Quantum Communications Feasibility Tests over a UK-Ireland 224 km Undersea Link.

The future quantum internet will leverage existing communication infrastructures, including deployed optical fibre networks, to enable novel applications that outperform current information technology. In this scenario, we perform a feasibility study of quantum communications over an industrial 224 km submarine optical fibre link deployed between Southport in the United Kingdom (UK) and Portrane in the Republic of Ireland (IE). With a characterisation of phase drift, polarisation stability and the arrival time of entangled photons, we demonstrate the suitability of the link to enable international UK-IE quantum communications for the first time.

New developments in prenatal diagnosis of congenital adrenal hyperplasia.

Congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency is an autosomal recessive disorder caused by mutations in the CYP21A2 gene. Females affected with classical CAH are at risk for genital ambiguity, but can be treated in utero with dexamethasone before 9 gestational weeks to prevent virilization. Early genetic diagnosis is unavailable through current invasive methods of chorionic villus sampling and amniocentesis. New developments in prenatal genetic testing utilize fetal DNA extracted from maternal blood through noninvasive methods, which allow the determination of fetal gender and the diagnosis of CAH at an early gestational age (<9 weeks). Noninvasive prenatal diagnosis allows for the establishment of early and effective management plans in fetuses at risk for CAH and avoids unnecessary prenatal dexamethasone treatment.

Functions of vasopressin and oxytocin in bone mass regulation.

Prior studies show that oxytocin (Oxt) and vasopressin (Avp) have opposing actions on the skeleton exerted through high-affinity G protein-coupled receptors. We explored whether Avp and Oxtr can share their receptors in the regulation of bone formation by osteoblasts. We show that the Avp receptor 1α (Avpr1α) and the Oxt receptor (Oxtr) have opposing effects on bone mass: Oxtr(-/-) mice have osteopenia, and Avpr1α(-/-) mice display a high bone mass phenotype. More notably, this high bone mass phenotype is reversed by the deletion of Oxtr in Oxtr(-/-):Avpr1α(-/-) double-mutant mice. However, although Oxtr is not indispensable for Avp action in inhibiting osteoblastogenesis and gene expression, Avp-stimulated gene expression is inhibited when the Oxtr is deleted in Avpr1α(-/-) cells. In contrast, Oxt does not interact with Avprs in vivo in a model of lactation-induced bone loss in which Oxt levels are high. Immunofluorescence microscopy of isolated nucleoplasts and Western blotting and MALDI-TOF of nuclear extracts show that Avp triggers Avpr1α localization to the nucleus. Finally, a specific Avpr2 inhibitor, tolvaptan, does not affect bone formation or bone mass, suggesting that Avpr2, which primarily functions in the kidney, does not have a significant role in bone remodeling.

Bisphosphonates inactivate human EGFRs to exert antitumor actions.

Bisphosphonates are the most commonly prescribed medicines for osteoporosis and skeletal metastases. The drugs have also been shown to reduce cancer progression, but only in certain patient subgroups, suggesting that there is a molecular entity that mediates bisphosphonate action on tumor cells. Using connectivity mapping, we identified human epidermal growth factor receptors (human EGFR or HER) as a potential new molecular entity for bisphosphonate action. Protein thermal shift and cell-free kinase assays, together with computational modeling, demonstrated that N-containing bisphosphonates directly bind to the kinase domain of HER1/2 to cause a global reduction in downstream signaling. By doing so, the drugs kill lung, breast, and colon cancer cells that are driven by activating mutations or overexpression of HER1. Knocking down HER isoforms thus abrogates cell killing by bisphosphonates, establishing complete HER dependence and ruling out a significant role for other receptor tyrosine kinases or the enzyme farnesyl pyrophosphate synthase. Consistent with this finding, colon cancer cells expressing low levels of HER do not respond to bisphosphonates. The results suggest that bisphosphonates can potentially be repurposed for the prevention and therapy of HER family-driven cancers.

Integrated Management of Sclerotinia Blight in Peanut: Utilizing Canopy Morphology, Mechanical Pruning, and Fungicide Timing.

Sclerotinia blight of peanut, caused by Sclerotinia minor, generally becomes severe only after vines meet in the row middles and a dense canopy develops. Dense foliage appears to support a microclimate conducive to the colonization of peanut limbs by S. minor. Removal of excess foliage before and during a Sclerotinia blight epidemic on the susceptible genotype NC 7 has been shown to reduce the rate of disease progress. Field tests in 1993 and 1994 examined control of Sclerotinia blight among four peanut genotypes (NC 7, VA 93B, NC Ac 18016, and Tam-span 90) with diverse canopy morphologies. Each cultivar had foliage pruned with a rotary mower once (1993 and 1994) or twice (1994) during the season. Applications of fluazinam (9.2 kg a.i./ha) were imposed on the genotype × pruning treatments. Soil temperatures under the canopy of each genotype and pruning treatment were measured and compared. Disease data were collected weekly by counting the number of feet of plants exhibiting lesions with visible fungus growth. Tamspan 90, a resistant Spanish peanut, had the least Sclerotinia blight incidence. Pruning measurably affected soil temperature for approximately 2 weeks following pruning. Removal of foliage reduced disease and increased disease control affected by fluazi-nam in fields with high disease pressure. In some tests, yields were increased by pruning through a reduction in disease pressure. Yields were lower when peanuts were pruned excessively, especially late in the season. Pruning of excessive vine growth can be an alternative, or complement, to fungicide treatments when done in midseason during favorable weather when moderate to high disease pressure occurs.