Determination of Interlaminar Toughness of IM7/977-2 Composites at Temperature Extremes and Different Thicknesses

Composite materials are being used in the aerospace industry as a means of reducing vehicle weight. In particular, polymer matrix composites (PMC) are good candidates due to their high strength-to-weight and high stiffness-to-weight ratios. Future reusable space launch vehicles and space exploration structures will need advanced light weight composites in order to minimize vehicle weight while demonstrating robustness and durability, guaranteeing high factors of safety. In particular, the implementation of composite cryogenic propellant fuel tanks (cryotanks) for future reusable launch vehicles (RLVs) could greatly reduce the vehicle's weight versus identically sized cryotanks constructed of metallic materials. One candidate composite material for future cryotank designs is IM7/977-2, which is a graphite/epoxy system. A successful candidate must demonstrate reasonable structural properties over a wide range of temperatures. Since the matrix material is normally the weak link in the composite, tests that emphasize matrix-dominated behavior need to be conducted. Therefore, the objective of this work is to determine the mode I interlaminar fracture toughness of "unidirectional" 8-ply and 16-ply IM7/977-2 through experimental testing. Tests were performed at -196 degrees Celsius (-320 degrees Fahrenheit), 22 degrees Celsius (72 degrees Fahrenheit), 93 degrees Celsius (200 degrees Fahrenheit) and 160 degrees C (320 degrees Fahrenheit). Low temperature testing was completed while the specimen was submerged in a liquid nitrogen bath. High temperature testing was completed in a temperature-controlled oven

Immune status of recipients following bone marrow - Augmented solid organ transplantation

It has been postulated that the resident “passenger” leukocytes of hematolymphoid origin that migrate from whole organ grafts and subsequently establish systemic chimerism are essential for graft acceptance and the induction of donor-specific nonreactivity. This phenomenon was augmented by infusing 3 × 108 unmodified donor bone-marrow cells into 40 patients at the time of organ transplantation. Fifteen of the first 18 analyzable patients had sequential immunological evaluation over postoperative intervals of 5 to 17 months, (which included 7 kidney (two with islets), 7 liver (one with islets), and one heart recipient). The evolution of changes was compared with that in 16 kidney and liver nonmarrow controls followed for 4 to5 months. The generic immune reactivity of peripheral blood mononuclear cells (PBMC) was determined by their proliferative responses to mitogens (PHA, ConA). Alloreactivity was measured by the recipient mixed lymphocyte reaction (MLR) to donor and HLA-mis-matched third-party panel cells. Based on all 3 tests,the recipients were classified as donor-specific hyporeactive, intermediate, and responsive; patients who were globally suppressed made up a fourth category. Eight (53%) of the 15 marrow-treated recipients exhibited progressive modulation of donor-specific reactivity (3 hyporeactive and 5 intermediate) while 7 remained antidonor-responsive. In the nonmarrow controls, 2 (12.5%) of the 16 patients showed donor-specific hyporeactivity, 10 (62.5%) were reactive, and 4 (25%) studied during a CMV infection had global suppression of responsiveness to all stimuli. © 1995 by Williams and Wilkins

Incidence of the V600K mutation among melanoma patients with BRAF mutations, and potential therapeutic response to the specific BRAF inhibitor PLX4032

Activating mutations in BRAF kinase are common in melanomas. Clinical trials with PLX4032, the mutant-BRAF inhibitor, show promising preliminary results in patients selected for the presence of V600E mutation. However, activating V600K mutation is the other most common mutation, yet patients with this variant are currently excluded from the PLX4032 trials. Here we present evidence that a patient bearing the BRAF V600K mutation responded remarkably to PLX4032, suggesting that clinical trials should include all patients with activating BRAF V600E/K mutations

Assessing Long-Distance Atmospheric Transport of Soilborne Plant Pathogens

Pathogenic fungi are a leading cause of crop disease and primarily spread through microscopic, durable spores adapted differentially for both persistence and dispersal. Computational Earth System Models and air pollution models have been used to simulate atmospheric spore transport for aerial-dispersal-adapted (airborne) rust diseases, but the importance of atmospheric spore transport for soil-dispersal-adapted (soilborne) diseases remains unknown. This study adapts the Community Atmosphere Model, the atmospheric component of the Community Earth System Model, to simulate the global transport of the plant pathogenic soilborne fungus Fusarium oxysporum, F. oxy. Our sensitivity study assesses the model's accuracy in long-distance aerosol transport and the impact of deposition rate on long-distance spore transport in Summer 2020 during a major dust transport event from Northern Sub-Saharan Africa to the Caribbean and southeastern U.S. We find that decreasing wet and dry deposition rates by an order of magnitude improves representation of long distance, trans-Atlantic dust transport. Simulations also suggest that a small number of viable spores can survive trans-Atlantic transport to be deposited in agricultural zones. This number is dependent on source spore parameterization, which we improved through a literature search to yield a global map of F. oxy spore distribution in source agricultural soils. Using this map and aerosol transport modeling, we show how viable spore numbers in the atmosphere decrease with distance traveled and offer a novel danger index for viable spore deposition in agricultural zones

Phase II assessment of talabostat and cisplatin in second-line stage IV melanoma

<p>Abstract</p> <p>Background</p> <p>Metastatic melanoma is an incurable disease with an average survival of less than one year. Talabostat is a novel dipeptidyl peptidase inhibitor with immunostimulatory properties.</p> <p>Methods</p> <p>This phase II, open label, single arm study was conducted to evaluate the safety and efficacy of 75–100 mg/m²cisplatin combined with 300–400 mcg talabostat bid for 6, 21-day cycles. The primary endpoint was overall response. The rate of complete responses, duration of overall objective response, progression-free survival (PFS), and overall survival were the secondary endpoints.</p> <p>Results</p> <p>Six objective partial responses were recorded in the 74 patients (8.1%) in the intention-to-treat population. Five of these responses involved the 40 evaluable patients (12.5%). Thirty-one percent of patients reported SAEs to the combination of talabostat and cisplatin.</p> <p>Conclusion</p> <p>Acceptable tolerability was observed in the intention-to-treat population and antitumor activity was observed in 12.5% of evaluable patients, which is not greater than historical expectation with cisplatin alone.</p

Mouse model of liver ischemia and reperfusion injury: method for studying reactive oxygen and nitrogen metabolites in vivo

The mouse model of liver ischemia and reperfusion injury has proven to be valuable for our understanding of the role that reactive oxygen and nitrogen metabolites play in postischemic tissue injury. This methods paper provides a detailed protocol for inducing partial liver ischemia followed by reperfusion. Liver ischemia is induced in anesthetized mice by cross-clamping the hepatic artery and portal vein for varying lengths of time resulting in deprivation of blood flow to approximately of 70% of the liver. Restoration of blood flow to the ischemic lobes enhances superoxide production concomitant with a rapid and marked decrease in the bioavailability of nitric oxide resulting in alterations in the redox state of the liver in favor of a more oxidative environment. This hepatocellular oxidative stress induces the activation of oxidant-sensitive transcription factors followed by the upregulation of pro-inflammatory cytokines and mediators that ultimately lead to liver injury. This model can be induced in any strain or sex of mouse and requires 1-2 months of practice to become proficient in the surgery and animal manipulation. The role of different reactive metabolites of oxygen and nitrogen may be evaluated using genetically-engineered mice as well as selective molecular, cellular and/or pharmacological agents

A Phase II Trial of the Epothilone B Analog Ixabepilone (BMS-247550) in Patients with Metastatic Melanoma

Ixabepilone (BMS-247550), an epothilone B analog, is a microtubule stabilizing agent which has shown activity in several different tumor types and preclinical models in melanoma. In an open label, one-arm, multi-center phase II trial the efficacy and toxicity of this epothilone was investigated in two different cohorts: chemotherapy-naïve (previously untreated) and previously treated patients with metastatic melanoma.Eligible patients had histologically-confirmed stage IV melanoma, with an ECOG performance status of 0 to 2. Ixabepilone was administered at a dose of 20 mg/m(2) on days 1, 8, and 15 during each 28-day cycle. The primary endpoint was response rate (RR); secondary endpoints were time to progression (TTP) and toxicity. Twenty-four patients were enrolled and 23 were evaluable for response. Initial serum lactate dehydrogenase (LDH) levels were elevated in 6/11 (55%) of the previously treated and in 5/13 (38%) of the previously untreated patients. No complete or partial responses were seen in either cohort. One patient in the previously treated group developed neutropenia and fatal septic shock. Seventeen patients (8 in the previously untreated group and 9 in the previously treated group) progressed after 2 cycles, whereas six patients (3 in each group) had stable disease after 2-6 cycles. Median TTP was 1.74 months in the previously untreated group (95% CI = 1.51 months, upper limit not estimated) and 1.54 months in the previously treated group (95% CI = 1.15 months, 2.72 months). Grade 3 and/or 4 toxicities occurred in 5/11 (45%) of previously untreated and in 5/13 (38%) of previously treated patients and included neutropenia, peripheral neuropathy, fatigue, diarrhea, and dyspnea.Ixabepilone has no meaningful activity in either chemotherapy-naïve (previously untreated) or previously treated patients with metastatic melanoma. Further investigation with ixabepilone as single agent in the treatment of melanoma is not warranted.Clinical Trials.gov NCT00036764

Decomposing uncertainties in the future terrestrial carbon budget associated with emission scenarios, climate projections, and ecosystem simulations using the ISI-MIP results

We examined the changes to global net primary production (NPP), vegetation biomass carbon (VegC), and soil organic carbon (SOC) estimated by six global vegetation models (GVMs) obtained from the Inter-Sectoral Impact Model Intercomparison Project. Simulation results were obtained using five global climate models (GCMs) forced with four representative concentration pathway (RCP) scenarios. To clarify which component (i.e., emission scenarios, climate projections, or global vegetation models) contributes the most to uncertainties in projected global terrestrial C cycling by 2100, analysis of variance (ANOVA) and wavelet clustering were applied to 70 projected simulation sets. At the end of the simulation period, changes from the year 2000 in all three variables varied considerably from net negative to positive values. ANOVA revealed that the main sources of uncertainty are different among variables and depend on the projection period. We determined that in the global VegC and SOC projections, GVMs are the main influence on uncertainties (60 % and 90 %, respectively) rather than climate-driving scenarios (RCPs and GCMs). Moreover, the divergence of changes in vegetation carbon residence times is dominated by GVM uncertainty, particularly in the latter half of the 21st century. In addition, we found that the contribution of each uncertainty source is spatiotemporally heterogeneous and it differs among the GVM variables. The dominant uncertainty source for changes in NPP and VegC varies along the climatic gradient. The contribution of GVM to the uncertainty decreases as the climate division becomes cooler (from ca. 80 % in the equatorial division to 40 % in the snow division). Our results suggest that to assess climate change impacts on global ecosystem C cycling among each RCP scenario, the long-term C dynamics within the ecosystems (i.e., vegetation turnover and soil decomposition) are more critical factors than photosynthetic processes. The different trends in the contribution of uncertainty sources in each variable among climate divisions indicate that improvement of GVMs based on climate division or biome type will be effective. On the other hand, in dry regions, GCMs are the dominant uncertainty source in climate impact assessments of vegetation and soil C dynamics