Engineered Immune Constructs Alter Antigen-Specific Immune Tolerance and Confer Durable Protection in Myelin-Driven Autoimmunity.

Autoimmune diseases are broadly characterized as a failure in immune tolerance. In multiple sclerosis (MS), autoreactive immune cells attack the protective myelin sheath lining neurons in the central nervous system. Therapeutic strategies that selectively and durably restore immune tolerance without broad immunosuppression are urgently needed for MS.

Opportunistic Identification of Coronary Artery Calcium and Valve/Vascular Calcifications on Chest X-Ray: Improvements With Single-Exposure Dual-Energy Imaging.

To evaluate whether single-exposure, dual-energy chest X-ray (DEX) improves visualization of coronary artery calcium (CAC) and valve/vascular calcifications compared to conventional X-ray. Sixty-one bone-marrow transplant patients (22- 79 years; median 61; IQR 15; w/m, 24/37), underwent single-exposure dual-energy X-ray (Reveal 35C, KA imaging) in pa and lateral projection, followed by a standard-of-care chest CT. Two DEX pairs (pa/lateral) were calculated: a composite image (COMP) and a bone image with soft-tissue subtraction (BI).

Development and Evaluation of an Automated Protocol Recommendation System for Chest CT Using Natural Language Processing With CLEVER Terminology Word Replacement.

To evaluate the clinical performance of a Protocol Recommendation System (PRS) automatic protocolling of chest CT imaging requests. 322 387 consecutive historical imaging requests for chest CT between 2017 and 2022 were extracted from a radiology information system (RIS) database containing 16 associated patient information values. Records with missing fields and protocols with <100 occurrences were removed, leaving 18 protocols for training.

Isotope hydrology of the intermontane Elk Valley, British Columbia: an assessment of water resources around coal mining operations.

This study aimed to synthesise and interpret stable isotopic data (H and O) from various sources to understand the isotope hydrology around coal mine operations in Elk Valley, B.C., Canada.

Short-term exposure to HIV Tat induces glial activation and changes in perineuronal nets.

Despite widespread use of combination antiretroviral therapy (cART), there remains a subset of individuals who display cognitive impairment broadly known as HIV-associated neurocognitive disorder (HAND). Interestingly, HIV-infected cells continuously release the HIV-1 protein Tat even in the presence of cART. Persistent exposure to Tat is proposed to increase both neuroinflammation and neurotoxicity.

Sleep, inflammation, and hemodynamics in rodent models of traumatic brain injury.

Traumatic brain injury (TBI) can induce dysregulation of sleep. Sleep disturbances include hypersomnia and hyposomnia, sleep fragmentation, difficulty falling asleep, and altered electroencephalograms. TBI results in inflammation and altered hemodynamics, such as changes in blood brain barrier permeability and cerebral blood flow.

Chest CT at X-Ray Dose Using a Noise-Mitigating Weighted Projection: The Thoracic Tomogram. Diagnostic Performance for Pneumonia Detection in Hemato-Oncology Patients.

Purpose: To compare the diagnostic performance of a thick-slab reconstruction obtained from an ultra-low-dose CT (termed thoracic tomogram) with standard-of-care low-dose CT (SOC-CT) for rapid interpretation and detection of pneumonia in hemato-oncology patients.

Methods: Hemato-oncology patients with a working diagnosis of pneumonia underwent an SOC-CT followed by an ultra-low-dose CT, from which the thoracic tomogram (TT) was reconstructed. Three radiologists evaluated the TT and SOC-CT in the following categories: (I) infectious/inflammatory opacities, (II) small airways infectious/inflammatory changes, (III) atelectasis, (IV) pleural effusions, and (V) interstitial abnormalities.

Harnessing Biomaterials to Study and Direct Antigen-Specific Immunotherapy.

Immunotherapies are an evolving treatment paradigm for addressing cancer, autoimmunity, and infection. While exciting, most of the existing therapies are limited by their specificity─unable to differentiate between healthy and diseased cells at an antigen-specific level. Biomaterials are a powerful tool that enable the development of next-generation immunotherapies due to their tunable synthesis properties.

Engineering the lymph node environment promotes antigen-specific efficacy in type 1 diabetes and islet transplantation.

Antigen-specific tolerance is a key goal of experimental immunotherapies for autoimmune disease and allograft rejection. This outcome could selectively inhibit detrimental inflammatory immune responses without compromising functional protective immunity. A major challenge facing antigen-specific immunotherapies is ineffective control over immune signal targeting and integration, limiting efficacy and causing systemic non-specific suppression.

Biomaterial Strategies for Selective Immune Tolerance: Advances and Gaps.

Autoimmunity and allergies affect a large number of people across the globe. Current approaches to these diseases target cell types and pathways that drive disease, but these approaches are not cures and cannot differentiate between healthy cells and disease-causing cells. New immunotherapies that induce potent and selective antigen-specific tolerance is a transformative goal of emerging treatments for autoimmunity and serious allergies.

Myosin 5a in the Urinary Bladder: Localization, Splice Variant Expression, and Functional Role in Neurotransmission.

Dysregulation of neurotransmission is a feature of several prevalent lower urinary tract conditions, but the mechanisms regulating neurotransmitter release in the bladder are not completely understood. The unconventional motor protein, Myosin 5a, transports neurotransmitter-containing synaptic vesicles along actin fibers towards the varicosity membrane, tethering them at the active zone prior to reception of a nerve impulse. Our previous studies indicated that Myosin 5a is expressed and functionally relevant in the peripheral nerves of visceral organs such as the stomach and the .

Spatial delivery of immune cues to lymph nodes to define therapeutic outcomes in cancer vaccination.

Recently approved cancer immunotherapies - including CAR-T cells and cancer vaccination, - show great promise. However, these technologies are hindered by the complexity and cost of isolating and engineering patient cells . Lymph nodes (LNs) are key tissues that integrate immune signals to coordinate adaptive immunity.

Biomaterial-enabled induction of pancreatic-specific regulatory T cells through distinct signal transduction pathways.

Autoimmune diseases-where the immune system mistakenly targets self-tissue-remain hindered by non-specific therapies. For example, even molecularly specific monoclonal antibodies fail to distinguish between healthy cells and self-reactive cells. An experimental therapeutic approach involves delivery of self-molecules targeted by autoimmunity, along with immune modulatory signals to produce regulatory T cells (T) that selectively stop attack of host tissue.

Optical properties of dissolved organic matter highlight peatland-like properties in a constructed wetland.

Constructing novel peatland ecosystems can help to restore the long-term carbon accumulating properties of northern soil systems that have been lost through resource extraction. Although mining companies are legally required to restore landscapes following extraction, there are limited tools to evaluate the effectiveness of restoring peat accumulating landscapes. This study analyzed the spatial patterns of the first seven years (n = 575) of dissolved organic matter (DOM) optical characteristics from a pilot watershed built to restore boreal plains peatlands on a former open pit oil sands mine.

Energy and carbon fluxes from an oil sands pit lake.

Currently, post-mining landscape plans in the Athabasca Oil Sand Region include large watersheds terminating in pit lakes. In 2012, Base Mine Lake (BML), was constructed with the aim of demonstrating technologies associated with lake reclamation in the region. This paper examines the first 6.

Self-Assembly as a Molecular Strategy to Improve Immunotherapy.

Immunotherapies harness an individual's immune system to battle diseases such as cancer and autoimmunity. During cancer, the immune system often fails to detect and destroy cancerous cells, whereas during autoimmune disease, the immune system mistakenly attacks self-tissue. Immunotherapies can help guide more effective responses in these settings, as evidenced by recent advances with monoclonal antibodies and adoptive cell therapies.

Comparison of conventional chest x ray with a novel projection technique for ultra-low dose CT.

Purpose: To compare a novel thick-slab projection technique for ultra-low dose computed tomography (CT; thoracic tomogram) with conventional chest x ray with respect to 13 diagnostic categories.

Methods: With the approval of the institutional ethics board, a dataset was retrospectively collected of 22 consecutive patients who had undergone a clinically requested emergency room conventional chest x ray (CXR) and a same-day standard-of-care non-contrast CT. Scanner specific noise was added to the CT images to simulate a target dose of 0.

HLA-C expression level in both unstimulated and stimulated human umbilical vein endothelial cells is defined by allotype.

Human leukocyte antigens (HLA) are present on the surface of all nucleated cells, with the level of expression dependent on the particular HLA locus, the cell type and cellular activation state. Human umbilical vein endothelial cells (HUVECs) are easily isolated from umbilical cords and may aid our understanding of HLA expression on the vascular endothelium in the setting of transplantation. Endothelial cells on the donor-recipient interface form the barrier between transplanted organs and the host immune system.

HLA expression levels of unstimulated and cytokine stimulated human umbilical vein endothelial cells.

Transplant rejection occurs following recipient recognition of mismatched HLA on donor tissue, but active rejection is dependent not only upon the severity of the T cell or alloantibody response, but also upon the cell surface expression of target HLA molecules. To investigate the variation in HLA expression using a model of endothelium, human umbilical vein endothelial cell (HUVEC) cultures were generated from 48 umbilical cords donated consecutively following planned caesarean section. HUVECs were stimulated using the cytokines tumour necrosis factor alpha and interferon gamma and HLA expression of unstimulated and stimulated cells determined using flow cytometry.

Bistable composite helices with thermal effects.

Morphing technologies use large, seamless changes in the shape of a structure to enable multi-functionality and reconfigurability. Several industrial sectors could benefit from morphing structures, including medical, energy and aerospace which require lightweight, simple and reliable solutions. Composite materials are key to lightweight morphing technologies due to their increased strength- and stiffness-to-mass ratios, stiffness tailorability and excellent fatigue properties, all of which reduce the mass and complexity of these types of structures.

Factors affecting HLA expression: A review.

The detection and semiquantitative measurement of circulating human leucocyte antigen (HLA)-specific antibodies is essential for the management of patients before and after transplantation. In addition, the pretransplant cross-match to assess the reactivity of recipient HLA antibody against donor lymphocytes has long been the gold standard to prevent hyperacute rejection. Whilst both of these tests assume that recipient HLA-specific antibody is the only variable in the assessment of transplant risk, this is not the case.

Climate-phenology-hydrology interactions in northern high latitudes: Assessing the value of remote sensing data in catchment ecohydrological studies.

We assessed the hydrological implications of climate effects on vegetation phenology in northern environments by fusion of data from remote-sensing and local catchment monitoring. Studies using satellite data have shown earlier and later dates for the start (SOS) and end of growing seasons (EOS), respectively, in the Northern Hemisphere over the last 3 decades. However, estimates of the change greatly depend on the satellite data utilized.

Using stable isotopes to estimate travel times in a data-sparse Arctic catchment: Challenges and possible solutions.

Use of isotopes to quantify the temporal dynamics of the transformation of precipitation into run-off has revealed fundamental new insights into catchment flow paths and mixing processes that influence biogeochemical transport. However, catchments underlain by permafrost have received little attention in isotope-based studies, despite their global importance in terms of rapid environmental change. These high-latitude regions offer limited access for data collection during critical periods (e.

Heat as a groundwater tracer in shallow and deep heterogeneous media: Analytical solution, spreadsheet tool, and field applications.

Groundwater flow advects heat, and thus, the deviation of subsurface temperatures from an expected conduction-dominated regime can be analysed to estimate vertical water fluxes. A number of analytical approaches have been proposed for using heat as a groundwater tracer, and these have typically assumed a homogeneous medium. However, heterogeneous thermal properties are ubiquitous in subsurface environments, both at the scale of geologic strata and at finer scales in streambeds.

Seven temperate terrestrial planets around the nearby ultracool dwarf star TRAPPIST-1.

One aim of modern astronomy is to detect temperate, Earth-like exoplanets that are well suited for atmospheric characterization. Recently, three Earth-sized planets were detected that transit (that is, pass in front of) a star with a mass just eight per cent that of the Sun, located 12 parsecs away. The transiting configuration of these planets, combined with the Jupiter-like size of their host star-named TRAPPIST-1-makes possible in-depth studies of their atmospheric properties with present-day and future astronomical facilities.