New roles for Fc receptors in neurodegeneration-the impact on immunotherapy for Alzheimer's disease

There are an estimated 18 million Alzheimer's disease (AD) sufferers worldwide and with no disease modifying treatment currently available, development of new therapies represents an enormous unmet clinical need. AD is characterized by episodic memory loss followed by severe cognitive decline and is associated with many neuropathological changes. AD is characterized by deposits of amyloid beta (A?), neurofibrillary tangles, and neuroinflammation. Active immunization or passive immunization against A? leads to the clearance of deposits in transgenic mice expressing human A?. This clearance is associated with reversal of associated cognitive deficits, but these results have not translated to humans, with both active and passive immunotherapy failing to improve memory loss. One explanation for these observations is that certain anti-A? antibodies mediate damage to the cerebral vasculature limiting the top dose and potentially reducing efficacy. Fc gamma receptors (Fc?R) are a family of immunoglobulin-like receptors which bind to the Fc portion of IgG, and mediate the response of effector cells to immune complexes. Data from both mouse and human studies suggest that cross-linking Fc?R by therapeutic antibodies and the subsequent pro-inflammatory response mediates the vascular side effects seen following immunotherapy. Increasing evidence is emerging that Fc?R expression on CNS resident cells, including microglia and neurons, is increased during aging and functionally involved in the pathogenesis of age-related neurodegenerative diseases. Therefore, we propose that increased expression and ligation of Fc?R in the CNS, either by endogenous IgG or therapeutic antibodies, has the potential to induce vascular damage and exacerbate neurodegeneration. To produce safe and effective immunotherapies for AD and other neurodegenerative diseases it will be vital to understand the role of Fc?R in the healthy and diseased brain. Here we review the literature on Fc?R expression, function and proposed roles in multiple age-related neurological diseases. Lessons can be learnt from therapeutic antibodies used for the treatment of cancer where antibodies have been engineered for optimal efficacy

MSW-like Enhancements without Matter

We study the effects of a scalar field, coupled only to neutrinos, on oscillations among weak interaction current eigenstates. The effect of a real scalar field appears as effective masses for the neutrino mass eigenstates, the same for \nbar as for \n. Under some conditions, this can lead to a vanishing of $\delta m^2$, giving rise to MSW-like effects. We discuss some examples and show that it is possible to resolve the apparent discrepancy in spectra required by r-process nucleosynthesis in the mantles of supernovae and by Solar neutrino solutions.Comment: 9 pages, latex, 1 figur

Characterizing precursors to stellar clusters with Herschel

Context. Despite their profound effect on the universe, the formation of massive stars and stellar clusters remains elusive. Recent advances in observing facilities and computing power have brought us closer to understanding this formation process. In the past decade, compelling evidence has emerged that suggests infrared dark clouds (IRDCs) may be precursors to stellar clusters. However, the usual method for identifying IRDCs is biased by the requirement that they are seen in absorption against background mid-IR emission, whereas dust continuum observations allow cold, dense pre-stellar-clusters to be identified anywhere. Aims: We aim to understand what dust temperatures and column densities characterize and distinguish IRDCs, to explore the population of dust continuum sources that are not IRDCs, and to roughly characterize the level of star formation activity in these dust continuum sources. Methods: We use Hi-GAL 70 to 500 $m data to identify dust continuum sources in the ell = 30deg and ell = 59deg Hi-GAL science demonstration phase (SDP) fields, to characterize and subtract the Galactic cirrus emission, and perform pixel-by-pixel modified blackbody fits on cirrus-subtracted Hi-GAL sources. We utilize archival Spitzer data to indicate the level of star-forming activity in each pixel, from mid-IR-dark to mid-IR-bright. Results: We present temperature and column density maps in the Hi-GAL ell = 30deg and ell = 59deg SDP fields, as well as a robust algorithm for cirrus subtraction and source identification using Hi-GAL data. We report on the fraction of Hi-GAL source pixels which are mid-IR-dark, mid-IR-neutral, or mid-IR-bright in both fields. We find significant trends in column density and temperature between mid-IR-dark and mid-IR-bright pixels; mid-IR-dark pixels are about 10 K colder and have a factor of 2 higher column density on average than mid-IR-bright pixels. We find that Hi-GAL dust continuum sources span a range of evolutionary states from pre- to star-forming, and that warmer sources are associated with more star formation tracers. Additionally, there is a trend of increasing temperature with tracer type from mid-IR-dark at the coldest, to outflow/maser sources in the middle, and finally to 8 and 24$m bright sources at the warmest. Finally, we identify five candidate IRDC-like sources on the far-side of the Galaxy. These are cold (20 K), high column density (N(H$_2$) gt 10$^22$ cm$^-2$) clouds identified with Hi-GAL which, despite bright surrounding mid-IR emission, show little to no absorption at 8 $m. These are the first inner Galaxy far-side candidate IRDCs of which the authors are aware. Herschel in an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation by NASA.The FITS files discussed in the paper would be released publicly WITH the Hi-GAL data (on the Hi-GAL website) when the Hi-GAL data is released publicly.Peer reviewe

Knowledge politics and new converging technologies: a social epistemological perspective

The “new converging technologies” refers to the prospect of advancing the human condition by the integrated study and application of nanotechnology, biotechnology, information technology and the cognitive sciences - or “NBIC”. In recent years, it has loomed large, albeit with somewhat different emphases, in national science policy agendas throughout the world. This article considers the political and intellectual sources - both historical and contemporary - of the converging technologies agenda. Underlying it is a fluid conception of humanity that is captured by the ethically challenging notion of “enhancing evolution”

Exact Solutions for Matter-Enhanced Neutrino Oscillations

The analogy between supersymmetric quantum mechanics and matter-enhanced neutrino oscillations is exploited to obtain exact solutions for a class of electron density profiles. This integrability condition is analogous to the shape-invariance in supersymmetric quantum mechanics. This method seems to be the most direct way to obtain the exact survival probabilities for a number of density profiles of interest, such as linear and exponential density profiles. The resulting neutrino amplitudes can also be utilized as comparison amplitudes for the uniform semiclassical treatment of neutrino propagation in arbitrary electron density profiles.Comment: Submitted to Physical Review D. Latex file, 8 pages. This paper is also available at http://nucth.physics.wisc.edu/preprints