‘Stick that knife in me’: Shane Meadows’ children

This article brings Shane Meadows’ Dead Man's Shoes (2004) into dialogue with the history of the depiction of the child on film. Exploring Meadows’ work for its complex investment in the figure of the child on screen, it traces the limits of the liberal ideology of the child in his cinema and the structures of feeling mobilised by its uses – at once aesthetic and sociological – of technologies of vision

A new liver perfusion and preservation system for transplantation Research in large animals

A kidney perfusion machine, model MOX-100 (Waters Instruments, Ltd, Rochester, MN) was modified to allow continuous perfusion of the portal vein and pulsatile perfusion of the hepatic artery of the liver. Additional apparatus consists of a cooling system, a membrane oxygenator, a filter for foreign bodies, and bubble traps. This system not only allows hypothermic perfusion preservation of the liver graft, but furthermore enables investigation of ex vivo simulation of various circulatory circumstances in which physiological perfusion of the liver is studied. We have used this system to evaluate the viability of liver allografts preserved by cold storage. The liver was placed on the perfusion system and perfused with blood with a hematocrit of approximately 20% and maintained at 37°C for 3 h. The flows of the hepatic artery and portal vein were adjusted to 0.33 mL and 0.67 mL/g of liver tissue, respectively. Parameters of viability consisted of hourly bile output, oxygen consumption, liver enzymes, electrolytes, vascular resistance, and liver histology. This method of liver assessment in large animals will allow the objective evaluation of organ viability for transplantation and thereby improve the outcome of organ transplantation. Furthermore, this pump enables investigation into the pathophysiology of liver ischemia and preservation. © 1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted

GABA-enhanced collective behavior in neuronal axons underlies persistent gamma-frequency oscillations

Gamma (30–80 Hz) oscillations occur in mammalian electroencephalogram in a manner that indicates cognitive relevance. In vitro models of gamma oscillations demonstrate two forms of oscillation: one occurring transiently and driven by discrete afferent input and the second occurring persistently in response to activation of excitatory metabotropic receptors. The mechanism underlying persistent gamma oscillations has been suggested to involve gap-junctional communication between axons of principal neurons, but the precise relationship between this neuronal activity and the gamma oscillation has remained elusive. Here we demonstrate that gamma oscillations coexist with high-frequency oscillations (>90 Hz). High-frequency oscillations can be generated in the axonal plexus even when it is physically isolated from pyramidal cell bodies. They were enhanced in networks by nonsomatic -aminobutyric acid type A (GABAA) receptor activation, were modulated by perisomatic GABAA receptor-mediated synaptic input to principal cells, and provided the phasic input to interneurons required to generate persistent gamma-frequency oscillations. The data suggest that high-frequency oscillations occurred as a consequence of random activity within the axonal plexus. Interneurons provide a mechanism by which this random activity is both amplified and organized into a coherent network rhythm

A role for fast rhythmic bursting neurons in cortical gamma oscillations in vitro

Basic cellular and network mechanisms underlying gamma frequency oscillations (30–80 Hz) have been well characterized in the hippocampus and associated structures. In these regions, gamma rhythms are seen as an emergent property of networks of principal cells and fast-spiking interneurons. In contrast, in the neocortex a number of elegant studies have shown that specific types of principal neuron exist that are capable of generating powerful gamma frequency outputs on the basis of their intrinsic conductances alone. These fast rhythmic bursting (FRB) neurons (sometimes referred to as "chattering" cells) are activated by sensory stimuli and generate multiple action potentials per gamma period. Here, we demonstrate that FRB neurons may function by providing a large-scale input to an axon plexus consisting of gap-junctionally connected axons from both FRB neurons and their anatomically similar counterparts regular spiking neurons. The resulting network gamma oscillation shares all of the properties of gamma oscillations generated in the hippocampus but with the additional critical dependence on multiple spiking in FRB cells

Optimization of sample preparation and instrumental parameters for the rapid analysis of drugs of abuse in hair samples by MALDI-MS/MS imaging

Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) has been employed to rapidly screen longitudinally sectioned drug user hair samples for cocaine and its metabolites using continuous raster imaging. Optimization of the spatial resolution and raster speed were performed on intact cocaine contaminated hair samples. The optimized settings (100 × 150 μm at 0.24 mm/s) were subsequently used to examine longitudinally sectioned drug user hair samples. The MALDI-MS/MS images showed the distribution of the most abundant cocaine product ion at m/z 182. Using the optimized settings, multiple hair samples obtained from two users were analyzed in approximately 3 h: six times faster than the standard spot-to-spot acquisition method. Quantitation was achieved using longitudinally sectioned control hair samples sprayed with a cocaine dilution series. A multiple reaction monitoring (MRM) experiment was also performed using the 'dynamic pixel' imaging method to screen for cocaine and a range of its metabolites, in order to differentiate between contaminated hairs and drug users. Cocaine, benzoylecgonine, and cocaethylene were detectable, in agreement with analyses carried out using the standard LC-MS/MS method. Graphical Abstract ᅟ

HER2 testing in breast cancer: Opportunities and challenges

Human epidermal growth factor receptor 2 (HER2) is overexpressed in 15-25% of breast cancers, usually as a result of HER2 gene amplification. Positive HER2 status is considered to be an adverse prognostic factor. Recognition of the role of HER2 in breast cancer growth has led to the development of anti-HER2 directed therapy, with the humanized monoclonal antibody trastuzumab (Herceptin (R)) having been approved for the therapy of HER2-positive metastatic breast cancer. Clinical studies have further suggested that HER2 status can provide important information regarding success or failure of certain hormonal therapies or chemotherapies. As a result of these developments, there has been increasing demand to perform HER2 testing on current and archived breast cancer specimens. This article reviews the molecular background of HER2 function, activation and inhibition as well as current opinions concerning its role in chemosensitivity and interaction with estrogen receptor biology. The different tissue-based assays used to detect HER2 amplification and overexpression are discussed with respect to their advantages and disadvantages, when to test (at initial diagnosis or pre-treatment), where to test (locally or centralized) and the need for quality assurance to ensure accurate and valid testing results

SerpinB2 regulates stromal remodelling and local invasion in pancreatic cancer

Pancreatic cancer has a devastating prognosis, with an overall 5-year survival rate of ~8%, restricted treatment options and characteristic molecular heterogeneity. SerpinB2 expression, particularly in the stromal compartment, is associated with reduced metastasis and prolonged survival in pancreatic ductal adenocarcinoma (PDAC) and our genomic analysis revealed that SERPINB2 is frequently deleted in PDAC. We show that SerpinB2 is required by stromal cells for normal collagen remodelling in vitro, regulating fibroblast interaction and engagement with collagen in the contracting matrix. In a pancreatic cancer allograft model, co-injection of PDAC cancer cells and SerpinB2(-/-) mouse embryonic fibroblasts (MEFs) resulted in increased tumour growth, aberrant remodelling of the extracellular matrix (ECM) and increased local invasion from the primary tumour. These tumours also displayed elevated proteolytic activity of the primary biochemical target of SerpinB2-urokinase plasminogen activator (uPA). In a large cohort of patients with resected PDAC, we show that increasing uPA mRNA expression was significantly associated with poorer survival following pancreatectomy. This study establishes a novel role for SerpinB2 in the stromal compartment in PDAC invasion through regulation of stromal remodelling and highlights the SerpinB2/uPA axis for further investigation as a potential therapeutic target in pancreatic cancer

Growth of Sobolev norms and controllability of Schr\"odinger equation

In this paper we obtain a stabilization result for the Schr\"odinger equation under generic assumptions on the potential. Then we consider the Schr\"odinger equation with a potential which has a random time-dependent amplitude. We show that if the distribution of the amplitude is sufficiently non-degenerate, then any trajectory of system is almost surely non-bounded in Sobolev spaces

Radiation hardness qualification of PbWO4 scintillation crystals for the CMS Electromagnetic Calorimeter

This is the Pre-print version of the Article. The official published version can be accessed from the link below - Copyright @ 2010 IOPEnsuring the radiation hardness of PbWO4 crystals was one of the main priorities during the construction of the electromagnetic calorimeter of the CMS experiment at CERN. The production on an industrial scale of radiation hard crystals and their certification over a period of several years represented a difficult challenge both for CMS and for the crystal suppliers. The present article reviews the related scientific and technological problems encountered

Broadened Population-Level Frequency Tuning in Human Auditory Cortex of Portable Music Player Users

Nowadays, many people use portable players to enrich their daily life with enjoyable music. However, in noisy environments, the player volume is often set to extremely high levels in order to drown out the intense ambient noise and satisfy the appetite for music. Extensive and inappropriate usage of portable music players might cause subtle damages in the auditory system, which are not behaviorally detectable in an early stage of the hearing impairment progress. Here, by means of magnetoencephalography, we objectively examined detrimental effects of portable music player misusage on the population-level frequency tuning in the human auditory cortex. We compared two groups of young people: one group had listened to music with portable music players intensively for a long period of time, while the other group had not. Both groups performed equally and normally in standard audiological examinations (pure tone audiogram, speech test, and hearing-in-noise test). However, the objective magnetoencephalographic data demonstrated that the population-level frequency tuning in the auditory cortex of the portable music player users was significantly broadened compared to the non-users, when attention was distracted from the auditory modality; this group difference vanished when attention was directed to the auditory modality. Our conclusion is that extensive and inadequate usage of portable music players could cause subtle damages, which standard behavioral audiometric measures fail to detect in an early stage. However, these damages could lead to future irreversible hearing disorders, which would have a huge negative impact on the quality of life of those affected, and the society as a whole