bluuebunny/crossref_metadata_2025 huggingface dataset:
Carotid artery revascularization in high surgical risk patients with the NexStent and the Filterwire EX/EZ
Authors: Hopkins L. Nelson , Myla Subbarao , Grube Eberhard , Wehman J. Christopher , Levy Elad I. , Bersin Robert M. , Joye James D. , Allocco Dominic J. , Kelley Lynne , Baim Donald S.
Published: April 2008

Objective:

The multicenter, single‐arm CABERNET trial evaluated outcomes in high‐surgical‐risk patients with carotid artery stenosis treated with the NexStent® plus FilterWire EX®/EZ™ Emboli Protection System.

Background:

For patients at high surgical risk, carotid artery stenting (CAS) offers a less invasive alternative to carotid endarterectomy (CEA).

Methods:

The trial enrolled 454 high‐surgical‐risk patients with carotid stenosis by angiography ≥50% for symptomatic patients and ≥60% for asymptomatic patients. The comparator primary endpoint was the 1‐year major adverse event (MAE, defined as any death, stroke, or myocardial infarction [MI]) rate. It was compared with a proportionally weighted objective performance criterion (OPC) of 12.1% representative of published CEA results in similar patients plus a prespecified noninferiority margin (delta) of 4%. A second primary endpoint was the composite rate of 30‐day MAE plus late (31–365 days) ipsilateral stroke.

Results:

Symptoms of carotid stenosis were present in 24.2% of patients; 36.6% of patients were considered high‐surgical‐risk due to comorbid risk factors and 63.4% due to anatomic risk factors. The rate of 30‐day MAE plus late ipsilateral stroke was 4.7% (20/438). The comparator primary endpoint of 1‐year MAE was 11.6% (51/438) and was noninferior to the OPC of 12.1% (95% upper confidence interval of 14.5% versus OPC plus delta of 16.1%, P = 0.005). Late ipsilateral stroke was 0.7% and target vessel revascularization at 1 year was 2.4%.

Conclusions:

The CABERNET trial demonstrates that CAS with NexStent and FilterWire is noninferior to (equivalent or better than) traditional CEA at 1 year in high‐surgical‐risk patients based on historical controls. © 2008 Wiley‐Liss, Inc.
Dynamic compartmentalization of protein tyrosine phosphatase receptor Q at the proximal end of stereocilia: Implication of myosin VI‐based transport
Authors: Sakaguchi Hirofumi , Tokita Joshua , Naoz Moshe , Bowen‐Pope Daniel , Gov Nir S. , Kachar Bechara
Published: April 2008

Hair cell stereocilia are apical membrane protrusions filled with uniformly polarized actin filament bundles. Protein tyrosine phosphatase receptor Q (PTPRQ), a membrane protein with extracellular fibronectin repeats has been shown to localize at the stereocilia base and the apical hair cell surface, and to be essential for stereocilia integrity. We analyzed the distribution of PTPRQ and a possible mechanism for its compartmentalization. Using immunofluorescence we demonstrate that PTPRQ is compartmentalized at the stereocilia base with a decaying gradient from base to apex. This distribution can be explained by a model of transport directed toward the stereocilia base, which counteracts diffusion of the molecules. By mathematical analysis, we show that this counter transport is consistent with the minus end‐directed movement of myosin VI along the stereocilia actin filaments. Myosin VI is localized at the stereocilia base, and exogenously expressed myosin VI and PTPRQ colocalize in the perinuclear endosomes in COS‐7 cells. In myosin VI‐deficient mice, PTPRQ is distributed along the entire stereocilia. PTPRQ‐deficient mice show a pattern of stereocilia disruption that is similar to that reported in myosin VI‐deficient mice, where the predominant features are loss of tapered base, and fusion of adjacent stereocilia. Thin section and freeze‐etching electron microscopy showed that localization of PTPRQ coincides with the presence of a dense cell surface coat. Our results suggest that PTPRQ and myosin VI form a complex that dynamically maintains the organization of the cell surface coat at the stereocilia base and helps maintain the structure of the overall stereocilia bundle. Cell Motil. Cytoskeleton 2008. Published 2008 Wiley‐Liss, Inc.
The changing epidemiology of invasive candidiasis
Authors: Hachem Ray , Hanna Hend , Kontoyiannis Dimitrios , Jiang Ying , Raad Issam
Published: April 2008

BACKGROUND.

The objective of the current retrospective study was to compare the epidemiology of candidemia and its risk factors in patients who had hematologic malignancies(HM) with those in patients who had solid tumors (ST).

METHODS.

The medical and electronic records of all patients with cancer who had candidemia at the authors' institution from 1993 to 2003 were reviewed for demographic data and clinical information, including the use of prophylactic fluconazole, the infecting Candida species, and the source of candidemia (catheter‐related vs other apparent sources).

RESULTS.

Six hundred thirty‐five patients with candidemia were analyzed. C. glabrata and C. krusei were the leading causes of candidemia in 31% and 24% of patients with HM, respectively, and in 18% and 2% of patients with ST, respectively (P < .001). A catheter was the source of candidemia in 36% of the patients with ST and in 12% of the patients with HM (P < .001). Response to antifungal therapy occurred in 73% of the ST group compared with 49% of the HM group (P < .001). Multivariate logistic regression analysis revealed that fluconazole prophylaxis was a risk factor for both C. glabrata and C. krusei candidemia. The analysis also identified neutropenia as a risk factor for all candidemia and catheter‐related infection as a risk factor for C. parapsilosis candidemia.

CONCLUSIONS.

The results of this study indicated that C. glabrata and C. krusei were the leading causes of candidemia in patients with HM. Neutropenia was the leading risk factor for all candidemia, whereas the catheter was the leading risk factor for C. parapsilosis candidemia. Cancer 2008. © 2008 American Cancer Society.
Gemcitabine plus oxaliplatin (GEMOX) combined with cetuximab in patients with progressive advanced stage hepatocellular carcinoma
Authors: Asnacios Amani , Fartoux Laetitia , Romano Olivier , Tesmoingt Chloe , Louafi S Samy , Mansoubakht Touraj , Artru Pascal , Poynard Thierry , Rosmorduc Olivier , Hebbar Mohamed , Taieb Julien
Published: April 2008

BACKGROUND.

The authors conducted a phase 2 trial of the antiepidermal growth factor receptor (EGFR) monoclonal antibody cetuximab in combination with the gemcitabine plus oxaliplatin (GEMOX) regimen in patients with documented progressive hepatocellular carcinoma (HCC).

METHODS.

Forty‐five untreated patients with advanced‐stage progressive HCC were prospectively enrolled. Treatment consisted of cetuximab at a dose of 400 mg/m2 initially then 250 mg/m2 weekly, plus gemcitabine at a dose of 1000 mg/m2 on Day 1 and oxaliplatin at a dose of 100 mg/m2 on Day 2, every 2 weeks. Treatment was continued until disease progression, unacceptable toxicity, or patient refusal.

RESULTS.

Overall, 306 cycles were administered. Grade 3 to 4 hematologic toxicity consisted of thrombocytopenia (24%), neutropenia (20%), and anemia (4%). Grade 3 oxaliplatin‐induced neurotoxicity occurred in 5 patients (11%) and grade 3 cutaneous toxicity in 7 patients (16%). There were no treatment‐related deaths. The confirmed response rate was 20% and disease stabilization was obtained in 40% of patients. The median progression‐free and overall survival times were 4.7 months and 9.5 months, respectively. The 1‐year survival rate was 40%.

CONCLUSIONS.

In poor‐prognosis patients with progressive advanced‐stage HCC, the GEMOX‐cetuximab combination appears to be active and to have manageable toxicity. A comparative randomized trial is now being planned. Cancer 2008. © 2008 American Cancer Society.
Microporous Niobia–Silica Membrane with Very Low CO2 Permeability
Authors: Boffa Vittorio , ten Elshof Johan E. , Petukhov Andrei V. , Blank Dave H. A.
Published: April 2008

A sol–gel‐derived microporous ceramic membrane with an exceptionally low permeability for CO2 from gaseous streams was developed and characterized. The sols were prepared from a mixture of niobium and silicon alkoxide precursors by acid‐catalyzed synthesis. Microporous films were formed by coating asymmetric γ‐alumina disks with the polymeric sol (Si/Nb=3:1), followed by calcination at 500 °C. The membrane consists of a 150‐nm‐thick layer with a Si/Nb atomic ratio of about 1.5. The single‐gas permeance of small gas molecules such as H2, CH4, N2, and SF6 decreases steadily with kinetic diameter. Hydrogen, helium, and carbon dioxide follow an activated transport mechanism through the membrane. The permeance of CO2 in this membrane is much lower than that in pure silica, and its behavior deviates strongly from the general trend observed with the other gases. This is attributed to a relatively strong interaction between CO2 and adsorption sites in the niobia–silica membrane.
Interferon‐γ limits Th1 lymphocyte adhesion to inflamed endothelium: A nitric oxide regulatory feedback mechanism
Authors: Norman M. Ursula , Zbytnuik Lori , Kubes Paul
Published: April 2008

CD4+ T helper (Th1 and Th2) cell localization to a site of inflammation is important for the development, maintenance and regulation of an immune response. The factors that regulate Th1 and Th2 cell recruitment into tissue are not fully understood. The aim of the present study was to examine the effect of different cytokine microenvironments on the recruitment of Th1 and Th2 lymphocytes into tissue. Fluorescently labelled Th1 or Th2 lymphocyte‐endothelial interactions were observed via intravital microscopy of the cytokine‐treated cremaster muscle. Our results show that TNF‐α alone is sufficient to maximally recruit Th1 cells. Surprisingly, treatment with TNF‐α + IFN‐γ significantly decreased Th1 adhesion and emigration in comparison to TNF‐α treatment alone. The decreased adhesion of Th1 cells in response to TNF‐α + IFN‐γ reflected a decreased ability to bind to ICAM‐1 and was iNOS‐dependent. This phenomenon was not observed with Th2 cells. These results suggest that IFN‐γ may play a key immunomodulatory role in the recruitment of different T lymphocyte subsets. Indeed, blockade of IFN‐γ or iNOS function during the Th1‐mediated contact hypersensitivity response resulted in an acceleration and exacerbation of the late‐phase inflammatory response.
Intercellular MHC transfer between thymic epithelial and dendritic cells
Authors: Millet Virginie , Naquet Philippe , Guinamard Rodolphe R.
Published: April 2008

Thymic dendritic cells (DC) and epithelial cells play a major role in central tolerance but their respective roles are still controversial. Epithelial cells have the unique ability to ectopically express peripheral tissue‐restricted antigens conferring self‐tolerance to tissues. Paradoxically, while negative selection seems to occur for some of these antigens, epithelial cells, contrary to DC, are poor negative selectors. Using a thymic epithelial cell line, we show the functional intercellular transfer of membrane material, including MHC molecules, occurring between epithelial cells. Using somatic and bone marrow chimeras, we show that this transfer occurs efficiently in vivo between epithelial cells and, in a polarized fashion, from epithelial to DC. This novel mode of transfer of MHC‐associated, epithelial cell‐derived self‐antigens onto DC might participate to the process of negative selection in the thymic medulla.
C‐reactive protein specifically binds to Fcγ receptor type I on a macrophage‐like cell line
Authors: Tron Kyrylo , Manolov Dimitar E. , Röcker Carlheinz , Kächele Martin , Torzewski Jan , Nienhaus G. Ulrich
Published: April 2008

C‐reactive protein (CRP) is a prototype acute‐phase protein that may be intimately involved in human disease. Its cellular receptors are still under debate; the main candidates are FcR for immunoglobulin G, as CRP was shown to bind specifically to FcγRI and FcγRIIa. Using ultrasensitive confocal live‐cell imaging, we have studied CRP binding to FcγR naturally expressed in the plasma membranes of cells from a human leukemia cell line (Mono Mac 6). These macrophage‐like cells express high levels of FcγRI and FcγRII. They were shown to bind fluorescently labeled CRP with micromolar affinity, KD = (6.6 ± 1.5) µM. CRP binding could be inhibited by pre‐incubation with human but not mouse IgG and was thus FcγR‐specific. Blocking of FcγRI by an FcγRI‐specific antibody abolished CRP binding essentially completely, whereas application of antibodies against FcγRII did not have a noticeable effect. In fluorescence images of Mono Mac 6 cells, the intensity patterns of bound CRP were correlated with those of FcγRI, but not FcγRII. These results provide clear evidence of specific interactions between CRP and FcγR (predominantly FcγRI) naturally expressed on macrophage‐like cells.
A Neutral DNA Sequence‐Selective Vector for Interaction Studies: Fluorescence Binding Experiments Directed Towards a Carbohydrate‐DNA Carrier
Authors: Peñalver Pablo , Abdelouahid Samadi , Bosch Paula , Hunter Christopher A. , Vicent Cristina
Published: April 2008

The distamycin‐type γ‐linked covalent dimer ‐Py‐γ‐Py‐Ind has been shown to be a neutral selective vector capable of transporting recognition elements to the minor groove of DNA for further structural studies. Comparison of fluorescence binding constants of the complexes formed by the vectors (R‐Py‐γ‐Py‐Ind 1 and 3) with ct‐DNA and poly(dA‐dT) showed that ‐Py‐γ‐Py‐Ind is a neutral (–ATAT–)‐selective vector. We also provide experimental data that show that the vector can be used as a sugar‐carrier to the DNA. Thus, modifying the vector at the C terminus with sugars of different configurations (4–7 D vs. 8 L), and with both α‐ and β‐linkages (5 and 4, respectively) to the oligoamide fragment provides efficient DNA binders (Ka = 1.1 × 104 to 3.2 × 105 M–1). Moreover, the sugar residue is able to modulate the binding to the different DNA polymers studied and, even more relevantly, the sugar contributes to the selectivity of binding: β‐D‐Gal‐Py‐γ‐Py‐Ind (6) is the most selective –ATAT–sugar–oligoamide ligand {ΔΔG° 6 [poly(dA‐dT) – ct‐DNA] = –4.0 kcal mol–1}. We have used fluorescence quantum yield values to ensure the presence of similar free state conformation for ligands 1–8 and we can thus correlate the differences in the measured binding energies with the changes in the shape of the structural elements. Finally, we have demonstrated that the sequence‐selective sugar carrier makes a 1:1 complex with the Drew–Dickerson oligonucleotide dodecamer, thus opening the road to more detailed structural and thermodynamic studies of sugar‐oligoamide DNA short oligonucleotide complexes in solution. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
The First Proline‐Catalyzed Friedlander Annulation: Regioselective Synthesis of 2‐Substituted Quinoline Derivatives
Authors: Jiang Biao , Dong Jia‐jia , Jin Yun , Du Xiao‐long , Xu Min
Published: April 2008

The first proline‐catalyzed Friedlander annulation for the synthesis of 2‐substituted 4‐trifluoromethyl quinoline derivatives is described. Excellent regioselectivity as well as good yields were shown in a variety of cases, and a tandem aldol‐cyclization pathway might be involved. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Enamine Catalysis in the Synthesis of Chiral Structural Analogues of gem‐Bisphosphonates Known To Be Biologically Active
Authors: Barros Maria Teresa , Faísca Phillips Ana Maria
Published: April 2008

The synthesis of chiral γ‐keto bisphosphonates is described. Michael addition of cyclic ketones to vinyl gem‐bisphosphonate catalyzed by 0.1 mol equiv. (S)‐(+)‐1‐(2‐pyrrolidinyl)pyrrolidine and benzoic acid gave the products in yields of up to 86 %, dr (cis/trans) > 1:99 and ee of up to 99 %. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Platinum Nanoparticles Decorated Multiwalled Carbon Nanotubes – Ionic Liquid Composite Film Coated Glassy Carbon Electrodes for Sensitive Determination of Theophylline
Authors: Liu Liqin , Xiao Fei , Li Jiangwen , Wu Weibing , Zhao Faqiong , Zeng Baizhao
Published: April 2008

Platinum nanoparticles (Ptnano) decorated multiwalled carbon nanotubes (MWCNTs)–1‐octyl‐3‐methylimidazolium hexafluorophosphate ([omim][PF6]) composite material (MWCNTs‐Ptnano‐[omim][PF6]) was fabricated and characterized for the first time. In the presence of [omim][PF6], more Ptnano could deposit on MWCNTs. The average diameter of the deposited Ptnano was about 5 nm. The composite material film coated glassy carbon electrode (GCE) exhibited sensitive voltammetric response to theophylline (TP). Under the optimized conditions (i.e., preconcentration for 2 minutes on open circuit in 0.10 M pH 3.0 phosphate buffer), the anodic peak current of TP at about 1.1 V (vs. SCE) was linear to TP concentration over the range of 1.0×10−8–1.0×10−5 M. The detection limit was estimated to be 8.0×10−9 M. The modified electrode was successfully applied to the determination of TP in medicine tablet and green tea. In addition, the voltammetric responses of hypoxanthine (HX), xanthine (Xan) and uric acid (UA) on the MWCNTs‐Ptnano‐[omim][PF6]/GCE were also discussed.
Inelastic response spectrum: Early history
Authors: Riddell Rafael
Published: April 2008

Detailing the time period from, roughly, 1950 through 1980, this Historical Note documents the development of the initial concept of the inelastic response spectrum and how it evolved to become the basis for rational procedures for earthquake‐resistant design, which are used even today. Copyright © 2008 John Wiley & Sons, Ltd.
Specific targeting of hepatitis C virus core protein by an intracellular single-chain antibody of human origin
Authors: Karthe Juliane , Tessmann Kathi , Li Jisu , Machida Raiki , Daleman Maaike , Häussinger Dieter , Heintges Tobias
Published: April 2008

The hepatitis C virus (HCV) core protein is essential for viral genome encapsidation and plays an important role in steatosis, immune evasion, and hepatocellular carcinoma. It may thus represent a promising therapeutic target to interfere with the HCV life-cycle and related pathogenesis. In this study, we used phage display to generate single-chain variable domain antibody fragments (scFv) to the core protein from bone marrow plasma cells of patients with chronic hepatitis C. An antibody with high-affinity binding (scFv42C) was thus identified, and the binding site was mapped to the PLXG motif (residues 84-87) of the core protein conserved among different genotypes. Whereas scFv42C displayed diffuse cytoplasmic fluorescence when expressed alone in the Huh7 human hepatoma cell line, cotransfection with the core gene shifted its subcellular distribution into that of core protein. The intracellular association of scFv42C with its target core protein was independently demonstrated by the fluorescence resonance energy transfer technique. Interestingly, expression of the single-chain antibody reduced core protein levels intracellularly, particularly in the context of full HCV replication. Moreover, cell proliferation as induced by the core protein could be reversed by scFv4C coexpression. Therefore, scFv42C may represent a novel anti-HCV agent, which acts by sequestering core protein and attenuating core protein–mediated pathogenesis. (Hepatology 2008.)
Cancer and mortality among users and nonusers of snus
Authors: Roosaar Ann , Johansson Anna L.V. , Sandborgh‐Englund Gunilla , Axéll Tony , Nyrén Olof
Published: April 2008

Scandinavian moist snuff (snus) is claimed to be a safer alternative to smoking. We aimed to quantify cancer incidence among male snus users and to shed light on the net health outcome by studying their overall mortality. A cohort, comprised of 9,976 men who participated in a population‐based survey, was compiled in 1973–74. Follow‐up until January 31, 2002, was accomplished through record‐linkages with nation‐wide and essentially complete registers of demographics, cancer and causes of deaths. Adjusted relative risks among exposed relative to unexposed men were estimated using Cox proportional hazards regression. The cohort members contributed more than 220,000 person‐years at risk for cancer. A statistically significant increase in the incidence of the combined category of oral and pharyngeal cancer among daily users of snus (incidence rate ratio 3.1, 95% confidence interval 1.5–6.6) was found. Overall mortality was also slightly increased (hazard ratio 1.10, 95% confidence interval 1.01–1.21). Although the combined previous literature on snus and oral cancer weigh toward no association, this population‐based prospective study provided suggestive evidence of snus‐related risks that cannot be lightly ignored. © 2008 Wiley‐Liss, Inc.
Instability of self‐assembled monolayers as a model material system for macrophage/FBGC cellular behavior
Authors: Jones Jacqueline A. , Qin L. Abby , Meyerson Howard , Kwon Il Keun , Matsuda Takehisa , Anderson James M.
Published: April 2008

Novel self‐assembled monolayers (SAMs) designed to present homogenous surface chemistries were utilized to further investigate the material surface chemistry dependent macrophage and foreign‐body giant cell (FBGC) behaviors, including macrophage adhesion, fusion, and apoptosis. Contact angle analysis revealed instabilities in the CH3 and COOH terminated SAM surfaces upon incubation in serum‐free media (SFM) at 37°C or under dry, room temperature conditions. Further analysis indicated that the CH3 terminated SAM surface degraded rapidly within 2 h and loss of sufficient SAM units to be comparable to the gold (Au) control surface, within 24 h of incubation in SFM at 37°C. After 5 days of incubation in SFM at 37°C, the contact angles for the COOH terminated SAM surfaces increased markedly. AFM analysis confirmed the desorption of CH3 terminated SAM molecules from the surface with increased roughness and marked appearance of peaks and valleys within 2 h. A decrease in the thickness of the COOH terminated SAM surface also suggests molecular desorption over time. No significant changes in contact angle or AFM analyses were observed on the OH terminated SAM surfaces. Cellular adhesion decreased more rapidly on the Au control and CH3 terminated SAM surfaces in comparison to the other surfaces. However by day 10, cellular adhesion, fusion, and apoptosis were comparable on all SAM surfaces and the Au control. These studies suggest that SAM surfaces may not be suitable for long‐term studies where material dependent properties are investigated. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Fibroblast growth factor‐2 regulates expression of osteopontin in periodontal ligament cells
Authors: Terashima Yoshimitsu , Shimabukuro Yoshio , Terashima Hiroaki , Ozasa Masao , Terakura Mami , Ikezawa Kazuhiko , Hashikawa Tomoko , Takedachi Masahide , Oohara Hiroyuki , Yamada Satoru , Murakami Shinya
Published: April 2008

Osteopontin is a protein found in the bone‐related matrix and plays multiple regulatory roles in mineralizing and non‐mineralizing tissue. In osteogenic cell‐lines, the expression of osteopontin increases with the progression of differentiation, but both the expression and function of osteopontin vary with the cell type and its activation state. In this study, we examined the expression of osteopontin by clones established from mouse periodontal ligament, in response to inorganic phosphate and fibroblast growth factor (FGF)‐2, which can induce periodontal tissue regeneration. The involvement of inorganic phosphate in the expression of osteopontin during the course of cell differentiation of a clone MPDL22 was confirmed by addition of foscarnet, an inorganic phosphate transport inhibitor. Although FGF‐2 decreased the mRNA expression of almost every bone‐related protein in MPDL22, FGF‐2 upregulated the expression of osteopontin in MPDL22 at both mRNA and protein levels. Interestingly, FGF‐2 enhanced the concentration of osteopontin in the culture supernatant of MPDL22, whereas inorganic phosphate did not. The FGF‐2‐induced osteopontin in the culture supernatant seems to be involved in cell survival activity. An immunohistochemical study showed that the FGF‐2‐induced osteopontin was mainly present in perinuclear matrices while the inorganic phosphate‐induced osteopontin was associated with extracellular matrices in addition to perinuclear matrices. The present results indicated that FGF‐2 induces unique expression of osteopontin, which may play a role different from the other bone‐related proteins during the process of periodontal tissue regeneration by FGF‐2. J. Cell. Physiol. 216: 640–650, 2008, © 2008 Wiley‐Liss, Inc.
The role of p38 MAPK and JNK in Arsenic trioxide‐induced mitochondrial cell death in human cervical cancer cells
Authors: Kang Young‐Hee , Lee Su‐Jae
Published: April 2008

Previously, we have shown that the release of AIF from mitochondria is required for As2O3‐induced cell death in human cervical cancer cells, and that reactive oxygen species (ROS) is necessary for AIF release from mitochondria. In this study, we further investigated the role of MAPKs in ROS‐mediated mitochondrial apoptotic cell death triggered by As2O3. As2O3‐induced apoptotic cell death in HeLa cells was associated with activation and mitochondrial translocation of Bax, a marked phosphorylation of Bcl‐2, reduction of Bcl‐2 and Bax interaction, dissipation of mitochondrial membrane potential. Using small interfering RNA, reduced Bax expression effectively attenuated As2O3‐induced mitochondrial membrane potential loss and apoptotic cell death. Moreover, the phosphorylation of Bcl‐2 induced by As2O3 diminished its ability to bind to Bax. Treatment of cells with As2O3 activated both the p38 MAPK and JNK pathways. Mitochondrial translocation of Bax was completely suppressed in the presence of p38 MAPK inhibitor PD169316 or si‐p38 MAPK. The As2O3‐induced Bcl‐2 phosphorylation was attenuated largely by JNK inhibition using SP600125 or si‐JNK and to some extent by p38 MAPK inhibition with PD169316 or si‐p38 MAPK. In addition, N‐acetyl‐L‐cystein (NAC), a thiol‐containing anti‐oxidant, completely blocked As2O3‐induced p38 MAPK and JNK activations, mitochondria translocation of Bax, and phosphorylation of Bcl‐2. These results support a notion that ROS‐mediated activations of p38 MAPK and JNK in response to As2O3 treatment signals activation of Bax and phosphorylation of Bcl‐2, resulting in mitochondrial apoptotic cell death in human cervical cancer cells. J. Cell. Physiol. 217: 23–33, 2008. © 2008 Wiley‐Liss, Inc.
Sonographic findings of uterine rupture with expulsion of the fetus into broad ligament
Authors: Attarde Vinod Yadav , Patil Parag , Chaudhari Ritu , Zope Narendra , Apte Abhang
Published: April 2008

We report the sonographic findings of a rare case of uterine rupture with extrusion of the fetus into the broad ligament during a second‐trimester abortion. Sonography revealed the empty uterus with an indistinct defect on the side wall and the dead fetus lying outside, surrounded by a thin membrane. At surgery, the uterine rupture was confirmed with the fetus lying in the broad ligament. This study shows the importance of timely sonography in second‐trimester abortion, enabling immediate management and preventing further complications. © 2008 Wiley Periodicals, Inc. J Clin Ultrasound, 2009
Evaluation of reanalysis rainfall estimates over Ethiopia
Authors: Diro G. T. , Grimes D. I. F. , Black E. , O'Neill A. , Pardo‐Iguzquiza E.
Published: April 2008

There is a pressing need for good rainfall data for the African continent both for humanitarian and climatological purposes. Given the sparseness of ground‐based observations, one source of rainfall information is Numerical Weather Prediction (NWP) model outputs. The aim of this article is to investigate the quality of two NWP products using Ethiopia as a test case. The two products evaluated are the ERA‐40 and NCEP reanalysis rainfall products. Spatial, seasonal and interannual variability of rainfall have been evaluated for Kiremt (JJAS) and Belg (FMAM) seasons at a spatial scale that reflects the local variability of the rainfall climate using a method which makes optimum use of sparse gauge validation data.

We found that the spatial pattern of the rainfall climatology is captured well by both models especially for the main rainy season Kiremt. However, both models tend to overestimate the mean rainfall in the northwest, west and central regions but underestimate in the south and east. The overestimation is greater for NCEP in Belg season and greater for ERA‐40 in Kiremt Season. ERA‐40 captures the annual cycle over most of the country better than NCEP, but strongly exaggerates the Kiremt peak in the northwest and west. The overestimation in Kiremt appears to have been reduced since the assimilation of satellite data increased around 1990. For both models the interannual variability is less well captured than the spatial and seasonal variability. Copyright © 2008 Royal Meteorological Society
Indian summer monsoon simulation studies with different orographic representations in a spectral GCM
Authors: Mohandas Saji , Dash S. K. , Mohanty P. K.
Published: April 2008

The current study focuses on two aspects of the representation of orography in a spectral general circulation model (GCM). The most important issue is the reduction of the ripple effect, especially the oceanic surface deformations, which can create tendency for unrealistic oceanic rainfall patches in the model climate. In this study, seven types of digital filters were tried at horizontal resolution equivalent to spectral truncation at T80 to identify the most effective filter. Digital filtering results in much greater reduction in orographic barrier, and hence, the blocking effect compared to mean orography. The second point is retention of the barrier effect. In the past, several attempts have been made to address this. Techniques have been developed in the past to construct an optimal orography, to enable more region‐specific enhancement of mountains with less impact over oceans and plains. These techniques include site‐specific kernels and the cost‐function‐minimization. An attempt has been made in the current study to develop a digitally filtered, locally enhanced, optimal orography called the Filtered‐Modified Orography (FMO), for its application to Indian summer monsoon simulation. A number of sensitivity experiments have been conducted to determine the possible impacts of FMO on the seasonal simulation and the medium‐range prediction of Indian summer monsoon. Results of this study show that two‐dimensional (2‐D) Lanczos filter is the most effective in reducing the ripples and the associated errors in the orographic representation. FMO is able to enhance the peaks of the Himalayan range and Western Ghats, and in consequence, it produces a better simulation of Indian summer monsoon circulation features and the associated rainfall in the seasonal and medium time scale. This procedure for local enhancement is found to be more beneficial than global enhancement of orography in a spectral GCM so far as the regional weather prediction is concerned. Copyright © 2008 Royal Meteorological Society
Photodynamic treatment as a novel approach in the therapy of arthritic joints
Authors: Hansch Andreas , Frey Oliver , Gajda Mieczyslaw , Susanna Graefe , Boettcher Joachim , Bräuer Rolf , Kaiser Werner A.
Published: April 2008

Background and Objective

Minimal invasive local treatment of joints is a desirable option in the therapy of rheumatoid arthritis (RA). Aim of this study was to evaluate the effects of photodynamic treatment (PDT) with different doses of the photosensitizer meta‐tetra(hydroxyphenyl)chlorin (m‐THPC; or temoporfin) in a murine model of RA (antigen‐induced arthritis, AIA).

Methods In vivo distribution

The distribution of native and liposomal m‐THPC (including a formulation with polyethylene glycol [PEG] coating) was assessed by fluorescence spectrometry in arthritic joints, normal joints, and skin.

Treatment

AIA mice received different concentrations of pegylated liposomal m‐THPC (0.1, 0.05, 0.01, or 0.005 mg/kg body weight; n = 5 per group) and subjected to PDT with a laser system 12 hours post‐injection of the photosensitizer. Treatment effects were evaluated histologically in comparison to untreated AIA (n = 5).

Results

Pegylated liposomal m‐THPC showed the most favorable accumulation in arthritic joints compared to native m‐THPC and to non‐peg‐liposomal m‐THPC, therefore it was selected as photosensitizer for PDT treatment. In comparison to untreated AIA, PDT reduced the arthritic score with all doses of pegylated liposomal m‐THPC; statistical significant effects were obtained with doses of 0.05 and 0.01 mg/kg.

Conclusion

Our study demonstrated that local PDT of arthritic joints is feasible. Application of pegylated liposomal m‐THPC for PDT resulted in significant reduction of arthritis scores. Lasers Surg. Med. 40:265–272, 2008. © 2008 Wiley‐Liss, Inc.
Rosacea treatment using the new‐generation, high‐energy, 595 nm, long pulse‐duration pulsed‐dye laser
Authors: Bernstein Eric F. , Kligman Albert
Published: April 2008

Background and Objectives

Rosacea results from sun‐induced hyper‐vascularity of exposed facial skin, often accompanied by acneiform papules and pustules. The pulsed‐dye laser has an unparalleled safety record and emits an ideal wavelength for treating the abnormal vessels that occur in rosacea patients. In this study we investigate the ability of the long pulse‐duration pulsed‐dye laser to improve rosacea.

Study Design/Materials and Methods

Twenty subjects with rosacea were treated with the high‐energy, long pulse‐duration pulsed‐dye laser. An elliptical spot and long pulse‐duration was used to spot‐treat linear telangiectasias, while a circular spot and short pulse‐duration was used to treat the entire face. Improvement was determined by blinded evaluation of photographs and by the treating physician's subjective evaluation, before and 8 weeks following the final treatment.

Results

The average rosacea score as estimated by the treating physician decreased from 2.7±1.1 to 1.4+ 0.7 (mean+SD) on a 0–6 scale with 0 representing no rosacea and 6 representing the most severe rosacea (P<0.001 level). The average rosacea score as rated by blinded physician observers scoring digital photos was 2.3±1.3 before treatment and 1.4±0.9 8 weeks following treatment, using a 0 (mild) to 6 (severe) scale.

Conclusions

The high‐energy, long pulse‐duration pulsed‐dye laser improves rosacea with a very favorable safety profile, and less purpura than resulted from earlier generation pulsed‐dye lasers. Lesers Surg. Med. 40:233–239, 2008. © 2008 Wiley‐Liss, Inc.
Scattered UV irradiation during VISX excimer laser keratorefractive surgery
Authors: Hope R.J. , Weber E.D. , Bower K.S. , Pasternak J.P. , Sliney D.H.
Published: April 2008

Purpose

To evaluate the potential occupational health hazards associated with scattered ultraviolet (UV) radiation during photorefractive keratectomy (PRK) using the VISX Star S3 excimer laser.

Setting

The Laser Vision Center, National Naval Medical Center, Bethesda, Maryland, USA.

Methods

Intraoperative radiometric measurements were made with the Ophir Power/Energy Meter (LaserStar Model PD‐10 with silicon detector) during PRK treatments as well as during required calibration procedures at a distance of 20.3 cm from the left cornea. These measurements were evaluated using a worst‐case scenario for exposure, and then compared with the American Conference of Governmental Industrial Hygeinists (ACGIH) Threshold Value Limits (TVL) to perform a risk/hazard analysis.

Results

During the PRK procedures, the highest measured value was 248.4 nJ/pulse. During the calibration procedures, the highest measured UV scattered radiation level was 149.6 nJ/pulse. The maximum treatment time was 52 seconds. Using a worst‐case scenario in which all treatments used the maximum power and time, the total energy per eye treated was 0.132 mJ/cm2 and the total UV radiation at close range (80 cm from the treated eye) was 0.0085 mJ/cm2. With a workload of 20 patients, the total occupational exposure at 80 cm to actinic UV radiation in an 8‐hour period would be 0.425 mJ/cm2.

Conclusions

The scattered actinic UV laser radiation from the VISX Star S3 excimer laser did not exceed occupational exposure limits during a busy 8‐hour workday, provided that operating room personnel were at least 80 cm from the treated eye. While the use of protective eyewear is always prudent, this study demonstrates that the trace amounts of scattered laser emissions produced by this laser do not pose a serious health risk even without the use of protective eyewear. Lesers Surg. Med. 40:243–246, 2008. © 2008 Wiley‐Liss, Inc.
Metastable States of Glassy Dynamics, Possibly Mimicking Confinement‐Effects in Thin Polymer Films
Authors: Serghei Anatoli , Kremer Friedrich
Published: April 2008

The impact of the preparation and thermal history on the dynamic glass transition in thin films of poly(methyl methacrylate) and poly(vinyl acetate) is systematically investigated by means of broadband dielectric spectroscopy. Metastable states of glassy dynamics are detected, exhibiting shifts in the mean‐relaxation time from the bulk values. These shifts ‐ possibly mimicking confinement‐effects in thin polymer films ‐ become weaker (or even disappear) after an extensive annealing.

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rCBF changes associated with PPN stimulation in a patient with Parkinson's disease: A PET study
Authors: Strafella Antonio P. , Lozano Andres M. , Ballanger Benedicte , Poon Yu‐Yan , Lang Anthony E. , Moro Elena
Published: April 2008

Gait disturbances and akinesia are disabling symptoms in advanced Parkinson's disease (PD). The pedunculopontine nucleus (PPN) is involved in locomotion, control of posture, and behavioral states [i.e. wakefulness, rapid eye movement (REM) sleep]. Some reports have suggested that modulation of the activity of the PPN with deep brain stimulation (DBS) may be beneficial in the treatment of gait dysfunction and akinesia. To gain some insights on effects of PPN‐DBS in the human brain, we used [15O] H2O positron emission tomography (PET) to measure changes in regional cerebral blood flow (rCBF) at rest during Off and On stimulation in an advanced PD patient with unilateral PPN‐DBS. PPN‐DBS increased rCBF in different subcortical areas most notably the thalamus, bilaterally. Double‐blinded clinical evaluation revealed an improvement in motor function by ∼20%. The PET changes provide for the first time evidence in the human brain that PPN‐DBS may be able to influence and modify rCBF of closely connected subcortical structures. Given the importance of the PPN in locomotion, control of posture, and behavioral states, DBS may have significant implication for more complicated forms of movement disorders where deterioration of gait, postural instability, and REM sleep behavior disorders are very disabling. © 2008 Movement Disorder Society
Approximation of Cahn–Hilliard diffuse interface models using parallel adaptive mesh refinement and coarsening with C1 elements
Authors: Stogner Roy H. , Carey Graham F. , Murray Bruce T.
Published: April 2008

A variational formulation and C1 finite element scheme with adaptive mesh refinement and coarsening are developed for phase‐separation processes described by the Cahn–Hilliard diffuse interface model of transport in a mixture or alloy. The adaptive scheme is guided by a Laplacian jump indicator based on the corresponding term arising from the weak formulation of the fourth‐order non‐linear problem, and is implemented in a parallel solution framework. It is then applied to resolve complex evolving interfacial solution behavior for 2D and 3D simulations of the classic spinodal decomposition problem from a random initial mixture and to other phase‐transformation applications of interest. Simulation results and adaptive performance are discussed. The scheme permits efficient, robust multiscale resolution and interface characterization. Copyright © 2008 John Wiley & Sons, Ltd.
Three‐dimensional non‐planar crack growth by a coupled extended finite element and fast marching method
Authors: Sukumar N. , Chopp D. L. , Béchet E. , Moës N.
Published: April 2008

A numerical technique for non‐planar three‐dimensional linear elastic crack growth simulations is proposed. This technique couples the extended finite element method (X‐FEM) and the fast marching method (FMM). In crack modeling using X‐FEM, the framework of partition of unity is used to enrich the standard finite element approximation by a discontinuous function and the two‐dimensional asymptotic crack‐tip displacement fields. The initial crack geometry is represented by two level set functions, and subsequently signed distance functions are used to maintain the location of the crack and to compute the enrichment functions that appear in the displacement approximation. Crack modeling is performed without the need to mesh the crack, and crack propagation is simulated without remeshing. Crack growth is conducted using FMM; unlike a level set formulation for interface capturing, no iterations nor any time step restrictions are imposed in the FMM. Planar and non‐planar quasi‐static crack growth simulations are presented to demonstrate the robustness and versatility of the proposed technique. Copyright © 2008 John Wiley & Sons, Ltd.
Robotic trajectory tracking for neurological rehabilitation
Authors: Hughes Ann‐Marie , Burridge Jane , Freeman Chris , Chappell Paul , Lewin Paul , Rogers Eric
Published: April 2008

The authors describe the initial phase of their work at the University of Southampton on testing an improved technique to help stroke patients regain the use of their arms.Useful arm movement is regarded as one of the most important factors for regaining functional independence among stroke patients. Copyright © 2008 Wiley Interface Ltd
Primhe: Primary Care Mental Health and Education
Authors: Martin Tasim M , Jones Alan , Woodward Catherine
Published: April 2008

Personality disorder in primary care: a unique approach

In this article, the authors describe an innovative community project in Camden and Islington that offers specialised support to members of the primary care team who work with people with personality disorder. Copyright © 2008 Wiley Interface Ltd
Structure of YraM, a protein essential for growth of Haemophilus influenzae
Authors: Vijayalakshmi J. , Akerley Brian J. , Saper Mark A.
Published: April 2008

Nontypeable Haemophilus influenzae is an obligate human parasite that often causes middle ear infections in children and exacerbates chronic obstructive pulmonary disorder, the fourth leading cause of death in the United States. There are no effective vaccines available for this strain. The lipoprotein YraM (gene HI1655) was identified as essential for the growth and viability of H. influenzae but its function is unknown. Sequence comparisons showed that YraM is a fusion of two protein modules. We grew crystals of the carboxyl‐terminal module of YraM comprising residues 257–573 (YraM‐C), phased the diffraction data by the multiwavelength anomalous diffraction technique, and refined the model to a crystallographic R‐factor of 0.16 (Rfree = 0.19) with data to 1.35 Å resolution. The two‐domain structure of YraM‐C adopts a fold similar to that observed for the open, unliganded forms of several periplasmic binding proteins (PBPs) involved in bacterial active transport. Sequence alignments of YraM homologues from other Gram‐negative species showed that the most conserved residues of YraM‐C cluster between the two domains in the location where other PBPs bind their cognate ligand. Modeling of YraM‐C into a closed conformation similar to the leucine‐bound form of the Leu/Ile/Val‐binding protein (LIVBP) shows a putative binding pocket larger than the leucine‐binding site in LIVBP. The pocket has both polar and nonpolar surfaces, with the latter located in the same area where a leucine side chain binds to LIVBP. We discuss possible biological functions of YraM considering its predicted location in the outer membrane, a novel place for such a binding protein. Proteins 2008. © 2008 Wiley‐Liss, Inc.
A QM/MM study of proton transport pathways in a [NiFe] hydrogenase
Authors: Fdez. Galván Ignacio , Volbeda Anne , Fontecilla‐Camps Juan C. , Field Martin J.
Published: April 2008

A theoretical QM/MM study of the [NiFe] hydrogenase from Desulfovibrio fructosovorans has been performed to investigate possible routes of proton transfer between the active site and the protein surface. We obtained the minimum energy paths, with a modified version of the nudged elastic band method, for a set of proposed pathways. The calculations were carried out for the crystallographic structure and for several structures of the protein obtained from a molecular dynamics simulation. The results show one of the studied pathways to be preferred for transport from the active site to the surface, but the preference is not so strong when transport occurs in the opposite direction. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Coarse‐grained dynamics of the receiver domain of NtrC: Fluctuations, correlations and implications for allosteric cooperativity
Authors: Liu Ming S. , Todd B. D. , Yao Shenggen , Feng Zhi‐Ping , Norton Raymond S. , Sadus Richard J.
Published: April 2008

Receiver domains are key molecular switches in bacterial signaling. Structural studies have shown that the receiver domain of the nitrogen regulatory protein C (NtrC) exists in a conformational equilibrium encompassing both inactive and active states, with phosphorylation of Asp54 allosterically shifting the equilibrium towards the active state. To analyze dynamical fluctuations and correlations in NtrC as it undergoes activation, we have applied a coarse‐grained dynamics algorithm using elastic network models. Normal mode analysis reveals possible dynamical pathways for the transition of NtrC from the inactive state to the active state. The diagonalized correlation between the inactive and the active (phosphorylated) state shows that most correlated motions occur around the active site of Asp54 and in the region Thr82 to Tyr101. This indicates a coupled correlation of dynamics in the “Thr82‐Tyr101” motion. With phosphorylation inducing significant flexibility changes around the active site and α3 and α4 helices, we find that this activation makes the active‐site region and the loops of α3/β4 and α4/β5 more stable. This means that phosphorylation entropically favors the receiver domain in its active state, and the induced conformational changes occur in an allosteric manner. Analyses of the local flexibility and long‐range correlated motion also suggest a dynamics criterion for determining the allosteric cooperativity of NtrC, and may be applicable to other proteins. Proteins 2008. © 2008 Wiley‐Liss, Inc.
Discriminative learning for protein conformation sampling
Authors: Zhao Feng , Li Shuaicheng , Sterner Beckett W. , Xu Jinbo
Published: April 2008

Protein structure prediction without using templates (i.e., ab initio folding) is one of the most challenging problems in structural biology. In particular, conformation sampling poses as a major bottleneck of ab initio folding. This article presents CRFSampler, an extensible protein conformation sampler, built on a probabilistic graphical model Conditional Random Fields (CRFs). Using a discriminative learning method, CRFSampler can automatically learn more than ten thousand parameters quantifying the relationship among primary sequence, secondary structure, and (pseudo) backbone angles. Using only compactness and self‐avoiding constraints, CRFSampler can efficiently generate protein‐like conformations from primary sequence and predicted secondary structure. CRFSampler is also very flexible in that a variety of model topologies and feature sets can be defined to model the sequence‐structure relationship without worrying about parameter estimation. Our experimental results demonstrate that using a simple set of features, CRFSampler can generate decoys with much higher quality than the most recent HMM model. Proteins 2008. © 2008 Wiley‐Liss, Inc.