Prioritizing investments in innovations to protect women from the leading causes of maternal death

PATH, an international nonprofit organization, assessed nearly 40 technologies for their potential to reduce maternal mortality from postpartum hemorrhage and preeclampsia and eclampsia in low-resource settings. The evaluation used a new Excel-based prioritization tool covering 22 criteria developed by PATH, the Maternal and Neonatal Directed Assessment of Technology (MANDATE) model, and consultations with experts. It identified five innovations with especially high potential: technologies to improve use of oxytocin, a uterine balloon tamponade, simplified dosing of magnesium sulfate, an improved proteinuria test, and better blood pressure measurement devices. Investments are needed to realize the potential of these technologies to reduce mortality

Neutron Scattering Study of Fluctuating and Static Spin Correlations in the Anisotropic Spin Glass Fe2_2TiO5_5

The anisotropic spin glass transition, in which spin freezing is observed only along the c-axis in pseudobrookite Fe$_2$TiO$_5$, has long been perplexing because the Fe$^{3+}$ moments (d$^5$) are expected to be isotropic. Recently, neutron diffraction demonstrated that surfboard-shaped antiferromagnetic nanoregions coalesce above the glass transition temperature, T$_g$ $\approx$ 55 K, and a model was proposed in which the freezing of the fluctuations of the surfboards' magnetization leads to the anisotropic spin glass state. Given this new model, we have carried out high resolution inelastic neutron scattering measurements of the spin-spin correlations to understand the temperature dependence of the intra-surfboard spin dynamics on neutron (picosecond) time-scales. Here, we report on the temperature-dependence of the spin fluctuations measured from single crystal Fe$_2$TiO$_5$. Strong quasi-elastic magnetic scattering, arising from intra-surfboard correlations, is observed well above T$_g$. The spin fluctuations possess a steep energy-wave vector relation and are indicative of strong exchange interactions, consistent with the large Curie-Weiss temperature. As the temperature approaches T$_g$ from above, a shift in spectral weight from inelastic to elastic scattering is observed. At various temperatures between 4 K and 300 K, a characteristic relaxation rate of the fluctuations is determined. Despite the freezing of the majority of the spin correlations, an inelastic contribution remains even at base temperature, signifying the presence of fluctuating intra-surfboard spin correlations to at least T/T$_g$ $\approx$ 0.1 consistent with a description of Fe$_2$TiO$_5$ as a hybrid between conventional and geometrically frustrated spin glasses.Comment: 6 figure

Synthesis and structure of metallated macrocycle-bearing cyclophophazenes. - Part I : The (Li, Mg, Zn)/SPIR0(30203) derivatives

Syntheses and molecular structures of three metallated (Li, Zn, Mg) derivatives of the macrocycle-bearing cyclophosphazene N3P3Cl4 [HN---(CH2)3---O---(CH2)2---O---(CH2)3---NH] (coded as SPIRO 30203, 1) are reported. These three molecular structures reveal three different patterns of metal coordination. In compound 2 one of the two hydrogen atoms in SPIRO 3O2O3 is substituted by lithium generating a dimeric structure with pentacoordinated lithium centers. This structure is further stabilized by N---H hydrogen bonds. In 3 both hydrogen atoms of the macrocyclic loop are replaced by two zinc atoms through a cross-link metallation leading again to a dimeric molecule. In this compound the Zn atom is found to be in a trigonal bipyramidal environment with one very long N---Zn interaction. The origin of the dimerization of the magnesium compound 4 is analogous to 3. Magnesium is in the center of a distorted octahedron, coordinated with the O- and N-donors of the macrocyclic loop and also one nitrogen atom of the N3P3 ring. 4 is the first example of a metallic center coordinated by a neutral phosphazene ligand. Typical metal-N and metal-O distances are (in Å): Li-O, 2.05—2.07; Li-N, 2.07—2.36; Zn-O, 2.08—2.14; Zn---N, 1.94—1.95 (2.49); Mg---O, 2.09—2.14; Mg---N, 2.07—2.31

Synthesis and structure of metallated macrocycle-bearing cyclophophazenes. - Part II : The (Al) /SPIRO (30203) derivatives

Synthesis and molecular structures of two metallated (aluminium) derivatives, [C9H19Cl4AlN5O2P3]· 1.5C7H8 and [C8H16Cl5AiN5O2P3] · 1.5C7H8, of the macrocycle-bearingcyclophosphazene N3P3Cl4 [HN--- (CH2)3---O---(CH2)2---O---(CH2)3-NH] (coded as SPIRO 30203) are reported. These two molecular structures reveal the same pattern of metal coordination where the two hydrogen atoms in SPIRO 30203 are substituted by aluminium generating monomeric structures with pentacoordinated aluminium centres in the inner cavities. In the first compound the exocyclic ligand at aluminium is a methyl group, in the second a chlorine atom. Typical Al---N, Al---O and Al-X distances are (Å):1.84-1.89, 1.97-2.04 and 1.93 in the former, 1.81-1.86, 1.93-2.01 and 2.12 in the latter, respectively

Genome characteristics of facultatively symbiotic Frankia sp. strains reflect host range and host plant biogeography

Soil bacteria that also form mutualistic symbioses in plants encounter two major levels of selection. One occurs during adaptation to and survival in soil, and the other occurs in concert with host plant speciation and adaptation. Actinobacteria from the genus Frankia are facultative symbionts that form N2-fixing root nodules on diverse and globally distributed angiosperms in the “actinorhizal” symbioses. Three closely related clades of Frankia sp. strains are recognized; members of each clade infect a subset of plants from among eight angiosperm families. We sequenced the genomes from three strains; their sizes varied from 5.43 Mbp for a narrow host range strain (Frankia sp. strain HFPCcI3) to 7.50 Mbp for a medium host range strain (Frankia alni strain ACN14a) to 9.04 Mbp for a broad host range strain (Frankia sp. strain EAN1pec.) This size divergence is the largest yet reported for such closely related soil bacteria (97.8%–98.9% identity of 16S rRNA genes). The extent of gene deletion, duplication, and acquisition is in concert with the biogeographic history of the symbioses and host plant speciation. Host plant isolation favored genome contraction, whereas host plant diversification favored genome expansion. The results support the idea that major genome expansions as well as reductions can occur in facultative symbiotic soil bacteria as they respond to new environments in the context of their symbioses

Isothermal Amplification Using a Chemical Heating Device for Point-of-Care Detection of HIV-1

Background: To date, the use of traditional nucleic acid amplification tests (NAAT) for detection of HIV-1 DNA or RNA has been restricted to laboratory settings due to time, equipment, and technical expertise requirements. The availability of a rapid NAAT with applicability for resource-limited or point-of-care (POC) settings would fill a great need in HIV diagnostics, allowing for timely diagnosis or confirmation of infection status, as well as facilitating the diagnosis of acute infection, screening and evaluation of infants born to HIV-infected mothers. Isothermal amplification methods, such as reversetranscription, loop-mediated isothermal amplification (RT-LAMP), exhibit characteristics that are ideal for POC settings, since they are typically quicker, easier to perform, and allow for integration into low-tech, portable heating devices. Methodology/Significant Findings: In this study, we evaluated the HIV-1 RT-LAMP assay using portable, non-instrumented nucleic acid amplification (NINA) heating devices that generate heat from the exothermic reaction of calcium oxide and water. The NINA heating devices exhibited stable temperatures throughout the amplification reaction and consistent amplification results between three separate devices and a thermalcycler. The performance of the NINA heaters was validated using whole blood specimens from HIV-1 infected patients. Conclusion: The RT-LAMP isothermal amplification method used in conjunction with a chemical heating device provides

Promising pre-clinical validation of targeted radionuclide therapy using a [131I] labelled iodoquinoxaline derivative for an effective melanoma treatment

Targeted internal radionuclide therapy (TRT) would be an effective alternative to current therapies for dissemi- nated melanoma treatment. At our institution, a class of iodobenzamides has been developed as potent melanoma- seeking agents. This review described the preclinical vali- dations of a quinoxaline derivative molecule (ICF01012) as tracer for TRT application. It was selected for its high, specific and long-lasting uptake in tumour with rapid clear- ance from non-target organs providing suitable dosimetry parameters for TRT. Extended in vivo study of metabolic profiles confirmed durable tumoural concentration of the unchanged molecule form. Moreover melanin specificity of ICF01012 was determined by binding assay with syn- thetic melanin and in vivo by SIMS imaging. Then, we showed in vivo that [131I] ICF01012 treatment drastically inhibited growth of B16F0, B16Bl6 and M4Beu tumours whereas [131I] NaI or unlabelled ICF01012 treatment was without significant effect. Histological analysis showed that residual tumour cells exhibit a significant loss of aggres- siveness after treatment. This anti-tumoural effect was associated with a lengthening of the treated-mice survival time and an inhibition of lung dissemination for B16Bl6 model. Results presented here support the concept of TRT using a [131I] labelled iodoquinoxaline derivative for an effective melanoma treatment.<br /

Feasibility study for a microwave-powered ozone sniffer aircraft

The preliminary design of a high-altitude, remotely-piloted, atmospheric-sampling aircraft powered by microwave energy beamed from ground-based antenna was completed. The vehicle has a gross weight of 6720 pounds and is sized to carry a 1000 pound payload at an altitude of 100,000 feet. The underside of the wing serves as the surface of a rectenna designed to receive microwave energy at a power density of 700 watts per square meter and the wing has a planform area of 3634 square feet to absorb the required power at an optimum Mach number M = 0.44. The aircraft utilizes a horizontal tail and a canard for longitudinal control and to enhance the structural rigidity of the twin fuselage configuration. The wing structure is designed to withstand a gust-induced load factor n = 3 at cruise altitude but the low-wing loading of the aircraft makes it very sensitive to gusts at low altitudes, which may induce load factors in excess of 20. A structural load alleviation system is therefore proposed to limit actual loads to the designed structural limit. Losses will require transmitted power on the order of megawatts to be radiated to the aircraft from the ground station, presenting environmental problems. Since the transmitting antenna would have a diameter of several hundred feet, it would not be readily transportable, so we propose that a single antenna be constructed at a site from which the aircraft is flown. The aircraft would be towed aloft to an initial altitude at which the microwave power would be utilized. The aircraft would climb to cruise altitude in a spiral flight path and orbit the transmitter in a gentle turn

Eukaryotic-like Ser/Thr Protein Kinases SpkC/F/K Are Involved in Phosphorylation of GroES in the Cyanobacterium Synechocystis

Serine/threonine protein kinases (STPKs) are the major participants in intracellular signal transduction in eukaryotes, such as yeasts, fungi, plants, and animals. Genome sequences indicate that these kinases are also present in prokaryotes, such as cyanobacteria. However, their roles in signal transduction in prokaryotes remain poorly understood. We have attempted to identify the roles of STPKs in response to heat stress in the prokaryotic cyanobacterium Synechocystis sp. PCC 6803, which has 12 genes for STPKs. Each gene was individually inactivated to generate a gene-knockout library of STPKs. We applied in vitro Ser/Thr protein phosphorylation and phosphoproteomics and identified the methionyl-tRNA synthetase, large subunit of RuBisCO, 6-phosphogluconate dehydrogenase, translation elongation factor Tu, heat-shock protein GrpE, and small chaperonin GroES as the putative targets for Ser/Thr phosphorylation. The expressed and purified GroES was used as an external substrate to screen the protein extracts of the individual mutants for their Ser/Thr kinase activities. The mutants that lack one of the three protein kinases, SpkC, SpkF, and SpkK, were unable to phosphorylate GroES in vitro, suggesting possible interactions between them towards their substrate. Complementation of the mutated SpkC, SpkF, and SpkK leads to the restoration of the ability of cells to phosphorylate the GroES. This suggests that these three STPKs are organized in a sequential order or a cascade and they work one after another to finally phosphorylate the GroES