Updated Constraints on the Minimal Supergravity Model

Recently, refinements have been made on both the theoretical and experimental determinations of the i.) mass of the lightest Higgs scalar (m_h), ii.) relic density of cold dark matter in the universe (Omega_CDM h^2), iii.) branching fraction for radiative B decay BF(b \to s \gamma), iv.) muon anomalous magnetic moment (a_\mu), and v.) flavor violating decay B_s \to \mu^+\mu^-. Each of these quantities can be predicted in the MSSM, and each depends in a non-trivial way on the spectra of SUSY particles. In this paper, we present updated constraints from each of these quantities on the minimal supergravity (mSUGRA) model as embedded in the computer program ISAJET. The combination of constraints points to certain favored regions of model parameter space where collider and non-accelerator SUSY searches may be more focussed.Comment: 20 pages, 6 figures. Version published in JHE

Linear Collider Capabilities for Supersymmetry in Dark Matter Allowed Regions of the mSUGRA Model

Recent comparisons of minimal supergravity (mSUGRA) model predictions with WMAP measurements of the neutralino relic density point to preferred regions of model parameter space. We investigate the reach of linear colliders (LC) with $\sqrt{s}=0.5$ and 1 TeV for SUSY in the framework of the mSUGRA model. We find that LCs can cover the entire stau co-annihilation region provided \tan\beta \alt 30. In the hyperbolic branch/focus point (HB/FP) region of parameter space, specialized cuts are suggested to increase the reach in this important ``dark matter allowed'' area. In the case of the HB/FP region, the reach of a LC extends well past the reach of the CERN LHC. We examine a case study in the HB/FP region, and show that the MSSM parameters $\mu$ and $M_2$ can be sufficiently well-measured to demonstrate that one would indeed be in the HB/FP region, where the lightest chargino and neutralino have a substantial higgsino component.Comment: 29 pages, 15 EPS figures; updated version slightly modified to conform with published versio

SARS-CoV-2 variant of concern fitness and adaptation in primary human airway epithelia

The severe acute respiratory syndrome coronavirus 2 pandemic is characterized by the emergence of novel variants of concern (VOCs) that replace ancestral strains. Here, we dissect the complex selective pressures by evaluating variant fitness and adaptation in human respiratory tissues. We evaluate viral properties and host responses to reconstruct forces behind D614G through Omicron (BA.1) emergence. We observe differential replication in airway epithelia, differences in cellular tropism, and virus-induced cytotoxicity. D614G accumulates the most mutations after infection, supporting zoonosis and adaptation to the human airway. We perform head-to-head competitions and observe the highest fitness for Gamma and Delta. Under these conditions, RNA recombination favors variants encoding the B.1.617.1 lineage 3′ end. Based on viral growth kinetics, Alpha, Gamma, and Delta exhibit increased fitness compared to D614G. In contrast, the global success of Omicron likely derives from increased transmission and antigenic variation. Our data provide molecular evidence to support epidemiological observations of VOC emergence

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Highly-parallelized simulation of a pixelated LArTPC on a GPU

The rapid development of general-purpose computing on graphics processing units (GPGPU) is allowing the implementation of highly-parallelized Monte Carlo simulation chains for particle physics experiments. This technique is particularly suitable for the simulation of a pixelated charge readout for time projection chambers, given the large number of channels that this technology employs. Here we present the first implementation of a full microphysical simulator of a liquid argon time projection chamber (LArTPC) equipped with light readout and pixelated charge readout, developed for the DUNE Near Detector. The software is implemented with an end-to-end set of GPU-optimized algorithms. The algorithms have been written in Python and translated into CUDA kernels using Numba, a just-in-time compiler for a subset of Python and NumPy instructions. The GPU implementation achieves a speed up of four orders of magnitude compared with the equivalent CPU version. The simulation of the current induced on 10^3 pixels takes around 1 ms on the GPU, compared with approximately 10 s on the CPU. The results of the simulation are compared against data from a pixel-readout LArTPC prototype