The glycoprotein precursor gene of the attenuated Junin virus vaccine strain (Candid #1)

A live attenuated virus vaccine has been recently developed to prevent Argentine hemorrhagic fever. In this paper, we report the nucleotide sequence of the glycoprotein precursor gene (GPC) of the Junin virus vaccine strain (Candid #1) and its flanking untranslated regions. The untranslated regions flanking the GPC genes of different arenaviruses are variable in length, sequence, and secondary structure. However, when this highly attenuated Junin virus strain is compared with the MC2 strain, which is of intermediate virulence, one nucleotide insertion and four nucleotide substitutions are found at positions that do not affect the predicted secondary structure. When Candid #1 and MC2 RNAs are compared, the nucleotide sequence changes in the GPC open reading frame are concentrated in the amino-proximal and the carboxy-proximal regions. The comparison of the amino acid residues shows that the major changes are located in the amino-proximal region of the GPC.     

Explaining category-related effects in the retrieval of conceptual and lexical knowledge for concrete entities: operationalization and analysis of factors

Category-related effects in the retrieval of conceptual and lexical knowledge for concrete entities have been well documented in lesion studies, and also with functional imaging and electrophysiological approaches. For example, brain-damaged subjects may be impaired in the ability to recognize or to name animals but not tools, or the opposite pattern may obtain. One reason for these dissociations is that different patterns of defects tend to be caused by distinct lesion profiles, suggesting a relative tendency for certain neural systems to be involved in category-related knowledge. But we and others have also hypothesized that a variety of traits of concrete entities co-determine category-related dissociations. Such traits ('factors') include homomorphy (similarity of form), familiarity, value to perceiver, manipulability, characteristic motion, characteristic sensory modality of transaction (vision, touch, hearing), and typical age of acquisition. It is our view that the mix of factors relative to different conceptual categories plays a key role in the neuroanatomical distribution of records for those different categories, and is thus behind the systematic correlations between certain retrieval defects and damage to certain neural systems [12, 52]. In this study, we operationalized these factors and analyzed their intercorrelations. Stimuli were slides of 215 items from the conceptual categories of animals, fruits/vegetables, tools/utensils, vehicles, and musical instruments. The factors were operationalized on the basis of ratings obtained from 227 normal control subjects and on the basis of computer analyses of the digitized outlines of the stimuli. Principal components analysis revealed that 81% of the variability across items could be accounted for by three components: Component 1 (practically useful, common items): high value to perceiver, tactile mode of transaction, high familiarity, low age of acquisition; Component 2 (homomorphic, non-manipulable items): high homomorphy, low characteristic motion and manipulability; Component 3 (items with characteristic sound): hearing mode of transaction, highly distinctive sounds. In another analysis, we found that the categories of animals versus tools/utensils differed significantly on the factors of homomorphy, familiarity, value, manipulability, characteristic motion, and touch. The factor structure we identified in this study may help explain category-related performance defects in brain-damaged subjects. The results lend support to our proposal that systematic differences in physical characteristics and contextual specification of concrete entities constitute a driving force behind the regionalization of neural systems related to the acquisition and retrieval of conceptual and lexical knowledge.     

弯曲成形动态模拟系统：BSIMU

本文针对自动弯曲机模具设计的关键环节之一——弯曲成形过程的实现,介绍了利用CAD技术进行动态模拟的BSIMU系统。描述了与其相关的模型的建立方法;成形动态模拟中所涉及的数据结构及处理方法;详细分析和介绍了模拟中从预处理、中间成形到边界成形全过程的整套算法及实施情况,并给出了算法框图;讨论了特殊情况的处理方法;叙述了工件在成形模拟中几何信息的获取和校正的方法;同时还讨论了本系统的适用范围。作为BSIMU的实际应用,本文最后给出了一个较为复杂的弯曲件动态成形模拟的实例。     

Mucociliary clearance in cystic fibrosis knockout mice infected with Pseudomonas aeruginosa

In this study, we examined whether mucociliary clearance differed between cystic fibrosis (CF) knockout mice and wildtype controls. Additionally, we investigated whether infection with Pseudomonas aeruginosa, a common pathogen in the CF lung, affected this important host defence mechanism. Ciliary beat frequency (fcb) and particle transport (PT) were recorded using an in vitro lung explant preparation. Measurements were made from uninfected cystic fibrosis transmembrane conductance regulator (CFTR) knockout (-/-) mice and littermate controls (+/+) and compared to measurements from infected animals. While there were no differences detectable in fcb between CFTR -/- mice and their +/+ controls either in the presence or absence of P. aeruginosa, PT rates were different between these groups; interestingly, PT rates appeared dependent on both CFTR and infection status, with uninfected CFTR +/+ animals demonstrating higher rates of PT than their -/- littermates, while CFTR +/+ P. aeruginosa-infected mice demonstrated lower PT than knockout mice. These data demonstrate differences in mucociliary clearance between cystic fibrosis transmembrane conductance regulator knockout mice and controls, and further that Pseudomonas aeruginosa infection affects mucociliary clearance in the peripheral airways of mice. Additionally, the observed differences in particle transport suggest that cystic fibrosis transmembrane conductance regulator knockout mice demonstrate different mucociliary responses to infection.     

How much protection is enough?

Infectious diseases are changing patient relations. Risk is a two-way street. Not only are health care providers at risk from patients, but patients also may be at risk from health care providers. Practical measures can be taken: identify the risks; determine how to reduce them; and educate others at risk.     

Prevalence and etiology of gastroduodenal ulcer in HIV-positive patients: a comparative study of 497 symptomatic subjects evaluated by endoscopy

Automatic detection and quantitation of contrast-enhanced lesions on MRI is expected to be useful in characterizing the disease state in multiple sclerosis (MS). The enhancing structures such as cerebral vasculature and regions with no blood-brain barrier complicate automated analysis of lesion enhancement. A pulse sequence that incorporates both stationary and marching saturation bands and gradient dephasing is described for suppressing the enhancements within the cerebral vasculature. A postprocessing technique based on automatic image segmentation is implemented for eliminating enhancing structures such as choroid plexus. All MS lesions larger than 5 mm3 have been successfully identified. The automated analysis produced no false-positives or false-negative lesions above this volume in 13 patients with MS who were evaluated using the acquisition and evaluation techniques described.     

Minimal residual disease status before allogeneic bone marrow transplantation is an important determinant of successful outcome for children and adolescents with acute lymphoblastic leukemia

The efficacy of allografting in acute lymphoblastic leukemia (ALL) is heavily influenced by remission status at the time of transplant. Using polymerase chain reaction (PCR)-based minimal residual disease (MRD) analysis, we have investigated retrospectively the impact of submicroscopic leukemia on outcome in 64 patients receiving allogeneic bone marrow transplantation (BMT) for childhood ALL. Remission BM specimens were taken 6 to 81 days (median, 23) before transplant. All patients received similar conditioning therapy; 50 received grafts from unrelated donors and 14 from related donors. Nineteen patients were transplanted in first complete remission (CR1) and 45 in second or subsequent CR. MRD was analyzed by PCR of Ig or T-cell receptor delta or gamma rearrangements, electrophoresis, and allele-specific oligoprobing. Samples were rated high-level positive (clonal band evident after electrophoresis; sensitivity 10(-2) to 10(-3)), low-level positive (MRD detected only after oligoprobing; sensitivity 10(-3) to 10(-5)), or negative. Excluding 8 patients transplanted in CR2 for isolated extramedullary relapse (all MRD-), MRD was detected at high level in 12 patients, low level in 11, and was undetectable in 33. Two-year event-free survival for these groups was 0%, 36%, and 73%, respectively (P <.001). Follow-up in patients remaining in continuing remission is 20 to 96 months (median, 35). These results suggest that MRD analysis could be used routinely in this setting. This would allow identification of patients with resistant leukemia (who may benefit from innovative BMT protocols) and of those with more responsive disease (who may be candidates for randomized trials of BMT versus modern intensive relapse chemotherapy).     

Allopurinol, an inhibitor of xanthine oxidase, reduces uric acid levels and modifies the signs associated with copper deficiency in rats fed fructose

This study was designed to focus on the potential stress that xanthine oxidase could produce in copper-deficient rats fed fructose. Fructose consumption results in an excess production of uric acid due to an increased degradation of nucleotides. The enzyme xanthine oxidase catalyzes the oxidation of both hypoxanthine and xanthine. During the oxidation process free radicals are generated, which in turn, induce lipid peroxidation and premature death. Allopurinol -- a competitive inhibitor of xanthine oxidase -- could alleviate the combined effects of fructose feeding and copper deficiency. Twenty-five male rats were fed for 4 weeks from weaning a copper-deficient or adequate diet containing fructose. Twelve rats were given a daily oral dose of 5 mg allopurinol/100 g b.wt. Two copper-deficient rats that were not treated with allopurinol died prematurely during the fourth week of the study. No mortality occurred in the group of copper-deficient rats that had been treated with allopurinol. Anemia was alleviated by allopurinol, which in turn, could be responsible for improved growth rate. Allopurinol was effective in inhibiting xanthine oxidase activity in vivo as measured by the dramatic reduction of uric acid production. Lipid peroxidation, however, was not affected by allopurinol. It is concluded that the beneficial effects of allopurinol in copper deficiency do not appear to be related to prevention of oxygen radicals, but rather, to the protection against the catabolic destruction of purines, which in turn, increases nucleotide pool.     

Mucosal exudation of plasma is a noninjurious intestinal defense mechanism

We have demonstrated in sensitized rats that the immediate response to endointestinal challenge with allergen (10(-6) M ovalbumin) is characterized by mucosal exudation of plasma with little or no concomitant change in the mucosal absorption capacity. The luminal entry of plasma macromolecules also leaves the light microscopic structure and the ultrastructure of the mucosa unaffected. It is possible that the plasticity of epithelial zonulae occludens allows a noninjurious and unidirectional paracellular flux of extravasated plasma into the gut lumen. We propose that inflammatory-stimulus-induced mucosal exudation of plasma belongs to the first-line defense mechanisms of the intact lining of the intestine.     

Impairment of vascular endothelial function by high-potassium storage solutions

High-potassium cold storage solutions are currently used to preserve myocardial function during heart transplantation. However, the effects of high potassium concentration on vascular endothelial function are not well known. We therefore tested vascular rings for endothelial-dependent and endothelial-independent relaxation during storage in normokalemic, normothermic buffers and then in buffers supplemented with 10 to 110 mmol/L KCl. Maximal endothelial-dependent relaxation was significantly reduced at all high potassium concentrations. Endothelial-independent relaxation was impaired only with 80 and 110 mmol/L KCl buffers. Both endothelial-dependent relaxation and endothelial-independent relaxation returned to normal values after washout of excess potassium. Similarly, endothelial-dependent relaxation and endothelial-independent relaxation were assessed in rings after 24 hours of hypothermic storage in normokalemic Krebs buffer, and in buffers containing 20 and 110 mmol/L KCl. Maximal endothelial-dependent relaxation was significantly reduced after preservation in the high-potassium solutions, whereas endothelial-independent relaxation was not impaired. We conclude that there is significant impairment of endothelial function after cold storage in a high-potassium buffer. Inadequate washout of potassium during normothermic conditions may lead to further functional impairment of vascular responsiveness. A low-potassium storage medium is recommended for improved vascular protection.