Propofol facilitates the development of long-term depression (LTD) and impairs the maintenance of long-term potentiation (LTP) in the CA1 region of the hippocampus of anesthetized rats

Memory is sensitive to the short-acting anesthetic (2,6-diisopropylphenol) propofol, but the underlying mechanism is little known. Here, we have examined the effects of propofol on synaptic plasticity in the CA1 region of the hippocampus of anesthetized rats. We found that low dose of propofol (20 mg/kg, i.p.) did not affect the basal transmission, but enhanced prominently the development of long-term depression (LTD) and impaired the maintenance of long-term potentiation (LTP). The impairment of LTP maintenance and enhancement of LTD development may contribute to propofol-induced deficits in memory following propofol anesthesia. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Stress-facilitated LTD induces output plasticity through a synchronized-spikes and spontaneous unitary discharges the CA1 region of the hippocampus

Long-term potentiation (LTP) and long-term depression (LTD) of the excitatory synaptic inputs plasticity in the hippocampus is believed to underlie certain types of learning and memory. Especially, stressful experiences, well known to produce long-lasting strong memories of the event themselves, enable LTD by low frequency stimulation (LFS, 3 Hz) but block LTP induction by high frequency stimulation (HFS, 200 Hz). However, it is unknown whether stress-affected synaptic plasticity has an impact on the output plasticity. Thus, we have simultaneously studied the effects of stress on synaptic plasticity and neuronal output in the hippocampal CA1 region of anesthetized Wistar rats. Our results revealed that stress increased basal power spectrum of the evoked synchronized-spikes and enabled LTD induction by LFS. The induction of stress-facilitated LTD but not LFS induced persistent decreases of the power spectrum of the synchronized-spikes and the frequency of the spontaneous unitary discharges; However, HFS induced UP in non-stressed animals and increased the power spectrum of the synchronized-spikes, without affecting the frequency of the spontaneous unitary discharges, but HFS failed to induce UP in stressed animals without affecting the power spectrum of the synchronized-spikes and the frequency of the spontaneous unitary discharges. These observations that stress-facilitated LTD induces the output plasticity through the synchronized-spikes and spontaneous unitary discharges suggest that these types of stress-related plasticity may play significant roles in distribution, amplification and integration of encoded information to other brain structures under stressful conditions. (C) 2004 Elsevier Ireland Ltd and The Japan Neuroscience Society. All rights reserved.

The effect of acute stress on LTP and LTD induction in the hippocampal CA1 region of anesthetized rats at three different ages

Not all experiences are memorized equally well. Especially, some types of stress are unavoidable in daily life and the stress experience can be memorized for life. Previous evidence has showed that synaptic plasticity, such as long-term potentiation (LTP) that may be the major cellular model of the mechanism underlying learning and memory, is influenced by behavioral stress. However, the effect of behavioral stress on age-related synaptic plasticity in-vivo was primarily known. Here we found that the LTP induction in the hippocampal CA1 region of anesthetized rats obviously showed inverted-U shape related to ages (4, 10 and 74 weeks old rats), but low-frequency stimulation was unable to induce reliable long-term depression (LTD) in these animals. Furthermore, acute elevated platform (EP) stress enabled reliable LTD significantly and completely blocked LTP induction at these ages. Importantly, LTD after exposure to acute EP stress showed similar magnitude over these ages. The present results that stress enables LTD but impairs LTP induction at these three ages strengthen a view that stress experience-dependent LTD (SLTD) may underlie stress form of aberrant memories. (C) 2004 Elsevier B.V. All rights reserved.

Bioenergetic responses of sub-adult sea cucumber Apostichopus japonicus (Selenka) (Echinodermata: Holothuroidea) to temperature with special discussion regarding its southernmost distribution limit in China

1. This paper investigated the bioenergetic responses of the sea cucumber Apostichopus japonicus (wet weights of 36.5 +/- 1.2 g) to different water temperatures (5, 10, 15, 20, 25 and 30 degrees C) in the laboratory. 2. Results showed that theoretically the optimal temperatures for energy intake and scope for growth (SFG) of sub-adult A. japonicus was at 15.6 and 16.0 degrees C, respectively. The aestivation threshold temperature for this life-stage sea cucumber could be 29.0 degrees C by taking feeding cessation as the indication of aestivation. 3. Our data suggests that A. japonicus is thermo-sensitive to higher temperature, which prevents it from colonising sub-tropical coastal zones. Therefore, water temperature plays an important role in its southernmost distribution limit in China. 4. The potential impact of global ocean warming on A. japonicus might be a northward shift in the geographical distribution. Crown Copyright (C) 2009 Published by Elsevier Ltd, All rights reserved.

Determining the Scope of English Quantifiers

How can one represent the meaning of English sentences in a formal logical notation such that the translation of English into this logical form is simple and general? This report answers this question for a particular kind of meaning, namely quantifier scope, and for a particular part of the translation, namely the syntactic influence on the translation. Rules are presented which predict, for example, that the sentence: Everyone in this room speaks at least two languages. has the quantifier scope AE in standard predicate calculus, while the sentence: At lease two languages are spoken by everyone in this room. has the quantifier scope EA. Three different logical forms are presented, and their translation rules are examined. One of the logical forms is predicate calculus. The translation rules for it were developed by Robert May (May 19 77). The other two logical forms are Skolem form and a simple computer programming language. The translation rules for these two logical forms are new. All three sets of translation rules are shown to be general, in the sense that the same rules express the constraints that syntax imposes on certain other linguistic phenomena. For example, the rules that constrain the translation into Skolem form are shown to constrain definite np anaphora as well. A large body of carefully collected data is presented, and used to assess the empirical accuracy of each of the theories. None of the three theories is vastly superior to the others. However, the report concludes by suggesting that a combination of the two newer theories would have the greatest generality and the highest empirical accuracy.

JUSTEIS (JISC Usage Surveys: Trends in Electronic Information Services) Strand A: survey of end users of all electronic information services (HE and FE), with Action research report. Final report 2002/2003 Cycle Four.

Urquhart, C. (editor for JUSTEIS team), Spink, S., Thomas, R., Yeoman, A., Durbin, J., Turner, J., Armstrong, A., Lonsdale, R. & Fenton, R. (2003). JUSTEIS (JISC Usage Surveys: Trends in Electronic Information Services) Strand A: survey of end users of all electronic information services (HE and FE), with Action research report. Final report 2002/2003 Cycle Four. Aberystwyth: Department of Information Studies, University of Wales Aberystwyth with Information Automation Ltd (CIQM). Sponsorship: JISC

John Adcock, In place of schools, New Education Press Ltd, Londyn 1994, ss. 112.

Recenzje i sprawozdania z książek

Synthesis and reactivity of α-diazo-β-keto sulfoxides: scope and synthetic potential

The research described in this thesis focuses on the design and synthesis of stable α-diazosulfoxides and investigation of their reactivity under a variety of conditions (transition-metal catalysis, thermal, photochemical and microwave) with a particular emphasis on the synthesis of novel heterocyclic compounds with potential biological activity. The exclusive reaction pathway for these α-diazosulfoxides was found to be hetero-Wolff rearrangement to give α-oxosulfine intermediates. In the first chapter, a literature review of sulfines is presented, including a discussion of naturally occurring sulfines, and an overview of the synthesis and reactivity of sulfines. The potential of sulfines in organic synthesis and recent developments in particular are highlighted. The second chapter discusses the synthesis and reactivity of α-diazosulfoxides, building on earlier results in this research group. The synthesis of lactone-based α-diazosulfoxides and, for the first time, ketone-based benzofused and monocyclic α-diazosulfoxides is described. The reactivity of these α-diazosulfoxides is then explored under a variety of conditions, such as transition-metal catalysis, photochemical and microwave, generating labile α-oxosulfine intermediates, which are trapped using amines and dienes, in addition to the spontaneous reaction pathways which occur with α-oxosulfines in the absence of a trap. A new reaction pathway was explored with the lactone based α-oxosulfines, involving reaction with amines to generate novel 3-aminofuran-2(5H)-ones via carbophilic attack, in very good yields. The reactivity of ketone-based α-diazosulfoxides was explored for the first time, and once again, pseudo-Wolff rearrangement to the α-oxosulfines was the exclusive reaction pathway observed. The intermediacy of the α-oxosulfines was confirmed by trapping as cycloadducts, with the stereochemical features dependant on the reaction conditions. In the absence of a diene trap, a number of reaction fates from the α-oxosulfines were observed, including complete sulfinyl extrusion to give indanones, sulfur extrusion to give indanediones, and, to a lesser extent, dimerisation. The indanediones were characterised by trapping as quinoxalines, to enable full characterisation. One of the overriding outcomes of this thesis was the provision of new insights into the behaviour of α-oxosulfines with different transition metal catalysts, and under thermal, microwave and photolysis conditions. A series of 3-aminofuran-2(5H)-ones and benzofused dihydro-2H-thiopyran S-oxides were submitted for anticancer screening at the U.S. National Cancer Institute. A number of these derivatives were identified as hit compounds, with excellent cell growth inhibition. One 3-aminofuran-2(5H)-one derivative has been chosen for further screening. The third chapter details the full experimental procedures, including spectroscopic and analytical data for the compounds prepared during this research. The data for the crystal structures are contained in the attached CD.

Optimised crystal morphologies for active pharmaceutical ingredients and related studies

The majority of active pharmaceutical ingredients (APIs) are crystalline solids in their pure forms. Crystalline solids have definable morphologies, i.e. shape and size. Crystal morphology is determined by both the internal structure of the crystals and external factors during growth from solution. The morphology of a crystal batch can affect key processes during manufacturing. Companies generally accept whatever morphology the manufacturing process provides and deal with any subsequent problems by costly trouble‒shooting. Rational design of optimised morphologies for crystalline pharmaceutical solids would be a very significant technical and commercial advance. Chapter one introduces the concept of crystal nucleation and growth. The phenomenon of polymorphism alongside the causes and impact is discussed. A summary of the scope of instrumentation used in the investigation of crystal polymorphism and morphology, including crystal size distribution (CSD), is also included. Chapter two examines the research carried out during an exploration of the optimum crystallisation parameters of phenacetin. Following a morphological study, the impact this induces on particle density and flow properties is examined. The impact of impurities on the crystallisation properties of phenacetin is investigated. Significantly, the location of impurities within individual crystals is also studied. The third chapter describes an industrial collaboration looking at the resolution and polymorphic study of trometamol and lysine salts of ketoprofen and 2‒phenylpropionic acid (2‒PPA). Chapter four incorporates a solid state study on three separate compounds: 2‒chloro‒4‒nitroaniline, 4‒hydroxy‒N‒phenylbenzenesulfonamide and N‒acetyl‒D‒glucosamine‒6‒O‒sulfate. 2‒Chloro‒4‒nitroaniline and 4‒hydroxy‒N‒phenylbenzenesulfonamide both produced interesting, extreme morphologies which warranted further investigation as part of a collaborative study. Following a summarisation of results in chapter five, chapter six contains the full experimental details, incorporating spectral and other analytical data for all compounds synthesised during the course of the research.

Missing data in randomized clinical trials for weight loss: scope of the problem, state of the field, and performance of statistical methods.

BACKGROUND: Dropouts and missing data are nearly-ubiquitous in obesity randomized controlled trails, threatening validity and generalizability of conclusions. Herein, we meta-analytically evaluate the extent of missing data, the frequency with which various analytic methods are employed to accommodate dropouts, and the performance of multiple statistical methods. METHODOLOGY/PRINCIPAL FINDINGS: We searched PubMed and Cochrane databases (2000-2006) for articles published in English and manually searched bibliographic references. Articles of pharmaceutical randomized controlled trials with weight loss or weight gain prevention as major endpoints were included. Two authors independently reviewed each publication for inclusion. 121 articles met the inclusion criteria. Two authors independently extracted treatment, sample size, drop-out rates, study duration, and statistical method used to handle missing data from all articles and resolved disagreements by consensus. In the meta-analysis, drop-out rates were substantial with the survival (non-dropout) rates being approximated by an exponential decay curve (e(-lambdat)) where lambda was estimated to be .0088 (95% bootstrap confidence interval: .0076 to .0100) and t represents time in weeks. The estimated drop-out rate at 1 year was 37%. Most studies used last observation carried forward as the primary analytic method to handle missing data. We also obtained 12 raw obesity randomized controlled trial datasets for empirical analyses. Analyses of raw randomized controlled trial data suggested that both mixed models and multiple imputation performed well, but that multiple imputation may be more robust when missing data are extensive. CONCLUSION/SIGNIFICANCE: Our analysis offers an equation for predictions of dropout rates useful for future study planning. Our raw data analyses suggests that multiple imputation is better than other methods for handling missing data in obesity randomized controlled trials, followed closely by mixed models. We suggest these methods supplant last observation carried forward as the primary method of analysis.

A New Approach to Media Cluster Research: Bringing the Human Factor back into Scope

This paper is part of a collaborative project being undertaken by the three leading universities of Brussels, VUB, ULB and USL-B supported by Innnoviris. The project called Media Clusters Brussels - MCB - started in October 2014 with the goal to analyze the development of a Media Park around the two public broadcasters at the site of Reyers in Brussels being host of a media cluster in the capital city. Not only policymakers but also many authors recognized in the last decade that the media industry is characterized from a geographical point of view by a heavy concentration to a limited number of large cities, where media clusters have emerged (Karlsson & Picard, 2011). The common assumption about media clusters is that locating inside a regional agglomeration of related actors brings advantages for these firms. Especially, the interrelations and interactions between the actors on a social level matter for the shape and efficiency of the agglomerations (Picard, 2008). However, even though the importance of the actors and their interrelations has been a common assumption, many authors solely focus on the macro-economical aspects of the clusters. Within this paper, we propose to realize a socio-economical analysis of media clusters to make informed decisions in the development and so, bring the social (human) factor back into scope. Therefore, this article focuses on the development of a novel valuable framework, the so-called 7P framework with a multilevel and interdisciplinary approach, which includes three aspects, which have been identified as emerging success-factors of media clusters: partnerships, (media) professionals and positive spillovers.

Computer modelling of human behaviour in aircraft fire accidents

The mathematical simulation of the evacuation process has a wide and largely untapped scope of application within the aircraft industry. The function of the mathematical model is to provide insight into complex behaviour by allowing designers, legislators, and investigators to ask ‘what if’ questions. Such a model, EXODUS, is currently under development, and this paper describes its evolution and potential applications. EXODUS is an egress model designed to simulate the evacuation of large numbers of individuals from an enclosure, such as an aircraft. The model tracks the trajectory of each individual as they make their way out of the enclosure or are overcome by fire hazards, such as heat and toxic gases. The software is expert system-based, the progressive motion and behaviour of each individual being determined by a set of heuristics or rules. EXODUS comprises five core interacting components: (i) the Movement Submodel — controls the physical movement of individual passengers from their current position to the most suitable neighbouring location; (ii) the Behaviour Submodel — determines an individual's response to the current prevailing situation; (iii) the Passenger Submodel — describes an individual as a collection of 22 defining attributes and variables; (iv) the Hazard Submodel — controls the atmospheric and physical environment; and (v) the Toxicity Submodel — determines the effects on an individual exposed to the fire products, heat, and narcotic gases through the Fractional Effective Dose calculations. These components are briefly described and their capabilities and limitations are demonstrated through comparison with experimental data and several hypothetical evacuation scenarios.

Earliness penalties on a single machine subject to precedence constraints: SLK due date assignment

The paper considers the single machine due date assignment and scheduling problems with n jobs in which the due dates are to be obtained from the processing times by adding a positive slack q. A schedule is feasible if there are no tardy jobs and the job sequence respects given precedence constraints. The value of q is chosen so as to minimize a function ϕ(F,q) which is non-decreasing in each of its arguments, where F is a certain non-decreasing earliness penalty function. Once q is chosen or fixed, the corresponding scheduling problem is to find a feasible schedule with the minimum value of function F. In the case of arbitrary precedence constraints the problems under consideration are shown to be NP-hard in the strong sense even for F being total earliness. If the precedence constraints are defined by a series-parallel graph, both scheduling and due date assignment problems are proved solvable in time, provided that F is either the sum of linear functions or the sum of exponential functions. The running time of the algorithms can be reduced to if the jobs are independent. Scope and purpose We consider the single machine due date assignment and scheduling problems and design fast algorithms for their solution under a wide range of assumptions. The problems under consideration arise in production planning when the management is faced with a problem of setting the realistic due dates for a number of orders. The due dates of the orders are determined by increasing the time needed for their fulfillment by a common positive slack. If the slack is set to be large enough, the due dates can be easily maintained, thereby producing a good image of the firm. This, however, may result in the substantial holding cost of the finished products before they are brought to the customer. The objective is to explore the trade-off between the size of the slack and the arising holding costs for the early orders.