Improved test of Lorentz Invariance in Electrodynamics using Rotating Cryogenic Sapphire Oscillators

We present new results from our test of Lorentz invariance, which compares two orthogonal cryogenic sapphire microwave oscillators rotating in the lab. We have now acquired over 1 year of data, allowing us to avoid the short data set approximation (less than 1 year) that assumes no cancelation occurs between the $\tilde{\kappa}_{e-}$ and $\tilde{\kappa}_{o+}$ parameters from the photon sector of the standard model extension. Thus, we are able to place independent limits on all eight $\tilde{\kappa}_{e-}$ and $\tilde{\kappa}_{o+}$ parameters. Our results represents up to a factor of 10 improvement over previous non rotating measurements (which independently constrained 7 parameters), and is a slight improvement (except for $\tilde{\kappa}_{e-}^{ZZ}$) over results from previous rotating experiments that assumed the short data set approximation. Also, an analysis in the Robertson-Mansouri-Sexl framework allows us to place a new limit on the isotropy parameter $P_{MM}=\delta-\beta+{1/2}$ of $9.4(8.1)\times10^{-11}$, an improvement of a factor of 2.Comment: Accepted for publication in Phys. Rev.

Identifying biological pathways that underlie primordial short stature using network analysis

Mutations in CUL7, OBSL1 and CCDC8, leading to disordered ubiquitination, cause one of the commonest primordial growth disorders, 3-M syndrome. This condition is associated with i) abnormal p53 function, ii) GH and/or IGF1 resistance, which may relate to failure to recycle signalling molecules, and iii) cellular IGF2 deficiency. However the exact molecular mechanisms that may link these abnormalities generating growth restriction remain undefined. In this study, we have used immunoprecipitation/mass spectrometry and transcriptomic studies to generate a 3-M ‘interactome’, to define key cellular pathways and biological functions associated with growth failure seen in 3-M. We identified 189 proteins which interacted with CUL7, OBSL1 and CCDC8, from which a network including 176 of these proteins was generated. To strengthen the association to 3-M syndrome, these proteins were compared with an inferred network generated from the genes that were differentially expressed in 3-M fibroblasts compared with controls. This resulted in a final 3-M network of 131 proteins, with the most significant biological pathway within the network being mRNA splicing/processing. We have shown using an exogenous insulin receptor (INSR) minigene system that alternative splicing of exon 11 is significantly changed in HEK293 cells with altered expression of CUL7, OBSL1 and CCDC8 and in 3-M fibroblasts. The net result is a reduction in the expression of the mitogenic INSR isoform in 3-M syndrome. From these preliminary data, we hypothesise that disordered ubiquitination could result in aberrant mRNA splicing in 3-M; however, further investigation is required to determine whether this contributes to growth failure

Mutations in SRD5B1 (AKR1D1), the gene encoding δ 4-3-oxosteroid 5β-reductase, in hepatitis and liver failure in infancy

Background: A substantial group of patients with cholestatic liver disease in infancy excrete, as the major urinary bile acids, the glycine and taurine conjugates of 7α-hydroxy-3-oxo-4-cholenoic acid and 7α,12α -dihydroxy-3-oxo-4-cholenoic acid. It has been proposed that some (but not all) of these have mutations in the gene encoding Δ4-3-oxosteroid 5β-reductase (SRD5B1; AKR1D1, OMIM 604741). Aims: Our aim was to identify mutations in the SRD5B1 gene in patients in whom chenodeoxycholic acid and cholic acid were absent or present at low concentrations in plasma and urine, as these seemed strong candidates for genetic 5β-reductase deficiency. Patients and subjects: We studied three patients with neonatal onset cholestatic liver disease and normal γ-glutamyl transpeptidase in whom 3-oxo-Δ4 bile acids were the major bile acids in urine and plasma and saturated bile acids were at low concentration or undetectable. Any base changes detected in SRD5B1 were sought in the parents and siblings and in 50 ethnically matched control subjects. Methods: DNA was extracted from blood and the nine exons of SRD5B1 were amplified and sequenced. Restriction enzymes were used to screen the DNA of parents, siblings, and controls. Results: Mutations in the SRD5B1 gene were identified in all three children. Patient MS was homozygous for a missense mutation (662 C>T) causing a Pro198Leu amino acid substitution; patient BH was homozygous for a single base deletion (511 delT) causing a frame shift and a premature stop codon in exon 5; and patient RM was homozygous for a missense mutation (385 C>T) causing a Leu106Phe amino acid substitution. All had liver biopsies showing a giant cell hepatitis; in two, prominent extramedullary haemopoiesis was noted. MS was cured by treatment with chenodeoxycholic acid and cholic acid; BH showed initial improvement but then deteriorated and required liver transplantation; RM had advanced liver disease when treatment was started and also progressed to liver failure. Conclusions: Analysis of blood samples for SRD5B1 mutations can be used to diagnose genetic 5β-reductase deficiency and distinguish these patients from those who have another cause of 3-oxo-Δ4 bile aciduria, for example, severe liver damage. Patients with genetic 5β-reductase deficiency may respond well to treatment with chenodeoxycholic acid and cholic acid if liver disease is not too advanced

Test of Lorentz Invariance in Electrodynamics Using Rotating Cryogenic Sapphire Microwave Oscillators

We present the first results from a rotating Michelson-Morley experiment that uses two orthogonally orientated cryogenic sapphire resonator-oscillators operating in whispering gallery modes near 10 GHz. The experiment is used to test for violations of Lorentz Invariance in the frame-work of the photon sector of the Standard Model Extension (SME), as well as the isotropy term of the Robertson-Mansouri-Sexl (RMS) framework. In the SME we set a new bound on the previously unmeasured $\tilde{\kappa}_{e-}^{ZZ}$ component of $2.1(5.7)\times10^{-14}$, and set more stringent bounds by up to a factor of 7 on seven other components. In the RMS a more stringent bound of $-0.9(2.0)\times 10^{-10}$ on the isotropy parameter, $P_{MM}=\delta - \beta + {1/2}$ is set, which is more than a factor of 7 improvement. More detailed description of the experiment and calculations can be found in: hep-ph/0506200Comment: Final published version, 4 pages, references adde

Low Cost Magnetometer Calibration and Distributed Simultaneous Multipoint Ionospheric Measurements from a Sounding Rocket Platform

Low cost and low size-weight-and-power magnetometers can provide greater accessibility for distributed simultaneous measurements in the ionosphere, either onboard sounding rockets or on CubeSats. The Space and Atmospheric Instrumentation Laboratory at Embry-Riddle Aeronautical University launched a midlatitude sounding rocket named SpEED Demon from Wallops Flight Facility in August 2022. SpEED Demon has a comprehensive suite of instruments for electrodynamics and neutral dynamics measurements. Among this suite is one high performance Billingsley magnetometer (TFM65VQS) and six commercial-off-the-shelf magnetometers manufactured by the PNI Corporation (RM3100). Of the six, two PNI magnetometers are situated on a deployable boom on the main payload that also carries the Billingsley magnetometer. The remaining four PNI magnetometers are distributed among four ejectable subpayloads. These low-cost and low SWaP magnetometers can achieve a resolution of approximately 1.5 nT and a precision of +/- 4 nT (one sigma) at 15 Hz in a uniform magnetic field. This performance is sufficient for detecting and measuring field aligned currents as well as a variety of other geomagnetic disturbances. The magnetometers are calibrated against an independently calibrated flux-gate magnetometer inside a Helmholtz cage. Zero field offsets are quantified inside a triple-layer mu-metal zero gauss chamber. This work will present the calibration process, the calibration results, and the flight performance of these sensors from the SpEED Demon sounding rocket launch

Balloon Borne GPSsondes that Enable Simultaneous Multi-Point Atmospheric Sensing with a Single Ground Station

Balloon-borne radiosondes provide measurements of in-situ atmospheric data such as wind velocity, temperature, and pressure, amongst many others. The Space and Atmospheric Instrumentation Laboratory at Embry-Riddle Aeronautical University has developed low cost (\u3c $150, all inclusive) GPS-enabled radiosondes that are capable of having multiple balloons simultaneously in the air communicating to a single omni-directional ground station antenna. Each GPS-sonde is equipped with a GPS Module for zonal and meridional winds, thermistor for in-situ temperature, and a pressure sensor. Slant range of greater than 120km is achieved through low-cost LoRa radio modules. Interference-free transmission timing between multiple payloads is done by time division multiplexing. The current design allows for up to six payloads to be simultaneously airborne and transmit live atmospheric data through one ground station. A higher number of simultaneous transmissions are also possible, albeit with a minor hit to spatial resolution. We present the system design, complete with hardware and software details, as well data from our current test flights and plans for future development

Improving the Targeting of Treatment: Evidence from College Remediation

At an annual cost of roughly $7 billion nationally, remedial coursework is one of the single largest interventions intended to improve outcomes for underprepared college students. But like a costly medical treatment with non-trivial side effects, the value of remediation overall depends upon whether those most likely to benefit can be identified in advance. This NBER working paper uses administrative data and a rich predictive model to examine the accuracy of remedial screening tests, either instead of or in addition to using high school transcript data to determine remedial assignment. The authors find that roughly one in four test-takers in math and one in three test-takers in English are severely mis-assigned under current test-based policies, with mis-assignments to remediation much more common than mis-assignments to college-level coursework. Using high school transcript information—either instead of or in addition to test scores—could significantly reduce the prevalence of assignment errors. Further, the choice of screening device has significant implications for the racial and gender composition of both remedial and college-level courses. Finally, if institutions took account of students’ high school performance, they could remediate substantially fewer students without lowering success rates in college-level courses

Antithymocyte Globulin Plus G-CSF Combination Therapy Leads to Sustained Immunomodulatory and Metabolic Effects in a Subset of Responders With Established Type 1 Diabetes.

Low-dose antithymocyte globulin (ATG) plus pegylated granulocyte colony-stimulating factor (G-CSF) preserves β-cell function for at least 12 months in type 1 diabetes. Herein, we describe metabolic and immunological parameters 24 months following treatment. Patients with established type 1 diabetes (duration 4-24 months) were randomized to ATG and pegylated G-CSF (ATG+G-CSF) (N = 17) or placebo (N = 8). Primary outcomes included C-peptide area under the curve (AUC) following a mixed-meal tolerance test (MMTT) and flow cytometry. "Responders" (12-month C-peptide ≥ baseline), "super responders" (24-month C-peptide ≥ baseline), and "nonresponders" (12-month C-peptide < baseline) were evaluated for biomarkers of outcome. At 24 months, MMTT-stimulated AUC C-peptide was not significantly different in ATG+G-CSF (0.49 nmol/L/min) versus placebo (0.29 nmol/L/min). Subjects treated with ATG+G-CSF demonstrated reduced CD4+ T cells and CD4+/CD8+ T-cell ratio and increased CD16+CD56hi natural killer cells (NK), CD4+ effector memory T cells (Tem), CD4+PD-1+ central memory T cells (Tcm), Tcm PD-1 expression, and neutrophils. FOXP3+Helios+ regulatory T cells (Treg) were elevated in ATG+G-CSF subjects at 6, 12, and 18 but not 24 months. Immunophenotyping identified differential HLA-DR expression on monocytes and NK and altered CXCR3 and PD-1 expression on T-cell subsets. As such, a group of metabolic and immunological responders was identified. A phase II study of ATG+G-CSF in patients with new-onset type 1 diabetes is ongoing and may support ATG+G-CSF as a prevention strategy in high-risk subjects

New Perspectives in Dried Blood Spot Biomarkers for Lysosomal Storage Diseases

Dried blood spots (DBSs) biomarkers are convenient for monitoring for specific lysosomal storage diseases (LSDs), but they could have relevance for other LSDs. To determine the specificity and utility of glycosphingolipidoses biomarkers against other LSDs, we applied a multiplexed lipid liquid chromatography tandem mass spectrometry assay to a DBS cohort of healthy controls (n = 10) and Gaucher (n = 4), Fabry (n = 10), Pompe (n = 2), mucopolysaccharidosis types I–VI (n = 52), and Niemann–Pick disease type C (NPC) (n = 5) patients. We observed no complete disease specificity for any of the markers tested. However, comparison among the different LSDs highlighted new applications and perspectives of the existing biomarkers. We observed elevations in glucosylceramide isoforms in the NPC and Gaucher patients relative to the controls. In NPC, there was a greater proportion of C24 isoforms, giving a specificity of 96–97% for NPC, higher than 92% for the NPC biomarker N-palmitoyl-O-phosphocholineserine ratio to lyso-sphingomyelin. We also observed significantly elevated levels of lyso-dihexosylceramide in Gaucher and Fabry disease as well as elevated lyso-globotriaosylceramide (Lyso-Gb3) in Gaucher disease and the neuronopathic forms of Mucopolysaccharidoses. In conclusion, DBS glucosylceramide isoform profiling has increased the specificity for the detection of NPC, thereby improving diagnostic accuracy. Low levels of lyso-lipids can be observed in other LSDs, which may have implications in their disease pathogenesis

FUSE Measurements of Far Ultraviolet Extinction. I. Galactic Sight Lines

We present extinction curves that include data down to far ultraviolet wavelengths (FUV; 1050 - 1200 A) for nine Galactic sight lines. The FUV extinction was measured using data from the Far Ultraviolet Spectroscopic Explorer. The sight lines were chosen for their unusual extinction properties in the infrared through the ultraviolet; that they probe a wide range of dust environments is evidenced by the large spread in their measured ratios of total-to-selective extinction, R_V = 2.43 - 3.81. We find that extrapolation of the Fitzpatrick & Massa relationship from the ultraviolet appears to be a good predictor of the FUV extinction behavior. We find that predictions of the FUV extinction based upon the Cardelli, Clayton & Mathis (CCM) dependence on R_V give mixed results. For the seven extinction curves well represented by CCM in the infrared through ultraviolet, the FUV extinction is well predicted in three sight lines, over-predicted in two sight lines, and under-predicted in 2 sight lines. A Maximum Entropy Method analysis using a simple three component grain model shows that seven of the nine sight lines in the study require a larger fraction of grain materials to be in dust when FUV extinction is included in the models. Most of the added grain material is in the form of small (radii < 200 A) grains.Comment: Accepted for publication in the Astrophysical Journal. 31 pages with 7 figure