Three-dimensional Acceleration Measurement Using Videogrammetry Tracking Data

In order to evaluate the feasibility of multi-point, non-contact, acceleration measurement, a high-speed, precision videogrammetry system has been assembled from commercially-available components and software. Consisting of three synchronized 640 X 480 pixel monochrome progressive scan CCD cameras each operated at 200 frames per second, this system has the capability to provide surface-wide position-versus-time data that are filtered and twice-differentiated to yield the desired acceleration tracking at multiple points on a moving body. The oscillating motion of targets mounted on the shaft of a modal shaker were tracked, and the accelerations calculated using the videogrammetry data were compared directly to conventional accelerometer measurements taken concurrently. Although differentiation is an inherently noisy operation, the results indicate that simple mathematical filters based on the well-known Savitzky and Golay algorithms, implemented using spreadsheet software, remove a significant component of the noise, resulting in videogrammetry-based acceleration measurements that are comparable to those obtained using the accelerometers

The development of HISPEC for Keck and MODHIS for TMT: science cases and predicted sensitivities

HISPEC is a new, high-resolution near-infrared spectrograph being designed for the W.M. Keck II telescope. By offering single-shot, R=100,000 between 0.98 - 2.5 um, HISPEC will enable spectroscopy of transiting and non-transiting exoplanets in close orbits, direct high-contrast detection and spectroscopy of spatially separated substellar companions, and exoplanet dynamical mass and orbit measurements using precision radial velocity monitoring calibrated with a suite of state-of-the-art absolute and relative wavelength references. MODHIS is the counterpart to HISPEC for the Thirty Meter Telescope and is being developed in parallel with similar scientific goals. In this proceeding, we provide a brief overview of the current design of both instruments, and the requirements for the two spectrographs as guided by the scientific goals for each. We then outline the current science case for HISPEC and MODHIS, with focuses on the science enabled for exoplanet discovery and characterization. We also provide updated sensitivity curves for both instruments, in terms of both signal-to-noise ratio and predicted radial velocity precision.Comment: 25 pages, 9 figures. To appear in the Proceedings of SPIE: Techniques and Instrumentation for Detection of Exoplanets XI, vol. 12680 (2023

Protein-metabolite interactomics of carbohydrate metabolism reveal regulation of lactate dehydrogenase

Metabolic networks are interconnected and influence diverse cellular processes. The protein-metabolite interactions that mediate these networks are frequently low affinity and challenging to systematically discover. We developed mass spectrometry integrated with equilibrium dialysis for the discovery of allostery systematically (MIDAS) to identify such interactions. Analysis of 33 enzymes from human carbohydrate metabolism identified 830 protein-metabolite interactions, including known regulators, substrates, and products as well as previously unreported interactions. We functionally validated a subset of interactions, including the isoform-specific inhibition of lactate dehydrogenase by long-chain acyl-coenzyme A. Cell treatment with fatty acids caused a loss of pyruvate-lactate interconversion dependent on lactate dehydrogenase isoform expression. These protein-metabolite interactions may contribute to the dynamic, tissue-specific metabolic flexibility that enables growth and survival in an ever-changing nutrient environment

CEBPA Overexpression Enhances β-Cell Proliferation and Survival

A commonality between type 1 and type 2 diabetes is the decline in functional β-cell mass. The transcription factor Nkx6.1 regulates β-cell development and is integral for proper β-cell function. We have previously demonstrated that Nkx6.1 depends on c-Fos mediated upregulation and the nuclear hormone receptors Nr4a1 and Nr4a3 to increase β-cell insulin secretion, survival, and replication. Here, we demonstrate that Nkx6.1 overexpression results in upregulation of the bZip transcription factor CEBPA and that CEBPA expression is independent of c-Fos regulation. In turn, CEBPA overexpression is sufficient to enhance INS-1 832/13 β-cell and primary rat islet proliferation. CEBPA overexpression also increases the survival of β-cells treated with thapsigargin. We demonstrate that increased survival in response to ER stress corresponds with changes in expression of various genes involved in the unfolded protein response, including decreased Ire1a expression. These data show that CEBPA is sufficient to enhance functional β-cell mass by increasing β-cell proliferation and modulating the unfolded protein response

Deferoxamine mesylate in patients with intracerebral haemorrhage (i-DEF): a multicentre, randomised, placebo-controlled, double-blind phase 2 trial

BackgroundIron from haemolysed blood is implicated in secondary injury after intracerebral haemorrhage. We aimed to assess the safety of the iron chelator deferoxamine mesylate in patients with intracerebral haemorrhage and to establish whether the drug merits investigation in a phase 3 trial.MethodsWe did a multicentre, futility-design, randomised, placebo-controlled, double-blind, phase 2 trial at 40 hospitals in Canada and the USA. Adults aged 18-80 years with primary, spontaneous, supratentorial intracerebral haemorrhage were randomly assigned (1:1) to receive deferoxamine mesylate (32 mg/kg per day) or placebo (saline) infusions for 3 consecutive days within 24 h of haemorrhage onset. Randomisation was done via a web-based trial-management system centrally in real time, and treatment allocation was concealed from both participants and investigators. The primary outcome was good clinical outcome, which was defined as a modified Rankin Scale score of 0-2 at day 90. We did a futility analysis: if the 90% upper confidence bound of the absolute risk difference between the two groups in the proportion of participants with a good clinical outcome was less than 12% in favour of deferoxamine mesylate, then to move to a phase 3 efficacy trial would be futile. Primary outcome and safety data were analysed in the modified intention-to-treat population, comprising only participants in whom the study infusions were initiated. This trial is registered with ClinicalTrials.gov, number NCT02175225, and is completed.FindingsWe recruited 294 participants between Nov 23, 2014, and Nov 10, 2017. The modified intention-to-treat population consisted of 144 patients assigned to the deferoxamine mesylate group and 147 assigned to the placebo group. At day 90, among patients with available data for the primary outcome, 48 (34%) of 140 participants in the deferoxamine mesylate group, and 47 (33%) of 143 patients in the placebo group, had modified Rankin Scale scores of 0-2 (adjusted absolute risk difference 0·6% [90% upper confidence bound 6·8%]). By day 90, 70 serious adverse events were reported in 39 (27%) of 144 patients in the deferoxamine mesylate group, and 78 serious adverse events were reported in 49 (33%) of 147 patients in the placebo group. Ten (7%) participants in the deferoxamine mesylate and 11 (7%) in the placebo group died. None of the deaths were judged to be treatment related.InterpretationDeferoxamine mesylate was safe. However, the primary result showed that further study of the efficacy of deferoxamine mesylate with anticipation that the drug would significantly improve the chance of good clinical outcome (ie, mRS score of 0-2) at day 90 would be futile.FundingUS National Institutes of Health and US National Institute of Neurological Disorders and Stroke