A zero-cost, real-time, Windows signal laboratory

This paper introduces a Windows-based signal capture, display, and waveform synthesis package called “Win-eLab”. The software is able to run on a conventional desktop or laptop with no additional hardware, and can perform real-time Fourier analysis on audio-frequency signals. This paper is intended as an introduction to Win-eLab, aimed at motivating further use of it in both teaching and self-directed learning contexts. The use of the software to familiarize students with the concept of “laboratory” instrumentation is discussed, as well as the usefulness of a simultaneous time-domain/frequency-domain display for understanding signals, particularly in signal processing and communications systems courses. It is anticipated that applications may extend beyond electrical & electronic engineering – for example, as an aid to understanding mechanical vibrations, acoustics, and in other discipline areas

Investigation of Colorado front range winter storms using a nonhydrostatic mesoscale numerical model designed for operational use

Fall 1993.Also issued as author's sdissertation (Ph.D.) -- Colorado State University, 1993.Includes bibliographical references.State-of-the-art data sources such as Doppler radar, automated surface observations, wind profiler, digital satellite, and aircraft reports are for the first time providing the capability to generate real-time, operational three-dimensional gridded data sets with sufficient spatial and temporal resolutions to diagnose the structure and evolution of mesoscale systems. A prototype data assimilation system of this type, called the Local Analysis and Prediction System (LAPS), is being developed at the National Oceanic and Atmospheric System's Forecast Systems Laboratory (FSL). The investigation utilizes the three-dimensional LAPS analyses for initialization of the full physics, nonhydrostatic Regional Atmospheric Modeling System (RAMS) model developed at the Colorado State University to create a system capable of generating operational mesoscale predictions. The LAPS/RAMS system structured for operational use can add significant value to existing operational model output and can provide an improved scientific understanding of mesoscale weather events. The results a.re presented through two case study analyses, the 7 January 1992 Colorado Front Range blizzard and the 8-9 March 1992 eastern Colorado snowstorm. Both cases a.re ideal for this investigation due to the significant mesoscale variation observed in the precipitation and flow structure. The case study results demonstrate the ability to successfully detect and predict mesoscale features using a mesoscale numerical model initialized with high resolution (10 km horizontal grid interval), non­ homogeneous data. Conceptual models of the two snowstorms are developed by utilizing the RAMS model output in combination with observations and other larger domain model simulations. The strong influence of the Colorado topography on the resultant flow is suggested by the generation of a lee vortex that frequently develops east of the Front Range and south of the Cheyenne Ridge in stable, northwest synoptic flow. The lee vortex, often called the "Longmont anticyclone", exhibits surface flow characteristics that are similar to results from low Froude number flow around an isolated obstacle. A series of numerical experiments using RAMS with idealized topography and horizontally homogeneous initial conditions are presented to investigate typical low Froude number flow characteristics in the vicinity of barriers representative of the Colorado topography. The results are compared to the findings of previous investigations and to the case study observations and numerical predictions. The findings suggest that the Colorado orography significantly altered the low-level flow in both case studies resulting in mesoscale variation of observed precipitation. Improved representation of the topography by the model led to the majority of the forecast improvement

Computerized crime linkage systems: A critical review and research agenda

Computerized crime linkage systems are meant to assist the police in determining whether crimes have been committed by the same offender. In this article, the authors assess these systems critically and identify four assumptions that affect the effectiveness of these systems. These assumptions are that (a) data in the systems can be coded reliably, (b) data in the systems are accurate, (c) violent serial offenders exhibit consistent but distinctive patterns of behavior, and (d) analysts have the ability to use the data in the systems to link crimes accurately. The authors argue that there is no compelling empirical support for any of the four assumptions, and they outline a research agenda for testing each assumption. Until evidence supporting these assumptions becomes available, the value of linkage systems will remain open to debate

Advances in Chimeric Antigen Receptor T-Cell Therapies for Solid Tumors.

In 2017, the US Food and Drug Administration approved the first two novel cellular immunotherapies using synthetic, engineered receptors known as chimeric antigen receptors (CARs), tisagenlecleucel (Kymriah) and axicabtagene ciloleucel (Yescarta), expressed by patient-derived T cells for the treatment of hematological malignancies expressing the B-cell surface antigen CD19 in both pediatric and adult patients. This approval marked a major milestone in the use of antigen-directed living drugs for the treatment of relapsed or refractory blood cancers, and with these two approvals, there is increased impetus to expand not only the target antigens but also the tumor types that can be targeted. This state-of-the-art review will focus on the challenges, advances, and novel approaches being used to implement CAR T-cell immunotherapy for the treatment of solid tumors

Modelling and Refinement in CODA

This paper provides an overview of the CODA framework for modelling and refinement of component-based embedded systems. CODA is an extension of Event-B and UML-B and is supported by a plug-in for the Rodin toolset. CODA augments Event-B with constructs for component-based modelling including components, communications ports, port connectors, timed communications and timing triggers. Component behaviour is specified through a combination of UML-B state machines and Event-B. CODA communications and timing are given an Event-B semantics through translation rules. Refinement is based on Event-B refinement and allows layered construction of CODA models in a consistent way.Comment: In Proceedings Refine 2013, arXiv:1305.563

GUCY2C maintains intestinal LGR5+ stem cells by opposing ER stress

Long-lived multipotent stem cells (ISCs) at the base of intestinal crypts adjust their phenotypes to accommodate normal maintenance and post-injury regeneration of the epithelium. Their long life, lineage plasticity, and proliferative potential underlie the necessity for tight homeostatic regulation of the ISC compartment. In that context, the guanylate cyclase C (GUCY2C) receptor and its paracrine ligands regulate intestinal epithelial homeostasis, including proliferation, lineage commitment, and DNA damage repair. However, a role for this axis in maintaining ISCs remains unknown. Transgenic mice enabling analysis of ISCs (Lgr5-GFP) in the context of GUCY2C elimination (Gucy2c-/-) were combined with immunodetection techniques and pharmacological treatments to define the role of the GUCY2C signaling axis in supporting ISCs. ISCs were reduced in Gucy2c-/- mice, associated with loss of active Lgr5+ cells but a reciprocal increase in reserve Bmi1+ cells. GUCY2C was expressed in crypt base Lgr5+ cells in which it mediates canonical cyclic (c) GMPdependent signaling. Endoplasmic reticulum (ER) stress, typically absent from ISCs, was elevated throughout the crypt base in Gucy2c-/- mice. The chemical chaperone tauroursodeoxycholic acid resolved this ER stress and restored the balance of ISCs, an effect mimicked by the GUCY2C effector 8Br-cGMP. Reduced ISCs in Gucy2c-/-mice was associated with greater epithelial injury and impaired regeneration following sub-lethal doses of irradiation. These observations suggest that GUCY2C provides homeostatic signals that modulate ER stress and cell vulnerability as part of the machinery contributing to the integrity of ISCs. © Kraft et al

Examples of data assimilation in mesoscale models

The keynote address was the problem of physical initialization of mesoscale models. The classic purpose of physical or diabatic initialization is to reduce or eliminate the spin-up error caused by the lack, at the initial time, of the fully developed vertical circulations required to support regions of large rainfall rates. However, even if a model has no spin-up problem, imposition of observed moisture and heating rate information during assimilation can improve quantitative precipitation forecasts, especially early in the forecast. The two key issues in physical initialization are the choice of assimilating technique and sources of hydrologic/hydrometeor data. Another example of data assimilation in mesoscale models was presented in a series of meso-beta scale model experiments with and 11 km version of the MASS model designed to investigate the sensitivity of convective initiation forced by thermally direct circulations resulting from differential surface heating to four dimensional assimilation of surface and radar data. The results of these simulations underscore the need to accurately initialize and simulate grid and sub-grid scale clouds in meso- beta scale models. The status of the application of the CSU-RAMS mesoscale model by the NOAA Forecast Systems Lab for producing real-time forecasts with 10-60 km mesh resolutions over (4000 km)(exp 2) domains for use by the aviation community was reported. Either MAPS or LAPS model data are used to initialize the RAMS model on a 12-h cycle. The use of MAPS (Mesoscale Analysis and Prediction System) model was discussed. Also discussed was the mesobeta-scale data assimilation using a triply-nested nonhydrostatic version of the MM5 model

Split tolerance permits safe Ad5-GUCY2C-PADRE vaccine-induced T-cell responses in colon cancer patients.

Background: The colorectal cancer antigen GUCY2C exhibits unique split tolerance, evoking antigen-specific CD8+, but not CD4+, T-cell responses that deliver anti-tumor immunity without autoimmunity in mice. Here, the cancer vaccine Ad5-GUCY2C-PADRE was evaluated in a first-in-man phase I clinical study of patients with early-stage colorectal cancer to assess its safety and immunological efficacy. Methods: Ten patients with surgically-resected stage I or stage II (pN0) colon cancer received a single intramuscular injection of 1011 viral particles (vp) of Ad5-GUCY2C-PADRE. Safety assessment and immunomonitoring were carried out for 6 months following immunization. This trial employed continual monitoring of both efficacy and toxicity of subjects as joint primary outcomes. Results: All patients receiving Ad5-GUCY2C-PADRE completed the study and none developed adverse events greater than grade 1. Antibody responses to GUCY2C were detected in 10% of patients, while 40% exhibited GUCY2C-specific T-cell responses. GUCY2C-specific responses were exclusively CD8+ cytotoxic T cells, mimicking pre-clinical studies in mice in which GUCY2C-specific CD4+ T cells are eliminated by self-tolerance, while CD8+ T cells escape tolerance and mediate antitumor immunity. Moreover, pre-existing neutralizing antibodies (NAbs) to the Ad5 vector were associated with poor vaccine-induced responses, suggesting that Ad5 NAbs oppose GUCY2C immune responses to the vaccine in patients and supported by mouse studies. Conclusions: Split tolerance to GUCY2C in cancer patients can be exploited to safely generate antigen-specific cytotoxic CD8+, but not autoimmune CD4+, T cells by Ad5-GUCY2C-PADRE in the absence of pre-existing NAbs to the viral vector. TRIAL REGISTRATION: This trial (NCT01972737) was registered at ClinicalTrials.gov on October 30th, 2013. https://clinicaltrials.gov/ct2/show/NCT01972737