Monitoring of the Heat Shock Response with a Real-Time Luciferase Reporter.

The heat shock response (HSR) is a cellular mechanism for counteracting acute proteotoxic stress. In eukaryotes, transcriptional activation of the HSR is regulated by heat shock factor 1 (HSF1). Activation of HSF1 induces the expression of heat shock proteins (HSPs) that function as molecular chaperones to fold and maintain the three-dimensional structure of misfolded proteins.

High-Dimensional Contact Network Epidemiology.

Contact network models are recent alternatives to equation-based models in epidemiology. In this paper, the spread of disease is modeled on contact networks using bond percolation. The weight of the edges in the contact graphs is determined as a function of several variables in which case the weight is the product of the probabilities of independent events involving each of the variables.

Quantifying the Value of the Molecular Tumor Board: Discordance Recommendation Rate and Drug Cost Avoidance.

Purpose: Molecular tumor boards (MTBs) provide interventions that assist the patient's primary oncologist's interpretation and application of precision oncology and avoid clinical and financial toxicities of prescribing inappropriate targeted therapy. In this article, we describe a novel method for illustrating MTBs value and recommendation discordance rate and report associated drug cost avoidance data.

Methods: From January 1, 2021, to December 31, 2021, patients assessed by our program's MTB were retrospectively evaluated.

GISS-E2.1: Configurations and Climatology.

This paper describes the GISS-E2.1 contribution to the Coupled Model Intercomparison Project, Phase 6 (CMIP6). This model version differs from the predecessor model (GISS-E2) chiefly due to parameterization improvements to the atmospheric and ocean model components, while keeping atmospheric resolution the same.

Persistent Supercooled Drizzle at Temperatures below -25°C Observed at McMurdo Station, Antarctica.

The rarity of reports in the literature of brief and spatially limited observations of drizzle at temperatures below -20°C suggest that riming and other temperature-dependent cloud microphysical processes such as heterogeneous ice nucleation and ice crystal depositional growth prevent drizzle persistence in cold environments. In this study, we report on a persistent drizzle event observed by ground-based remote-sensing measurements at McMurdo Station, Antarctica. The temperatures in the drizzle-producing cloud were below -25°C and the drizzle persisted for a period exceeding 7.

Vertical Profiles of Droplet Size Distributions Derived from Cloud-Side Observations by the Research Scanning Polarimeter: Tests on Simulated Data.

The Research Scanning Polarimeter (RSP) is an airborne along-track scanner measuring the polarized and total reflectances with high angular resolution. It allows for accurate characterization of liquid water cloud droplet sizes using the rainbow structure in the polarized reflectance. RSP's observations also provide constraints on the cumulus cloud's 2D cross section, yielding estimates of its geometric shape.

HSF1: Primary Factor in Molecular Chaperone Expression and a Major Contributor to Cancer Morbidity.

Heat shock factor 1 (HSF1) is the primary component for initiation of the powerful heat shock response (HSR) in eukaryotes. The HSR is an evolutionarily conserved mechanism for responding to proteotoxic stress and involves the rapid expression of heat shock protein (HSP) molecular chaperones that promote cell viability by facilitating proteostasis. HSF1 activity is amplified in many tumor contexts in a manner that resembles a chronic state of stress, characterized by high levels of gene expression as well as HSF1-mediated non- gene regulation.

Comparison of Clinical Outcomes among Intensive Care Unit Patients Receiving One or Two Grams of Ceftriaxone Daily.

Intensive care unit (ICU) patients may experience ceftriaxone underexposure, but clinical outcomes data are lacking. The objective of this study was to determine the impact of ceftriaxone dosing on clinical outcomes among ICU patients without central nervous system (CNS) infection. A retrospective study of ICU patients receiving intravenous, empirical ceftriaxone for non-CNS infections was conducted.

Heat Shock Proteins Are Essential Components in Transformation and Tumor Progression: Cancer Cell Intrinsic Pathways and Beyond.

Heat shock protein (HSP) synthesis is switched on in a remarkably wide range of tumor cells, in both experimental animal systems and in human cancer, in which these proteins accumulate in high levels. In each case, elevated HSP concentrations bode ill for the patient, and are associated with a poor outlook in terms of survival in most cancer types. The significance of elevated HSPs is underpinned by their essential roles in mediating tumor cell intrinsic traits such as unscheduled cell division, escape from programmed cell death and senescence, de novo angiogenesis, and increased invasion and metastasis.

Application of Urinary Volatile Organic Compounds (VOCs) for the Diagnosis of Prostate Cancer.

Background: Prostate cancer (PCa) screening using serum prostate-specific antigen (PSA) testing has caused unnecessary biopsies and overdiagnosis owing to its low accuracy and reliability. Therefore, there is an increased interest in identifying better PCa biomarkers. Studies showed that trained dogs can discriminate patients with PCa from unaffected men by sniffing urine.

Simulation of mesoscale cellular convection in marine stratocumulus.: Part I: Drizzling conditions.

This study uses eddy-permitting simulations to investigate the mechanisms that promote mesoscale variability of moisture in drizzling stratocumulus-topped marine boundary layers. Simulations show that precipitation tends to increase horizontal scales. Analysis of terms in the prognostic equation for total water mixing ratio variance indicates that moisture stratification plays a leading role in setting horizontal scales.

Dual targeting of HSP70 does not induce the heat shock response and synergistically reduces cell viability in muscle invasive bladder cancer.

Muscle invasive bladder cancer (MIBC) is a common malignancy and major cause of morbidity worldwide. Over the last decade mortality rates for MIBC have not decreased as compared to other cancers indicating a need for novel strategies. The molecular chaperones HSP70 and HSP90 fold and maintain the 3-dimensional structures of numerous client proteins that signal for cancer cell growth and survival.

On the role of ice-nucleating aerosol in the formation of ice particles in tropical mesoscale convective systems.

Over decades, the cloud physics community has debated the nature and role of aerosol particles in ice initiation. The present study shows that the measured concentration of ice crystals in tropical mesoscale convective systems exceeds the concentration of ice nucleating particles (INPs) by several orders of magnitude. The concentration of INPs was assessed from the measured aerosol particles concentration in the size range of 0.

Select strengths and biases of models in representing the Arctic winter boundary layer over sea ice: the Larcform 1 single column model intercomparison.

Weather and climate models struggle to represent lower tropospheric temperature and moisture profiles and surface fluxes in Arctic winter, partly because they lack or misrepresent physical processes that are specific to high latitudes. Observations have revealed two preferred states of the Arctic winter boundary layer. In the cloudy state, cloud liquid water limits surface radiative cooling, and temperature inversions are weak and elevated.

Effects of environmental features and sport hunting on caribou migration in northwestern Alaska.

Background: Ungulate movements are influenced by a variety of biotic and abiotic factors, which may affect connectivity between key resource areas and seasonal ranges. In northwestern Alaska, one important question regarding human impacts on ungulate movement involves caribou () response to autumn hunting and related aircraft activity. While concerns have been voiced by local hunters about the influence of transporter aircraft and non-local sport hunters, there has been little quantitative analysis of the effects of hunter activity on caribou movement.

Vertical variation of ice particle size in convective cloud tops.

A novel technique is used to estimate derivatives of ice effective radius with respect to height near convective cloud tops ( /) from airborne shortwave reflectance measurements and lidar. Values of / are about -6 m/km for cloud tops below the homogeneous freezing level, increasing to near 0 m/km above the estimated level of neutral buoyancy. Retrieved / compares well with previously documented remote sensing and in situ estimates.

The impact of cloud vertical profile on liquid water path retrieval based on the bispectral method: A theoretical study based on large-eddy simulations of shallow marine boundary layer clouds.

Passive optical retrievals of cloud liquid water path (LWP), like those implemented for Moderate Resolution Imaging Spectroradiometer (MODIS), rely on cloud vertical profile assumptions to relate optical thickness () and effective radius ( ) retrievals to LWP. These techniques typically assume that shallow clouds are vertically homogeneous; however, an adiabatic cloud model is plausibly more realistic for shallow marine boundary layer cloud regimes. In this study a satellite retrieval simulator is used to perform MODIS-like satellite retrievals, which in turn are compared directly to the large-eddy simulation (LES) output.

On polarimetric radar signatures of deep convection for model evaluation: columns of specific differential phase observed during MC3E.

The representation of deep convection in general circulation models is in part informed by cloud-resolving models (CRMs) that function at higher spatial and temporal resolution; however, recent studies have shown that CRMs often fail at capturing the details of deep convection updrafts. With the goal of providing constraint on CRM simulation of deep convection updrafts, ground-based remote-sensing observations are analyzed and statistically correlated for four deep convection events observed during the Midlatitude Continental Convective Clouds Experiment (MC3E). Since positive values of specific differential phase () observed above the melting level are associated with deep convection updraft cells, so-called " columns" are analyzed using two scanning polarimetric radars in Oklahoma: the National Weather Service Vance WSR-88D (KVNX) and the Department of Energy C-band Scanning Atmospheric Radiation Measurement (ARM) Precipitation Radar (C-SAPR).

On averaging aspect ratios and distortion parameters over ice crystal population ensembles for estimating effective scattering asymmetry parameters.

The use of ensemble-average values of aspect ratio and distortion parameter of hexagonal ice prisms for the estimation of ensemble-average scattering asymmetry parameters is evaluated. Using crystal aspect ratios greater than unity generally leads to ensemble-average values of aspect ratio that are inconsistent with the ensemble-average asymmetry parameters. When a definition of aspect ratio is used that limits the aspect ratio to below unity () for both hexagonal plates and columns, the effective asymmetry parameters calculated using ensemble-average aspect ratios are generally consistent with ensemble-average asymmetry parameters, especially if aspect ratios are geometrically averaged.

Frequency and causes of failed MODIS cloud property retrievals for liquid phase clouds over global oceans.

Moderate Resolution Imaging Spectroradiometer (MODIS) retrieves cloud droplet effective radius ( ) and optical thickness () by projecting observed cloud reflectances onto a precomputed look-up table (LUT). When observations fall outside of the LUT, the retrieval is considered "failed" because no combination of and within the LUT can explain the observed cloud reflectances. In this study, the frequency and potential causes of failed MODIS retrievals for marine liquid phase (MLP) clouds are analyzed based on 1 year of Aqua MODIS Collection 6 products and collocated CALIOP and CloudSat observations.

Imaging for spine tumors and new applications.

Objectives: Discuss intramedullary, intradural/extramedullary, and extradural spinal tumors including imaging characteristics with emphasis on MR and advances in treatment.

Methods: Literature and institutional review.

Results: Spinal tumors: intramedullary, intradural/extramedullary, and extradural, comprise a wide range of histological tumors with an even wider range of clinical symptoms and prognostic features.

The impact of humidity above stratiform clouds on indirect aerosol climate forcing.

Some of the global warming from anthropogenic greenhouse gases is offset by increased reflection of solar radiation by clouds with smaller droplets that form in air polluted with aerosol particles that serve as cloud condensation nuclei. The resulting cooling tendency, termed the indirect aerosol forcing, is thought to be comparable in magnitude to the forcing by anthropogenic CO2, but it is difficult to estimate because the physical processes that determine global aerosol and cloud populations are poorly understood. Smaller cloud droplets not only reflect sunlight more effectively, but also inhibit precipitation, which is expected to result in increased cloud water.

Evidence for the predominance of mid-tropospheric aerosols as subtropical anvil cloud nuclei.

NASA's recent Cirrus Regional Study of Tropical Anvils and Cirrus Layers-Florida Area Cirrus Experiment focused on anvil cirrus clouds, an important but poorly understood element of our climate system. The data obtained included the first comprehensive measurements of aerosols and cloud particles throughout the atmospheric column during the evolution of multiple deep convective storm systems. Coupling these new measurements with detailed cloud simulations that resolve the size distributions of aerosols and cloud particles, we found several lines of evidence indicating that most anvil crystals form on mid-tropospheric rather than boundary-layer aerosols.