A fluorimetric enzyme assay for the diagnosis of Sanfilippo disease type D (MPS IIID)

4-Methylumbelliferyl-α-N-acetylglucosamine 6-sulphate was synthesized and shown to be a substrate for the lysosomal N-acetylglucosamine-6-sulphate sulphatase (GlcNAc-6S sulphatase). Fibroblasts and leukocytes from 3 different Sanfilippo D patients showed <1% of mean normal GlcNAc-6S sulphatase activity. The enzymatic liberation of the fluorochrome from 4-methyl-umbelliferyl-α-N-acetylglucosamine 6-sulphate requires the sequential action of the GlcNAc-6S sulphatase and α-N-acetylglucosaminidase. A normal level of α-N-acetylglucosaminidase activity was insufficient to complete the hydrolysis of the reaction intermediate 4-methylumbelliferyl-α-N-acetylgluco-saminide formed by the GlcNAc-6S sulphatase. A second incubation in the presence of excess α-N-acetyglucosaminidase is needed to avoid underestimation of the GlcNAc-6S sulphatase activity

Slow fluctuations in enhanced Raman scattering and surface roughness relaxation

We propose an explanation for the recently measured slow fluctuations and ``blinking'' in the surface enhanced Raman scattering (SERS) spectrum of single molecules adsorbed on a silver colloidal particle. We suggest that these fluctuations may be related to the dynamic relaxation of the surface roughness on the nanometer scale and show that there are two classes of roughness with qualitatively different dynamics. The predictions agree with measurements of surface roughness relaxation. Using a theoretical model for the kinetics of surface roughness relaxation in the presence of charges and optical electrical fields, we predict that the high-frequency electromagnetic field increases both the effective surface tension and the surface diffusion constant and thus accelerates the surface smoothing kinetics and time scale of the Raman fluctuations in manner that is linear with the laser power intensity, while the addition of salt retards the surface relaxation kinetics and increases the time scale of the fluctuations. These predictions are in qualitative agreement with the Raman experiments

Molecular Changes in Pre-Metastatic Lymph Nodes of Esophageal Cancer Patients

Lymph node metastasis indicates poor prognosis in esophageal cancer. To understand the underlying mechanisms, most studies so far focused on investigating the tumors themselves and/or invaded lymph nodes. However they neglected the potential events within the metastatic niche, which precede invasion. Here we report the first description of these regulations in patients on transcription level. We determined transcriptomic profiles of still metastasis-free regional lymph nodes for two patient groups: patients classified as pN1 (n = 9, metastatic nodes exist) or pN0 (n = 5, no metastatic nodes exist). All investigated lymph nodes, also those from pN1 patients, were still metastasis-free. The results show that regional lymph nodes of pN1 patients differ decisively from those of pN0 patients--even before metastasis has taken place. In the pN0 group distinct immune response patterns were observed. In contrast, lymph nodes of the pN1 group exhibited a clear profile of reduced immune response and reduced proliferation, but increased apoptosis, enhanced hypoplasia and morphological conversion processes. DKK1 was the most significant gene associated with the molecular mechanisms taking place in lymph nodes of patients suffering from metastasis (pN1). We assume that the two molecular profiles observed constitute different stages of a progressive disease. Finally we suggest that DKK1 might play an important role within the mechanisms leading to lymph node metastasis

Where to place wim stations? The brazilian approach including a novel data-driven spatial decision support system

The current most advanced WIM systems distributed worldwide have already proven their capacity for weight enforcement. The question of whether or not precise weight measurements are possible in highway speeds is no longer open, as many systems have shown good results in this direction. Now, other questions start to arise in the industry. One of the main questions is: in large road networks, where should we install WIM sensors so that they achieve their maximum efficiency? It is proven that the enforcement system as a whole is ineffective if improper locations are chosen, and effective if the locations are well chosen. In this paper, the method that is currently being used by the Brazilian National Land Infrastructure Department (DNIT) is presented. It is a spatial decision support system (SDSS) that includes a multi-criteria method developed to facilitate decision-making in this process by summarizing a set of important information into a single index named IVFP. The adopted philosophy is not to make the decision on behalf of the road entity but, rather, to provide the planner with accessible information regarding the road network and a unified index that highlights segments for weight enforcement. The Brazilian approach is presented so that it can serve as a starting point for the international community, as this is a problem that will become common in the next few years.Papers presented at the 40th International Southern African Transport Conference on 04 -08 July 202

Correction model for hs-wim systems based on pavement temperature and vehicle speed

Weight enforcement is essential for highway infrastructure conservation. Overweight vehicles represent an exponentially higher degradation for the pavement then those inside the legal limits. They also represent increased danger to their own safety and of the other road users, due to the possibility that the excessive load compromises the truck’s ability to maneuver and break efficiently. However, performing high-precision weight measurements nowadays demand that the vehicle reduce their speed in order to enter weight enforcement stations. In this aspect, high-speed weight-in-motion (HS-WIM) technology is a viable alternative, where the vehicles’ weights are measured in operational speeds. However, current HS-WIM systems face a challenge of increasing their accuracy in order to compete with low-speed weighing systems. In this context, this paper presents a statistical model for error correction in HS-WIM systems as a function of the pavement temperature and the measured speed, which are parameters that are repeatedly shown to be related to error in these systems. The proposed model is based on a set of fitted linear equations that are created considering temperature and speed intervals, which are determined according to data collected in the field with known-weight trucks. A practical application of the proposed method is presented that shows that it is capable of increasing the system’s performance both by displacing the average closer to zero and also by reducing the deviation of the resulting errors. Therefore, the proposed method is presented as a tool to increase HS-WIM systems’ performance, in hopes that it contributes to the growth of HS-WIM technology and its viability in practical applications.Papers presented at the 40th International Southern African Transport Conference on 04 -08 July 202

The Pliocene Model Intercomparison Project (PlioMIP) Phase 2: Scientific Objectives and Experimental Design

The Pliocene Model Intercomparison Project (PlioMIP) is a co-ordinated international climate modelling initiative to study and understand climate and environments of the Late Pliocene, and their potential relevance in the context of future climate change. PlioMIP examines the consistency of model predictions in simulating Pliocene climate, and their ability to reproduce climate signals preserved by geological climate archives. Here we provide a description of the aim and objectives of the next phase of the model intercomparison project (PlioMIP Phase 2), and we present the experimental design and boundary conditions that will be utilised for climate model experiments in Phase 2. Following on from PlioMIP Phase 1, Phase 2 will continue to be a mechanism for sampling structural uncertainty within climate models. However, Phase 1 demonstrated the requirement to better understand boundary condition uncertainties as well as uncertainty in the methodologies used for data-model comparison. Therefore, our strategy for Phase 2 is to utilise state-of-the-art boundary conditions that have emerged over the last 5 years. These include a new palaeogeographic reconstruction, detailing ocean bathymetry and land/ice surface topography. The ice surface topography is built upon the lessons learned from offline ice sheet modelling studies. Land surface cover has been enhanced by recent additions of Pliocene soils and lakes. Atmospheric reconstructions of palaeo-CO2 are emerging on orbital timescales and these are also incorporated into PlioMIP Phase 2. New records of surface and sea surface temperature change are being produced that will be more temporally consistent with the boundary conditions and forcings used within models. Finally we have designed a suite of prioritized experiments that tackle issues surrounding the basic understanding of the Pliocene and its relevance in the context of future climate change in a discrete way