12,279 research outputs found
Insolubility Theorems and EPR Argument
I wish to thank in particular Arthur Fine for very perceptive comments on a previous draft of this paper. Many thanks also to Theo Nieuwenhuizen for inspiration, to Max Schlosshauer for correspondence, to two anonymous referees for shrewd observations, and to audiences at Aberdeen, Cagliari and Oxford (in particular to Harvey Brown, Elise Crull, Simon Saunders, Chris Timpson and David Wallace) for stimulating questions. This paper was written during my tenure of a Leverhulme Grant on ‘The Einstein Paradox’: The Debate on Nonlocality and Incompleteness in 1935 (Project Grant nr. F/00 152/AN), and it was revised for publication during my tenure of a Visiting Professorship in the Doctoral School of Philosophy and Epistemology, University of Cagliari (Contract nr. 268/21647).Peer reviewedPostprin
Identification of 2-Aminothiazole-4-Carboxylate Derivatives Active against Mycobacterium tuberculosis H37Rv and the β-Ketoacyl-ACP Synthase mtFabH
Background
Tuberculosis (TB) is a disease which kills two million people every year and infects approximately over one-third of the world's population. The difficulty in managing tuberculosis is the prolonged treatment duration, the emergence of drug resistance and co-infection with HIV/AIDS. Tuberculosis control requires new drugs that act at novel drug targets to help combat resistant forms of Mycobacterium tuberculosis and reduce treatment duration.
Methodology/Principal Findings
Our approach was to modify the naturally occurring and synthetically challenging antibiotic thiolactomycin (TLM) to the more tractable 2-aminothiazole-4-carboxylate scaffold to generate compounds that mimic TLM's novel mode of action. We report here the identification of a series of compounds possessing excellent activity against M. tuberculosis H37Rv and, dissociatively, against the β-ketoacyl synthase enzyme mtFabH which is targeted by TLM. Specifically, methyl 2-amino-5-benzylthiazole-4-carboxylate was found to inhibit M. tuberculosis H37Rv with an MIC of 0.06 µg/ml (240 nM), but showed no activity against mtFabH, whereas methyl 2-(2-bromoacetamido)-5-(3-chlorophenyl)thiazole-4-carboxylateinhibited mtFabH with an IC50 of 0.95±0.05 µg/ml (2.43±0.13 µM) but was not active against the whole cell organism.
Conclusions/Significance
These findings clearly identify the 2-aminothiazole-4-carboxylate scaffold as a promising new template towards the discovery of a new class of anti-tubercular agents
Inhalation characteristics of asthma patients, COPD patients and healthy volunteers with the Spiromax® and Turbuhaler® devices: a randomised, cross-over study.
BACKGROUND: Spiromax® is a novel dry-powder inhaler containing formulations of budesonide plus formoterol (BF). The device is intended to provide dose equivalence with enhanced user-friendliness compared to BF Turbuhaler® in asthma and chronic obstructive pulmonary disease (COPD). The present study was performed to compare inhalation parameters with empty versions of the two devices, and to investigate the effects of enhanced training designed to encourage faster inhalation. METHODS: This randomised, open-label, cross-over study included children with asthma (n = 23), adolescents with asthma (n = 27), adults with asthma (n = 50), adults with COPD (n = 50) and healthy adult volunteers (n = 50). Inhalation manoeuvres were recorded with each device after training with the patient information leaflet (PIL) and after enhanced training using an In-Check Dial device. RESULTS: After PIL training, peak inspiratory flow (PIF), maximum change in pressure (∆P) and the inhalation volume (IV) were significantly higher with Spiromax than with the Turbuhaler device (p values were at least <0.05 in all patient groups). After enhanced training, numerically or significantly higher values for PIF, ∆P, IV and acceleration remained with Spiromax versus Turbuhaler, except for ∆P in COPD patients. After PIL training, one adult asthma patient and one COPD patient inhaled <30 L/min through the Spiromax compared to one adult asthma patient and five COPD patients with the Turbuhaler. All patients achieved PIF values of at least 30 L/min after enhanced training. CONCLUSIONS: The two inhalers have similar resistance so inhalation flows and pressure changes would be expected to be similar. The higher flow-related values noted for Spiromax versus Turbuhaler after PIL training suggest that Spiromax might have human factor advantages in real-world use. After enhanced training, the flow-related differences between devices persisted; increased flow rates were achieved with both devices, and all patients achieved the minimal flow required for adequate drug delivery. Enhanced training could be useful, especially in COPD patients
Is there a no-go theorem for superradiant quantum phase transitions in cavity and circuit QED ?
In cavity quantum electrodynamics (QED), the interaction between an atomic
transition and the cavity field is measured by the vacuum Rabi frequency
. The analogous term "circuit QED" has been introduced for Josephson
junctions, because superconducting circuits behave as artificial atoms coupled
to the bosonic field of a resonator. In the regime with comparable
to the two-level transition frequency, "superradiant" quantum phase transitions
for the cavity vacuum have been predicted, e.g. within the Dicke model. Here,
we prove that if the time-independent light-matter Hamiltonian is considered, a
superradiant quantum critical point is forbidden for electric dipole atomic
transitions due to the oscillator strength sum rule. In circuit QED, the
capacitive coupling is analogous to the electric dipole one: yet, such no-go
property can be circumvented by Cooper pair boxes capacitively coupled to a
resonator, due to their peculiar Hilbert space topology and a violation of the
corresponding sum rule
Native American Tribes in Wisconsin Improve Health Care Delivery
This program report discusses the results and lessons learned from an Inter-Tribal managed care demonstration project in Wisconsin. The project was implemented from 1996 to 2000 to develop a more coordinated, cost-effective approach to health care among the nine Wisconsin Indian tribes belonging to GLITC, a nonprofit organization that aids tribes in delivery of health and other tribal services.
Live to cheat another day: bacterial dormancy facilitates the social exploitation of beta-lactamases
The breakdown of antibiotics by β-lactamases may be cooperative, since resistant cells can detoxify their environment and facilitate the growth of susceptible neighbours. However, previous studies of this phenomenon have used artificial bacterial vectors or engineered bacteria to increase the secretion of β-lactamases from cells. Here, we investigated whether a broad-spectrum β-lactamase gene carried by a naturally occurring plasmid (pCT) is cooperative under a range of conditions. In ordinary batch culture on solid media, there was little or no evidence that resistant bacteria could protect susceptible cells from ampicillin, although resistant colonies could locally detoxify this growth medium. However, when susceptible cells were inoculated at high densities, late-appearing phenotypically susceptible bacteria grew in the vicinity of resistant colonies. We infer that persisters, cells that have survived antibiotics by undergoing a period of dormancy, founded these satellite colonies. The number of persister colonies was positively correlated with the density of resistant colonies and increased as antibiotic concentrations decreased. We argue that detoxification can be cooperative under a limited range of conditions: if the toxins are bacteriostatic rather than bacteridical; or if susceptible cells invade communities after resistant bacteria; or if dormancy allows susceptible cells to avoid bactericides. Resistance and tolerance were previously thought to be independent solutions for surviving antibiotics. Here, we show that these are interacting strategies: the presence of bacteria adopting one solution can have substantial effects on the fitness of their neighbours
Holography at an Extremal De Sitter Horizon
Rotating maximal black holes in four-dimensional de Sitter space, for which
the outer event horizon coincides with the cosmological horizon, have an
infinite near-horizon region described by the rotating Nariai metric. We show
that the asymptotic symmetry group at the spacelike future boundary of the
near-horizon region contains a Virasoro algebra with a real, positive central
charge. This is evidence that quantum gravity in a rotating Nariai background
is dual to a two-dimensional Euclidean conformal field theory. These results
are related to the Kerr/CFT correspondence for extremal black holes, but have
two key differences: one of the black hole event horizons has been traded for
the cosmological horizon, and the near-horizon geometry is a fiber over dS_2
rather than AdS_2.Comment: 15 page
Measurement of the antineutrino neutral-current elastic differential cross section
arXiv:1309.7257v1 [hep-ex
Sustainable deltas in the Anthropocene
What are the possible trajectories of delta development over the coming decades? Trajectories will be determined by the interactions of biophysical trends such as changing sediment supplies, subsidence due to compaction of sediment and climate change, along with key socio-economic trends of migration and urbanisation, agricultural intensification, demographic transition, economic growth and structural change of the economy. Knowledge and understanding of plausible trajectories can inform management choices for deltas in the Anthropocene, including new policy perspectives and innovative adaptation. The emergence of visionary delta management plans in some large deltas, such as the Bangladesh Delta Plan 2100, is an important and necessary component. This chapter synthesises the state of knowledge and highlights key elements of science that will inform decisions on future management of deltas.<br/
Annual variation in the levels of transcripts of sex-specific genes in the mantle of the common mussel, Mytilus edulis
Mytilus species are used as sentinels for the assessment of environmental health but sex or stage in the reproduction cycle is rarely considered even though both parameters are likely to influence responses to pollution. We have validated the use of a qPCR assay for sex identification and related the levels of transcripts to the reproductive cycle. A temporal study of mantle of Mytilus edulis found transcripts of male-specific vitelline coat lysin (VCL) and female-specific vitelline envelope receptor for lysin (VERL) could identify sex over a complete year. The levels of VCL/VERL were proportional to the numbers of sperm/ova and are indicative of the stage of the reproductive cycle. Maximal levels of VCL and VERL were found in February 2009 declining to minima between July - August before increasing and re-attaining a peak in February 2010. Water temperature may influence these transitions since they coincide with minimal water temperature in February and maximal temperature in August. An identical pattern of variation was found for a cryptic female-specific transcript (H5) but a very different pattern was observed for oestrogen receptor 2 (ER2). ER2 varied in a sex-specific way with male > female for most of the cycle, with a female maxima in July and a male maxima in December. Using artificially spawned animals, the transcripts for VCL, VERL and H5 were shown to be present in gametes and thus their disappearance from mantle is indicative of spawning. VCL and VERL are present at equivalent levels in February and July-August but during gametogenesis (August to January) and spawning (March to June) VCL is present at lower relative amounts than VERL. This may indicate sex-specific control mechanisms for these processes and highlight a potential pressure point leading to reduced reproductive output if environmental factors cause asynchrony to gamete maturation or release
- …
