“Plasminogen steal” and clot lysis

AbstractAlthough initially developed to reduce the risk of bleeding, second-generation (clot-selective) thrombolytic agents have been found to induce more prompt and frequent recanalizatton than do nonselective, first-generation agents. To determine whether they do so in part by preserving clot-associated plasminogen, human whole blood clots formed in Chandler tubes were studied. Addition of suprapharmacologic concentrations of recombinant tissue-type plasminogen activator (rt-PA) to the media bathing mature clots led to a paradoxic impairment of clot lysis and a concomitant concentration-dependent depletion of clot-associated plasminogen (Western blot analysis). In contrast, supplementation of the plasma with plasminogen (0.27 mg/ml) led to significant conservation of both plasma and clot-associated plasminogen (p ≤ 0.05, n = 4), and prevented the diminution of clot lysis (p ≤ 0.05; n = 4).Fibrinogen degradation products did not account for the attenuation of lysis with the highest concentrations of rt-PA. In concentrations equivalent to those that were induced by the highest concentrations of rt-PA evaluated, fibrinogen degradation products potentiated rather than inhibited lysis (p ≤ 0.05, n = 4), probably by stimulating rt-PA activity directly. When preformed clots were incubated with plasminogen-depleted plasma plus 1,000 ng/ml rt-PA, the plasminogen content in residual clot declined (9.36 ± 0.46 versus 12.39 ± 0.69 ng/mg clot found in nondepleted plasma; p ≤ 0.05; n = 6). Furthermore, clot lysis was attenuated completely.Thus, clot lysis induced by activation of plasminogen is dependent on clot-associated plasminogen, which in turn depends on the concentration of plasminogen in plasma. Depletion of both is likely to contribute to the lower frequency and rapidity of coronary recanalization induced with nonclot-selective compared with selective fibrinolytic agents because of the depletion of plasma plasminogen and the plasminogen steal they characteristically induce

Neutrino-induced deuteron disintegration experiment

Cross sections for the disintegration of the deuteron via neutral-current (NCD) and charged-current (CCD) interactions with reactor antineutrinos are measured to be 6.08 +/- 0.77 x 10^(-45) cm-sq and 9.83 +/- 2.04 x 10^(-45) cm-sq per neutrino, respectively, in excellent agreement with current calculations. Since the experimental NCD value depends upon the CCD value, if we use the theoretical value for the CCD reaction, we obtain the improved value of 5.98 +/- 0.54 x 10^(-45) for the NCD cross section. The neutral-current reaction allows a unique measurement of the isovector-axial vector coupling constant in the hadronic weak interaction (beta). In the standard model, this constant is predicted to be exactly 1, independent of the Weinberg angle. We measure a value of beta^2 = 1.01 +/- 0.16. Using the above improved value for the NCD cross section, beta^2 becomes 0.99 +/- 0.10.Comment: 22pages, 9 figure

A low energy optimization of the CERN-NGS neutrino beam for a theta_{13} driven neutrino oscillation search

The possibility to improve the CERN to Gran Sasso neutrino beam performances for theta_{13} searches is investigated. We show that by an appropriate optimization of the target and focusing optics of the present CNGS design, we can increase the flux of low energy neutrinos by about a factor 5 compared to the current tau optimized focalisation. With the ICARUS 2.35 kton detector at LNGS and in case of negative result, this would allow to improve the limit to sin^22 theta_{13} by an order of magnitude better than the current limit of CHOOZ at Delta m^2 approximately 3 times 10^{-3} eV^2 within 5 years of nominal CNGS running. This is by far the most sensitive setup of the currently approved long-baseline experiments and is competitive with the proposed JHF superbeam.Comment: 19 pages, 8 figure

Identification And Characterization Of A Second Encephalitogenic Determinant Of Myelin Proteolipid Protein (Residues 178-191) For SJL Mice

We previously described a synthetic peptide of myelin proteolipid protein (PLP), peptide 139-151, which induces experimental allergic encephalomyelitis in SJL/J (H-2s) mice. We have now identified an additional determinant, PLP residues 178-191, that is also a potent encephalitogen in this strain. When PLP peptide 178-191 was compared with peptide 139-151 on an equimolar basis, the day of onset of disease induced by PLP 178-191 was earlier, but the incidence, severity, and histologic features were indistinguishable. Lymph node cells from animals immunized with the whole PLP molecule responded to both PLP 178-191 and 139-151, suggesting immunologic codominance of the two epitopes. PLP 178-191 elicited stronger proliferative responses and this may relate to the earlier onset of disease induced with this peptide. Two CD4+, peptide-specific, I-A(s)-restricted T cell lines, selected by stimulation of lymph node cells with either PLP 178-191 or 139-151, were each encephalitogenic in naive syngeneic mice. The presence of multiple encephalitogenic codominant PLP epitopes within a single mouse strain emphasizes the complexity of the immune response to PLP and its potential as a target Ag in autoimmune demyelinating diseases

Adaptive Markets and the New World Order

In the adaptive markets hypothesis (AMH) intelligent but fallible investors learn from and adapt to changing economic environments. This implies that markets are not always efficient but are usually competitive and adaptive, varying in their degree of efficiency as the environment and investor population change over time. The AMH has several implications, including the possibility of negative risk premiums, alpha converging to beta, and the importance of macro factors and risk budgeting in asset allocation policies

Expression of Interest: The Atmospheric Neutrino Neutron Interaction Experiment (ANNIE)

Submitted for the January 2014 Fermilab Physics Advisory Committee meetingSubmitted for the January 2014 Fermilab Physics Advisory Committee meetingSubmitted for the January 2014 Fermilab Physics Advisory Committee meetingSubmitted for the January 2014 Fermilab Physics Advisory Committee meetingNeutron tagging in Gadolinium-doped water may play a significant role in reducing backgrounds from atmospheric neutrinos in next generation proton-decay searches using megaton-scale Water Cherenkov detectors. Similar techniques might also be useful in the detection of supernova neutrinos. Accurate determination of neutron tagging efficiencies will require a detailed understanding of the number of neutrons produced by neutrino interactions in water as a function of momentum transferred. We propose the Atmospheric Neutrino Neutron Interaction Experiment (ANNIE), designed to measure the neutron yield of atmospheric neutrino interactions in gadolinium-doped water. An innovative aspect of the ANNIE design is the use of precision timing to localize interaction vertices in the small fiducial volume of the detector. We propose to achieve this by using early production of LAPPDs (Large Area Picosecond Photodetectors). This experiment will be a first application of these devices demonstrating their feasibility for Water Cherenkov neutrino detectors

Expression of Interest: The Atmospheric Neutrino Neutron Interaction Experiment (ANNIE)

Neutron tagging in Gadolinium-doped water may play a significant role in reducing backgrounds from atmospheric neutrinos in next generation proton-decay searches using megaton-scale Water Cherenkov detectors. Similar techniques might also be useful in the detection of supernova neutrinos. Accurate determination of neutron tagging efficiencies will require a detailed understanding of the number of neutrons produced by neutrino interactions in water as a function of momentum transferred. We propose the Atmospheric Neutrino Neutron Interaction Experiment (ANNIE), designed to measure the neutron yield of atmospheric neutrino interactions in gadolinium-doped water. An innovative aspect of the ANNIE design is the use of precision timing to localize interaction vertices in the small fiducial volume of the detector. We propose to achieve this by using early production of LAPPDs (Large Area Picosecond Photodetectors). This experiment will be a first application of these devices demonstrating their feasibility for Water Cherenkov neutrino detectors.Comment: Submitted for the January 2014 Fermilab Physics Advisory Committee meetin

Majorana Neutrinos and Gravitational Oscillation

We analyze the possibility of encountering resonant transitions of high energy Majorana neutrinos produced in Active Galactic Nuclei (AGN). We consider gravitational, electromagnetic and matter effects and show that the latter are ignorable. Resonant oscillations due to the gravitational interactions are shown to occur at energies in the PeV range for magnetic moments in the $10^{-17} \mu_B$ range. Coherent precession will dominate for larger magnetic moments. The alllowed regions for gravitational resonant transitions are obtained.Comment: 11 pages, 8 figures, Latex; requires revtex and epsf.tex submitted to Physical Review