Calibration and evaluation of optical systems for full-field strain measurement

The design and testing of a reference material for the calibration of optical systems for strain measurement is described, together with the design and testing of a standardized test material that allows the evaluation and assessment of fitness for purpose of the most sophisticated optical system for strain measurement. A classification system for the steps in the measurement process is also proposed and allows the development of a unified approach to diagnostic testing of components or sub-systems in an optical system for strain measurement based on any optical technique. The results described arise from a European study known as SPOTS whose objectives were to begin to fill the gap caused by a lack of standards

Nemesis Reconsidered

The hypothesis of a companion object (Nemesis) orbiting the Sun was motivated by the claim of a terrestrial extinction periodicity, thought to be mediated by comet showers. The orbit of a distant companion to the Sun is expected to be perturbed by the Galactic tidal field and encounters with passing stars, which will induce variation in the period. We examine the evidence for the previously proposed periodicity, using two modern, greatly improved paleontological datasets of fossil biodiversity. We find that there is a narrow peak at 27 My in the cross-spectrum of extinction intensity time series between these independent datasets. This periodicity extends over a time period nearly twice that for which it was originally noted. An excess of extinction events are associated with this periodicity at 99% confidence. In this sense we confirm the originally noted feature in the time series for extinction. However, we find that it displays extremely regular timing for about 0.5 Gy. The regularity of the timing compared with earlier calculations of orbital perturbation would seem to exclude the Nemesis hypothesis as a causal factor.Comment: 10 pages, 2 figures, accepted for publication in Monthly Notices of the Royal Astronomical Societ

The PDK1 master kinase is over-expressed in acute myeloid leukemia and promotes PKC-mediated survival of leukemic blasts

PDK1 is a master kinase that activates at least six protein kinase groups including AKT, PKC and S6K and is a potential target in the treatment of a range of malignancies. Here we show overexpression of PDK1 in over 40% of myelomonocytic acute leukemia patients. Overexpression of PDK1 occurred uniformly throughout the leukemic population, including putative leukemia-initiating cells. Clinical outcome analysis revealed PDK1 overexpression was associated with poorer treatment outcome. Primary acute myeloid leukemia blasts over-expressing PDK1 showed improved in vitro survival and ectopic expression of PDK1 promoted the survival of myeloid cell lines. Analysis of PDK1 target kinases revealed that PDK1 overexpression was most closely associated with increased phosphorylation of PKC isoenzymes and inhibition of PKC strongly inhibited the survival advantage of PDK1 over-expressing cells. Membrane localization studies implicated PKCα as a major target for PDK1 in this disease. PDK1 over-expressing blasts showed differential sensitivity to PDK1 inhibition (in the low micromolar range) suggesting oncogene addiction, whilst normal bone marrow progenitors were refractory to PDK1 inhibition at effective inhibitor concentrations. PDK1 inhibition also targeted subpopulations of leukemic blasts with a putative leukemia-initiating cell phenotype. Together these data show that overexpression of PDK1 is common in acute myelomonocytic leukemia and is associated with poorer treatment outcome, probably arising from the cytoprotective function of PDK1. We also show that therapeutic targeting of PDK1 has the potential to be both an effective and selective treatment for these patients, and is also compatible with current treatment regimes

Does wage rank affect employees' well-being?

How do workers make wage comparisons? Both an experimental study and an analysis of 16,000 British employees are reported. Satisfaction and well-being levels are shown to depend on more than simple relative pay. They depend upon the ordinal rank of an individual's wage within a comparison group. “Rank” itself thus seems to matter to human beings. Moreover, consistent with psychological theory, quits in a workplace are correlated with pay distribution skewness

Cord blood-derived quiescent CD34+ cells are more transcriptionally matched to AML blasts than cytokine-induced normal human hematopoietic CD34+ cells

Acute myeloid leukemia (AML) is characterized by developmental arrest, which is thought to arise from transcriptional dysregulation of myeloid development programs. Hematopoietic stem and progenitor cells (HSPCs) isolated from human blood are frequently used as a normal comparator in AML studies. Previous studies have reported changes in the transcriptional program of genes involved in proliferation, differentiation, apoptosis, and homing when HSPCs were expanded ex vivo. The intrinsic functional differences between quiescent and dividing CD34+ HSPCs prompted us to determine whether fresh or cytokine-induced cord blood-derived CD34+ HSPCs are a more appropriate normal control compared to AML blasts. Based on principal component analysis and gene expression profiling we demonstrate that CD34+ HSPCs that do not undergo ex vivo expansion are transcriptionally similar to minimally differentiated AML blasts. This was confirmed by comparing the cell cycle status of the AML blasts and the HSPCs. We suggest that freshly isolated CD34+ HSPCs that do not undergo ex vivo expansion would serve as a better control to identify novel transcriptional targets in the AML blast population

Chemical and kinematical properties of BSSs and HB stars in NGC 6397

We used three sets of high-resolution spectra acquired with the multifiber facility FLAMES at the Very Large Telescope of the European Southern Observatory to investigate the chemical and kinematical properties of a sample of 42 horizontal branch (HB) stars, 18 Blue Straggler Stars (BSSs) and 86 main sequence turn-off and sub-giant branch stars in the nearby globular cluster NGC 6397. We measured rotational velocities and Fe, O and Mg abundances. All the unevolved stars in our sample turn out to have low rotational velocites (v sin i< 10\kms), while HB stars and BSSs show a broad distribution, with values ranging from 0 to 70 \kms. For HB stars with T<10500 K there is a clear temperature-oxygen anti-correlation, that can be understood if the star position along the HB is mainly determined by the He content. The hottest BSSs and HB stars (with temperatures T>8200 K and T> 10500 K, respectively) also show significant deviations in their iron abundance with respect to the cluster metallicity (as traced by the unevolved stars, [Fe/H]=-2.12). While similar chemical patterns have been already observed in other hot HB stars, this is the first evidence ever collected for BSSs. We interprete these abundance anomalies as due to the metal radiative levitation, occurring in stars with shallow or no convective envelopes

Evaluating drug treatments for Parkinson's disease: how good are the trials?

The prevalence of Parkinson's disease will increase as the population ages, making it important to identify reliably the most effective drug therapy Although many randomised controlled trials have evaluated the efficacy of different classes of drugs in both early and later Parkinson's disease, uncertainty about best treatment remains because of small numbers, inadequate follow up, and inappropriate end points Much larger trials are needed with long term follow up and end points of relevance to patients Large simple pragmatic trials have improved treatment of heart disease, stroke, and cancer and their methods should be applied to Parkinson's disease and other neurodegenerative disease

Prostanoid receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Prostanoid receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Prostanoid Receptors [644]) are activated by the endogenous ligands prostaglandins PGD2, PGE1, PGE2 , PGF2&#945;, PGH2, prostacyclin [PGI2] and thromboxane A2. Measurement of the potency of PGI2 and thromboxane A2 is hampered by their instability in physiological salt solution; they are often replaced by cicaprost and U46619, respectively, in receptor characterization studies

The technologies of isolation: apocalypse and self in Kurosawa Kiyoshi's Kairo

In this investigation of the Japanese film Kairo, I contemplate how the horrors present in the film relate to the issue of self, by examining a number of interlocking motifs. These include thematic foci on disease and technology which are more intimately and inwardly focused that the film's conclusion first appears to suggest. The true horror here, I argue, is ontological: centred on the self and its divorcing from the exterior world, especially founded in an increased use of and reliance on communicative technologies. I contend that these concerns are manifested in Kairo by presenting the spread of technology as disease-like, infecting the city and the individuals who are isolated and imprisoned by their urban environment. Finally, I investigate the meanings of the apocalypse, expounding how it may be read as hopeful for the future rather than indicative of failure or doom

Prostanoid receptors (version 2020.4) in the IUPHAR/BPS Guide to Pharmacology Database

Prostanoid receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Prostanoid Receptors [661]) are activated by the endogenous ligands prostaglandins PGD2, PGE1, PGE2 , PGF2&#945;, PGH2, prostacyclin [PGI2] and thromboxane A2. Differences and similarities between human and rodent prostanoid receptor orthologues, and their specific roles in pathophysiologic conditions are reviewed in [423]. Measurement of the potency of PGI2 and thromboxane A2 is hampered by their instability in physiological salt solution; they are often replaced by cicaprost and U46619, respectively, in receptor characterization studies