Denmark is striving towards 100% renewable energy system in 2050. Residential heat pumps are expected to be a part of that system.
We propose two novel approaches to improve the representation of ...residential heat pumps: Coefficients of performance (COPs) are modelled as dependent on air and ground temperature while installation of ground-source heat pumps is constrained by available ground area. In this study, TIMES-DK model is utilised to test the effects of improved modelling of residential heat pumps on the Danish energy system until 2050.
The analysis of the Danish energy system was done for politically agreed targets which include: at least 50% of electricity consumption from wind power starting from 2020, fossil fuel free heat and power sector from 2035 and 100% renewable energy system starting from 2050. Residential heat pumps supply around 25% of total residential heating demand after 2035. The improved modelling of residential heat pumps proved to have influence on the results. First, it would be optimal to invest in more ground-source heat pumps, but there is not enough available ground area. Second, the total system costs are higher when COPs are modelled as temperature-dependent compared to fixed COPs over a year.
•Temperature-dependant coefficients of performance are used.•Spatial analysis revealed is there enough space for ground-source heat pumps.•TIMES-DTU model of the Danish energy system is utilised for analysis until 2050.•Heat pumps are producing 24–28% of residential heating demand after 2035.•More ground-source heat pumps would be optimal, but there is not enough ground.
The benefit of Ginkgo biloba has been discussed controversially. The aim of this review was to assess the effects of Ginkgo biloba in Alzheimer's disease as well as vascular and mixed dementia ...covering a variety of outcome domains.
We searched MEDLINE, EMBASE, the Cochrane databases, CINAHL and PsycINFO for controlled trials of ginkgo for Alzheimer's, vascular or mixed dementia. Studies had to be of a minimum of 12 weeks duration with at least ten participants per group. Clinical characteristics and outcomes were extracted. Meta-analysis results were expressed as risk ratios or standardized mean differences (SMD) in scores.
Nine trials using the standardized extract EGb761(R) met our inclusion criteria. Trials were of 12 to 52 weeks duration and included 2372 patients in total. In the meta-analysis, the SMDs in change scores for cognition were in favor of ginkgo compared to placebo (-0.58, 95% confidence interval CI -1.14; -0.01, p = 0.04), but did not show a statistically significant difference from placebo for activities in daily living (ADLs) (SMD = -0.32, 95% CI -0.66; 0.03, p = 0.08). Heterogeneity among studies was high. For the Alzheimer subgroup, the SMDs for ADLs and cognition outcomes were larger than for the whole group of dementias with statistical superiority for ginkgo also for ADL outcomes (SMD = -0.44, 95% CI -0.77; -0.12, p = 0.008). Drop-out rates and side effects did not differ between ginkgo and placebo. No consistent results were available for quality of life and neuropsychiatric symptoms, possibly due to the heterogeneity of the study populations.
Ginkgo biloba appears more effective than placebo. Effect sizes were moderate, while clinical relevance is, similar to other dementia drugs, difficult to determine.
Advances in covalent kinase inhibitors Abdeldayem, Ayah; Raouf, Yasir S; Constantinescu, Stefan N ...
Chemical Society reviews,
05/2020, Letnik:
49, Številka:
9
Journal Article
Recenzirano
Over the past decade, covalent kinase inhibitors (CKI) have seen a resurgence in drug discovery. Covalency affords a unique set of advantages as well as challenges relative to their non-covalent ...counterpart. After reversible protein target recognition and binding, covalent inhibitors irreversibly modify a proximal nucleophilic residue on the protein via reaction with an electrophile. To date, the acrylamide group remains the predominantly employed electrophile in CKI development, with its incorporation in the majority of clinical candidates and FDA approved covalent therapies. Nonetheless, in recent years considerable efforts have ensued to characterize alternative electrophiles that exhibit irreversible or reversibly covalent binding mechanisms towards cysteine thiols and other amino acids. This review article provides a comprehensive overview of CKIs reported in the literature over a decade period, 2007-2018. Emphasis is placed on the rationale behind warhead choice, optimization approach, and inhibitor design. Current FDA approved CKIs are also highlighted, in addition to a detailed analysis of the common trends and themes observed within the listed data set.
The prevalence of autism spectrum disorders (ASDs) has increased markedly in recent decades, which researchers have suggested could be caused in part by nonetiologic factors such as changes in ...diagnosis reporting practices. To our knowledge, no study has quantified the degree to which changes in reporting practices might explain this increase. Danish national health registries have undergone a change in diagnostic criteria in 1994 and the inclusion of outpatient contacts to health registries in 1995.
To quantify the effect of changes in reporting practices in Denmark on reported ASD prevalence.
We used a population-based birth cohort approach that includes information on all individuals with permanent residence in Denmark. We assessed all children born alive from January 1, 1980, through December 31, 1991, in Denmark (n=677915). The children were followed up from birth until ASD diagnosis, death, emigration, or the end of follow-up on December 31, 2011, whichever occurred first. The analysis uses a stratified Cox proportional hazards regression model with the changes in reporting practices modeled as time-dependent covariates.
The change in diagnostic criteria in 1994 and the inclusion of outpatient diagnoses in 1995.
Autism spectrum disorders.
For Danish children born during the study period, 33% (95% CI, 0%-70%) of the increase in reported ASD prevalence could be explained by the change in diagnostic criteria alone; 42% (95% CI, 14%-69%), by the inclusion of outpatient contacts alone; and 60% (95% CI, 33%-87%), by the change in diagnostic criteria and the inclusion of outpatient contacts.
Changes in reporting practices can account for most (60%) of the increase in the observed prevalence of ASDs in children born from 1980 through 1991 in Denmark. Hence, the study supports the argument that the apparent increase in ASDs in recent years is in large part attributable to changes in reporting practices.
STAT3 and STAT5 proteins are oncogenic downstream mediators of the JAK-STAT pathway. Deregulated STAT3 and STAT5 signaling promotes cancer cell proliferation and survival in conjunction with other ...core cancer pathways. Nuclear phosphorylated STAT3 and STAT5 regulate cell-type-specific transcription profiles via binding to promoter elements and exert more complex functions involving interaction with various transcriptional coactivators or corepressors and chromatin remodeling proteins. The JAK-STAT pathway can rapidly reshape the chromatin landscape upon cytokine, hormone, or growth factor stimulation and unphosphorylated STAT proteins also appear to be functional with respect to regulating chromatin accessibility. Notably, cancer genome landscape studies have implicated mutations in various epigenetic modifiers as well as the JAK-STAT pathway as underlying causes of many cancers, particularly acute leukemia and lymphomas. However, it is incompletely understood how mutations within these pathways can interact and synergize to promote cancer. We summarize the current knowledge of oncogenic STAT3 and STAT5 functions downstream of cytokine signaling and provide details on prerequisites for DNA binding and gene transcription. We also discuss key interactions of STAT3 and STAT5 with chromatin remodeling factors such as DNA methyltransferases, histone modifiers, cofactors, corepressors, and other transcription factors.
Myeloproliferative neoplasms (MPNs) are clonal disorders characterized by excessive production of mature blood cells. In the majority of classic MPN—polycythemia vera, essential thrombocythemia, and ...primitive myelofibrosis—driver oncogenic mutations affecting Janus kinase 2 (JAK2) or MPL lead to constitutive activation of cytokine-regulated intracellular signaling pathways. LNK, c-CBL, or SOCSs (all negative regulators of signaling pathways), although infrequently targeted, may either drive the disease or synergize with JAK2 and MPL mutations. IZF1 deletions or TP53 mutations are mainly found at transformation phases and are present at greater frequency than in de novo acute myeloid leukemias. Loss-of-function mutations in 3 genes involved in epigenetic regulation, TET2, ASXL1, and EZH2, may be early events preceding JAK2V617F but may also occur late during disease progression. They are more frequently observed in PMF than PV and ET and are also present in other types of malignant myeloid diseases. A likely hypothesis is that they facilitate clonal selection, allowing the dominance of the JAK2V617F subclone during the chronic phase and, together with cooperating mutations, promote blast crisis. Their precise roles in hematopoiesis and in the pathogenesis of MPN, as well as their prognostic impact and potential as a therapeutic target, are currently under investigation.
As the solar photovoltaic market booms, so will the volume of photovoltaic (PV) systems entering the waste stream. The same is forecast for lithium-ion batteries from electric vehicles, which at the ...end of their automotive life can be given a second life by serving as stationary energy storage units for renewable energy sources, including solar PV. The main objective of this paper is to systematically review the “state-of-the-art” research on the solar PV value chain (i.e., from product design to product end-of-life), including its main stages, processes, and stakeholder relationships, in order to identify areas along the value chain where circular strategies could be implemented, thereby advancing the transition of the PV industry towards circularity. To achieve this goal, we conducted a systematic literature review of 148 peer-reviewed articles, published in English between 2000 and 2020. Results show the PV value chain has been studied from a forward flow supply chain perspective and mostly from a technological point of view, with little regard for circular design, circular business models, and PV reuse. This article thus takes an integrated value chain perspective, introduces some of the barriers to circularity that industry players face, and argues that these barriers represent future opportunities for incumbent and new entrants to innovate within a circular PV industry.
Abstract
Two univariate indices of the Madden–Julian oscillation (MJO) based on outgoing longwave radiation (OLR) are developed to track the convective component of the MJO while taking into account ...the seasonal cycle. These are compared with the all-season Real-time Multivariate MJO (RMM) index of Wheeler and Hendon derived from a multivariate EOF of circulation and OLR. The gross features of the OLR and circulation of composite MJOs are similar regardless of the index, although RMM is characterized by stronger circulation. Diversity in the amplitude and phase of individual MJO events between the indices is much more evident; this is demonstrated using examples from the Dynamics of the Madden–Julian Oscillation (DYNAMO) field campaign and the Year of Tropical Convection (YOTC) virtual campaign. The use of different indices can lead to quite disparate conclusions concerning MJO timing and strength, and even as to whether or not an MJO has occurred. A disadvantage of using daily OLR as an EOF basis is that it is a much noisier field than the large-scale circulation, and filtering is necessary to obtain stable results through the annual cycle. While a drawback of filtering is that it cannot be done in real time, a reasonable approximation to the original fully filtered index can be obtained by following an endpoint smoothing method. When the convective signal is of primary interest, the authors advocate the use of satellite-based metrics for retrospective analysis of the MJO for individual cases, as well as for the analysis of model skill in initiating and evolving the MJO.
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