2,086 research outputs found
The non-Abelian gauge theory of matrix big bangs
We study at the classical and quantum mechanical level the time-dependent
Yang-Mills theory that one obtains via the generalisation of discrete
light-cone quantisation to singular homogeneous plane waves. The non-Abelian
nature of this theory is known to be important for physics near the
singularity, at least as far as the number of degrees of freedom is concerned.
We will show that the quartic interaction is always subleading as one
approaches the singularity and that close enough to t=0 the evolution is driven
by the diverging tachyonic mass term. The evolution towards asymptotically flat
space-time also reveals some surprising features.Comment: 29 pages, 8 eps figures, v2: minor changes, references added: v3
small typographical changes
Impact of long-term elosulfase alfa treatment on respiratory function in patients with Morquio A syndrome
OBJECTIVE: To present long-term respiratory function outcomes from an open-label, multi-center, phase 3 extension study (MOR-005) of elosulfase alfa enzyme replacement therapy (ERT) in patients with Morquio A syndrome. METHODS: In part 1 of MOR-005, patients initially randomized to ERT in the 24-week pivotal study (MOR-004) remained on their regimen (2.0 mg/kg/week or every other week); placebo patients were re-randomized to one of the two regimens. During part 2, all patients received elosulfase alfa 2.0 mg/kg/week. Respiratory function was one of the efficacy endpoints evaluated in MOR-005. Change from MOR-004 baseline to 120 weeks of treatment for the combined population was determined and compared with results from untreated patients from a Morquio A natural history study (MorCAP). RESULTS: Maximum voluntary ventilation (MVV) improved up to week 72 and then stabilized; forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) increased continuously over 120 weeks. Mean increases in the modified per-protocol population was 9.2 % for FVC, 8.8 % for FEV1, and 6.1 % for MVV after 120 weeks. All patients ≤14 years showed respiratory improvements, presumably in part related to growth; however, these were greater in treated patients. For those >14 years, treated patients showed improvements, while deterioration occurred in untreated. Altogether, the improvements were significantly greater (P < 0.05) in treated patients. CONCLUSIONS: Long-term ERT is associated with sustained improvements in respiratory function in Morquio A. In younger patients (≤14 years), some improvement may be ascribed to growth. In older patients, other mechanisms, e.g., decreased glycosaminoglycan storage, are likely involved
Quantization of Midisuperspace Models
We give a comprehensive review of the quantization of midisuperspace models.
Though the main focus of the paper is on quantum aspects, we also provide an
introduction to several classical points related to the definition of these
models. We cover some important issues, in particular, the use of the principle
of symmetric criticality as a very useful tool to obtain the required
Hamiltonian formulations. Two main types of reductions are discussed: those
involving metrics with two Killing vector fields and spherically symmetric
models. We also review the more general models obtained by coupling matter
fields to these systems. Throughout the paper we give separate discussions for
standard quantizations using geometrodynamical variables and those relying on
loop quantum gravity inspired methods.Comment: To appear in Living Review in Relativit
Long-term endurance and safety of elosulfase alfa enzyme replacement therapy in patients with Morquio A syndrome
Long-term efficacy and safety of elosulfase alfa enzyme replacement therapy were evaluated in Morquio A patients over 96weeks (reaching 120weeks in total from pre-treatment baseline) in an open-label, multi-center, phase III extension study. During this extension of a 24-week placebo-controlled phase III study, all patients initially received 2.0mg/kg elosulfase alfa either weekly or every other week, prior to establishment of 2.0mg/kg/week as the recommended dose, at which point all patients received weekly treatment. Efficacy measures were compared to baseline of the initial 24-week study, enabling analyses of changes over 120weeks. In addition to performing analyses for the entire intent-to-treat (ITT) population (N=173), analyses were also performed for a modified per-protocol (MPP) population (N=124), which excluded patients who had orthopedic surgery during the extension study or were non-compliant with the study protocol (as determined by ≥20% missed infusions). Six-minute walk test (6MWT) was the primary efficacy measure; three-minute stair climb test (3MSCT) and normalized urine keratan sulfate (uKS) were secondary efficacy measures. Mean (SE) change from baseline to Week 120 in 6MWT distance was 32.0 (11.3)m and 39.9 (10.1)m for patients receiving elosulfase alfa at 2.0mg/kg/week throughout the study (N=56) and 15.1 (7.1)m and 31.7 (6.8)m in all patients combined, regardless of dosing regimen, for the ITT and MPP populations, respectively. Further analyses revealed that durability of 6MWT improvements was not impacted by baseline 6MWT distance, use of a walking aid, or age. Mean (SE) change at Week 120 in the 3MSCT was 5.5 (1.9) and 6.7 (2.0)stairs/min for patients receiving elosulfase alfa at 2.0mg/kg/week throughout the study and 4.3 (1.2) and 6.8 (1.3)stairs/min in all patients combined, regardless of dosing regimen, for the ITT and MPP populations, respectively Across all patients, mean (SE) change at Week 120 in normalized uKS was -59.4 (1.8)% and -62.3 (1.8)% in the ITT and MPP populations, respectively. In the absence of a placebo group, significance of the sustained improvements could not be evaluated directly. However, to provide context for interpretation of results, comparisons were performed with untreated patients from a Morquio A natural history study. In contrast to the results of the extension study, the untreated patients experienced constant uKS levels and a gradual decline in endurance test results over a similar period of time. Differences from the untreated natural history study patients were significant for 6MWT, 3MSCT, and uKS outcomes for the cohort of patients receiving optimal dosing throughout the study and for all cohorts pooled together, for both ITT and MPP populations (P<0.05). Safety findings were consistent with those of the initial 24-week study, with no new safety signals identified
Target profiling of an antimetastatic RAPTA agent by chemical proteomics: relevance to the mode of action.
The clinical development of anticancer metallodrugs is often hindered by the elusive nature of their molecular targets. To identify the molecular targets of an antimetastatic ruthenium organometallic complex based on 1,3,5-triaza-7-phosphaadamantane (RAPTA), we employed a chemical proteomic approach. The approach combines the design of an affinity probe featuring the pharmacophore with mass-spectrometry-based analysis of interacting proteins found in cancer cell lysates. The comparison of data sets obtained for cell lysates from cancer cells before and after treatment with a competitive binder suggests that RAPTA interacts with a number of cancer-related proteins, which may be responsible for the antiangiogenic and antimetastatic activity of RAPTA complexes. Notably, the proteins identified include the cytokines midkine, pleiotrophin and fibroblast growth factor-binding protein 3. We also detected guanine nucleotide-binding protein-like 3 and FAM32A, which is in line with the hypothesis that the antiproliferative activity of RAPTA compounds is due to induction of a G2/M arrest and histone proteins identified earlier as potential targets
Higher Dimensional Cylindrical or Kasner Type Electrovacuum Solutions
We consider a D dimensional Kasner type diagonal spacetime where metric
functions depend only on a single coordinate and electromagnetic field shares
the symmetries of spacetime. These solutions can describe static cylindrical or
cosmological Einstein-Maxwell vacuum spacetimes. We mainly focus on
electrovacuum solutions and four different types of solutions are obtained in
which one of them has no four dimensional counterpart. We also consider the
properties of the general solution corresponding to the exterior field of a
charged line mass and discuss its several properties. Although it resembles the
same form with four dimensional one, there is a difference on the range of the
solutions for fixed signs of the parameters. General magnetic field vacuum
solution are also briefly discussed, which reduces to Bonnor-Melvin magnetic
universe for a special choice of the parameters. The Kasner forms of the
general solution are also presented for the cylindrical or cosmological cases.Comment: 16 pages, Revtex. Text and references are extended, Published versio
Bigger, Better, Faster, More at the LHC
Multijet plus missing energy searches provide universal coverage for theories
that have new colored particles that decay into a dark matter candidate and
jets. These signals appear at the LHC further out on the missing energy tail
than two-to-two scattering indicates. The simplicity of the searches at the LHC
contrasts sharply with the Tevatron where more elaborate searches are necessary
to separate signal from background. The searches presented in this article
effectively distinguish signal from background for any theory where the LSP is
a daughter or granddaughter of the pair-produced colored parent particle
without ever having to consider missing energies less than 400 GeV.Comment: 26 pages, 8 Figures. Minor textual changes, typos fixed and
references adde
KamLAND Sensitivity to Neutrinos from Pre-Supernova Stars
In the late stages of nuclear burning for massive stars (M>8~M_{\sun}), the
production of neutrino-antineutrino pairs through various processes becomes the
dominant stellar cooling mechanism. As the star evolves, the energy of these
neutrinos increases and in the days preceding the supernova a significant
fraction of emitted electron anti-neutrinos exceeds the energy threshold for
inverse beta decay on free hydrogen. This is the golden channel for liquid
scintillator detectors because the coincidence signature allows for significant
reductions in background signals. We find that the kiloton-scale liquid
scintillator detector KamLAND can detect these pre-supernova neutrinos from a
star with a mass of 25~M_{\sun} at a distance less than 690~pc with 3
significance before the supernova. This limit is dependent on the neutrino mass
ordering and background levels. KamLAND takes data continuously and can provide
a supernova alert to the community.Comment: 19 pages, 6 figures, 1 tabl
Design, synthesis, nuclear localization, and biological activity of a fluorescent duocarmycin analog, HxTfA
HxTfA 4 is a fluorescent analog of a potent cytotoxic and antimalarial agent, TfA 3, which is currently being investigated for the development of an antimalarial vaccine, PlasProtect®. HxTfA contains a p-anisylbenzimidazole or Hx moiety, which is endowed with a blue emission upon excitation at 318 nm; thus enabling it to be used as a surrogate for probing the cellular fate of TfA using confocal microscopy, and addressing the question of nuclear localization. HxTfA exhibits similar selectivity to TfA for A-tract sequences of DNA, alkylating adenine-N3, albeit at 10-fold higher concentrations. It also possesses in vitro cytotoxicity against A549 human lung carcinoma cells and Plasmodium falciparum. Confocal microscopy studies showed for the first time that HxTfA, and by inference TfA, entered A549 cells and localized in the nucleus to exert its biological activity. At biologically relevant concentrations, HxTfA elicits DNA damage response as evidenced by a marked increase in the levels of γH2AX observed by confocal microscopy and immunoblotting studies, and ultimately induces apoptosis
Theorems on existence and global dynamics for the Einstein equations
This article is a guide to theorems on existence and global dynamics of
solutions of the Einstein equations. It draws attention to open questions in
the field. The local-in-time Cauchy problem, which is relatively well
understood, is surveyed. Global results for solutions with various types of
symmetry are discussed. A selection of results from Newtonian theory and
special relativity that offer useful comparisons is presented. Treatments of
global results in the case of small data and results on constructing spacetimes
with prescribed singularity structure or late-time asymptotics are given. A
conjectural picture of the asymptotic behaviour of general cosmological
solutions of the Einstein equations is built up. Some miscellaneous topics
connected with the main theme are collected in a separate section.Comment: Submitted to Living Reviews in Relativity, major update of Living
Rev. Rel. 5 (2002)
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