A terminal molybdenum carbide prepared by methylidyne deprotonation

The carbide anion [CMo{N(R)Ar}_3]– [R = C(CD_3)_2CH_3, Ar = C_6H_3Me_2-3,5], is obtained by deprotonation of the corresponding methylidyne compound, [HCMo{N(R)Ar}_3], and is characterized by X-ray diffraction as its {K(benzo-15-crown-5)_2}+ salt, thereby providing precedent for the carbon atom as a terminal substituent in transition-metal chemistry

Preliminary study of minimum performance approaches to automated Mars sample return missions Final report, 19 Oct. - 20 Nov. 1970

Alternative mission/system approaches to automated Mars surface sample return based on utilization of Titan 3 or Saturn Intermediate-20 launch vehicle

Determinants of anemia and hemoglobin concentration in haitian school-aged children

Anemia diminishes oxygen transport in the body, resulting in potentially irreversible growth and developmental consequences for children. Limited evidence for determinants of anemia exists for school-aged children. We conducted a cluster randomized controlled trial in Haiti from 2012 to 2013 to test the efficacy of a fortified school snack. Children (N = 1,047) aged 3–13 years were followed longitudinally at three time points for hemoglobin (Hb) concentrations, anthropometry, and bioelectrical impedance measures. Dietary intakes, infectious disease morbidities, and socioeconomic and demographic factors were collected at baseline and endline. Longitudinal regression modeling with generalized least squares and logit models with random effects identified anemia risk factors beyond the intervention effect. At baseline, 70.6% of children were anemic and 2.6% were severely anemic. Stunting increased the odds of developing anemia (adjusted odds ratio [OR]: 1.48, 95% confidence interval [CI]: 1.05–2.08) and severe anemia (adjusted OR: 2.47, 95% CI: 1.30–4.71). Parent-reported vitamin A supplementation and deworming were positively associated with Hb concentrations, whereas fever and poultry ownership showed a negative relationship with Hb concentration and increased odds of severe anemia, respectively. Further research should explore the full spectrum of anemia etiologies in school children, including genetic causes

MEPicides: Potent antimalarial prodrugs targeting isoprenoid biosynthesis

AbstractThe emergence of Plasmodium falciparum resistant to frontline therapeutics has prompted efforts to identify and validate agents with novel mechanisms of action. MEPicides represent a new class of antimalarials that inhibit enzymes of the methylerythritol phosphate (MEP) pathway of isoprenoid biosynthesis, including the clinically validated target, deoxyxylulose phosphate reductoisomerase (Dxr). Here we describe RCB-185, a lipophilic prodrug with nanomolar activity against asexual parasites. Growth of P. falciparum treated with RCB-185 was rescued by isoprenoid precursor supplementation, and treatment substantially reduced metabolite levels downstream of the Dxr enzyme. In addition, parasites that produced higher levels of the Dxr substrate were resistant to RCB-185. Notably, environmental isolates resistant to current therapies remained sensitive to RCB-185, the compound effectively treated sexually-committed parasites, and was both safe and efficacious in malaria-infected mice. Collectively, our data demonstrate that RCB-185 potently and selectively inhibits Dxr in P. falciparum, and represents a promising lead compound for further drug development.</jats:p

Assembly of Molybdenum/Titanium μ-Oxo Complexes via Radical Alkoxide C−O Cleavage

Three-coordinate Ti(NRAr)_3 [R = C(CD_3)_2(CH_3), Ar = C_6H_3Me_2] was prepared in 73% yield by sodium amalgam reduction of ClTi(NRAr)_3 and in 83% yield upon treatment of TiCl_3(THF)_3 with 3 equiv of Li(NRAr)(OEt_2) in the presence of TMEDA. Ti(^tBuNPh)_3 was prepared similarly in 75% yield by treatment of TiCl_3(THF)_3 with 3 equiv of Li(^tBuNPh)(OEt_2) in the presence of TMEDA. Reaction of Ti(NRAr)_3 with NMo(O^tBu)_3 in hydrocarbon solvents at −35 °C generates a thermally unstable intermediate formulated as (^tBuO)_3Mo[μ-N]Ti(NRAr)_3, which readily loses a tert-butyl radical and isomerizes at 25 °C. Kinetics of the latter process were obtained over the temperature range 20−60 °C; the process exhibits clean first-order behavior. The following activation parameters were obtained:  ΔH⧧ = 21.4 ± 0.2 kcal mol^(-1) and ΔS⧧ = −3.7 ± 0.6 cal mol^(-1) K^(-1). The oxo-bridged product (^tBuO)_2(N)Mo[μ-O]Ti(NRAr)_3 was isolated in 83% yield from this reaction. Full characterization of the latter diamagnetic complex included an X-ray crystal structure and an ^(15)N NMR study. Ti(NRAr)_3 (1 equiv) reacts further with (^tBuO)_2(N)Mo[μ-O]Ti(NRAr)_3 to generate a species formulated as a second paramagnetic nitrido-bridged intermediate, (^tBuO)_2Mo{[μ-O]Ti(NRAr)_3}{[μ-N]Ti(NRAr)_3}, which at 25 °C loses a tert-butyl radical and isomerizes to give the final product, (^tBuO)(N)Mo{[μ-O]Ti(NRAr)_3}_2, isolated as an orange powder in 91% yield. Characterization of the latter diamagnetic complex included an ^(15)N NMR study. Attempts to displace a third tert-butyl radical by treatment of (^tBuO)(N)Mo{[μ-O]Ti(NRAr)_3}_2 with Ti(NRAr)_3 led to no reaction. Treatment of (^tBuO)(N)Mo{[μ-O]Ti(NRAr)_3}_2 with neat methyl iodide led to the isolation of (MeO)(N)Mo{[μ-O]Ti(NRAr)_3}_2 in 51% yield; ^(13)C and nitrido-^(15)N derivatives of this species were prepared for spectroscopic characterization. O_2Mo{[μ-O]Ti(^tBuNPh)_3}_2 was prepared in 59% yield upon treatment of MoO_2(O^tBu)_2 with 2 equiv of Ti(^tBuNPh)_3 in benzene at 65 °C. Full characterization of O_2Mo{[μ-O]Ti(^tBuNPh)_3}_2 included a single-crystal X-ray diffraction study. Previously reported (^iPrO)_3V[μ-O]Ti(NRAr)_3 was oxidized with ferrocenium triflate to give TfOTi(NRAr)_3 and OV(O^iPr)_3. TfOTi(NRAr)_3 was prepared independently in 80% yield by treatment of Ti(NRAr)_3 with ferrocenium triflate. (^iPrO)_3V[μ-O]Ti(NRAr)_3 is stable in the presence of methyl iodide. ITi(NRAr)_3 was prepared independently by treatment of Ti(NRAr)_3 with the stoichiometric amount of iodine. Paramagnetic (^tBuO)_3V[μ-O]Ti(NRAr)_3 was prepared as orange-brown needles in 94% yield and was found to be thermally stable. The relatively robust μ-nitrido compound (Me_2N)_3Mo[μ-N]Ti(^tBuNPh)_3, which was prepared in 77% isolated yield, showed no decomposition when heated in benzene at 70 °C for 13 h

Latent regulatory potential of human-specific repetitive elements

At least half of the human genome is derived from repetitive elements, which are often lineage specific and silenced by a variety of genetic and epigenetic mechanisms. Using a transchromosomic mouse strain that transmits an almost complete single copy of human chromosome 21 via the female germline, we show that a heterologous regulatory environment can transcriptionally activate transposon-derived human regulatory regions. In the mouse nucleus, hundreds of locations on human chromosome 21 newly associate with activating histone modifications in both somatic and germline tissues, and influence the gene expression of nearby transcripts. These regions are enriched with primate and human lineage-specific transposable elements, and their activation corresponds to changes in DNA methylation at CpG dinucleotides. This study reveals the latent regulatory potential of the repetitive human genome and illustrates the species specificity of mechanisms that control it

Effect of Vortex-Induced Physical Stress on Fluorescent Properties of Dye-Containing Poly(Ethylene Glycol)-Block-Poly(Lactic Acid) Micelles

The effect of vortex-induced mechanical stresses on the fluorescent properties of dye-containing poly(ethylene glycol)-block-poly(lactic acid) (PEG-b-PLA) block copolymer micelles has been investigated. PEG-b-PLA block copolymer micelles containing fluorescent dyes, 3,3′-dioctadecyloxacarbocyanine perchlorate (DiO) and/or 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI), are prepared by a simple one-step procedure that involves the self-assembly of block copolymers and spontaneous incorporation of hydrophobic dyes into the core of the micelles. Upon vortexing, the micelle dispersion samples showed a decrease in fluorescence intensity in a rotational speed- and time-dependent manner. The results demonstrated that the vortexing can alter the fluorescent properties of the dye-containing PEG-b-PLA block copolymer micelle dispersion samples, suggesting the potential utility of block copolymer micelles as a mechanical stress-responsive nanomaterial

Subband population in a single-wall carbon nanotube diode

We observe current rectification in a molecular diode consisting of a semiconducting single-wall carbon nanotube and an impurity. One half of the nanotube has no impurity, and it has a current-voltage (I-V) charcteristic of a typical semiconducting nanotube. The other half of the nanotube has the impurity on it, and its I-V characteristic is that of a diode. Current in the nanotube diode is carried by holes transported through the molecule's one-dimensional subbands. At 77 Kelvin we observe a step-wise increase in the current through the diode as a function of gate voltage, showing that we can control the number of occupied one-dimensional subbands through electrostatic doping.Comment: to appear in Physical Review Letters. 4 pages & 3 figure

Zebrafish promoter microarrays identify actively transcribed embryonic genes.

We have designed a zebrafish genomic microarray to identify DNA-protein interactions in the proximal promoter regions of over 11,000 zebrafish genes. Using these microarrays, together with chromatin immunoprecipitation with an antibody directed against tri-methylated lysine 4 of Histone H3, we demonstrate the feasibility of this method in zebrafish. This approach will allow investigators to determine the genomic binding locations of DNA interacting proteins during development and expedite the assembly of the genetic networks that regulate embryogenesis.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are