Mid-infrared frequency comb for broadband high precision and sensitivity molecular spectroscopy.

We report on the experimental demonstration of the metrological and spectroscopic performances of a mid-infrared comb generated by a nonlinear downconversion process from a Ti:sapphire-based near-infrared comb. A quantum cascade laser at 4330 nm was phase-locked to a single tooth of this mid-infrared comb and its frequency-noise power spectral density was measured. The mid-infrared comb itself was also used as a multifrequency highly coherent source to perform ambient air direct comb spectroscopy with the Vernier technique, by demultiplexing it with a high-finesse Fabry-Perot cavity.

Subkilohertz linewidth room-temperature mid-infrared quantum cascade laser using a molecular sub-Doppler reference.

We report on the narrowing of a room-temperature mid-IR quantum cascade laser by frequency locking it to a CO2 sub-Doppler transition obtained by polarization spectroscopy. A locking bandwidth of 250 kHz has been achieved. The laser linewidth is narrowed by more than two orders of magnitude below 1 kHz, and its absolute frequency is stabilized at the same level.

Measuring frequency noise and intrinsic linewidth of a room-temperature DFB quantum cascade laser.

The frequency-noise power spectral density of a room-temperature distributed-feedback quantum cascade laser emitting at λ = 4.36 µm has been measured. An intrinsic linewidth value of 260 Hz is retrieved, in reasonable agreement with theoretical calculations. A noise reduction of about a factor 200 in most of the frequency interval is also found, with respect to a cryogenic laser at the same wavelength. A quantitative treatment shows that it can be explained by a temperature-dependent mechanism governing the transport processes in resonant tunnelling devices. This confirms the predominant effect of the heterostructure in determining shape and magnitude of the frequency noise spectrum in QCLs.

High survival rate of 6 cases of pulmonary large cell neuroendocrine carcinoma formerly classified as small cell carcinoma.

UNLABELLED: In the revised WHO classification of lung cancer, published in 1999, large cell neuroendocrine carcinoma (LCNEC) was employed as a new histological entity. LCNEC is generally considered a high-grade malignant lung cancer, and appropriate treatment remains to be determined. Before its new classification, LCNEC had long been classified into several entities. Advancing the review of previous cases in Nippon Medical School Hospital, we noticed that some LCNEC patients were formally diagnosed as having small cell lung cancer (SCLC), and they showed long-term survival. MATERIAL AND METHODS: All histological specimens of surgically resected SCLC in Nippon Medical School Hospital were reclassified according to the 1999 WHO classification manual. Their neuroendocrine differentiations were confirmed by the use of immunostainings with chromogranin A and synaptophysin. RESULTS: Fourteen cases satisfied the qualifications for both histological and clinical reevaluation. Among them, 6 patients were reclassified as LCNEC, and their stage distribution was as follow: IA; 1, IB; 2, IIIA; 2, and IIIB; 1. Their survival term ranged from 33.8 to 78.0 months; 5 were still alive, and 1 (IIIB) died 57.6 months after surgery. DISCUSSION: According to this study, all the LCNEC patients who were treated as SCLC patients showed more favorable prognoses than patients described in published studies, even overall lung cancer. Therefore, it is suggested that multimodality therapy for SCLC may improve the prognoses of patients with LCNEC.

Risk of alanine aminotransferase flare-up among asymptomatic hepatitis C virus RNA carriers: a 10-year follow-up study.

AIMS: The aim of this study was to determine the cumulative rate of flare-up of serum alanine aminotransferase (ALT) level during a 10-year follow-up period, and characterize the clinical, virologic features in 120 hepatitis C virus (HCV) RNA-positive asymptomatic carriers with persistently normal ALT levels for 6 months. RESULTS: All flare-up cases occurred during the first 5 years of the present study, 27.4% of carriers showed ALT flare-up during this period, but none in the second half of the study. Multivariate analysis showed that C100-3 antibody (Ab) and anti-human T cell leukemia virus (HTLV)-I Ab were two independent and significant predictors of ALT flare-up in hepatitis C virus (HCV) RNA asymptomatic carriers (P = 0.04, P = 0.03, respectively). Liver biopsy was performed in 44 patients (11 with flare-up of ALT level, whereas 33 had normal ALT levels). Histological features of chronic hepatitis with lymphoid infiltration in the portal tracts were commonly observed in all specimens, and no differences were noted between the flare-up ALT group and the persistently normal ALT group. CONCLUSIONS: Our results indicated that flare-up of ALT levels in asymptomatic HCV-RNA carriers with normal ALT levels occurs during the first 5 years of diagnosis, and that the presence of C100-3 and anti-HTLV-I antibodies are good predictors of a transient rise in ALT.

Retention of relative force in the scaling of a serial force pattern with an attenuated-force tap.

The present study was designed to examine the retention of relative force in the scaling of a serial force pattern in a finger-tapping sequence using an attenuated tap. On practice trials, 12 undergraduate students tapped a force plate connected to strain gauges that gave them feedback about the force. On test trials, participants recalled the force pattern (200 gm-200 gm-200 gm-100 gm) and the intertap interval (400 msec.) practiced during the practice period without the feedback (recalled task). Then, they adaptively produced a halved (halved task) or doubled force profile (doubled task) at the fixed intertap interval. Analyses showed that mean peak forces at the first three tap positions of the tapping sequence undershot the expected forces across all tasks. Hence, the ratios of the forces in Serial Positions 1:4, 2:4, and 3:4 were considerably lower than 2.0. This is a contextual effect suggesting that the last attenuated tap affected the first three taps of the tapping sequence. Thus, because the relative force of movements appears to be a weaker invariant feature than sequencing and relative timing for generalized motor program theory of Schmidt and Lee, this finding does not support the relative force for a generalized motor program.

Retention of relative force in the scaling of a serial force pattern.

The present study was designed to examine the retention of relative force in the scaling of a serial force pattern in finger-tapping sequences. On practice trials, 11 male college students tapped a force plate connected to strain gauges which provided feedback. On test trials, subjects recalled both the force pattern (100 g-100 g-100 g-300 g) and intertap interval (400 msec.) acquired during practice without feedback (recalled task) and then produced a halved (halved task) or doubled-force (doubled task) at the fixed intertap interval. Analysis showed that, although there was no difference for absolute forces between the recalled task and the halved task, the forces at the doubled task were three times as great as those at the recalled task. For relative forces, on the other hand, although there was no difference among the three tasks, the force ratios were closer to 1:1:1:2 than 1:1:1:3. This indicated that the scaling of force pattern was a more difficult adaptive task than that of the intertap interval in the previous study (Inui, Ishida, & Yamanishi, 1999).

Retention and adaptive control of force pattern on a finger-tapping sequence with an attenuated force tap.

The present study was designed to examine the retention and adaptive control of a force pattern in the scaling of speed profiles in a finger-tapping sequence with an attenuated tap. On practice trials, 11 college students tapped on a force plate connected to strain gauges with feedback. On test trials, participants recalled the force pattern (200 gm-200 gm-200 gm-100 gm) and the intertap interval 1400 msec.) acquired during practice without feedback (recalled task). Then, participants adaptively tapped the acquired force pattern at the half (speeded task) and double (slowed task) the intertap interval acquired during the practice. Analyses showed that mean peak forces increased across tasks as the tapping speed was slowed down. Mean peak forces at the first three tap positions in sequence were smaller than the required forces in both the recall and speeded tasks. So, although the slowed task had the lowest ratio of forces in serial positions 1:4, 2:4, and 3:4, the ratios were less than 2 across tasks. These indicated that changing to a slow pace creates a more difficult adaptive task than changing to a fast pace, and further that a serial force pattern with an attenuated force creates a more difficult motor task for fine control than that with an accentuated force.

Wideband squeezing in photon number fluctuations from a high-speed light-emitting diode.

Wideband, highly noise-suppressed squeezing was observed by using a high-speed, high-quantum-efficiency light-emitting diode. The squeezing bandwidth extended over 200 MHz. We also have investigated the dependence of the squeezing bandwidth on the pump-current at low temperature. The experimental result was compared with the theoretical predictions based on a unified model of the pump and recombination process and was well explained by the model at the thermionic emission limit.

Retention and adaptive control of force patterns in finger-tapping sequences.

The present study was designed to examine whether a serial force pattern in the finger-tapping sequences was retained and adaptively controlled. On practice trials, 15 male college students tapped a force plate connected to strain gauges which provided feedback. On test trials, subjects recalled the force pattern and the intertap interval acquired during practice without feedback (recalled task). Next, subjects adaptively tapped the acquired force pattern at the half (speeded task) and twice the intertap interval acquired during practice (slowed task). Analysis showed that the force patterns were quite precisely retained across tasks, and the relative force pattern was retained. Although there was no difference for force between the slowed and the recalled task, the force in the speeded task differed from that in the recalled task. This indicated that changing to a fast pace creates a more difficult adaptive task than changing to a slow pace.

Wideband deep penetration of photon-number fluctuations into the quantum regime in series-coupled light-emitting diodes.

Experimental results on the squeezing of photon-number fluctuations of series-coupled LED's driven by a constant-voltage source are presented that illustrate the advantage of series-coupled LED's, namely, a greater squeezing capability than that of a single LED driven through an equivalent series resistor. We discuss the microscopic origin of the deep squeezing on the basis of quantum-mechanical Langevin equations.

EPR spectroscopic evidence for the mechanism-based inactivation of adenosylcobalamin-dependent diol dehydratase by coenzyme analogs.

EPR spectra were measured upon incubation of the complex of diol dehydratase with coenzyme analogs in the presence of 1,2-propanediol, a physiological substrate. When the analog in which the D-ribose moiety of the nucleotide loop was replaced by a trimethylene group was used as coenzyme, essentially the same EPR spectrum as that with adenosylcobalamin was obtained. The higher-field doublet and the lower-field broad signals derived from an organic radical and low-spin Co(II) of cob(II)alamin, respectively, were observed. With the imidazolyl counterpart, base-on cob(II)alamin-like species accumulated, but signals due to an organic radical quickly disappeared. When a coenzyme analog lacking the nucleotide moiety was incubated with apoenzyme in the presence of substrate, the EPR spectrum resembling cob(II)inamide was obtained, but no signals due to an organic radical were observed. From these results, it was concluded that the extinction of organic radical intermediates results in inactivation of the enzyme by these coenzyme analogs. Upon suicide inactivation with a [15N2]imidazolyl analog, the octet signals due to Co(II) showed superhyperfine splitting into doublets, indicating axial coordination of 5,6-dimethylbenzimidazole to the cobalamin bound to diol dehydratase.

Evidence for axial coordination of 5,6-dimethylbenzimidazole to the cobalt atom of adenosylcobalamin bound to diol dehydratase.

It was demonstrated by electron paramagnetic resonance (EPR) spectroscopy that organic radical intermediates disappeared and cob(II)alamin accumulated upon suicide inactivation of diol dehydratase by 2-methyl-1,2-propanediol. The resulting EPR spectra showed that the eight hyperfine lines due to the divalent cobalt atom of cob(II)alamin further split into triplets by the superhyperfine coupling to the 14N nucleus. Essentially the same superhyperfine splitting of the octet into triplets was observed with [14N]- and [15N]apoenzyme. When the adenosyl form of [14N2]- and [15N2]imidazolyl analogues of the coenzyme [Toraya, T., and Ishida, A. (1991) J. Biol. Chem. 266, 5430-5437] was used with unlabeled apoenzyme, the octet showed superhyperfine splitting into triplets and doublets, respectively. Therefore, it was concluded that cobalamin is bound to this enzyme with 5,6-dimethylbenzimidazole coordinating to the cobalt atom. This conclusion is consistent with the fact that the consensus sequence forming part of a cobalamin-binding motif, conserved in methionine synthase and some of the other cobalamin enzymes, was not found in the deduced amino acid sequences of the subunits of diol dehydratase. Adenosylcobinamide methyl phosphate, a coenzyme analogue lacking the nucleotide moiety, underwent cleavage of the cobalt-carbon bond upon binding to the enzyme in the presence of substrate, forming a cob(II)inamide derivative without nitrogenous base coordination, as judged by EPR and optical spectroscopy. Therefore, this analogue may be a useful probe for determining whether the replacement of the 5, 6-dimethylbenzimidazole ligand by a histidine residue takes place upon binding of cobalamin to proteins.

Lymph node abscess due to Actinomyces viscosus in a cat.

In a four-year-old male cat, a subcutaneous phyma about 3.5 cm in diameter was surgically removed from the left inframandibular region. Histopathologically, the phyma was found to be the swollen medial retropharyngeal lymph node containing an actinomycotic abscess. The filamentous organisms in the abscess stained positively by the Gram's, Grocott's and periodic acid-Schiff methods, and were negative by the Ziehl-Neelsen method. By the immunoperoxidase method, the organisms were specifically identified as Actinomyces viscosus serotype 2 by its antiserum absorbed with A. viscosus serotype 1 antigen.

An electron paramagnetic resonance study on the mechanism-based inactivation of adenosylcobalamin-dependent diol dehydrase by glycerol and other substrates.

Adenosylcobalamin-dependent diol dehydrase undergoes mechanism-based inactivation by glycerol or other substrates during catalysis. X-band electron paramagnetic resonance spectra of holoenzyme were measured at -130 degrees C after reaction with such substrates. After short time of incubation, broad signals assigned to low-spin Co(II) of cob(II)alamin and doublet signals assigned to an organic radical intermediate derived from each substrate were observed with 1,2-propanediol, 1,2-ethanediol, glycerol and meso-2,3-butanediol with the magnitude of their exchange interaction (J-value) decreasing in this order. A substrate with the smaller magnitude of exchange interaction between low-spin Co(II) and an organic radical intermediate seems to be an efficient mechanism-based inactivator. Since the magnitude of exchange interaction decreases with the distance between radical species in a radical pair, these results suggest that a stabilizing effect of holoenzyme on radical intermediates during reactions decreases with the distance between Co(II) and a radical.

Simple reaction times and timing of serial reactions of adolescents with mental retardation, autism, and Down syndrome.

The purpose of this study was to examine the serial information processing in adolescents with mental retardation, autism, and Down syndrome by using a serially patterned tracking task. Analyses indicated that 7 adolescents with mental retardation, 8 with autism, and 3 with Down syndrome had significantly slower and more variable simple reaction times than did 10 college students. Also, the autistic adolescents had significantly faster mean simple reaction time than those with Down syndrome. On a task of tracking serial light stimulation, mentally retarded adolescents had significantly faster reaction time than college students. The autistic subjects excessively had faster anticipatory reaction time than did the subjects in the other three groups. On the other hand, adolescents with Down syndrome had markedly slower and more variable reaction time than did adolescents with non-Down-syndrome mental retardation. As for motor organization of keystrokes on the tracking task, mentally retarded adolescents responded with six movements, in which these individuals pressed a series of keys 1, 2, 3, 4, 5, and 6, as a chunk, as exhibited by college students. Adolescents with autism and Down syndrome, however, did not produce this movement-output chunking.

Synthesis, properties and microbiological activity of hydrophobic derivatives of vitamin B12.

Long chain alkylcobalamins and long chain acyl-cyanocobalamins, two types of hydrophobic derivatives of vitamin B12, were synthesized. It was shown by TLC and determination of the partition coefficient between organic and aqueous phases that the hydrophobicity of alkylcobalamins and acyl-cyanocobalamins increased with the chain length of the alkyl or acyl group introduced into cobalamin. Long chain alkylcobalamins were easily converted to aquacobalamin by photoirradiation, but the first-order rate constant of photolysis decreased with the length of an alkyl group. Long chain acyl-cyanocobalamins were gradually hydrolyzed to cyanocobalamin in neutral or alkaline solution with the pseudo-first order rate constant increasing with the pH of the solution. Stabilization of acyl-cyanocobalamins toward hydrolysis was achieved by introducing a methyl group into the alpha-position of an acyl group. All the long chain alkylcobalamins tested supported the growth of Escherichia coli 215, a cobalamin- or L-methionine-auxotroph, and Lactobacillus leichmannii, although their activity as cobalamin was at most 28% and 15% that of cyanocobalamin for E. coli 215 and L. leichmannii, respectively.