The CMS Electromagnetic Calorimeter at the LHC

The CMS detector at the LHC is in the final stages of preparation. The high resolution Electromagnetic Calorimeter, which consists of nearly 76000 lead tungstate crystals, will play a crucial role in the coming physics searches undertaken by CMS. The design, status, and initial performance of the calorimeter, in test beams and with cosmic rays, will be reviewed.Comment: ICHEP0

Blockade of T-cell activation by dithiocarbamates involves novel mechanisms of inhibition of nuclear factor of activated T cells.

Dithiocarbamates (DTCs) have recently been reported as powerful inhibitors of NF-kappaB activation in a number of cell types. Given the role of this transcription factor in the regulation of gene expression in the inflammatory response, NF-kappaB inhibitors have been suggested as potential therapeutic drugs for inflammatory diseases. We show here that DTCs inhibited both interleukin 2 (IL-2) synthesis and membrane expression of antigens which are induced during T-cell activation. This inhibition, which occurred with a parallel activation of c-Jun transactivating functions and expression, was reflected by transfection experiments at the IL-2 promoter level, and involved not only the inhibition of NF-kappaB-driven reporter activation but also that of nuclear factor of activated T cells (NFAT). Accordingly, electrophoretic mobility shift assays (EMSAs) indicated that pyrrolidine DTC (PDTC) prevented NF-kappaB, and NFAT DNA-binding activity in T cells stimulated with either phorbol myristate acetate plus ionophore or antibodies against the CD3-T-cell receptor complex and simultaneously activated the binding of AP-1. Furthermore, PDTC differentially targeted both NFATp and NFATc family members, inhibiting the transactivation functions of NFATp and mRNA induction of NFATc. Strikingly, Western blotting and immunocytochemical experiments indicated that PDTC promoted a transient and rapid shuttling of NFATp and NFATc, leading to their accelerated export from the nucleus of activated T cells. We propose that the activation of an NFAT kinase by PDTC could be responsible for the rapid shuttling of the NFAT, therefore transiently converting the sustained transactivation of this transcription factor that occurs during lymphocyte activation, and show that c-Jun NH2-terminal kinase (JNK) can act by directly phosphorylating NFATp. In addition, the combined inhibitory effects on NFAT and NF-KB support a potential use of DTCs as immunosuppressants

Heat Transfer Modeling and Optimal Thermal Management of Electric Vehicle Battery Systems

Lithium ion (Li-ion) battery packs have become the most popular option for powering electric vehicles (EVs). However, they have certain drawbacks, such as high temperatures and potential safety concerns as a result of chemical reactions that occur during their charging and discharging processes. These can cause thermal runaway and sudden deterioration, and therefore, efficient thermal management systems are essential to boost battery life span and overall performance. An electrochemical-thermal (ECT) model for Li-ion batteries and a conjugate heat transfer model for three-dimensional (3D) fluid flow and heat transfer are developed using COMSOL Multiphysics®. These are used within a novel computational fluid dynamics (CFD)-enabled multi-objective optimization approach, which is used to explore the effect of the mini-channel cold plates’ geometrical parameters on key performance metrics (battery maximum temperature (Tmax), pressure drop (∆P), and temperature standard deviation (Tσ)). The performance of two machine learning (ML) surrogate methods, radial basis functions (RBFs) and Gaussian process (GP), is compared. The results indicate that the GP ML approach is the most effective. Global minima for the maximum temperature, temperature standard deviation, and pressure drop (Tmax, Tσ, and ∆P, respectively) are identified using single objective optimization. The third version of the generalized differential evaluation (GDE3) algorithm is then used along with the GP surrogate models to perform multi-objective design optimization (MODO). Pareto fronts are generated to demonstrate the potential trade-offs between Tmax, Tσ, and ∆P. The obtained optimization results show that the maximum temperature dropped from 36.38 to 35.98 °C, the pressure drop dramatically decreased from 782.82 to 487.16 Pa, and the temperature standard deviation decreased from 2.14 to 2.12 K; the corresponding optimum design parameters are the channel width of 8 mm and the horizontal spacing near the cold plate margin of 5 mm.</jats:p

A system for success: BMC Systems Biology, a new open access journal

BMC Systems Biology is the first open access journal spanning the growing field of systems biology from molecules up to ecosystems. The journal has launched as more and more institutes are founded that are similarly dedicated to this new approach. BMC Systems Biology builds on the ongoing success of the BMC series, providing a venue for all sound research in the systems-level analysis of biology

Remasking of Candida albicans β-Glucan in Response to Environmental pH Is Regulated by Quorum Sensing

Candida albicans is a commensal yeast of the human gut which is tolerated by the immune system but has the potential to become an opportunistic pathogen. One way in which C. albicans achieves this duality is through concealing or exposing cell wall pathogen-associated molecular patterns (PAMPs) in response to host-derived environment cues (pH, hypoxia, and lactate). This cell wall remodeling allows C. albicans to evade or hyperactivate the host’s innate immune responses, leading to disease. Previously, we showed that adaptation of C. albicans to acidic environments, conditions encountered during colonization of the female reproductive tract, induces significant cell wall remodeling resulting in the exposure of two key fungal PAMPs (β-glucan and chitin). Here, we report that this pH-dependent cell wall remodeling is time dependent, with the initial change in pH driving cell wall unmasking, which is then remasked at later time points. Remasking of β-glucan was mediated via the cell density-dependent fungal quorum sensing molecule farnesol, while chitin remasking was mediated via a small, heat-stable, nonproteinaceous secreted molecule(s). Transcript profiling identified a core set of 42 genes significantly regulated by pH over time and identified the transcription factor Efg1 as a regulator of chitin exposure through regulation of CHT2. This dynamic cell wall remodeling influenced innate immune recognition of C. albicans, suggesting that during infection, C. albicans can manipulate the host innate immune responses

RUNX1-ETO and RUNX1-EVI1 Differentially Reprogram the Chromatin Landscape in t(8;21) and t(3;21) AML

Acute myeloid leukemia (AML) is a heterogeneous disease caused by mutations in transcriptional regulator genes, but how different mutant regulators shape the chromatin landscape is unclear. Here, we compared the transcriptional networks of two types of AML with chromosomal translocations of the RUNX1 locus that fuse the RUNX1 DNA-binding domain to different regulators, the t(8;21) expressing RUNX1-ETO and the t(3;21) expressing RUNX1-EVI1. Despite containing the same DNA-binding domain, the two fusion proteins display distinct binding patterns, show differences in gene expression and chromatin landscape, and are dependent on different transcription factors. RUNX1-EVI1 directs a stem cell-like transcriptional network reliant on GATA2, whereas that of RUNX1-ETO-expressing cells is more mature and depends on RUNX1. However, both types of AML are dependent on the continuous expression of the fusion proteins. Our data provide a molecular explanation for the differences in clinical prognosis for these types of AML

Opti-Owecs: Final Report Vol. 0: Executive Summary

It was the particular mission of the project 'Structural and Economic Optimisation of Bottom-Mounted Offshore Wind Energy Converters' (Opti-OWECS) to extend the state-of-the-art, to determine required methods and to demonstrate practical solutions which will significantly reduce the electricity cost. This will facilitate the exploitation of true offshore sites on a commercial base in a medium time scale of 5 to 10 years from now. In several fields, e.g. support structure design, installation of the offshore wind energy converters, operation and maintenance, dynamics of the entire offshore wind energy converter, structural reliability considerations, etc., the study demonstrated new propositions which will contribute significantly to a mature offshore wind energy technology. This was achieved due to a smooth cooperation of leading industrial engineers and researchers from the wind energy field, offshore technology and power management. Moreover, an innovative design methodology devoted particularly to offshore wind energy conversion systems (OWECS) was developed and successfully demonstrated. The so-called 'integrated OWECS design approach' considers the components of an offshore wind farm as parts of an entire system. Therefore interactions between sub-systems are considered in a complete and practical form as possible so that the design solution is governed by overall criteria such as: levelised production costs, adaptation to the actual site conditions, dynamics of the entire system, installation effort as well as OWECS availability. Furthermore, a novel OWECS cost model was developed which led among other work of the project to the identification of the main cost drivers, i.e. annual mean wind speed, distance from shore, operation and maintenance aspects including wind turbine reliability and availability. A link between these results and a database of the offshore wind energy potential in Europe, developed by the previous Joule project JOUR 0072, facilitated the first estimate of energy cost consistent over entire regions of Northern Europe. The European Commission has supported the project in the scope of the framework of the Non Nuclear Energy Programme JOULE Ill (Research and Technical Development) under grant JOR3-CT95-0087

DNA profile components predict malignant outcomes in select cases of intraductal papillary mucinous neoplasm with negative cytology

Predicting malignancy in intraductal papillary mucinous neoplasm remains challenging. Integrated molecular pathology combines pancreatic fluid DNA and clinical factors into a malignant potential score. We sought to determine the utility of DNA components alone in predicting high-grade dysplasia/invasive disease. Methods We reviewed prospectively the records from 1,106 patients with intraductal papillary mucinous neoplasm. We excluded non-intraductal papillary mucinous neoplasm cases and cases with definitive malignant cytology. A total 225 patients had 283 DNA profiles (98 followed by surgery, 185 followed by ≥23-month surveillance). High-grade dysplasia/invasive outcomes were high-grade dysplasia, intraductal papillary mucinous neoplasm-invasive, and adenocarcinoma on surgical pathology or mesenteric or vascular invasion, metastases, or biopsy with high-grade dysplasia or adenocarcinoma during surveillance. Results High-quantity DNA predicted (P = .004) high-grade dysplasia/invasive disease outcomes with sensitivity of 78.3%, but 52.7% specificity, indicating benign cases may exhibit high-quantity DNA. High clonality loss of heterozygosity of tumor suppressor genes was 98.0% specific, strongly predicted high-grade dysplasia/invasive disease but lacked sensitivity (20.0%). High-quantity DNA + high clonality loss of heterozygosity had 99.0% specificity for high-grade dysplasia/invasive disease. KRAS mutation alone did not predict high-grade dysplasia/invasive disease, but, when combined with high-quantity DNA (specificity 84.7%) and high clonality loss of heterozygosity (specificity 99.0%) strongly predicted high-grade dysplasia/invasive outcomes. Conclusion Certain DNA components are highly specific for high-grade dysplasia/invasive disease and may indicate aggressive lesions, requiring resection when cytology fails