Impact of different time series aggregation methods on optimal energy system design

Modelling renewable energy systems is a computationally-demanding task due to the high fluctuation of supply and demand time series. To reduce the scale of these, this paper discusses different methods for their aggregation into typical periods. Each aggregation method is applied to a different type of energy system model, making the methods fairly incomparable. To overcome this, the different aggregation methods are first extended so that they can be applied to all types of multidimensional time series and then compared by applying them to different energy system configurations and analyzing their impact on the cost optimal design. It was found that regardless of the method, time series aggregation allows for significantly reduced computational resources. Nevertheless, averaged values lead to underestimation of the real system cost in comparison to the use of representative periods from the original time series. The aggregation method itself, e.g. k means clustering, plays a minor role. More significant is the system considered: Energy systems utilizing centralized resources require fewer typical periods for a feasible system design in comparison to systems with a higher share of renewable feed-in. Furthermore, for energy systems based on seasonal storage, currently existing models integration of typical periods is not suitable

PITX2 gain-of-function induced defects in mouse forelimb development

BACKGROUND: Limb development and patterning originate from a complex interplay between the skeletal elements, tendons, and muscles of the limb. One of the genes involved in patterning of limb muscles is the homeobox transcription factor Pitx2 but its role in forelimb development is uncharacterized. Pitx2 is expressed in the majority of premature presumptive forelimb musculature at embryonic day 12.5 and then maintained throughout embryogenesis to adult skeletal muscle. RESULTS: To further study the role of Pitx2 in forelimb development we have generated transgenic mice that exhibit a pulse of PITX2 over-expression at embryonic day 13.5 and 14.5 in the developing forelimb mesenchyme. These mice exhibit a distal misplacement of the biceps brachii insertion during embryogenesis, which twists the forelimb musculature resulting in severe skeletal malformations. The skeletal malformations have some similarities to the forearm deformities present in Leri-Weill dyschondrosteosis. CONCLUSION: Taken together, the tendon, muscle, and bone anomalies further support a role of Pitx2 in forelimb development and may also shed light on the interaction between the skeletal elements and muscles of the limb during embryogenesis

Are gadolinium-based contrast media really safer than iodinated media for digital subtraction angiography in patients with azotemia?

Gadolinium chelates, intended as intravenous contrast media for magnetic resonance imaging, have been regarded as nonnephrotoxic and recommended to replace iodinated contrast media in patients with azotemia who are undergoing digital subtraction angiography (DSA). High intraarterial doses (up to 220 mmol of gadodiamide) have been used, with a 40% incidence of nephropathy. The authors discourage the use of gadolinium for DSA for several reasons. (a) There exist no randomized studies comparing the nephrotoxic effects of gadolinium-based and iodinated media at equal-attenuating concentrations and doses. (b) Gadolinium-based media are hypertonic, a pathogenetic factor in contrast medium-induced nephropathy after renal angiography, with an osmolality two to seven times that of plasma. Iodinated media in concentrations that are equally attenuating with gadolinium-based media can be made isotonic. (c) In vitro measurements indicate that 0.5 mol/L gadolinium chelates are equally attenuating with 60-80 mg iodine per milliliter at the commonly used 70-90-kV range used for DSA. Thus, 50 mL of 0.5 mol/L gadolinium chelate ( approximately 0.3 mmol/kg in an 80-kg person) would be equally attenuating with a dose of 3-4 g of iodine in an iodinated medium (eg, 50 mL iohexol at 60-80 mg I/mL or 10-13 mL at 300 mg I/mL). (d) By combining these data on attenuation and results of toxicity studies in mice, the general toxicity of gadolinium chelates may be six to 25 times higher than that of equal-attenuating doses of iodinated media at 70-kV DSA. Thus, the authors believe that at equal-attenuating doses for DSA, modern iodinated contrast media should result in a lower toxic load on the body than with presently available gadolinium chelates

Azobenzene-based inhibitors of human carbonic anhydrase II

Aryl sulfonamides are a widely used drug class for the inhibition of carbonic anhydrases. In the context of our program of photochromic pharmacophores we were interested in the exploration of azobenzene-containing sulfonamides to block the catalytic activity of human carbonic anhydrase II (hCAII). Herein, we report the synthesis and in vitro evaluation of a small library of nine photochromic sulfonamides towards hCAII. All molecules are azobenzene-4-sulfonamides, which are substituted by different functional groups in the 4 '-position and were characterized by X-ray crystallography. We aimed to investigate the influence of electrondonating or electron-withdrawing substituents on the inhibitory constant Ki. With the aid of an hCAII crystal structure bound to one of the synthesized azobenzenes, we found that the electronic structure does not strongly affect inhibition. Taken together, all compounds are strong blockers of hCAII with K-i = 25-65 nM that are potentially photochromic and thus combine studies from chemical synthesis, crystallography and enzyme kinetics

The association between BCG scars and self-reported chronic diseases:A cross-sectional observational study within an RCT of Danish health care workers

IntroductionThe live-attenuated vaccines Bacillus Calmette-Guérin (BCG) and Vaccinia have been associated with beneficial non-specific effects. We assessed the prevalence of BCG and Vaccinia vaccine scars in a cohort of Danish health care workers and investigated the association between the presence of vaccine scars and self-reported chronic diseases.MethodsCross-sectional study utilizing baseline data collected during 2020–2021 at enrollment in a BCG trial aiming to assess the effect of BCG vaccination on absenteeism and infectious disease morbidity during the SARS-COV-2 pandemic. In Denmark, Vaccinia was discontinued in 1977, and BCG was phased out in the early 1980s. We used logistic regression analysis (adjusted for sex, birth year, and smoking status) to estimate the association between scar status and chronic diseases, providing adjusted Odds Ratios (aORs) with 95 % Confidence Intervals, for participants born before 1977, and born from 1965 to 1976.ResultsThe cohort consisted of 1218 participants (206 males; 1012 females) with a median age of 47 years (Q1–Q3: 36–56). Among participants born 1965–1976 (n = 403), who experienced the phase-outs, having BCG and/or Vaccinia scar(s) vs. having no vaccine scars yielded an aOR of 0.51 (0.29–0.90) of self-reported chronic disease; an effect primarily driven by BCG. In the same birth cohort, having vaccine scar(s) was most strongly associated with a lower prevalence of chronic respiratory and allergic diseases; the aORs being 0.39 (0.16–0.97) and 0.39 (0.16–0.91), respectively.ConclusionHaving a BCG scar was associated with a lower prevalence of self-reported chronic disease

Distribution patterns of arterial affection and the influence of glucocorticoids on 18 F-fluorodeoxyglucose positron emission tomography/CT in patients with giant cell arteritis

Background Giant cell arteritis (GCA) with the involvement of extracranial vessels is increasingly coming into focus. Isolated aortic involvement in the acute phase of GCA is probably more frequent than estimated because only a minority of patients show typical symptoms. 18 F-fluorodeoxyglucose positron emission tomography/CT (PET/CT) is a reliable imaging tool to diagnose patients with extracranial GCA. The aim of this retrospective study was to quantify arterial involvement at the onset of a newly diagnosed GCA by PET/CT and to evaluate the influence of glucocorticoid (GC) treatment on the diagnostic performance of this imaging technique. Methods The study included 60 patients with GCA at the onset of a GCA. All patients had undergone a PET/CT scan. 44 patients were GC naïve and 16 patients received GC. Results The most affected arteries were the ascending aorta (72%), followed by the brachiocephalic trunk (62%), aortic arch (60%) and descending aorta (60%). The aorta and its branches showed an inflammatory involvement in 83.3% of patients. A singular affection of the aorta and the brachiocephalic trunk was revealed in 20% of cases. GC-naïve patients (95.5%) had more frequently affected arteries compared with GC-treated patients (50%). Conclusion Our study showed the frequent involvement of the thoracic aorta and brachiocephalic trunk in patients with GCA using PET/CT. Since these vascular compartments cannot be visualised by ultrasound, we advocate screening imaging of the aorta with PET/CT when GCA is suspected. Because the use of GC is associated with a marked decrease in the inflamed vascular segment in GCA, PET/CT should be performed as soon as possible

Array-Based DNA Methylation Profiling for Breast Cancer Subtype Discrimination

BACKGROUND: Abnormal DNA methylation is well established for breast cancer and contributes to its progression by silencing tumor suppressor genes. DNA methylation profiling platforms might provide an alternative approach to expression microarrays for accurate breast tumor subtyping. We sought to determine whether the distinction of the inflammatory breast cancer (IBC) phenotype from the non-IBC phenotype by transcriptomics could be sustained by methylomics. METHODOLOGY/PRINCIPAL FINDINGS: We performed methylation profiling on a cohort of IBC (N = 19) and non-IBC (N = 43) samples using the Illumina Infinium Methylation Assay. These results were correlated with gene expression profiles. Methylation values allowed separation of breast tumor samples into high and low methylation groups. This separation was significantly related to DNMT3B mRNA levels. The high methylation group was enriched for breast tumor samples from patients with distant metastasis and poor prognosis, as predicted by the 70-gene prognostic signature. Furthermore, this tumor group tended to be enriched for IBC samples (54% vs. 24%) and samples with a high genomic grade index (67% vs. 38%). A set of 16 CpG loci (14 genes) correctly classified 97% of samples into the low or high methylation group. Differentially methylated genes appeared to be mainly related to focal adhesion, cytokine-cytokine receptor interactions, Wnt signaling pathway, chemokine signaling pathways and metabolic processes. Comparison of IBC with non-IBC led to the identification of only four differentially methylated genes (TJP3, MOGAT2, NTSR2 and AGT). A significant correlation between methylation values and gene expression was shown for 4,981 of 6,605 (75%) genes. CONCLUSIONS/SIGNIFICANCE: A subset of clinical samples of breast cancer was characterized by high methylation levels, which coincided with increased DNMT3B expression. Furthermore, an association was observed with molecular signatures indicative of poor patient prognosis. The results of the current study also suggest that aberrant DNA methylation is not the main force driving the molecular biology of IBC

Anharmonic Strong-Coupling Effects at the Origin of the Charge Density Wave in CsV3_3Sb5_5

The formation of charge density waves (CDW) is a long-standing open problem particularly in dimensions higher than one. Various observations in the vanadium antimonides discovered recently, such as the missing Kohn anomaly in the acoustic phonons or the latent heat at the transition $T_{\rm CDW}$ = 95 K , further underpin this notion. Here, we study the Kagome metal CsV$_3$Sb$_5$ using polarized inelastic light scattering. The electronic energy gap $2\Delta$ as derived from the redistribution of the continuum is much larger than expected from mean-field theory and reaches values above 20 for $2\Delta/k_{\rm B}T_{\rm CDW}$. The A$_{1g}$ phonon has a discontinuity at $T_{\rm CDW}$ and a precursor starting 20 K above $T_{\rm CDW}$. Density functional theory qualitatively reproduces the redistribution of the electronic continuum at the CDW transition and the phonon energies of the pristine and distorted structures. The linewidths of all A$_{1g}$ and E$_{2g}$ phonon lines including those emerging below $T_{\rm CDW}$ were analyzed in terms of anharmonic symmetric decay revealing strong phonon-phonon coupling. In addition, we observe two CDW amplitude modes (AMs): one in A$_{1g}$ symmetry and one in E$_{2g}$ symmetry. The temperature dependence of both modes deviates from the prediction of mean-field theory. The A$_{1g}$ AM displays an asymmetric Fano-type lineshape, suggestive of strong electron-phonon coupling. The asymmetric A$_{1g}$ AM, along with the discontinuity of the A$_{1g}$ phonon, the large phonon-phonon coupling parameters and the large gap ratio, indicate the importance of anharmonic strong phonon-phonon and electron-phonon coupling for the CDW formation in CsV$_3$Sb$_5$.Comment: 19 pages, 5 figure