: Michaels Andrew D. , Khan Farman U. , Moyers Brian
Published: February 2010

Background

Clinical assessment of diastolic heart sounds is challenging.

Hypothesis

We sought to examine whether visual inspection of acoustic cardiographic tracings augments the accuracy of medical students' and physicians' detection of third and fourth heart sounds (S3, S4) compared to auscultation alone.

Methods

A total of 90 adults referred for left heart catheterization underwent digital precordial heart sound recordings by computerized acoustic cardiography. Two blinded, experienced readers using a consensus method determined the presence of the S3/S4 on each file. There were 35 subjects from the following 5 groups participating in this study from 1 teaching institution: first‐year medical students (n = 5), fourth‐year medical students (n = 5), interns (n = 5), medicine residents (n = 5), cardiology fellows (n = 5), and attendings (n = 10). Using a computer module, each subject listened to the heart sounds alone and documented whether an S3/S4 was present. Next, subjects listened to each recording in random order while viewing phonocardiographic tracings, and recorded S3/S4 presence.

Results

An S3 was present in 21 patients (23%) and an S4 in 31 patients (34%) by consensus overread in 90 recordings. Baseline accuracy for auscultation of S3/S4 did not change with level of experience. While viewing the acoustic cardiogram, first‐year medical students had minimal improvement in S3 (2%) and S4 (11%) accuracy. More experienced subjects improved S3 accuracy by 8% to 18% and S4 by 15% to 32% (P < .05). Accuracy was superior for S3 compared to S4 in all ausculatory groups.

Conclusions

While listening to heart sound recordings, viewing acoustic cardiography increased subjects' accuracy in detecting diastolic heart sounds, particularly among more experienced subjects. There was greater improvement for S4 compared to S3 detection. Copyright © 2009 Wiley Periodicals, Inc.
The influence of proteasome inhibitor MG132, external radiation, and unlabeled antibody on the tumor uptake and biodistribution of 188Re‐labeled anti‐E6 C1P5 antibody in cervical cancer in mice
Authors: Phaeton Rébécca , Wang Xing Guo , Einstein Mark H. , Goldberg Gary L. , Casadevall Arturo , Dadachova Ekaterina
Published: February 2010

BACKGROUND:

Human papillomavirus (HPV) infection is considered a necessary step for the development of cervical cancer, and >95% of all cervical cancers have detectable HPV sequences. The authors of this report recently demonstrated the efficacy of radioimmunotherapy (RIT) targeting viral oncoprotein E6 in the treatment of experimental cervical cancer. They hypothesized that the pretreatment of tumor cells with various agents that cause cell death and/or elevation of E6 levels would increase the accumulation of radiolabeled antibodies to E6 in cervical tumors.

METHODS:

HPV type 16 (HPV‐16)‐positive CasKi cells were treated in vitro with up to 6 grays of external radiation, or with the proteasome inhibitor MG‐132, or with unlabeled anti‐E6 antibody C1P5; and cell death was assessed. The biodistribution of 188Re‐labeled C1P5 antibody was determined in both control and radiation MG‐132‐treated CasKi tumor‐bearing nude mice.

RESULTS:

188Re‐C1P5 antibody demonstrated tumor specificity, very low uptake, and fast clearance from the major organs. The amount of tumor uptake was enhanced by MG‐132 but was unaffected by pretreatment with radiation. In addition, in vitro studies demonstrated an unanticipated effect of unlabeled antibody on the amount of cell death, a finding that was suggested by the authors' previous in vivo studies in a CasKi tumor model.

CONCLUSIONS:

The current results indicated that pretreatment of cervical tumors with the proteasome inhibitor MG‐132 and with unlabeled antibody to E6 can serve as a means to generate nonviable cancer cells and to elevate the levels of target oncoproteins in the cells for increasing the accumulation of targeted radiolabeled antibodies in tumors. These results favor the further development of RIT for cervical cancers targeting viral antigens. Cancer 2010;116(4 suppl):1067–74. © 2010 American Cancer Society.
177Lu‐[DOTA0,Tyr3] octreotate therapy in patients with disseminated neuroendocrine tumors: Analysis of dosimetry with impact on future therapeutic strategy
Authors: Garkavij Michael , Nickel Mattias , Sjögreen‐Gleisner Katarina , Ljungberg Michael , Ohlsson Tomas , Wingårdh Karin , Strand Sven‐Erik , Tennvall Jan
Published: February 2010

BACKGROUND:

177Lu‐(DOTA0,Tyr3) octreotate is a new treatment modality for disseminated neuroendocrine tumors. According to a consensus protocol, the calculated maximally tolerated absorbed dose to the kidney should not exceed 27 Gy. In commonly used dosimetry methods, planar imaging is used for determination of the residence time, whereas the kidney mass is determined from a computed tomography (CT) scan.

METHODS:

Three different quantification methods were used to evaluate the absorbed dose to the kidneys. The first method involved common planar activity imaging, and the absorbed dose was calculated using the medical internal radiation dose (MIRD) formalism, using CT scan‐based kidney masses. For this method, 2 region of interest locations for the background correction were investigated. The second method also included single‐photon emission computed tomography (SPECT) data, which were used to scale the amplitude of the time‐activity curve obtained from planar images. The absorbed dose was calculated as in the planar method. The third method used quantitative SPECT images converted to absorbed dose rate images, where the median absorbed dose rate in the kidneys was calculated in a volume of interest defined over the renal cortex.

RESULTS:

For some patients, the results showed a large difference in calculated kidney‐absorbed doses, depending on the dosimetry method. The 2 SPECT‐based methods generally gave consistent values, although the calculations were based on different assumptions. Dosimetry using the baseline planar method gave higher absorbed doses in all patients. The values obtained from planar imaging with a background region of interest placed adjacent to the kidneys were more consistent with dosimetry also including SPECT. For the accumulated tumor absorbed dose, the first 2 of the 4 planned therapy cycles made the major contribution.

CONCLUSIONS:

The results suggested that patients evaluated according to the conventional planar‐based dosimetry method may have been undertreated compared with the other methods. Hematology and creatinine did not indicate any restriction for a more aggressive approach, which would be especially useful in patients with more aggressive tumors where there is not time for more protracted therapy. Cancer 2010;116(4 suppl):1084–92. © 2010 American Cancer Society.
Three methods assessing red marrow dosimetry in lymphoma patients treated with radioimmunotherapy
Authors: Ferrer Ludovic , Kraeber‐Bodéré Françoise , Bodet‐Milin Caroline , Rousseau Caroline , Gouill Stephen Le , Wegener William A. , Goldenberg David M. , Bardiès Manuel
Published: February 2010

BACKGROUND:

Maximum injected activity in radioimmunotherapy (RIT) is limited by bone marrow toxicity. Many dosimetric approaches have been proposed, leading to high variability in the results and elusive absorbed dose‐effect relations. This study presents the results of red marrow (RM) absorbed dose estimates performed with 3 methods.

METHODS:

Five patients received 2 co‐infusions of 90Y‐labeled (370 MBq/m2) and 111In‐ labeled (120 MBq) epratuzumab (1.5 mg/kg) 1 week apart. RM‐absorbed dose was estimated by 3 methodologies. The first approach (M1) used L2‐L4 lumbar vertebrae imaging. M2 and M3 methods used different red marrow to blood ratios (RMBLR) to assess RM‐absorbed dose. RMBLR was set to a fixed value of 0.36 in M2 or assessed according to each patient's hematocrit in M3.

RESULTS:

Median RM‐absorbed doses were 4.1 (2.9‐8.4), 2.3 (2.0‐2.7), and 2.3 (1.6‐2.5) mGy/MBq for M1, M2, and M3, respectively. No trend could be found between total RM‐absorbed dose and toxicity for M2 and M3. Conversely, M1 seemed to provide the best absorbed dose‐effect relation. The 4 patients with the highest RM‐absorbed doses exhibited grade 4 toxicity. The fifth patient, with the lowest RB absorbed dose, exhibited only a mild (grade 2) toxicity.

CONCLUSIONS:

Image‐based methodology (M1) seems to better predict hematological toxicity as compared with blood‐based methods. Only this method provides for bone marrow involvement. Cancer 2010;116(4 suppl):1093–100. © 2010 American Cancer Society.
Improving the treatment of non‐Hodgkin lymphoma with antibody‐targeted radionuclides
Authors: Sharkey Robert M. , Karacay Habibe , Goldenberg David M.
Published: February 2010

Radioimmunotherapy of non‐Hodgkin lymphoma comprises a 90Y‐ or 131I‐labeled murine anti‐CD20 IgG, but both agents also include a substantial dose of unlabeled anti‐CD20 IgG given immediately before the radioconjugate to reduce its uptake in the spleen (primary normal B‐cell antigen sink); this extends its plasma half‐life and improves tumor visualization. Thus, these treatments combine an effective anti‐CD20 radioconjugate with an unconjugated anti‐CD20 antibody that is also therapeutically active, but the large anti‐CD20 IgG predose (∼900 mg) may diminish the tumor localization of the radioimmunoconjugate (eg, 10‐35 mg). We have examined alternative approaches that enhance radionuclide targeting and improve antitumor responses. One uses a 90Y‐labeled anti‐CD22 IgG (epratuzumab) combined with an antibody therapy regimen of a humanized anti‐CD20 IgG (veltuzumab). Pretargeted radionuclide therapy using a trivalent, humanized, recombinant bispecific anti‐CD20 antibody with a 90Y‐hapten‐peptide is another highly effective method that is also less toxic than directly radiolabeled IgG. Finally, all approaches benefit from the addition of a consolidation‐dosing regimen of the anti‐CD20 IgG antibody. This article reviews these various options and discusses how some fundamental changes could potentially enhance the response and duration from radionuclide‐targeted therapy Cancer 2010;116(4 suppl):1134–45. © 2010 American Cancer Society.
Singlet Energy Dissipation in the Photosystem II Light‐Harvesting Complex Does Not Involve Energy Transfer to Carotenoids
Authors: Müller Marc G. , Lambrev Petar , Reus Michael , Wientjes Emilie , Croce Roberta , Holzwarth Alfred R.
Published: February 2010

The energy dissipation mechanism in oligomers of the major light‐harvesting complex II (LHC II) from Arabidopsis thaliana mutants npq1 and npq2, zeaxanthin‐deficient and zeaxanthin‐enriched, respectively, has been studied by femtosecond transient absorption. The kinetics obtained at different excitation intensities are compared and the implications of singlet–singlet annihilation are discussed. Under conditions where annihilation is absent, the two types of LHC II oligomers show distributive biexponential (bimodal) kinetics with lifetimes of ≈5–20 ps and ≈200–400 ps having transient spectra typical for chlorophyll excited states. The data can be described kinetically by a two‐state compartment model involving only chlorophyll excited states. Evidence is provided that neither carotenoid excited nor carotenoid radical states are involved in the quenching mechanism at variance with earlier proposals. We propose instead that a chlorophyll–chlorophyll charge‐transfer state is formed in LHC II oligomers which is an intermediate in the quenching process. The relevance to non‐photochemical quenching in vivo is discussed.