Outburst Flooding Under Ice Sheets as Turbulently Driven Hydraulic Fracture

Earth and Planetary SciencesEngineering and Applied Science

Study of Acoustic Emisison Characteristics for Fracture Assessment

Inspection for structural integrity of the Space Shuttle Solid Rocket Boosters (SRBs) is of paramount importance to mission safety. After every shuttle launch, the booster rockets are retrieved and an extensive inspection operation performed to detect any mission-related anomaly. If damage occurs to the structure during shuttle mission, Acoustic Emission (AE) from cracks could be monitored and used as a means for initial screening to identify potential damage locations for selective postlaunch inspection

Unanticipated differences between α- and γ-diaminobutyric acid-linked hairpin polyamide-alkylator conjugates

Hairpin polyamide–chlorambucil conjugates containing an {alpha}-diaminobutyric acid ({alpha}-DABA) turn moiety are compared to their constitutional isomers containing the well-characterized {gamma}-DABA turn. Although the DNA-binding properties of unconjugated polyamides are similar, the {alpha}-DABA conjugates display increased alkylation specificity and decreased rate of reaction. Treatment of a human colon carcinoma cell line with {alpha}-DABA versus {gamma}-DABA hairpin conjugates shows only slight differences in toxicities while producing similar effects on cell morphology and G2/M stage cell cycle arrest. However, striking differences in animal toxicity between the two classes are observed. Although mice treated with an {alpha}-DABA hairpin polyamide do not differ significantly from control mice, the analogous {gamma}-DABA hairpin is lethal. This dramatic difference from a subtle structural change would not have been predicted

Latanoprost with high precision, piezo-print microdose delivery for IOP lowering: clinical results of the PG21 study of 0.4 µg daily microdose.

Background:Topical high-precision piezo-print delivery of microdoses of latanoprost achieved significant IOP reduction consistent with the eyedropper effect but with a 75% reduced exposure to drugs and preservatives. Prostaglandin analogs are a mainstay glaucoma therapy. However, conventional eyedroppers deliver 30-50 µL drops that greatly exceed the physiologic 7-µL ocular tear film capacity. Eyedropper overdosing floods the eye with excess drug compounds and preservatives, resulting in ocular surface toxicity, periorbitopathy, and other well-characterized ocular side effects. Piezoelectric high-precision microdosing provides targeted delivery that can reduce exposure to both drug and preservatives compared to conventional eyedropper delivery, with the potential to deliver similar biologic effect. Methods:Both eyes (N=60) of 30 healthy volunteers received single 8-µL microdoses of 0.005% latanoprost (0.4 µg; µRx-latanoprost) on the morning of Days 1 and 2 using a high-precision, piezo-print horizontal delivery system. Diurnal IOP was measured before and 2 days after microdosing. Main efficacy outcomes were diurnal IOP change after µRx-latanoprost microdosing and accurate microdosing success rates, and the primary safety outcome was adverse event (AE) incidence. Results:µRx-latanoprost reduced baseline IOP by 26% and 30% at 1 and 2 days postadministration, respectively. Successful topical dosing was achieved in 100% of technician-assisted deliveries. All patients successfully self-administered microdoses after receiving training. Microdose administration was well tolerated and did not result in any AEs. Conclusion:Microdosing of 0.4 µg of µRx-latanoprost achieved significant IOP reduction. Lower ocular exposure with topical prostaglandin analog microdosing can enable new therapeutic opportunities for optimizing glaucoma treatment. Microdosing may also be beneficial in reducing ocular side effects associated with excessive drug product and preservatives often used to treat chronic ocular diseases such as glaucoma

Possible Mechanisms for Glacial Earthquakes

The large glacial earthquakes reported on by Ekström et al. (2003, 2006) and Tsai and Ekström (2007) have previously been evaluated in terms of their seismic characteristics. In this paper we attempt to take constraints such as known glacial ice properties, outlet glacier size, calving style, and meltwater variability to construct a self-consistent physical model of the glacial earthquake process. Since many glaciological parameters are poorly constrained, we parameterize a number of important processes and estimate a wide range of possible values for some properties. The range of model outputs is thus fairly large, but it is still difficult to match observational constraints under most conditions. We find that only a small class of models is able to satisfy the major observational constraints. These models are characterized by (1) lost basal resistance coupled to viscoelastic deformation with extensive internal crevassing or with low effective elastic modulus and possibly low effective viscosity or (2) by nonequilibrium calving, such as having large icebergs capsize into the glacier front. Although observational constraints cannot definitively rule out any of the proposed classes of mechanisms, the calving model has much stronger support. Fortunately, the various models make different predictions regarding observables that can potentially be measured in the near future.Earth and Planetary SciencesEngineering and Applied Science

Time Scale for Rapid Draining of a Surficial Lake Into the Greenland Ice Sheet

A 2008 report by Das et al. documented the rapid drainage during summer 2006 of a supraglacial lake, of approximately 44×10^6 m^3, into the Greenland ice sheet over a time scale moderately longer than 1 hr. The lake had been instrumented to record the time-dependent fall of water level and the uplift of the ice nearby. Liquid water, denser than ice, was presumed to have descended through the sheet along a crevasse system and spread along the bed as a hydraulic facture. The event led two of the present authors to initiate modeling studies on such natural hydraulic fractures. Building on results of those studies, we attempt to better explain the time evolution of such a drainage event. We find that the estimated time has a strong dependence on how much a pre-existing crack/crevasse system, acting as a feeder channel to the bed, has opened by slow creep prior to the time at which a basal hydraulic fracture nucleates. We quantify the process and identify appropriate parameter ranges, particularly of the average temperature of the ice beneath the lake (important for the slow creep opening of the crevasse). We show that average ice temperatures 5–7  °C below melting allow such rapid drainage on a time scale which agrees well with the 2006 observations

Fully Mediated Effects of Formative Measures Using MIMIC Constructs

Formatively-measured constructs are increasingly applied in information system research models.Recent work shows that exogenous formatively-measured constructs suffer from a number of problems that include interpretational confounding and a lack of external consistency. Yet replacement by reflectively-measured constructs can lead to bias if not theoretically appropriate. One solution may be to use a MIMIC construct composed of the formative measures as well as two additional reflective measures. A simulation study indicates that a MIMIC so composed mitigates the problems of interpretational confounding and poor external consistency allowing use broader use in a variety of structural models. Available at: https://aisel.aisnet.org/pajais/vol4/iss2/2

Single-cell zeroth-order protein degradation enhances the robustness of synthetic oscillator

In Escherichia coli, protein degradation in synthetic circuits is commonly achieved by the ssrA-tagged degradation system. In this work, we show that the degradation kinetics for the green fluorescent protein fused with the native ssrA tag in each cell exhibits the zeroth-order limit of the Michaelis–Menten kinetics, rather than the commonly assumed first-order. When measured in a population, the wide distribution of protein levels in the cells distorts the true kinetics and results in a first-order protein degradation kinetics as a population average. Using the synthetic gene-metabolic oscillator constructed previously, we demonstrated theoretically that the zeroth-order kinetics significantly enlarges the parameter space for oscillation and thus enhances the robustness of the design under parametric uncertainty

Modeling Turbulent Hydraulic Fracture Near a Free Surface

Motivated by observations of the subglacial drainage of water, we consider a hydraulic fracture problem in which the crack grows parallel to a free surface, subject to fully turbulent fluid flow. Using a hybrid Chebyshev/series-minimization numerical approach, we solve for the pressure profile, crack opening displacement, and crack growth rate for a crack that begins relatively short but eventually becomes long compared with the distance to the free surface. We plot nondimensionalized results for a variety of different times, corresponding with different fracture lengths, and find substantial differences when free-surface effects are important

Meeting the Emerging Public Health Needs of Persons With Blood Disorders

In its decades-long history, the Division of Blood Disorders (DBD) at CDC has evolved from a patient-focused, services-supporting entity at inception, to one of the world leaders in the practice of public health to improve the lives of people at risk for or affected by nonmalignant blood disorders. The DBD’s earliest public health activities consisted of working with care providers in a network of hemophilia treatment centers to provide AIDS risk reduction services to people with hemophilia. Because this infectious disease threat has been reduced over time as a result of the development of safer treatment products, the DBD—under the auspices of congressional appropriations guidance—has expanded its core activities to encompass blood disorders other than hemophilia, including hemoglobinopathies such as thalassemia and sickle cell disease, and Diamond Blackfan anemia. Simultaneously, in transitioning to a greater public health role, the DBD has expanded its network of partners to new consumer and professional organizations, as well as state and other federal health agencies. The DBD has also developed and maintains many surveillance and registry activities beyond the Universal Data Collection system aimed at providing a better understanding of the health status, health needs, and health-related quality of life of people with nonmalignant blood disorders. The DBD has integrated applicable components of the Essential Services of Public Health successfully to promote and advance the agenda of blood disorders in public health