Modelling end-pumped passively Q-switched Nd-doped crystal lasers: manifestation by a Nd:YVO4/Cr4+:YAG system with a concave-convex resonator.

A theoretical model for the passively Q-switched (PQS) operation which includes the spatial overlapping between the pump and lasing modes under the thermal lensing effect is developed to give a transcendental equation that can directly determine the critical parameters such as pulse energy, pulse repetition rate, and pulse width for the PQS performance. More importantly, an analytical function which gives the approximate solution for the transcendental equation as well as a specific critical criterion for good PQS operation are derived for practical analyses and design. A Nd:YVO4/Cr4+:YAG system with a concave-convex resonator which can achieve fairly stable PQS pulse trains even at a high pump level is further exploited to manifest the proposed spatially dependent model. The good agreement between the experimental results and the theoretical predictions is verified to show the feasibility of the proposed model for designing high-power PQS lasers with high accuracy.

Exploiting concave-convex linear resonators to design end-pumped solid-state lasers with flexible cavity lengths: Application for exploring the self-mode-locked operation.

The characteristics of a convex-concave linear resonator under the thermal lensing effect are theoretically analyzed to find an analytical model for designing end-pumped solid-state lasers with flexible cavity lengths. By exploiting the design model, the power scaling for continuous-wave operation under strong thermal lensing can be easily achieved in the proposed resonator with different cavity lengths. Furthermore, the proposed resonator is applied to explore the exclusive influence of cavity length on the self-mode-locked (SML) operation. It is discovered that the lasing longitudinal modes will split into multiple groups in optical spectrum to lead to a multi-pulse mode-locked temporal state when the cavity length increases. Finally, a theoretical model is derived to reconstruct the experimental results of SML operation to deduce a simple relationship between the group number of lasing modes and the cavity length.

Monolithic dual-polarization self-mode-locked Nd:YAG 946-nm lasers: controlling beat frequency and observation of temporal chaos.

The self-mode-locked (SML) operation at 946 nm can be achieved with a monolithic Nd:YAG crystal when the pump power is above the threshold of the multiple-longitudinal-mode generation. The SML output is further found to include two orthogonal polarization components with a beat frequency coming from the birefringence effect in the laser crystal. The beat frequency can be widely adjusted in the range of 5-220 MHz by controlling the cooling temperature. The present experiment also confirms the theoretical prediction that the two-mode operation generally exhibits the chaotic dynamics when the frequency difference is sufficiently close to the relaxation frequency.

Synchronized self-mode-locked 1061-nm and 1064-nm monolithic Nd:YAG laser at cryogenic temperatures with two orthogonally polarized emissions: generation of 670 GHz beating.

A dual-wavelength self-mode-locked monolithic Nd:YAG laser at 1061 and 1064 nm is realized at cryogenic temperatures. At an incident pump power of 5.5 W, the total output power can reach 2.5 W and the mode-locked pulse width is 29 ps at a pulse repetition rate of 7.75 GHz. The synchronization of the dual-wavelength emissions leads to a beat frequency of 670 GHz in the individual mode-locked pulse. It is further discovered that the laser output consists of two orthogonally polarized components with a central frequency difference of 127 MHz. The central frequency difference between two orthogonal polarizations mainly arises from the external mechanical stress introduced by the copper holder for the laser crystal.

Generation of orthogonally polarized self-mode-locked Nd:YAG lasers with tunable beat frequencies from the thermally induced birefringence.

The simultaneous self-mode-locking of two orthogonally polarized states in a Nd:YAG laser is demonstrated by using a short linear cavity. A total output power of 3.8 W can be obtained at an incident pump power of 8.2 W. The beat frequency Δfc between two orthogonally polarized mode-locked components is observed and measured precisely. It is found that the beat frequency increases linearly with an increase in the absorbed pump power. The origin of the beat frequency can be utterly manifested by considering the thermally induced birefringence in the Nd:YAG crystal. The present result offers a promising approach to generate orthogonally polarized mode-locked lasers with tunable beat frequency.

Analysis of the optimal temperature for the cryogenic monolithic Nd:YAG laser at 946-nm.

The optimal temperature for the cryogenic monolithic Nd:YAG laser at 946-nm is theoretically and experimentally analyzed. It is clear that decreasing temperature can considerably eliminate the thermal population at the lower laser level to enhance the quantum efficiency. However, the narrowing of the absorption bandwidth for the gain medium leads to a reduction of the effective absorption efficiency as the temperature is decreased. Consequently, an optimal temperature for the maximum output power is found to be in the range of approximately 120 K to 140 K. It is experimentally verified that employing a pump source with a narrower emission spectrum linewidth contributes a more efficient output for the cryogenic laser.

Cryogenically monolithic self-Raman lasers: observation of single-longitudinal-mode operation.

A cryogenically monolithic Nd:YVO4 self-Raman laser is experimentally explored and theoretically analyzed. The variation of the stimulated Raman scattering (SRS) threshold on the temperature is found to be nonlinear because the reduction of thermal lensing enlarges the cavity mode size. In spite of the nonlinear variation of the SRS threshold on the temperature, the overall SRS output power can be efficiently increased from 0.78 to 1.36 W for temperature decreasing from 285 to 80 K at an absorbed power of 17.2 W. More interestingly, the single-longitudinal-mode operation is experimentally achieved when temperature is lower than 125 K.

24-W cryogenically cooled Nd:YAG monolithic 946-nm laser with a slope efficiency >70.

A high-power efficient monolithic Nd:YAG 946-nm laser is demonstrated at the cryogenic temperature. By exploring the absorption and the fluorescence spectra of the Nd:YAG crystal, it reveals the fact that the absorption bandwidth at 808 nm is narrowing and the fluorescence intensity at 1061 nm is significant enhanced when the temperature is decreased. The temperature dependence of the lasing threshold at 946 nm is found to display a minimum value near a temperature of 170 K. At an incident pump power of 34.5 W, the local heating leads the optimum temperature to be approximately 120 K and the maximum output power can reach 24.4 W with the conversion efficiency of 71% as well as the slope efficiency up to 75%.

An energy adjustable linearly polarized passively Q-switched bulk laser with a wedged diffusion-bonded Nd:YAG/Cr4⁺:YAG crystal.

An energy adjustable passively Q-switched laser is demonstrated with a composite Nd:YAG/Cr4⁺:YAG crystal by applying a wedged interface inside the crystal. The theoretical model of the monolithic laser resonator is explored to show the energy adjustable feature with different initial transmissions of the saturable absorber at the horizontal axis. By adjusting the pump beam location across the Nd:YAG crystal, the output pulse energy can be flexibly changed from 10.9 µJ to 17.6 µJ while maintaining the same output efficiency. The polarization state of the laser output is found to be along with the polarization of the C-mount pump diode. Finally, the behavior of the multi-transverse-mode oscillation is also discussed for eliminating the instability of the pulse train.

Nd:YLF laser at cryogenic temperature with orthogonally polarized simultaneous emission at 1047 nm and 1053 nm.

A Nd:YLF laser at cryogenic temperature is demonstrated for the first time with orthogonally polarized simultaneous emission at 1047 nm and 1053 nm. By exploring the temperature dependence of the fluorescence and the absorption spectra from the Nd:YLF crystal, the feasibility of simultaneous emission at low temperature is achieved. Due to the local heating from the pump absorption, the optimal temperature with respect to the pump power for balancing output powers of simultaneous emission is thoroughly explored. At the optimal temperature of 138 K, the total output power of the simultaneous emission can reach 3.1 W at an incident pump power of 7.9 W, corresponding to the optical to optical slope efficiency up to 43%.

High-repetition-rate quasi-CW side-pumped mJ eye-safe laser with a monolithic KTP crystal for intracavity optical parametric oscillator.

We demonstrate a high-repetition-rate millijoule passively Q-switched eye-safe Nd:YVO(4) laser pumped by a quasi-CW diode stack. A theoretical analysis has been explored for the design criteria of generating TEM(n,0) mode in the diode-stack directly side-pumping configuration. We successfully generate TEM(n,0) modes at 1064 nm by adjusting the gain medium with respected to the laser axis. We further observe the spatial cleaning ability for generating an nearly TEM(0,0) mode output at 1573 nm with a monolithic OPO cavity. At the repetition rate up to 200 Hz, the output pulse energy reaches 1.21 mJ with the threshold pump energy of 17.9 mJ.

Influence of output coupling on the performance of a passively Q-switched Nd:YAG laser with intracavity optical parametric oscillator.

A singly-resonant intracavity optical parametric oscillator (OPO), pumped by a passively Q-switched Nd:YAG laser, is systematically investigated by means of a series of the output mirrors with various reflectivities for the fundamental wavelength at 1064 nm. Experimental results reveal that the output mirror with partial reflectivity instead of high reflection at 1064 nm not only is practicable to avoid the optical coatings damaged, but also enhances the dual-wavelength output efficiency for the OPO signal and fundamental laser waves. The overall optical-to-optical conversion efficiency is enhanced from 6.4% to 8.2% for the reflectivity decreasing from 99.8% to 90%.

Compact high-pulse-energy passively Q-switched Nd:YLF laser with an ultra-low-magnification unstable resonator: application for efficient optical parametric oscillator.

We exploit an ultra-low-magnification unstable resonator to develop a high-pulse-energy side-pumped passively Q-switched Nd:YLF/Cr4⁺:YAG laser with improving beam quality. A wedged laser crystal is employed in the cavity to control the emissions at 1047 nm and 1053 nm independently through the cavity alignment. The pulse energies at 1047 nm and 1053 nm are found to be 19 mJ and 23 mJ, respectively. The peak powers for both wavelengths are higher than 2 MW. Furthermore, the developed Nd:YLF lasers are employed to pump a monolithic optical parametric oscillator for confirming the applicability in nonlinear wavelength conversions.

CXCR4 activation maintains a stem cell population in tamoxifen-resistant breast cancer cells through AhR signalling.

BACKGROUND: Tamoxifen is commonly used for breast cancer therapy. However, tamoxifen resistance is an important clinical problem. Continuous treatment with conventional therapy may contribute to cancer progression in recurring cancers through the accumulation of drug-resistant cancer progenitors. METHODS: To investigate signalling mechanisms important for the maintenance and viability of drug-resistant cancer progenitors, we used microarray analysis, PCR array for genes involved in cancer drug resistance and metabolism, flow cytometry, soft agar colony formation assay, in vivo tumourigenicity assay and immunohistochemical analysis using tamoxifen-sensitive and tamoxifen-resistant breast cancer MCF7 cells. RESULTS: Downregulation of CXCR4 signalling by small molecule antagonist AMD3100 specifically inhibits growth of progenitor cell population in MCF7(TAM-R) cells both in vitro and in vivo. Microarray analysis revealed aryl hydrocarbon receptor (AhR) signalling as one of the top networks that is differentially regulated in MCF7(TAM-R) and MCF7 xenograft tumours treated with AMD3100. Further, small molecule antagonists of AhR signalling specifically inhibit the progenitor population in MCF7(TAM-R) cells and growth of MCF7(TAM-R) xenografts in vivo. CONCLUSION: The chemokine receptor CXCR4 maintains a cancer progenitor population in tamoxifen-resistant MCF7 cells through AhR signalling and could be a putative target for the treatment of tamoxifen-resistant breast cancers.

Microsatellite DNA markers indicate three genetic lineages in East Asian indigenous goat populations.

The genetic differentiation and phylogenetic relationships of 18 indigenous goat populations from seven East Asian countries were analysed based on data obtained from 26 microsatellite DNA markers. The mean number of alleles (MNA) per population ranged from 2.5 to 7.6, with an average of 5.8. Genetic variability estimated from MNA and heterozygosity (H(E) and H(O) ) were relatively low in coastal and island populations. A heterozygous deficiency within populations (F(IS) = 0.054, P < 0.001) and total inbreeding (F(IT) = 0.181, P < 0.01) were observed, and genetic differentiation in the populations (F(ST) ) was 13.4%. The results of Bayesian model-based clustering and a neighbour-joining tree based on Nei's genetic distance showed that Asian goat populations could be subdivided into at least the following three genetic clusters: East Asian, Southeast Asian and Mongolian. These results are in close accordance with conventional morphological and geographical classifications and migration history.

Orthogonally polarized dual-wavelength Nd:LuVO4 laser at 1086 nm and 1089 nm.

A comparison between the fluorescence spectra of the Nd-doped vanadate crystals (Nd:YVO4, Nd:GdVO4, Nd:LuVO4) for the 4F3/2 → 4I11/2 transition is studied. We numerically analyze the condition of gain-to-loss balance via an uncoated intracavity etalon to achieve the dual-wavelength operation. We further experimentally demonstrate the orthogonally polarized dual-wavelength laser with a single Nd:LuVO4 crystal. The simultaneous dual-wavelength Nd:LuVO4 laser at 1085.7 nm in σ polarization and 1088.5 nm in π polarization is realized. At an incident pump power of 12 W, the average output power obtained at 1085.7 nm and 1088.5 nm is 0.4 W and 1.7 W, respectively.

Sporadic paediatric and adult Burkitt lymphomas share similar phenotypic and genotypic features.

AIMS: To characterize the clinicopathological features of sporadic Burkitt lymphoma (BL). METHODS AND RESULTS: A retrospective study of 17 paediatric and 14 adult BLs with history and histopathology review, immunohistochemistry, Epstein-Barr virus (EBV) in situ hybridization (EBER) and fluorescence in situ hybridization. There was no statistically significant difference in gender, frequency of central nervous system (CNS) involvement and leukaemic change at presentation, or frequency of CD10+/Bcl-2-/Bcl-6+ (88% versus 86%), Ki67 labelling index, EBER (24% versus 21%), or C-MYC translocation (100% versus 92%) between paediatric and adult tumours. Correct pretreatment diagnoses were made in 13/17 (76%) paediatric and in 9/14 (64%) adult tumours. Twenty-eight patients received chemotherapy including 13/16 (81%) paediatric and 3/12 (25%) adult patients with appropriate regimens; 16 (57%) received CNS prophylaxis. The 1- and 5-year overall survival (OS) rates for paediatric patients were 80% and 50%, respectively, whereas 1-year OS for adults was 15%. CONCLUSIONS: Sporadic paediatric and adult BLs were phenotypically and genotypically similar. The significant prognosticators were age (P = 0.001), with or without CNS prophylaxis (P = 0.004), and CNS involvement (P = 0.008) and leukaemic change (P = 0.019) in disease course. The poor outcome in adult patients might be related to incorrect diagnosis and inappropriate treatment.

Muscle control associated with isometric contraction in different joint positions.

The purpose of this study was to investigate the dependence of the surface EMG and varied internal effort due to different joint positions, and its muscle control strategies. Ten healthy subjects performed a fixed level (40% MVC measured in the neutral position) of isometric dorsiflexion and plantarflexion contraction in the ankle neutral, dorsiflexion, and plantarflexion positions. Quantitative EMG analyses with feature extraction in the time, frequency domain, as well as time-varying spectrum were employed to estimate recruitment pattern, code rating, and recruitment stationarity of activated motor units. Both RMS and median frequency of the tibial anterior (TA) and gastrocnemius (GS) were strongly dependent on foot position (p < .001). Dominant firing rate of the TA muscle during the effort related isometric contraction was significant different with respect to ankle position (p < .05). Irrespective of ankle position, the regression slope of median frequency across time was not different from zero for both TA and GS muscles (p > .05). Identical torque exertion in different ankle positions called for considerable changes of control strategies of motor units. Possible mechanisms could be augmented excitatory central afferents and release of inhibition from Golgi tendon organs in compensation for biomechanical disadvantage in shorter muscle length.

A double-blind, placebo-controlled, multicenter study of Cerebrolysin for Alzheimer's disease.

OBJECTIVE: To assess the efficacy and safety of Cerebrolysin over 4 weeks in patients with probable Alzheimer's disease (AD). DESIGN: A 4-week randomized, double-blind, placebo-controlled, multicenter clinical trial. An unequal (Cerebrolysin:placebo = 2:1) randomization was used to assign more patients to the treatment group. SETTINGS: University medical centers and community geriatric hospitals in Korea. PARTICIPANTS: Fifty-three men and women at least 50 years of age admitted to hospitals with mild to moderate AD and otherwise in good health. INTERVENTION: The treatment group (n = 34) received Cerebrolysin (30 mL Cerebrolysin in 100 mL physiologic saline IV) once a day from Monday to Friday for 4 weeks. The control group (n = 19) received placebo. MEASUREMENTS: Primary outcome measures were the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and the Clinical Global Impression of Severity/ Change (CGIS/C). Secondary outcome measures included Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS), Katz Index of Activities of Daily Living (ADL), and Lawton Instrumental Activities of Daily Living (IADL) Scale. RESULTS: After 4 weeks of treatment, Cerebrolysin-treated patients demonstrated significant improvements in the ADAS-Cog (P = .02), CGIS/C (P = .01), and MMSE (P = .04) compared with placebo-treated patients. Among Cerebrolysin-treated patients, 82%, 62%, and 44% were rated improved on ADAS-Cog, CGIS/C, and MMSE, respectively, compared with 31.6%, 22%, and 17% of placebo-treated patients, respectively. However, there were no significant improvements in the Cerebrolysin group compared with the placebo group on the GDS, ADL, and IADL. There were no dropouts in either groups, with 100% compliance to Cerebrolysin and placebo. Only one patient reported a febrile sensation, which was transient and mild in severity. CONCLUSIONS: This study indicates that Cerebrolysin is a safe drug that improves the cognitive deficits and global function in patients with mild to moderate AD. Long-term efficacy and safety of Cerebrolysin in Alzheimer's patients should be evaluated in the future.

Ligand-dependent interactions of coactivators steroid receptor coactivator-1 and peroxisome proliferator-activated receptor binding protein with nuclear hormone receptors can be imaged in live cells and are required for transcription.

Members of the nuclear receptor superfamily are thought to activate transcription by recruitment of one or more recently identified coactivator complexes. Here we demonstrate that both peroxisome proliferator-activated receptor binding protein (PBP) and steroid receptor coactivator-1 (SRC-1) are required for ligand-dependent transcription of transiently transfected and chromosomally integrated reporter genes by the estrogen receptor (ER) and retinoic acid receptor (RAR). To examine ligand-dependent interactions between nuclear receptors and specific coactivators in living cells, these proteins were tagged with cyan (CFP) and yellow (YFP) mutants of the green fluorescent protein. Fluorescence resonance energy transfer (FRET) from the CFP to the YFP indicated interaction between the receptor and coactivator. CFP fusions to RAR or its ligand-binding domain exhibited rapid ligand-dependent FRET to YFP-tagged nuclear receptor interaction domains of the coactivators SRC-1 and PBP. The ER-ligand-binding domain, unlike RAR, also exhibited some basal interaction with coactivators in unstimulated cells that was abolished by the receptor antagonists tamoxifen or ICI182,780. Inhibition of FRET by tamoxifen but not ICI182,780 could be reversed by estradiol, whereas estradiol-enhanced FRET could not be inhibited by either antagonist, indicating that ligand effects can show varying degrees of hysteresis. These findings suggest that ligand-dependent transcriptional activities of the RAR and ER require concurrent or sequential recruitment of SRC-1 and PBP-containing coactivator complexes.