Early stages of phase selection in MOF formation observed in molecular Monte Carlo simulations

Metal-organic frameworks (MOF) comprising metal nodes bridged by organic linkers show great promise because of their guest-specific gas sorption, separation, drug-delivery, and catalytic properties. The selection of metal node, organic linker, and synthesis conditions in principle offers engineered control over both structure and function. For MOFs to realise their potential and to become more than just promising materials, a degree of predictability in the synthesis and a better understanding of the self-assembly or initial growth processes is of paramount importance. Using cobalt succinate, a MOF that exhibits a variety of phases depending on synthesis temperature and ligand to metal ratio, as proof of concept, we present a molecular Monte Carlo approach that allows us to simulate the early stage of MOF assembly. We introduce a new Contact Cluster Monte Carlo (CCMC) algorithm which uses a system of overlapping "virtual sites" to represent the coordination environment of the cobalt and both metal-metal and metal-ligand associations. Our simulations capture the experimentally observed synthesis phase distinction in cobalt succinate at 348 K. To the best of our knowledge this is the first case in which the formation of different MOF phases as a function of composition is captured by unbiased molecular simulations. The CCMC algorithm is equally applicable to any system in which short-range attractive interactions are a dominant feature, including hydrogen-bonding networks, metal-ligand coordination networks, or the assembly of particles with "sticky" patches, such as colloidal systems or the formation of protein complexes.</p

A Modified Synthetic Aperture Focussing Technique Utilising the Spatial Impulse Response of the Ultrasound Transducer

In B-mode imaging, lateral resolution is impeded by the size and shape of the ultrasound beam used to create the image. For improved lateral resolution, a focussing method that utilises a beam model calculated using the Fraunhofer far field approximations to enhance the Synthetic Aperture Focussing Technique (SAFT) is proposed. The Beam Model Weighted Synthetic Aperture Focussing Technique (BMW-SAFT) method uses an approximation of the beam model to weight the focussing algorithm and adjust the aperture size based on distance from the transducer. Through application to simulated data the method is compared with the conventional SAFT, where the proposed algorithm is found to provide significant improvements over the conventional SAFT methods

Cosmic Strings from Supersymmetric Flat Directions

Flat directions are a generic feature of the scalar potential in supersymmetric gauge field theories. They can arise, for example, from D-terms associated with an extra abelian gauge symmetry. Even when supersymmetry is broken softly, there often remain directions in the scalar field space along which the potential is almost flat. Upon breaking a gauge symmetry along one of these almost flat directions, cosmic strings may form. Relative to the standard cosmic string picture based on the abelian Higgs model, these flat-direction cosmic strings have the extreme Type-I properties of a thin gauge core surrounded by a much wider scalar field profile. We perform a comprehensive study of the microscopic, macroscopic, and observational characteristics of this class of strings. We find many differences from the standard string scenario, including stable higher winding mode strings, the dynamical formation of higher mode strings from lower ones, and a resultant multi-tension scaling string network in the early universe. These strings are only moderately constrained by current observations, and their gravitational wave signatures may be detectable at future gravity wave detectors. Furthermore, there is the interesting but speculative prospect that the decays of cosmic string loops in the early universe could be a source of ultra-high energy cosmic rays or non-thermal dark matter. We also compare the observational signatures of flat-direction cosmic strings with those of ordinary cosmic strings as well as (p,q) cosmic strings motivated by superstring theory.Comment: 58 pages, 16 figures, v2. accepted to PRD, added comments about baryogenesis and boosted decay products from cusp annihilatio

Protein flexibility is key to cisplatin crosslinking in calmodulin

Chemical crosslinking in combination with Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) has significant potential for studying protein structures and proteinprotein interactions. Previously, cisplatin has been shown to be a crosslinker and crosslinks multiple methionine (Met) residues in apo-calmodulin (apo-CaM). However, the inter-residue distances obtained from nuclear magnetic resonance structures are inconsistent with the measured distance constraints by crosslinking. Met residues lie too far apart to be crosslinked by cisplatin. Here, by combining FTICR MS with a novel computational flexibility analysis, the flexible nature of the CaM structure is found to be key to cisplatin crosslinking in CaM. It is found that the side chains of Met residues can be brought together by flexible motions in both apo-CaM and calcium-bound CaM (Ca4-CaM). The possibility of cisplatin crosslinking Ca4-CaM is then confirmed by MS data. Therefore, flexibility analysis as a fast and low-cost computational method can be a useful tool for predicting crosslinking pairs in protein crosslinking analysis and facilitating MS data analysis. Finally, flexibility analysis also indicates that the crosslinking of platinum to pairs of Met residues will effectively close the nonpolar groove and thus will likely interfere with the binding of CaM to its protein targets, as was proved by comparing assays for cisplatin-modified/unmodified CaM binding to melittin. Collectively, these results suggest that cisplatin crosslinking of apo-CaM or Ca4-CaM can inhibit the ability of CaM to recognize its target proteins, which may have important implications for understanding the mechanism of tumor resistance to platinum anticancer drugs

Virtual effects of light gauginos and higgsinos: a precision electroweak analysis of split supersymmetry

We compute corrections to precision electroweak observables in supersymmetry in the limit that scalar superpartners are very massive and decoupled. This leaves charginos and neutralinos and a Standard Model-like Higgs boson as the only states with unknown mass substantially affecting the analysis. We give complete formulas for the chargino and neutralino contributions, derive simple analytic results for the pure gaugino and higgsino cases, and study the general case. We find that in all circumstances, the precision electroweak fit improves when the charginos and neutralinos are near the current direct limits. Larger higgsino and gaugino masses worsen the fit as the theory predictions asymptotically approach those of the Standard Model. Since the Standard Model is considered by most to be an adequate fit to the precision electroweak data, an important corollary to our analysis is that all regions of parameter space allowed by direct collider constraints are also allowed by precision electroweak constraints in split supersymmetry.Comment: 22 pages, 5 figures, v2: typos fixed and note adde

Highly effective yet simple transmembrane anion transporters based upon ortho-phenylenediamine bis-ureas

Simple, highly fluorinated receptors are shown to function as highly effective transmembrane anion antiporters with the most active transporters rivalling the transport efficacy of natural anion transporter prodigiosin for bicarbonate

Laboratory-Reported Normal Value Ranges Should Not Be Used to Diagnose Periprosthetic Joint Infection.

INTRODUCTION: Clinical laboratories offer several multipurpose tests, such as the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), which are not intended to diagnose any specific disease but are used by clinicians in multiple fields. The results and laboratory interpretation (normal/abnormal) of these multipurpose tests are based on laboratory-reported normal thresholds, which vary across clinical laboratories. In 2018, the International Consensus Meeting on Musculoskeletal Infection (2018 ICM) provided a gold-standard definition to diagnose periprosthetic joint infection (PJI) which included many multipurpose laboratory tests, along with thresholds optimized to diagnose PJI. The discrepancy between laboratory-reported normal thresholds and 2018 ICM-recommended PJI-optimized test thresholds has never been studied. The purpose of this study was to assess the existing variation in laboratory-reported normal thresholds for tests commonly used to diagnose PJI and evaluate the potential diagnostic impact of using laboratory-reported normal thresholds instead of 2018 ICM-recommended PJI-optimized thresholds. METHODS: Clinical laboratories (N=85) were surveyed to determine the laboratory-reported units of measure and normal thresholds for common multipurpose tests to diagnose PJI, including the ESR, CRP, D-dimer, synovial fluid white blood cells (SF-WBC), and polymorphonuclear cell percent (SF-PMN%). The variability of units of measure and normal thresholds for each test was then assessed among the 85 included clinical laboratories. A representative dataset from patients awaiting a revision arthroplasty was used to determine the clinical significance of the existing discrepancy between laboratory-reported normal test interpretations and 2018 ICM-recommended PJI-optimized test interpretations. RESULTS: Two units of measure for the CRP and six units of measure for the D-dimer were observed, with only 59% of laboratories reporting the CRP in terms of mg/L and only 16% reporting the D-dimer in ng/ml, as needed to utilize the 2018 ICM definition of PJI. Across clinical laboratories surveyed, the mean laboratory-reported normal thresholds for the ESR (20 mm/h), CRP (7.69 mg/L), D-dimer (500 ng/mL), SF-WBC (5 cells/uL), and SF-PMN% (25%) were substantially lower than the 2018 ICM-recommended PJI-optimized thresholds of 30 mm/h, 10 mg/L, 860 ng/mL, 3,000 cells/uL, and 70%, respectively. Interpretation of test results from a representative PJI dataset using each laboratory\u27s normal test thresholds yielded mean false-positive rates of 14% (ESR), 18% (CRP), 42% (D-dimer), 93% (SF-WBC), and 36% (SF-PMN%) versus the ICM-recommended PJI-optimized thresholds. CONCLUSION: When reporting the results for multipurpose laboratory tests, such as the ESR, CRP, D-dimer, SF-WBC, and SF-PMN%, clinical laboratories utilize laboratory-reported units of measure and normal thresholds that are not intended to diagnose PJI, and therefore may not match the 2018 ICM recommendations. Our findings reveal that laboratory-reported normal thresholds for these multipurpose tests are well below the 2018 ICM recommendations to diagnose PJI. Clinical reliance on laboratory-reported results and interpretations, instead of strict use of the 2018 ICM-recommended units and PJI-optimized thresholds, may lead to false-positive interpretation of multipurpose laboratory tests