Volume-checking tool

Tool, consisting of a graduated storage vessel and a control panel, can determine the amount of gas entrained by fluid in a closed system, the amount of fluid remaining in a dried system of known volume, or the volume of a container of unknown size

Forecasting the Response of Earth’s Surface to Future Climatic and Land Use Changes: A Review of Methods and Research Needs

In the future, Earth will be warmer, precipitation events will be more extreme, global mean sea level will rise, and many arid and semiarid regions will be drier. Human modifications of landscapes will also occur at an accelerated rate as developed areas increase in size and population density. We now have gridded global forecasts, being continually improved, of the climatic and land use changes (C&LUC) that are likely to occur in the coming decades. However, besides a few exceptions, consensus forecasts do not exist for how these C&LUC will likely impact Earth-surface processes and hazards. In some cases, we have the tools to forecast the geomorphic responses to likely future C&LUC. Fully exploiting these models and utilizing these tools will require close collaboration among Earth-surface scientists and Earth-system modelers. This paper assesses the state-of-the-art tools and data that are being used or could be used to forecast changes in the state of Earth’s surface as a result of likely future C&LUC. We also propose strategies for filling key knowledge gaps, emphasizing where additional basic research and/or collaboration across disciplines are necessary. The main body of the paper addresses cross-cutting issues, including the importance of nonlinear/threshold-dominated interactions among topography, vegetation, and sediment transport, as well as the importance of alternate stable states and extreme, rare events for understanding and forecasting Earth-surface response to C&LUC. Five supplements delve into different scales or process zones (global-scale assessments and fluvial, aeolian, glacial/periglacial, and coastal process zones) in detail

Data gaps in electronic health record (EHR) systems: An audit of problem list completeness during the COVID-19 pandemic

OBJECTIVE: To evaluate the completeness of diagnosis recording in problem lists in a hospital electronic health record (EHR) system during the COVID-19 pandemic. DESIGN: Retrospective chart review with manual review of free text electronic case notes. SETTING: Major teaching hospital trust in London, one year after the launch of a comprehensive EHR system (Epic), during the first peak of the COVID-19 pandemic in the UK. PARTICIPANTS: 516 patients with suspected or confirmed COVID-19. MAIN OUTCOME MEASURES: Percentage of diagnoses already included in the structured problem list. RESULTS: Prior to review, these patients had a combined total of 2841 diagnoses recorded in their EHR problem lists. 1722 additional diagnoses were identified, increasing the mean number of recorded problems per patient from 5.51 to 8.84. The overall percentage of diagnoses originally included in the problem list was 62.3% (2841 / 4563, 95% confidence interval 60.8%, 63.7%). CONCLUSIONS: Diagnoses and other clinical information stored in a structured way in electronic health records is extremely useful for supporting clinical decisions, improving patient care and enabling better research. However, recording of medical diagnoses on the structured problem list for inpatients is incomplete, with almost 40% of important diagnoses mentioned only in the free text notes

Hillslope Asymmetry Maps Reveal Widespread, Multi-Scale Organization

Hillslope asymmetry is the condition in which oppositely-facing hillslopes within an area have differing average slope angles, and indicates aspect-related variability in hillslope evolution. As such, the presence, orientation and magnitude of asymmetry may be a useful diagnostic for understanding process dominance. We present a new method for quantifying and mapping the spatial distribution of hillslope asymmetry across large areas. Resulting maps for the American Cordillera of the Western Hemisphere and the western United States reveal that hillslope asymmetry is widespread, with distinct trends at continental to drainage scales. Spatial patterns of asymmetry correlate with latitude along the American Cordillera, mountain-range orientation for many ranges in the western United States, and elevation in the Idaho Batholith of the Northern Rocky Mountains. Spatial organization suggests that non-stochastic, process-driven controls cause these patterns. The hillslope asymmetry metric objectively captures previously-documented extents and frequencies of valley asymmetry for the Gabilan Mesa of the central California Coast Range. Broad-scale maps of hillslope asymmetry are of interest to a wide range of disciplines, as spatial patterns may reflect the influence of tectonics, atmospheric circulation, topoclimate, geomorphology, hydrology, soils and ecology on landscape evolution. These maps identify trends and regions of hillslope asymmetry, allow possible drivers to be spatially constrained, and facilitate the extrapolation of site-specific results to broader regions

Structural Basis for Isoform Selective Nitric Oxide Synthase Inhibition by Thiophene-2-Carboximidamides

The over production of nitric oxide in the brain by neuronal nitric oxide synthase (nNOS) is associated with a number of neurodegenerative diseases. Although inhibiting nNOS is an important therapeutic goal, it is important not to inhibit endothelial NOS (eNOS) owing to the critical role played by eNOS in maintaining vascular tone. While it has been possible to develop nNOS selective aminopyridine inhibitors, many of the most potent and selective inhibitors exhibit poor bioavailability properties. Our group and others have turned to more biocompatible thiophene-2-carboximidamides (T2C) inhibitors as potential nNOS selective inhibitors. We have used crystallography and computational methods to better understand how and why 2 commercially developed T2C inhibitors exhibit selectivity for human nNOS over human eNOS. As with many of the aminopyridine inhibitors, a critical active site Asp residue in nNOS vs Asn in eNOS is largely responsible for controlling selectivity. We also present thermodynamic integration results to better understand the change in pKa and thus charge of inhibitors once bound to the active site. In addition, relative free energy calculations underscore the importance of enhanced electrostatic stabilization of inhibitors bound to the nNOS active site compared to eNOS

Thoracoschisis: case report and review of the literature

Introduction: Thoracoschisis is a rare congenital malformation characterized by herniation of intraabdominal contents through a thoracic wall defect. There have been six previously reported cases. We describe our novel approach incorporating closure of the chest wall defect with temporary abdominal wall expansion utilizing a silastic pouch.Case report: A male child born at 29 weeks’ gestation was transferred to our institution for the management of a right anterior chest wall defect with herniation of intraabdominal contents through this defect. The patient was taken to the operating room for reduction of the herniated viscera from the right chest wall defect into the abdomen utilizing a spring-loaded silastic pouch to cover the abdominal viscera.Discussion: The cause of thoracoschisis is unclear. Multiple mechanisms have been proposed for the development of thoracoschisis, including amnionic rupture, vascular injury, and embryologic maldevelopment. In previously reported cases, a majority of patients had associated limb abnormalities. It has been proposed that this association between extremity agenesis/deformity  and chest wall defects is related to the limb–body wall complex. In addition, most of the cases reported also had an accompanying diaphragmatic defect, allowing the abdominal viscera to enter the chest and then herniate through the thoracic defect.Conclusion: Overall, thoracoschisis is a very rare congenital abnormality characterized by a chest wall defect with herniation of intra-abdominal organs through this defect. Previously, only six cases have been reported, most of which had an associated limb anomaly or diaphragmatic hernia.Keywords: gastroschisis, limb–body wall complex, thoracoabdominal schisis, thoracoschisi

Engineered ascorbate peroxidase as a genetically encoded reporter for electron microscopy

Electron microscopy (EM) is the standard method for imaging cellular structures with nanometer resolution, but existing genetic tags are inactive in most cellular compartments[superscript 1] or require light and can be difficult to use[superscript 2]. Here we report the development of 'APEX', a genetically encodable EM tag that is active in all cellular compartments and does not require light. APEX is a monomeric 28-kDa peroxidase that withstands strong EM fixation to give excellent ultrastructural preservation. We demonstrate the utility of APEX for high-resolution EM imaging of a variety of mammalian organelles and specific proteins using a simple and robust labeling procedure. We also fused APEX to the N or C terminus of the mitochondrial calcium uniporter (MCU), a recently identified channel whose topology is disputed[superscript 3, 4]. These fusions give EM contrast exclusively in the mitochondrial matrix, suggesting that both the N and C termini of MCU face the matrix. Because APEX staining is not dependent on light activation, APEX should make EM imaging of any cellular protein straightforward, regardless of the size or thickness of the specimen.National Institutes of Health (U.S.) (Grant DP1 OD003961)National Science Foundation (U.S.). Graduate Research Fellowship ProgramUnited States. Dept. of Defense (National Defense Science and Engineering Graduate (NDSEG) Fellowships

Engineered ascorbate peroxidase as a genetically-encoded reporter for electron microscopy

Electron microscopy (EM) is the standard method for imaging cellular structures with nanometer resolution, but existing genetic tags are inactive in most cellular compartments1 or require light and are difficult to use2. Here we report the development of a simple and robust EM genetic tag, called “APEX,” that is active in all cellular compartments and does not require light. APEX is a monomeric 28 kDa peroxidase that withstands strong EM fixation to give excellent ultrastructural preservation. We demonstrate the utility of APEX for high-resolution EM imaging of a variety of mammalian organelles and specific proteins. We also fused APEX to the N- or C-terminus of the mitochondrial calcium uniporter (MCU), a newly identified channel whose topology is disputed3,4. MCU-APEX and APEX-MCU give EM contrast exclusively in the mitochondrial matrix, suggesting that both the N-and C-termini of MCU face the matrix

Interrogating marine virus-host interactions and elemental transfer with BONCAT and nanoSIMS-based methods

While the collective impact of marine viruses has become more apparent over the last decade, a deeper understanding of virus-host dynamics and the role of viruses in nutrient cycling would benefit from direct observations at the single-virus level. We describe two new complementary approaches - stable isotope probing coupled with nanoscale secondary ion mass spectrometry (nanoSIMS) and fluorescence-based biorthogonal non-canonical amino acid tagging (BONCAT) - for studying the activity and biogeochemical influence of marine viruses. These tools were developed and tested using several ecologically relevant model systems (Emiliania huxleyi/EhV207, Synechococcus sp. WH8101/Syn1, and Escherichia coli/T7). By resolving carbon and nitrogen enrichment in viral particles, we demonstrate the power of nanoSIMS tracer experiments in obtaining quantitative estimates for the total number of viruses produced directly from a particular production pathway (by isotopically labeling host substrates). Additionally, we show through laboratory experiments and a pilot field study that BONCAT can be used to directly quantify viral production (via epifluorescence microscopy) with minor sample manipulation and no dependency on conversion factors. This technique can also be used to detect newly synthesized viral proteins. Together these tools will help fill critical gaps in our understanding of the biogeochemical impact of viruses in the ocean