Triplet fusion upconversion nanocapsules for volumetric 3D printing.

Three-dimensional (3D) printing has exploded in interest as new technologies have opened up a multitude of applications1-6, with stereolithography a particularly successful approach4,7-9. However, owing to the linear absorption of light, this technique requires photopolymerization to occur at the surface of the printing volume, imparting fundamental limitations on resin choice and shape gamut. One promising way to circumvent this interfacial paradigm is to move beyond linear processes, with many groups using two-photon absorption to print in a truly volumetric fashion3,7-9. Using two-photon absorption, many groups and companies have been able to create remarkable nanoscale structures4,5, but the laser power required to drive this process has limited print size and speed, preventing widespread application beyond the nanoscale. Here we use triplet fusion upconversion10-13 to print volumetrically with less than 4 milliwatt continuous-wave excitation. Upconversion is introduced to the resin by means of encapsulation with a silica shell and solubilizing ligands. We further introduce an excitonic strategy to systematically control the upconversion threshold to support either monovoxel or parallelized printing schemes, printing at power densities several orders of magnitude lower than the power densities required for two-photon-based 3D printing.

Bright Luminescence by Combining Chiral [2.2]Paracyclophane with a Boron-Nitrogen-Doped Polyaromatic Hydrocarbon Building Block.

Novel BN-doped compounds based on chiral, tetrasubstituted [2.2]paracyclophane and NBN-benzo[f,g]tetracene were synthesized by Sonogashira-Hagihara coupling. Conjugated ethynyl linkers allow electronic communication between the π-electron systems through-bond, whereas through-space interactions are provided by strong π-π overlap between the pairs of NBN-building blocks. Excellent optical and chiroptical properties in racemic and enantiopure conditions were measured, with molar absorption coefficients up to ϵ=2.04×105  M-1 cm-1 , fluorescence quantum yields up to ΦPL =0.70, and intense, mirror-image electronic circular dichroism and circularly polarized luminescence signals of the magnitude of 10-3 for the absorption and luminescence dissymmetry factors. Computed glum,calcd. values match the experimental ones. Electroanalytical data show both oxidation and reduction of the ethynyl-linked tetra-NBN-substituted paracyclophane, with an overlap of two redox processes for oxidation leading to a diradical dication.

Strongly Red-Emissive Molecular Ruby [Cr(bpmp)2]3+ Surpasses [Ru(bpy)3]2.

Gaining chemical control over the thermodynamics and kinetics of photoexcited states is paramount to an efficient and sustainable utilization of photoactive transition metal complexes in a plethora of technologies. In contrast to energies of charge transfer states described by spatially separated orbitals, the energies of spin-flip states cannot straightforwardly be predicted as Pauli repulsion and the nephelauxetic effect play key roles. Guided by multireference quantum chemical calculations, we report a novel highly luminescent spin-flip emitter with a quantum chemically predicted blue-shifted luminescence. The spin-flip emission band of the chromium complex [Cr(bpmp)2]3+ (bpmp = 2,6-bis(2-pyridylmethyl)pyridine) shifted to higher energy from ca. 780 nm observed for known highly emissive chromium(III) complexes to 709 nm. The photoluminescence quantum yields climb to 20%, and very long excited state lifetimes in the millisecond range are achieved at room temperature in acidic D2O solution. Partial ligand deuteration increases the quantum yield to 25%. The high excited state energy of [Cr(bpmp)2]3+ and its facile reduction to [Cr(bpmp)2]2+ result in a high excited state redox potential. The ligand's methylene bridge acts as a Brønsted acid quenching the luminescence at high pH. Combined with a pH-insensitive chromium(III) emitter, ratiometric optical pH sensing is achieved with single wavelength excitation. The photophysical and ground state properties (quantum yield, lifetime, redox potential, and acid/base) of this spin-flip complex incorporating an earth-abundant metal surpass those of the classical precious metal [Ru(α-diimine)3]2+ charge transfer complexes, which are commonly employed in optical sensing and photo(redox) catalysis, underlining the bright future of these molecular ruby analogues.

A Vanadium(III) Complex with Blue and NIR-II Spin-Flip Luminescence in Solution.

Luminescence from Earth-abundant metal ions in solution at room temperature is a very challenging objective due to the intrinsically weak ligand field splitting of first-row transition metal ions, which leads to efficient nonradiative deactivation via metal-centered states. Only a handful of 3dn metal complexes (n ≠ 10) show sizable luminescence at room temperature. Luminescence in the near-infrared spectral region is even more difficult to achieve as further nonradiative pathways come into play. No Earth-abundant first-row transition metal complexes have displayed emission >1000 nm at room temperature in solution up to now. Here, we report the vanadium(III) complex mer-[V(ddpd)2][PF6]3 yielding phosphorescence around 1100 nm in valeronitrile glass at 77 K as well as at room temperature in acetonitrile with 1.8 × 10-4% quantum yield (ddpd = N,N'-dimethyl-N,N'-dipyridine-2-ylpyridine-2,6-diamine). In addition, mer-[V(ddpd)2][PF6]3 shows very strong blue fluorescence with 2% quantum yield in acetonitrile at room temperature. Our comprehensive study demonstrates that vanadium(III) complexes with d2 electron configuration constitute a new class of blue and NIR-II luminophores, which complement the classical established complexes of expensive precious metals and rare-earth elements.

Modulating the Electronic and Solid-State Structure of Organic Semiconductors by Site-Specific Substitution: The Case of Tetrafluoropentacenes.

The properties as well as solid-state structures, singlet fission, and organic field-effect transistor (OFET) performance of three tetrafluoropentacenes (1,4,8,11: 10, 1,4,9,10: 11, 2,3,9,10: 12) are compared herein. The novel compounds 10 and 11 were synthesized in high purity from the corresponding 6,13-etheno-bridged precursors by reaction with dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate at elevated temperatures. Although most of the molecular properties of the compounds are similar, their chemical reactivity and crystal structures differ considerably. Isomer 10 undergoes the orbital symmetry forbidden thermal [4+4] dimerization, whereas 11 and 12 are much less reactive. The isomers 11 and 12 crystallize in a herringbone motif, but 10 prefers π-π stacking. Although the energy of the first electric dipole-allowed optical transition varies only within 370 cm-1 (0.05 eV) for the neutral compounds, this amounts to roughly 1600 cm-1 (0.20 eV) for radical cations and 1300 cm-1 (0.16 eV) for dications. Transient spectroscopy of films of 11 and 12 reveals singlet-fission time constants (91±11, 73±3 fs, respectively) that are shorter than for pentacene (112±9 fs). OFET devices constructed from 11 and 12 show close to ideal thin-film transistor (TFT) characteristics with electron mobilities of 2×10-3 and 6×10-2  cm2 V-1 s-1 , respectively.

Comparative evaluation of tissue damage induced by ultrasound and impact dual-mode endoscopic lithotripsy versus conventional single-mode ultrasound lithotripsy.

OBJECTIVE: The aim of our study was to perform comparative investigation of the tissue safety of three different endoscopic lithotripter devices including a new single-probe/dual-energy lithotripter in an in vivo animal model. The Swiss LithoClast Trilogy was compared to the Storz Calcuson and the Swiss LithoClast Vario. The safety test simulated the accidental direct contact between lithotripter probes and the urothelium, which can occur when sliding off a stone or drilling through a calculus during lithotripsy. The safety test included a smallest (1.5 mm) and largest (3.3/3.4 mm) probe diameter per device. METHODS: Testing was performed in nine pigs (three animals per device). The bladder tissue was exposed to direct lithotripter probe contact at maximum power for 10 s to produce visible tissue lesions. Acute tissue trauma was evaluated using a simplified scoring model describing the expected bladder wall injuries for histological examination. After 7 days, all animals were killed, necropsied and examined post mortem. For between-group comparisons regarding microscopic histopathologic features, a Chi-square test was used. A p value < 0.05 was considered to be statistically significant. RESULTS: Irrespective of the lithotripter used, no systemic signs of toxicity were observed. Histologically, signs of normal ongoing healing were observed on the bladder mucosa. There were no significant differences in histological findings taking changes of the epithelium (p = 0.360), the leucocyte infiltration (p = 0.123), the vascular congestion (p = 0.929) and the edema (p = 1.0) between the groups into account. CONCLUSIONS: The results of this study demonstrated a comparable safety between all lithotripsy devices.

Near-IR to Near-IR Upconversion Luminescence in Molecular Chromium Ytterbium Salts.

Upconversion photoluminescence in hetero-oligonuclear metal complex architectures featuring organic ligands is an interesting but still rarely observed phenomenon, despite its great potential from a basic research and application perspective. In this context, a new photonic material consisting of molecular chromium(III) and ytterbium(III) complex ions was developed that exhibits excitation-power density-dependent cooperative sensitization of the chromium-centered 2 E/2 T1 phosphorescence at approximately 775 nm after excitation of the ytterbium band 2 F7/2 →2 F5/2 at approximately 980 nm in the solid state at ambient temperature. The upconversion process is insensitive to atmospheric oxygen and can be observed in the presence of water molecules in the crystal lattice.

Radiative Lifetime, Non-Radiative Relaxation, and Sensitization Efficiency in Luminescent Europium and Neodymium Cryptates - The Roles of 2,2'-Bipyridine-N,N'-dioxide and Deuteration.

Five luminescent tris(bipyridine)-based cryptates with the lanthanoids Eu and Nd have been prepared with a systematic increase in the number of 2,2'-bipyridine-N,N'-dioxide units and with different deuteration levels in the complexing cryptands for the europium species. Careful analysis of the radiative lifetime τrad in these systems reveals that an increase in N-oxide units around the metal centers uniformly lowers τrad by about 30-40 %. The potential involvement of nephelauxetic effects is discussed. Exchange of 30 C-D for C-H oscillators around the europium centers does not affect the radiative lifetimes but decreases non-radiative deactivation and increases the overall luminescence quantum yield in D2 O by 45 %.

Efficient Ytterbium Near-Infrared Luminophore Based on a Nondeuterated Ligand.

A novel molecular ytterbium complex is reported with a new tetradentate ligand based on the 2,2'-bipyridine-6,6'-dicarboxylic acid scaffold. The photophysical properties are investigated, especially with respect to near-infrared luminescence. The ytterbium complex shows a rather high absolute luminescence quantum yield of Φ = 3.0% and a luminescence lifetime of τobs = 72 µs at room temperature in CD3OD solution.

Understanding the Optical and Magnetic Properties of Ytterbium(III) Complexes.

The absorption and emission spectra of three Yb3+ complexes possessing D3, D2, and C2 symmetries were analyzed with the aid of ab initio calculations based on Complete Active Space (CAS) self-consistent field wave functions (CAS(13,7)). The absorption spectra present contributions from both cold and hot bands, involving thermally populated excited sublevels of the 2F7/2 manifold. The high-resolution emission spectrum of the tris-picolinate complex [Yb(DPA)3]3- recorded at 77 K presents four components, while the complexes with macrocyclic ligands show both cold and hot emission bands, resulting in more than four components for the 2F5/2 → 2F7/2 transition. The combined information provided by the absorption and emission spectra allowed to identify most of the crystal field sublevels of the 2F5/2 and 2F7/2 states. The energies of these crystal field components are well-reproduced by the ab initio calculations, with deviations typically lower than 100 cm-1. The crystal field splitting is very sensitive to subtle changes of the Yb3+ coordination environment. The magnetic anisotropy of [Yb(DPA)3]3- obtained with ab initio calculations was found to be extremely sensitive to changes in the twist angle of the upper and lower faces of the tricapped trigonal prismatic coordination polyhedron. Ab initio ligand field theory provides a straightforward chemical justification for the changes in magnetic anisotropy, which are responsible for the observed pseudocontact shifts in the NMR spectra.

Minimally Invasive Aortic Valve Replacement Via Right Anterior Mini-Thoracotomy: Propensity Matched Initial Experience.

BACKGROUND: Aortic valve replacement by way of a right anterior mini-thoracotomy (RAMT) has shown excellent results in terms of mortality and morbidity. The aim of the present study was to compare RAMT aortic valve replacement (AVR) with conventional full sternotomy in regards to early perioperative outcomes and mortality. METHODS: This was a retrospective, observational, cohort study of prospectively collected data from patients who underwent isolated, first time AVR between January 2013 and October 2016. Fifty-three RAMT patients were matched to a control group (conventional full sternotomy) using propensity score analysis. RESULTS: The characteristics of the two cohorts were similar. The in-hospital mortality was 1.9% utilising the RAMT approach versus 5.7% using the sternotomy approach (p=0.34). Ventilation times were similar in both groups (7 [5-2] vs 8 [5-13] hrs; p=0.61). However, ICU length of stay was significantly longer in the RAMT group (median, 46.5 [23-59.5] vs 20 [14-23] hrs; p<0.001), which translated into a significantly longer postoperative hospital length of stay for the RAMT group (median, 8 [6-12] vs 6 [5.5-9.5] days; p=0.04) compared to the sternotomy group. RAMT was associated with a trend towards a higher incidence of postoperative AF in comparison to the sternotomy group, although this was not statistically significant (41.5% vs 28.3%; p=0.17). Patients in the RAMT group had lower 4-hour chest drain output (102.5 vs 1141ml; p=0.0.07). There was no statistically significant difference in rates of non-red cell transfusions between the two groups, (17%vs28.3%; p=0.10). The occurrence of stroke, re-exploration for bleeding, red-cell transfusion and wound infection was similar in both groups. CONCLUSIONS: Right anterior mini-thoracotomy in patients undergoing isolated aortic valve surgery is a safe approach in select patients, although associated with longer cardiopulmonary bypass times and ICU length of stay.

Investigating the Randomness of Passengers' Seating Behavior in Suburban Trains.

In pedestrian dynamics, individual-based models serve to simulate the behavior of crowds so that evacuation times and crowd densities can be estimated or the efficiency of public transportation optimized. Often, train systems are investigated where seat choice may have a great impact on capacity utilization, especially when passengers get in each other's way. Therefore, it is useful to reproduce passengers' behavior inside trains. However, there is surprisingly little research on the subject. Do passengers distribute evenly as it is most often assumed in simulation models and as one would expect from a system that obeys the laws of thermodynamics? Conversely, is there a higher degree of order? To answer these questions, we collect data on seating behavior in Munich's suburban trains and analyze it. Clear preferences are revealed that contradict the former assumption of a uniform distribution. We subsequently introduce a model that matches the probability distributions we observed. We demonstrate the applicability of our model and present a qualitative validation with a simulation example. The model's implementation is part of the free and open-source Vadere simulation framework for pedestrian dynamics and thus available for further studies. The model can be used as one component in larger systems for the simulation of public transport.

Luminescence and Light-Driven Energy and Electron Transfer from an Exceptionally Long-Lived Excited State of a Non-Innocent Chromium(III) Complex.

Photoactive metal complexes employing Earth-abundant metal ions are a key to sustainable photophysical and photochemical applications. We exploit the effects of an inversion center and ligand non-innocence to tune the luminescence and photochemistry of the excited state of the [CrN6 ] chromophore [Cr(tpe)2 ]3+ with close to octahedral symmetry (tpe=1,1,1-tris(pyrid-2-yl)ethane). [Cr(tpe)2 ]3+ exhibits the longest luminescence lifetime (τ=4500 µs) reported up to date for a molecular polypyridyl chromium(III) complex together with a very high luminescence quantum yield of Φ=8.2 % at room temperature in fluid solution. Furthermore, the tpe ligands in [Cr(tpe)2 ]3+ are redox non-innocent, leading to reversible reductive chemistry. The excited state redox potential and lifetime of [Cr(tpe)2 ]3+ surpass those of the classical photosensitizer [Ru(bpy)3 ]2+ (bpy=2,2'-bipyridine) enabling energy transfer (to oxygen) and photoredox processes (with azulene and tri(n-butyl)amine).

Immuno-monitoring reveals an extended subclinical disease activity in tocilizumab-treated giant cell arteritis.

Objective: Tocilizumab is effective in inducing and maintaining remission of GCA. Despite clinical and serological control of disease, magnetic resonance angiography may show persistence of inflammatory signals of unknown significance in arterial walls. Thus, there is an unmet need for tools to detect subclinical disease activity. Methods: Immune-inflammatory markers were measured in prospectively collected sera of the first randomized, double-blind, placebo-controlled trial investigating the use of tocilizumab in GCA. As a comparison, immune-inflammatory markers were also measured in sera from age- and sex-matched healthy volunteers. The biomarkers were quantified using luminex technology. Results: Of all the parameters determined, only MMP-3, pentraxin-3 and sTNFR2 were significantly elevated, while ICAM-1 and CD163 were significantly decreased during the early stages of the study, at time points of full clinical remission under treatment with tocilizumab plus glucocorticoids. In contrast, tocilizumab monotherapy towards the end of the study resulted in an almost complete normalization of immune-inflammatory molecules, as defined by the healthy controls. MMP-3 levels showed a weak association with magnetic resonance signal intensity; none of the biomarkers predicted relapse occurring within 6 months after study end. Conclusion: The data documented a subclinical disease activity in GCA that was more pronounced during the early stages of treatment and almost disappeared towards the study end. They indicated that tocilizumab treatment of at least 52 weeks is necessary in order to reset a broad range of immune-inflammatory pathways. Trial registration: ClinicalTrials.gov, http://clinicaltrials.gov, NCT01450137.

Magnetic resonance angiography in giant cell arteritis: results of a randomized controlled trial of tocilizumab in giant cell arteritis.

Objective: To analyse magnetic resonance angiographic (MRA) vessel wall signals from a randomized controlled trial of tocilizumab (TCZ) to treat GCA. Methods: Participants were assigned in a 2:1 ratio to receive either TCZ + glucocorticoids (GCs) or placebo + GC infusions at 4-week intervals for 52 weeks. GCs were started at 1 mg/kg/day, then tapered to 0.1 mg/kg/day at week 12 and thereafter down to zero. Patients with initial positive MRA findings underwent control MRA at weeks 12 and 52. Vessel wall signals were scored from 0 (normal) to 3 (intense late enhancement). Outcomes were the number of patients with complete MRA remission at weeks 12 and 52, and changes in vasculitis score, vessel anatomy and atherosclerosis. Results: Of the 30 randomized participants, nine TCZ and two placebo patients had no vessel wall enhancement on initial MRA. At week 12, MRAs were performed in nine TCZ and four placebo patients (nine and three in clinical remission, respectively). Three (33%) TCZ patients showed normalization of vessel wall signals compared with one (25%) placebo patient. At week 52, there was additional MRA improvement in some TCZ patients, but one-third showed persistent or increased late vessel wall enhancement. There was no formation of aneurysms or stenosis and no increase in atherosclerosis. Conclusions: Although TCZ resulted in complete clinical and laboratory remission of GCA over 52 weeks, MRA signals in vessel walls normalized in only one-third of patients. Whether these signals are of prognostic importance remains to be determined.

Circularly Polarised Luminescence in Enantiopure Samarium and Europium Cryptates.

Circularly polarised luminescence (CPL) is a chiroptical phenomenon gaining more and more attention, as the availability of the necessary spectrometers is getting better and first applications in bioimaging or for the preparation of OLEDs (organic light emitting diodes) are coming within range. Until now most examples of distinctly CPL-active compounds were europium and terbium complexes though theoretically the electronic structure of samarium should be as suitable as the one of terbium. This discrepancy can be accounted for by the high susceptibility of samarium to non-radiative deactivation processes. The aim of this study was to strategically circumvent this difficulty by the use of a ligand scaffold which has already proven to efficiently suppress these processes, namely the cryptates. The prepared partly deuterated samarium and europium complexes exhibit distinct circularly polarised luminescence with dissymmetry factors up to glum =+0.13 (SmIII ) or glum =-0.19 (EuIII ).

Long Wavelength Excitation of Europium Luminescence in Extended, Carboline-Based Cryptates.

Two new ß-carboline-based tris(biaryl) europium cryptates are introduced. The extended antenna moiety incorporated into the cryptand frameworks enables the sensitization of europium emission with excitation wavelengths well above 450 nm. In aqueous solution, the cryptates show great complex stability, luminescence lifetimes around 0.5 ms, and absolute quantum yields of ca. 3%. In addition, the europium luminescence shows a well-defined pH-dependence in the physiologically interesting pH range 7-9.

Anion dependent ion pairing in concentrated ytterbium halide solutions.

We have studied ion pairing of ytterbium halide solutions. THz spectra (30-400 cm-1) of aqueous YbCl3 and YbBr3 solutions reveal fundamental differences in the hydration structures of YbCl3 and YbBr3 at high salt concentrations: While for YbBr3 no indications for a changing local hydration environment of the ions were experimentally observed within the measured concentration range, the spectra of YbCl3 pointed towards formation of weak contact ion pairs. The proposed anion specificity for ion pairing was confirmed by supplementary Raman measurements.

Deuterated Molecular Ruby with Record Luminescence Quantum Yield.

The recently reported luminescent chromium(III) complex 13+ ([Cr(ddpd)2 ]3+ ; ddpd=N,N'-dimethyl-N,N'-dipyridine-2-yl-pyridine-2,6-diamine) shows exceptionally strong near-IR emission at 775 nm in water under ambient conditions (Φ=11 %) with a microsecond lifetime as the ligand design in 13+ effectively eliminates non-radiative decay pathways, such as photosubstitution, back-intersystem crossing, and trigonal twists. In the absence of energy acceptors, such as dioxygen, the remaining decay pathways are energy transfer to high energy solvent and ligand oscillators, namely OH and CH stretching vibrations. Selective deuteration of the solvents and the ddpd ligands probes the efficiency of these oscillators in the excited state deactivation. Addressing these energy-transfer pathways in the first and second coordination sphere furnishes a record 30 % quantum yield and a 2.3 millisecond lifetime for a metal complex with an earth-abundant metal ion in solution at room temperature.

Tocilizumab for induction and maintenance of remission in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Giant cell arteritis is an immune-mediated disease of medium and large-sized arteries that affects mostly people older than 50 years of age. Treatment with glucocorticoids is the gold-standard and prevents severe vascular complications but is associated with substantial morbidity and mortality. Tocilizumab, a humanised monoclonal antibody against the interleukin-6 receptor, has been associated with rapid induction and maintenance of remission in patients with giant cell arteritis. We therefore aimed to study the efficacy and safety of tocilizumab in the first randomised clinical trial in patients with newly diagnosed or recurrent giant cell arteritis. METHODS: In this single centre, phase 2, randomised, double-blind, placebo-controlled trial, we recruited patients aged 50 years and older from University Hospital Bern, Switzerland, who met the 1990 American College of Rheumatology criteria for giant cell arteritis. Patients with new-onset or relapsing disease were randomly assigned (2:1) to receive either tocilizumab (8 mg/kg) or placebo intravenously. 13 infusions were given in 4 week intervals until week 52. Both groups received oral prednisolone, starting at 1 mg/kg per day and tapered down to 0 mg according to a standard reduction scheme defined in the study protocol. Allocation to treatment groups was done using a central computerised randomisation procedure with a permuted block design and a block size of three, and concealed using central randomisation generated by the clinical trials unit. Patients, investigators, and study personnel were masked to treatment assignment. The primary outcome was the proportion of patients who achieved complete remission of disease at a prednisolone dose of 0·1 mg/kg per day at week 12. All analyses were intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01450137. RESULTS: Between March 3, 2012, and Sept 9, 2014, 20 patients were randomly assigned to receive tocilizumab and prednisolone, and ten patients to receive placebo and glucocorticoid; 16 (80%) and seven (70%) patients, respectively, had new-onset giant cell arteritis. 17 (85%) of 20 patients given tocilizumab and four (40%) of ten patients given placebo reached complete remission by week 12 (risk difference 45%, 95% CI 11-79; p=0·0301). Relapse-free survival was achieved in 17 (85%) patients in the tocilizumab group and two (20%) in the placebo group by week 52 (risk difference 65%, 95% CI 36-94; p=0·0010). The mean survival-time difference to stop glucocorticoids was 12 weeks in favour of tocilizumab (95% CI 7-17; p<0·0001), leading to a cumulative prednisolone dose of 43 mg/kg in the tocilizumab group versus 110 mg/kg in the placebo group (p=0·0005) after 52 weeks. Seven (35%) patients in the tocilizumab group and five (50%) in the placebo group had serious adverse events. INTERPRETATION: Our findings show, for the first time in a trial setting, the efficacy of tocilizumab in the induction and maintenance of remission in patients with giant cell arteritis. FUNDING: Roche and the University of Bern.