73 research outputs found
Extreme Nonlinear Optics in a Femtosecond Enhancement Cavity
Intrinsic to the process of high-order harmonic generation is the creation of
plasma and the resulting spatiotemporal distortions of the driving laser pulse.
Inside a high finesse cavity where the driver pulse and gas medium are reused,
this can lead to optical bistability of the cavity-plasma system, accumulated
self-phase modulation of the intracavity pulse, and coupling to higher order
cavity modes. We present an experimental and theoretical study of these effects
and discuss their implications for power scaling of intracavity high-order
harmonic generation and extreme ultraviolet frequency combs
Variation of the Fine-Structure Constant and Laser Cooling of Atomic Dysprosium
Radio-frequency electric-dipole transitions between nearly degenerate,
opposite parity levels of atomic dysprosium (Dy) were monitored over an
eight-month period to search for a variation in the fine-structure constant,
. The data provide a rate of fractional temporal variation of
of yr or a value of for , the variation coefficient for in a changing
gravitational potential. All results indicate the absence of significant
variation at the present level of sensitivity. We also present initial results
on laser cooling of an atomic beam of dysprosium.Comment: 10 pages, 6 figures, fixed typos in section 5, updated result
Investigation of the Gravitational Potential Dependence of the Fine-Structure Constant Using Atomic Dysprosium
Radio-frequency E1 transitions between nearly degenerate, opposite parity
levels of atomic dysprosium were monitored over an eight month period to search
for a variation in the fine-structure constant. During this time period, data
were taken at different points in the gravitational potential of the Sun. The
data are fitted to the variation in the gravitational potential yielding a
value of for the fit parameter . This
value gives the current best laboratory limit. In addition, our value of
combined with other experimental constraints is used to extract
the first limits on k_e and k_q. These coefficients characterize the variation
of m_e/m_p and m_q/m_p in a changing gravitational potential, where m_e, m_p,
and m_q are electron, proton, and quark masses. The results are and .Comment: 6 pages, 3 figure
Transverse laser cooling of a thermal atomic beam of dysprosium
A thermal atomic beam of dysprosium (Dy) atoms is cooled using the
transition at 421 nm. The cooling is
done via a standing light wave orthogonal to the atomic beam. Efficient
transverse cooling to the Doppler limit is demonstrated for all observable
isotopes of dysprosium. Branching ratios to metastable states are demonstrated
to be . A scheme for enhancement of the
nonzero-nuclear-spin-isotope cooling, as well as a method for direct
identification of possible trap states, is proposed.Comment: 5 pages, 4 figures v2: 7 pages, 7 figure
Collisional perturbation of radio-frequency E1 transitions in an atomic beam of dysprosium
We have studied collisional perturbations of radio-frequency (rf)
electric-dipole (E1) transitions between the nearly degenerate opposite-parity
levels in atomic dysprosium (Dy) in the presence of 10 to 80 Torr of
H, N, He, Ar, Ne, Kr, and Xe. Collisional broadening and
shift of the resonance, as well as the attenuation of the signal amplitude are
observed to be proportional to the foreign-gas density with the exception of
H and Ne, for which no shifts were observed. Corresponding rates and cross
sections are presented. In addition, rates and cross sections for O are
extracted from measurements using air as foreign gas. The primary motivation
for this study is the need for accurate determination of the shift rates, which
are needed in a laboratory search for the temporal variation of the
fine-structure constant [A. T. Nguyen, D. Budker, S. K. Lamoreaux, and J. R.
Torgerson, Phys. Rev. A \textbf{69}, 22105 (2004)].Comment: 11 pages, 8 figure
Epigenetic-focused CRISPR/Cas9 screen identifies (absent, small, or homeotic)2-like protein (ASH2L) as a regulator of glioblastoma cell survival
Background: Glioblastoma is the most common and aggressive primary brain tumor with extremely poor prognosis, highlighting an urgent need for developing novel treatment options. Identifying epigenetic vulnerabilities of cancer cells can provide excellent therapeutic intervention points for various types of cancers.
Method: In this study, we investigated epigenetic regulators of glioblastoma cell survival through CRISPR/Cas9 based genetic ablation screens using a customized sgRNA library EpiDoKOL, which targets critical functional domains of chromatin modifiers.
Results: Screens conducted in multiple cell lines revealed ASH2L, a histone lysine methyltransferase complex subunit, as a major regulator of glioblastoma cell viability. ASH2L depletion led to cell cycle arrest and apoptosis. RNA sequencing and greenCUT&RUN together identified a set of cell cycle regulatory genes, such as TRA2B, BARD1, KIF20B, ARID4A and SMARCC1 that were downregulated upon ASH2L depletion. Mass spectrometry analysis revealed the interaction partners of ASH2L in glioblastoma cell lines as SET1/MLL family members including SETD1A, SETD1B, MLL1 and MLL2. We further showed that glioblastoma cells had a differential dependency on expression of SET1/MLL family members for survival. The growth of ASH2L-depleted glioblastoma cells was markedly slower than controls in orthotopic in vivo models. TCGA analysis showed high ASH2L expression in glioblastoma compared to low grade gliomas and immunohistochemical analysis revealed significant ASH2L expression in glioblastoma tissues, attesting to its clinical relevance. Therefore, high throughput, robust and affordable screens with focused libraries, such as EpiDoKOL, holds great promise to enable rapid discovery of novel epigenetic regulators of cancer cell survival, such as ASH2L.
Conclusion: Together, we suggest that targeting ASH2L could serve as a new therapeutic opportunity for glioblastoma
Subtelomeric study of 132 patients with mental retardation reveals 9 chromosomal anomalies and contributes to the delineation of submicroscopic deletions of 1pter, 2qter, 4pter, 5qter and 9qter
BACKGROUND: Cryptic chromosome imbalances are increasingly acknowledged as a cause for mental retardation and learning disability. New phenotypes associated with specific rearrangements are also being recognized. Techniques for screening for subtelomeric rearrangements are commercially available, allowing the implementation in a diagnostic service laboratory. We report the diagnostic yield in a series of 132 subjects with mental retardation, and the associated clinical phenotypes. METHODS: We applied commercially available subtelomeric fluorescence in situ hybridization (FISH). All patients referred for subtelomeric screening in a 5-year period were reviewed and abnormal cases were further characterized clinically and if possible molecularly. RESULTS: We identified nine chromosomal rearrangements (two of which were in sisters) corresponding to a diagnostic yield of approx. 7%. All had dysmorphic features. Five had imbalances leading to recognizable phenotypes. CONCLUSION: Subtelomeric screening is a useful adjunct to conventional cytogenetic analyses, and should be considered in mentally retarded subjects with dysmorphic features and unknown cause
Varying constants, Gravitation and Cosmology
Fundamental constants are a cornerstone of our physical laws. Any constant
varying in space and/or time would reflect the existence of an almost massless
field that couples to matter. This will induce a violation of the universality
of free fall. It is thus of utmost importance for our understanding of gravity
and of the domain of validity of general relativity to test for their
constancy. We thus detail the relations between the constants, the tests of the
local position invariance and of the universality of free fall. We then review
the main experimental and observational constraints that have been obtained
from atomic clocks, the Oklo phenomenon, Solar system observations, meteorites
dating, quasar absorption spectra, stellar physics, pulsar timing, the cosmic
microwave background and big bang nucleosynthesis. At each step we describe the
basics of each system, its dependence with respect to the constants, the known
systematic effects and the most recent constraints that have been obtained. We
then describe the main theoretical frameworks in which the low-energy constants
may actually be varying and we focus on the unification mechanisms and the
relations between the variation of different constants. To finish, we discuss
the more speculative possibility of understanding their numerical values and
the apparent fine-tuning that they confront us with.Comment: 145 pages, 10 figures, Review for Living Reviews in Relativit
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