Experimental and numerical investigations on the effect of fracture geometry and fracture aperture distribution on flow and solute transport in natural fractures.

The impact of fracture geometry and aperture distribution on fluid movement and on non-reactive solute transport was investigated experimentally and numerically in single fractures. For this purpose a hydrothermally altered and an unaltered granite drill core with axial fractures were investigated. Using three injection and three extraction locations at top and bottom of the fractured cores, different dipole flow fields were examined. The conservative tracer (Amino-G) breakthrough curves were measured using fluorescence spectroscopy. Based on 3-D digital data obtained by micro-computed tomography 2.5-D numerical models were generated for both fractures by mapping the measured aperture distributions to the 2-D fracture geometries (x-y plane). Fluid flow and tracer transport were simulated using COMSOL Multiphysics®. By means of numerical simulations and tomographic imaging experimentally observed breakthrough curves can be understood and qualitatively reproduced. The experiments and simulations suggest that fluid flow in the altered fracture is governed by the 2-D fracture geometry in the x-y plane, while fluid flow in the unaltered fracture seems to be controlled by the aperture distribution. Moreover, we demonstrate that in our case simplified parallel-plate models fail to describe the experimental findings and that pronounced tailings can be attributed to complex internal heterogeneities. The results presented, implicate the necessity to incorporate complex domain geometries governing fluid flow and mass transport into transport modeling.

Impact of gravity, collector surface roughness and fracture orientation on colloid retention kinetics in an artificial fracture.

The interaction of monodisperse fluorescent carboxylated polystyrene colloids (25nm and 1000nm diameter) with a cut granodiorite surface (Grimsel granodiorite; Switzerland) and with acrylic glass is investigated both experimentally and numerically. Colloid transport experiments are conducted in a parallel plate type fracture flow cell with an aperture of 0.75mm at pH5 under low ionic strength (1mM NaCl) and under laminar flow (7mL/h) conditions. The study focuses on the effect of residence time, colloid size, collector material and fracture orientation on colloid retention. Long colloid residence times are achieved by stop-flow experiments. Using atomic force microscopy and, more specifically, the colloid probe technique surface roughness and force distance information of the collector material (granodiorite or acrylic glass) as a function of probe size (cantilever) are obtained. The experiments are modeled using COMSOL Multiphysics® (2-D numerical simulations). The experimental and the modeled results lead to the conclusion that large colloids (1000nm diameter) undergo sedimentation and deposition on the surface during stop-flow. Collector interaction is not affected by the surface roughness variation. Contrariwise, for the investigated 25nm colloids sedimentation does not play a role under the experimental conditions and collector interaction is triggered by surface inhomogeneities such as surface roughness.

Case report: exertional heat stroke after moderate effort as a neurological emergency.

Exertional heat stroke can occur even after moderate efforts in persons predisposed to the condition. Consequences can be far-reaching, potentially leading to multi-organ failure and possibly death. We discuss the case of a 23-year old army recruit presenting with altered consciousness and hyperthermia after a training march. Following initial clinical improvement, rising CK and liver enzyme levels as well as increasing INR were recorded. Facing the risk of multi-organ failure, the patient was transferred to a specialized ICU. The condition could be stabilized without recurring to molecular adsorbent recirculation system (MARS). Exertional heat stroke must be readily recognized as such for correct treatment to be initiated. A multi-disciplinary approach is urgently warranted.

Creutzfeldt-Jakob disease with slow progression. A mimickry of progressive supranuclear palsy.

Sporadic Creutzfeldt-Jakob disease (sCJD) does not always present with typical clinical signs, such as myoclonus in association with periodic sharp-wave complexes. We present a 67-year old female patient with initial falls and vertical gaze palsy, suggesting the diagnosis of Progressive Supranuclear Palsy (PSP). EEG and MRI were not contributory. Typical clinical and paraclinical CJD signs were only seen after 17 months. The diagnosis was confirmed by autopsy. - CJD can be a neurodegenerative chameleon. The present case adds to the scare literature of slowly evolving CJD mimicking Parkinsonism related to tauopathies.

Terminal stages in the biosynthesis of tylosin.

Tylosin, a macrolide antibiotic, was co-produced with four structurally similar antibiotics in fermentation cultures of Streptomyces fradiae. Macrocin, desmycosin, lactenocin, and relomycin were found to be components of a common pathway that functions in tylosin biosynthesis. Data obtained by the addition of the purified (14)C-labeled antibiotics to cultures of S. fradiae revealed that macrocin and desmycosin were direct precursors of tylosin, whereas lactenocin was an immediate precursor of both macrocin and desmycosin. Incubation of these cultures with [(14)C]tylosin resulted in an equivalent distribution of radioactive label between relomycin and an unidentified component. The kinetics of incorporation of label into the two species were similar, suggesting that both were derived directly from tylosin. A system that supported that methylation of macrocin to tylosin by cell-free extracts of S. fradiae was developed. A proposed scheme defining the terminal stages of tylosin biosynthesis is presented.

Detection of a cephalosporin C acetyl esterase in the carbamate cephalosporin antibiotic-producing culture, Streptomyces clavuligerus.

The possible role of a cephalosporin C acetyl esterase in the formation of the beta-lactam antibiotic A16886A, 7-(5-amino-5-carboxyvaleramido)-3-carbamoyloxy-methyl-3-cephem-4-carboxylic acid, by Streptomyces clavuligerus was studied. Addition of dl-valine-(14)C-1 to a fermentation of Cephalosporium acremonium gave cephalosporin C-(14)C-9 (I). The formation of deacetylcephalosporin C-(14)C-9 from I occurred at a greater rate in broths of S. clavuligerus than in the broths of C. acremonium, or in the autoclaved broths of S. clavuligerus. Diisopropylfluorophosphate partially inhibited the deacetylation of I in S. clavuligerus broth. An intracellular cephalosporin C esterase in S. clavuligerus could not be demonstrated. Although A16886A has been chemically synthesized from deacetylcephalosporin C, this reaction could not be demonstrated with S. clavuligerus.

Antibiotic synthesis and morphological differentiation of Cephalosporium acremonium.

In submerged cultures, Cephalosporium acremonium exists in four morphological forms: hyphae, arthrospores, conidia, and germlings. The phase of hyphal differentiation into arthrospores coincides with the maximum rate of beta-lactam antibiotic synthesis. Furthermore, arthrospores, separated by density-gradient centrifugation, possess 40% greater antibiotic-producing activity than any other morphological cell type. In a series of mutants, each with an increased potential to produce beta-lactam antibiotics, differentiation into arthrospores was proportional to the increased titer of these antibiotics. Thus, arthrospores exhibit enhanced synthesis of beta-lactam antibiotics and appear to be a determining factor in high-yielding mutants. Since a non-antibiotic-producing mutant readily differentiated into arthrospores, antibiotic synthesis and cellular differentiation are not obligately related.

Effect of Methionine and Sulfate on the Metabolism of Cephalosporium acremonium.

The metabolism of Cephalosporium acremonium grown in a complex medium supplemented with DL-methionine or inorganic sulfate was studied. More growth occurred in a sulfate medium than in a methionine medium. Methionine-grown cells had an increased rate of respiration, a higher rate of catabolism with acetate and glucose as substrate, and higher specific activities of certain respiratory enzymes than sulfate-grown cells. Labeled acetate and glucose were assimilated at a faster rate by methionine-grown cells than sulfate-grown cells. Taurine, cystathionine, and small quantities of four acidic compounds were present in the amino acid pool of methionine-grown cells, but they were not detected in the pool of sulfate-grown cells. The differences in metabolic activity of sulfate and methionine-grown cells are discussed in regard to cephalosporin C synthesis.

Formation of desacetylcephalosporin C in cephalosporin C fermentation.

The origin of desacetylcephalosporin C in cephalosporin C fermentation broths was investigated. Esterase activity was detected in cell-free extracts of Cephalosporium acremonium, but these extracts failed to deesterify cephalosporin C. When cephalosporin C was added to sterile and inoculated fermentation media, the antibiotic decayed at nearly identical rates. The formation of desacetylcephalosporin C during the fermentation was measured by quantitative chromatography and by the incorporation of valine-1-(14)C into the molecule. The rate constants obtained from the results of these experiments were equivalent to those for the decay of cephalosporin C in sterile and inoculated media. The data demonstrate that desacetylcephalosporin C is produced by nonenzymatic hydrolysis of cephalosporin C.