Reduced drug accumulation and multidrug resistance in human breast cancer cells without associated P-glycoprotein or MRP overexpression

MCF-7 human breast cancer cells selected in Adriamycin in the presence of verapamil developed a multidrug resistant phenotype, which was characterized by as much as 100,000-fold resistance to mitoxantrone, 667-fold resistance to daunorubicin, and 600-fold resistance to doxorubicin. Immunoblot and PCR analyses demonstrated no increase in MDR-1 or MRP expression in resistant cells, relative to parental cells. This phenotype is similar to one previously described in mitoxantrone-selected cells. The cells, designated MCF-7 AdVp, displayed a slower growth rate without alteration in topoisomerase II alpha level or activity. Increased efflux and reduced accumulation of daunomycin and rhodamine were observed when compared to parental cells. Depletion of ATP resulted in complete abrogation of efflux of both daunomycin and rhodamine. No apparent alterations in subcellular daunorubicin distribution were observed by confocal microscopy. No differences were noted in intracellular pH. Molecular cloning studies using DNA differential display identified increased expression of the alpha subunit of the amiloride-sensitive sodium channel in resistant cells. Quantitative PCR studies demonstrated an eightfold overexpression of the alpha subunit of the Na+ channel in the resistant subline. This channel may be linked to the mechanism of drug resistance in the AdVp cells. The results presented here support the hypothesis that a novel energy-dependent protein is responsible for the efflux in the AdVp cells. Further identification awaits molecular cloning studies.     

Two-level optimal output feedback stabilizer design

The paper addresses the design of two-level power system stabilizers using an optimal reduced order model whose state variables are torque angles and speeds. The reduced order model retains their physical meaning and is used to design a two-level linear feedback controller that takes into account the realities and constraints of electrical power systems. The two-level control strategy is used, and a global control signal is generated from the output variables to minimize the effect of interactions. The effectiveness of this controller is evaluated and a multimachine system is given as an example to illustrate the advantages of the proposed method. Responses of the system with a two-level scheme and an optimal reduced order scheme are included for comparative analysis.     

Degradation of junction leakage in devices subjected to gateoxidation in nitrous oxide [MOS transistors]

Nitrided gate oxides offer several electrical and reliability advantages over conventional oxides and also provide a good barrier against impurity diffusion. Oxidation in nitrous oxide (N₂O) has been very successful in overcoming some of the problems associated with nitridation in ammonia. The authors have observed that the extent of N₂O oxidation has a strong detrimental effect on the drain leakage current of MOS transistors in the off state. This phenomenon has been identified to be caused by an increase in the active area junction leakage current     

Neutral endopeptidase inhibition increases the potency of ANP in isolated rat pulmonary resistance vessels and isolated blood perfused lungs

We have investigated the effects of the neutral endopeptidase inhibitor, SCH 42354, on the vasoreactivity of atrial natriuretic peptide (ANP) in rat isolated pulmonary resistance vessels (PRV) and isolated perfused lungs (IPL). PRV (n = 37) were mounted onto the jaws of a myograph and precontracted with PGF2alpha (100 mu M). Concentration-responses to ANP (0.17 to 340 nM) were determined before and after the addition of SCH 42354 (10, 30 and 100 nM). Each concentration of SCH 42354 caused a significant increase in potency (- log EC50) of ANP in isolated PRV. Lungs from normoxic rats (n = 13) were isolated and perfused with whole blood. An increase in pulmonary artery pressure was achieved by ventilating with an hypoxic gas mixture and concentration-responses obtained by incremental additions of ANP (40 nM to 12 mu M), before and after the addition of SCH 42354 (100 nM). SCH 42354 significantly increased the potency (- log EC50) of ANP in the rat IPL. ANP is partly metabolized by NEP. That an inhibitor of NEP increased the potency of ANP in isolated pulmonary vessels, and in isolated perfused whole lungs, suggested that SCH 42354 may be having a local action within the pulmonary vasculature.     

Multi-H phase-coded modulations with asymmetric modulationindexes

Multi-H phase-coded modulation (MHPM) is a bandwidth-efficient modulation scheme which offers substantial coding gain over conventional digital modulation schemes. MHPM with asymmetric modulation indices corresponding to the bipolar data +1 and -1 is considered, and numerical results for the minimum Euclidean distances are provided. It is shown that performance improvements on the error probability over conventional MHPM are gained with essentially the same bandwidth and a very slight modification in implementation. The upper bounds on the error probabilities as functions of observation intervals and received E_b/N₀ are also investigated in detail. It is concluded that the concept of asymmetric modulation indices for MHPM is attractive for bandwidth and power-efficient modulation     

Patient thermal comfort requirement for hospital environments in Taiwan

This study examines the comfort criteria of ASHRAE Standard 55-2004 for their applicability in hospital environments. Through an extensive field survey conducted in a university hospital in Taiwan, 927 sets of data have been collected. Above half of the measured samples failed to meet the specifications of Standard 55 comfort zone due to improper humidity control. Acceptability votes by patients exceeded the Standard's 80% criterion, regardless of whether the physical conditions were in or out of the comfort zone. Thermal neutrality, preference and comfort range are compared with other studies conducted in office environments and Standard 55 criteria. Results of chi-square tests revealed that patients’ physical strength significantly effected their thermal requirements. The net effect of health yields a marked difference in thermal neutrality and preference, and also in the comfortable temperature range.     

I-WAP: an intelligent WAP site management system

The popularity regarding wireless communications is such that more and more WAP sites have been developed with wireless markup language (WML). Meanwhile, to translate hypertext markup language (HTML) pages into proper WML ones becomes imperative since it is difficult for WAP users to read most contents designed for PC users via their mobile phone screens. However, for those sites that have been maintained with hypertext markup language (HTML), considerable time and manpower costs will be incurred to rebuild them with WML. In this paper, we propose an intelligent WAP site management system to cope with these problems. With the help of the intelligent management system, the original contents of HTML Web sites can be automatically translated to proper WAP content in an efficient way. As a consequence, the costs associated with maintaining WAP sites could be significantly reduced. The management system also allows the system manager to define the relevance of numerals and keywords for removing unimportant or meaningless contents. The original contents will be reduced and reorganized to fit the size of mobile phone screens, thus reducing the communication cost and enhancing readability. Numerical results gained through various experiments have evinced the effective performance of the WAP management system.     

Phase II trial of paclitaxel and granulocyte colony-stimulating factor in patients with pancreatic carcinoma: a Southwest Oncology Group study

PURPOSE: Pancreatic cancer is difficult to treat, with most patients surgically unresectable at the time of diagnosis. Radiotherapy and chemotherapy can offer palliation, but more effective therapy is needed. This trial evaluated the effects of an aggressive schedule of paclitaxel given with granulocyte colony-stimulating factor (G-CSF) to patients with advanced pancreatic cancer. PATIENTS AND METHODS: All patients were required to have a histologic diagnosis of pancreatic adenocarcinoma with measurable disease and no prior chemotherapy or radiation therapy. Patients had to have performance status of 0 to 2, pretreatment absolute granulocyte count > or = 1,500/microL, and platelet count greater than or equal to the institutional lower limit of normal. Following pretreatment with dexamethasone, diphenhydramine, and cimetidine, patients received paclitaxel at a dose of 250 mg/m2 by 24-hour infusion on day 1, repeated every 21 days. G-CSF was given at a dose of 5 microg/kg/d on days 3 to 18 or until two consecutive absolute neutrophil counts (ANCs) > or = 10,000/microL were obtained. Doses of paclitaxel were modified depending on nadir counts. RESULTS: Forty-five patients were entered onto this study, with six ineligible. For the 39 eligible patients, there was one complete response (CR) and two partial responses (PRs), five stable/no responses, 23 increasing disease, two early deaths, and six patients whose assessment was inadequate to determine response. The response rate was therefore three of 39 or 8% (95% confidence interval [CI], 2% to 21%). The median survival time for the 39 eligible patients was 5 months. The most common toxicities were anemia, leukopenia/granulocytopenia, malaise/fatigue, nausea/vomiting, alopecia, thrombocytopenia, paresthesias, and liver function abnormalities. There was one death due to sepsis. CONCLUSION: Single-agent paclitaxel in this dose and schedule has minimal activity in pancreatic adenocarcinoma patients.