The poet at war.

The artist, whether he was novelist, poet, painter or essayist, was caught in the maelstrom of violence and destruction that was World War I. Conscription was employed in most nations participating in the War and the artist, with his accurate, discerning eye and his sensitivity, was destined to report the War as he actually saw it unfold before him. A great part of the creative activity these artists engaged in was an analysis and reportage of the years from 1914, to 1918. Before the Armistice had been signed on November 11, 1918, Henri Barbusse had published his indictment of war, Le Feu, in 1917. The novel was awarded the Prix Goncourt for that year. Barbusse\u27s work was the beginning of a stream of war books, poems, dramas and essays that was to come in the nineteen twenties and the nineteen thirties of the Twentieth Century. Practically every participant nation in the War was represented in this tremendous output of\u27 war literature. Such Americans of literary talents as John Dos Passos, Ernest Hemingway, William Faulkner, Paul Green, Robert E. Sherwood, Laurence Stallings, E. E. Cummings and Archibald MacLeish served at the front and later expressed themselves regarding war

Responses of an experimental solid tumour to irradiation: A comparison of modes of fractionation.

Several radiotherapeutic schedules compatible with continued structural-functional integrity of the gastrointestinal (GI) mucosa were compared utilizing the P815X2 murine mastocytoma grown as a solid subcutaneous tumour. Both the tumour and underlying normal tissues were irradiated during the treatments. The tumour exhibited a Do that increased from 210 rad to 397 rad as the tumour aged and in all instances demonstrated minimal shoulders in survival curves. In spite of a relative radioresistance of cells within the solid tumour, quite effective control of localized disease could be accomplished with radiotherapy schemes compatible with GI tolerance limits. Schedules evaluated utilizing this model included acute exposures to 1122 rad, daily exposure to 187 rad, 5 days/week exposures to 281 rad, twice weekly exposures (561 rad on Mondays and 374 rad on Thursdays) and a high dose, two fractions per day, schedule. Tumours were followed for changes in growth patterns during these schedules. Efficacy of tumour control was determined and schedules were compared on this basis. Aggressive radiotherapy approaching the tolerance limits of any of the fractionation schemes proved most effective

TDP-43 and FUS mislocalization in VCP mutant motor neurons is reversed by pharmacological inhibition of the VCP D2 ATPase domain

RNA binding proteins have been shown to play a key role in the pathogenesis of amyotrophic lateral sclerosis (ALS). Mutations in valosin-containing protein (VCP/p97) cause ALS and exhibit the hallmark nuclear-to-cytoplasmic mislocalization of RNA binding proteins (RBPs). However, the mechanism by which mutations in VCP lead to this mislocalization of RBPs remains incompletely resolved. To address this, we used human-induced pluripotent stem cell-derived motor neurons carrying VCP mutations. We first demonstrate reduced nuclear-to-cytoplasmic ratios of transactive response DNA-binding protein 43 (TDP-43), fused in sarcoma/translocated in liposarcoma (FUS) and splicing factor proline and glutamine rich (SFPQ) in VCP mutant motor neurons. Upon closer analysis, we also find these RBPs are mislocalized to motor neuron neurites themselves. To address the hypothesis that altered function of the D2 ATPase domain of VCP causes RBP mislocalization, we used pharmacological inhibition of this domain in control motor neurons and found this does not recapitulate RBP mislocalization phenotypes. However, D2 domain inhibition in VCP mutant motor neurons was able to robustly reverse mislocalization of both TDP-43 and FUS, in addition to partially relocalizing SFPQ from the neurites. Together these results argue for a gain-of-function of D2 ATPase in VCP mutant human motor neurons driving the mislocalization of TDP-43 and FUS. Our data raise the intriguing possibility of harnessing VCP D2 ATPase inhibitors in the treatment of VCP-related ALS

AXL modulates extracellular matrix protein expression and is essential for invasion and metastasis in endometrial cancer

The receptor tyrosine kinase AXL promotes migration, invasion, and metastasis. Here, we evaluated the role of AXL in endometrial cancer. High immunohistochemical expression of AXL was found in 76% (63/83) of advanced-stage, and 77% (82/107) of high-grade specimens and correlated with worse survival in uterine serous cancer patients. In vitro, genetic silencing of AXL inhibited migration and invasion but had no effect on proliferation of ARK1 endometrial cancer cells. AXL-deficient cells showed significantly decreased expression of phospho-AKT as well as uPA, MMP-1, MMP-2, MMP-3, and MMP-9. In a xenograft model of human uterine serous carcinoma with AXL-deficient ARK1 cells, there was significantly less tumor burden than xenografts with control ARK1 cells. Together, these findings underscore the therapeutic potentials of AXL as a candidate target for treatment of metastatic endometrial cancer

Visual span and change detection in soccer: an expertise study

There is evidence to suggest that sports experts are able to extract more perceptual information from a single fixation than novices when exposed to meaningful tasks that are specific to their field of expertise. In particular, Reingold et al. (2001) showed that chess experts use a larger visual span including fewer fixations when compared to their less skilled counterparts. The aim of the present study was to examine whether also in a more complex environment, namely soccer, skilled players use a larger visual span and fewer fixations than less skilled players when attempting to recognise players' positions. To this end, we combined the gaze-contingent window technique with the change detection paradigm. Results seem to suggest that skilled soccer players do not use a larger visual span than less skilled players. However, skilled soccer players showed significantly fewer fixations of longer duration than their less skilled counterparts, supporting the notion that experts may extract more information from a single glance. © 2011 Psychology Press

Tumor Treating Fields (TTFields) Therapy Concomitant with Taxanes for Cancer Treatment

Non-small cell lung cancer; Ovarian cancer; Pancreatic cancerCáncer de pulmón de células no pequeñas; Cáncer de ovarios; Cáncer de páncreasCàncer de pulmó de cèl·lules no petites; Càncer d'ovaris; Càncer de pàncreesNon-small cell lung cancer, ovarian cancer, and pancreatic cancer all present with high morbidity and mortality. Systemic chemotherapies have historically been the cornerstone of standard of care (SOC) regimens for many cancers, but are associated with systemic toxicity. Multimodal treatment combinations can help improve patient outcomes; however, implementation is limited by additive toxicities and potential drug–drug interactions. As such, there is a high unmet need to develop additional therapies to enhance the efficacy of SOC treatments without increasing toxicity. Tumor Treating Fields (TTFields) are electric fields that exert physical forces to disrupt cellular processes critical for cancer cell viability and tumor progression. The therapy is locoregional and is delivered noninvasively to the tumor site via a portable medical device that consists of field generator and arrays that are placed on the patient’s skin. As a noninvasive treatment modality, TTFields therapy-related adverse events mainly consist of localized skin reactions, which are manageable with effective acute and prophylactic treatments. TTFields selectively target cancer cells through a multi-mechanistic approach without affecting healthy cells and tissues. Therefore, the application of TTFields therapy concomitant with other cancer treatments may lead to enhanced efficacy, with low risk of further systemic toxicity. In this review, we explore TTFields therapy concomitant with taxanes in both preclinical and clinical settings. The summarized data suggest that TTFields therapy concomitant with taxanes may be beneficial in the treatment of certain cancers.All costs related to publication were funded by Novocure Inc