Exploring the origins of topological frustration: Design of a minimally frustrated model of fragment B of protein A

Topological frustration in an energetically unfrustrated off-lattice model of the helical protein fragment B of protein A from Staphylococcus aureus was investigated. This Gō-type model exhibited thermodynamic and kinetic signatures of a well-designed two-state folder with concurrent collapse and folding transitions and single exponential kinetics at the transition temperature. Topological frustration is determined in the absence of energetic frustration by the distribution of Fersht φ values. Topologically unfrustrated systems present a unimodal distribution sharply peaked at intermediate φ, whereas highly frustrated systems display a bimodal distribution peaked at low and high φ values. The distribution of φ values in protein A was determined both thermodynamically and kinetically. Both methods yielded a unimodal distribution centered at φ = 0.3 with tails extending to low and high φ values, indicating the presence of a small amount of topological frustration. The contacts with high φ values were located in the turn regions between helices I and II and II and III, intimating that these hairpins are in large part required in the transition state. Our results are in good agreement with all-atom simulations of protein A, as well as lattice simulations of a three- letter code 27-mer (which can be compared with a 60-residue helical protein). The relatively broad unimodal distribution of φ values obtained from the all-atom simulations and that from the minimalist model for the same native fold suggest that the structure of the transition state ensemble is determined mostly by the protein topology and not energetic frustration.

Increased levels of plasma lysosomal enzymes in patients with Lowe syndrome

Lowe syndrome is an X-linked disorder that has a complex phenotype that includes progressive renal failure and blindness. The disease is caused by mutations in an inositol polyphosphate 5-phosphatase designated OCRL. It has been shown that the OCRL protein is found on the surface of lysosomes and that a renal tubular cell line deficient in OCRL accumulated substrate phosphatidylinositol 4,5-bisphosphate. Because this lipid is required for vesicle trafficking from lysosomes, we postulate that there is a defect in lysosomal enzyme trafficking in patients with Lowe syndrome that leads to increased extracellular lysosomal enzymes and might lead to tissue damage and contribute to the pathogenesis of the disease. We have measured seven lysosomal enzymes in the plasma of 15 patients with Lowe syndrome and 15 age-matched male controls. We find a 1.6- to 2.0-fold increase in all of the enzymes measured. When the data was analyzed by quintiles of activity for all of the enzymes, we found that 95% of values in the lowest quintile come from normal subjects whereas in the highest quintile 85% of the values are from patients with Lowe syndrome. The increased enzyme levels are not attributable to renal insufficiency because there was no difference in enzyme activity in the four patients with the highest creatinine levels compared with the six patients with the lowest creatinine values.

An equilibrium statistical model for the spreading phase of open-ocean convection

A “most probable state” equilibrium statistical theory for random distributions of hetons in a closed basin is developed here in the context of two-layer quasigeostrophic models for the spreading phase of open-ocean convection. The theory depends only on bulk conserved quantities such as energy, circulation, and the range of values of potential vorticity in each layer. The simplest theory is formulated for a uniform cooling event over the entire basin that triggers a homogeneous random distribution of convective towers. For a small Rossby deformation radius typical for open-ocean convection sites, the most probable states that arise from this theory strongly resemble the saturated baroclinic states of the spreading phase of convection, with a stabilizing barotropic rim current and localized temperature anomaly.

Physical properties of sediment core AND-2A

Whole-core measurements of Wet Bulk Density (WBD), compressional (P)-wave velocity (Vp), and Magnetic Susceptibility were measured at a sampling interval of 1 or 2 centimetres (cm) throughout the AND-2A drill core for initial core characterisation and on-site correlation with seismic modeling to predict target-reflector depth. Measurements were made using a GEOTEK (Multi-Sensor-Core-Logger MSCL). Density and velocity standards were measured together with core runs of 3-6 metres (m) (and occasionally up to 18 m) throughout the entire depth range to monitor data quality. Drift of the magnetic susceptibility sensor was also monitored and corrected where necessary. These physical properties show a large range of values, reflecting the different nature of the various lithologies including extremely high velocity and density values in individual clasts, and the effects of cementation on porosity. A downcore increase in WBD and Vp occurs in the upper 200 m, however, no systematic trend exists at greater depths although large fluctuations on a m-decimetre- (dm) scale occur. Magnetic susceptibility is generally low (<100 x 10-5 SI), however, four intervals of high (>600 x 10-5 SI) susceptibility occur at 560, 800, 980 and 1 080 mbsf, indicating a relatively greater contribution of volcanic-derived material to the core site in the lower half of the AND-2A core.

(Table 1) Ooze/chalk cycles: frequency of occurrence at DSDP Leg 74 Sites

Shallow- to deep-water environments are represented by the sediments and rocks recovered from the Walvis Ridge- Angola Basin transect. These calcareous oozes, chalks, limestones, and volcaniclastic sedimentary rocks are used to define and correlate four lithostratigraphic units. The sediments were deposited in cycles which represent recurring tectonic or Oceanographic events and may be related to climatic fluctuations and orbital perturbations. Turbidites are the most common and easily identified sedimentary cycle. They are Late Cretaceous to Paleocene in age and are repeated in intervals ranging from thousands to tens of thousands of years. They are also found interbedded between basalt layers. Turbidites are easily distinguished from the other cycles present by their sedimentary structures, mineral composition, alteration products, and physical properties (GRAPE) data. Large-scale turbidites, debris, or slump breccias are found at or just above the Cretaceous/Tertiary boundary and indicate an event of considerable energy possibly related to intense tectonic activity. Diagenetic cycles, interpreted as small-scale dissolution cycles or sequences produced by biogenic activity, occur in early Paleocene chalks. The recurrence intervals average -20,000 y. but have a wide range of values. Variations in CaCO3 content, color, gradational boundaries, and trace fossil content characterize these sediments. These cycles reflect bottom-water conditions. Ooze-chalk cycles occur in upper Oligocene to upper Paleocene sediments and represent conditions that once existed at the sediment/water interface where they obtained their diagenetic potential. These oscillations are repeated over tens of thousands of years and may have no modern analogs. Color variations in sediments at the Cretaceous/Tertiary boundary indicate local fluctuations in oxygen content within the sediments or the water column. This situation lasted for several hundred thousand years and is not repeated elsewhere in the sequence. Large dissolution cycles are recorded in the sediments at Site 527 that are of middle Miocene and early Oligocene to middle Eocene age. During this time the seafloor at this site appears to have been located at or subsided to a depth occupied by a fluctuating CCD and lysocline.

Lithology of ODP Leg 138 holes

During Leg 138, we measured reflectance spectra in the visible and near-infrared bands (455-945 nm) every few centimeters on split core surfaces from eastern tropical Pacific Ocean sediments. Here, we evaluate predictions of the content of biogenic calcite, biogenic opal, and nonbiogenic sediments from the reflectance spectra. For Sites 844 through 847, which contain a significant nonbiogenic component, reflectance spectra yielded a useful proxy for the percentages of CaCO3 over a wide range of values from nearly 0% to 100%, with root-mean-square (RMS) errors of about 9%. Direct estimates of "nonbiogenic" sediment percentages, approximated by 100 - (CaCO3 + opal), were reasonably successful (RMS error of 10%), however, were incorrect in some intervals. This suggests that mineralogy of the nonbiogenic material changes through time and that further subdivision of this component will be needed for useful estimation from reflectance. For percentages of biogenic opal, calibration equations appear to work well (RMS error of 6%) at concentrations of less than 30%, but for higher opal concentrations, reflectance equations often underestimate the true contents of opal. Improvements in multiparameter lithologic estimates from reflectance spectra may come from (1) expanding the wavelengths measured to better capture unique mineral reflectance bands, and (2) adding the ability to measure diffuse, rather than directional, reflectance to minimize the effects of surface roughness.

National Petroleum Reserve in Alaska : 105(c) final study for the Secretary of the Interior /

Errata slip tipped in at front of v.1.

Reanalysis of wave runup on structures and beaches /

Example problems and methods of data analysis, together with general observations, are given. Smooth-slope runup results for both breaking and nonbreaking waves are presented in a set of curves similar to but revised from those in the Shore Protection Manual (SPM) (U.S. Army, Corps of Engineerings, Coastal Engineering Research Center, 1977). The curves are for structure slopes fronted by horizontal and 1 on 10 bottom slopes. The range of values of d sub s/H' sub o was extended to d sub s/H' sub o = 8; relative depth (d sub s/H' sub o) is important even for d sub s/H' sub o> 3 for waves which do not break on the structure slope. Rough-slope results are presented in similar curves if sufficient data were available. Otherwise, results are given as values of r, which is the ratio of rough-slope runup to smooth-slope runup. Scale-effect in runup is discussed.

Geometry of profiles across Inner Continental Shelves of the Atlantic and Gulf coasts of the United States /

Along most of the U.S. east and gulf coasts from Long Island to the Mexican Border, bottom profiles extending over the Inner Continental Shelves normal from the coast display a characteristic two-sector shape. Near the coast, the 'shoreface' profile sector is steep and concave-up; the seaward 'ramp' sector is planar with a gradual slope away from the coast. As part of the Beach Evaluation Program at this Center, 9 profiles extending from the coast 30.5 km (19 miles) seaward at each of 49 localities were averaged to mathematically characterize the profiles and to develop and test criteria for discriminating among groups of profiles. Results indicate Inner Continental Shelf profiles can be mathematically defined by 4 parameters: a = ramp slope (0 - 0.00107); b = depth of the ramp at the shoreline, when the ramp is extended as a straight line below the shoreface sector (0 - 24.7 meters, 0 - 81 feet); c = distance from the shoreline to the shoreface-ramp boundary (0.2 - 20.6 km, 0.12 - 12.9 miles); and f = index of concavity of the shoreface sector (0.21 - 1.72). Values in parentheses are the range of values obtained for the 49 averaged profiles. An equation was developed to define bottom depth as a function of distance from shore incorporating these four parameters. Computed depths using the equation were found to be generally within 5% of actual profile depths. In most cases, no relationship was found between the geometric characteristics of the shoreface and the ramp.

Values, immediate and contributory, and their interrelation,

Published also as thesis (Ph.D.) New York university, 1919.

Teleonomic entropy: measuring the phase-space of end-directed systems

We introduce a novel way of measuring the entropy of a set of values undergoing changes. Such a measure becomes useful when analyzing the temporal development of an algorithm designed to numerically update a collection of values such as artificial neural network weights undergoing adjustments during learning. We measure the entropy as a function of the phase-space of the values, i.e. their magnitude and velocity of change, using a method based on the abstract measure of entropy introduced by the philosopher Rudolf Carnap. By constructing a time-dynamic two-dimensional Voronoi diagram using Voronoi cell generators with coordinates of value- and value-velocity (change of magnitude), the entropy becomes a function of the cell areas. We term this measure teleonomic entropy since it can be used to describe changes in any end-directed (teleonomic) system. The usefulness of the method is illustrated when comparing the different approaches of two search algorithms, a learning artificial neural network and a population of discovering agents. (C) 2004 Elsevier Inc. All rights reserved.

Effects of hydrogen-air non-equilibrium chemistry on the performance of a model scramjet thrust nozzle

Two aspects of hydrogen-air non-equilibrium chemistry related to scramjets are nozzle freezing and a process called 'kinetic afterburning' which involves continuation of combustion after expansion in the nozzle. These effects were investigated numerically and experimentally with a model scramjet combustion chamber and thrust nozzle combination. The overall model length was 0.5m, while precombustion Mach numbers of 3.1 +/- 0.3 and precombustion temperatures ranging from 740K to 1,400K were involved. Nozzle freezing was investigated at precombustion pressures of 190kPa and higher, and it was found that the nozzle thrusts were within 6% of values obtained from finite rate numerical calculations, which were within 7% of equilibrium calculations. When precombustion pressures of 70kPa or less were used, kinetic afterburning was found to be partly responsible for thrust production, in both the numerical calculations and the experiments. Kinetic afterburning offers a means of extending the operating Mach number range of a fixed geometry scramjet.

Application of central composite rotatable design to modelling the effect of some operating variables on the performance of the three-product cyclone

The central composite rotatable design (CCRD) was used to design an experimental program to model the effects of inlet pressure, feed density, and length and diameter of the inner vortex finder on the operational performance of a 150-min three-product cyclone. The ranges of values of the variables used in the design were: inlet pressure: 80-130 kPa, feed density: 30 60%; length of IVF below the OVF: 50-585 mm; diameter of IVF: 35-50 mm. A total of 30 tests were conducted, which is 51 less; an that required for a three-level full factorial design. Because the model allows confident performance prediction by interpolation over the range of data in the database, it was used to construct response surface graphs to describe the effects of the variables on the performance of the three-product cyclone. To obtain a simple and yet a realistic model, it was refitted using only the variable terms that are significant at greater than or equal to 90% confidence level. Considering the selected operating variables, the resultant model is significant and predicts the experimental data well. (c) 2005 Elsevier B.V. All rights reserved.

Testing the reliability of a new ultrasonic cardiac output monitor, the USCOM, by using aortic flowprobes in anesthetized dogs

We have used an animal model to test the reliability of a new portable continuous-wave Doppler ultrasonic cardiac output monitor, the USCOM. In six anesthetized dogs, cardiac output was measured with a high-precision transit time ultrasonic flowprobe placed on the ascending aorta. The dogs' cardiac output was increased with a dopamine infusion (0-15 mug (.) kg(-1) (.) min(-1)). Simultaneous flowprobe and USCOM cardiac output measurements were made. Up to 64 pairs of readings were collected from each dog. Data were compared by using the Bland and Altman plot method and Lin's concordance correlation coefficient. A total of 319 sets of paired readings were collected. The mean (+/-SD) cardiac output was 2.62 +/- 1.04 L/min, and readings ranged from 0.79 to 5.73 L/min. The mean bias between the 2 sets of readings was -0.01 L/min, with limits of agreement (95% confidence intervals) of -0.34 to 0.31 L/min. This represents a 13% error. In five of six dogs, there was a high degree of concordance, or agreement, between the 2 methods, with coefficients >0.9. The USCOM provided reliable measurements of cardiac output over a wide range of values. Clinical trials are needed to validate the device in humans.

A combined spectrophotometric and morphometric study of the lunar mare dome fields near Cauchy, Arago, Hortensius, and Milichius

In this Study we examine the spectral and morphometric properties of the four important lunar mare dome fields near Cauchy, Arago, Hortensius. and Milichius. We utilize Clementine UV vis mulfispectral data to examine the soil composition of the mare domes while employing telescopic CCD imagery to compute digital elevation maps in order to determine their morphometric properties, especially flank slope, height, and edifice Volume. After reviewing previous attempts to determine topographic data for lunar domes, we propose an image-based 3D reconstruction approach which is based on a combination of photoclinometry and shape from shading. Accordingly, we devise a classification scheme for lunar Marc domes which is based on a principal component analysis of the determined spectral and morphometric features. For the effusive mare domes of the examined fields we establish four Classes, two of which are further divided into two subclasses, respectively, where each class represents distinct combinations of spectral and morphometric dome properties. As a general trend, shallow and steep domes formed out of low-TiO2 basalts are observed in the Hortensius and Milichius dome fields, while the domes near Cauchy and Arago that consist of high-TiO2 basalts are all very shallow. The intrusive domes of our data set cover a wide continuous range of spectral and morphometric quantities, generally characterized by larger diameters and shallower flank slopes than effusive domes. A comparison to effusive and intrusive mare domes in other lunar regions, highland domes, and lunar cones has shown that the examined four mare dome fields display Such a richness in spectral properties and 3D dome shape that the established representation remains valid in a more global context. Furthermore, we estimate the physical parameters of dome formation for the examined domes based on a rheologic model. Each class of effusive domes defined in terms of spectral and morphometric properties is characterized by its specific range of values for lava viscosity, effusion rate, and duration of the effusion process. For our data set we report lava viscosities between about 10(2) and 10(8) Pas, effusion rates between 25 and 600 m(3) s(-1), and durations of the effusion process between three weeks and 18 years. Lava viscosity decreases with increasing R-415/R-750 spectral ratio and thus TiO2 content; however, the correlation is not strong, implying an important influence of further parameters like effusion temperature on lava viscosity.