Point Absorber Limits to Future Gravitational-Wave Detectors.

High-quality optical resonant cavities require low optical loss, typically on the scale of parts per million. However, unintended micron-scale contaminants on the resonator mirrors that absorb the light circulating in the cavity can deform the surface thermoelastically and thus increase losses by scattering light out of the resonant mode. The point absorber effect is a limiting factor in some high-power cavity experiments, for example, the Advanced LIGO gravitational-wave detector. In this Letter, we present a general approach to the point absorber effect from first principles and simulate its contribution to the increased scattering. The achievable circulating power in current and future gravitational-wave detectors is calculated statistically given different point absorber configurations. Our formulation is further confirmed experimentally in comparison with the scattered power in the arm cavity of Advanced LIGO measured by in situ photodiodes. The understanding presented here provides an important tool in the global effort to design future gravitational-wave detectors that support high optical power and thus reduce quantum noise.

Modeling circulating cavity fields using the discrete linear canonical transform.

Fabry-Perot cavities are central to many optical measurement systems. In high-precision experiments, such as aLIGO and AdVirgo, coupled cavities are often required, leading to complex optical behavior. We show, for the first time to our knowledge, that discrete linear canonical transforms (LCTs) can be used to compute circulating optical fields for cavities in which the optics have arbitrary apertures, reflectance and transmittance profiles, and shape. We compare the predictions of LCT models with those of alternative methods. To further highlight the utility of the LCT, we present a case study of point absorbers on the aLIGO mirrors and compare it with recently published results.

Approaching the motional ground state of a 10-kg object.

The motion of a mechanical object, even a human-sized object, should be governed by the rules of quantum mechanics. Coaxing them into a quantum state is, however, difficult because the thermal environment masks any quantum signature of the object's motion. The thermal environment also masks the effects of proposed modifications of quantum mechanics at large mass scales. We prepared the center-of-mass motion of a 10-kilogram mechanical oscillator in a state with an average phonon occupation of 10.8. The reduction in temperature, from room temperature to 77 nanokelvin, is commensurate with an 11 orders-of-magnitude suppression of quantum back-action by feedback and a 13 orders-of-magnitude increase in the mass of an object prepared close to its motional ground state. Our approach will enable the possibility of probing gravity on massive quantum systems.

Mode matching error signals using radio-frequency beam shape modulation.

Precise mode matching is needed to maximize performance in coupled cavity interferometers such as Advanced Laser Interferometer Gravitational-Wave Observatory (LIGO). In this paper, we present a new mode matching sensing scheme, to the best of our knowledge, that uses a single radio-frequency higher-order-mode sideband and single-element photodiodes. It is first-order insensitive to misalignment and can serve as an error signal in a closed loop control system for a set of mode matching actuators. We also discuss how it may be implemented in Advanced LIGO. The proposed mode matching error signal has been successfully demonstrated on a tabletop experiment, where the error signal increased the mode matching of a beam to a cavity to 99.9%.

Quantum-Enhanced Advanced LIGO Detectors in the Era of Gravitational-Wave Astronomy.

The Laser Interferometer Gravitational Wave Observatory (LIGO) has been directly detecting gravitational waves from compact binary mergers since 2015. We report on the first use of squeezed vacuum states in the direct measurement of gravitational waves with the Advanced LIGO H1 and L1 detectors. This achievement is the culmination of decades of research to implement squeezed states in gravitational-wave detectors. During the ongoing O3 observation run, squeezed states are improving the sensitivity of the LIGO interferometers to signals above 50 Hz by up to 3 dB, thereby increasing the expected detection rate by 40% (H1) and 50% (L1).

Combined Increases in Muscle-Strengthening Activity Frequency and Protein Intake Reveal Graded Relationship with Fat-Free Mass Percentage in U.S. Adults, NHANES (1999-2004).

BACKGROUND: Age-related loss of muscle mass and related ailments are of concern due to associations with disabilities and morbidity as well as constituting a substantial healthcare burden. Muscle-strengthening activities and adequate protein ingestion are recommended for all-age adults in an effort to stave off age-related muscle atrophy. Muscle building abilities decline with age but most research focuses on muscle wasting in the elderly. OBJECTIVES: To examine the independent and combined associations of protein intake (g∙kg-1∙day-1) and muscle-strengthening frequency (times∙week-1, MSF) on fat-free mass percentage (FFM%). DESIGN SETTING AND PARTICIPANTS: This cross-sectional analysis of a population-based sample with data from the non-institutionalized persons in the United States participating in the National Health and Nutrition Examination Survey (cycles 1999-2000, 2001-2002, 2003-2004) consisted of male (n=2,499) and female (n=2,373) participants 20-49 years of age for analyses. MEASUREMENTS: MSF was determined by self-report and protein intake was calculated from a 24-hour recall. Differences in FFM% from bioelectrical impedance analysis was estimated using multiple linear regression models controlling for education, race-ethnicity, standing height, and total Caloric intake. RESULTS: One unit increase in MSF or protein intake (ß-coefficient, ±E) was associated with significantly more FFM% in males (0.6±0.1%; 3.5±0.4%) and females (0.4±0.1%; 5.9±0.4%). Independent of protein intake, males and females with MSF=0 had mean ±SE FFM% of 74.4±0.4 and 60.7±0.3, respectively, while mean ±SE FFM% of males and females who met the recommendation of ≥2 times per week were 77.9±0.5 and 63.0±0.4. Independent of MSF, males and females with protein intakes below the recommended dietary allowance (RDA) of 0.8 g∙kg-1∙day-1 had mean ±SE FFM% of 74.0±0.6 and 58.2±0.6, respectively, while mean ±SE FFM% of those whose intakes exceeded the recommendation were 75.6±0.4 and 62.0±0.4. The subgroup with the highest mean ±SE FFM% (80.9 ±0.73) comprised males with MSF ≥2 times per week who also consumed >1.4 g∙kg-1∙day-1. CONCLUSION: The MSF-protein intake dose relationship with FFM% suggests that performing muscle-strengthening activities >2 times per week while consuming protein above the RDA may result in more fat-free mass and slow age-related losses of muscle mass.

Effect of leg length on ROM, VJ and leg dexterity in dance.

We investigated the associations between leg length and specific ballet movements in different skill groups. Volunteers were from an undergraduate dance programme (n=18), a pre-professional school (n=43) and from an elite classical ballet company (n=45). Individual data were collected for anthropometry, vertical jump, leg dexterity, and leg active and passive ROM. ANCOVA identified both main effects as significant with regard to vertical jump (gender P<0.001 and skill P=0.017); leg length was also identified as a significant covariate (P=0.023). Analysis of leg dexterity identified no significant effects with gender, skill or leg length. Active and passive range of motion noted gender (P=0.001) and skill (P<0.001) differences. Leg length was found to be negatively associated with both active and passive ROM (P=0.002). In conclusion, the present data highlight the diverse and conflicting effects of leg length on fundamental ballet skills. The longer legs that benefit vertical jump have a negative influence on range of motion and leg dexterity except for highly skilled dancers, who through skill, seem to have overcome the effects of some of these dichotomies.

Dietary energy density increases during early childhood irrespective of familial predisposition to obesity: results from a prospective cohort study.

OBJECTIVE: This study compared 4-year changes in daily energy density (ED; kcal/g) in children born at different risk for obesity, characterized the stability of ED and examined associations between ED and child body composition. DESIGN: Prospective cohort study to measure habitual dietary ED of children who are born at different risk for obesity. SUBJECTS: Children who were born at high risk (n=22) or low risk (n=27) for obesity based on maternal pre-pregnancy weight. MEASUREMENTS: Three-day food records were collected from children's mothers at child ages 3, 4, 5 and 6 years. Three categories of ED were computed (food only, food and milk, and food and all beverages) and body composition assessed at each year. RESULTS: The mean (+/-s.e.m.) ED increased over time across all children (linear trend: P<0.003): 2.18+/-0.07 to 2.32+/-0.06 kcal/g (food only); 1.66+/-0.07 to 1.82+/-0.06 kcal/g (food and milk); and 1.24+/-0.04 to 1.37+/-0.05 kcal/g (food and all beverages). Intraindividual coefficients of variation were smaller than those previously reported for adults. Weight indices were not correlated with dietary ED (P>0.05). CONCLUSION: Dietary ED increased in young children, irrespective of their predisposition to obesity, between the ages of 3 and 6 years. The genes that promote childhood obesity may not exert their influence through dietary ED, which may be more strongly influenced by environmental factors.

'Rescue' of mini-genomic constructs and viruses by combinations of morbillivirus N, P and L proteins.

Chloramphenicol acetyltransferase (CAT)-expressing negative-sense mini-genomic constructs of measles virus (MV) and rinderpest virus (RPV) were rescued by standard technology with helper plasmids expressing the nucleocapsid (N), phospho- (P) and large (L) proteins of MV, canine distemper virus (CDV) or RPV in order to determine whether the proteins of different viruses can function together. Homogeneous sets consisting of N, P and L plasmids derived from one virus were able to generate reporter gene expression from either mini-genomic construct. Heterogeneous sets of proteins from different viruses were not functional, with the exception that a low level of activity was obtained when MV N and P protein were combined with RPV L protein in the rescue of the MV mini-genomic construct, or CDV N was combined with RPV P and L in the rescue of the RPV mini-genome. However, only homogeneous sets of plasmids were able to rescue infectious virus from full-length anti-genome-expressing plasmids.

Diverse developmental programs of Xenopus laevis metamorphosis are inhibited by a dominant negative thyroid hormone receptor.

Metamorphosis of anuran tadpoles is controlled by thyroid hormone (TH). Here we demonstrate that transgenic Xenopus laevis tadpoles expressing a dominant negative form of TH receptor-alpha are resistant to a wide variety of the metamorphic changes induced by TH. This result confirms that TH receptors mediate both early and late developmental programs of metamorphosis as diverse as growth in the brain, limb buds, nose and Meckel's cartilage, remodeling of the intestine, and death and resorption of the gills and tail.

Timing of metamorphosis and the onset of the negative feedback loop between the thyroid gland and the pituitary is controlled by type II iodothyronine deiodinase in Xenopus laevis.

Two important features of amphibian metamorphosis are the sequential response of tissues to different concentrations of thyroid hormone (TH) and the development of the negative feedback loop between the pituitary and the thyroid gland that regulates TH synthesis by the thyroid gland. At the climax of metamorphosis in Xenopus laevis (when the TH level is highest), the ratio of the circulating precursor thyroxine (T4) to the active form 3,5,3'-triiodothyronine (T3) in the blood is many times higher than it is in tissues. This difference is because of the conversion of T4 to T3 in target cells of the tadpole catalyzed by the enzyme type II iodothyronine deiodinase (D2) and the local effect (cell autonomy) of this activity. Limb buds and tails express D2 early and late in metamorphosis, respectively, correlating with the time that these organs undergo TH-induced change. T(3) is required to complete metamorphosis because the peak concentration of T4 that is reached at metamorphic climax cannot induce the final morphological changes. At the climax of metamorphosis, D2 expression is activated specifically in the anterior pituitary cells that express the genes for thyroid-stimulating hormone but not in the cells that express proopiomelanocortin. Physiological concentrations of T3 but not T4 can suppress thyrotropin subunit beta gene expression. The timing and the remarkable specificity of D2 expression in the thyrotrophs of the anterior pituitary coupled with the requirement for locally synthesized T3 strongly support a role for D2 in the onset of the negative feedback loop at the climax of metamorphosis.

Overexpression of Xenopus laevis growth hormone stimulates growth of tadpoles and frogs.

The role of growth hormone (GH) in amphibian metamorphosis is ambiguous based on experiments in which mammalian GH was administered to tadpoles and frogs. We have reexamined the effects of GH by producing transgenic Xenopus laevis that overexpress the cDNA encoding X. laevis GH. These transgenic tadpoles take the same length of time to reach metamorphosis as control tadpoles, but the transgenic tadpoles are twice as large. After metamorphosis, the transgenic frogs grow at a greatly accelerated rate and develop skeletal abnormalities reminiscent of acromegaly. The transgenic frogs are larger than mature frogs in a few months and die in about 1 year. At as early as 10 months of age, the males have mature sperm. We conclude that the growth-promoting effects of GH in this amphibian closely resemble those described for mammals. Although excess GH increases the size of the tadpole, it does not alter the developmental programs involved in metamorphosis.

Prolactin is not a juvenile hormone in Xenopus laevis metamorphosis.

Prolactin (PRL) is widely considered to be the juvenile hormone of anuran tadpoles and to counteract the effects of thyroid hormone (TH), the hormone that controls amphibian metamorphosis. This putative function was concluded mainly from experiments in which mammalian PRL was injected into tadpoles or added to cultured tadpole tissues. In this study, we show that overexpression of ovine or Xenopus laevis PRL in transgenic X. laevis does not prolong tadpole life, establishing that PRL does not play a role in the life cycle of amphibians that is equivalent to that of juvenile hormone in insect metamorphosis. However, overexpression of PRL produces tailed frogs by reversing specifically some but not all of the programs of tail resorption and stimulating growth of fibroblasts in the tail. Whereas TH induces muscle resorption in tails of these transgenics, the tail fibroblasts continue to proliferate resulting in a fibrotic tail that is resistant to TH.

In vitro and in vivo analysis of the regulation of a transcription factor gene by thyroid hormone during Xenopus laevis metamorphosis.

A novel, basic region leucine zipper transcription factor (TH/bZIP) is dramatically up-regulated at the climax of metamorphosis in Xenopus laevis. It can be induced in tadpoles prematurely by thyroid hormone (TH) with kinetics that are intermediate between early and late Xenopus TH response genes. A small amount of early, cycloheximide-resistant up-regulation is observed, but the majority of TH/ bZIP mRNA accumulation occurs after 12 h of treatment in parallel with late response gene induction. There are two genomic TH/bZIP genes in the pseudotetraploid X. laevis genome that are coordinately regulated. They have highly conserved regulatory regions that contain two conserved, adjoining DR+4 thyroid response elements (TRE) in opposite orientation. The early/late TH induction kinetics has been reproduced in transient transfection assays. The secondary rise of transcriptional activity requires DNA regions other than the TREs and, therefore, the interaction of transcription factors other than the TH receptors. Finally, the regulatory region of the TH/bZIP gene has been used to drive green fluorescent protein in transgenic X. laevis tadpoles. Regulation of the transgene during spontaneous and induced metamorphosis mimics that of the endogenous TH/bZIP gene. The newly developed X. laevis transgenesis method has distinct advantages for the analysis of transcriptional regulatory elements over transient transfection assays and will be useful for further in vivo studies of TH-response gene regulation during development.

Germ-line transmission of transgenes in Xenopus laevis.

Adult Xenopus laevis frogs made transgenic by restriction enzyme-mediated integration were bred to test the feasibility of establishing lines of frogs that express transgenes. All of the 19 animals raised to sexual maturity generated progeny that expressed the transgene(s). The patterns and levels of expression of green fluorescent protein transgenes driven by a viral promoter, rat promoter, and four X. laevis promoters were all unaffected by passage through the germ line. These results demonstrate the ease of establishing transgenic lines in X. laevis.

Novel structural elements identified during tail resorption in Xenopus laevis metamorphosis: lessons from tailed frogs.

When the tail of the Xenopus laevis tadpole resorbs at the end of metamorphosis, various cell types, including muscle, fibroblasts, skin, and spinal cord, are lost at about the same time. However, feeding frogs with tails can be produced by inhibiting thyroid hormone production at the climax of metamorphosis with the goitrogen methimazole. These tails lose their fast muscle preferentially, showing that the different cell types of the tail have different fates and confirming that more than one cell death program is involved in tail resorption. Both normal and methimazole tails contain "cords," novel structures that consist of two dorsal and two ventral parallel rows of slow muscle bundles joined by collagen fibers that run the length of the tail. The cords persist until the very end of tail resorption, being the last structure to dissolve. When thyroid hormone induces expression of proteolytic enzymes in the notochord sheath, the notochord, a structural rod that runs the length of the tail, begins to buckle, demonstrating that the tail is under tension. When sections of the tail that contain cords are surgically separated from the notochord, they contract in vitro, suggesting that the cords contribute to the tension that augments tail resorption.

Simulation technology for health care professional skills training and assessment.

Changes in medical practice that limit instruction time and patient availability, the expanding options for diagnosis and management, and advances in technology are contributing to greater use of simulation technology in medical education. Four areas of high-technology simulations currently being used are laparoscopic techniques, which provide surgeons with an opportunity to enhance their motor skills without risk to patients; a cardiovascular disease simulator, which can be used to simulate cardiac conditions; multimedia computer systems, which includes patient-centered, case-based programs that constitute a generalist curriculum in cardiology; and anesthesia simulators, which have controlled responses that vary according to numerous possible scenarios. Some benefits of simulation technology include improvements in certain surgical technical skills, in cardiovascular examination skills, and in acquisition and retention of knowledge compared with traditional lectures. These systems help to address the problem of poor skills training and proficiency and may provide a method for physicians to become self-directed lifelong learners.

Implementation of a four-year multimedia computer curriculum in cardiology at six medical schools.

The pressures of a changing health care system are making inroads on the commitment and effort that both basic science and clinical faculty can give to medical education. A tool that has the potential to compensate for decreased faculty time and thereby to improve medical education is multimedia computer instruction that is applicable at all levels of medical education, developed according to instructional design principles, and supported by evidence of effectiveness. The authors describe the experiences of six medical schools in implementing a comprehensive computer-based four-year curriculum in bedside cardiology developed by a consortium of university cardiologists and educational professionals. The curriculum consisted of ten interactive, patient-centered, case-based modules focused on the history, physical examination, laboratory data, diagnosis, and treatment. While an optimal implementation plan was recommended, each institution determined its own strategy. Major goals of the project, which took place from July 1996 to June 1997, were to identify and solve problems of implementation and to assess learners' and instructors' acceptance of the system and their views of its value. A total of 1,586 students used individual modules of the curriculum 6,131 times. Over 80% of students rated all aspects of the system highly, especially its clarity and educational value compared with traditional lectures. The authors discuss the aspects of the curriculum that worked, problems that occurred (such as difficulties in scheduling use of the modules in the third year), barriers to change and ways to overcome them (such as the type of team needed to win acceptance for and oversee implementation of this type of curriculum), and the need in succeeding years to formally assess the educational effectiveness of this and similar kinds of computer-based curricula.

Metamorphosis is inhibited in transgenic Xenopus laevis tadpoles that overexpress type III deiodinase.

One of the genes that is up-regulated by thyroid hormone (TH) during Xenopus laevis metamorphosis encodes a type III deiodinase (D3) that inactivates TH. Transgenic X. laevis tadpoles overexpressing a GFP-D3 fusion protein were produced. These transgenic tadpoles had high levels of deiodinase activity and were resistant to exogenous TH added 1 week after fertilization. They developed normally throughout embryogenesis and premetamorphic stages but became retarded in their development late in prometamorphosis when endogenous TH reaches its highest level. Gill and tail resorption were delayed and most of the animals arrested and died. One tadpole completed its metamorphosis without resorbing its tail. These results demonstrate that D3 can modulate the action of TH in vivo, and document the value of the new transgenic method for functional analysis of genes involved in metamorphosis.