We present a novel method to recontruct the mass distribution of galaxy
clusters from their gravitational lens effect on background galaxies. The
method is based on a least-chisquare fit of the ...two-dimensional gravitational
cluster potential. The method combines information from shear and magnification
by the cluster lens and is designed to easily incorporate possible additional
information. We describe the technique and demonstrate its feasibility with
simulated data. Both the cluster morphology and the total cluster mass are well
reproduced.
The image distortions of high-redshift galaxies caused by gravitational light deflection of foreground clusters of galaxies can be used to reconstruct the two-dimensional surface mass density of ...these clusters. We apply an unbiased parameter-free reconstruction technique to the cluster CL0939+4713 (Abell 851), observed with the WFPC2 on board of the HST. We demonstrate that a single deep WFPC2 observation can be used for cluster mass reconstruction despite its small field of view and the irregular shape of the data field (especially for distant clusters). For CL0939, we find a strong correlation between the reconstructed mass distribution and the bright cluster galaxies indicating that mass follows light on average. The detected anti-correlation between the faint galaxies and the reconstructed mass is most likely an effect of the magnification (anti) bias, which was detected previously in the cluster A1689. Because of the high redshift of CL0939 (z_d=0.41), the redshift distribution of the lensed, faint galaxies has to be accounted for in the reconstruction technique. We derive an approximate global transformation for the surface mass density which leaves the mean image ellipticities invariant, resulting in an uncertainty in the normalization of the mass. From the non-negativity of the surface mass density, we derive lower limits on the mass inside the observed field. We can break the invariance transformation for the mass using the magnification effect on the observed number density of the background galaxies. Assuming a mean redshift of 0.8 and a fraction of 15 % (20 %) of cluster galaxies in the observed galaxy sample with 23<R<25.5 we obtain for the mass inside the field approximately 5 (7) x 10**{14}/ h_{50} solar masses which corresponds to M/L ~ 100 (140) h_{50}.
We report the detection of the first 2 microlensing candidates from the Wendelstein Calar Alto Pixellensing Project (WeCAPP). Both are detected with a high signal-to-noise-ratio and were filtered out ...from 4.5 mill. pixel light curves using a variety of selection criteria. Here we only consider well-sampled events with timescales of 1 d < t_fwhm < 20 d, high amplitude, and low chi^2 of the microlensing fit. The two-color photometry (R,I) shows that the events are achromatic and that giant stars with colors of (R-I) ~ 1.1 mag in the bulge of M31 have been lensed. The magnification factors are 64 and 10 which are obtained for typical giant luminosities of M_I = -2.5 mag. Both lensing events lasted for only a few days (t_fwhm^GL1 = 1.7 d and t_fwhm^GL2 = 5.4 d). The event GL1 is likely identical with PA-00-S3 reported by the POINT-AGAPE project. Our calculations favor in both cases the possibility that MACHOs in the halo of M31 caused the lensing events. The most probable masses, 0.08 M_sun for GL1 and 0.02 M_sun for GL2, are in the range of the brown dwarf limit of hydrogen burning. Solar mass objects are a factor of two less likely.
We present a novel method to recontruct the mass distribution of galaxy clusters from their gravitational lens effect on background galaxies. The method is based on a least-chisquare fit of the ...two-dimensional gravitational cluster potential. The method combines information from shear and magnification by the cluster lens and is designed to easily incorporate possible additional information. We describe the technique and demonstrate its feasibility with simulated data. Both the cluster morphology and the total cluster mass are well reproduced.
Astron.Astrophys. 379 (2001) 362-373 We present WeCAPP, a long term monitoring project searching for microlensing
events towards M 31. Since 1997 the bulge of M 31 was monitored in two
different ...wavebands with the Wendelstein 0.8 m telescope. In 1999 we extended
our observations to the Calar Alto 1.23 m telescope. Observing simultaneously
at these two sites we obtained a time coverage of 53 % during the observability
of M 31. To check thousands of frames for variability of unresolved sources, we
used the optimal image subtraction method (OIS) by Alard & Lupton (1998) This
enabled us to minimize the residuals in the difference image analysis (DIA) and
to detect variable sources with amplitudes at the photon noise level. Thus we
can detect microlensing events with corresponding amplifications A > 10 of red
clump giants with M_I = 0.
We present WeCAPP, a long term monitoring project searching for microlensing events towards M 31. Since 1997 the bulge of M 31 was monitored in two different wavebands with the Wendelstein 0.8 m ...telescope. In 1999 we extended our observations to the Calar Alto 1.23 m telescope. Observing simultaneously at these two sites we obtained a time coverage of 53 % during the observability of M 31. To check thousands of frames for variability of unresolved sources, we used the optimal image subtraction method (OIS) by Alard & Lupton (1998) This enabled us to minimize the residuals in the difference image analysis (DIA) and to detect variable sources with amplitudes at the photon noise level. Thus we can detect microlensing events with corresponding amplifications A > 10 of red clump giants with M_I = 0.
SETX (senataxin) is an RNA/DNA helicase that has been implicated in transcriptional regulation and the DNA damage response through resolution of R-loop structures. Mutations in SETX result in either ...of two distinct neurodegenerative disorders. SETX dominant mutations result in a juvenile form of amyotrophic lateral sclerosis (ALS) called ALS4, whereas recessive mutations are responsible for ataxia called ataxia with oculomotor apraxia type 2 (AOA2). How mutations in the same protein can lead to different phenotypes is still unclear. To elucidate AOA2 disease mechanisms, we first examined gene expression changes following SETX depletion. We observed the effects on both transcription and RNA processing, but surprisingly observed decreased R-loop accumulation in SETX-depleted cells. Importantly, we discovered a strong connection between SETX and the macroautophagy/autophagy pathway, reflecting a direct effect on transcription of autophagy genes. We show that SETX depletion inhibits the progression of autophagy, leading to an accumulation of ubiquitinated proteins, decreased ability to clear protein aggregates, as well as mitochondrial defects. Analysis of AOA2 patient fibroblasts also revealed a perturbation of the autophagy pathway. Our work has thus identified a novel function for SETX in the regulation of autophagy, whose modulation may have a therapeutic impact for AOA2.
Abbreviations: 3ʹREADS: 3ʹ region extraction and deep sequencing; ACTB: actin beta; ALS4: amyotrophic lateral sclerosis type 4; AOA2: ataxia with oculomotor apraxia type 2; APA: alternative polyadenylation; AS: alternative splicing; ATG7: autophagy-related 7; ATP6V0D2: ATPase H+ transporting V0 subunit D2; BAF: bafilomycin A
1
; BECN1: beclin 1; ChIP: chromatin IP; Chloro: chloroquine; CPT: camptothecin; DDR: DNA damage response; DNMT1: DNA methyltransferase 1; DRIP: DNA/RNA IP; DSBs: double strand breaks; EBs: embryoid bodies; FTD: frontotemporal dementia; GABARAP: GABA type A receptor-associated protein; GO: gene ontology; HR: homologous recombination; HTT: huntingtin; IF: immunofluorescence; IP: immunoprecipitation; iPSCs: induced pluripotent stem cells; KD: knockdown; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MN: motor neuron; MTORC1: mechanistic target of rapamycin kinase complex 1; PASS: PolyA Site Supporting; PFA: paraformaldehyde; RNAPII: RNA polymerase II; SCA: spinocerebellar ataxia; SETX: senataxin; SMA: spinal muscular atrophy; SMN1: survival of motor neuron 1, telomeric; SQSTM1/p62: sequestosome 1; TFEB: transcription factor EB; TSS: transcription start site; TTS: transcription termination site; ULK1: unc-51 like autophagy activating kinase 1; WB: western blot; WIPI2: WD repeat domain, phosphoinositide interacting 2; XRN2: 5ʹ-3ʹ exoribonuclease 2.
The NCI has undertaken a twenty-year project to characterize compound sensitivity patterns in a selected set of sixty tumor derived cell lines. Previous studies have explored the relationship between ...compound sensitivity patterns to gene expression, protein expression, and DNA copy number for these same cell lines. A strong correlation between the pattern of expression of a biomarker and sensitivity to a compound could suggest a clinically interesting biological relationship between the two.
We isolated RNA's and measured expression of 40000 genes using cDNA microarrays from the fifty-nine publicly available cell lines. Analysis of this data set in comparison with published gene expression data sets demonstrates a high degree of reproducibility in expression level measurements even using completely independent RNA preparations and array technologies. Using the fifty-nine cell lines for discovery and an additional seven cell lines for which extensive compound sensitivity data were available as a test set, we determined that gene-compound pairs with a correlation coefficient above 0.6 had a false discovery rate of approximately 5%. Large scale features of the gene expression and chemosensitivity data, such as tissue of origin and other physiological factors, did not seem to explain the majority of correlations between gene and compound patterns.
A comparison of gene expression and compound sensitivity in panels of cell lines was demonstrated to have a relatively high validation and low false discovery rate supporting the use of this approach and datasets for identifying candidate biomarkers and targeted biologically active compounds.