Dedication in Memory of William Dewey Rollison

William Dewey Rollison, Professor of Law Emeritus: University of Notre Dame 1897-197

Repressive Interactions Between Transcription Factors Separate Different Embryonic Ectodermal Domains.

The embryonic ectoderm is composed of four domains: neural plate, neural crest, pre-placodal region (PPR) and epidermis. Their formation is initiated during early gastrulation by dorsal-ventral and anterior-posterior gradients of signaling factors that first divide the embryonic ectoderm into neural and non-neural domains. Next, the neural crest and PPR domains arise, eithe

NASA Crew Launch Vehicle Flight Test Options

Options for development flight testing (DFT) of the Ares I Crew Launch Vehicle (CLV) are discussed. The Ares-I Crew Launch Vehicle (CLV) is being developed by the U.S. National Aeronautics and Space Administration (NASA) to launch the Crew Exploration Vehicle (CEV) into low Earth Orbit (LEO). The Ares-I implements one of the components of the Vision for Space Exploration (VSE), providing crew and cargo access to the International Space Station (ISS) after retirement of the Space Shuttle and, eventually, forming part of the launch capability needed for lunar exploration. The role of development flight testing is to demonstrate key sub-systems, address key technical risks, and provide flight data to validate engineering models in representative flight environments. This is distinguished from certification flight testing, which is designed to formally validate system functionality and achieve flight readiness. Lessons learned from Saturn V, Space Shuttle, and other flight programs are examined along with key Ares-I technical risks in order to provide insight into possible development flight test strategies. A strategy for the first test flight of the Ares I, known as Ares I-1, is presented

Optimization of Mitochondrial Isolation Techniques for Intraspinal Transplantation Procedures

Background—Proper mitochondrial function is essential to maintain normal cellular bioenergetics and ionic homeostasis. In instances of severe tissue damage, such as traumatic brain and spinal cord injury, mitochondria become damaged and unregulated leading to cell death. The relatively unexplored field of mitochondrial transplantation following neurotrauma is based on the theory that replacing damaged mitochondria with exogenous respiratory-competent mitochondria can restore overall tissue bioenergetics. New Method—We optimized techniques in vitro to prepare suspensions of isolated mitochondria for transplantation in vivo. Mitochondria isolated from cell culture were genetically labeled with turbo-green fluorescent protein (tGFP) for imaging and tracking purposes in vitro and in vivo. Results—We used time-lapse confocal imaging to reveal the incorporation of exogenous fluorescently-tagged mitochondria into PC-12 cells after brief co-incubation. Further, we show that mitochondria can be injected into the spinal cord with immunohistochemical evidence of host cellular uptake within 24 hours. Comparison to Existing Methods—Our methods utilize transgenic fluorescent labeling of mitochondria for a nontoxic and photostable alternative to other labeling methods. Substrate addition to isolated mitochondria helped to restore state III respiration at room temperature prior to transplantation. These experiments delineate refined methods to use transgenic cell lines for the purpose of isolating well coupled mitochondria that have a permanent fluorescent label that allows real time tracking of transplanted mitochondria in vitro, as well as imaging in situ. Conclusions—These techniques lay the foundation for testing the potential therapeutic effects of mitochondrial transplantation following spinal cord injury and other animal models of neurotrauma

Real-world clinical experience in the Connect® chronic lymphocytic leukaemia registry: a prospective cohort study of 1494 patients across 199 US centres.

The clinical course of chronic lymphocytic leukaemia (CLL) is heterogeneous, and treatment options vary considerably. The Connect® CLL registry is a multicentre, prospective observational cohort study that provides a real-world perspective on the management of, and outcomes for, patients with CLL. Between 2010 and 2014, 1494 patients with CLL and that initiated therapy, were enrolled from 199 centres throughout the USA (179 community-, 17 academic-, and 3 government-based centres). Patients were grouped by line of therapy at enrolment (LOT). We describe the clinical and demographic characteristics of, and practice patterns for, patients with CLL enrolled in this treatment registry, providing patient-level observational data that represent real-world experiences in the USA. Fluorescence in situ hybridization (FISH) analyses were performed on 49·3% of patients at enrolment. The most common genetic abnormalities detected by FISH were del(13q) and trisomy 12 (45·7% and 20·8%, respectively). Differences in disease characteristics and comorbidities were observed between patients enrolled in LOT1 and combined LOT2/≥3 cohorts. Important trends observed include the infrequent use of genetic prognostic testing, and differences in patient characteristics for patients receiving chemoimmunotherapy combinations. These data represent experiences of patients with CLL in the USA, which may inform treatment decisions in everyday practice

Pion-nucleus elastic scattering on 12C, 40Ca, 90Zr, and 208Pb at 400 and 500 MeV

Pion-nucleus elastic scattering at energies above the Delta(1232) resonance is studied using both pi+ and pi- beams on 12C, 40Ca, 90Zr, and 208Pb. The present data provide an opportunity to study the interaction of pions with nuclei at energies where second-order corrections to impulse approximation calculations should be small. The results are compared with other data sets at similar energies, and with four different first-order impulse approximation calculations. Significant disagreement exists between the calculations and the data from this experiment

Factors affecting outcomes of open surgical repair of pararenal aortic aneurysms: A 10-year experience

PurposeFew large series document surgical outcomes for patients with pararenal abdominal aortic aneurysms (PAAAs), defined as aneurysms including the juxtarenal aorta or renal artery origins that require suprarenal aortic clamping. No standard endovascular alternatives presently exist; however, future endovascular branch graft repairs ultimately must be compared with the gold standard of open repair. To this end, we present a 10-year experience.MethodsBetween 1993 and 2003, 3058 AAAs were repaired. Perioperative variables, morbidity, and mortality were retrospectively assessed. Renal insufficiency was defined as a rise in the concentration of serum creatinine by ≥0.5 mg/dL. Factors predicting complications were identified by multivariate analyses. Morbidity and 30-day mortality were evaluated with multiple logistic regression analysis.ResultsOf a total of 3058 AAA repairs performed, 247 were PAAAs (8%). Mean renal ischemia time was 23 minutes (range, 5 to 60 minutes). Cardiac complications occurred in 32 patients (13%), pulmonary complications in 38 (16%), and renal insufficiency in 54 (22%). Multivariate analysis associated myocardial infarction with advanced age (P = .01) and abnormal preoperative serum creatinine (>1.5 mg/dL) (P = .08). Pulmonary complications were associated with advanced age (P = .03), renal artery bypass (P = .02), increased mesenteric ischemic time (P = .01), suprarenal aneurysm repair (P < .0008), and left renal vein division (P = .01). Renal insufficiency was associated with increased mesenteric ischemic time (P = .001), supravisceral clamping (P = .04), left renal vein division (P = .04), and renal artery bypass (P = .0002), but not renal artery reimplantation or endarterectomy. New dialysis was required in 3.7% (9/242). Abnormal preoperative serum creatinine (>1.5 mg/dL) was predictive of the need for postoperative dialysis (10% vs 2%; P = .04). Patients with normal preoperative renal function had improved recovery (93% vs 36%; P = .0002). The 30-day surgical mortality was 2.5% (6/247) but was not predicted by any factors, and in-hospital mortality was 2.8% (7/247). Median intensive care and hospital stays were 3 and 9 days, respectively, and longer stays were associated with age at surgery (P = .007 and P = .0002, respectively) and any postoperative complication.ConclusionsPAAA repair can be performed with low mortality. Renal insufficiency is the most frequent complication, but avoiding renal artery bypass, prolonged mesenteric ischemia time, or left renal vein transection may improve results

Occurrence and mechanisms of formation of a dramatic thin layer of marine snow in a shallow Pacific fjord

Huge accumulations of diatom-dominated marine snow (aggregates \u3e0.5 mm in diameter) were observed in a layer approximately 50 cm thick persisting over a 24 h period in a shallow fjord in the San Juan Islands, Washington, USA. The layer was associated with the 22.4 σt density surface. A second thin layer of elevated phytoplankton concentration located at a density discontinuity 1.5 to 2 m above the marine snow layer occurred within a dense diatom bloom near the surface. At the end of the study period, isopycnals shoaled and the 2 layers merged. More than 80% of the diatom bloom consisted of Thalassiosira spp. (50 to 59%), Odontella longicruris (5 to 14%), Asterionellopsis glacialis, and Thalassionema nitzschioides. A much higher proportion of O. longicruris occurred in marine snow (about 53%) than among suspended cells suggesting that this species differentially aggregated. Most zooplankton avoided the mucus-rich aggregate layer. The layer of marine snow was formed when sinking aggregated diatoms reached neutral buoyancy at the 22.4 isopycnal, probably due to the presence of low salinity mucus resistant to salt exchange in the interstices of the aggregates. Rates of turbulent kinetic energy dissipation throughout the water column rarely exceeded 10-8 m2 s-3 and aggregates below the thin layer were largely detrital in composition indicating that small-scale shears due to turbulence did not erode the layer of marine snow. The accumulation of marine snow and phytoplankton in persistent, discrete layers at density discontinuities results in habitat partitioning of the pelagic zone, impacts the distribution and interactions of planktonic organisms as well as the intensity and location of biological processes in the water column, and helps maintain species diversity