Carboplatin binding to a model protein in non-NaCl conditions to eliminate partial conversion to cisplatin, and the use of different criteria to choose the resolution limit

Hen egg white lysozyme (HEWL) co-crystallisation conditions of carboplatin without sodium chloride (NaCl) have been utilised to eliminate partial conversion of carboplatin to cisplatin observed previously. Tetragonal HEWL crystals were successfully obtained in 65% MPD with 0.1M citric acid buffer at pH 4.0 including DMSO. The X-ray diffraction data resolution to be used for the model refinement was reviewed using several topical criteria together. The CC1/2 criterion implemented in XDS led to data being significant to 2.0{\AA}, compared to the data only being able to be processed to 3.0{\AA} using the Bruker software package (SAINT). Then using paired protein model refinements and DPI values based on the FreeR value, the resolution limit was fine tuned to be 2.3{\AA}. Interestingly this was compared with results from the EVAL software package which gave a resolution limit of 2.2{\AA} solely using crossing 2, but 2.8{\AA} based on the Rmerge values (60%). The structural results showed that carboplatin bound to only the N{\delta} binding site of His-15 one week after crystal growth, whereas five weeks after crystal growth, two molecules of carboplatin are bound to the His-15 residue. In summary several new results have emerged: - firstly non-NaCl conditions showed a carboplatin molecule bound to His-15 of HEWL; secondly binding of one molecule of carboplatin was seen after one week of crystal growth and two molecules were bound after five weeks of crystal growth; and thirdly the use of several criteria to determine the diffraction resolution limit led to the successful use of data to higher resolution.Comment: 14 pages; submitted to Acta Cryst D Biological Crystallography reference number tz504

The Physical Properties of Some Short Period Anneal Products of White Cast Iron

Since very little study of the malleableizing process had been made and also because the properties that were considered of primary importance to the average user of malleable iron were ease of machining and ductility, no attention has been paid to the industrial possibilities of partially graphitized white iron. In annealing periods of less than 11 hours total duration it has been found possible to produce irons ranging from 70,000 strength and 5% stretch to 55,000 and 10% stretch depending on varying rates of cooling of 6°F. per minute to 3°F. per minute from the annealing temperature. The unusual properties of 85,000 strength and 6% stretch has been obtained by a slightly longer annealing method which involves a grain refining process. There should be important industrial uses for these products

Self-stabilizing positron acceleration in a plasma column

Plasma accelerators sustain extreme field gradients, and potentially enable future compact linear colliders. Although tremendous progress has been achieved in accelerating electron beams in a plasma accelerator, positron acceleration with collider-relevant parameters is challenging. A recently proposed positron acceleration scheme relying on the wake generated by an electron drive beam in a plasma column has been shown to be able to accelerate positron witness beams with low emittance and low energy spread. However, since this scheme relies on cylindrical symmetry, it is possibly prone to transverse instabilities that could lead, ultimately, to beam break-up. In this article, we show that the witness beam itself is subject to various damping mechanisms and, therefore, this positron acceleration scheme is inherently stable towards misalignment of the drive and witness beams. This enables stable, high-quality plasma-based positron acceleration

Time-Dependent Model for Brittle Rocks Considering the Long-Term Strength Determined from Lab Data

The excavation of tunnels in brittle rocks with high in-situ strengths under large deviatoric stresses has been shown to exhibit brittle failure at the periphery of tunnels parallel to the maximum in-situ stress. This failure can either occur instantaneously or after several hours due to the strength degradation that is implicitly and indirectly considered in typical brittle constitutive models. While these models are powerful tools for engineering analyses, they cannot predict the time at which brittle rupture occurs, but rather, they show a possible failure pattern occurring instantaneously. In this paper, a model referred to as the long-term strength (LTS) model is introduced and implemented into FLAC2D. The model is built as a modified version of the CVISC model, introduced by Itasca, by adding a strength decay function. This function is developed from lab-scale time-to-failure (TTF) data. The LTS model is verified against its corresponding analytical solution using a constant stress creep lab test and implemented into a tunnel-scale model using the geometry, stress, and geologic conditions from the Atomic Energy of Canada Limited Underground Research Laboratory (AECL URL). The results of the LTS tunnel model are then compared to an identical model using the Cohesion Weakening Friction Strengthening (CWFS) approach

Assessing Retinal Structure In Complete Congenital Stationary Night Blindness and Oguchi Disease

Purpose To examine retinal structure and changes in photoreceptor intensity after dark adaptation in patients with complete congenital stationary night blindness and Oguchi disease. Design Prospective, observational case series. Methods We recruited 3 patients with complete congenital stationary night blindness caused by mutations in GRM6, 2 brothers with Oguchi disease caused by mutations in GRK1, and 1 normal control. Retinal thickness was measured from optical coherence tomography images. Integrity of the rod and cone mosaic was assessed using adaptive optics scanning light ophthalmoscopy. We imaged 5 of the patients after a period of dark adaptation and examined layer reflectivity on optical coherence tomography in a patient with Oguchi disease under light- and dark-adapted conditions. Results Retinal thickness was reduced in the parafoveal region in patients with GRM6 mutations as a result of decreased thickness of the inner retinal layers. All patients had normal photoreceptor density at all locations analyzed. On removal from dark adaptation, the intensity of the rods (but not cones) in the patients with Oguchi disease gradually and significantly increased. In 1 Oguchi disease patient, the outer segment layer contrast on optical coherence tomography was 4-fold higher under dark-adapted versus light-adapted conditions. Conclusions The selective thinning of the inner retinal layers in patients with GRM6 mutations suggests either reduced bipolar or ganglion cell numbers or altered synaptic structure in the inner retina. Our finding that rods, but not cones, change intensity after dark adaptation suggests that fundus changes in Oguchi disease are the result of changes within the rods as opposed to changes at a different retinal locus