Doubly-charged ethane ions: Solution to the dilemma of stability predicted by theory and instability observed in experiment

Potential energy curves have been computed for [C2H6]2+ ions and the results used to interpret the conspicuous absence of these ions in 2E mass spectra and in charge-stripping experiments. The energies and structures of geometry-optimized ground-state singlet and excited-state triplet [C2H6]2+ ions have been determined along with energies for different decomposition barriers and dissociation asymptotes. Although singlet and triplet [C2H6]2+ ions can exist as stable entities, they possess low energy barriers to decomposition. Vertical Franck-Condon transitions, involving electron impact ionization of ethane as well as charge-stripping collisions of [C2H6]+ ions, produce [C2H6]2+ ions which promptly dissociate since they are formed with energies in excess of various decomposition barriers. Appearance energies computed for doubly-charged ethane fragment ions are in accordance with experimental values.

Varying spin state composition by the choice of capping ligand in a family of molecular chains: detailed analysis of magnetic properties of chromium(III) horseshoes

We report a detailed physical analysis on a family of isolated, antiferro-magnetically (AF) coupled, chromium(III) finite chains, of general formula (Cr(RCO(2))(2)F)(n) where the chain length n = 6 or 7. Additionally, the chains are capped with a selection of possible terminating ligands, including hfac (= 1,1,1,5,5,5-hexafluoropentane-2,4-dionate(1-)), acac (= pentane-2,4-dionate(1-)) or (F)(3). Measurements by inelastic neutron scattering (INS), magnetometery and electron paramagnetic resonance (EPR) spectroscopy have been used to study how the electronic properties are affected by n and capping ligand type. These comparisons allowed the subtle electronic effects the choice of capping ligand makes for odd member spin 3/2 ground state and even membered spin 0 ground state chains to be investigated. For this investigation full characterisation of physical properties have been performed with spin Hamiltonian parameterisation, including the determination of Heisenberg exchange coupling constants and single ion axial and rhombic anisotropy. We reveal how the quantum spin energy levels of odd or even membered chains can be modified by the type of capping ligand terminating the chain. Choice of capping ligands enables Cr-Cr exchange coupling to be adjusted by 0, 4 or 24%, relative to Cr-Cr exchange coupling within the body of the chain, by the substitution of hfac, acac or (F)(3) capping ligands to the ends of the chain, respectively. The manipulation of quantum spin levels via ligands which play no role in super-exchange, is of general interest to the practise of spin Hamilton modelling, where such second order effects are generally not considered of relevance to magnetic properties.

Anti-HIV state but not apoptosis depends on IFN signature in CD4+ T cells

To gain insights into the molecular mechanisms underlying early host responses to HIV in the CD4(+) T cell target population, we examined gene expression in CD4(+) T cells isolated 24 h after ex vivo HIV infection of lymphocyte aggregate cultures derived from human tonsils. Gene profiling showed a distinct up-regulation of genes related to immune response and response to virus, notably of IFN-stimulated genes (ISGs), irrespective of the coreceptor tropism of the virus. This mostly IFN-alpha-dependent gene signature suggested the involvement of plasmacytoid dendritic cells, a principal component of the antiviral immune response. Indeed, depletion of plasmacytoid dendritic cells before HIV inoculation abrogated transcriptional up-regulation of several ISGs and resulted in increased levels of HIV replication. Treatment with a blocking anti-IFN-alphaR Ab yielded increased HIV replication; conversely, HIV replication was decreased in pDC-depleted cultures treated with IFN-alpha. Among up-regulated ISGs was also TRAIL, indicating a potential role of the IFN signature in apoptosis. However, a blocking anti-TRAIL Ab did not abrogate apoptosis of CD4(+) T cells in CXCR4-tropic HIV-infected cultures, suggesting the involvement of pathways other than TRAIL mediated. We conclude that acute HIV infection of lymphoid tissue results in up-regulation of ISGs in CD4(+) T cells, which induces an anti-HIV state but not apoptosis.

Crystal structure of the Leishmania major phosphodiesterase LmjPDEB1 and insight into the design of the parasite-selective inhibitors

Human leishmaniasis is a major public health problem in many countries, but chemotherapy is in an unsatisfactory state. Leishmania major phosphodiesterases (LmjPDEs) have been shown to play important roles in cell proliferation and apoptosis of the parasite. Thus LmjPDE inhibitors may potentially represent a novel class of drugs for the treatment of leishmaniasis. Reported here are the kinetic characterization of the LmjPDEB1 catalytic domain and its crystal structure as a complex with 3-isobutyl-1-methylxanthine (IBMX) at 1.55 A resolution. The structure of LmjPDEB1 is similar to that of human PDEs. IBMX stacks against the conserved phenylalanine and forms a hydrogen bond with the invariant glutamine, in a pattern common to most inhibitors bound to human PDEs. However, an extensive structural comparison reveals subtle, but significant differences between the active sites of LmjPDEB1 and human PDEs. In addition, a pocket next to the inhibitor binding site is found to be unique to LmjPDEB1. This pocket is isolated by two gating residues in human PDE families, but constitutes a natural expansion of the inhibitor binding pocket in LmjPDEB1. The structure particularity might be useful for the development of parasite-selective inhibitors for the treatment of leishmaniasis.

On the modeling of drug induced respiratory depression in the non-steady-state

The ability of anesthetic agents to provide adequate analgesia and sedation is limited by the ventilatory depression associated with overdosing in spontaneously breathing patients. Therefore, quantitation of drug induced ventilatory depression is a pharmacokinetic-pharmacodynamic problem relevant to the practice of anesthesia. Although several studies describe the effect of respiratory depressant drugs on isolated endpoints, an integrated description of drug induced respiratory depression with parameters identifiable from clinically available data is not available. This study proposes a physiological model of CO2 disposition, ventilatory regulation, and the effects of anesthetic agents on the control of breathing. The predictive performance of the model is evaluated through simulations aimed at reproducing experimental observations of drug induced hypercarbia and hypoventilation associated with intravenous administration of a fast-onset, highly potent anesthetic mu agonist (including previously unpublished experimental data determined after administration of 1 mg alfentanil bolus). The proposed model structure has substantial descriptive capability and can provide clinically relevant predictions of respiratory inhibition in the non-steady-state to enhance safety of drug delivery in the anesthetic practice.

Conformational preferences of natural and C3-modified epothilones in aqueous solution

The conformational properties of the microtubule-stabilizing agent epothilone A ( 1a) and its 3-deoxy and 3-deoxy-2,3-didehydro derivatives 2 and 3 have been investigated in aqueous solution by a combination of NMR spectroscopic methods, Monte Carlo conformational searches, and NAMFIS calculations. The tubulin-bound conformation of epothilone A ( 1a), as previously proposed on the basis of solution NMR data, was found to represent a significant fraction of the ensemble of conformations present for the free ligands in aqueous solution.

The Effect of the Cu:Fe''' Ratio Upon the Current Efficiency in the Electrolysis of a Copper Sulfate Solution Containing Iron Sulfate

It is a well-known fact that, in the electrolysis of a CuSO4 solution containing iron sulfate, using insoluble anodes, with the depletion of copper, the point is finally reached where the current efficiency becomes zero. This decrease in current efficiency is due to the oxidation of the ferrous sulfate to the ferric condition at the anode, by the oxygen liberated. The resulting ferric sulfate diffuses over to the cathode and there dissolves copper from the cathode according to the chemical equation Cu + Fe2 (SO4)3 = CuSO4 + 2FeSO4. This copper, which has been deposited at the cathode by the electric current, is thus redissolved by the Fe2(SO4)3. The solution of the copper causes at the same time a formation of FeSO4 which in turn diffuses over to the anode and is there oxidized to Fe2(SO4)3; and so the cycle continues, using electric current without rendering useful work. E. H. Larison has noted that a definite amount of ferric salts must be reduced to the ferrous condition before all the copper will remain on the cathode; he does not state, however, just what this point is. L. Addicks has plotted the relation between current efficiency and ferric sulphate content. The existence of the results scattered the points more or less, although the decrease in current efficiency with increased ferric sulphate content is clearly indicated. E. T.Kern has likewise noted that the smaller the amount of copper in the solution, the greater is the reduction of current efficiency. In this work, therefore, it was desired to determine what amount of ferric iron was permissible in a copper sulfate solution of definite concentration before the current efficiency would drop to zero, and what, if any, was the effect of definite Cu:Fe’’’ratio upon the current efficiency of the electrolysis.

Development and characterization of fluorescent pH sensors based on porous silica and hydrogel support matrices

The hydrogen ion activity (pH) is a very important parameter in environment monitoring, biomedical research and other applications. Optical pH sensors have several advantages over traditional potentiometric pH measurement, such as high sensitivity, no need of constant calibration, easy for miniaturization and possibility for remote sensing. Several pH indicators has been successfully immobilized in three different solid porous materials to use as pH sensing probes. The fluorescent pH indicator fluorescein-5-isothiocyanate (FITC) was covalently bound onto the internal surface of porous silica (pore size ~10 nm) and retained its pH sensitivity. The excited state pK* a of FITC in porous silica (5.58) was slightly smaller than in solution (5.68) due to the free silanol groups (Si-OH) on the silica surface. The pH sensitive range for this probe is pH 4.5 - 7.0 with an error less than 0.1 pH units. The probe response was reproducible and stable for at least four month, stored in DI water, but exhibit a long equilibrium of up to 100 minutes. Sol-gel based pH sensors were developed with immobilization of two fluorescent pH indicators fluorescein-5-(and-6)-sulfonic acid, trisodium salt (FS) and 8-hydroxypyrene- 1,3,6-trisulfonic acid (HPTS) through physical entrapment. Prior to immobilization, the indicators were ion-paired with a common surfactant hexadecyltrimethylammonium bromide (CTAB) in order to prevent leaching. The sol-gel films were synthesized through the hydrolysis of two different precursors, ethyltriethoxysilane (ETEOS) and 3- glycidoxypropyltrimethoxysilane (GPTMS) and deposited on a quartz slide through spin coating. The pK a of the indicators immobilized in sol-gel films was much smaller than in solutions due to silanol groups on the inner surface of the sol-gel films and ammonium groups from the surrounding surfactants. Unlike in solution, the apparent pK a of the indicators in sol-gel films increased with increasing ionic strength. The equilibrium time for these sensors was within 5 minutes (with film thickness of ~470 nm). Polyethylene glycol (PEG) hydrogel was of interest for optical pH sensor development because it is highly proton permeable, transparent and easy to synthesize. pH indicators can be immobilized in hydrogel through physical entrapment and copolymerization. FS and HPTS ion-pairs were physically entrapped in hydrogel matrix synthesized via free radical initiation. For covalent immobilization, three indicators, 6,8-dihydroxypyrene-1,3- disulfonic acid (DHPDS), 2,7-dihydroxynaphthalene-3,6-disulfonic acid (DHNDS) and cresol red were first reacted with methacrylic anhydride (MA) to form methacryloylanalogs for copolymerization. These hydrogels were synthesized in aqueous solution with a redox initiation system. The thickness of the hydrogel film is controlled as ~ 0.5 cm and the porosity can be adjusted with the percentage of polyethylene glycol in the precursor solutions. The pK a of the indicators immobilized in the hydrogel both physically and covalently were higher than in solution due to the medium effect. The sensors are stable and reproducible with a short equilibrium time (less than 4 minutes). In addition, the color change of cresol red immobilized hydrogel is vivid from yellow (acidic condition) to purple (basic condition). Due to covalently binding, cresol red was not leaching out from the hydrogel, making it a good candidate of reusable "pH paper".

A Closed-Form, Consistent and Robust Solution to Uncalibrated Photometric Stereo Via Local Diffuse Reflectance Maxima

Images of an object under different illumination are known to provide strong cues about the object surface. A mathematical formalization of how to recover the normal map of such a surface leads to the so-called uncalibrated photometric stereo problem. In the simplest instance, this problem can be reduced to the task of identifying only three parameters: the so-called generalized bas-relief (GBR) ambiguity. The challenge is to find additional general assumptions about the object, that identify these parameters uniquely. Current approaches are not consistent, i.e., they provide different solutions when run multiple times on the same data. To address this limitation, we propose exploiting local diffuse reflectance (LDR) maxima, i.e., points in the scene where the normal vector is parallel to the illumination direction (see Fig. 1). We demonstrate several noteworthy properties of these maxima: a closed-form solution, computational efficiency and GBR consistency. An LDR maximum yields a simple closed-form solution corresponding to a semi-circle in the GBR parameters space (see Fig. 2); because as few as two diffuse maxima in different images identify a unique solution, the identification of the GBR parameters can be achieved very efficiently; finally, the algorithm is consistent as it always returns the same solution given the same data. Our algorithm is also remarkably robust: It can obtain an accurate estimate of the GBR parameters even with extremely high levels of outliers in the detected maxima (up to 80 % of the observations). The method is validated on real data and achieves state-of-the-art results.

Pyroelectric and piezoelectric scanning microscopy applied to reveal the bipolar state of 4-iodo-4′-nitrobiphenyl (INBP)

Two recent scanning probe techniques were applied to investigate the bipolar twin state of 4-iodo-4′-nitrobiphenyl (INBP) crystals. Solution grown crystals of INBP show typically a morphology which does not express that of a mono-domain polar structure (Fdd2, mm2). From previous X-ray diffraction a twinning volume ratio of [similar]70 : 30 is now explained by two unipolar domains (Flack parameter: 0.075(29)) of opposite orientation of the molecular dipoles, joined by a transition zone showing a width of [similar]140 μm. Scanning pyroelectric microscopy (SPEM) demonstrates a continuous transition of the polarization P from +P into −P across the zone. Application of piezoelectric force microscopy (PFM) confirms unipolar alignment of INBP molecules down to a resolution of [similar]20 nm. A previously proposed real structure for INBP crystals built from lamellae with antiparallel alignment is thus rejected. Anomalous X-ray scattering was used to determine the absolute molecular orientation in the two domains. End faces of the polar axis 2 are thus made up by NO2 groups. Using a previously determined negative pyroelectric coefficient pc leads to a confirmation also by a SPEM analysis. Calculated values for functional group interactions (DA), (AA), (DD) and the stochastic theory of polarity formation allow us to predict that NO2 groups should terminate corresponding faces. Following the present analysis, INBP may represent a first example undergoing dipole reversal upon growth to end up in a bipolar state.

Scheduling the production of rolling ingots: Industrial context, model, and solution method

We study a real-world scheduling problem arising in the context of a rolling ingots production. First we review the production process and discuss peculiarities that have to be observed when scheduling a given set of production orders on the production facilities. We then show how to model this scheduling problem using prescribed time lags between operations, different kinds of resources, and sequence-dependent changeovers. A branch-and-bound solution procedure is presented in the second part. The basic principle is to relax the resource constraints by assuming infinite resource availability. Resulting resource conflicts are then stepwise resolved by introducing precedence relationships among operations competing for the same resources. The algorithm has been implemented as a beam search heuristic enumerating alternative sets of precedence relationships.

Motile response patterns and ultrastructural observations of the isolated outer hair cell

The tonotopic organization of the mammalian cochlea is accompanied by structural gradients which include the somatic lengths of outer hair cells (OHCs). These receptors rest upon the vibrating portion of the basilar membrane and have been reported to exhibit motile responses following chemical and electrical stimulation. These movements were examined in detail in this dissertation. It was found that isolated OHCs cultured in vitro respond to chemical depolarization with slow tonic movements, and to electrical waveforms with bi-directional, frequency following movements extending from DC to at least 10 kHz.^ Slow contractions were also elicited following electrical stimulation, bath incubation in carbachol (a cholinergic agonist), and increases in extracellular K+ concentration as little as 50 mM.^ Isolated OHCs display anatomical features which are remarkable when contrasted with those prepared from intact receptor organs. A complex structure located between the cuticular plate and the nuclear membrane was consistently observed and was examined by serial cross-sections which revealed a network of non-membrane bound densities. This corresponded to a granular complex seen at the light microscope level. The complex was composed of dense regions of organelles, striated structures embedded within the core, and a circumferential network of microtubules residing in the peri-nuclear portion of the cell. In cells which had lost their nuclear attachment to the terminal synaptic body, the granular complex could be made to contract without effecting any change in cellular length, implying that the complex may be the driving force behind certain aspects of the motile response.^ Most cells displayed movements which revealed asymmetries analogous to those reported for OHC receptor potentials in vivo. The contraction phase (for longer cells) was shown to have a small time constant (approximately 400 microseconds) and saturated with limited displacements. The expansion phase had time constants as large as 1.3 milliseconds but yielded displacements as much as 60 percent larger than those seen for contractions.^ Additional waveform characteristics seen in the in vivo response could be emulated either by biasing the cell's resting length with either direct current, triggering contractions via large electrical displacements, or incubation with depolarizing compounds.^ Alternatively, short (20-30 um) cells revealed more linear response characteristics to the probe stimulus. Partial saturation was achieved and revealed a DC component which was opposite in polarity to that seen in longer cells. (Abstract shortened with permission of author.) ^

Ultrafast Relaxation Dynamics of Osmium-Polypyridine Complexes in Solution

We present steady-state absorption and emission spectroscopy and femtosecond broadband photoluminescence up-conversion spectroscopy studies of the electronic relaxation of Os(dmbp)3 (Os1) and Os(bpy)2(dpp) (Os2) in ethanol, where dmbp is 4,4′-dimethyl-2,2′-biypridine, bpy is 2,2′-biypridine, and dpp is 2,3-dipyridyl pyrazine. In both cases, the steady-state phosphorescence is due to the lowest 3MLCT state, whose quantum yield we estimate to be ≤5.0 × 10–3. For Os1, the steady-state phosphorescence lifetime is 25 ns. In both complexes, the photoluminescence excitation spectra map the absorption spectrum, pointing to an excitation wavelength-independent quantum yield. The ultrafast studies revealed a short-lived (≤100 fs) fluorescence, which stems from the lowest singlet metal-to-ligand-charge-transfer (1MLCT) state and decays by intersystem crossing to the manifold of 3MLCT states. In addition, Os1 exhibits a 50 ps lived emission from an intermediate triplet state at an energy 2000 cm–1 above that of the long-lived (25 ns) phosphorescence. In Os2, the 1MLCT–3MLCT intersystem crossing is faster than that in Os1, and no emission from triplet states is observed other than the lowest one. These observations are attributed to a higher density of states or a smaller energy spacing between them compared with Os1. They highlight the importance of the energetics on the rate of intersystem crossing.

Measurement of isolated-photon pair production in pp collisions at sqrts=7 TeV with the ATLAS detector

The ATLAS experiment at the LHC has measured the production cross section of events with two isolated photons in the final state, in proton-proton collisions at root s = 7 TeV. The full data set collected in 2011, corresponding to an integrated luminosity of 4.9 fb(-1), is used. The amount of background, from hadronic jets and isolated electrons, is estimated with data-driven techniques and subtracted. The total cross section, for two isolated photons with transverse energies above 25 GeV and 22 GeV respectively, in the acceptance of the electromagnetic calorimeter (vertical bar eta vertical bar < 1.37 and 1.52 < vertical bar eta vertical bar 2.37) and with an angular separation Delta R > 0.4, is 44.0(-4.2)(+3.2) pb. The differential cross sections as a function of the di-photon invariant mass, transverse momentum, azimuthal separation, and cosine of the polar angle of the largest transverse energy photon in the Collins-Soper di-photon rest frame are also measured. The results are compared to the prediction of leading-order parton-shower and next-to-leading-order and next-to-next-to-leading-order parton-level generators.

Search for pair production of heavy top-like quarks decaying to a high-pT W boson and a b quark in the lepton plus jets final state at sqrts=7 TeV with the ATLAS detector

A search is presented for production of a heavy up-type quark (t') together with its antiparticle, assuming a significant branching ratio for subsequent decay into a W boson and a b quark. The search is based on 4.7 fb(-1) of pp collisions root s = 7 TeV recorded in 2011 with the ATLAS detector at the CERN Large Hadron Collider. Data are analyzed in the lepton + jets final state, characterized by a high-transverse-momentum isolated electron or muon, large missing transverse momentum and at least three jets. The analysis strategy relies on the substantial boost of the W bosons in the t'(t') over bar signal when m(t') greater than or similar to 400 GeV. No significant excess of events above the Standard Model expectation is observed and the result of the search is interpreted in the context of fourth-generation and vector-like quark models. Under the assumption of a branching ratio BR(t' -> W b) = I, a fourth-generation t' quark with mass lower than 656 GeV is excluded at 95% confidence level. In addition, in light of the recent discovery of a new boson of mass similar to 126 GeV at the LHC, upper limits are derived in the two-dimensional plane of BR(t' -> Wb) versus BR(t' -> Ht), where H is the Standard Model Higgs boson, for vector-like quarks of various masses.