Drug Induced Statements

No serious attempt appears to have been made to check the opinions of scientific authorities in regard to drug-induced statements, beyond a cursory survey in 1941, and the courts have gone their way without much information, often, as has been charged in other areas involving forensic psychiatry, substituting the claims of the more articulate and aggressive members of the profession for the consensus of knowledgeable opinion within the entire group. This paper, therefore, is an attempt to learn from a sample of psychiatrists the present state of professional belief about the legal value and reliability of barbiturate drugs in forensic matters

Other‐Sacrificing Options

I argue that you can be permitted to discount the interests of your adversaries even though doing so would be impartially suboptimal. This means that, in addition to the kinds of moral options that the literature traditionally recognises, there exist what I call other-sacrificing options. I explore the idea that you cannot discount the interests of your adversaries as much as you can favour the interests of your intimates; if this is correct, then there is an asymmetry between negative partiality toward your adversaries and positive partiality toward your intimates

Mechano-sensing and cell migration: A 3D model approach

Cell migration is essential for tissue development in different physiological and pathological conditions. It is a complex process orchestrated by chemistry, biological factors, microstructure and surrounding mechanical properties. Focusing on the mechanical interactions, cells do not only exert forces on the matrix that surrounds them, but they also sense and react to mechanical cues in a process called mechano-sensing. Here, we hypothesize the involvement of mechano-sensing in the regulation of directional cell migration through a three-dimensional (3D) matrix. For this purpose, we develop a 3D numerical model of individual cell migration, which incorporates the mechano-sensing process of the cell as the main mechanism regulating its movement. Consistent with this hypothesis, we found that factors, such as substrate stiffness, boundary conditions and external forces, regulate specific and distinct cell movements

Cell Cytoskeleton Dynamics: Mechano-Sensing Properties

`The actin cytoskeleton network is the dominant structure of eukaryotic cells. It is highlydynamic and plays a central role in a wide range of mechanical and biological functions.Cytoskeleton is composed mainly of actin filaments (F-actin) resulting from the self-assemblyof monomeric actin (G-actin) and cross-linked by actin cross-linking proteins (ACPs) whosenature and concentration determine the morphological and rheological properties of thenetwork. These actin filaments are reversibly coupled to membrane proteins (critical to theresponse of cells to external stress) and in conjunction with motor proteins from the myosinfamily, are able to generate contractile force during cell migration. Knowledge of actincytoskeleton and its rheological properties is therefore indispensable for understanding theunderlying mechanics and various biological processes of cells. Here, we present a 3-DBrownian dynamics (BD) computational model in which actin monomers polymerize andbecome cross-linked by two types of ACPs, forming either parallel filament bundles ororthogonal networks. Also, the active and dynamic behaviour of motors is included. In thissimulation, actin monomers, filaments, ACPs, and motors experience thermal motion andinteract with each other with binding probabilities and defined potentials. Displacements aregoverned by the Langevin equation, and positions of all elements are updated using the Eulerintegration scheme.In this first part of the work, the mechano-sensing properties of active networks are investigatedby evaluating stress and strain rate in response to different substrate stiffness

Open areas in a landscape enhance pollen-mediated gene flow of a tree species: evidence from northern Switzerland

Habitat fragmentation often has negative consequences for genetic diversity, and thereby for the viability of populations. However, these negative consequences might be counteracted by gene flow as the latter provides functional connectivity between apparently isolated habitat fragments. Gene flow is itself influenced by landscape structure and composition, and it is therefore important to understand the relationship between gene flow and landscape structure and composition. We used linear LAD regression models to investigate the relationship between contemporary gene flow by pollen in the rare, insect-pollinated forest tree Sorbus domestica and several landscape features. None of the landscape components—which included closed forest, deep valleys, open land and settlements—proved to be an impermeable barrier to gene flow by pollen. We found evidence that settlements, large open areas, and a pronounced topography increased long-distance gene flow in the landscape as compared to a random model including all possible gene flow trajectories. These results are encouraging from a conservation view, as gene flow in species pollinated by generalist insects seems to provide functional connectivity and may help to maintain genetic diversity in rare plant species in fragmented landscape

Digital Deblurring of CMB Maps II: Asymmetric Point Spread Function

In this second paper in a series dedicated to developing efficient numerical techniques for the deblurring Cosmic Microwave Background (CMB) maps, we consider the case of asymmetric point spread functions (PSF). Although conceptually this problem is not different from the symmetric case, there are important differences from the computational point of view because it is no longer possible to use some of the efficient numerical techniques that work with symmetric PSFs. We present procedures that permit the use of efficient techniques even when this condition is not met. In particular, two methods are considered: a procedure based on a Kronecker approximation technique that can be implemented with the numerical methods used with symmetric PSFs but that has the limitation of requiring only mildly asymmetric PSFs. The second is a variant of the classic Tikhonov technique that works even with very asymmetric PSFs but that requires discarding the edges of the maps. We provide details for efficient implementations of the algorithms. Their performance is tested on simulated CMB maps.Comment: 9 pages, 13 Figure

Effect of Surface Patterning and Presence of Collagen I on the Phenotypic Changes of Embryonic Stem Cell Derived Cardiomyocytes

Embryonic stem cell derived cardiomyocytes have been widely investigated for stem cell therapy or in vitro model systems. This study examines how two specific biophysical stimuli, collagen I and cell alignment, affect the phenotypes of embryonic stem cell derived cardiomyocytes in vitro. Three phenotypic indicators are assessed: sarcomere organization, cell elongation, and percentage of binucleation. Murine embryonic stem cells were differentiated in a hanging drop assay and cardiomyocytes expressing GFP-α-actinin were isolated by fluorescent sorting. First, the effect of collagen I was investigated. Addition of soluble collagen I markedly reduced binucleation as a result of an increase in cytokinesis. Laden with a collagen gel layer, myocyte mobility and cell shape change were impeded. Second, the effect of cell alignment by microcontact printing and nanopattern topography was investigated. Both patterning techniques induced cell alignment and elongation. Microcontact printing of 20 μm line pattern accelerated binucleation and nanotopography with 700 nm ridges and 3.5 μm grooves negatively regulated binucleation. This study highlights the importance of biophysical cues in the morphological changes of differentiated cardiomyocytes and may have important implications on how these cells incorporate into the native myocardium.Singapore-MIT Alliance for Research and TechnologyNational Science Foundation (U.S.) ((Science and Technology Center (EBICS): Emergent Behaviors of Integrated Cellular Systems, Grant CBET-0939511)Charles Stark Draper Laboratory (Internal Research and Development Program

Cell Invasion Dynamics into a Three Dimensional Extracellular Matrix Fibre Network

The dynamics of filopodia interacting with the surrounding extracellular matrix (ECM) play a key role in various cell-ECM interactions, but their mechanisms of interaction with the ECM in 3D environment remain poorly understood. Based on first principles, here we construct an individual-based, force-based computational model integrating four modules of 1) filopodia penetration dynamics; 2) intracellular mechanics of cellular and nuclear membranes, contractile actin stress fibers, and focal adhesion dynamics; 3) structural mechanics of ECM fiber networks; and 4) reaction-diffusion mass transfers of seven biochemical concentrations in related with chemotaxis, proteolysis, haptotaxis, and degradation in ECM to predict dynamic behaviors of filopodia that penetrate into a 3D ECM fiber network. The tip of each filopodium crawls along ECM fibers, tugs the surrounding fibers, and contracts or retracts depending on the strength of the binding and the ECM stiffness and pore size. This filopodium-ECM interaction is modeled as a stochastic process based on binding kinetics between integrins along the filopodial shaft and the ligands on the surrounding ECM fibers. This filopodia stochastic model is integrated into migratory dynamics of a whole cell in order to predict the cell invasion into 3D ECM in response to chemotaxis, haptotaxis, and durotaxis cues. Predicted average filopodia speed and that of the cell membrane advance agreed with experiments of 3D HUVEC migration at r[superscript 2] > 0.95 for diverse ECMs with different pore sizes and stiffness.Singapore. National Research Foundation (Singapore-MIT Alliance for Research and Technology)National Science Foundation (U.S.). Science and Technology Center and Emergent Behaviors of Integrated Cellular Systems (Grant EFRI-0735997)National Science Foundation (U.S.). Science and Technology Center and Emergent Behaviors of Integrated Cellular Systems (Grant STC-0902396)National Science Foundation (U.S.). Science and Technology Center and Emergent Behaviors of Integrated Cellular Systems (Grant CBET-0939511

Randomised trial of once- or twice-daily MMX mesalazine for maintenance of remission in ulcerative colitis

AIM: Maintenance treatment in ulcerative colitis should be as convenient as possible, to increase the chance of compliance. MMX mesalazine is a once-daily, high-strength (1.2 g/tablet) formulation of 5-aminosalicylic acid. This study evaluated the safety and efficacy of MMX mesalazine dosed once or twice daily as maintenance therapy in patients with ulcerative colitis. METHODS: This multicentre, randomised, open-label trial enrolled patients with strictly defined clinical and endoscopic remission, immediately following an episode of mild to moderate ulcerative colitis. Patients were randomised to MMX mesalazine 2.4 g/day as a single (2x1.2 g tablet) or divided dose (1x1.2 g tablet twice daily) for 12 months. RESULTS: 174 patients (37.9%; safety population n = 459) experienced 384 adverse events, the majority of which were mild or moderate in intensity. Eighteen patients (3.9%), nine in each group, experienced a total of 22 serious adverse events (10 in the once-daily and 12 in the twice-daily group). Most serious adverse events were gastrointestinal, experienced by 5 patients in the once-daily and 4 in the twice-daily group. At month 12, 64.4% (efficacy population, n = 451) of patients in the once-daily and 68.5% of patients in the twice-daily group were in clinical and endoscopic remission (p = 0.351). At month 12, 88.9% and 93.2% in each group, respectively, had maintained clinical remission (were relapse free). CONCLUSIONS: MMX mesalazine 2.4 g/day administered as a single or divided dose demonstrated a good safety profile, was well tolerated and was effective as maintenance treatment. High clinical and endoscopic remission rates can be achieved with once-daily dosing. TRIAL REGISTRATION NUMBER: NCT00151944

Post-Collision Interaction with Wannier electrons

A theory of the Post-Collision Interaction (PCI) is developed for the case when an electron atom impact results in creation of two low-energy Wannier electrons and an ion excited into an autoionizing state. The following autoionization decay exposes the Wannier pair to the influence of PCI resulting in variation of the shape of the line in the autoionization spectrum. An explicit dependence of the autoionization profile on the wave function of the Wannier pair is found. PCI provides an opportunity to study this wave function for a wide area of distancesComment: 33 pages, Latex, IOP style, and 3 figures fig1.ps, fig2.ps, fig3.p