Quantifying the stratigraphic completeness of delta shoreline trajectories

Understanding the incomplete nature of the stratigraphic record is fundamental for interpreting stratigraphic sequences. Methods for quantifying stratigraphic completeness for one-dimensional stratigraphic columns, defined as the proportion of time intervals of some length that contain stratigraphy, are commonplace; however, quantitative assessments of completeness in higher dimensions are lacking. Here we present a metric for defining stratigraphic completeness of two-dimensional shoreline trajectories using topset-foreset rollover positions in dip-parallel sections and describe the preservation potential of a shoreline trajectory derived from the geometry of the delta surface profile and the kinematics of the geomorphic shoreline trajectory. Two end-member forward models are required to fully constrain the preservation potential of the shoreline dependent on whether or not a topset is eroded during base level fall. A laboratory fan-delta was constructed under nonsteady boundary conditions, and one-dimensional stratigraphic column and two-dimensional shoreline completeness curves were calculated. Results are consistent with the hypothesis derived from conservation of sediment mass that completeness over all timescales should increase given increasing dimensions of analysis. Stratigraphic trajectories and completeness curves determined from forward models using experimental geomorphic trajectories compare well to values from transects when subsampled to the equivalent stratigraphic resolution as observed in the actual preserved sequence. The concept of stratigraphic completeness applied to two-dimensional trajectory analysis and the end-member forward models presented here provide novel tools for a conceptual understanding of the nature of stratigraphic preservation at basin scales

Space Station Engineering Design Issues

Space Station Freedom topics addressed include: general design issues; issues related to utilization and operations; issues related to systems requirements and design; and management issues relevant to design

Elucidating the functions of fibroblast growth factor 9 in multiple sclerosis

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system. In around 85% of cases, the disease progresses through two distinct stages: relapsing-remitting MS (RRMS) is driven by repeated bouts of demyelination caused by autoimmune inflammation; and progressive MS, in which inflammation gives way to neurodegenerative processes that lead to axonal loss and the steady accumulation of disability. There is no cure for MS and the majority of disease-slowing treatments target the immune response in RRMS. These interventions are ineffective in progressive MS and other treatment options are extremely limited. Understanding the mechanisms underlying neurodegeneration in MS is critically important to developing therapeutics for progressive disease. Fibroblast growth factor 9 (FGF9) has recently been implicated in the pathogenesis of MS. FGF9 inhibits myelination and promotes the production of inflammatory chemokines. This led to the hypothesis that FGF9 is involved in remyelination failure and may promote neurodegeneration via tissue remodelling and inflammatory pathways. FGF signaling is complex and the findings in MS raised many questions: what cells respond to FGF9 in MS? Why is FGF9 expression induced in the first place? Can FGF9 cause demyelination as well as inhibit myelination? This thesis has focused on the roles of FGF9 in MS and tried to answer these questions. Through in vitro models, astrocytes, oligodendrocytes, and macrophages were shown to express feedback inhibitors of FGF signaling when treated with FGF9. Astrocytes produced FGF9 in response to hypoxic stress, macrophages expressed FGF9 when polarized towards an anti-inflammatory phenotype, suggesting hypoxia, and repair processes may drive FGF9 expression in the CNS. FGF9 did not cause demyelination in vitro but over-expression in vivo induced severe demyelination over the course of several months. Oligodendrocytes exposed to FGF9 failed to differentiate properly when the factor was removed which led to aberrant myelination. Long-term treatment with FGF9 induced axonal pathology, potentially via deficits in axon-transport. Over-expression of FGF9 in rat cortex also produced an axonal pathology, which suggests chronic exposure is detrimental to neurons. Together, these findings indicate that increased levels of FGF9 are detrimental to myelination and neurons in the CNS. Demyelination, and axonal pathology are hallmarks of MS and these studies provide evidence that FGF9 can mediate these processes in in vitro and in vivo models

Fibroblast growth factor signalling in multiple sclerosis: inhibition of myelination and induction of pro-inflammatory environment by FGF9

The failure of remyelination in multiple sclerosis is largely unexplained. Lindner et al. report that glial cells in demyelinating lesions show increased expression of fibroblast growth factor 9 (FGF9). This induces astrocyte-dependent responses that inhibit remyelination and stimulate expression of pro-inflammatory chemokines, supporting a feedback loop that amplifies disease activit

Discovery of a Novel Class of Orally Active Trypanocidal N-Myristoyltransferase Inhibitors

N-Myristoyltransferase (NMT) represents a promising drug target for human African trypanosomiasis (HAT), which is caused by the parasitic protozoa Trypanosoma brucei. We report the optimization of a high throughput screening hit (1) to give a lead molecule DDD85646 (63), which has potent activity against the enzyme (IC50 = 2 nM) and T. brucei (EC50 = 2 nM) in culture. The compound has good oral pharmacokinetics and cures rodent models of peripheral HAT infection. This compound provides an excellent tool for validation of T. brucei NMT as a drug target for HAT as well as a valuable lead for further optimization.</p

A State University’s Assessment of ACUE: Feasible Model for Evaluating the Impact of a Faculty Instruction Quality Program

State comprehensive universities often stress the development of teaching quality to improve the outcomes and retention of students, especially for recently matriculated students. These universities invest in teaching quality programs, but often lack a feasible method to examine the longitudinal impacts of these programs. The purpose of this paper is to provide a model for universities to evaluate outcomes related teaching quality programs. ACUE, a teaching quality program, was implemented across 30 instructors, which equated to 463 course sections. ACUE instructors were matched to non-ACUE instructors using propensity score matching (PSM) and compared on the rate of end-of-the-semester students with DFW (underperformance) standing across course sections. PSM was based on if courses were honors sections, lower level classes, size of enrollment in the sections, and if the section occurred after the completion of the program. DFW rate is a parsimonious metric that predict retention. The ACUE recipients had an average treatment effect of -.37, or 3.7% fewer students receiving a DFW. That translated to 171 fewer DFW grades. Implications include that the use of PSM and DFW rates could help universities examine longitudinal outcomes for teaching quality programs. Given the financial and personnel resources needed for program like ACUE, comprehensive regional universities could use similar methods to determine if the investment yields satisfactory returns

Performance of Foundations and Retaining Structures

The design, construction, and performance of several building foundations and temporary earth retaining structures located in the downtown area of White Plains, New York are presented in this paper. High rise structures were supported on shallow mat or spread foundations bearing on erratic saturated alluvial silt and sand deposits. Additionally, the construction of two and three level underground parking structures required the use of cantilevered and braced excavation support systems to retain the adjacent streets and utilities. Several assumptions were required to design and predict the performance of the building foundations and retaining structures. The accuracy of these assumptions was verified through the use of precise field measurements during and after construction. The results of these field measurements and comparison with predicted values are presented and discussed

Methanol along the path from envelope to protoplanetary disc

Interstellar methanol is considered to be a parent species of larger, more complex organic molecules. A physicochemical simulation of infalling parcels of matter is performed for a low-mass star-forming system to trace the chemical evolution from cloud to disc. An axisymmetric 2D semi-analytic model generates the time-dependent density and velocity distributions, and full continuum radiative transfer is performed to calculate the dust temperature and the UV radiation field at each position as a function of time. A comprehensive gas–grain chemical network is employed to compute the chemical abundances along infall trajectories. Two physical scenarios are studied, one in which the dominant disc growth mechanism is viscous spreading, and another in which continuous infall of matter prevails. The results show that the infall path influences the abundance of methanol entering each type of disc, ranging from complete loss of methanol to an enhancement by a factor of >1 relative to the prestellar phase. Critical chemical processes and parameters for the methanol chemistry under different physical conditions are identified. The exact abundance and distribution of methanol is important for the budget of complex organic molecules in discs, which will be incorporated into forming planetary system objects such as protoplanets and comets. These simulations show that the comet-forming zone contains less methanol than in the precollapse phase, which is dominantly of prestellar origin, but also with additional layers built up in the envelope during infall. Such intriguing links will soon be tested by upcoming data from the Rosetta mission

Cardiac Tamponade: Innovative Sternotomy Simulation Model for Training Pediatric Cardiac Intensive Care Team

Introduction: Cardiac tamponade occurring after cardiac surgery is rare but life threatening and requires simultaneous resuscitation and emergent sternotomy by the intensive care team. A simulated scenario using innovative mannequin with sternotomy wound has the capability of reproducing cardiac arrest associated with postoperative tamponade. We evaluated the face validity of this innovative mannequin, the confidence level and crisis resource management skills of the team during sternotomy to manage postoperative cardiac tamponade. Methods: The simulation case scenario was developed using innovative sternotomy mannequin for children’s hospital cardiac intensive care unit (CICU) teams. The case involved a 3-year old male, intubated, mechanically ventilated after surgical repair of CHD, progressing to cardiac arrest due to cardiac tamponade. We conducted a structured, video debriefing following each scenario. We conducted a formative learner assessment before and after each scenario and analyzed the data using student t-test. Results: Of the 72 CICU providers, a statistically significant proportion of providers (p \u3c 0.0001) showed improved confidence in assessing and managing cardiac arrest occurring following postoperative cardiac tamponade. All the providers scored ≥ 3 for impact of the scenario on practice, teamwork, communication, assessment skills, improvement in CPR and opening the chest and their confidence in attending similar clinical situation in future. Most (96–100%) scored ≥ 3 for perception on realism of mannequin, the scenario, re-opening the sternotomy and level of stress. Conclusions: Innovative adaptation of a high-fidelity mannequin for cardiac tamponade simulation can achieve a realistic and reproducible training model with a positive impact on multi-disciplinary team training