93 research outputs found
Development of low-gain avalanche detectors in the frame of the acceptor removal phenomenon
Low-gain avalanche detectors (LGAD) suffer from an acceptor removal phenomenon due to irradiation. This acceptor removal phenomenon is investigated in boron, gallium, and indium implanted samples by 4-point-probe (4pp) measurements, low-temperature photoluminescence spectroscopy (LTPL), and secondary ion mass spectrometry (SIMS) before and after irradiation with electrons and protons. Different co-implantation species are evaluated with respect to their ability to reduce the acceptor removal phenomenon. In case of boron, the beneficial effect is found to be most pronounced for the low-dose fluorine and high-dose nitrogen co-implantation. In case of gallium, the low-dose implantations of carbon and oxygen are found to be beneficial. For indium, the different co-implantation species have no beneficial effect. SIMS boron concentration depth profiles measured before and after irradiation show no indication of a fast movement of boron at room temperature. Hence, the discussed BSi-Sii-defect explanation approach of the acceptor removal phenomenon seems to be more likely than the other discussed Bi-Oi-defect explanation approach
Effect of inelastic ion collisions on low-gain avalanche detectors explained by an A_Si-Si_i-defect mode
The acceptor removal phenomenon (ARP), which hampers the functionality of
low-gain avalanche detectors (LGAD), is discussed in frame of the
A_Si-Si_i-defect model. The assumption of fast diffusion of interstitial
silicon is shown to be superfluous for the explanation of the B_Si-Si_i-defect
formation under irradiation, particular at very low temperatures. The
experimentally observed properties of the ARP are explained by the donor
properties of the B_Si-Si_i-defect in its ground state. Additionally, low
temperature photoluminescence spectra are reported for quenched boron doped
silicon showing so far unidentified PL lines, which change due to well-known
light-induced degradation (LID) treatments
Context-dependent neocentromere activity in synthetic yeast chromosome VIII
Pioneering advances in genome engineering, and specifically in genome writing, have revolutionized the field of synthetic biology, propelling us toward the creation of synthetic genomes. The Sc2.0 project aims to build the first fully synthetic eukaryotic organism by assembling the genome of Saccharomyces cerevisiae. With the completion of synthetic chromosome VIII (synVIII) described here, this goal is within reach. In addition to writing the yeast genome, we sought to manipulate an essential functional element: the point centromere. By relocating the native centromere sequence to various positions along chromosome VIII, we discovered that the minimal 118-bp CEN8 sequence is insufficient for conferring chromosomal stability at ectopic locations. Expanding the transplanted sequence to include a small segment (~500 bp) of the CDEIII-proximal pericentromere improved chromosome stability, demonstrating that minimal centromeres display context-dependent functionality </p
A highly magnified candidate for a young galaxy seen when the Universe was 500 Myrs old
The early Universe at redshift z\sim6-11 marks the reionization of the
intergalactic medium, following the formation of the first generation of stars.
However, those young galaxies at a cosmic age of \lesssim 500 million years
(Myr, at z \gtrsim 10) remain largely unexplored as they are at or beyond the
sensitivity limits of current large telescopes. Gravitational lensing by galaxy
clusters enables the detection of high-redshift galaxies that are fainter than
what otherwise could be found in the deepest images of the sky. We report the
discovery of an object found in the multi-band observations of the cluster
MACS1149+22 that has a high probability of being a gravitationally magnified
object from the early universe. The object is firmly detected (12 sigma) in the
two reddest bands of HST/WFC3, and not detected below 1.2 {\mu}m, matching the
characteristics of z\sim9 objects. We derive a robust photometric redshift of z
= 9.6 \pm 0.2, corresponding to a cosmic age of 490 \pm 15Myr (i.e., 3.6% of
the age of the Universe). The large number of bands used to derive the redshift
estimate make it one of the most accurate estimates ever obtained for such a
distant object. The significant magnification by cluster lensing (a factor of
\sim15) allows us to analyze the object's ultra-violet and optical luminosity
in its rest-frame, thus enabling us to constrain on its stellar mass,
star-formation rate and age. If the galaxy is indeed at such a large redshift,
then its age is less than 200 Myr (at the 95% confidence level), implying a
formation redshift of zf \lesssim 14. The object is the first z>9 candidate
that is bright enough for detailed spectroscopic studies with JWST,
demonstrating the unique potential of galaxy cluster fields for finding highly
magnified, intrinsically faint galaxies at the highest redshifts.Comment: Submitted to the Nature Journal. 39 Pages, 13 figure
Synthetic chromosome fusion: Effects on mitotic and meiotic genome structure and function
We designed and synthesized synI, which is ~21.6% shorter than native chrI, the smallest chromosome in Saccharomyces cerevisiae. SynI was designed for attachment to another synthetic chromosome due to concerns surrounding potential instability and karyotype imbalance and is now attached to synIII, yielding the first synthetic yeast fusion chromosome. Additional fusion chromosomes were constructed to study nuclear function. ChrIII-I and chrIX-III-I fusion chromosomes have twisted structures, which depend on silencing protein Sir3. As a smaller chromosome, chrI also faces special challenges in assuring meiotic crossovers required for efficient homolog disjunction. Centromere deletions into fusion chromosomes revealed opposing effects of core centromeres and pericentromeres in modulating deposition of the crossover-promoting protein Red1. These effects extend over 100 kb and promote disproportionate Red1 enrichment, and thus crossover potential, on small chromosomes like chrI. These findings reveal the power of synthetic genomics to uncover new biology and deconvolute complex biological systems  </p
Debugging and consolidating multiple synthetic chromosomes reveals combinatorial genetic interactions
The Sc2.0 project is building a eukaryotic synthetic genome from scratch. A major milestone has been achieved with all individual Sc2.0 chromosomes assembled. Here, we describe the consolidation of multiple synthetic chromosomes using advanced endoreduplication intercrossing with tRNA expression cassettes to generate a strain with 6.5 synthetic chromosomes. The 3D chromosome organization and transcript isoform profiles were evaluated using Hi-C and long-read direct RNA sequencing. We developed CRISPR Directed Biallelic URA3-assisted Genome Scan, or ââCRISPR D-BUGS,ââ to map phenotypic variants caused by specific designer modifications, known as ââbugs.ââ We first fine-mapped a bug in synthetic chromosome II (synII) and then discovered a combinatorial interaction associated with synIII and synX, revealing an unexpected genetic interaction that links transcriptional regulation, inositol metabolism, and tRNASer CGA abundance. Finally, to expedite consolidation, we employed chromosome substitution to incorporate the largest chromosome (synIV), thereby consolidating >50% of the Sc2.0 genome in one strain </p
The Eighth Data Release of the Sloan Digital Sky Survey: First Data from SDSS-III
The Sloan Digital Sky Survey (SDSS) started a new phase in August 2008, with
new instrumentation and new surveys focused on Galactic structure and chemical
evolution, measurements of the baryon oscillation feature in the clustering of
galaxies and the quasar Ly alpha forest, and a radial velocity search for
planets around ~8000 stars. This paper describes the first data release of
SDSS-III (and the eighth counting from the beginning of the SDSS). The release
includes five-band imaging of roughly 5200 deg^2 in the Southern Galactic Cap,
bringing the total footprint of the SDSS imaging to 14,555 deg^2, or over a
third of the Celestial Sphere. All the imaging data have been reprocessed with
an improved sky-subtraction algorithm and a final, self-consistent photometric
recalibration and flat-field determination. This release also includes all data
from the second phase of the Sloan Extension for Galactic Understanding and
Evolution (SEGUE-2), consisting of spectroscopy of approximately 118,000 stars
at both high and low Galactic latitudes. All the more than half a million
stellar spectra obtained with the SDSS spectrograph have been reprocessed
through an improved stellar parameters pipeline, which has better determination
of metallicity for high metallicity stars.Comment: Astrophysical Journal Supplements, in press (minor updates from
submitted version
Manipulating the 3D organization of the largest synthetic yeast chromosome
Whether synthetic genomes can power life has attracted broad interest in the synthetic biology field. Here, we report de novo synthesis of the largest eukaryotic chromosome thus far, synIV, a 1,454,621-bp yeast chromosome resulting from extensive genome streamlining and modification. We developed megachunk assembly combined with a hierarchical integration strategy, which significantly increased the accuracy and flexibility of synthetic chromosome construction. Besides the drastic sequence changes, we further manipulated the 3D structure of synIV to explore spatial gene regulation. Surprisingly, we found few gene expression changes, suggesting that positioning inside the yeast nucleoplasm plays a minor role in gene regulation. Lastly, we tethered synIV to the inner nuclear membrane via its hundreds of loxPsym sites and observed transcriptional repression of the entire chromosome, demonstrating chromosome-wide transcription manipulation without changing the DNA sequences. Our manipulation of the spatial structure of synIV sheds light on higher-order architectural design of the synthetic genomes. </p
The Seventh Data Release of the Sloan Digital Sky Survey
This paper describes the Seventh Data Release of the Sloan Digital Sky Survey
(SDSS), marking the completion of the original goals of the SDSS and the end of
the phase known as SDSS-II. It includes 11663 deg^2 of imaging data, with most
of the roughly 2000 deg^2 increment over the previous data release lying in
regions of low Galactic latitude. The catalog contains five-band photometry for
357 million distinct objects. The survey also includes repeat photometry over
250 deg^2 along the Celestial Equator in the Southern Galactic Cap. A
coaddition of these data goes roughly two magnitudes fainter than the main
survey. The spectroscopy is now complete over a contiguous area of 7500 deg^2
in the Northern Galactic Cap, closing the gap that was present in previous data
releases. There are over 1.6 million spectra in total, including 930,000
galaxies, 120,000 quasars, and 460,000 stars. The data release includes
improved stellar photometry at low Galactic latitude. The astrometry has all
been recalibrated with the second version of the USNO CCD Astrograph Catalog
(UCAC-2), reducing the rms statistical errors at the bright end to 45
milli-arcseconds per coordinate. A systematic error in bright galaxy photometr
is less severe than previously reported for the majority of galaxies. Finally,
we describe a series of improvements to the spectroscopic reductions, including
better flat-fielding and improved wavelength calibration at the blue end,
better processing of objects with extremely strong narrow emission lines, and
an improved determination of stellar metallicities. (Abridged)Comment: 20 pages, 10 embedded figures. Accepted to ApJS after minor
correction
Efficient Colonization and Therapy of Human Hepatocellular Carcinoma (HCC) Using the Oncolytic Vaccinia Virus Strain GLV-1h68
Virotherapy using oncolytic vaccinia virus strains is one of the most promising new strategies for cancer therapy. In this study, we analyzed for the first time the therapeutic efficacy of the oncolytic vaccinia virus GLV-1h68 in two human hepatocellular carcinoma cell lines HuH7 and PLC/PRF/5 (PLC) in cell culture and in tumor xenograft models. By viral proliferation assays and cell survival tests, we demonstrated that GLV-1h68 efficiently colonized, replicated in, and did lyse these cancer cells in culture. Experiments with HuH7 and PLC xenografts have revealed that a single intravenous injection (i.v.) of mice with GLV-1h68 resulted in a significant reduction of primary tumor sizes compared to uninjected controls. In addition, replication of GLV-1h68 in tumor cells led to strong inflammatory and oncolytic effects resulting in intense infiltration of MHC class II-positive cells like neutrophils, macrophages, B cells and dendritic cells and in up-regulation of 13 pro-inflammatory cytokines. Furthermore, GLV-1h68 infection of PLC tumors inhibited the formation of hemorrhagic structures which occur naturally in PLC tumors. Interestingly, we found a strongly reduced vascular density in infected PLC tumors only, but not in the non-hemorrhagic HuH7 tumor model. These data demonstrate that the GLV-1h68 vaccinia virus may have an enormous potential for treatment of human hepatocellular carcinoma in man
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