MRKAd5 HIV-1 Gag/Pol/Nef Vaccine-Induced T-Cell Responses Inadequately Predict Distance of Breakthrough HIV-1 Sequences to the Vaccine or Viral Load

Background: The sieve analysis for the Step trial found evidence that breakthrough HIV-1 sequences for MRKAd5/HIV-1 Gag/Pol/Nef vaccine recipients were more divergent from the vaccine insert than placebo sequences in regions with predicted epitopes. We linked the viral sequence data with immune response and acute viral load data to explore mechanisms for and consequences of the observed sieve effect. Methods: Ninety-one male participants (37 placebo and 54 vaccine recipients) were included; viral sequences were obtained at the time of HIV-1 diagnosis. T-cell responses were measured 4 weeks post-second vaccination and at the first or second week post-diagnosis. Acute viral load was obtained at RNA-positive and antibody-negative visits. Findings: Vaccine recipients had a greater magnitude of post-infection CD8+ T cell response than placebo recipients (median 1.68% vs 1.18%; p = 0.04) and greater breadth of post-infection response (median 4.5 vs 2; p = 0.06). Viral sequences for vaccine recipients were marginally more divergent from the insert than placebo sequences in regions of Nef targeted by pre-infection immune responses (p = 0.04; Pol p = 0.13; Gag p = 0.89). Magnitude and breadth of pre-infection responses did not correlate with distance of the viral sequence to the insert (p. 0.50). Acute log viral load trended lower in vaccine versus placebo recipients (estimated mean 4.7 vs 5.1) but the difference was not significant (p = 0.27). Neither was acute viral load associated with distance of the viral sequence to the insert (p>0.30). Interpretation: Despite evidence of anamnestic responses, the sieve effect was not well explained by available measures of T-cell immunogenicity. Sequence divergence from the vaccine was not significantly associated with acute viral load. While point estimates suggested weak vaccine suppression of viral load, the result was not significant and more viral load data would be needed to detect suppression.

Thermal design of a tray-type distillation column of an ammonia/water absorption refrigeration cycle

The goal of this paper is to present an analysis of a segmented weir sieve-tray distillation column for a 17.58 kW (5 TR) ammonia/water absorption refrigeration cycle. Balances of mass and energy were performed based on the method of Ponchon-Savarit, from which it was possible to determine the ideal number of trays. The analysis showed that four ideal trays were adequate for that small absorption refrigeration system having the feeding system to the column right above the second tray. It was carried out a sensitivity analysis of the main parameters. Vapor and liquid pressure drop constraint along with ammonia and water mass flow ratios defined the internal geometrical sizes of the column, such as the column diameter and height, as well as other designing parameters. Due to the lack of specific correlations, the present work was based on practical correlations used in the petrochemical and beverage production industries. The analysis also permitted to obtain the recommended values of tray spacing in order to have a compact column. The geometry of the tray turns out to be sensitive to the charge of vapor and, to a lesser extent, to the load of the liquid, being insensible to the diameter of tray holes. It was found a column efficiency of 50%. Finally, the paper presents some recommendations in order to have an optimal geometry for a compact size distillation column. (c) 2011 Elsevier Ltd. All rights reserved.

Entwicklung einer Fokalebenen-Driftkammer für niederenergetische Pionen und experimentelle Bestimmung einer inversen Transfermatrix für das Short-Orbit-Spektrometer

Die Drei-Spektrometer-Anlage am Mainzer Institut für Kernphysik wurde um ein zusätzliches Spektrometer ergänzt, welches sich durch seine kurze Baulänge auszeichnet und deshalb Short-Orbit-Spektrometer (SOS) genannt wird. Beim nominellen Abstand des SOS vom Target (66 cm) legen die nachzuweisenden Teilchen zwischen Reaktionsort und Detektor eine mittlere Bahnlänge von 165 cm zurück. Für die schwellennahe Pionproduktion erhöht sich dadurch im Vergleich zu den großen Spektrometern die Überlebenswahrscheinlichkeit geladener Pionen mit Impuls 100 MeV/c von 15% auf 73%. Demzufolge verringert sich der systematische Fehler ("Myon-Kontamination"), etwa bei der geplanten Messung der schwachen Formfaktoren G_A(Q²) und G_P(Q²), signifikant. Den Schwerpunkt der vorliegenden Arbeit bildet die Driftkammer des SOS. Ihre niedrige Massenbelegung (0,03% X_0) zur Reduzierung der Kleinwinkelstreuung ist auf den Nachweis niederenergetischer Pionen hin optimiert. Aufgrund der neuartigen Geometrie des Detektors musste eine eigene Software zur Spurrekonstruktion, Effizienzbestimmung etc. entwickelt werden. Eine komfortable Möglichkeit zur Eichung der Driftweg-Driftzeit-Relation, die durch kubische Splines dargestellt wird, wurde implementiert. Das Auflösungsvermögen des Spurdetektors liegt in der dispersiven Ebene bei 76 µm für die Orts- und 0,23° für die Winkelkoordinate (wahrscheinlichster Fehler) sowie entsprechend in der nicht-dispersiven Ebene bei 110 µm bzw. 0,29°. Zur Rückrechnung der Detektorkoordinaten auf den Reaktionsort wurde die inverse Transfermatrix des Spektrometers bestimmt. Hierzu wurden an Protonen im ¹²C-Kern quasielastisch gestreute Elektronen verwendet, deren Startwinkel durch einen Lochkollimator definiert wurden. Daraus ergeben sich experimentelle Werte für die mittlere Winkelauflösung am Target von sigma_phi = 1,3 mrad bzw. sigma_theta = 10,6 mrad. Da die Impulseichung des SOS nur mittels quasielastischer Streuung (Zweiarmexperiment) durchgeführt werden kann, muss man den Beitrag des Protonarms zur Breite des Piks der fehlenden Masse in einer Monte-Carlo-Simulation abschätzen und herausfalten. Zunächst lässt sich nur abschätzen, dass die Impulsauflösung sicher besser als 1% ist.

Enteric coated mucoadhesive micropellets in rotary agglomeration process for wet spheronization

In this work a generally applicable method for the preparation of mucoadhesive micropellets of 250 to 600µm diameter is presented using rotor processing without the use of electrolytes. The mucoadhesive micropellets were developed to combine the advantages of mucoadhesion and microparticles. It was possible to produce mucoadhesive micropellets based on different mucoadhesive polymers Na-CMC, Na-alginate and chitosan. These micropellets are characterized by a lower friability (6 to 17%) when compared to industrial produced cellulose pellets (Cellets®) (41.5%). They show great tapped density and can be manufactured at high yields. The most influencing variables of the process are the water content at the of the end spraying period, determined by the liquid binder amount, the spraying rate, the inlet air temperature, the airflow and the humidity of the inlet air and the addition of the liquid binder, determined by the spraying rate, the rotor speed and the type of rotor disc. In a subsequent step a fluidized bed coating process was developed. It was possible to manifest a stable process in the Hüttlin Mycrolab® in contrast to the Mini-Glatt® apparatus. To reach enteric resistance, a 70% coating for Na-CMC micropellets, an 85% for chitosan micropellets and a 140% for Na-alginate micropellets, based on the amount of the starting micropellets, was necessary. Comparative dissolution experiments of the mucoadhesive micropellets were performed using the paddle apparatus with and without a sieve inlay, the basket apparatus, the reciprocating cylinder and flow-through cell. The paddle apparatus and the modified flow-through cell method turned out to be successful methods for the dissolution of mucoadhesive micropellets. All dissolution profiles showed an initial burst release followed by a slow release due to diffusion control. Depending on the method, the dissolution profiles changed from immediate release to slow release. The dissolution rate in the paddle apparatus was mainly influenced by the agitation rate whereas the flow-through cell pattern was mainly influenced by the particle size. Also, the logP and the HLB values of different emulsifiers were correlated to transfer HLB values of excipients into logP values and logP values of API´s into HLB values. These experiments did not show promising results. Finally, it was shown that manufacture of mucoadhesive micropellets is successful resulting in product being characterized by enteric resistency combined with high yields and convincing morphology.

Experimental and computational study of methane and methyl formate pyrolysis and oxidation in a flow reactor

A study of the pyrolysis and oxidation (phi 0.5-1-2) of methane and methyl formate (phi 0.5) in a laboratory flow reactor (Length = 50 cm, inner diameter = 2.5 cm) has been carried out at 1-4 atm and 300-1300 K temperature range. Exhaust gaseous species analysis was realized using a gas chromatographic system, Varian CP-4900 PRO Mirco-GC, with a TCD detector and using helium as carrier for a Molecular Sieve 5Å column and nitrogen for a COX column, whose temperatures and pressures were respectively of 65°C and 150kPa. Model simulations using NTUA [1], Fisher et al. [12], Grana [13] and Dooley [14] kinetic mechanisms have been performed with CHEMKIN. The work provides a basis for further development and optimization of existing detailed chemical kinetic schemes.

Frost heave testing of norwegian materials for road infrastructure

In areas of seasonal frost, frost susceptibility composed by frost heaving during the winter and thaw softening during the spring is one of the most dangerous phenomenon for transportation, road and railway infrastructure. Therefore, the need for frost protection layer becomes imperative. The purpose of frost protection layer is to prevent frost from penetrating down through the pavement and into the sub-soils. Frost susceptible soils under the road can be cause damages on the roads or other structures due to frost heave or reduced capacity characteristics thaw period. "Frost heave" is the term given to the upwards displacement of the ground surface caused by the formation of ice within soils or aggregates (Rempel et al., 2004). Nowadays in Scandinavia the most common material used in frost protection layer in the pavement structure of roads and in the ballast of the railway tracks are coarse-grain crushed rocks aggregates. Based on the capillary rise, the mechanics of frost heave phenomenon is based on the interaction between aggregates and water, as suggested by Konrad and Lemieux in 2005 that said that the fraction of material below the 0.063 mm sieve for coarse-grained soils must be controlled so as to reduce the sensitivity to frost heave. The study conducted in this thesis project is divided in two parts: - the analysis of the coarse grained aggregates used in frost protection layer in Norway; - the analysis of the frost heave phenomenon in the laboratory under known boundary conditions, through the use of the most widely used method, the frost heave test, in” closed system” (without access of water).

3D-ultrastructure, functions and stress responses of rhogocytes from the freshwater gastropods Biomphalaria glabrata and Lymnaea stagnalis

Rhogocytes, also termed ‘pore cells’, exist free in the hemolymph or embedded in the connective tissue of different body parts of molluscs, notably gastropods. These unique cells can be round, elongated or irregularly shaped, and up to 30 μm in diameter. Their hallmark is the so-called slit apparatus: i.e. pocket-like invaginations of the plasma membrane creating extracellular lacunae, bridged by cytoplasmic bars. These bars form distinctive slits of ca. 20 nm width. A slit diaphragm composed of proteins establishes a molecular sieve with holes of 20 x 20 nm. Different functions have been assigned to this special molluscan cell type, notably biosynthesis of the hemolymph respiratory protein hemocyanin. It has further been proposed, but not proven, that in the case of red-blooded snail species rhogocytes might synthesize the hemoglobin. However, the secretion pathway of these hemolymph proteins, and the functional role of the enigmatic slit apparatus remained unclear. Additionally proposed functions of rhogocytes, such as heavy metal detoxification or hemolymph protein degradation, are also not well studied. This work provides more detailed electron microscopical, histological and immunobiochemical information on the structure and function of rhogocytes of the freshwater snails Biomphalaria glabrata and Lymnaea stagnalis. By in situ hybridization on mantle tissues, it proves that B. glabrata rhogocytes synthesize hemoglobin and L. stagnalis rhogocytes synthesize hemocyanin. Hemocyanin is present, in endoplasmic reticulum lacunae and in vesicles, as individual molecules or pseudo-crystalline arrays. The first 3D reconstructions of rhogocytes are provided by means of electron tomography and show unprecedented details of the slit apparatus. A highly dense material in the cytoplasmic bars close to the diaphragmatic slits was shown, by immunogold labeling, to contain actin. By immunofluorescence microscopy, the protein nephrin was localized at the periphery of rhogocytes. The presence of both proteins in the slit apparatus supports the previous hypothesis, hitherto solely based on similarities of the ultrastructure, that the molluscan rhogocytes are phylogenetically related to mammalian podocytes and insect nephrocytes. A possible secretion pathway of respiratory proteins that includes a transfer mechanism of vesicles through the diaphragmatic slits is proposed and discussed. We also studied, by electron microscopy, the reaction of rhogocytes in situ to two forms of animal stress: deprivation of food and cadmium contamination of the tank water. Significant cellular reactions to both stressors were observed and documented. Notably, the slit apparatus surface and the number of electron-dense cytoplasmic vesicles increased in response to cadmium stress. Food deprivation led to an increase in hemocyanin production. These observations are also discussed in the framework of using such animals as potential environmental biomarkers.

Una applicazione per la valutazione delle prestazioni di architetture parallele a basso consumo

In questa tesi si descrive il lavoro svolto presso l’istituto INFN-CNAF, che consiste nello sviluppo di un’applicazione parallela e del suo utilizzo su di un’architettura a basso consumo, allo scopo di valutare il comportamento della stessa, confrontandolo a quello di architetture ad alta potenza di calcolo. L’architettura a basso consumo utilizzata `e un system on chip mutuato dal mondo mobile e embedded contenente una cpu ARM quad core e una GPU NVIDIA, mentre l’architettura ad alta potenza di calcolo `e un sistema x86 64 con una GPU NVIDIA di classe server. L’applicazione `e stata sviluppata in C++ in due differenti versioni: la prima utilizzando l’estensione OpenMP e la seconda utilizzando l’estensione CUDA. Queste due versioni hanno permesso di valutare il comportamento dell’architettura a basso consumo sotto diversi punti di vista, utilizzando nelle differenti versioni dell’applicazione la CPU o la GPU come unita` principale di elaborazione.

[Alban Köhler (1874-1947): Inventor of grid therapy]

Grid (or sieve) therapy ("Gitter-" oder "Siebtherapie"), spatially fractionated kilo- and megavolt X-ray therapy, was invented in 1909 by Alban Köhler, a radiologist in Wiesbaden, Germany. He tested it on several patients before 1913 using approximately 60-70kV Hittorf-Crookes tubes. Köhler pushed the X-ray tube's lead-shielded housing against a stiff grid of 1 mm-square iron wires woven 3.0-3.5mm on center, taped tightly to the skin over a thin chamois. Numerous islets unshielded by iron in the pressure-blanched skin were irradiated with up to about 6 erythema doses (ED). The skin was then thoroughly cleansed, disinfected, and bandaged; delayed punctate necrosis healed in several weeks. Although grid therapy was disparaged or ignored until the 1930s, it has been used successfully since then to shrink bulky malignancies. Also, advanced cancers in rats and mice have been mitigated or ablated using Köhler's concept since the early 1990s by unidirectional or stereotactic exposure to an array of nearly parallel microplanar (25-75μm-wide) beams of very intense, moderately hard (median energy approximately 100 keV) synchrotron-generated X rays spaced 0.1-0.4mm on center. Such beams maintain sharp edges at high doses well beneath the skin yet confer little toxicity. They could palliate some otherwise intractable malignancies, perhaps in young children too, with tolerable sequelae. There are plans for such studies in larger animals.

MATURE FINE TAILINGS (MFTs): A STUDY OF COMPRESSIVE STRENGTH AND RHEOLOGICAL PROPERTIES OF ATHABASCA OIL SANDS PETROLEUM MINING WASTE APPLIED IN CONCRETE MIXTURES

This study investigates the compressive properties of concrete incorporating Mature Fine Tailings (MFTs) waste stream from a tar sands mining operation. The objectives of this study are to investigate material properties of the MFT material itself, as well as establish general feasibility of the utilization of MFT material in concrete mixtures through empirical data and visual observations. Investigations undertaken in this study consist of moisture content, materials finer than No. 200 sieve, Atterburg Limits as well as visual observations performed on MFT material as obtained. Control concrete mixtures as well as MFT replacement mixture designs (% by wt. of water) were guided by properties of the MFT material that were experimentally established. The experimental design consists of compression testing of 4”-diameter concrete cylinders of a control mixture, 30% MFT, 50% MFT and 70% MFT replacement mixtures with air-entrainer additive, as well as a control mixture and 30% MFT replacement mixture with no air-entrainer. A total of 6 mixtures (2 control mixtures, 4 replacement mixtures) moist-cured in lime water after 24 hours initial curing were tested for ultimate compressive strength at 7 days and 28 days in accordance to ASTM C39. The test results of fresh concrete material show that the addition of air-entrainer to the control mixture increases slump from 4” to 5.5”. However, the use of MFT material in concrete mixtures significantly decreases slump as compared to controls. All MFT replacement mixtures (30%, 50%, and 70%) with air-entrainer present slumps of 1”. 30% MFT with no air-entrainer presents a slump of 1.5”. It was found that 7-day ultimate compressive stress was not a good predictor of 28-day ultimate compressive stress. 28-day results indicate that the use of MFT material in concrete with air-entrainer decreases ultimate compressive stress for 30%, 50% and 70% MFT replacement amounts by 14.2%, 17.3% and 25.1% respectively.

A re-examination of petrogenesis and 40Ar/39Ar systematics in the the Chain of Ponds K-feldspar: "diffusion domain" archetype versus polyphase hygrochronology

K-feldspar (Kfs) from the Chain of Ponds Pluton (CPP) is the archetypal reference material, on which thermochronological modeling of Ar diffusion in discrete “domains” was founded. We re-examine the CPP Kfs using cathodoluminescence and back-scattered electron imaging, transmission electron microscopy, and electron probe microanalysis. 40Ar/39Ar stepwise heating experiments on different sieve fractions, and on handpicked and unpicked aliquots, are compared. Our results reproduce the staircase-shaped age spectrum and the Arrhenius trajectory of the literature sample, confirming that samples collected from the same locality have an identical Ar isotope record. Even the most pristine-looking Kfs from the CPP contains successive generations of secondary, metasomatic/retrograde mineral replacements that post-date magmatic crystallization. These chemically and chronologically distinct phases are responsible for its staircase-shaped age spectra, which are modified by handpicking. While genuine within-grain diffusion gradients are not ruled out by these data, this study demonstrates that the most important control on staircase-shaped age spectra is the simultaneous presence of heterochemical, diachronous post-magmatic mineral growth. At least five distinct mineral species were identified in the Kfs separate, three of which can be traced to external fluids interacting with the CPP in a chemically open system. Sieve fractions have size-shifted Arrhenius trajectories, negating the existence of the smallest “diffusion domains”. Heterochemical phases also play an important role in producing non-linear trajectories. In vacuo degassing rates recovered from Arrhenius plots are neither related to true Fick’s Law diffusion nor to the staircase shape of the age spectra. The CPP Kfs used to define the "diffusion domain" model demonstrates the predominance of metasomatic alteration by hydrothermal fluids and recrystallization in establishing the natural Ar distribution amongst different coexisting phases that gives rise to the staircase-shaped age spectrum. Microbeam imaging of textures is as essential for 40Ar-39Ar hygrochronology as it is for U-Pb geochronology.

Effects of PEG-Induced Water Deficit in Solanum nigrum on Zn and Ni Uptake and Translocation in Split Root Systems

Drought strongly influences root activities in crop plants and weeds. This paper is focused on the performance of the heavy metal accumulator Solanum nigrum, a plant which might be helpful for phytoremediation. The water potential in a split root system was decreased by the addition of polyethylene glycol (PEG 6000). Rubidium, strontium and radionuclides of heavy metals were used as markers to investigate the uptake into roots, the release to the shoot via the xylem, and finally the basipetal transport via the phloem to unlabeled roots. The uptake into the roots (total contents in the plant) was for most makers more severely decreased than the transport to the shoot or the export from the shoot to the unlabeled roots via the phloem. Regardless of the water potential in the labeling solution, 63Ni and 65Zn were selectively redistributed within the plant. From autoradiographs, it became evident that 65Zn accumulated in root tips, in the apical shoot meristem and in axillary buds, while 63Ni accumulated in young expanded leaves and roots but not in the meristems. Since both radionuclides are mobile in the phloem and are, therefore, well redistributed within the plant, the unequal transfer to shoot and root apical meristems is most likely caused by differences in the cell-to-cell transport in differentiation zones without functional phloem (immature sieve tubes).

TRANSMISSION DYNAMICS OF ENTERIC BACTERIA IN DAY-CARE CENTERS, HOUSTON, TEXAS

An investigation was undertaken to evaluate the role of fomites in the transmission of diarrhea in day-care centers (DCC) and to elucidate the paths by which enteric organisms spread within this setting.^ During a nine-month period (December 1980-August 1981) extensive culturing of inanimate objects, as well as children and staff was done routinely each month and again repeated during diarrhea outbreaks. Air was sampled from the classrooms and toilets using a Single-Stage Sieve Sampler (Ross Industries, Midland, VA.). Stool samples were collected from both ill and well children and staff in the affected rooms only during outbreaks. Environmental samples were processed for Shigella, salmonella and fecal coliforms while stools were screened for miscellaneous enteropathogens.^ A total of 11 outbreaks occurred in the 5 DCC during the study period. Enteric pathogens were recovered in 7 (64%) of the outbreaks. Multiple pathogens were identified in 3 outbreaks. The most frequently identified pathogen in stools was Giardia lamblia which was recovered in 5 (45%) of the outbreaks. Ten of the 11 (91%) outbreaks occurred in children less than 12 months of age.^ Environmental microbiology studies together with epidemiologic information revealed that enteric organisms were transmitted from person-to-person. On routine sampling, fecal coliforms were most frequently isolated from tap handles and diaper change areas. Contamination with fetal coliforms was wide-spread during diarrhea outbreaks. Fecal coliforms were recovered with significantly greater frequency from hands, toys and other classroom objects during outbreaks than during non-outbreak period. Salmonella typhimurium was recovered from a table top during an outbreak of Salmonellosis. There was no association between the level of enteric microbial contamination in the toilet areas and the occurrence of outbreaks. No evidence was found to indicate that enteric organisms were spread by the airborne route via aerosols.^ Toys, other classroom objects and contaminated hands probably play a major role in the transmission of enteropathogens during day-care center outbreaks. The presence of many enteric agents in the environment undoubtedly explains the polymicrobial etiology of the day-care center associated diarrhea outbreaks. ^

Grain size analysis of sediment core CRP-3 from the Ross Sea, Antarctica

Grain-size analyses by sieve and Sedigraph are presented for 115 samples of core from CRP-3, 12 km off the coast of south Victoria Land. The data provide a useful check on visual core descriptions. The geographic setting for the strata sampled, some 790 m of early Oligocene nearshore marine sediments with a persistent glacial influence, is reviewed, and sediment textures interpreted in that context. Sand textures from the CRP-3 samples in the lower part of the core suggest that deposition was initially primarily wave-dominated, but that at times the influence of the waves was over-ridden by episodes of rapid sedimentation. Sedimentary cycles, recognised in the visual description of the core above 485 mbsf, show an increasing proportion of mudstone in the middle of each cycle above 330 mbsf that is interpreted to record periodic sedimentation in deeper water. Sandstone textures in the lower and upper parts of each cycle are interpreted to record departure from and return to shoreface deposition with changes in sea level. Mudstone textures above 176 mbsf indicate sedimentation below wave base. Many of the textures in both sand and mud samples show the coarse 'tail' characteristic of ice-rafted debris, but others do not, indicating ice-free periods. Many sandstones below c. 200 mbsf have virtually no silt, but significant amounts of clay (6 to 17%) that is thought to be of post-depositional origin.

Grain size analysis of sediment coring site CRP-2 from the Ross Sea, Antarctica

The purpose of this note is to present results of grain size analyses from 118 samples of the CRP-2/2A core using sieve and Sedigraph techniques. The samples were selected to represent the range of facies encountered, and tend to become more widely spaced with depth. Fifteen came from the upper 27 m of Quaternary and Pliocene sediments, 62 from the early Miocene-late Oligocene strata (27 to 307 mbsf), and 41 from the early Oligocene strata beneath (307 to 624 mbsf). The results are intended to provide reference data for lithological descriptions in the core logs (Cape Roberts Science Team, 1999), and to help with facies interpretation. The analytical technique used for determining size frequency of the sand fraction in our samples (sieving) is simple, physical and widely practised for over a century. Thus it provides a useful reference point for analyses produced by other faster and more sophisticated techniques, such as the Malvern laser particle size analysis system (Woolfe et al., 2000), and estimates derived from measurements taken with down-hole logging tools (Bücker, pers. com., 1999).