Magnetometer suitable for Earth field measurement based on transient atomic response

We describe the development of a simple atomic magnetometer using $^{87}$Rb vapor suitable for Earth magnetic field monitoring. The magnetometer is based on time-domain determination of the transient precession frequency of the atomic alignment around the measured field. A sensitivity of 1.5 nT/$\sqrt{Hz}$ is demonstrated on the measurement of the Earth magnetic field in the laboratory. We discuss the different parameters determining the magnetometer precision and accuracy and predict a sensitivity of 30 pT/$\sqrt{Hz}$Comment: 6 pages, 5 figure

Ontologies for the study of neurological disease

We have begun work on two separate but related ontologies for the study of neurological diseases. The first, the Neurological Disease Ontology (ND), is intended to provide a set of controlled, logically connected classes to describe the range of neurological diseases and their associated signs and symptoms, assessments, diagnoses, and interventions that are encountered in the course of clinical practice. ND is built as an extension of the Ontology for General Medical Sciences — a high-level candidate OBO Foundry ontology that provides a set of general classes that can be used to describe general aspects of medical science. ND is being built with classes utilizing both textual and axiomatized definitions that describe and formalize the relations between instances of other classes within the ontology itself as well as to external ontologies such as the Gene Ontology, Cell Ontology, Protein Ontology, and Chemical Entities of Biological Interest. In addition, references to similar or associated terms in external ontologies, vocabularies and terminologies are included when possible. Initial work on ND is focused on the areas of Alzheimer’s and other diseases associated with dementia, multiple sclerosis, and stroke and cerebrovascular disease. Extensions to additional groups of neurological diseases are planned. The second ontology, the Neuro-Psychological Testing Ontology (NPT), is intended to provide a set of classes for the annotation of neuropsychological testing data. The intention of this ontology is to allow for the integration of results from a variety of neuropsychological tests that assay similar measures of cognitive functioning. Neuro-psychological testing is an important component in developing the clinical picture used in the diagnosis of patients with a range of neurological diseases, such as Alzheimer’s disease and multiple sclerosis, and following stroke or traumatic brain injury. NPT is being developed as an extension to the Ontology for Biomedical Investigations

New statistical method identifes cytokines that distinguish stool microbiomes

Regressing an outcome or dependent variable onto a set of input or independent variables allows the analyst to measure associations between the two so that changes in the outcome can be described by and predicted by changes in the inputs. While there are many ways of doing this in classical statistics, where the dependent variable has certain properties (e.g., a scalar, survival time, count), little progress on regression where the dependent variable are microbiome taxa counts has been made that do not impose extremely strict conditions on the data. In this paper, we propose and apply a new regression model combining the Dirichlet-multinomial distribution with recursive partitioning providing a fully non-parametric regression model. This model, called DM-RPart, is applied to cytokine data and microbiome taxa count data and is applicable to any microbiome taxa count/metadata, is automatically fit, and intuitively interpretable. This is a model which can be applied to any microbiome or other compositional data and software (R package HMP) available through the R CRAN website

There is a low rate of major adverse cardiovascular events in chest pain patients with a moderate risk heart score referred from urgent care for expedited outpatient cardiology evaluation: a multi-center study

Background The HEART score is an effective method of risk stratifying emergency department (ED) patients with chest pain. The rate of major adverse cardiovascular events (MACE) in patients with moderate HEART score referred from an urgent care (UC) for an expedited outpatient cardiology evaluation for 11 months was described in 133 patients in a previous study. This is a follow-up study with 18 months of data and 206 patients.Aim. The primary outcome was to examine the rate of MACE when patients with moderate HEART score were referred for an expedited outpatient cardiology follow-up after evaluation in urgent care. The secondary outcome was to determine if there is a decrease in rate of ED transfer after this protocol was introduced.Methods. A cross-sectional study was conducted by a multispecialty group in Las Vegas, Nevada, which included 206 patients with a HEART score of 4 to 6 (i.e.: moderate risk) who presented to one of five UC centers with chest pain or an anginal equivalent. A streamlined evaluation protocol to assess each HEART score component was adopted by all UC providers to facilitate an expedited outpatient cardiology follow-up, as an alternative to referral to the emergency department. Data was collected from February 14, 2019 through August 13, 2020. The population was followed for 6 weeks with a primary endpoint of MACE determined by electronic medical record review and direct phone contact with patients. Outcomes were confirmed in 98% of patients. Chest pain transfer data was compared between 12 months prior to implementing HEART protocol and 18 months of data analysis while using the new protocol.Results. Over the course of 18 months, 206 patients with a moderate risk HEART score were referred to outpatient cardiology in an expedited manner. The average age was 65 with 53% female and 47% male patients. 150 patients (73% of the 206) were seen within 3 days, 114 (55%) underwent stress testing, 6 (3%) had coronary computed tomography angiogram, and 6 (3%) received an invasive coronary angiogram. Five patients were found to have MACE: one patient who had a non-ST-elevation myocardial infarction and subsequent coronary stent, two patients were found to have obstructive disease after coronary angiography with subsequent coronary artery bypass graft, one patient had an abnormal stress test and subsequent coronary stent, and one patient had critical mitral stenosis, multi-vessel coronary artery disease and underwent coronary artery bypass graft with mitral valve replacement with complications of renal failure and COVID-19 and expired. The emergency department referral rate declined by 21%.Conclusion. Patients with a moderate risk HEART score referred from UC for an expedited outpatient cardiology evaluation had a low rate of MACE and no deaths due to delay of care. There was also a significant decrease in the rate of ED referrals.Background. The HEART score is an effective method of risk stratifying emergency department (ED) patients with chest pain. The rate of major adverse cardiovascular events (MACE) in patients with moderate HEART score referred from an urgent care (UC) for an expedited outpatient cardiology evaluation for 11 months was described in 133 patients in a previous study. This is a follow-up study with 18 months of data and 206 patients.Aim. The primary outcome was to examine the rate of MACE when patients with moderate HEART score were referred for an expedited outpatient cardiology follow-up after evaluation in urgent care. The secondary outcome was to determine if there is a decrease in rate of ED transfer after this protocol was introduced.Methods. A cross-sectional study was conducted by a multispecialty group in Las Vegas, Nevada, which included 206 patients with a HEART score of 4 to 6 (i.e.: moderate risk) who presented to one of five UC centers with chest pain or an anginal equivalent. A streamlined evaluation protocol to assess each HEART score component was adopted by all UC providers to facilitate an expedited outpatient cardiology follow-up, as an alternative to referral to the emergency department. Data was collected from February 14, 2019 through August 13, 2020. The population was followed for 6 weeks with a primary endpoint of MACE determined by electronic medical record review and direct phone contact with patients. Outcomes were confirmed in 98% of patients. Chest pain transfer data was compared between 12 months prior to implementing HEART protocol and 18 months of data analysis while using the new protocol.Results. Over the course of 18 months, 206 patients with a moderate risk HEART score were referred to outpatient cardiology in an expedited manner. The average age was 65 with 53% female and 47% male patients. 150 patients (73% of the 206) were seen within 3 days, 114 (55%) underwent stress testing, 6 (3%) had coronary computed tomography angiogram, and 6 (3%) received an invasive coronary angiogram. Five patients were found to have MACE: one patient who had a non-ST-elevation myocardial infarction and subsequent coronary stent, two patients were found to have obstructive disease after coronary angiography with subsequent coronary artery bypass graft, one patient had an abnormal stress test and subsequent coronary stent, and one patient had critical mitral stenosis, multi-vessel coronary artery disease and underwent coronary artery bypass graft with mitral valve replacement with complications of renal failure and COVID-19 and expired. The emergency department referral rate declined by 21%.Conclusion. Patients with a moderate risk HEART score referred from UC for an expedited outpatient cardiology evaluation had a low rate of MACE and no deaths due to delay of care. There was also a significant decrease in the rate of ED referrals

Amyloid beta and diabetic pathology cooperatively stimulate cytokine expression in an Alzheimer's mouse model

Background Diabetes is a risk factor for developing Alzheimer's disease (AD); however, the mechanism by which diabetes can promote AD pathology remains unknown. Diabetes results in diverse molecular changes in the brain, including dysregulation of glucose metabolism and loss of cerebrovascular homeostasis. Although these changes have been associated with increased A beta pathology and increased expression of glial activation markers in APPswe/PS1dE9 (APP/PS1) mice, there has been limited characterization, to date, of the neuroinflammatory changes associated with diabetic conditions. Methods To more fully elucidate neuroinflammatory changes associated with diabetes that may drive AD pathology, we combined the APP/PS1 mouse model with either high-fat diet (HFD, a model of pre-diabetes), the genetic db/db model of type 2 diabetes, or the streptozotocin (STZ) model of type 1 diabetes. We then used a multiplexed immunoassay to quantify cortical changes in cytokine proteins. Results Our analysis revealed that pathology associated with either db/db, HFD, or STZ models yielded upregulation of a broad profile of cytokines, including chemokines (e.g., MIP-1 alpha, MIP-1 beta, and MCP-1) and pro-inflammatory cytokines, including IL-1 alpha, IFN-gamma, and IL-3. Moreover, multivariate partial least squares regression analysis showed that combined diabetic-APP/PS1 models yielded cooperatively enhanced expression of the cytokine profile associated with each diabetic model alone. Finally, in APP/PS1xdb/db mice, we found that circulating levels of A beta 1-40, A beta 1-42, glucose, and insulin all correlated with cytokine expression in the brain, suggesting a strong relationship between peripheral changes and brain pathology. Conclusions Altogether, our multiplexed analysis of cytokines shows that Alzheimer's and diabetic pathologies cooperate to enhance profiles of cytokines reported to be involved in both diseases. Moreover, since many of the identified cytokines promote neuronal injury, A beta and tau pathology, and breakdown of the blood-brain barrier, our data suggest that neuroinflammation may mediate the effects of diabetes on AD pathogenesis. Therefore, strategies targeting neuroinflammatory signaling, as well as metabolic control, may provide a promising strategy for intervening in the development of diabetes-associated AD

Northrop Grumman TR202 LOX/LH2 Deep Throttling Engine Project Status

NASA's Propulsion and Cryogenic Advanced Development (PCAD) project is currently developing enabling propulsion technologies in support of the Exploration Initiative, with a particular focus on the needs of the Altair Project. To meet Altair requirements, several technical challenges need to be overcome, one of which is the ability for the lunar descent engine(s) to operate over a deep throttle range with cryogenic propellants. To address this need, PCAD has enlisted Northrop Grumman Aerospace Systems (NGAS) in a technology development effort associated with the TR202, a LOX/LH2 expander cycle engine driven by independent turbopump assemblies and featuring a variable area pintle injector similar to the injector used on the TR200 Apollo Lunar Module Descent Engine (LMDE). Since the Apollo missions, NGAS has continued to mature deep throttling pintle injector technology. The TR202 program has completed two phases of pintle injector testing. The first phase of testing used ablative thrust chambers and demonstrated igniter operation as well as stable performance at several power levels across the designed 10:1 throttle range. The second phase of testing was performed on a calorimeter chamber and demonstrated injector performance at various power levels (75%, 50%, 25%, 10%, and 7.5%) across the throttle range as well as chamber heat flux to show that the engine can close an expander cycle design across the throttle range. This paper provides an overview of the TR202 program. It describes the different phases of the program with the key milestones of each phase. It then shows when those milestones were met. Next, it describes how the test data was used to update the conceptual design and how the test data has created a database for deep throttling cryogenic pintle technology that is readily scaleable and can be used to again update the design once the Altair program's requirements are firm. The final section of the paper describes the path forward, which includes demonstrating continuously throttling with an actuator and pursuing a path towards integrated engine sea-level test-bed testing

DNA as a universal substrate for chemical kinetics

Molecular programming aims to systematically engineer molecular and chemical systems of autonomous function and ever-increasing complexity. A key goal is to develop embedded control circuitry within a chemical system to direct molecular events. Here we show that systems of DNA molecules can be constructed that closely approximate the dynamic behavior of arbitrary systems of coupled chemical reactions. By using strand displacement reactions as a primitive, we construct reaction cascades with effectively unimolecular and bimolecular kinetics. Our construction allows individual reactions to be coupled in arbitrary ways such that reactants can participate in multiple reactions simultaneously, reproducing the desired dynamical properties. Thus arbitrary systems of chemical equations can be compiled into real chemical systems. We illustrate our method on the Lotka–Volterra oscillator, a limit-cycle oscillator, a chaotic system, and systems implementing feedback digital logic and algorithmic behavior

CD4+ cytolytic effectors are inefficient in the clearance of Listeria monocytogenes

Cytotoxic T lymphocytes (CTL) recognize and lyse target cells through the interaction of the T-cell receptor complex with the class I or class II major histocompatibility complex (MHC). The production of class I-restricted CTL has been shown to be critical to the elimination of specific pathogens including . However, the function of class II-restricted CTL in the clearance of intracellular pathogens is poorly understood. H-2β-microglobulin-deficient mice (βM−/−) are not able to produce CD8 CTL in response to infection with . We used this model to evaluate the efficacy of class II-restricted CTL, in the absence of a class I-restricted response, during a primary infection with . We demonstrate that, despite their effectiveness in adoptive transfer of protection, -specific CD4 class II-restricted cytotoxic lymphocytes are ineffective in decreasing titres of in the spleen after an established infection. In βM−/− mice, persistence of in the spleen was found preferentially in class II-negative cells. Surprisingly, class I-restricted CTL from C57BL/6 mice were capable of decreasing bacterial titres during an established infection even in the absence of detectable class I on the surface of cells from βM−/− mice. These data strongly suggest that, in the absence of a class I-restricted response, pathogens that elicit a class II-restricted cytotoxic response may escape prompt eradication by the immune system

Validation of the Harvard Lyman-α in situ water vapor instrument: Implications for the mechanisms that control stratospheric water vapor

Building on previously published details of the laboratory calibrations of the Harvard Lyman-α photofragment fluorescence hygrometer (HWV) on the NASA ER-2 and WB-57 aircraft, we describe here the validation process for HWV, which includes laboratory calibrations and intercomparisons with other Harvard water vapor instruments at water vapor mixing ratios from 0 to 10 ppmv, followed by in-flight intercomparisons with the same Harvard hygrometers. The observed agreement exhibited in the laboratory and during intercomparisons helps corroborate the accuracy of HWV. In light of the validated accuracy of HWV, we present and evaluate a series of intercomparisons with satellite and balloon borne water vapor instruments made from the upper troposphere to the lower stratosphere in the tropics and midlatitudes. Whether on the NASA ER-2 or WB-57 aircraft, HWV has consistently measured about 1–1.5 ppmv higher than the balloon-borne NOAA/ESRL/GMD frost point hygrometer (CMDL), the NOAA Cryogenic Frost point Hygrometer (CFH), and the Microwave Limb Sounder (MLS) on the Aura satellite in regions of the atmosphere where water vapor is <10 ppmv. Comparisons in the tropics with the Halogen Occultation Experiment (HALOE) on the Upper Atmosphere Research Satellite show large variable differences near the tropopause that converge to ~10% above 460 K, with HWV higher. Results we show from the Aqua Validation and Intercomparison Experiment (AquaVIT) at the AIDA chamber in Karlsruhe do not reflect the observed in-flight differences. We illustrate that the interpretation of the results of comparisons between modeled and measured representations of the seasonal cycle of water entering the lower tropical stratosphere is dictated by which data set is used