Digital memory sense amplifying means Patent

Digital magnetic core memory with sensing amplifier circuit

Digital data command bus

Command bus constructed from coaxial cable has short segments of its outer jacket and shield removed and replaced with small ferrite cores carrying multiturn windings connected to decoder. Device reduces number of wire pairs required to communicate command data to systems and subsystems

Transfluxor circuit amplifies sensing current for computer memories

To transfer data from the magnetic memory core to an independent core, a reliable sensing amplifier has been developed. Later the data in the independent core is transferred to the arithmetical section of the computer

Opioid regulation of Mu receptor internalisation: relevance to the development of tolerance and dependence

Internalisation of the mu opioid receptor from the surface of cells is generally achieved by receptor occupancy with agonist ligands of high efficacy. However, in many situations the potent analgesic morphine fails to promote internalisation effectively and whether there is a direct link between this and the propensity for the sustained use of morphine to result in both tolerance and dependence has been studied intensely. Although frequently described as a partial agonist, this characteristic appears insufficient to explain the poor capacity of morphine to promote internalisation of the mu opioid receptor. Experiments performed using both transfected cell systems and ex vivo/in vivo models have provided evidence that when morphine can promote internalisation of the mu receptor there is a decrease in the development of tolerance and dependence. Although aspects of this model are controversial, such observations suggest a number of approaches to further enhance the use of morphine as an analgesic

Nae too bad: a survey of job satisfaction, staff morale and qualifications in residential child care in Scotland

The report of the National Children’s Bureau study of staff morale, qualifications and retention in England (Mainey, 2003) rightly highlighted a number of crucial issues facing providers of residential child care. Entitled Better Than You Think the key finding was that the rates of morale and job satisfaction were not low despite the adverse environment in which residential care operates. Residential care in the modern world is intended to be mainly a temporary placement for some of the most demanding young people who require out-of-home care. However, as with foster care, significant numbers of young people are spending years in out-of-home care and many residential services have to accommodate a wide variety of needs within a single unit. This general remit is challenging enough but the sector also continues to struggle with the aftermath of a number of high profile public inquiries which have identified instances of abuse of children and young people in residential care (Kent, 1997; Utting, 1997; Waterhouse, 2000)

Brayton cycle 3.2-inch radial compressor performance evaluation

Brayton cycle 3.2 inch radial compressor performance evaluation over wide range of Reynolds number

Solar Flare X-ray Source Motion as a Response to Electron Spectral Hardening

Context: Solar flare hard X-rays (HXRs) are thought to be produced by nonthermal coronal electrons stopping in the chromosphere, or remaining trapped in the corona. The collisional thick target model (CTTM) predicts that sources produced by harder power-law injection spectra should appear further down the legs or footpoints of a flare loop. Therefore, hardening of the injected power-law electron spectrum during flare onset should be concurrent with a descending hard X-ray source. Aims: To test this implication of the CTTM by comparing its predicted HXR source locations with those derived from observations of a solar flare which exhibits a nonthermally-dominated spectrum before the peak in HXRs, known as an early impulsive event. Methods: HXR images and spectra of an early impulsive C-class flare were obtained using the Ramaty High-Energy Solar Spectroscopic Imager (RHESSI). Images were reconstructed to produce HXR source height evolutions for three energy bands. Spatially-integrated spectral analysis was performed to isolate nonthermal emission, and to determine the power-law index of the electron injection spectrum. The observed height-time evolutions were then fit with CTTM-based simulated heights for each energy. Results: A good match between model and observed source heights was reached, requiring a density model that agreed well with previous studies of flare loop densities. Conclusions: The CTTM has been used to produce a descent of model HXR source heights that compares well with observations of this event. Based on this interpretation, downward motion of nonthermal sources should indeed occur in any flare where there is spectral hardening in the electron distribution during a flare. However, this would often be masked by thermal emission associated with flare plasma pre-heating.Comment: 8 pages, 5 figure

A single amino acid determines preference between phospholipids and reveals length restriction for activation ofthe S1P₄ receptor

Background<br/><br/> Sphingosine-1-phosphate and lysophosphatidic acid (LPA) are ligands for two related families of G protein-coupled receptors, the S1P and LPA receptors, respectively. The lysophospholipid ligands of these receptors are structurally similar, however recognition of these lipids by these receptors is highly selective. A single residue present within the third transmembrane domain (TM) of S1P receptors is thought to determine ligand selectivity; replacement of the naturally occurring glutamic acid with glutamine (present at this position in the LPA receptors) has previously been shown to be sufficient to change the specificity of S1P<sub>1</sub> from S1P to 18:1 LPA.<br/><br/> Results<br/><br/> We tested whether mutation of this "ligand selectivity" residue to glutamine could confer LPA-responsiveness to the related S1P receptor, S1P<sub>4</sub>. This mutation severely affected the response of S1P<sub>4</sub> to S1P in a [<sup>35</sup>S]GTPγS binding assay, and imparted sensitivity to LPA species in the order 14:0 LPA > 16:0 LPA > 18:1 LPA. These results indicate a length restriction for activation of this receptor and demonstrate the utility of using LPA-responsive S1P receptor mutants to probe binding pocket length using readily available LPA species. Computational modelling of the interactions between these ligands and both wild type and mutant S1P<sub>4</sub> receptors showed excellent agreement with experimental data, therefore confirming the fundamental role of this residue in ligand recognition by S1P receptors.<br/><br/> Conclusions<br/><br/> Glutamic acid in the third transmembrane domain of the S1P receptors is a general selectivity switch regulating response to S1P over the closely related phospholipids, LPA. Mutation of this residue to glutamine confers LPA responsiveness with preference for short-chain species. The preference for short-chain LPA species indicates a length restriction different from the closely related S1P<sub>1</sub> receptor

Orexin-1 receptor-cannabinoid CB1 receptor heterodimerization results in both ligand-dependent and -independent coordinated alterations of receptor localization and function

Following inducible expression in HEK293 cells, the human orexin-1 receptor was targeted to the cell surface but became internalized following exposure to the peptide agonist orexin A. By contrast, constitutive expression of the human cannabinoid CB1 receptor resulted in a predominantly punctate, intracellular distribution pattern consistent with spontaneous, agonistindependent internalization. Expression of the orexin-1 receptor in the presence of the CB1 receptor resulted in both receptors displaying the spontaneous internalization phenotype. Single cell fluorescence resonance energy transfer imaging indicated the two receptors were present as heterodimers/oligomers in intracellular vesicles. Addition of the CB1 receptor antagonist SR-141716A to cells expressing only the CB1 receptor resulted in re-localization of the receptor to the cell surface. Although SR-141716A has no significant affinity for the orexin-1 receptor, in cells co-expressing the CB1 receptor, the orexin-1 receptor was also re-localized to the cell surface by treatment with SR-141716A. Treatment of cells co-expressing the orexin-1 and CB1 receptors with the orexin-1 receptor antagonist SB-674042 also resulted in re-localization of both receptors to the cell surface. Treatment with SR-141716A resulted in decreased potency of orexin A to activate the mitogen-activated protein kinases ERK1/2 only in cells co-expressing the two receptors. Treatment with SB-674042 also reduced the potency of a CB1 receptor agonist to phosphorylate ERK1/2 only when the two receptors were co-expressed. These studies introduce an entirely novel pharmacological paradigm, whereby ligands modulate the function of receptors for which they have no significant inherent affinity by acting as regulators of receptor heterodimers

'A Ransom for Many'

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