Heterobimetallic Gold/Ruthenium Complexes Synthesized via Post-functionalization and Applied in Dual Photoredox Gold Catalysis.

The synthesis of heterobimetallic AuI /RuII complexes of the general formula syn- and anti-[{AuCl}(L1∩L2){Ru(bpy)2 }][PF6 ]2 is reported. The ditopic bridging ligand L1∩L2 refers to a P,N hybrid ligand composed of phosphine and bipyridine substructures, which was obtained via a post-functionalization strategy based on Diels-Alder reaction between a phosphole and a maleimide moiety. It was found that the stereochemistry at the phosphorus atom of the resulting 7-phosphanorbornene backbone can be controlled by executing the metal coordination and the cycloaddition reaction in a different order. All precursors, as well as the mono- and multimetallic complexes, were isolated and fully characterized by various spectroscopic methods such as NMR, IR, and UV-vis spectroscopy as well as cyclic voltammetry. Photophysical measurements show efficient phosphorescence for the investigated monometallic complex anti-[(L1∩L2){Ru(bpy)2 }][PF6 ]2 and the bimetallic analogue syn-[{AuCl}(L1∩L2){Ru(bpy)2 }][PF6 ]2 , thus indicating a small influence of the {AuCl} fragment on the photoluminescence properties. The heterobimetallic AuI /RuII complexes syn- and anti-[{AuCl}(L1∩L2){Ru(bpy)2 }][PF6 ]2 are both active catalysts in the P-arylation of aryldiazonium salts promoted by visible light with H-phosphonate affording arylphosphonates in yields of up to 91 %. Both dinuclear complexes outperform their monometallic counterparts.

Multistimuli-Responsive [3]Dioxaphosphaferrocenophanes with Orthogonal Switches.

Novel multistimuli-responsive phosphine ligands comprising a redox-active [3]dioxaphosphaferrocenophane backbone and a P-bound imidazolin-2-ylidenamino entity that allows switching by protonation are reported. Investigation of the corresponding metal complexes and their redox behaviour are reported and show the sensitivity of the system towards protonation and metal coordination. The experimental findings are supported by DFT calculations. Protonation and oxidation events are applied in Rh-catalysed hydrosilylations and demonstrate a remarkable influence on reactivity and/or selectivity.

Echocardiographic Predictors of Recoarctation After Surgical Repair: A Swedish National Study.

BACKGROUND: After surgical repair of aortic coarctation (CoA) there is a risk for restenosis (reCoA), particularly in the first year of life. This study aimed to identify reCoA risk factors by analyzing postoperative predischarge echocardiograms. METHODS: This was a retrospective analysis of echocardiograms of children born operated on for CoA in Sweden in 2011 to 2017. RESULTS: A total of 253 children were included. Median age at surgery was 10 days; median follow-up was 4.6 years. Risk for restenosis occurred in 34 patients (13%; 74% by 6 months and 91% by 12 months). We generated 2 reCoA risk models applying aortic dimensions and the respective Z-scores combined with surgical and demographic factors. We defined reCoA risk categories as low (≤10%), moderate (11% to 29%), moderate to high (30% to 49%), or high (≥50%). Patients with either isthmus of 3.3 mm or less (1- and 5-year event-free survival of 38% and 32%, respectively) or isthmus Z-score of -2.8 or less with a weight at surgery of less than 4.4 kg (1- and 5-year event free survival of 21% and 16%, respectively) were at highest risk for reCoA. Conversely, patients at low risk had isthmus greater than 3.7 mm and distal aortic arch greater than 3.5mm (1- and 5-year event free survival of 97% and 97%, respectively), and isthmus and proximal aortic arch Z-score greater than -2.8 or operative weight greater than 4.4 kg with an isthmus Z-score of -2.8 or less (1- and 5-year event-free survival of 97% and 97%, respectively). CONCLUSIONS: Risk for reCoA can be predicted based on postoperative predischarge echocardiographic variables combined with surgical and demographic factors. We suggest tailoring follow-up intervals individually according to the predicted reCoA risk.

Multimodal assessment of vascular and ventricular function in children and adults with repaired aortic coarctation.

BACKGROUND: Coarctation of the Aorta (CoA) is associated with increased aortic stiffness and diastolic left ventricular dysfunction. The mechanisms involved and impact of age remain unclear. It was the aim of this study to characterize arterial and cardiac function, their correlation, and the effect of age in children and adults with repaired CoA. METHODS: Multimodal cardiovascular assessment from the ascending aorta to microcirculation and endothelial function was performed prospectively. Statistical analyses included multivariable linear regression and correlation of vascular parameters with age and diastolic function. RESULTS: Fifty-seven patients with well-repaired CoA and 77 healthy controls were included (age 8-59). There was no significant difference in age, gender, body surface area and BMI between the groups. Ascending aortic distensibility was decreased while common carotid intima media thickness, central augmentation index corrected to a heart rate of 75/min [Aix75], peripheral Aix75 and aging index were increased in the CoA group. Interestingly, in a subgroup analysis of CoA patients with tricuspid vs. bicuspid aortic valves (BAV), only the latter had increased Aix75. Carotid-femoral pulse wave velocity [cfPWV], reactive hyperemia index and microcirculation were not significantly different between CoA and control patients. Diastolic function was impaired in the CoA group relative to controls. Both diastolic function and age correlated moderate-strongly with arterial parameters. CONCLUSIONS: Patients with well repaired CoA have increased proximal arterial stiffness which correlates with diastolic function and age. Increased Aix75 may be attributed to a high prevalence of associated BAV. Neither cfPWV nor peripheral endothelial or microcirculatory function are impaired.

Search for γ-Ray Line Signals from Dark Matter Annihilations in the Inner Galactic Halo from 10 Years of Observations with H.E.S.S.

Spectral lines are among the most powerful signatures for dark matter (DM) annihilation searches in very-high-energy γ rays. The central region of the Milky Way halo is one of the most promising targets given its large amount of DM and proximity to Earth. We report on a search for a monoenergetic spectral line from self-annihilations of DM particles in the energy range from 300 GeV to 70 TeV using a two-dimensional maximum likelihood method taking advantage of both the spectral and spatial features of the signal versus background. The analysis makes use of Galactic center observations accumulated over ten years (2004-2014) with the H.E.S.S. array of ground-based Cherenkov telescopes. No significant γ-ray excess above the background is found. We derive upper limits on the annihilation cross section ⟨σv⟩ for monoenergetic DM lines at the level of 4×10^{-28} cm^{3} s^{-1} at 1 TeV, assuming an Einasto DM profile for the Milky Way halo. For a DM mass of 1 TeV, they improve over the previous ones by a factor of 6. The present constraints are the strongest obtained so far for DM particles in the mass range 300 GeV-70 TeV. Ground-based γ-ray observations have reached sufficient sensitivity to explore relevant velocity-averaged cross sections for DM annihilation into two γ-ray photons at the level expected from the thermal relic density for TeV DM particles.

Conformational control of nonplanar free base porphyrins: towards bifunctional catalysts of tunable basicity.

For the first time, free base and N-methylated porphyrins have been utilized as bifunctional organocatalysts in Michael additions and it was found that distortion of the macrocycle is a vital prerequisite for their catalytic activity. Conformational design has been used to tailor the properties of nonplanar porphyrins with regards to availability of the N-H units for hydrogen bonding (distortion-dependent hydrogen bonding) and the basicity of the heterocyclic groups. NMR spectroscopic- and catalyst screening studies provided insight into the likely mode of catalyst action. This unprecedented use of free base and N-substituted porphyrins as organocatalysts opens a new functional role for porphyrins.

H.E.S.S. Limits on Linelike Dark Matter Signatures in the 100 GeV to 2 TeV Energy Range Close to the Galactic Center.

A search for dark matter linelike signals iss performed in the vicinity of the Galactic Center by the H.E.S.S. experiment on observational data taken in 2014. An unbinned likelihood analysis iss developed to improve the sensitivity to linelike signals. The upgraded analysis along with newer data extend the energy coverage of the previous measurement down to 100 GeV. The 18 h of data collected with the H.E.S.S. array allow one to rule out at 95% C.L. the presence of a 130 GeV line (at l=-1.5°, b=0° and for a dark matter profile centered at this location) previously reported in Fermi-LAT data. This new analysis overlaps significantly in energy with previous Fermi-LAT and H.E.S.S. RESULTS: No significant excess associated with dark matter annihilations was found in the energy range of 100 GeV to 2 TeV and upper limits on the gamma-ray flux and the velocity weighted annihilation cross section are derived adopting an Einasto dark matter halo profile. Expected limits for present and future large statistics H.E.S.S. observations are also given.

Search for Dark Matter Annihilations towards the Inner Galactic Halo from 10 Years of Observations with H.E.S.S.

The inner region of the Milky Way halo harbors a large amount of dark matter (DM). Given its proximity, it is one of the most promising targets to look for DM. We report on a search for the annihilations of DM particles using γ-ray observations towards the inner 300 pc of the Milky Way, with the H.E.S.S. array of ground-based Cherenkov telescopes. The analysis is based on a 2D maximum likelihood method using Galactic Center (GC) data accumulated by H.E.S.S. over the last 10 years (2004-2014), and does not show any significant γ-ray signal above background. Assuming Einasto and Navarro-Frenk-White DM density profiles at the GC, we derive upper limits on the annihilation cross section ⟨σv⟩. These constraints are the strongest obtained so far in the TeV DM mass range and improve upon previous limits by a factor 5. For the Einasto profile, the constraints reach ⟨σv⟩ values of 6×10^{-26} cm^{3} s^{-1} in the W^{+}W^{-} channel for a DM particle mass of 1.5 TeV, and 2×10^{-26} cm^{3} s^{-1} in the τ^{+}τ^{-} channel for a 1 TeV mass. For the first time, ground-based γ-ray observations have reached sufficient sensitivity to probe ⟨σv⟩ values expected from the thermal relic density for TeV DM particles.

Aortic stiffness and left ventricular diastolic function in children with well-functioning bicuspid aortic valves.

AIMS: Aortic stiffness and diastolic function are abnormal in adults with bicuspid aortic valves (BAVs). The goal of this study was to determine the relationship between aortic stiffness and left ventricular (LV) diastolic impairment in children with well-functioning BAV and no associated congenital heart disease. METHODS AND RESULTS: This is a retrospective review of echocardiograms in children with isolated BAV (group BAV; N = 50) and healthy frequency-matched controls (group Control; N = 50). We analysed LV systolic and diastolic function, proximal and distal ascending aortic stiffness index (SI), distensibility, and strain. Age range was 0.2-20 (median 11) years. There was no significant difference in blood pressure, normalized LV size and systolic function between the groups. Several parameters of LV diastolic function were lower in group BAV compared with group Control (e.g. septal E': BAV 12 ± 2.3 cm/s; Control 13.5 ± 1.8 cm/s, P < 0.001). All parameters of proximal and distal ascending aortic elasticity were abnormal in group BAV vs. Control (SI proximal ascending aorta: BAV 4.2 ± 1.6; Control 3.0 ± 0.9, P < 0.001). There was no significant correlation between parameters of aortic elasticity and diastolic function. In a subgroup analysis of children with fusion of the right-non vs. right-left coronary cusps, there was no significant difference for any of the parameters analysed. CONCLUSION: Even children with well-functioning isolated BAV have abnormalities in aortic elasticity and diastolic function when compared with the Control group. However, a relationship between the two could not be established.

Parametric uncertainty and global sensitivity analysis in a model of the carotid bifurcation: Identification and ranking of most sensitive model parameters.

In computational cardiovascular models, parameters are one of major sources of uncertainty, which make the models unreliable and less predictive. In order to achieve predictive models that allow the investigation of the cardiovascular diseases, sensitivity analysis (SA) can be used to quantify and reduce the uncertainty in outputs (pressure and flow) caused by input (electrical and structural) model parameters. In the current study, three variance based global sensitivity analysis (GSA) methods; Sobol, FAST and a sparse grid stochastic collocation technique based on the Smolyak algorithm were applied on a lumped parameter model of carotid bifurcation. Sensitivity analysis was carried out to identify and rank most sensitive parameters as well as to fix less sensitive parameters at their nominal values (factor fixing). In this context, network location and temporal dependent sensitivities were also discussed to identify optimal measurement locations in carotid bifurcation and optimal temporal regions for each parameter in the pressure and flow waves, respectively. Results show that, for both pressure and flow, flow resistance (R), diameter (d) and length of the vessel (l) are sensitive within right common carotid (RCC), right internal carotid (RIC) and right external carotid (REC) arteries, while compliance of the vessels (C) and blood inertia (L) are sensitive only at RCC. Moreover, Young's modulus (E) and wall thickness (h) exhibit less sensitivities on pressure and flow at all locations of carotid bifurcation. Results of network location and temporal variabilities revealed that most of sensitivity was found in common time regions i.e. early systole, peak systole and end systole.

The vista paradox: Framing or contrast?

The vista paradox is the illusion in which an object seen through a window appears to shrink in apparent size (and appears farther away) as the observer approaches the window. Paradoxically, the distal object appears smaller as its visual angle increases. We investigated the effect in four experiments varying object size, distance, point of fixation, and texture of the frame and of the object. In the first experiment, we tried to confirm the illusion and to test the robustness of the phenomenon. In the second experiment, we manipulated where subjects fixated (on the frame or on the object) as well as the texture of the object and the frame. Fixation was essential for the illusion: fixating the frame led to an apparent shrinking of the object, whereas fixation on the object did not. Texture of the frame intensified the apparent shrinking of the object. In a third experiment, we separated the point of fixation from the frame in a between-subjects design. Finally, in Experiment 4, we showed that the paradox does not require a frame, but it requires a fixation on a location different from the object. That is, the window or frame is dispensable for the vista paradox, but fixation is critical.

Constraints on an annihilation signal from a core of constant dark matter density around the milky way center with H.E.S.S.

An annihilation signal of dark matter is searched for from the central region of the Milky Way. Data acquired in dedicated on-off observations of the Galactic center region with H.E.S.S. are analyzed for this purpose. No significant signal is found in a total of ∼9 h of on-off observations. Upper limits on the velocity averaged cross section, ⟨σv⟩, for the annihilation of dark matter particles with masses in the range of ∼300 GeV to ∼10 TeV are derived. In contrast to previous constraints derived from observations of the Galactic center region, the constraints that are derived here apply also under the assumption of a central core of constant dark matter density around the center of the Galaxy. Values of ⟨σv⟩ that are larger than 3×10^{-24} cm^{3}/s are excluded for dark matter particles with masses between ∼1 and ∼4 TeV at 95% C.L. if the radius of the central dark matter density core does not exceed 500 pc. This is the strongest constraint that is derived on ⟨σv⟩ for annihilating TeV mass dark matter without the assumption of a centrally cusped dark matter density distribution in the search region.

[Comparison of contrast-enhanced MR angiography of the aortoiliac vessels using a 1.0 molar contrast agent at 1.0 T with intra-arterial digital subtraction angiography]. / Ergebnisse der kontrastverstärkten MR-Angiographie der aortoiliakalen Gefässe mit einem 1-molaren Kontrastmittel bei 1,0 T: Vergleich zur i. a. DSA.

PURPOSE: To evaluate the diagnostic accuracy of contrast-enhanced MR angiography (CE-MRA) using a 1.0 molar contrast agent at 1.0 T for the diagnosis of abdominal aortic aneurysms and stenoses of renal or iliac arteries in comparison to intraarterial digital subtraction angiography (DSA). MATERIALS AND METHODS: A total of 19 patients with the suspicion of abdominal aortic aneurysm or stenosis of renal or iliac arteries were examined with CE-MRA at 1.0 T. Intra-arterial DSA served as reference in all cases. After test bolus tracking, 10 or 8 ml of the 1.0 molar contrast agent Gadobutrol corresponding to a dose of 0.1 - 0.15 mmol/kg bw were injected and imaging performed using a FLASH-3D sequence. To evaluate the interobserver-variability, the blinded images were analyzed by two radiologists. Besides the rating of overall image quality on a 4-point-scale, the images were evaluated for aneurysms and arteriosclerotic lesions with a stenosis of < 50 % or > 50 % or occlusion. RESULTS: A total of 144 segments were analyzed. The mean value of the CE-MRA image quality was 3.4 on a 4-point-scale. The sensitivity of CE-MRA in depicting relevant pathological findings was 96 % and the specificity 99 %. The positive predictive value was 96 % and the negative predictive value 99 %. Inter-observer variability was low with a kappa value of 0.82. CONCLUSION: CE-MRA using a 1.0 molar contrast agent at 1.0 T enables an excellent diagnosis or exclusion of pathologies of the aortoiliac vessels.

Cloning and characterization of a member of the Hsp70 gene family from Locusta migratoria, a highly thermotolerant insect.

A complementary deoxyribonucleic acid (cDNA) and the corresponding gene segment encoding a member of the 70-kDa heat shock protein (Hsp70) family have been cloned and sequenced from Locusta migratoria, the African migratory locust. These animals are noted for their thermotolerance, which can exceed temperatures of 50 degrees C. Conceptually translated, the sequence shows a 654-residue protein with theoretical molecular weight of 71.4 kDa, which more closely resembles the mammalian Hsp70 (84-85% similarity) than Hsp70 from other insects, with approximately 75% similarity to the sequence from the fruit fly. Comparisons of cDNA and genomic sequences show that the gene contains 2 introns, a 245-bp intron located in the 5' untranslated region and a 91-bp intron in the coding region. Transcript abundance, as estimated by Northern blot analysis and reverse transcription-polymerase chain reaction, shows that heat shock treatment (45 degrees C for 3 hours) does not elevate hsp70 messenger ribonucleic acid levels in fat bodies or in neural tissues. Immunological assays of Hsp70 show that the protein is constitutively expressed, with a modest, approximately 2-fold induction after a 3-hour heat shock in fat body preparations. Although this sequence could be an hsc70 rather than an hsp70, it was the only cDNA isolated from heat-shocked tissue. Whatever the formal designation, such modest induction and constitutive expression may be ideally suited as an adaptation to the locust's chronic exposure to heat shock temperatures and the consequent demand for chaperone proteins.

Amperometric TNT biosensor based on the oriented immobilization of a nitroreductase maltose binding protein fusion.

The preparation and characterization of an amperometric 2,4,6-trinitrotoluene (TNT) biosensor based on the surface immobilization of a maltose binding protein (MBP) nitroreductase (NR) fusion (MBP-NR) onto an electrode modified with an electropolymerized film of N-(3-pyrrol-1-ylpropyl)-4,4'-bipyridine (PPB) are described. The MBP domain of MBP-NR exhibits a high and specific affinity toward electropolymerized films of PPB with the immobilized enzyme retaining virtually all of its enzymatic activity. Under similar conditions, the wild-type NR enzyme (i.e., without the MBP domain) loses most of its enzymatic activity. The kinetics of the catalytic reaction between the biosensor and TNT and 2,4-dinitrotoluene (DNT) were characterized using rotated disk electrode and cyclic voltammetry techniques, and values of 1.4 x 10(4) and 7.1 x 10(4) M(-1) s(-1) were obtained for TNT and DNT, respectively. The apparent Michaelis-Menten constants (KM) for MBP-NR in solution and on the surface, using TNT as substrate, were determined to be 27 and 95 microM, respectively. The corresponding value for "wild-type" NR in solution containing TNT was 78 microM, which is very close to the value obtained for MBP-NR on the surface. The limits of detection for both TNT and DNT were estimated to be 2 microM, and the sensitivities were determined to be 205 and 222 nA/microM, respectively.

Enantiomerically pure chiral coordination polymers: synthesis, spectroscopy, and electrochemistry in solution and on surfaces.

The two enantiomerically pure bridging ligands (+/-)-[ctpy-x-ctpy] have been prepared employing a two-fold stereospecific alkylation reaction of the enantiomerically pure, chiral terpyridyl-type ligands (+/-)-ctpy. The reaction of each of the enantiomerically pure bridging ligands with Fe(2+) gives rise to chiral coordination polymers whose formation and stoichiometry were followed spectrophotometrically. An assignment of the absolute configuration of the formed helical polymeric structures was carried out on the basis of circular dichroism studies. Highly ordered domains (as determined from STM imaging) of the enantiomerically pure chiral redox polymers could be prepared via the interfacial reaction, over an HOPG substrate, of the bridging ligand in CH(2)Cl(2) and FeSO(4) in water. The degree of polymerization was estimated to be up to 60 from analysis of the STM images of the highly ordered domains on HOPG. The helicality of the domains was compared to the configuration obtained from the circular dichroism studies. The electrochemical properties of the polymers were investigated using cyclic voltammetry and the results compared to those of the respective monomeric complexes. The redox behavior of the iron centers in the polymer was comparable to that of the monomeric complex [Fe((-)-ctpy)(2)](PF(6))(2) as well as to that of [Fe(tpy)(2)](PF(6))(2). The polymeric materials undergo electrodeposition following the two-electron reduction of each bridging ligand unit (one electron per terpyridine group). No ligand-mediated metal-metal interactions were evident from the cyclic voltammetric measurements, suggesting that the metal centers act independently. Moreover, oxidation of the metal centers within the polymeric materials did not give rise to electrodeposition.

The radical cation of anti-tricyclooctadiene and its rearrangement products

The anti dimer of cyclobutadiene (anti-tricyclo[4.2.0.0(2.5)]octa-3,7-diene, TOD) is subjected to ionization by gamma-irradiation in Freon matrices, pulse radiolysis in hydrocarbon matrices, and photoinduced electron transfer in solution. The resulting species are probed by optical and ESR spectroscopy (solid phase) as well as by CIDNP spectroscopy (solution). Thereby it is found that ionization of anti-TOD invariably leads to spontaneous decay to two products, that is bicyclo[4.2.0]octa-2,4,7-triene (BOT) and 1,4-dihydropentalene (1,4-DHP), whose relative yield strongly depends on the conditions of the experiment. Exploration of the C8H8*+ potential energy surface by the B3LYP/6-31G* density functional method leads to a mechanistic hypothesis for the observed rearrangements which involves a bifurcation between a pathway leading to the simple valence isomer, BOT*+, and another one leading to an unprecedented other valence isomer, the anti form of the bicyclo[3.3.0]octa-2,6-diene-4,8-diyl radical cation (anti-BOD*+). The latter product undergoes a very facile H-shift to yield the radical cation of 1,3a-dihydropentalene (1,3a-DHP*+) which ultimately rearrranges by a further H-shift to the observed product, 1,4-DHP*+.

The radical cation of syn-tricyclooctadiene and its rearrangement products

The syn dimer of cyclobutadiene (tricyclo[4.2.0.0(2.5)]octa-3,7-diene, TOD) is subjected to ionization under different conditions and the resulting species are probed by optical and ESR spectroscopy. By means of quantum chemical modelling of the potential energy surfaces and the optical spectra, it is possible to assign the different products that arise spontaneously after ionization or after subsequent warming or illumination of the samples. Based on these findings, we propose a mechanistic scheme which involves a partitioning of the incipient radical cation of TOD between two electronic states. These two states engage in (near) activation-less decay to the more stable valence isomers, cyclooctatetraene (COT*+) and a bis-cyclobutenylium radical cation BCB*+. The latter product undergoes further rearrangement, first to tetracyclo[4.2.0.0(2,4).0(3,5]oct-7-ene (TCO*+) and eventually to bicyclo[4.2.0]octa-2,4,7-triene (BOT*+) which can also be generated photochemically from BCB*+ or TCO*+. The surprising departure of syn-TOD*+ from the least-motion reaction path leading to BOT*+ can be traced to strong vibronic interactions (second-order Jahn-Teller effects) which prevail in both possible ground states of syn-TOD*+. Such effects seem to be more important in determining the intramolecular reactivity of radical cations than orbital or state symmetry rules.