Exploiting Locally Imposed Anisotropies in (Ga,Mn)As: a Non-volatile Memory Device

Progress in (Ga,Mn)As lithography has recently allowed us to realize structures where unique magnetic anisotropy properties can be imposed locally in various regions of a given device. We make use of this technology to fabricate a device in which we study transport through a constriction separating two regions whose magnetization direction differs by 90 degrees. We find that the resistance of the constriction depends on the flow of the magnetic field lines in the constriction region and demonstrate that such a structure constitutes a non-volatile memory device

Electrical detection of magnetic skyrmions by non-collinear magnetoresistance

Magnetic skyrmions are localised non-collinear spin textures with high potential for future spintronic applications. Skyrmion phases have been discovered in a number of materials and a focus of current research is the preparation, detection, and manipulation of individual skyrmions for an implementation in devices. Local experimental characterization of skyrmions has been performed by, e.g., Lorentz microscopy or atomic-scale tunnel magnetoresistance measurements using spin-polarised scanning tunneling microscopy. Here, we report on a drastic change of the differential tunnel conductance for magnetic skyrmions arising from their non-collinearity: mixing between the spin channels locally alters the electronic structure, making a skyrmion electronically distinct from its ferromagnetic environment. We propose this non-collinear magnetoresistance (NCMR) as a reliable all-electrical detection scheme for skyrmions with an easy implementation into device architectures

Population-Based Precision Cancer Screening: A Symposium on Evidence, Epidemiology, and Next Steps

Precision medicine, an emerging approach for disease treatment that takes into account individual variability in genes, environment, and lifestyle, is under consideration for preventive interventions, including cancer screening. On September 29, 2015, the National Cancer Institute sponsored a symposium entitled “Precision Cancer Screening in the General Population: Evidence, Epidemiology, and Next Steps”. The goal was two-fold: to share current information on the evidence, practices, and challenges surrounding precision screening for breast, cervical, colorectal, lung, and prostate cancers, and to allow for in-depth discussion among experts in relevant fields regarding how epidemiology and other population sciences can be used to generate evidence to inform precision screening strategies. Attendees concluded that the strength of evidence for efficacy and effectiveness of precision strategies varies by cancer site, that no one research strategy or methodology would be able or appropriate to address the many knowledge gaps in precision screening, and that issues surrounding implementation must be researched as well. Additional discussion needs to occur to identify the high priority research areas in precision cancer screening for pertinent organs and to gather the necessary evidence to determine whether further implementation of precision cancer screening strategies in the general population would be feasible and beneficial

Survivability Is More Fundamental Than Evolvability

For a lineage to survive over long time periods, it must sometimes change. This has given rise to the term evolvability, meaning the tendency to produce adaptive variation. One lineage may be superior to another in terms of its current standing variation, or it may tend to produce more adaptive variation. However, evolutionary outcomes depend on more than standing variation and produced adaptive variation: deleterious variation also matters. Evolvability, as most commonly interpreted, is not predictive of evolutionary outcomes. Here, we define a predictive measure of the evolutionary success of a lineage that we call the k-survivability, defined as the probability that the lineage avoids extinction for k generations. We estimate the k-survivability using multiple experimental replicates. Because we measure evolutionary outcomes, the initial standing variation, the full spectrum of generated variation, and the heritability of that variation are all incorporated. Survivability also accounts for the decreased joint likelihood of extinction of sub-lineages when they 1) disperse in space, or 2) diversify in lifestyle. We illustrate measurement of survivability with in silico models, and suggest that it may also be measured in vivo using multiple longitudinal replicates. The k-survivability is a metric that enables the quantitative study of, for example, the evolution of 1) mutation rates, 2) dispersal mechanisms, 3) the genotype-phenotype map, and 4) sexual reproduction, in temporally and spatially fluctuating environments. Although these disparate phenomena evolve by well-understood microevolutionary rules, they are also subject to the macroevolutionary constraint of long-term survivability

Quantitative cross-species extrapolation between humans and fish: The case of the anti-depressant fluoxetine

This article has been made available through the Brunel Open Access Publishing Fund.Fish are an important model for the pharmacological and toxicological characterization of human pharmaceuticals in drug discovery, drug safety assessment and environmental toxicology. However, do fish respond to pharmaceuticals as humans do? To address this question, we provide a novel quantitative cross-species extrapolation approach (qCSE) based on the hypothesis that similar plasma concentrations of pharmaceuticals cause comparable target-mediated effects in both humans and fish at similar level of biological organization (Read-Across Hypothesis). To validate this hypothesis, the behavioural effects of the anti-depressant drug fluoxetine on the fish model fathead minnow (Pimephales promelas) were used as test case. Fish were exposed for 28 days to a range of measured water concentrations of fluoxetine (0.1, 1.0, 8.0, 16, 32, 64 μg/L) to produce plasma concentrations below, equal and above the range of Human Therapeutic Plasma Concentrations (HTPCs). Fluoxetine and its metabolite, norfluoxetine, were quantified in the plasma of individual fish and linked to behavioural anxiety-related endpoints. The minimum drug plasma concentrations that elicited anxiolytic responses in fish were above the upper value of the HTPC range, whereas no effects were observed at plasma concentrations below the HTPCs. In vivo metabolism of fluoxetine in humans and fish was similar, and displayed bi-phasic concentration-dependent kinetics driven by the auto-inhibitory dynamics and saturation of the enzymes that convert fluoxetine into norfluoxetine. The sensitivity of fish to fluoxetine was not so dissimilar from that of patients affected by general anxiety disorders. These results represent the first direct evidence of measured internal dose response effect of a pharmaceutical in fish, hence validating the Read-Across hypothesis applied to fluoxetine. Overall, this study demonstrates that the qCSE approach, anchored to internal drug concentrations, is a powerful tool to guide the assessment of the sensitivity of fish to pharmaceuticals, and strengthens the translational power of the cross-species extrapolation

Low Mate Encounter Rate Increases Male Risk Taking in a Sexually Cannibalistic Praying Mantis

Male praying mantises are forced into the ultimate trade-off of mating versus complete loss of future reproduction if they fall prey to a female. The balance of this trade-off will depend both on (1) the level of predatory risk imposed by females and (2) the frequency of mating opportunities for males. We report the results of a set of experiments that examine the effects of these two variables on male risk-taking behavior and the frequency of sexual cannibalism in the praying mantis Tenodera sinensis. We experimentally altered the rate at which males encountered females and measured male approach and courtship behavior under conditions of high and low risk of being attacked by females. We show that male risk taking depends on prior access to females. Males with restricted access to females showed greater risk-taking behavior. When males were given daily female encounters, they responded to greater female-imposed risk by slowing their rate of approach and remained a greater distance from a potential mate. In contrast, males without recent access to mates were greater risk-takers; they approached females more rapidly and to closer proximity, regardless of risk. In a second experiment, we altered male encounter rate with females and measured rates of sexual cannibalism when paired with hungry or well-fed females. Greater risk-taking behavior by males with low mate encounter rates resulted in high rates of sexual cannibalism when these males were paired with hungry females

A novel IgE antibody targeting the prostate-specific antigen as a potential prostate cancer therapy

Prostate cancer (PCa) is the second leading cause of cancer deaths in men in the United States. The prostate-specific antigen (PSA), often found at high levels in the serum of PCa patients, has been used as a marker for PCa detection and as a target of immunotherapy. The murine IgG1 monoclonal antibody AR47.47, specific for human PSA, has been shown to enhance antigen presentation by human dendritic cells and induce both CD4 andCD8 T-cell activation when complexed with PSA. In this study, we explored the properties of a novel mouse/human chimeric anti-PSA IgE containing the variable regions of AR47.47 as a potential therapy for PCa. Our goal was to take advantage of the unique properties of IgE in order to trigger immune activation against PCa.Fil: Daniels-Wells, Tracy R. University of California. David Geffen School of Medicine. Department of Surgery. Division of Surgical Oncology; Estados Unidos de América;Fil: Helguera, Gustavo Fernando. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Departamento de Tecnologia Farmaceutica; Argentina; University of California. David Geffen School of Medicine. Department of Surgery. Division of Surgical Oncology; Estados Unidos de América;Fil: Leuchter, Richard K. University of California. David Geffen School of Medicine. Department of Surgery. Division of Surgical Oncology; Estados Unidos de América;Fil: Quintero, Rafael. University of California. David Geffen School of Medicine. Department of Surgery. Division of Surgical Oncology; Estados Unidos de América;Fil: Kozman, Maggie. University of California. David Geffen School of Medicine. Department of Surgery. Division of Surgical Oncology; Estados Unidos de América;Fil: Rodríguez, José A.. University of California. David Geffen School of Medicine. Department of Surgery. Division of Surgical Oncology; Estados Unidos de América; University of California. The Molecular Biology Institute; Estados Unidos de América;Fil: Ortiz-Sánchez, E. University of California. David Geffen School of Medicine. Department of Surgery. Division of Surgical Oncology; Estados Unidos de América; Biomedical Research in Cancer. Basic Research Division. National Institute of Cancerology; Mexico.;Fil: Martínez-Maza, Otonel. University of California. David Geffen School of Medicine. Department of Surgery. Division of Surgical Oncology; Estados Unidos de América;Fil: Schultes, Brigit C.. Advanced Immune Therapeutics; Estados Unidos de América;Fil: Nicodemus Christopher. Advanced Immune Therapeutics; Estados Unidos de América;Fil: Penichet, Manuel. University of California. David Geffen School of Medicine. Department of Surgery. Division of Surgical Oncology; Estados Unidos de América; University of California. The Molecular Biology Institute; Estados Unidos de América

XMeis3 Is Necessary for Mesodermal Hox Gene Expression and Function

Hox transcription factors provide positional information during patterning of the anteroposterior axis. Hox transcription factors can co-operatively bind with PBC-class co-factors, enhancing specificity and affinity for their appropriate binding sites. The nuclear localisation of these co-factors is regulated by the Meis-class of homeodomain proteins. During development of the zebrafish hindbrain, Meis3 has previously been shown to synergise with Hoxb1 in the autoregulation of Hoxb1. In Xenopus XMeis3 posteriorises the embryo upon ectopic expression. Recently, an early temporally collinear expression sequence of Hox genes was detected in Xenopus gastrula mesoderm (see intro. P3). There is evidence that this sequence sets up the embryo's later axial Hox expression pattern by time-space translation. We investigated whether XMeis3 is involved in regulation of this early mesodermal Hox gene expression. Here, we present evidence that XMeis3 is necessary for expression of Hoxd1, Hoxb4 and Hoxc6 in mesoderm during gastrulation. In addition, we show that XMeis3 function is necessary for the progression of gastrulation. Finally, we present evidence for synergy between XMeis3 and Hoxd1 in Hoxd1 autoregulation in mesoderm during gastrulation

Tumor classification: molecular analysis meets Aristotle

BACKGROUND: Traditionally, tumors have been classified by their morphologic appearances. Unfortunately, tumors with similar histologic features often follow different clinical courses or respond differently to chemotherapy. Limitations in the clinical utility of morphology-based tumor classifications have prompted a search for a new tumor classification based on molecular analysis. Gene expression array data and proteomic data from tumor samples will provide complex data that is unobtainable from morphologic examination alone. The growing question facing cancer researchers is, "How can we successfully integrate the molecular, morphologic and clinical characteristics of human cancer to produce a helpful tumor classification?" DISCUSSION: Current efforts to classify cancers based on molecular features ignore lessons learned from millennia of experience in biological classification. A tumor classification must include every type of tumor and must provide a unique place for each tumor within the classification. Groups within a classification inherit the properties of their ancestors and impart properties to their descendants. A classification was prepared grouping tumors according to their histogenetic development. The classification is simple (reducing the complexity of information received from the molecular analysis of tumors), comprehensive (providing a place for every tumor of man), and consistent with recent attempts to characterize tumors by cytogenetic and molecular features. The clinical and research value of this historical approach to tumor classification is discussed. SUMMARY: This manuscript reviews tumor classification and provides a new and comprehensive classification for neoplasia that preserves traditional nomenclature while incorporating information derived from the molecular analysis of tumors. The classification is provided as an open access XML document that can be used by cancer researchers to relate tumor classes with heterogeneous experimental and clinical tumor databases

Visual Recognition of Age Class and Preference for Infantile Features: Implications for Species-Specific vs Universal Cognitive Traits in Primates

Despite not knowing the exact age of individuals, humans can estimate their rough age using age-related physical features. Nonhuman primates show some age-related physical features; however, the cognitive traits underlying their recognition of age class have not been revealed. Here, we tested the ability of two species of Old World monkey, Japanese macaques (JM) and Campbell's monkeys (CM), to spontaneously discriminate age classes using visual paired comparison (VPC) tasks based on the two distinct categories of infant and adult images. First, VPCs were conducted in JM subjects using conspecific JM stimuli. When analyzing the side of the first look, JM subjects significantly looked more often at novel images. Based on analyses of total looking durations, JM subjects looked at a novel infant image longer than they looked at a familiar adult image, suggesting the ability to spontaneously discriminate between the two age classes and a preference for infant over adult images. Next, VPCs were tested in CM subjects using heterospecific JM stimuli. CM subjects showed no difference in the side of their first look, but looked at infant JM images longer than they looked at adult images; the fact that CMs were totally naïve to JMs suggested that the attractiveness of infant images transcends species differences. This is the first report of visual age class recognition and a preference for infant over adult images in nonhuman primates. Our results suggest not only species-specific processing for age class recognition but also the evolutionary origins of the instinctive human perception of baby cuteness schema, proposed by the ethologist Konrad Lorenz