Is Radiation of Quantized Black Holes Observable?

If primordial black holes (PBH) saturate the present upper limit on the dark matter density in our Solar system and if their radiation spectrum is discrete, the sensitivity of modern detectors is close to that necessary for detecting this radiation. This conclusion is not in conflict with the upper limits on the PBH evaporation rate.Comment: 6 pages, 1 figure (reproduced properly in pdf file

Multi-fluid simulations of chromospheric magnetic reconnection in a weakly ionized reacting plasma

We present results from the first self-consistent multi-fluid simulations of chromospheric magnetic reconnection in a weakly ionized reacting plasma. We simulate two dimensional magnetic reconnection in a Harris current sheet with a numerical model which includes ion-neutral scattering collisions, ionization, recombination, optically thin radiative loss, collisional heating, and thermal conduction. In the resulting tearing mode reconnection the neutral and ion fluids become decoupled upstream from the reconnection site, creating an excess of ions in the reconnection region and therefore an ionization imbalance. Ion recombination in the reconnection region, combined with Alfv\'{e}nic outflows, quickly removes ions from the reconnection site, leading to a fast reconnection rate independent of Lundquist number. In addition to allowing fast reconnection, we find that these non-equilibria partial ionization effects lead to the onset of the nonlinear secondary tearing instability at lower values of the Lundquist number than has been found in fully ionized plasmas.These simulations provide evidence that magnetic reconnection in the chromosphere could be responsible for jet-like transient phenomena such as spicules and chromospheric jets.Comment: 8 Figures, 32 pages tota

Patchy Reconnection in a Y-Type Current Sheet

We study the evolution of the magnetic field in a Y-type current sheet subject to a brief, localized magnetic reconnection event. The reconnection produces up- and down-flowing reconnected flux tubes which rapidly decelerate when they hit the Y-lines and underlying magnetic arcade loops at the ends of the current sheet. This localized reconnection outflow followed by a rapid deceleration reproduces the observed behavior of post-CME downflowing coronal voids. These simulations support the hypothesis that these observed coronal downflows are the retraction of magnetic fields reconnected in localized patches in the high corona.Comment: 4 pages, 3 figure

Low Secondary Risks for Captive Coyotes from a Sodium Nitrite Toxic Bait for Invasive Wild Pigs

An acute toxic bait is being developed to deliver micro‐encapsulated sodium nitrite (SN) to stimulate severe methemoglobinemia and humane death for invasive wild pigs (Sus scrofa), thereby providing a new tool for reducing their populations. During April 2016, we evaluated sensitivity to SN and outcomes of secondary consumption in the ubiquitous mammalian scavenger, coyote (Canis latrans), to determine secondary risks of consuming carcasses of wild pigs that died from consuming the SN toxic bait. At the National Wildlife Research Center in Fort Collins, Colorado, USA, we first evaluated whether coyotes fed carcasses of domestic pigs killed by consumption of SN bait showed signs of SN intoxication. Second, we conducted chemical analysis of residual SN in the coyotes for evidence of SN passing from pigs to coyotes. Last, we conducted an acute oral toxicity test (LD50) with SN for coyotes by feeding them meatballs containing capsules of SN. We found no evidence that captive coyotes experienced SN intoxication from consuming on carcasses that had been freshly poisoned with SN, despite consuming ¯ x = 1.6 kg of tissues/coyote within 24 hours. None of the captive coyotes consumed digestive tracts or stomach contents from poisoned carcasses, which contained the highest levels of residual SN. Chemical analysis indicated that only ≤34.14 mg/kg of residual SN were passed from the tissues of the pigs into the coyotes, confirming that SN does not bioaccumulate. All coyotes quickly vomited various doses of SN during the LD50 test and fully recovered, suggesting a natural defense against secondary poisoning from SN. Testing with captive coyotes indicates that the risks of secondary poisoning for free‐ranging coyotes are likely low, although field‐testing should be used to confirm

Structural basis for the modulation of MRP2 activity by phosphorylation and drugs.

Multidrug resistance-associated protein 2 (MRP2/ABCC2) is a polyspecific efflux transporter of organic anions expressed in hepatocyte canalicular membranes. MRP2 dysfunction, in Dubin-Johnson syndrome or by off-target inhibition, for example by the uricosuric drug probenecid, elevates circulating bilirubin glucuronide and is a cause of jaundice. Here, we determine the cryo-EM structure of rat Mrp2 (rMrp2) in an autoinhibited state and in complex with probenecid. The autoinhibited state exhibits an unusual conformation for this class of transporter in which the regulatory domain is folded within the transmembrane domain cavity. In vitro phosphorylation, mass spectrometry and transport assays show that phosphorylation of the regulatory domain relieves this autoinhibition and enhances rMrp2 transport activity. The in vitro data is confirmed in human hepatocyte-like cells, in which inhibition of endogenous kinases also reduces human MRP2 transport activity. The drug-bound state reveals two probenecid binding sites that suggest a dynamic interplay with autoinhibition. Mapping of the Dubin-Johnson mutations onto the rodent structure indicates that many may interfere with the transition between conformational states

Compartmentalized PDE4A5 signaling impairs hippocampal synaptic plasticity and long-term memory

Alterations in cAMP signaling are thought to contribute to neurocognitive and neuropsychiatric disorders. Members of the cAMP-specific phosphodiesterase 4 (PDE4) family, which contains >25 different isoforms, play a key role in determining spatial cAMP degradation so as to orchestrate compartmentalized cAMP signaling in cells. Each isoform binds to a different set of protein complexes through its unique N-terminal domain, thereby leading to targeted degradation of cAMP in specific intracellular compartments. However, the functional role of specific compartmentalized PDE4 isoforms has not been examined in vivo. Here, we show that increasing protein levels of the PDE4A5 isoform in mouse hippocampal excitatory neurons impairs a long-lasting form of hippocampal synaptic plasticity and attenuates hippocampus-dependent long-term memories without affecting anxiety. In contrast, viral expression of a truncated version of PDE4A5, which lacks the unique N-terminal targeting domain, does not affect long-term memory. Further, overexpression of the PDE4A1 isoform, which targets a different subset of signalosomes, leaves memory undisturbed. Fluorescence resonance energy transfer sensor-based cAMP measurements reveal that the full-length PDE4A5, in contrast to the truncated form, hampers forskolin-mediated increases in neuronal cAMP levels. Our study indicates that the unique N-terminal localization domain of PDE4A5 is essential for the targeting of specific cAMP-dependent signaling underlying synaptic plasticity and memory. The development of compounds to disrupt the compartmentalization of individual PDE4 isoforms by targeting their unique N-terminal domains may provide a fruitful approach to prevent cognitive deficits in neuropsychiatric and neurocognitive disorders that are associated with alterations in cAMP signaling

Measurement of the Zero Crossing in a Feshbach Resonance of Fermionic 6-Li

We measure a zero crossing in the scattering length of a mixture of the two lowest hyperfine states of 6-Li. To locate the zero crossing, we monitor the decrease in temperature and atom number arising from evaporation in a CO2 laser trap as a function of magnetic field B. The temperature decrease and atom loss are minimized for B=528(4) G, consistent with no evaporation. We also present preliminary calculations using potentials that have been constrained by the measured zero crossing and locate a broad Feshbach resonance at approximately 860 G, in agreement with previous theoretical predictions. In addition, our theoretical model predicts a second and much narrower Feshbach resonance near 550 G.Comment: Five pages, four figure

The AP-2 adaptor β2 appendage scaffolds alternate cargo endocytosis

The independently folded appendages of the large α and β2 subunits of the endocytic adaptor protein (AP)-2 complex coordinate proper assembly and operation of endocytic components during clathrin-mediated endocytosis. The β2 subunit appendage contains a common binding site for β-arrestin or the autosomal recessive hypercholesterolemia (ARH) protein. To determine the importance of this interaction surface in living cells, we used small interfering RNA-based gene silencing. The effect of extinguishing β2 subunit expression on the internalization of transferrin is considerably weaker than an AP-2 α subunit knockdown. We show the mild sorting defect is due to fortuitous substitution of the β2 chain with the closely related endogenous β1 subunit of the AP-1 adaptor complex. Simultaneous silencing of both β1 and β2 subunit transcripts recapitulates the strong α subunit RNA interference (RNAi) phenotype and results in loss of ARH from endocytic clathrin coats. An RNAi-insensitive β2-yellow fluorescent protein (YFP) expressed in the β1 + β2-silenced background restores cellular AP-2 levels, robust transferrin internalization, and ARH colocalization with cell surface clathrin. The importance of the β appendage platform subdomain over clathrin for precise deposition of ARH at clathrin assembly zones is revealed by a β2-YFP with a disrupted ARH binding interface, which does not restore ARH colocalization with clathrin. We also show a β-arrestin 1 mutant, which engages coated structures in the absence of any G protein-coupled receptor stimulation, colocalizes with β2-YFP and clathrin even in the absence of an operational clathrin binding sequence. These findings argue against ARH and β-arrestin binding to a site upon the β2 appendage platform that is later obstructed by polymerized clathrin. We conclude that ARH and β-arrestin depend on a privileged β2 appendage site for proper cargo recruitment to clathrin bud sites

Assessing a risk tailored intervention to prevent disabling low back pain - protocol of a cluster randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Although most patients with low back pain (LBP) recover within a few weeks a significant proportion has recurrent episodes or will develop chronic low back pain. Several mainly psychosocial risk factors for developing chronic LBP have been identified. However, effects of preventive interventions aiming at behavioural risk factors and unfavourable cognitions have yielded inconsistent results. Risk tailored interventions may provide a cost efficient and effective means to take systematic account of the individual risk factors but evidence is lacking.</p> <p>Methods/Design</p> <p>This study will be a cluster-randomised controlled trial comparing screening and a subsequent risk tailored intervention for patients with low back pain to prevent chronic low back pain compared to treatment as usual in primary care. A total of 600 patients from 20 practices in each study arm will be recruited in Berlin and Goettingen. The intervention comprises the following elements: Patients will be assigned to one of four risk groups based on a screening questionnaire. Subsequently they receive an educational intervention including information and counselling tailored to the risk group. A telephone/email consulting service for back pain related problems are offered independent of risk group assignment. The primary outcomes will be functional capacity and sick leave.</p> <p>Discussion</p> <p>This trial will evaluate the effectiveness of screening for risk factors for chronic low back pain followed by a risk tailored intervention to prevent chronic low back pain. This trial will contribute new evidence regarding the flexible use of individual physical and psychosocial risk factors in general practice.</p> <p>Trial registration</p> <p>ISRCTN 68205910</p