Analysis of electrical phenomena accompanying the growth of Neurospora crassa hyphae: theory and experiment

To describe electrical phenomena observed in growth of Neurospora crassa hyphae, a theoretical model was developed considering the hypha as a one-dimensional electric cable with non-uniform longitudinal distribution of current sources reflecting the activity of proton pumps. A profile of the density of the pump current along the hypha is proposed, at which the results of simulation quantitatively coincide with the results of physiological experiments. The model values of energy coupling in the growth zones were estimated. The experimental dependence of the elongation rate of regenerating apical hypha fragments on their lengths was determined. Based on the comparison of these experimental results with the results of analysis of the model, the contribution of the axial metabolite transport, from the distal parts of the hypha to the apical part, to the dynamics of the apical cell growth was estimated. The possibility of evaluating the intensity of high-molecular-weight syntheses and/or accumulation of substances in granules was demonstrated. The growth rate of the regenerating hypha fragments was shown to correlate with the electric current flowing into the apical fragment 0.2-mm in length.     

Pancreatic mucinous ductal ectasia and intraductal papillary neoplasms. A single malignant clinicopathologic entity

OBJECTIVE: The purpose of the study is to review a single institutional experience with mucinous ductal ectasia (MDE) and intraductal papillary neoplasms (IPNs) and to compare the clinicopathologic features of the two groups of tumors. SUMMARY BACKGROUND DATA: Mucinous ductal ectasia and IPNs represent newly recognized categories of pancreatic exocrine tumors, previously confused with pancreatic cystic neoplasms. The natural history of MDE and IPN is not well understood, and it is unclear whether MDE and IPN represent two distinct tumors or the same clinicopathologic entity. METHODS: The authors reviewed the clinical presentation, treatment, histopathology, and outcomes of 23 patients diagnosed with MDE or IPN at their institution over the past 6 years. RESULTS: The mean age at presentation for the cohort of patients with MDE and IPN was 62.5 years. The prevalence of abdominal pain was 75%, jaundice 25%, weight loss 42%, steatorrhea 37.5%, diabetes 37.5%, and history of pencreatitis 29%. Serum CA 19-9 levels ranged from 0 to 5350 units/mL with high levels reflecting advanced disease. There were no significant differences between MDE and IPN with respect to these parameters. Both MDE and IPN comprised papillary villous epithelial neoplasms involving the main and large pancreatic ducts. The tumors ranged from a few millimeters in size to panductal and were distinguished easily from cystic neoplasms in all cases. Invasive carcinoma was present in 11 (46%) of 24 patients, carcinoma in situ in an additional 10 (42%) of 24 patients, and low grade dysplasia in the remaining 3 (12%) of 24 patients. Mucinous ductal ectasia and IPN differed histopathologically only in degree of mucin secretion and tumor location. Mucinous ductal ectasia, but not IPN, was characteristically mucin-hypersecreting and more frequently involved the head of the gland than did IPN (11/16 vs. 1/8 p < 0.04). All patients were explored surgically and 20 (83%) of 24 of the tumors were resectable with frozen section control of the duct margins (9 pancreatoduodenectomies, 4 distal pencreatectomies, 7 total pancreatectomies). Despite the 88% prevalence of cancer, the overall survival at a mean follow-up of 21 months was 13 (87%) of 15 for MDE and 5 (71%) of 7 for IPN. CONCLUSIONS: Intraductal papillary neoplasms with or without MDE represent a spectrum of main duct papillary tumors ranging from adenoma to carcinoma with differing amounts of extracellular mucin production. Malignant IPNs with or without MDE typically exhibit extensive intraductal growth but are slow to invade the periductal tissues and slow to metastasize. The majority of patients with these tumors have resectable disease and a favorable prognosis; endoscopic therapy is inappropriate. The encompessing term intraductal papillary-mucinous tumors is appropriate.     

The pharmacokinetics of Kefzol in patients with acute pancreatitis when administered intravenously and endolymphatically

Pharmacokinetics was studied of kefsole administered by intravenous and endolymphatic routes to patients (n = 23) with acute pancreatitis. The studies made showed that intravenous route for the drug administration makes for a quicker entering of the antibiotic into the peritoneal exudate. Apart from these reasons, endolymphatic antibacterial therapy does not appear to avert the development of complications involving pus-formation/discharging in acute pancreatitis and does not seem to be essential in the complex of therapeutic measures to be applied for treating the above patients.     

Strategic Allocation of Inspection Effort In A Serial, Multi-Product Production System

For a multi-stage production system, optimal location of inspection activities is an important consideration in minimizing the inspection-related and salvage costs. Set-up and inventory carrying costs also become important factors when several products are produced on the same line due to the product changeovers involved.

In this paper we discuss the effect of these additional costs (set-up and inventory carrying) on the inspection strategy, i.e., “all or none” versus partial inspection. We suggest a shortest path heuristic to determine the strategic location of inspection activities and the production lot sizes.     

Csk homologous kinase, a novel signaling molecule, directly associates with the activated ErbB-2 receptor in breast cancer cells and inhibits their proliferation

Substantial evidence exists supporting direct roles for ErbB-2/neu and Src kinase activation in breast cancer. The Csk homologous kinase (CHK) is a recently identified tyrosine kinase which, like Csk, phosphorylates the C-terminal tyrosine of Src kinases, resulting in inactivation of these enzymes. Recently, we observed that CHK is associated with the ErbB-2/neu receptor upon heregulin stimulation of breast cancer cells. Here, we report that CHK expression was observed in 70 out of 80 primary breast cancer specimens but not in normal breast tissues (0/19). Confocal microscopy analysis revealed co-localization of CHK with ErbB-2 in these primary specimens (6/6). In addition, we observed that the cytoplasmic domain of the ErbB-2/neu receptor is sufficient for its interaction with the CHKSH2 domain. Phosphopeptide inhibition of the in vitro interaction of CHKSH2 or native CHK with ErbB-2/neu, as well as site-directed mutagenesis of ErbB-2/neu, indicated that CHKSH2 binds to Tyr1253 of ErbB-2/neu. Interestingly, autophosphorylation at this site confers oncogenicity to this receptor. Moreover, CHK was able to down-regulate ErbB-2/neu-activated Src kinases. Overexpression of CHK in MCF-7 breast cancer cells markedly inhibited cell growth and proliferative response to heregulin as well as decreased colony formation in soft agar. These studies indicate that CHK binds, via its SH2 domain, to Tyr1253 of the activated ErbB-2/neu and down-regulates the ErbB-2/neu-mediated activation of Src kinases, thereby inhibiting breast cancer cell growth. These data strongly suggest that CHK is a novel negative growth regulator in human breast cancer.     

Design and synthesis of a series of potent and orally bioavailable noncovalent thrombin inhibitors that utilize nonbasic groups in the P1 position

As part of an ongoing effort to prepare therapeutically useful orally active thrombin inhibitors, we have synthesized a series of compounds that utilize nonbasic groups in the P1 position. The work is based on our previously reported lead structure, compound 1, which was discovered via a resin-based approach to varying P1. By minimizing the size and lipophilicity of the P3 group and by incorporating hydrogen-bonding groups on the N-terminus or on the 2-position of the P1 aromatic ring, we have prepared a number of derivatives in this series that exhibit subnanomolar enzyme potency combined with good in vivo antithrombotic and bioavailability profiles. The oxyacetic amide compound 14b exhibited the best overall profile of in vitro and in vivo activity, and crystallographic studies indicate a unique mode of binding in the thrombin active site.     

Robustness for time-varying systems

We consider robust optimization for time-varying systems in terms of perturbations of fractional representations. Upper and lower bounds are given for the maximal radius of the operator ball around a given plant which can be stabilized by a single compensator. In the time-invariant case, these numbers are equal.     

Osteoprotegerin mRNA is expressed in primary human osteoblast-like cells: down-regulation by glucocorticoids

Oryzacystatins (OCs) are protease inhibitors (PIs) that inhibit Colorado potato beetle (CPB) digestive proteases, and transgenic potato plants containing these PIs are currently under test. However, OCs could interfere with the digestive system of beneficial insects. Protease activity and susceptibility to class-specific protease inhibitors were studied in protein extracts of Perillus bioculatus, a stinkbug predator that has shown potential for biological control of the CPB. At physiological pH, the analysis of protease activity showed that up to 90% of P. bioculatus protease activity is of the cysteine type. All active life stages of the predator were tested, and electrophoretic characterization detected no major qualitative variation in protease pattern between stages. Protease activity in extracts of P. bioculatus nymphs was significantly reduced, up to 70%, by the two recombinant cystatins from rice (OCI and OCII), and by stefin A, a PI encoded by a human gene. These results clearly indicate that cysteine PIs are active not only against the CPB digestive protease complex, but also against proteases of one of its most important natural predators.