Sex Reversal in C57BL/6J XY Mice Caused by Increased Expression of Ovarian Genes and Insufficient Activation of the Testis Determining Pathway

Sex reversal can occur in XY humans with only a single functional WT1 or SF1 allele or a duplication of the chromosome region containing WNT4. In contrast, XY mice with only a single functional Wt1, Sf1, or Wnt4 allele, or mice that over-express Wnt4 from a transgene, reportedly are not sex-reversed. Because genetic background plays a critical role in testis differentiation, particularly in C57BL/6J (B6) mice, we tested the hypothesis that Wt1, Sf1, and Wnt4 are dosage sensitive in B6 XY mice. We found that reduced Wt1 or Sf1 dosage in B6 XYB6 mice impaired testis differentiation, but no ovarian tissue developed. If, however, a YAKR chromosome replaced the YB6 chromosome, these otherwise genetically identical B6 XY mice developed ovarian tissue. In contrast, reduced Wnt4 dosage increased the amount of testicular tissue present in Sf1+/− B6 XYAKR, Wt1+/− B6 XYAKR, B6 XYPOS, and B6 XYAKR fetuses. We propose that Wt1B6 and Sf1B6 are hypomorphic alleles of testis-determining pathway genes and that Wnt4B6 is a hypermorphic allele of an ovary-determining pathway gene. The latter hypothesis is supported by the finding that expression of Wnt4 and four other genes in the ovary-determining pathway are elevated in normal B6 XX E12.5 ovaries. We propose that B6 mice are sensitive to XY sex reversal, at least in part, because they carry Wt1B6 and/or Sf1B6 alleles that compromise testis differentiation and a Wnt4B6 allele that promotes ovary differentiation and thereby antagonizes testis differentiation. Addition of a “weak” Sry allele, such as the one on the YPOS chromosome, to the sensitized B6 background results in inappropriate development of ovarian tissue. We conclude that Wt1, Sf1, and Wnt4 are dosage-sensitive in mice, this dosage-sensitivity is genetic background-dependant, and the mouse strains described here are good models for the investigation of human dosage-sensitive XY sex reversal

An Analysis of the Effects of Sociodemographic Factors on Daily Per Capita Residential Water Use in Texas Cities

Water is a key resource of concern to residents and decision makers in the State of Texas and in many other parts of the United States. Careful planning for its use is of utmost importance for the State and the Nation. Such planning requires careful consideration of numerous factors including hydrologic and physiographic factors, engineering feasibility and economic feasibility. At the same time, it is increasingly evident that water needs are closely tied to population growth and to the social, economic and demographic characteristics of the population (Murdock et al., 1985). Thus, attempts to plan for the use of water resources have become increasingly inclusive of socioeconomic as well as physical variables as the costs of incorrectly projecting water demand and misallocating funds for facility construction and management have become apparent (Stees et al., 1976; McFarland and Hyatt, 1973; Reid, 1971; Texas Department of Water Resources, 1984). To date, however, water-related socioeconomic research has concentrated on: 1. water use policy and water use planning 2. the demographic and social correlates of water and other resource use 3. the effects of water use and availability on demographic and social patterns 4. methodologies for projecting demands for resources and the implications of the use of resources An extensive body of research addresses both the need for, and the dimensions that must be considered in, water use policy formation and planning (Markusen, 1978; U.S. Water Resources Council, 1978; Council for Agriculture Science and Technology, 1982; National Water Commission, 1973; Office of Technology Assessment, 1983; Texas Department of Water Resources, 1984). Such analyses persuasively argue for the use of comprehensive, multidisciplinary planning formats, but as several recent reviews of water resources research efforts have noted (Francis, 1982; Napier et al., 1983), much of the basic research necessary to establish the relationships that should form the bases of the information used in such planning has not been completed. The demographic and social correlates of water use have not been sufficiently established. Although total population and demographic structure characteristics are often used in projecting demands for water resources (Mercer and Morgan, 1978; Texas Department of Water Resources, 1984), several recent efforts evaluating the use of demographic and social variables in water use planning have noted that few of the relationships between demographic and social factors and water use have been established empirically (Murdock et al., 1985; Korsching and Nowak, 1983; Francis, 1982). Thus, it is unclear what effects differences in household or family composition patterns or the age structure of a population have on usage of water and related resources. In like manner, although given some attention in the literature (Larson and Hudson, 1951; Bogue, 1963; Kubat et al., 1968; Francis, 1982; Napier et al., 1983), the relationships between such crucial social variables as socioeconomic status, ethnic status and perceptions of water conservation requirements and water use have not been adequately examined. Since other resource uses, such as energy use (Morrison, 1976), show substantial variation across demographic, social and cultural variables, similar effects are likely to be found between demographic, social and cultural variables and water use. The effects of water use and availability on population and social patterns have been given considerable attention (Williford et al., 1976; Doeksen and Pierce, 1976; Albrecht et al., 1984; Murdock et al., 1984; Albrecht and Hurdock, 1985). Such analyses suggest that changes in water resource availability or in the use of water-related forms of technology may lead to substantial changes in the population bases of areas (Albrecht and Murdock, 1985; Fitzsimmons and Salama, 1977) and may lead to related economic and community service changes (Williford et al., 1976). However, such analyses have tended to use only general and very unrefined assumptions concerning the relationships between water availability, use and technology and demographic and social factors. An extensive body of research has also developed related to the modeling of economic and demographic factors associated with resource use and development (Leistritz and Murdock, 1981; Murdock and Leistritz, 1980; Ford, 1976; Stenehjem and Metzger, 1976; Dunn and Larson, 1963; Nercer and Morgan, 1978). Although such models have become increasingly complex, several recent reviews of these models suggest that validation of the parameter assumptions underlying them is needed (Leistritz and Murdock, 1981; Markusen, 1978). In particular, most such models project water demand and use on the basis of per capita or per population unit factors. Population composition is not taken into account. Overall, then, although a few studies have attempted to include demographic variables--age, household size and patterns, race/ethnicity-and social, cultural and behavioral variables--such as water use preferences and cultural patterns of water use--in planning and projection efforts (Kubat et al., 1968; Dunn and Larson, 1963; Korsching and Nowak, 1983; Portney, 1982), water planning and analyses efforts have largely ignored the effects of demographic factors (other than total population size) and social factors in planning for water use and facility construction. Such neglect is particularly unfortunate in states, such as Texas, where populations display wide demographic and social diversity (Skrabanek et al., 1985) and where per capita water use varies widely from one area to another (Texas Department of Water Resources, 1984). Only if analyses of the relationships between demographic and social variables and water use and demand are completed, will it be possible to adequately employ such variables in projections of water demand. Because the inclusion of such variables in projection models should increase the accuracy of projections and improve our understanding of the numerous factors that determine patterns of water use, studies of the effects of demographic and social factors on water use and on projections of water demand deserve additional consideration. This report presents the results of one such study sponsored by the Texas Water Resources Institute. The study has two major objectives: 1. to determine the relationships between key demographic, social and cultural variables and water use in Texas 2. to analyze the implications of the relationships between demographic, social and cultural variables and water use and demand for projections of water use and demand in Texas Specifically, this report presents the results of an analysis of secondary and primary data in which the relationships between water use and other sociodemographic variables are examined, and it reports the effects of using sociodemographic characteristics to project water use. These relationships are of intrinsic interest to professionals involved in water planning and policy formulation, and the results will hopefully be of utility to a wide range of policy and decision makers. The report is organized into five sections. Section I describes the data and methodologies employed in the analysis. Section II presents and discusses the results of the secondary analysis. Section III examines the results of our analysis of survey data from over 800 respondents from 8 communities selected from across the State of Texas. Section IV describes the implications of using demographic and social factors in projecting water use. The final section, Section V, presents generalizations regarding the overall effects of demographic and social factors on water use and demand ant presents our preliminary recommendations regarding the use of such variables in formulating water use and demand projections. Throughout the report, it should be recognized that the fact that the study is limited to one period of time and to only selected areas of the Stste, clearly limits the ability to formulate generalizations that have statewide applicability. The fact that the study is limited in several regards must be recognized

The status of GEO 600

The GEO 600 laser interferometer with 600m armlength is part of a worldwide network of gravitational wave detectors. GEO 600 is unique in having advanced multiple pendulum suspensions with a monolithic last stage and in employing a signal recycled optical design. This paper describes the recent commissioning of the interferometer and its operation in signal recycled mode

A theory of power laws in human reaction times: insights from an information-processing approach

Human reaction time (RT) can be defined as the time elapsed from stimulus presentation until a reaction/response occurs (e.g., manual, verbal, saccadic, etc.). RT has been a fundamental measure of the sensory-motor latency at suprathreshold conditions for more than a century and is one of the hallmarks of human performance in everyday tasks (Luce, 1986; Meyer et al., 1988). Some examples are the measurement of RTs in sports science, driving safety or in aging. Under repeated experimental conditions the RT is not a constant value but fluctuates irregularly over time. Stochastic fluctuations of RTs are considered a benchmark for modeling neural latency mechanisms at a macroscopic scale (Luce, 1986; Smith and Ratcliff, 2004). Power-law behavior has been reported in at least three major types of experiments

Upper limits on the strength of periodic gravitational waves from PSR J1939+2134

The first science run of the LIGO and GEO gravitational wave detectors presented the opportunity to test methods of searching for gravitational waves from known pulsars. Here we present new direct upper limits on the strength of waves from the pulsar PSR J1939+2134 using two independent analysis methods, one in the frequency domain using frequentist statistics and one in the time domain using Bayesian inference. Both methods show that the strain amplitude at Earth from this pulsar is less than a few times $10^{-22}$.Comment: 7 pages, 1 figure, to appear in the Proceedings of the 5th Edoardo Amaldi Conference on Gravitational Waves, Tirrenia, Pisa, Italy, 6-11 July 200

Improving the sensitivity to gravitational-wave sources by modifying the input-output optics of advanced interferometers

We study frequency dependent (FD) input-output schemes for signal-recycling interferometers, the baseline design of Advanced LIGO and the current configuration of GEO 600. Complementary to a recent proposal by Harms et al. to use FD input squeezing and ordinary homodyne detection, we explore a scheme which uses ordinary squeezed vacuum, but FD readout. Both schemes, which are sub-optimal among all possible input-output schemes, provide a global noise suppression by the power squeeze factor, while being realizable by using detuned Fabry-Perot cavities as input/output filters. At high frequencies, the two schemes are shown to be equivalent, while at low frequencies our scheme gives better performance than that of Harms et al., and is nearly fully optimal. We then study the sensitivity improvement achievable by these schemes in Advanced LIGO era (with 30-m filter cavities and current estimates of filter-mirror losses and thermal noise), for neutron star binary inspirals, and for narrowband GW sources such as low-mass X-ray binaries and known radio pulsars. Optical losses are shown to be a major obstacle for the actual implementation of these techniques in Advanced LIGO. On time scales of third-generation interferometers, like EURO/LIGO-III (~2012), with kilometer-scale filter cavities, a signal-recycling interferometer with the FD readout scheme explored in this paper can have performances comparable to existing proposals. [abridged]Comment: Figs. 9 and 12 corrected; Appendix added for narrowband data analysi

Search for gravitational wave bursts in LIGO's third science run

We report on a search for gravitational wave bursts in data from the three LIGO interferometric detectors during their third science run. The search targets subsecond bursts in the frequency range 100-1100 Hz for which no waveform model is assumed, and has a sensitivity in terms of the root-sum-square (rss) strain amplitude of hrss ~ 10^{-20} / sqrt(Hz). No gravitational wave signals were detected in the 8 days of analyzed data.Comment: 12 pages, 6 figures. Amaldi-6 conference proceedings to be published in Classical and Quantum Gravit

Quantum state preparation and macroscopic entanglement in gravitational-wave detectors

Long-baseline laser-interferometer gravitational-wave detectors are operating at a factor of 10 (in amplitude) above the standard quantum limit (SQL) within a broad frequency band. Such a low classical noise budget has already allowed the creation of a controlled 2.7 kg macroscopic oscillator with an effective eigenfrequency of 150 Hz and an occupation number of 200. This result, along with the prospect for further improvements, heralds the new possibility of experimentally probing macroscopic quantum mechanics (MQM) - quantum mechanical behavior of objects in the realm of everyday experience - using gravitational-wave detectors. In this paper, we provide the mathematical foundation for the first step of a MQM experiment: the preparation of a macroscopic test mass into a nearly minimum-Heisenberg-limited Gaussian quantum state, which is possible if the interferometer's classical noise beats the SQL in a broad frequency band. Our formalism, based on Wiener filtering, allows a straightforward conversion from the classical noise budget of a laser interferometer, in terms of noise spectra, into the strategy for quantum state preparation, and the quality of the prepared state. Using this formalism, we consider how Gaussian entanglement can be built among two macroscopic test masses, and the performance of the planned Advanced LIGO interferometers in quantum-state preparation