Human RanGTPase-activating protein RanGAP1 is a homologue of yeast Rna1p involved in mRNA processing and transport

RanGAP1 is the GTPase activator for the nuclear Ras-related regulatory protein Ran, converting it to the putatively inactive GDP-bound state. Here, we report the amino acid sequence of RanGAP1, derived from cDNA and peptide sequences. We found it to be homologous to murine Fug1, implicated in early embryonic development, and to Rna1p from Saccharomyces cerevisiae and Schizosaccharomyces pombe. Mutations of budding yeast RNA1 are known to result in defects in RNA processing and nucleocytoplasmic mRNA transport. Concurrently, we have isolated Rna1p as the major RanGAP activity from Sc. pombe. Both this protein and recombinant Rna1p were found to stimulate RanGTPase activity to an extent almost identical to that of human RanGAP1, indicating the functional significance of the sequence homology. The Ran-specific guanine nucleotide exchange factor RCC1 and its yeast homologues are restricted to the nucleus, while Rna1p is reported to be localized to the cytoplasm. We suggest a model in which both activities, nuclear GDP-to-GTP exchange on Ran and cytoplasmic hydrolysis of Ran-bound GTP, are essential for shuttling of Ran between the two cellular compartments. Thus, a defect in either of the two antagonistic regulators of Ran would result in a shutdown of Ran-dependent transport processes, in agreement with the almost identical phenotypes described for such defects in budding yeast.     

Treatment of complex loss of substance in acute leg injuries

Solving the problems inherent in the treatment of Gustillo type III open fractures of leg requires the intervention of multiple surgical disciplines: orthopedic, plastic and vascular. Consensus exists with respect to many therapeutic principles, but several points remain the subject of debate. Based on an extensive literature review, the indications, results and prognosis for both skin covery and bone reconstruction are defined as precisely as possible. Early treatment is essential, the loss of soft tissue substance being repaired within the first two weeks, particularly if the use of a free flap is envisaged. Two stage treatment, cutaneous and bony, offers the advantage of safety, with additional benefits if conventional grafts are applied within 1 to 2 months. Overall therapeutic results are dependent on good interdisciplinary team work and, to an increasing extent, on the urgent participation of plastic surgeons experienced in microsurgical techniques.     

Evaluation of sequential thallium and gallium scans of the chest in AIDS patients

With decreasing incidence of pneumocystis carinii pneumonia (PCP) in AIDS as a result of prophylactic regimens, there is a higher incidence of tuberculosis (TB), mycobacterium avii complex (MAC), kaposi sarcoma and malignant lymphoma. There is a need for differentiating these various pathological entities. The purpose of this study was for a retrospective evaluation of sequential thallium and gallium scans in AIDS patients for differentiating intrathoracic kaposi sarcoma from malignant lymphoma and opportunistic infections. METHODS: A total of 181 patients had both studies completed between March 1992 and May 1994. The final diagnosis was verified only in 83 patients. Results were correlated with the CD4 counts, bronchoscopic and chest radiograph findings. RESULTS: In patients with pulmonary kaposi sarcoma and no opportunistic infections (19 patients), a thallium-positive, gallium-negative pattern was detected in 17 patients with a sensitivity of 89%. In the presence of kaposi sarcoma plus opportunistic infections, this pattern was only detected in 7 of 19 patients (sensitivity dropped to 37%). In 45 patients with opportunistic infections and no kaposi sarcoma, only two false-positive findings were found in patients with cytomegalic virus pneumonia for a specificity of 96%. For the whole group of 83 patients, sensitivity was 63%; specificity 95%; positive predictive value 92%; accuracy 81%; and negative predictive value 75%. CONCLUSION: A thallium-positive, gallium-negative pattern in AIDS patients has a high specificity for the diagnosis of kaposi sarcoma, however, the sensitivity dropped from 89% to 37% in the presence of opportunistic infections.     

Comparison of serological tests for detection of Mycoplasma gallisepticum antibodies in eggs and chicks hatched from experimentally infected hens

Specific pathogen free hens and males were experimentally infected with Mycoplasma gallisepticum. Eggs were then collected, and a part was incubated and set for hatching. Mycoplasma cultures were performed on infected adults and antibodies to MG were analysed by use of slide agglutination (SA) test and commercial ELISA tests on adults and chicks sera and on yolks from non incubated eggs. Both ELISA tests could detect antibodies in yolks from non incubated eggs laid three weeks after infection. SA and the three ELISA tests revealed positive sera in chicks hatched from eggs laid as soon as one week after infection.     

Gleno-humeral arthroscopic arthrolysis for shoulder stiffness. Apropos of 26 cases. Société Fran?aise d'Arthroscopie

Shoulder stiffness is a problem which covers many different conditions. In fact there is still a semantic and pathogenetic confusion. The words: capsulite retractile, frozen shoulder, adhesive capsulitis, stiff shoulder contracture have been successively used and this ambiguity renders the literature difficult to interpret. Moreover the cause of the stiffness which depends on the aetiology, is not always clearly known: capsular contraction, capsular adhesion, capsular scarring following trauma or surgery, extra capsular phenomenons in the subacromial bursa, muscles or tendons. MATERIALS AND METHODS: 26 shoulders (25 patients) were reviewed with a follow up of 21 months using the Constant's scoring system. Patients had an average duration of symptoms for 13 months (1 to 27). Pre op passive motion was: abduction: 74 degrees, external rotation: 6 degrees, forward flexion: 84 degrees. The average motion core was 12.9/40. We distinguished three groups: primary frozen shoulder (13 cases) ; bipolar stiffness (3 cases) due to rotator cuff disease ; acquired "surgical" stiffness, (10 cases). The capsular release was performed, at the anterior rim of the glenoid fossa, purely anterior or anterior and inferior, followed by gentle manipulation. If external rotation was not improved the coraco-humeral ligament was detached from its coracoid attachment. Additional procedures were performed:acromioplasty (5 cases), bursectomy (3 cases), SLAP lesion debridement (1 case). Only 2 out 13 primary shoulders required an additional procedure. RESULTS: 1-There were no intra-operative complications (vascular or neural). 2-Range of Motion: the average gain under anesthesia was: abduction: 72 degrees, external rotation: 34 degrees, forward flexion: 86 degrees. Final result was obtained with a mean duration of seven months. There was no difference according to the aetiology. Gain was more important in the primary group (9.69 to 34.9 vs 15.8 to 30.6). 3-Subjective results were better in the primary group. 4-Objective results demonstrated an absolute Constant's score of 70.3, that is to say 83.4 per cent of the contralateral supposed healthy shoulder. There were 3 excellent, 5 very good, 7 good, but 11 fair or poor results. The relative Constant's score was 91 per cent in the primary group and only 76 per cent in the acquired group. The difference was due to the pain and strength which were greatly improved in the primary group. DISCUSSION: Arthroscopic release of shoulder contracture is feasible, safe and effective. For primary frozen shoulder, there is usually spontaneous recovery. Indications for surgery are very few. There is no evidence that arthroscopic release shortens spontaneous evolution. Therefore, we propose it in very selected cases of dramatically limited motion. One year of evolution is an acceptable time. For bipolar stiffnesses, arthroscopy allows one to recognize the exact cause of the stiffness and to treat it, especially the subacromial pathology. In this occurrence, buroscopy must be performed and cuff pathology treated. For acquired surgical stiffnesses, gain of motion is significant. Subjective and objective results are less satisfactory than those of primary frozen shoulder, due to persistance of pain and lack of strength. The alternative is open release, but arthroscopic release has less morbidity. It can be proposed early as soon as capsular tissue has healed (for instance 6 months).     

Product variety strategies for vertically differentiated products in a two-stage supply chain

In this paper, we study how the presence of coordination, competition and cost structures affect the product variety and pricing decisions in a two-stage supply chain. We consider vertically differentiated industries. Products reach the end customers via assembly companies positioned in the middle-tier between the producers and end customers. The assembly operations incur bill-of-materials (BOM) cost, which includes the cost of raw materials and components as well as the cost of producing, managing and synchronising supply, storage and distribution of these materials and components. We consider three coordination scenarios in the supply chain, and compare an uncoordinated supply chain with a horizontal and a vertical coordination scenario using the Nash equilibria of a multi-leader Stackelberg game between the producers and assembly companies. For exogenously given quality levels, we show that producers and assembly companies should either differentiate their product offering, or offer the high-end product only depending on the BOM cost. In addition, the uncoordinated scenario helps reduce the intensity of competition in the supply chain. For endogenous quality levels, partial product-differentiation equilibrium can emerge. Numerical experiments are performed to illustrate the impacts of BOM cost and quality levels on the equilibrium.     

Elastic Moduli and Hardness of Cubic Silicon Nitride

The bulk modulus B ₀= 290(5) GPa and its first pressure derivative B '₀= 4.9(6) were obtained for c -Si₃N₄ from volume versus pressure dependence. Measurements were performed under quasi-hydrostatic conditions in a diamond anvil cell to 53 GPa using synchrotron radiation and energy dispersive X-ray powder diffraction. This combined with nanoindentation measurements determined the shear modulus G ₀ of c -Si₃N₄ to be 148(16) GPa. The Vickers microhardness H _V(0.5) for dense, oxygen-free c -Si₃N₄ was estimated to be between 30 and 43 GPa. Both the elastic moduli and microhardness of c -Si₃N₄ exceed those of the hexagonal counterparts, α- and β-phases.     

Error analysis of large-eddy simulation of the turbulent non-premixed sydney bluff-body flame

A computational error analysis is applied to the large-eddy simulation of the turbulent non-premixed Sydney bluff-body flame, where the error is defined with respect to experimental data. The error-landscape approach is extended to heterogeneous compressible turbulence, which is coupled to combustion as described by a flamelet model. The Smagorinsky model formulation is used to model the unknown turbulent stresses. We introduce several measures to quantify the total simulation error and observe a striking ‘valley-structure’ in the error that arises as function of the spatial resolution and the Smagorinsky length parameter. The optimal refinement strategy that can be extracted from this error-landscape is reminiscent of that for non-reacting turbulent flow.