A trapper keeper for TRAPP, its structures and functions

During biosynthesis many membrane and secreted proteins are transported from the endoplasmic reticulum, through the Golgi and on to the plasma membrane in small transport vesicles. These transport vesicles have to undergo budding, movement, tethering, docking, and fusion at each organelle of the biosynthetic pathway. The transport protein particle (TRAPP) complex was initially identified as the tethering factor for endoplasmic reticulum (ER)—derived COPII vesicles, but the functions of TRAPP may extend to other areas of biology. Three forms of TRAPP complexes have been discovered to date, and recent advances in research have provided new insights on the structures and functions of TRAPP. Here we provide a comprehensive review of the recent findings in TRAPP biology.     

Fresnel's laws,ceteris paribus

This article is about structural realism, historical continuity, laws of nature, and ceteris paribus clauses. Fresnel's Laws of optics support Structural Realism because they are a scientific structure that has survived theory change. However, the history of Fresnel's Laws which has been depicted in debates over realism since the 1980s is badly distorted. Specifically, claims that J. C. Maxwell or his followers believed in an ontologically-subsistent electromagnetic field, and gave up the aether, before Einstein's annus mirabilis in 1905 are indefensible. Related claims that Maxwell himself did not believe in a luminiferous aether are also indefensible. This paper corrects the record. In order to trace Fresnel's Laws across significant ontological changes, they must be followed past Einstein into modern physics and nonlinear optics. I develop the philosophical implications of a more accurate history, and analyze Fresnel's Laws' historical trajectory in terms of dynamic ceteris paribus clauses. Structuralists have not embraced ceteris paribus laws, but they continue to point to Fresnel's Laws to resist anti-realist arguments from theory change. Fresnel's Laws fit the standard definition of a ceteris paribus law as a law applicable only in particular circumstances. Realists who appeal to the historical continuity of Fresnel's Laws to combat anti-realists must incorporate ceteris paribus laws into their metaphysics.     

Leibniz's Observations on Hydrology: An Unpublished Letter on the Great Lombardy Flood of 1705

Although the historical reputation of Gottfried Wilhelm Leibniz (1646–1716) largely rests on his philosophical and mathematical work, it is widely known that he made important contributions to many of the emerging but still inchoate branches of natural science of his day. Among the many scientific papers Leibniz published during his lifetime are ones on the nascent science we now know as hydrology. While Leibniz's other scientific work has become of increasing interest to scholars in recent years, his thinking about hydrology has been neglected, despite being relatively broad in extent, including as it does papers on the ‘raising of vapours’ and the formation of ice, as well as the separation of salt and fresh water. That list can now be extended still further following the discovery of a previously unpublished letter of Leibniz's on the causes of the devastating Lombardy flood of October and November 1705. This letter, which will be the focus of our paper, reveals the depth of Leibniz's understanding of key hydrological processes. In it, he considers various mechanisms for the flood, such as heavy rains on high ground, underwater earthquakes, and a mountain collapse. Over the course of the paper we examine each of these mechanisms in depth, and show that Leibniz was in the vanguard of hydrological thinking. We also show that the letter contains one of the first scholarly attempts to apply aspects of the still-forming notion of the hydrological cycle to account for a flood event.     

Clonal selection drives genetic divergence of metastatic medulloblastoma

Medulloblastoma, the most common malignant paediatric brain tumour, arises in the cerebellum and disseminates through the cerebrospinal fluid in the leptomeningeal space to coat the brain and spinal cord. Dissemination, a marker of poor prognosis, is found in up to 40% of children at diagnosis and in most children at the time of recurrence. Affected children therefore are treated with radiation to the entire developing brain and spinal cord, followed by high-dose chemotherapy, with the ensuing deleterious effects on the developing nervous system. The mechanisms of dissemination through the cerebrospinal fluid are poorly studied, and medulloblastoma metastases have been assumed to be biologically similar to the primary tumour. Here we show that in both mouse and human medulloblastoma, the metastases from an individual are extremely similar to each other but are divergent from the matched primary tumour. Clonal genetic events in the metastases can be demonstrated in a restricted subclone of the primary tumour, suggesting that only rare cells within the primary tumour have the ability to metastasize. Failure to account for the bicompartmental nature of metastatic medulloblastoma could be a major barrier to the development of effective targeted therapies.     

A beautiful sea: P. A. M. Dirac's epistemology and ontology of the vacuum

This paper charts P.A.M. Dirac's development of his theory of the electron, and its radical picture of empty space as an almost-full plenum. Dirac's Quantum Electrodynamics famously accomplished more than the unification of special relativity and quantum mechanics. It also accounted for the ‘duplexity phenomena’ of spectral line splitting that we now attribute to electron spin. But the extra mathematical terms that allowed for spin were not alone, and this paper charts Dirac's struggle to ignore or account for them as a sea of strange, negative-energy, particles with positive ‘holes’. This work was not done in solitude, but rather in exchanges with Dirac's correspondence network. This social context for Dirac’s work contests his image as a lone genius, and documents a community wrestling with the ontological consequences of their work. Unification, consistency, causality, and community are common factors in explanations in the history of physics. This paper argues on the basis of materials in Dirac's archive that --- in addition --- mathematical beauty was an epistemological factor in the development of the electron and hole theory. In fact, if we believe that Dirac's beautiful mathematics captures something of the world, then there is both an epistemology and an ontology of mathematical beauty.     

Dystrophin expression in the mdx mouse restored by stem cell transplantation.

The development of cell or gene therapies for diseases involving cells that are widely distributed throughout the body has been severely hampered by the inability to achieve the disseminated delivery of cells or genes to the affected tissues or organ. Here we report the results of bone marrow transplantation studies in the mdx mouse, an animal model of Duchenne's muscular dystrophy, which indicate that the intravenous injection of either normal haematopoietic stem cells or a novel population of muscle-derived stem cells into irradiated animals results in the reconstitution of the haematopoietic compartment of the transplanted recipients, the incorporation of donor-derived nuclei into muscle, and the partial restoration of dystrophin expression in the affected muscle. These results suggest that the transplantation of different stem cell populations, using the procedures of bone marrow transplantation, might provide an unanticipated avenue for treating muscular dystrophy as well as other diseases where the systemic delivery of therapeutic cells to sites throughout the body is critical. Our studies also suggest that the inherent developmental potential of stem cells isolated from diverse tissues or organs may be more similar than previously anticipated.     

Designing a Management System for a Rural Community Development Organization Using a Systemic Action Research Process

This paper describes the first phase, 'finding out', of a systemic participatory action research intervention in the management systems of a rural community development organization in the KwaZulu-Natal province of South Africa. The aims of the intervention were to (a) improve the management system of this organization, and (b) evaluate the usefulness of particular systems methodologies for the improvement of management systems of organizations involved in community development in under-resourced rural contexts. The second phase, "implementation," needs to be completed and thoroughly evaluated before any final conclusions can be drawn about the suitability of the chosen systems framework for Third World type rural contexts. However, the second phase is, at the time of writing, underway and all indications are that an interpretive ('Soft') Systems Methodology, combined with insights from a more functionalist ('hard') approach (with methods chosen through a Critical Systems Thinking framework) holds much promise for participatory systemic interventions in these contexts.     

High energy femtosecond mid-infrared generation pumped by a two-color Ti:sapphire multipass amplifier

Intense mid-infrared was generated by direct frequency mixing two pulses from a dual-wavelength Ti：sapphire system. From a multipass amplifier we generated two tunable wavelength femtosecond pulses with a total energy of 15 mJ. Pulse energy of 1.6 μJ and 7.4 μJ of mid-infrared light is achieved with and without its multipass amplifier at 9-11μm, with pulse duration of 500 fs.