Experimental cerebral malaria progresses independently of the Nlrp3 inflammasome

Cerebral malaria is the most severe complication of Plasmodium falciparum infection in humans and the pathogenesis is still unclear. Using the P. berghei ANKA infection model of mice, we investigated a potential involvement of Nlrp3 and the inflammasome in the pathogenesis of cerebral malaria. Nlrp3 mRNA expression was upregulated in brain endothelial cells after exposure to P. berghei ANKA. Although Β-hematin, a synthetic compound of the parasites heme polymer hemozoin, induced the release of IL-1Β in macrophages through Nlrp3, we did not obtain evidence for a role of IL-1Β in vivo . Nlrp3 knock-out mice displayed a delayed onset of cerebral malaria; however, mice deficient in caspase-1, the adaptor protein ASC or the IL-1 receptor succumbed as WT mice. These results indicate that the role of Nlrp3 in experimental cerebral malaria is independent of the inflammasome and the IL-1 receptor pathway.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69193/1/764_ftp.pd

Avalanche amplification of a single exciton in a semiconductor nanowire

Interfacing single photons and electrons is a crucial ingredient for sharing quantum information between remote solid-state qubits. Semiconductor nanowires offer the unique possibility to combine optical quantum dots with avalanche photodiodes, thus enabling the conversion of an incoming single photon into a macroscopic current for efficient electrical detection. Currently, millions of excitation events are required to perform electrical read-out of an exciton qubit state. Here we demonstrate multiplication of carriers from only a single exciton generated in a quantum dot after tunneling into a nanowire avalanche photodiode. Due to the large amplification of both electrons and holes (> 10^4), we reduce by four orders of magnitude the number of excitation events required to electrically detect a single exciton generated in a quantum dot. This work represents a significant step towards single-shot electrical read-out and offers a new functionality for on-chip quantum information circuits

CHANDRA/VLA Follow-up of TeV J2032+4131, the Only Unidentified TeV Gamma-ray Source

The HEGRA Cherenkov telescope array group recently reported a steady and extended unidentified TeV gamma-ray source lying at the outskirts of Cygnus OB2. This is the most massive stellar association known in the Galaxy, estimated to contain ~2600 OB type members alone. It has been previously argued that the large scale shocks and turbulence induced by the multiple interacting supersonic winds from the many young stars in such associations may play a role in accelerating Galactic cosmic rays. Indeed, Cyg OB2 also coincides with the non-variable MeV-GeV range unidentified EGRET source, 3EG 2033+4118. We report on the near-simultaneous follow-up observations of the extended TeV source region with the CHANDRA X-ray Observatory and the Very Large Array (VLA) radio telescope obtained in order to explore this possibility. Analysis of the CO, HI, and IRAS 100 micron emissions shows that the TeV source region coincides with an outlying sub-group of powerful OB stars which have evacuated or destroyed much of the ambient atomic, molecular and dust material, and which may be related to the very high-energy emissions. An interesting SNR-like structure is also revealed near the TeV source region in the CO, HI and radio emission maps. Applying a numerical simulation which accurately tracks the radio to gamma-ray emission from primary hadrons as well as primary and secondary e+/-, we find that the broadband spectrum of the TeV source region favors a predominantly nucleonic - rather than electronic - origin of the high-energy flux, though deeper X-ray and radio observations are needed to confirm this. A very reasonable, ~0.1%, conversion efficiency of Cyg OB2's extreme stellar wind mechanical luminosity to nucleonic acceleration to ~PeV (10^15 eV) energies is sufficient to explain the multifrequency emissions.Comment: ApJ accepte

Outlets of 2D invasion percolation and multiple-armed incipient infinite clusters

We study invasion percolation in two dimensions, focusing on properties of the outlets of the invasion and their relation to critical percolation and to incipient infinite clusters (IIC's). First we compute the exact decay rate of the distribution of both the weight of the kth outlet and the volume of the kth pond. Next we prove bounds for all moments of the distribution of the number of outlets in an annulus. This result leads to almost sure bounds for the number of outlets in a box B(2^n) and for the decay rate of the weight of the kth outlet to p_c. We then prove existence of multiple-armed IIC measures for any number of arms and for any color sequence which is alternating or monochromatic. We use these measures to study the invaded region near outlets and near edges in the invasion backbone far from the origin.Comment: 38 pages, 10 figures, added a thorough sketch of the proof of existence of IIC's with alternating or monochromatic arms (with some generalizations

Is amino acid racemization a useful tool for screening for ancient DNA in bone?

Many rare and valuable ancient specimens now carry the scars of ancient DNA research, as questions of population genetics and phylogeography require larger sample sets. This fuels the demand for reliable techniques to screen for DNA preservation prior to destructive sampling. Only one such technique has been widely adopted: the extent of aspartic acid racemization (AAR). The kinetics of AAR are believed to be similar to the rate of DNA depurination and therefore a good measure of the likelihood of DNA survival. Moreover, AAR analysis is only minimally destructive. We report the first comprehensive test of AAR using 91 bone and teeth samples from temperate and high-latitude sites that were analysed for DNA. While the AAR range of all specimens was low (0.02 -0.17), no correlation was found between the extent of AAR and DNA amplification success. Additional heating experiments and surveys of the literature indicated that D/L Asx is low in bones until almost all the collagen is lost. This is because aspartic acid is retained in the bone within the constrained environment of the collagen triple helix, where it cannot racemize for steric reasons. Only if the helix denatures to soluble gelatin can Asx racemize readily, but this soluble gelatine is readily lost in most burial environments. We conclude that Asx D/L is not a useful screening technique for ancient DNA from bone

IntCal04 terrestrial radiocarbon age calibration, 0-26 cal kyr BP

Author Posting. © Arizona Board of Regents on behalf of the University of Arizona, 2004. This article is posted here by permission of Dept. of Geosciences, University of Arizona for personal use, not for redistribution. The definitive version was published in Radiocarbon 46 (2004): 1029-1058.A new calibration curve for the conversion of radiocarbon ages to calibrated (cal) ages has been constructed and internationally ratified to replace IntCal98, which extended from 0–24 cal kyr BP (Before Present, 0 cal BP = AD 1950). The new calibration data set for terrestrial samples extends from 0–26 cal kyr BP, but with much higher resolution beyond 11.4 cal kyr BP than IntCal98. Dendrochronologically-dated tree-ring samples cover the period from 0–12.4 cal kyr BP. Beyond the end of the tree rings, data from marine records (corals and foraminifera) are converted to the atmospheric equivalent with a site-specific marine reservoir correction to provide terrestrial calibration from 12.4–26.0 cal kyr BP. A substantial enhancement relative to IntCal98 is the introduction of a coherent statistical approach based on a random walk model, which takes into account the uncertainty in both the calendar age and the 14C age to calculate the underlying calibration curve (Buck and Blackwell, this issue). The tree-ring data sets, sources of uncertainty, and regional offsets are discussed here. The marine data sets and calibration curve for marine samples from the surface mixed layer (Marine04) are discussed in brief, but details are presented in Hughen et al. (this issue a). We do not make a recommendation for calibration beyond 26 cal kyr BP at this time; however, potential calibration data sets are compared in another paper (van der Plicht et al., this issue)

Fermi Large Area Telescope Constraints on the Gamma-ray Opacity of the Universe

The Extragalactic Background Light (EBL) includes photons with wavelengths from ultraviolet to infrared, which are effective at attenuating gamma rays with energy above ~10 GeV during propagation from sources at cosmological distances. This results in a redshift- and energy-dependent attenuation of the gamma-ray flux of extragalactic sources such as blazars and Gamma-Ray Bursts (GRBs). The Large Area Telescope onboard Fermi detects a sample of gamma-ray blazars with redshift up to z~3, and GRBs with redshift up to z~4.3. Using photons above 10 GeV collected by Fermi over more than one year of observations for these sources, we investigate the effect of gamma-ray flux attenuation by the EBL. We place upper limits on the gamma-ray opacity of the Universe at various energies and redshifts, and compare this with predictions from well-known EBL models. We find that an EBL intensity in the optical-ultraviolet wavelengths as great as predicted by the "baseline" model of Stecker et al. (2006) can be ruled out with high confidence.Comment: 42 pages, 12 figures, accepted version (24 Aug.2010) for publication in ApJ; Contact authors: A. Bouvier, A. Chen, S. Raino, S. Razzaque, A. Reimer, L.C. Reye

Coordinating Tissue Regeneration Through Transforming Growth Factorâ β Activated Kinase 1 Inactivation and Reactivation

Aberrant wound healing presents as inappropriate or insufficient tissue formation. Using a model of musculoskeletal injury, we demonstrate that loss of transforming growth factorâ β activated kinase 1 (TAK1) signaling reduces inappropriate tissue formation (heterotopic ossification) through reduced cellular differentiation. Upon identifying increased proliferation with loss of TAK1 signaling, we considered a regenerative approach to address insufficient tissue production through coordinated inactivation of TAK1 to promote cellular proliferation, followed by reactivation to elicit differentiation and extracellular matrix production. Although the current regenerative medicine paradigm is centered on the effects of drug treatment (â drug onâ ), the impact of drug withdrawal (â drug offâ ) implicit in these regimens is unknown. Because current TAK1 inhibitors are unable to phenocopy genetic Tak1 loss, we introduce the dualâ inducible COmbinational Sequential Inversion ENgineering (COSIEN) mouse model. The COSIEN mouse model, which allows us to study the response to targeted drug treatment (â drug onâ ) and subsequent withdrawal (â drug offâ ) through genetic modification, was used here to inactivate and reactivate Tak1 with the purpose of augmenting tissue regeneration in a calvarial defect model. Our study reveals the importance of both the â drug onâ (Creâ mediated inactivation) and â drug offâ (Flpâ mediated reactivation) states during regenerative therapy using a mouse model with broad utility to study targeted therapies for disease. Stem Cells 2019;37:766â 778Manipulating transforming growth factor βâ activated kinase 1 for cell and scaffold free tissue regeneration using a dualâ inducible Combinational Sequential Inversion Engineering mouse model.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149573/1/stem2991_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149573/2/stem2991.pd

Quantitative separation of the anisotropic magnetothermopower and planar Nernst effect by the rotation of an in-plane thermal gradient

Reimer O, Meier D, Bovender M, et al. Quantitative separation of the anisotropic magnetothermopower and planar Nernst effect by the rotation of an in-plane thermal gradient. Scientific Reports. 2017;7(1): 40586.A thermal gradient as the driving force for spin currents plays a key role in spin caloritronics. In this field the spin Seebeck effect (SSE) is of major interest and was investigated in terms of in-plane thermal gradients inducing perpendicular spin currents (transverse SSE) and out-of-plane thermal gradients generating parallel spin currents (longitudinal SSE). Up to now all spincaloric experiments employ a spatially fixed thermal gradient. Thus, anisotropic measurements with respect to well defined crystallographic directions were not possible. Here we introduce a new experiment that allows not only the in-plane rotation of the external magnetic field, but also the rotation of an in-plane thermal gradient controlled by optical temperature detection. As a consequence, the anisotropic magnetothermopower and the planar Nernst effect in a permalloy thin film can be measured simultaneously. Thus, the angular dependence of the magnetothermopower with respect to the magnetization direction reveals a phase shift, that allows the quantitative separation of the thermopower, the anisotropic magnetothermopower and the planar Nernst effect