Progressive lung cancer determined by expression profiling and transcriptional regulation

Clinically, our ability to predict disease outcome for patients with early stage lung cancer is currently poor. To address this issue, tumour specimens were collected at surgery from non-small cell lung cancer (NSCLC) patients as part of the European Early Lung Cancer (EUELC) consortium. The patients were followed-up for three years post-surgery and patients who suffered progressive disease (PD, tumour recurrence, metastasis or a second primary) or remained disease-free (DF) during follow-up were identified. RNA from both tumour and adjacent-normal lung tissue was extracted from patients and subjected to microarray expression profiling. These samples included 36 adenocarcinomas and 23 squamous cell carcinomas from both PD and DF patients. The microarray data was subject to a series of systematic bioinformatics analyses at gene, network and transcription factor levels. The focus of these analyses was 2-fold: firstly to determine whether there were specific biomarkers capable of differentiating between PD and DF patients, and secondly, to identify molecular networks which may contribute to the progressive tumour phenotype. The experimental design and analyses performed permitted the clear differentiation between PD and DF patients using a set of biomarkers implicated in neuroendocrine signalling and allowed the inference of a set of transcription factors whose activity may differ according to disease outcome. Potential links between the biomarkers, the transcription factors and the genes p21/CDKN1A and Myc, which have previously been implicated in NSCLC development, were revealed by a combination of pathway analysis and microarray meta-analysis. These findings suggest that neuroendocrine-related genes, potentially driven through p21/CDKN1A and Myc, are closely linked to whether or not a NSCLC patient will have poor clinical outcome.

Influence of progressive renal dysfunction in chronic heart failure

Chronic heart failure (CHF) is often associated with impaired renal function due to hypoperfusion. Such patients are very sensitive to changes in renal perfusion pressure, and may develop acute tubular necrosis if the pressure falls too far. The situation is complicated by the use of diuretics, ACE inhibitors and spironolactone, all of which may affect renal function and potassium balance. Chronic renal failure (CRF) may also be associated with fluid overload. Anaemia and hypertension in CRF contribute to the development of left ventricular hypertrophy (LVH), which carries a poor prognosis, so correction of these factors is important.

A progressive failure model for composite laminates subjected to low velocity impact damage

This paper presents a 3-D failure model for predicting the dynamic material response of composite laminates under impact loading. The formulation is based on the Continuum Damage Mechanics (CDM) approach and enables the control of the energy dissipation associated with each failure mode regardless of mesh refinement and fracture plane orientation. Internal thermodynamically irreversible damage variables were defined in order to quantify damage concentration associated with each possible failure mode and predict the gradual stiffness reduction during the impact damage process. The material model has been implemented into LS-DYNA explicit finite element code within solid elements and it has proven to be capable of reproducing experimental results with good accuracy in terms of static/dynamic responses, absorbed energy and extent of damage.

Le survivant de la Shoah face au texte de fiction: un écran protecteur ou un écran projecteur? L’exemple d’Anna Langfus

La terminologie ‘écriture écran’ est souvent utilisée dans un sens proche de celui que lui donne Annie Ernaux lorsqu’elle écrit que ‘la fiction protège’ en permettant à un auteur de dire tout en gardant le lecteur à distance. Pourtant, de Blanchot à Genette, de nombreux critiques ont souligné que le texte est par essence un espace qui n’existe que dans et par cet échange, le lecteur – surtout dans le cas des textes de fiction – devant s’investir, se projeter dans le texte lu. Le texte de fiction serait-il donc un écran protecteur pour celui qui tient la plume et un écran projecteur pour celui qui tient le livre ? En nous basant principalement sur des textes de la psychanalyste Rachel Rosenblum et de l’auteure et survivante de la Shoah Anna Langfus, nous suggèrerons que, pour l’auteur comme pour le lecteur, le texte de fiction est à la fois un écran protecteur et un écran projecteur, ces deux fonctions étant étroitement liées et nullement contradictoires. Nous montrerons en effet qu’aucun genre n’est a priori protecteur puisque c’est l’acte de lecture ou d’écriture qui peut se transformer en morbide compulsion de répétition quand la mémoire d’un lecteur ou d’un auteur est devenue pathologique.