Xenogeneic, extracorporeal liver perfusion in primates improves the ratio of branched-chain amino acids to aromatic amino acids (Fischer's ratio)

In fulminant hepatic failure (FHF), the development of hepatic encephalopathy is associated with grossly abnormal concentrations of plasma amino acids (PAA). Normalization of the ratio of branched-chain amino acids to aromatic amino acids (Fischer's ratio) correlates with clinical improvement. This study evaluated changes in PAA metabolism during 4 h of isolated, normothermic extracorporeal liver perfusion using a newly designed system containing human blood and a rhesus monkey liver. Bile and urea production were within the physiological range. Release of the transaminases AST, ALT and LDH were minimal. The ratio of branched (valine, leucine, isoleucine) to aromatic (tyrosine, phenylalanine) amino acids increased significantly. These results indicate that a xenogeneic extracorporeal liver perfusion system is capable of significantly increasing Fischer's ratio and may play a role in treating and bridging patients in FHF in the future

C-Jun N-terminal kinase 2 promotes liver injury via the mitochondrial permeability transition after hemorrhage and resuscitation

Hemorrhagic shock leads to hepatic hypoperfusion and activation of mitogen-activated stress kinases (MAPK) like c-Jun N-terminal kinase (JNK) 1 and 2. Our aim was to determine whether mitochondrial dysfunction leading to hepatic necrosis and apoptosis after hemorrhage/resuscitation (H/R) was dependent on JNK2. Under pentobarbital anesthesia, wildtype (WT) and JNK2 deficient (KO) mice were hemorrhaged to 30 mm Hg for 3 h and then resuscitated with shed blood plus half the volume of lactated Ringer's solution. Serum alanine aminotransferase (ALT), necrosis, apoptosis and oxidative stress were assessed 6 h after resuscitation. Mitochondrial polarization was assessed by intravital microscopy. After H/R, ALT in WT-mice increased from 130 U/L to 4800 U/L. In KO-mice, ALT after H/R was blunted to 1800 U/l (P < 0.05). Necrosis, caspase-3 activity and ROS were all substantially decreased in KO compared to WT mice after H/R. After sham operation, intravital microscopy revealed punctate mitochondrial staining by rhodamine 123 (Rh123), indicating normal mitochondrial polarization. At 4 h after H/R, Rh123 staining became dim and diffuse in 58% of hepatocytes, indicating depolarization and onset of the mitochondrial permeability transition (MPT). By contrast, KO mice displayed less depolarization after H/R (23%, P < 0.05). In conclusion, JNK2 contributes to MPT-mediated liver injury after H/R

Scaling similarities of multiple fracturing of solid materials

It has recently reported that electromagnetic flashes of low-energy <IMG WIDTH='12' HEIGHT='29' ALIGN='MIDDLE' BORDER='0' src='http://www.nonlin-processes-geophys.net/11/137/2004/npg-11-137-img1.gif' ALT='$gamma$'>-rays emitted during multi-fracturing on a neutron star, and electromagnetic pulses emitted in the laboratory by a disordered material subjected to an increasing external load, share distinctive statistical properties with earthquakes, such as power-law energy distributions (Cheng et al., 1996; Kossobokov et al., 2000; Rabinovitch et al., 2001; Sornette and Helmstetter, 2002). The neutron starquakes may release strain energies up to <IMG WIDTH='32' HEIGHT='16' ALIGN='BOTTOM' BORDER='0' src='http://www.nonlin-processes-geophys.net/11/137/2004/npg-11-137-img2.gif' ALT='$10^{46}$'>erg, while, the fractures in laboratory samples release strain energies approximately a fraction of an erg. An earthquake fault region can build up strain energy up to approximately <IMG WIDTH='32' HEIGHT='16' ALIGN='BOTTOM' BORDER='0' src='http://www.nonlin-processes-geophys.net/11/137/2004/npg-11-137-img3.gif' ALT='$10^{26}$'>erg for the strongest earthquakes. Clear sequences of kilohertz-megahertz electromagnetic avalanches have been detected from a few days up to a few hours prior to recent destructive earthquakes in Greece. A question that arises effortlessly is if the pre-seismic electromagnetic fluctuations also share the same statistical properties. Our study justifies a positive answer. Our analysis also reveals 'symptoms' of a transition to the main rupture common with earthquake sequences and acoustic emission pulses observed during laboratory experiments (Maes et al., 1998)

Planetary Candidates Observed by Kepler. VIII. A Fully Automated Catalog with Measured Completeness and Reliability Based on Data Release 25

We present the Kepler Object of Interest (KOI) catalog of transiting exoplanets based on searching 4 yr of Kepler time series photometry (Data Release 25, Q1–Q17). The catalog contains 8054 KOIs, of which 4034 are planet candidates with periods between 0.25 and 632 days. Of these candidates, 219 are new, including two in multiplanet systems (KOI-82.06 and KOI-2926.05) and 10 high-reliability, terrestrial-size, habitable zone candidates. This catalog was created using a tool called the Robovetter, which automatically vets the DR25 threshold crossing events (TCEs). The Robovetter also vetted simulated data sets and measured how well it was able to separate TCEs caused by noise from those caused by low signal-to-noise transits. We discuss the Robovetter and the metrics it uses to sort TCEs. For orbital periods less than 100 days the Robovetter completeness (the fraction of simulated transits that are determined to be planet candidates) across all observed stars is greater than 85%. For the same period range, the catalog reliability (the fraction of candidates that are not due to instrumental or stellar noise) is greater than 98%. However, for low signal-to-noise candidates between 200 and 500 days around FGK-dwarf stars, the Robovetter is 76.7% complete and the catalog is 50.5% reliable. The KOI catalog, the transit fits, and all of the simulated data used to characterize this catalog are available at the NASA Exoplanet Archive

Protocol TOP-Study (tacrolimus organ perfusion): a prospective randomized multicenter trial to reduce ischemia reperfusion injury in transplantation of marginal liver grafts with an "ex vivo" tacrolimus perfusion

Background: Critical organ shortage results in the utilization of extended donor criteria (EDC) liver grafts. These marginal liver grafts are prone to increased ischemia reperfusion injury (IRI) which may contribute to deteriorated graft function and survival. Experimental data have shown that the calcineurin inhibitor tacrolimus exerts protective effects on hepatic IRI when applied intravenously or directly as a hepatic rinse. Therefore, the aim of the present study is to examine the effects of an ex vivo tacrolimus perfusion on IRI in transplantation of EDC liver grafts. Methods/Design: The TOP-Study (tacrolimus organ perfusion) is a randomized multicenter trial comparing the ex vivo tacrolimus perfusion of marginal liver grafts with placebo. We hypothesize that a tacrolimus rinse reduces IRI, potentially improving organ survival following transplantation of EDC livers. The study includes livers with two or more EDC, according to Eurotransplant International Foundation’s definition of EDC livers. Prior to implantation, livers randomized to the treatment group are rinsed with tacrolimus at a concentration of 20 ng/ml in 1000 ml Custodiol solution and in the placebo group with Custodiol alone. The primary endpoint is the maximum serum alanine transamninase (ALT) level within the first 48 hours after surgery; however, the study design also includes a 1-year observation period following transplantation. The TOP-Study is an investigator-initiated trial sponsored by the University of Munich Hospital. Seven other German transplant centers are participating (Berlin, Frankfurt, Heidelberg, Mainz, Münster, Regensburg, Tübingen) and aim to include a total of 86 patients. Discussion: Tacrolimus organ perfusion represents a promising strategy to reduce hepatic IRI following the transplantation of marginal liver grafts. This treatment may help to improve the function of EDC grafts and therefore safely expand the donor pool in light of critical organ shortage. Trial register: EudraCT number: 2010-021333-31, ClinicalTrials.gov identifier: NCT0156409

State of New York Public Employment Relations Board Decisions from December 18, 1990

12_18_1990_PERB_BD_DecisionsOCR.pdf: 138 downloads, before Oct. 1, 2020

Space Shuttle separation mechanisms

The development of space shuttle separation devices is reviewed to illustrate the mechanisms involved in separating the orbiter from the Boeing 747 carrier aircraft and from the externally mounted propellant tank. Other aspects of the separation device development discussed include design evolution, operational experience during the orbiter approach and landing tests, and the work to be accomplished before an operational system becomes a reality

Abnormal liver function tests in acute heart failure: relationship with clinical characteristics and outcome in the PROTECT study

Aims: Episodes of acute heart failure (AHF) unfavourably affect multiple organs, which may have an adverse impact on the outcomes. We investigated the prevalence and clinical consequences of abnormal liver function tests (LFTs) in AHF patients enrolled in the PROTECT study. Methods and results: The LFTs comprised serial assessment of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and albumin at baseline and during follow-up (daily until discharge, on days 7 and 14). The prevalence of abnormal LFTs (above upper limit of normal for AST and ALT or below lower limit of normal for albumin) was: at baseline AST 20%, ALT 12%, albumin 40%; and at day 14: AST 15%, ALT 9%, albumin 26%. Abnormal LFTs at baseline were associated with a higher risk of in-hospital death with odds ratios [95% confidence interval (CI)] of 3.5 (1.7–7.3) for AST, 3.9 (1.8–8.4) for ALT, and 2.8 (1.3–5.9) for albumin (all P &lt; 0.01). Abnormal baseline and discharge LFTs had an unfavourable impact on 180-day mortality with hazard ratios (95% CI) for baseline AST, ALT, and albumin of 1.3 (1.0–1.7), 1.1 (1.0–1.2), 1.4 (1.1–1.8), respectively, and 1.5 (1.1–2.0), 1.5 (1.0–2.2), and 1.6 (1.2–2.1), for discharge AST, ALT, albumin, respectively (all P &lt; 0.05). Analysis of LFTs trajectories (calculated as changes in LFTs over time) revealed that increasing AST and ALT on day 3 as well as decreasing albumin on day 4 were independent prognosticators of 180-day outcome (all P &lt; 0.05). Conclusions: Abnormal LFTs are frequent in AHF at baseline and during hospital stay and predict worse outcomes. Whether this association is causal and what are the underlying mechanisms involved require further study

Functional immunoglobulin transgenes guide ordered B-cell differentiation in Rag-1-deficient mice

We have examined the regulatory role of the individual components of the immunoglobulin antigen receptor in B-cell development by transgenic complementation of Rag-1 deficient (Rag-1⁻) mice. Complementation with a membrane µ heavy chain (µHC) gene allows progression of developmentally arrested Rag-1⁻ pro-B-cells to the small pre-B cell stage, whereas the introduction of independently integrated µHC and κ light chain (κLC) transgenes promotes the appearance of peripheral lymphocytes which, however, remain unresponsive to external stimuli. Complete reconstitution of the B-cell lineage and the emergence of functionally nature Rag-1⁻ peripheral B cells is achieved by the introduction of cointegrated heavy and light chain transgenes encoding an anti-H-2^k antibody. This experimental system demonstrates the competence of the µHC and κLC to direct and regulate the sequential stages of B-cell differentiation, defines the time at which negative selection of self-reactive B cells occurs, and shows that elimination of these cells occurs equally well in the absence of Rag-1 as in its presence. These data also support the hypothesis that Rag-1 directly participates in the V(D)J recombination process