Tunneling magnetoresistance in devices based on epitaxial NiMnSb with uniaxial anisotropy

We demonstrate tunnel magnetoresistance (TMR) junctions based on a tri layer system consisting of an epitaxial NiMnSb, aluminum oxide and CoFe tri layer. The junctions show a tunnelling magnetoresistance of Delta R/R of 8.7% at room temperature which increases to 14.7% at 4.2K. The layers show clear separate switching and a small ferromagnetic coupling. A uniaxial in plane anisotropy in the NiMnSb layer leads to different switching characteristics depending on the direction in which the magnetic field is applied, an effect which can be used for sensor applications.Comment: 8 pages, 3 figures, submitted to Appl. Phys. Let

Strongly reduced bias dependence in spin-tunnel junctions obtained by ultraviolet light assisted oxidation

For future implementation of ferromagnetic tunnel junctions, we need a better understanding of the influence of the insulating barrier preparation method on the junction resistance, tunnel magnetoresistance (TMR), and its voltage bias dependence. In this letter, we focus on the bias dependence of junctions (Co-Al2O3-Ni80Fe20) prepared by ultraviolet light assisted in situ oxidation in an O-2 ambient. For an initial Al thickness of 1.3 nm, the resistance times area product of the junctions is 60 k Omega mu m(2), while showing up to 20% TMR at 5 mV bias. The decrease of TMR with bias voltage up to 1 V is remarkably small leading to V-1/2, for which half of the low-bias TMR remains, well over 0.6 V. (C) 2000 American Institute of Physics. [S0003-6951(00)02908-9]

Novologues Containing a Benzamide Side Chain Manifest Anti-proliferative Activity Against Two Breast Cancer Cell Lines

The heat shock protein 90 (Hsp90) folding machinery is essential for the maturation of nascent polypeptides into their biologically active three-dimensional-structures and for the rematuration/clearance of misfolded proteins that form under cellular stress.1–3 As a prosurvival chaperone, Hsp90 overexpression is commonly observed in transformed cells, which is required to sustain the hostile tumor micro-environment associated with nutrient deprivation and hypoxia. Pharmacological inhibition of Hsp90 has been shown to induce the degradation of oncogenic proteins associated with all six hallmarks of cancer that rely upon Hsp90.4–8 Consequently, Hsp90 represents a highly sought after target for the treatment of cancer. In fact, 17 small molecules that bind competitively to the N-terminal ATP-binding pocket are under clinical evaluation against various cancers.9,10 However, heat shock factor 1 (HSF-1), the master regulator of the pro-survival heat shock response also binds Hsp90. Ultimately, Hsp90 N-terminal inhibition results in HSF-1 release, and upon phosphorylation, trimerizes and translocates to the nucleus wherein it binds the heat shock elements to activate the pro-survival, heat shock response (HSR). The HSR serves to expand the cellular buffering capacity and to assist in the maturation of mutated and oncogenic substrates.11 This concomitant heat shock response is detrimental to the treatment of cancer and may lead to drug resistance and tumor metastasis.12 Recent studies have demonstrated that allosteric modulation of the Hsp90 C-terminus can separate the pro-survival heat shock response from pro-apoptotic, client protein degradation.13–20 Two classes of small molecules derived from novobiocin 1, (Figure 1) the first identified Hsp90 C-terminal inhibitor, were discovered via the structure-activity relationship studies. KU-32 (2), which lacks a 4-hydroxyl, the 3’-carbamate, and contains an acetamide in lieu of a prenylated benzamide, represents a lead compound that induces the heat shock response at concentrations much lower than that needed for client protein degradation.2,21 Consequently, this class of analogues has been evaluated as neuroprotective agents to refold protein aggregates.22–24 In contrast, KU-174 (3) contains a biarylamide side chain in lieu of the acetamide, and induces Hsp90 client protein degradation without induction of the heat shock response.25–26 Therefore, this class of novobiocin analogues manifests optimal properties for the treatment of cancer, as no HSR is observed with such compounds

PP165—Evaluation of JNJ-26489112, a Novel Antiepileptic Drug: A Placebo-Controlled, Exploratory Study

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Staff perspectives on the feasibility of a clinical pathway for anxiety and depression in cancer care, and mid-implementation adaptations.

BACKGROUND: Clinical pathways (CPs) are intended to standardise and improve care but do not always produce positive outcomes, possibly because they were not adapted to suit the specific context in which they were enacted. This qualitative study aimed to explore staff perspectives of implementation of a CP for routine screening, assessment, referral and management of anxiety and depression (the ADAPT CP) for patients with cancer, focussing on perceived feasibility of the CP and negotiated adaptations made during the implementation phase. METHODS: The ADAPT CP was implemented in 12 urban and regional oncology services in Australia. Services were randomised to receive core versus enhanced implementation strategies. Core sites received support until implementation commencement and could access progress reports. Enhanced sites received proactive, ongoing support during the 12-month implementation. Purposively selected staff were interviewed prior to implementation (n = 88) and 6 months later, half-way through the implementation period (n = 89). Monthly meetings with lead multi-disciplinary teams at the eight enhanced sites were recorded. Data were thematically analysed. RESULTS: Six overarching themes were identified: ADAPT is of high value; timing for introducing the CP and screening is difficult; online screening is challenging; a burden too much; no-one to refer patients to; and micro-logistics are key. While early screening was deemed desirable, diverse barriers meant this was complex, with adaptations made to time and screening location. Online screening prompted by email, seen as time-saving and efficient, also proved unsuccessful in some services, with adaptations made to in-clinic or phone screening, or repeated email reminders. Staff negative attitudes to ADAPT, time constraints, and perceived poor fit of ADAPT to work roles and flows, all impacted implementation, with key tasks often devolving to a few key individuals. Nevertheless, services remained committed to the ADAPT CP, and worked hard to create, review and adapt strategies to address challenges to optimise success. CONCLUSIONS: This study demonstrates the interactive nature of health service change, with staff actively engaging with, forming views on, and problem-solving adaptations of the ADAPT CP to overcome barriers. Obtaining staff feedback is critical to ensure health service change is sustainable, meaningful and achieves its promise of improving patient outcomes. TRIAL REGISTRATION: The study was registered prospectively with the ANZCTR on 22/3/2017. Trial ID ACTRN12617000411347

Adolescent self-control predicts midlife hallucinatory experiences:40-year follow-up of a national birth cohort

Associations between self-control in adolescence and adult mental health are unclear in the general population; to our knowledge, no study has investigated self-control in relation to psychotic-like symptoms

Calcitonin Gene Peptides: The Diagnostic Value of Measurement in Medullary Thyroid Carcinoma

The calcitonin gene encodes a family of peptides, at least three of which normally circulate in man: calcitonin (CT), a calcium-lowering hormone; katacalcin (KC), a peptide of unknown function; and calcitonin gene-related peptide (CGRP), a neuropeptide and potent vasodilator. In a study of 45 patients with medullary thyroid carcinoma (MTC), plasma CGRP was elevated in approximately 50% of cases. Furthermore, CGRP levels did not correlate with CT levels. However, plasma KC was elevated in all cases, with a good correlation with CT levels, as has been noted previously. Measurement of CT or KC appears to be superior to measurement of CGRP for the detection of MTC

1,25-Dihydroxycholecalciferol (calcitriol) modifies uptake and release of 25-hydroxycholecalciferol in skeletal muscle cells in culture

© 2017 Elsevier Ltd The major circulating metabolite of vitamin D 3 , 25-hydroxycholecalciferol [25(OH)D], has a remarkably long half-life in blood for a (seco)steroid. Data from our studies and others are consistent with the hypothesis that there is a role for skeletal muscle in the maintenance of vitamin D status. Muscle cells internalise vitamin D-binding protein (DBP) from the circulation by means of a megalin/cubilin plasma membrane transport mechanism. The internalised DBP molecules then bind to actin and thus provide an intracellular array of high affinity binding sites for its specific ligand, 25(OH)D. There is evidence that the residence time for DBP in muscle cells is short and that it undergoes proteolytic degradation, releasing bound 25(OH)D. The processes of internalisation of DBP and its intracellular residence time, bound to actin, appear to be regulated. To explore whether 1,25-dihydroxycholecalciferol (calcitriol) has any effect on this process, cell cultures of myotubes and primary skeletal muscle fibers were incubated in a medium containing 10 −10 M calcitriol but with no added DBP. After 3 h pre-incubation with calcitriol, the net uptake of 25(OH)D by these calcitriol-treated cells over a further 4 h was significantly greater than that in vehicle-treated control cells. This was accompanied by a significant increase in intracellular DBP protein. However, after 16 h of pre-incubation with calcitriol, the muscle cells showed a significantly depressed ability to accumulate 25(OH)D compared to control cells over a further 4 or 16 hours. These effects of pre-incubation with calcitriol were abolished in fibers from VDR-knockout mice. The effect was also abolished by the addition of 4,4\u27-diisothiocyano-2,2\u27-stilbenedisulfonic acid (DIDS), which inhibits chloride channel opening. Incubation of C2 myotubes with calcitriol also significantly reduced retention of previously accumulated 25(OH)D after 4 or 8 h. It is concluded from these in vitro studies that calcitriol can modify the DBP-dependent uptake and release of 25(OH)D by skeletal muscle cells in a manner that suggests some inducible change in the function of these cells