Archives, Room Use Only - TK5105.S35 1926

Archives, Room Use Only - TK5123.V35 1845

Archives, Room Use Only - TK5295.W47 1875

Archives, Room Use Only - ZTK143.N532

Archives, Room Use Only - TK5123.V35 1847

Archives, Room Use Only - TK5241.T35 1893

Archives, Room Use Only - T19.B35 1860

Archives, Room Use Only - UG582.V5 R63 1886

Archives, Room Use Only - TK5445.T37 1889

Archives, Room Use Only - TK5262.R46 1924

Archives, Room Use Only - TK5261.N38 1928

Archives, Room Use Only - UG605.F8 F7313 1917

Archives, Room Use Only - QC527.T73 1895

Archives, Room Use Only - TK5811.B83 1920

Archives, Room Use Only - UG582.H4 G78 1920z

Archives, Room Use Only - HE9723.H48 1932

A drug used for treating breast cancer, known as exemestane, is more effective than a common breast cancer prevention drug, tamoxifen, in preventing breast cancer recurrence in young women who also receive post-surgical treatment to suppress ovarian function. The combined results of the Tamoxifen and Exemestane Trial and Suppression of Ovarian Function Trial were presented at the 2014 ASCO Annual Meeting in Chicago.

McKinnon appears to be on pace for a strong recovery, but 49ers general manager John Lynch is taking a wait-and-see approach.

This isn't quite the way Anthony McFarland expected his NFL career to begin. Pittsburgh's fourth-round draft pick is doing what he can to keep up during the first - and the NFL hopes only - ''virtual'' offseason amid the COVID-19 pandemic. Sure, he'd rather be at the Steelers' practice facility with the rest of the newcomers.

This article explains JavaScript engine optimization pipeline trade-offs, and describes how engines such as V8 speed up accesses to prototype properties. As a JavaScript developer, having a deeper understanding of how JavaScript engines work helps you reason about the performance characteristics of your code.

As sales and exports of fish crash, another huge crisis is staring at Sri Lanka’s fisherfolk.

Despite these times of distress, the Bannerghatta Biological Park’s (BBP) animal adoption programme has been generating a good response. On Saturday,

While many companies are sharing documents digitally, some have also opened their servers to auditors to access the data they require

Petrol sales were down 60.43 per cent to 9,73,000 tonnes in April

Efficient sample delivery is an essential aspect of serial crystallography at both synchrotrons and X-ray free-electron lasers. Rastering fixed target chips through the X-ray beam is an efficient method for serial delivery from the perspectives of both sample consumption and beam time usage. Here, an approach for loading fixed targets using acoustic drop ejection is presented that does not compromise crystal quality, can reduce sample consumption by more than an order of magnitude and allows serial diffraction to be collected from a larger proportion of the crystals in the slurry.

The high temporal resolution in data acquisition, possible in the quick-scanning EXAFS (QEXAFS) mode of operation, provides new challenges in efficient data processing methods. Here a new approach is developed that combines an easy to use interactive graphical interface with highly optimized and fully parallelized Python-based routines for extracting, normalizing and interpolating oversampled time-resolved XAS spectra from a raw binary stream of data acquired during operando QEXAFS studies. The programs developed are freely available via a Github repository.

X-ray absorption linear dichroism of rutile TiO2 at the Ti K-edge provides information about the electronic states involved in the pre-edge transitions. Here, linear dichroism with high energy resolution is analyzed in combination with ab initio finite difference method calculations and spherical tensor analysis. It provides an assignment of the three pre-edge peaks beyond the octahedral crystal field splitting approximation and estimates the spatial extension of the corresponding final states. It is then discussed for the first time the X-ray absorption (XAS) of pentacoordinated titanium atoms due to oxygen vacancies and it is found that, similarly to anatase TiO2, rutile is expected to exhibit a transition on the low-energy side of peak A3. Its apparent absence in the experiment is related to the degree of p–d orbital mixing which is small in rutile due to its centrosymmetric point group. A recent XAS linear dichroism study on anatase TiO2 single crystals has shown that peak A2 has an intrinsic origin and is due to a quadrupolar transition to the 3d energy levels. In rutile, due to its centrosymmetric point group, the corresponding peak A2 has a small dipole moment explaining the weak transition. The results are confronted with recent picosecond X-ray absorption spectroscopy on rutile TiO2 nanoparticles.

Ripon sinkhole: British Geological Survey says area susceptible to holes  BBC News

Crystals of the dimethyl sulfoxide (DMSO) solvate of [1–9-NαC]-linusorb B3 (Cyclo­linopeptide A; CLP-A; C57H84N9O9·C2H6OS), a cyclic polypeptide were obtained following peptide extraction and purification from flaxseed oil. There are four intramolecular N—H⋯O hydrogen bonds. In the crystal, the mol­ecules are linked in chains along the a axis by N—H⋯O hydrogen bonds. Each DMSO O atom accepts a hydrogen bond from an NH group at the Phe6 location in the CLP-A mol­ecule.

A peptide biphenyl hybrid compound {systematic name: dimethyl 2,2'-[((2S,2'S)-2,2'-{[(2S,2'S)-1,1'-([1,1'-biphen­yl]-2,2'-dicarbon­yl)bis­(pyrrolidine-1,2-diyl-2-carbon­yl)]bis­(aza­nedi­yl)}bis­(3-phenyl­propano­yl))bis­(aza­nedi­yl)](2S,2'S)-dipropionate hemihydrate}, C50H56N6O10·0.5H2O, was prepared by coupling of [1,1'-biphen­yl]-2,2'-dicarbonyl dichloride, tri­ethyl­amine and the tripeptide Pro–Phe–Ala in CH2Cl2 at 273 K under an N2 atmosphere. In the crystal, the asymmetric unit contains the peptide biphenyl hybrid accompanied by one-half of a water mol­ecule. A C atom of one of the proline rings is disordered between two positions in a 0.746 (11):0.254 (11) ratio. An important structural aspect of peptide compounds is their capacity to self-associate mediated by inter­molecular and intra­molecular hydrogen bonding. This characteristic can be useful in understanding the inter­actions between peptides and biomacromolecular targets, as well as to explain peptide properties.

A rational way to find the appropriate conditions to grow crystal samples for bio-crystallography is to determine the crystallization phase diagram, which allows precise control of the parameters affecting the crystal growth process. First, the nucleation is induced at supersaturated conditions close to the solubility boundary between the nucleation and metastable regions. Then, crystal growth is further achieved in the metastable zone – which is the optimal location for slow and ordered crystal expansion – by modulation of specific physical parameters. Recently, a prototype of an integrated apparatus for the rational optimization of crystal growth by mapping and manipulating temperature–precipitant–concentration phase diagrams has been constructed. Here, it is demonstrated that a thorough knowledge of the phase diagram is vital in any crystallization experiment. The relevance of the selection of the starting position and the kinetic pathway undertaken in controlling most of the final properties of the synthesized crystals is shown. The rational crystallization optimization strategies developed and presented here allow tailoring of crystal size and diffraction quality, significantly reducing the time, effort and amount of expensive protein material required for structure determination.

Total scattering measurements enable understanding of the structural disorder in crystalline materials by Fourier transformation of the total structure factor, S(Q), where Q is the magnitude of the scattering vector. In this work, the direct calculation of total scattering from a crystalline structural model is proposed. To calculate the total scattering intensity, a suitable Q-broadening function for the diffraction profile is needed because the intensity and the width depend on the optical parameters of the diffraction apparatus, such as the X-ray energy resolution and divergence, and the intrinsic parameters. X-ray total scattering measurements for CeO2 powder were performed at beamline BL04B2 of the SPring-8 synchrotron radiation facility in Japan for comparison with the calculated S(Q) under various optical conditions. The evaluated Q-broadening function was comparable to the full width at half-maximum of the Bragg peaks in the experimental total scattering pattern. The proposed calculation method correctly accounts for parameters with Q dependence such as the atomic form factor and resolution function, enables estimation of the total scattering factor, and facilitates determination of the reduced pair distribution function for both crystalline and amorphous materials.

Indanomycin is biosynthesized by a hybrid nonribosomal peptide synthase/polyketide synthase (NRPS/PKS) followed by a number of `tailoring' steps to form the two ring systems that are present in the mature product. It had previously been hypothesized that the indane ring of indanomycin was formed by the action of IdmH using a Diels–Alder reaction. Here, the crystal structure of a selenomethionine-labelled truncated form of IdmH (IdmH-Δ99–107) was solved using single-wavelength anomalous dispersion (SAD) phasing. This truncated variant allows consistent and easy crystallization, but importantly the structure was used as a search model in molecular replacement, allowing the full-length IdmH structure to be determined to 2.7 Å resolution. IdmH is a homodimer, with the individual protomers consisting of an α+β barrel. Each protomer contains a deep hydrophobic pocket which is proposed to constitute the active site of the enzyme. To investigate the reaction catalysed by IdmH, 88% of the backbone NMR resonances were assigned, and using chemical shift perturbation of [15N]-labelled IdmH it was demonstrated that indanomycin binds in the active-site pocket. Finally, combined quantum mechanical/molecular mechanical (QM/MM) modelling of the IdmH reaction shows that the active site of the enzyme provides an appropriate environment to promote indane-ring formation, supporting the assignment of IdmH as the key Diels–Alderase catalysing the final step in the biosynthesis of indanomycin through a similar mechanism to other recently characterized Diels–Alderases involved in polyketide-tailoring reactions. An animated Interactive 3D Complement (I3DC) is available in Proteopedia at https://proteopedia.org/w/Journal:IUCrJ:S2052252519012399.

Tannerella forsythia is an oral dysbiotic periodontopathogen involved in severe human periodontal disease. As part of its virulence factor armamentarium, at the site of colonization it secretes mirolysin, a metallopeptidase of the unicellular pappalysin family, as a zymogen that is proteolytically auto-activated extracellularly at the Ser54–Arg55 bond. Crystal structures of the catalytically impaired promirolysin point mutant E225A at 1.4 and 1.6 Å revealed that latency is exerted by an N-terminal 34-residue pro-segment that shields the front surface of the 274-residue catalytic domain, thus preventing substrate access. The catalytic domain conforms to the metzincin clan of metallopeptidases and contains a double calcium site, which acts as a calcium switch for activity. The pro-segment traverses the active-site cleft in the opposite direction to the substrate, which precludes its cleavage. It is anchored to the mature enzyme through residue Arg21, which intrudes into the specificity pocket in cleft sub-site S1'. Moreover, residue Cys23 within a conserved cysteine–glycine motif blocks the catalytic zinc ion by a cysteine-switch mechanism, first described for mammalian matrix metallopeptidases. In addition, a 1.5 Å structure was obtained for a complex of mature mirolysin and a tetradecapeptide, which filled the cleft from sub-site S1' to S6'. A citrate molecule in S1 completed a product-complex mimic that unveiled the mechanism of substrate binding and cleavage by mirolysin, the catalytic domain of which was already preformed in the zymogen. These results, including a preference for cleavage before basic residues, are likely to be valid for other unicellular pappalysins derived from archaea, bacteria, cyanobacteria, algae and fungi, including archetypal ulilysin from Methanosarcina acetivorans. They may further apply, at least in part, to the multi-domain orthologues of higher organisms.

The first ab initio aspherical structure refinement against experimental X-ray structure factors for polypeptides and proteins using a fragmentation approach to break up the protein into residues and solvent, thereby speeding up quantum-crystallographic Hirshfeld atom refinement (HAR) calculations, is described. It it found that the geometric and atomic displacement parameters from the new fragHAR method are essentially unchanged from a HAR on the complete unfragmented system when tested on dipeptides, tripeptides and hexapeptides. The largest changes are for the parameters describing H atoms involved in hydrogen-bond interactions, but it is shown that these discrepancies can be removed by including the interacting fragments as a single larger fragment in the fragmentation scheme. Significant speed-ups are observed for the larger systems. Using this approach, it is possible to perform a highly parallelized HAR in reasonable times for large systems. The method has been implemented in the TONTO software.

Serial crystallography has enabled the study of complex biological questions through the determination of biomolecular structures at room temperature using low X-ray doses. Furthermore, it has enabled the study of protein dynamics by the capture of atomically resolved and time-resolved molecular movies. However, the study of many biologically relevant targets is still severely hindered by high sample consumption and lengthy data-collection times. By combining serial synchrotron crystallography (SSX) with 3D printing, a new experimental platform has been created that tackles these challenges. An affordable 3D-printed, X-ray-compatible microfluidic device (3D-MiXD) is reported that allows data to be collected from protein microcrystals in a 3D flow with very high hit and indexing rates, while keeping the sample consumption low. The miniaturized 3D-MiXD can be rapidly installed into virtually any synchrotron beamline with only minimal adjustments. This efficient collection scheme in combination with its mixing geometry paves the way for recording molecular movies at synchrotrons by mixing-triggered millisecond time-resolved SSX.

Transforming growth factor β-1 (TGFβ-1) is a secreted signalling protein that directs many cellular processes and is an attractive target for the treatment of several diseases. The primary endogenous activity regulatory mechanism for TGFβ-1 is sequestration by its pro-peptide, latency-associated peptide (LAP), which sterically prohibits receptor binding by caging TGFβ-1. As such, recombinant LAP is promising as a protein-based therapeutic for modulating TGFβ-1 activity; however, the mechanism of binding is incompletely understood. Comparison of the crystal structure of unbound LAP (solved here to 3.5 Å resolution) with that of the bound complex shows that LAP is in a more open and extended conformation when unbound to TGFβ-1. Analysis suggests a mechanism of binding TGFβ-1 through a large-scale conformational change that includes contraction of the inter-monomer interface and caging by the `straight-jacket' domain that may occur in partnership through a loop-to-helix transition in the core jelly-roll fold. This conformational change does not appear to include a repositioning of the integrin-binding motif as previously proposed. X-ray scattering-based modelling supports this mechanism and reveals possible orientations and ensembles in solution. Although native LAP is heavily glycosylated, solution scattering experiments show that the overall folding and flexibility of unbound LAP are not influenced by glycan modification. The combination of crystallography, solution scattering and biochemical experiments reported here provide insight into the mechanism of LAP sequestration of TGFβ-1 that is of fundamental importance for therapeutic development.

Human septins 3, 9 and 12 are the only members of a specific subgroup of septins that display several unusual features, including the absence of a C-terminal coiled coil. This particular subgroup (the SEPT3 septins) are present in rod-like octameric protofilaments but are lacking in similar hexameric assemblies, which only contain representatives of the three remaining subgroups. Both hexamers and octamers can self-assemble into mixed filaments by end-to-end association, implying that the SEPT3 septins may facilitate polymerization but not necessarily function. These filaments frequently associate into higher order complexes which associate with biological membranes, triggering a wide range of cellular events. In the present work, a complete compendium of crystal structures for the GTP-binding domains of all of the SEPT3 subgroup members when bound to either GDP or to a GTP analogue is provided. The structures reveal a unique degree of plasticity at one of the filamentous interfaces (dubbed NC). Specifically, structures of the GDP and GTPγS complexes of SEPT9 reveal a squeezing mechanism at the NC interface which would expel a polybasic region from its binding site and render it free to interact with negatively charged membranes. On the other hand, a polyacidic region associated with helix α5', the orientation of which is particular to this subgroup, provides a safe haven for the polybasic region when retracted within the interface. Together, these results suggest a mechanism which couples GTP binding and hydrolysis to membrane association and implies a unique role for the SEPT3 subgroup in this process. These observations can be accounted for by constellations of specific amino-acid residues that are found only in this subgroup and by the absence of the C-terminal coiled coil. Such conclusions can only be reached owing to the completeness of the structural studies presented here.

The structure of BgaR, a transcriptional regulator of the lactose operon in Clostridium perfringens, has been solved by SAD phasing using a mercury derivative. BgaR is an exquisite sensor of lactose, with a binding affinity in the low-micromolar range. This sensor and regulator has been captured bound to lactose and to lactulose as well as in a nominal apo form, and was compared with AraC, another saccharide-binding transcriptional regulator. It is shown that the saccharides bind in the N-terminal region of a jelly-roll fold, but that part of the saccharide is exposed to bulk solvent. This differs from the classical AraC saccharide-binding site, which is mostly sequestered from the bulk solvent. The structures of BgaR bound to lactose and to lactulose highlight how specific and nonspecific interactions lead to a higher binding affinity of BgaR for lactose compared with lactulose. Moreover, solving multiple structures of BgaR in different space groups, both bound to saccharides and unbound, verified that the dimer interface along a C-terminal helix is similar to the dimer interface observed in AraC.

Noncrystallographic symmetry (NCS) averaging following molecular-replacement phasing is generally the major technique used to solve a structure with several molecules in one asymmetric unit, such as a spherical icosahedral viral particle. As an alternative method to NCS averaging, a new approach to optimize or to refine the electron density directly under NCS constraints is proposed. This method has the same effect as the conventional NCS-averaging method but does not include the process of Fourier synthesis to generate the electron density from amplitudes and the corresponding phases. It has great merit for the solution of structures with limited data that are either twinned or incomplete at low resolution. This method was applied to the case of the T = 1 shell-domain subviral particle of Penaeus vannamei nodavirus with data affected by twinning using the REFMAC5 refinement software.

The structure of sodium saccharinate 1.875-hydrate is presented in three- and (3+1)-dimensional space. The present model is more accurate than previously published superstructures, due to an excellent data set collected up to a high resolution of 0.89 Å−1. The present study confirms the unusual complexity of the structure comprising a very large primitive unit cell with Z' = 16. A much smaller degree of correlated disorder of parts of the unit cell is found than is present in the previously published models. As a result of pseudo-symmetry, the structure can be described in a higher-dimensional space. The X-ray diffraction data clearly indicate a (3+1)-dimensional periodic structure with stronger main reflections and weaker superstructure reflections. Furthermore, the structure is established as being commensurate. The structure description in superspace results in a four times smaller unit cell with an additional base centring of the lattice, resulting in an eightfold substructure (Z' = 2) of the 3D superstructure. Therefore, such a superspace approach is desirable to work out this high-Z' structure. The displacement and occupational modulation of the saccharinate anions have been studied, as well as their conformational variation along the fourth dimension.

A tandem-double-slit optical system was constructed to evaluate the practical beam emittance of undulator radiation. The optical system was a combination of an upstream slit (S1) and downstream slit (S2) aligned on the optical axis with an appropriate separation. The intensity distribution after the double slits, I(x1, x2), was measured by scanning S1 and S2 in the horizontal direction. Coordinates having 1/sqrt e intensity were extracted from I(x1, x2), whose contour provided the standard deviation ellipse in the x1–x2 space. I(x1, x2) was converted to the corresponding distribution in the phase space, I(x1, x1'). The horizontal beam emittance was evaluated to be 3.1 nm rad, which was larger than the value of 2.4 nm rad estimated by using ray-tracing. It was found that the increase was mainly due to an increase in beam divergence rather than size.

Enhancement of X-ray excited optical luminescence in a 100 µm-thick diamond plate by introduction of defect states via electron beam irradiation and subsequent high-temperature annealing is demonstrated. The resulting X-ray transmission-mode scintillator features a linear response to incident photon flux in the range 7.6 × 108 to 1.26 × 1012 photons s−1 mm−2 for hard X-rays (15.9 keV) using exposure times from 0.01 to 5 s. These characteristics enable a real-time transmission-mode imaging of X-ray photon flux density without disruption of X-ray instrument operation.

The composition of occupied and unoccupied electronic states in the vicinity of Fermi energies is vital for all materials and relates to their physical, chemical and mechanical properties. This work demonstrates how the combination of resonant and non-resonant X-ray emission spectroscopies supplemented with theoretical modelling allows for quantitative analysis of electronic states in 5d transition metal and metal-oxide materials. Application of X-rays provides element selectivity that, in combination with the penetrating properties of hard X-rays, allows determination of the composition of electronic states under working conditions, i.e. non-vacuum environment. Tungsten metal and tungsten oxide are evaluated to show the capability to simultaneously assess composition of around-band-gap electronic states as well as the character and magnitude of the crystal field splitting.

Time-resolved X-ray absorption spectroscopy (XAS) offers the possibility to monitor the state of materials during chemical reactions. While this technique has been established for transmission measurements for a number of years, XAS measurements in fluorescence mode are challenging because of limitations in signal collection as well as detectors. Nevertheless, measurements in fluorescence mode are often the only option to study complex materials containing heavy matrices or in samples where the element of interest is in low concentration. Here, it has been demonstrated that high-quality quick-scanning full extended X-ray absorption fine-structure data can be readily obtained with sub-second time resolution in fluorescence mode, even for highly diluted samples. It has also been demonstrated that in challenging samples, where transmission measurements are not feasible, quick fluorescence can yield significant insight in reaction kinetics. By studying the fast high-temperature oxidation of a reduced LaFe0.8Ni0.8O3 perovskite type, an example where the perovskite matrix elements prevent measurements in fluorescence, it is shown that it is now possible to follow the state of Ni in situ at a 3 s time resolution.