Physics in Design:Real-time Numerical Simulation Integrated into the CAD Environment

As today's markets are more susceptible to rapid changes and involve global players, a short time to market is required to keep a competitive edge. Concurrently, products are integrating an increasing number of functions and technologies, thus becoming progressively complex. Therefore, efficient and effective product development is essential. For early design phases, in which a large portion of the product cost is determined, it is important that different concepts can be developed and evaluated quickly. An established way of evaluating a design is using numerical methods, such as Finite Element Analysis (FEA). However, setting up numerical simulations in early design phases when concepts change repeatedly is time consuming. This is largely due to the fact that for each design change concepts need to be re-meshed, boundary conditions re-applied and solutions re-calculated. In this paper, a framework is proposed that establishes a real-time connection between the CAD environment and FEA software. Simulation results are automatically updated when the CAD model is updated. Partial re-meshing and smart boundary condition re-application techniques allow for a real-time assessment of design changes. The developed framework is especially interesting for the assessment of multi-physics phenomena in early design phases, as multiple fields can be interpreted by a design engineer that is usually specialized in a specific field

Comparative analysis of lanthanide excited state quenching by electronic energy and electron transfer processes

The relative sensitivities of structurally related Eu(III) complexes to quenching by electron and energy transfer processes have been compared. In two sets of 9-coordinate complexes based on 1,4,7-triazacyclononane, the Eu emission lifetime decreased as the number of conjugated sensitising groups and the number of unbound ligand N atoms increased, consistent with photoinduced electron transfer to the excited Eu(III) ion that is suppressed by N-protonation. Quenching of the Eu 5D0 excited state may also occur by electronic energy transfer, and the quenching of a variety of 9-coordinate complexes by a cyanine dye with optimal spectral overlap occurs by an efficient FRET process, defined by a Förster radius (R0) value of 68 Å and characterised by second rate constants in the order of 109 M−1 s−1; these values were insensitive to changes in the ligand structure and to the overall complex hydrophilicity. Quenching of the Eu and Tb excited states by energy transfer to Mn(II) and Cu(II) aqua ions occurred over much shorter distances, with rate constants of around 106 M−1 s−1, owing to the much lower spectral overlap integral. The calculated R0 values were estimated to be between 2.5 to 4 Å in the former case, suggesting the presence of a Dexter energy transfer mechanism that requires much closer contact, consistent with the enhanced sensitivity of the rate of quenching to the degree of steric shielding of the lanthanide ion provided by the ligand

DNA methylation plays a crucial role during early <i>Nasonia</i> development

Although the role of DNA methylation in insect development is still poorly understood, the number and role of DNA methyltransferases in insects vary strongly between species. DNA methylation appears to be widely present among the social hymenoptera and functional studies in Apis have suggested a crucial role for de novo methylation in a wide variety of developmental processes. The sequencing of three parasitoid Nasonia genomes revealed the presence of three Dnmt1 (Dnmt1a, Dnmt1b and Dnmt1c) genes and one Dnmt2 and Dnmt3 gene, suggesting a role of DNA methylation in Nasonia development. In the present study we show that in Nasonia vitripennis all Dnmt1 messenger RNAs (mRNAs) and Dnmt3 mRNA are maternally provided to the embryo and, of these, Dnmt1a is essential during early embryogenesis. Lowering of maternal Dnmt1a mRNA results in embryonic lethality during the onset of gastrulation. This dependence on maternal Dnmt1a during embryogenesis in an organismal group outside the vertebrates, suggests evolutionary conservation of the function of Dnmt1 during embryogenesis.</p

Identification and tunable optical coherent control of transition-metal spins in silicon carbide

Color centers in wide-bandgap semiconductors are attractive systems for quantum technologies since they can combine long-coherent electronic spin and bright optical properties. Several suitable centers have been identified, most famously the nitrogen-vacancy defect in diamond. However, integration in communication technology is hindered by the fact that their optical transitions lie outside telecom wavelength bands. Several transition-metal impurities in silicon carbide do emit at and near telecom wavelengths, but knowledge about their spin and optical properties is incomplete. We present all-optical identification and coherent control of molybdenum-impurity spins in silicon carbide with transitions at near-infrared wavelengths. Our results identify spin $S=1/2$ for both the electronic ground and excited state, with highly anisotropic spin properties that we apply for implementing optical control of ground-state spin coherence. Our results show optical lifetimes of $\sim$60 ns and inhomogeneous spin dephasing times of $\sim$0.3 $\mu$s, establishing relevance for quantum spin-photon interfacing.Comment: Updated version with minor correction, full Supplementary Information include

Association of HBsAg levels with differential gene expression in NK, CD8 T, and memory B cells in treated patients with chronic HBV

Background &amp; Aims: HBsAg secretion may impact immune responses to chronic HBV infection. Thus, therapeutic approaches to suppress HBsAg production are being investigated. Our study aims to examine the immunomodulatory effects of high and low levels of circulating HBsAg and thereby improve our understanding of anti-HBV immunity. Methods: An optimized 10x Genomics single-cell RNA sequencing workflow was applied to blood samples and liver fine-needle aspirates from 18 patients undergoing tenofovir/entecavir (NUC) treatment for chronic HBV infection. They were categorized based on their HBsAg levels: high (920-12,447 IU/ml) or low (1-100 IU/ml). Cluster frequencies, differential gene expression, and phenotypes were analyzed. Results: In the blood of HBV-infected patients on NUC, the proportion of KLRC2+ “adaptive” natural killer (NK) cells was significantly lower in the HBsAg-high group and, remarkably, both KLRC2+ NK and KLRG1+ CD8 T cells display enrichment of lymphocyte activation-associated gene sets in the HBsAg-low group. High levels of HBsAg were associated with mild immune activation in the liver. However, no suppression of liver-resident CXCR6+ NCAM1+ NK or CXCR6+ CD69+ CD8 T cells was detected, while memory B cells showed signs of activation in both the blood and liver. Conclusions: Among NUC-treated patients, we observed a minimal impact of HBsAg on leukocyte populations in the blood and liver. However, for the first time, we found that HBsAg has distinct effects, restricted to NK-, CD8 T-, and memory B-cell subsets, in the blood and liver. Our findings are highly relevant for current clinical studies evaluating treatment strategies aimed at suppressing HBsAg production and reinvigorating immunity to HBV. Impact and implications: This study provides unique insight into the impact of HBsAg on gene expression levels of immune cell subsets in the blood and liver, particularly in the context of NUC-treated chronic HBV infection. It holds significant relevance for current and future clinical studies evaluating treatment strategies aimed at suppressing HBsAg production and reinvigorating immunity to HBV. Our findings raise questions about the effectiveness of such treatment strategies and challenge the previously hypothesized immunomodulatory effects of HBsAg on immune responses against HBV.</p

EuroTracker (R) dyes: design, synthesis, structure and photophysical properties of very bright europium complexes and their use in bioassays and cellular optical imaging

The development of the brightest luminescent europium(III) complexes is traced, including analysis of the C3-symmetric core complex based on a functionalized triazacyclononane and identification of the most suitable strongly absorbing chromophore. Strategies for the synthesis of the complexes, including enantiopure analogues, are outlined and opportunities for applications in time-resolved microscopy and spectral imaging emphasised. Practicable examples are introduced, including selective organelle staining for cellular optical imaging at 65 nm resolution and the development of new bioassays using time resolved FRET methods

Comparative analysis of conjugated alkynyl chromophore-triazacyclononane ligands for sensitized emission of europium and terbium

A series of europium and terbium complexes based on a functionalized triazacyclononane carboxylate or phosphinate macrocyclic ligand is described. The influence of the anionic group, that is, carboxylate, methylphosphinate, or phenylphosphinate, on the photophysical properties was studied and rationalized on the basis of DFT calculated structures. The nature, number, and position of electron-donating or electron-withdrawing aryl substituents were varied systematically within the same phenylethynyl scaffold in order to optimize the brightness of the corresponding europium complexes and investigate their two-photon absorption properties. Finally, the europium complexes were examined in cell-imaging applications, and selected terbium complexes were studied as potential oxygen sensors

INTERNAL MIXING, PHENYL RING TORSION AND EXCITONIC INTERACTION IN DIPHENYLMETHANE

Author Institution: Department of Chemistry, Purdue University, West Lafayette, IN 47907-2084The close proximity of two identical ultraviolet chromophores render diphenylmethane~(\mbox{DPM}) an interesting case for the study of the dependence of excitonic coupling on the distortion along low-frequency large-amplitude vibrational coordinates, in particular the phenyl ring torsional coordinates present in~\mbox{DPM}. We have studied the fluorescence excitation spectrum and several single vibronic level fluorescence~(\mbox{SVLF}) spectra of the $\tilde{A}^{1}B(\mathrm{S}_{1})$\,$\leftarrow$\,$\tilde{X}^{1}A(\mathrm{S}_{0})$ and the $\tilde{B}^{1}A(\mathrm{S}_{2})$\,$\leftarrow$\,$\tilde{X}^{1}A(\mathrm{S}_{0})$ transition of~\mbox{DPM} cooled in a supersonic jet. The band in the excitation spectrum blue-shifted by~$123\,\mathrm{cm}^{-1}$ from the $\mathrm{S}_{1}$\,$\leftarrow$\,$\mathrm{S}_{0}$ origin was assigned to the $\mathrm{S}_{2}$\,$\leftarrow$\,$\mathrm{S}_{0}$ origin. Its \mbox{SVLF} spectrum shows two-region fluorescence reminiscent of that previously observed in the gas-phase and supersonic jet spectra of naphthalene$^{1}$ and~ovalene$^{2}$. The high-energy region of this $\mathrm{S}_{2}$~$0^{0}$~\mbox{SVLF} spectrum was tentatively assigned to transitions originating in vibrationally excited levels of the $\mathrm{S}_{1}$~state. This finding indicates the presence of efficient internal mixing of the $\mathrm{S}_{2}$~$0^{0}$ level with the sparse manifold of $\mathrm{S}_{1}$ vibronic background levels. The quantum number changes in the non-totally symmetric torsional mode~(see\,figure) upon internal mixing suggest that additional to the internal conversion transitions accounted for by the Jortner-Berry $\Delta v$\,$=$\,$\pm 1$ rule higher order vibronic mechanisms$^{3}$ have to be considered as well. \vspace*{0.2cm} (1) S.~M.~Beck, D.~E.~Powers, J.~B.~Hopkins and R.~E.~Smalley, \textit{J.~Chem. Phys.}, \textbf{1980}, \textit{73}, 2019.\\ (2) A.~Amirav, U.~Even and J.~Jortner, \textit{J.~Chem. Phys.}, \textbf{1981}, \textit{74}, 3745.\\ (3) B.~Scharf, \textit{Chem. Phys.}, \textbf{1975}, \textit{7}, 478

Evaluation of IL-28B Polymorphisms and Serum IP-10 in Hepatitis C Infected Chimpanzees

In humans, clearance of hepatitis C virus (HCV) infection is associated with genetic variation near the IL-28B gene and the induction of interferon-stimulated genes, like IP-10. Also in chimpanzees spontaneous clearance of HCV is observed. To study whether similar correlations exist in these animals, a direct comparison of IP-10 and IL-28B polymorphism between chimpanzees and patients was performed. All chimpanzees studied were monomorphic for the human IL-28B SNPs which are associated with spontaneous and treatment induced HCV clearance in humans. As a result, these particular SNPs cannot be used for clinical association studies in chimpanzees. Although these human SNPs were absent in chimpanzees, gene variation in this region was present however, no correlation was observed between different SNP-genotypes and HCV outcome. Strikingly, IP-10 levels in chimpanzees correlated with HCV-RNA load and γGT, while such correlations were not observed in humans. The correlation between IP-10, γGT and virus load in chimpanzees was not found in patients and may be due to the lack of lifestyle-related confounding factors in chimpanzees. Direct comparison of IP-10 and IL-28B polymorphism between chimpanzees and patients in relation to HCV infection, illustrates that the IFN-pathways are important during HCV infection in both species. The Genbank EMBL accession numbers assigned to chimpanzees specific sequences near the IL-28B gene are HE599784 and HE599785

De Europees- en internationaalrechtelijke status van de Waddenzee: Een analyse van de relevantie van EU-richtlijnen en internationale verdragen voor de bescherming en het beheer van de Waddenzee met een doorkijk naar de Nederlandse implementatie

In nauwe afstemming en samenwerking met de ministeries van LNV en IenW heeft Rijkswaterstaat de Waddenacademie gevraagd een onderzoek uit te voeren naar voor de Waddenzee geldende internationale verdragen en Europese richtlijnen op het gebied van natuur- en waterbescherming. Doelstelling van het onderzoek is om een gedegen overzicht te krijgen van de inhoud en concrete consequenties van de internationale en Europese beschermingsregimes voor de Waddenzee. Wat zijn de doelen die bereikt moeten worden, welke verboden en verplichtingen vloeien er uit verdragen en EU-richtlijnen voort en besteden de beschermingsregimes ook aandacht aan onderwerpen zoals klimaatverandering, cumulatieve effecten, actief natuurherstel en monitoring? Deze en andere vragen worden voor 13 regimes in afzonderlijke hoofdstukken door juridische experts beantwoord en de bevindingen zijn samengebracht in een uitvoerig samenvattend hoofdstuk