PSGL-1 and E/P-selectins are essential for T-cell rolling in inflamed CNS microvessels but dispensable for initiation of EAE

T-cell migration across the blood-brain barrier is a crucial step in the pathogenesis of EAE, an animal model for MS. Live cell imaging studies demonstrated that P-selectin glycoprotein ligand-1 (PSGL-1) and its endothelial ligands E- and P-selectin mediate the initial rolling of T cells in brain vessels during EAE. As functional absence of PSGL-1 or E/P-selectins does not result in ameliorated EAE, we speculated that T-cell entry into the spinal cord is independent of PSGL-1 and E/P-selectin. Performing intravital microscopy, we observed the interaction of WT or PSGL-1(-/-) proteolipid protein-specific T cells in inflamed spinal cord microvessels of WT or E/P-selectin(-/-) SJL/J mice during EAE. T-cell rolling but not T-cell capture was completely abrogated in the absence of either PSGL-1 or E- and P-selectin, resulting in a significantly reduced number of T cells able to firmly adhere in the inflamed spinal cord microvessels, but did not lead to reduced T-cell invasion into the CNS parenchyma. Thus, PSGL-1 interaction with E/P-selectin is essential for T-cell rolling in inflamed spinal cord microvessels during EAE. Taken together with previous observations, our findings show that T-cell rolling is not required for successful T-cell entry into the CNS and initiation of EAE.

Generation of long, fully modified, and serum-resistant oligonucleotides by rolling circle amplification

Rolling Circle Amplification (RCA) is an isothermal enzymatic method generating single-stranded DNA products consisting of concatemers containing multiple copies of the reverse complement of the circular template precursor. Little is known on the compatibility of modified nucleoside triphosphates (dN*TPs) with RCA, which would enable the synthesis of long, fully modified ssDNA sequences. Here, dNTPs modified at any position of the scaffold were shown to be compatible with rolling circle amplification, yielding long (>1 kb), and fully modified single-stranded DNA products. This methodology was applied for the generation of long, cytosine-rich synthetic mimics of telomeric DNA. The resulting modified oligo-nucleotides displayed an improved resistance to fetal bovine serum.

A simulation study of the standard design, the rolling six design, the CRM, and the modified CRM in Phase I clinical trials

The Phase I clinical trial is considered the "first in human" study in medical research to examine the toxicity of a new agent. It determines the maximum tolerable dose (MTD) of a new agent, i.e., the highest dose in which toxicity is still acceptable. Several phase I clinical trial designs have been proposed in the past 30 years. The well known standard method, so called the 3+3 design, is widely accepted by clinicians since it is the easiest to implement and it does not need a statistical calculation. Continual reassessment method (CRM), a design uses Bayesian method, has been rising in popularity in the last two decades. Several variants of the CRM design have also been suggested in numerous statistical literatures. Rolling six is a new method introduced in pediatric oncology in 2008, which claims to shorten the trial duration as compared to the 3+3 design. The goal of the present research was to simulate clinical trials and compare these phase I clinical trial designs. Patient population was created by discrete event simulation (DES) method. The characteristics of the patients were generated by several distributions with the parameters derived from a historical phase I clinical trial data review. Patients were then selected and enrolled in clinical trials, each of which uses the 3+3 design, the rolling six, or the CRM design. Five scenarios of dose-toxicity relationship were used to compare the performance of the phase I clinical trial designs. One thousand trials were simulated per phase I clinical trial design per dose-toxicity scenario. The results showed the rolling six design was not superior to the 3+3 design in terms of trial duration. The time to trial completion was comparable between the rolling six and the 3+3 design. However, they both shorten the duration as compared to the two CRM designs. Both CRMs were superior to the 3+3 design and the rolling six in accuracy of MTD estimation. The 3+3 design and rolling six tended to assign more patients to undesired lower dose levels. The toxicities were slightly greater in the CRMs.^

Water Infiltration following Land Rolling of Soybeans

Land rolling of soybean fields has become a popular practice in north central and northwest Iowa during the past five years. Although this technique was first utilized to push rocks into the ground to avoid combine damage and aid in harvesting lodged crops in Canada, producers in Iowa quickly learned that pushing corn root-balls flat at the time of planting and pushing small rocks into the ground can increase harvest efficiency. Typically fields are rolled shortly after planting. One disturbing trend that was noticed, however, was that rolled fields tended to have more water standing between the rows after moderate or heavy rain events. This would imply that water infiltration was slower in fields that had been rolled compared with fields that had not been rolled. Infiltration measurements were taken on a few plots in 2010 at the ISU Northern Research Farm. It seemed that water infiltration was less on the rolled plots. However, we wanted more measurements before publishing any results. In 2011 infiltration measurements were taken on the research farm and on neighboring farms where soybeans had been rolled. The goal was to determine if water infiltration had been reduced by land rolling.

Metro de Madrid rolling stock models and comparative studies relating to comfort

This paper presents the work carried out by Metro de Madrid and the Railway Technology Research Centre (Polytechnic University of Madrid), aimed at setting up rolling stock simulation models with a high level of detail. To do this, the features of the SIMPACK simulation tool used to create models have been briefly outlined, explaining the main features of models in two of the series modelled: 7000 and 8000. Finally, the results obtained from comparing comfort in the 7000 and 8000 series are presented.

Comparison of vibration and rolling noise emission of resilient and solid monobloc railway wheels in underground lines

Flat or worn wheels rolling on rough or corrugated tracks can provoke airborne noise and ground-borne vibration, which can be a serious concern for nearby neighbours of urban rail transit lines. Among the various treatments used to reduce vibration and noise, resilient wheels play an important role. In conventional resilient wheels, a slightly prestressed V­shaped rubber ring is mounted between the steel wheel centre and tyre. The elastic layer enhances rolling noise and vibration suppression, as well as impact reduction on the track. In this paper the effectiveness of resilient wheels in underground lines, in comparison to monobloc ones, is assessed. The analysed resilient wheel is able to carry greater loads than standard resilient wheels used for light vehicles. It also presents a greater radial resiliency and a higher axial stiffness than conventional V­wheels. The finite element method was used in this study. A quarter car model was defined, in which the wheelset was modelled as an elastic body. Several simulations were performed in order to assess the vibrational behaviour of elastic wheels, including modal, harmonic and random vibration analysis, the latter allowing the introduction of realistic vertical track irregularities, as well as the influence of the running speed. Due to numerical problems some simplifications were needed. Parametric variations were also performed, in which the sensitivity of the whole system to variations of rubber prestress and Poisson’s ratio of the elastic material was assessed.Results are presented in the frequency domain, showing a better performance of the resilient wheels for frequencies over 200 Hz. This result reveals the ability of the analyzed design to mitigate rolling noise, but not structural vibrations, which are primarily found in the lower frequency range.

Robust rolling stock in rapid transit network

This paper focuses on the railway rolling stock circulation problem in rapid transit networks, in which frequencies are high and distances are relatively short. Although the distances are not very large, service times are high due to the large number of intermediate stops required to allow proper passenger flow. The main complicating issue is the fact that the available capacity at depot stations is very low, and both capacity and rolling stock are shared between different train lines. This forces the introduction of empty train movements and rotation maneuvers, to ensure sufficient station capacity and rolling stock availability. However, these shunting operations may sometimes be difficult to perform and can easily malfunction, causing localized incidents that could propagate throughout the entire network due to cascading effects. This type of operation will be penalized with the goal of selectively avoiding them and ameliorating their high malfunction probabilities. Critic trains, defined as train services that come through stations that have a large number of passengers arriving at the platform during rush hours, are also introduced. We illustrate our model using computational experiments drawn from RENFE (the main Spanish operator of suburban passenger trains) in Madrid, Spain. The results of the model, achieved in approximately 1 min, have been received positively by RENFE planners

Integration of Timetable Planning and Rolling Stock in Rapid Transit Networks

The aim of this paper is to propose an integrated planning model to adequate the offered capacity and system frequencies to attend the increased passenger demand and traffic congestion around urban and suburban areas. The railway capacity is studied in line planning, however, these planned frequencies were obtained without accounting for rolling stock flows through the rapid transit network. In order to provide the problem more freedom to decide rolling stock flows and therefore better adjusting these flows to passenger demand, a new integrated model is proposed, where frequencies are readjusted. Then, the railway timetable and rolling stock assignment are also calculated, where shunting operations are taken into account. These operations may sometimes malfunction, causing localized incidents that could propagate throughout the entire network due to cascading effects. This type of operations will be penalized with the goal of selectively avoiding them and ameliorating their high malfunction probabilities. Swapping operations will also be ensured using homogeneous rolling stock material and ensuring parkings in strategic stations. We illustrate our model using computational experiments drawn from RENFE (the main Spanish operator of suburban passenger trains) in Madrid, Spain. The results show that through this integrated approach a greater robustness degree can be obtained

An experimental study on the effect of rolling shutters on the field measurements of airborne sound insulation of façades

The façade is the visible part of a building, and generally consists of various different constructive systems. The sound reduction index of the closing elements for the openings on a room’s façade is a determining factor in the sound insulation from airborne noise inside the space. Windows are the transparent part of the façade, and to improve their thermal behaviour and control solar radiation, they are often fitted with a series of external and internal protections such as shutters, slats and blinds. This work contains a summary of studies carried out using field measurements of airborne sound insulation on façades in rooms, in application of the standard UNE-EN ISO 140-5:1999. In all the rooms the windows were fitted with shutter boxes and rolling shutters, and the acoustic tests were made with the shutter in two positions (extended and fully retracted). The results were analysed considering the window opening system (openable or sliding) and the type of glass pane (monolithic or insulating glass unit, IGU). In the case of sliding windows, the airborne sound insulation of façades is greater when the shutter is extended than when it is retracted, and this should be taken into account when applying the aforementioned standard.

Non invasive moisture measurement in agricultural fiel using a rolling spherical robot

Irrigation management in large crop fields is a very important practice. Since the farm management costs and the crop results are directly connected with the environmental moisture, water control optimization is a critical factor for agricultural practices, as well as for the planet sustainability. Usually, the crop humidity is measured through the water stress index (WSI), using imagery acquired from satellites or airplanes. Nevertheless, these tools have a significant cost, lack from availability, and dependability from the weather. Other alternative is to recover to ground tools, such as ground vehicles and even static base stations. However, they have an outstanding impact in the farming process, since they can damage the cultivation and require more human effort. As a possible solution to these issues, a rolling ground robot have been designed and developed, enabling non-invasive measurements within crop fields. This paper addresses the spherical robot system applied to intra-crop moisture measurements. Furthermore, some experiments were carried out in an early stage corn field in order to build a geo-referenced WSI map.

Robust rolling stock under uncertain demand in rapid transit networks

This paper focuses on the railway rolling stock circulation problem in rapid transit networks where the known demand and train schedule must be met by a given fleet. In rapid transit networks the frequencies are high and distances are relatively short. Although the distances are not very large, service times are high due to the large number of intermediate stops required to allow proper passenger flow. The previous circumstances and the reduced capacity of the depot stations and that the rolling stock is shared between the different lines, force the introduction of empty trains and a careful control on shunting operation. In practice the future demand is generally unknown and the decisions must be based on uncertain forecast. We have developed a stochastic rolling stock formulation of the problem. The computational experiments were developed using a commercial line of the Madrid suburban rail network operated by RENFE (The main Spanish operator of suburban trains of passengers). Comparing the results obtained by deterministic scenarios and stochastic approach some useful conclusions may be obtained.

Numerical and experimental study of the parametric rolling of a fisihing vessel in regular head waves

The dynamic behaviour of a fishing vessel in waves is studied in order to reveal its parametric rolling characteristics. This paper presents experimental and numerical results in longitudinal regular waves. The experimental results are compared against the results of a time-domain non-linear strip theory model of ship motions in six degrees-of-freedom. These results contribute to the validation of the parametric rolling prediction method, so that it can be used as an assessment tool to evaluate both the susceptibility and severity of occurrence of parametric rolling at the early design stage of these types of vessels.