Presentation by the University of Nevada, Las Vegas: College of Fine Arts

Program listing performers and works performe

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas

A conserved motif flags acyl carrier proteins for β-branching in polyketide synthesis

Type I PKSs often utilise programmed β-branching, via enzymes of an “HMG-CoA synthase (HCS) cassette”, to incorporate various side chains at the second carbon from the terminal carboxylic acid of growing polyketide backbones. We identified a strong sequence motif in Acyl Carrier Proteins (ACPs) where β-branching is known. Substituting ACPs confirmed a correlation of ACP type with β-branching specificity. While these ACPs often occur in tandem, NMR analysis of tandem β-branching ACPs indicated no ACP-ACP synergistic effects and revealed that the conserved sequence motif forms an internal core rather than an exposed patch. Modelling and mutagenesis identified ACP Helix III as a probable anchor point of the ACP-HCS complex whose position is determined by the core. Mutating the core affects ACP functionality while ACP-HCS interface substitutions modulate system specificity. Our method for predicting β-carbon branching expands the potential for engineering novel polyketides and lays a basis for determining specificity rules

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease

Critter-Copter

The goal of this project is to aid marine biologists in their search for whales to tag and study. This is achieved by creating an audio subsystem on a quadcopter in order to extend the biologists' search range. This audio subsystem will wirelessly transmit audio from the drone's search area back to the boat. Assuming the drone already has a camera, this payload will effectively extend the hearing and sight capabilities of the researchers on the boat

Origin of silicic magmas along the Central American volcanic front: Genetic relationship to mafic melts

Silicic pyroclastic flows and related deposits are abundant along the Central American volcanic front. These silicic magmas erupted through both the non-continental Chorotega block to the southeast and the Paleozoic continental Chortis block to the northwest. The along-arc variations of the silicic deposits with respect to diagnostic trace element ratios (Ba/La, U/Th, Ce/Pb), oxygen isotopes, Nd and Sr isotope ratios mimic the along-arc variation in the basaltic and andesitic lavas. This variation in the lavas has been interpreted to indicate relative contributions from the slab and asthenosphere to the basaltic magmas [Carr, M.J., Feigenson, M.D., Bennett, E.A., 1990. Incompatible element and isotopic evidence for tectonic control of source mixing and melt extraction along the Central American arc. Contributions to Mineralogy and Petrology, 105, 369–380.; Patino, L.C., Carr, M.J. and Feigenson, M.D., 2000. Local and regional variations in Central American arc lavas controlled by variations in subducted sediment input. Contributions to Mineralogy and Petrology, 138 (3), 265–283.]. With respect to along-arc trends in basaltic lavas the largest contribution of slab fluids is in Nicaragua and the smallest input from the slab is in central Costa Rica — similar trends are observed in the silicic pyroclastic deposits. Data from melting experiments of primitive basalts and basaltic andesites demonstrate that it is difficult to produce high K2O/Na2O silicic magmas by fractional crystallization or partial melting of low-K2O/Na2O sources. However fractional crystallization or partial melting of medium- to high-K basalts can produce these silicic magmas. We interpret that the high-silica magmas associated Central America volcanic front are partial melts of penecontemporaneous, mantle-derived, evolved magmas that have ponded and crystallized in the mid-crust — or are melts extracted from these nearly completely crystallized magmas

Hadean age for a post-magma-ocean zircon confirmed by atom-probe tomography

The only physical evidence from the earliest phases of Earth’s evolution comes from zircons, ancient mineral grains that can be dated using the U–Th–Pb geochronometer1. Oxygen isotope ratios from such zircons have been used to infer when the hydrosphere and conditions habitable to life were established2, 3. Chemical homogenization of Earth’s crust and the existence of a magma ocean have not been dated directly, but must have occurred earlier4. However, the accuracy of the U–Pb zircon ages can plausibly be biased by poorly understood processes of intracrystalline Pb mobility5, 6, 7. Here we use atom-probe tomography8 to identify and map individual atoms in the oldest concordant grain from Earth, a 4.4-Gyr-old Hadean zircon with a high-temperature overgrowth that formed about 1 Gyr after the mineral’s core. Isolated nanoclusters, measuring about 10 nm and spaced 10–50 nm apart, are enriched in incompatible elements including radiogenic Pb with unusually high 207Pb/206Pb ratios. We demonstrate that the length scales of these clusters make U–Pb age biasing impossible, and that they formed during the later reheating event. Our tomography data thereby confirm that any mixing event of the silicate Earth must have occurred before 4.4 Gyr ago, consistent with magma ocean formation by an early moon-forming impact4 about 4.5 Gyr ago

The seismo-hydro-mechanical behaviour during deep geothermal reservoir stimulations: open question tackled in a decameter-scale in-situ stimulation experiment

In this contribution we present a review of scientific research results that address seismo-hydro-mechanical coupled processes relevant for the development of a sustainable heat exchanger in low permeability crystalline rock and introduce the design of the In-situ Stimulation and Circulation (ISC) experiment at the Grimsel Test Site dedicated to study such processes under controlled conditions. The review shows that research on reservoir stimulation for deep geothermal energy exploitation has been largely based on laboratory observations, large-scale projects and numerical models. Observations of full-scale reservoir stimulations have yielded important results. However, the limited access to the reservoir and limitations in the control on the experimental conditions during deep reservoir stimulations is insufficient to resolve the details of the hydro-mechanical processes that would enhance process understanding in a way that aids future stimulation design. Small scale laboratory experiments provide a fundamental insights into various processes relevant for enhanced geothermal energy, but suffer from 1) difficulties and uncertainties in upscaling the results to the field-scale and 2) relatively homogeneous material and stress conditions that lead to an over-simplistic fracture flow and/or hydraulic fracture propagation behaviour that is not representative for a heterogeneous reservoir. Thus, there is a need for intermediate-scale hydraulic stimulation experiments with high experimental control that bridge the various scales, and for which access to the target rock mass with a comprehensive monitoring system is possible. Only few intermediate-scale hydro-shearing and hydro-fracturing experiments have recently been performed in a densely instrumented rock mass. No such measurements have been performed on faults in crystalline basement rocks. The In-situ Stimulation and Circulation (ISC) experiment currently performed in a naturally fractured and faulted crystalline rock mass at the Grimsel Test Site (Switzerland) is designed to address open research questions, which could not be investigated in the required detail so far. Two hydraulic injection phases were executed to enhance the permeability of the rock mass: a hydro-shearing phase and then a hydraulic fracturing phase. During the injection phases the rock mass deformation across fractures and within intact rock, the pore pressure distribution and propagation and the micro-seismic response were monitored at a high spatial and temporal resolution.ISSN:1869-953

Early identification of patients admitted to hospital for covid-19 at risk of clinical deterioration: model development and multisite external validation study

ObjectiveTo create and validate a simple and transferable machine learning model from electronic health record data to accurately predict clinical deterioration in patients with covid-19 across institutions, through use of a novel paradigm for model development and code sharing.DesignRetrospective cohort study.SettingOne US hospital during 2015-21 was used for model training and internal validation. External validation was conducted on patients admitted to hospital with covid-19 at 12 other US medical centers during 2020-21.Participants33 119 adults (≥18 years) admitted to hospital with respiratory distress or covid-19.Main outcome measuresAn ensemble of linear models was trained on the development cohort to predict a composite outcome of clinical deterioration within the first five days of hospital admission, defined as in-hospital mortality or any of three treatments indicating severe illness: mechanical ventilation, heated high flow nasal cannula, or intravenous vasopressors. The model was based on nine clinical and personal characteristic variables selected from 2686 variables available in the electronic health record. Internal and external validation performance was measured using the area under the receiver operating characteristic curve (AUROC) and the expected calibration error-the difference between predicted risk and actual risk. Potential bed day savings were estimated by calculating how many bed days hospitals could save per patient if low risk patients identified by the model were discharged early.Results9291 covid-19 related hospital admissions at 13 medical centers were used for model validation, of which 1510 (16.3%) were related to the primary outcome. When the model was applied to the internal validation cohort, it achieved an AUROC of 0.80 (95% confidence interval 0.77 to 0.84) and an expected calibration error of 0.01 (95% confidence interval 0.00 to 0.02). Performance was consistent when validated in the 12 external medical centers (AUROC range 0.77-0.84), across subgroups of sex, age, race, and ethnicity (AUROC range 0.78-0.84), and across quarters (AUROC range 0.73-0.83). Using the model to triage low risk patients could potentially save up to 7.8 bed days per patient resulting from early discharge.ConclusionA model to predict clinical deterioration was developed rapidly in response to the covid-19 pandemic at a single hospital, was applied externally without the sharing of data, and performed well across multiple medical centers, patient subgroups, and time periods, showing its potential as a tool for use in optimizing healthcare resources