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Wefabricate transistors from chemical vapor deposition-grown monolayerMoS2crystals and demonstrate excellent current saturationat large drain voltages (Vd). The low-fieldcharacteristics of these devices indicate that the electron mobilityis likely limited by scattering from charged impurities. The current–voltagecharacteristics exhibit variable range hopping at low Vdand evidence of velocity saturation at higher Vd. This work confirms the excellent potentialof MoS2as a possible channel-replacement material andhighlights the role of multiple transport phenomena in governing itstransistor action. [ABSTRACT FROM AUTHOR]

The carbamate group is a key structuralmotif in many approveddrugs and prodrugs. There is an increasing use of carbamates in medicinalchemistry and many derivatives are specifically designed to make drug–targetinteractions through their carbamate moiety. In this Perspective,we present properties and stabilities of carbamates, reagents andchemical methodologies for the synthesis of carbamates, and recentapplications of carbamates in drug design and medicinal chemistry. [ABSTRACT FROM AUTHOR]

We report the design, synthesis, biological evaluation, and the X-ray crystal structure of a novel inhibitor bound to the HIV-1 protease. Various C3-functionalized cyclopentanyltetrahydrofurans (Cp-THF) were designed to interact with the flap Gly48 carbonyl or amide NH in the S2-subsite of the HIV-1 protease. We investigated the potential of those functionalized ligands in combination with hydroxyethylsulfonamide isosteres. Inhibitor 26containing a 3-(R)-hydroxyl group on the Cp-THF core displayed the most potent enzyme inhibitory and antiviral activity. Our studies revealed a preference for the 3-(R)-configuration over the corresponding 3-(S)-derivative. Inhibitor 26exhibited potent activity against a panel of multidrug-resistant HIV-1 variants. A high resolution X-ray structure of 26-bound HIV-1 protease revealed important molecular insight into the ligand-binding site interactions. [ABSTRACT FROM AUTHOR]

Metal–ligand complexes of Cu(OTf)2with an appropriate bisphosphine ligand have been shown to effectively catalyze the formation of substituted tetrahydropyrans via a sequential olefin migration and Prins-type cyclization. This methodology provides convenient access to a variety of functionalized tetrahydropyrans in excellent diastereoselectivities and good to excellent yields. [ABSTRACT FROM AUTHOR]

The design, synthesis, and evaluation of a new series of hexahydrofuropyranol-derived HIV-1 protease inhibitors are described. We have designed a stereochemically defined hexahydrofuropyranol-derived urethane as the P2-ligand. The current ligand is designed based upon the X-ray structure of 1a-bound HIV-1 protease. The synthesis of (3aS,4S,7aR)-hexahydro-2H-furo[2,3-b]pyran-4-ol, (−)-7, was carried out in optically active form. Incorporation of this ligand provided inhibitor 35a, which has shown excellent enzyme inhibitory activity and antiviral potency. Our structure−activity studies have indicated that the stereochemistry and the position of oxygens in the ligand are important to the observed potency of the inhibitor. Inhibitor 35ahas maintained excellent potency against multidrug-resistant HIV-1 variants. An active site model of 35awas created based upon the X-ray structure of 1b-bound HIV-1 protease. The model offers molecular insights regarding ligand-binding site interactions of the hexahydrofuropyranol-derived novel P2-ligand. [ABSTRACT FROM AUTHOR]

A stereoselective synthesis of ()-herboxidiene is described. The convergent synthesis utilized a Suzuki cross-coupling reaction to assemble the key segments. The synthesis of the functionalized tetrahydropyran ring utilized an Achmatowicz reaction as the key step. The synthesis of the C10−C19 segment was accomplished using Brown’s crotylboration, asymmetric alkylation, and a stereoselective allylic chlorination reactions. [ABSTRACT FROM AUTHOR]

The X-ray crystallographic study of various anionic complexes have been performed on two laterally non-symmetric aza-oxa cryptands Loand Lmhaving different cavity dimension. The anions are bound through various N/C/O–HX (X = anion) bonding interactions with the cryptand receptors. For the chloride complex of Lo(complex 1), the encapsulated chloride resides perfectly on C3axis and prefers to stay at the ‘oxa’ end despite H- bonding interactions with protonated ‘aza’ N atoms. In case of the perchlorate (complex 2), the anion remains outside the cavity. The anions occupy the cavity created by four arms of two cryptand molecules and also the space provided by the two arms of a single cryptand molecule. Although, Lmhas a larger cavity, perchlorate still remains outside (complex 3). To probe preferences for encapsulation, cryptand Lmis allowed to react with three different binary mixtures of acids. For the case of HCl–H2SO4and HCl-HNO3binary systems (complex 4and 5, respectively), Cl−is incorporated in the cavity leaving SO4−or NO3−outside. In case of HBr-HNO3mixture, NO3−is preferred over Br−in the cavity (complex 6). In each case for Lm, the encapsulated anion is displaced away from ‘oxa’ end to the ‘aza’ end of the cavity. Interestingly, in 2–6the secondary amino N in the bridges and the bridgehead N at the ‘aza’ end gets protonated. In these compounds, water clusters of various nuclearity have been identified. [ABSTRACT FROM AUTHOR]

Enantioselective total syntheses of the proposed structures of macrolide cytotoxic agents iriomoteolide-1a and -1b have been accomplished. The synthesis was carried out in a convergent and stereoselective manner. However, the present work suggests that the reported structures have been assigned incorrectly. The synthesis features Julia−Kocienski olefination, Sharpless asymmetric epoxidation, Brown asymmetric crotylboration, a Sakurai reaction, an aldol reaction, and enzymatic resolution as the key steps. [ABSTRACT FROM AUTHOR]

An X-ray crystallographic study of binding of nitrate and sulfate anions with two laterally asymmetric aza cryptands (Loand Lm) having different cavity dimensions is reported. A variety of binding modes for these anions have been observed. Cryptand Lmhaving a larger cavity than that of Lo, prefers to encapsulate a planar nitrate over Td sulfate in its cavity when both anions are available for complexation. A discrete (H2O)29cluster can be identified as surrounded by six sulfate ions attached to two Lmunits. 1H NMR titration results indicate that either [H3Lo]3+or [H3Lm]3+binds strongly with sulfate rather than nitrate in solution. [ABSTRACT FROM AUTHOR]

The structure-based design, synthesis, and biological evaluationof a series of nonpeptidic macrocyclic HIV protease inhibitors aredescribed. The inhibitors are designed to effectively fill in thehydrophobic pocket in the S1′−S2′ subsites andretain all major hydrogen bonding interactions with the protein backbonesimilar to darunavir (1)or inhibitor 2.The ring size, the effect of methyl substitution, and unsaturationwithin the macrocyclic ring structure were assessed. In general, cyclicinhibitors were significantly more potent than their acyclic homologues,saturated rings were less active than their unsaturated analoguesand a preference for 10- and 13-membered macrocylic rings was revealed.The addition of methyl substituents resulted in a reduction of potency.Both inhibitors 14band 14cexhibited markedenzyme inhibitory and antiviral activity, and they exerted potentactivity against multidrug-resistant HIV-1 variants. Protein−ligandX-ray structures of inhibitors 2and 14cprovided critical molecular insights into the ligand-binding siteinteractions. [ABSTRACT FROM AUTHOR]

An enantioselective synthesis of marine alkaloid brevisamide was accomplished in a convergent manner. The synthesis utilized an enantioselective hetero-Diels−Alder reaction which sets three chiral centers in compound 11. The synthesis also features a modified Wolff−Kishner reduction, Rubottom oxidation, and Suzuki−Miyaura coupling to furnish brevisamide. [ABSTRACT FROM AUTHOR]

We describe here the design, synthesis, molecular modeling, and biological evaluation of a series of small molecule, nonpeptide inhibitors of SARS-CoV PLpro. Our initial lead compound was identified via high-throughput screening of a diverse chemical library. We subsequently carried out structure−activity relationship studies and optimized the lead structure to potent inhibitors that have shown antiviral activity against SARS-CoV infected Vero E6 cells. Upon the basis of the X-ray crystal structure of inhibitor 24-bound to SARS-CoV PLpro, a drug design template was created. Our structure-based modification led to the design of a more potent inhibitor, 2(enzyme IC50= 0.46 μM; antiviral EC50= 6 μM). Interestingly, its methylamine derivative, 49, displayed good enzyme inhibitory potency (IC50= 1.3 μM) and the most potent SARS antiviral activity (EC50= 5.2 μM) in the series. We have carried out computational docking studies and generated a predictive 3D-QSAR model for SARS-CoV PLpro inhibitors. [ABSTRACT FROM AUTHOR]

(S)-N-(2-Pyrrolidinylmethyl)pyrrolidine/trifluoroacetic acid (3:1) combination catalyzed the direct addition of alkyl methyl ketones to β-dimethyl(phenyl)silylmethylene malonate at the methyl terminal with high yield and excellent regio- and enantioselectivity. The silyl group played crucial roles in regioselection and substrate reactivity. [ABSTRACT FROM AUTHOR]

The total synthesis of the proposed structure of anticancer agent stereocalpin A is described. The synthesis features a diastereoselective synthesis of a 5-hydroxy-2,4-dimethyl-3-oxooctanoic acid unit with asymmetric anti- and syn-aldol reactions as the key steps. Initial cycloamidation led to complete epimerization at the C-11 stereocenter due to unique steric constraints in the 12-membered depsipeptide ring. A late-stage methylation strategy led to the synthesis of the proposed structure of stereocalpin A. [ABSTRACT FROM AUTHOR]

Pyridine-2,4,6-tricarboxylic acid (ptcH3) reacts with Cd(ii), Mn(ii), Ni(ii), Mg(ii), Ca(ii), Sr(ii), Ba(ii), Dy(iii) salts forming different products depending on the reaction conditions. In the presence of pyridine at room temperature the acetate, chloride or nitrate salt of Cd(ii) breaks the ligand to form an open framework structure with the empirical formula, {[Cd(Ox)(H2O)2]H2O}n(Ox = oxalate), 1. In the absence of pyridine, no crystalline compound could be isolated at room temperature (RT). However, under hydrothermal conditions and in the absence of pyridine, a discrete tetrameric complex with the formula, {[Cd2(cda)2(H2O)4](H2O)3}2(cdaH2= 4-hydroxypyridine-2,6-dicarboxylic acid), 2, is formed where the carboxylate group at the 4-position of the ligand is reduced to a hydroxyl group. When Ni(ii), Mn(ii), Mg(ii), Ca(ii), Sr(ii), Ba(ii), Dy(iii) salts are used in place of Cd(ii), no crystalline product could be isolated at RT. But under hydrothermal conditions, coordination polymers ({[Ni1.5(ptc)(pip)0.5(H2O)4]·H2O}n, (pip = piperazine), 3; {Mn1.5(ptc)·2H2O}n, 4; {Mg3(ptc)2·8H2O}n, 5; {[Mg(ptc)(H2O)2]·1/2[Mg(H2O)6]·H2O}n, 6; {Ca1.5(ptc)·2H2O}n, 7; {Sr1.5(ptc)·5H2O}n, 8; {[Ba(ptc)(H2O)][Ba(ptcH2)H2O]}n, 9; {[Dy(ptc)·3H2O]·H2O}n, 10) are formed. The structures exhibit different dimensionality depending on the nature of the metal ions. In 1a discrete acyclic water hexamer is also identified. All the compounds are characterized in the solid state by X-ray crystallography, IR and elemental analysis. [ABSTRACT FROM AUTHOR]

Three novel three-dimensional (3D) coordination polymers have been synthesized by the self-assembly of a flexible tricarboxylate ligand and Cd(II) metal ion in dimethylformamide (DMF), diethylformamide (DEF) and isopropanol (PrOH), where changes of solvent with different size and shape lead to the formation of solvent templated neutral and anionic frameworks with different pore sizes and shapes as shown by X-ray crystallography. [ABSTRACT FROM AUTHOR]

L-Selectride reduction of a chiral or achiral enone followed by reaction of the resulting enolate with optically active α-alkoxy aldehydes proceeded with excellent diastereoselectivity. The resulting α,α-dimethyl-β-hydroxy ketones are inherent to a variety of biologically active natural products. [ABSTRACT FROM AUTHOR]

Darunavir, a potent antiviral drug, showed an unusual second binding site on the HIV-1 protease dimer surface of the V32I drug resistant mutant and normal binding in the active site cavity. Kinetic analysis for wild type and mutant protease showed mixed-type competitive−uncompetitive inhibition for darunavir and the chemically related amprenavir, while saquinavir showed competitive inhibition. The inhibition model is consistent with the observed second binding site for darunavir and helps to explain its antiviral potency. [ABSTRACT FROM AUTHOR]

We report the design, synthesis, and biological evaluation of a series of novel HIV-1 protease inhibitors. The inhibitors incorporate stereochemically defined flexible cyclic ethers/polyethers as high affinity P2-ligands. Inhibitors containing small ring 1,3-dioxacycloalkanes have shown potent enzyme inhibitory and antiviral activity. Inhibitors 3dand 3hare the most active inhibitors. Inhibitor 3dmaintains excellent potency against a variety of multi-PI-resistant clinical strains. Our structure−activity studies indicate that the ring size, stereochemistry, and position of oxygens are important for the observed activity. Optically active synthesis of 1,3-dioxepan-5-ol along with the syntheses of various cyclic ether and polyether ligands have been described. A protein−ligand X-ray crystal structure of 3d-bound HIV-1 protease was determined. The structure revealed that the P2-ligand makes extensive interactions including hydrogen bonding with the protease backbone in the S2-site. In addition, the P2-ligand in 3dforms a unique water-mediated interaction with the NH of Gly-48. [ABSTRACT FROM AUTHOR]

An enantioselective total synthesis of ()-peloruside A (1) is described. Peloruside A (1) is a potent microtubule stabilizer with significant clinical potential. The synthesis is convergent and involves the assembly of C1−C10 segment 2 and C11−C24 segment 3 by a novel aldol protocol followed by Yamaguchi macrolactonization of the resulting seco-acid, selective methylation of hemi-ketal and removal of the protecting groups to peloruside A. [ABSTRACT FROM AUTHOR]

We propose a generalized one-dimensional energy diffusion approach for describing the dynamics of multidimensional dynamical processes in the condensed phase. On the basis of a formalism originally due to Zwanzig, we obtain a one-dimensional kinetic equation for a properly selected relevant dynamical quantity and derive new analytical results for the dynamics of a multidimensional electron-transfer process, nonequilibrium solvation, and diffusive escape from a potential well. The calculated results for electron-transfer reactions in solvent-separated and contact ion pair systems are found to be in good agreement with the experimental results. We are able to explain the rate of the electron-transfer reaction using much smaller and reasonable values of the solvent reorganization energy in contrast to earlier works that had to use a much larger value. The proposed theory is not only conceptually simpler than the conventional approaches but is also free from many of their limitations. More importantly, it provides a single theoretical framework for describing a wide class of dynamical phenomena. [ABSTRACT FROM AUTHOR]

It is demonstrated that the doping of alkali metal atoms on fullerene, C60, remarkably enhances the molecular hydrogen adsorption capacity of fullerenes, which is higher than that of conventionally known other fullerene complexes. This effect is observed to be more pronounced for sodium than lithium atom. The formation of stable complex forms of a sodium-doped fullerene molecule, Na8C60, and the corresponding hydrogenated species, Na(H2)68C60, with 48 hydrogen molecules has been demonstrated to lead to a hydrogen adsorption density of ∼9.5 wt %. One of the main factors favoring the interactions involved is attributed to the pronounced charge transfer from the sodium atom to the C60molecule and electrostatic interaction between the ion and the dihydrogen. The suitability of these complexes for developing fullerene-based hydrogen storage materials is discussed. [ABSTRACT FROM AUTHOR]

The appropriate choice of dimethylsulfonium methylide generation conditions enables the highly regioselective tandem ylide addition−eliminative olefination to 1,3-dienedioates providing 1,3-butadien-2-ylmalonates, a novel class of 2-substituted 1,3-dienes suitable for quick assembly of precursors for type 2 intramolecular Diels−Alder reactions. [ABSTRACT FROM AUTHOR]

An enantioselective route to the oxatetracyclic core of (−)-platensimycin (1) has been investigated by using an intramolecular Diels−Alder reaction as the key step. The thermal reaction of E/Zmixture (1:1) provided oxatetracyclic core 2from the E-diene and the Z-diene was recovered unchanged. The Diels−Alder substrate was conveniently assembled in optically active form with use of (S)-carvone as the starting material. [ABSTRACT FROM AUTHOR]

For the first time, the dispersion stability of silica nanoparticles has been investigated in high-temperature and high-pressure ethanol by measuring the hydrodynamic diffusion coefficient of the particles by means of dynamic light scattering. The silica nanoparticles remain stable in ethanol within a wide temperature range of 24−304 °C at 12.3 MPa, and they start to aggregate at T≥ 305 °C. Numerical analysis reveals that the net interparticle repulsive potential barrier decreases dramatically with increasing temperature due to the changes in the properties of the medium. We observed that particles remain highly stable in the nonpolar supercritical ethanol in the temperature regime 241−304 °C, where the DLVO potential barrier is only 5−2 kBT. The dispersion stability of silica nanoparticles at this low potential barrier in high-temperature and high-pressure ethanol, especially in the supercritical ethanol, is fascinating. The silica−ethanol system might be a unique and special example in the colloidal dispersions. Results suggest that silica nanoparticles may be used as a model colloid to investigate the colloidal transport phenomena in the supercritical ethanol. [ABSTRACT FROM AUTHOR]

Structure-based design and synthesis of a number of potent and selective memapsin 2 inhibitors are described. These inhibitors were designed based upon the X-ray structure of memapsin 2-bound inhibitor 3that incorporates methylsulfonyl alanine as the P2-ligand and a substituted pyrazole as the P3-ligand. Of particular importance, we examined the ability of the substituted isophthalic acid amide derivative to mimic the key interactions in the S2−S3regions of the enzyme active sites of 3-bound memapsin 2. We investigated various substituted phenylethyl, -methylbenzyl, and oxazolylmethyl groups as the P3-ligands. A number of inhibitors exhibited very potent inhibitory activity against mempasin 2 and good selectivity against memapsin 1. Inhibitor 5dhas shown low nanomolar enzyme inhibitory potency (Ki1.1 nM) and very good cellular inhibitory activity (IC5039 nM). Furthermore, in a preliminary study, inhibitor 5dhas shown 30% reduction of A40production in transgenic mice after a single intraperitoneal administration (8 mg/kg). A protein−ligand X-ray crystal structure of 5d-bound memapsin 2 provided vital molecular insight that can serve as an important guide to further design of novel inhibitors. [ABSTRACT FROM AUTHOR]

An enantioselective total synthesis of (−)-lasonolide A is described. The upper tetrahydropyran ring was constructed stereoselectively by an intramolecular 1,3-dipolar cycloaddition reaction. The bicyclic isooxazoline led to the tetrahydropyran ring as well as the quaternary stereocenter present in the molecule. The lower tetrahydropyran ring was assembled by a catalytic asymmetric hetero-Diels−Alder reaction as the key step. Three stereocenters were enantioselectively installed in this single step reaction. [ABSTRACT FROM AUTHOR]

We report the observation of an intermediate mesh phase with rhombohedral symmetry, corresponding to the space group Rm, in a mixed surfactant system formed by the cationic surfactant cetyltrimethylammonium bromide (CTAB) and the organic salt 3-sodium-2-hydroxy naphthoate (SHN). It occurs between a random mesh phase (%@mt;sys@%L%@sx@%%@be@%D%@sxx@%%@mx@%) and a lamellar phase (L) at low temperatures; at higher temperatures, the %@mt;sys@%L%@sx@%%@be@%D%@sxx@%%@mx@%phase transforms continuously into the Lphase with an increasing surfactant concentration (s). To separate the effects of salt and son the phase behavior, the ternary system consisting of cetyltrimethylammonium 3-hydroxy-naphthalene-2-carboxylate (CTAHN), sodium bromide (NaBr), and water was studied. The intermediate mesh phase is found in this system at high NaBr concentrations. The micellar aggregates, both in the intermediate and random mesh phases, are found to be made up of a two-dimensional network of rod-like segments, with three rods meeting at each node. The average mesh size increases with s, and the transition from the random mesh phase to the intermediate phase is found to occur when it is approximately 1.5 times the lamellar periodicity. The intermediate mesh phase is absent in the equimolar dodecyltrimethylammonium bromide (DTAB)−SHN system, indicating the role of the surfactant chain length in the formation of this phase. This system exhibits a random mesh phase over a very wide range of water content, with the average mesh size decreasing upon an increasing s, contrary to the trend seen in the CTAB−SHN system. [ABSTRACT FROM AUTHOR]

Dispersion stability of colloids has been investigated in sub- and supercritical water by measuring the hydrodynamic diffusion coefficients of the particles by means of dynamic light scattering. It is interestingly found that coagulation of the colloids in sub- and supercritical water is a universal phenomenon irrespective of the material of the colloids. Highly charged colloids were found to be more stable in water against high temperature. Numerical analysis reveals that the stability of the colloids at elevated temperature and pressure is primarily governed by the temperature dependence of the dielectric constant of the medium. The effect of the temperature dependence of the ion product of water (pKw) was found to be very little. Surface charge density and Stern potential may change with respect to temperature due to the readjustment of the ion concentration in the diffuse layer through the enhanced ion product and reduced dielectric constant of water. These are the secondary causes of the particle coagulations in sub- and supercritical water. [ABSTRACT FROM AUTHOR]

The application of dynamic light scattering to measure viscosity of water at high temperatures and pressures is demonstrated. Viscosity was obtained from the translational diffusion coefficient of probe particles dispersed in the medium by the Einstein−Stokes relationship. Measurements were carried out with polystyrene latex, colloidal silica, and colloidal gold. Under a constant pressure of 25 MPa, good agreement was found between the measured and calculated viscosities up to 275 °C with the polystyrene latex, 200 °C with the colloidal silica, and 297 °C with the colloidal gold. It was found that failure of the measurements at high temperatures is ascribed to change in either the dispersion stability or chemical stability of the probe particles. The present results indicate that the technique could also be used for other supercritical fluids having high critical temperature and pressure, such as methanol (Tc 239.4 °C, Pc 8.1 MPa) and ethanol (Tc 243.1 °C, Pc 6.4 MPa). [ABSTRACT FROM AUTHOR]

Six coordination complexes, {[M(H2biim)2(H2O)2]2+X2-}·(nH2O) [(H2biim = biimidazole); {M = Zn (1), Cd (2); X = squarate; n = 2} {M = Zn (3), Cd (4); X = glutarate; n = 4} {M = Zn (5), X = succinate; n = 4} {M = Cd (6), X = succinate; n = 2}], have been synthesized and characterized by X-ray single-crystal structure determination. The crystal packing of all the complexes reveals that cationic [M(H2biim)2(H2O)2]2+ fragments are self-assembled by recognition of enolate/dicarboxylate anions by the uncoordinated N−H motif of H2biim resulting in one-dimensional supramolecular ribbons. The parallel ribbons are stitched across by water-mediated hydrogen bonding and π−π interactions leading to two types of topology:  one is a two-dimensional brick wall (1, 2, 6), and the other is a three-dimensional architecture (3−5). In two structures (1, 2) interesting “sandwiched” π−π interactions were observed. [ABSTRACT FROM AUTHOR]

Transforming growth factor β (TGFβ) induces profibrotic responses in normal fibroblasts, and plays a fundamental role in the pathogenesis of fibrosis in scleroderma (systemic sclerosis [SSc]). The intensity of cellular responses elicited by cytokines is modulated by transcriptional coactivators such as the histone acetylase p300. The objective of these studies was to delineate the physiologic role of p300 in Smad‐dependent profibrotic responses elicited by TGFβ.Ectopic p300 was transiently expressed in normal dermal fibroblasts. Cellular p300 levels were suppressed using p300‐specific ribozymes. The regulation of gene expression was examined by transient transfection assays, Northern blotting, and immunoblot analysis. The expression of p300 in normal and scleroderma fibroblasts was evaluated by confocal microscopy and immunoblotting, and p300 levels in skin from mice with experimental scleroderma were assessed by immunohistochemistry.In normal fibroblasts, TGFβ induced an increase in the levels of p300. Forced expression of ectopic p300 in these cells dramatically enhanced the magnitude of TGFβ responses, whereas selective depletion of p300 using ribozyme resulted in abrogation of TGFβ‐induced collagen synthesis and promoter activity. Furthermore, TGFβ lost its ability to induce Smad‐dependent transcription in p300‐depleted fibroblasts. These responses could be fully rescued with ectopic p300. Abrogation of Smad‐mediated TGFβ signaling was not due to alterations in the levels or the ligand‐dependent phosphorylation or intracellular trafficking of endogenous Smads. Immunohistochemical analysis demonstrated substantially increased p300 expression in lesional skin from mice with chronic graft‐versus‐host disease, an animal model of scleroderma. Furthermore, levels of p300 were 2–3–fold higher in cultured fibroblasts derived from SSc patients than in fibroblasts from matched normal controls.These results establish, for the first time, that the coactivator histone acetylase p300, itself a target of TGFβ regulation, is an essential component of the cellular TGFβ signal transduction pathways mediating stimulation of collagen synthesis in fibroblasts. Since the cellular abundance of p300 appears to govern the intensity of profibrotic responses elicited by TGFβ, elevated p300 expression in lesional tissue may contribute to the progression of skin fibrosis in scleroderma. [ABSTRACT FROM AUTHOR]

We studied the morphology of bipolar cells in fixed vertical tissue sections (slices) of the mouse retina by injecting the cells with Lucifer Yellow and Neurobiotin. Nine different cone bipolar cell types and one rod bipolar cell type were distinguished. The major criteria for classifying the cells were the branching pattern and stratification level of their axon terminals in the inner plexiform layer (IPL). To assess this, the IPL was subdivided into five strata of equal width. The slices were immunostained for calretinin, which labels three horizontal bands serving as a standard measure for the precise localization of the axon terminals. Immunostaining the retina with antibodies against the G-protein Gγ13, a marker for ON-bipolar cells, made it possible to separate OFF- and ON-bipolar cells. At least two OFF-cone bipolar cells (Types 1 and 2) were immunolabeled with antibodies against the neurokinin 3 receptors (NK3R). A further OFF- and an ON-cone bipolar cell (Types 3 and 5) were immunostained with antibodies against the calcium-binding protein CaB5. The bipolar cell types described here were compared with previous schemes of rat and primate bipolar cells. Homologous types between the three species are discussed. J. Comp. Neurol. 469:70–82, 2004. © 2003 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

We report herein the fluorescence response of pyrene in the presence of sodium dodecyl sulfate (SDS) micelle and poly(acrylic acid) (PAA) with Cu2+as an ionic quencher. Pyrene present in the PAA−SDS complex is quenched by Cu2+at pH ∼ 2 (“off” state). Quenched pyrene emission is recovered at pH ∼ 8 (“on” state). Due to easy protonation and deprotonation of the PAA chain in aqueous solution, this pH-controlled micellar ternary system exhibits a highly reversible “off−on−off” switch of the pyrene emission. [ABSTRACT FROM AUTHOR]

An enantioselective total synthesis of the cytotoxic natural product (+)-largazole ( 1) is described. It is a potent histone deacetylase inhibitor. Our synthesis is convergent and involves the assembly of thiazole 3-derived carboxylic acid with amino ester 4followed by cycloamidation of the corresponding amino acid. The synthesis features an efficient cross-metathesis, an enzymatic kinetic resolution of a β-hydroxy ester, a selective removal of a Boc-protecting group, a HATU/HOAt-promoted cycloamidation reaction, and synthetic manipulations to a sensitive thioester functional group. [ABSTRACT FROM AUTHOR]

An enantioselective total synthesis of ()-jasplakinolide is described. The synthesis of the polyketide template utilized a diastereoselective syn-aldol, ortho-ester Claisen rearrangement followed by efficient conversion to a cyanide. The -amino acid unit was constructed in a highly diastereoselective manner utilizing nucleophilic addition to a chiral sulfinimine. Yamaguchi macrocyclization and removal of the protecting group provided a convenient access to ()-jasplakinolide. [ABSTRACT FROM AUTHOR]

The quantization of many-body systems with balanced loss and gain is investigated. Two types of models characterized by either translational invariance or rotational symmetry under rotation in a pseudo-Euclidean space are considered. A partial set of integrals of motion are constructed for each type of model. Specific examples for the translational invariant systems include Calogero-type many-body systems with balanced loss and gain, where each particle is interacting with other particles via four-body inverse-square potential plus pair-wise two-body harmonic terms. A many-body system interacting via short range four-body plus six-body inverse square potential with pair-wise two-body harmonic terms in presence of balanced loss and gain is also considered. In general, the eigenvalues of these two models contain quantized as well as continuous spectra. A completely quantized spectra and bound states involving all the particles may be obtained by employing box-normalization on the particles having continuous spectra. The normalization of the ground state wave functions in appropriate Stoke wedges is discussed. The exact n-particle correlation functions of these two models are obtained through a mapping of the relevant integrals to known results in random matrix theory. It is shown that a rotationally symmetric system with generic many-body potential does not have entirely real spectra, leading to unstable quantum modes. The eigenvalue problem of a Hamiltonian system with balanced loss and gain and admitting dynamical symmetry is also considered. [ABSTRACT FROM AUTHOR]

The kinetic energy term of Hamiltonian systems with balanced loss and gain is not semi-positive-definite, leading to instabilities at the classical as well quantum level. It is shown that an additional Lorentz interaction in the Hamiltonian allows the kinetic energy term to be semi-positive-definite and thereby, improving the stability properties of the system. Further, a consistent quantum theory admitting bound states may be obtained on the real line instead of Stoke wedges on the complex plane. The Landau Hamiltonian in presence of balanced loss and gain is considered for elucidating the general result. The kinetic energy term is semi-positive-definite provided the magnitude of the applied external magnetic field is greater than the magnitude of the ‘analogous magnetic field’ due to the loss-gain terms. It is shown that the classical particle moves on an elliptical orbit with a cyclotron frequency that is less than its value in absence of the loss-gain terms. The quantum system share the properties of the standard Landau Hamiltonian, but, with the modified cyclotron frequency. It is shown that the Hall current has non-vanishing components along the direction of the external uniform electric field and to its transverse direction. The Pauli equation in presence of balanced loss and gain is shown to be supersymmetric. [ABSTRACT FROM AUTHOR]

The momentum scattering time for electron–phonon interaction in β-Ga2O3 was derived within the relaxation time approximation considering all infra-red active optical modes. A first principle calculation was applied to separately obtain the scattering rates due to polar and non-polar phonon–electron interactions, and then spherically averaged coupling coefficients for each polar optical mode were calculated. The method was tested to analyze, in the framework of the relaxation time approximation, transport data in semiconductors having different optical phonons. This approach can be reliably applied if the band may be considered as isotropic. Hall density and mobility curves were fitted simultaneously with the same parameters, after Hall-to-drift data conversion through a Hall scattering factor calculated self-consistently within the routine. In the theoretical mobility calculations, both polar and non-polar phonon interactions were considered besides impurity scattering. The Farvacque correction was included in the momentum scattering rate for electron interaction with the optical phonons, and its effect on mobility calculation is critically discussed. Hall transport data of β-Ga2O3 taken from the literature were fitted to test the approach, and good agreement between the experimental and calculated mobilities was obtained. [ABSTRACT FROM AUTHOR]

We present theoretical results for electron emission in collisions between helium atoms and dressed projectiles at high energies. Double-differential cross sections (DDCSs) as a function of the emitted electron energies and angles are calculated. In our study we have applied the three-body formalism using the three-Coulomb wave (3CW–3B) model. The interaction between the dressed projectile and the active electron in the target has been approximated by a model potential having both a long-range Coulomb potential part and a short-range part. However, the active electron in the target has been treated as hydrogenic. We have also studied the projectile charge state dependence of the DDCS. Our theoretical results are compared with available experimental data as well as other theoretical calculations. The comparison shows a good agreement between the present calculations and the measurements. The obtained results are also compatible with other theoretical findings. [ABSTRACT FROM AUTHOR]

A topic of intense current investigation pursues the question of how the highly crowded environment of biological cells affects the dynamic properties of passively diffusing particles. Motivated by recent experiments we report results of extensive simulations of the motion of a finite sized tracer particle in a heterogeneously crowded environment made up of quenched distributions of monodisperse crowders of varying sizes in finite circular two-dimensional domains. For given spatial distributions of monodisperse crowders we demonstrate how anomalous diffusion with strongly non-Gaussian features arises in this model system. We investigate both biologically relevant situations of particles released either at the surface of an inner domain or at the outer boundary, exhibiting distinctly different features of the observed anomalous diffusion for heterogeneous distributions of crowders. Specifically we reveal an asymmetric spreading of tracers even at moderate crowding. In addition to the mean squared displacement (MSD) and local diffusion exponent we investigate the magnitude and the amplitude scatter of the time averaged MSD of individual tracer trajectories, the non-Gaussianity parameter, and the van Hove correlation function. We also quantify how the average tracer diffusivity varies with the position in the domain with a heterogeneous radial distribution of crowders and examine the behaviour of the survival probability and the dynamics of the tracer survival probability. Inter alia, the systems we investigate are related to the passive transport of lipid molecules and proteins in two-dimensional crowded membranes or the motion in colloidal solutions or emulsions in effectively two-dimensional geometries, as well as inside supercrowded, surface adhered cells. [ABSTRACT FROM AUTHOR]

Generation of chaos from acousto-optic modulators with an electronic feedback has been studied for several years. Such chaotic signals have an important application in providing secure encryption in free-space optical communication systems. Lyapunov exponent is an important parameter for analysis of chaos generated by a nonlinear system. The Lyapunov exponent of an acousto-optic system is determined and calculated in this paper to understand the dependence of the chaotic response on the system parameters such as bias, feedback gain, input intensity and initial condition exciting the cell. Analysis of chaos using Lyapunov exponent is consistent with bifurcation analysis and is useful in encrypting data signals. [ABSTRACT FROM AUTHOR]

The clinical profile, commonly involved precipitating factors, comorbid conditions, treatment options and outcome of conversion disorder in 40 children in a tertiary level hospital in North India were studied, retrospectively. Majority of the patients were from rural India. Most common presenting symptom was psychogenic non-epileptic seizures; depression and anxiety were among the commonest comorbid conditions. Precipitating factors were predominantly scholastic problems. Treatment option included either psychotherapy only or combination of psychotherapy and pharmacotherapy. No significant difference was found in terms of outcome between the in-patient and out-patient treatment groups. This observation could be cost effective for developing countries like India, where the resources are very limited. [ABSTRACT FROM AUTHOR]

Mg(tart)(tart = tartrate) was invoked in a recent scheme of potashrecovery from sea bittern employing tartaric acid as a selective precipitant.In the present study, Mg(l-tart) and Mg(d,l-tart) were prepared through room temperature stoichiometric reactionsof an aqueous slurry of magnesium hydroxide with aqueous solutionsof l- and d,l-tartaric acid, respectively.The racemic suspension was found to be more readily filterable, withlower moisture retention in the wet cake. The findings were consistentwith the larger average particle size and lower surface area of Mg(d,l-tart) compared to Mg(l-tart). Morphologicalexamination of the dry solids revealed that Mg(l-tart) particleshad irregular shapes, whereas Mg(d,l-tart) was obtainedmostly in the form of rectangular tubes, with copresence of a fewcross structures. Some of the crosses were intact, while others wereseen to be fractured at the junction. Their complete cleavage maybe one mechanism for formation of the rectangular tubes. Cross structureshave, so far, not been reported for any metal organic framework. PowderXRD (X-ray diffraction) profiles of the solids matched well with thosesimulated from previously reported single crystal XRD data of layeredMg(d-tart)(H2O)·1.5H2O and dimericMg(d,l-tart)(H2O)2·3H2O. The TGA profiles and elemental analyses were also in goodagreement. The results were largely similar when the solids were synthesizedfrom potassium bitartrate salts. The only exception was the higherwater retention by the racemate, which was attributed to agglomerationeffects. [ABSTRACT FROM AUTHOR]

Although the boron hydrides are well-known in the literature, the aluminum hydride chemistry is limited to very few systems such as AlH3, its dimer, and its polymeric form. In view of the recent experimental studies on the possible existence of the aluminum hydrides, herein, we have undertaken a systematic study on the electronic structure and properties of these aluminum hydrides. Under this, we have studied different classes of hydrides, viz., closo(AlnHn+2), nido(AlnHn+4), and arachno(AlnHn+6), similar to the boranes. All the aluminum hydrides are found to have exceptionally large highest-occupied molecular orbital−lowest-unoccupied molecular orbital gaps, low electron affinities, large ionization potentials and also large enthalpy and free energy of atomization. In addition, most of the structures are also found to have high symmetries. These exceptional properties can be indicative of the pronounced stability, and hence, it is expected that other aluminum hydride complexes can indeed be observed experimentally. [ABSTRACT FROM AUTHOR]

Leach liquor of uranium concentrates are generated at Uranium Corporation of India Limited (UCIL), Jaduguda, India. Application of the emulsion liquid membrane (ELM) technique was tested for the efficient recovery of uranium from the leach liquor, in the presence of metal ions such as Fe, Ca, Mg, and Mn. The liquid membrane employed consisted of a diluent (light and heavy paraffin), a surfactant (Span 80), and an extractant (Alamine 336), and sodium carbonate was used as the stripping solution. Initially, the ELM process parameters were optimized by using synthetic leach liquor as the feed phase. The role of the acidic feed-phase pH, which enhances the cotransport of H+ions along with uranium inside the emulsion globules, was found to be significant, as it helped in achieving the complete extraction and stripping of uranium. The best optimized parameters were directly used for the separation and concentration of uranium from industrial leach solutions. In one step, in the presence of various metal ions, the selective permeation of uranyl ions through the liquid membrane was observed to be greater than 90%, and the concentration of uranium inside the strip phase was observed to be nearly 7 times higher. Separation factors of uranium with respect to Fe, Mg, Ca, and Mn were experimentally found to be 129, 781, 43, and 1462, respectively, in 12 min. Finally, application of the process in uranium ore processing is demonstrated. [ABSTRACT FROM AUTHOR]

Block copolymers and nanostructured materials derived therefrom are becoming increasingly ubiquitous in a wide variety of (nano)technologies. Recently, we have demonstrated that triblock copolymer organogels composed of physically cross-linked copolymer networks swollen with a midblock-selective solvent exhibit excellent electromechanical behavior as dielectric elastomers. In-plane actuation of such organogels, collectively referred to as electroactive nanostructured polymers (ENPs) to reflect the existence of a self-organized copolymer morphology, is attributed to the development of an electric-field-induced surface-normal Maxwell stress. In this study, we examine the composition and molecular weight dependence of the electromechanical properties afforded by organogels prepared from poly[styrene- b-(ethylene- co-butylene)- b-styrene] (SEBS) triblock copolymers selectively swollen with EB-compatible aliphatic oligomers. These materials undergo ultrahigh actuation displacement at significantly reduced electric fields relative to previously reported dielectric elastomers and possess electromechanical coupling efficiencies, which relate the conversion from electrical input to mechanical output, greater than 90%. The design of ENPs with broadly tunable electromechanical properties represents an attractive route to responsive materials for advanced engineering, biomimetic and biomedical applications. [ABSTRACT FROM AUTHOR]

We derive a one-dimensional energy diffusion equation for describing the dynamics of multidimensional electron transfer reactions in condensed phase, which is conceptually simpler and computationally more economic than the conventional approaches. We also obtain an analytical expression for the rate of electron transfer reactions for a general one-dimensional effective potential as well as an energy dependent diffusitivity. As an illustrative example, we consider application to electron transfer in a contact ion pair system modeled through harmonic potentials consisting of two slow classical modes and a high frequency vibrational mode for which the numerical results calculated using the proposed one-dimensional approach are shown to be in good agreement with experimental results. The energy diffusion equation and the rate expression for electron transfer obtained from the present theory, therefore, open up the possibility of describing the dynamics of electron transfer in complex systems, through a simpler approach. [ABSTRACT FROM AUTHOR]