Grains and grain boundaries in single-layer graphene atomic patchwork quilts

The properties of polycrystalline materials are often dominated by the size of their grains and by the atomic structure of their grain boundaries. These effects should be especially pronounced in two-dimensional materials, where even a line defect can divide and disrupt a crystal. These issues take on practical significance in graphene, which is a hexagonal, two-dimensional crystal of carbon atoms. Single-atom-thick graphene sheets can now be produced by chemical vapour deposition on scales of up to metres, making their polycrystallinity almost unavoidable. Theoretically, graphene grain boundaries are predicted to have distinct electronic, magnetic, chemical and mechanical properties that strongly depend on their atomic arrangement. Yet because of the five-order-of-magnitude size difference between grains and the atoms at grain boundaries, few experiments have fully explored the graphene grain structure. Here we use a combination of old and new transmission electron microscopy techniques to bridge these length scales. Using atomic-resolution imaging, we determine the location and identity of every atom at a grain boundary and find that different grains stitch together predominantly through pentagon-heptagon pairs. Rather than individually imaging the several billion atoms in each grain, we use diffraction-filtered imaging to rapidly map the location, orientation and shape of several hundred grains and boundaries, where only a handful have been previously reported. The resulting images reveal an unexpectedly small and intricate patchwork of grains connected by tilt boundaries. By correlating grain imaging with scanning probe and transport measurements, we show that these grain boundaries severely weaken the mechanical strength of graphene membranes but do not as drastically alter their electrical properties. These techniques open a new window for studies on the structure, properties and control of grains and grain boundaries in graphene and other two-dimensional materials.     

Interferon-γ links ultraviolet radiation to melanomagenesis in mice

Cutaneous malignant melanoma is a highly aggressive and frequently chemoresistant cancer, the incidence of which continues to rise. Epidemiological studies show that the major aetiological melanoma risk factor is ultraviolet (UV) solar radiation, with the highest risk associated with intermittent burning doses, especially during childhood. We have experimentally validated these epidemiological findings using the hepatocyte growth factor/scatter factor transgenic mouse model, which develops lesions in stages highly reminiscent of human melanoma with respect to biological, genetic and aetiological criteria, but only when irradiated as neonatal pups with UVB, not UVA. However, the mechanisms underlying UVB-initiated, neonatal-specific melanomagenesis remain largely unknown. Here we introduce a mouse model permitting fluorescence-aided melanocyte imaging and isolation following in vivo UV irradiation. We use expression profiling to show that activated neonatal skin melanocytes isolated following a melanomagenic UVB dose bear a distinct, persistent interferon response signature, including genes associated with immunoevasion. UVB-induced melanocyte activation, characterized by aberrant growth and migration, was abolished by antibody-mediated systemic blockade of interferon-γ (IFN-γ), but not type-I interferons. IFN-γ was produced by macrophages recruited to neonatal skin by UVB-induced ligands to the chemokine receptor Ccr2. Admixed recruited skin macrophages enhanced transplanted melanoma growth by inhibiting apoptosis; notably, IFN-γ blockade abolished macrophage-enhanced melanoma growth and survival. IFN-γ-producing macrophages were also identified in 70% of human melanomas examined. Our data reveal an unanticipated role for IFN-γ in promoting melanocytic cell survival/immunoevasion, identifying a novel candidate therapeutic target for a subset of melanoma patients.     

Experimental infection of bats with Geomyces destructans causes white-nose syndrome

White-nose syndrome (WNS) has caused recent catastrophic declines among multiple species of bats in eastern North America. The disease's name derives from a visually apparent white growth of the newly discovered fungus Geomyces destructans on the skin (including the muzzle) of hibernating bats. Colonization of skin by this fungus is associated with characteristic cutaneous lesions that are the only consistent pathological finding related to WNS. However, the role of G. destructans in WNS remains controversial because evidence to implicate the fungus as the primary cause of this disease is lacking. The debate is fuelled, in part, by the assumption that fungal infections in mammals are most commonly associated with immune system dysfunction. Additionally, the recent discovery that G. destructans commonly colonizes the skin of bats of Europe, where no unusual bat mortality events have been reported, has generated further speculation that the fungus is an opportunistic pathogen and that other unidentified factors are the primary cause of WNS. Here we demonstrate that exposure of healthy little brown bats (Myotis lucifugus) to pure cultures of G. destructans causes WNS. Live G. destructans was subsequently cultured from diseased bats, successfully fulfilling established criteria for the determination of G. destructans as a primary pathogen. We also confirmed that WNS can be transmitted from infected bats to healthy bats through direct contact. Our results provide the first direct evidence that G. destructans is the causal agent of WNS and that the recent emergence of WNS in North America may represent translocation of the fungus to a region with a naive population of animals. Demonstration of causality is an instrumental step in elucidating the pathogenesis and epidemiology of WNS and in guiding management actions to preserve bat populations against the novel threat posed by this devastating infectious disease.     

The evolutionary context of the first hominins

The relationships among the living apes and modern humans have effectively been resolved, but it is much more difficult to locate fossil apes on the tree of life because shared skeletal morphology does not always mean shared recent evolutionary history. Sorting fossil taxa into those that belong on the branch of the tree of life that leads to modern humans from those that belong on other closely related branches is a considerable challenge.     

Ordinary language philosophy,explanation, and the historical turn in philosophy of science

Taking a cue from remarks Thomas Kuhn makes in 1990 about the historical turn in philosophy of science, I examine the history of history and philosophy of science within parts of the British philosophical context in the 1950s and early 1960s. During this time, ordinary language philosophy's influence was at its peak. I argue that the ordinary language philosophers' methodological recommendation to analyze actual linguistic practice influences several prominent criticisms of the deductive-nomological model of scientific explanation and that these criticisms relate to the historical turn in philosophy of science. To show these connections, I primarily examine the work of Stephen Toulmin, who taught at Oxford from 1949 to 1954, and Michael Scriven, who completed a dissertation on explanation under Gilbert Ryle and R.B. Braithwaite in 1956. I also consider Mary Hesse's appeal to an ordinary language-influenced account of meaning in her account of the role of models and analogies in scientific reasoning, and W.H. Watson's Wittgensteinian philosophy of science, an early influence on Toulmin. I think there are two upshots to my historical sketch. First, it fills out details of the move away from logical positivism to more historical- and practice-focused philosophies of science. Second, questions about linguistic meaning and the proper targets and aims of philosophical analysis are part and parcel of the historical turn, as well as its reception. Looking at the philosophical background during which so-called linguistic philosophers also had a hand in bringing these questions to prominence helps us understand why.     

Norton's material theory of analogy

In his book, The Material Theory of Induction, Norton argues that the quest for a universal formal theory or ‘schema’ for analogical inference should be abandoned. In its place, he offers the “material theory of analogy”: each analogical inference is “powered” by a local fact of analogy rather than by any formal schema. His minimalist model promises a straightforward, fact-based approach to the evaluation and justification of analogical inferences. This paper argues that although the rejection of universal schemas is justified, Norton's positive theory is limited in scope: it works well only for a restricted class of analogical inferences. Both facts and quasi-formal criteria have roles to play in a theory of analogical reasoning.