Stabilization of the Outenberg Hill in Geraardsbergen

A road, winding across the Oudenberg hill at Geraardsbergen, Belgium, and built partly in embankment and in excavation, suffered from three landslides from 1937 to 1966. Bored piles were used to nail the surface layers to the stable substratum, subsurface drainage to limit the fluctuations of the water table and a 220 m long low viaduct founded directly on bored piles to re-establish the traffic. Since the end of the works no additional movement appeared

Negative Friction and Lateral Loading on Piles

An example is first given of a structure founded on piles and having suffered damages caused by negative friction and passive lateral loading on the supporting piles. It appears that the effects of negative friction are in general less disastrous than should be expected from a simplified theoretical approach. The described case shows that, at the contrary, the passive lateral loadings, when not accounted for, become rapidly detrimental. Both influences are time delayed, with the consequence that the critical situation does mostly not occur during construction, but a certain time after completion. The design of a second structure, in which the passive lateral loading and negative friction on the piles were taken into account, and whose construction was successful, illustrated that the passive lateral loading is usually a much more determining factor than the negative friction and even every now and then than the dead and live loads

Nondestructive assessment of freshness in packaged sliced chicken breasts using SW-NIR spectroscopy

A technique was developed to predict the freshness of packaged sliced chicken breast employing a nondestructive visible and short-wavelength near-infrared (SW-NIR) spectroscopy method. Spectra were recorded at 0, 7 and 14days using a camera, spectral filter (400-1000nm) and a halogen flood lighting system which were developed and calibrated for the purpose. Physicochemical, biochemical and microbiological properties such as moisture (x w), water activity (a w), pH, total volatile basic nitrogen (TVB-N), ATP breakdown compounds (K 1 values) and mesophilic bacteria (cfu g -1) were determined to predict freshness degradation. The spectra obtained were related to the storage time of the samples. The best wavelengths for modeling freshness were 413, 426, 449, 460, 473, 480, 499, 638, 942, 946, 967, 970 and 982nm. A linear correlation was found between the visible and SW-NIR spectroscopy and parameters such as microbiological counts, K 1 and T-VBN indexes. © 2010 Elsevier Ltd.We wish to thank the Polytechnic University of Valencia and Generalitat Valenciana for the financial support they provided through the PAID-06-08-3251 and GVPRE/2008/170 Projects, respectively.Grau Meló, R.; Sánchez Salmerón, AJ.; Girón Hernández, LJ.; Ivorra Martínez, E.; Fuentes López, A.; Barat Baviera, JM. (2011). Nondestructive assessment of freshness in packaged sliced chicken breasts using SW-NIR spectroscopy. Food Research International. 44:331-337. doi:10.1016/j.foodres.2010.10.011S3313374

Antiretroviral effect of lovastatin on HIV-1-infected individuals without highly active antiretroviral therapy (The LIVE study): a phase-II randomized clinical trial

<p>Abstract</p> <p>Background</p> <p>Highly active antiretroviral therapy produces a significant decrease in HIV-1 replication and allows an increase in the CD4 T-cell count, leading to a decrease in the incidence of opportunistic infections and mortality. However, the cost, side effects and complexity of antiretroviral regimens have underscored the immediate need for additional therapeutic approaches. Statins exert pleiotropic effects through a variety of mechanisms, among which there are several immunoregulatory effects, related and unrelated to their cholesterol-lowering activity that can be useful to control HIV-1 infection.</p> <p>Methods/design</p> <p>Randomized, double-blinded, placebo controlled, single-center, phase-II clinical trial. One hundred and ten chronically HIV-1-infected patients, older than 18 years and naïve for antirretroviral therapy (i.e., without prior or current management with antiretroviral drugs) will be enrolled at the outpatient services from the most important centres for health insurance care in Medellin-Colombia. The interventions will be lovastatin (40 mg/day, orally, for 12 months; 55 patients) or placebo (55 patients). Our primary aim will be to determine the effect of lovastatin on viral replication. The secondary aim will be to determine the effect of lovastatin on CD4+ T-cell count in peripheral blood. As tertiary aims we will explore differences in CD8+ T-cell count, expression of activation markers (CD38 and HLA-DR) on CD4 and CD8 T cells, cholesterol metabolism, LFA-1/ICAM-1 function, Rho GTPases function and clinical evolution between treated and not treated HIV-1-infected individuals.</p> <p>Discussion</p> <p>Preliminary descriptive studies have suggested that statins (lovastatin) may have anti HIV-1 activity and that their administration is safe, with the potential effect of controlling HIV-1 replication in chronically infected individuals who had not received antiretroviral medications. Considering that there is limited clinical data available on this topic, all these findings warrant further evaluation to determine if long-term administration of statins may benefit the virological and immunological evolution in HIV-1-infected individuals before the use of antiretroviral therapy is required.</p> <p>Trial registration</p> <p>Registration number NCT00721305.</p

Translational models for vascular cognitive impairment: a review including larger species.

BACKGROUND: Disease models are useful for prospective studies of pathology, identification of molecular and cellular mechanisms, pre-clinical testing of interventions, and validation of clinical biomarkers. Here, we review animal models relevant to vascular cognitive impairment (VCI). A synopsis of each model was initially presented by expert practitioners. Synopses were refined by the authors, and subsequently by the scientific committee of a recent conference (International Conference on Vascular Dementia 2015). Only peer-reviewed sources were cited. METHODS: We included models that mimic VCI-related brain lesions (white matter hypoperfusion injury, focal ischaemia, cerebral amyloid angiopathy) or reproduce VCI risk factors (old age, hypertension, hyperhomocysteinemia, high-salt/high-fat diet) or reproduce genetic causes of VCI (CADASIL-causing Notch3 mutations). CONCLUSIONS: We concluded that (1) translational models may reflect a VCI-relevant pathological process, while not fully replicating a human disease spectrum; (2) rodent models of VCI are limited by paucity of white matter; and (3) further translational models, and improved cognitive testing instruments, are required

VEGF-D deficiency in mice does not affect embryonic or postnatal lymphangiogenesis but reduces lymphatic metastasis.

Vascular endothelial growth factor-D (VEGF-D) is one of the two ligands of the VEGFR-3 receptor on lymphatic endothelial cells. Gene-silencing studies in mice and Xenopus tadpoles recently showed that the role of endogenous VEGF-D in lymphatic development is moderate. By contrast, exogenous VEGF-D is capable of stimulating lymphangiogenesis. Nonetheless, its endogenous role in pathological conditions remains largely unknown. Hence, we reassessed its role in disease, using Vegf-dnull mice. Vegf-dnull mice were generated that, under physiological conditions, displayed normal embryonic and postnatal lymphangiogenesis and lymphatic remodelling, efficient lymphatic functioning and normal health. Vegf-dnull mice also reponded normally in models of skin wound healing and healing of infarcted myocardium, despite enhanced expression of VEGF-D in these models in wild-type mice. In contrast, Vegf-dnull mice displayed reduced peritumoral lymphangiogenesis and lymph node metastasis in an orthotopic pancreatic tumour model. Together, our data indicate that endogenous VEGF-D in mice is dispensible for lymphangiogenesis during development, in postnatal and adult physiology and in several pathological conditions, but significantly contributes to lymphatic metastasis

Variable region heavy chain glycosylation determines the anticoagulant activity of a factor VIII antibody.

BACKGROUND: N-glycosylation occurs in the variable region of about 10% of antibodies but the role of carbohydrate at this location is still poorly understood. OBJECTIVES: We investigated the function of N-glycosylation in the variable region of the heavy chain of a human monoclonal antibody, mAb-LE2E9, that partially inhibits factor VIII (FVIII) activity during coagulation. METHODS AND RESULTS: Enzymatic deglycosylation indicated that the oligosaccharides do not determine the affinity of the antibody but enhance its FVIII neutralizing activity. A mutant antibody lacking the N-glycosylation site in the variable region of the heavy chain inhibited FVIII activity by up to 40%, while inhibition by the native antibody was 80%. To evaluate the physiological effect of such a FVIII inhibition, we investigated the ability of the mutant antibody devoid of N-glycosylation in the variable region to prevent thrombosis in mice with a strong prothombotic phenotype resulting from a type II deficiency mutation in the heparin binding site of antithrombin. Despite its moderate inhibition of FVIII activity, the mutant antibody significantly prevented thrombosis in treated animals. We also carried out glycan analysis of native and mutant antibodies. CONCLUSIONS: Modification of glycosylation in the variable region of antibodies contributes to the diversity of FVIII type II inhibition possibly by steric hindrance of the active site of FVIII by glycans, and may provide a novel strategy to modulate the functional activity of therapeutic antibodies