Muscle fatigue resistance during stimulated contractions is reduced in young male smokers.

Aim: To determine whether muscle function is compromised in healthy smokers in comparison with activity-matched non-smokers. Methods: Nine male smokers (aged 22.2 ± 2.5 years: mean ± SD) with a smoking history of 2.5 ± 3.1 pack years, and ten male control participants (25.4 ± 2.9 years) matched for physical activity level participated in this study. Knee extensor strength was measured using isometric maximal voluntary contractions. Voluntary activation of the quadriceps and co-activation of the biceps femoris were determined using interpolated twitches and surface electromyography respectively. The frequency-torque relationship and fatigue resistance were assessed with electrically evoked contractions. A fatigue index was determined as the ratio of final torque to initial torque during a series of isometric contractions (2 min; 30 Hz; 1 s contraction/1 s rest). Quadriceps anatomical cross sectional area was measured with MRI at 50% of femur length. Results: Maximal voluntary contraction torque, quadriceps anatomical cross sectional area, knee extensor torque/quadriceps cross sectional area, activation, co-activation and force-frequency relationship were similar, whereas the fatigue index was 17% lower in smokers than non-smokers. Conclusion: In young men smoking does not significantly affect quadriceps muscle mass and contractile properties, but does reduce fatigue resistance of the quadriceps muscle, which was not attributable to differences in physical activity. © 2007 The Authors

Cosmology with clusters of galaxies

In this Chapter I review the role that galaxy clusters play as tools to constrain cosmological parameters. I will concentrate mostly on the application of the mass function of galaxy clusters, while other methods, such as that based on the baryon fraction, are covered by other Chapters of the book. Since most of the cosmological applications of galaxy clusters rely on precise measurements of their masses, a substantial part of my Lectures concentrates on the different methods that have been applied so far to weight galaxy clusters. I provide in Section 2 a short introduction to the basics of cosmic structure formation. In Section 3 I describe the Press--Schechter (PS) formalism to derive the cosmological mass function, then discussing extensions of the PS approach and the most recent calibrations from N--body simulations. In Section 4 I review the methods to build samples of galaxy clusters at different wavelengths. Section 5 is devoted to the discussion of different methods to derive cluster masses. In Section 6 I describe the cosmological constraints, which have been obtained so far by tracing the cluster mass function with a variety of methods. Finally, I describe in Section 7 the future perspectives for cosmology with galaxy clusters and the challenges for clusters to keep playing an important role in the era of precision cosmology.Comment: 49 pages, 19 figures, Lectures for 2005 Guillermo Haro Summer School on Clusters, to appear in "Lecture notes in Physics" (Springer

A Machine Learning Model of Complete Response to Radiation in Rectal Cancer Reveals Immune Infiltrate and TGFβ Signalling as Key Predictors

Background: It is uncertain which biological features underpin the response of rectal cancer (RC) to radiotherapy. No biomarker is currently in clinical use to select patients for treatment modifications. Methods: We identified two cohorts of patients (total N=249) with RC treated with neoadjuvant radiotherapy (45Gy/25) plus fluoropyrimidine. This discovery set included 57 cases with pathological complete response (pCR) to chemoradiotherapy (23%). Pre-treatment cancer biopsies were assessed using transcriptome-wide mRNA expression and targeted DNA sequencing for copy number and driver mutations. Biological candidate and machine learning (ML) approaches were used to identify predictors of pCR to radiotherapy independent of tumour stage. Findings were assessed in 107 cases from an independent validation set (GSE87211). Findings: Three gene expression sets showed significant independent associations with pCR: Fibroblast-TGFβ Response Signature (F-TBRS) with radioresistance; and cytotoxic lymphocyte (CL) expression signature and consensus molecular subtype CMS1 with radiosensitivity. These associations were replicated in the validation cohort. In parallel, a gradient boosting machine model comprising the expression of 33 genes was generated in the discovery cohort, and showed high performance in GSE87211 with 90% sensitivity, 86% specificity. Biological and ML signatures indicated similar mechanisms underlying radiation response, and showed better AUC and p-values than published transcriptomic signatures of radiation response in RC. Interpretation: RCs responding completely to chemoradiotherapy (CRT) have biological characteristics of immune response and absence of immune inhibitory TGFb signalling. These tumours can be identified by measurement of expression of a 33 gene signature. This could help select patients likely to respond to treatment with a primary radiotherapy approach as for anal cancer. Conversely, those with predicted radioresistance may be candidates for clinical trials evaluating addition of immune-oncology agents and stromal TGFb signalling inhibition. Funding Information: The Stratification in Colorectal Cancer Consortium (S:CORT) was funded by the Medical Research Council and Cancer Research UK (MR/M016587/1). Declaration of Interests: V.H.K. gratefully acknowledges funding by the Swiss National Science Foundation (P2SKP3_168322/1 and P2SKP3_168322/2) and the Promedica Foundation (F-87701-41-01). N.P.W acknowledges payment to institution from Yorkshire Cancer Research and CRU. P.D. acknowledges funding by Cancer Research UK (CRUK) early detection project grant (grant no. A29834. I.T and TSM acknowledge funding from CRUK and MRC. Other authors declare no conflict of interests. Ethics Approval Statement: The S:CORT consortium including this specific analysis was reviewed and approved by the South Cambs Research Ethics committee (REC ref 15/EE/0241; IRAS reference 169363)

Organogênese direta de Orthophytum mucugense Direct organogenesis of Orthophytum mucugense

Orthophytum mucugense é uma bromélia ornamental endêmica do município de Mucugê-BA que está passível de extinção. O objetivo deste trabalho foi estabelecer um protocolo de regeneração via organogênese direta para a espécie. Os explantes raiz, caule e folha, oriundos de plantas com diferentes idades, foram inoculados em meio de cultura MS½ suplementado com BAP e ANA. Os brotos foram inoculados em meio contendo AIB e carvão ativo. As plantas foram transferidas para substrato composto de vermiculita e terra. A maior taxa de brotação foi obtida com o explante caule com 20 e 40 dias de idade em meio com 0,65mM de ANA. Na fase de enraizamento, a presença de carvão ativo interferiu positivamente no comprimento da parte aérea e do sistema radicular das plantas. As plantas foram aclimatizadas com 100% de sobrevivência.<br>Orthophytum mucugense is an ornamental bromeliad endemic to the municipality of Mucugê-BA which is vulnerable to extinction. The aim of this study was to establish a regeneration protocol via direct organogenesis for the species. The explants root, stem and leaf from plants of different ages were inoculated in the MS½ culture medium supplemented with BAP and NAA. The shoots were inoculated on medium supplemented with IBA and activated charcoal. The plants were transferred to a substrate composed of vermiculite and soil. The highest rate of sprouting was obtained with stem explants of 20 and 40 days old in medium supplemented with 0.65mM of NAA. For rooting the presence of activated charcoal had a positive influence on the length of shoot and root plants system. The plants were acclimatized with 100% survival