Coherent Amplification of Continuous Laser Field via Superfluorescence.

Superfluorescence (SF) is collective spontaneous emission wherein radiators spontaneously synchronize, resulting in an intense single-pulse emission. The avalanche radiation of photons is initiated by the first photon emitted into the SF propagation mode. Because this process is stochastic, the absolute phase of the SF changes randomly from shot to shot. We demonstrate that this phase can be controlled by seeding the SF with a resonant continuous-wave (CW) laser. The seed light was weak enough not to cause the stimulated emission but strong enough to inject the first photon into the SF propagation mode prior to injection by the radiators themselves. Cross-correlation measurements between the seeded SF and CW laser revealed that the seed light was coherently amplified by the SF. The amplification factor for the instantaneous intensity was estimated to be 7 orders of magnitude. These results will pave the way for the development of new types of quantum optical amplifiers.

Cascade and yoked superfluorescence detected by sum frequency generation spectroscopy.

We investigated the superfluorescent decay process of dense rubidium atomic vapor in a cell. Using a femtosecond laser pulse, the atoms were excited from the 5S ground state to the 6P state. The 2.73µm and 1.37µm fields were generated on the cascaded decay, 6P → 6S → 5P, which further stimulated the 780 nm forward emission on the 5P → 5S transition. Using sum frequency generation (SFG) spectroscopy, we observed all emission fields and the time delay between them, with sufficient temporal resolution. The experimental results were successfully reproduced using semiclassical simulations.

Polarization correlation in the superfluorescent decay process.

We investigated the polarization properties of superfluorescence (SF) emitted from dense cesium atomic vapor in a cell. The atoms were excited from the 6S ground to the 8P state using a femtosecond laser pulse. The SF fields generated on the cascaded decay, 8P→8S→7P, mediated the nonlinear optical process. We observed 4.2-µm and 456-nm forward directional emissions generated on the 8S→7P and 7P→6S transitions, respectively. The polarizations of the two fields were correlated in each laser shot, and their directions fluctuated from shot to shot, reflecting the noise that initiated the 4.2-µm emission.

Rabi oscillations in the spatial profiles of superfluorescent pulses from rubidium vapor.

In this study, we investigate 420-nm yoked superfluorescence (YSF) emitted from the atomic vapor of rubidium (Rb) by driving the Rb 5S - 5D two-photon transition with an ultrashort pulsed laser. When the pump pulse is close to its transform limit (~ 100 fs) or down-chirped up to around 200 fs, the 420-nm YSF appears as a low-divergence beam with a ring-shaped radial profile. Although such a beam profile is less sensitive to the vapor pressure of Rb in a cell, its diameter rigorously varies as a function of the pump-pulse power. By numerically solving a time-dependent Schrödinger equation for a single-Rb atom, we well reproduce our experimental observation, indicating that a single-atom Rabi oscillation is responsible for the spatial beam profile of the 420-nm emission.

Sub-two-cycle, carrier-envelope phase-stable, intense optical pulses at 1.6 µm from a BiB3O6 optical parametric chirped-pulse amplifier.

We report on the generation of 9.0 fs, 550 µJ, carrier-envelope phase (CEP)-stabilized optical pulses around 1.6 µm at 1 kHz. Few-cycle IR pulses are obtained from a BiB(3)O(6) optical parametric chirped-pulse amplifier. The amplification of nearly octave-spanning ultrabroad pulses without spectral broadening results in good stability in output energy (0.85% rms) and CEP (160 mrad rms). We observed high harmonics in the water window from a neon cell that corresponds to a laser intensity of 4.1×10(14) W/cm(2).

Highly precise and compact ultrahigh vacuum rotary feedthrough.

The precision and rigidity of compact ultrahigh vacuum (UHV) rotary feedthroughs were substantially improved by preparing and installing an optimal crossed roller bearing with mounting holes. Since there are mounting holes on both the outer and inner races, the bearing can be mounted directly to rotary and stationary stages without any fixing plates and housing. As a result, it is possible to increase the thickness of the bearing or the size of the rolling elements in the bearing without increasing the distance between the rotating and fixing International Conflat flanges of the UHV rotary feedthrough. Larger rolling elements enhance the rigidity of the UHV rotary feedthrough. Moreover, owing to the structure having integrated inner and outer races and mounting holes, the performance is almost entirely unaffected by the installation of the bearing, allowing for a precise optical encoder to be installed in the compact UHV rotary feedthrough. Using position feedback via a worm gear system driven by a stepper motor and a precise rotary encoder, the actual angle of the compact UHV rotary feedthrough can be controlled with extremely high precision.

TS-071 is a novel, potent and selective renal sodium-glucose cotransporter 2 (SGLT2) inhibitor with anti-hyperglycaemic activity.

BACKGROUND AND PURPOSE: The renal sodium-glucose cotransporter 2 (SGLT2) plays an important role in the reuptake of filtered glucose in the proximal tubule and therefore may be an attractive target for the treatment of diabetes mellitus. This study characterizes the pharmacological profile of TS-071 ((1S)-1,5-anhydro-1-[5-(4-ethoxybenzyl)-2-methoxy-4-methylphenyl]-1-thio-D-glucitol hydrate), a novel SGLT2 inhibitor in vitro and in vivo. EXPERIMENTAL APPROACH: Inhibition of glucose uptake by TS-071 was studied in CHO-K1 cells stably expressing either human SGLT1 or SGLT2. Single oral dosing studies were performed in rats, mice and dogs to assess the abilities of TS-071 to increase urinary glucose excretion and to lower plasma glucose levels. KEY RESULTS: TS-071 inhibited SGLT2 activity in a concentration-dependent manner and was a potent and highly selective inhibitor of SGLT2. Orally administered TS-071 increased urinary glucose excretion in Zucker fatty rats and beagle dogs at doses of 0.3 and 0.03 mg·kg(-1) respectively. TS-071 improved glucose tolerance in Zucker fatty rats without stimulating insulin secretion and reduced hyperglycaemia in streptozotocin (STZ)-induced diabetic rats and db/db mice at a dose of 0.3 mg·kg(-1). CONCLUSION AND IMPLICATIONS: These data indicate that TS-071 is a potent and selective SGLT2 inhibitor that improves glucose levels in rodent models of type 1 and 2 diabetes and may be useful for the treatment for diabetes mellitus.

[Multiple presentation of undifferentiated pleomorphic sarcoma in the mediastinum].

A case of undifferentiated pleomorphic sarcoma in the mediastinum is presented. A 74-year-old man with no complaint was referred to our department for treatment of mediastinal mass pointed out by chest X-ray. Chest computed tomography (CT) revealed 3 tumors located in the left mediastinum. The largest one was adjacent to the esophagus with 10 cm in diameter. The other one was located beneath the left inferior pulmonary vein, and the last adjacent to the pulmonary artery trunk. Complete extirpation of the tumors was unsuccessful because of the invasion to the pulmonary artery trunk. A diagnosis of undifferentiated pleomorphic sarcoma was made with negative immunohistochemical staining for markers except for vimentin. Tumor cells were found to be scattered in the partially resected thymus. We assume this is a rare presentation of mediastinal dissemination of the tumor.

[Thymoma with synchronous pulmonary metastasis; report of a case].

We report a resected case of thymoma with a solitary pulmonary metastasis. A 63-year-old woman had pointed out a solitary nodule in right lung field on chest X-ray. Computed tomography (CT) scan showed an anterior mediastinal tumor and a solitary lung nodule in the right lower lobe. Extended thymectomy and partial resection of right lung was performed. Pathological diagnosis showed an invasive thymoma (type B3) and a pulmonary metastasis. Post operative radiotherapy was administered and she is doing well 19 months following the resection. Thymoma with a solitary synclonous pulmonary metastasis is rare and is classified into Masaoka stage IVb. Generally, thymoma cases with distant metastasis are not indication for operation. But, if radical resection is possible, operation is recommended for good prognosis.

Effects of a complex balance task on soleus H-reflex and presynaptic inhibition in humans.

Spinal modulation of motoneuron excitability has been extensively investigated during various tasks in humans. Previous studies have revealed that balance tasks induce a decrease in Ia-motoneuron communication which has been attributed to increased levels of presynaptic inhibition (PI). Moreover, this depression in Ia-motoneuron connectivity takes place subsequent to the elevation of muscle activity. Therefore, it is hypothesized that motor learning has inhibitory effects on the spinal mechanisms in spite of the increased muscle activity during a motor task. The purpose of this study was to explore the effects of a complex balance task on the H-reflex. Soleus H-reflexes were measured from 11 healthy adult subjects both before and after 20 minutes of a complex balance task. A commonly reported H-reflex conditioning technique was applied in order to measure changes in spinal PI: an electrical volley to the heteronymous Ia (common peroneal nerve conditioning, CPN). Subjects stood on a custom designed balance board and performed a continuous series of plantar and dorsiflexion. To ensure that the task was performed similarly between subjects, auditory cues for movement were given by a metronome with a frequency of 1 Hz. The initial amplitude of the unconditioned soleus H-reflex was set at 50% of H-max, and unconditioned and conditioned (PI) reflexes were recorded before, during, and after the balance task. The unconditioned soleus H-reflex was significantly decreased 59% after the balance task and PI was increased by 50%. Further, during a period of rest following the task (20 minutes) the unconditioned H-reflex returned to near baseline levels whereas the PI conditioned H-reflex was not altered The results suggest that the initial depression in motoneuron excitability immediately after the balance task is accompanied by an increase in PI, but also that the recovery of the depressed H-reflex after the task appears to be independent of PI.

Protective effect of 17beta-estradiol on ischemic acute renal failure through the PI3K/Akt/eNOS pathway.

Estrogens attenuate renal injury induced by ischemia/reperfusion (I/R), an effect that is related to nitric oxide production in the post-ischemic kidney. The compound 17beta-estradiol (E(2)-beta) acting via estrogen receptors (ERs) is known to activate endothelial nitric oxide synthase (eNOS) through the phosphatidylinositol-3 kinase (PI3K)/Akt pathway. We determined if this pathway contributes to the renoprotective effect of E(2)-beta in the uninephrectomized ischemia reperfusion rat model of acute renal injury. Treatment with E(2)-beta suppressed the I/R-induced increases in blood urea nitrogen, plasma creatinine, urine flow, and fractional excretion of sodium while augmenting creatinine clearance, renal blood flow, and urine osmolality, indicating attenuation of renal injury. Phosphorylation of Akt and eNOS protein was significantly increased 30-60 min after reperfusion in estradiol-treated compared to vehicle-treated rats. The protective effects of E(2)-beta and protein phosphorylation were reversed by the PI3K inhibitor wortmannin or the ER antagonist tamoxifen. Furthermore, the E(2)-beta-induced renoprotective effects were not seen in eNOS knockout mice with renal injury. We conclude that the E(2)-beta-induced renoprotective effect is due to activation of the PI3K/Akt pathway followed by increased eNOS phosphorylation in the post-ischemic kidney.

Change of autonomic nervous activity during pregnancy and its modulation of labor assessed by spectral heart rate variability analysis.

PURPOSE OF INVESTIGATION: To elucidate the sequential changes of autonomic nervous activity during pregnancy, we examined heart rate variability on two positions and whether autonomic nervous activity affected duration of labor. METHODS: Thirty-eight normal pregnant women were studied. Frequency domain parameters (HF, LF, LF/HF ratio) and heart rate were obtained by spectral HRV analysis in the supine and left recumbent position in three trimesters. RESULTS: We found HF was significantly higher in early pregnancy, while the LF/HF ratio was significantly higher in late pregnancy. The LF/HF ratio was significantly lower when the left recumbent position was assumed. The LF/HF ratio was significantly higher in the longer labor group of primiparous women. CONCLUSION: Our findings demonstrate that sympathovagal balance shifted progressively from a higher vagal modulation towards a higher sympathetic modulation, and the recumbent position activated vagal activity. It is suggested that increased sympathetic activity in late pregnancy could affect the duration of labor.

Shortening of distal motor latency in anode distal stimulation.

OBJECTIVE: Distal motor latency (DML) is shortened when the anode is held distally instead of the cathode by increasing the stimulus intensity. The objective of this study was to clarify the mechanism responsible for this shortening. METHODS: In seven healthy subjects, compound muscle action potential (CMAP) was obtained from the thenar muscle by bipolar stimulation of the median nerve at the wrist, and the intensity at which the first motor units were stimulated was defined as the threshold. Bipolar stimulation with extended interpole distance was employed to identify the generating site of the CMAP and F-wave. RESULTS: The shortening of DML was dependent on the stimulus intensity and threshold. For the low threshold condition, the CMAP generating site was replaced from the proximal cathodal pole to the distal anodal pole by increasing the stimulus intensity. The generating site of the F-wave remained at the proximal cathodal pole irrespective of stimulus intensity. CONCLUSIONS: Replacement of the generating site results in the shortening of DML. When the F-wave is recorded after being induced by anode distal stimulation, CMAP should not be simultaneously evaluated. SIGNIFICANCE: This study clarified the generation sites of CMAP and the F-wave when induced by anode distal stimulation.

Time representing cortical activities: two models inspired by prefrontal persistent activity.

Timing information in the range of seconds is significantly correlated with our behavior. There is growing interest in the cognitive behaviors that rely on perception, comparison, or generation of timing. However, little is known about the neural mechanisms underlying such behaviors. Here we model two different neural mechanisms to represent timing information in the range of seconds. In one model, a recurrent network of bistable spiking neurons shows a quasistable state that is initiated by a brief input and typically lasts for a few to several seconds. The duration of this quasistable activity may be regarded as the neural representation of internal time obeying a psychophysical law of time recognition. Another model uses synfire chains to provide the timing information necessary for predicting the times of anticipated events. In this model, the neurons projected to by multiple synfire chains are conditioned to fire synchronously at the times when an external event (GO signal) is expected. The conditioning is accomplished by spike-timing-dependent plasticity. The two models are inspired by the prefrontal activities of the monkeys engaging in different timing-information-related tasks. Thus, this cortical region may provide the timing information required for organizing various behaviors.

Induction of apoptosis and CD10/neutral endopeptidase expression by jaspamide in HL-60 line cells.

Jaspamide (asplakinolide) is a natural peptide isolated from marine sponges of Jaspis species and has fungicidal and growth-inhibiting activities. We characterized the jasplakinolide-induced loss of viability by programmed cell death in the HL-60 human promyelocytic leukemia cell line and found that this process was accompanied by neutral endopeptidase (NEP)/CD10 expression on the surface of the apoptotic cells. HL-60 cells do not normally express detectable amounts of NEP/CD10 on their surface or intracytoplasmically, but upon jaspamide treatment, CD10 was synthesized de novo, its expression being inhibited by cycloheximide pretreatment. Once synthesized, NEP/CD10 interfered with the jasplakinolide signal delivered to HL-60 cells. Inhibition of NEP/CD10 by the NEP inhibitor phosphoramidon or by an anti-CD10 monoclonal antibody significantly increased apoptosis induction. The appearance of CD10 on the cell surface was blocked by preincubation of the cells with the monocytic/macrophage-differentiating agents vitamin D3 and phorbol 12-myristate 13-acetate, but not by the granulocytic differentiating agents retinoic acid or dimethyl sulfoxide. Moreover, in the promonocytic U937 and mature monocytic THP-1 cell lines, jaspamide induced apoptosis but not CD10 expression. In HL-60 cells, CD10 expression was partially but not totally blocked by the broad-spectrum caspase inhibitor benzyloxacarbonyl-Val-Ala-Asp-fluoromethylketone, indicating a connection between apoptosis induction and CD10 synthesis. Our findings suggest that the CD10 expression is related to the programmed cell death induction by jaspamide, and also with the process of granulocytic differentiation in HL-60 cells.

Mutagenicity and DNA-damaging activity caused by decomposed products of potassium sorbate reacting with ascorbic acid in the presence of Fe salt.

Although potassium sorbate (PS), ascorbic acid and ferric or ferrous salts (Fe-salts) are used widely in combination as food additives, the strong reactivity of PS and oxidative potency of ascorbic acid in the presence of Fe-salts might form toxic compounds in food during its deposit and distribution. In the present paper, the reaction mixture of PS, ascorbic acid and Fe-salts was evaluated for mutagenicity and DNA-damaging activity by means of the Ames test and rec-assay. Effective lethality was observed in the rec-assay. No mutagenicity was induced in either Salmonella typhimurium strains TA98 (with or without S-9 mix) or TA100 (with S-9 mix). In contrast, a dose-dependent mutagenic effect was obtained when applied to strain TA100 without S-9 mix. The mutagenic activity became stronger increasing with the reaction period. Furthermore, the reaction products obtained in a nitrogen atmosphere did not show any mutagenic and DNA-damaging activity. PS, ascorbic acid and Fe-salts were inactive when they were used separately. Omission of one component from the mixture of PS, ascorbic acid and Fe-salt turned the reaction system inactive. These results demonstrate that ascorbic acid and Fe-salt oxidized PS and the oxidative products caused mutagenicity and DNA-damaging activity.

Extraction of knowledge on protein-protein interaction by association rule discovery.

MOTIVATION: Protein-protein interactions are systematically examined using the yeast two-hybrid method. Consequently, a lot of protein-protein interaction data are currently being accumulated. Nevertheless, general information or knowledge on protein-protein interactions is poorly extracted from these data. Thus we have been trying to extract the knowledge from the protein-protein interaction data using data mining. RESULTS: A data mining method is proposed to discover association rules related to protein-protein interactions. To evaluate the detected rules by the method, a new scoring measure of the rules is introduced. The method allowed us to detect popular interaction rules such as "An SH3 domain binds to a proline-rich region." These results indicate that the method may detect novel knowledge on protein-protein interactions.

Apoptosis induction by hypercross-linking of the surface antigen CD5 with anti-CD5 monoclonal antibodies in B cell chronic lymphocytic leukemia.

We evaluated cells from 24 patients with B cell chronic lymphocytic leukemia (B-CLL) to determine apoptosis induced by CD5 hypercross-linking. Following the CD5 hypercross-linking with anti-CD5 monoclonal antibodies (MoAbs), we identified 10 patients where CD5 hypercross-linking induced apoptosis (group A) and 14 patients whose cells were resistant to the anti-CD5 MoAbs (group B). The programmed cell death pathway of the cells from patient group A was caspase-3 and poly (ADP-ribose) polymerase (PARP)-dependent, involved a reduction of the mitochondrial transmembrane potential DeltaPsi and a down-regulation of the anti-apoptotic Bcl-2, Mcl-1 and iNOS proteins. Early activation-associated molecules such as CD25 and CD69 were expressed at higher levels than in controls after 6 h of culture with anti-CD5 MoAb. The expression of CD5 and of CD72, the ligand for CD5, were significantly lower in group A compared with group B. Anti-CD20 MoAb had similar activity with anti-CD5 MoAb and the combination of the two MoAbs seemed to be additive. In this study, it is suggested that the cells from some B-CLL patients can be induced into programmed cell death by CD5 hypercross-linking with anti-CD5 MoAbs.

Lactone formation of N-acetylneuraminic acid oligomers and polymers as examined by capillary electrophoresis.

We examined lactone-formation reaction of oligomers and polymers of N-acetylneuraminic acid in diluted hydrochloric acid solution and found that the time course of the lactonization reaction was easily traced by capillary electrophoresis. The reaction proceeded more rapidly with increasing the molecular mass of oligomers because the conformation of inner units became rigid and more favorable for the formation of lactone linkage. Present results obtained using capillary electrophoresis will be useful in understanding of physical and chemical properties of oligo/polysialic acids.

Analysis of prognostic factors in newly diagnosed patients with acute promyelocytic leukemia: the APL92 study of the Japan Adult Leukemia Study Group (JALSG).

All-trans-retinoic acid (ATRA) has been incorporated in front-line therapy for newly diagnosed acute promyelocytic leukemia (APL). We conducted a multicenter study of differentiation therapy with ATRA alone or in combination with chemotherapy followed by intensive postremission chemotherapy in patients with APL (the JALSG APL92 study), and analyzed prognostic factors to increase the cure rate in our subsequent trial. From 1992 to 1997, adult patients with newly diagnosed APL received oral ATRA 45 mg/m2 daily alone until complete remission (CR) if initial leukocyte counts were < 3.0x10(9)/l, and ATRA daily plus daunorubicin (DNR) 40 mg/m2x3 days plus enocitabine (BHAC) 200 mg/m2x5 days if leukocyte counts were > or =3.0 x 10(9)/l. If peripheral blasts exceeded 1.0x10(9)/l during therapy, DNRx3 days plus BHACx5 days was added. After CR was achieved, three courses of consolidation and six courses of maintenance/intensification chemotherapy were administered. Of 376 patients enrolled, 369 were evaluable (median age 46 years, range 15-86 years; median leukocyte counts 2.0x10(9)/l), and 333 (90%) achieved CR (94% of patients treated with ATRA alone, 88% with ATRA plus later chemotherapy, 89% with ATRA plus initial chemotherapy, and 86% with ATRA plus initial and later chemotherapy). At a median follow-up of 45 months, the predicted 6-year overall and event-free survival (EFS) rates for all patients were 65% and 52%, respectively. Favorable prognostic factors for CR were younger age, no or mild purpura, high serum total protein level, low lactate dehydrogenase level, and no or mild disseminated intravascular coagulation (DIC). Favorable prognostic factors for EFS were leukocyte counts < 10.0x10(9)/l, mild DIC, and no sepsis during induction therapy. In the JALSG APL97 study, we intensified chemotherapy for patients with leukocyte counts > or =3.0x10(9)/l, and are randomly testing whether further chemotherapy is required for APL patients with negative PCR for PML/retinoic acid receptor alpha in the maintenance phase.