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The (18)F-labeling of unprotected peptides and sugars with a Au(III)-[(18)F]fluoroaryl complex is reported. The chemoselective method generates (18)F-labeled S-aryl bioconjugates in an aqueous environment in 15 min with high radiochemical yields and displays excellent functional group tolerance. This approach utilizes an air and moisture stable, robust organometallic Au(III) complex and highlights the versatility of designer organometallic reagents as efficient agents for rapid radiolabeling.

Multivalency plays a key role in achieving strong, yet reversible interactions in nature, and provides critical chemical organization in biological recognition processes. Chemists have taken an interest in designing multivalent synthetic assemblies to both better understand the underlying principles governing these interactions, and to build chemical tools that either enhance or prevent such recognition events from occurring in biology. Rationally tailoring synthetic strategies to achieve the high level of chemical control and tunability required to mimic these interactions, however, is challenging. Here, we introduce a systematic and modular synthetic approach to the design of well-defined molecular multivalent protein-binding constructs that allows for control over size, morphology, and valency. A series of supramolecular mono-, bi-, and tetrametallic Fe(ii) complexes featuring a precise display of peripheral saccharides was prepared through coordination-driven self-assembly from simple building blocks. The molecular assemblies are fully characterized, and we present the structural determination of one complex in the series. The mannose and maltose-appended assemblies display strong multivalent binding to model lectin, Concanavalin A (K d values in μM), where the strength of the binding is a direct consequence of the number of saccharide units decorating the molecular periphery. This versatile synthetic strategy provides chemical control while offering an easily accessible approach to examine important design principles governing structure-function relationships germane to biological recognition and binding properties.

Synthetic bioconjugation at cysteine (Cys) residues in peptides and proteins has emerged as a powerful tool in chemistry. Soft nucleophilicity of the sulfur in Cys renders an exquisite chemoselectivity with which various functional groups can be placed onto this residue under benign conditions. While a variety of reactions have been successful at producing Cys-based bioconjugates, the majority of these feature sulfur-carbon bonds. We report Cys-borylation, wherein a benchtop stable Pt(II)-based organometallic reagent can be used to transfer a boron-rich cluster onto a sulfur moiety in unprotected peptides forging a boron-sulfur bond. Cys-borylation proceeds at room temperature and tolerates a variety of functional groups present in complex polypeptides. Further, the bioconjugation strategy can be applied to a model protein modification of Cys-containing DARPin (designed ankyrin repeat protein). The resultant bioconjugates show no additional toxicity compared to their Cys alkyl-based congeners. Finally, we demonstrate how the developed Cys-borylation can enhance the proteolytic stability of the resultant peptide bioconjugates while maintaining the binding affinity to a protein target.

A set of two dodecaborate [B(12)(OR)(12)](1−) radical cluster anions containing a dense layer of fluorinated end-groups provide nuclear spin hyperpolarization via the dissolution dynamic nuclear polarization (D-DNP) technique. We show that these clusters can enhance (19)F nuclear magnetic resonance (NMR) signals. Importantly, given the inherent radical delocalization in dodecaborate-based radicals, these species are compatible with reactive compounds such as Lewis acids, providing ~ 1000 – 2000 times of signal enhancement for B(C(6)F(5))(3) in liquid state NMR experiments at 9.4 T. This observation suggests that 3D aromatic radicals can provide advantages over the conventional radical species that are currently used for DNP, such as 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) by showing superior chemical compatibility. The ability to hyperpolarize reactive compounds using [B(12)(OR)(12)](1−) cluster radicals opens up new applications of reaction monitoring by D-DNP NMR spectroscopy, including the observation of catalytically active species in complex reaction mixtures.

The expanding field of boron clusters has attracted continuous theoretical efforts to understand their diverse structures and unique bonding. We recently discovered a new reversible redox event of B12(O-3-methylbutyl)12 in which the superoxidized radical cationic form [B12(O-3-methylbutyl)12]•+ was identified and isolated for the first time. Herein, comprehensive (TD-)DFT studies in tandem with electrochemical experiments were employed to demonstrate the generality of the reported behavior across perfunctionalized B12(OR)12 clusters (R = aryl or alkyl). While the spin density of radical cationic clusters is delocalized in the core region, the oxidation brings about notable gains of positive partial charges on the supporting groups whose electronics can readily tune the redox potential of the 0/•+ couple. The underlying changes of frontier orbitals were elucidated, and the resulting [B12(OR)12]•+ species manifest a general diagnostic absorption as a consequence of mixed local/charge-transfer excitations.

Synthetic bioconjugation at cysteine (Cys) residues in peptides and proteins has emerged as a powerful tool in chemistry. Soft nucleophilicity of the sulfur in Cys renders an exquisite chemoselectivity with which various functional groups can be placed onto this residue under benign conditions. While a variety of reactions have been successful at producing Cys-based bioconjugates, the majority of these feature sulfur-carbon bonds. We report Cys-borylation, wherein a benchtop stable Pt(II)-based organometallic reagent can be used to transfer a boron-rich cluster onto a sulfur moiety in unprotected peptides forging a boron-sulfur bond. Discovered Cysborylation proceeds at room temperature and is tolerant to a variety of functional groups present in complex polypeptides. The resultant bioconjugates show no additional toxicity compared to their Cys aryl-based congeners. Finally, we demonstrate how the developed Cys-borylation can enhance the proteolytic stability of the produced peptide bioconjugates while maintaining the binding affinity to a protein target.

Organometallic complexes have recently gained attention as competent bioconjugation reagents capable of introducing a diverse array of substrates to biomolecule substrates. Here, we detail the synthesis and characterization of an aminophosphine-supported Au(III) platform that provides rapid and convenient access to a wide array of peptide-based assemblies via cysteine S-arylation. This strategy results in the formation of robust C‒S covalent linkages and is an attractive method for the modification of complex biomolecules due to the high functional group tolerance, chemoselectivity, and rapid reaction kinetics associated with these arylation reactions. This work expands upon existing metal-mediated cysteine arylation by introducing a class of air-stable organometallic complexes that serve as competent bioconjugation reagents enabling the synthesis of conjugates of higher structural complexity including macrocyclic stapled and bicyclic peptides, as well as a peptide-functionalized multivalent hybrid nanocluster. This organometallic-based approach provides a convenient, one-step method of peptide functionalization and macrocyclization, and has the potential to contribute to efforts directed towards developing efficient synthetic strategies of building new and diverse hybrid peptide-based assemblies of high complexit

Carrier mobility in doped conjugated polymers is limited by Coulomb interactions with dopant counterions. This complicates studying the effect of the dopant's oxidation potential on carrier generation because different dopants have different Coulomb interactions with polarons on the polymer backbone. Here, dodecaborane (DDB)‐based dopants are used, which electrostatically shield counterions from carriers and have tunable redox potentials at constant size and shape. DDB dopants produce mobile carriers due to spatial separation of the counterion, and those with greater energetic offsets produce more carriers. Neutron reflectometry indicates that dopant infiltration into conjugated polymer films is redox‐potential‐driven. Remarkably, X‐ray scattering shows that despite their large 2‐nm size, DDBs intercalate into the crystalline polymer lamellae like small molecules, indicating that this is the preferred location for dopants of any size. These findings elucidate why doping conjugated polymers usually produces integer, rather than partial charge transfer: dopant counterions effectively intercalate into the lamellae, far from the polarons on the polymer backbone. Finally, it is shown that the IR spectrum provides a simple way to determine polaron mobility. Overall, higher oxidation potentials lead to higher doping efficiencies, with values reaching 100% for driving forces sufficient to dope poorly crystalline regions of the film.

While the icosahedral closo-[B12H12]2– cluster does not display reversible electrochemical behavior, perfunctionalization of this species via substitution of all twelve B–H vertices with alkoxy orbenzyloxy (OR) substituents engenders reversible redox chemistry, providing access to clusters in the dianionic,monoanionic, and neutral forms. Here, we evaluated the electrochemical behavior of the electron-rich B12(O-3-methylbutyl)12 (1) cluster and discovered that a new reversible redox event that gives rise to a fourth electronic state is accessible through one-electron oxidation of the neutral species. Chemical oxidation of 1 with [N(2,4-Br2C6H3)3]•+ afforded the isolable[1] •+ cluster, which is the first example of an open-shell cationic B12 cluster in which the unpaired electron is proposed to be delocalized throughout the boron cluster core. The oxidation of 1 is also chemically reversible, where treatment of [1]•+ with ferrocene resulted in its reduction back to 1. The identity of [1]•+ is supported by EPR, UV-vis, multinuclear NMR (1H, 11B), and X-ray photoelectron spectroscopic characterization.

Bromination of the luminescent borane, anti-B18H22, via electrophilic substitution using AlCl3 and Br2, yields the monosubstituted derivative 4-Br-anti-B18H21 as an air-stable crystalline solid. In contrast to the unsubstituted parent compound, 4-Br-anti-B18H21 possesses dual emission upon excitation with UV light and exhibits fluorescence at 410 nm and phosphorescence at 503 nm, with Φtotal = 0.07 in oxygen-free cyclohexane. Increased oxygen content in cyclohexane solution quenches the phosphorescence signal. The fluorescent signal intensity remains unaffected by oxygen, suggesting that this molecule could be used as a ratiometric oxygen probe.

A dicobalt(II) complex, [Co2(mBDCA-5t)](2-) (1), demonstrates a cofacial arrangement of trigonal monopyramidal Co(II) ions with an inter-metal separation of 6.2710(6) A. Reaction of 1 with potassium superoxide generates an encapsulated Co-O-Co core in the dianionic complex, [Co2O(mBDCA-5t)](2-) (2); to form the linear Co-O-Co core, the inter-metal distance has diminished to 3.994(3) A. Co K-edge X-ray absorption spectroscopy data are consistent with a +2 oxidation state assignment for Co in both 1 and 2. Multireference complete active space calculations followed by second-order perturbation theory support this assignment, with hole equivalents residing on the bridging O-atom and on the cryptand ligand for the case of 2. Complex 2 acts as a 2-e(-) oxidant toward substrates including CO and H2, in both cases efficiently regenerating 1 in what represent net oxygen-atom-transfer reactions. This dicobalt system also functions as a catalase upon treatment with H2O2.

Bromination of the luminescent borane, anti-B18H22, via electrophilic substitution using AlCl3 and Br2 yields the monosubstituted derivative 4-Br-anti-B18H21 as an air-stable crystalline solid. In contrast to the unsubstituted parent compound, 4-Br-anti-B18H21 product possesses dual emission upon excitation with UV light and exhibits fluorescence at 410 nm and phosphorescence at 503 nm, with Фtotal = 0.07 in oxygen-free cyclohexane. Increased oxygen content in cyclohexane solution quenches the phosphorescence signal. The fluorescent signal intensity remains unaffected by oxygen, suggesting that this molecule could be used as a ratiometric oxygen probe.

Bromination of the luminescent borane, anti-B18H22, via electrophilic substitution using AlCl3 and Br2 yields the monosubstituted derivative 4-Br-anti-B18H21 as an air-stable crystalline solid. In contrast to the unsubstituted parent compound, 4-Br-anti-B18H21 product possesses dual emission upon excitation with UV light and exhibits fluorescence at 410 nm and phosphorescence at 503 nm, with Фtotal = 0.07 in oxygen-free cyclohexane. Increased oxygen content in cyclohexane solution quenches the phosphorescence signal. The fluorescent signal intensity remains unaffected by oxygen, suggesting that this molecule could be used as a ratiometric oxygen probe.

The preparation of a selective turn-on colorimetric fluoride sensor was achieved through single cobalt(II) ion insertion into a macrobicyclic cryptand. Monometallic [Co(mBDCA-5t-H3)]− (1) and [Zn(mBDCA-5t-H3)]− (2) complexes were prepared in 74 and 84% yields, respectively. Structural characterization of 1 confirmed the presence of a proximal hydrogen-bonding network consisting of carboxamide N–H donors. The reaction of 1 with F– was accompanied by a distinct colorimetric turn-on response in mixed aqueous/organic media, and 1 was capable of selective fluoride sensing in the presence of large quantities of potentially competitive anions. Complex 1 represents a unique example of a fluoride sensor wherein selective F– binding takes place directly at a transition-metal center and induces a color change based upon metal-centered transitions. The metal(II) fluoride complexes [F⊂Co(mBDCA-5t-H3)]2– (3) and [F⊂Zn(mBDCA-5t-H3)]2– (4) were both fully characterized, including single crystal X-ray analyses. Fluoride b...

Despite the large number of judiciously designed ligands that have been exploited in palladium-catalyzed cross-coupling protocols, the incorporation of ligands bearing appreciable π-acidic properties has remained significantly underexplored. Herein, we demonstrate that well-defined and low-coordinate Pd0 complexes supported by m-terphenyl isocyanides function as competent catalysts for the Suzuki–Miyaura cross-coupling of aryl bromides and arylboronic acids. Two-coordinate Pd(CNArDipp2)2 was active for the coupling of unhindered aryl bromides at room temperature in 2-propanol, while increasing the temperature to 60 °C allowed for the use of mono- or di-ortho-substituted aryl bromides. Oxidative addition of the aryl bromide was shown to proceed via a dissociative mechanism, implicating monoligated Pd(CNArDipp2) as the catalytically active intermediate. Attempts to access this fleeting species via activation of the PdII monoisocyanide PdCl(η3-C3H5)(CNArDipp2) with alkoxide base yielded the dinuclear PdI spe...

For decades, chemists have strived to mimic the intricate design and diverse functions of naturally occurring systems through the bioinspired synthesis of programmable inorganic nanomaterials. The development of thiol-capped gold nanoparticles (AuNPs) has driven advancement in this area; however, although versatile and readily accessible, hybrid AuNPs are rarely atomically precise, which limits control over their surface topology and therefore the study of complex structure-function relationships. Here, we present a bottom-up approach to the systematic assembly of atomically precise hybrid nanoclusters employing a strategy that mimics the synthetic ease with which thiol-capped AuNPs are normally constructed, while producing welldefined covalent nanoscale assemblies with diverse surface topologies. For the first time, using a structurally characterized cluster-based organometallic building block, we demonstrate the systematic synthesis of nanoclusters with multivalent binding capabilities to complex protein targets.

Metaphosphate acids cannot be thoroughly studied in aqueous media because their acidity is leveled by the solvent, and the resulting metaphosphates are susceptible to acid-catalyzed hydrolysis. Exploration of metaphosphate acid chemistry has now been made possible with the development of a general synthetic method for organic media soluble metaphosphate acids. Protonation of the [PPN](+) salts ([PPN](+) = [N(PPh3)2](+)) of tri-, tetra-, and hexametaphosphates results in five new metaphosphate acids, [PPN]2[P3O9H] (2), [PPN]4[(P4O12)3H8] (3), [PPN]4[P6O18H2]·2H2O (4), [PPN]3[P6O18H3] (5), and [PPN]2[P6O18H2(H3O)2] (6), obtained in yields of 80, 71, 66, 88, and 76%, respectively. Additionally, our synthetic method can be extended to pyrophosphate to produce [PPN][P2O7H3] (7) in 77% yield. The structural configurations of these oxoacids are dictated by strong hydrogen bonds and the anticooperative effect. Intramolecular hydrogen bonds are observed in 2, 4, and 5 and the previously reported [PPN]2[P4O12H2] (1), while intermolecular hydrogen bonds are observed in 3, 6, and 7. The hydrogen bonds in 3-7 possess short distances and are classified as low-barrier hydrogen bonds. Gas-phase acidity computations reveal that the parent tri- and tetrametaphosphoric acids are superacids. Their remarkable acidity is attributable to the stabilization of their corresponding conjugate bases via intramolecular hydrogen bonding.

Cofacial bimetallic tin( II ) ([Sn 2 ( m BDCA-5t)] 2-, 1) and lead( II ) ([Pb₂(mBDCA-5t)]²-, 2) complexes have been prepared by hexadeprotonation of hexacarboxamide cryptand m BDCA-5t-H₆ together with double Sn(II) or Pb(II) insertion. Reaction of 1 with elemental sulfur or selenium generates di-tin polychalcogenide complexes containing m -E and bridging m -E 5 ligands where E ¼ S or Se, and the Sn( II ) centers have both been oxidized to Sn( IV ). Solution and solid-state UV-Vis spectra of [( m -S 5 )Sn 2 ( m -S)( m BDCA-5t)] 2 ( 4 ) indicate that the complex acts reversibly as a source of S 3 c in DMF solution with a K eq ¼ 0.012 0.002. Reductive removal of all six chalcogen atoms is achieved through treatment of [( m -E 5 )Sn 2 ( m -E)( m BDCA- 5t)] 2 with PR 3 (R ¼ t Bu, Ph, O i Pr) to produce six equiv. of the corresponding EPR 3 compound with regeneration of di-tin( II ) cryptand complex 1., National Science Foundation (U.S.) (CHE-1305124)

An electrochemical cell consisting of cobalt ([CoII/III(P3O9)2]4–/3–) and vanadium ([VIII/II(P3O9)2]3–/4–) bistrimetaphosphate complexes as catholyte and anolyte species, respectively, was constructed with a cell voltage of 2.4 V and Coulombic efficiencies >90% for up to 100 total cycles. The [Co(P3O9)2]4– (1) and [V(P3O9)2]3– (2) complexes have favorable properties for flow-battery applications, including reversible redox chemistry, high stability toward electrochemical cycling, and high solubility in MeCN (1.09 ± 0.02 M, [PPN]4[1]·2MeCN; 0.77 ± 0.06 M, [PPN]3[2]·DME). The [PPN]4[1]·2MeCN and [PPN]3[2]·DME salts were isolated as crystalline solids in 82 and 68% yields, respectively, and characterized by 31P NMR, UV/vis, ESI-MS(−), and IR spectroscopy. The [PPN]4[1]·2MeCN salt was also structurally characterized, crystallizing in the monoclinic P21/c space group. Treatment of 1 with [(p-BrC6H4)3N]+ allowed for isolation of the one-electron-oxidized spin-crossover (SCO) complex, [Co(P3O9)2]3– (3), which is...

The neural networks that generate stepping in complete spinal adult rats remain poorly defined. To address this problem we used c-fos (an activity-dependent marker) to identify active interneurons and motoneurons in the lumbar spinal cord of adult spinal rats during a 30-minute bout of bipedal stepping. Spinal rats were either step trained (30 min/day, 3 days/week for 7.5 weeks) or not step-trained. Stepping was enabled by epidural stimulation and the administration of the serotonergic agonists quipazine and 8-OHDPAT. A third group of spinal rats served as untreated (no stimulation, drugs, or stepping) controls. The number of activated cholinergic central canal cluster cells and partition neurons was higher in both step-trained and non-trained than untreated rats, and higher in non-trained than step-trained rats. The latter finding suggests that daily treatment with epidural stimulation plus serotonergic agonist treatment without step training enhanced the excitability of a broader cholinergic interneuronal population than step training. The number of activated interneurons in laminae II-VI of lumbar cross sections was higher in both step-trained and non-trained than untreated rats, and highest in step-trained rats. This finding suggests that this population of interneurons was responsive to epidural stimulation plus serotonergic treatment and that load-bearing induced when stepping had an additive effect. The number of activated motoneurons of all size categories was higher in the step-trained than the other two groups, reflecting a strong effect of loading on motoneuron recruitment. In general, these results indicate that the spinal networks for locomotion are similar with and without brain input.

The synthesis and characterization of tri- and tetrametaphosphate titanium(IV) oxo and peroxo complexes is described. Addition of 0.5 equiv of [OTi(acac)2]2 to dihydrogen tetrametaphosphate ([P4O12H2]2–) and monohydrogen trimetaphosphate ([P3O9H]2–) provided a bis(μ2,κ2,κ2) tetrametaphosphate titanyl dimer, [OTiP4O12]24– (1; 70% yield), and a trimetaphosphate titanyl acetylacetonate complex, [OTiP3O9(acac)]2– (2; 59% yield). Both 1 and 2 have been structurally characterized, crystallizing in the triclinic P1 and monoclinic P21 space groups, respectively. These complexes contain Ti≡O units with distances of 1.624(7) and 1.644(2) A, respectively, and represent rare examples of structurally characterized terminal titanyls within an all-oxygen coordination environment. Complexes 1 and 2 react with hydrogen peroxide to produce the corresponding peroxotitanium(IV) metaphosphate complexes [O2TiP4O12]24–(3; 61% yield) and [O2TiP3O9(acac)]2– (4; 65% yield), respectively. Both 3 and 4 have been characterized by si...

International audience; Phenolic foams derived from natural precursors, condensed tannin extracts from mimosa trees, were prepared for the first time by curing and drying liquid foams obtained by aeration of tannin solutions containing surfactant and crosslinker. The materials derived from the new method were called tannin-based meringues in reference to the lightweight pastry made in a similar way by whipping egg whites. The new foams were compared with more standard cellular solids having very close composition but obtained by physical or chemical foaming. No significant differences were observed in terms of mechanical and thermal properties. The porous structure was also similar, except the cell sizes which were much higher in tannin-based meringues. The new method is not only easy, fast and cost-effective, but allows producing solid foams having a very broad range of bulk densities and cell sizes, which can be controlled by the concentration of tannin in the initial solution, all other things being equal.

International audience; New macro-cellular carbons, called carbon meringues, have been prepared by whipping until stiff an aqueous solution of tannin until liquid foam was obtained, which was next stabilized in an oven and pyrolysed, hence their name. With such cheap, fast and very easy process, flawless, homogeneous carbon foams were obtained in a wider range of density than that of more conventional cellular vitreous carbon (CVC) foams derived from similar formulations but made by physical foaming. The porosity, the average cell size and the cell wall thickness were only controlled by the initial concentration of tannin, all other things being equal. The resultant carbon meringues were fully investigated by electron microscopy, X-ray tomography, mercury porosimetry, Kr and N-2 adsorption, thermal conductivity and mechanical compression studies. Differences with former CVC foams, and advantages of the new process and materials have been emphasised.

A collaborative study on Raman spectroscopy and microspectrophotometry (MSP) was carried out by members of the ENFSI (European Network of Forensic Science Institutes) European Fibres Group (EFG) on different dyed cotton fabrics. The detection limits of the two methods were tested on two cotton sets with a dye concentration ranging from 0.5 to 0.005% (w/w).This survey shows that it is possible to detect the presence of dye in fibres with concentrations below that detectable by the traditional methods of light microscopy and microspectrophotometry (MSP). The MSP detection limit for the dyes used in this study was found to be a concentration of 0.5% (w/w). At this concentration, the fibres appear colourless with light microscopy. Raman spectroscopy clearly shows a higher potential to detect concentrations of dyes as low as 0.05% for the yellow dye RY145 and 0.005% for the blue dye RB221. This detection limit was found to depend both on the chemical composition of the dye itself and on the analytical conditions, particularly the laser wavelength.Furthermore, analysis of binary mixtures of dyes showed that while the minor dye was detected at 1.5% (w/w) (30% of the total dye concentration) using microspectrophotometry, it was detected at a level as low as 0.05% (w/w) (10% of the total dye concentration) using Raman spectroscopy.This work also highlights the importance of a flexible Raman instrument equipped with several lasers at different wavelengths for the analysis of dyed fibres. The operator and the set up of the analytical conditions are also of prime importance in order to obtain high quality spectra. Changing the laser wavelength is important to detect different dyes in a mixture. © 2012 Elsevier Ireland Ltd.

A dicobalt(II) complex, [Co2(mBDCA-5t)](2-) (1), demonstrates a cofacial arrangement of trigonal monopyramidal Co(II) ions with an inter-metal separation of 6.2710(6) A. Reaction of 1 with potassium superoxide generates an encapsulated Co-O-Co core in the dianionic complex, [Co2O(mBDCA-5t)](2-) (2); to form the linear Co-O-Co core, the inter-metal distance has diminished to 3.994(3) A. Co K-edge X-ray absorption spectroscopy data are consistent with a +2 oxidation state assignment for Co in both 1 and 2. Multireference complete active space calculations followed by second-order perturbation theory support this assignment, with hole equivalents residing on the bridging O-atom and on the cryptand ligand for the case of 2. Complex 2 acts as a 2-e(-) oxidant toward substrates including CO and H2, in both cases efficiently regenerating 1 in what represent net oxygen-atom-transfer reactions. This dicobalt system also functions as a catalase upon treatment with H2O2.

Identification of patients at low risk presenting to the emergency department with chest pain is a continuing challenge. We examined a cohort of low-risk women with negative cardiac injury markers, electrocardiogram with normal results, and clinical stability. We hypothesized that these patients can be safely and accurately managed in a chest pain unit (CPU), may not require predischarge cardiac testing, and have an excellent short-term prognosis. The primary end point was major cardiovascular events during index admission or follow-up. Mean age of the 403 women was 42 ± 4.3 years (30 to 50 years). No patient had a cardiovascular event in the CPU, and none of the 321 patients followed for 6 months had a late cardiovascular event. Most (211, 52%) did not receive predischarge cardiac testing. The remaining 192 patients (48%) had predischarge exercise treadmill test, stress imaging, or cardiac catheterization. Of those patients who underwent treadmill testing, almost 90% had no exercise-induced chest pain and approximately 50% had functional capacity 8 to 14 METs. In addition, 166 patients (41%) were discharged from the CPU after

The manner in which the extreme modes of droplet evaporation (namely, the constant contact radius and the constant contact angle modes) become indistinguishable on strongly hydrophobic substrates is described. Simple asymptotic expressions are obtained which provide good approximations to the evolutions of the contact radius, the contact angle, and the volume of droplets evaporating in the extreme modes for a wide range of hydrophobic substrates. As a consequence, on strongly hydrophobic substrates it is appropriate to use the so-called "2/3 power law" to extrapolate the lifetimes of droplets evaporating in the constant contact radius mode as well as in the constant contact angle mode.

The goal of our study was to evaluate two newly developed implant designs and their behavior in terms of subsidence in lumbar vertebral bodies under cyclic loading. The new implants were evaluated in two different configurations (two small prototypes vs. one large prototype with similar load-bearing area) in comparison to a conventional screw-based implant (MACS TL). A pool of 13 spines with a total of 65 vertebrae was used to establish five testing groups of similar bone mineral density (BMD) distribution with eight lumbar vertebrae each. In additional to BMD assessment via dual-energy X-ray absorptiometry, cancellous BMD and structural parameters were determined using a new generation in vivo 3D-pQCT. The specimens were loaded sinusoidally in force control at 1 Hz for 1000 cycles at three load levels (100, 200, and 400 N). A survival analysis using the number of cycles until failure (Cox regression with covariates) was applied to reveal differences between implant groups. All new prototype configurations except the large cylinder survived significantly longer than the control group. The number of cycles until failure was significantly correlated with the structural parameter Tb.Sp. and similarly with the cancellous BMD for three of five implants. In both large prototypes the cycle number until failure significantly correlated with the preoperative distance to the upper endplates. Although the direct relationship between bone structure or density and mechanical breakage behavior cannot be conclusively proven, all the prototypes adapted for poor bone structure performed better than the comparable conventional implant. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res

The neural networks that generate stepping in complete spinal adult rats remain poorly defined. To address this problem, we used c-fos (an activity-dependent marker) to identify active interneurons and motoneurons in the lumbar spinal cord of adult spinal rats during a 30-min bout of bipedal stepping. Spinal rats were either step trained (30 min/day, 3 days/week, for 7.5 weeks) or not step trained. Stepping was enabled by epidural stimulation and the administration of the serotonergic agonists quipazine and 8-OHDPAT. A third group of spinal rats served as untreated (no stimulation, drugs, or stepping) controls. The numbers of activated cholinergic central canal cluster cells and partition neurons were higher in both step-trained and nontrained rats than in untreated rats and were higher in nontrained than in step-trained rats. The latter finding suggests that daily treatment with epidural stimulation plus serotonergic agonist treatment without step training enhances the excitability of a broader cholinergic interneuronal population than does step training. The numbers of activated interneurons in laminae II-VI of lumbar cross-sections were higher in both step-trained and nontrained rats than in untreated rats, and they were highest in step-trained rats. This finding suggests that this population of interneurons is responsive to epidural stimulation plus serotonergic treatment and that load-bearing induced when stepping has an additive effect. The numbers of activated motoneurons of all size categories were higher in the step-trained group than in the other two groups, reflecting a strong effect of loading on motoneuron recruitment. In general, these results indicate that the spinal networks for locomotion are similar with and without brain input.We identified neurons within the spinal cord networks that are activated during assisted stepping in paraplegic rats. We stimulated the spinal cord and administered a drug to help the rats step. One group was trained to step and another was not trained. We observed a lower percentage of activated neurons in specific spinal cord regions in trained rats than in nontrained rats after a 1-hr stepping bout, suggesting that step training reduces activation of some types of spinal neurons. This observation indicates that training makes the spinal networks more efficient and suggests a "learning" phenomenon in the spinal cord without any brain input.

Suchterkrankungen bei Frauen beinhalten in der gynakologischen Praxis eine Reihe von Implikationen. Die psychosomatische Sorgfaltspflicht erfordert v. a. im Bereich der Geburtshilfe, die Gesundheit des Ungeborenen mit zu beachten und somit den Muttern fruhzeitig seelische und korperliche Unterstutzung anzubieten. Die wesentlichen Elemente dieses Behandlungskonzepts werden dargestellt. Eingegangen wird auch auf die Komorbiditat der Patientinnen, den Umgang mit Drogennotfallen und die perioperative Substitution.

In den letzten Jahrzehnten gewannen bei der Therapie von Patientinnen mit Mammakarzinom zunehmend psychosomatische Aspekte an Bedeutung. Der vorliegende Beitrag behandelt aktuelle Themen psychoonkologischer Forschung: psychosoziale Belastungen fur Patientinnen mit Mammakarzinom und ihre Angehorigen, Coping und Lebensqualitat. Psychotherapeutische Indikationen, mogliche Zielsetzungen und verschiedene psychotherapeutische Interventionen werden erlautert. Die Autoren skizzieren Forschungsfragen aktueller Studien ihrer Arbeitsgruppe an der I. Universitatsfrauenklinik Munchen.

Purpose: Research on long-term quality of life after breast cancer has produced conflicting results. We investigated the impact of age, recurrence, and type of primary surgery on different aspects of long-term quality of life in women treated for breast cancer. Methods: A total of 306 women completed the QLQ-C30 (Version 2.0) questionnaire an average of 4.2 years after primary treatment for stage I - III breast cancer. Supplementary scales included body image, satisfaction with surgical treatment, and fear of recurrence. Results: The women had minor impairment of quality of life (67.0) and body image (25.9), a high degree of satisfaction with surgical treatment (6.8), and considerable fear of recurrence (61.4). There was no correlation between age and quality of life. Women with recurrence did not differ from those without recurrence in the symptom scales of the questionnaire. Women with recurrence reported lower quality of life (P < 0.01), less satisfaction with surgical treatment (P

The enthalpy of oxygen atom transfer (OAT) to V[(Me3SiNCH2CH2)3N], 1, forming OV[(Me3SiNCH2CH2)3N], 1-O, and the enthalpies of sulfur atom transfer (SAT) to 1 and V(N[t-Bu]Ar)3, 2 (Ar = 3,5-C6H3Me2), forming the corresponding sulfides SV[(Me3SiNCH2CH2)3N], 1-S, and SV(N[t-Bu]Ar)3, 2-S, have been measured by solution calorimetry in toluene solution using dbabhNO (dbabhNO = 7-nitroso-2,3:5,6-dibenzo-7-azabicyclo[2.2.1]hepta-2,5-diene) and Ph3SbS as chalcogen atom transfer reagents. The V-O BDE in 1-O is 6.3 ± 3.2 kcal·mol(-1) lower than the previously reported value for 2-O and the V-S BDE in 1-S is 3.3 ± 3.1 kcal·mol(-1) lower than that in 2-S. These differences are attributed primarily to a weakening of the V-Naxial bond present in complexes of 1 upon oxidation. The rate of reaction of 1 with dbabhNO has been studied by low temperature stopped-flow kinetics. Rate constants for OAT are over 20 times greater than those reported for 2. Adamantyl isonitrile (AdNC) binds rapidly and quantitatively to both 1 and 2 forming high spin adducts of V(III). The enthalpies of ligand addition to 1 and 2 in toluene solution are -19.9 ± 0.6 and -17.1 ± 0.7 kcal·mol(-1), respectively. The more exothermic ligand addition to 1 as compared to 2 is opposite to what was observed for OAT and SAT. This is attributed to less weakening of the V-Naxial bond in ligand binding as opposed to chalcogen atom transfer and is in keeping with structural data and computations. The structures of 1, 1-O, 1-S, 1-CNAd, and 2-CNAd have been determined by X-ray crystallography and are reported.

The complete description of the lifetime of a droplet on a solid substrate evaporating in a ‘stick–slide’ mode is obtained. The unexpectedly subtle relationship between the lifetime of such a droplet and the lifetimes of initially identical droplets evaporating in the extreme modes (namely the constant contact radius and constant contact angle modes) is described and summarised in an appropriate master diagram. In particular, it is shown that the lifetime of a droplet is not, in general, constrained by the lifetimes of the extreme modes.

Treatment of P4 with in situ generated [Na][SnPh3] leads to the formation of the sodium monophosphide [Na][P(SnPh3)2] and the Zintl salt [Na]3[P7]. The former was isolated in 46% yield as the crystalline salt [Na(benzo-15-crown-5)][P(SnPh3)2] and used to prepare the homoleptic phosphine P(SnPh3)3, isolated in 67% yield, as well as the indium derivative (XL)2InP(SnPh3)2 (XL = S(CH2)2NMe2), isolated in 84% yield, and the gold complex (Ph3P)AuP(SnPh3)2. The compounds [Na(benzo-15-crown-5)][P(SnPh3)2], P(SnPh3)3, (XL)2InP(SnPh3)2, and (Ph3P)AuP(SnPh3)2 were characterized using multinuclear NMR spectroscopy and X-ray crystallography. The bonding in (Ph3P)AuP(SnPh3)2 was dissected using natural bond orbital (NBO) methods, in response to the observation from the X-ray crystal structure that the dative P:→Au bond is slightly shorter than the shared electron-pair P-Au bond. The bonding in (XL)2InP(SnPh3)2 was also interrogated using (31)P and (13)C solid-state NMR and computational methods. Co-product [Na]3[P7] was isolated in 57% yield as the stannyl heptaphosphide P7(SnPh3)3, following salt metathesis with ClSnPh3. Additionally, we report that treatment of P4 with sodium naphthalenide in dimethoxyethane at 22 °C is a convenient and selective method for the independent synthesis of Zintl ion [Na]3[P7]. The latter was isolated as the silylated heptaphosphide P7(SiMe3)3, in 67% yield, or as the stannyl heptaphosphide P7(SnPh3)3 in 65% yield by salt metathesis with ClSiMe3 or ClSnPh3, respectively.

Background: Ideas of social Darwinism and eugenics and nationalism intertwined in Germany around 1905 and led to the concept of racial hygiene. This was put into practice by the Nazi regime. Under the Law for the Prevention of Congenitally Deformed Descendents, between 300,000 and 400,000 people were involuntarily sterilized between 1933 and 1945. Method: A total of 1345 enforced sterilizations, including 58 compulsory abortions, were performed at the First Department of Gynecology at the University of Munich. 33.2% of these women were sterilized because they were considered mentally deficient but in 27.9% the records contained no explicit indication. Results: Financial compensation for the victims has been possible since 1980 but has been complicated by the passage of time and social stigmatization. Conclusion: The First Department of Gynecology undertook an attempt to contact the involuntarily sterilized women to express a belated apology on behalf of the department, to provide support for applications for financial compensation, and to offer counselling for coping with the physical and emotional trauma of compulsory sterilization. The reaction of the women has been very positive.

Partnerschaftskonflikte konnen bei verschiedenen gynakologischen Problemen auftreten: Ungewollte Kinderlosigkeit, Ubergang zur Elternschaft, Schwangerschafts- und Wochenbettdepression, sexuelle Probleme, chronische Schmerzsyndrome wie Unterbauchschmerzen und Vulvodynie, Krebserkrankung. Im Umgang mit Partnerschaftskonflikten werden verschiedene therapeutische Ansatze beschrieben: psychoanalytische Therapie, systemische Therapie, Verhaltenstherapie, klientenzentrierte Therapie. Psychoanalytische Konzepte konzentrieren sich auf das Paar als zwei Individuen mit ihren jeweiligen individuellen Lebensgeschichten, die im Zusammenwirken zu Beziehungskonflikten fuhren konnen. Die systemische Therapie hat primar das Aushandeln und die Veranderung von Beziehungs- und Kommunikationsregeln durch Reflexion, Erprobung und Experimentieren zum Ziel. Die verhaltenstherapeutische Paartherapie basiert auf Ubungen zur Steigerung der Reziprozitat, Kommunikations- und Konfliktlosungstraining sowie Problemlosetraining. In klientenzentrierten Ansatzen geht es hauptsachlich darum, durch wachsende Kongruenz mit sich selbst zunehmend Klarheit in der Beziehung zum anderen zu finden. Der Artikel zeigt auf, dass Partnerschaftskonflikte im Rahmen eines biopsychosozialen Storungsmodells in der Entstehung, Aufrechterhaltung oder als Folge der gynakologischen Symptomatik berucksichtigt und therapeutisch behandelt werden sollten.

For screening efforts to maximally reduce mortality in the general population, a large proportion of women need to utilize mammography routinely. To investigate utilization of mammography in a community setting, the authors used population-based data collected by the New Mexico Mammography Project for residents of the Albuquerque, New Mexico, metropolitan area for the period 1994-1997. The authors computed screening rates and the proportion of women who routinely use mammography. The utilization of mammography was low. Only 50% of the women aged 50-74 years were screened each year. Less than one third of women aged 40-49 years or 75 years and older were screened annually. The percentage of women who routinely used mammography on an annual or biennial basis was low in all age groups, especially among Hispanics and American Indians. Women aged 50-74 years had the highest percentage of routine annual mammography use, ranging from 30% in non-Hispanic Whites to 20% in Hispanics. Current utilization of mammography in community-based screening efforts is unlikely to achieve a potential 30% reduction in breast cancer mortality. Interventions are needed to increase the routine use of mammography.

Background: Interval breast cancer is defined as a cancer that is detected within 12 months after a negative mammogram. The failure of mammography to detect breast cancer depends on testing procedures, radiologist interpretation, patient characteristics, and tumor properties. Although errors by radiologists explain some interval cancers, another explanation is that the tumor is rapidly growing and was too small to be detected on the last mammogram. To determine whether markers of tumor growth rate are associated with risk of an interval cancer, we conducted a population-based study with the use of data collected statewide by the New Mexico Mammography Project. Methods: Among women who received a mammographic examination from 1991 throughout 1993, we ascertained records of all patients with breast cancer diagnosed within 12 months of a negative screening mammographic examination (interval cancers) and corresponding tumor samples, when available. We selected an age-and ethnicity-matched comparison group of control patients with screen-detected breast cancers diagnosed during the same period. In tumor samples, p53, bcl-2, and Ki-67 were examined immunologically and the apoptotic index was assessed histologically. We used logistic regression to determine whether interval cancers were associated with selected demographic, radiologic, and biologic characteristics. Results: It is more likely that mammography did not detect tumors with a high proportion of proliferating cells (>20%) than tumors with a low proportion of proliferating cells (