A philosophical inquiry concerning human liberty /

Not in Crook.

A vindication of the Church of England from the aspersions of a late libel intituled, Priestcraft in perfection, &c. : Wherein the controverted clause of the church's power in the XXth article is shewn to be of equal authority with all the rest of the articles; and the fraud and forgery, charged upon the clergy on the account of that clause, are retorted upon their accusers. With a preface containing some remarks upon the Reflections on that pamphlet. /

By Hilkiah Bedford. Cf. ESTC.

Recueil de diverses pieces sur la philosophie, la religion naturelle, Phistoire, les mathematiques, &c.

t. 1. Difficultez de mr. Leibniz contre les sentimens de quelques célèbres ecrivains anglois, touchant les principes de la philosophie, & de la la théologie naturelle: avec les Réponses de mr. Clarke.--Recherches philosophiques sur la liberté de l'homme: par mr. Collins.--Remarques...par mr. Clarke.--t. 2. Lettres de mrs. Leibniz, Newton, & c.--Opuscules de mr. Leibniz.

Understanding file access mechanisms for embedded ubicomp collaboration interfaces

This paper explores the nature of interfaces to support people in accessing their files at tabletop displays embedded in the environment. To do this, we designed a study comparing people's interaction with two very different classes of file system access interface: Focus, explicitly designed for tabletops, and the familiar hierarchical Windows Explorer. In our within-subjects double-crossover study, participants collaborated on 4 planning tasks. Based on video, logs, questionnaires and interviews, we conclude that both classes of interface have a place. Notably, Focus contributed to improved collaboration and more efficient use of the workspace than with Explorer. Our results inform a set of recommendations for future interfaces enabling this important class of interaction -- supporting access to files for collaboration at tabletop devices embedded in an ubicomp environment.

Inward rectifier potassium channels in the HL-1 cardiomyocyte-derived cell line.

HL-1 is a line of immortalized cells of cardiomyocyte origin that are a useful complement to native cardiomyocytes in studies of cardiac gene regulation. Several types of ion channel have been identified in these cells, but not the physiologically important inward rectifier K(+) channels. Our aim was to identify and characterize inward rectifier K(+) channels in HL-1 cells. External Ba(2+) (100?µM) inhibited 44?±?0.05% (mean?±?s.e.m., n?=?11) of inward current in whole-cell patch-clamp recordings. The reversal potential of the Ba(2+)-sensitive current shifted with external [K(+)] as expected for K(+)-selective channels. The slope conductance of the inward Ba(2+)-sensitive current increased with external [K(+)]. The apparent Kd for Ba(2+) was voltage dependent, ranging from 15?µM at -150 ?mV to 148?µM at -75 ?mV in 120 ?mM external K(+). This current was insensitive to 10?µM glybenclamide. A component of whole-cell current was sensitive to 150?µM 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), although it did not correspond to the Ba(2+)-sensitive component. The effect of external 1 mM Cs(+) was similar to that of Ba(2+). Polymerase chain reaction using HL-1 cDNA as template and primers specific for the cardiac inward rectifier K(ir)2.1 produced a fragment of the expected size that was confirmed to be K(ir)2.1 by DNA sequencing. In conclusion, HL-1 cells express a current that is characteristic of cardiac inward rectifier K(+) channels, and express K(ir)2.1 mRNA. This cell line may have use as a system for studying inward rectifier gene regulation in a cardiomyocyte phenotype.

Distinctive Profile of IsomiR Expression and Novel MicroRNAs in Rat Heart Left Ventricle

MicroRNAs (miRNAs) are single-stranded non-coding RNAs that negatively regulate target gene expression through mRNA cleavage or translational repression. There is mounting evidence that they play critical roles in heart disease. The expression of known miRNAs in the heart has been studied at length by microarray and quantitative PCR but it is becoming evident that microRNA isoforms (isomiRs) are potentially physiologically important. It is well known that left ventricular (patho)physiology is influenced by transmural heterogeneity of cardiomyocyte phenotype, and this likely reflects underlying heterogeneity of gene expression. Given the significant role of miRNAs in regulating gene expression, knowledge of how the miRNA profile varies across the ventricular wall will be crucial to better understand the mechanisms governing transmural physiological heterogeneity. To determinine miRNA/isomiR expression profiles in the rat heart we investigated tissue from different locations across the left ventricular wall using deep sequencing. We detected significant quantities of 145 known rat miRNAs and 68 potential novel orthologs of known miRNAs, in mature, mature* and isomiR formation. Many isomiRs were detected at a higher frequency than their canonical sequence in miRBase and have different predicted targets. The most common miR-133a isomiR was more effective at targeting a construct containing a sequence from the gelsolin gene than was canonical miR-133a, as determined by dual-fluorescence assay. We identified a novel rat miR-1 homolog from a second miR-1 gene; and a novel rat miRNA similar to miR-676. We also cloned and sequenced the rat miR-486 gene which is not in miRBase (v18). Signalling pathways predicted to be targeted by the most highly detected miRNAs include Ubiquitin-mediated Proteolysis, Mitogen-Activated Protein Kinase, Regulation of Actin Cytoskeleton, Wnt signalling, Calcium Signalling, Gap junctions and Arrhythmogenic Right Ventricular Cardiomyopathy. Most miRNAs are not expressed in a gradient across the ventricular wall, with exceptions including miR-10b, miR-21, miR-99b and miR-486.

Der Geist des Judenthums

Anthony Collins

L' esprit du judaisme ou examen raisonné de la loi moyse & de son influence sur la religion chrétienne

[Anthony Collins. Übers.[[Elektronische Ressource]] : Paul Heinrich Dietrich Frhr von Holbach]

Scanning mutagenesis of the putative transmembrane segments of Kir2.1, an inward rectifier potassium channel

Structural models of inward rectifier K+ channels incorporate four identical or homologous subunits, each of which has two hydrophobic segments (M1 and M2) which are predicted to span the membrane as α helices. Since hydrophobic interactions between proteins and membrane lipids are thought to be generally of a nonspecific nature, we attempted to identify lipid-contacting residues in Kir2.1 as those which tolerate mutation to tryptophan, which has a large hydrophobic side chain. Tolerated mutations were defined as those which produced measurable inwardly rectifying currents in Xenopus oocytes. To distinguish between water-accessible positions and positions adjacent to membrane lipids or within the protein interior we also mutated residues in M1 and M2 individually to aspartate, since an amino acid with a charged side chain should not be tolerated at lipid-facing or interior positions, due to the energy cost of burying a charge in a hydrophobic environment. Surprisingly, 17 out of 20 and 17 out of 22 non-tryptophan residues in M1 and M2, respectively, tolerated being mutated to tryptophan. Moreover, aspartate was tolerated at 15 out of 22 and 15 out of 21 non-aspartate M1 and M2 positions respectively. Periodicity in the pattern of tolerated vs. nontolerated mutations consistent with α helices or β strands did not emerge convincingly from these data. We consider the possibility that parts of M1 and M2 may be in contact with water.

Anthony Browne and the cultural capital of classic fairy tales

Prolific British author/illustrator Anthony Browne both participates in the classic fairy-tale tradition and appropriates its cultural capital, ultimately undertaking a process of self-canonisation alongside the dissemination of fairy tales. In reading Browne’s Hansel and Gretel (1981), The Tunnel (1989) and Into the Forest (2004), a trajectory emerges that moves from broadly intertextual to more exclusively self-referential modes of representation which reward readers of “Anthony Browne”, rather than readers of “fairy tales”. All three books depict ‘babes in the woods’ stories wherein child characters must negotiate some form of threat outside the home in order to return home safely. Thus, they represent childhood agency. However, these visions of agency are ultimately subordinated to logics of capital, which means that child readers of Browne’s fairy-tale books are overtly invited to identify with children who act, but are interpellated as privileged if they ‘know’. Bourdieu’s model of ‘cultural capital’ offers a lens for considering Browne’s production of ‘value’ for his own works within a broader cultural landscape which privileges literary fairy tales as a register of juvenile cultural competency. If cultural capital can be formulated most simply as the symbolic exchange value of approved modes of knowing and being, it is clearly helpful when trying to unpack logics of meaning within heavily intertextual or citational texts. It is also helpful thinking about what kinds of stories we as a culture choose to disseminate, choose to privilege, or choose to suppress. Zipes notes of fairy tales that, “the genre itself becomes a kind of institute that is involved in the socialization and acculturation of readers” (22). He elaborates that, “We initiate readers and expect them to learn the fairy-tale code as part of our responsibility in the civilizing process” (Zipes 29), so it is little wonder that Tatar describes fairy tales as “a vital part of our cultural capital” (xix). Although Browne is clearly interested in literary fairy tales, the most obvious strategies of self-canonisation take place in Browne’s work not in words but in pictures: hidden in plain sight, as illustration becomes self-reflexive citation.

Virtually real : Suzanne Collins's the Hunger Games Trilogy

The Hunger Games trilogy by Suzanne Cololins deals with a dystopian future society in which a punitive ruling elite provide 'entertainment' for the masses in the form of mediatised 'games' featuring young people who must fight to kill one another until there is only one winner. The purpose of these games is to remind the populace of the power of the government and its ability to dispose of any who dare defy it. In acknowledging violent 'games' as virtual entertainments which can be used to political effect, Collins suggests that they possess a disturbing capacity to undermine ethical perspective on the human,the humane and the real. Drawing on Baudrillard's ideas about simulation and simulacra as well as Elaine Scarry's and Susan Sontag's concerns for media representations of the body in pain, this paper discusses the ways in which the texts highlight the dangers of virtual modes while also risking perpetuating their entertainment value.

The short-term accommodation response to aniso-accommodative stimuli in isometropia

Purpose There have been only a limited number of studies examining the accommodative response that occurs when the two eyes are provided with disparate accommodative stimuli, and the results from these studies to date have been equivocal. In this study, we therefore aimed to examine the capacity of the visual system to aniso-accommodate by objectively measuring the interocular difference in the accommodation response between fellow dominant and non-dominant eyes under controlled monocular and binocular viewing conditions during short-term exposure to aniso-accommodative stimuli. Methods The accommodative response of each eye of sixteen young isometropic adults (mean age 22 ± 2 years) with normal binocular vision was measured using an open-field autorefractor during a range of testing conditions; monocularly (accommodative demands ranging from 1.32 to 4.55 D) and binocularly while altering the accommodation demand for each eye (aniso-accommodative stimuli ranging from 0.24 to 2.05 D). Results Under monocular viewing conditions, the dominant and non-dominant eyes displayed a highly symmetric accommodative response; mean interocular difference in spherical equivalent 0.01 ± 0.06 D (relative) and 0.22 ± 0.06 D (absolute) (p>0.05). During binocular viewing, the dominant eye displayed a greater accommodative response (0.11 ± 0.34 D relative and 0.24 ± 0.26 D absolute) irrespective of whether the demand of the dominant or non-dominant eye was altered (p = 0.01). Astigmatic power vectors J0 and J45 did not vary between eyes or with increasing accommodation demands under monocular or binocular viewing conditions (p>0.05). Conclusion The dominant and non-dominant eyes of young isometropic individuals display a similar consensual lag of accommodation under both monocular and binocular viewing conditions, with the dominant eye showing a small but significantly greater (by 0.12 to 0.25 D) accommodative response. Evidence of short-term aniso-accommodation in response to asymmetric accommodation demands was not observed.