Purification and characterization of heparan sulfate from human primary osteoblasts

Heparan sulfate (HS) is a linear, highly variable, highly sulfated glycosaminoglycan sugar whose biological activity largely depends on internal sulfated domains that mediate specific binding to an extensive range of proteins. In this study we employed anion exchange chromatography, molecular sieving and enzymatic cleavage on HS fractions purified from three compartments of cultured osteoblasts-soluble conditioned media, cell surface, and extracellular matrix (ECM). We demonstrate that the composition of HS chains purified from the different compartments is structurally non-identical by a number of parameters, and that these differences have significant ramifications for their ligand-binding properties. The HS chains purified of conditioned medium had twice the binding affinity for FGF2 when compared with either cell surface or ECM HS. In contrast, similar binding of BMP2 to the three types of HS was observed. These results suggest that different biological compartments of cultured cells have structurally and functionally distinct HS species that help to modulate the flow of HS-dependent factors between the ECM and the cell surface.

Studies of granulosa cell maturation in dominant and subordinate bovine follicles : novel extracellular matrix focimatrix is co-ordinately regulated with cholesterol side-chain cleavage CYP11A1

During growth of antral ovarian follicles granulosa cells first become associated with a novel type of extracellular matrix, focimatrix, and at larger sizes follicles become either subordinate or dominant. To examine this, bovine subordinate (9.0±s.e.m. 0.4 mm; n=16), partially dominant (12.0±0.6 mm; n=18) and fully dominant (15.0±0.4 mm; n=14) follicles were examined by real time RT-PCR analyses of granulosa cells and by immunohistochemistry of focimatrix. Changes in the expression of FSH receptor, LH receptor, cholesterol side-chain cleavage (CYP11A1), 3β-hydroxysteroid dehydrogenase, aromatase (CYP19A1) and inhibin-α and β-B were observed as expected for follicle sizes examined. After adjusting for size differences, only CYP11A1 was significantly different between the groups, and elevated in dominant follicles. Also after adjusting for differences in size there were no significant differences in expression of focimatrix components collagen type IV α-1 (COL4A1), laminin β-2, nidogen 1 (NID1), and perlecan (HSPG2) or the volume density of NID1 and -2 and HSPG2. The volume density of focimatrix components in laminin 111 was significantly elevated in dominant follicles. Adjusting for analysis of more than one follicle per animal and for multiple correlations, CYP11A1 mRNA levels were highly correlated with the focimatrix genes COL4A1, NID1 and -2 and HSPG2. Thus, focimatrix may potentially regulate CYP11A1 expression, and the regulation of both could be important in follicular dominance.

Mortality, fertility, and persistent income inequality

Many developing countries are plagued by persistent inequality in income distribution. While a growing body of economic-demographic literature emphasizes differential fertility channel, this paper investigates differential child mortality--differences in child mortality across income groups--as a critical link through which income inequality persists. Using an overlapping generations model in which both child mortality and fertility are endogenously determined by parental choice, this paper demonstrates that differential child mortality and its interaction with differential fertility may generate an "income inequality trap." The trap is characterized by higher child mortality and lower degree of skill formation among the poorer households. The model can also explain the behavior of aggregate fertility and mortality rates for countries at various stages of development, consonant with patterns of demographic transition. The results indicate that provision of public health that raises the productivity of private health spending may be an effective way to reduce income inequality

Optimistic linear programming gives logarithmic regret for irreducible MDPs

We present an algorithm called Optimistic Linear Programming (OLP) for learning to optimize average reward in an irreducible but otherwise unknown Markov decision process (MDP). OLP uses its experience so far to estimate the MDP. It chooses actions by optimistically maximizing estimated future rewards over a set of next-state transition probabilities that are close to the estimates, a computation that corresponds to solving linear programs. We show that the total expected reward obtained by OLP up to time T is within C(P) log T of the reward obtained by the optimal policy, where C(P) is an explicit, MDP-dependent constant. OLP is closely related to an algorithm proposed by Burnetas and Katehakis with four key differences: OLP is simpler, it does not require knowledge of the supports of transition probabilities, the proof of the regret bound is simpler, but our regret bound is a constant factor larger than the regret of their algorithm. OLP is also similar in flavor to an algorithm recently proposed by Auer and Ortner. But OLP is simpler and its regret bound has a better dependence on the size of the MDP.

High-probability regret bounds for bandit online linear optimization

We present a modification of the algorithm of Dani et al. [8] for the online linear optimization problem in the bandit setting, which with high probability has regret at most O ∗ ( √ T) against an adaptive adversary. This improves on the previous algorithm [8] whose regret is bounded in expectation against an oblivious adversary. We obtain the same dependence on the dimension (n 3/2) as that exhibited by Dani et al. The results of this paper rest firmly on those of [8] and the remarkable technique of Auer et al. [2] for obtaining high probability bounds via optimistic estimates. This paper answers an open question: it eliminates the gap between the high-probability bounds obtained in the full-information vs bandit settings.

Linear models for endocytic transformations from live cell imaging

Endocytosis is the process by which cells internalise molecules including nutrient proteins from the extracellular media. In one form, macropinocytosis, the membrane at the cell surface ruffles and folds over to give rise to an internalised vesicle. Negatively charged phospholipids within the membrane called phosphoinositides then undergo a series of transformations that are critical for the correct trafficking of the vesicle within the cell, and which are often pirated by pathogens such as Salmonella. Advanced fluorescent video microscopy imaging now allows the detailed observation and quantification of these events in live cells over time. Here we use these observations as a basis for building differential equation models of the transformations. An initial investigation of these interactions was modelled with reaction rates proportional to the sum of the concentrations of the individual constituents. A first order linear system for the concentrations results. The structure of the system enables analytical expressions to be obtained and the problem becomes one of determining the reaction rates which generate the observed data plots. We present results with reaction rates which capture the general behaviour of the reactions so that we now have a complete mathematical model of phosphoinositide transformations that fits the experimental observations. Some excellent fits are obtained with modulated exponential functions; however, these are not solutions of the linear system. The question arises as to how the model may be modified to obtain a system whose solution provides a more accurate fit.

Compensation of unmodeled aircraft dynamics in airborne inspection of linear infrastructure assets

Fixed-wing aircraft equipped with downward pointing cameras and/or LiDAR can be used for inspecting approximately piecewise linear assets such as oil-gas pipelines, roads and power-lines. Automatic control of such aircraft is important from a productivity and safety point of view (long periods of precision manual flight at low-altitude is not considered reasonable from a safety perspective). This paper investigates the effect of any unwanted coupling between guidance and autopilot loops (typically caused by unmodeled delays in the aircraft’s response), and the specific impact of any unwanted dynamics on the performance of aircraft undertaking inspection of piecewise linear corridor assets (such as powerlines). Simulation studies and experimental flight tests are used to demonstrate the benefits of a simple compensator in mitigating the unwanted lateral oscillatory behaviour (or coupling) that is caused by unmodeled time constants in the aircraft dynamics.

Vision based control for fixed wing UAVs inspecting locally linear infrastructure using skid-to-turn maneuvers

The following paper proposes a novel application of Skid-to-Turn maneuvers for fixed wing Unmanned Aerial Vehicles (UAVs) inspecting locally linear infrastructure. Fixed wing UAVs, following the design of manned aircraft, traditionally employ Bank-to-Turn maneuvers to change heading and thus direction of travel. Commonly overlooked is the effect these maneuvers have on downward facing body fixed sensors, which as a result of bank, point away from the feature during turns. By adopting Skid-to-Turn maneuvers, the aircraft is able change heading whilst maintaining wings level flight, thus allowing body fixed sensors to maintain a downward facing orientation. Eliminating roll also helps to improve data quality, as sensors are no longer subjected to the swinging motion induced as they pivot about an axis perpendicular to their line of sight. Traditional tracking controllers that apply an indirect approach of capturing ground based data by flying directly overhead can also see the feature off center due to steady state pitch and roll required to stay on course. An Image Based Visual Servo controller is developed to address this issue, allowing features to be directly tracked within the image plane. Performance of the proposed controller is tested against that of a Bank-to-Turn tracking controller driven by GPS derived cross track error in a simulation environment developed to simulate the field of view of a body fixed camera.