SUSY Simplified Models at 14, 33, and 100 TeV Proton Colliders

Results are presented for a variety of SUSY Simplified Models at the 14 TeV LHC as well as a 33 and 100 TeV proton collider. Our focus is on models whose signals are driven by colored production. We present projections of the upper limit and discovery reach in the gluino-neutralino (for both light and heavy flavor decays), squark-neutralino, and gluino-squark Simplified Model planes. Depending on the model a jets + MET, mono-jet, or same-sign di-lepton search is applied. The impact of pileup is explored. This study utilizes the Snowmass backgrounds and combined detector. Assuming 3000 fb^{-1} of integrated luminosity, a gluino that decays to light flavor quarks can be discovered below 2.3 TeV at the 14 TeV LHC and below 11 TeV at a 100 TeV machine.Comment: 81 pages, 55 figures; v2 journal versio

Stabilizing A Vascularized Autologous Matrix with Flexible Magnesium Scaffolds to Reconstruct Dysfunctional Left Ventricular Myocardium in a Large-Animal Feasibility Study

The surgical reconstruction of dysfunctional myocardium is necessary for patients with severe heart failure. Autologous biomaterials, such as vascularized patch materials, have a regenerative potential due to in vivo remodeling. However, additional temporary mechanical stabilization of the biomaterials is required to prevent aneurysms or rupture. Degradable magnesium scaffolds could prevent these life-threatening risks. A left ventricular transmural defect was reconstructed in minipigs with a piece of the autologous stomach. Geometrically adaptable and degradable scaffolds made of magnesium alloy LA63 were affixed on the epicardium to stabilize the stomach tissue. The degradation of the magnesium structures, their biocompatibility, physiological remodeling of the stomach, and the heart’s function were examined six months after the procedure via MRI (Magnetic Resonance Imaging), angiography, µ-CT, and light microscopy. All animals survived the surgery. Stable physiological integration of the stomach patch could be detected. No ruptures of the grafts occurred. The magnesium scaffolds showed good biocompatibility. Regenerative surgical approaches for treating severe heart failure are a promising therapeutic alternative to the currently available, far from optimal options. The temporary mechanical stabilization of viable, vascularized grafts facilitates their applicability in clinical scenarios

Qualitative and quantitative evaluation of computed tomography changes in adults with cystic fibrosis treated with elexacaftor-tezacaftor-ivacaftor: a retrospective observational study

Introduction: The availability of highly effective triple cystic fibrosis transmembrane conductance regulator (CFTR) modulator combination therapy with elexacaftor–tezacaftor–ivacaftor (ETI) has improved pulmonary outcomes and quality of life of people with cystic fibrosis (pwCF). The aim of this study was to assess computed tomography (CT) changes under ETI visually with the Brody score and quantitatively with dedicated software, and to correlate CT measures with parameters of clinical response.Methods: Twenty two adult pwCF with two consecutive CT scans before and after ETI treatment initiation were retrospectively included. CT was assessed visually employing the Brody score and quantitatively by YACTA, a well-evaluated scientific software computing airway dimensions and lung parenchyma with wall percentage (WP), wall thickness (WT), lumen area (LA), bronchiectasis index (BI), lung volume and mean lung density (MLD) as parameters. Changes in CT metrics were evaluated and the visual and quantitative parameters were correlated with each other and with clinical changes in sweat chloride concentration, spirometry [percent predicted of forced expiratory volume in one second (ppFEV1)] and body mass index (BMI).Results: The mean (SD) Brody score improved with ETI [55 (12) vs. 38 (15); p < 0.001], incl. sub-scores for mucus plugging, peribronchial thickening, and parenchymal changes (all p < 0.001), but not for bronchiectasis (p = 0.281). Quantitatve WP (p < 0.001) and WT (p = 0.004) were reduced, conversely LA increased (p = 0.003), and BI improved (p = 0.012). Lung volume increased (p < 0.001), and MLD decreased (p < 0.001) through a reduction of ground glass opacity areas (p < 0.001). Changes of the Brody score correlated with those of quantitative parameters, exemplarily WT with the sub-score for mucus plugging (r = 0.730, p < 0.001) and peribronchial thickening (r = 0.552, p = 0.008). Changes of CT parameters correlated with those of clinical response parameters, in particular ppFEV1 with the Brody score (r = −0.606, p = 0.003) and with WT (r = −0.538, p = 0.010).Discussion: Morphological treatment response to ETI can be assessed using the Brody score as well as quantitative CT parameters. Changes in CT correlated with clinical improvements. The quantitative analysis with YACTA proved to be an objective, reproducible and simple method for monitoring lung disease, particularly with regard to future interventional clinical trials

The revised GOLD 2017 COPD categorization in relation to comorbidities

Introduction: The COPD classification proposed by the Global Initiative for Obstructive Lung Disease was recently revised, and the A to D grouping is now based on symptoms and exacerbations only. Potential associations with comorbidities have not been assessed so far. Thus the aim of the present study was to determine the relationship between the revised (2017) GOLD groups A-D and major comorbidities. Methods: We used baseline data from the COPD cohort COSYCONET. Comorbidities were identified from patient self-reports and disease-specific medication: gastrointestinal disorders, asthma, sleep apnea, hyperuricemia, hyperlipidemia, diabetes, osteoporosis, mental disorders, heart failure, hypertension, coronary artery disease. The A-D groups were based on either the COPD Assessment Test or the modified Medical Research Council scale. Exacerbations were also categorized as per GOLD recommendations. Results: Data from 2228 patients were analyzed. Using GOLD group A as a reference, group D was associated with nearly all comorbidities, followed by group B and C. When groups A-D were dichotomized as AC vs. BD (symptoms) and AB vs. CD (exacerbations), all comorbidities correlated with symptoms and/or exacerbations. This was true for both mMRC- and CAT-based categorizations. Conclusions: These findings suggest that the recently modified GOLD categorization is clinically relevant beyond being purely an assessment of symptoms and exacerbations. As the A-D groups correlated with the risk of important comorbidities, with some differences in terms of the correlation with symptoms and exacerbations, the findings underline the importance of identifying comorbidities in COPD, particularly in non-responders to therapy who have high symptoms and/or exacerbation rates

Cosmogenic radionuclides reveal an extreme solar particle storm near a solar minimum 9125 years BP

During solar storms, the Sun expels large amounts of energetic particles (SEP) that can react with the Earth’s atmospheric constituents and produce cosmogenic radionuclides such as 14C, 10Be and 36Cl. Here we present 10Be and 36Cl data measured in ice cores from Greenland and Antarctica. The data consistently show one of the largest 10Be and 36Cl production peaks detected so far, most likely produced by an extreme SEP event that hit Earth 9125 years BP (before present, i.e., before 1950 CE), i.e., 7176 BCE. Using the 36Cl/10Be ratio, we demonstrate that this event was characterized by a very hard energy spectrum and was possibly up to two orders of magnitude larger than any SEP event during the instrumental period. Furthermore, we provide 10Be-based evidence that, contrary to expectations, the SEP event occurred near a solar minimum

Mechanism of Disruption of the Amt-GlnK Complex by PII-Mediated Sensing of 2-Oxoglutarate

GlnK proteins regulate the active uptake of ammonium by Amt transport proteins by inserting their regulatory T-loops into the transport channels of the Amt trimer and physically blocking substrate passage. They sense the cellular nitrogen status through 2-oxoglutarate, and the energy level of the cell by binding both ATP and ADP with different affinities. The hyperthermophilic euryarchaeon Archaeoglobus fulgidus possesses three Amt proteins, each encoded in an operon with a GlnK ortholog. One of these proteins, GlnK2 was recently found to be incapable of binding 2-OG, and in order to understand the implications of this finding we conducted a detailed structural and functional analysis of a second GlnK protein from A. fulgidus, GlnK3. Contrary to Af-GlnK2 this protein was able to bind both ATP/2-OG and ADP to yield inactive and functional states, respectively. Due to the thermostable nature of the protein we could observe the exact positioning of the notoriously flexible T-loops and explain the binding behavior of GlnK proteins to their interaction partner, the Amt proteins. A thermodynamic analysis of these binding events using microcalorimetry evaluated by microstate modeling revealed significant differences in binding cooperativity compared to other characterized PII proteins, underlining the diversity and adaptability of this class of regulatory signaling proteins

Extreme Solar Events: Setting up a Paradigm

The Sun is magnetically active and often produces eruptive events on different energetic and temporal scales. Until recently, the upper limit of such events was unknown and believed to be roughly represented by direct instrumental observations. However, two types of extreme events were discovered recently: extreme solar energetic particle events on the multi-millennial time scale and super-flares on sun-like stars. Both discoveries imply that the Sun might rarely produce events, called extreme solar events (ESE), whose energy could be orders of magnitude greater than anything we have observed during recent decades. During the years following these discoveries, great progress has been achieved in collecting observational evidence, uncovering new events, making statistical analyses, and developing theoretical modelling. The ESE paradigm lives and is being developed. On the other hand, many outstanding questions still remain open and new ones emerge. Here we present an overview of the current state of the art and the forming paradigm of ESE from different points of view: solar physics, stellar–solar projections, cosmogenic-isotope data, modelling, historical data, as well as terrestrial, technological and societal effects of ESEs. Special focus is paid to open questions and further developments. This review is based on the joint work of the International Space Science Institute (ISSI) team #510 (2020–2022)