Association Between Blood Pressure and Adverse Renal Events in Type 1 Diabetes.

ObjectiveTo compare different blood pressure (BP) levels in their association with the risk of renal outcomes in type 1 diabetes and to determine whether an intensive glycemic control strategy modifies this association.Research design and methodsWe included 1,441 participants with type 1 diabetes between the ages of 13 and 39 years who had previously been randomized to receive intensive versus conventional glycemic control in the Diabetes Control and Complications Trial (DCCT). The exposures of interest were time-updated systolic BP (SBP) and diastolic BP (DBP) categories. Outcomes included macroalbuminuria (>300 mg/24 h) or stage III chronic kidney disease (CKD) (sustained estimated glomerular filtration rate <60 mL/min/1.73 m2).ResultsDuring a median follow-up time of 24 years, there were 84 cases of stage III CKD and 169 cases of macroalbuminuria. In adjusted models, SBP in the <120 mmHg range was associated with a 0.59 times higher risk of macroalbuminuria (95% CI 0.37-0.95) and a 0.32 times higher risk of stage III CKD (95% CI 0.14-0.75) compared with SBPs between 130 and 140 mmHg. DBP in the <70 mmHg range were associated with a 0.73 times higher risk of macroalbuminuria (95% CI 0.44-1.18) and a 0.47 times higher risk of stage III CKD (95% CI 0.21-1.05) compared with DBPs between 80 and 90 mmHg. No interaction was noted between BP and prior DCCT-assigned glycemic control strategy (all P > 0.05).ConclusionsA lower BP (<120/70 mmHg) was associated with a substantially lower risk of adverse renal outcomes, regardless of the prior assigned glycemic control strategy. Interventional trials may be useful to help determine whether the currently recommended BP target of 140/90 mmHg may be too high for optimal renal protection in type 1 diabetes

Prethermalization and Persistent Order in the Absence of a Thermal Phase Transition

We numerically study the dynamics after a parameter quench in the one-dimensional transverse-field Ising model with long-range interactions ($\propto 1/r^\alpha$ with distance $r$), for finite chains and also directly in the thermodynamic limit. In nonequilibrium, i.e., before the system settles into a thermal state, we find a long-lived regime that is characterized by a prethermal value of the magnetization, which in general differs from its thermal value. We find that the ferromagnetic phase is stabilized dynamically: as a function of the quench parameter, the prethermal magnetization shows a transition between a symmetry-broken and a symmetric phase, even for those values of $\alpha$ for which no finite-temperature transition occurs in equilibrium. The dynamical critical point is shifted with respect to the equilibrium one, and the shift is found to depend on $\alpha$ as well as on the quench parameters.Comment: 6 pages, 4 figure

Factors affecting B/Ca ratios in synthetic aragonite

Author Posting. © The Author(s), 2015. This is the author's version of the work. It is posted here for personal use, not for redistribution. The definitive version was published in Chemical Geology 437 (2016): 67-76, doi:10.1016/j.chemgeo.2016.05.007.Measurements of B/Ca ratios in marine carbonates have been suggested to record seawater carbonate chemistry, however experimental calibration of such proxies based on inorganic partitioning remains limited. Here we conducted a series of synthetic aragonite precipitation experiments to evaluate the factors influencing the partitioning of B/Ca between aragonite and seawater. Our results indicate that the B/Ca ratio of synthetic aragonites depends primarily on the relative concentrations of borate and carbonate ions in the solution from which the aragonite precipitates; not on bicarbonate concentration as has been previously suggested. The influence of temperature was not significant over the range investigated (20 – 40°C), however, partitioning may be influenced by saturation state (and/or growth rate). Based on our experimental results, we suggest that aragonite B/Ca ratios can be utilized as a proxy of [CO32-]. Boron isotopic composition (δ11B) is an established pH proxy, thus B/Ca and δ11B together allow the full carbonate chemistry of the solution from which the aragonite precipitated to be calculated. To the extent that aragonite precipitation by marine organisms is affected by seawater chemistry, B/Ca may also prove useful in reconstructing seawater chemistry. A simplified boron purification protocol based on amberlite resin and the organic buffer TRIS is also described.This work was supported by the Australian Research Council (ARC) Centre of Excellence for Coral Reef Studies. Research conducted at WHOI was supported by NSF grant OCE-1338320. M.H. was supported by an ARC Super Science Fellowship and an NSF International Postdoctoral Fellowship. T.D. was supported by a NSF Graduate Research Fellowship. M.M. was supported by a Western Australian Premiers Fellowship and an ARC Laureate Fellowship

Modeling effects of L-type ca(2+) current and na(+)-ca(2+) exchanger on ca(2+) trigger flux in rabbit myocytes with realistic T-tubule geometries.

The transverse tubular system of rabbit ventricular myocytes consists of cell membrane invaginations (t-tubules) that are essential for efficient cardiac excitation-contraction coupling. In this study, we investigate how t-tubule micro-anatomy, L-type Ca(2+) channel (LCC) clustering, and allosteric activation of Na(+)/Ca(2+) exchanger by L-type Ca(2+) current affects intracellular Ca(2+) dynamics. Our model includes a realistic 3D geometry of a single t-tubule and its surrounding half-sarcomeres for rabbit ventricular myocytes. The effects of spatially distributed membrane ion-transporters (LCC, Na(+)/Ca(2+) exchanger, sarcolemmal Ca(2+) pump, and sarcolemmal Ca(2+) leak), and stationary and mobile Ca(2+) buffers (troponin C, ATP, calmodulin, and Fluo-3) are also considered. We used a coupled reaction-diffusion system to describe the spatio-temporal concentration profiles of free and buffered intracellular Ca(2+). We obtained parameters from voltage-clamp protocols of L-type Ca(2+) current and line-scan recordings of Ca(2+) concentration profiles in rabbit cells, in which the sarcoplasmic reticulum is disabled. Our model results agree with experimental measurements of global Ca(2+) transient in myocytes loaded with 50 μM Fluo-3. We found that local Ca(2+) concentrations within the cytosol and sub-sarcolemma, as well as the local trigger fluxes of Ca(2+) crossing the cell membrane, are sensitive to details of t-tubule micro-structure and membrane Ca(2+) flux distribution. The model additionally predicts that local Ca(2+) trigger fluxes are at least threefold to eightfold higher than the whole-cell Ca(2+) trigger flux. We found also that the activation of allosteric Ca(2+)-binding sites on the Na(+)/Ca(2+) exchanger could provide a mechanism for regulating global and local Ca(2+) trigger fluxes in vivo. Our studies indicate that improved structural and functional models could improve our understanding of the contributions of L-type and Na(+)/Ca(2+) exchanger fluxes to intracellular Ca(2+) dynamics

A Stochastic Multiscale Model of Cardiac Thin Filament Activation Using Brownian-Langevin Dynamics.

We use Brownian-Langevin dynamics principles to derive a coarse-graining multiscale myofilament model that can describe the thin-filament activation process during contraction. The model links atomistic molecular simulations of protein-protein interactions in the thin-filament regulatory unit to sarcomere-level activation dynamics. We first calculate the molecular interaction energy between tropomyosin and actin surface using Brownian dynamics simulations. This energy profile is then generalized to account for the observed tropomyosin transitions between its regulatory stable states. The generalized energy landscape then served as a basis for developing a filament-scale model using Langevin dynamics. This integrated analysis, spanning molecular to thin-filament scales, is capable of tracking the events of the tropomyosin conformational changes as it moves over the actin surface. The tropomyosin coil with flexible overlap regions between adjacent tropomyosins is represented in the model as a system of coupled stochastic ordinary differential equations. The proposed multiscale approach provides a more detailed molecular connection between tropomyosin dynamics, the trompomyosin-actin interaction-energy landscape, and the generated force by the sarcomere

A genetic and computational approach to structurally classify neuronal types

The importance of cell types in understanding brain function is widely appreciated but only a tiny fraction of neuronal diversity has been catalogued. Here, we exploit recent progress in genetic definition of cell types in an objective structural approach to neuronal classification. The approach is based on highly accurate quantification of dendritic arbor position relative to neurites of other cells. We test the method on a population of 363 mouse retinal ganglion cells. For each cell, we determine the spatial distribution of the dendritic arbors, or “arbor density” with reference to arbors of an abundant, well-defined interneuronal type. The arbor densities are sorted into a number of clusters that is set by comparison with several molecularly defined cell types. The algorithm reproduces the genetic classes that are pure types, and detects six newly clustered cell types that await genetic definition

Building the Working City Designs on Home and Life in Boomtown Detroit, 1914-1932.

The modern worker’s home made Detroit’s Fordist industrialization possible. Between the 1914 announcement of Ford’s “Five Dollar Day” and the Great Depression, Detroit industrialists, real estate developers and workers produced a building boom in housing, reshaping the urban society and negotiating the terms of what Antonio Gramsci called “a new type of worker and of man.” Expanding the architectural history of Fordism beyond the factory, this dissertation argues that it was through the modernization of the larger city—a Fordist Urbanism dominated by worker’s housing developments between the city’s peripheral industrial plants—that Detroit’s Fordist culture was constructed. Industrialists promoted modern worker’s housing, pursuing social control of the city’s largely-immigrant workforce, but shifted the risk of housing construction costs to individual workers by pushing them to seek houses on the open market. Real estate developers responded, and with government support built tens of thousands of bungalows and duplexes for sale to workers on credit. Realtors presented homeownership as a source of financial security for workers yet a realty culture of speculative investment and racial segregation undermined that security from the beginning. At the same time workers had significant agency in this city-building process. They produced more than industrial products in Fordist Detroit, making domestic lives and identities in the pluralistic ways that they chose, outfitted, lived in and cared for their homes, giving meaning and purpose to their routinized labor. Detroit’s industrial modernization—in and through its modern worker’s houses—elaborated crises of racial violence and home foreclosure in the mid 1920s and early 1930s, in which workers fought against one another, and ultimately in solidarity, demanding that the Fordist promise of hard work in exchange for domestic security be honored. Detroit’s houses of the early twentieth century—the extant and the demolished—still contain a great deal: a history of power negotiated through the modernization of the built environment. This past suggests that the city’s future housing—its design, location, financing and use—can influence the management of risk within society, the social construction of difference, and workers’ continued struggle for security.PhDArchitectureUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/113446/1/mccullmp_1.pd