High spatial-density, cladding-pumped 6-mode 7-core fiber amplifier for C-band operation.

We present a C-band 6-mode 7-core fiber amplifier in an all-fiberized cladding-pumped configuration for space division multiplexed transmission supporting a record 42 spatial channels. With optimized fiber components (e.g. passively cooled pump laser diode, pump coupler, pump stripper), high power multimode pump light is coupled to the active fiber without any noticeable thermal degradation and an average gain of 18 dB and noise figure of 5.4 dB are obtained with an average differential modal gain of 3.4 dB.

Low-loss Kagome hollow-core fibers operating from the near- to the mid-IR.

We report the fabrication and characterization of Kagome hollow-core antiresonant fibers, which combine low attenuation (as measured at ∼30 cm bend diameter) with a wide operating bandwidth and high modal purity. Record low attenuation values are reported: 12.3 dB/km, 13.9 dB/km, and 9.6 dB/km in three different fibers optimized for operation at 1 µm, 1.55 µm, and 2.5 µm, respectively. These fibers are excellent candidates for ultra-high power delivery at key laser wavelengths including 1.064 µm and 2.94 µm, as well as for applications in gas-based sensing and nonlinear optics.

Optoelectronic oscillator incorporating hollow-core photonic bandgap fiber.

We demonstrate, to the best of our knowledge, the first optoelectronic oscillator that uses hollow-core photonic bandgap fiber (HC-PBGF) as a delay element of a sufficient length to allow for low-noise operation. We show experimentally that HC-PBGF can improve the temperature stability of the oscillator by a factor of more than 15, as compared to standard optical fiber. We also measured the oscillator's phase noise, allowing evaluation of the suitability of HC-PBGF for this application. Additionally, this Letter also provides, to the best of our knowledge, the first characterization of the temperature stability of a long length (>800 m in our Letter) of low-thermal sensitivity (2 ps/km/K) HC-PBGF wound on a spool.

100 Gbit/s WDM transmission at 2 µm: transmission studies in both low-loss hollow core photonic bandgap fiber and solid core fiber.

We show for the first time 100 Gbit/s total capacity at 2 µm waveband, using 4 × 9.3 Gbit/s 4-ASK Fast-OFDM direct modulation and 4 × 15.7 Gbit/s NRZ-OOK external modulation, spanning a 36.3 nm wide wavelength range. WDM transmission was successfully demonstrated over 1.15 km of low-loss hollow core photonic bandgap fiber (HC-PBGF) and over 1 km of solid core fiber (SCF). We conclude that the OSNR penalty associated with the SCF is minimal, while a ~1-2 dB penalty was observed after the HC-PBGF probably due to mode coupling to higher-order modes.

Dense WDM transmission at 2 µm enabled by an arrayed waveguide grating.

We show, for the first time, dense WDM (8×20 Gbit/s) transmission at 2 µm enabled by advanced modulation formats (4-ASK Fast-OFDM) and the development of key components, including a new arrayed waveguide grating (AWGr) at 2 µm. The AWGr shows -12.8±1.78 dB of excess loss with an 18-dB extinction ratio and a thermal tunability of 0.108 nm/°C.

Demonstration of amplified data transmission at 2 µm in a low-loss wide bandwidth hollow core photonic bandgap fiber.

The first demonstration of a hollow core photonic bandgap fiber (HC-PBGF) suitable for high-rate data transmission in the 2 µm waveband is presented. The fiber has a record low loss for this wavelength region (4.5 dB/km at 1980 nm) and a >150 nm wide surface-mode-free transmission window at the center of the bandgap. Detailed analysis of the optical modes and their propagation along the fiber, carried out using a time-of-flight technique in conjunction with spatially and spectrally resolved (S2) imaging, provides clear evidence that the HC-PBGF can be operated as quasi-single mode even though it supports up to four mode groups. Through the use of a custom built Thulium doped fiber amplifier with gain bandwidth closely matched to the fiber's low loss window, error-free 8 Gbit/s transmission in an optically amplified data channel at 2008 nm over 290 m of 19 cell HC-PBGF is reported.

High-power Er:YAG laser with quasi-top-hat output beam.

A simple method for simultaneously exciting the fundamental (TEM00) transverse mode and first order Laguerre-Gaussian (LG01) donut mode in an end-pumped solid-state laser to yield a quasi-top-hat output beam is reported. This approach has been applied to an Er:YAG laser, in-band pumped by an Er,Yb fiber laser, yielding 9.6 W of continuous-wave output at 1645 nm in a top-hat-like beam with beam propagation factor (M2)<2.1 for 24 W of incident pump power at 1532 nm. The corresponding slope efficiency with respect to incident pump power was 49%. The prospects of further scaling of output power and improved overall efficiency are considered.

High power Er:YAG laser with radially-polarized Laguerre-Gaussian (LG01) mode output.

A simple method for conditioning the pump beam in an end-pumped solid-state laser to allow direct excitation of the first order Laguerre-Gaussian doughnut (LG01) mode is reported. This approach has been applied to a hybrid (fiber-laser-pumped) Er:YAG laser yielding 13.1 W of continuous-wave output at 1645 nm in a radially-polarized LG01 doughnut beam with beam propagation factor (M(2)) < 2.4 for 34 W of incident pump power at 1532 nm. The corresponding slope efficiency with respect to incident pump power was 48%. The prospects of further power scaling and improved laser performance are discussed.

The effect of periodicity on the defect modes of large mode area microstructured fibers.

It is well known that periodic variations in refractive index can be used to create guidance in an optical fiber via photonic bandgap effects. It has also been shown that periodic structure in index-guiding microstructured fibers can lead to the guidance of additional leaky higher-order modes due to bandgap effects. Here we demonstrate that this additional guidance mechanism can have important practical implications in large mode area silica microstructured fibers. We also demonstrate that similar modes can exist when a bandgap is not present and attribute this guidance to a low density of states. Excellent agreement between theoretical predictions and experimental observations is demonstrated. We explore the impact of these additional modes on the practical operation of these fibers and explore ways of minimizing their effects via the fiber geometry.

Pathogenic characteristics of the Korean 2002 isolate of foot-and-mouth disease virus serotype O in pigs and cattle.

Experimental infection of susceptible cattle and pigs showed that the O/SKR/AS/2002 pig strain of foot-and-mouth disease virus (FMDV) causes an infection that is highly virulent and contagious in pigs but very limited in cattle. Pigs directly inoculated with, or exposed to swine infected with, strain O/SKR/AS/2002 showed typical clinical signs, including gross vesicular lesions in mouth and pedal sites. In addition, FMDV was isolated from, and FMDV genomic RNA was detected in, blood, serum, nasal swabs and oesophageal-pharyngeal (OP) fluid early in the course of infection. Antibodies against the non-structural protein (NSP) 3ABC were detected in both directly inoculated and contact pigs, indicating active virus replication. In contrast, the disease in cattle was atypical. After inoculation, lesions were confined to the infection site. A transient viraemia occurred 1 and 2 days after inoculation, and this was followed by the production of antibodies to NSP 3ABC, indicating subclinical infection. No clinical disease was seen, and no antibodies to NSP 3ABC were present in contact cattle. Additionally, no virus or viral nucleic acid was detected in blood, nasal swab and OP fluid samples from contact cattle. Thus, the virus appeared not to be transmitted from infected cattle to contact cattle. In its behaviour in pigs and cattle, strain O/SKR/AS/2002 resembled the porcinophilic FMDV strain of Cathay origin, O/TAW/97. However, the latter, unlike O/SKR/AS/2002, has reduced ability to grow in bovine-derived cells. The porcinophilic character of O/TAW/97 has been attributed to a deletion in the 3A coding region of the viral genome. However, O/SKR/AS/2002 has an intact 3A coding region.

Effect of a flue-curing process that reduces tobacco specific nitrosamines on the tumor promotion in SENCAR mice by cigarette smoke condensate.

A 30-week dermal tumor promotion study was conducted to evaluate the dermal tumor-promoting potential of cigarette smoke condensate (CSC) collected from cigarettes containing flue-cured tobacco cured by a heat-exchange process (HE) relative to that of cigarettes containing flue-cured tobacco cured by the traditional direct-fire process (DF). Heat-exchange process cured tobacco contains significantly lower concentrations of tobacco specific nitrosamines (TSNAs) compared to traditional direct-fire cured tobacco. Mainstream CSCs were collected by cold trap from smoke generators using the Federal Trade Commission puffing regimen. Groups of 40 female SENCAR mice were initiated by a single application of 75 micro g 7,12-dimethylbenz[a]anthracene (DMBA) to the shaved dorsal skin. CSCs were then applied to the skin three times/week for 29 weeks at 9, 18, or 36mg tar/application. End-points included body weights, clinical observations, organ weights, dermal tumor development and histopathology. The numbers of dermal tumors and the numbers of tumor-bearing mice for each CSC were statistically different from the DMBA/acetone control group and increased with increasing dose. When corresponding doses of each CSC were compared, only the DMBA/mid-dose HE CSC group was statistically significantly different (lower) from the corresponding DMBA/mid-dose DF CSC group. In this assay, the dermal tumor-promotion potential of CSC from heat-exchange flue-cured tobacco did not differ from that of traditional direct-fire flue-cured tobacco CSC.

Dietary lipotropes, hepatic microsomal mixed-function oxidase activities, and in vivo covalent binding of aflatoxin B1 in rats.

Weanling male Sprague-Dawley rats were fed either a nutritionally complete synthetic diet (Diet 1) or a diet marginally deficient in choline and methionine, and lacking folacin (lipotrope deficient, Diet 2) to determine the role of hepatic mixed-function oxidase metabolism of aflatoxin B1 (AFB1) in the Diet 2-induced enhancement of AFB1 hepatocarcinogenesis previously reported. Hepatic microsomal mixed-function oxidase activities, as assayed by ethylmorphine N-demethylation, ethoxycoumarin O-dealkylation, cytochrome c reduction, AFB1 metabolism, and cytochrome P-450 content, were all depressed by Diet 2. Furthermore, the proportion of an i.p. dose of AFB (1 mg/kg) that became covalently bonded to DNA and RNA was similarly reduced when measured 6 hr after administration. The formation of AFB1-protein adducts was not influenced by dietary treatment. The depression of DNA and RNA adduct formation in the Diet 2 animals was probably related to the lower mixed-function oxidase activities and not to an alteration of glutathione levels, which remained unchanged by dietary treatment. These results suggest that the marginally lipotrope-deficient diet does not enhance tumor formation through an increased microsomal activation of AFB1. Alternative hypotheses without data are suggested.

Impaired vasoconstriction to endothelin 1 in patients with NIDDM.

Microvascular disease is an important cause of morbidity in diabetes. There is evidence that impaired autoregulation of blood flow is involved in the pathogenesis of diabetic microangiopathy. The vascular endothelium plays a central role in the regulation of vascular tone. Endothelin (ET)-1 is a potent endothelium-derived vasoconstrictor substance that contributes to basal vascular tone. Impaired vasoconstriction in response to endogenous ET could result in hyperperfusion and subsequent microvascular damage. The purpose of our study was to determine whether vascular responses to locally administered ET-1 are impaired in NIDDM. Nine patients with NIDDM and 12 control subjects underwent cannulation of the nondominant brachial artery. Forearm blood flow (FBF) was measured at baseline and during the drug infusion using strain-gauge venous occlusion plethysmography. ET-1 (5 pmol/min) was infused for 60 min at a rate of 1 ml/min. FBF was measured during the first 5 min of the infusion and at 5-min intervals thereafter. Results were expressed as change in FBF from baseline (ml.100 ml-1.min-1) and were analyzed using repeated measures analysis of variance and Dunnett's test of multiple comparisons. Control subjects showed a gradual onset of vasoconstriction in response to ET-1, which reached maximum at 35 min (1.1 ml.100 ml-1.min-1; P < 0.01). There was no reduction in FBF in response to ET-1 in the diabetic group. The differences between the diabetic and control groups were significant (P < 0.03). In conclusion, ET-1 infused locally at 5 pmol/min does not cause vasoconstriction in patients with NIDDM.

Autonomic function in neuropathic diabetic patients with foot ulceration.

OBJECTIVE: The aim of this study was to compare peripheral autonomic function in neuropathic diabetic subjects with and without foot ulceration. RESEARCH DESIGN AND METHODS: Measurements were made on 57 diabetic subjects; 35 subjects had evidence of peripheral neuropathy, 14 of these had a history of foot ulceration, and 22 subjects had no evidence of peripheral neuropathy. No patient had peripheral vascular disease. Measurements were made of motor and sensory nerve conduction. Autonomic function was investigated by using standard cardiovascular reflex tests and by measuring blood flow variability in the foot. The vasoconstrictor responses to deep breathing and body cooling were measured by using venous occlusion plethysmography. RESULTS: Peripheral sympathetic function was significantly worse in the DU group. The vasoconstrictor response to deep breathing in the DU group was significantly smaller than the response in the DN group (15.3 +/- 2.7 vs. 38 +/- 4%, P < 0.001). The response to body cooling in the DU group was significantly smaller than the response in the DN group (6.2 +/- 3.1 vs. 20.8 +/- 3.5%, P < 0.01). Tests of cardiac autonomic function and measurements of motor and sensory nerve conduction were similar in both neuropathic groups. CONCLUSIONS: Peripheral autonomic neuropathy is associated with the development of foot ulceration in diabetic subjects.

Peripheral autonomic impairment in patients newly diagnosed with type II diabetes.

OBJECTIVE: To measure both peripheral and central autonomic function in patients newly diagnosed with type II diabetes. RESEARCH DESIGN AND METHODS: Measurements were made on 49 diabetic patients (8 with long-standing diabetes and neuropathic complications, 41 with newly diagnosed type II diabetes) and on 49 healthy, age- and sex-matched, control subjects. Five of the 41 newly diagnosed type II diabetic patients had retinopathy, and 4 had clinical evidence of neuropathy. No patient or control subject had significant vascular disease. Cardiac autonomic function was investigated by using standard cardiovascular reflex tests. The digital vasoconstrictor responses to deep breathing and body cooling were measured using venous occlusion plethysmography. RESULTS: The vasoconstrictor responses to a deep breath and body cooling were significantly reduced (P < 0.001) in the fingers and toes of the neuropathic patients compared with their matched control subjects, as were the heart rate responses (P < 0.02). The vasoconstrictor responses were significantly reduced in the toes (P < 0.001) and fingers (P < 0.05, P < 0.01) of the newly diagnosed patients compared with the corresponding responses in the control subjects. There was no significant difference in the heart rate or blood pressure responses of these patients and control subjects during standard tests of cardiac autonomic function. CONCLUSIONS: Patients with type II diabetes may have impaired peripheral autonomic function at diagnosis.

Psychomotor performance and counterregulatory responses during mild hypoglycemia in healthy volunteers.

The effect of mild hypoglycemia on psychomotor performance and counterregulatory responses was studied among 12 healthy volunteers. Each volunteer received two modified hyperinsulinemic glucose clamps. One morning, plasma glucose was held constant at euglycemic levels (4.9 mM) for 95 min, and another morning, it was lowered over 35 min and then held constant at hypoglycemic levels (3.4 mM) for 60 min. A battery of psychomotor tests and a questionnaire assessing hypoglycemic symptoms were administered before and repeated during the last 30 min of each clamp. The questionnaire and three selected psychomotor tests were also administered repetitively during the 1st h of each clamp. During the hypoglycemic studies, a rise was seen in plasma epinephrine and pancreatic polypeptide at 45 min. An increase in symptom scores was first recorded at 50 min during the hypoglycemic studies [median 4 (range 0-13) vs. 2 (5-6), P less than .05]. Performance was impaired on two psychomotor tests included in the battery. One was the trail making test on fine motor performance (-19.3 +/- 4.2 targets/min, mean +/- SE vs. 1.2 +/- 4.8 targets/min, P less than .05), and the other was the digit-symbol substitution (DSS) test on information processing and memory (18 +/- 3 vs. 29 +/- 4 symbols/min, P less than .03). Of the tests administered during the 1st h, performance was impaired on the DSS. This impairment became significant at 45 min (14 +/- 4 vs. 22 +/- 4 symbols/min, P less than .005). In conclusion, mild hypoglycemia selectively impairs psychomotor performance in healthy volunteers but not before the onset of glucose counterregulation and warning symptoms.

The effect on gastrin secretion of agents which increase the intracellular concentration of 3',5'-adenosine monophosphate.

An in vitro technique that allows study of gastrin secretion from isolated pieces of rat gastric antrum was used to study the effect on gastrin release of agents known to increase intracellular cAMP levels. Isuprel (10(-5)M), PGE1 (10(-5)M), theophylline (10(-4)M), and dibutyryl cAMP (5 X 10(-4)M) did not affect gastrin release when used alone, but each enhanced arginine-stimulated gastrin release. A biphasic pattern of gastrin release in response to arginine was seen in all experiments. The studies emphasize the close functional similarity between the antral G cells and the B cells of the pancreatic islet.

Inhibition of gastrin release by somatosatin in vitro.

An in vitro system which uses perifused pieces from the antrum of rat stomach has been used to study the effect of dihydrosomatostatin on gastrin release. The gastrin concentration in fractions of the perfusate was measured by radioimmunoassay. Dihydrosomatostatin (2 x 10-7M) had no effect on basal gastrin levels but virtually abolished the biphasic response seen with argine stimulation. The study demonstrates close functional similarities between G cells and pancreatic islet cells.

Tamoxifen aziridines: effective inactivators of the estrogen receptor.

Two analogs of the antiestrogen tamoxifen, which bear a chemically reactive aziridine function in place of the dimethylamino group, bind to the estrogen receptor from rat uterus and from MCF-7 human breast cancer cells and appear to react irreversibly with the receptor at the estrogen binding site, in a time-and concentration-dependent fashion. BEcause these compounds are effective receptor inactivators in uterus and breast cancer cells, they should prove to be useful probes for investigating the role of receptor in regulating cellular responses to estrogen and in studying the dynamics of estrogen receptor synthesis and turnover.

Changes in mitochondrial and microsomal lipid peroxidation and fatty acid profiles in adrenal glands, testes, and livers from alpha-tocopherol-deficient rats.

Studies were done to evaluate the effects of alpha-tocopherol deficiency in rats on the fatty acid composition and sensitivity to lipid peroxidation (LP) of mitochondria and microsomes from adrenal glands, testes, and livers. In control (alpha-tocopherol-sufficient) animals, adrenal concentrations of alpha-tocopherol were approximately 10 times greater than those in livers and testes. Dietary deficiency of alpha-tocopherol for 8 weeks decreased adrenal and hepatic concentrations by 80-90% and testicular concentrations by approximately 60-70%. Incubation of testicular or hepatic mitochondria and microsomes from control rats with FeSO(4) (1.0 mM) caused a time-dependent stimulation of LP as indicated by the formation of thiobarbituric acid reactive substances (TBARS); the rate of TBARS production increased in preparations from alpha-tocopherol-deficient animals. TBARS formation was not demonstrable in adrenal mitochondria or microsomes from alpha-tocopherol sufficient rats, but reached high levels in alpha-tocopherol-deficient preparations. The fatty acid composition of mitochondria and microsomes was tissue-dependent. In particular, arachidonic acid comprised approximately 40% of the total fatty acids in adrenal membranes, but only 20-25% in testes and livers. alpha-Tocopherol deficiency increased oleic acid concentrations in adrenal and hepatic mitochondria and microsomes but not in testes. In all three tissues, linoleic acid concentrations decreased by approximately 50%, but arachidonic acid levels were unaffected by alpha-tocopherol deficiency. The results indicate a close relationship between tissue sensitivity to LP in vitro and alpha-tocopherol concentrations. Nonetheless, any oxidative stress in vivo caused by alpha-tocopherol deficiency seems to spare arachidonic acid in mitochondria and microsomes but decreases linoleic acid concentrations. It is possible that because of the important physiological functions of arachidonic acid, metabolic adaptations serve to maintain membrane content during periods of oxidative stress.