Crystallization of Arthrobacter sp. strain 1C N-(1-D-carboxyethyl)-L-norvaline dehydrogenase and its complex with NAD+

The novel NAD+-linked opine dehydrogenase from a soil isolate Arthrobacter sp. strain 1C belongs to an enzyme superfamily whose members exhibit quite diverse substrate specificites. Crystals of this opine dehydrogenase, obtained in the presence or absence of co-factor and substrates, have been shown to diffract to beyond 1.8 ? resolution. X-ray precession photographs have established that the crystals belong to space group P21212, with cell parameters a = 104.9, b = 80.0, c = 45.5 ? and a single subunit in the asymmetric unit. The elucidation of the three-dimensional structure of this enzyme will provide a structural framework for this novel class of dehydrogenases to enable a comparison to be made with other enzyme families and also as the basis for mutagenesis experiments directed towards the production of natural and synthetic opine-type compounds containing two chiral centres.     

RNA-tethered phenyl azide photocrosslinking via a short-lived indiscriminant electrophile

Arylazide mediated photocrosslinking has been widely used to obtain structural constraints in biological systems, even though the reactive species generated upon photolysis in aqueous solution have not been well characterized. We establish a mechanistic framework for formation of adducts between photoactivated 3-hydroxyphenyl azide and RNA. Tethered to an internal site in an RNA duplex via a 2'-amido linkage, photolysis of the aryl azide yields a cross-strand cross-link. Analysis of the ability of reagents with diagnostic reactivities to intercept formation of this cross-strand cross-link supports the assignment that the photoactivated intermediate is the ketenimine or a ketenimine-derived ring expansion product. Neither the initially produced singlet nitrene nor the subsequently formed triplet nitrene contribute to cross-link formation. Argon matrix and time-resolved solution experiments show that photolysis of free 3-hydroxyphenyl azide releases (in 相似文献   

Likelihood analysis of the minimal AMSB model

We perform a likelihood analysis of the minimal anomaly-mediated supersymmetry-breaking (mAMSB) model using constraints from cosmology and accelerator experiments. We find that either a wino-like or a Higgsino-like neutralino LSP, \(\tilde{\chi }^0_{1}\), may provide the cold dark matter (DM), both with similar likelihoods. The upper limit on the DM density from Planck and other experiments enforces \(m_{\tilde{\chi }^0_{1}} \lesssim 3 \,\, \mathrm {TeV}\) after the inclusion of Sommerfeld enhancement in its annihilations. If most of the cold DM density is provided by the \(\tilde{\chi }^0_{1}\), the measured value of the Higgs mass favours a limited range of \(\tan \beta \sim 5\) (and also for \(\tan \beta \sim 45\) if \(\mu > 0\)) but the scalar mass \(m_0\) is poorly constrained. In the wino-LSP case, \(m_{3/2}\) is constrained to about \(900\,\, \mathrm {TeV}\) and \(m_{\tilde{\chi }^0_{1}}\) to \(2.9\pm 0.1\,\, \mathrm {TeV}\), whereas in the Higgsino-LSP case \(m_{3/2}\) has just a lower limit \(\gtrsim 650\,\, \mathrm {TeV}\) (\(\gtrsim 480\,\, \mathrm {TeV}\)) and \(m_{\tilde{\chi }^0_{1}}\) is constrained to \(1.12 ~(1.13) \pm 0.02\,\, \mathrm {TeV}\) in the \(\mu >0\) (\(\mu <0\)) scenario. In neither case can the anomalous magnetic moment of the muon, \((g-2)_\mu \), be improved significantly relative to its Standard Model (SM) value, nor do flavour measurements constrain the model significantly, and there are poor prospects for discovering supersymmetric particles at the LHC, though there are some prospects for direct DM detection. On the other hand, if the \(\tilde{\chi }^0_{1}\) contributes only a fraction of the cold DM density, future LHC Open image in new window -based searches for gluinos, squarks and heavier chargino and neutralino states as well as disappearing track searches in the wino-like LSP region will be relevant, and interference effects enable \(\mathrm{BR}(B_{s, d} \rightarrow \mu ^+\mu ^-)\) to agree with the data better than in the SM in the case of wino-like DM with \(\mu > 0\).     

Extending the language of DNA molecular recognition by polyamides: unexpected influence of imidazole and pyrrole arrangement on binding affinity and specificity

Pyrrole (Py) and imidazole (Im) polyamides can be designed to target specific DNA sequences. The effect that the pyrrole and imidazole arrangement, plus DNA sequence, have on sequence specificity and binding affinity has been investigated using DNA melting (DeltaT(M)), circular dichroism (CD), and surface plasmon resonance (SPR) studies. SPR results obtained from a complete set of triheterocyclic polyamides show a dramatic difference in the affinity of f-ImPyIm for its cognate DNA (K(eq) = 1.9 x 10(8) M(-1)) and f-PyPyIm for its cognate DNA (K(eq) = 5.9 x 10(5) M(-1)), which could not have been anticipated prior to characterization of these compounds. Moreover, f-ImPyIm has a 10-fold greater affinity for CGCG than distamycin A has for its cognate, AATT. To understand this difference, the triamide dimers are divided into two structural groupings: central and terminal pairings. The four possible central pairings show decreasing selectivity and affinity for their respective cognate sequences: -ImPy > -PyPy- > -PyIm- approximately -ImIm-. These results extend the language of current design motifs for polyamide sequence recognition to include the use of "words" for recognizing two adjacent base pairs, rather than "letters" for binding to single base pairs. Thus, polyamides designed to target Watson-Crick base pairs should utilize the strength of -ImPy- and -PyPy- central pairings. The f/Im and f/Py terminal groups yielded no advantage for their respective C/G or T/A base pairs. The exception is with the -ImPy- central pairing, for which f/Im has a 10-fold greater affinity for C/G than f/Py has for T/A.     

Frequentist analysis of the parameter space of minimal supergravity

We make a frequentist analysis of the parameter space of minimal supergravity (mSUGRA), in which, as well as the gaugino and scalar soft supersymmetry-breaking parameters being universal, there is a specific relation between the trilinear, bilinear and scalar supersymmetry-breaking parameters, A ₀=B ₀+m ₀, and the gravitino mass is fixed by m _3/2=m ₀. We also consider a more general model, in which the gravitino mass constraint is relaxed (the VCMSSM). We combine in the global likelihood function the experimental constraints from low-energy electroweak precision data, the anomalous magnetic moment of the muon, the lightest Higgs boson mass M _h , B physics and the astrophysical cold dark matter density, assuming that the lightest supersymmetric particle (LSP) is a neutralino. In the VCMSSM, we find a preference for values of m _1/2 and m ₀ similar to those found previously in frequentist analyses of the constrained MSSM (CMSSM) and a model with common non-universal Higgs masses (NUHM1). On the other hand, in mSUGRA we find two preferred regions: one with larger values of both m _1/2 and m ₀ than in the VCMSSM, and one with large m ₀ but small m _1/2. We compare the probabilities of the frequentist fits in mSUGRA, the VCMSSM, the CMSSM and the NUHM1: the probability that mSUGRA is consistent with the present data is significantly less than in the other models. We also discuss the mSUGRA and VCMSSM predictions for sparticle masses and other observables, identifying potential signatures at the LHC and elsewhere.     

Likelihood analysis of the pMSSM11 in light of LHC 13-TeV data

We use MasterCode to perform a frequentist analysis of the constraints on a phenomenological MSSM model with 11 parameters, the pMSSM11, including constraints from \(\sim 36\)/fb of LHC data at 13 TeV and PICO, XENON1T and PandaX-II searches for dark matter scattering, as well as previous accelerator and astrophysical measurements, presenting fits both with and without the \((g-2)_\mu \) constraint. The pMSSM11 is specified by the following parameters: 3 gaugino masses \(M_{1,2,3}\), a common mass for the first-and second-generation squarks \(m_{\tilde{q}}\) and a distinct third-generation squark mass \(m_{\tilde{q}_3}\), a common mass for the first-and second-generation sleptons \(m_{\tilde{\ell }}\) and a distinct third-generation slepton mass \(m_{\tilde{\tau }}\), a common trilinear mixing parameter A, the Higgs mixing parameter \(\mu \), the pseudoscalar Higgs mass \(M_A\) and \(\tan \beta \). In the fit including \((g-2)_\mu \), a Bino-like \(\tilde{\chi }^0_{1}\) is preferred, whereas a Higgsino-like \(\tilde{\chi }^0_{1}\) is mildly favoured when the \((g-2)_\mu \) constraint is dropped. We identify the mechanisms that operate in different regions of the pMSSM11 parameter space to bring the relic density of the lightest neutralino, \(\tilde{\chi }^0_{1}\), into the range indicated by cosmological data. In the fit including \((g-2)_\mu \), coannihilations with \(\tilde{\chi }^0_{2}\) and the Wino-like \(\tilde{\chi }^\pm _{1}\) or with nearly-degenerate first- and second-generation sleptons are active, whereas coannihilations with the \(\tilde{\chi }^0_{2}\) and the Higgsino-like \(\tilde{\chi }^\pm _{1}\) or with first- and second-generation squarks may be important when the \((g-2)_\mu \) constraint is dropped. In the two cases, we present \(\chi ^2\) functions in two-dimensional mass planes as well as their one-dimensional profile projections and best-fit spectra. Prospects remain for discovering strongly-interacting sparticles at the LHC, in both the scenarios with and without the \((g-2)_\mu \) constraint, as well as for discovering electroweakly-interacting sparticles at a future linear \(e^+ e^-\) collider such as the ILC or CLIC.     

Likelihood analysis of the sub-GUT MSSM in light of LHC 13-TeV data

We describe a likelihood analysis using MasterCode of variants of the MSSM in which the soft supersymmetry-breaking parameters are assumed to have universal values at some scale \(M_\mathrm{in}\) below the supersymmetric grand unification scale \(M_\mathrm{GUT}\), as can occur in mirage mediation and other models. In addition to \(M_\mathrm{in}\), such ‘sub-GUT’ models have the 4 parameters of the CMSSM, namely a common gaugino mass \(m_{1/2}\), a common soft supersymmetry-breaking scalar mass \(m_0\), a common trilinear mixing parameter A and the ratio of MSSM Higgs vevs \(\tan \beta \), assuming that the Higgs mixing parameter \(\mu > 0\). We take into account constraints on strongly- and electroweakly-interacting sparticles from \(\sim 36\)/fb of LHC data at 13 TeV and the LUX and 2017 PICO, XENON1T and PandaX-II searches for dark matter scattering, in addition to the previous LHC and dark matter constraints as well as full sets of flavour and electroweak constraints. We find a preference for \(M_\mathrm{in}\sim 10^5\) to \(10^9 \,\, \mathrm {GeV}\), with \(M_\mathrm{in}\sim M_\mathrm{GUT}\) disfavoured by \(\Delta \chi ^2 \sim 3\) due to the \(\mathrm{BR}(B_{s, d} \rightarrow \mu ^+\mu ^-)\) constraint. The lower limits on strongly-interacting sparticles are largely determined by LHC searches, and similar to those in the CMSSM. We find a preference for the LSP to be a Bino or Higgsino with \(m_{\tilde{\chi }^0_{1}} \sim 1 \,\, \mathrm {TeV}\), with annihilation via heavy Higgs bosons H / A and stop coannihilation, or chargino coannihilation, bringing the cold dark matter density into the cosmological range. We find that spin-independent dark matter scattering is likely to be within reach of the planned LUX-Zeplin and XENONnT experiments. We probe the impact of the \((g-2)_\mu \) constraint, finding similar results whether or not it is included.     

Intercalation of Toluidines into α-Zirconium Hydrogenphosphate

Intercalates of o-, m-, and p-toluidine into α-Zr(HPO₄)₂ · H₂O were prepared and characterized by powder X-ray diffraction, thermogravimetric analysis and infrared spectroscopy. As follows from IR, toludine molecules are protonated in the interlayer space. Toluidine molecules are arranged in a bimolecular way in the intercalates containing more than 1.5 toluidine molecules per Zr atom. On the other hand, a monolayer of the toluidine molecules is supposed in the intercalates with less than one toluidine molecule per Zr atom.     

The free energy of a reaction coordinate at multiple constraints: a concise formulation

The free energy as a function of the reaction coordinate (rc) is the key quantity for the computation of equilibrium and kinetic quantities. When it is considered as the potential of mean force, the problem is the calculation of the mean force for given values of the rc. We reinvestigate the PMCF (potential of mean constraint force) method which applies a constraint to the rc to compute the mean force as the mean negative constraint force and a metric tensor correction. The latter allows for the constraint imposed to the rc and possible artefacts due to multiple constraints of other variables which for practical reasons are often used in numerical simulations. Two main results are obtained that are of theoretical and practical interest. First, the correction term is given a very concise and simple shape which facilitates its interpretation and evaluation. Secondly, a theorem describes various rcs and possible combinations with constraints that can be used without introducing any correction to the constraint force. The results facilitate the computation of free energy by molecular dynamics simulations.