Hybrid learning for interval type-2 fuzzy logic systems based on orthogonal least-squares and back-propagation methods

This paper presents a novel learning methodology based on a hybrid algorithm for interval type-2 fuzzy logic systems. Since only the back-propagation method has been proposed in the literature for the tuning of both the antecedent and the consequent parameters of type-2 fuzzy logic systems, a hybrid learning algorithm has been developed. The hybrid method uses a recursive orthogonal least-squares method for tuning the consequent parameters and the back-propagation method for tuning the antecedent parameters. Systems were tested for three types of inputs: (a) interval singleton, (b) interval type-1 non-singleton, and (c) interval type-2 non-singleton. Experiments were carried out on the application of hybrid interval type-2 fuzzy logic systems for prediction of the scale breaker entry temperature in a real hot strip mill for three different types of coil. The results proved the feasibility of the systems developed here for scale breaker entry temperature prediction. Comparison with type-1 fuzzy logic systems shows that hybrid learning interval type-2 fuzzy logic systems provide improved performance under the conditions tested.     

Molecular modeling optimization of anticoagulant pyridine derivatives

Intravascular clotting remains a major health problem in the United States, the most prominent being deep vein thrombosis, pulmonary embolism and thromboembolic stroke. Previous reports on the use of pyridine derivatives in cardiovascular drug development encourage us to pursue new types of compounds based on a pyridine scaffold. Eleven pyridine derivatives (oximes, semicarbazones, N-oxides) previously synthesized in our laboratories were tested as anticoagulants on pooled normal plasma using the prothrombin time (PT) protocol. The best anticoagulant within the oxime series was compound AF4, within the oxime N-oxide series was compound AF4-N-oxide, and within the semicarbazone series, compound MD1-30Y. We also used a molecular modeling approach to guide our efforts, and found that there was good correlation between coagulation data and computational energy scores. Molecular docking was performed to target the active site of thrombin with the DOCK v5.2 package. The results of molecular modeling indicate that improvement in anticoagulant activities can be expected by functionalization at the three-position of the pyridine ring and by N-oxide formation. Results reported here prove the suitability of DOCK in the lead optimization process.     

Acute-stage para- and tetraplegia

A quarter of a century ago, in October 1964, the first spinal cord injury center in Switzerland was opened at Geneva University Hospital. At that time all para- and tetraplegics were classified as "high-risk" patients. Early mortality, covering the initial four weeks following trauma, was still around 15%. The available resources for diagnostic assessment were limited to clinical examination and neuroradiological assessment (subsequently improved by the introduction of tomography and gas myelography). A great many patients suffered a deteriorated neurological level due to inadequate, multiple transfers between hospitals. Most patients who are paralyzed following a road-traffic accident show severe polytrauma. Their chances of survival and functional recovery have greatly improved in recent years due to efficient emergency transport by helicopter, admission to an intensive care unit (respiratory therapy, prophylactic anticoagulation, gastrointestinal cytoprotection, prevention of pressure sores, etc.) and a comprehensive medico-surgical team approach (orthopedic surgeons, neurosurgeons, ICU specialists, internists, etc.). Evaluation of the spine and spinal cord by NMR and CT scan allows precise assessment of the extent of CNS damage and provides additional guide-lines regarding efficient surgical reposition and spinal fusion. Ongoing experimental research in neurophysiology and neurobiochemistry of the brain and spinal cord is presently yielding some interesting results which hold out new hopes for functional recovery in some specific types of incomplete spinal cord trauma.     

Double contrast examination of the stomach. Definition, technic and indications

Double contrast examination constitutes an important element in radiological gastric examination. The author examines the history of the term "double contrast" and defines the designation of "double contrast examination". The exclusive use of the double contrast method reduces the diagnostic value of gastric X-ray examinations. Thus a method is suggested that will avoid the disadvantages of exclusive double contrast examination while adequately including double contrast in the gastric examination. This is done by using various methods - according to the problem posed - in order to achieve the double contrast.     

Syncillin in bacterial skin diseases

A multicentric open clinical trial was carried out by 8 practising specialists in dermatology or paediatrics in patients with bacterial skin diseases who were subjected to a systemic therapy with Syncillin (=Azidocillin). The Syncillin presentation for adults and schoolchildren was tablets of 750 mg each, and sachets of 125 mg or 250 mg for infants. The duration of treatment was 10 days. The parameters analyzed were bacteriological findings and the clinical course of disease. 71 (=74%) of the 96 patients included in this study were considered as cured, 21 (=22%) as improved and 4 patients (=4%) as unchanged. Bacterial identification was still positive in 10 cases after the termination of treatment. However, this did not preclude the assessments of "cured' (3 cases) or "improved' (7 cases). The tolerance of the preparation was considered as "very good' or "good' in 91 and as "poor' in 5 patients. The most common side effects were nausea and diarrhoea. Exanthema was observed in 2 cases. None of these side effects, however, made a discontinuation of medication necessary. The era of rational and well-directed chemotherapy enables good therapeutic approach also to bacterial skin diseases.     

p21WAF1/Cip1 expression is associated with cell differentiation but not with p53 mutations in squamous cell carcinomas of the larynx

The anti-metastatic effect of Z-100, an immunomodulatory arabinomannan extracted from Mycobacterium tuberculosis, was investigated in mice bearing B16 melanoma cells. Treatment of BF10 mice implanted with high metastatic B16F10 melanoma cells with a 10 mg/kg dose of Z-100 resulted in the reduction of experimental pulmonary metastasis as compared with that of BF10 mice treated with saline. The number of pulmonary metastatic colonies in BF1 mice (mice implanted with low metastatic B16F1 melanoma cells) was greatly increased after the inoculation of CD4+ CD11b+ CD281+ TCR alphabeta+ type 2 T cells (F10-Th2 cells) derived from BF10 mice, while only a few metastatic colonies were demonstrated in lungs of BF1 mice inoculated with naive CD4+ T cells. However, the numbers of metastatic colonies in BF1 mice were not increased when they were inoculated with the F10-Th2 cell fraction derived from Z-100-treated BF10 mice and the generation of F10-Th2 cells in BF10 mice was effectively suppressed by the Z-100 treatment. These results suggest that Z-100 inhibits pulmonary metastasis of B16 melanoma through the regulation of tumor-associated Th2 cells, which are a key cell in the acceleration of tumor metastasis.     

Deletions and loss of expression of p16INK4a and p21Waf1 genes are associated with aggressive variants of mantle cell lymphomas

Mantle cell lymphoma (MCL) is molecularly characterized by bcl-1 rearrangement and cyclin D1 gene overexpression. Some aggressive variants of MCL have been described with blastic or large cell morphology, higher proliferative activity, and shorter survival. The cyclin-dependent kinase inhibitors (CDKIs) p21Waf1 and p16INK4a have been suggested as candidates for tumor-suppressor genes. To determine the role of p21Waf1 and p16INK4a gene alterations in MCLs, we examined the expression, deletions, and mutations of these genes in a series of 24 MCLs, 18 typical, and 6 aggressive variants. Loss of expression and/or deletions of p21Waf1 and p16INK4a genes were detected in 4 (67%) aggressive MCLs but in none of the typical variants. Two aggressive MCLs showed a loss of p16INK4a expression. These cases showed homozygous deletions of p16INK4a gene by Southern blot analysis. An additional aggressive MCL in which expression could not be examined showed a hemizygous 9p12 deletion. Loss of p21Waf1 expression at both protein and mRNA levels was detected in an additional aggressive MCL. No p21Waf1 gene deletions or mutations were found in this case. The p21Waf1 expression in MCLs was independent of p53 mutations. The two cases with p53 mutations showed p21Waf1 and p16INK4a expression whereas the 4 aggressive MCLs with p16INK4a and p21Waf1 gene alterations had a wild-type p53. p21Waf1 and p16INK4a were expressed at mRNA and protein levels in all typical MCLs examined. No gene deletions or point mutations were found in typical variants. Two typical MCLs showed an anomalous single-stranded conformation polymorphism corresponding to the known polymorphisms at codon 148 of p16INK4a gene and codon 31 of p21Waf1 gene. These findings indicate that p21Waf1 and p16INK4a alterations are rare in typical MCLs but the loss of p21Waf1 and p16INK4a expression, and deletions of p16INK4a gene are associated with aggressive variants of MCLs, and they occur in a subset of tumors with a wild-type p53 gene.