The apolipoprotein E allele epsilon 4 is overrepresented in patients with the Lewy body variant of Alzheimer's disease

We determined apolipoprotein E (ApoE) genotypes in 122 autopsied demented patients. The frequency of the ApoE epsilon 4 allele was 39.6% in Alzheimer's disease (AD), 29.0% in the Lewy body variant of AD (LBV), and 6.25% in diffuse Lewy body disease. For AD and LBV patients, the epsilon 4 frequency was significantly higher than that reported in nondemented controls (10 to 15%). Therefore, LBV and AD share ApoE epsilon 4 as a genetic risk factor, providing further evidence that these conditions overlap.     

The band areas of proteins determined by fluorescent scanning in the commercial automated gel electrophoresis apparatus

An automated gel electrophoresis apparatus, recently available commercially, allows one to follow the band during electrophoresis in real time, and lends itself therefore to an evaluation of bandwidth as a function of migration time (the dispersion coefficient), resolution and band shape. These determinations assume the constancy of band area with migration time and at various gel concentrations. The purpose of the present study was to verify these assumptions. Representative proteins and sodium dodecyl sulfate (SDS)-proteins, either natively fluorescent or fluorescein carboxylate labeled, were found to exhibit band areas which approach constancy as a function of migration time in both agarose and polyacrylamide gel electrophoresis, provided that (i) the protein concentration under the band was low enough to obviate self-quenching of fluorescence; (ii) the separation of the protein of interest from contaminants had progressed sufficiently during the time at which band areas were measured; (iii) the baseline under the peak was sufficiently well defined. However, band areas decrease with increasing gel concentration. Protein peaks exhibited leading and trailing tails. The ratio of the combined tail area to total area appeared to be near-constant at varying migration times. However, that ratio increases with increasing gel concentration. The tail area does not appear to be an artifact of fluorometric detection since it is reproduced upon fluorimetric analysis of the protein eluted from gel slices after electrophoresis. However, it may be due to photochemical destruction under the conditions of repetitive fluorometric peak detection.     

Parallel path consistency

Filtering algorithms are well accepted as a means of speeding up the solution of the consistent labeling problem (CLP). Despite the fact that path consistency does a better job of filtering than arc consistency, AC is still the preferred technique because it has a much lower time complexity. We are implementing parallel path consistency algorithms on multiprocessors and comparing their performance to the best sequential and parallel arc consistency algorithms.^(1,2) (See also work by Kerethoet al. ⁽³⁾ and Kasif⁽⁴⁾) Preliminary work has shown linear performance increases for parallelized path consistency and also shown that in many cases performance is significantly better than the theoretical worst case. These two results lead us to believe that parallel path consistency may be a superior filtering technique. Finally, we have implemented path consistency as an outer product computation and have obtained good results (e.g., linear speedup on a 64K-node Connection Machine 2).     

Phase I study of mitoxantrone plus etoposide with multidrug blockade by SDZ PSC-833 in relapsed or refractory acute myelogenous leukemia

PURPOSE: Expression of the multidrug resistance gene (MDR1) p170 protein is frequent in leukemic blasts from patients with relapsed acute myelogenous leukemia (AML). A phase I study using the nonimmunosuppressive MDR1 blocker SDZ PSC-833 (PSC) in combination with mitoxantrone (MITO) and etoposide (VP) was performed. PATIENTS AND METHODS: Starting doses (LVL0) of MITO (3.25 mg/m2/d on days 1 and 3 to 6) and VP (210 mg/m2/d on days 1 and 3 to 5) were 40% of the maximal-tolerated dose (MTD) from a prior study. A 1.5-mg/kg loading dose of PSC was followed by a 120-hour continuous infusion of 10 mg/kg/d on days 2 to 6. Blood samples for PSC, MITO, and VP pharmacokinetics (PK) were taken on days 1 and 3, and samples for MDR1 expression were taken on day 0. RESULTS: Severe mucositis developed in all patients at LVL0; therefore, MITO and VP doses were reduced to 2.5 and 170 mg/m2 (LVL-1) for the next seven patients, and this dose proved to be MTD. All LVL0 and three LVL-1 patients had transient elevations in the serum bilirubin level to > or = 4 mg/dL. Serum creatinine level increased to greater than 2 mg/dL in one case. There were no other grade 3 or 4 nonhematologic toxicities observed. The peripheral blood was cleared of leukemia in three LVL0 and four LVL-1 patients. The marrow was cleared of leukemic cells in one LVL0 and five LVL-1 patients, and a significant reduction in marrow leukemic infiltrate was observed in eight of 10. No patient achieved complete remission (CR), and all died of progressive disease (n = 8) or infection (n = 2). MDR1 expression was detected by fluorescent-activated cell sorter (FACS) analysis in five of seven cases. An elevated MDR1 mRNA level was detected by quantitative polymerase chain reaction (Q-PCR) in six of eight cases studied. Clearing of leukemia cells from the marrow occurred in four of six MDR1-positive and one of three MDR1-negative patients. Despite the fact that LVL0 doses had to be reduced due to toxicity, coadministration of PSC did not produce a consistent effect on MITO PK; however, it did repeatedly lead to increased levels of VP in the serum. CONCLUSION: We conclude that PSC-MITO-VP is a tolerable regimen with antileukemic activity. Addition of PSC necessitated a 66% reduction in MITO and VP doses from a prior study without PSC.     

重馏分油加氢脱氮反应动力学模型的研究

简要地介绍了一些典型的模型氮化物的ＨＤＮ反应规律。根据胜利ＶＧＯ在３７２２Ｂ催化剂上的大量ＨＤＮ实验数据，提出了如下的ＨＤＮ基本反应动力学方程：ｄＣＮｄｔ＝－ｋ１＋Ｋ＊ＣＮＣＮＰＨ２为了扩大上式的应用范围，详细分析了各种因素（如原料油种类和馏程及Ｈ２Ｓ等）对ＨＤＮ的影响，并开发了相应的经验关联式，从而得到了一个较完整的馏分油ＨＤＮ反应动力学模型。验证实验表明，该模型是成功的。     

A new boundary-layer wind tunnel at the Danish Maritime Institute

The paper describes a new boundary-layer wind tunnel at the Danish Maritime Institute in Lyngby. The wind tunnel is of the open-circuit type and is integrated into a building raised for the purpose. The design was constrained by the need to provide a simulation of the atmospheric boundary layer (without thermal stratification) and alternatively a uniform flow without excessive turbulence.The wind tunnel has a working section of principal dimensions: length 20.8 m, width 2.6 m and height 1.8 m (adjustable from 1.8 to 2.3 m). The maximum wind speed in the working section when empty is about 26 m s^?1.Data acquisition, analysis and instrumentation in relation to the new wind tunnel are discussed and, finally, an example of a simulated natural wind is presented.     

2 cm long monolithic multisection laser for active modelocking at 2.2 GHz

A 2 cm long three-contact multisection laser has been fabricated for modelocking at very low repetition rates. Active modelocking yields 8.0-12.3 ps pulses at 2.2, 4.3 and 6.5 GHz corresponding to the fundamental, first, and second harmonics of the cavity resonance frequency. This device demonstrates the feasibility of fabricating monolithic pulse sources operating at rates as low as the OC-48 Sonet transmission rate (2.488 Gbit/s).<>     

The amphiphysin family of proteins and their role in endocytosis at the synapse

Clathrin-mediated endocytosis at the plasma membrane is a major pathway of synaptic vesicle recycling in neurones, but little is known about the molecular machinery that orchestrates the process. The amphiphysin protein has recently emerged into the limelight since its discovery in 1992 as a synaptic vesicle-associated protein. It was subsequently found to interact in vitro with the GTPase dynamin through its SH3 domain. However, only in the past year has its role in endocytosis been confirmed, with the demonstration that the introduction of dominant-negative-acting SH3 domains into living cells causes a potent blockade of clathrin-mediated endocytosis. This, together with the discovery by several groups of a second nerve terminal-enriched amphiphysin isoform, and the finding that the two proteins heterodimerize, further suggests that the amphiphysins are closely connected with dynamin-mediated vesicle budding. This review summarizes current views in the field, and draws on data that suggest intriguing alternative roles--including possible involvement in the cytoskeleton and in tumour suppression--for certain members of the amphiphysin family.     

A nonlinear operator-based speech feature analysis method withapplication to vocal fold pathology assessment

Traditional speech processing methods for laryngeal pathology assessment assume linear speech production with measures derived from an estimated glottal flow waveform. They normally require the speaker to achieve complete glottal closure, which for many vocal fold pathologies cannot be accomplished. To address this issue, a nonlinear signal processing approach is proposed which does not require direct glottal flow waveform estimation. This technique is motivated by earlier studies of airflow characterization for human speech production. The proposed nonlinear approach employs a differential Teager energy operator and the energy separation algorithm to obtain formant AM and FM modulations from filtered speech recordings. A new speech measure is proposed based on parameterization of the autocorrelation envelope of the AM response. This approach is shown to achieve impressive detection performance for a set of muscular tension dysphonias. Unlike flow characterization using numerical solutions of Navier-Stokes equations, this method is extremely computationally attractive, requiring only a small time window of speech samples. The new noninvasive method shows that a fast, effective digital speech processing technique can be developed for vocal fold pathology assessment without the need for direct glottal flow estimation or complete glottal closure by the speaker. The proposed method also confirms that alternative nonlinear methods can begin to address the limitations of previous linear approaches for speech pathology assessment