178 research outputs found
Dynamics of stick-slip in peeling of an adhesive tape
We investigate the dynamics of peeling of an adhesive tape subjected to a
constant pull speed. We derive the equations of motion for the angular speed of
the roller tape, the peel angle and the pull force used in earlier
investigations using a Lagrangian. Due to the constraint between the pull
force, peel angle and the peel force, it falls into the category of
differential-algebraic equations requiring an appropriate algorithm for its
numerical solution. Using such a scheme, we show that stick-slip jumps emerge
in a purely dynamical manner. Our detailed numerical study shows that these set
of equations exhibit rich dynamics hitherto not reported. In particular, our
analysis shows that inertia has considerable influence on the nature of the
dynamics. Following studies in the Portevin-Le Chatelier effect, we suggest a
phenomenological peel force function which includes the influence of the pull
speed. This reproduces the decreasing nature of the rupture force with the pull
speed observed in experiments. This rich dynamics is made transparent by using
a set of approximations valid in different regimes of the parameter space. The
approximate solutions capture major features of the exact numerical solutions
and also produce reasonably accurate values for the various quantities of
interest.Comment: 12 pages, 9 figures. Minor modifications as suggested by refere
Diagnostic accuracy of a sequence-specific Mtb-DNA hybridization assay in urine: a case-control study including subclinical TB cases.
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) remains one of the deadliest infectious diseases globally. Timely diagnosis is a key step in the management of TB patients and in the prevention of further transmission events. Current diagnostic tools are limited in these regards. There is an urgent need for new accurate non-sputum-based diagnostic tools for the detection of symptomatic as well as subclinical TB. In this study, we recruited 52 symptomatic TB patients (sputum Xpert MTB/RIF positive) and 58 household contacts to assess the accuracy of a sequence-specific hybridization assay that detects the presence of Mtb cell-free DNA in urine. Using sputum Xpert MTB/RIF as a reference test, the magnetic bead-capture assay could discriminate active TB from healthy household contacts with an overall sensitivity of 72.1% [confidence interval (CI) 0.59-0.86] and specificity of 95.5% (CI 0.90-1.02) with a positive predictive value of 93.9% and negative predictive value of 78.2%. The detection of Mtb-specific DNA in urine suggested four asymptomatic TB infection cases that were confirmed in all instances either by concomitant Xpert MTB/RIF sputum testing or by follow-up investigation raising the specificity of the index test to 100%. We conclude that sequence-specific hybridization assays on urine specimens hold promise as non-invasive tests for the detection of subclinical TB.
There is an urgent need for a non-sputum-based diagnostic tool allowing sensitive and specific detection of all forms of tuberculosis (TB) infections. In that context, we performed a case-control study to assess the accuracy of a molecular detection method enabling the identification of cell-free DNA from Mycobacterium tuberculosis that is shed in the urine of tuberculosis patients. We present accuracy data that would fulfill the target product profile for a non-sputum test. In addition, recent epidemiological data suggested that up to 50% of individuals secreting live bacilli do not present with symptoms at the time of screening. We report, here, that the investigated index test could also detect instances of asymptomatic TB infections among household contacts
Case-control diagnostic accuracy study of a non-sputum CD38-based TAM-TB test from a single milliliter of blood
Background: CD4 T cell phenotyping-based blood assays have the potential to meet WHO target product profiles (TPP) of non-sputum-biomarker-based tests to diagnose tuberculosis (TB). Yet, substantial refinements are required to allow their implementation in clinical settings. This study assessed the real time performance of a simplified T cell activation marker (TAM)-TB assay to detect TB in adults from one millilitre of blood with a 24h turnaround time. Methods: We recruited 479 GeneXpert® positive cases and 108 symptomatic but GeneXpert® negativecontrols from presumptive adult TB patients in the Temeke District of Dar-es-Salaam, Tanzania. TAM-TB assay accuracy was assessed by comparison with a composite reference standard comprising GeneXpert® and solid culture. A single millilitre of fresh blood was processed to measure expression of CD38 or CD27 by CD4 T cells producing INF-γ and/or TNF-α in response to a synthetic peptide pool covering the sequences of Mycobacterium tuberculosis (Mtb) ESAT-6, CFP-10 and TB10.4 antigens on a 4-color FACSCalibur apparatus. Results: Significantly superior to CD27 in accurately diagnosing TB, the CD38-based TAM-TB assay specificity reached 93.4% for a sensitivity of 82.2% with an area under the receiver operating characteristics curve of 0.87 (95% CI 0.84-0.91). The assay performance was not significantly affected by HIV status. Conclusions: Wesuccessfully implemented TAM-TB immunoassay routine testing with a 24h turnaround time at district level in a resource limited setting. Starting from one millilitre of fresh blood and being not influenced by HIV status, TAM-TB assay format and performance appears closely compatible with the optimal TPP accuracy criteria defined by WHO for a non-sputum confirmatory TB test
CD38 expression by antigen-specific CD4 t cells is significantly restored 5 months after treatment initiation independently of sputum bacterial load at the time of tuberculosis diagnosis
T cell activation markers (TAM) expressed by antigen-specific T cells constitute promising candidates to attest the presence of an active infection by Mycobacterium tuberculosis (Mtb). Reciprocally, their modulation may be used to assess antibiotic treatment efficacy and eventually attest disease resolution. We hypothesized that the phenotype of Mtb-specific T cells may be quantitatively impacted by the load of bacteria present in a patient. We recruited 105 Tanzanian adult tuberculosis (TB) patients and obtained blood before and after 5 months of antibiotic treatment. We studied relationships between patients' clinical characteristics of disease severity and microbiological as well as molecular proxies of bacterial load in sputum at the time of diagnosis. Besides, we measured by flow cytometry the expression of CD38 or CD27 on CD4+ T cells producing interferon gamma (IFN-γ) and/or tumor necrosis factor alpha (TNF-α) in response to a synthetic peptide pool covering the sequences of Mtb antigens ESAT-6, CFP-10, and TB10.4. Reflecting the difficulty to extrapolate bacterial burden from a single end-point read-out, we observed statistically significant but weak correlations between Xpert MTB/RIF, molecular bacterial load assay and time to culture positivity. Unlike CD27, the resolution of CD38 expression by antigen-specific T cells was observed readily following 5 months of antibiotic therapy. However, the intensity of CD38-TAM signals measured at diagnosis did not significantly correlate with Mtb 16S RNA or rpoB DNA detected in patients' sputa. Altogether, our data support CD38-TAM as an accurate marker of infection resolution independently of sputum bacterial load
Scaling Behaviour and Complexity of the Portevin-Le Chatelier Effect
The plastic deformation of dilute alloys is often accompanied by plastic
instabilities due to dynamic strain aging and dislocation interaction. The
repeated breakaway of dislocations from and their recapture by solute atoms
leads to stress serrations and localized strain in the strain controlled
tensile tests, known as the Portevin-Le Chatelier (PLC) effect. In this present
work, we analyse the stress time series data of the observed PLC effect in the
constant strain rate tensile tests on Al-2.5%Mg alloy for a wide range of
strain rates at room temperature. The scaling behaviour of the PLC effect was
studied using two complementary scaling analysis methods: the finite variance
scaling method and the diffusion entropy analysis. From these analyses we could
establish that in the entire span of strain rates, PLC effect showed Levy walk
property. Moreover, the multiscale entropy analysis is carried out on the
stress time series data observed during the PLC effect to quantify the
complexity of the distinct spatiotemporal dynamical regimes. It is shown that
for the static type C band, the entropy is very low for all the scales compared
to the hopping type B and the propagating type A bands. The results are
interpreted considering the time and length scales relevant to the effect.Comment: 35 pages, 6 figure
Critical Dynamics of Burst Instabilities in the Portevin-Le Chatelier Effect
We investigate the Portevin-Le Chatelier effect (PLC), by compressing Al-Mg
alloys in a very large deformation range, and interpret the results from the
viewpoint of phase transitions and critical phenomena. The system undergoes two
dynamical phase transitions between intermittent (or "jerky") and "laminar"
plastic dynamic phases. Near these two dynamic critical points, the order
parameter 1/\tau of the PLC effect exhibits large fluctuations, and "critical
slowing down" (i.e., the number of bursts, or plastic instabilities, per
unit time slows down considerably).Comment: the published 4-page version is in the PRL web sit
Relaxation oscillations and negative strain rate sensitivity in the Portevin - Le Chatelier effect
A characteristic feature of the Portevin - Le Chatelier effect or the jerky
flow is the stick-slip nature of stress-strain curves which is believed to
result from the negative strain rate dependence of the flow stress. The latter
is assumed to result from the competition of a few relevant time scales
controlling the dynamics of jerky flow. We address the issue of time scales and
its connection to the negative strain rate sensitivity of the flow stress
within the framework of a model for the jerky flow which is known to reproduce
several experimentally observed features including the negative strain rate
sensitivity of the flow stress. We attempt to understand the above issues by
analyzing the geometry of the slow manifold underlying the relaxational
oscillations in the model. We show that the nature of the relaxational
oscillations is a result of the atypical bent geometry of the slow manifold.
The analysis of the slow manifold structure helps us to understand the time
scales operating in different regions of the slow manifold. Using this
information we are able to establish connection with the strain rate
sensitivity of the flow stress. The analysis also helps us to provide a proper
dynamical interpretation for the negative branch of the strain rate
sensitivity.Comment: 7 figures, To appear in Phys. Rev.
The role of acyl-coenzyme A carboxylase complex in lipstatin biosynthesis of Streptomyces toxytricini
Streptomyces toxytricini produces lipstatin, a specific inhibitor of pancreatic lipase, which is derived from two fatty acid moieties with eight and 14 carbon atoms. The pccB gene locus in 10.6 kb fragment of S. toxytricini chromosomal DNA contains three genes for acyl-coenzyme A carboxylase (ACCase) complex accA3, pccB, and pccE that are presumed to be involved in secondary metabolism. The pccB gene encoding a β subunit of ACCase [carboxyltransferase (CT)] was identified upstream of pccE gene for a small protein of ε subunit. The accA3 encoding the α subunit of ACCase [biotin carboxylase (BC)] was also identified downstream of pccB gene. When the pccB and pccE genes were inactivated by homologous recombination, the lipstatin production was reduced as much as 80%. In contrast, the accumulation of another compound, tetradeca-5.8-dienoic acid (the major lipstatin precursor), was 4.5-fold increased in disruptant compared with wild-type. It implies that PccB of S. toxytricini is involved in the activation of octanoic acid to hexylmalonic acid for lipstatin biosynthesis
Ethnic Variation in Inflammatory Profile in Tuberculosis
PMCID: PMC3701709This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Mycobacterium tuberculosis Rv3802c Encodes a Phospholipase/Thioesterase and Is Inhibited by the Antimycobacterial Agent Tetrahydrolipstatin
The cell wall of M. tuberculosis is central to its success as a pathogen. Mycolic acids are key components of this cell wall. The genes involved in joining the α and mero mycolates are located in a cluster, beginning with Rv3799c and extending at least until Rv3804c. The role of each enzyme encoded by these five genes is fairly well understood, except for Rv3802c. Rv3802 is one of seven putative cutinases encoded by the genome of M. tuberculosis. In phytopathogens, cutinases hydrolyze the waxy layer of plants, cutin. In a strictly mammalian pathogen, such as M. tuberculosis, it is likely that these proteins perform a different function. Of the seven, we chose to focus on Rv3802c because of its location in a mycolic acid synthesis gene cluster, its putative essentiality, its ubiquitous presence in actinomycetes, and its conservation in the minimal genome of Mycobacterium leprae. We expressed Rv3802 in Escherichia coli and purified the enzymatically active form. We probed its activities and inhibitors characterizing those relevant to its possible role in mycolic acid biosynthesis. In addition to its reported phospholipase A activity, Rv3802 has significant thioesterase activity, and it is inhibited by tetrahydrolipstatin (THL). THL is a described anti-tuberculous compound with an unknown mechanism, but it reportedly targets cell wall synthesis. Taken together, these data circumstantially support a role for Rv3802 in mycolic acid synthesis and, as the cell wall is integral to M. tuberculosis pathogenesis, identification of a novel cell wall enzyme and its inhibition has therapeutic and diagnostic implications
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