Accumulation is late and brief in preferential choice

Preferential choices are often explained using models within the evidence accumulation framework: value drives the drift rate at which evidence is accumulated until a threshold is reached and an option is chosen. Although rarely stated explicitly, almost all such models assume that decision makers have knowledge at the onset of the choice of all available attributes and options. In reality however, choice information is viewed piece-by-piece, and is often not completely acquired until late in the choice, if at all. Across four eye-tracking experiments, we show that whether the information was acquired early or late is irrelevant in predicting choice: all that matters is whether or not it was acquired at all. Models with potential alternative assumptions were posited and tested, such as 1) accumulation of instantaneously available information or 2) running estimates as information is acquired. These provided poor fits to the data. We are forced to conclude that participants either are clairvoyant, accumulating using information before they have looked at it, or delay accumulating evidence until very late in the choice, so late that the majority of choice time is not time in which evidence is accumulated. Thus, although the evidence accumulation framework may still be useful in measurement models, it cannot account for the details of the processes involved in decision making

Investigation into background levels of small organic samples at the NERC Radiocarbon Laboratory

Recent progress in preparation/combustion of submilligram organic samples at our laboratories is presented. Routine methods had to be modified/refined to achieve acceptable and consistent procedural blanks for organic samples smaller than 1000 g C. A description of the process leading to a modified combustion method for smaller organic samples is given in detail. In addition to analyzing different background materials, the influence of different chemical reagents on the overall radiocarbon background level was investigated, such as carbon contamination arising from copper oxide of different purities and from different suppliers. Using the modified combustion method, small amounts of background materials and known-age standard IAEA-C5 were individually combusted to CO2. Below 1000 g C, organic background levels follow an inverse mass dependency when combusted with the modified method, increasing from 0.13 0.05 pMC up to 1.20 0.04 pMC for 80 g C. Results for a given carbon mass were lower for combustion of etched Iceland spar calcite mineral, indicating that part of the observed background of bituminous coal was probably introduced by handling the material in atmosphere prior to combustion. Using the modified combustion method, the background-corrected activity of IAEA-C5 agreed to within 2 s of the consensus value of 23.05 pMC down to a sample mass of 55 g C

Progress in AMS target production in sub-milligram samples at the NERC Radiocarbon Laboratory

. Recent progress in graphite target production for sub-milligram environmental samples in our facility is presented. We describe an optimized hydrolysis procedure now routinely used for the preparation of CO2 from inorganic samples, a new high-vacuum line dedicated to small sample processing (combining sample distillation and graphitization units), as well as a modified graphitization procedure. Although measurements of graphite targets as small as 35 µg C have been achieved, system background and measurement uncertainties increase significantly below 150 µg C. As target lifetime can become critically short for targets <150 µg C, the facility currently only processes inorganic samples down to 150 µg C. All radiocarbon measurements are made at the Scottish Universities Environmental Research Centre (SUERC) accelerator mass spectrometry (AMS) facility. Sample processing and analysis are labor-intensive, taking approximately 3 times longer than samples ≥500 µg C. The technical details of the new system, graphitization yield, fractionation introduced during the process, and the system blank are discussed in detail

Accumulation is late and brief in preferential choice

Preferential choices are often explained using models within the evidence accumulation framework: value drives the drift rate at which evidence is accumulated until a threshold is reached and an option is chosen. Although rarely stated explicitly, almost all such models assume that decision makers have knowledge at the onset of the choice of all available attributes and options. In reality however, choice information is viewed piece-by-piece, and is often not completely acquired until late in the choice, if at all. Across four eye-tracking experiments, we show that whether the information was acquired early or late is irrelevant in predicting choice: all that matters is whether or not it was acquired at all. Models with potential alternative assumptions were posited and tested, such as 1) accumulation of instantaneously available information or 2) running estimates as information is acquired. These provided poor fits to the data. We are forced to conclude that participants either are clairvoyant, accumulating using information before they have looked at it, or delay accumulating evidence until very late in the choice, so late that the majority of choice time is not time in which evidence is accumulated. Thus, although the evidence accumulation framework may still be useful in measurement models, it cannot account for the details of the processes involved in decision making

Measuring the effects of fractionated radiation therapy in a 3D prostate cancer model system using SERS nanosensors.

Multicellular tumour spheroids (MTS) are three-dimensional cell cultures that possess their own microenvironments and provide a more meaningful model of tumour biology than monolayer cultures. As a result, MTS are becoming increasingly used as tumor models when measuring the efficiency of therapies. Monitoring the viability of live MTS is complicated by their 3D nature and conventional approaches such as fluorescence often require fixation and sectioning. In this paper we detail the use of Surface Enhanced Raman Spectroscopy (SERS) to measure the viability of MTS grown from prostate cancer (PC3) cells. Our results show that we can monitor loss of viability by measuring pH and redox potential in MTS and furthermore we demonstrate that SERS can be used to measure the effects of fractionation of a dose of radiotherapy in a way that has potential to inform treatment planning.EaStCHEM, NHS Lothian, Jamie King Cancer Research FundThis is the final version of the article. It first appeared from the Royal Society of Chemistry via http://dx.doi.org/10.1039/C6AN01032

Actin-myosin–based contraction is responsible for apoptotic nuclear disintegration

Membrane blebbing during the apoptotic execution phase results from caspase-mediated cleavage and activation of ROCK I. Here, we show that ROCK activity, myosin light chain (MLC) phosphorylation, MLC ATPase activity, and an intact actin cytoskeleton, but not microtubular cytoskeleton, are required for disruption of nuclear integrity during apoptosis. Inhibition of ROCK or MLC ATPase activity, which protect apoptotic nuclear integrity, does not affect caspase-mediated degradation of nuclear proteins such as lamins A, B1, or C. The conditional activation of ROCK I was sufficient to tear apart nuclei in lamin A/C null fibroblasts, but not in wild-type fibroblasts. Thus, apoptotic nuclear disintegration requires actin-myosin contractile force and lamin proteolysis, making apoptosis analogous to, but distinct from, mitosis where nuclear disintegration results from microtubule-based forces and from lamin phosphorylation and depolymerization

Functions of the nuclear envelope and lamina in development and disease

Abstract Recent findings that some 24 inherited diseases and anomalies are caused by defects in proteins of the NE (nuclear envelope) and lamina have resulted in a fundamental reassessment of the functions of the NE and underlying lamina. Instead of just regarding the NE and lamina as a molecular filtering device, regulating the transfer of macromolecules between the cytoplasm and nucleus, we now envisage the NE/lamina functioning as a key cellular 'hub' in integrating critical functions that include chromatin organization, transcriptional regulation, mechanical integrity of the cell and signalling pathways, as well as acting as a key component in the organization and function of the cytoskeleton

Abnormal nuclear shape and impaired mechanotransduction in emerin-deficient cells

Emery-Dreifuss muscular dystrophy can be caused by mutations in the nuclear envelope proteins lamin A/C and emerin. We recently demonstrated that A-type lamin-deficient cells have impaired nuclear mechanics and altered mechanotransduction, suggesting two potential disease mechanisms (Lammerding, J., P.C. Schulze, T. Takahashi, S. Kozlov, T. Sullivan, R.D. Kamm, C.L. Stewart, and R.T. Lee. 2004. J. Clin. Invest. 113:370–378). Here, we examined the function of emerin on nuclear mechanics and strain-induced signaling. Emerin-deficient mouse embryo fibroblasts have abnormal nuclear shape, but in contrast to A-type lamin-deficient cells, exhibit nuclear deformations comparable to wild-type cells in cellular strain experiments, and the integrity of emerin-deficient nuclear envelopes appeared normal in a nuclear microinjection assay. Interestingly, expression of mechanosensitive genes in response to mechanical strain was impaired in emerin-deficient cells, and prolonged mechanical stimulation increased apoptosis in emerin-deficient cells. Thus, emerin-deficient mouse embryo fibroblasts have apparently normal nuclear mechanics but impaired expression of mechanosensitive genes in response to strain, suggesting that emerin mutations may act through altered transcriptional regulation and not by increasing nuclear fragility