The U.S. continues a broad spectrum of research to provide the scientific underpinnings for electromagnetic launch. These efforts include fundamental research on materials, properties of materials ...subjected to electromagnetic and thermal stresses, railguns (particularly the rail-armature sliding interface), coilguns, and energy storage and power conditioning. There is also broad and growing interest in novel applications of electromagnetic launch. For example, a supersonic beam of neon atoms have been slowed and stopped, opening the door for investigating the atomic and molecular properties of most of the periodic table of atoms and certain molecules. Research is continuing on magnetic brakes and the more traditional research on the launch of materials to hypervelocities. More recently, the launching of materials into the Earth's orbit or even deeper in space is obtaining renewed interest. Consequently, some attention is being given to the types of materials of projectiles for hypersonic flight. The U.S. Navy has initiated new multidisciplinary university research teams including physics, chemistry, and materials science to develop new diagnostic tools and to provide a more detailed examination of the rail-armature interface. Most significantly, the U.S. Army has elevated its emphasis from electromagnetic launch science and technology development to the operational consequences of long-range precision fires. In concert with the recent U.S. Navy efforts on long-range fires, it is anticipated that the pull of these applications will enable even greater advances in the science and technology of electromagnetic launch.
Dissolved organic matter (DOM) helps regulate aquatic ecosystem structure and function. In small streams, DOM concentrations are controlled by transport of terrestrial materials to waterways, and are ...thus highly variable. As rivers become larger, the River Continuum Concept hypothesizes that internal primary production is an increasingly important DOM source, but direct evidence is limited. Recently, the Pulse-Shunt Concept postulated that terrestrial DOM concentrations in larger rivers increase with flow and temperature, which seemingly contradicts previously reported DOM chemostasis in large rivers. This study estimates daily gross primary production (GPP) in 13 streams and rivers across the Connecticut River watershed (watershed areas 0.4–25,019 km
2
) from 2015 through 2017. Chemostasis of DOM concentrations is maintained by a switch from autochthonous sources of DOM at low flows to terrestrial sources of DOM at high flows in a large temperate river and to a lesser degree in smaller tributaries. At low flow, autochthonous DOM linked to aquatic GPP is the dominant fraction of the DOM pool in large rivers. This autochthonous DOM maintains chemostasis in the main stem and to a lesser extent upstream. Thus, in larger rivers, low-flow autochthonous production stabilizes DOM concentrations during the summer, a critical time for riverine ecology. Consistent with the Pulse-Shunt Concept, terrigenous DOM is the dominant fraction of DOM during higher flow periods and about 70% of annual DOM fluxes to the coast are terrestrial. This pattern of DOM switching is potentially widespread in temperate watersheds with implications to both inland waters and coastal ecosystems.
Electromagnetic (EM) launch science and technology in the United States continues to advance at a significant pace. The computational and experimental tools for understanding the critical physics ...issues are sufficiently mature that they are being utilized to provide insight and resolution of the remaining major technical challenges. For example, the primary computational electrodynamics code, EMAP3D, is now implemented in a hybrid finite element-boundary element configuration with moving conductors, providing faster computation and increased understanding of these complex systems. An increased focus on railgun tribology and experiments to understand the interface between railgun armatures and the rail surface is providing important insight for improved railgun lifetimes. Control algorithms for counter-rotating pulsed alternators have been developed and validated experimentally with physical scale simulators. Solid-state switches are replacing the more traditional vacuum switches for high-current and high-voltage railgun power sources. Silicon is the material of choice, but silicon carbide shows great promise for reduced size and increased electrical performance. As a consequence of these and other advances, the U.S. Army has initiated an effort to build a power source with a matched pair of counter-rotating pulsed alternators and a cantilevered railgun to accelerate projectiles to 2-MJ kinetic energy. The U.S. Navy has initiated a new effort to launch large projectiles to hypervelocity. Because of the large naval platform, the size and weight of the power source are not significant issues for the U.S. Navy, whose primary interest is in providing precision fire support to ranges in excess of 200nmi (500 km). The critical technical issues in implementing this application for the Navy are railgun bore lifetime and high-acceleration-tolerant guidance and control. This paper highlights the recent major achievements in hypervelocity physics, pulsed power, and railgun lifetimes that provide the critical science and technology underpinnings for the Army and Navy EM gun programs
Patients considering living donor liver transplantation (LDLT) need to know the risk and severity of complications compared to deceased donor liver transplantation (DDLT). One aim of the ...Adult‐to‐Adult Living Donor Liver Transplantation Cohort Study (A2ALL) was to examine recipient complications following these procedures. Medical records of DDLT or LDLT recipients who had a living donor evaluated at the nine A2ALL centers between 1998 and 2003 were reviewed. Among 384 LDLT and 216 DDLT, at least one complication occurred after 82.8% of LDLT and 78.2% of DDLT (p = 0.17). There was a median of two complications after DDLT and three after LDLT. Complications that occurred at a higher rate (p < 0.05) after LDLT included biliary leak (31.8% vs. 10.2%), unplanned reexploration (26.2% vs. 17.1%), hepatic artery thrombosis (6.5% vs. 2.3%) and portal vein thrombosis (2.9% vs. 0.0%). There were more complications leading to retransplantation or death (Clavien grade 4) after LDLT versus DDLT (15.9% vs. 9.3%, p = 0.023). Many complications occurred more commonly during early center experience; the odds of grade 4 complications were more than two‐fold higher when centers had performed ≤20 LDLT (vs. >40). In summary, complication rates were higher after LDLT versus DDLT, but declined with center experience to levels comparable to DDLT.
This retrospective study conducted by the A2ALL consortium compares the complication rates in recipients of living donor and deceased donor liver transplants.
We examined mortality and recurrence of hepatocellular carcinoma (HCC) among 106 transplant candidates with cirrhosis and HCC who had a potential living donor evaluated between January 1998 and ...February 2003 at the nine centers participating in the Adult‐to‐Adult Living Donor Liver Transplantation Cohort Study (A2ALL). Cox regression models were fitted to compare time from donor evaluation and time from transplant to death or HCC recurrence between 58 living donor liver transplant (LDLT) and 34 deceased donor liver transplant (DDLT) recipients. Mean age and calculated Model for End‐Stage Liver Disease (MELD) scores at transplant were similar between LDLT and DDLT recipients (age: 55 vs. 52 years, p = 0.21; MELD: 13 vs. 15, p = 0.08). Relative to DDLT recipients, LDLT recipients had a shorter time from listing to transplant (mean 160 vs. 469 days, p < 0.0001) and a higher rate of HCC recurrence within 3 years than DDLT recipients (29% vs. 0%, p = 0.002), but there was no difference in mortality or the combined outcome of mortality or recurrence. LDLT recipients had lower relative mortality risk than patients who did not undergo LDLT after the center had more experience (p = 0.03). Enthusiasm for LDLT as HCC treatment is dampened by higher HCC recurrence compared to DDLT.
Of 106 transplant candidates with cirrhosis and HCC who had a potential living donor evaluated, LDLT recipients had lower relative mortality risk than patients who did not undergo LDLT; but LDLT to supplement DDLT in HCC treatment had a cost of higher HCC recurrence in LDLT patients.
Living donor liver transplantation (LDLT) may have better immunological outcomes compared to deceased donor liver transplantation (DDLT). The aim of this study was to analyze the incidence of acute ...cellular rejection (ACR) after LDLT and DDLT. Data from the adult‐to‐adult living donor liver transplantation (A2ALL) retrospective cohort study on 593 liver transplants done between May 1998 and March 2004 were studied (380 LDLT; 213 DDLT). Median LDLT and DDLT follow‐up was 778 and 713 days, respectively. Rates of clinically treated and biopsy‐proven ACR were compared. There were 174 (46%) LDLT and 80 (38%) DDLT recipients with ≥1 clinically treated episodes of ACR, whereas 103 (27%) LDLT and 58 (27%) DDLT recipients had ≥1 biopsy‐proven ACR episode. A higher proportion of LDLT recipients had clinically treated ACR (p = 0.052), but this difference was largely attributable to one center. There were similar proportions of biopsy‐proven rejection (p = 0.97) and graft loss due to rejection (p = 0.16). Longer cold ischemia time was associated with a higher rate of ACR in both groups despite much shorter median cold ischemia time in LDLT. These data do not show an immunological advantage for LDLT, and therefore do not support the application of unique posttransplant immunosuppression protocols for LDLT recipients.
Live donor and deceased donor liver transplants demonstrate a similar rate of biopsy proven rejection, and direct correlation between cold ischemia and the risk for acute cellular rejection in both settings.
Stem cell transplantation to the liver is a promising therapeutic strategy for a variety of disorders. Hepatocyte transplantation has short-term efficacy but can be problematic due to portal ...hypertension, inflammation, and sinusoidal thrombosis. We have previously transplanted small mouse endoderm progenitor (EP) cells to successfully reverse a murine model of hemophilia B, and labeling these cells with iron nanoparticles renders them responsive to magnetic fields, which can be used to enhance engraftment. The mechanisms mediating progenitor cell migration from the sinusoidal space to the hepatocyte compartment are unknown. Here we find human EP and hepatic progenitor (HP) cells can be produced from human embryonic stem cells with high efficiency, and they also readily uptake iron nanoparticles. This provides a simple manner through which one can readily identify transplanted cells in vivo using electron microscopy, shortly after delivery. High resolution imaging shows progenitor cell morphologies consistent with epithelial-to-mesenchymal transition (EMT) mediating invasion into the hepatic parenchyma. This occurs in as little as 3 h, which is considerably faster than observed when hepatocytes are transplanted. We confirmed activated EMT in transplanted cells in vitro, as well as in vivo 24 h after transplantation. We conclude that EMT naturally occurs concurrent with EP and HP cell engraftment, which may mediate the rate, safety, and efficacy of early cell engraftment in the undamaged quiescent liver.
Hedgehog signaling through its receptor, Patched, activates transcription of genes, including Patched, that regulate the fate of various progenitors. Although Hedgehog signaling is required for ...endodermal commitment and hepatogenesis, the possibility that it regulates liver turnover in adults had not been considered because mature liver epithelial cells lack Hedgehog signaling. Herein, we show that this pathway is essential throughout life for maintaining hepatic progenitors. Patched-expressing cells have been identified among endodermally lineage-restricted, murine embryonic stem cells as well as in livers of fetal and adult Ptc-lacZ mice. An adult-derived, murine hepatic progenitor cell line expresses Patched, and Hedgehog-responsive cells exist in stem cell compartments of fetal and adult human livers. In both species, manipulation of Hedgehog activity influences hepatic progenitor cell survival. Therefore, Hedgehog signaling is conserved in hepatic progenitors from fetal development through adulthood and may be a new therapeutic target in patients with liver damage.
Myofibroblast activation is a cellular response elicited by a variety of physiological or pathological insults whereby cells initiate a coordinated response intended to eradicate the insult and then ...revert back to a basal state. However, an underlying theme in various disease states is persistent myofibroblast activation that fails to resolve. Based on multiple observations, we hypothesized that the secreted factors harvested from co-culturing amniotic stem cells might mimic the anti-inflammatory state that cell-free amniotic fluid (AF) elicits. We optimized an amnion epithelial and amniotic fluid cell co-culture system, and tested this hypothesis in the context of myofibroblast activation. However, we discovered that co-cultured amniotic cell conditioned media (coACCM) and AF have opposing effects on myofibroblast activation: coACCM activates the epithelial–mesenchymal transition (EMT) and stimulates gene expression patterns associated with myofibroblast activation, while AF does the opposite. Intriguingly, extracellular vesicles (EVs) purified from AF are necessary and sufficient to activate EMT and inflammatory gene expression patterns, while the EV-depleted AF potently represses these responses. In summary, these data indicate that coACCM stimulates myofibroblast activation, while AF represses it. We interpret these findings to suggest that coACCM, AF, and fractionated AF represent unique biologics that elicit different cellular responses that are correlated with a wide variety of pathological states, and therefore could have broad utility in the clinic and the lab.
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