The Incompressible Navier-Stokes Limit of the Boltzmann Equation for Hard Cutoff Potentials

The present paper proves that all limit points of sequences of renormalized solutions of the Boltzmann equation in the limit of small, asymptotically equivalent Mach and Knudsen numbers are governed by Leray solutions of the Navier-Stokes equations. This convergence result holds for hard cutoff potentials in the sense of H. Grad, and therefore completes earlier results by the same authors [Invent. Math. 155, 81-161(2004)] for Maxwell molecules.Comment: 56 pages, LaTeX, a few typos have been corrected, a few remarks added, one uncited reference remove

Development of Protacs to Target Cancer-promoting Proteins for Ubiquitination and Degradation

The proteome contains hundreds of proteins that in theory could be excellent therapeutic targets for the treatment of human diseases. However, many of these proteins are from functional classes that have never been validated as viable candidates for the development of small molecule inhibitors. Thus, to exploit fully the potential of the Human Genome Project to advance human medicine, there is a need to develop generic methods of inhibiting protein activity that do not rely on the target protein’s function. We previously demonstrated that a normally stable protein, methionine aminopeptidase-2 or MetAP-2, could be artificially targeted to an Skp1-Cullin-F-box (SCF) ubiquitin ligase complex for ubiquitination and degradation through a chimeric bridging molecule or Protac (proteolysis targeting chimeric molecule). This Protac consisted of an SCFß-TRCP-binding phosphopeptide derived from I{kappa}B{alpha} linked to ovalicin, which covalently binds MetAP-2. In this study, we employed this approach to target two different proteins, the estrogen (ER) and androgen (AR) receptors, which have been implicated in the progression of breast and prostate cancer, respectively. We show here that an estradiol-based Protac can enforce the ubiquitination and degradation of the {alpha} isoform of ER in vitro, and a dihydroxytestosterone-based Protac introduced into cells promotes the rapid disappearance of AR in a proteasome-dependent manner. Future improvements to this technology may yield a general approach to treat a number of human diseases, including cancer

A Simulation-Based Approach for Evaluating Cost and Performance of a Sediment Removal and Processing System for the Lower Susquehanna River Dams

A series of three major dams and reservoirs located along the Lower Susquehanna River have historically acted as a system of sediment and nutrient pollution traps.  However, episodic pulses of these pollution loads are released following short-term extreme storm events, affecting subaquatic vegetation, benthic organisms, and the overall water quality in the Upper Chesapeake Bay.  In addition, all three reservoirs have reached a state of near maximum storage capacity termed as dynamic equilibrium.  Based on prior research, this study seeks to reduce the sediment buildup behind the dams through a sediment removal and processing operation, and thereby reduce the ecological impact of major storms.  A set of scour performance curves derived from a regression analysis, and a stochastic lifecycle cost model were used to evaluate the sediment scouring reduction and economic feasibility of three processing alternatives:  Plasma Vitrification, Cement-Lock, and Quarry/Landfill, and three removal amount cases:  Nominal, Moderate, and Maximum.  Since the scour performance curves treat the dams as static, a fluid system dynamics model was used to determine if the dynamic interaction between the capacitance of the dams during major scouring events is negligible or considerable.  A utility vs. cost analysis factoring in time, performance, and suitability of the alternatives indicates that a Cement-Lock processing plant at moderate dredging for the Safe Harbor and Conowingo Dams is the most cost-performance effective solution

The Geologic Remote Sensing Field Experiment (GRSFE)

Field measurements for the Geologic Remote Sensing Field Experiment (GRSFE) were concentrated in the Lunar Lake area of Nevada. The GRSFE data are meant to be used in a variety of investigations, including tests of multispectral radiative transfer models for scattering and emission from planetary surfaces in support of the Earth Observing System (EOS), Mars Observer, and Magellan Missions. Studies will also be pursued to establish the neotectonic and paleoclimatic history of the arid southwestern United States. The data will also be used to support Mars Rover Sample Return (MRSR) simulation studies

On one-dimensional models for hydrodynamics

To date it has not been possible to prove whether or not the three-dimensional incompressible Euler equations develop singular behaviour in finite time. Some possible singular scenarios, as for instance shock-waves, are very important from a physical point of view, since they imply the connection among the macroscopic and the microscopic scale. Therefore, the appearence of this type of singularity or a similar one might be interpreted as a possible explanation of the transition to turbulence. In order to clarify the question, some one-dimensional models for ideal incompressible hydrodynamics have been introduced and analyzed, and it was proven that shock-waves appear in finite time within this type of flow. In this work we question the validity of these models and analyze the physical meaning that the occurrence of a singularity in an incompressible flow, if it happens, may have

Bone mineral density and risk of heart failure in older adults: The Cardiovascular Health Study

Background Despite increasing evidence of a common link between bone and heart health, the relationship between bone mineral density ( BMD ) and heart failure ( HF ) risk remains insufficiently studied. Methods and Results We investigated whether BMD measured by dual‐energy x‐ray absorptiometry was associated with incident HF in an older cohort. Cox models were stratified by sex and interactions of BMD with race assessed. BMD was examined at the total hip and femoral neck separately, both continuously and by World Health Organization categories. Of 1250 participants, 442 (55% women) developed HF during the median follow‐up of 10.5 years. In both black and nonblack women, neither total hip nor femoral neck BMD was significantly associated with HF ; there was no significant interaction by race. In black and nonblack men, total hip, but not femoral neck, BMD was significantly associated with HF , with evidence of an interaction by race. In nonblack men, lower total hip BMD was associated with higher HF risk (hazard ratio, 1.13 [95% CI, 1.01–1.26] per 0.1 g/cm 2 decrement), whereas in black men, lower total hip BMD was associated with lower HF risk (hazard ratio, 0.74 [95% CI, 0.59–0.94]). There were no black men with total hip osteoporosis. Among nonblack men, total hip osteoporosis was associated with higher HF risk (hazard ratio, 2.83 [95% CI, 1.39–5.74]) compared with normal BMD . Conclusions Among older adults, lower total hip BMD was associated with higher HF risk in nonblack men but lower risk in black men, with no evidence of an association in women. Further research is needed to replicate these findings and to study potential underlying pathways. </jats:sec

Swirling Instability of the Microtubule Cytoskeleton.

In the cellular phenomena of cytoplasmic streaming, molecular motors carrying cargo along a network of microtubules entrain the surrounding fluid. The piconewton forces produced by individual motors are sufficient to deform long microtubules, as are the collective fluid flows generated by many moving motors. Studies of streaming during oocyte development in the fruit fly Drosophila melanogaster have shown a transition from a spatially disordered cytoskeleton, supporting flows with only short-ranged correlations, to an ordered state with a cell-spanning vortical flow. To test the hypothesis that this transition is driven by fluid-structure interactions, we study a discrete-filament model and a coarse-grained continuum theory for motors moving on a deformable cytoskeleton, both of which are shown to exhibit a swirling instability to spontaneous large-scale rotational motion, as observed.Wellcome Trust, EPSRC, ER

Molecular mechanism of cytokinin-activated cell division in Arabidopsis

Mitogens trigger cell division in animals. In plants, cytokinins, a group of phytohormones derived from adenine, stimulate cell proliferation. Cytokinin signalling is initiated by membrane-associated histidine kinase receptors and transduced through a phosphorelay system. Here we show, in the Arabidopsis shoot apical meristem (SAM), that cytokinin regulates cell division by promoting nuclear shuttling of Myb-domain protein 3R4 (MYB3R4), a transcription factor that activates mitotic gene expression. Newly synthesized MYB3R4 protein resides predominantly in the cytoplasm. At the G2/M transition, rapid nuclear accumulation of MYB3R4—consistent with an associated transient peak in cytokinin concentration—feeds a positive-feedback loop involving importins, and initiates a transcriptional cascade that drives mitosis and cytokinesis. An engineered nuclear-restricted MYB3R4 mimics the cytokinin effects in enhancement of cell proliferation and meristem growth.Gatsby Charitable Foundatio