Sequence-Specific Binding of Recombinant Zbed4 to DNA: Insights into Zbed4 Participation in Gene Transcription and Its Association with Other Proteins

Zbed4, a member of the BED subclass of Zinc-finger proteins, is expressed in cone photoreceptors and glial Müller cells of human retina whereas it is only present in Müller cells of mouse retina. To characterize structural and functional properties of Zbed4, enough amounts of purified protein were needed. Thus, recombinant Zbed4 was expressed in E. coli and its refolding conditions optimized for the production of homogenous and functionally active protein. Zbed4’s secondary structure, determined by circular dichroism spectroscopy, showed that this protein contains 32% α-helices, 18% β-sheets, 20% turns and 30% unordered structures. CASTing was used to identify the target sites of Zbed4 in DNA. The majority of the DNA fragments obtained contained poly-Gs and some of them had, in addition, the core signature of GC boxes; a few clones had only GC-boxes. With electrophoretic mobility shift assays we demonstrated that Zbed4 binds both not only to DNA and but also to RNA oligonucleotides with very high affinity, interacting with poly-G tracts that have a minimum of 5 Gs; its binding to and GC-box consensus sequences. However, the latter binding depends on the GC-box flanking nucleotides. We also found that Zbed4 interacts in Y79 retinoblastoma cells with nuclear and cytoplasmic proteins Scaffold Attachment Factor B1 (SAFB1), estrogen receptor alpha (ERα), and cellular myosin 9 (MYH9), as shown with immunoprecipitation and mass spectrometry studies as well as gel overlay assays. In addition, immunostaining corroborated the co-localization of Zbed4 with these proteins. Most importantly, in vitro experiments using constructs containing promoters of genes directing expression of the luciferase gene, showed that Zbed4 transactivates the transcription of those promoters with poly-G tracts

Role of trans-Planckian modes in cosmology

Motivated by the old trans-Planckian (TP) problem of inflationary cosmology, it has been conjectured that any consistent effective field theory should keep TP modes `hidden' behind the Hubble horizon, so as to prevent them from turning classical and thereby affecting macroscopic observations. In this paper we present two arguments against the Hubble horizon being a scale of singular significance as has been put forward in the TP Censorship Conjecture (TCC). First, refinements of TCC are presented that allow for the TP modes to grow beyond the horizon while still keeping the de-Sitter conjecture valid. Second, we show that TP modes can turn classical even well within the Hubble horizon, which, as such, negates this rationale behind keeping them from crossing it. The role of TP modes is known to be less of a problem in warm inflation, because fluctuations start out usually as classical. This allows warm inflation to be more resilient to the TP problem compared to cold inflation. To understand how robust this is, we identity limits where quantum modes can affect the primordial power spectrum in one specific case.Comment: 33 pages, comments welcome; v2: References updated, matches published versio

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

The CMS Statistical Analysis and Combination Tool: Combine

Metrics: https://link.springer.com/article/10.1007/s41781-024-00121-4/metricsThis paper describes the Combine software package used for statistical analyses by the CMS Collaboration. The package, originally designed to perform searches for a Higgs boson and the combined analysis of those searches, has evolved to become the statistical analysis tool presently used in the majority of measurements and searches performed by the CMS Collaboration. It is not specific to the CMS experiment, and this paper is intended to serve as a reference for users outside of the CMS Collaboration, providing an outline of the most salient features and capabilities. Readers are provided with the possibility to run Combine and reproduce examples provided in this paper using a publicly available container image. Since the package is constantly evolving to meet the demands of ever-increasing data sets and analysis sophistication, this paper cannot cover all details of Combine. However, the online documentation referenced within this paper provides an up-to-date and complete user guide.CERN (European Organization for Nuclear Research)STFC (United Kingdom)Marie-Curie programme and the European Research Council and Horizon 2020 Grant, contract Nos. 675440, 724704, 752730, 758316, 765710, 824093, 101115353, 101002207, and COST Action CA16108 (European Union); the Leventis Foundation; the Alfred P. Sloan Foundatio

Portable Acceleration of CMS Computing Workflows with Coprocessors as a Service

A preprint version of the article is available at: arXiv:2402.15366v2 [physics.ins-det], https://arxiv.org/abs/2402.15366 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/MLG-23-001 (CMS Public Pages). Report numbers: CMS-MLG-23-001, CERN-EP-2023-303.Data Availability: No datasets were generated or analyzed during the current study.Computing demands for large scientific experiments, such as the CMS experiment at the CERN LHC, will increase dramatically in the next decades. To complement the future performance increases of software running on central processing units (CPUs), explorations of coprocessor usage in data processing hold great potential and interest. Coprocessors are a class of computer processors that supplement CPUs, often improving the execution of certain functions due to architectural design choices. We explore the approach of Services for Optimized Network Inference on Coprocessors (SONIC) and study the deployment of this as-a-service approach in large-scale data processing. In the studies, we take a data processing workflow of the CMS experiment and run the main workflow on CPUs, while offloading several machine learning (ML) inference tasks onto either remote or local coprocessors, specifically graphics processing units (GPUs). With experiments performed at Google Cloud, the Purdue Tier-2 computing center, and combinations of the two, we demonstrate the acceleration of these ML algorithms individually on coprocessors and the corresponding throughput improvement for the entire workflow. This approach can be easily generalized to different types of coprocessors and deployed on local CPUs without decreasing the throughput performance. We emphasize that the SONIC approach enables high coprocessor usage and enables the portability to run workflows on different types of coprocessors.SCOAP3. Open access funding provided by CERN (European Organization for Nuclear Research

Compact design of planar stepped micro combustor for portable thermoelectric power generation

An efficient prototype of a micro power generator with integrated micro combustor has been developed in the present study. The proposed design of the integrated micro-combustor provides high surface temperature with superior temperature uniformity and enhanced flame stability limits, a prerequisite for a thermoelectric power generation system. This novel micro combustor configuration consists of three backward facing steps with a recirculation hole fabricated in a rectangular heating medium of aluminium material. Parametric studies are carried out by varying the mixture inlet velocity, equivalence ratio and coolant flow rate to obtain the optimized operating conditions for maximum power generation. Two thermoelectric modules are mounted on the system operating with liquefied petroleum gas as fuel. A maximum conversion efficiency of 3.3% is obtained at phi = 0.95 with a mixture velocity of 7.5 m/s and a load resistance of 4 Omega across the thermoelectric generator. The effect of porous media is investigated to enhance the flame stability limits in the micro combustor. Porous media significantly enhances the upper flame stability limits and maximum conversion efficiencies (3.8%, 4.03%, and 3.73% at phi = 1, 0.9 and 0.8 at 10 m/s). A significantly higher power density (similar to 50% higher than existing systems) of 0.12 mW/mm(3) of system volume is achieved. A compact design of the prototype system with high conversion efficiency shows the possibility of its application for various systems requiring portable power for remote, stand-alone, military and aerospace applications

Design of pre-diffuser cones for dump diffusers for aero gas turbine engines

The main concern of any dump diffuser designer is to design the geometry to achieve the highest possible static pressure recovery within the given envelop of the aero gas turbine engine. In this paper design optimization of dump diffusers with three multiple-steps pre-diffuser divergent cones with the aerodynamically-shaped flame tube have been performed using a validated density based steady standard k-ε turbulence model. The code is validated using the exact solution obtained from the closed-form analytical model of V.R. Sanal Kumar (AIP Advances, 8, 025315, 2018) at the Sanal flow choking condition. This is the continuation of our previous AIAA paper (AIAA 2016-5009). We observed that the boundary layer displacement thickness at the pre-diffuser upstream port is having an effect on the static pressure recovery in the dump diffuser. We also observed that the static pressure recovery can be increased profitably during the flight by designing a dump diffuser with adjustable dump gap facilitated with multiple-steps pre-diffuser cones. We concluded that the dump diffuser with geometrically optimized pre-diffuser upstream port and its divergent cone along with the aerodynamically-shaped adjustable flame tube for attaining variable dump gap effect is a profitable and viable option for improving the performance characteristics of aero gas turbine engines under a wide range of operating conditions. © 2019, American Institute of Aeronautics and Astronautics Inc, AIAA