bluuebunny/crossref_metadata_2025 huggingface dataset:
An upper bound to time-averaged space-charge limited diode currents
Authors: Griswold M. E. , Fisch N. J. , Wurtele J. S.
Published: November 2010

The Child–Langmuir law limits the steady-state current density across a one-dimensional planar diode. While it is known that the peak current density can surpass this limit when the boundary conditions vary in time, it remains an open question of whether the average current can violate the Child–Langmuir limit under time-dependent conditions. For the case where the applied voltage is constant but the electric field at the cathode is allowed to vary in time, one-dimensional particle-in-cell simulations suggest that such a violation is impossible. Although a formal proof is not given, an upper bound on the time-averaged current density is offered.
Influence of surfactant on drop deformation in an electric field
Authors: Teigen Knut Erik , Munkejord Svend Tollak
Published: November 2010

The deformation of a surfactant-covered, viscous drop suspended in a viscous fluid under the influence of an electric field is investigated using numerical simulations. The full Navier–Stokes equations are solved in both fluid phases, and the motion of the interface and the interfacial discontinuities are handled using the level-set method. The leaky-dielectric model is used to take into account the effect of an electric field. The surfactant is assumed to be insoluble, and an evolution equation for the motion of surfactant is solved along the drop surface. The surfactant concentration and the interfacial tension are coupled through a nonlinear equation of state. The numerical results show that the effect of surfactant strongly depends on the relative permittivity and conductivity between the fluids. The presence of surfactant can both increase and reduce the deformation, depending on the shape of the deformation and the direction of the electrically induced circulation.
Nonuniversal velocity probability densities in two-dimensional turbulence: The effect of large-scale dissipation
Authors: Tsang Yue-Kin
Published: November 2010

We show that some statistical properties of forced two-dimensional turbulence have an important sensitivity to the form of large-scale dissipation, which is required to damp the inverse cascade. We consider three models of large-scale dissipation: linear “Ekman” drag, nonlinear quadratic drag, and scale-selective hypo-drag that damps only low-wavenumber modes. In all cases, the statistically steady vorticity field is dominated by almost axisymmetric vortices, and the probability density function of vorticity is non-Gaussian. However, in the case of linear and quadratic drag, we find that the velocity statistics is close to Gaussian, with non-negligible contribution coming from the background turbulent flow. On the other hand, with hypo-drag, the probability density function of velocity is non-Gaussian and is predominantly determined by the properties of the vortices. With hypo-drag, the relative positions of the vortices and the exponential distribution of the vortex extremum are important factors responsible for the non-Gaussian velocity statistics.
Dependence of glass forming ability on liquid fragility: Thermodynamics versus kinetics
Authors: Wang Li-Min , Tian Yongjun , Liu Riping
Published: November 2010

The dependence of glass forming ability on liquid fragility is studied with thermodynamic and kinetic analyses. A general expression of the Gibbs free energy difference between an undercooled liquid and its equilibrium crystal is presented to address thermodynamically the fragility effect on glass formation. It is found that increasing fragility thermodynamically favors glass formation, remarkably contrasting with the fragility effect from the kinetic point of view. The dependences of glass forming ability on fragility in metallic alloys and molecular isomers are compared, and kinetics and thermodynamics of glass formation are, respectively, emphasized.
Retrieval of terahertz spectroscopic signatures in the presence of rough surface scattering using wavelet methods
Authors: Arbab M. H. , Winebrenner D. P. , Thorsos E. I. , Chen A.
Published: November 2010

Scattering of terahertz waves by surface roughness can obscure spectral signatures of chemicals at these frequencies. We demonstrate this effect using controlled levels of surface scattering on α-lactose monohydrate pellets. Furthermore, we show an implementation of wavelet methods that can retrieve terahertz spectral information from rough surface targets. We use a multiresolution analysis of the rough-surface-scattered signal utilizing the maximal overlap discrete wavelet transform (MODWT) to extract the resonant signature of lactose. We present a periodic extension technique to circumvent the circular boundary conditions of MODWT, which can be robustly used in an automated terahertz stand-off detection device.
Efficiency droop alleviation in InGaN/GaN light-emitting diodes by graded-thickness multiple quantum wells
Authors: Wang C. H. , Chang S. P. , Chang W. T. , Li J. C. , Lu Y. S. , Li Z. Y. , Yang H. C. , Kuo H. C. , Lu T. C. , Wang S. C.
Published: November 2010

InGaN/GaN light-emitting diodes (LEDs) with graded-thickness multiple quantum wells (GQW) was designed and grown by metal-organic chemical vapor deposition. The GQW structure, in which the well-thickness increases along [0001] direction, was found to have superior hole distribution as well as radiative recombination distribution by performing simulation modeling. Accordingly, the experimental investigation of electroluminescence spectrum reveals additional emission from the narrower wells within GQWs. Consequently, the efficiency droop can be alleviated to be about 16% from maximum at current density of 30 to 200 A/cm2, which is much smaller than that for conventional LED (32%). Moreover, the light output power was enhanced from 18.0 to 24.3 mW at 20 A/cm2.
Experimental study of the interaction between convective and elliptical instabilities
Authors: Lavorel Guillaume , Le Bars Michael
Published: November 2010

The reciprocal influence of convective and elliptical instabilities is studied experimentally in an elliptically deformed rotating cylindrical shell with an imposed temperature at the inner cylinder using the centrifugal force to mimic a radial gravity field. When the temperature contrast is stabilizing, we observe that the elliptical instability can grow and that the heat flux scales as the inverse of the viscous boundary layer depth. When the temperature profile is destabilizing, we observe (i) that the elliptical instability can still grow on the established convective motions, (ii) that for the experimental range of parameters, its growth rate progressively decreases when the intensity of convection increases, and (iii) that the elliptical instability modifies the heat transfer when the viscous boundary layer is smaller than the thermal one. Scaling laws for both cases are derived analytically and validated experimentally. We conclude that in geophysical and astrophysical systems, thermal effects have to be taken into account when looking for inertial instabilities and that these inertial instabilities have to be taken into account when evaluating heat transfers.
The effect of spectral anisotropy of fast magnetosonic turbulence on the plasma heating at the proton kinetic scales
Authors: Markovskii S. A. , Vasquez Bernard J.
Published: November 2010

The energy transport associated with the fast magnetosonic turbulence in a low-beta plasma is one of the possible driving forces of the solar wind. Two different kinds of the turbulence spectra are discussed in this paper: a unidirectional spectrum of the fluctuations propagating away from the sun and a bidirectional spectrum composed of the sunward and antisunward modes. The evolution of the system is analyzed with the help of hybrid numerical simulations at the proton kinetic scales. It is shown that in the unidirectional case, the heating is always preferentially across the background magnetic field. It is this property that allows the solar wind plasma to be propelled away from the sun by the mirror force of the inhomogeneous magnetic field. Adding the counterpropagating modes reverses the sense of the energy deposition with the parallel heating now dominating the process. However, the parallel heating is produced mostly by fast modes propagating along the magnetic field. If these modes are eliminated, the heating becomes perpendicular again.
Plasmon modes of silver nanowire on a silica substrate
Authors: Zou C.-L. , Sun F.-W. , Xiao Y.-F. , Dong C.-H. , Chen X.-D. , Cui J.-M. , Gong Q. , Han Z.-F. , Guo G.-C.
Published: November 2010

Plasmon mode in a silver nanowire is theoretically studied when the nanowire is placed on or near a silica substrate. It is found that the substrate has much influence on the plasmon mode. For the nanowire on the substrate, the plasmon (hybrid) mode possesses not only a long propagation length but also an ultrasmall mode area. From the experimental point of view, this cavity-free structure holds a great potential to study a strong coherent interaction between the plasmon mode and single quantum system (for example, quantum dots) embedded in the substrate.
Blue-green light photochromism in europium doped BaMgSiO4
Authors: Akiyama Morito
Published: November 2010

BaMgSiO 4 (BMS) can be sensed to blue light (wavelength λ=405 nm) by doped europium (Eu). Eu doped BMS turns to bright pink, and is bleached by green light (λ=475–532 nm) irradiation in several seconds. The coloration-decoloration process is repeatable and first. The colored state hardly changes for over 480 h (20 days), and is stable even at 100 °C. The blue-green light photochromism can be explained by electron transfers between doped Eu and oxygen defects. The doped Eu broadens the absorption band of BMS, and supplies excited electrons. The oxygen defects form electron traps, which catch excited electrons, and become F-like color centers.
Growth of thick heavily boron-doped diamond single crystals: Effect of microwave power density
Authors: Issaoui R. , Achard J. , Silva F. , Tallaire A. , Tardieu A. , Gicquel A. , Pinault M. A. , Jomard F.
Published: November 2010

The fabrication of diamond-based vertical power devices which are the most suited for high current applications requires the use of thick heavily boron-doped (B-doped) diamond single crystals. Although the growth of thin B-doped diamond films is well controlled over a large concentration range, little is known about the growth conditions leading to heavily doped thick single crystals. In this paper, it was found that the microwave power densities (MWPD) coupled to the plasma used to synthesize B-doped diamond by chemical vapor deposition is one of the key parameters allowing tuning doping efficiencies over two orders of magnitude. At high MWPD (above 100 W cm−3) the boron doping efficiency (DE) is extremely low while further increasing the boron concentration in the gas phase is no use as this leads to plasma instability. On the other hand, when low MWPD are used (<50 W cm−3), DE can be strongly increased but twinning and defects formation hampers the surface morphology. The use of intermediate MWPD densities has been demonstrated as the key in obtaining thick heavily B-doped diamond crystals (>1020 cm−3) with good morphologies.
Experimental verification of negative refraction for a wedge-type negative index metamaterial operating at terahertz
Authors: Wang Shengxiang , Garet Frédéric , Blary Karine , Lheurette Eric , Coutaz Jean Louis , Lippens Didier
Published: November 2010

We report on angle-resolved time domain spectroscopy (TDS) carried out on a prismlike negative index metamaterial operating around 0.5 THz. The wedge-type devices are constituted of hole arrays etched in gold thin films, which are stacked according to a sequential mask shift. By means of a goniometric TDS setup and subsequent analysis of the temporal waveforms, negative refraction is demonstrated with values close to n=−1 around 0.5 THz. The dispersion of refractive index retrieved from the Snell–Descartes law shows comparable trends in comparison with the dispersion deduced from complex transmission and reflection measurements on slab-type samples.
Rashba and Dresselhaus spin-orbit coupling in GaN-based heterostructures probed by the circular photogalvanic effect under uniaxial strain
Authors: Yin Chunming , Shen Bo , Zhang Qi , Xu Fujun , Tang Ning , Cen Longbin , Wang Xinqiang , Chen Yonghai , Yu Jinling
Published: November 2010

The spin splitting in GaN-based heterostructures has been investigated by means of circular photogalvanic effect experiments under uniaxial strain. The ratios of Rashba and Dresselhaus spin-orbit coupling coefficients (R/D ratios) have been measured in AlxGa1−xN/GaN heterostructures with various Al compositions. It is found that the R/D ratio increases from 4.1 to 19.8 with the Al composition of the AlxGa1−xN barrier varied from 15% to 36%. The Dresselhaus coefficient of bulk GaN is experimentally obtained to be 0.4 eV Å3. The results indicate that the spin splitting in GaN-based heterostructures can be modulated effectively by the polarization-induced electric fields.
Incentive prizes reinvented to solve problems
Authors: Feder Toni
Published: November 2010

The public and private sectors are recognizing that in casting a wide net and paying only for success, incentive prizes have the potential to spur breakthroughs
NIH is first to sponsor research on a ‘national laboratory’ in space
Authors: Kramer David
Published: November 2010

Three biomedical research projects are selected to fly on the International Space Station, but NASA can’t say when
A time-symmetric formulation of quantum mechanics
Authors: Aharonov Yakir , Popescu Sandu , Tollaksen Jeff
Published: November 2010

Quantum mechanics allows one to independently select both the initial and final states of a single system. Such pre- and postselection reveals novel effects that challenge our ideas about what time is and how it flows.
String theory and the real world
Authors: Kane Gordon
Published: November 2010

Although string theory is formulated in 10 or 11 dimensions, specific string theory solutions make unambiguous, testable predictions about our four-dimensional universe.
Jammed particles, from sandy beaches to sunscreens
Authors: Brujic Jasna
Published: November 2010

Ubiquitous features of particle collections whose individual elements are locked in place have inspired physicists to search for general principles that describe random packing.
Relativistic effects seen at everyday distances and speeds
Authors: Levi Barbara Goss
Published: November 2010

Recent results highlight the precision reached by the latest optical clocks.
002.Human spermatozoa: fruits of creation, seed of doubt
Authors: Aitken R. J.
Published: November 2010

Defective sperm function is the largest defined cause of human infertility, affecting one in twenty Australian males. Despite its prevalence, we are only just beginning to understand the underlying mechanisms. The past decade has seen two major advances in this field: (1) the discovery that Y chromosome deletions play a key role in the aetiology of non-obstructive azoospermia/oligozoospermia; and (2) recognition that oxidative stress can impact upon the functional competence of human spermatozoa through peroxidative damage to the sperm plasma membrane. Oxidative stress has also been found to disrupt the integrity of DNA in the male germ line and may represent an important mechanism by which environmental impacts on human health are mediated. Thus, paternal exposure to various toxicants (cigarette smoke, organic solvents, heavy metals) has been linked with oxidative DNA damage in spermatozoa and developmental defects, including cancer, in the F1 generation. The male germ line becomes particularly vulnerable to such factors during the post meiotic stages of differentiation. Pre-meiotic germ cells always have the option of undergoing apoptosis if DNA damage is severe. However, post meiotic germ cells have lost both the ability to mount an apoptotic response and the capacity for DNA repair. As a result, germ cells are particularly vulnerable to genotoxic agents during spermiogenesis and epididymal maturation. If the fertilizing capacity of the spermatozoa is retained following toxicant exposure, then DNA damage will be transferred to the zygote and must be repaired subsequently by the oocyte and/or early embryo. Aberrant DNA repair at this stage has the potential to create mutations that will compromise embryonic development and, ultimately, the normality of the offspring. Elucidating the causes of oxidative damage in spermatozoa should help resolve the aetiology of conditions such as male infertility, early pregnancy loss and childhood disease, including cancer.
003.Uterine and placental factors regulating conceptus growth: insights from the ewe
Authors: Spencer T. E.
Published: November 2010

Uterine adenogenesis is the process whereby endometrial glands differentiate and develop and is primarily a postnatal event in all mammals. In domestic animals and humans, adenogenesis involves initial differentiation and budding of glandular epithelium followed by invagination and extensive tubular coiling and branching morphogenesis through the endometrial stroma to the myometrium. Transient exposure of the neonatal ewe to a progestin from birth to postnatal Day 56 resulted in a uterine gland knock out (UGKO) phenotype in the adult. UGKO ewes exhibit a peri-implantation defect in conceptus (embryo/fetus and associated extraembryonic membranes) survival, indicating the functional importance of uterine glands and their secretions. Genomic and proteomic analysis of uterine endometrium from UGKO ewes has identified many candidate genes that regulate conceptus development and implantation, including endogenous Jaagsiekte sheep retroviruses (enJSRVs), glycosylated cell adhesion molecule one (GlyCAM-1), osteopontin and galectin-15. Galectin-15, also known as OVGAL11, and a previously uncharacterised member of the galectin family of secreted β-galactoside lectins, was discovered in the endometrium of sheep. In endometria of cyclic and pregnant sheep, galectin-15 mRNA was expressed specifically in the endometrial luminal epithelium but not in the conceptus. In pregnant sheep, galectin-15 mRNA expression appeared in the epithelia between Days 10 and 12 and increased between Days 12 and 16. Progesterone induced and interferon tau stimulated galectin-15 mRNA in the endometrial epithelium. Galectin-15 protein was concentrated near and on the apical surface of the endometrial luminal epithelia and localised within discrete cytoplasmic crystalline structures of conceptus trophectoderm. Galectin-15 is hypothesised to function extracellularly to regulate trophectoderm migration and adhesion to the endometrial epithelium and intracellularly to regulate cell survival, growth and differentiation. In sheep, the sequential actions of ovarian steroid hormones (oestrogen and progesterone), interferon tau, placental lactogen and placental growth hormone constitute a servomechanism that directly regulates endometrial gland morphogenesis and terminal differentiated function to provide increasing histotrophic nutrition for conceptus growth and development. Knowledge gained from this research will be used to prevent or treat infertility, fetal growth retardation and disease in domestic animals and humans.
010.Coordinating the transition from egg to embryo in mammals
Authors: Carroll J.
Published: November 2010

At fertilization of mammalian oocytes, the sperm induces a series of increases in the concentration of intracellular Ca2+. These Ca2+ oscillations trigger all the events of egg activation, including cortical granule exocytosis, completion of meiosis and entry into the first mitotic division. Thus, intracellular Ca2+ plays a pivotal role in coordinating the transition from egg to embryo. Our work is focussed on understanding how the oocyte prepares for fertilisation, how the Ca2+ oscillations are controlled and how Ca2+ stimulates signalling pathways that lead to optimal early embryonic development. In this lecture I will focus on the downstream pathways of Ca2+ signalling at fertilisation. Conventional Protein Kinase C (cPKC) is the major downstream target of Ca2+ in many cell functions. Using PKC-GFP fusion proteins we have found that cPKC is recruited to the membrane in a manner that is dependent on the frequency and amplitude of the Ca2+ oscillations. Recruitment of cPKC appears to promote the Ca2+ influx necessary to sustain the generation of long lasting Ca2+ oscillations. In other cell types cytosolic Ca2+ increases are known to stimulate mitochondrial respiration. We have found that maintenance of resting Ca2+ levels and sperm-induced Ca2+ oscillations are critically dependent on mitochondrial ATP production: a feature not shared by many cell types. Since Ca2+ release increases ATP consumption we investigated whether the Ca2+ transients increase mitochondrial activity so as to meet this increase in demand. Monitoring autofluorescence from NADH and flavoproteins reveals that Ca2+ transients stimulate a change in redox state of mitochondria, presumably by activating Ca2+-sensitive dehydrogenases of the TCA cycle. Thus, through activation of downstream pathways, including PKC, cyclin B degradation and mitochondrial activity, intracellular Ca2+ provides a signal that orchestrates the activation of early mammalian development.
011.Waking up the egg. How the sperm regulates exit out of the meiotic cell cycle
Authors: Jones K. T.
Published: November 2010

A series of calcium spikes are induced in the mammalian egg cytoplasm at fertilisation. These calcium spikes, which last for several hours, are the necessary and sufficient signal that stimulates the egg to escape from arrest at metaphase of the second meiotic division. Metaphase arrest is achieved by preventing the destruction of cyclin B1, the regulatory component of Maturation (M-Phase) Promoting Factor, and securin, which prevents segregation of sister chromatids. Both these proteins are destroyed by tagging with ubiquitin, using an E3 ligase the Anaphase-Promoting Complex (APC). Ubiquitination tags them for proteolysis by the 26S proteasome. Work from my lab has demonstrated that the sperm calcium signal works through activating the APC, not the 26S proteasome. Although we do not know which APC component is affected by calcium, this activation appears specific to a metaphase-arrested cell cycle state. More recently we have found that the APC is differently regulated at specific points during exit from meiosis II. Before extrusion of the second polar body it is the APC activator cdc20 that regulates APC activity. However, following extrusion of the second polar body cdh1 appears the major regulator. It is probable, therefore, that the calcium spiking affects the activity of both APCcdc20 and APCcdh1. This swap in APC activator at the time of second polar body extrusion has not been reported in eggs of other species, in fact non-mammalian eggs all lack cdh1. Since APCcdc20 and APCcdh1 have different substrate specificities, the function of APCcdh1 in mammalian eggs warrants further investigation.
013.The regulation of survival of the pre-implantation embryo
Authors: O'Neill C.
Published: November 2010

There are many aspects of the regulation of the growth and survival of the pre-implantation embryo that remain enigmatic. The increasing production of such embryos by assisted reproductive technologies (ART) in human medicine, animal production and conservation biology has highlighted the relatively poor viability of such embryos. Many embryos fail to survive past the normal time of implantation. Population biology theory predicts that any circumstance that results in high death rates within a population creates a potential for genetic selection. This occurs if the surviving individuals have a genetic make up that preferentially favours survival.
Since ART clearly favours the survival of some embryos over others, it is a high priority to develop a sound understanding of those factors that normally govern embryo survival and how they may be affected by ART. It raises the question, do embryos that survive ART have a genetic make up that favours their survival compared to the proportion of the population that does not survive?
It is now demonstrated that autocrine and paracrine factors are essential for embryo survival and that these act via the 1-o-phosphatidylinositol-3-kinase (PI3K) survival signalling pathway (1). PI3K activates many downstream pro-survival and anti-apoptotic mediators.
ART changes the expression of some of these mediators. Pharmacological and genetic moderation of their expression can influence embryo survival, highlighting potential targets for genetic selection through ART. Studies in appropriate models will allow rational approaches to safety assessment of ART and spawn new strategies for media and procedural design.
(1) Lu, D. P., Chandrakanthan, V., Cahana, A., Ishii, S., O'Neill, C. (2004) J. Cell Sci. 117, 1567–1576.
014.Novel uterine genes in regulation of embryo implantation
Authors: Nie G. , Li Y. , Luu K. , Findlay J. , Salamonsen L.
Published: November 2010

Implantation of the embryo into the maternal endometrium is the first and critical step leading to the establishment of a pregnancy. It has been well established that only during the 'window' of implantation, a limited time span when the uterine environment is receptive, can a blastocyst successfully implant into the uterus. The development of uterine receptivity is accompanied by remarkable morphological and physiological changes in the endometrium, and this is primarily driven by the coordinated effects of the ovarian steroid hormones. Uterine tissue remodelling during implantation also contributes significantly to the development of the placenta. Insufficient uterine remodelling causes implantation failure and infertility. To date, the exact molecular events occurring in the uterus during the establishment of receptivity and at the actual site of implantation are still not well understood. We used the mouse as a model and identified a number of previously unrecognised molecules that are uniquely regulated in the early stages of implantation: one of these is proprotein convertase 6 (PC6). The potential importance of these genes and their products in modulating fertility in the primate, including the human, was demonstrated by their unique spatial and temporal expression in the endometrium of human and rhesus monkey during the phase of uterine receptivity and at implantation. The importance of the genes for implantation was ultimately confirmed by functional studies in vivo using morpholino antisense oligonucleotides. These molecules will be discussed in terms of their identity, expression and functions.
015.Disrupted decidualisation in SOCS3 gene mutant mice
Authors: Robb L. , Rakar S. , Alexander W.
Published: November 2010

Cytokines comprise a large family of secreted glycoproteins that regulate many fundamental biological processes. Cytokine signals are relayed to target cells via binding to cell surface receptors. The receptors signal via members of the Janus kinases (JAKs) and signal transduction and activators of transcription family (STATs). The SOCS proteins negatively regulate cytokine signalling by inhibiting components of the JAK/STAT pathway. Genetically modified mice in which individual SOCS genes are ablated have revealed key biological roles for these proteins. SOCS3 null mice die at mid gestation due to placental insufficiency. By embryonic Day (E) 9.5 there is a marked decrease in the spongiotrophoblast layer and an increase in trophoblast giant cells in SOCS3 null placentae. With increasing gestational age, there is progressive disorganisation of the SOCS3 null placental labyrinth. Takahashi et al. (1) used tetraploid aggregation to demonstrate that the placental defect was attributable to intrinsic defects in the SOCS3-deficient trophoblast cells or yolk sac endoderm. Based on evidence from in vitro assays, SOCS3 has a role in downstream negative regulation of signalling via a large number of cytokines. To identify the cytokine responsible for the placental phenotype, we crossed SOCS3 null embryos with mice lacking leukaemia inhibitory factor (LIF). This rescued the placental phenotype of the SOCS3 null mice, thereby demonstrating that alterations in LIF signalling are responsible for profound abnormalities of the murine placenta.
(1) Takahashi et al. (2003) EMBO J. 22, 372–384.
016.Role of cited genes in placental morphogenesis: studies in null mutant mice
Authors: Dunwoodie S. L. , Withington S. L. , Sparrow D. B. , Scott A. N. , Preis J. I. , Michalicek J.
Published: November 2010

Cited1 and Cited2 interact with CBP and p300. CBP/p300 bind numerous proteins and evidence exists, for Cited2 at least, that Cited binding prevents the binding of other proteins to CBP/p300. Since CBP/p300 interact with many proteins, can acetylate protein and DNA, and act as a ubiquitin ligase, it is likely that Cited1 and Cited2 function at a number of sites during development. We have generated mice that carry a null mutant allele for each of these genes. Analysis of null mutant embryos demonstrates that both Cited1 and Cited2 are required for normal embryonic development and survival. Although both Cited1 and Cited2 are expressed in the developing embryo and placenta, it appears that abnormal placental development and function is the cause of embryonic death.
The defect that develops in the placentas of Cited1 null mutants is not apparent until late in gestation (16.5dpc). Cited1 null mutants are smaller than controls at birth and die during the early postnatal period. The placentas of these mutants are disorganised, with spongiotrophoblasts projecting in to the labyrinthine layer. In addition, resin casts of the maternal blood spaces within these placentas revealed extremely enlarged blood sinuses. We are searching for factors that could result in the increased size of the maternal blood sinuses.
Cited2 null placentas and embryos are significantly smaller than controls; mutants die 3/4 the way through gestation (15.5dpc). The null mutant placentas have proportionally fewer spongiotrophoblasts, trophoblast giant cells and invasive trophoblasts. In addition, resin casts of fetal vasculature of the placenta reveal that the capillary network is underdeveloped. Through the isolation of trophoblast stem (TS) cells we are exploring the possibility that TS cell proliferation and/or differentiation is impaired due to a lack of Cited2. We suspect that the development of the phenotype may relate to the Hypoxia Inducible Factor-1a (HIF1a) transcription factor as Cited2 expression is induced by HIF1 and it acts to negatively regulate its activity.
021.Identification and study of genes important for fetal germ cell biology in mice
Authors: Koopman P. , Browne C. , Jackson A. , Ewen K. , Aitken R. J. , Van Den Bergen J. , Western P. , Sinclair A.
Published: November 2010

We are using a multi-pronged approach to discovering genes and proteins that regulate the allocation, proliferation, migration, differentiation and apoptosis of primordial germ cells (PGCs) in the developing mouse embryo. First, we are using suppression PCR and microarray screening methods to identify genes whose expression is restricted to, or enriched in, gonads of a specific sex or developmental stage. In this way several genes were identified whose expression is restricted to germ cells. Second, we are using a proteomic approach to identify important proteins and the genes that encode them. Protein expression profiles are being compared between different sexes and stages of mouse fetal gonad development. Data so far indicate that this method is a useful adjunct to transcriptional profiling, capable of identifying not only proteins that are differentially expressed, but also those that are differentially modified, for example by phosphorylation. Third, in silico screening of mouse EST databases identified 23 new candidate genes whose expression appears to be limited to pluripotent cells and the germline. Many of these genes are novel uncharacterised transcripts. Preliminary in situ expression analyses show that eight of these genes are indeed limited to the germline and to pluripotent cells. These genes may have important functions in germline specification and function. We are currently developing approaches, including inducible RNAi-based methods, for examining the function of these genes, initially in vitro but also ultimately in vivo.
024. Post meiotic gene transcripts — sense, antisense, or nonsense
Authors: Ivell R. , Anand-Ivell R. J. K.
Published: November 2010

The mature spermatid is a highly specialised cell type whose structure and physiology have evolved to convey a haploid genome intact through a relatively inimical environment to find, interact with and achieve fertilisation of a mature female gamete, thus to produce a healthy diploid embryo. It is logical to assume that these highly specialist functions are the product of a unique set of genes or transcripts, expressed in late germ cell stages. It is equally logical to see the protein products of these genes as likely targets for a post meiotic approach to male contraception. Indeed many such spermatocyte- and spermatid-specific transcripts have been identified by differential cloning approaches. Some transcripts appear to represent novel sperm-specific genes, some represent sperm-specific alternative splice products, or alternatively initiated transcripts. However, for many such transcripts, there are features that lend doubt to the notion that they are truly functional in the context of sperm physiology. Many transcripts derive from undefined, TATA-less promoters. Some gene products have no legible open reading frame. Some transcripts are even produced as antisense molecules. Some appear as functional transcripts, but are not translated. Some appear to be highly species specific. Some appear to be functionally redundant, when tested in gene ablation experiments. The male gamete is under extreme selection pressure. It is therefore plausible that these apparently aberrant transcripts may have a function beyond that of conventionally generating physiologically relevant proteins, as in most somatic cells. This presentation reviews current ideas about the sperm transcriptome and presents various hypotheses to help us understand the mechanisms and purpose of post meiotic gene expression.
026.Endometriosis — linkage, positional cloning and genome wide association
Authors: Montgomery G. W. , Wicks J. , Zhao Z. Z. , Nyholt D. R. , Martin N. G. , Rogers P. A. W. , Treloar S. A.
Published: November 2010

Endometriosis is a complex disease which affects up to 10% of women in their reproductive years. Common symptoms include severe dysmenorrhea and pelvic pain. The disease is associated with subfertility and some malignancies. Genetic and environmental factors both influence endometriosis. The aim of our studies is to identify genetic variation contributing to endometriosis and define pathways leading to disease. We recruited a large cohort of affected sister pair (ASP) families where two sisters have had surgically confirmed disease and conducted a 10�cM genome scan. The results of the linkage analysis identified one chromosomal region with significant linkage and one region of suggestive linkage. The regions implicated by these studies are generally of the order of 20–30�cM and include several hundred genes. Locating the gene or genes contributing to disease within the region is a challenging task. The best approach to the problem is association studies using a high density of SNP markers. The recent development of human SNP maps and high throughput SNP genotyping platforms makes this task easier. We have developed high throughput SNP typing at QIMR using the Sequenom MassARRAY platform. The method allows multiple SNP assays to be genotyped on the same sample in a single experiment. Throughput and genotyping costs depend critically on this level of multiplexing and we routinely genotype 6–8 SNPs in a single assay. We are using bioinformatics and functional approaches to develop a priority list of genes to screen early in the project. SNP markers in these genes are being genotyped using the MassARRAY platform to search for genes contributing to endometriosis. In the future, genome wide association studies with our families may locate additional genes contributing to endometriosis.
027.Mapping novel breast cancer susceptibility genes by linkage analysis of Australian multiple case kindreds
Authors: Mann Graham J. , Pupo Gulietta M. , Newman Beth , Venter Deon J. , Hopper John L. , Chenevix-Trench Georgia , kConFab
Published: November 2010

We have been using the resources of the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab) and of the Australian Breast Cancer Family Study (ABCFS) to identify kindreds suitable for mapping high penetrance breast cancer susceptibility loci other than BRCA1 and BRCA2. A 10 cM genomewide search was carried out in 40 families in which BRCA1 and BRCA2 mutations had been excluded with high probability. The highest LOD score under heterogeneity (HLOD) was 2.16 (non-parametric LOD 1.83, P = 0.04) at the 11p telomere; several other regions with HLODs = 1.5–2.0 also merited investigation using fine mapping but have so far neither been confirmed or rejected by these analyses. Subsets based on age of onset and presence of other cancers correlated to some extent with particular linkage peaks and several regions (notably 2q and 13q) corresponded to areas of suggestive linkage reported recently in more limited studies of other cohorts. A large collaborative analysis of these data together with those from similar studies undertaken by members of the international Breast Cancer Linkage Consortium (BCLC) is under way. It is therefore likely that further major breast cancer susceptibility loci will be localised in the near future. The complementarity of these studies with genetic association, candidate gene and tumour-based approaches will be discussed.
040.Ovarian research in the post genomic era: analyses of GDF-9 and other paracrine signalling pathways
Authors: Hsueh A. J.
Published: November 2010

Recent publication of the genomic sequences for human and multiple model organisms allows the elucidation of the evolutionary origins of human genes. Because of the coevolution of polypeptide ligands and their cognate receptors, analysis of human genomic sequences allows one to predict the pairing of these elements. Based on a genomic approach, we identified the known BMPRII and ALK5 as the receptors for GDF-9 (1,2) and elucidated downstream signalling Smad molecules in ovarian follicles. We also identified LGR7 and LGR8 as receptors for relaxin and INSL3 respectively (3,4). Based on the known production of INLS3 by testicular Leydig cells and ovarian theca cells, we investigated the expression of the INSL3 receptor, LGR8, in male and female gonads. Of interest, LGR8 expression was found exclusively in oocytes in the ovary and male germ cells in the testis. We further found that LH stimulates INSL3 transcripts in ovarian theca and testicular Leydig cells. INSL3, in turn, binds LGR8 expressed in germ cells to initiate meiotic progression of arrested oocytes in preovulatory follicles in vitro and in vivo and to suppress male germ cell apoptosis in vivo (5). In contrast to its stimulation of cAMP production by somatic cells, INSL3 interacts with germ cells to activate the inhibitory G protein, thus leading to decreases in cAMP production. Our data demonstrate the importance of the INSL3–LGR8 paracrine system in mediating gonadotropin actions in gonads. We have set up an ovarian gene database (Ovarian Kaleidoscope database at http://ovary.stanford.edu) in which more than 1A 600 ovarian gene pages can be accessed online and searched by gene name, function, mutation phenotype, expression pattern, cellular location and other parameters. Database analysis of polypeptide ligand and receptor genes provides a functional genomic paradigm for the identification of novel ligands and receptors in the ovary. To assist ovarian researchers in the analyses of their DNA array datasets, a Microarray Data Interpreter has been set up in the OKdb to facilitate searches and comparisons of known and novel genes in the ovary.
043. Role of TGFβ in adrenal steroidogenesis before birth
Authors: Coulter C. L.
Published: November 2010

During mammalian development there are periods when the fetal adrenal is either relatively refractory or increasingly sensitive to trophic stimulation. This pattern of regulation of adrenal growth and function ensures that the fetal lungs, liver, brain and kidney are exposed in a programmed temporal sequence to the genomic actions of circulating glucocorticoids. A range of studies in the rat and sheep have also demonstrated that exposure to excess glucocorticoids at inappropriate times in fetal life inhibits fetal growth and permanently reprograms the development of the cardiovascular and metabolic systems resulting in postnatal hypertension, abnormal hepatic glucose production and poor glucose tolerance In most mammalian species, there are therefore a range of mechanisms that protect the fetus from exposure to glucocorticoids of either maternal or fetal origin at inappropriate times in gestation. The factors that act to maintain periods of adrenal quiescence are not known. There is evidence that intra-adrenal transforming growth factor beta 1 (TGFβ1) is an inhibitor of adrenocortical steroidogenesis in the adult. In recent studies, we have demonstrated that expression of TGFβ1 is high in the fetal sheep adrenal at around 100�days gestation and that adrenal TGFβ1 expression then falls with increasing gestational age and is lowest immediately after birth. Following the activation of adrenal cytochrome P450 C17 (CYP17), there is an inverse relationship between adrenal TGFβ1 and CYP17 expression and TGFβ1 may therefore play a novel inhibitory role in the regulation of adrenal steroidogenesis during mid and late gestation. Whilst functional activation of the fetal adrenal is dependent on the fetal hypothalamo–pituitary axis, adrenal TGFβ1 mRNA expression is not altered by disconnection of the fetal hypothalamus and pituitary in late gestation. It therefore appears unlikely that TGFβ1 mRNA expression is regulated directly by either bioactive ACTH or cortisol in late gestation. The mechanism by which TGFβ1 expression is upregulated in mid gestation remains to be determined.
124.Tetrahydrogestrinone (THG) is a potent androgen and progestin
Authors: Death A. K. , McGrath K. C.Y. , Tsatralis T. , Kazlauskas R. , Handelsman D. J.
Published: November 2010

Tetrahydrogestrinone (THG) is a novel steroid recently identified by a sports doping laboratory as an illicit agent sold to improve elite athletic performance. While its structure is closely related to gestrinone, a 19-nor progestin, and resembles that of trenbolone, a potent banned synthetic androgen, THG was never marketed, so no information on its hormonal properties are known. We therefore examined THG for steroidal bioactivity using yeast transformed with a steroid receptor-reporter system, comparing its bioactivity to other known androgens, nandrolone, 7α nandrolone (MENT), norbolethone, 5α-norbolethone, norethandrolone and trenbolone, as well as THG's parent compound, gestrinone. Yeast were stably transformed with human androgen receptor (AR) or progesterone receptor A (PR) cDNA, together with a reporter plasmid containing a β-galactosidase gene under the transcriptional control of an androgen (ARE) or progestin (PRE) reporter element. Bioassays were established by culturing transformed yeast in the presence of the steroids over the range of 1.2�×�10–6 to 5.9�–�10–10�M.The bioassay end-point was β-galactosidase activity in yeast cell lysates. THG showed dose-dependent highly potent activation of AR activity with an EC50 of 0.29�nM compared with other steroids nandrolone (0.12�nM), norbolethone (0.3�nM), 5α-norbolethone (0.026�nM), gestrinone (0.59�nM), trenbolone (0.78�nM), norethandrolone (0.19�nM) and MENT (0.01�nM). THG also activated PR (EC50 0.7�nM) with much higher potency than its parent steroid, gestrinone (EC50 30�nM). We conclude that THG is a potent androgen and progestin. It shows similar potency to the comparator androgens, nandrolone, norbolethone, 5α-norbolethone and trenbolone. The discovery of this illicit designer androgen raises concern about the possibility of other novel androgens being produced from other marketed synthetic sex steroids.
126.A repository of ENU mutant mouse lines and their potential for male fertility research
Authors: Kennedy C. L. , O’Connor A. E. , Sanchez-Partida L. G. , Goodnow C. C. , De Kretser D. M. , O'Bryan M. K.
Published: November 2010

One in 25 western men are infertile and the causal factor is frequently unknown, although it is expected that many are genetic in origin. My project aims to identify genes critical to mouse spermatogenesis using ENU mutagenesis. A further aim was to develop a repository of mutant mice and data on their fertility parameters for use by the reproductive biology community. This research will aid the diagnosis and development of specific treatments for human infertility and the development of contraceptive agents. The potent mutagen N-ethyl-N-nitrosourea (ENU) was utilized to generate libraries of C57BL/6 mice with random point mutations throughout their genomes. A 3 generational breeding program produced mice that were homozygous for a number of mutations. I subsequently performed a number of large scale screens on 3rd generation males, identifying lines carrying recessive mutations specifically affecting male fertility. Thus far we have observed a wide range of abnormal testis phenotypes including Sertoli Cell only, hypospermatogenesis, meiosis arrest, abnormal sperm morphology and abnormal hormone levels. From these analyses a repository including all data and tissues collected from 1200 3rd generation male mice from 122 different lines has been developed and will become publicly available. This includes testis and epididymal histology and serum levels of FSH, LH, activin A and inhibin. Further, I have stored gDNA long term and cryopreserved sperm to enable regeneration of lines in the future. In addition, I have developed a high throughput mutation screening protocol for the detection of mutations within genes of interest using denaturing high performance liquid chromatography (DHPLC). Collectively, our repository and gene screening techniques can be used in conjunction with artificial reproductive technologies to generate mouse models reflective of human conditions and altered specific gene function.