Expression patterns of chondrocyte genes cloned by differential display in tibial dyschondroplasia

AbstractTibial dyschondroplasia (TD) appears to involve a failure of the growth plate chondrocytes within growing long bones to differentiate fully to the hypertrophic stage, resulting in a mass of prehypertrophic chondrocytes which form the avascular TD lesion. Many biochemical and molecular markers of chondrocyte hypertrophy are absent from the lesion, or show reduced expression, but the cause of the disorder remains to be identified. As differentiation to the hypertrophic state is impaired in TD, we hypothesised that chondrocyte genes that are differentially expressed in the growth plate should show altered expression in TD. Using differential display, four genes, B-cadherin, EF2, HT7 and Ex-FABP were cloned from chondrocytes stimulated to differentiate to the hypertrophic stage in vitro, and their differential expression confirmed in vivo. Using semi-quantitative RT-PCR, the expression patterns of these genes were compared in chondrocytes from normal and TD growth plates. Surprisingly, none of these genes showed the pattern of expression that might be expected in TD lesion chondrocytes, and two of them, B-cadherin and Ex-FABP, were upregulated in the lesion. This indicates that the TD phenotype does not merely reflect the absence of hypertrophic marker genes, but may be influenced by more complex developmental mechanisms/defects than previously thought

Abundance of conserved CRISPR-Cas9 target sites within the highly polymorphic genomes of Anopheles and Aedes mosquitoes.

A number of recent papers report that standing genetic variation in natural populations includes ubiquitous polymorphisms within target sites for Cas9-based gene drive (CGD) and that these "drive resistant alleles" (DRA) preclude the successful application of CGD for managing these populations. Here we report the results of a survey of 1280 genomes of the mosquitoes Anopheles gambiae, An. coluzzii, and Aedes aegypti in which we determine that ~90% of all protein-encoding CGD target genes in natural populations include at least one target site with no DRAs at a frequency of ≥1.0%. We conclude that the abundance of conserved target sites in mosquito genomes and the inherent flexibility in CGD design obviates the concern that DRAs present in the standing genetic variation of mosquito populations will be detrimental to the deployment of this technology for population modification strategies

Ferromagnetic resonance force microscopy on a thin permalloy film

Ferromagnetic Resonance Force Microscopy (FMRFM) offers a means of performing local ferromagnetic resonance. We have studied the evolution of the FMRFM force spectra in a continuous 50 nm thick permalloy film as a function of probe-film distance and performed numerical simulations of the intensity of the FMRFM probe-film interaction force, accounting for the presence of the localized strongly nonuniform magnetic field of the FMRFM probe magnet. Excellent agreement between the experimental data and the simulation results provides insight into the mechanism of FMR mode excitation in an FMRFM experiment.Comment: 9 pages, 2 figure

Quantum noise of non-ideal Sagnac speed meter interferometer with asymmetries

The speed meter concept has been identified as a technique that can potentially provide laser-interferometric measurements at a sensitivity level which surpasses the Standard Quantum Limit (SQL) over a broad frequency range. As with other sub-SQL measurement techniques, losses play a central role in speed meter interferometers and they ultimately determine the quantum noise limited sensitivity that can be achieved. So far in the literature, the quantum noise limited sensitivity has only been derived for lossless or lossy cases using certain approximations (for instance that the arm cavity round trip loss is small compared to the arm cavity mirror transmission). In this article we present a generalised, analytical treatment of losses in speed meters that allows accurate calculation of the quantum noise limited sensitivity of Sagnac speed meters with arm cavities. In addition, our analysis allows us to take into account potential imperfections in the interferometer such as an asymmetric beam splitter or differences of the reflectivities of the two arm cavity input mirrors. Finally,we use the examples of the proof-of-concept Sagnac speed meter currently under construction in Glasgow and a potential implementation of a Sagnac speed meter in the Einstein Telescope (ET) to illustrate how our findings affect Sagnac speed meters with meter- and kilometre-long baselines.Comment: 22 pages, 8 figures, 1 table, (minor corrections and changes made to text and figures in version 2

The roles of the DAZ family in spermatogenesis: More than just translation?

The DAZ family of genes are important fertility factors in animals, including humans. The family consists of Y-linked DAZ, and autosomal homologs Boule and Dazl. All three genes encode RNA-binding proteins that are nearly exclusively expressed in germ cells. The DAZ family is highly conserved, with ancestral Boule present in sea anemones through humans, Dazl conserved among vertebrates, and DAZ present only in higher primates. Here we review studies on DAZ family genes from multiple organisms, and summarize the common features of each DAZ gene and their roles during spermatogenesis in animals. DAZ family proteins are thought to activate the translation of RNA targets, but recent work has uncovered additional functions. Boule, Dazl, and DAZ likely function through similar mechanisms, and we present known functions of the DAZ family in spermatogenesis, and discuss possible mechanisms in addition to translation activation

Control of threshold voltage in E-mode and D-mode GaN-on-Si metal-insulator-semiconductor heterostructure field effect transistors by in-situ fluorine doping of atomic layer deposition Al2O3 gate dielectrics

We report the modification and control of threshold voltage in enhancement and depletion mode AlGaN/GaN metal-insulator-semiconductor heterostructure field effect transistors through the use of in-situ fluorine doping of atomic layer deposition Al2O3. Uniform distribution of F ions throughout the oxide thickness are achievable, with a doping level of up to 5.5 × 1019 cm−3 as quantified by secondary ion mass spectrometry. This fluorine doping level reduces capacitive hysteretic effects when exploited in GaN metal-oxide-semiconductor capacitors. The fluorine doping and forming gas anneal also induces an average positive threshold voltage shift of between 0.75 and 1.36 V in both enhancement mode and depletion mode GaN-based transistors compared with the undoped gate oxide via a reduction of positive fixed charge in the gate oxide from +4.67 × 1012 cm−2 to −6.60 × 1012 cm−2. The application of this process in GaN based power transistors advances the realisation of normally off, high power, high speed devices

Joint Action in Deaf and Hearing Toddlers: A Mobile Eye-Tracking Study

Infants experience the world through their actions with objects and their interactions with other people, especially their parents. Prior research has shown that school-age children with hearing loss experience poorer quality interactions with typically hearing parents, and difficulties in controlling their visual attention. In the current study, we used mobile eye-tracking to investigate parent-child interactions in toddlers with and without hearing loss. Parents and toddlers engaged in a goal-directed, interactive task that involved inserting coins into a slot and required joint coordination between the parent and the child. We examined the visual behaviors of the toddlers and the scaffolding behaviors of the parents. In contrast to previous work, preliminary findings reveal a pattern of potential similarities between deaf and hearing toddlers or their parents

A Study of Feasibility of State Water User Fees for Financing Water Development

Water user fees imposed by a state on major water uses is a possible new alternative source of state water development funds. A fee, similar to an excise tax, might be charged for the use of the water resource per se, which in a number of states is declared to be the property of the public of the state. States generally have not employed such fees as a source of operating funds for water agencies or of development capital. Only in the area of water based recreation-fishing, coating, camping, etc.—have states extensively employed user fees. The revenues from these fees, however, are used only to defray management and operating expenses associated with these activities. The implementation of user-fee financing would result in some shifts of financing burden connected with water programs from the general taxpayers of the state to specific water users. Although this approach has not been utilized by states to a significant extent, the “user pay” principle is well established in economic theory. The theory indicated that user fees would be an economically more efficient and equitable source for financing water development than general tax revenues. In the design of fee structures for major water uses, several characteristics of fees are appropriate to consider. Five which were identified in this study are as follows: equity, economic efficiency, allocational effectiveness, administrative simplicity, and revenue generating potential. These were used to evaluate different structures for extracting fees from the user. These rate design considerations may relate only indirectly to a state system of user fees since the state fees envisioned in this study in many cases may be only an add-on or surcharge to a basic charge imposed by a local entity, such as a municipality or an irrigation district. Revenue generating potential, the last of the five characteristics listed, was of primary interest in this study. Estimates of revenue potential for four major water uses—irrigation, municipal, industrial, and recreations—were made with a formula developed in this study for this purpose. Gross estimates of potential from public supply and irrigation uses were made for several selected states, and somewhat more detailed estimates were made for the four major uses in Utah. The calculations indicated that substantial amounts of funds could be generated with only modest increases in current charges. A preliminary assessment of legal and administrative implications of implementing water user fees in the State of Utah was made in this study. The results indicated that some fee alternatives probably could be implemented by administrative action; others would require legislative approval. Constitutional issues related to some alternatives would have to be resolved by the state supreme court. New uses associated with developing Utah’s vast energy resources appear to offer a particularly promising prospect for instituting a user fee program with minimal legal complications