Relationship Between Vascular Access Flow and Hemodynamically Significant Stenoses in Arteriovenous Grafts

Background: Vascular access dysfunction is a major source of hemodialysis patient morbidity. The NKF K/DOQI Guidelines promote access flow monitoring as the most preferred access surveillance method and have established access flow thresholds for fistulography: an absolute threshold of 600 ml/min and a dynamic threshold of flow less than 1000 ml/min that has decreased by more than 25% over 4 months. The Guidelines apply universally to accesses of different types, sizes, locations, and initial flow rates.
Methods: This article studies the application of access flow guidelines with human experimental data, animal experimental data, and a mathematical model of the arteriovenous graft system.
Results and conclusions: Analysis of experimental data and the mathematical model shows that a 20 to 30% and greater decrease in graft flow generally suggests the appearance of hemodynamically significant stenosis as defined by flow criteria. The model suggests that not all 50 to 60% stenoses may be hemodynamically significant or the most flow limiting. The mathematical model also suggests that positive predictive value of access surveillance may be increased for high‐flow upper arm grafts by increasing the dynamic K/DOQI threshold from 1000 ml/min to 1200 ml/min.     

On-chip surface-based detection with nanohole arrays

A microfluidic device with integrated surface plasmon resonance (SPR) chemical and biological sensors based on arrays of nanoholes in gold films is demonstrated. Widespread use of SPR for surface analysis in laboratories has not translated to microfluidic analytical chip platforms, in part due to challenges associated with scaling down the optics and the surface area required for common reflection mode operation. The resonant enhancement of light transmission through subwavelength apertures in a metallic film suggests the use of nanohole arrays as miniaturized SPR-based sensing elements. The device presented here takes advantage of the unique properties of nanohole arrays: surface-based sensitivity; transmission mode operation; a relatively small footprint; and repeatability. Proof-of-concept measurements performed on-chip indicated a response to small changes in refractive index at the array surfaces. A sensitivity of 333 nm per refractive index unit was demonstrated with the integrated device. The device was also applied to detect spatial microfluidic concentration gradients and to monitor a biochemical affinity process involving the biotin-streptavidin system. Results indicate the efficacy of nanohole arrays as surface plasmon-based sensing elements in a microfluidic platform, adding unique surface-sensitive diagnostic capabilities to the existing suite of microfluidic-based analytical tools.     

Direct adaptive longitudinal control of vehicle platoons

An important aspect of an automated highway system design is the synthesis of an automatic vehicle following system. Associated with automatic vehicle following systems is the problem of the stability of a string of vehicles, i.e., the problem of spacing error propagation, and in some cases, amplification upstream from one vehicle to another, due to some disturbance at the head of the string. Realistic vehicle following designs must also address parametric uncertainties such as mass of the vehicle, aerodynamic drag, and tire drag. The mass of the vehicle varies with the number of passengers. At small intervehicular separations, aerodynamic drag force changes significantly with the distance to be maintained. We address the problem of stability of a vehicle string in the presence of parametric uncertainty and present a Lyapunov-based decentralized adaptive control algorithm to compensate for such parametric variations. We examine this direct adaptive control algorithm for platoon performance and parameter convergence. We present the simulation results to demonstrate the effectiveness of the adaptive controller     

“Deep approaches to learning” in a project-based nanofabrication graduate course

We describe a graduate-level, laboratory course that is structured as a “master class” in experimental research project planning and execution. Students work in teams to engage in project topics of their choosing, ideally relevant to their own areas of research, that make use of the university's shared fabrication and characterization facilities. After developing their project plans, which includes a schedule, budget, and milestones, students execute them under the guidance of their mentors. The aim of the course is that the students develop deep conceptual knowledge of the practice of experimental science, with regard to: project planning and execution, effective communication and teamwork, technical rigor, and peer review. Because students learn by applying these skills to topics that are personally relevant to them, this course can be described as using on deep approaches to learning.     

Mutation of a gene encoding a protein with extracellular matrix motifs in Usher syndrome type IIa

Usher syndrome type IIa (OMIM 276901), an autosomal recessive disorder characterized by moderate to severe sensorineural hearing loss and progressive retinitis pigmentosa, maps to the long arm of human chromosome 1q41 between markers AFM268ZD1 and AFM144XF2. Three biologically important mutations in Usher syndrome type IIa patients were identified in a gene (USH2A) isolated from this critical region. The USH2A gene encodes a protein with a predicted size of 171.5 kilodaltons that has laminin epidermal growth factor and fibronectin type III motifs; these motifs are most commonly observed in proteins comprising components of the basal lamina and extracellular matrixes and in cell adhesion molecules.     

A novel locus (RP24) for X-linked retinitis pigmentosa maps to Xq26-27

Two genetic loci, RP2 and RP3, for X-linked retinitis pigmentosa (XLRP) have been localized to Xp11.3-11.23 and Xp21.1, respectively. RP3 appears to account for 70% of XLRP families; however, mutations in the RPGR gene (isolated from the RP3 region) are identified in only 20% of affected families. Close location of XLRP loci at Xp and a lack of unambiguous clinical criteria do not permit assignment of genetic subtype in a majority of XLRP families; nonetheless, in some pedigrees, both RP2 and RP3 could be excluded as the causative locus. We report the mapping of a novel locus, RP24, by haplotype and linkage analysis of a single XLRP pedigree. The RP24 locus was identified at Xq26-27 by genotyping 52 microsatellite markers spanning the entire X chromosome. A maximum LOD score of 4.21 was obtained with DXS8106. Haplotype analysis assigned RP24 within a 23-cM region between the DXS8094 (proximal) and DXS8043 (distal) markers. Other chromosomal regions and known XLRP loci were excluded by obligate recombination events between markers in those regions and the disease locus. Hemizygotes from the RP24 family have early onset of rod photoreceptor dysfunction; cone receptor function is normal at first, but there is progressive loss. Patients at advanced stages show little or no detectable rod or cone function and have clinical hallmarks of typical RP. Mapping of the RP24 locus expands our understanding of the genetic heterogeneity in XLRP and will assist in development of better tools for diagnosis.     

Analysis of Climate and Melt-runoff in Dunagiri Glacier of Garhwal Himalaya (India)

The hydrology of high altitude glacierized basin in Himalaya is complex to understand due to high variability in climate and lack of hydro-meteorological data. In this study, analysis of hydrological, glacier ablation and meteorological records have been made for Dunagiri Glacier (~4,200 m) during the melt season (July - September), for the years 1985 and 1987–1989. In the daily cycle of mean diurnal discharge in summer months during 1985–1989, maximum discharge occurred at midnight, and minimum discharge occurred in the morning. Mean daytime and nighttime discharge volume was contributing approximately equal amounts. Such type of analysis will be the basis for designing/developing Run-off-the river type hydroelectric power projects which are heavily dependent on snow and glacier melt in Himalaya. Time series analysis of available hydro-meteorological records have been used to understand governing hydrological processes within the basin and to develop regression model for future development in runoff forecasting using climate data.     

Aggregation of a class of interconnected, linear dynamical systems

In this paper, we introduce the notion of a “meaningful” average of a collection of dynamical systems as distinct from an “ensemble” average. Such a notion is useful for the study of a variety of dynamical systems such as traffic flow, power systems, and econometric systems. We also address the associated issue of the existence and computation of such an average for a class of interconnected, linear, time invariant dynamical systems. Such an “average” dynamical system is not only attractive from a computational perspective, but also represents the average behavior of the interconnected dynamical systems. The problem of analysis and control of heirarchical, large scale control systems can be simplified by approximating the lower level dynamics of such systems with such an average dynamical system.     

Dynamic Load Simulator: Actuation Strategies and Applications

The development of a multiple-actuator dynamic load simulator (DLS), for the simulation of correlated dynamic loads on small-scale structural components and substructures, or on bench-scale system assemblage is presented in this paper. Conceptually, the DLS employs actuators to simulate a desired dynamic loading environment due to wind, waves, or earthquakes, which in special cases may serve as a replacement for conventional facilities such as wind tunnels, wave tanks and shaking tables. The actuation strategy of the DLS is based on force-control rather than the customary motion control (displacement/velocity) scheme. The load simulator is ideal for structural components and for systems that can be idealized as lumped mass systems. An actuation strategy for the DLS based on an innovative scheme that utilizes the coupled control system is developed. For implementation of this scheme, the nonlinear control system toolbox in MATLAB is used. In this scheme, the tuning of control parameters in the time domain is carried out by solving a constrained optimization problem. A suite of loading protocols that includes sinusoidal, two-point correlated fluctuations in wind loading, earthquake induced loading and loads characterized by strong non-Gaussian features is simulated by employing the control scheme introduced here. The load simulation examples presented here demonstrate that the loading time histories generated by utilizing the DLS matched the target values with high fidelity.     

Leber congenital amaurosis caused by a homozygous mutation (R90W) in the homeodomain of the retinal transcription factor CRX: direct evidence for the involvement of CRX in the development of photoreceptor function

Adipocyte differentiation takes place via a complex series of steps. While PPARgamma2 and C/EBPalpha are known to be master regulators, the events at the earliest stage of adipocyte differentiation are not yet known. In this study, we cloned the genes which are induced at the beginning of differentiation of 3T3-L1 preadipocyte cells. Of 58 clones obtained, only a few were already reported as the genes that are expressed differentially during adipocyte development. More than 30 clones are known but have been newly identified here as differentially expressed genes. Nineteen clones seemed to be unknown genes. The expression of RGS2, HSP105, Rho (TC10), VDR, and HIF-1alpha genes isolated here rapidly increased after the addition of inducers, and after 3-12 h the levels of expression decreased. The expression patterns of these mRNAs were different among growth-arrested and proliferating 3T3-L1 cells and NIH-3T3 cells, strongly indicating that some of the proteins identified here have crucial roles in the program of adipocyte differentiation.