24 research outputs found
Conversion of short fatigue cracks into a long crack
This paper presents a method for the statistical processing of results of initiation and propagation of short fatigue cracks. The distribution of the lengths of these cracks followed a Weibull distribution function. The value of the size parameter of this distribution grows with the number of cycles, but the value of the shape parameter declines as the number of cycles increases. A study of the modal value of fatigue crack lengths as a function of the number of cycles yielded a statistical criterion defining the conversion of the short fatigue crack initiation and propagation stage into the long fatigue crack propagation stage. One condition for this conversion is a zero magnitude of the first derivative of the modal value of fatigue crack lengths by the number of cycles. When the dependence of the Weibull distribution shape parameter and size parameter upon the number of cycles was inserted in this condition, solution of the resultant expression revealed the critical number of cycles that is necessary for the formation of a long fatigue crack
On the development of crack closure and the threshold condition for short and long fatigue cracks in 7150 aluminum alloy
A critical role for donor-derived IL-22 in cutaneous chronic GVHD
Graft-versus-host disease (GVHD) is the major cause of nonrelapse morbidity and mortality after allogeneic stem cell transplantation (allo-SCT). Prevention and treatment of GVHD remain inadequate and commonly lead to end-organ dysfunction and opportunistic infection. The role of interleukin (IL)-17 and IL-22 in GVHD remains uncertain, due to an apparent lack of lineage fidelity and variable and contextually determined protective and pathogenic effects. We demonstrate that donor T cell-derived IL-22 significantly exacerbates cutaneous chronic GVHD and that IL-22 is produced by highly inflammatory donor CD4āŗ T cells posttransplantation. IL-22 and IL-17A derive from both independent and overlapping lineages, defined as T helper (Th)22 and IL-22āŗ Th17 cells. Donor Th22 and IL-22āŗ Th17 cells share a similar IL-6-dependent developmental pathway, and while Th22 cells arise independently of the IL-22āŗ Th17 lineage, IL-17 signaling to donor Th22 directly promotes their development in allo-SCT. Importantly, while both IL-22 and IL-17 mediate skin GVHD, Th17-induced chronic GVHD can be attenuated by IL-22 inhibition in preclinical systems. In the clinic, high levels of both IL-17A and IL-22 expression are present in the skin of patients with GVHD after allo-SCT. Together, these data demonstrate a key role for donor-derived IL-22 in patients with chronic skin GVHD and confirm parallel but symbiotic developmental pathways of Th22 and Th17 differentiation.Kate H. Gartlan, Hemamalini Bommiasamy, Katelyn Paz, Andrew N. Wilkinson, Mary Owen, Dawn K. Reichenbach, Tatjana Banovic, Kimberly Wehner, Faith Buchanan, Antiopi Varelias, Rachel D. Kuns, Karshing Chang, Yuri Fedoriw, Thomas Shea, James Coghill, Michael Zaiken, Maximilian W. Plank, Paul S. Foster, Andrew D. Clouston, Bruce R. Blazar, Jonathan S. Serody, Geoffrey R. Hil
Influence of sharp microstructural gradients on the fatigue crack growth resistance of alpha+beta and near-alpha titanium alloys
Research on the detection of methane concentration using sensor with supporter catalyst filled element on constant temperature
Based on the basic principle of sensors with supporter filled element that measures the methane concentration, a method for designing Weston bridge by using the sensor and the reference element is proposed and the mathematical model of the automatic temperature control and the measurement of methane concentration is developed. The measurement results show that this design expands the measuring range, reduces burning-knot and vaporization of catalyst and extends the service life of the supporter catalyst filled element.link_to_subscribed_fulltex
Effects of Age, Sex, and Race on the Safety and Pharmacokinetics of Single and Multiple Doses of Azilsartan Medoxomil in Healthy Subjects
Pharmacokinetics of a Single Dose of Azilsartan in Pediatric Patients: A Phase 3, Open-Label, Multicenter Study
Targeting PI3KĪ“ function for amelioration of murine chronic graftāversusāhost disease
Chronic graftāversusāhost disease (cGVHD) is a leading cause of morbidity and mortality following allotransplant. Activated donor effector T cells can differentiate into pathogenic T helper (Th)ā17 cells and germinal center (GC)āpromoting T follicular helper (Tfh) cells, resulting in cGVHD. Phosphoinositideā3ākinaseāĪ“ (PI3KĪ“), a lipid kinase, is critical for activated T cell survival, proliferation, differentiation, and metabolism. We demonstrate PI3KĪ“ activity in donor T cells that become Tfh cells is required for cGVHD in a nonsclerodermatous multiorgan system disease model that includes bronchiolitis obliterans (BO), dependent upon GC B cells, Tfhs, and counterbalanced by T follicular regulatory cells, each requiring PI3KĪ“ signaling for function and survival. Although B cells rely on PI3KĪ“ pathway signaling and GC formation is disrupted resulting in a substantial decrease in Ig production, PI3KĪ“ kinaseādead mutant donor bone marrowāderived GC B cells still supported BO cGVHD generation. A PI3KĪ“āspecific inhibitor, compound GSā649443, that has superior potency to idelalisib while maintaining selectivity, reduced cGVHD in mice with active disease. In a Th1ādependent and Th17āassociated scleroderma model, GSā649443 effectively treated mice with active cGVHD. These data provide a foundation for clinical trials of US Food and Drug Administration (FDA)āapproved PI3KĪ“ inhibitors for cGVHD therapy in patients