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951.
The L1 cell adhesion molecule (L1CAM) plays an important role in axon growth, fasciculation, and neural migration. Mutations in the L1CAM gene produce a phenotype characterised by X linked hydrocephalus, mental retardation, spastic paraplegia, adducted thumbs, and agenesis of the corpus callosum. We have conducted a detailed analysis of the phenotypic effects of missense mutations in the extracellular portion of L1CAM, following a study that differentiated between "key" amino acid residues critical for maintaining the conformation of the extracellular immunoglobulin type C-like (Ig) or fibronectin type III-like (FN) domains and surface residues of less certain significance. We have analysed the data from 71 published cases and seven patients whose mutations were detected in our laboratory to determine if the site of a missense mutation in the Ig or FN domains correlated with the severity of hydrocephalus, presence of adducted thumbs, or survival past infancy. Mutations affecting the key residues in either type of domain were more likely to produce a phenotype with severe hydrocephalus, adducted thumbs, and lifespan less than one year than were mutations affecting surface residues. In addition, mutations affecting the FN domains were more likely than those affecting Ig domains to produce a phenotype with severe hydrocephalus, with less certain effects on adducted thumbs and lifespan. Mutations in key residues of the FN domains were particularly deleterious to infant survival. These data provide information that may be useful in predicting some aspects of the phenotypic effects of certain L1CAM mutations. 相似文献
952.
LL Nielsen M Gurnani J Syed J Dell B Hartman M Cartwright RC Johnson 《Canadian Metallurgical Quarterly》1998,9(5):681-694
Type 5 adenoviral (Ad) vectors have been the "vector-of-choice" for preclinical studies on p53 tumor suppressor gene therapy of cancer. Previous studies have examined the in vivo efficacy of p53 Ad when given intratumorally. However published information does little to guide clinicians in the design of intraperitoneal (i.p.) dosing trials for i.p. tumors, e.g., ovarian, or clinical trials using regional organ perfusion, e.g., for lung tumors. Therefore, we examined several parameters with special significance for these routes of administration. Lung metastases from p53mut MDA-MB-231 mammary xenografts were treated with therapeutic levels of intravenous buffer, beta-galactosidase (beta-Gal) Ad, or p53 Ad. Treatment with intravenous p53 Ad significantly reduced the number of metastases per lung and there was a dramatic reduction in the surface area occupied by these tumors as compared to control groups. Two types of i.p. tumor xenografts were used for preclinical modeling of i.p. gene therapy, the p53null SK-OV-3 ovarian and the p53mut DU-145 prostate human cancers. In a study examining the effect of different vehicle volumes on the efficacy of a constant drug dose, all mice treated with p53 Ad had reduced tumor burden compared to controls. Dosing volumes between 0.2 and 1 ml were equally effective and all were more effective than a dosing volume of 0.1 ml. However, reduced efficacy was observed when a volume of 1.5 ml was used. When the effect of dosing frequency on antitumor efficacy was examined, fractionated doses of p53 Ad had somewhat greater efficacy than fewer, bolus injections. One of the significant elements in the emerging toxicology associated with recombinant adenoviruses is the hepatocyte pathology caused by high systemic concentrations of adenovirus. For recombinant Ad used in this study, there was a pronounced dose-dependence for the liver response, with very high, repeated doses causing significant hepatocellular insult. Expression of cytoplasmic beta-Gal protein coincided with areas of greatest damage in mice treated with high doses of beta-Gal Ad. Ultrastructural examination of hepatocyte intranuclear inclusions revealed moderately electron-dense, tightly packed granular material interspersed with more electron-dense nuclear material. Human tumor xenografts, but not mouse tissues, expressed viral hexon protein. In summary, hepatic toxicity caused by high concentrations of recombinant adenovirus was observed in murine cancer models. However, therapeutic levels of p53 Ad could be achieved which had dramatic efficacy without significant pathology. 相似文献
953.
William Jason Mixter was born in 1880 and graduated from the Harvard Medical School class of 1906. Like his father, Mixter was a prominent surgeon at the Massachusetts General Hospital, and in 1911 the two shared the job of overseeing all neurosurgery at that institution. By the early 1930s, W. J. Mixter was considered to be one of the nation's leading experts in spinal surgery, and he went on to become the first chief of the neurosurgery department at Massachusetts General Hospital. He served in the U. S. Army in both world wars and was actively involved in his local church community in Boston for many years. In 1934, at the age of 54, Mixter and Joseph S. Barr published an article on the intervertebral disc lesion in the New England Journal of Medicine. That article fundamentally changed the popular understanding of sciatica at that time, and for this work Mixter is generally credited by his contemporaries as being the man who best clarified the relation between the intervertebral disc and sciatica. Mixter and Barr's landmark report helped to establish surgery's prominent role in the management of sciatica at the time. Over the next few decades, discectomy surgery increased in popularity tremendously, and some refer to that period as the "dynasty of the disc." 相似文献
954.
AA Eyler E Baker L Cromer AC King RC Brownson RJ Donatelle 《Canadian Metallurgical Quarterly》1998,25(5):640-652
Few physical activity research studies have been conducted with minority women. The purpose of this study was to explore patterns of physical activity among minority women. Focus groups were conducted with volunteers older than age 40. Each group was led by a trained moderator familiar with the ethnic community targeted. The sessions were audiotaped and professionally transcribed. Constructs were researched and codes were developed. Data were analyzed using NUD*IST qualitative analysis program. While participants did not identify themselves as "exercisers," they indicated they got enough physical activity from caregiving, housekeeping, and workday activities. The most common environmental barriers to becoming more physically active included safety, availability, and cost. Personal barriers included lack of time, health concerns, and lack of motivation. Results indicate the importance of terminology and assessment when conducting physical activity research in these populations. Also, results suggest many barriers are changeable with policies and interventions. 相似文献
955.
C Silveira RM Soares M Ferreira RC Ferreira C Cotrim ML Ferreira AM Antunes 《Canadian Metallurgical Quarterly》1998,17(11):881-885
Cowden syndrome (CS) or multiple hamartoma syndrome (MIM 158350) is an autosomal dominant disorder with an increased risk for breast and thyroid carcinoma. The diagnosis of CS, as operationally defined by the International Cowden Consortium, is made when a patient, or family, has a combination of pathognomonic major and/or minor criteria. The CS gene has recently been identified as PTEN, which maps at 10q23.3 and encodes a dual specificity phosphatase. PTEN appears to function as a tumour suppressor in CS, with between 13-80% of CS families harbouring germline nonsense, missense, and frameshift mutations predicted to disrupt normal PTEN function. To date, only a small number of tumour suppressor genes, including BRCA1, BRCA2, and p53, have been associated with familial breast or breast/ovarian cancer families. Given the involvement of PTEN in CS, we postulated that PTEN was a likely candidate to play a role in families with a "CS-like" phenotype, but not classical CS. To answer these questions, we gathered a series of patients from families who had features reminiscent of CS but did not meet the Consortium Criteria. Using a combination of denaturing gradient gel electrophoresis (DGGE), temporal temperature gel electrophoresis (TTGE), and sequence analysis, we screened 64 unrelated CS-like subjects for germline mutations in PTEN. A single male with follicular thyroid carcinoma from one of these 64 (2%) CS-like families harboured a germline point mutation, c.209T-->C. This mutation occurred at the last nucleotide of exon 3 and within a region homologous to the cytoskeletal proteins tensin and auxilin. We conclude that germline PTEN mutations play a relatively minor role in CS-like families. In addition, our data would suggest that, for the most part, the strict International Cowden Consortium operational diagnostic criteria for CS are quite robust and should remain in place. 相似文献
956.
WN Bloch Z Karcioglu JM Felner JS Miller PN Symbas RC Schlant 《Canadian Metallurgical Quarterly》1978,74(5):579-581
The report of a failure of glutaraldehyde-preserved porcine aortic xenograft bioprosthesis in the aortic position after 13 months is presented. Severe aortic regurgitation resulted from three "idiopathic" perforations in one of the cusps, and a linear tear in another cusp. Light and electron microscopy showed generalized degeneration of collagen thoughout the faulty valve. The absence of a platelet-fibrin coat on edges of the tear suggested a recent origin, compatible with cardiac catheter manipulation during unsuccessful attempts to cross the valve. The histopathologic data from this valve correlate with previously reported failures with formaldehyde preserved xenograft valves. 相似文献
957.
A task-based statistical model of a worker's exposure distribution for an airborne chemical toxicant is applied to estimating the long-term average exposure level, mu. The precision in estimation is represented by the variance of the sample estimator, denoted by Var[mu]. A traditional sampling strategy consists of integratively measuring the 8-hr time-weighted average exposure level on randomly selected workdays, and computing the sample mean; this strategy is termed "simple one-stage cluster sampling," where each 8-hr workday is a cluster of thirty-two 15-min periods. Three alternative strategies involving measurements of 15-min TWAs are examined: simple random sampling of 15-min periods, and stratified random sampling of 15-min periods with proportional allocation by task, and with optimum allocation by task. All four survey designs provide unbiased estimates of mu. However, for a fixed cost, the stratified sampling designs may provide a lower Var[mu] than simple one-stage cluster sampling for less work time monitored. 相似文献
958.
Swamy R. Bates S. Brandon T.L. Cockburn B.F. Elliott D.G. Koob J.C. Zhengang Chen 《Solid-State Circuits, IEEE Journal of》2007,42(10):2245-2256
Low-density parity-check block codes (LDPC-BCs) are quickly becoming the forward error correcting code of choice for emerging communication standards. However, low-density parity-check convolutional codes (LDPC-CCs), the convolutional counterpart of LDPC-BCs, seem to be better suited in applications with streaming data or variable sized packets. A rate-1/2, (128,3,6) LDPC-CC ASIC has been implemented in 180-nm, 1.8-V CMOS technology. We present the VLSI architecture of a register-based LDPC-CC encoder and decoder that includes an on-chip, pseudo-random additive white Gaussian noise channel emulator. The decoder comprises a pipeline of ten identical processing units and attains up to 175 Mb/s of decoded throughput. 相似文献
959.
The force required to pull a 2400 tex glass roving through a melt impregnation compounding process was studied. Pulling force was continuously measured by suspending the double belt puller in a sling held stationary by a force transducer. Process variables such as roving pulling speed, number of cylindrical pins, pin diameter, and melt temperature were studied using polymide 66 and polypropylene polymers. The results suggest that the tension build‐up in the roving is caused by a combination of two effects: viscous shear stresses in a thin polymer‐rich layer between the roving and the pin, as well as frictional forces caused by roving contact with the pin. A simple mathematical model is developed and used to adequately describe the experimental results. 相似文献
960.
A. Adedeji T. Grünfelder F. S. Bates C. W. Macosko M. Stroup-Gardiner D. E. Newcomb 《Polymer Engineering and Science》1996,36(12):1707-1723
Microstructural transformation of a poly(styrene-b-butadiene-b-styrene), SBS, triblock copolymer blended with asphalt was studied as the asphalt composition was varied from 0 wt% to 96 wt%. Transmission electron microscopy (TEM), dynamic mechanical spectrometry (DMS), and differential scanning calorimetry (DSC) were used. The blends were made in batch mixers at 200°C, or by solution casting from a nonselective solvent (trichloroethane) at ∼28°C. Asphalt partially solubilizes the polybutadene (PB) midblock of the SBS producing saturated PB microdomains along with macrodomains of asphalt. When the asphalt concentration was varied from 10 to 90 wt%, the asphalt phase separated into a variable number of large domains, while the SBS-rich regions formed a continuous matrix. Networks of SBS-rich regions were observed at low magnification; these are referred to as macro-networks. At higher magnification, networks that are stabilized by polystyrene (PS) microdomains (denoted micro-networks) are also formed. The presence of a macro-network is also confirmed by stress relaxation tests. The macro-network broke down into microgel-like structures when the asphalt composition exceeded 90 wt%. Examination of the interior of the SBS-rich regions showed that the shape of the PS microdomains transformed from short cylinders to lamellae, hexagonally perforated lamellae (HPL), back to lamellae, short cylinders, and finally to spheres. DMS and DSC indicate a systematic increase in the PB glass transition temperature (Tg) and negligible change in the Tg of PS as the asphalt content increases. Triblock copolymers that can form a macro-network at low concentration will be more desirable for highway pavement modification. 相似文献