Heat pipe collectors with overheating prevention in a cost-optimized system concept: Monitoring of system performance and stagnation loads under real conditions

Heat pipe collectors can significantly reduce stagnation loads in solar thermal systems due to their thermophysical properties. The paper experimentally investigates a novel system concept based on both evacuated tube collectors and flat-plate collectors with overheating prevention. Due to the resulting temperature limitation in the collector, the use of polymeric pipes as well as a significantly downsized expansion volume is possible. We implemented this concept in five demonstration plants and monitored their behavior over more than one year of operation. Both domestic hot water systems and combi-systems with space heating support in residential and office buildings are under consideration. The measured collector performance in all the systems matches the theoretical collector efficiency curve with a maximum deviation of five percentage points. Depending on the individual system configurations, the specific annual yield ranges between 174 kWh/m² and 445 kWh/m². During stagnation, we report a maximum temperature between 105 °C and 127 °C. In comparison to state-of-the-art systems, the maximum temperature in the solar circuit is 80–100 K lower and evaporation does not occur. The approach leads to reductions in investment costs of up to 16% and can significantly decrease the annual maintenance effort. Assuming a system lifetime of 25 years, we estimate a cost reduction of up to 22% in Levelized Cost of Heat (LCoH) compared to common system configurations

Economic impacts of EU clean air policies assessed in a CGE framework

This paper assesses the macroeconomic and sectoral impacts of the “Clean Air Policy Package” proposed by the European Commission in December 2013. The analysis incorporates both the expenditures necessary to implement the policy by 2030 and the resulting positive feedback effects on human health and crop production. A decomposition analysis identifies the important drivers of the macroeconomic impacts. We show that while expenditure on pollution abatement is a cost for the abating sectors, it also generates an increased demand for the sectors that produce the goods required for pollution abatement. Moreover, we find that positive feedback effects, particularly those related to health can offset the resource costs associated to the clean air policy and result in positive macroeconomic impacts for the economy of the European Union

The Whistler\u27s Mother-In-Law

Photograph of a manhttps://scholarsjunction.msstate.edu/cht-sheet-music/10562/thumbnail.jp

IgH gene rearrangements as plasma biomarkers in Non-Hodgkin's Lymphoma patients

New biomarkers with improved accuracy could be helpful for monitoring disease in patients with Non-Hodgkin's lymphomas (NHL). Towards this end, we have explored the feasibility of identifying the sequence of rearranged IgH genes using next-generation sequencing, then using PCR to detect specific rearranged DNA fragments in patients' plasma. By capturing and sequencing the IgH genomic regions (IgCap), we were able to detect and precisely determine the sequence of rearranged IgH loci in the tumors of three NHL patients. Moreover, circulating rearranged DNA fragments could be identified in the plasma of all three patients. Even in cases wherein tumor biopsies were unavailable, we were able to use the IgH capture approach to identify rearranged DNA loci in the plasma of 8 of 14 patients. IgCap may enable a more informed management of selected patients with NHL and other B-cell malignancies in the future

Assessment of Covalently Binding Warhead Compounds in the Validation of the Cytomegalovirus Nuclear Egress Complex as an Antiviral Target

Herpesviral nuclear egress is a regulated process of viral capsid nucleocytoplasmic release. Due to the large capsid size, a regular transport via the nuclear pores is unfeasible, so that a multistageregulated export pathway through the nuclear lamina and both leaflets of the nuclear membrane has evolved. This process involves regulatory proteins, which support the local distortion of the nuclear envelope. For human cytomegalovirus (HCMV), the nuclear egress complex (NEC) is determined by the pUL50–pUL53 core that initiates multicomponent assembly with NEC-associated proteins and capsids. The transmembrane NEC protein pUL50 serves as a multi-interacting determinant that recruits regulatory proteins by direct and indirect contacts. The nucleoplasmic core NEC component pUL53 is strictly associated with pUL50 in a structurally defined hook-into-groove complex and is considered as the potential capsid-binding factor. Recently, we validated the concept of blocking the pUL50–pUL53 interaction by small molecules as well as cell-penetrating peptides or an overexpression of hook-like constructs, which can lead to a pronounced degree of antiviral activity. In this study, we extended this strategy by utilizing covalently binding warhead compounds, originally designed as binders of distinct cysteine residues in target proteins, such as regulatory kinases. Here, we addressed the possibility that warheads may likewise target viral NEC proteins, building on our previous crystallization-based structural analyses that revealed distinct cysteine residues in positions exposed from the hook-into-groove binding surface. To this end, the antiviral and NEC-binding properties of a selection of 21 warhead compounds were investigated. The combined findings are as follows: (i) warhead compounds exhibited a pronounced anti-HCMV potential in cell-culturebased infection models; (ii) computational analysis of NEC primary sequences and 3D structures revealed cysteine residues exposed to the hook-into-groove interaction surface; (iii) several of the active hit compounds exhibited NEC-blocking activity, as shown at the single-cell level by confocal imaging; (iv) the clinically approved warhead drug ibrutinib exerted a strong inhibitory impact on the pUL50–pUL53 core NEC interaction, as demonstrated by the NanoBiT assay system; and (v) the generation of recombinant HCMV ∆UL50-ΣUL53, allowing the assessment of viral replication under conditional expression of the viral core NEC proteins, was used for characterizing viral replication and a mechanistic evaluation of ibrutinib antiviral efficacy. Combined, the results point to a ratelimiting importance of the HCMV core NEC for viral replication and to the option of exploiting this determinant by the targeting of covalently NEC-binding warhead compounds

Fluorescent-Probe Characterization for Pore-Space Mapping with Single-Particle Tracking

Porous solids often contain complex pore networks with pores of various sizes. Tracking individual fluorescent probes as they diffuse through porous materials can be used to characterize pore networks at tens of nanometers resolution. However, understanding the motion behavior of fluorescent probes in confinement is crucial to reliably derive pore network properties. Here, we introduce well-defined lithography-made model pores developed to study probe behavior in confinement. We investigated the influence of probe-host interactions on diffusion and trapping of confined single-emitter quantum-dot probes. Using the pH-responsiveness of the probes, we were able to largely suppress trapping at the pore walls. This enabled us to define experimental conditions for mapping of the accessible pore space of a one-dimensional pore array as well as a real-life polymerization-catalyst-support particle

An Antiherpesviral Host-Directed Strategy Based on CDK7 Covalently Binding Drugs: Target-Selective, Picomolar-Dose, Cross-Virus Reactivity

The repertoire of currently available antiviral drugs spans therapeutic applications against a number of important human pathogens distributed worldwide. These include cases of the pandemic severe acute respiratory coronavirus type 2 (SARS-CoV-2 or COVID-19), human immunodeficiency virus type 1 (HIV-1 or AIDS), and the pregnancy- and posttransplant-relevant human cytomegalovirus (HCMV). In almost all cases, approved therapies are based on direct-acting antivirals (DAAs), but their benefit, particularly in long-term applications, is often limited by the induction of viral drug resistance or side effects. These issues might be addressed by the additional use of host-directed antivirals (HDAs). As a strong input from long-term experiences with cancer therapies, host protein kinases may serve as HDA targets of mechanistically new antiviral drugs. The study demonstrates such a novel antiviral strategy by targeting the major virus-supportive host kinase CDK7. Importantly, this strategy focuses on highly selective, 3D structure-derived CDK7 inhibitors carrying a warhead moiety that mediates covalent target binding. In summary, the main experimental findings of this study are as follows: (1) the in vitro verification of CDK7 inhibition and selectivity that confirms the warhead covalent-binding principle (by CDK-specific kinase assays), (2) the highly pronounced antiviral efficacies of the hit compounds (in cultured cell-based infection models) with half-maximal effective concentrations that reach down to picomolar levels, (3) a particularly strong potency of compounds against strains and reporter-expressing recombinants of HCMV (using infection assays in primary human fibroblasts), (4) additional activity against further herpesviruses such as animal CMVs and VZV, (5) unique mechanistic properties that include an immediate block of HCMV replication directed early (determined by Western blot detection of viral marker proteins), (6) a substantial drug synergism in combination with MBV (measured by a Loewe additivity fixed-dose assay), and (7) a strong sensitivity of clinically relevant HCMV mutants carrying MBV or ganciclovir resistance markers. Combined, the data highlight the huge developmental potential of this host-directed antiviral targeting concept utilizing covalently binding CDK7 inhibitors

Chancengerechtigkeit durch Bildung – Chancengerechtigkeit in der Bildung (Auszug)

Der hier mit freundlicher Genehmigung des AWO Bundesverbands abgedruckte Text ist ein Auszug aus der Broschüre: Arbeiterwohlfahrt Bundesverband (Hrsg.): Standpunkte 2006. Chancengerechtigkeit durch Bildung – Chancengerechtigkeit in der Bildung, Bonn 2006. Unser Bildungssystem für die Kinder im Alter von 6 bis 16 Jahren wird den Herausforderungen der Zukunft nicht gerecht. Ein Umsteuern ist dringend notwendig, da ohne Bildung der Wandel in die Wissensgesellschaft nicht zu bewältigen ist. Bildung, Qualifikation und Kompetenzen und das Erlernen von Diskurs- und Konfliktfähigkeit entscheiden über die beruflichen und gesellschaftlichen Chancen eines jeden Menschen und davon abhängig über seine Zukunftschancen. Bildung bedeutet Entwicklung der Persönlichkeit, der Identität. Bildung bedeutet aber auch, die gemeinschaftsfähige Persönlichkeit zu gestalten. Und somit bekommt Bildung gerade in der Lebensphase der 6- bis 16-Jährigen über die eher traditionelle Dimension hinaus auch einen emanzipatorischen Charakter. Wenn Bildung also für den Einzelnen diese entscheidende Rolle spielt, dann bekommt die öffentliche Verantwortung für dieses Bildungswesen eine ganz zentrale Bedeutung. (DIPF/Orig.

A cluster randomized trial to improve adherence to evidence-based guidelines on diabetes and reduce clinical inertia in primary care physicians in Belgium: study protocol [NTR 1369]

Contains fulltext : 70617.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: Most quality improvement programs in diabetes care incorporate aspects of clinician education, performance feedback, patient education, care management, and diabetes care teams to support primary care physicians. Few studies have applied all of these dimensions to address clinical inertia. AIM: To evaluate interventions to improve adherence to evidence-based guidelines for diabetes and reduce clinical inertia in primary care physicians. DESIGN: Two-arm cluster randomized controlled trial. PARTICIPANTS: Primary care physicians in Belgium. INTERVENTIONS: Primary care physicians will be randomly allocated to 'Usual' (UQIP) or 'Advanced' (AQIP) Quality Improvement Programs. Physicians in the UQIP will receive interventions addressing the main physician, patient, and office system factors that contribute to clinical inertia. Physicians in the AQIP will receive additional interventions that focus on sustainable behavior changes in patients and providers. OUTCOMES: Primary endpoints are the proportions of patients within targets for three clinical outcomes: 1) glycosylated hemoglobin < 7%; 2) systolic blood pressure differences </=130 mmHg; and 3) low density lipoprotein/cholesterol < 100 mg/dl. Secondary endpoints are individual improvements in 12 validated parameters: glycosylated hemoglobin, low and high density lipoprotein/cholesterol, total cholesterol, systolic blood pressure, diastolic blood pressure, weight, physical exercise, healthy diet, smoking status, and statin and anti-platelet therapy. PRIMARY AND SECONDARY ANALYSIS: Statistical analyses will be performed using an intent-to-treat approach with a multilevel model. Linear and generalized linear mixed models will be used to account for the clustered nature of the data, i.e., patients clustered withinimary care physicians, and repeated assessments clustered within patients. To compare patient characteristics at baseline and between the intervention arms, the generalized estimating equations (GEE) approach will be used, taking the clustered nature of the data within physicians into account. We will also use the GEE approach to test for differences in evolution of the primary and secondary endpoints for all patients, and for patients in the two interventions arms, accounting for within-patient clustering. TRIAL REGISTRATION: number: NTR 1369

Differences in patient outcomes and chronic care management of oral anticoagulant therapy: an explorative study

Contains fulltext : 96817.pdf (publisher's version ) (Open Access)BACKGROUND: The oral anticoagulant therapy - provided to prevent thrombosis - is known to be associated with substantial avoidable hospitalization. Improving the quality of the oral anticoagulant therapy could avoid drug related hospitalizations. Therefore, this study compared the patient outcomes between Dutch anticoagulant clinic (AC) regions taking the variation in chronic care management into account in order to explore whether chronic care management elements could improve the quality of oral anticoagulant therapy. METHODS: Two data sources were combined. The first source was a questionnaire that was send to all ACs in the Netherlands in 2008 (response = 100%) to identify the application of chronic care management elements in the AC regions. The Chronic Care Model of Wagner was used to make the concept of chronic care management operational. The second source was the report of the Dutch National Network of ACs which contains patient outcomes of the ACs. RESULTS: Patient outcomes achieved by the ACs were good, yet differences existed; for instance the percentage of patients in the appropriate therapeutic ranges varied from 67 to 87% between AC regions. Moreover, differences existed in the use of chronic care management elements of the chronic care model, for example 12% of the ACs had multidisciplinary meetings and 58% of the ACs had formal agreements with at least one hospital within their region. Patient outcomes were significantly associated with patient orientation and the number of specialized nurses versus doctors (p-values < 0.05). Furthermore, the overall extent to which chronic care management elements were applied was positively associated with patient outcomes (p-values < 0.05). CONCLUSIONS: Substantial differences in the patient outcomes as well as chronic care management of oral anticoagulant therapy existed. Since our results showed a positive association between overall application of chronic care management and patient outcomes, additional research is needed to fully understand the working mechanism of chronic care management