The SL synchronous language

We present SL, a new programming language of the synchronous reactive family in which hypotheses about signal presence/absence are disallowed. One can decide that a signal is absent during an instant only at the end of this instant, and so reaction to this absence is delayed to the next instant. Sources of causal circularities are avoided, while only weak preemption remains. A structural operational semantics is provided through rewrite rules, and an implementation is described. In addition to directly executing programs, this implementation can also be used to produce automata by symbolic evaluation     

A method to find all solutions of a system of multivariate polynomial equalities and inequalities in the max algebra

In this paper we show that finding solutions of a system of multivariate polynomial equalities and inequalities in the max algebra is equivalent to solving an Extended Linear Complementarity Problem. This allows us to find all solutions of such a system of multivariate polynomial equalities and inequalities and provides a geometrical insight in the structure of the solution set. We also demonstrate that this enables us to solve many important problems in the max algebra and the max-min-plus algebra such as matrix decompositions, construction of matrices with a given characteristic polynomial, state space transformations and the (minimal) state space realization problem.Research assistant with the N.F.W.O. (Belgian National Fund for Scientific Research).Senior research associate with the N.F.W.O.     

Cleavage of Müllerian inhibiting substance activates antiproliferative effects in vivo

Müllerian inhibiting substance (MIS), an inhibitor of growth and development of the female reproductive ducts in male fetuses, requires precise proteolytic cleavage to yield its biologically active species. Human plasmin is now used to cleave and, thereby, activate immunoaffinity-purified recombinant human MIS at its monobasic arginine-serine site at residues 427-428. To avoid the need for exogenous enzymatic cleavage and to simplify purification, we created an arginine-arginine dibasic cleavage site (MIS RR) using site-directed mutagenesis to change the serine at position 428 (AGC) to an arginine (cGC). The mutant cDNA was then stably transfected into a MIS-responsive ocular melanoma cell line, OM431, followed by cloning for amplified expression to test its biological activity in vitro and in vivo. Media from each clone were assayed for production of MIS RR by a sensitive ELISA for holo-MIS, and high- and low-producing clones were selected for further study. Media from the highest MIS RR producer caused Müllerian duct regression in an organ culture bioassay. Other transfections were done with an empty vector (pcDNAI Neo) or a construct lacking the leader sequence and thus failing to secrete MIS, to serve as controls. The OM431 clones containing the MIS RR mutant were growth inhibited in monolayer culture. The high- and low-producing MIS RR OM431 clones, along with transfected OM431 controls, were injected into the tail veins of immunosuppressed severe combined immunodeficiency mice for in vivo analyses. Four to 6 weeks later, pulmonary metastases were counted in uniformly inflated lungs. OM431 clones containing the more easily cleaved MIS RR displayed a significant dose-dependent reduction in pulmonary metastases when compared to the lungs of animals given injections of OM431 clones containing empty vector, leaderless MIS, or wild-type MIS that requires activation by plasmin cleavage. Since the purification protocol of MIS RR is less complicated than that for wild-type MIS, which requires subsequent enzymatic activation, MIS RR can be used for scale-up production with increased yields for further therapeutic trials against MIS-sensitive tumors.     

Loss of heterozygosity of the von Hippel Lindau gene locus in polypoid dysplasia but not flat dysplasia in ulcerative colitis or sporadic adenomas

Carcinoma in ulcerative colitis (UC) develops from dysplastic precursor lesions, which include flat dysplasia (FD) and polypoid dysplasias (PD). PD may present as single or multiple polypoid structures or as plaque-like lesions that, independent of histological grade, are an indication for colectomy. PDs are histologically similar to adenomas and may not be readily distinguished by light microscopy. It is not known whether FD and PD are different entities, or whether they represent etiologically similar lesions with different morphological expression. We microdissected 25 cases of UC with PD and 19 samples of FD with surrounding chronic colitis (CC) in UC. Loss of heterozygosity (LOH) at the von Hippel Lindau (vHL) gene locus and the putative tumor suppressor genes APC, INK4A (9p16), and p53 was studied. LOH of the vHL gene, INK4A (9p16), and APC was also studied in 11 sporadic adenomas of the colon. LOH at the vHL locus was present in 50% of the samples of PD and in 12% of the samples of FD. LOH was seen in CC close to PD and FD in 26% and 12% of cases, respectively. No adenoma showed LOH of the vHL gene markers studied. LOH in p53 was seen in PD in 16% cases and in FD in 42% cases and in CC close to PD and FD in 0% and 14% cases, respectively. LOH patterns between PD and FD of the markers for APC and 9p16 were not different. LOH in APC was seen in two of five cases of adenoma. We conclude that PD and FD share genetic alterations in APC and 9p16 genes. More frequent involvement of the VHL gene in PD and surrounding CC and involvement of p53 in HGD and CC in FD may represent genetic differences between the development of PD and FD and may be the cause of the different morphology. The infrequency of LOH at the vHL locus in adenomas versus PD may serve as a discriminator between adenomas and PD in diagnostically problematic cases.     

Antigenic stimuli do not influence thymic B lymphocytes: a morphological and functional study in germ-free and conventionally reared piglets

We have recently reported that thymic B lymphocytes (TBL) are the first B-cell subpopulation undergoing isotype switching to IgG and IgA during embryonic life. The aim of this study is to analyze the influence of antigenic stimulation on TBL location and activity using a germ-free (GF) newborn pig model, in which maternal antibodies and antigens do not affect B-cell development. Immunohistological analysis showed that TBL were disseminated mainly in the thymic medulla. There were no differences in the distribution of TBL, both in GF newborn piglets before and after colonization with Escherichia coli and in older conventionally reared (CONV) piglets. The number of immunoglobulin (Ig)-secreting cells measured by the ELISPOT method was not influenced by microflora and food antigens. IgM-positive cells secreting IgM and CD45RC-positive cells spontaneously producing IgM, IgG, and IgA were detected in newborn thymus. Our findings suggest that TBL differentiation and Ig switching to IgG and IgA-secreting cells is not influenced by external antigens and that the thymic microenvironment plays an important role in this process.     

7-Deazapurine 2'-deoxyribofuranosides are noncleavable competitive inhibitors of Escherichia coli purine nucleoside phosphorylase (PNP)

A series of 7-deazapurine 2'-deoxyribofuranosides were synthesized according to already known procedures and their substrate and inhibitor properties with purified E. coli purine nucleoside phosphorylase were examined. In agreement with previous findings, substrate activity was not detected for any of the compounds tested. Most of the nucleosides showed weak inhibition in the preliminary screening, i.e. at a concentration of about 100 microM. However some combinations of 6-chloro, 6-amino or 6-methoxy substituents with bulky hydrophobic groups at position 7 of the base and/or chloro, amino, methoxy or methylthio group at position 2 markedly enhanced affinity of such modified nucleosides for the E. coli enzyme. The most potent inhibition was observed for two nucleosides: 6-chloro- and 2-amino-6-chloro-7-deazapurine 2'-deoxyribofuranosides that show inhibition constants Ki = 2.4 and 2.3 microM, respectively. Several other compounds were also found to be good inhibitors, with inhibition constants in the range 5-50 microM. In all instances the inhibition was competitive vs. the nucleoside substrate 7-methylguanosine. Inhibition constants for 7-deazapurine nucleosides are in general several-fold lower than those observed for their purine counterparts. Therefore 7-deaza modification together with substitutions at positions 2, 6 and 7 of the base is a very promising approach to obtain competitive noncleavable inhibitors of E. coli PNP that may bind to the enzyme with inhibition constants in the microM range.     

Effects of nitric oxide annealing of thermally grown silicondioxide characteristics

The effects of nitric oxide (NO) annealing on conventional thermal oxides are reported in this letter. The oxide thickness increase, resulting from NO annealing, is found to be only a few angstroms (<0.5 nm) and independent on the initial oxide thickness. Furthermore, both the electrical and physical characteristics are improved. This technique is expected to achieve sub-5 nm high quality ultrathin dielectric films for the applications in EEPROM's and ULSI     

Analysis of an arbitrarily inclined slot on the ground plane of amicrostrip line

The analysis of an arbitrarily inclined slot on the ground plane of a microstrip line is presented using the spectral domain approach and reciprocity theorem. Comparison of numerical results for the special case of a perpendicular slot with other available computed and measured data shows a good agreement. It is found that the impedance level can be controlled over a wide range by varying inclination angle. Results should be useful in antenna and multilayer circuit integration applications     

Diagnosis and treatment of iatrogenic ureteral injury

Diagnosis and treatment of 17 patients who sustained 20 iatrogenic ureteral injuries were analyzed. Primary operations in which ureteral injury occurred are almost gynecologic procedures and general surgery. Injuries were managed by ureteroureterostomy in four, ureteral stent in one, removal suture ligation and ureteral double J-catheter in one, ureteroneocystostomy in ten, psoas-hitch technique and ureteroneocystostomy in one, nephrectomy in two. All patients with appropriate repair were followed-up periods of three to five years. Renal function of these patients had optimal results. When ureteral injury occurs, B-US, IVU, cystoscopy, retrograde ureterography or infusion of dye may be useful. An appropriate repair should be chosen according to length and position of ureteral injuries. Reoperation was optimal in two to three weeks. Immediate recognition of accidental ureteral injury provides optimal results. Patients with unrecognized injuries had suboptimal results.