Assessment of crash fire hazard of LH sub 2 fueled aircraft

The relative safety of passengers in LH2 - fueled aircraft, as well as the safety of people in areas surrounding a crash scene, has been evaluated in an analytical study. Four representative circumstances were postulated involving a transport aircraft in which varying degrees of severity of damage were sustained. Potential hazard to the passengers and to the surroundings posed by the spilled fuel was evaluated for each circumstance. Corresponding aircraft fueled with liquid methane, Jet A, and JP-4 were also studied in order to make comparisons of the relative safety. The four scenarios which were used to provide a basis for the evaluation included: (1) a small fuel leak internal to the aircraft, (2) a survivable crash in which a significant quantity of fuel is spilled in a radial pattern as a result of impact with a stationary object while taxiing at fairly low speed, (3) a survivable crash in which a significant quantity of fuel is spilled in an axial pattern as a result of impact during landing, and (4) a non-survivable crash in which a massive fuel spill occurs instantaneously

Transport composite fuselage technology: Impact dynamics and acoustic transmission

A program was performed to develop and demonstrate the impact dynamics and acoustic transmission technology for a composite fuselage which meets the design requirements of a 1990 large transport aircraft without substantial weight and cost penalties. The program developed the analytical methodology for the prediction of acoustic transmission behavior of advanced composite stiffened shell structures. The methodology predicted that the interior noise level in a composite fuselage due to turbulent boundary layer will be less than in a comparable aluminum fuselage. The verification of these analyses will be performed by NASA Langley Research Center using a composite fuselage shell fabricated by filament winding. The program also developed analytical methodology for the prediction of the impact dynamics behavior of lower fuselage structure constructed with composite materials. Development tests were performed to demonstrate that the composite structure designed to the same operating load requirement can have at least the same energy absorption capability as aluminum structure

Discovery of FNDR-20123, a histone deacetylase inhibitor for the treatment of Plasmodium falciparum malaria

BACKGROUND: Emergence of anti-malarial drug resistance and perpetual increase in malaria incidence necessitates the development of novel anti-malarials. Histone deacetylases (HDAC) has been shown to be a promising target for malaria, despite this, there are no HDAC inhibitors in clinical trials for malaria treatment. This can be attributed to the poor pharmacokinetics, bioavailability and selectivity of the HDAC inhibitors. METHODS: A collection of HDAC inhibitors were screened for anti-malarial activity, and the best candidate was profiled in parasite-killing kinetics, growth inhibition of sensitive and multi-drug resistant (MDR) strains and against gametocytes. Absorption, distribution, metabolism and excretion pharmacokinetics (ADME-PK) parameters of FNDR-20123 were determined, and in vivo efficacy was studied in a mouse model for Plasmodium falciparum infection. RESULTS: A compound library of HDAC inhibitors (180 in number) was screened for anti-malarial activity, of which FNDR-20123 was the most potent candidate. The compound had been shown to inhibit Plasmodium HDAC with IC50 of 31 nM and human HDAC with IC50 of 3 nM. The IC50 obtained for P. falciparum in asexual blood-stage assay was 42 nM. When compared to atovaquone and pyrimethamine, the killing profiles of FNDR-20123 were better than atovaquone and comparable to pyrimethamine. The IC50 values for the growth inhibition of sensitive and MDR strains were similar, indicating that there is no cross-resistance and a low risk of resistance development. The selected compound was also active against gametocytes, indicating a potential for transmission control: IC50 values being 190 nM for male and > 5 microM for female gametocytes. FNDR-20123 is a stable candidate in human/mouse/rat liver microsomes (> 75% remaining post 2-h incubation), exhibits low plasma protein binding (57% in humans) with no human Ether-a-go-go-Related Gene (hERG) liability (> 100 microM), and does not inhibit any of the cytochrome P450 (CYP) isoforms tested (IC50 > 25 microM). It also shows negligible cytotoxicity to HepG-2 and THP-1 cell lines. The oral pharmacokinetics in rats at 100 mg/kg body weight shows good exposures (Cmax = 1.1 microM) and half-life (T1/2 = 5.5 h). Furthermore, a 14-day toxicokinetic study at 100 mg/kg daily dose did not show any abnormality in body weight or gross organ pathology. FNDR-20123 is also able to reduce parasitaemia significantly in a mouse model for P. falciparum infection when dosed orally and subcutaneously. CONCLUSION: FNDR-20123 may be a suitable candidate for the treatment of malaria, which can be further developed

Complex microwave conductivity of Na-DNA powders

We report the complex microwave conductivity, $\sigma=\sigma_1-i\sigma_2$, of Na-DNA powders, which was measured from 80 K to 300 K by using a microwave cavity perturbation technique. We found that the magnitude of $\sigma_1$ near room temperature was much larger than the contribution of the surrounding water molecules, and that the decrease of $\sigma_1$ with decreasing temperature was sufficiently stronger than that of the conduction of counterions. These results clearly suggest that the electrical conduction of Na-DNA is intrinsically semiconductive.Comment: 16 pages, 7 figure

Arylmethylamino steroids as antiparasitic agents

In search of antiparasitic agents, we here identify arylmethylamino steroids as potent compounds and characterize more than 60 derivatives. The lead compound 1o is fast acting and highly active against intraerythrocytic stages of chloroquine-sensitive and resistant Plasmodium falciparum parasites (IC50 1–5?nM) as well as against gametocytes. In P. berghei-infected mice, oral administration of 1o drastically reduces parasitaemia and cures the animals. Furthermore, 1o efficiently blocks parasite transmission from mice to mosquitoes. The steroid compounds show low cytotoxicity in mammalian cells and do not induce acute toxicity symptoms in mice. Moreover, 1o has a remarkable activity against the blood-feeding trematode parasite Schistosoma mansoni. The steroid and the hydroxyarylmethylamino moieties are essential for antimalarial activity supporting a chelate-based quinone methide mechanism involving metal or haem bioactivation. This study identifies chemical scaffolds that are rapidly internalized into blood-feeding parasites

Influence of substitutional disorder on the electrical transport and the superconducting properties of Fe1+z_{1+z}Te1−x−y_{1-x-y}Sex_{x}Sy_{y}

We have carried out an investigation of the structural, magnetic, transport and superconducting properties of Fe$_{1+z}$Te$_{1-x-y}$Se$_x$S$_y$ ceramic compounds, for $z=0$ and some specific Se (0$\leq$ x $\leq$ 0.5) and S (0 $\leq$ y $\leq$0.12) contents. The incorporation of Se and S to the FeTe structure produces a progressive reduction of the crystallographic parameters as well as different degrees of structural disorder associated with the differences of the ionic radius of the substituting cations. In the present study, we measure transport properties of this family of compounds and we show the direct influence of disorder in the normal and superconductor states. We notice that the structural disorder correlates with a variable range hopping conducting regime observed at temperatures $T >$ 200 K. At lower temperatures, all the samples except the one with the highest degree of disorder show a crossover to a metallic-like regime, probably related to the transport of resilient-quasi-particles associated with the proximity of a Fermi liquid state at temperatures below the superconducting transition. Moreover, the superconducting properties are depressed only for that particular sample, in accordance to the condition that superconductivity is affected by disorder when the electronic localization length $\xi_L$ becomes smaller than the coherence length $\xi_{SC}$.Comment: 23 pages, 9 figure

The anomaly of the oxygen bond-bending mode at 320 cm−1^{-1} and the additional absorption peak in the c-axis infrared conductivity of underdoped YBa2_{2}Cu3_{3}O7−δ_{7-\delta} single crystals revisited by ellipsometricmeasurements

We have performed ellipsometric measurements of the far-infrared c-axis dielectric response of underdoped YBa$_{2}$Cu$_{3}$O$_{7-\delta}$ single crystals. Here we report a detailed analysis of the temperature-dependent renormalization of the oxygen bending phonon mode at 320 cm$^{-1}$ and the formation of the additional absorption peak around 400-500 cm$^{-1}$. For a strongly underdoped YBa$_{2}$Cu$_{3}$O$_{6.5}$ crystal with T$_{c}$=52 K we find that, in agreement with previous reports based on conventional reflection measurements, the gradual onset of both features occurs well above T$_{c}$ at T*$\sim$150 K. Contrary to some of these reports, however, our data establish that the phonon anomaly and the formation of the additional peak exhibit very pronounced and steep changes right at T$_{c}$. For a less underdoped YBa$_{2}$Cu$_{3}$O$_{6.75}$ crystal with T$_{c}$=80 K, the onset temperature of the phonon anomaly almost coincides with T$_{c}$. Also in contrast to some previous reports, we find for both crystals that a sizeable fraction of the spectral weight of the additional absorption peak cannot be accounted for by the spectral-weight loss of the phonon modes but instead arises from a redistribution of the electronic continuum. Our ellipsometric data are consistent with a model where the bilayer cuprate compounds are treated as a superlattice of intra- and inter-bilayer Josephson-junctions

The Parasite Reduction Ratio (PRR) assay version 2: standardized assessment of Plasmodium falciparum viability after antimalarial treatment in vitro

With artemisinin-resistant Plasmodium falciparum parasites emerging in Africa, the need for new antimalarial chemotypes is persistently high. The ideal pharmacodynamic parameters of a candidate drug are a rapid onset of action and a fast rate of parasite killing or clearance. To determine these parameters, it is essential to discriminate viable from nonviable parasites, which is complicated by the fact that viable parasites can be metabolically inactive, whilst dying parasites can still be metabolically active and morphologically unaffected. Standard growth inhibition assays, read out via microscopy or [3H] hypoxanthine incorporation, cannot reliably discriminate between viable and nonviable parasites. Conversely, the in vitro parasite reduction ratio (PRR) assay is able to measure viable parasites with high sensitivity. It provides valuable pharmacodynamic parameters, such as PRR, 99.9% parasite clearance time (PCT99.9%) and lag phase. Here we report the development of the PRR assay version 2 (V2), which comes with a shorter assay duration, optimized quality controls and an objective, automated analysis pipeline that systematically estimates PRR, PCT99.9% and lag time and returns meaningful secondary parameters such as the maximal killing rate of a drug (Emax) at the assayed concentration. These parameters can be fed directly into pharmacokinetic/pharmacodynamic models, hence aiding and standardizing lead selection, optimization, and dose prediction. © 2023 by the authors

Search for time-dependent B0s - B0s-bar oscillations using a vertex charge dipole technique

We report a search for B0s - B0s-bar oscillations using a sample of 400,000 hadronic Z0 decays collected by the SLD experiment. The analysis takes advantage of the electron beam polarization as well as information from the hemisphere opposite that of the reconstructed B decay to tag the B production flavor. The excellent resolution provided by the pixel CCD vertex detector is exploited to cleanly reconstruct both B and cascade D decay vertices, and tag the B decay flavor from the charge difference between them. We exclude the following values of the B0s - B0s-bar oscillation frequency: Delta m_s < 4.9 ps-1 and 7.9 < Delta m_s < 10.3 ps-1 at the 95% confidence level.Comment: 18 pages, 3 figures, replaced by version accepted for publication in Phys.Rev.D; results differ slightly from first versio

Measurement of the branching ratios of the Z0 into heavy quarks

We measure the hadronic branching ratios of the Z0 boson into heavy quarks: Rb=Gamma(Z0->bb)/Gamma(Z0->hadrons) and Rc=Gamma(Z0->cc/Gamma(Z0->hadrons) using a multi-tag technique. The measurement was performed using about 400,000 hadronic Z0 events recorded in the SLD experiment at SLAC between 1996 and 1998. The small and stable SLC beam spot and the CCD-based vertex detector were used to reconstruct bottom and charm hadron decay vertices with high efficiency and purity, which enables us to measure most efficiencies from data. We obtain, Rb=0.21604 +- 0.00098(stat.) +- 0.00073(syst.) -+ 0.00012(Rc) and, Rc= 0.1744 +- 0.0031(stat.) +- 0.0020(syst.) -+ 0.0006(Rb)Comment: 37 pages, 8 figures, to be submitted to Phys. Rev. D version 2: changed title to ratios, used common D production fractions for Rb and Rc and corrected Zgamma interference. Identical to PRD submissio