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The C-terminus of the intracellular retinal rod outer segment disk protein peripherin-2 binds to membranes, adopts a helical conformation, and promotes membrane fusion, which suggests an analogy to the structure and function of viral envelope fusion proteins. Nuclear magnetic resonance (NMR) data and fluorescence data show that a 63-residue polypeptide comprising the C-terminus of bovine peripherin-2 (R284-G346) binds to the membrane mimetic, dodecylphosphocholine micelles. High-resolution NMR studies reveal that although this C-terminal fragment is unstructured in solution, the same fragment adopts helical structure when bound to the micelles. The C-terminus may be a member of the class of intrinsically unstructured protein domains. Using methods developed for the G-protein coupled receptor rhodopsin, a model for the structure of the transmembrane domain of peripherin-2 was constructed. Previously published data showed that both peripherin-2 and viral fusion proteins are transmembrane proteins that promote membrane fusion and have a fusion peptide sequence within the protein that independently promotes membrane fusion. Furthermore, the fusion-active sequence of peripherin-2 exhibits a sequence motif that matches the viral fusion peptide of influenza hemagglutinin (HA). These observations collectively suggest that the mechanism of intracellular membrane fusion induced by peripherin-2 and the mechanism of enveloped viral fusion may have features in common. [ABSTRACT FROM AUTHOR]

STUDY DESIGN:: A group of people with incomplete spinal cord injuries (SCI) were evaluated and compared with able-bodied individuals during several walking conditions. OBJECTIVES:: To evaluate the functional community ambulation and estimated energy expenditure in persons with incomplete SCI and able-bodied individuals. METHODS:: A list of criteria was used to evaluate functional community ambulation among participants. Physiological variables, such as the heart rate, oxygen uptake and the lactate concentration, were also measured. RESULTS:: Three of nine incomplete SCI subjects and all able-bodied subjects were able to meet all the criteria measured. The required velocity to safely cross an intersection was the criterion that the incomplete SCI group had the most difficulty reaching. The able-bodied subjects had a comfortable walking velocity twice that of the incomplete SCI subjects' preferred velocity. When walking at the same velocity (incomplete SCI subjects' preferred velocity), the incomplete SCI subjects had a rate of oxygen uptake 26% greater than the healthy subjects and were 200% less efficient. The lactate concentration also proved to be a useful tool when evaluating the incomplete SCI subjects' walking efficiency. The incomplete SCI subjects lactate concentration increased after walking at their preferred velocity, meaning that the anaerobic pathways were used to meet energy demands. CONCLUSION:: Rehabilitation centers should adapt their evaluation forms and increase their criteria requirements to more suitable criteria that are found in the SCI patient's community. The physiological cost should also be taken into consideration when evaluating the SCI patient's functional ambulation.Spinal Cord (2001) 39, 327–335. [ABSTRACT FROM AUTHOR]

The results of an ongoing test program to evaluate the performance of polymer-modified cement-based mortars for repairing surfaces of concrete structures up to a depth of 75 mm (3 inches) damaged due to exposure to cold climates are presented. Twenty-five selected commercially available polymer-modified products, seven containing styrene butadiene rubber (SBR) and 18 containing acrylics were evaluated. They were compared with those of a pure cement-based mortar containing 8% silica fume by weight of the cement, with a water/cementitious materials (cement+silica fume) ratio (W/CM) of 0.31. All of the mortars were subjected to thermal compatibility with base concrete, drying shrinkage, permeability, abrasion-erosion resistance, bond strength, compressive strength and freezing and thawing cycling tests. The thermal compatibility with the base concrete at temperatures from −50 to +50 °C was used as a pre-selection test. This paper also presents the satisfactory performance of the three best selected polymer-modified cement-based mortars (included in the 25 mortars), after 6 years in service on two operating spillways of a dam in a severe cold climate. [Copyright &y& Elsevier]

Background: Although the number of colorectal liver metastases (CLM) is decreasingly considered as a contraindication to surgery, patients with 10 CLM or more are often denied liver surgery. This study aimed to evaluate the outcome after liver surgery and to identify prognostic factors of survival in such patients.Methods: The study population consisted of a multicentre cohort of patients with CLM (N=12 406) operated on, with intention to resect, from January 2005-June 2013 and whose data were prospectively collected in the LiverMetSurvey registry.Results: Overall, the group ⩾10 CLM (N=529, 4.3%) experienced a 5-year overall survival (OS) of 30%. A macroscopically complete (R0/R1) resection (72.8% of patients) was associated with a 3- and 5-year OS of 61% and 39% vs 29% and 5% for R2/no resection patients (P<0.0001). At multivariate analysis, R0/R1 resection emerged as the strongest favourable factor of OS (HR 0.35 (0.26-0.48)). Other independent favourable factors were as follows: maximal tumour size <40 mm (HR 0.67 (0.49-0.92)); age <60 years (HR 0.66 (0.50-0.88)); preoperative MRI (HR 0.65 (0.47-0.89)); and adjuvant chemotherapy (HR 0.73 (0.55-0.98)). The model showed that 5-year OS rates of 30% was possible provided R0/R1 resection associated with at least an additional favourable factor.Conclusions: Liver resection might provide long-term survival in patients with ⩾10 CLM staged with preoperative MRI, provided R0/R1 resection followed by adjuvant therapy. A validation of these results in another cohort is needed. [ABSTRACT FROM AUTHOR]

CD40/ CD40-ligand ( CD40 L) signalling is a key stimulatory pathway which triggers the tryptophan ( Trp) catabolizing enzyme IDO in dendritic cells and is immunosuppressive in cancer. We reported IDO-induced Trp catabolism results in a T helper type 17 ( Th17)/regulatory T cell ( Treg) imbalance, and favours microbial translocation in HIV chronic infection. Here we assessed the link between sCD40 L, Tregs and IDO activity in HIV-infected patients with different clinical outcomes. Plasmatic sCD40 L and inflammatory cytokines were assessed in anti-retroviral therapy ( ART)-naive, ART-successfully treated ( ST), elite controllers ( EC) and healthy subjects ( HS). Plasma levels of Trp and its metabolite Kynurenine ( Kyn) were measured by isotope dilution tandem mass spectrometry and sCD14 was assessed by enzyme-linked immunosorbent assay ( ELISA). IDO- mRNA expression was quantified by reverse transcription-polymerase chain reaction ( RT-PCR). The in-vitro functional assay of sCD40 L on Treg induction and T cell activation were assessed on peripheral blood mononuclear cells ( PBMCs) from HS. sCD40 L levels in ART-naive subjects were significantly higher compared to ST and HS, whereas EC showed only a minor increase. In ART-naive alone, sCD40 L was correlated with T cell activation, IDO- mRNA expression and CD4 T cell depletion but not with viral load. sCD40 L was correlated positively with IDO enzymatic activity ( Kyn/ Trp ratio), Treg frequency, plasma sCD14 and inflammatory soluble factors in all HIV-infected patients. In-vitro functional sCD40 L stimulation induced Treg expansion and favoured Treg differentiation by reducing central memory and increasing terminal effector Treg proportion. sCD40 L also increased T cell activation measured by co-expression of CD38/human leucocyte antigen D-related ( HLA- DR). These results indicate that elevated sCD40 L induces immunosuppression in HIV infection by mediating IDO-induced Trp catabolism and Treg expansion. [ABSTRACT FROM AUTHOR]

Background The multidisciplinary management of metastatic melanoma now occasionally includes major hepatic resection. The objective of this work was to conduct a systematic review of the literature on liver resection for metastatic melanoma. Methods MEDLINE, Embase, the Cochrane Library and Scopus were searched (1990 to December 2012). Studies with at least ten patients undergoing liver resection for metastatic melanoma were included. Data on the outcomes of overall survival ( OS) and/or disease-free survival ( DFS) were abstracted and synthesized. Hazard ratios ( HRs) were derived from survival curves and subjected to meta-analysis using random-effects models. Results Twenty-two studies involving 579 patients (13 per cent weighted resection rate) who underwent liver resection were included. Study quality was poor to moderate. Median follow-up ranged from 9 to 59 months. Median DFS ranged from 8 to 23 months, and median OS ranged from 14 to 41 months ( R0, 22-66 months, R2, 10-16 months; R0 versus R1/ R2: HR 0.52, 95 per cent confidence interval (c.i.) 0.37 to 0.73). The OS rate was 56-100 per cent at 1 year, 34-53 per cent at 3 years and 11-36 per cent at 5 years. Median OS with non-operative management ranged from 4 to 12 months. Comparison of OS with resection and non-operative management favoured resection ( HR 0.32, 95 per cent c.i. 0.22 to 0.46). Conclusion Radical resection of liver metastases from melanoma appears to improve overall survival compared with non-operative management or incomplete resection, but this observation requires future confirmation as selection bias may have confounded the results. [ABSTRACT FROM AUTHOR]

Abstract: For sound field reproduction using multichannel spatial sound systems such as Wave Field Synthesis and Ambisonics, sound field extrapolation is a useful tool for the measurement, description and characterization of a sound environment to be reproduced in a listening area. In this paper, the inverse problem theory is adapted to sound field extrapolation around a microphone array for further spatial sound and sound environment reproduction. A general review of inverse problem theory and analysis tools is given and used for the comparative evaluation of various microphone array configurations. Classical direct regularization methods such as truncated singular value decomposition and Tikhonov regularization are recalled. On the basis of the reviewed background, a new regularization method adapted to the problem at hand is introduced. This method involves the use of an a priori beamforming measurement to define a data-dependent discrete smoothing norm for the regularization of the inverse problem. This method which represents the main contribution of this paper shows promising results and opens new research avenues. [Copyright &y& Elsevier]

Abstract: This good laboratory practice (GLP) study of aluminum salts in Sprague–Dawley rats was conducted according to double-blind, vehicle-controlled randomized design by exposing offspring to aluminum citrate in-utero, through lactation, and then in drinking water post-weaning. Three dose levels were used: 30, 100, 300 mg Al/kg bw/day, in addition to control groups that received either water or a sodium citrate solution (27.2 g/L). Endpoints were assessed in both female and male pups: behavioral (motor activity, T-maze, auditory startle, the Functional Observational Battery (FOB) with domains targeting autonomic function, activity, neuromuscular function, sensimotor function, and physiological function), cognitive function (Morris swim maze), brain weight, clinical chemistry, hematology, tissue/blood levels of aluminum and neuropathology. The most notable treatment-related effect observed in the offspring was renal pathology, most prominently in the male pups. Higher mortality and significant morbidity were observed in the male pups in the high Al-citrate dose group; leading to euthanization of this group at day 89. There was evidence for dose–response relationships between neuromuscular measurements—hind-limb and fore-limb grip strength—and Al-treatment in both males and females, although some of the effects may be secondary to body weight changes. No consistent treatment-related effects were observed in ambulatory counts (motor activity) in the different cohorts. No significant effects were observed for the auditory startle response, T-maze tests (pre-weaning day 23 cohort) or the Morris water maze test (day 120 cohort). None of the lesions seen on histopathological examination of brain tissues of the day 364 group was reported as treatment-related and, as these were also seen in the control group, were likely due to aging. In conclusion, these results indicate that concentrations of aluminum in the drinking water that are required to produce minimally detectable neurobiological effects in the rat are about 10,000 times higher than what is typically found in potable drinking water. [Copyright &y& Elsevier]

OBJECTIVES:: This paper presents the exposure assessment and job-exposure matrix (JEM) used to estimate coal tar pitch volatile (CTPV) exposure for a study of mortality and cancer incidence in aluminum smelter workers in Quebec, Canada. METHODS:: Historical CTPV exposure was assessed by estimating benzene-soluble material (BSM) and benzo[a]pyrene (B[a]P) levels for combinations of job and time period. Estimates were derived by using several procedures including averaging measurement data, a deterministic mathematical model using process-related correction factors, and expert-based extrapolation. RESULTS:: The JEM comprised 28,910 jobs, covering 7 facilities from 1916 to 1999. Estimated exposures ranged from 0.01 mug/m[3] to 68.08 mug/m[3] (B[a]P) and 0.01 mg/m to 3.64 mg/m[3] (BSM) and were lowest before 1940 and after 1980. CONCLUSION:: This methodology constitutes an improvement compared with methods used for previous studies of the Quebec cohort. [ABSTRACT FROM AUTHOR]

In addition to new tumour antigens, new prognostic and diagnostic markers are needed for common cancers. In this study, we report the expression of Dickkopf-1 (DKK1) in multiple common cancers. This constitutes a comprehensive analysis of the DKK1 expression profile. Dickkopf-1 expression was evaluated by classical and quantitative reverse transcriptase–polymerase chain reaction (RT–PCR) and enzyme-linked immunosorbant assay for protein determination, in cancer lines and clinical specimens of several cancer origins. For breast cancer, expression was correlated with clinicopathological parameters. Dickkopf-1 expression was confirmed in several cancer cell lines derived from breast and other common cancers. Dickkopf-1 protein secretion was documented in breast, prostate and lung cancer lines, but was negligible in melanoma. Analysis of DKK1 expression in human cancer specimens revealed DKK1 expression in breast (21 out of 73), lung (11 out of 23) and kidney cancers (six out of 20). Interestingly, DKK1 was preferentially expressed in oestrogen and progesterone receptor-negative tumours (ER−/PR−; P=0.005) and in tumours from women with a family history of breast cancer (P=0.024). Importantly, DKK1 protein production was confirmed in multiple breast cancer specimens that were positive by RT–PCR. This work establishes DKK1 as a potential prognostic and diagnostic marker for cohorts of breast cancer patients with poor prognosis. Dickkopf-1 may also become a relevant candidate target for immunotherapy of different cancers.British Journal of Cancer (2007) 96, 646–653. doi:10.1038/sj.bjc.6603579 www.bjcancer.com Published online 23 January 2007 [ABSTRACT FROM AUTHOR]

The aim of this study is to report our experience using self-expandable covered metallic stents (Wallstent) to treat different types of biliary strictures after orthotopic liver transplantation (OLT).Between January 1999 and July 2004, 222 OLTs were performed with choledocho-choledochostomy (CC) bile duct reconstruction. An anastomotic biliary stricture was diagnosed and treated by endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous procedures in 100 patients (45%). The group of 21 patients (mean age 57.0±5.6 years) that were eventually treated with a biliary Wallstent was studied retrospectively.Significant persistent proximal or anastomotic strictures were diagnosed in 4 and 17 patients, respectively. A Wallstent was inserted by ERCP or through a percutaneous route in 18 and 3 patients, respectively. The mean interval between diagnosis and Wallstent insertion was 179.7±292.8 (0–1113) days. The mean total number of procedures required per patient was 7.4±5.5. The mean stent primary patency duration was 10.8±7.8 (0.9–25.1) months with a 24-month primary patency rate of 26% at a mean follow-up time of 37.8±17.2 months. A hepatico-jejunostomy was performed in five patients (24%). Two patients (10%) underwent retransplantation for diffuse ischemic cholangitis or chronic rejection. The overall complication rate was 4%.Treatment of post-transplant biliary stenosis using a Wallstent is a valuable option for delaying or avoiding surgery in up to 70% of patients. Proximal stenosis can be treated in the same manner in selected patients with major comorbidities. [ABSTRACT FROM AUTHOR]

Heat flow studies on the exposed part of the Trans-Hudson Orogen (THO) in northern Manitoba and Saskatchewan allow constraints on crustal composition and lithosphere structure. The average of all heat flow values in the THO is the same as in other geological provinces of the Canadian Shield. However, where juvenile crust is exposed, heat flow is on average lower than in the Superior and Grenville provinces (37 vs. 41 mW m–2). Heat flow increases towards the surrounding Archean provinces, Rae–Hearne to the west, Sask to the south, and Superior to the east. There are strong differences in heat flow within and between the belts of the THO. The poor correlation between heat flow and heat production in the rocks exposed at the surface implies that these differences involve a large fraction of the crustal column. One new heat flow determination confirms the existence of a ``cold spot'' around the town of Lynn Lake in the northern part of the THO. Heat flow data in the Kisseynew and Glennie domains remain sparse, but they indicate that this low heat flow region extends as far south as the Flin Flon – Snow Lake Belt. The Lynn Lake Belt is underlain by poorly radiogenic rocks, possibly Kisseynew-type crust with oceanic basement. Northward increase in heat flow along the Thompson Belt is consistent with the view that the belt is thrust over Kisseynew-type basement only in the south. Heat flow increases southward in the Paleozoic basin because of higher heat production in basement rocks, probably from the Sask craton. We used the low heat flow regions to obtain an upper bound of 15 mW m–2 for the mantle heat flow in the THO. The effective elastic thickness of the lithosphere can be determined from the coherence between the topography and the Bouguer gravity. The effective elastic thickness is high (>40 km) thoughout the Canadian Shield and is highest in the central part of the shield, in particular in the Lynn Lake region. There seems to be a negative correlation between elastic thickness and heat flow in the central and western Canadian Shield. This indicates that, even in stable continents, the elastic thickness is largely controlled by the lithospheric temperatures that depend strongly on crustal heat generation and hence crustal structure. [ABSTRACT FROM AUTHOR]