Evaluating Process Improvement Courses of Action Through Modeling and Simulation

Quantifying an expected improvement when considering moderate-complexity changes to a process is time consuming and has potential to overlook stochastic effects. By modeling a process as a Numerical Design Structure Matrix (NDSM), simulating the proposed changes, and evaluating performance, quantification can be rapidly accomplished to understand stochastic effects. This thesis explores a method to evaluate complex process changes within Six Sigma DMAIC process improvement to identify the most desirable outcome amongst several improvement options. A tool to perform the modeling and evaluation is developed. This process evaluation tool is verified for functionality, then is demonstrated against generic processes, a case study, and a real world Continuous Process Improvement event. The application of modeling and simulation to improve and control a process is found to be a positive return on investment under moderate complexity or continuous improvement events. The process evaluation tool is demonstrated to be accurate in prediction, scalable in complexity and fidelity, and capable of simulating a wide variety or evaluation types. Experimentation identifies the importance of understanding the evaluation criteria prior to “Measurement” in DMAIC, which increases the consistency of process improvement efforts

Purification and Partial Characterization of Relaxin and Relaxin Precursors from the Hamster Placenta

Previous immunological studies have indicated that the molecular structure of hamster relaxin is quite different from that of porcine relaxin. In the present study, hamster relaxin was purified from placentas and characterized in order to investigate its biochemical properties. Placentas from Days 14 and 15 of gestation were homogenized in 0.26 N HCl-62.5% acetone containing protease inhibitors. After centrifugation, soluble proteins were acetone precipitated. Soluble proteins were applied to a carboxymethyl cellulose ion-exchange column and bound proteins were eluted with 0.1 and 0.3 M NaCl. Western blot analysis detected 16.5-, 18.7-, and 36.0-kDa relaxin-immunoreactive (IR) proteins within the 0.1 M NaCl eluant and detected a 5.6-kDa relaxin-IR protein within the 0.3 M NaCl eluant. The 5.6-kDa protein was purified to homogeneity by gel filtration (Sephadex G-50), ion-exchange HPLC, and C18 -HPLC. Reduction of the 5.6-kDa protein prior to electrophoresis resulted in a single band of lower molecular mass, suggesting that hamster relaxin consists of two chains of approximately equal molecular mass. Isoelectric point of the 5.6-kDa protein was 7.78. The 16.5- and 18.7-kDa IR proteins were copurified by gel filtration and ion-exchange HPLC. At least five isoelectric point variants were observed for the 16.5- and 18.7-kDa proteins. The N-terminal amino acid for the 5.6 and 18.7 relaxin-IR proteins was arginine, and subsequent cycles indicated an identical partial sequence that was consistent with that for relaxins from other species. Originally published Biology of Reproduction, Vol. 49, No. 1, July 199

Evidence for a Molecular Cloud Origin for Gamma-Ray Bursts: Implications for the Nature of Star Formation in the Universe

It appears that the majority of rapidly-, well-localized gamma-ray bursts with undetected, or dark, optical afterglows, or `dark bursts' for short, occur in clouds of size R > 10L_{49}^{1/2} pc and mass M > 3x10^5L_{49} M_{sun}, where L is the isotropic-equivalent peak luminosity of the optical flash. We show that clouds of this size and mass cannot be modeled as a gas that is bound by pressure equilibrium with a warm or hot phase of the interstellar medium (i.e., a diffuse cloud): Such a cloud would be unstable to gravitational collapse, resulting in the collapse and fragmentation of the cloud until a burst of star formation re-establishes pressure equilibrium within the fragments, and the fragments are bound by self-gravity (i.e., a molecular cloud). Consequently, dark bursts probably occur in molecular clouds, in which case dark bursts are probably a byproduct of this burst of star formation if the molecular cloud formed recently, and/or the result of lingering or latter generation star formation if the molecular cloud formed some time ago. We then show that if bursts occur in Galactic-like molecular clouds, the column densities of which might be universal, the number of dark bursts can be comparable to the number of bursts with detected optical afterglows: This is what is observed, which suggests that the bursts with detected optical afterglows might also occur in molecular clouds. We confirm this by modeling and constraining the distribution of column densities, measured from absorption of the X-ray afterglow, of the bursts with detected optical afterglows: We find that this distribution is consistent with the expectation for bursts that occur in molecular clouds, and is not consistent with the expectation for bursts that occur in diffuse clouds. More...Comment: Accepted to The Astrophysical Journal, 22 pages, 6 figures, LaTe

Unmanned Aircraft Systems (UAS) Traffic Management (UTM) National Campaign II

The Unmanned Aircraft System (UAS) Traffic Management (UTM) effort at NASA aims to enable access to low-altitude airspace for small UAS. This goal is being pursued partly through partnerships that NASA has developed with the UAS stakeholder community, the FAA, other government agencies, and the designated FAA UAS Test Sites. By partnering with the FAA UAS Test Sites, NASA's UTM project has performed a geographically diverse, simultaneous set of UAS operations at locations in six states. The demonstrations used an architecture that was developed by NASA in partnership with the FAA to safely coordinate such operations. These demonstrations-the second or 'Technical Capability Level (TCL 2)' National Campaign of UTM testing-was performed from May 15 through June 9, 2017. Multiple UAS operations occurred during the testing at sites located in Alaska, Nevada, Texas, North Dakota, Virginia, and New York with multiple organizations serving as UAS Service Suppliers and/or UAS Operators per the specifications provided by NASA. By engaging various members of the UAS community in development and operational roles, this campaign provided initial validation of different aspects of the UTM concept including: UAS Service Supplier technologies and procedures; geofencing technologies/conformance monitoring; ground-based surveillance/sense and avoid; airborne sense and avoid; communication, navigation, surveillance; and human factors related to UTM data creation and display. Additionally, measures of performance were defined and calculated from the flight data to establish quantitative bases for comparing flight test activities and to provide potential metrics that might be routinely monitored in future operational UTM systems

Stochastic Model of Tsc1 Lesions in Mouse Brain

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder due to mutations in either TSC1 or TSC2 that affects many organs with hamartomas and tumors. TSC-associated brain lesions include subependymal nodules, subependymal giant cell astrocytomas and tubers. Neurologic manifestations in TSC comprise a high frequency of mental retardation and developmental disorders including autism, as well as epilepsy. Here, we describe a new mouse model of TSC brain lesions in which complete loss of Tsc1 is achieved in multiple brain cell types in a stochastic pattern. Injection of an adeno-associated virus vector encoding Cre recombinase into the cerebral ventricles of mice homozygous for a Tsc1 conditional allele on the day of birth led to reduced survival, and pathologic findings of enlarged neurons, cortical heterotopias, subependymal nodules, and hydrocephalus. The severity of clinical and pathologic findings as well as survival was shown to be dependent upon the dose and serotype of Cre virus injected. Although several other models of TSC brain disease exist, this model is unique in that the pathology reflects a variety of TSC-associated lesions involving different numbers and types of cells. This model provides a valuable and unique addition for therapeutic assessment

Tethered Satellites as an Enabling Platform for Operational Space Weather Monitoring Systems

Tethered satellites offer the potential to be an important enabling technology to support operational space weather monitoring systems. Space weather "nowcasting" and forecasting models rely on assimilation of near-real-time (NRT) space environment data to provide warnings for storm events and deleterious effects on the global societal infrastructure. Typically, these models are initialized by a climatological model to provide "most probable distributions" of environmental parameters as a function of time and space. The process of NRT data assimilation gently pulls the climate model closer toward the observed state (e.g., via Kalman smoothing) for nowcasting, and forecasting is achieved through a set of iterative semi-empirical physics-based forward-prediction calculations. Many challenges are associated with the development of an operational system, from the top-level architecture (e.g., the required space weather observatories to meet the spatial and temporal requirements of these models) down to the individual instruments capable of making the NRT measurements. This study focuses on the latter challenge: we present some examples of how tethered satellites (from 100s of m to 20 km) are uniquely suited to address certain shortfalls in our ability to measure critical environmental parameters necessary to drive these space weather models. Examples include long baseline electric field measurements, magnetized ionospheric conductivity measurements, and the ability to separate temporal from spatial irregularities in environmental parameters. Tethered satellite functional requirements are presented for two examples of space environment observables

Thrombin promotes diet-induced obesity through fibrin-driven inflammation

Obesity promotes a chronic inflammatory and hypercoagulable state that drives cardiovascular disease, type 2 diabetes, fatty liver disease, and several cancers. Elevated thrombin activity underlies obesity-linked thromboembolic events, but the mechanistic links between the thrombin/fibrin(ogen) axis and obesity-associated pathologies are incompletely understood. In this work, immunohistochemical studies identified extravascular fibrin deposits within white adipose tissue and liver as distinct features of mice fed a high-fat diet (HFD) as well as obese patients. Fibγ390–396A mice carrying a mutant form of fibrinogen incapable of binding leukocyte αMβ2-integrin were protected from HFD-induced weight gain and elevated adiposity. Fibγ390–396A mice had markedly diminished systemic, adipose, and hepatic inflammation with reduced macrophage counts within white adipose tissue, as well as near-complete protection from development of fatty liver disease and glucose dysmetabolism. Homozygous thrombomodulin-mutant ThbdPro mice, which have elevated thrombin procoagulant function, gained more weight and developed exacerbated fatty liver disease when fed a HFD compared with WT mice. In contrast, treatment with dabigatran, a direct thrombin inhibitor, limited HFD-induced obesity development and suppressed progression of sequelae in mice with established obesity. Collectively, these data provide proof of concept that targeting thrombin or fibrin(ogen) may limit pathologies in obese patients

International criteria for electrocardiographic interpretation in athletes: Consensus statement.

Sudden cardiac death (SCD) is the leading cause of mortality in athletes during sport. A variety of mostly hereditary, structural or electrical cardiac disorders are associated with SCD in young athletes, the majority of which can be identified or suggested by abnormalities on a resting 12-lead electrocardiogram (ECG). Whether used for diagnostic or screening purposes, physicians responsible for the cardiovascular care of athletes should be knowledgeable and competent in ECG interpretation in athletes. However, in most countries a shortage of physician expertise limits wider application of the ECG in the care of the athlete. A critical need exists for physician education in modern ECG interpretation that distinguishes normal physiological adaptations in athletes from distinctly abnormal findings suggestive of underlying pathology. Since the original 2010 European Society of Cardiology recommendations for ECG interpretation in athletes, ECG standards have evolved quickly, advanced by a growing body of scientific data and investigations that both examine proposed criteria sets and establish new evidence to guide refinements. On 26-27 February 2015, an international group of experts in sports cardiology, inherited cardiac disease, and sports medicine convened in Seattle, Washington (USA), to update contemporary standards for ECG interpretation in athletes. The objective of the meeting was to define and revise ECG interpretation standards based on new and emerging research and to develop a clear guide to the proper evaluation of ECG abnormalities in athletes. This statement represents an international consensus for ECG interpretation in athletes and provides expert opinion-based recommendations linking specific ECG abnormalities and the secondary evaluation for conditions associated with SCD

Prime movers : mechanochemistry of mitotic kinesins

Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation