Geometry relaxation-mediated localization and delocalization of excitons in organic semiconductors: A quantum chemical study.

Photo-induced relaxation processes leading to excimer formations or other traps are in the focus of many investigations of optoelectronic materials because they severely affect the efficiencies of corresponding devices. Such relaxation effects comprise inter-monomer distortions in which the orientations of the monomer change with respect to each other, whereas intra-monomer distortions are variations in the geometry of single monomers. Such distortions are generally neglected in quantum chemical investigations of organic dye aggregates due to the accompanied high computational costs. In the present study, we investigate their relevance using perylene-bisimide dimers and diindenoperylene tetramers as model systems. Our calculations underline the importance of intra-monomer distortions on the shape of the potential energy surfaces as a function of the coupling between the monomers. The latter is shown to depend strongly on the electronic state under consideration. In particular, it differs between the first and second excited state of the aggregate. Additionally, the magnitude of the geometrical relaxation decreases if the exciton is delocalized over an increasing number of monomers. For the interpretation of the vibronic coupling model, pseudo-Jahn-Teller or Marcus theory can be employed. In the first part of this paper, we establish the accuracy of density functional theory-based approaches for the prediction of vibrationally resolved absorption spectra of organic semiconductors. These investigations underline the accuracy of those approaches although shortcomings become obvious as well. These calculations also indicate the strength of intra-monomer relaxation effects.

The ortho-benzyne cation is not planar.

A recent review on the photoionisation of the C6H4 isomer ortho-benzyne suggests that bands reported in earlier photoelectron spectra might be due to side products or contaminations, while computations raise doubts, whether the cation has a planar geometry. We therefore reinvestigate the photoionisation of ortho-benzyne, generated by pyrolysis from benzocyclobutenedione, by photoion mass-selected threshold photoelectron (ms-TPE) spectroscopy using synchrotron radiation. The experiments are accompanied by a theoretical study that investigates the structure of the ortho-benzyne cation systematically as a function of the computational method, up to CASPT2(11,14) ab initio computations. Our study leads to a re-evaluation of the ionisation energy of ortho-benzyne. It reveals that the ortho-benzyne cation has indeed a twisted C2 geometry rather than a C2v structure. A vertical ionisation energy IEvert of 9.77 eV and an adiabatic ionisation energy of IEad = 9.56 eV are computed for ortho-benzyne. A Franck-Condon simulation of the photoelectron spectrum based on the CASPT2 results and including three electronic states of the cation is in agreement with the experiment and yields IEad = 9.51 eV (+50 meV/-100 meV). Since this value is in contrast with previous work, the ionisation energy has to be revised based on our study. Computational methods based on density functional theory give a reasonable description of the cationic ground state, but fail for the corresponding excited electronic states that are indispensible for a proper assignment of the photoelectron spectrum.

Violation of the Leggett-Garg Inequality in Neutrino Oscillations.

The Leggett-Garg inequality, an analogue of Bell's inequality involving correlations of measurements on a system at different times, stands as one of the hallmark tests of quantum mechanics against classical predictions. The phenomenon of neutrino oscillations should adhere to quantum-mechanical predictions and provide an observable violation of the Leggett-Garg inequality. We demonstrate how oscillation phenomena can be used to test for violations of the classical bound by performing measurements on an ensemble of neutrinos at distinct energies, as opposed to a single neutrino at distinct times. A study of the MINOS experiment's data shows a greater than 6σ violation over a distance of 735 km, representing the longest distance over which either the Leggett-Garg inequality or Bell's inequality has been tested.

First measurement of the helicity asymmetry for γp → pπ0 in the resonance region.

The first measurement of the helicity dependence of the photoproduction cross section of single neutral pions off protons is reported for photon energies from 600 to 2300 MeV, covering nearly the full solid angle. The data are compared to predictions from the SAID, MAID, and BnGa partial wave analyses. Strikingly large differences between data and predictions are observed, which are traced to differences in the helicity amplitudes of well-known and established resonances. Precise values for the helicity amplitudes of several resonances are reported.

N(1520) 3/2(-) helicity amplitudes from an energy-independent multipole analysis based on new polarization data on photoproduction of neutral pions.

New data on the polarization observables T, P, and H for the reaction γp→pπ(0) are reported. The results are extracted from azimuthal asymmetries when a transversely polarized butanol target and a linearly polarized photon beam are used. The data were taken at the Bonn electron stretcher accelerator ELSA using the CBELSA/TAPS detector. These and earlier data are used to perform a truncated energy-independent partial wave analysis in sliced-energy bins. This energy-independent analysis is compared to the results from energy-dependent partial wave analyses.

[Lesions of the paravertebral mediastinum]. / Läsionen des paravertebralen Mediastinums.

BACKGROUND: Lesions of the paravertebral mediastinum are rare, and knowledge of possible differential diagnoses is essential for clinical practice. OBJECTIVE/METHODS: To review common lesions of the paravertebral mediastinum. RESULTS: The paravertebral mediastinum mainly includes fatty tissue and neurogenic structures. Imaging is commonly performed using computed tomography (CT) and magnetic resonance imaging (MRI). Neurogenic tumors are the most common lesions of the paravertebral mediastinum. Other pathologies include extramedullary hematopoiesis, lipomatous, lymphogenic, inflammatory, and cystic lesions. Moreover, also diaphragmatic hernias, vascular and esophageal pathologies may be found in the paravertebral mediastinum.

Disease evolution in systemic juvenile idiopathic arthritis: an international, observational cohort study through JIRcohort.

BACKGROUND: Systemic juvenile idiopathic arthritis (systemic JIA) is a severe disease with both systemic and joint inflammation. This study aims to identify predictors of disease evolution within the systemic JIA population enrolled in the Juvenile Inflammatory Rheumatism cohort (JIRcohort). METHODS: Observational patient cohort study with 201 recruited children from 4 countries (3 European, 1 North Africa) from 2005 until 2019, using retrospectively (2005-2015) and prospectively (2015-2019) routine care collected data. RESULTS: Sixty-five patients with complete follow-up data for 24 months after first diagnosis were classified as monophasic (n = 23), polyphasic (n = 6) or persistent group (n = 36) corresponding to their evolution (unique flare, recurrent flares, or persistent disease activity respectively). The patients of the persistent group were more likely to have an earlier disease onset, before the age of 6 (OR 2.57, 95%-CI 0.70-9.46), persistence of arthritis at 12-months post-diagnosis (OR 4.45, 95%-CI 0.58-34.20) and higher use of synthetic DMARD (sDMARD, OR 5.28, 95%-CI 1.39-20.01). Other variables like global assessment by physician and by patient and C Reactive Protein levels at 12-months post-diagnosis were assessed but without any predictive value after adjusting for confounding factors. CONCLUSIONS: Our results suggest that the earlier disease onset, the persistence of arthritis throughout the first year of disease evolution and the need of sDMARD might predict a persistent disease course.

Well-established nucleon resonances revisited by double-polarization measurements.

The first measurement is reported of the double-polarization observable G in the photoproduction of neutral pions off protons, covering the photon energy range from 620 to 1120 MeV and the full solid angle. G describes the correlation between the photon polarization plane and the scattering plane for protons polarized along the direction of the incoming photon. The observable is highly sensitive to contributions from baryon resonances. The new results are compared to the predictions from SAID, MAID, and BnGa partial wave analyses. In spite of the long-lasting efforts to understand γp→pπ(0) as the simplest photoproduction reaction, surprisingly large differences between the new data and the latest predictions are observed which are traced to different contributions of the N(1535) resonance with spin parity J(P)=1/2(-) and N(1520) with J(P)=3/2(-). In the third resonance region, where N(1680) with J(P)=5/2(+) production dominates, the new data are reasonably close to the predictions.

Evaluation of third-generation ELISA and a rapid immunochromatographic assay for the detection of norovirus infection in fecal samples from inpatients of a German tertiary care hospital.

The analytical accuracy of the RIDASCREEN Norovirus 3rd Generation ELISA assay and the rapid immunochromatographic RIDAQUICK Norovirus assay were determined in comparison to PCR. In a prospective study 410 consecutive samples were collected from inpatients of a tertiary care hospital in Germany. All samples were tested with the two antigen detection assays, as well as with three different real-time reverse transcription PCR methods as the reference standard. A sample was considered true-positive if at least 2 out of 3 PCR methods yielded a positive signal (137 positive samples, >99% genogroup II). Compared with the PCR-based reference the overall diagnostic sensitivities of the ELISA and the immunochromatographic assay were 77% and 69% and the diagnostic specificities were 96% and 97% respectively. Both assays allow the rapid and economic screening of large numbers of samples and thus are useful diagnostic tools for the detection of suspected norovirus infections.

An uncommon C1 fracture with longitudinal split of the transverse ligament.

We present a unique variant of C1 fracture, which, at the best of our knowledge, has never been previously reported. This lesion consists in a lateral mass atlas fracture with a longitudinal separation of the transverse ligament that remains functionally preserved. We considered this lesion to be stable and treated the patient conservatively with good recovery. Even if many classifications of atlas fractures have been proposed, none of them ever described this uncommon variant. We debate about biomechanical aspects and therapeutic implication of the reported case.

[Curative surgical treatment options for patients with non-small cell lung cancer (NSCLC) and solitary pulmonary metastasis]. / Kurativer chirurgischer Therapieansatz bei solitär pulmonal metastasierten nicht-kleinzelligen Lungenkarzinomen (NSCLC).

INTRODUCTION: The treatment of synchronous solitary lung metastasis in non-small cell lung cancer (NSCLC) remains controversial. Satellite lesions in the same lobe are now classified as T3 which may result in stage IIB (T3N0M0). In contrast, ipsilateral lesions in different lobes are associated with a worse prognosis and classified as T4 tumors (stage IIIA), but operation is usually withheld from these patients. Contralateral lung metastases have been classified more recently as M1a which usually results in a conservative therapy. We analysed survival data of all patients with primary lung tumour and synchronous pulmonary metastasis outside of the tumour-bearing lobe, who underwent surgery. METHODS: Between 1997 - 2007 we operated on 57 patients with NSCLC and simultaneous second (solitary) malignant lesions of the lung, outside of the tumour-bearing lobe, after informed consent. Survival was documented and analysed by Kaplan-Meier statistics (log-rank). RESULTS: The primary tumour was treated in 67 % of cases by lobectomy, in 9 % by pneumonectomy, by bilobectomy in 2 % and in 22 % by segment or wedge resection. The second malignant lesion, and thus potential solitary metastasis, was treated in 83 % by segment or wedge resection. The overall survival of all patients (n = 57) was a median of 82 months (75 - 89 95%CI). In the synchronous second primaries (n = 7) the median survival was 76 months (0.1 to 151 95%CI) and in the synchronous metastases (n = 50) 82 months (95 % CI 75 - 88). This results in a 5-year survival rate of 56 % and 77 %, respectively. The median survival of patients with solitary metastasis, ipsilateral (T4 after UICC7) was 79 months (76 - 82 95 %CI) and with contralateral metastasis (M1a according UICC7) 84 months (60 - 107 95 %CI, p = 0.634). CONCLUSIONS: This analysis shows that patients with solitary pulmonary metastasis (outside of the tumour-bearing lobe) and otherwise operable NSCLC may profit from surgical intervention comprising resection of the primary tumour, lymphadenectomy, and resection of the solitary pulmonary metastasis. Long-term survival can be achieved independent of the localisation of lung metastases (ipsilateral vs. contralateral lung).

Flow Diversion for ICA Aneurysms with Compressive Neuro-Ophthalmologic Symptoms: Predictors of Morbidity, Mortality, and Incomplete Aneurysm Occlusion.

BACKGROUND AND PURPOSE: Flow diversion is an effective treatment for aneurysms of the ICA with compression-related neuro-ophthalmologic symptoms, especially when treatment is initiated early after symptom onset and aneurysm occlusion is complete. However, non-negligible complication rates have been reported. Our aim was to identify risk factors for morbidity/mortality and incomplete aneurysm occlusion. MATERIALS AND METHODS: We performed a secondary analysis of a previous publication, which included all patients treated with flow diversion for an unruptured aneurysm of the ICA with compression-related symptoms. RESULTS: Fifty-four patients with 54 aneurysms (48 women, 88.9%; mean age, 59.2 [SD, 15.9] years; range, 21-86 years) treated with flow diversion were included. We observed morbidity and mortality rates of 7.4% and 3.7%. Increasing age (OR per decade, 3.2; 95% CI, 1.23-8.49; P = .02) and dual-antiplatelet therapy with ticagrelor (OR, 13.9; 95% CI, 1.16-165.97; P = .04) were significantly associated with morbidity/mortality. After a median follow-up of 13.3 [SD, 10.5] months, the rates of complete aneurysm occlusion, neck remnant, and aneurysm remnant were 74%, 14%, and 12%. Incomplete occlusion at follow-up was less frequently observed in aneurysms treated with additional coil embolization (OR, 0.1; 95% CI, 0.01-0.86; P = .04). CONCLUSIONS: Although a promising treatment for compressive ICA aneurysms, flow diversion carries a relevant risk for complications and incomplete aneurysm occlusion. Our results may help identify patients in which flow diversion may not be the ideal treatment method. Additional coil embolization increased the likelihood of complete aneurysm occlusion at follow-up.

Dissociation of lipotoxicity and glucotoxicity in a mouse model of obesity associated diabetes: role of forkhead box O1 (FOXO1) in glucose-induced beta cell failure.

AIMS/HYPOTHESIS: Carbohydrate-free diet prevents hyperglycaemia and beta cell destruction in the New Zealand Obese (NZO) mouse model. Here we have used a sequential dietary regimen to dissociate the effects of obesity and hyperglycaemia on beta cell function and integrity, and to study glucose-induced alterations of key transcription factors over 16 days. METHODS: Mice were rendered obese by feeding a carbohydrate-free diet for 18 weeks. Thereafter, a carbohydrate-containing diet was given. Plasma glucose, plasma insulin and total pancreatic insulin were determined, and forkhead box O1 protein (FOXO1) phosphorylation and the transcription factors pancreatic and duodenal homeobox 1 (PDX1), NK6 homeobox 1 protein (NKX6.1) and v-maf musculoaponeurotic fibrosarcoma oncogene family, protein A (avian) (MAFA) were monitored by immunohistochemistry for 16 days. RESULTS: Dietary carbohydrates produced a rapid and continuous increase in plasma glucose in NZO mice between day 2 and 16 after the dietary challenge. Hyperglycaemia caused a dramatic dephosphorylation of FOXO1 at day 2, followed by a progressive depletion of insulin stores. The loss of beta cells was triggered by apoptosis (detectable at day 8), associated with reduction of crucial transcription factors (PDX1, NKX6.1 and MAFA). Incubation of isolated islets from carbohydrate-restricted NZO mice or MIN6 cells with palmitate and glucose for 48 h resulted in a dephosphorylation of FOXO1 and thymoma viral proto-oncogene 1 (AKT) without changing the protein levels of both proteins. CONCLUSIONS/INTERPRETATION: The dietary regimen dissociates the effects of obesity (lipotoxicity) from those of hyperglycaemia (glucotoxicity) in NZO mice. Obese NZO mice are unable to compensate for the carbohydrate challenge by increasing insulin secretion or synthesising adequate amounts of insulin. In response to the hyperglycaemia, FOXO1 is dephosphorylated, leading to reduced levels of beta cell-specific transcription factors and to apoptosis of the cells.

Interaction of WASP/Scar proteins with actin and vertebrate Arp2/3 complex.

The Wiskott-Aldrich-syndrome protein (WASP) regulates polymerization of actin by the Arp2/3 complex. Here we show, using fluorescence anisotropy assays, that the carboxy-terminal WA domain of WASP binds to a single actin monomer with a Kd of 0.6 microM in an equilibrium with rapid exchange rates. Both WH-2 and CA sequences contribute to actin binding. A favourable DeltaH of -10 kcal mol(-1) drives binding. The WA domain binds to the Arp2/3 complex with a Kd of 0.9 microM; both the C and A sequences contribute to binding to the Arp2/3 complex. Wiskott-Aldrich-syndrome mutations in the WA domain that alter nucleation by the Arp2/3 complex over a tenfold range without affecting affinity for actin or the Arp2/3 complex indicate that there may be an activation step in the nucleation pathway. Actin filaments stimulate nucleation by producing a fivefold increase in the affinity of WASP-WA for the Arp2/3 complex.

The perspectives, barriers, and willingness of Utah dentists to engage in human papillomavirus (HPV) vaccine practices.

Including dental health providers in human papillomavirus (HPV) vaccination could reduce rising rates in HPV-associated oropharyngeal cancer (HPV-OPC). This study assessed Utah dentists' perspectives on providing HPV vaccination education and services in the dental setting. A cross-sectional, 70-item self-administered survey was conducted among a convenience sample of N = 203 practicing Utah dentists. Statistical analyses included Chi Square tests of independence, scaled scores and Cronbach's alpha coefficients. Majority of Utah dentists surveyed perceived that discussing the link between HPV and OPC and recommending the HPV vaccine is within their scope of practice, but not administration of the HPV vaccine. Dentists with >10 minutes of patient education per week were less likely to be concerned about the cultural, social norms or religious ideology of discussing HPV with their patients (p = .024). Rural dentists were more concerned about the safety and liability of the HPV vaccine (p = .011). Good internal consistency was observed survey items regarding barriers and willing to engage in HPV vaccination practices. Dental providers were interested in HPV training and patient education brochures as strategies, but less interested in administering the HPV vaccine. Dental associations support dentists' engagement in HPV education and HPV-OPC prevention. This is the first study in Utah to examine dentists' perspectives on HPV vaccination. Findings have implications for program planning, intervention development, and future research.

Acanthamoeba actin and profilin can be cross-linked between glutamic acid 364 of actin and lysine 115 of profilin.

Acanthamoeba profilin was cross-linked to actin via a zero-length isopeptide bond using carbodiimide. The covalently linked 1:1 complex was purified and treated with cyanogen bromide. This cleaves actin into small cyanogen bromide (CNBr) peptides and leaves the profilin intact owing to its lack of methionine. Profilin with one covalently attached actin CNBr peptide was purified by gel filtration followed by gel electrophoresis and electroblotting on polybase-coated glass-fiber membranes. Since the NH2 terminus of profilin is blocked, Edman degradation gave only the sequence of the conjugated actin CNBr fragment beginning with Trp-356. The profilin-actin CNBr peptide conjugate was digested further with trypsin and the cross-linked peptide identified by comparison with the tryptic peptide pattern obtained from carbodiimide-treated profilin. Amino-acid sequence analysis of the cross-linked tryptic peptides produced two residues at each cycle. Their order corresponds to actin starting at Trp-356 and profilin starting at Ala-94. From the absence of the phenylthiohydantoin-amino acid residues in specific cycles, we conclude that actin Glu-364 is linked to Lys-115 in profilin. Experiments with the isoforms of profilin I and profilin II gave identical results. The cross-linked region in profilin is homologous with sequences in the larger actin filament capping proteins fragmin and gelsolin.

Monoclonal antibodies demonstrate limited structural homology between myosin isozymes from Acanthamoeba.

We used a library of 31 monoclonal and six polyclonal antibodies to compare the structures of the two classes of cytoplasmic myosin isozymes isolated from Acanthamoeba: myosin-I, a 150,000-mol-wt, globular molecule; and myosin-II, a 400,000-mol-wt molecule with two heads and a 90-nm tail. This analysis confirms that myosin-I and -II are unique gene products and provides the first evidence that these isozymes have at least one structurally homologous region functionally important for myosin's role in contractility. Characterization of the 23 myosin-II monoclonal antibody binding sites by antibody staining of one-dimensional peptide maps and solid phase, competitive binding assays demonstrate that they bind to at least 15 unique sites on the myosin-II heavy chain. The antibodies can be grouped into six families, whose members bind close to one another. None of the monoclonal antibodies bind to myosin-II light chains and polyclonal antibodies against myosin-II light or heavy chain bind only to myosin-II light or heavy chains, respectively: no antibody binds both heavy and light chains. Six of eight monoclonal antibodies and one of two polyclonal sera that react with the myosin-I heavy chain also bind to determinants on the myosin-II heavy chain. The cross-reactive monoclonal antibodies bind to the region of myosin-II recognized by the largest family of myosin-II monoclonal antibodies. In the two papers that immediately follow, we show that this family of monoclonal antibodies to myosin-II binds to the myosin-II tail near the junction with the heads and inhibits both the actin-activated ATPase of myosin-II and contraction of gelled cytoplasmic extracts of Acanthamoeba cytoplasm. Further, this structurally homologous region may play a key role in energy transduction by cytoplasmic myosins.

Direct localization of monoclonal antibody-binding sites on Acanthamoeba myosin-II and inhibition of filament formation by antibodies that bind to specific sites on the myosin-II tail.

Electron microscopy of myosin-II molecules and filaments reacted with monoclonal antibodies demonstrates directly where the antibodies bind and shows that certain antibodies can inhibit the polymerization of myosin-II into filaments. The binding sites of seven of 23 different monoclonal antibodies were localized by platinum shadowing of myosin monomer-antibody complexes. The antibodies bind to a variety of sites on the myosin-II molecule, including the heads, the proximal end of the tail near the junction of the heads and tail, and the tip of the tail. The binding sites of eight of the 23 antibodies were also localized on myosin filaments by negative staining. Antibodies that bind to either the myosin heads or to the proximal end of the tail decorate the ends of the bipolar filaments. Some of the antibodies that bind to the tip of the myosin-II tail decorate the bare zone of the myosin-II thin filament with 14-nm periodicity. By combining the data from these electron microscope studies and the peptide mapping and competitive binding studies we have established the binding sites of 16 of 23 monoclonal antibodies. Two of the 23 antibodies block the formation of myosin-II filaments and given sufficient time, disassemble preformed myosin-II filaments. Both antibodies bind near one another at the tip of the myosin-II tail and are those that decorate the bare zone of preformed bipolar filaments with 14-nm periodicity. None of the other antibodies affect myosin filament formation, including one that binds to another site near the tip of the myosin-II tail. This demonstrates that antibodies can inhibit polymerization of myosin-II, but only when they bind to key sites on the tail of the molecule.

Purification and characterization of two isoforms of Acanthamoeba profilin.

Acanthamoeba profilin purified according to E. Reichstein and E.D. Korn (1979, J. Biol. Chem. 254:6174-6179) consists of two isoforms (profilin-I and-II) with approximately the same molecular weight and reactivity to a monoclonal antibody but different isoelectric points and different mobilities on carboxymethyl-agarose chromatography and reversed-phase high-performance liquid chromatography. The isoelectric points of profilin-I is approximately 5.5 and that of profilin-II is greater than or equal to 9.0. Tryptic peptides from the two proteins are substantially different, which suggests that there are major differences in their sequences. At similar concentrations, both profilins prolong the lag phase at the outset of spontaneous polymerization and inhibit the extent of polymerization. Both forms also inhibit elongation weakly at the barbed end and strongly at the pointed end of actin filaments.

Characterization of monoclonal antibodies to Acanthamoeba myosin-I that cross-react with both myosin-II and low molecular mass nuclear proteins.

We characterized nine monoclonal antibodies that bind to the heavy chain of Acanthamoeba myosin-IA. Eight of these antibodies bind to myosin-IB and eight cross-react with Acanthamoeba myosin-II. All but one of the antibodies bind to a 30-kD chymotryptic peptide of myosin-IA that derives from the COOH terminus of the molecule, and to tryptic peptides as small as 17 kD, hence these epitopes are clustered closely together on the heavy chain. None of the antibodies prevent heavy chain phosphorylation by myosin-I heavy chain kinase. One antibody inhibits the K+-EDTA ATPase activity and three antibodies inhibit the actin-activated Mg++-ATPase activity of myosin-I under the set of conditions that we tested. When fluorescent antibody staining of both whole cells and isolated nuclei is done, several of these monoclonal antibodies react strongly with nuclei. These antibodies also stain the cytoplasmic matrix, especially the cortex near the plasma membrane. All nine of the monoclonal antibodies bind to polypeptides of 30-34 kD that are highly enriched in nuclei isolated from Acanthamoeba. There is no myosin-I in the isolated nuclei, so the 30-34-kD polypeptides, not myosin-I, are responsible for the nuclear staining.