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The first-order hyperpolarizability β of magnetite nanoparticles in colloidal dispersion was measured in the presence and absence of an external magnetic field of magnitude H=800  G, applied with permanent neodymium magnets. For that, the (linear) attenuation spectrum was measured, and the nonlinear properties were obtained through the hyper-Rayleigh scattering technique. The attenuation spectrum is the same regardless of the external magnetic field, indicating that large aggregates of nanoparticles were not formed on our system. The first hyperpolarizability, on the other hand, increased when the incident beam polarization was parallel to the magnetic field lines and decreased when the directions were orthogonal, due to the alignment of crystallographic planes of the material when nanoparticles rotate in order to align their individual magnetic momentum, with respect to the external field. In the absence of a magnetic field, the hyperpolarizability β_H=0=8.5(1)×10^−28  cm^5/esu. For the parallel case, β_∥=9.8(2)×10^−28  cm^5/esu, while for the perpendicular configuration, β_⊥=8.1(1)×10^−28  cm^5/esu. Defining the x axis of the particle reference frame parallel to the ⟨111⟩ crystallographic direction, which corresponds to the direction of easy magnetization, β_∥=β_xxx, and β_⊥ corresponds to an average from β_yyy and β_zzz. When there is no external field applied, the nanoparticles are randomly oriented, and the measured hyperpolarizability corresponds to an average over the three orthogonal directions; that is, ⟨β_H⟩=13(β_∥+2β_⊥)=8.6(1)×10^−28  cm^5/esu, which is compatible with the measured value for the system without a magnetic field β_H=0.

High-energy particle accelerators have been crucial in providing a deeper understanding of fundamental particles and the forces that govern their interactions. To increase the energy of the particles or to reduce the size of the accelerator, new acceleration schemes need to be developed. Plasma wakefield acceleration1–5, in which the electrons in a plasma are excited, leading to strong electric fields (so called ‘wakefields’), is one such promising acceleration technique. Experiments have shown that an intense laser pulse6–9or electron bunch10,11traversing a plasma can drive electric fields of tens of gigavolts per metre and above—well beyond those achieved in conventional radio-frequency accelerators (about 0.1 gigavolt per metre). However, the low stored energy of laser pulses and electron bunches means that multiple acceleration stages are needed to reach very high particle energies5,12. The use of proton bunches is compelling because they have the potential to drive wakefields and to accelerate electrons to high energy in a single acceleration stage13. Long, thin proton bunches can be used because they undergo a process called self-modulation14–16, a particle–plasma interaction that splits the bunch longitudinally into a series of high-density microbunches, which then act resonantly to create large wakefields. The Advanced Wakefield (AWAKE) experiment at CERN17–19uses high-intensity proton bunches—in which each proton has an energy of 400 gigaelectronvolts, resulting in a total bunch energy of 19 kilojoules—to drive a wakefield in a ten-metre-long plasma. Electron bunches are then injected into this wakefield. Here we present measurements of electrons accelerated up to two gigaelectronvolts at the AWAKE experiment, in a demonstration of proton-driven plasma wakefield acceleration. Measurements were conducted under various plasma conditions and the acceleration was found to be consistent and reliable. The potential for this scheme to produce very high-energy electron bunches in a single accelerating stage20means that our results are an important step towards the development of future high-energy particle accelerators21,22.

Despite therapeutic advances, multiple myeloma remains incurable, with limited options for patients with refractory disease. We conducted a large, multi-cohort clinical trial testing various doses and treatment schedules of pomalidomide and dexamethasone (Pom/dex) in patients with refractory multiple myeloma. Overall, 345 patients were enrolled to six cohorts based on number and type of prior lines of therapy, pomalidomide dose and schedule. Median prior lines of therapy were three with near universal prior exposure to proteasome inhibitors and/or immunomodulatory drugs. A confirmed response rate of 35% was noted for all cohorts (range 23–65%) with higher responses in cohorts with fewer prior lines of therapy. Median time to confirmed response was ?2 months and the longest progression-free survival and overall survival seen in any cohort were 13.1 and 47.9 months, respectively. Observed adverse reactions were as expected, with myelosuppression and fatigue being the most common hematologic and non-hematologic adverse events (AEs), respectively. Longer durations of treatment and response, higher response rates and fewer AEs were noted with the 2?mg pomalidomide dose. This is the longest follow-up data for Pom/dex in refractory multiple myeloma and will help shape the real-world utilization of this regimen.

Little real-world evidence is available to describe the recent trends in treatment costs and outcomes for patients with multiple myeloma (MM). Using the Truven Health MarketScan Research Databases linked with social security administration death records, this study found that the percentage of MM patients using novel therapy continuously increased from 8.7% in 2000 to 61.3% in 2014. Compared with MM patients diagnosed in earlier years, those diagnosed after 2010 had higher rates of novel therapy use and better survival outcomes; patients diagnosed in 2012 were 1.25 times more likely to survive 2 years than those diagnosed in 2006. MM patients showed improved survival over the study period, with the 2-year survival gap between MM patients and matched controls decreasing at a rate of 3% per year. Total costs among MM patients have increased in all healthcare services over the years; however, the relative contribution of drug costs has remained fairly stable since 2009 despite new novel therapies coming to market. Findings from this study corroborate clinical data, suggesting a paradigm shift in MM treatment over the past decade that is associated with substantial survival gains. Future studies should focus on the impact on specific novel agents on patients’ outcomes.

Random regression models (RRM) and multitrait models (MTM) were used to estimate genetic parameters for growth traits in Brazilian Brahman cattle and to compare the estimated breeding values obtained by these 2 methodologies. For RRM, 78,641 weight records taken between 60 and 550 d of age from 16,204 cattle were analyzed, and for MTM, the analysis consisted of 17,385 weight records taken at the same ages from 12,925 cattle. All models included the fixed effects of contemporary group and the additive genetic, maternal genetic, and animal permanent environmental effects and the quadratic effect of age at calving (AAC) as covariate. For RRM, the AAC was nested in the animal's age class. The best RRM considered cubic polynomials and the residual variance heterogeneity (5 levels). For MTM, the weights were adjusted for standard ages. For RRM, additive heritability estimates ranged from 0.42 to 0.75, and for MTM, the estimates ranged from 0.44 to 0.72 for both models at 60, 120, 205, 365, and 550 d of age. The maximum maternal heritability estimate (0.08) was at 140 d for RRM, but for MTM, it was highest at weaning (0.09). The magnitude of the genetic correlations was generally from moderate to high. The RRM adequately modeled changes in variance or covariance with age, and provided there was sufficient number of samples, increased accuracy in the estimation of the genetic parameters can be expected. Correlation of bull classifications were different in both methods and at all the ages evaluated, especially at high selection intensities, which could affect the response to selection.

This study was designed to estimate genetic parameters for the following traits of Brahman cattle in Brazil: age at first calving (AFC), calving interval (CI), rebreeding (REB), and stayability (STAY). For REB, the value 1 was assigned to heifers that rebred and calved after first calving and the value 0 was assigned to heifers that failed to rebreed after first calving. Likewise, for STAY, the value 1 was assigned to cows that calved at least 3 times by the time they reach 6 yr of age; otherwise, the value 0 was assigned. A bivariate analysis was used to estimate covariances components by using linear animal model for CI and AFC and threshold animal model for REB and STAY. The mean h2were 0.10, 0.02, 0.22, and 0.10 for AFC, CI, REB, and STAY, respectively. The genetic correlations were –0.13 between AFC and CI, –0.35 between AFC and REB, –0.57 between AFC and STAY, and 0.32 between REB and STAY, which reveal that cows that remain productive for longer periods in the herd also start breeding younger and present greater chances to REB. The selection of Brahman cattle for reproductive traits, such as AFC, CI, REB, and STAY, will render low magnitude and long-term responses.

Root architecture is strongly linked to plant survival under abiotic and biotic stress conditions. The objective of this study was to investigate the inheritance of the primary root system complexity in maize (Zea maysL.). For a total of 231 recombinant inbred lines (RIL) derived from the IBM (B73×Mo17) population multiple primary root systems were produced by applying a replicated alpha lattice experimental design. Digital images of each root system were taken at days four and eight after germination. For each root system image, the fractal dimension (FD) was computed. Significant differences between RILs were found in the FD calculated after four (FD1) and eight (FD2) days. For FD1 22 QTLs, for FD2 13, and for FD change over time (ΔFD) 12 QTLs were found on all ten maize chromosomes explaining between 24.6 and 46.8% of the phenotypic variation. Both parental inbreds contributed FD-increasing QTL alleles. FD1 and FD2 had five chromosomal BIN locations in common. Four unique QTLs were identified for the dynamics of root growth between days four and eight. Maize root mutants involved in root morphology were located in chromosomal BINs carrying QTLs for FD1 or FD2. This study demonstrated the usefulness of the IBM population as a maize community resource to investigate the genetic basis of root complexity in maize.

We discuss here some of the physical problems related to the recently proposed scheme for solar sailing, using an artificial magnetosphere. We will concentrate on the forces acting on the plasma bubble, and their transfer to the spacecraft. Upper and lower limits of the force acting on the bubble are established. The results of test particle dynamics are presented, concerning the interaction of the solar wind with the modified magnetic dipole resulting from the spacecraft coils and the plasma expansion. Propagation of the forces along the magnetic flux tubes, from the bubble magnetopause down to the spacecraft vicinity, is discussed by using a simple MHD theoretical model. Emphasis is made on the distribution of currents flowing in the immediate vicinity of the spacecraft. Finally, results of PIC code simulations of the magnetized plasma expansion are presented and an overall qualitative picture of the physical processes is given, with a discussion of the strategy for obtaining more quantitative estimates of the magnetospheric propulsion efficiency.

Various protonic zeolites (H‐Y, H‐ZSM‐5, and H‐MOR) were tested for the total combustion of dichloromethane (DCM) as a model reaction for the catalytic destruction of chlorinated organic pollutants. The order of catalytic activity decreased in the following order: H‐MOR > H‐ZSM‐5 > H‐Y. Strong Brønsted acidity played a determining role in controlling the active catalytic behavior as revealed by TPD of ammonia and IR measurements of adsorbed pyridine. DCM oxidative decomposition gave rise to CO and HCl as main products along with small amounts of CO2 and Cl2. In addition, methyl chloride was detected as a reaction intermediate between 250 and 500°C. The presence of water in the feed stream led to an inhibition of the zeolite activity and resulted in a noticeable change in the reaction product distribution. Water effectively promoted the selectivity toward environmentally desirable reaction products, that is, HCl and CO2, and completely suppressed the formation of methyl chloride.

Several H-zeolites (H-Y, H-ZSM-5 and H-MOR) were investigated for the catalytic combustion of chlorinated ethylenes, namely 1,1-dichloroethylene and trichloroethylene. Conversion was inversely related to the chlorine content of the feed molecule. H-ZSM-5 zeolite was the most active catalyst in 1,1-dichloroethylene combustion whereas H-MOR was the most effective zeolite for trichloroethylene destruction. Temperature-programmed desorption of ammonia and diffuse reflectance FT-IR measurements of adsorbed pyridine revealed that strong Brønsted acidity plays an important role in controlling the activity of H-zeolites. The main combustion products were CO, CO₂, HCl, and Cl₂. Additionally, small amounts of highly chlorinated by-products were also detected, namely trichloroethylene and tetrachloroethylene. H-zeolites showed a great selectivity to HCl formation.
© 2002 Society of Chemical Industry

Cells of Rhodococcus erythropolis DCL14 present a limonene epoxide hydrolase activity when grown on terpenes, which enables them to convert cis-limonene-1,2-epoxide to limonene-1, 2-diol. Trans-limonene-1,2-epoxide is only converted when no cis is present. An organic/aqueous system was developed to overcome the low solubility and instability of limonene-1,2-epoxide in the aqueous phase. The presence of the organic solvent allowed high epoxide concentrations to be used which resulted in high limonene-1,2-diol production rates. Relatively cheap solvents were tested without any significant loss of epoxide hydrolase activity. Using a 500 ml fed-batch mechanically stirred reactor it was possible to produce 197.2 g of diol per g of protein and to obtain a yield of 98.2% and 67.9% for the trans-epoxide and the diol, respectively. Production of 72.4 g of diol per g of protein was obtained using a magnetically stirred reactor with an external loop for product separation. In this case, trans-epoxide and diol yields were 98.5% and 94.1%, respectively.A downstream process, based both on the preference of the substrate for organic solvents and that of the product for the aqueous phase, allowed the recovery of limonene- 1,2-diol, as well as of the trans-epoxide, with a purity higher than 99%.

We identified 24 cases of multiple myeloma with the t(11;14)(q13;q32). In 22 cases, the t(11;14)(q13;q32) was part of a complex karyotype, and in 2 cases it was an isolated abnormality. All patients had clinical and laboratory features consistent with multiple myeloma. The median degree of plasma cell involvement in the bone marrow was 60%, and in 10 cases, the plasma cells had a lymphoplasmacytoid appearance. Of the 24 cases, 21 had intermediate or high proliferative rates based on labeling index studies. Immunohistochemical studies performed on all bone marrow biopsy specimens showed strong cyclin D1 nuclear positivity in 19 cases. There also was strong cyclin D1 nuclear positivity found in 6 of 30 additional cases without the t(11;14)(q13;q32) demonstrated by routine cytogenetics. The t(11;14)(q13;q32) in multiple myeloma results in overexpression of the cyclin D1 protein, which can be demonstrated by immunohistochemical stain. The cyclin D1 stain results in the additional cases of multiple myeloma suggest that the t(11;14)(q13;q32) may be more common than previously thought and may be missed by routine cytogenetics, particularly if the proliferative rate is low.

Hexagonal phase (H(II))-preferring lipids such as phosphatidate, cardiolipin, and phosphatidylserine form nonbilayer molecular arrangements in lipid bilayers. While their presence in biological membranes has not been established, in vitro studies suggest that alterations in membrane properties modify their function. In this study, antiphospholipid monoclonal antibodies were developed against nonbilayer structures. One of the monoclonal antibodies identifies nonplanar surfaces in liposomes and in membranes of cultured cells. These results are the first evidence that natural membranes maintain a fragile balance between bilayer and nonbilayer lipid arrangements. Therefore, these antibodies can be used to evaluate the role of H(II)-preferring lipids in the modulation of membrane activities. Our studies demonstrated that nonplanar surfaces are highly immunogenic. Although these structures are normally transient, their formation can be stabilized by temperature variations, drugs, antibiotics, apolar peptides, and divalent cations. Our studies demonstrated that abnormal exposure of nonbilayer arrangements may induce autoimmune responses as found in the antiphospholipid syndrome.

Strains of Escherichia coli that host a plasmid that codes for the heat-stable (ST) enterotoxin showed 160 times more extracellular enterotoxin than intracellular activity. However, when washed bacteria were sonicated and incubated at between 50 and 85 degrees C, an activity similar to that of the ST enterotoxin was detected. No such effect was present in strains lacking the plasmid, in a plasmid ST- mutant, or in chromosomal mutants that lack a cyclic AMP-linked positive regulatory system which previously were shown to yield an ST- phenotype. The thermoactivation was inhibited by iodoacetamide and N-ethylmaleimide; chloramphenicol did not affect the phenomenon. The heat-activated ST-like enterotoxin was localized in the periplasmic space. The results are discussed in relation to the export of the toxin from the periplasm to the outside of the cell.

Analyte transport of both aqueous solutions and slurry samples was studied with the use of ultrasonic slurry sampling electrothermal vaporization inductively coupled plasma mass spectrometry (USS-ETV-ICP-MS). The elements studied included V, Mn, Ni, Cu, and Pb, and the materials analyzed included NIST SRM 1548 Total Diet, SRM 1632a Coal, SRM 1566a Oyster Tissue, and NRCC LUTS-1 Lobster Hepatopancreas. The effect of microgram amounts of Pd as well as the effect of oxygen ashing on analyte transport were studied. Slurry samples were found to have better analyte transport in comparison to aqueous solutions when no physical carriers were added. Under these experimental conditions, the determined slurry concentrations were apparently high when quantified with the use of external calibration. Microgram amounts of Pd were used to investigate whether it was possible to reduce the difference in analyte transport between slurry samples and aqueous standards. The use of microgram amounts of Pd resulted in signal intensity suppression. Such a signal reduction could be related to the presence of space charge effects or losses of analyte due to condensation of the physical carrier together with the analyte on different parts of the ETV cell or the transfer line. On the other hand, quantitation for slurry samples was improved by the use of Pd as a physical carrier. Pd by itself was not completely effective for samples with high carbon content; therefore the effect of oxygen ashing combined with Pd was studied. An enhancement of signal intensities was observed when oxygen ashing was used, as well as a shift in the carbon signal to earlier times. In this case, signal enhancement was associated with an improvement in analyte transport caused by an increased number of carbon particles leaving the furnace at the same time as the analytes studied. With oxygen ashing, slurry samples behaved more similarly to aqueous solutions, facilitating quantitation with aqueous standards.

Oxygen ashing has been used in electrothermal atomic absorption spectroscopy to eliminate organic matrix sample components and is particularly useful when doing direct solids analysis of biologicals using ultrasonic slurry sampling. Oxygen ashing has also proven to be useful for the analysis of slurry samples using ultrasonic slurry sampling electrothermal vaporization inductively coupled plasma mass spectrometry (USS-ETV-ICP-MS). In this work, the effect of oxygen ashing on analyte transport in USS-ETV-ICP-MS was evaluated. Oxygen ashing in the presence of Pd modifier (Pd/O2) enhances analyte transport efficiency, possibly as a result of an increase in the number of carbon particles present in the graphite furnace during the vaporization step. These carbon particles act as a physical carrier, providing a surface on which the analytes can condense to be transported more efficiently. The carbon produced at earlier times, with Pd/O2, may be the result of either dissociation or fracture of the graphite during the rapid heating of the furnace. Pd, which was initially added to act as a physical carrier, also seems to be acting as a catalyst for carbon oxidation. The shift in the carbon signal toward earlier times when using oxygen ashing was observed only when Pd was present. In addition, scanning electron micrographs of a home-made graphite platform revealed that portions of the graphite substrate were missing when Pd/O2was used and that clearly visible pits were found in the graphite. Oxygen ashing combined with 1 μg Pd improves quantitative results by removing the organic part of the matrix present in slurry samples while enhancing analyte transport efficiency by providing carbon particles that serve as a physical carrier.

Chromogranin polypeptides of Mr 100,000, Mr 85,000, Mr 75,000, and Mr 65,000 have been detected in adrenal medulla chromaffin granules using anti-chromogranin antiserum. Monoclonal antibodies to this protein also detect the multiple molecular weight chromogranin polypeptides. Analysis of phosphorylated amino acids gives a value of 5 phosphoserine residues/mol of Mr 75,000 chromogranin polypeptide. Immunological analysis of dephosphorylated chromogranin shows that the anti-chromogranin serum reacts with both the phosphorylated and unphosphorylated forms of the protein. Each of the chromogranin polypeptides has been isolated using a combination of DEAE-cellulose chromatography and reverse phase high pressure liquid chromatography. Sequencer analysis of each protein revealed a high degree of amino acid identities at the amino terminal of these proteins. Amino-terminal Sequencer analysis of chromogranin fragments also provides evidence for a gene duplication event. Preliminary studies also show that chromogranin may be degraded in the chromaffin granules by a calcium-dependent mechanism.

Recent upward reevaluation of Canadian peat resources has renewed the interest in its possible use as a source of energy. Attention is focused on the eventual transformation of peat into heavy liquid fuels by taking advantage of the cleavage ability and the hydrogenation characteristics of carbon monoxide in the presence of liquid water. Yields of benzene soluble materials as high as 54% (maf peat) have been obtained in our batch autoclave experiments carried out at 350 – 360°C, 10.3 MPa (cold pressure) and up to 120 min as reaction time. Catalytic action by alkali seems to enhance the conversion of the humic materials present in peat. The work also relates to the dewatering of peat, since the conversion is carried out in the presence of water thus eliminating the need for the drying steps prior to the processing of the peat material. Une récente réévaluation à la hausse des ressources canadiennes en tourbe a renouvelé l'intérêt dans l'emploi possible de celle ci comme source d'énergie. L'attention se porte surtout sur l'éventuelle transformation de la tourbe en combustibles liquides et lourds, en mettant à profit la capacité de clivage et les caractéristiques d'hydrogénation que possède le monoxyde de carbonne en présence de l'eau à l'état liquide. Dans des expériences, discontinues eu autoclave, faites à une température variant entre 350°C et 360°C, une pression absolue (à froid) de 10.3 MP et un temps de réaction allant jusqu'à 120 minutes, on a obtenu des rendements atteignant 54% en matières solubles dans le benzène. L'action catalytique des alcali semble promouvoir la transformation des matières humiques présentes dans la tourbe. On traite aussi, dans le présent travail, de la déshydratation de la tourbe, étant donné que la transformation se fait en présence d'eau, ce qui élimine la nécessité de sécher la tourbe avant de la traiter.

In an Escherichia coli strain of human origin, ampicillin resistance and heat-stable enterotoxin activity were shown by EcoRI restriction endonuclease and genetic analysis to be in an 80-megadalton plasmid.