A small population of hypothalamic neurons govern fertility: the critical role of VAX1 in GnRH neuron development and fertility maintenance.

Fertility depends on the correct maturation and function of approximately 800 gonadotropin-releasing hormone (GnRH) neurons in the brain. GnRH neurons are at the apex of the hypothalamic-pituitary-gonadal axis that regulates fertility. In adulthood, GnRH neurons are scattered throughout the anterior hypothalamic area and project to the median eminence, where GnRH is released into the portal vasculature to stimulate release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary. LH and FSH then regulate gonadal steroidogenesis and gametogenesis. Absence of GnRH neurons or inappropriate GnRH release leads to infertility. Despite the critical role of GnRH neurons in fertility, we still have a limited understanding of the genes responsible for proper GnRH neuron development and function in adulthood. GnRH neurons originate in the olfactory placode then migrate into the brain. Homeodomain transcription factors expressed within GnRH neurons or along their migratory path are candidate genes for inherited infertility. Using a combined in vitro and in vivo approach, we have identified Ventral Anterior Homeobox 1 (Vax1) as a novel homeodomain transcription factor responsible for GnRH neuron maturation and fertility. GnRH neuron counts in Vax1 knock-out embryos revealed Vax1 to be required for the presence of GnRH-expressing cells at embryonic day 17.5 (E17.5), but not at E13.5. To localize the effects of Vax1 on fertility, we generated Vax1flox mice and crossed them with Gnrhcre mice to specifically delete Vax1 within GnRH neurons. GnRH staining in Vax1flox/flox:GnRHcre mice show a total absence of GnRH expression in the adult. We performed lineage tracing in Vax1flox/flox:GnRHcre:RosaLacZ mice which proved GnRH neurons to be alive, but incapable of expressing GnRH. The absence of GnRH leads to delayed puberty, hypogonadism and complete infertility in both sexes. Finally, using the immortalized model GnRH neuron cell lines, GN11 and GT1-7, we show that VAX1 is a direct regulator of Gnrh1 transcription by binding key ATTA sites within the Gnrh1 promoter. This study identifies VAX1 as a key transcription factor regulating GnRH expression and establishes VAX1 as a novel candidate gene implicated in heritable infertility

Cepheid Variables in the Maser-Host Galaxy NGC 4258

We present results of a ground-based survey for Cepheid variables in NGC 4258. This galaxy plays a key role in the Extragalactic Distance Scale due to its very precise and accurate distance determination via VLBI observations of water masers. We imaged two fields within this galaxy using the Gemini North telescope and GMOS, obtaining 16 epochs of data in the SDSS gri bands over 4 years. We carried out PSF photometry and detected 94 Cepheids with periods between 7 and 127 days, as well as an additional 215 variables which may be Cepheids or Population II pulsators. We used the Cepheid sample to test the absolute calibration of theoretical gri Period-Luminosity relations and found good agreement with the maser distance to this galaxy. The expected data products from the Large Synoptic Survey Telescope (LSST) should enable Cepheid searches out to at least 10 Mpc.Comment: Accepted for publication in the Astronomical Journa

Designable buried waveguides in sapphire by proton implantation

Buried and stacked planar as well as buried single and parallel channel waveguides are fabricated in sapphire by proton implantation. Good control of the implantation parameters provides excellent confinement of the guided light in each structure. Low propagation losses are obtained in fundamental-mode, buried channel waveguides without postimplantation annealing. Choice of the implantation parameters allows one to design mode shapes with different ellipticity and/or mode asymmetry in each orthogonal direction, thus demonstrating the versatility of the fabrication method. Horizontal and vertical parallelization is demonstrated for the design of one- or two-dimensional waveguide arrays in hard crystalline materials

Sapphire planar waveguides fabricated by H+ ion beam implantation

1.1-MeV proton-implanted sapphire waveguides are investigated for the first time. Optical measurements show that the planar waveguides support low-order transverse-mode propagation with good guiding properties without the need to anneal the samples

Proton implanted sapphire planar and channel waveguides

We report low-order transverse-mode planar waveguides in sapphire fabricated for the first time by proton implantation. The waveguides show good guiding properties without post-implantation annealing. Channel waveguiding was achieved by polyimide strip-loading

Crystal water induced switching of magnetically active orbitals in CuCl2

The dehydration of CuCl2*2(H2O) to CuCl2 leads to a dramatic change in magnetic behavior and ground state. Combining density functional electronic structure and model calculations with thermodynamical measurements we reveal the microscopic origin of this unexpected incident -- a crystal water driven switching of the magnetically active orbitals. This switching results in a fundamental change of the coupling regime from a three-dimensional antiferromagnet to a quasi one-dimensional behavior. CuCl2 can be well described as a frustrated J1-J2 Heisenberg chain with ferromagnetic exchange J1 and J2/J1 ~ -1.5 for which a helical ground state is predicted.Comment: 6 pages, 5 figures, 1 table (PRB, accepted

Dosimetric evidence confirms computational model for magnetic field induced dose distortions of therapeutic proton beams

Given the sensitivity of proton therapy to anatomical variations, this cancer treatment modality is expected to benefit greatly from integration with magnetic resonance (MR) imaging. One of the obstacles hindering such an integration are strong magnetic field induced dose distortions. These have been predicted in simulation studies, but no experimental validation has been performed so far. Here we show the first measurement of planar distributions of dose deposited by therapeutic proton pencil beams traversing a one-Tesla transversal magnetic field while depositing energy in a tissue-like phantom using film dosimetry. The lateral beam deflection ranges from one millimeter to one centimeter for 80 to 180 MeV beams. Simulated and measured deflection agree within one millimeter for all studied energies. These results proof that the magnetic field induced proton beam deflection is both measurable and accurately predictable. This demonstrates the feasibility of accurate dose measurement and hence validates dose predictions for the framework of MR-integrated proton therapy