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1.
MA Nowak AL Lloyd GM Vasquez TA Wiltrout LM Wahl N Bischofberger J Williams A Kinter AS Fauci VM Hirsch JD Lifson 《Canadian Metallurgical Quarterly》1997,71(10):7518-7525
Mathematical modeling of viral replication dynamics, based on sequential measurements of levels of virion-associated RNA in plasma during antiretroviral treatment, has led to fundamental new insights into human immunodeficiency virus type 1 pathogenesis. We took advantage of the simian immunodeficiency virus (SIV)-infected macaque model to perform detailed measurements and mathematical modeling during primary infection and during treatment of established infection with the antiretroviral drug (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA). The calculated clearance half-life for productively infected cells during resolution of the peak viremia of primary infection was on the order of 1 day, with slightly shorter clearance half-lives calculated during PMPA treatment. Viral reproduction rates upon discontinuation of PMPA treatment after 2 weeks were approximately twofold greater than those obtained just prior to initiation of treatment in the same animals, likely reflecting accumulation of susceptible target cells during treatment. The basic reproductive ratio (R0) for the spread of SIV infection in vivo, which represents the number of productively infected cells derived from each productively infected cell at the beginning of infection, was also estimated. This parameter quantifies the extent to which antiviral therapy or vaccination must limit the initial spread of virus to prevent establishment of chronic disseminated infection. The results thus provide an important guide for efforts to develop vaccines against SIV and, by extension, human immunodeficiency virus. 相似文献
2.
Networkable Windows-based operating system devices present information security challenges to both vendors and users of such devices. This article highlights some of those threats and offers measures to improve the link between a firm's business strategy, its operational activities, and its information security strategy. 相似文献
3.
C Faure M Besnard A Hirsch JF Mougenot M Peuchmaur JP Cezard J Navarro 《Canadian Metallurgical Quarterly》1996,23(4):419-421
N-(phosphonacetyl)-disodium L-aspartic acid (PALA) demonstrates a synergistic antitumor effect when combined with 5-Fluorouracil (5-FU) in in vitro studies. In a Phase II trial, 23 eligible patients with unresectable or metastatic adenocarcinoma of the stomach were treated with weekly i.v. bolus PALA (250 mg/M2) followed 24 hours later by a 24-hour infusion of 5-FU (2600 mg/M2) for an initial period of 8 weeks. No objective responses were noted. PALA and 5-FU is inactive against gastric adenocarcinoma at the doses and schedule used in this trial. 相似文献
4.
Alpidem, an imidazopyridine that acts at the gamma-aminobutyric acid/benzodiazepine receptor complex, has been reported to be an effective anxiolytic with a more favorable side effect profile than benzodiazepines. The effect of alpidem was investigated in an 8-week, open, clinical trial in 13 patients with panic disorder, with or without agoraphobia. Three patients were responders (much improved or very much improved), five patients were nonresponders, and five patients dropped out after less than 6 weeks of treatment. Significant improvement was seen in the sample as a whole for spontaneous panic attacks, phobic avoidance, and anticipatory anxiety. Most improvement occurred during the first 4 weeks of treatment, and responders had milder panic disorder at baseline. Adverse effects were generally mild. After 8 weeks of treatment, taper of medication over 2 weeks occurred without significant worsening of panic disorder symptoms. The efficacy of alpidem in the treatment of panic disorder remains uncertain and requires assessment in a controlled trial. 相似文献
5.
Niklas Schlimm Mirko Novakovic Robert Spielmann Tobias Knierim 《Informatik-Spektrum》2007,48(6):251-258
Nicht-funktionale Anforderungen an ein Softwaresystem beschreiben Aspekte, die nicht direkt die Funktionalit?t, wie sie der
Benutzer sieht, betreffen. 相似文献
6.
Robert L. Hirsch 《Journal of Fusion Energy》2002,21(2):113-116
Assuming significant technical success in the ITER project by the year 2015, it is likely that governments will want to develop a more comprehensive plan for DT tokamak fusion power commercialization. To provide a glimpse into many of the related issues, we construct conversations between the director of the U.S. fusion program and three specialists key to commercial fusion success: an environment and safety regulator, an environmentalist, and an electric generation investor. The insights from these imagined conversations will hopefully be of value as tokamak fusion power proponents plan beyond ITER. 相似文献
7.
Describes long-term divergent selection for geotaxis in lines of the fruit fly. After 26 yrs (600+ generations) of intermittent selection, the initial experimental procedure showed that the mean geotactic scores remained stable on relaxed selection, a result suggesting that evolutionary changes had occurred in these lines. Because the stability was not due to genetic fixation (homozygosity) of the lines, it is concluded that it was due to either (a) close linkage of genes associated with geotaxis (which would not result in enduring change) or (b) the development of new coadapted gene complexes utilizing genes associated with extreme geotaxis expression (which should result in enduring change). Better evidence for the latter hypothesis was obtained, during the 2nd experimental procedure, from the low- than the high-geotaxis line. The notions of coadaptation and genetic homeostasis are considered, as well as the prospective use of the geotaxis lines to study such concepts experimentally. The geotactic behavior expressed in each line is defined as instinctive: It increases reproductive success and is characteristic of a population. (30 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
8.
PT Fox RJ Ingham JC Ingham TB Hirsch JH Downs C Martin P Jerabek T Glass JL Lancaster 《Canadian Metallurgical Quarterly》1996,382(6587):158-161
The cause of stuttering is unknown. Failure to develop left-hemispheric dominance for speech is a long-standing theory although others implicated the motor system more broadly, often postulating hyperactivity of the right (language nondominant) cerebral hemisphere. As knowledge of motor circuitry has advanced, theories of stuttering have become more anatomically specific, postulating hyperactivity of premotor cortex, either directly or through connectivity with the thalamus and basal ganglia. Alternative theories target the auditory and speech production systems. By contrasting stuttering with fluent speech using positron emission tomography combined with chorus reading to induce fluency, we found support for each of these hypotheses. Stuttering induced widespread overactivations of the motor system in both cerebrum and cerebellum, with right cerebral dominance. Stuttered reading lacked left-lateralized activations of the auditory system, which are thought to support the self-monitoring of speech, and selectively deactivated a frontal-temporal system implicated in speech production. Induced fluency decreased or eliminated the overactivity in most motor areas, and largely reversed the auditory-system underactivations and the deactivation of the speech production system. Thus stuttering is a disorder affecting the multiple neural systems used for speaking. 相似文献
9.
CB Granger J Hirsch RM Califf J Col HD White A Betriu LH Woodlief KL Lee EG Bovill RJ Simes EJ Topol 《Canadian Metallurgical Quarterly》1996,93(5):870-878
BACKGROUND: Although intravenous heparin is commonly used after thrombolytic therapy, few reports have addressed the relationship between the degree of anticoagulation and clinical outcomes. We examined the activated partial thromboplastin time (aPTT) in 29,656 patients in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO-I) trial and analyzed the relationship between the aPTT and both baseline patient characteristics and clinical outcomes. METHODS AND RESULTS: Intravenous heparin was administered as a 5000-U bolus followed by an initial infusion of 1000 U/h, with dose adjustment to achieve a target aPTT of 60 to 85 seconds. aPTTs were collected 6, 12, and 24 hours after thrombolytic administration. Higher aPTT at 24 hours was strongly related to lower patient weight (P < .00001) as well as older age, female sex, and lack of cigarette smoking (all PT< .0001). At 12 hours, the aPTT associated with the lowest 30-day mortality, stroke, and bleeding rates was 50 to 70 seconds. There was an unexpected direct relationship between the aPTT and the risk of subsequent reinfarction. There was a clustering of reinfarction in the first 10 hours after discontinuation of intravenous heparin. CONCLUSIONS: Although the relationship between aPTT and clinical outcome was confounded to some degree by the influence of baseline prognostic characteristics, aPTTs higher than 70 seconds were found to be associated with higher likelihood of mortality, stroke, bleeding, and reinfarction. These findings suggest that until proven otherwise, we should consider the aPTT range of 50 to 70 seconds as optimal with intravenous heparin after thrombolytic therapy. 相似文献
10.