405 research outputs found
Speech rhythm: a metaphor?
Is speech rhythmic? In the absence of evidence for a traditional view that languages strive to coordinate either syllables or stress-feet with regular time intervals, we consider the alternative that languages exhibit contrastive rhythm subsisting merely in the alternation of stronger and weaker elements. This is initially plausible, particularly for languages with a steep âprominence gradientâ, i.e. a large disparity between stronger and weaker elements; but we point out that alternation is poorly achieved even by a âstress-timedâ language such as English, and, historically, languages have conspicuously failed to adopt simple phonological remedies that would ensure alternation. Languages seem more concerned to allow âsyntagmatic contrastâ between successive units and to use durational effects to support linguistic functions than to facilitate rhythm. Furthermore, some languages (e.g. Tamil, Korean) lack the lexical prominence which would most straightforwardly underpin prominence alternation. We conclude that speech is not incontestibly rhythmic, and may even be antirhythmic. However, its linguistic structure and patterning allow the metaphorical extension of rhythm in varying degrees and in different ways depending on the language, and that it is this analogical process which allows speech to be matched to external rhythms
Analysis of the first gigantic jet recorded over continental North America
[1] Two low-light cameras near Marfa, Texas, recorded a gigantic jet over northern Mexico on 13 May 2005 at approximately 0423:50 UTC. Assuming that the farthest of two candidate storm systems was its source, the bright lower channel ended in a fork at around 50â59 km height with the very dim upper branches extended to 69â80 km altitude. During the time window containing the jet, extremely low frequency magnetic field recordings show that there was no fast charge moment change larger than 50 coulomb times kilometers (C km) but there was a larger and slower charge moment change of 520 C km over 70 ms. The likely parent thunderstorm was a high-precipitation supercell cluster containing a persistent mesocyclone, with radar echo tops of at least 17 km. However, photogrammetric analysis suggests that the gigantic jet occurred over the forward flank downdraft region with echo tops of 14 km. This part of the supercell may have had an inverted-polarity charge configuration as evidenced by positive cloud-to-ground lightning flashes (+CG) dominating over negative flashes (-CG), while -CGs occurred under the downwind anvil. Four minutes before the gigantic jet, -CG activity practically ceased in this area, while +CG rates increased, culminating during the 20 s leading up to the gigantic jet with four National Lightning Detection Networkâdetected +CGs. A relative lull in lightning activity of both polarities was observed for up to 1.5 min after the gigantic jet. The maturing storm subsequently produced 30 sprites between 0454 and 0820 UTC, some associated with extremely large impulse charge moment change values.Peer ReviewedPostprint (published version
The association between serum biomarkers and disease outcome in influenza A(H1N1)pdm09 virus infection: results of two international observational cohort studies
BACKGROUND
Prospective studies establishing the temporal relationship between the degree of inflammation and human influenza disease progression are scarce. To assess predictors of disease progression among patients with influenza A(H1N1)pdm09 infection, 25 inflammatory biomarkers measured at enrollment were analyzed in two international observational cohort studies.
METHODS
Among patients with RT-PCR-confirmed influenza A(H1N1)pdm09 virus infection, odds ratios (ORs) estimated by logistic regression were used to summarize the associations of biomarkers measured at enrollment with worsened disease outcome or death after 14 days of follow-up for those seeking outpatient care (FLU 002) or after 60 days for those hospitalized with influenza complications (FLU 003). Biomarkers that were significantly associated with progression in both studies (p<0.05) or only in one (p<0.002 after Bonferroni correction) were identified.
RESULTS
In FLU 002 28/528 (5.3%) outpatients had influenza A(H1N1)pdm09 virus infection that progressed to a study endpoint of complications, hospitalization or death, whereas in FLU 003 28/170 (16.5%) inpatients enrolled from the general ward and 21/39 (53.8%) inpatients enrolled directly from the ICU experienced disease progression. Higher levels of 12 of the 25 markers were significantly associated with subsequent disease progression. Of these, 7 markers (IL-6, CD163, IL-10, LBP, IL-2, MCP-1, and IP-10), all with ORs for the 3(rd) versus 1(st) tertile of 2.5 or greater, were significant (p<0.05) in both outpatients and inpatients. In contrast, five markers (sICAM-1, IL-8, TNF-α, D-dimer, and sVCAM-1), all with ORs for the 3(rd) versus 1(st) tertile greater than 3.2, were significantly (pâ€.002) associated with disease progression among hospitalized patients only.
CONCLUSIONS
In patients presenting with varying severities of influenza A(H1N1)pdm09 virus infection, a baseline elevation in several biomarkers associated with inflammation, coagulation, or immune function strongly predicted a higher risk of disease progression. It is conceivable that interventions designed to abrogate these baseline elevations might affect disease outcome
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Methods for measuring benthic nutrient flux on the California Margin: Comparing shipboard core incubations to in situ lander results
The objective of this study was to compare two techniques for estimating benthic fluxes of nutrients (nitrate, phosphate, and silicic acid) and Ge/Si flux ratios. In situ flux chambers were deployed, and cores were collected and incubated at 9 sites along the California margin in July 2001. Both techniques were successful at 8 sites, at depths from 100 to 3300 m. Flux chambers were deployed for 1 to 2 d, and cores were incubated for slightly longer on board the ship in a cold room. In some cases, core incubation flux temperature varied by up to 5°C from in situ temperature, and core incubation results were adjusted for this factor based on the effects of temperature on diffusivities and the adsorption of silicic acid. Sites studied had a range in nutrient fluxes of more than an order of magnitude, based on in situ chambers. The temperature-adjusted core incubation fluxes showed a similar, but slightly smaller range. Both methods had similar precision based on replicates, with uncertainties for high flux stations that were 5% to 20% of the mean. Only phosphate showed significant (95% confidence level) spatial variability in replicate cores; the larger in situ flux chambers had less spatial variability. The two techniques did show some systematic differences that are attributed to several artifacts created by core recovery. Silicic acid fluxes from cores were significantly lower than in situ fluxes at 2 sites; overall averages were about 80% of those for in situ chambers. The differences are attributed to reduced macrofaunal irrigation in incubated cores. Nitrate uptake in core incubations at 5 of 8 stations was significantly lower than in situ uptake; shipboard rates for all sites averaged about 66% of in situ chamber rates. This difference is attributed primarily to decreased denitrification rates in recovered cores in response to altered temperature and pressure. Phosphate fluxes from cores were significantly lower at only one site; overall, results for the two techniques were indistinguishable. Only one site had a significantly different Ge/Si flux ratio
Scheme for the implementation of a universal quantum cloning machine via cavity-assisted atomic collisions in cavity QED
We propose a scheme to implement the universal quantum cloning
machine of Buzek et.al [Phys. Rev.A 54, 1844(1996)] in the context of cavity
QED. The scheme requires cavity-assisted collision processes between atoms,
which cross through nonresonant cavity fields in the vacuum states. The cavity
fields are only virtually excited to face the decoherence problem. That's why
the requirements on the cavity quality factor can be loosened.Comment: to appear in PR
Two-Stage Rotational Disordering of a Molecular Crystal Surface: C60
We propose a two-stage mechanism for the rotational surface disordering phase
transition of a molecular crystal, as realized in C fullerite. Our
study, based on Monte Carlo simulations, uncovers the existence of a new
intermediate regime, between a low temperature ordered state,
and a high temperature disordered phase. In the intermediate
regime there is partial disorder, strongest for a subset of particularly
frustrated surface molecules. These concepts and calculations provide a
coherent understanding of experimental observations, with possible extension to
other molecular crystal surfaces.Comment: 4 pages, 2 figure
Adjuvant tyrosine kinase inhibitor therapy improves outcome for children and adolescents with acute lymphoblastic leukaemia who have an ABLâclass fusion
Patients with an ABLâclass fusion have a high risk of relapse on standard chemotherapy but are sensitive to tyrosine kinase inhibitors (TKI). In UKALL2011, we screened patients with postâinduction MRD â„1% and positive patients (12%) received adjuvant TKI. As the intervention started during UKALL2011, not all eligible patients were screened prospectively. Retrospective screening of eligible patients allowed the outcome of equivalent ABLâclass patients who did and did not receive a TKI in first remission to be compared. ABLâclass patients who received a TKI in first remission had a reduced risk of relapse/refractory disease: 0% vs. 63% at four years (P = 0·009)
Freshwater Tertiary of northwestern Texas
p. 617-635, [7] leaves of plates (1 folded) : ill., maps ; 24 cm.Includes bibliographical references."Following is a summary of the conclusions reached by the writer from this study of the formations of northwestern Texas: (1) There has been no great disturbance or change of level in the region of the Staked Plains since the close of the Triassic, hence the strata of the Triassic which underlie this whole region are for the most part nearly horizontal, and the country at the beginning of the Miocene was comparatively level. (2) The Panhandle (Lower or Middle Miocene) beds were comparatively evenly distributed over the vast area now occupied by the Staked Plains and in addition extended westward to the Rocky Mountains in New Mexico, and spread out to the eastward over a much greater territiory than they now occupy. These deposits seem to be, at least partially, lacustrine in origin. (3) All the formations of the Staked Plains that are of more recent date than the Lower or Middle Miocene are represented by comparatively small areas, and are fluviatile, or aeolian and fluvaiatile, in origin. These later depositions are represented by the Clarendon beds in the vicinity of Clarendon, the Blanco Beds at Mount Blanco, and the Rock Creek beds at Tule Cañon and Rock Creek"--P. 635
Novel SMAC-mimetics synergistically stimulate melanoma cell death in combination with TRAIL and Bortezomib
BACKGROUND: XIAP (X-linked inhibitor of apoptosis protein) is an anti-apoptotic protein exerting its activity by binding and suppressing caspases. As XIAP is overexpressed in several tumours, in which it apparently contributes to chemoresistance, and because its activity in vivo is antagonised by second mitochondria-derived activator of caspase (SMAC)/direct inhibitor of apoptosis-binding protein with low pI, small molecules mimicking SMAC (so called SMAC-mimetics) can potentially overcome tumour resistance by promoting apoptosis.
METHODS: Three homodimeric compounds were synthesised tethering a monomeric SMAC-mimetic with different linkers and their affinity binding for the baculoviral inhibitor repeats domains of XIAP measured by fluorescent polarisation assay. The apoptotic activity of these molecules, alone or in combination with tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and/or Bortezomib, was tested in melanoma cell lines by MTT viability assays and western blot analysis of activated caspases.
RESULTS: We show that in melanoma cell lines, which are typically resistant to chemotherapeutic agents, XIAP knock-down sensitises cells to TRAIL treatment in vitro, also favouring the accumulation of cleaved caspase-8. We also describe a new series of 4-substituted azabicyclo[5.3.0] alkane monomeric and dimeric SMAC-mimetics that target various members of the IAP family and powerfully synergise at submicromolar concentrations with TRAIL in inducing cell death. Finally, we show that the simultaneous administration of newly developed SMAC-mimetics with Bortezomib potently triggers apoptosis in a melanoma cell line resistant to the combined effect of SMAC-mimetics and TRAIL.
CONCLUSION: Hence, the newly developed SMAC-mimetics effectively synergise with TRAIL and Bortezomib in inducing cell death. These findings warrant further preclinical studies in vivo to verify the anticancer effectiveness of the combination of these agents
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