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

Optical Quantum Computation with Perpetually Coupled Spins

The possibility of using strongly and continuously interacting spins for quantum computation has recently been discussed. Here we present a simple optical scheme that achieves this goal while avoiding the drawbacks of earlier proposals. We employ a third state, accessed by a classical laser field, to create an effective barrier to information transfer. The mechanism proves to be highly efficient both for continuous and pulsed laser modes; moreover it is very robust, tolerating high decay rates for the excited states. The approach is applicable to a broad range of systems, in particular dense structures such as solid state self-assembled (e.g., molecular) devices. Importantly, there are existing structures upon which `first step' experiments could be immediately performed.Comment: 5 pages including 3 figures. Updated to published versio

Ensemble based quantum metrology

The field of quantum metrology promises measurement devices that are fundamentally superior to conventional technologies. Specifically, when quantum entanglement is harnessed the precision achieved is supposed to scale more favourably with the resources employed, such as system size and the time required. Here we consider measurement of magnetic field strength using an ensemble of spins, and we identify a third essential resource: the initial system polarisation, i.e. the low entropy of the original state. We find that performance depends crucially on the form of decoherence present; for a plausible dephasing model, we describe a quantum strategy which can indeed beat the standard quantum limit

Quantum metrology with molecular ensembles

This work was supported by the EPSRC through QIP IRC (Grants No. GR/S82176/01 and No. GR/S15808/01), the National Research Foundation and Ministry of Education, Singapore, the DAAD, and the Royal Society.The field of quantum metrology promisesmeasurement devices that are fundamentally superior to conventional technologies. Specifically, when quantum entanglement is harnessed, the precision achieved is supposed to scale more favorably with the resources employed, such as system size and time required. Here, we consider measurement of magnetic-field strength using an ensemble of spin-active molecules. We identify a third essential resource: the change in ensemble polarization (entropy increase) during the metrology experiment. We find that performance depends crucially on the form of decoherence present; for a plausible dephasing model, we describe a quantum strategy, which can indeed beat the standard strategy.Publisher PDFPeer reviewe

Metagenetic analysis of patterns of distribution and diversity of marine meiobenthic eukaryotes

AimMeiofaunal communities that inhabit the marine benthos offer unique opportunities to simultaneously study the macroecology of numerous phyla that exhibit different life-history strategies. Here, we ask: (1) if the macroecology of meiobenthic communities is explained mainly by dispersal constraints or by environmental conditions; and (2) if levels of meiofaunal diversity surpass existing estimates based on morphological taxonomy. LocationUK and mainland European coast. MethodsNext-generation sequencing techniques (NGS; Roche 454 FLX platform) using 18S nuclear small subunit ribosomal DNA (rDNA) gene. Pyrosequences were analysed using AmpliconNoise followed by chimera removal using Perseus. ResultsRarefaction curves revealed that sampling saturation was only reached at 15% of sites, highlighting that the bulk of meiofaunal diversity is yet to be discovered. Overall, 1353 OTUs were recovered and assigned to 23 different phyla. The majority of sampled sites had c. 60-70 unique operational taxonomic units (OTUs) per site, indicating high levels of beta diversity. The environmental parameters that best explained community structure were seawater temperature, geographical distance and sediment size, but most of the variability (R-2=70%-80%) remains unexplained. Main conclusionsHigh percentages of endemic OTUs suggest that meiobenthic community composition is partly niche-driven, as observed in larger organisms, but also shares macroecological features of microorganisms by showing high levels of cosmopolitanism (albeit on a much smaller scale). Meiobenthic communities exhibited patterns of isolation by distance as well as associations between niche, latitude and temperature, indicating that meiobenthic communities result from a combination of niche assembly and dispersal processes. Conversely, isolation-by-distance patterns were not identified in the featured protists, suggesting that animals and protists adhere to radically different macroecological processes, linked to life-history strategies.Natural Environment Research Council (NERC) [NE/E001505/1, NE/F001266/1, MGF-167]; Portuguese Foundation for Science and Technology (FCT) [SFRH/BD/27413/2006, SFRH/BPD/80447/2014]; EPSRC [EP/H003851/1]; BBSRC CASE studentship; Unilever; Biotechnology and Biological Sciences Research Council [987347]; Engineering and Physical Sciences Research Council [EP/H003851/1]; Natural Environment Research Council [NE/F001290/1, NE/F001266/1, NE/E001505/1, NBAF010002]info:eu-repo/semantics/publishedVersio

Intraocular pressure in inbred mouse strains

PURPOSE: To develop a protocol to measure the intraocular pressure (IOP) of living mice and to determine the IOP of genetically different mouse strains. METHODS: Eyes of anesthetized animals were cannulated with a very fine fluid-filled glass microneedle. The microneedle was connected to a pressure transducer, and the pressure signal was analyzed with a computer system. Intraocular pressures of male C3H/He iota, C57BL/ 6 iota, A/iota, and BALB/c iota mice were determined. RESULTS: Differences in IOP were detected between genetically distinct mouse strains maintained in virtually identical environments. C3H/He iota was the strain with the highest average IOP (13.7 +/- 0.8 mm Hg). This strain average was 1.4 mm Hg higher than that for C57BL/6 iota (12.3 +/- 0.5 mm Hg; P = 0.14), 4.3 mm Hg higher than that for A/iota (9.4 +/- 0.5 mm Hg; P < 0.001), and 6 mm Hg higher than that for BALB/c iota (7.7 +/- 0.5 mm Hg; P < 0.001). CONCLUSIONS: The authors have developed an accurate and reliable procedure for measuring intraocular pressure in living mice. This procedure can detect IOP differences between groups of mice that differ by genotype

Погляд на архіви

The International Union of Crystallography has for many years been advocating archiving of raw data to accompany structural papers. Recently, it initiated the formation of the Diffraction Data Deposition Working Group with the aim of developing standards for the representation of these data. A means of studying this issue is to submit exemplar publications with associated raw data and metadata. A recent study on the effects of dimethyl sulfoxide on the binding of cisplatin and carboplatin to histidine in 11 different lysozyme crystals from two diffractometers led to an investigation of the possible effects of the equipment and X-ray diffraction data processing software on the calculated occupancies and B factors of the bound Pt compounds. 35.3 Gb of data were transferred from Manchester to Utrecht to be processed with EVAL. A systematic comparison shows that the largest differences in the occupancies and B factors of the bound Pt compounds are due to the software, but the equipment also has a noticeable effect. A detailed description of and discussion on the availability of metadata is given. By making these raw diffraction data sets available via a local depository, it is possible for the diffraction community to make their own evaluation as they may wish

Towards smart self-clearing glaucoma drainage device.

For patients who are unresponsive to pharmacological treatments of glaucoma, an implantable glaucoma drainage devices (GDD) are often used to manage the intraocular pressure. However, the microscale channel that removes excess aqueous humor from the anterior chamber often gets obstructed due to biofouling, which necessitates additional surgical intervention. Here we demonstrate the proof-of-concept for smart self-clearing GDD by integrating magnetic microactuators inside the drainage tube of GDD. The magnetic microactuators can be controlled using externally applied magnetic fields to mechanically clear biofouling-based obstruction, thereby eliminating the need for surgical intervention. In this work, our prototype magnetic microactuators were fabricated using low-cost maskless photolithography to expedite design iteration. The fabricated devices were evaluated for their static and dynamic mechanical responses. Using transient numerical analysis, the fluid–structure interaction of our microactuator inside a microtube was characterized to better understand the amount of shear force generated by the device motion. Finally, the anti-biofouling performance of our device was evaluated using fluorescein isothiocyanate labeled bovine serum albumin. The microactuators were effective in removing proteinaceous film deposited on device surface as well as on the inner surface of the microchannel, which supports our hypothesis that a smart self-clearing GDD may be possible by integrating microfabricated magnetic actuators in chronically implanted microtubes