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 $\gamma=1.2373(2)$, $\nu=0.63012(16)$, $\alpha=0.1096(5)$, $\eta=0.03639(15)$, $\beta=0.32653(10)$, $\delta=4.7893(8)$. Moreover, biased analyses of the 25th-order series of the standard Ising model provide the estimate $\Delta=0.52(3)$ 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 $(n+1)$-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