1,216 research outputs found
Philadelphia's Changing Schools and What Parents Want From Them
Based on a survey, examines parents' expectations from and perceptions of school reforms, performance, and options among district-run, charter, private, and Catholic schools; priorities; and challenges by race/ethnicity, age, and income
On Locality in Quantum General Relativity and Quantum Gravity
The physical concept of locality is first analyzed in the special
relativistic quantum regime, and compared with that of microcausality and the
local commutativity of quantum fields. Its extrapolation to quantum general
relativity on quantum bundles over curved spacetime is then described. It is
shown that the resulting formulation of quantum-geometric locality based on the
concept of local quantum frame incorporating a fundamental length embodies the
key geometric and topological aspects of this concept. Taken in conjunction
with the strong equivalence principle and the path-integral formulation of
quantum propagation, quantum-geometric locality leads in a natural manner to
the formulation of quantum-geometric propagation in curved spacetime. Its
extrapolation to geometric quantum gravity formulated over quantum spacetime is
described and analyzed.Comment: Mac-Word file translated to postscript for submission. The author may
be reached at: [email protected] To appear in Found. Phys. vol. 27,
199
Estrogenic activity assessment of environmental chemicals using in vitro assays: identification of two new estrogenic compounds.
Environmental chemicals with estrogenic activities have been suggested to be associated with deleterious effects in animals and humans. To characterize estrogenic chemicals and their mechanisms of action, we established in vitro and cell culture assays that detect human estrogen receptor [alpha] (hER[alpha])-mediated estrogenicity. First, we assayed chemicals to determine their ability to modulate direct interaction between the hER[alpha] and the steroid receptor coactivator-1 (SRC-1) and in a competition binding assay to displace 17ss-estradiol (E(2)). Second, we tested the chemicals for estrogen-associated transcriptional activity in the yeast estrogen screen and in the estrogen-responsive MCF-7 human breast cancer cell line. The chemicals investigated in this study were o,p'-DDT (racemic mixture and enantiomers), nonylphenol mixture (NPm), and two poorly analyzed compounds in the environment, namely, tris-4-(chlorophenyl)methane (Tris-H) and tris-4-(chlorophenyl)methanol (Tris-OH). In both yeast and MCF-7 cells, we determined estrogenic activity via the estrogen receptor (ER) for o,p'-DDT, NPm, and for the very first time, Tris-H and Tris-OH. However, unlike estrogens, none of these xenobiotics seemed to be able to induce ER/SRC-1 interactions, most likely because the conformation of the activated receptor would not allow direct contacts with this coactivator. However, these compounds were able to inhibit [(3)H]-E(2) binding to hER, which reveals a direct interaction with the receptor. In conclusion, the test compounds are estrogen mimics, but their molecular mechanism of action appears to be different from that of the natural hormone as revealed by the receptor/coactivator interaction analysis
Restricting HIV-1 pathways for escape using rationally designed anti–HIV-1 antibodies
Recently identified broadly neutralizing antibodies (bNAbs) that potently neutralize most HIV-1 strains are key to potential antibody-based therapeutic approaches to combat HIV/AIDS in the absence of an effective vaccine. Increasing bNAb potencies and resistance to common routes of HIV-1 escape through mutation would facilitate their use as therapeutics. We previously used structure-based design to create the bNAb NIH45-46G54W, which exhibits superior potency and/or breadth compared with other bNAbs. We report new, more effective NIH45-46^(G54W) variants designed using analyses of the NIH45-46–gp120 complex structure and sequences of NIH45-46^(G54W)–resistant HIV-1 strains. One variant, 45-46m2, neutralizes 96% of HIV-1 strains in a cross-clade panel and viruses isolated from an HIV-infected individual that are resistant to all other known bNAbs, making it the single most broad and potent anti–HIV-1 antibody to date. A description of its mechanism is presented based on a 45-46m2–gp120 crystal structure. A second variant, 45-46m7, designed to thwart HIV-1 resistance to NIH45-46G54W arising from mutations in a gp120 consensus sequence, targets a common route of HIV-1 escape. In combination, 45-46m2 and 45-46m7 reduce the possible routes for the evolution of fit viral escape mutants in HIV-1_(YU-2)–infected humanized mice, with viremic control exhibited when a third antibody, 10–1074, was added to the combination
Boson-fermion unification, superstrings, and Bohmian mechanics
Bosonic and fermionic particle currents can be introduced in a more unified
way, with the cost of introducing a preferred spacetime foliation. Such a
unified treatment of bosons and fermions naturally emerges from an analogous
superstring current, showing that the preferred spacetime foliation appears
only at the level of effective field theory, not at the fundamental superstring
level. The existence of the preferred spacetime foliation allows an objective
definition of particles associated with quantum field theory in curved
spacetime. Such an objective definition of particles makes the Bohmian
interpretation of particle quantum mechanics more appealing. The superstring
current allows a consistent Bohmian interpretation of superstrings themselves,
including a Bohmian description of string creation and destruction in terms of
string splitting. The Bohmian equations of motion and the corresponding
probabilistic predictions are fully relativistic covariant and do not depend on
the preferred foliation.Comment: 30 pages, 1 figure, revised, to appear in Found. Phy
Effect of angular momentum on equilibrium properties of a self-gravitating system
The microcanonical properties of a two dimensional system of N classical
particles interacting via a smoothed Newtonian potential as a function of the
total energy E and the total angular momentum L are discussed. In order to
estimate suitable observables a numerical method based on an importance
sampling algorithm is presented. The entropy surface shows a negative specific
heat region at fixed L for all L. Observables probing the average mass
distribution are used to understand the link between thermostatistical
properties and the spatial distribution of particles. In order to define a
phase in non-extensive system we introduce a more general observable than the
one proposed by Gross and Votyakov [Eur. Phys. J. B:15, 115 (2000)]: the sign
of the largest eigenvalue of the entropy surface curvature. At large E the
gravitational system is in a homogeneous gas phase. At low E there are several
collapse phases; at L=0 there is a single cluster phase and for L>0 there are
several phases with 2 clusters. All these pure phases are separated by first
order phase transition regions. The signal of critical behaviour emerges at
different points of the parameter space (E,L). We also discuss the ensemble
introduced in a recent pre-print by Klinko & Miller; this ensemble is the
canonical analogue of the one at constant energy and constant angular momentum.
We show that a huge loss of informations appears if we treat the system as a
function of intensive parameters: besides the known non-equivalence at first
order phase transitions, there exit in the microcanonical ensemble some values
of the temperature and the angular velocity for which the corresponding
canonical ensemble does not exist, i.e. the partition sum diverges.Comment: 17 pages, 11 figures, submitted to Phys. Rev.
The role of lumbar puncture in children with suspected central nervous system infection
BACKGROUND: The use of the lumbar puncture in the diagnosis of central nervous system infection in acutely ill children is controversial. Recommendations have been published but it is unclear whether they are being followed. METHODS: The medical case notes of 415 acute medical admissions in a children's hospital were examined to identify children with suspected central nervous system infection and suspected meningococcal septicaemia. We determined whether lumbar punctures were indicated or contraindicated, whether they had been performed, and whether the results contributed to the patients' management. RESULTS: Fifty-two children with suspected central nervous system infections, and 43 with suspected meningococcal septicaemia were identified. No lumbar punctures were performed in patients with contraindications, but only 25 (53%) of 47 children with suspected central nervous system infection and no contraindications received a lumbar puncture. Lumbar puncture findings contributed to the management in 18 (72%) of these patients, by identifying a causative organism or excluding bacterial meningitis. CONCLUSION: The recommendations for undertaking lumbar punctures in children with suspected central nervous system infection are not being followed because many children that should receive lumbar punctures are not getting them. When they are performed, lumbar puncture findings make a useful contribution to the patients' management
Maternal LAMP/p55gagHIV-1 DNA Immunization Induces In Utero Priming and a Long-Lasting Immune Response in Vaccinated Neonates
Infants born to HIV-infected mothers are at high risk of becoming infected during gestation or the breastfeeding period. A search is thus warranted for vaccine formulations that will prevent mother-to-child HIV transmission. The LAMP/gag DNA chimeric vaccine encodes the HIV-1 p55gag fused to the lysosome-associated membrane protein-1 (LAMP-1) and has been shown to enhance anti-Gag antibody (Ab) and cellular immune responses in adult and neonatal mice; such a vaccine represents a new concept in antigen presentation. In this study, we evaluated the effect of LAMP/gag DNA immunization on neonates either before conception or during pregnancy. LAMP/gag immunization of BALB/c mice before conception by the intradermal route led to the transfer of anti-Gag IgG1 Ab through the placenta and via breastfeeding. Furthermore, there were an increased percentage of CD4+CD25+Foxp3+T cells in the spleens of neonates. When offspring were immunized with LAMP/gag DNA, the anti-Gag Ab response and the Gag-specific IFN-γ-secreting cells were decreased. Inhibition of anti-Gag Ab production and cellular responses were not observed six months after immunization, indicating that maternal immunization did not interfere with the long-lasting memory response in offspring. Injection of purified IgG in conjunction with LAMP/gag DNA immunization decreased humoral and cytotoxic T-cell responses. LAMP/gag DNA immunization by intradermal injection prior to conception promoted the transfer of Ab, leading to a diminished response to Gag without interfering with the development of anti-Gag T- and B-cell memory. Finally, we assessed responses after one intravenous injection of LAMP/gag DNA during the last five days of pregnancy. The intravenous injection led to in utero immunization. In conclusion, DNA vaccine enconding LAMP-1 with Gag and other HIV-1 antigens should be considered in the development of a protective vaccine for the maternal/fetal and newborn periods
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