138 research outputs found
Running mechanics adjustments to perceptually-regulated interval runs in hypoxia and normoxia
Objectives We determined whether perceptually-regulated, high-intensity intermittent runs in hypoxia and normoxia induce similar running mechanics adjustments within and between intervals. Design Within-participants repeated measures. Methods Nineteen trained runners completed a high-intensity intermittent running protocol (4×4-min intervals at a perceived rating exertion of 16 on the 6–20 Borg scale, 3-min passive recoveries) in either hypoxic (FiO2 =0.15) or normoxic (FiO2 =0.21) conditions. Running mechanics were collected over 10 consecutive steps, at constant velocity (∼15.0±2.0km.h−1), at the beginning and the end of each 4-min interval. Repeated measure ANOVA were used to assess within intervals (onset vs. end of each interval), between intervals (interval 1, 2, 3 vs. 4) and FiO2 (0.15 vs. 0.21) main effects and any potential interaction. Results Participants progressively reduced running velocity from interval 1–4, and more so in hypoxia compared to normoxia for intervals 2, 3 and 4 (P 0.298) and FiO2 (across all intervals P >0.082) main effects or any significant between intervals×within intervals×FiO2 interactions (all P >0.098) for any running mechanics variables. Irrespective of interval number or FiO2, peak loading rate (+10.6±7.7%; P <0.001) and duration of push-off phase (+2.0±3.1%; P =0.001) increased from the onset to the end of 4-min intervals, whereas peak push-off force decreased (−4.0±4.0%; P <0.001). Conclusions When carrying out perceptually-regulated interval treadmill runs, runners adjust to progressively slower velocities in hypoxia compared to normoxia. However, only subtle constant-velocity modifications of their mechanical behaviour occurred within each set, independently of FiO2 or interval number
Targeting HOX-PBX interactions causes death in oral potentially malignant and squamous carcinoma cells but not normal oral keratinocytes
YesBackground: High HOX gene expression has been described in many cancers, including oral squamous cell
carcinoma and the functional roles of these genes are gradually being understood. The pattern of overexpression
suggests that inhibition may be useful therapeutically. Inhibition of HOX protein binding to PBX cofactors by the
use of synthetic peptides, such as HXR9, results in apoptosis in multiple cancers.
Methods: Activity of the HOX-PBX inhibiting peptide HXR9 was tested in immortalised normal oral (NOK),
potentially-malignant (PMOL) and squamous cell carcinoma (OSCC) cells, compared to the inactive peptide
CXR9. Cytotoxicity was assessed by LDH assay. Expression of PBX1/2 and c-Fos was assessed by qPCR and
western blotting. Apoptosis was assessed by Annexin-V assay.
Results: PMOL and OSCC cells expressed PBX1/2. HOX-PBX inhibition by HXR9 caused death of PMOL and
OSCC cells, but not NOKs. HXR9 treatment resulted in apoptosis and increased expression of c-Fos in some
cells, whereas CXR9 did not. A correlation was observed between HOX expression and resistance to HXR9.
Conclusion: Inhibition of HOX-PBX interactions causes selective apoptosis of OSCC/PMOL, indicating selective
toxicity that may be useful clinically.Intercalated Degree Scholarship from the Harry Bottom Trust; scholarship by Becas Chile, Comisión Nacional de Investigación Científica y Tecnológica de Chile (CONICYT), Grant 7216004
Fluid Models of Many-server Queues with Abandonment
We study many-server queues with abandonment in which customers have general
service and patience time distributions. The dynamics of the system are modeled
using measure- valued processes, to keep track of the residual service and
patience times of each customer. Deterministic fluid models are established to
provide first-order approximation for this model. The fluid model solution,
which is proved to uniquely exists, serves as the fluid limit of the
many-server queue, as the number of servers becomes large. Based on the fluid
model solution, first-order approximations for various performance quantities
are proposed
HOPX functions as a tumour suppressor in head and neck cancer.
Head and neck squamous cell carcinoma (HNSCC) is generalized term that encompasses a diverse group of cancers that includes tumours of the oral cavity (OSCC), oropharynx (OPSCC) and nasopharynx (NPC). Genetic alterations that are common to all HNSCC types are likely to be important for squamous carcinogenesis. In this study, we have investigated the role of the homeodomain-only homeobox gene, HOPX, in the pathogenesis of HNSCC. We show that HOPX mRNA levels are reduced in OSCC and NPC cell lines and tissues and there is a general reduction of HOPX protein expression in these tumours and OPSCCs. HOPX promoter methylation was observed in a subset of HNSCCs and was associated with a worse overall survival in HPV negative tumours. RNAseq analysis of OSCC cells transfected with HOPX revealed a widespread deregulation of the transcription of genes related to epithelial homeostasis and ectopic over-expression of HOPX in OSCC and NPC cells inhibited cell proliferation, plating efficiency and migration, and enhanced sensitivity to UVA-induced apoptosis. Our results demonstrate that HOPX functions as a tumour suppressor in HNSCC and suggest a central role for HOPX in suppressing epithelial carcinogenesis
25th-order high-temperature expansion results for three-dimensional Ising-like systems on the simple cubic lattice
25th-order high-temperature series are computed for a general
nearest-neighbor three-dimensional Ising model with arbitrary potential on the
simple cubic lattice. In particular, we consider three improved potentials
characterized by suppressed leading scaling corrections. Critical exponents are
extracted from high-temperature series specialized to improved potentials,
obtaining , , ,
, , . Moreover, biased
analyses of the 25th-order series of the standard Ising model provide the
estimate for the exponent associated with the leading scaling
corrections. By the same technique, we study the small-magnetization expansion
of the Helmholtz free energy. The results are then applied to the construction
of parametric representations of the critical equation of state, using a
systematic approach based on a global stationarity condition. Accurate
estimates of several universal amplitude ratios are also presented.Comment: 40 pages, 15 figure
Critical exponents and equation of state of the three-dimensional Heisenberg universality class
We improve the theoretical estimates of the critical exponents for the
three-dimensional Heisenberg universality class. We find gamma=1.3960(9),
nu=0.7112(5), eta=0.0375(5), alpha=-0.1336(15), beta=0.3689(3), and
delta=4.783(3). We consider an improved lattice phi^4 Hamiltonian with
suppressed leading scaling corrections. Our results are obtained by combining
Monte Carlo simulations based on finite-size scaling methods and
high-temperature expansions. The critical exponents are computed from
high-temperature expansions specialized to the phi^4 improved model. By the
same technique we determine the coefficients of the small-magnetization
expansion of the equation of state. This expansion is extended analytically by
means of approximate parametric representations, obtaining the equation of
state in the whole critical region. We also determine a number of universal
amplitude ratios.Comment: 40 pages, final version. In publication in Phys. Rev.
A diagnostic PCR assay for the detection of an Australian epidemic strain of Pseudomonas aeruginosa
Background Chronic lung infection with the bacterium Pseudomonas aeruginosa is one of the hallmarks of cystic fibrosis (CF) and is associated with worsening lung function, increased hospitalisation and reduced life expectancy. A virulent clonal strain of P. aeruginosa (Australian epidemic strain I; AES-I) has been found to be widespread in CF patients in eastern Australia. Methods Suppression subtractive hybridization (SSH) was employed to identify genetic sequences that are present in the AES-I strain but absent from the sequenced reference strain PAO1. We used PCR to evaluate the distribution of several of the AES-I loci amongst a collection of 188 P. aeruginosa isolates which was comprised of 35 AES-I isolates (as determined by PFGE), 78 non-AES-I CF isolates including other epidemic CF strains as well as 69 P. aeruginosa isolates from other clinical and environmental sources. Results We have identified a unique AES-I genetic locus that is present in all 35 AES-I isolates tested and not present in any of the other 153 P. aeruginosa strains examined. We have used this unique AES-I locus to develop a diagnostic PCR and a real-time PCR assay to detect the presence of P. aeruginosa and AES-I in patient sputum samples
Thermodynamics of higher dimensional topological charged AdS black branes in dilaton gravity
In this paper, we study topological AdS black branes of -dimensional
Einstein-Maxwell-dilaton theory and investigate their properties. We use the
area law, surface gravity and Gauss law interpretations to find entropy,
temperature and electrical charge, respectively. We also employ the modified
Brown and York subtraction method to calculate the quasilocal mass of the
solutions. We obtain a Smarr-type formula for the mass as a function of the
entropy and the charge, compute the temperature and the electric potential
through the Smarr-type formula and show that these thermodynamic quantities
coincide with their values which are calculated through using the geometry.
Finally, we perform a stability analysis in the canonical ensemble and
investigate the effects of the dilaton field and the size of black brane on the
thermal stability of the solutions. We find that large black branes are stable
but for small black brane, depending on the value of dilaton field and type of
horizon, we encounter with some unstable phases.Comment: 21 pages, 21 figures, references updated, minor editing, accepted in
EPJC (DOI: 10.1140/epjc/s10052-010-1483-3
Mutation of a single residue, β-glutamate-20, alters protein–lipid interactions of light harvesting complex II
It is well established that assembly of the peripheral antenna complex, LH2, is required for proper photosynthetic membrane biogenesis in the purple bacterium Rhodobacter sphaeroides. The underlying interactions are, as yet, not understood. Here we examined the relationship between the morphology of the photosynthetic membrane and the lipid–protein interactions at the LH2–lipid interface. The non-bilayer lipid, phosphatidylethanolamine, is shown to be highly enriched in the boundary lipid phase of LH2. Sequence alignments indicate a putative lipid binding site, which includes β-glutamate-20 and the adjacent carotenoid end group. Replacement of β-glutamate-20 with alanine results in significant reduction of phosphatidylethanolamine and concomitant raise in phosphatidylcholine in the boundary lipid phase of LH2 without altering the lipid composition of the bulk phase. The morphology of the LH2 housing membrane is, however, unaffected by the amino acid replacement. In contrast, simultaneous modification of glutamate-20 and exchange of the carotenoid sphaeroidenone with neurosporene results in significant enlargement of the vesicular membrane invaginations. These findings suggest that the LH2 complex, specifically β-glutamate-20 and the carotenoids' polar head group, contribute to the shaping of the photosynthetic membrane by specific interactions with surrounding lipid molecules
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