Metal Hydride Component Design (MHy-CoDe) Tool for the Selection of Hydrides in Thermal Systems

A system has been developed to enable the targeted down-selection of an extensive database of metal hydrides to identify the most promising materials for use in thermal systems. The materials’ database contains over 300 metal hydrides with various physical and thermodynamic properties included for each material. Submodels for equilibrium pressure, thermophysical data, and default properties are used to predict the behavior of each material within the given system. The application used at this time is a stationary combined heat and power system containing a hightemperature proton exchange membrane (PEM) fuel cell, a hot water tank, and two metal hydride beds used as a heat pump to increase the efficiency of a natural gas system. The targeted down-selection for this system focuses on the system’s coefficient of performance (COP) for each potential pair and the corresponding sensitivity of the COP and has been used to identify the top 20 pairs, with COPs \u3e1.3, for use in this application

Bedrijfsuitkomsten in de Nederlandse particuliere bosbouw over 2004

Annual overview of yields, costs and farm results of private forestry holdings with more than 5 hectares of forest, based on an accountancy network consisting of about 150 holdings. This edition contains the results for 2004 and previous years, specified by area of forest and region. In addition, the yield prices for wood and the size of wood sales are shown. Finally, this report further specifies costs and yields by the functions private forestry companies serve, such as wood production, nature conservation, recreation and landscape, and game management.Resource /Energy Economics and Policy,

Transition transferases prime bacterial capsule polymerization

Capsules are long-chain carbohydrate polymers that envelop the surfaces of many bacteria, protecting them from host immune responses. Capsule biosynthesis enzymes are potential drug targets and valuable biotechnological tools for generating vaccine antigens. Despite their importance, it remains unknown how structurally variable capsule polymers of Gram-negative pathogens are linked to the conserved glycolipid anchoring these virulence factors to the bacterial membrane. Using Actinobacillus pleuropneumoniae as an example, we demonstrate that CpsA and CpsC generate a poly(glycerol-3-phosphate) linker to connect the glycolipid with capsules containing poly(galactosylglycerol-phosphate) backbones. We reconstruct the entire capsule biosynthesis pathway in A. pleuropneumoniae serotypes 3 and 7, solve the X-ray crystal structure of the capsule polymerase CpsD, identify its tetratricopeptide repeat domain as essential for elongating poly(glycerol-3-phosphate) and show that CpsA and CpsC stimulate CpsD to produce longer polymers. We identify the CpsA and CpsC product as a wall teichoic acid homolog, demonstrating similarity between the biosynthesis of Gram-positive wall teichoic acid and Gram-negative capsules

The Tumor Immune Landscape and Architecture of Tertiary Lymphoid Structures in Urothelial Cancer

Candidate immune biomarkers have been proposed for predicting response to immunotherapy in urothelial cancer (UC). Yet, these biomarkers are imperfect and lack predictive power. A comprehensive overview of the tumor immune contexture, including Tertiary Lymphoid structures (TLS), is needed to better understand the immunotherapy response in UC. We analyzed tumor sections by quantitative multiplex immunofluorescence to characterize immune cell subsets in various tumor compartments in tumors without pretreatment and tumors exposed to preoperative anti-PD1/CTLA-4 checkpoint inhibitors (NABUCCO trial). Pronounced immune cell presence was found in UC invasive margins compared to tumor and stroma regions. CD8+PD1+ T-cells were present in UC, particularly following immunotherapy. The cellular composition of TLS was assessed by multiplex immunofluorescence (CD3, CD8, FoxP3, CD68, CD20, PanCK, DAPI) to explore specific TLS clusters based on varying immune subset densities. Using a k-means clustering algorithm, we found five distinct cellular composition clusters. Tumors unresponsive to anti-PD-1/CTLA-4 immunotherapy showed enrichment of a FoxP3+ T-cell-low TLS cluster after treatment. Additionally, cluster 5 (macrophage low) TLS were significantly higher after pre-operative immunotherapy, compared to untreated tumors. We also compared the immune cell composition and maturation stages between superficial (submucosal) and deeper TLS, revealing that superficial TLS had more pronounced T-helper cells and enrichment of early TLS than TLS located in deeper tissue. Furthermore, superficial TLS displayed a lower fraction of secondary follicle like TLS than deeper TLS. Taken together, our results provide a detailed quantitative overview of the tumor immune landscape in UC, which can provide a basis for further studies

The clonal relation of primary upper urinary tract urothelial carcinoma and paired urothelial carcinoma of the bladder

The risk of developing urothelial carcinoma of the bladder (UCB) in patients treated by radical nephroureterectomy (RNU) for an upper urinary tract urothelial carcinoma (UTUC) is 22% to 47% in the 2 years after surgery. Subject of debate remains whether UTUC and the subsequent UCB are clonally related or represent separate origins. To investigate the clonal relationship between both entities, we performed targeted DNA sequencing of a panel of 41 genes on matched normal and tumor tissue of 15 primary UTUC patients treated by RNU who later developed 19 UCBs. Based on the detected tumor-specific DNA aberrations, the paired UTUC and UCB(s) of 11 patients (73.3%) showed a clonal relation, whereas in four patients the molecular results did not indicate a clear clonal relationship. Our results support the hypothesis that UCBs following a primary surgically resected UTUC are predominantly clonally derived recurrences and not separate entities

Sensory hypersensitivity after acquired brain injury: the patient perspective

Purpose: Sensory hypersensitivity is a frequently reported complaint after acquired brain injury (ABI). This study explores patients’ perceptions of sensory hypersensitivity following ABI and its impact on everyday life. Materials and Methods: Semi-structured interviews were conducted with 18 patients with ABI (stroke, brain tumour, TBI) who reported complaints of sensory hypersensitivity. Interview data were analysed using qualitative thematic analysis. Results: Six themes emerged from the data: (1) definition of sensory hypersensitivity, relating to individual perceptions of sensory hypersensitivity; (2) type of sensory stimuli, relating to the variety of stimuli that patients may be sensitive to; (3) course, relating to changes in sensory hypersensitivity following ABI; (4) fatigue, relating to its association with sensory hypersensitivity; (5) consequences of sensory hypersensitivity, relating to the physical, social and emotional impact of sensory hypersensitivity on patients’ lives; and (6) coping strategies, relating to behaviours used to cope with sensory hypersensitivity. Conclusions: Sensory hypersensitivity can have a major impact on patients’ physical well-being, return to work and (social) participation after ABI. Characteristics of sensory hypersensitivity vary between patients with ABI. To develop treatments for sensory hypersensitivity, future studies should focus on cognitive (e.g., filtering information) and psychological factors (e.g., coping) in relation to sensory hypersensitivity

Treatment success for overactive bladder with urinary urge incontinence refractory to oral antimuscarinics: a review of published evidence

<p>Abstract</p> <p>Background</p> <p>Treatment options for overactive bladder (OAB) with urinary urge incontinence (UUI) refractory to oral antimuscarinics include: botulinum toxin type A (BoNTA), sacral neuromodulation (SNM), and augmentation cystoplasty (AC). A standard treatment success metric that can be used in both clinical and economic evaluations of the above interventions has not emerged. Our objective was to conduct a literature review and synthesis of published measures of treatment success for OAB with UUI interventions and to identify a treatment success outcome.</p> <p>Methods</p> <p>We performed a literature review of primary studies that used a definition of treatment success in the OAB with UUI population receiving BoNTA, SNM, or AC. The recommended success outcome was compared to generic and disease-specific health-related quality-of-life (HRQoL) measures using data from a BoNTA treatment study of neurogenic incontinent patients.</p> <p>Results</p> <p>Across all interventions, success outcomes included: complete continence (n = 23, 44%), ≥ 50% improvement in incontinence episodes (n = 16, 31%), and subjective improvement (n = 13, 25%). We recommend the OAB with UUI treatment success outcome of ≥ 50% improvement in incontinence episodes from baseline. Using data from a neurogenic BoNTA treatment study, the average change in the Incontinence Quality of Life questionnaire was 8.8 (95% CI: -4.7, 22.3) higher for those that succeeded (N = 25) versus those that failed (N = 26). The average change in the SF-6D preference score was 0.07 (95% CI: 0.02, 0.12) higher for those that succeeded versus those that failed.</p> <p>Conclusion</p> <p>A treatment success definition that encompasses the many components of underlying OAB with UUI symptoms is currently not practical as a consequence of difficulties in measuring urgency. The treatment success outcome of ≥ 50% improvement in incontinence episodes was associated with a clinically meaningful improvement in disease-specific HRQoL for those with neurogenic OAB with UUI. The recommended success definition is less restrictive than a measure such as complete continence but includes patients who are satisfied with treatment and experience meaningful improvement in symptoms. A standardized measure of treatment success will be useful in clinical and health economic applications.</p