557 research outputs found
Quantum geometry and the Schwarzschild singularity
In homogeneous cosmologies, quantum geometry effects lead to a resolution of
the classical singularity without having to invoke special boundary conditions
at the singularity or introduce ad-hoc elements such as unphysical matter. The
same effects are shown to lead to a resolution of the Schwarzschild
singularity. The resulting quantum extension of space-time is likely to have
significant implications to the black hole evaporation process. Similarities
and differences with the situation in quantum geometrodynamics are pointed out.Comment: 31 pages, 1 figur
'A new kind of rays': gothic fears, cultural anxieties and the discovery of X-rays in the 1890s
In 1895, the world of modern physics was effectively ushered in with the discovery of X-rays by the German physicist, Wilhelm Conrad Röntgen. X-rays rapidly changed the ways in which the human body was perceived, and their discovery was documented and fiercely debated in scientific articles, newspaper reports, literary writings, cartoons and films. This article examines a range of these responses, both 'scientific' and 'popular', and considers the particular significance of their repeated recourse to the Gothic and the uncanny as a means of expressing both excitement and disquiet at what the new X-ray phenomenon might mean
Targeted delivery of C/EBPα -saRNA by pancreatic ductal adenocarcinoma-specific RNA aptamers inhibits tumor growth in vivo
The 5-year survival rate for pancreatic ductal adenocarcinoma (PDAC) remains dismal despite current chemotherapeutic agents and inhibitors of molecular targets. As the incidence of PDAC constantly increases, more effective multidrug approaches must be made. Here, we report a novel method of delivering antitumorigenic therapy in PDAC by upregulating the transcriptional factor CCAAT/enhancer-binding protein-α (C/EBPα), recognized for its antiproliferative effects. Small activating RNA (saRNA) duplexes designed to increase C/EBPα expression were linked onto PDAC-specific 2′-Fluropyrimidine RNA aptamers (2′F-RNA) - P19 and P1 for construction of a cell type–specific delivery vehicle. Both P19- and P1-C/EBPα-saRNA conjugates increased expression of C/EBPα and significantly suppressed cell proliferation. Tail vein injection of the saRNA/aptamer conjugates in PANC-1 and in gemcitabine-resistant AsPC-1 mouse-xenografts led to reduced tumor size with no observed toxicity. To exploit the specificity of the P19/P1 aptamers for PDAC cells, we also assessed if conjugation with Cy3 would allow it to be used as a diagnostic tool on archival human pancreatic duodenectomy tissue sections. Scoring pattern from 72 patients suggested a positive correlation between high fluorescent signal in the high mortality patient groups. We propose a novel aptamer-based strategy for delivery of targeted molecular therapy in advanced PDAC where current modalities fail
Degenerate Configurations, Singularities and the Non-Abelian Nature of Loop Quantum Gravity
Degenerate geometrical configurations in quantum gravity are important to
understand if the fate of classical singularities is to be revealed. However,
not all degenerate configurations arise on an equal footing, and one must take
into account dynamical aspects when interpreting results: While there are many
degenerate spatial metrics, not all of them are approached along the dynamical
evolution of general relativity or a candidate theory for quantum gravity. For
loop quantum gravity, relevant properties and steps in an analysis are
summarized and evaluated critically with the currently available information,
also elucidating the role of degrees of freedom captured in the sector provided
by loop quantum cosmology. This allows an outlook on how singularity removal
might be analyzed in a general setting and also in the full theory. The general
mechanism of loop quantum cosmology will be shown to be insensitive to recently
observed unbounded behavior of inverse volume in the full theory. Moreover,
significant features of this unboundedness are not a consequence of
inhomogeneities but of non-Abelian effects which can also be included in
homogeneous models.Comment: 28 pages, 1 figure; v2: extended discussion of singularity removal
and summar
The nuclear immune receptor RPS4 is required for RRS1SLH1-dependent constitutive defense activation in Arabidopsis thaliana
Plant nucleotide-binding leucine-rich repeat (NB-LRR) disease resistance (R) proteins recognize specific ‘‘avirulent’’ pathogen effectors and activate immune responses. NB-LRR proteins structurally and functionally resemble mammalian Nod-like receptors (NLRs). How NB-LRR and NLR proteins activate defense is poorly understood. The divergently transcribed Arabidopsis R genes, RPS4 (resistance to Pseudomonas syringae 4) and RRS1 (resistance to Ralstonia solanacearum 1), function together to confer recognition of Pseudomonas AvrRps4 and Ralstonia PopP2. RRS1 is the only known recessive NBLRR R gene and encodes a WRKY DNA binding domain, prompting suggestions that it acts downstream of RPS4 for transcriptional activation of defense genes. We define here the early RRS1-dependent transcriptional changes upon delivery of PopP2 via Pseudomonas type III secretion. The Arabidopsis slh1 (sensitive to low humidity 1) mutant encodes an RRS1 allele (RRS1SLH1) with a single amino acid (leucine) insertion in the WRKY DNA-binding domain. Its poor growth due to constitutive defense activation is rescued at higher temperature. Transcription profiling data indicate that RRS1SLH1-mediated defense activation overlaps substantially with AvrRps4- and PopP2-regulated responses. To better understand the genetic basis of RPS4/RRS1-dependent immunity, we performed a genetic screen to identify suppressor of slh1 immunity (sushi) mutants. We show that many sushi mutants carry mutations in RPS4, suggesting that RPS4 acts downstream or in a complex with RRS1. Interestingly, several mutations were identified in a domain C-terminal to the RPS4 LRR domain. Using an Agrobacterium-mediated transient assay system, we demonstrate that the P-loop motif of RPS4 but not of RRS1SLH1 is required for RRS1SLH1 function. We also recapitulate the dominant suppression of RRS1SLH1 defense activation by wild type RRS1 and show this suppression requires an intact RRS1 P-loop. These analyses of RRS1SLH1 shed new light on mechanisms by which NB-LRR protein pairs activate defense signaling, or are held inactive in the absence of a pathogen effector
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Generation of an ultrabroadband supercontinuum in the mid-infrared region using dispersion-engineered GeAsSe photonic crystal fiber
An ultrabroadband mid-infrared (MIR) region supercontinuum (SC) is demonstrated numerically through dispersion-engineered traditional chalcogenide (ChG) photonic crystal fiber (PCF). By varying structural parameters pitch (hole to hole spacing) and air-hole diameter to pitch ratio, a number of 10-mm-long hexagonal PCFs made employing GeAsSe ChG glass as a core and air-holes of hexagonal lattice running through their lengths as a cladding are optimized to predict an efficient mid-infrared region SC spectral emission by pumping them using a tunable pump source between 2.9 and 3.3 µm. Simulations are carried out using an ultrashort pump pulse of 100-fs duration with a low pulse peak powers of between 3 and 4 kW into the optimized designs. It is found through numerical analysis that efficient SC spectral broadening with flattened output can be obtained by increasing the PCF pitch rather than increasing the PCF cladding containing air-hole diameter although a larger nonlinear coefficient could be obtained through increasing air-hole diameter of an optimized design. Simulation results show that the SC spectra can be broadened up to 12.2 µm for a certain design with a peak power of 3 kW. Using a peak power of 4 kW, it is possible to obtain SC spectral broadening beyond 14 µm with an optimized design spanning the wavelength range from 1.8 to 14 µm which covers the electromagnetic spectrum required for MIR molecular fingerprint region applications such as sensing and biological imaging
Modelling of the effect of ELMs on fuel retention at the bulk W divertor of JET
Effect of ELMs on fuel retention at the bulk W target of JET ITER-Like Wall was studied with multi-scale calculations. Plasma input parameters were taken from ELMy H-mode plasma experiment. The energetic intra-ELM fuel particles get implanted and create near-surface defects up to depths of few tens of nm, which act as the main fuel trapping sites during ELMs. Clustering of implantation-induced vacancies were found to take place. The incoming flux of inter-ELM plasma particles increases the different filling levels of trapped fuel in defects. The temperature increase of the W target during the pulse increases the fuel detrapping rate. The inter-ELM fuel particle flux refills the partially emptied trapping sites and fills new sites. This leads to a competing effect on the retention and release rates of the implanted particles. At high temperatures the main retention appeared in larger vacancy clusters due to increased clustering rate
Hyaluronic Acid Enhances Gene Delivery into the Cochlea
Abstract Cochlear gene therapy can be a new avenue for the treatment of severe hearing loss by inducing regeneration or phenotypic rescue. One necessary step to establish this therapy is the development of a safe and feasible inoculation surgery, ideally without drilling the bony cochlear wall. The round window membrane (RWM) is accessible in the middle-ear space, but viral vectors placed on this membrane do not readily cross the membrane to the cochlear tissues. In an attempt to enhance permeability of the RWM, we applied hyaluronic acid (HA), a nontoxic and biodegradable reagent, onto the RWM of guinea pigs, prior to delivering an adenovirus carrying enhanced green fluorescent protein (eGFP) reporter gene (Ad-eGFP) at the same site. We examined distribution of eGFP in the cochlea 1 week after treatment, comparing delivery of the vector via the RWM, with or without HA, to delivery by a cochleostomy into the perilymph. We found that cochlear tissue treated with HA-assisted delivery of Ad-eGFP demonstrated wider expression of transgenes in cochlear cells than did tissue treated by cochleostomy injection. HA-assisted vector delivery facilitated expression in cells lining the scala media, which are less accessible and not transduced after perilymphatic injection. We assessed auditory function by measuring auditory brainstem responses and determined that thresholds were significantly better in the ears treated with HA-assisted Ad-eGFP placement on the RWM as compared with cochleostomy. Together, these data demonstrate that HA-assisted delivery of viral vectors provides an atraumatic and clinically feasible method to introduce transgenes into cochlear cells, thereby enhancing both research methods and future clinical application.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98453/1/hum%2E2011%2E086.pd
Light fragments production and isospin dependences in Sn+Ni and Sn+Al central collisions at 25MeV/A and 35MeV/A from reverse/isospin experiments
This paper presents the physical analysis results for the following reactions: 124Sn+64Ni, 124Sn+27Al, 124Sn+58Ni at 35MeV/A and 25MeV/A. The main goal of this studies was to find observables sensitive to isospin effects and to present the similarities/differences between the systems characterised
by various charge asymmetry factor, defined as I = (NZ)=A. Theoretical simulations based on the Quantum Molecular Dynamics (QMD) model have been performed in order to compare them with the results
of the analysis of experimental data. The first phase of the reaction was carried out with the code CHIMERA [1]. The sequential decay of hot fragments was simulated by the code COOLER [2]. The conclusions are as
follows: there are observables sensitive to the isospin of the system, such as the Light Charged Particles (LCP) emission and their sensitivity is demonstrated more prominently in the analysis of central collisions at 35MeV/A.
The theoretical calculations do not reproduce these relations well
Mid-infrared supercontinuum generation to 125μm in large NA chalcogenide step-index fibres pumped at 45μm
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