Global optimization of multilayer dielectric coatings for precision measurements.

We describe the design of optimized multilayer dielectric coatings for precision laser interferometry. By setting up an appropriate cost function and then using a global optimizer to find a minimum in the parameter space, we were able to realize coating designs that meet the design requirements for spectral reflectivity, thermal noise, absorption, and tolerances to coating fabrication errors. We also present application of a Markov-Chain Monte Carlo (MCMC) based parameter estimation algorithm that can infer thicknesses of dielectric layers in a coating, given a measurement of the spectral reflectivity. This technique can be a powerful diagnostic tool for both commercial coating manufacturers, and the community using dielectric mirrors for precision metrology experiments.

Scattering loss in precision metrology due to mirror roughness.

Optical losses degrade the sensitivity of laser interferometric instruments. They reduce the number of signal photons and introduce technical noise associated with diffuse light. In quantum-enhanced metrology, they break the entanglement between correlated photons. Such decoherence is one of the primary obstacles in achieving high levels of quantum noise reduction in precision metrology. In this work, we compare direct measurements of cavity and mirror losses in the Caltech 40 m gravitational-wave detector prototype interferometer with numerical estimates obtained from semi-analytic intra-cavity wavefront simulations using mirror surface profile maps. We show a unified approach to estimating the total loss in optical cavities (such as the LIGO gravitational detectors) that will lead towards the engineering of systems with minimum decoherence for quantum-enhanced precision metrology.

Constraints on Cosmic Strings Using Data from the Third Advanced LIGO-Virgo Observing Run.

We search for gravitational-wave signals produced by cosmic strings in the Advanced LIGO and Virgo full O3 dataset. Search results are presented for gravitational waves produced by cosmic string loop features such as cusps, kinks, and, for the first time, kink-kink collisions. A template-based search for short-duration transient signals does not yield a detection. We also use the stochastic gravitational-wave background energy density upper limits derived from the O3 data to constrain the cosmic string tension Gµ as a function of the number of kinks, or the number of cusps, for two cosmic string loop distribution models. Additionally, we develop and test a third model that interpolates between these two models. Our results improve upon the previous LIGO-Virgo constraints on Gµ by 1 to 2 orders of magnitude depending on the model that is tested. In particular, for the one-loop distribution model, we set the most competitive constraints to date: Gµâ‰²4×10^{-15}. In the case of cosmic strings formed at the end of inflation in the context of grand unified theories, these results challenge simple inflationary models.

Point absorbers in Advanced LIGO.

Small, highly absorbing points are randomly present on the surfaces of the main interferometer optics in Advanced LIGO. The resulting nanometer scale thermo-elastic deformations and substrate lenses from these micron-scale absorbers significantly reduce the sensitivity of the interferometer directly though a reduction in the power-recycling gain and indirect interactions with the feedback control system. We review the expected surface deformation from point absorbers and provide a pedagogical description of the impact on power buildup in second generation gravitational wave detectors (dual-recycled Fabry-Perot Michelson interferometers). This analysis predicts that the power-dependent reduction in interferometer performance will significantly degrade maximum stored power by up to 50% and, hence, limit GW sensitivity, but it suggests system wide corrections that can be implemented in current and future GW detectors. This is particularly pressing given that future GW detectors call for an order of magnitude more stored power than currently used in Advanced LIGO in Observing Run 3. We briefly review strategies to mitigate the effects of point absorbers in current and future GW wave detectors to maximize the success of these enterprises.

Frequency-Dependent Squeezed Vacuum Source for Broadband Quantum Noise Reduction in Advanced Gravitational-Wave Detectors.

The astrophysical reach of current and future ground-based gravitational-wave detectors is mostly limited by quantum noise, induced by vacuum fluctuations entering the detector output port. The replacement of this ordinary vacuum field with a squeezed vacuum field has proven to be an effective strategy to mitigate such quantum noise and it is currently used in advanced detectors. However, current squeezing cannot improve the noise across the whole spectrum because of the Heisenberg uncertainty principle: when shot noise at high frequencies is reduced, radiation pressure at low frequencies is increased. A broadband quantum noise reduction is possible by using a more complex squeezing source, obtained by reflecting the squeezed vacuum off a Fabry-Perot cavity, known as filter cavity. Here we report the first demonstration of a frequency-dependent squeezed vacuum source able to reduce quantum noise of advanced gravitational-wave detectors in their whole observation bandwidth. The experiment uses a suspended 300-m-long filter cavity, similar to the one planned for KAGRA, Advanced Virgo, and Advanced LIGO, and capable of inducing a rotation of the squeezing ellipse below 100 Hz.

Type IV collagen aggregates promote keratinocyte proliferation and formation of epidermal layer in human skin equivalents.

Type IV collagen isolated from lens capsule without enzymatic treatment is known to form a gel under physiological condition and influences cellular activities. In case of human keratinocytes, the suppression of proliferation on reconstituted type IV collagen gels was reported in monolayer culture. In this study, we examined effects of type IV collagen isolated from porcine lens capsule on epidermal formation in human skin equivalents (HSEs). Type IV collagen aggregates were prepared under the culture condition and the aggregates suppressed keratinocyte proliferation in monolayer culture as well as the culture on the gels. In HSEs, type IV collagen aggregates were reconstituted on the surface of contracted collagen gels containing human dermal fibroblasts and the keratinocytes were then cultured on the aggregates for 14 days. Interestingly, in HSEs with type IV collagen aggregates, the BrdU-positive keratinocytes were increased and the thickness of the epidermal layer was around twice than that of control culture. Epidermal differentiation markers were expressed in the upper layer of the epidermis and the defined deposition of human basement membrane components were increased at the dermal-epidermal junction. These results indicate that the type IV collagen aggregates stimulate the proliferation of basal keratinocytes and improve the stratification of epidermal layers in HSEs.

External quantum efficiency enhancement by photon recycling with backscatter evasion.

The nonunity quantum efficiency (QE) in photodiodes (PD) causes deterioration of signal quality in quantum optical experiments due to photocurrent loss as well as the introduction of vacuum fluctuations into the measurement. In this paper, we report that the external QE enhancement of a PD was demonstrated by recycling the reflected photons. The external QE for an InGaAs PD was increased by 0.01-0.06 from 0.86-0.92 over a wide range of incident angles. Moreover, we confirmed that this technique does not increase backscattered light when the recycled beam is properly misaligned.

Achilles Tendon Ultrasonography for Diagnosis of Familial Hypercholesterolemia Among Japanese Subjects.

BACKGROUND: Difficulty in detecting and measuring Achilles tendon (AT) xanthomas may be responsible for underdiagnosis of familial hypercholesterolemia (FH). We aimed to determine a cutoff value for AT thickness (AT-T) using ultrasonography to diagnose FH, and to investigate the relationship between AT-T and atherosclerosis.Methods and Results:Ultrasonographic AT-T and carotid intima-media thickness (IMT) were evaluated in 130 genetically diagnosed FH patients and 155 non-FH patients. The outline and internal properties of the AT could be clearly determined using ultrasonography, and a good correlation in AT-T was observed between ultrasonography and the conventional method of X-ray radiography (r=0.924, P<0.001). Cutoff values for the diagnosis of FH derived from receiver-operating curves were 5.8 mm (sensitivity 71%, specificity 78%) in men, and 5.5 mm (sensitivity 80%, specificity 81%) in women. Importantly, increased AT-T was positively associated with carotid IMT only in the FH group. Additionally, increased AT-T was associated with the presence of coronary artery disease in a logistic regression analysis adjusted for traditional cardiovascular risk factors. CONCLUSIONS: This is the first study to determine a cutoff value for AT-T based on ultrasonography for the diagnosis of FH in Japanese subjects. Clearer detection and easier measurement of AT-T using ultrasonography would encourage clinicians to diagnose FH more actively, and could solve the problem of underdiagnosis of FH.

Guided lock of a suspended optical cavity enhanced by a higher-order extrapolation.

Lock acquisition of a suspended optical cavity can be a highly stochastic process and is therefore nontrivial. Guided lock is a method to make lock acquisition less stochastic by decelerating the motion of the cavity length based on an extrapolation of the motion from an instantaneous velocity measurement. We propose an improved scheme that is less susceptible to seismic disturbances by incorporating the acceleration as a higher-order correction in the extrapolation. We implemented the new scheme in a 300-m suspended Fabry-Perot cavity and improved the success rate of lock acquisition by a factor of 30.

Observation of Parametric Instability in Advanced LIGO.

Parametric instabilities have long been studied as a potentially limiting effect in high-power interferometric gravitational wave detectors. Until now, however, these instabilities have never been observed in a kilometer-scale interferometer. In this Letter, we describe the first observation of parametric instability in a gravitational wave detector, and the means by which it has been removed as a barrier to progress.

Stimulatory effect of fibroblast-derived prostaglandin E2 on keratinocyte stratification in the skin equivalent.

Epidermal-dermal interaction plays important roles in physiological events such as wound healing. In this study, we examined a double paracrine mechanism between keratinocytes and fibroblasts through interleukin-1 (IL-1) and an IL-1-induced inflammatory mediator prostaglandin E2 (PGE2) using the skin equivalent. The epidermal layer of the skin equivalent expressed high levels of IL-1α mRNA (IL1A mRNA) and relatively low levels of IL-1ß mRNA (IL1B mRNA). IL1A mRNA was not detected in fibroblasts. Fibroblasts also expressed low but not negligible levels of IL1B mRNA only in the presence of keratinocytes. Expression of prostaglandin-endoperoxide synthase 2 mRNA (PTGS2 mRNA) and production of PGE2 in three-dimensionally cultured fibroblasts were noticeably stimulated by co-culture with keratinocytes, whereas PTGS2 mRNA expression in the epidermal layer was very low. In addition, hydroxyprostaglandin dehydrogenase 15-(NAD) mRNA was highly expressed in keratinocytes but not in fibroblasts, and exogenous IL-1ß stimulated PTGS2 mRNA expression in the dermal equivalent. The thickness of the epidermal layer and the number of MKI67-positive keratinocytes in the skin equivalent were decreased by treatment with indomethacin, and the decrease recovered when exogenous PGE2 was added. These results indicate that keratinocytes stimulate their own proliferation through a double paracrine mechanism mediated by IL-1 and PGE2.

Residual amplitude modulation in interferometric gravitational wave detectors.

The effects of residual amplitude modulation (RAM) in laser interferometers using heterodyne sensing can be substantial and difficult to mitigate. In this work, we analyze the effects of RAM on a complex laser interferometer used for gravitational wave detection. The RAM introduces unwanted offsets in the cavity length signals and thereby shifts the operating point of the optical cavities from the nominal point via feedback control. This shift causes variations in the sensing matrix, and leads to degradation in the performance of the precision noise subtraction scheme of the multiple-degree-of-freedom control system. In addition, such detuned optical cavities produce an optomechanical spring, which also perturbs the sensing matrix. We use our simulations to derive requirements on RAM for the Advanced LIGO (aLIGO) detectors, and show that the RAM expected in aLIGO will not limit its sensitivity.

Repeated folding stress-induced morphological changes in the dermal equivalent.

BACKGROUND/PURPOSE: Repeated mechanical stresses applied to the same region of the skin are thought to induce morphological changes known as wrinkle. However, the underlying mechanisms are not fully understood. To study the mechanisms, we examined effects of repeated mechanical stress on the dermal equivalent. METHODS: We developed a novel device to apply repeated folding stress to the dermal equivalent. After applying the mechanical stress, morphological changes of the dermal equivalent and expression of several genes related to extracellular matrix turn over and cell contraction were examined. RESULTS: The repeated folding stress induced a noticeable decrease in the width of the dermal equivalent. The mechanical stress altered orientations of collagen fibrils. Hydroxyproline contents, dry weights and cell viability of the dermal equivalents were not affected by the mechanical stress. On the other hand, Rho-associated coiled-coil-containing kinase (ROCK) specific inhibitor Y27632 completely suppressed the decrease in the width of the dermal equivalent. CONCLUSION: The present results revealed that either degradation of collagen or changes in the number of cells were not responsible for the decrease in the width of the dermal equivalent and indicate that the repeated mechanical stress induces unidirectional contraction in the dermal equivalent through the RhoA-ROCK signaling pathway.

Interlaboratory evaluation of LC-MS-based biomarker assays.

Validation of biomarker assays is crucial for effective drug development and clinical applications. Interlaboratory reproducibility is vital for reliable comparison and combination of data from different centers. This review summarizes interlaboratory studies of quantitative LC-MS-based biomarker assays using reference standards for calibration curves. The following points are discussed: trends in reports, reference and internal standards, evaluation of analytical validation parameters, study sample analysis and normalization of biomarker assay data. Full evaluation of these parameters in interlaboratory studies is limited, necessitating further research. Some reports suggest methods to address variations in biomarker assay data among laboratories, facilitating organized studies and data combination. Method validation across laboratories is crucial for reducing interlaboratory differences and reflecting target biomarker responses.

Angiotensin-converting enzyme inhibitor (enalapril maleate) accelerates recovery of mouse skin from UVB-induced wrinkles.

Angiotensin-converting enzyme (ACE) activity and angiotensin II signaling regulate cell proliferation, differentiation, and tissue remodeling, as well as blood pressure, while in skin, angiotensin II signaling is involved in wound healing, inflammation, and pathological scar formation. Therefore, we hypothesized that angiotensin II is also involved in photoaging of skin. In this study, we examined the effect of enalapril maleate, an ACE inhibitor, on recovery of wrinkled skin of hairless mice exposed to long-term UVB irradiation. Immunohistochemical observation revealed that expression of ACE, angiotensin II, and angiotensin II type 1 (AT1) and type 2 (AT2) receptors in the skin was increased after UVB irradiation (3 times/week at increasing intensities for 8 weeks). Administration of enalapril maleate (5 times/week for 6 weeks, starting 1 week after 10-week irradiation) accelerated recovery from UVB-induced wrinkles, epidermal hyperplasia and epidermal barrier dysfunction, as compared with the vehicle control. Our results indicate that ACE and angiotensin II activity are involved in skin photoaging, and suggest that ACE inhibitor such as enalapril maleate may have potential for improvement of photoaged skin.

Pulsed electric current induces the differentiation of human keratinocytes.

Although normal human keratinocytes are known to migrate toward the cathode in a direct current (DC) electric field, other effects of the electric stimulation on keratinocyte activities are still unclear. We have investigated the keratinocyte differentiation under monodirectional pulsed electric stimulation which reduces the electrothermal and electrochemical hazards of a DC application. When cultured keratinocytes were exposed to the electric field of 3 V (ca. 100 mV/mm) or 5 V (ca. 166 mV/mm) at a frequency of 4,800 Hz for 5 min a day for 5 days, cell growth under the 5-V stimulation was significantly suppressed as compared with the control culture. Expression of mRNAs encoding keratinocyte differentiation markers such as keratin 10, involucrin, transglutaminase 1, and filaggrin was significantly increased in response to the 5-V stimulation, while the 3-V stimulation induced no significant change. After the 5-V stimulation, enhanced immunofluorescent stainings of involucrin and filaggrin were observed. These results indicate that monodirectional pulsed electric stimulation induces the keratinocyte differentiation with growth arrest.

Aneurysm appearing at the anastomosis site 11 years after superficial temporal artery-middle cerebral artery bypass surgery: moyamoya disease with a rapidly growing aneurysm. Illustrative case.

BACKGROUND: Superficial temporal artery-middle cerebral artery (STA-MCA) bypass surgery is performed to prevent ischemia and hemorrhage in patients with moyamoya disease. Only a few reports have described aneurysms appearing around the anastomosis site after bypass surgery, and the underlying mechanism remains unknown. OBSERVATIONS: The present case involved a 62-year-old woman who underwent STA-MCA bypass surgery for ischemic quasi-moyamoya disease at 46 years of age. Postoperatively, she underwent annual magnetic resonance imaging examinations. At 11 years after STA-MCA bypass surgery, a 3-mm aneurysm appeared at the anastomosis site. Four years later, headache developed and the aneurysm had grown to 5 mm. Craniotomy clipping was performed to prevent rupture. The patient was discharged home 2 weeks after surgery without any apparent complications. LESSONS: Long-term observation is crucial after direct bypass surgery for moyamoya disease. Measures to prevent rupture should be considered for cases involving aneurysm complications.

Multi-laboratory evaluation of immunoaffinity LC-MS-based glucagon-like peptide-1 assay.

Background: Although the fit-for-purpose approach has been proposed for biomarker assay validation, practical data should be compiled to facilitate the predetermination of acceptance criteria. Methods: Immunoaffinity LC-MS was used to analyze glucagon-like peptide-1 as a model biomarker in six laboratories. Calibration curve, carryover, parallelism, precision, relative accuracy and processed sample stability were evaluated, and their robustness among laboratories was assessed. The rat glucagon-like peptide-1 concentrations in four blinded samples were also compared. Results: The obtained results and determined concentrations in the blinded samples at all laboratories were similar, with a few exceptions, and robust, despite the difference in optimization techniques among laboratories. Conclusion: The results provide insights into the predefinition of the acceptance criteria of immunoaffinity LC-MS-based biomarker assays.

Reduction of thermal fluctuations in a cryogenic laser interferometric gravitational wave detector.

The thermal fluctuation of mirror surfaces is the fundamental limitation for interferometric gravitational wave (GW) detectors. Here, we experimentally demonstrate for the first time a reduction in a mirror's thermal fluctuation in a GW detector with sapphire mirrors from the Cryogenic Laser Interferometer Observatory at 17 and 18 K. The detector sensitivity, which was limited by the mirror's thermal fluctuation at room temperature, was improved in the frequency range of 90 to 240 Hz by cooling the mirrors. The improved sensitivity reached a maximum of 2.2×10(-19) m/√Hz at 165 Hz.

Multicolor cavity metrology.

Long-baseline laser interferometers used for gravitational-wave detection have proven to be very complicated to control. In order to have sufficient sensitivity to astrophysical gravitational waves, a set of multiple coupled optical cavities comprising the interferometer must be brought into resonance with the laser field. A set of multi-input, multi-output servos then lock these cavities into place via feedback control. This procedure, known as lock acquisition, has proven to be a vexing problem and has reduced greatly the reliability and duty factor of the past generation of laser interferometers. In this article, we describe a technique for bringing the interferometer from an uncontrolled state into resonance by using harmonically related external fields to provide a deterministic hierarchical control. This technique reduces the effect of the external seismic disturbances by 4 orders of magnitude and promises to greatly enhance the stability and reliability of the current generation of gravitational-wave detectors. The possibility for using multicolor techniques to overcome current quantum and thermal noise limits is also discussed.