Erbium-doped multi-element fiber amplifiers for space-division multiplexing operations.

Erbium-doped multi-element fiber (MEF) amplifiers have been fabricated to simultaneously amplify multiple transmission channels. MEF devices comprise of multiple single-core fibers (elements) combined in a common coating, with each element working as a single fiber in isolation. MEFs containing 3-elements and 7-elements have been fabricated and characterized. Each element of the fabricated MEFs provides nearly 32 dB of gain with a noise figure of <5 dB for an input signal level of -23 dBm at 1530 nm. Different permutations of element pairs within the MEFs were checked for crosstalk and none was detected, confirming the simultaneous multi-channel amplification capabilities of MEFs.

Q-switched neodymium-doped Y3Al5O12-based silica fiber laser.

We present pulsed laser operation in a Nd-doped, Y3Al5O12-based silica fiber. The fiber was fabricated using the rod-in-tube technique with a Nd:YAG crystal rod as the core material and a silica tube for the cladding material. A spectroscopy study revealed that the core region had become amorphous in the process of fiber drawing. Q-switched pulsed laser operation was realized at a wavelength of 1058 nm when the fiber was cladding pumped at a wavelength of 808 nm. The laser delivered 38 µJ of energy in 65 ns pulses. The extracted energy was limited due to the multimodal operation of the fiber. Laser slope efficiency in continuous wave operation reached 52%. The spectroscopic properties of the fabricated fiber are discussed and compared to a Nd:YAG crystal and a Nd:Al-doped silica fiber.

Effects of ractopamine and protein source on growth performance and carcass characteristics of feedlot heifers.

An experiment was conducted to determine the relationship between feeding ractopamine and different amounts of MP on growth and carcass characteristics of feedlot heifers. Seventy-two crossbred heifers (475 kg of initial BW) were fed individually a diet based on steam-flaked corn for ad libitum intake for 29 d. Heifers were implanted with 140 mg of trenbolone acetate and 14 mg of estradiol-17beta 60 d before the experiment. Treatments were arranged as a 2 x 3 factorial and included 0 or 200 mg of ractopamine-HCl (23 ppm)/ d, and urea, solvent soybean meal, or expeller soybean meal (ESBM) as the predominant protein supplement. The amounts of MP supplied by the urea, solvent soybean meal, and ESBM diets were 688, 761, and 808 g/ d, respectively, calculated according to level 1 of the NRC model. Body weights were obtained 1 d before ractopamine feeding and at slaughter. Blood samples were obtained 1 d before starting the experiment and 13 d later. Ractopamine improved ADG, efficiency of gain, carcass-adjusted ADG, and carcass-adjusted efficiency of gain (P < 0.01). For ADG, heifers demonstrated a ractopamine x protein source interaction (P < 0.05); heifers not fed ractopamine had greater ADG when fed ESBM than when fed urea, whereas for heifers fed ractopamine there were no differences (P > or = 0.10) among protein supplements. This interaction was not observed for carcass-adjusted ADG (P = 0.60). Final live weights (P = 0.02) and carcass weights (P = 0.01) were greater with ractopamine feeding. Carcass marbling scores and yield grades were not affected by ractopamine or protein source (P > or = 0.39). Plasma total alpha-amino N and glucose concentrations decreased more from pretreatment concentrations when heifers were fed ractopamine (P < 0.05). Feeding ractopamine to heifers for 28 d before slaughter improved ADG and efficiency of gain without any large effects on carcass characteristics. The MP supply does not need to be increased from that provided by finishing diets based on steam-flaked corn with urea as the primary N supplement to allow the maximal response to ractopamine by finishing heifers.

Selective inhibition of mammalian lanosterol 14 alpha-demethylase by RS-21607 in vitro and in vivo.

The discovery of selective lanosterol 14 alpha-demethylase inhibitors may lead to novel hypolipidemic drugs. RS-21607, (2S,4S)-cis-2[1H-imidazol-1-yl)methyl]-2-[2-(4-chlorophenyl)ethyl]-4- [[(4-aminophenyl)thio]methyl]-1,3-dioxolane, was characterized as a tight-binding, competitive inhibitor of lanosterol 14 alpha-demethylase purified from rat liver. The apparent Ki was determined to be 840 pM and found to be similar in hepatic microsomes from human, rat, and hamster. RS-21607, which contains two chiral centers, was a more effective lanosterol 14 alpha-demethylase inhibitor than its three stereoisomers. In vitro, RS-21607 had a greater affinity for lanosterol 14 alpha-demethylase than the other cytochromes P450 evaluated: CYP7, CYP27, CYP11A1, CYP19, CYP17, CYP11B1, CYP21, CYP3A4, CYP4A, CYP2D6, CYP1A2, CYP2C9, and 27-hydroxycholesterol 7 alpha-hydroxylase. The other stereoisomers were not as selective as RS-21607. Doses of 3-30 mg/kg RS-21607 given orally to hamsters caused a dose-dependent decrease in cholesterol biosynthesis with a corresponding accumulation of 24,25-dihydrolanosterol. RS-21607 inhibited the enzyme and cholesterol biosynthesis in hamster liver by 50% at 18 h following a 30 mg/kg oral dose. This was interpreted to indicate that RS-21607 is able to distribute to the site of action in hamsters and inhibit the target enzyme. In the same dose range, the plasma concentrations of testosterone, corticosterone, and progesterone, the endpoints for the cytochromes P450 involved in steroid biosynthesis, were relatively unaffected. These data show RS-21607 to be an effective and selective inhibitor of lanosterol 14 alpha-demethylase, both in vivo and in vitro. RS-21607 interacted with the purified enzyme to produce a type II binding spectrum, consistent with an interaction between the imidazole moiety and the heme. The electrostatic contribution of the imidazole binding was investigated using the desimidazole analog of RS-21607. The apparent Ki for the desimidazole compound (65 microM) was similar to the apparent Km for the substrate DHL (79 microM). Together, these data confirm that the ligand attached to the imidazole in RS-21607 is a good non-sterol substitute for DHL, i.e., binding to the enzyme with similar affinity, and that the coordination of the imidazole to the heme provides a major electrostatic contribution for the inhibition of lanosterol 14 alpha-demethylase by RS-21607. RS-21607 was also observed to increase the accumulation of 3 beta-hydroxy-24,25-dihydrolanost-8-en-32-al, the second intermediate in the multistep oxidation, but not the first intermediate. 24,25-dihydrolanost-8-ene-3 beta,32-diol.(ABSTRACT TRUNCATED AT 400 WORDS)

A novel rat hepatic clofibrate-inducible cytochrome P450 that is not a lauric acid hydroxylase.

2-Methoxy-6-[1-methylethyl]naphthalene (MMEN) was hydroxylated in an NADPH-dependent manner to the (omega-1)-alcohol and the (R)-omega- and (S)-omega-alcohols by rat hepatic microsomes. (S)-omega-Hydroxylation was selectively induced 7-fold by clofibrate treatment. Phenobarbital, 3-methyl-cholanthrene, dexamethasone, cholestyramine, and MMEN did not induce this activity to the same extent. Incubation of the racemic omega-alcohols with microsomes isolated from rats resulted in a greater rate of degradation of the (S)- than the (R)-omega-alcohol confirming (S)-omega-hydroxylation to be an initial catalytic event. MMEN and lauric acid were not competitive inhibitors of each other in microsomes from clofibrate-treated rats, indicating the (S)-omega-MMEN hydroxylase to be a different enzyme from the characterized clofibrate-inducible lauric acid hydroxylases, CYP4A1 and CYP4A3. This was confirmed by the observations that (1) lauric acid hydroxylation was inhibited by 0.02% Tween 20 or Tween 80 and 25 microM capric or myristic acids, whereas omega-MMEN hydroxylation was not, (2) omega-MMEN hydroxylation was inhibited by ketoconazole, cholesterol and acetone, whereas lauric acid hydroxylation was not, and (3) CYP4A1 and CYP4A3 expressed in Hep G2 cells did not catalyze MMEN hydroxylation. Microsomes from the lungs of rabbits treated with progesterone and kidney of untreated rats did not support selective (S)-omega-MMEN hydroxylation, indicating that this activity is not associated with CYP4A4 or CYP4A2, respectively. Leukotriene B4 (LTB4) hepatic microsomal hydroxylation was not inhibited by MMEN and microsomes from human neutrophils did not support the reaction. These data identify a hitherto uncharacterized cytochrome P450 which is selectively induced by clofibrate and does not catalyze the omega-hydroxylation of the fatty acids or prostaglandins investigated. It is proposed that the enzyme catalyzing the selective (S)-omega-hydroxylation of MMEN is a novel rat P450 and that it is either a new member of the CYP4 family or a clofibrate-inducible P450 from another gene family.

Disposition of detirelix, a potent luteinizing hormone-releasing hormone antagonist, in rats and monkeys.

The disposition of detirelix, a potent luteinizing hormone-releasing hormone (LHRH) antagonist, was studied in rats and monkeys. After a single 300-microgram/kg intravenous dose in rats, the plasma elimination t1/2 was 1.6 hr and the plasma clearance was 3.3 ml/min/kg. In the monkey, the mean t1/2 and plasma clearance were 7.1 hr and 1.3 ml/min/kg, respectively, after an 80-microgram/kg intravenous dose. Long plasma t1/2 values of 18.7 and 31.6 hr were observed after single 0.2- and 1.0-mg/kg subcutaneous doses in the monkey, suggesting the possibility of subcutaneous depot formation at the injection site. Biliary excretion was the predominant route of elimination of detirelix in both species. Less than 10% of the detirelix was excreted renally. A major metabolite, isolated from the rat bile, was the 1-4 tetrapeptide fragment of detirelix. This metabolite was formed by enzymatic hydrolysis of the Ser4-Tyr5 bond, one of the only two peptide bonds in detirelix not containing a D-amino acid.

Bioavailability of soil-bound TCDD: dermal bioavailability in the rat.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), an unwanted by-product formed during the manufacture of hexachlorophene and phenoxyherbicides, has been found as an environmental contaminant in many U.S. and Western European sites. This study examines in the rat the degree of dermal absorption of TCDD bound to soil. Such information would assist regulatory agencies in evaluating the degree of exposure of humans who come in contact with TCDD-contaminated soil. Several parameters which may influence dermal absorption were studied, including TCDD dose, duration of contact, presence of crankcase oil as a co-contaminant, and environmentally contaminated vs laboratory-prepared soil. The dermal penetration of TCDD following 4 hr of contact with skin was approximately 60% of that following 24 hr of contact (P less than or equal to 0.05). Following 24 hr of contact with the skin, the degree of dermal uptake of TCDD contaminated soil was approximately 1% of the administered dose. Under the conditions of the present study, the degree of uptake does not appear to be influenced to any significant extent by the concentration of TCDD on soil, the presence of crankcase oil as co-contaminants, or by environmentally vs laboratory-contaminated soil. Although a number of parameters examined in this study did not significantly influence the degree of dermal absorption of TCDD in the rat following 24 hr of contact with the contaminated soil, the unqualified use of the 1% value to estimate human exposure would overestimate human exposure, since there is general agreement among researchers that rat skin tends to be more permeable than human skin to highly lipid-soluble compounds such as TCDD.