27 research outputs found
The metastable Q state of ThO: A new resource for the ACME electron EDM search
The best upper limit for the electron electric dipole moment was recently set
by the ACME collaboration. This experiment measures an electron spin-precession
in a cold beam of ThO molecules in their metastable state.
Improvement in the statistical and systematic uncertainties is possible with
more efficient use of molecules from the source and better magnetometry in the
experiment, respectively. Here, we report measurements of several relevant
properties of the long-lived state of ThO, and show that this
state is a very useful resource for both these purposes. The state lifetime
is long enough that its decay during the time of flight in the ACME beam
experiment is negligible. The large electric dipole moment measured for the
state, giving rise to a large linear Stark shift, is ideal for an electrostatic
lens that increases the fraction of molecules detected downstream. The measured
magnetic moment of the state is also large enough to be used as a sensitive
co-magnetometer in ACME. Finally, we show that the state has a large
transition dipole moment to the state, which allows for efficient
population transfer between the ground state and the state
via Stimulated Raman Adiabatic Passage (STIRAP). We demonstrate %
STIRAP transfer efficiency. In the course of these measurements, we also
determine the magnetic moment of state, the transition
dipole moment, and branching ratios of decays from the state.Comment: 21 pages, 6 figures, 5 pages appendice
Reevaluation of the role of nuclear uncertainties in experiments on atomic parity violation with isotopic chains
In light of new data on neutron distributions from experiments with
antiprotonic atoms [ Trzcinska {\it et al.}, Phys. Rev. Lett. 87, 082501
(2001)], we reexamine the role of nuclear-structure uncertainties in the
interpretation of measurements of parity violation in atoms using chains of
isotopes of the same element. With these new nuclear data, we find an
improvement in the sensitivity of isotopic chain measurements to ``new
physics'' beyond the standard model. We compare possible constraints on ``new
physics'' with the most accurate to date single-isotope probe of parity
violation in the Cs atom. We conclude that presently isotopic chain experiments
employing atoms with nuclear charges Z < 50 may result in more accurate tests
of the weak interaction.Comment: 6 pages, 1 fig., submitted to Phys. Rev.
Variant-specific pathophysiological mechanisms of AFF3 differently influence transcriptome profiles
Background
We previously described the KINSSHIP syndrome, an autosomal dominant disorder associated with intellectual disability (ID), mesomelic dysplasia and horseshoe kidney, caused by de novo variants in the degron of AFF3. Mouse knock-ins and overexpression in zebrafish provided evidence for a dominant-negative mode of action, wherein an increased level of AFF3 resulted in pathological effects.
Methods
Evolutionary constraints suggest that other modes-of-inheritance could be at play. We challenged this hypothesis by screening ID cohorts for individuals with predicted-to-be damaging variants in AFF3. We used both animal and cellular models to assess the deleteriousness of the identified variants.
Results
We identified an individual with a KINSSHIP-like phenotype carrying a de novo partial duplication of AFF3 further strengthening the hypothesis that an increased level of AFF3 is pathological. We also detected seventeen individuals displaying a milder syndrome with either heterozygous Loss-of-Function (LoF) or biallelic missense variants in AFF3. Consistent with semi-dominance, we discovered three patients with homozygous LoF and one compound heterozygote for a LoF and a missense variant, who presented more severe phenotypes than their heterozygous parents. Matching zebrafish knockdowns exhibit neurological defects that could be rescued by expressing human AFF3 mRNA, confirming their association with the ablation of aff3. Conversely, some of the human AFF3 mRNAs carrying missense variants identified in affected individuals did not rescue these phenotypes. Overexpression of mutated AFF3 mRNAs in zebrafish embryos produced a significant increase of abnormal larvae compared to wild-type overexpression further demonstrating deleteriousness.
To further assess the effect of AFF3 variation, we profiled the transcriptome of fibroblasts from affected individuals and engineered isogenic cells harboring + / + , KINSSHIP/KINSSHIP, LoF/ + , LoF/LoF or KINSSHIP/LoF AFF3 genotypes. The expression of more than a third of the AFF3 bound loci is modified in either the KINSSHIP/KINSSHIP or the LoF/LoF lines. While the same pathways are affected, only about one third of the differentially expressed genes are common to the homozygote datasets, indicating that AFF3 LoF and KINSSHIP variants largely modulate transcriptomes differently, e.g. the DNA repair pathway displayed opposite modulation.
Conclusions
Our results and the high pleiotropy shown by variation at this locus suggest that minute changes in AFF3 function are deleterious
Variant-specific pathophysiological mechanisms of AFF3 differently influence transcriptome profiles
Background: We previously described the KINSSHIP syndrome, an autosomal dominant disorder associated with intellectual disability (ID), mesomelic dysplasia and horseshoe kidney, caused by de novo variants in the degron of AFF3. Mouse knock-ins and overexpression in zebrafish provided evidence for a dominant-negative mode of action, wherein an increased level of AFF3 resulted in pathological effects. Methods: Evolutionary constraints suggest that other modes-of-inheritance could be at play. We challenged this hypothesis by screening ID cohorts for individuals with predicted-to-be damaging variants in AFF3. We used both animal and cellular models to assess the deleteriousness of the identified variants. Results: We identified an individual with a KINSSHIP-like phenotype carrying a de novo partial duplication of AFF3 further strengthening the hypothesis that an increased level of AFF3 is pathological. We also detected seventeen individuals displaying a milder syndrome with either heterozygous Loss-of-Function (LoF) or biallelic missense variants in AFF3. Consistent with semi-dominance, we discovered three patients with homozygous LoF and one compound heterozygote for a LoF and a missense variant, who presented more severe phenotypes than their heterozygous parents. Matching zebrafish knockdowns exhibit neurological defects that could be rescued by expressing human AFF3 mRNA, confirming their association with the ablation of aff3. Conversely, some of the human AFF3 mRNAs carrying missense variants identified in affected individuals did not rescue these phenotypes. Overexpression of mutated AFF3 mRNAs in zebrafish embryos produced a significant increase of abnormal larvae compared to wild-type overexpression further demonstrating deleteriousness. To further assess the effect of AFF3 variation, we profiled the transcriptome of fibroblasts from affected individuals and engineered isogenic cells harboring + / +, KINSSHIP/KINSSHIP, LoF/ +, LoF/LoF or KINSSHIP/LoF AFF3 genotypes. The expression of more than a third of the AFF3 bound loci is modified in either the KINSSHIP/KINSSHIP or the LoF/LoF lines. While the same pathways are affected, only about one third of the differentially expressed genes are common to the homozygote datasets, indicating that AFF3 LoF and KINSSHIP variants largely modulate transcriptomes differently, e.g. the DNA repair pathway displayed opposite modulation. Conclusions: Our results and the high pleiotropy shown by variation at this locus suggest that minute changes in AFF3 function are deleterious.</p
Variant-specific pathophysiological mechanisms of AFF3 differently influence transcriptome profiles
Background: We previously described the KINSSHIP syndrome, an autosomal dominant disorder associated with intellectual disability (ID), mesomelic dysplasia and horseshoe kidney, caused by de novo variants in the degron of AFF3. Mouse knock-ins and overexpression in zebrafish provided evidence for a dominant-negative mode of action, wherein an increased level of AFF3 resulted in pathological effects. Methods: Evolutionary constraints suggest that other modes-of-inheritance could be at play. We challenged this hypothesis by screening ID cohorts for individuals with predicted-to-be damaging variants in AFF3. We used both animal and cellular models to assess the deleteriousness of the identified variants. Results: We identified an individual with a KINSSHIP-like phenotype carrying a de novo partial duplication of AFF3 further strengthening the hypothesis that an increased level of AFF3 is pathological. We also detected seventeen individuals displaying a milder syndrome with either heterozygous Loss-of-Function (LoF) or biallelic missense variants in AFF3. Consistent with semi-dominance, we discovered three patients with homozygous LoF and one compound heterozygote for a LoF and a missense variant, who presented more severe phenotypes than their heterozygous parents. Matching zebrafish knockdowns exhibit neurological defects that could be rescued by expressing human AFF3 mRNA, confirming their association with the ablation of aff3. Conversely, some of the human AFF3 mRNAs carrying missense variants identified in affected individuals did not rescue these phenotypes. Overexpression of mutated AFF3 mRNAs in zebrafish embryos produced a significant increase of abnormal larvae compared to wild-type overexpression further demonstrating deleteriousness. To further assess the effect of AFF3 variation, we profiled the transcriptome of fibroblasts from affected individuals and engineered isogenic cells harboring + / +, KINSSHIP/KINSSHIP, LoF/ +, LoF/LoF or KINSSHIP/LoF AFF3 genotypes. The expression of more than a third of the AFF3 bound loci is modified in either the KINSSHIP/KINSSHIP or the LoF/LoF lines. While the same pathways are affected, only about one third of the differentially expressed genes are common to the homozygote datasets, indicating that AFF3 LoF and KINSSHIP variants largely modulate transcriptomes differently, e.g. the DNA repair pathway displayed opposite modulation. Conclusions: Our results and the high pleiotropy shown by variation at this locus suggest that minute changes in AFF3 function are deleterious.</p
Electric dipole moments and the search for new physics
Static electric dipole moments of nondegenerate systems probe mass scales for
physics beyond the Standard Model well beyond those reached directly at high
energy colliders. Discrimination between different physics models, however,
requires complementary searches in atomic-molecular-and-optical, nuclear and
particle physics. In this report, we discuss the current status and prospects
in the near future for a compelling suite of such experiments, along with
developments needed in the encompassing theoretical framework.Comment: Contribution to Snowmass 2021; updated with community edits and
endorsement
Neutrinos
229 pages229 pages229 pagesThe Proceedings of the 2011 workshop on Fundamental Physics at the Intensity Frontier. Science opportunities at the intensity frontier are identified and described in the areas of heavy quarks, charged leptons, neutrinos, proton decay, new light weakly-coupled particles, and nucleons, nuclei, and atoms