Models of verbal working memory capacity: What does it take to make them work?

Theories of working memory (WM) capacity limits will be more useful when we know what aspects of performance are governed by the limits and what aspects are governed by other memory mechanisms. Whereas considerable progress has been made on models of WM capacity limits for visual arrays of separate objects, less progress has been made in understanding verbal materials, especially when words are mentally combined to form multiword units or chunks. Toward a more comprehensive theory of capacity limits, we examined models of forced-choice recognition of words within printed lists, using materials designed to produce multiword chunks in memory (e.g., leather brief case). Several simple models were tested against data from a variety of list lengths and potential chunk sizes, with test conditions that only imperfectly elicited the interword associations. According to the most successful model, participants retained about 3 chunks on average in a capacity-limited region of WM, with some chunks being only subsets of the presented associative information (e.g., leather brief case retained with leather as one chunk and brief case as another). The addition to the model of an activated long-term memory component unlimited in capacity was needed. A fixed-capacity limit appears critical to account for immediate verbal recognition and other forms of WM. We advance a model-based approach that allows capacity to be assessed despite other important processing contributions. Starting with a psychological-process model of WM capacity developed to understand visual arrays, we arrive at a more unified and complete model

Non-Contact Measurement of Thermal Diffusivity in Ion-Implanted Nuclear Materials

Knowledge of mechanical and physical property evolution due to irradiation damage is essential for the development of future fission and fusion reactors. Ion-irradiation provides an excellent proxy for studying irradiation damage, allowing high damage doses without sample activation. Limited ion-penetration-depth means that only few-micron-thick damaged layers are produced. Substantial effort has been devoted to probing the mechanical properties of these thin implanted layers. Yet, whilst key to reactor design, their thermal transport properties remain largely unexplored due to a lack of suitable measurement techniques. Here we demonstrate non-contact thermal diffusivity measurements in ion-implanted tungsten for nuclear fusion armour. Alloying with transmutation elements and the interaction of retained gas with implantation-induced defects both lead to dramatic reductions in thermal diffusivity. These changes are well captured by our modelling approaches. Our observations have important implications for the design of future fusion power plants.Comment: 15 pages, 3 figure

Defining epitope coverage requirements for T cell-based HIV vaccines: Theoretical considerations and practical applications

<p>Abstract</p> <p>Background</p> <p>HIV vaccine development must address the genetic diversity and plasticity of the virus that permits the presentation of diverse genetic forms to the immune system and subsequent escape from immune pressure. Assessment of potential HIV strain coverage by candidate T cell-based vaccines (whether natural sequence or computationally optimized products) is now a critical component in interpreting candidate vaccine suitability.</p> <p>Methods</p> <p>We have utilized an N-mer identity algorithm to represent T cell epitopes and explore potential coverage of the global HIV pandemic using natural sequences derived from candidate HIV vaccines. Breadth (the number of T cell epitopes generated) and depth (the variant coverage within a T cell epitope) analyses have been incorporated into the model to explore vaccine coverage requirements in terms of the number of discrete T cell epitopes generated.</p> <p>Results</p> <p>We show that when multiple epitope generation by a vaccine product is considered a far more nuanced appraisal of the potential HIV strain coverage of the vaccine product emerges. By considering epitope breadth and depth several important observations were made: (1) epitope breadth requirements to reach particular levels of vaccine coverage, even for natural sequence-based vaccine products is not necessarily an intractable problem for the immune system; (2) increasing the valency (number of T cell epitope variants present) of vaccine products dramatically decreases the epitope requirements to reach particular coverage levels for any epidemic; (3) considering multiple-hit models (more than one exact epitope match with an incoming HIV strain) places a significantly higher requirement upon epitope breadth in order to reach a given level of coverage, to the point where low valency natural sequence based products would not practically be able to generate sufficient epitopes.</p> <p>Conclusions</p> <p>When HIV vaccine sequences are compared against datasets of potential incoming viruses important metrics such as the minimum epitope count required to reach a desired level of coverage can be easily calculated. We propose that such analyses can be applied early in the planning stages and during the execution phase of a vaccine trial to explore theoretical and empirical suitability of a vaccine product to a particular epidemic setting.</p

A Deeper Look at the New Milky Way Satellites: Sagittarius II, Reticulum II, Phoenix II, and Tucana III

We present deep Magellan/Megacam stellar photometry of four recently discovered faint Milky Way satellites: Sagittarius II (Sgr II), Reticulum II (Ret II), Phoenix II (Phe II), and Tucana III (Tuc III). Our photometry reaches ~2-3 magnitudes deeper than the discovery data, allowing us to revisit the properties of these new objects (e.g., distance, structural properties, luminosity measurements, and signs of tidal disturbance). The satellite color-magnitude diagrams show that they are all old (~13.5 Gyr) and metal-poor ([Fe/H]$\lesssim-2.2$). Sgr II is particularly interesting as it sits in an intermediate position between the loci of dwarf galaxies and globular clusters in the size-luminosity plane. The ensemble of its structural parameters is more consistent with a globular cluster classification, indicating that Sgr II is the most extended globular cluster in its luminosity range. The other three satellites land directly on the locus defined by Milky Way ultra-faint dwarf galaxies of similar luminosity. Ret II is the most elongated nearby dwarf galaxy currently known for its luminosity range. Our structural parameters for Phe II and Tuc III suggest that they are both dwarf galaxies. Tuc III is known to be associated with a stellar stream, which is clearly visible in our matched-filter stellar density map. The other satellites do not show any clear evidence of tidal stripping in the form of extensions or distortions. Finally, we also use archival HI data to place limits on the gas content of each object.Comment: Accepted for publication in ApJ. Minor updates to match accepted versio

Documenting Pressures Used for Manual Diagnosis and Treatment of Cervical Spine Somatic Dysfunction

Background: Palpatory assessment of free or restricted motion patterns is part of the diagnosis of spinal somatic dysfunction (SD). Diagnostically, local soft tissues are compressed (pre-loaded) over the structure of interest followed by one or more test impulses to assess the quality of the “end-feel” motion in several planes. These barrier sensations are often described qualitatively but have not been objectively quantified. Noninvasive, tactile pressure sensors built into a digital palpation monitoring system (IsoTOUCH®; Neuromuscular Engineering; Nashville TN, USA) were used to document loading and impulse pressures for palpatory segmental diagnosis and to first engage and then quickly move through a restrictive SD barrier using an osteopathic manipulative treatment (OMT) technique

Modified Annexin V/Propidium Iodide Apoptosis Assay For Accurate Assessment of Cell Death

Studies of cellular apoptosis have been significantly impacted since the introduction of flow cytometry-based methods. Propidium iodide (PI) is widely used in conjunction with Annexin V to determine if cells are viable, apoptotic, or necrotic through differences in plasma membrane integrity and permeability1,2. The Annexin V/ PI protocol is a commonly used approach for studying apoptotic cells3. PI is used more often than other nuclear stains because it is economical, stable and a good indicator of cell viability, based on its capacity to exclude dye in living cells 4,5. The ability of PI to enter a cell is dependent upon the permeability of the membrane; PI does not stain live or early apoptotic cells due to the presence of an intact plasma membrane 1,2,6. In late apoptotic and necrotic cells, the integrity of the plasma and nuclear membranes decreases7,8, allowing PI to pass through the membranes, intercalate into nucleic acids, and display red fluorescence 1,2,9. Unfortunately, we find that conventional Annexin V/ PI protocols lead to a significant number of false positive events (up to 40%), which are associated with PI staining of RNA within the cytoplasmic compartment10. Primary cells and cell lines in a broad range of animal models are affected, with large cells (nuclear: cytoplasmic ratios <0.5) showing the highest occurrence10. Herein, we demonstrate a modified Annexin V/ PI method that provides a significant improvement for assessment of cell death compared to conventional methods. This protocol takes advantage of changes in cellular permeability during cell fixing to promote entry of RNase A into cells following staining. Both the timing and concentration of RNase A have been optimized for removal of cytoplasmic RNA. The result is a significant improvement over conventional Annexin V/ PI protocols (< 5% events with cytoplasmic PI staining)

Multiple major increases and decreases in mitochondrial substitution rates in the plant family Geraniaceae

Background: Rates of synonymous nucleotide substitutions are, in general, exceptionally low in plant mitochondrial genomes, several times lower than in chloroplast genomes, 10-20 times lower than in plant nuclear genomes, and 50-100 times lower than in many animal mitochondrial genomes. Several cases of moderate variation in mitochondrial substitution rates have been reported in plants, but these mostly involve correlated changes in chloroplast and/or nuclear substitution rates and are therefore thought to reflect whole-organism forces rather than ones impinging directly on the mitochondrial mutation rate. Only a single case of extensive, mitochondrial-specific rate changes has been described, in the angiosperm genus Plantago. Results: We explored a second potential case of highly accelerated mitochondrial sequence evolution in plants. This case was first suggested by relatively poor hybridization of mitochondrial gene probes to DNA of Pelargonium hortorum (the common geranium). We found that all eight mitochondrial genes sequenced from P. hortorum are exceptionally divergent, whereas chloroplast and nuclear divergence is unexceptional in P. hortorum. Two mitochondrial genes were sequenced from a broad range of taxa of variable relatedness to P. hortorum, and absolute rates of mitochondrial synonymous substitutions were calculated on each branch of a phylogenetic tree of these taxa. We infer one major, similar to 10-fold increase in the mitochondrial synonymous substitution rate at the base of the Pelargonium family Geraniaceae, and a subsequent similar to 10-fold rate increase early in the evolution of Pelargonium. We also infer several moderate to major rate decreases following these initial rate increases, such that the mitochondrial substitution rate has returned to normally low levels in many members of the Geraniaceae. Finally, we find unusually little RNA editing of Geraniaceae mitochondrial genes, suggesting high levels of retroprocessing in their history. Conclusion: The existence of major, mitochondrial-specific changes in rates of synonymous substitutions in the Geraniaceae implies major and reversible underlying changes in the mitochondrial mutation rate in this family. Together with the recent report of a similar pattern of rate heterogeneity in Plantago, these findings indicate that the mitochondrial mutation rate is a more plastic character in plants than previously realized. Many molecular factors could be responsible for these dramatic changes in the mitochondrial mutation rate, including nuclear gene mutations affecting the fidelity and efficacy of mitochondrial DNA replication and/or repair and consistent with the lack of RNA editing - exceptionally high levels of mutagenic retroprocessing. That the mitochondrial mutation rate has returned to normally low levels in many Geraniaceae raises the possibility that, akin to the ephemerality of mutator strains in bacteria, selection favors a low mutation rate in plant mitochondria