Clock stability characterization and measurement intelecommunications

Clock stability characterization and measurement for telecommunications pose peculiar issues and requirements. This paper aims to provide an overview on this subject. After briefly recalling the background work, the key features and issues of clock stability characterization and measurement in telecommunications are described. The timing signal reference model and the stability quantities adopted in the new international standards are introduced and the impact of the measurement configuration and of the time error sampling period on their behavior are elucidated. The measurement of clock stability in telecommunications is then addressed, and a standard practical measurement procedure is outlined. Several measurement results are provided to support the concepts expounded with experimental evidence. The results shown have been chosen among those obtained throughout the last three years by testing clerks of digital switching exchanges, clocks for synchronous digital hierarchy (SDH) equipment, and state-of-the-art stand-alone slave clocks for synchronization networks. They thus represent a survey of the actual performance of clocks currently deployed in telecommunications networks     

Phase I study of mitoxantrone plus etoposide with multidrug blockade by SDZ PSC-833 in relapsed or refractory acute myelogenous leukemia

PURPOSE: Expression of the multidrug resistance gene (MDR1) p170 protein is frequent in leukemic blasts from patients with relapsed acute myelogenous leukemia (AML). A phase I study using the nonimmunosuppressive MDR1 blocker SDZ PSC-833 (PSC) in combination with mitoxantrone (MITO) and etoposide (VP) was performed. PATIENTS AND METHODS: Starting doses (LVL0) of MITO (3.25 mg/m2/d on days 1 and 3 to 6) and VP (210 mg/m2/d on days 1 and 3 to 5) were 40% of the maximal-tolerated dose (MTD) from a prior study. A 1.5-mg/kg loading dose of PSC was followed by a 120-hour continuous infusion of 10 mg/kg/d on days 2 to 6. Blood samples for PSC, MITO, and VP pharmacokinetics (PK) were taken on days 1 and 3, and samples for MDR1 expression were taken on day 0. RESULTS: Severe mucositis developed in all patients at LVL0; therefore, MITO and VP doses were reduced to 2.5 and 170 mg/m2 (LVL-1) for the next seven patients, and this dose proved to be MTD. All LVL0 and three LVL-1 patients had transient elevations in the serum bilirubin level to > or = 4 mg/dL. Serum creatinine level increased to greater than 2 mg/dL in one case. There were no other grade 3 or 4 nonhematologic toxicities observed. The peripheral blood was cleared of leukemia in three LVL0 and four LVL-1 patients. The marrow was cleared of leukemic cells in one LVL0 and five LVL-1 patients, and a significant reduction in marrow leukemic infiltrate was observed in eight of 10. No patient achieved complete remission (CR), and all died of progressive disease (n = 8) or infection (n = 2). MDR1 expression was detected by fluorescent-activated cell sorter (FACS) analysis in five of seven cases. An elevated MDR1 mRNA level was detected by quantitative polymerase chain reaction (Q-PCR) in six of eight cases studied. Clearing of leukemia cells from the marrow occurred in four of six MDR1-positive and one of three MDR1-negative patients. Despite the fact that LVL0 doses had to be reduced due to toxicity, coadministration of PSC did not produce a consistent effect on MITO PK; however, it did repeatedly lead to increased levels of VP in the serum. CONCLUSION: We conclude that PSC-MITO-VP is a tolerable regimen with antileukemic activity. Addition of PSC necessitated a 66% reduction in MITO and VP doses from a prior study without PSC.     

Chicken acidic leucine-rich EGF-like domain containing brain protein (CALEB), a neural member of the EGF family of differentiation factors, is implicated in neurite formation

Chicken acidic leucine-rich EGF-like domain containing brain protein (CALEB) was identified by combining binding assays with immunological screens in the chicken nervous system as a novel member of the EGF family of differentiation factors. cDNA cloning indicates that CALEB is a multidomain protein that consists of an NH2-terminal glycosylation region, a leucine-proline-rich segment, an acidic box, a single EGF-like domain, a transmembrane, and a short cytoplasmic stretch. In the developing nervous system, CALEB is associated with glial and neuronal surfaces. CALEB is composed of a 140/130-kD doublet, an 80-kD band, and a chondroitinsulfate-containing 200-kD component. The latter two components are expressed in the embryonic nervous system and are downregulated in the adult nervous system. CALEB binds to the extracellular matrix glycoproteins tenascin-C and -R. In vitro antibody perturbation experiments reveal a participation of CALEB in neurite formation in a permissive environment.     

Prostate enlargement in mice due to fetal exposure to low doses of estradiol or diethylstilbestrol and opposite effects at high doses

On the basis of results of studies using high doses of estrogens, exposure to estrogen during fetal life is known to inhibit prostate development. However, it is recognized in endocrinology that low concentrations of a hormone can stimulate a tissue, while high concentrations can have the opposite effect. We report here that a 50% increase in free-serum estradiol in male mouse fetuses (released by a maternal Silastic estradiol implant) induced a 40% increase in the number of developing prostatic glands during fetal life; subsequently, in adulthood, the number of prostatic androgen receptors per cell was permanently increased by 2-fold, and the prostate was enlarged by 30% (due to hyperplasia) relative to untreated males. However, as the free serum estradiol concentration in male fetuses was increased from 2- to 8-fold, adult prostate weight decreased relative to males exposed to the 50% increase in estradiol. As a model for fetal exposure to man-made estrogens, pregnant mice were fed diethylstilbestrol (DES) from gestation days 11 to 17. Relative to controls, DES doses of 0.02, 0.2, and 2.0 ng per g of body weight per day increased adult prostate weight, whereas a 200-ng-per-g dose decreased adult prostate weight in male offspring. Our findings suggest that a small increase in estrogen may modulate the action of androgen in regulating prostate differentiation, resulting in a permanent increase in prostatic androgen receptors and prostate size. For both estradiol and DES, prostate weight first increased then decreased with dose, resulting in an inverted-U dose-response relationship.     

3 cases of post-stapedectomy labyrinthine fistula

Three cases are presented of labyrinthine fistula which suddenly arose in patients who had undergone stapedectomy interposing a vein graft from the back of the hand. These patients had all enjoyed 12-15 years apparently problem free period before the fistula occurred. In all three cases the fistula was accompanied by objective dizziness and varying degrees of sensorineural or mixed hearing loss. The patients underwent revision surgery which identified the fistula and the endolymph oozing out of the graft from the previously installed prosthesis. The authors present the cases, describe how the symptoms arose and the results obtained with revision surgery. Finally, they discuss the need to first perform stapedotomy with a platinar hole; they indicate that the number of cases of total or partial stapedectomy should be limited only to those cases characterized by anatomical variations and/or whenever complications arise during surgery.     

Protective effects of CD-832 on organ damage in stroke-prone spontaneously hypertensive rats

Effects of a newly developed Ca2+ channel antagonist, (4R)-(-)-2-(nicotinoylamino)ethyl 3 nitrooxypropyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl) 3,5-pyridine-dicarboxylate (CD-832), on hypertensive complications in stroke-prone spontaneously hypertensive rats (SHRSPs) were compared with effects of diltiazem. We examined changes in histological and hematological parameters in SHRSPs given the following treatments at 8 to 20 weeks of age: (a) CD-832; (b) diltiazem; (c) no treatment. CD-832 and diltiazem were added to the diet, in doses of 0.05 and 0.15% (approximately 30 and 100 mg/kg per day), respectively, throughout the experimental period. In untreated control SHRSPs, systolic blood pressure increased and severe renal lesions such as fibrinoid necrosis, smooth muscle proliferation, glomerular and tubular lesions and some cardiac fibrosis were observed at age 20 weeks. 12-week repeated-administration of CD-832 and diltiazem led to a comparable hypotension and decreased heart rate. CD-832 and diltiazem decreased the ratios of weights of kidney and heart to body weight and the concentration of blood urea nitrogen and creatinine in serum, compared to values in controls. In SHRSPs treated with CD-832 and diltiazem, the incidence of renal lesions and myocardial fibrosis was significantly reduced when compared with control SHRSPs. These results suggest that 12-week repeated-administration of CD-832 prevents the development of hypertension and the incidence of organ damage in SHRSPs. CD-832 and diltiazem were equally efficacious in preventing organ damage but this organ-protective effect was obtained at a lower dose for CD-832 (30 mg/kg per day) than that of diltiazem (100 mg/kg per day).     

Dopamine and the regulation of cell proliferation in gerbil (Meriones unguiculatus) pyloric mucosa

The epithelium of the digestive system mucosa consists of a highly dynamic cell population. The conditions under which mitotic activity in the gastrointestinal epithelium is regulated is as yet poorly understood. Nevertheless, it is assumed that some biogenic amines might be involved. Having demonstrated that dopaminergic cells occur in the stomach of gerbils (Meriones unguiculatus), in the present study we examined the influence of dopamine antagonist haloperidol on the proliferation of epithelial cells in the mucosa of the stomach. Proliferating cells were detected immunocytochemically and quantified after in-vivo labeling with 5-bromo-2'-desoxyuridine in both haloperidol- and saline-treated animals. The results show that acute doses of haloperidol significantly increases the proliferation rate in the pyloric mucosa, suggesting that dopamine plays a probable modulatory role in the regulation of mitotic activity. These findings are discussed with regard to the role of paraneurons in regulating epithelial mitosis.     

Human discrimination of the implicit orientation of simple symmetrical patterns

A hydraulic calcium phosphate cement made of beta-tricalcium phosphate [beta-Ca3(PO4)2], monocalcium phosphate monohydrate [Ca(H2PO4)2-H2O], and water was used as a delivery system for the antibiotic gentamicin sulfate (GS). GS, added as powder or as aqueous solution, was very beneficial to the physicochemical properties of the cement. The setting time increased from 2 to 4.5 min with 3% (w/w) GS and then slowly decreased to 3.75 min with 16% (w/w) GS. The tensile strength increased from 0.4 to 1.6 MPa with 16% (w/w) GS. These effects were attributed to the presence of sulfate ions in GS. The release of GS from the cement was measured in a pH 7.4 phosphate-buffered saline solution at 37 degrees C by USP paddle method. Factors such as cement porosity, GS content and presence of sulfate ions or polymeric additives were investigated. The amount of GS released was roughly proportional to the square root of time up to approximately 50% release. Afterwards, the release rate markedly slowed down to zero. In all but two cement formulations, the total dose of GS was released within 7 days, indicating that no irreversible binding occurred between the cement paste and the antibiotic. When small amounts of hydroxypropylcellulose or poly(acrylic acid) were added to the cement, the maximum fraction released was a few percent lower than the total GS dose, suggesting some binding between the polymer and GS. The GS release rate was strongly influenced by the presence of sulfate ions in the cement paste and by the cement porosity. The higher the sulfate ion content of the cement paste, the lowe the GS release rate. This influence was attributed to the finer cement micro-structure induced by the presence of sulfate ions. Furthermore, when the initial cement porosity was increased from 38 to 69%, the release rate almost tripled (0.16 to 0.45 h-1/2). Finally, the biological activity of GS in the cement was maintained, as measured by assaying the release medium.