Novel KCND3 Variant Underlying Nonprogressive Congenital Ataxia or SCA19/22 Disrupt KV4.3 Protein Expression and K+ Currents with Variable Effects on Channel Properties

KCND3 encodes the voltage-gated potassium channel K_V4.3 that is highly expressed in the cerebellum, where it regulates dendritic excitability and calcium influx. Loss-of-function K_V4.3 mutations have been associated with dominant spinocerebellar ataxia (SCA19/22). By targeted NGS sequencing, we identified two novel KCND3 missense variants of the K_V4.3 channel: p.S347W identified in a patient with adult-onset pure cerebellar syndrome and p.W359G detected in a child with congenital nonprogressive ataxia. Neuroimaging showed mild cerebellar atrophy in both patients. We performed a two-electrode voltage-clamp recording of K_V4.3 currents in Xenopus oocytes: both the p.G345V (previously reported in a SCA19/22 family) and p.S347W mutants exhibited reduced peak currents by 50%, while no K+ current was detectable for the p.W359G mutant. We assessed the effect of the mutations on channel gating by measuring steady-state voltage-dependent activation and inactivation properties: no significant alterations were detected in p.G345V and p.S347W disease-associated variants, compared to controls. K_V4.3 expression studies in HEK293T cells showed 53% (p.G345V), 45% (p.S347W) and 75% (p.W359G) reductions in mutant protein levels compared with the wildtype. The present study broadens the spectrum of the known phenotypes and identifies additional variants for KCND3-related disorders, outlining the importance of SCA gene screening in early-onset and congenital ataxia.     

Comparison of alteplase (tissue plasminogen activator) high‐dose vs. low‐dose protocol in restoring hemodialysis catheter function: The ALTE‐DOSE study

Hemodialysis catheter (HDC) dysfunction due to thrombosis is common, and dysfunction incidence can reach up to 50% within 1 year of use. Although administration of intraluminal alteplase (tissue plasminogen activator [tPA]) is the standard of practice to pharmacologically restore HDC function, there are no evidence‐based guidelines concerning the optimal tPA dose. The purpose of this study was to compare the efficacy of 1.0‐mg vs. 2.0‐mg tPA dwell protocols in restoring the HDC function in thrombotic dysfunctional catheters. A retrospective, single‐center study was conducted on two independent cohorts of patients; the first (n = 129) received 2.0 mg tPA/catheter lumen, while the second (n = 108) received 1.0 mg tPA/catheter lumen. Kaplan–Meier and Cox regression analyses were performed to compare the catheter survival time between patients who received 1.0 mg tPA and those who received 2.0 mg tPA. Catheter removal occurred in 25 (19.4%) of those catheters treated with 1.0 mg tPA compared with 11 (10.2%) of catheters treated with 2.0 mg tPA (P = 0.05). The hazard ratio (HR) for catheter removal was 2.75 (95% confidence interval [^95%CI] = 1.25–6.04) for the 1.0‐mg tPA cohort compared with the 2.0‐mg tPA cohort. Correction added on 3 December 2012, after first online publication: The tPA cohort values were changed. Female gender (HR = 2.51; ^95%CI = 1.20–5.27) and age (HR = 0.96; ^95%CI = 0.94–0.98) were also associated with catheter survival. Our findings suggest that treatment of dysfunctional HDC with 2.0‐mg tPA dwells is superior to 1.0‐mg tPA dwells.     

Numerical method for the analysis of queuing models with priority jumps1

An algorithmic approach to study queuing models with common finite and infinite buffer and jump priorities is developed. It is assumed that upon arrival of a low-priority call, one call of such kind can be transferred with some probability to the end of the queue of high-priority calls. The transition probability depends on the state of the queue of heterogeneous calls. The algorithms are proposed to calculate the quality of service metrics of such queuing models.     

Evaluation of current criteria in predicting the separation necessary to prevent seismic pounding between nonlinear hysteretic structural systems

This study evaluates the accuracy of four different criteria to calculate the separation necessary to prevent seismic pounding between nonlinear hysteretic structural systems. All of the criteria considered in this paper make use of the same basic equation of the Double Difference Combination rule, but they adopt different procedures to estimate the correlation between displacement responses of nonlinear hysteretic systems. The seismic excitation was modeled as a nonstationary random process, and adjacent structures were modeled as 5%-damped bilinear hysteretic SDOF systems having a 5% post-yielding stiffness ratio. Results obtained through Monte Carlo simulations indicate that none of the criteria evaluated in this study is completely satisfactory in the sense that none of them can consistently provide “exact” or “somewhat conservative” results.     

Probability-Based Optimization of Inter-Sensing Duration and Power Control in Cognitive Radio

Probability-based strategies are proposed in this letter to determine the optimal inter-sensing duration and power control for cognitive radio (CR). With utilization of the statistics of licensed band occupancy, appropriate inter-sensing duration is determined to capture the recurrence of spectrum opportunity in time when the licensed signal is detected, or to achieve the maximum spectrum efficiency under a certain level of interference with licensed communication when the licensed signal is declared absent. Transmit power is varied dynamically according to the non-interfering probability at each sample so as to increase the transmission rate and decrease the interference power.     

The Flood and Sediment Characteristics of the Lower Yellow River in China

Abstract

The Lower Yellow River is well known for its high sediment content and disastrous floods. For thousands of years, roaring floods have run through China's populated Northern Plain and caused countless damages. Understanding the basic characteristics of floods andsedimentation and their relationship is crucial to the development of a comprehensive flood protection plan for the Lower Yellow River By illustrating the erosion/deposition patterns under different flood and sediment inputs, this article explains these characteristics and discusses principles for controlling sediment distributions in this complex river system.     

Fundamental mechanisms of bonding of glass fiber reinforced polymer reinforcement to concrete

Fundamental mechanisms of bonding between glass fiber reinforced polymer (GFRP) bar and concrete are presented. Contributions from chemical bonding, bearing resistance, and frictional resistance to bond were delineated by measuring the following: the load corresponding to complete debonding of the bar, the load corresponding to onset of sliding and pullout of the bar along the entire embedment length, and the frictional load corresponding to frictional resistance to sliding. Research findings indicate that while chemical bonding was the main contributor to the interfacial bond strength, the other two mechanisms contributed to the pullout strength of the bar. Correlation between the bar’s surface geometry and the contributions from the three mechanisms are discussed.     

Novel high-speed induction motor for a commercial centrifugalcompressor

This paper describes the electrical, mechanical and metallurgical design, construction, and testing of a novel low-cost high-speed high-efficiency induction motor to drive a new type of small centrifugal compressor in industrial cooling applications. The 28-shaft-hp 50-kr/min motor features a unique laminated rotor with a multifunction high-strength copper-alloy cage brazed with a novel process. Relatively thin high-silicon steel laminations were used to achieve low losses and high mechanical strength at low cost, Different heat treatments for the stator and rotor laminations were used to optimize the mechanical and magnetic properties, The preprototype motors achieved about 94% (electromagnetic) efficiency at the rated point, including inverter harmonics, while meeting cost (less than one-tenth of aerospace practice) and produceability goals     

NUMERICAL INVESTIGATION OF HEAT TRANSFER UNDER CONFINED IMPINGING TURBULENT SLOT JETS

This work numerically in vestigates confined impinging turbulent slot jets. Eight turbulence models, including one standard and seven low-Reynolds-number k-epsilon models, are employed and tested to predict the heat transfer performance of multiple impinging jets. Validation results indicate that the prediction by each turbulence model depends on grid distribution and numerical scheme used in spatial discretization. In addition, spent fluid exits are set between impinging jets to reduce the cross-flow effect in degradation of the heat transfer of downstream impinging jets. The overall heat transfer performance can be enhanced by proper spent fluid removal.