Laser frequency stabilization in the 10 -14 range via optimized modulation transfer spectroscopy on the 87Rb D2 line.

We present a high-performance laser frequency stabilization method using modulation transfer spectroscopy (MTS) on the rubidium 87D2 transition line. A substantial improvement of the laser frequency stability was achieved by searching for the optimal diameter and intensity settings of the probe and pump beam. The frequency instability measured from the beat frequency of two locked external cavity diode lasers (ECDLs) reached a short-term stability of 4.5×10-14/τ and did not exceed 2 × 10-12 until 105 s, which is the best performance reported thus far with a D2 transition. The long-term stability is limited by the offset fluctuations of the baseline induced by the residual amplitude modulation (RAM), which can be further improved by reducing the current temperature variation of about 0.2 K by means of temperature stabilization or through a further reduction of the RAM.

Deciphering the mechanism and function of Hsp100 unfoldases from protein structure.

Hsp100 chaperones, also known as Clp proteins, constitute a family of ring-forming ATPases that differ in 3D structure and cellular function from other stress-inducible molecular chaperones. While the vast majority of ATP-dependent molecular chaperones promote the folding of either the nascent chain or a newly imported polypeptide to reach its native conformation, Hsp100 chaperones harness metabolic energy to perform the reverse and facilitate the unfolding of a misfolded polypeptide or protein aggregate. It is now known that inside cells and organelles, different Hsp100 members are involved in rescuing stress-damaged proteins from a previously aggregated state or in recycling polypeptides marked for degradation. Protein degradation is mediated by a barrel-shaped peptidase that physically associates with the Hsp100 hexamer to form a two-component system. Notable examples include the ClpA:ClpP (ClpAP) and ClpX:ClpP (ClpXP) proteases that resemble the ring-forming FtsH and Lon proteases, which unlike ClpAP and ClpXP, feature the ATP-binding and proteolytic domains in a single polypeptide chain. Recent advances in electron cryomicroscopy (cryoEM) together with single-molecule biophysical studies have now provided new mechanistic insight into the structure and function of this remarkable group of macromolecular machines.

Moving-frame imaging of transiting cold atoms for precise long-range transport.

Transporting cold atoms between interconnected vacuum chambers is an important technique for increasing the versatility of cold atom setups, particularly for those that couple atoms to photonic devices. In this report, we introduce a method where we are able to image the atoms at all points during transport via moving optical dipole trap. Cooled 87Rb atoms are transported ∼50 cm into an auxiliary vacuum chamber while being monitored with a moving-frame imaging system for which in-situ characterization of the atom transport is demonstrated. Precise positioning of the atoms near photonic devices is also tested across several tapered fibers showing an axial positioning resolution of ∼450 µm.

Maximized atom number for a grating magneto-optical trap via machine-learning assisted parameter optimization.

We present a parameter set for obtaining the maximum number of atoms in a grating magneto-optical trap (gMOT) by employing a machine learning algorithm. In the multi-dimensional parameter space, which imposes a challenge for global optimization, the atom number is efficiently modeled via Bayesian optimization with the evaluation of the trap performance given by a Monte-Carlo simulation. Modeling gMOTs for six representative atomic species - 7Li, 23Na, 87Rb, 88Sr, 133Cs, 174Yb - allows us to discover that the optimal grating reflectivity is consistently higher than a simple estimation based on balanced optical molasses. Our algorithm also yields the optimal diffraction angle which is independent of the beam waist. The validity of the optimal parameter set for the case of 87Rb is experimentally verified using a set of grating chips with different reflectivities and diffraction angles.

Chip-Scale Ultra-Low Field Atomic Magnetometer Based on Coherent Population Trapping.

We report a chip-scale atomic magnetometer based on coherent population trapping, which can operate near zero magnetic field. By exploiting the asymmetric population among magnetic sublevels in the hyperfine ground state of cesium, we observe that the resonance signal acquires sensitivity to magnetic field in spite of degeneracy. A dispersive signal for magnetic field discrimination is obtained near-zero-field as well as for finite fields (tens of micro-tesla) in a chip-scale device of 0.94 cm3 volume. This shows that it can be readily used in low magnetic field environments, which have been inaccessible so far in miniaturized atomic magnetometers based on coherent population trapping. The measured noise floor of 300 pT/Hz1/2 at the zero-field condition is comparable to that of the conventional finite-field measurement obtained under the same conditions. This work suggests a way to implement integrated atomic magnetometers with a wide operating range.

Administration of encapsulated L-tryptophan improves duodenal starch digestion and increases gastrointestinal hormones secretions in beef cattle.

OBJECTIVE: This study investigated the effects of oral administration of rumen-protected L-tryptophan (RPL-T) on duodenal starch digestion and gastrointestinal hormones (GIH) secretions using Hanwoo beef steers as the animal models. METHODS: Four steers (423±24 kg) fitted with ruminal and duodenal cannulas were employed in a crossover design replicated twice. Treatments were control (basal diet) and RPL-T (basal diet+191.1 mg/kg body weight [BW]) group. Blood and duodenal samples were collected to measure serum GIH levels and pancreatic α-amylase activity at day 0, 1, 3, and 5 (-30, 30, 90, 150, and 210 min) of the study. Samples from each segment of the gastrointestinal tract were collected via ruminal and duodenal cannulas and were used to determine soluble protein and the starch digestion rate at days 6 (-30, 180, 360, and 540 min) and 8 (-30, 90, 270, and 450 min) of the experiment. RESULTS: No significant difference in ruminal pH, NH3-N, and total volatile fatty acid including the levels of acetate, propionate, butyrate, isobutyrate, valerate, isovalerate, and the acetate-to-propionate ratio was observed between groups (p>0.05). Crude protein uptake was higher and feces starch content was lower in RPL-T group than the control group (p<0.05). The D-glucose contents of feces in RPL-T group decreased at day 5 compared to those in the control group (p<0.05), however, no change was found at day 0, 1, or 3 compared to the control group (p>0.05). Serum cholecystokinin (CCK), melatonin, duodenal pancreatic α-amylase activity, and starch digestion were significantly higher in RPL-T group than the control group (p<0.05). CONCLUSION: Taken together, oral administration of RPL-T at the rate of 191.1 mg/kg BW consistently increased CCK concentration, pancreatic α-amylase activity in duodenal fluids, and starch digestion rate in the small intestine and thus found to be beneficial.

Optical phase-locking of two extended-cavity diode lasers by serrodyne modulation.

We report the optical phase-locking of two extended-cavity diode lasers with a frequency difference of 6.9 GHz by serrodyne modulation. The bandwidth of the phase-locking loop is extended up to 9.5 MHz. The residual phase noise of the two phase-locked lasers reaches -130 dBrad2/Hz in the offset frequency range of 1.5 kHz to 9 kHz and below -120 dBrad2/Hz in the range of 150 Hz to 350 kHz, respectively. It is expected that the sensitivity limit of atom interferometers will be enhanced when the phase-locked lasers are used.

Mie resonance-enhanced pumping and detection efficiency for shallow nitrogen-vacancy centers in diamond.

We investigate Mie resonances of a diamond nano-resonator as a means to enhance the pumping and detection efficiency of shallow nitrogen-vacancy color centers. We show it is possible to tune a couple of high-order modes of a single resonator to each absorption and emission spectrum of the color center, and thereby the resonator plays a dual role of pump field concentration and emission field guiding. Furthermore superposition of the resonator field and the uncoupled near field results in even stronger pump intensity in the shallow top layer of the resonator. We also examine possible coupling between adjacent resonators when they form a periodic array. This approach allows us to achieve lower excitation power and higher signal intensity at local sites defined by resonators providing a way to enhance wide-field metrology in the sampled region of shallow color centers.

Improvement of Milk Fatty Acid Composition for Production of Functional Milk by Dietary Phytoncide Oil Extracted from Discarded Pine Nut Cones (Pinus koraiensis) in Holstein Dairy Cows.

This study was conducted to examine the effects of adding phytoncide oil extracted from Korean pine nut cone byproduct to the diet of dairy cows on milk yield and compositions, fatty acid characteristics, complete blood count and stress response. A total of 74 Holstein cows were used for 30 days and divided into two groups. Each group was given a basal diet (C) or an experimental diet containing phytoncide additives at 0.016% (T) in feed. The results showed that phytoncide feeding had no effect on milk yield. In addition, there were no observed effects on milk composition, but the ratio of fatty acid in milk was significantly affected by the phytoncide diet, and it showed a positive effect. Not only were the major functional fatty acids, conjugated linoleic acid and eicosapentaenoic acid increased, but also ω6:ω3 fatty acid ratio was reduced in milk of T group (p<0.05). In blood analysis, the complete blood count showed no significant difference between C and T group on all parameters. However, the cortisol concentration was significantly decreased in T group compared to control (p<0.05). Taken together, we suggest that phytoncide oil does not have a great influence on the physiological changes, but can be a potential feed additive that improves the milk fatty acid and stress resilience in dairy cows. In addition, it will contribute to the development of feed resource, a reduction in feed cost and a lessening of environmental pollution.

Association of protein expression in isolated milk epithelial cells and cis-9, trans-11 conjugated linoleic acid proportions in milk from dairy cows.

BACKGROUND: The effects of the individual variation among dairy cows on the synthesis of cis-9, trans-11 conjugated linoleic acid (CLA) are still not well characterised. Therefore, the protein expression profiles of isolated milk epithelial cells (MECs) were detected by two-dimensional electrophoresis and their correlation with the various proportion of cis-9, trans-11 CLA were evaluated. RESULTS: Although animals were offered the same diet, the proportion of cis-9, trans-11 CLA in group High (1.02 ± 0.10%) was twice as high as that in group Low (0.59 ± 0.14%) (P < 0.05). MECs with the characteristics of native epithelial cells were successfully isolated from the milk and these cells had no obvious RNA degradation or were hardly contaminated with leucocytes or blood red cells. Moreover, the protein expression pattern of cathelicidin 5 in isolated MECs was positive, whereas annexin I (confirmed by real-time polymerase chain reaction), ZW10 interactor and κ-casein were negatively related to the proportion of cis-9, trans-11 CLA in the milk fat. CONCLUSION: The varied individual content of cis-9, trans-11 CLA in cows may be associated with annexin I. These findings may provide some theoretical basis for studies concerning the effects of the individual variation among dairy cows of the synthesis of cis-9, trans-11 CLA. © 2013 Society of Chemical Industry.

2,3,6-Trisubstituted quinoxaline derivative, a small molecule inhibitor of the Wnt/beta-catenin signaling pathway, suppresses cell proliferation and enhances radiosensitivity in A549/Wnt2 cells.

GDK-100017, a 2,3,6-trisubstituted quinoxaline derivative, reduced ß-catenin-T-cell factor/lymphoid enhancer factor (TCF/LEF)-dependent transcriptional activity and inhibited cell proliferation in a dose-dependent manner with an IC50 value of about 10 µM in A549/Wnt2 cells. GDK-100017 down-regulated the expression of Wnt/ß-catenin pathway target genes such as cyclin D1 and Dkk1 but not c-myc or survivin. GDK-100017 inhibited cell proliferation by arresting the cell cycle in the G1 phase not only in A549/wnt2 cells but also in SW480 colon cancer cells. In addition to its wnt signaling inhibitory properties, GDK-100017 also enhanced the radiosensitivity of the A549 human NSCLC line. These results suggest that GDK-100017 possesses potential anti-cancer activity by inhibiting the Wnt/ß-catenin signal pathway, blocking the ß-catenin-TCF/LEF interaction, and enhancing radiosensitivity.

Co-expression of human cytochrome b5 increases expression of cytochrome P450 3A4 in Escherichia coli by stabilizing mRNA.

CYP3A4 is the most abundant cytochrome P450 in the human liver. The expression level of CYP3A4 when coexpressed with cytochrome b(5) (cyt b(5)) in Escherichia coli was 20-60% higher than that when it was expressed alone over an extended period (48-72 h). This time-dependent elevation in coexpression with cyt b(5) was a result of an increase in CYP3A4 mRNA half-life; no significant change in CYP3A4 degradation was seen in the bacterial protease fraction. These results suggest that the higher CYP3A4 levels observed upon coexpression with cyt b(5) primarily resulted from CYP3A4 mRNA stabilization by cyt b(5).

Structural basis of impaired disaggregase function in the oxidation-sensitive SKD3 mutant causing 3-methylglutaconic aciduria.

Mitochondria are critical to cellular and organismal health. To prevent damage, mitochondria have evolved protein quality control machines to survey and maintain the mitochondrial proteome. SKD3, also known as CLPB, is a ring-forming, ATP-fueled protein disaggregase essential for preserving mitochondrial integrity and structure. SKD3 deficiency causes 3-methylglutaconic aciduria type VII (MGCA7) and early death in infants, while mutations in the ATPase domain impair protein disaggregation with the observed loss-of-function correlating with disease severity. How mutations in the non-catalytic N-domain cause disease is unknown. Here, we show that the disease-associated N-domain mutation, Y272C, forms an intramolecular disulfide bond with Cys267 and severely impairs SKD3Y272C function under oxidizing conditions and in living cells. While Cys267 and Tyr272 are found in all SKD3 isoforms, isoform-1 features an additional α-helix that may compete with substrate-binding as suggested by crystal structure analyses and in silico modeling, underscoring the importance of the N-domain to SKD3 function.

Generation of 578-nm yellow light over 10 mW by second harmonic generation of an 1156-nm external-cavity diode laser.

578-nm yellow light with an output power of more than 10 mW was obtained using a waveguide periodically-poled-lithium-niobate crystal as a nonlinear medium for second harmonic generation, which is the highest output power at this wavelength using second harmonic generation of a solid state laser source without an enhancement ring cavity, to our knowledge. To achieve this result we made a high power 1156-nm external-cavity diode laser with the maximum output power of more than 250 mW. This system is expected to be an excellent alternative to the system using the sum-frequency generation with the advantage of simplicity and cost-effectiveness, and will be used as a clock laser of the ytterbium optical lattice clock with robust and reliable operation.

A novel 3-arylethynyl-substituted pyrido[2,3,-b]pyrazine derivatives and pharmacophore model as Wnt2/ß-catenin pathway inhibitors in non-small-cell lung cancer cell lines.

We developed Wnt/ß-catenin inhibitors by identifying 13 number of 3-arylethynyl-substituted pyrido[2,3,-b]pyrazine derivatives that were able to inhibit the Wnt/ß-catenin signal pathway and cancer cell proliferation. In the optimization process, a series of 2,3,6-trisubstituted pyrido[2,3,-b]pyrazine core skeletons showed were shown to higher activity than 2,3,6-trisubstituted quinoxaline's and thus hold promise for use as potential small-molecule inhibitors of the Wnt/ß-catenin signal pathway in non-small-cell lung cancer cell (NSCLC) lines. And we have studied the pharmacophore mapping for compound 954, which presented the highest activity with a fit value of 2.81. The pharmacophore mapping for the compounds including 954, pyrido[2,3,-b]pyrazine core had hydrogen-bond acceptor site and hydrophobic center roles.

Epidemiological features of Kawasaki disease in Korea, 2006-2008.

BACKGROUND: The aim of this study was to estimate the incidence and describe the epidemiological characteristics of Kawasaki disease among children in Korea. METHODS: Questionnaires for surveying the epidemiology of Kawasaki disease were distributed to a total of 101 hospitals that conduct pediatric residency programs. Then, we retrospectively obtained the data, which covered a three-year period (2006-2008) and analyzed them. RESULTS: During the three-year study period, a total of 9039 cases of Kawasaki disease were reported from 84 hospitals (response rate, 83.2%), comprising 5375 boys and 3664 girls (male:female ratio, 1.47:1). The outbreak rate per 100,000 children <5 years old was 108.7 in 2006, 118.3 in 2007 and 112.5 in 2008 (average rate, 113.1). The seasonal distribution showed a slightly higher incidence rate in winter and summer. The patients' mean age of onset was 32.6 months, while the proportions of sibling cases and recurrent cases were 0.17% and 2.2%, respectively. Coronary arterial abnormalities were detected during follow up by echocardiogram in 17.5% of all cases including dilatations (16.4%) and aneurysms (2.1%). CONCLUSIONS: The average annual incidence rate of Kawasaki disease in Korea has been continuously increasing, and reached 113.1/100,000 children <5 years old, which is the second highest rate in the world.

Observation of resonance effects in the pump transmission of a chaotic microcavity.

We observed resonance effects on the transmission of a pump beam in a chaotic microcavity in an optimal free-space optical-pumping configuration. The far-field pattern of cavity transmission was significantly modified when the pump laser was resonant with a scar mode. From the difference between the non-resonant and on-resonance transmission patterns, we obtained the efficiency of the pump coupling into the scar mode to be as high as 45%, which is consistent with the recent excitation spectroscopy results of Yang et al. [Phys. Rev. Lett. 104, 243601 (2010)].

Pump-induced dynamical tunneling in a deformed microcavity laser.

Pump-induced dynamical tunneling has been observed in free-space resonant optical pumping of a deformed microcavity by employing excitation spectroscopy. A focused-pump beam was injected into the cavity by refraction and then coupled to a high-Q cavity mode via dynamical tunneling. Pump-coupling efficiency as high as 50% and an effective coupling constant responsible for the tunneling were obtained from the observed pumping efficiency with a mode-mode coupling model.

Identification of 2,3,6-trisubstituted quinoxaline derivatives as a Wnt2/ß-catenin pathway inhibitor in non-small-cell lung cancer cell lines.

We screened 1434 small heterocyclic molecules and identified thirteen 2,3,6-trisubstituted quinoxaline derivatives that were able to inhibit the Wnt/ß-catenin signal pathway and cell proliferation. In the screen, some of the hit compounds such as the ethylene group-coupled quinoxaline derivatives were shown to hold promise for use as potential small-molecule inhibitors of the Wnt/ß-catenin signal pathway in non-small-cell lung cancer cell lines.