Repeat doses of antibody to serum amyloid P component clear amyloid deposits in patients with systemic amyloidosis

Systemic amyloidosis is a fatal disorder caused by pathological extracellular deposits of amyloid fibrils that are always coated with the normal plasma protein, serum amyloid P component (SAP). The small-molecule drug, miridesap, [(R)-1-[6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC)] depletes circulating SAP but leaves some SAP in amyloid deposits. This residual SAP is a specific target for dezamizumab, a fully humanized monoclonal IgG1 anti-SAP antibody that triggers immunotherapeutic clearance of amyloid. We report the safety, pharmacokinetics, and dose-response effects of up to three cycles of miridesap followed by dezamizumab in 23 adult subjects with systemic amyloidosis (ClinicalTrials.gov identifier: NCT01777243). Amyloid load was measured scintigraphically by amyloid-specific radioligand binding of 123I-labeled SAP or of 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid. Organ extracellular volume was measured by equilibrium magnetic resonance imaging and liver stiffness by transient elastography. The treatment was well tolerated with the main adverse event being self-limiting early onset rashes after higher antibody doses related to whole body amyloid load. Progressive dose-related clearance of hepatic amyloid was associated with improved liver function tests. 123I-SAP scintigraphy confirmed amyloid removal from the spleen and kidneys. No adverse cardiac events attributable to the intervention occurred in the six subjects with cardiac amyloidosis. Amyloid load reduction by miridesap treatment followed by dezamizumab has the potential to improve management and outcome in systemic amyloidosis

Cavity Induced Interfacing of Atoms and Light

This chapter introduces cavity-based light-matter quantum interfaces, with a single atom or ion in strong coupling to a high-finesse optical cavity. We discuss the deterministic generation of indistinguishable single photons from these systems; the atom-photon entanglement intractably linked to this process; and the information encoding using spatio-temporal modes within these photons. Furthermore, we show how to establish a time-reversal of the aforementioned emission process to use a coupled atom-cavity system as a quantum memory. Along the line, we also discuss the performance and characterisation of cavity photons in elementary linear-optics arrangements with single beam splitters for quantum-homodyne measurements.Comment: to appear as a book chapter in a compilation "Engineering the Atom-Photon Interaction" published by Springer in 2015, edited by A. Predojevic and M. W. Mitchel

Second-hand smoke in four English prisons: an air quality monitoring study

BACKGROUND: To measure levels of indoor pollution in relation to smoking in four English prisons. METHODS: TSI SidePak AM510 Personal Aerosol Monitors were used to measure concentrations of particulate matter less than 2.5 mum in diameter (PM2.5) for periods of up to 9 h in selected smoking and non-smoking areas, and personal exposure monitoring of prison staff during a work shift, in four prisons. RESULTS: PM2.5 data were collected for average periods of 6.5 h from 48 locations on 25 wing landings where smoking was permitted in cells, on 5 non-smoking wings, 13 prisoner cells, and personal monitoring of 22 staff members. Arithmetic mean PM2.5 concentrations were significantly higher on smoking than non-smoking wing landings (43.9 mug/m(3) and 5.9 mug/m(3) respectively, p < 0.001) and in smoking than non-smoking cells (226.2 mug/m(3) and 17.0 mug/m(3) respectively, p < 0.001). Staff members wore monitors for an average of 4.18 h, during which they were exposed to arithmetic mean PM2.5 concentration of 23.5 mug/m(3). CONCLUSIONS: The concentration of PM2.5 pollution in smoking areas of prisons are extremely high. Smoking in prisons therefore represents a significant health hazard to prisoners and staff members

QTLs for oil yield components in an elite oil palm (Elaeis guineensis) cross

Increased modern farming of superior types of the oil palm, Elaeis guineensis Jacq., which has naturally efficient oil biosynthesis, has made it the world’s foremost edible oil crop. Breeding improvement is, however, circumscribed by time and costs associated with the tree’s long reproductive cycle, large size and 10–15 years of field testing. Marker-assisted breeding has considerable potential for improving this crop. Towards this, quantitative trait loci (QTL) linked to oil yield component traits were mapped in a high-yield population. In total, 164 QTLs associated with 21 oil yield component traits were discovered, with cumulative QTL effects increasing in tandem with the number of QTL markers and matching the QT+ alleles for each trait. The QTLs confirmed all traits to be polygenic, with many genes of individual small effects on independent loci, but epistatic interactions are not ruled out. Furthermore, several QTLs maybe pleiotropic as suggested by QTL clustering of inter-related traits on almost all linkage groups. Certain regions of the chromosomes seem richer in the genes affecting a particular yield component trait and likely encompass pleiotropic, epistatic and heterotic effects. A large proportion of the identified additive effects from QTLs may actually arise from genic interactions between loci. Comparisons with previous mapping studies show that most of the QTLs were for similar traits and shared similar marker intervals on the same linkage groups. Practical applications for such QTLs in marker-assisted breeding will require seeking them out in different genetic backgrounds and environments

Hindered rolling and friction anisotropy in supported carbon nanotubes

Carbon nanotubes (CNTs) are well known for their exceptional thermal, mechanical and electrical properties. For many CNT applications it is of the foremost importance to know their frictional properties. However, very little is known about the frictional forces between an individual nanotube and a substrate or tip. Here, we present a combined theoretical and experimental study of the frictional forces encountered by a nanosize tip sliding on top of a supported multiwall CNT along a direction parallel or transverse to the CNT axis. Surprisingly, we find a higher friction coefficient in the transverse direction compared with the parallel direction. This behaviour is explained by a simulation showing that transverse friction elicits a soft 'hindered rolling' of the tube and a frictional dissipation that is absent, or partially absent for chiral CNTs, when the tip slides parallel to the CNT axis. Our findings can help in developing better strategies for large-scale CNT assembling and sorting on a surface.Comment: 8 pages, 5 figure

Dynamics of Wind Setdown at Suez and the Eastern Nile Delta

BACKGROUND: Wind setdown is the drop in water level caused by wind stress acting on the surface of a body of water for an extended period of time. As the wind blows, water recedes from the upwind shore and exposes terrain that was formerly underwater. Previous researchers have suggested wind setdown as a possible hydrodynamic explanation for Moses crossing the Red Sea, as described in Exodus 14. METHODOLOGY/PRINCIPAL FINDINGS: This study analyzes the hydrodynamic mechanism proposed by earlier studies, focusing on the time needed to reach a steady-state solution. In addition, the authors investigate a site in the eastern Nile delta, where the ancient Pelusiac branch of the Nile once flowed into a coastal lagoon then known as the Lake of Tanis. We conduct a satellite and modeling survey to analyze this location, using geological evidence of the ancient bathymetry and a historical description of a strong wind event in 1882. A suite of model experiments are performed to demonstrate a new hydrodynamic mechanism that can cause an angular body of water to divide under wind stress, and to test the behavior of our study location and reconstructed topography. CONCLUSIONS/SIGNIFICANCE: Under a uniform 28 m/s easterly wind forcing in the reconstructed model basin, the ocean model produces an area of exposed mud flats where the river mouth opens into the lake. This land bridge is 3-4 km long and 5 km wide, and it remains open for 4 hours. Model results indicate that navigation in shallow-water harbors can be significantly curtailed by wind setdown when strong winds blow offshore

Comparative maturation of cynomolgus monkey oocytes in vivo and in vitro

BACKGROUND: In vitro maturation (IVM) of oocytes followed by fertilization in vitro (IVF) and embryo transfer offers an alternative to conventional IVF treatment that minimises drug administration and avoids ovarian hyperstimulation. However, the technique is less efficient than maturation in vivo. In the present study, a non-human primate model was used to address the hypothesis that the number of oocytes is increased and their nuclear and cytoplasmic maturity after IVM are improved when maturation is initiated in vivo by priming with hCG. METHODS: Young, adult cynomolgus monkeys were given recombinant human (rh) gonadotropins to stimulate the development of multiple follicles, and oocytes were aspirated 0, 12, 24, or 36 h after injection of an ovulatory dose of rhCG. The nuclear status of oocytes was determined at the time of recovery and after culture for a total elapsed time of 40–44 hours after hCG. RESULTS: Priming with hCG significantly increased the number of oocytes harvested, especially after delaying aspiration for 24 h or longer. Nuclear maturation after the full period in culture was also enhanced by priming: 71.5, 83.6, and 94.6% of oocytes collected at 0, 12, and 24 h hCG had progressed to MII by the end of the culture period, compared to 87.8% of oocytes that were retrieved at 36 h. A large proportion of oocytes reaching the MII stage had either or both abnormal spindles (>40%) and misaligned chromosomes (>60%), judging by immunofluorescence microscopy, but these abnormalities were independent of culture time. The mitochondria were evenly distributed throughout the cytoplasm at all stages of maturation. Importantly, there was no microscopic evidence that the duration of culture had any injurious effects on the cells. CONCLUSION: In conclusion, the evidence supports this non-human primate as a model for human IVM and the practice of priming with hCG to promote developmental potential

Mismatch negativity generation in the human 5HT2A agonist and NMDA antagonist model of psychosis

RATIONALE: Many studies have reported deficits of mismatch negativity (MMN) in schizophrenic patients. Pharmacological challenges with hallucinogens in healthy humans are used as models for psychotic states. Previous studies reported a significant reduction of MMN after ketamine (N-methyl-D-aspartate acid [NMDA] antagonist model) but not after psilocybin (5HT2A agonist model). OBJECTIVES: The aim of the present study was to directly compare the two models of psychosis using an intraindividual crossover design. MATERIALS AND METHODS: Fifteen healthy subjects participated in a randomized, double-blind, crossover study with a low and a high dose of the 5HT2A agonist dimethyltryptamine (DMT) and the NMDA antagonist S-ketamine. During electroencephalographic recording, the subjects were performing the AX-version of a continuous performance test (AX-CPT). A source analysis of MMN was performed on the basis of a four-source model of MMN generation. RESULTS: Nine subjects completed both experimental days with the two doses of both drugs. Overall, we found blunted MMN and performance deficits in the AX-CPT after both drugs. However, the reduction in MMN activity was overall more pronounced after S-ketamine intake, and only S-ketamine had a significant impact on the frontal source of MMN. CONCLUSIONS: The NDMA antagonist model and the 5HT2A agonist model of psychosis display distinct neurocognitive profiles. These findings are in line with the view of the two classes of hallucinogens modeling different aspects of psychosis

Mitigation of Quantum Dot Cytotoxicity by Microencapsulation

When CdSe/ZnS-polyethyleneimine (PEI) quantum dots (QDs) are microencapsulated in polymeric microcapsules, human fibroblasts are protected from acute cytotoxic effects. Differences in cellular morphology, uptake, and viability were assessed after treatment with either microencapsulated or unencapsulated dots. Specifically, QDs contained in microcapsules terminated with polyethylene glycol (PEG) mitigate contact with and uptake by cells, thus providing a tool to retain particle luminescence for applications such as extracellular sensing and imaging. The microcapsule serves as the “first line of defense” for containing the QDs. This enables the individual QD coating to be designed primarily to enhance the function of the biosensor