The Electronic Structures of Azaphenanthrenes and Their Dimers.

Insertion of a nitrogen atom modifies the electronic structures and photochemistry of polycyclic aromatic hydrocarbons by introducing nπ* states into the molecules. To better understand the electronic structures of isolated polycyclic aromatic nitrogen-containing hydrocarbons (PANHs) and their dimers as well as the influence of the position of the nitrogen atom in the molecule, we investigate three different azaphenanthrenes, benzo[f]quinoline, benzo[h]quinoline, and phenanthridine, in a joint experimental and computational study. Experimentally, resonance-enhanced multiphoton ionization (REMPI) spectroscopy is applied to characterize the excited electronic states. The REMPI spectra of the azaphenanthrene monomers have a rather similar appearance, with origins between 3.645 and 3.670 eV for the 1ππ* ← S0 transition. In contrast to the phenanthrene parent, 2ππ* ← S0 is broad and unstructured even at the band origin. The experiments are accompanied by density functional theory computation, and vibrationally resolved spectra are simulated using a time-independent approach. The differences between phenanthrene and the azaphenanthrenes are assigned to perturbations due to the low-lying 1(nπ*) state, which accelerates nonradiative deactivation. For the dimers, it is found that two π-stacked isomers with two electronic transitions each contribute to the electronic spectrum, leading to overlapping bands that are difficult to assign.

Pelvic lymphadenectomy in vulvar cancer and its impact on prognosis and outcome.

BACKGROUND: The value of pelvic lymphadenectomy (LAE) has been subject of discussions since the 1980s. This is mainly due to the fact that the relation between lymph node involvement of the groin and pelvis is poorly understood and therewith the need for pelvic treatment in general. PATIENTS AND METHODS: N = 514 patients with primary vulvar squamous cell cancer (VSCC) FIGO stage ≥ IB were treated at the University Medical Center Hamburg-Eppendorf between 1996 and 2018. In this analysis, patients with pelvic LAE (n = 21) were analyzed with regard to prognosis and the relation of groin and pelvic lymph node involvement. RESULTS: The majority had T1b/T2 tumors (n = 15, 78.9%) with a median diameter of 40 mm (11-110 mm). 17/21 patients showed positive inguinal nodes. Pelvic nodal involvement without groin metastases was not observed. 6/17 node-positive patients with positive groin nodes also had pelvic nodal metastases (35.3%; median number of affected pelvic nodes 2.5 (1-8)). These 6 patients were highly node positive with median 4.5 (2-9) affected groin nodes. With regard to the metastatic spread between groins and pelvis, no contralateral spread was observed. Five recurrences were observed after a median follow-up of 33.5 months. No pelvic recurrences were observed in the pelvic nodal positive group. Patients with pelvic metastasis at first diagnosis had a median progression-free survival of only 9.9 months and overall-survival of 31.1 months. CONCLUSION: A relevant risk for pelvic nodal involvement only seems to be present in highly node-positive disease, therefore pelvic staging (and radiotherapy) is probably unnecessary in the majority of patients with node-positive VSCC.

Plectin dysfunction in neurons leads to tau accumulation on microtubules affecting neuritogenesis, organelle trafficking, pain sensitivity and memory.

AIMS: Plectin, a universally expressed multi-functional cytolinker protein, is crucial for intermediate filament networking, including crosstalk with actomyosin and microtubules. In addition to its involvement in a number of diseases affecting skin, skeletal muscle, heart, and other stress-exposed tissues, indications for a neuropathological role of plectin have emerged. Having identified P1c as the major isoform expressed in neural tissues in previous studies, our aim for the present work was to investigate whether, and by which mechanism(s), the targeted deletion of this isoform affects neuritogenesis and proper nerve cell functioning. METHODS: For ex vivo phenotyping, we used dorsal root ganglion and hippocampal neurons derived from isoform P1c-deficient and plectin-null mice, complemented by in vitro experiments using purified proteins and cell fractions. To assess the physiological significance of the phenotypic alterations observed in P1c-deficient neurons, P1c-deficient and wild-type littermate mice were subjected to standard behavioural tests. RESULTS: We demonstrate that P1c affects axonal microtubule dynamics by isoform-specific interaction with tubulin. P1c deficiency in neurons leads to altered dynamics of microtubules and excessive association with tau protein, affecting neuritogenesis, neurite branching, growth cone morphology, and translocation and directionality of movement of vesicles and mitochondria. On the organismal level, we found P1c deficiency manifesting as impaired pain sensitivity, diminished learning capabilities and reduced long-term memory of mice. CONCLUSIONS: Revealing a regulatory role of plectin scaffolds in microtubule-dependent nerve cell functions, our results have potential implications for cytoskeleton-related neuropathies.

Photoelectron spectroscopy of boron-containing reactive intermediates using synchrotron radiation: BH2, BH, and BF.

Mass selected slow photoelectron spectra (SPES) of three boron-containing reactive species, BH2, BH, and BF were recorded by double imaging photoion-photoelectron coincidence spectroscopy (i2PEPICO) using synchrotron radiation. All species were generated in a flow reactor from the H-abstraction of B2H6 by F atoms created in a F2 microwave discharge. The spectrum of BH2+ exhibits a long bending mode progression with a 970 cm-1 spacing due to the large geometry change from bent to linear upon ionization. Its ionization energy was determined as 8.12 ± 0.02 eV. For BH, photoionisation from both X1Σ+ singlet and a3Π triplet state was observed, permitting the experimental determination of the singlet/triplet gap (ΔEST) from the observed IE's of 9.82 eV and 8.48 eV. In addition, a threshold photoelectron spectrum of BF was recorded, which leads to an IE of 11.11 eV and an improved value for νBF+ of 1690 cm-1. All spectra were simulated by calculating Franck-Condon factors from optimised structures based on quantum chemical calculations.

Cross-predicting the dynamics of an optically injected single-mode semiconductor laser using reservoir computing.

In real-world dynamical systems, technical limitations may prevent complete access to their dynamical variables. Such a lack of information may cause significant problems, especially when monitoring or controlling the dynamics of the system is required or when decisions need to be taken based on the dynamical state of the system. Cross-predicting the missing data is, therefore, of considerable interest. Here, we use a machine learning algorithm based on reservoir computing to perform cross-prediction of unknown variables of a chaotic dynamical laser system. In particular, we chose a realistic model of an optically injected single-mode semiconductor laser. While the intensity of the laser can often be acquired easily, measuring the phase of the electric field and the carriers in real time, although possible, requires a more demanding experimental scheme. We demonstrate that the dynamics of two of the three dynamical variables describing the state of the laser can be reconstructed accurately from the knowledge of only one variable, if our algorithm has been trained beforehand with all three variables for a limited period of time. We analyze the accuracy of the method depending on the parameters of the laser system and the reservoir. Finally, we test the robustness of the cross-prediction method when adding noise to the time series. The suggested reservoir computing state observer might be used in many applications, including reconstructing time series, recovering lost time series data and testing data encryption security in cryptography based on chaotic synchronization of lasers.

[Identification of patients with axial spondylarthritis in primary care (AWARE study)]. / Identifikation von Patienten mit axialer Spondyloarthritis in der Primärversorgung (AWARE-Studie).

BACKGROUND: Early detection of patients with axial spondylarthritis (axSpA) in primary care is difficult. The combination of various parameters indicative of inflammatory back pain (AWARE criteria) was found to be beneficial in an initial study. OBJECTIVE: Review of the criteria for the identification of young patients with axSpA and chronic back pain (≥3 months of back pain). MATERIAL AND METHODS: In adult patients with chronic back pain and age at onset of symptoms <45 years, orthopedic surgeons documented various possible axSpA characteristics before referral to the rheumatologist. RESULTS: Overall, the data from 1306 patients were recorded. Of these, ultimately 500 patients were also seen by rheumatologists, 199 patients (39.8%) were diagnosed with axSpA while 301 (60.2%) had non-specific back pain. A total of 87 patients had ankylosing spondylitis (44%) and 112 non-radiographic axSpA (56%). The ASAS classification criteria were fulfilled by 226 patients (45.2%). The mean age of axSpA patients was 38 years, 56% were male with a mean duration of back pain of 98 months. The AWARE criteria had a sensitivity and specificity of 69.3% and 40.3% (n = 343), respectively, when ≥4/5 criteria were chosen. Positive imaging for sacroiliitis using magnetic resonance imaging (MRI) or X­ray was present in 77% of patients and positive HLA-B27 was identified in 59% of axSpA patients. The combination of positive imaging and HLA-B27 had the highest likelihood ratio for diagnosis of axSpA. CONCLUSION: Although the study design used here led to a preselection and thus to a bias in the statistical evaluation, the study confirmed the benefit of the AWARE criteria for the early detection of patients with axSpA. In further studies, the 2­stage approach with initially 3 clinical questions and then an optional HLA-B27 test is currently being investigated further.

A history of obesity leaves an inflammatory fingerprint in liver and adipose tissue.

BACKGROUND/OBJECTIVES: Dieting is a popular yet often ineffective way to lower body weight, as the majority of people regain most of their pre-dieting weights in a relatively short time. The underlying molecular mechanisms driving weight regain and the increased risk for metabolic disease are still incompletely understood. Here we investigate the molecular alterations inherited from a history of obesity. METHODS: In our model, male high-fat diet (HFD)-fed obese C57BL/6J mice were switched to a low caloric chow diet, resulting in a decline of body weight to that of lean mice. We measured body composition, as well as metrics of glucose, insulin and lipid homeostasis. This was accompanied by histological and gene expression analysis of adipose tissue and liver to assess adipose tissue inflammation and hepatosteatosis. Moreover, acute hypothalamic response to (re-) exposure to HFD was assessed by qPCR. RESULTS & CONCLUSIONS: Within 7 weeks after diet switch, most obesity-associated phenotypes, such as body mass, glucose intolerance and blood metabolite levels were reversed. However, hepatic inflammation, hepatic steatosis as well as hypertrophy and inflammation of perigonadal, but not subcutaneous, adipocytes persisted in formerly obese mice. Transcriptional profiling of liver and perigonadal fat revealed an upregulation of pathways associated with immune function and cellularity. Thus, we show that weight reduction leaves signs of inflammation in liver and perigonadal fat, indicating that persisting proinflammatory signals in liver and adipose tissue could contribute to an increased risk of formerly obese subjects to develop the metabolic syndrome upon recurring weight gain.

Accelerated barrier recovery and enhancement of the barrier integrity and properties by topical application of a pH 4 vs. a pH 5·8 water-in-oil emulsion in aged skin.

BACKGROUND: Increased skin-surface pH is an important host-related factor for deteriorated barrier function in aged skin. OBJECTIVES: We investigated whether restoration of skin pH through topical application of a water-in-oil emulsion with pH 4 improved the barrier homeostasis in aged skin, and compared the effects with an identical galenic formulation with pH 5·8. METHODS: The effects of the test formulations on barrier recovery were investigated by repeated measurements of transepidermal water loss (TEWL) and skin pH 3 h, 6 h and 24 h after acetone-induced impairment of barrier function in aged skin. The long-term effects of the pH 4 and pH 5·8 emulsions were analysed by investigation of the barrier integrity and cohesion, the skin-surface pH and the skin roughness and scaliness before and after a 4-week, controlled application of the formulations. RESULTS: The application of the pH 4 emulsion accelerated barrier recovery in aged skin: 3 h and 6 h after acetone-induced barrier disruption the differences in the TEWL recovery between the pH 4 treated and acetone control fields were significant. Furthermore, long-term application of the pH 4 formulation resulted in significantly decreased skin pH, enhanced barrier integrity and reduced skin-surface roughness and scaliness. At the same time points, the pH 5·8 formulation exerted only minor effects on the barrier function parameters. CONCLUSIONS: Exogenous acidification through topical application of a water-in-oil emulsion with pH 4 leads to improvement of the skin barrier function and maintenance of the barrier homeostasis in aged skin.

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.

Kinetics of the a-C3H5 + O2 reaction, investigated by photoionization using synchrotron radiation.

The kinetics of the combustion-relevant reaction of the allyl radical, a-C3H5, with molecular oxygen has been studied in a flow tube reactor at the vacuum ultraviolet (VUV) beamline of the Swiss Light Source storage ring, using the CRF-PEPICO (Combustion Reactions Followed by Photoelectron Photoion Coincidence Spectroscopy) setup. The ability to measure threshold photoelectron spectra enables a background-free detection of reactive species as well as an isomer-specific analysis of reaction products. Allyl was generated by direct photodissociation of allyl iodide at 266 nm and 213 nm and indirectly by the reaction of propene with Cl atoms, which were generated by photolysis from oxalyl chloride at 266 nm. Experiments were conducted at room temperature at low pressures between 0.8 and 3 mbar using Ar as the buffer gas and with excess O2 to maintain nearly pseudo-first-order reaction conditions. Whereas allyl was detected by photoionisation using synchrotron radiation, the main reaction product allyl peroxy was not observed due to dissociative ionisation of this weakly bound species. From the concentration-time profiles of the allyl signal, second-order rate constants between 1.35 × 1011 cm3 mol-1 s-1 at 0.8 mbar and 1.75 × 1011 cm3 mol-1 s-1 at 3 mbar were determined. The rates obtained for the different allyl radical generation schemes agree well with each other, but are about a factor of 2 higher than the ones reported previously using He as a buffer gas. The discrepancy is partly attributed to the higher collision efficiency of Ar causing a varying fall-off behavior. When allyl is produced by the reaction of propene with Cl atom, an unexpected product is observed at m/z = 68, which was identified as 1,3-butadienal in the threshold photoelectron spectrum. It is formed in a secondary reaction of allyl with the OCCl radical, which is generated in the 266 nm photolysis of oxalyl chloride.

Normal and resonant Auger spectroscopy of isocyanic acid, HNCO.

In this paper, we investigate HNCO by resonant and nonresonant Auger electron spectroscopy at the K-edges of carbon, nitrogen, and oxygen, employing soft X-ray synchrotron radiation. In comparison with the isosteric but linear CO2 molecule, spectra of the bent HNCO molecule are similar but more complex due to its reduced symmetry, wherein the degeneracy of the π-orbitals is lifted. Resonant Auger electron spectra are presented at different photon energies over the first core-excited 1s → 10a' resonance. All Auger electron spectra are assigned based on ab initio configuration interaction computations combined with the one-center approximation for Auger intensities and moment theory to consider vibrational motion. The calculated spectra were scaled by a newly introduced energy scaling factor, and generally, good agreement is found between experiment and theory for normal as well as resonant Auger electron spectra. A comparison of resonant Auger spectra with nonresonant Auger structures shows a slight broadening as well as a shift of the former spectra between -8 and -9 eV due to the spectating electron. Since HNCO is a small molecule and contains the four most abundant atoms of organic molecules, the reported Auger electron decay spectra will provide a benchmark for further theoretical approaches in the computation of core electron spectra.

Semiconductor laser linewidth reduction by six orders of magnitude via delayed optical feedback.

We demonstrate a coherence increase by six orders of magnitude of a standard quantum well semiconductor laser. Using a simple, optical-fiber-based feedback scheme, we stabilize the laser in a high-gain mode of a long external cavity. In a modified self-heterodyne measurement, we mix the high-gain mode with a strongly suppressed side mode and obtain an interference linewidth of only 12.6 Hz, corresponding to a decoherence of (3.1±2.9) Hz. In an independent characterization using an etalon, we deduce an upper limit of 300 Hz for the laser linewidth. The laser stably resides in this mode for tens of seconds. Our results agree with theoretical predictions.

Femtosecond time-resolved photoelectron spectroscopy of the benzyl radical.

We present a joint experimental and computational study of the nonradiative deactivation of the benzyl radical, C7H7, after UV excitation. Femtosecond time-resolved photoelectron imaging was applied to investigate the photodynamics of the radical. The experiments were accompanied by excited state dynamics simulations using surface hopping. Benzyl has been excited at 265 nm into the D-band (ππ*) and the dynamics was probed using probe wavelengths of 398 nm or 798 nm. At a probe wavelength of 398 nm a single time constant of around 70-80 fs was observed. When the dynamics was probed at 798 nm, a second time constant τ2 = 1.5 ps was visible, which can be attributed to further non-radiative deactivation to the lower-lying D1/D2 states.

Products of the Propargyl Self-Reaction at High Temperatures Investigated by IR/UV Ion Dip Spectroscopy.

The propargyl radical is considered to be of key importance in the formation of the first aromatic ring in combustion processes. Here we study the bimolecular (self-) reactions of propargyl in a high-temperature pyrolysis flow reactor. The aromatic reaction products are identified by IR/UV ion dip spectroscopy, using the free electron laser FELIX as mid-infrared source. This technique combines mass selectivity with structural sensitivity. We identified several aromatic reaction products based on their infrared spectra, among them benzene, naphthalene, phenanthrene, indene, biphenyl, and surprisingly a number of aromatic compounds with acetylenic (ethynyl) side chains. The observation of benzene confirms that propargyl is involved in the formation of the first aromatic ring. The observation of compounds with acetylenic side chains shows that, in addition to a propargyl- and phenyl-based mechanism, the HACA (hydrogen abstraction C2H2 addition) mechanism of polycyclic aromatic hydrocarbons formation is present, although no acetylene was used as a reactant. On the basis of the experimental results we suggest a mechanism that connects the two pathways.

Role of dynamical injection locking and characteristic pulse events for low frequency fluctuations in semiconductor lasers.

We investigate the dynamics of semiconductor lasers subject to time-delayed optical feedback from the perspective of dynamical self-injection locking. Based on the Lang-Kobayashi model, we perform an analysis of the well-known Low Frequency Fluctuations (LFFs) in the frequency-intensity plane. Moreover, we investigate a recently found dynamical regime of fragmented LFFs by means of a locking-range analysis, spectral comparison and precursor pulse identification. We show that LFF dynamics can be explained by dynamical optical injection locking due to the delayed optical feedback. Moreover, the fragmented LFFs occur due to a re-injection locking induced by a particular optical pulse structure in the chaotic feedback dynamics. This is corroborated by experiments with a semiconductor laser experiencing delayed feedback from an optical fiber loop. The dynamical nature of the feedback injection results in an eventual loss, but also possible regaining, of the locking, explaining the recently observed phenomenon of fragmented LFFs.

Venlafaxine and oxycodone effects on human spinal and supraspinal pain processing: a randomized cross-over trial.

Severe pain is often treated with opioids. Antidepressants that inhibit serotonin and norepinephrine reuptake (SNRI) have also shown a pain relieving effect, but for both SNRI and opioids, the specific mode of action in humans remains vague. This study investigated how oxycodone and venlafaxine affect spinal and supraspinal pain processing. Twenty volunteers were included in this randomized cross-over study comparing 5-day treatment with venlafaxine, oxycodone and placebo. As a proxy of the spinal pain transmission, the nociceptive withdrawal reflex (NWR) to electrical stimulation on the sole of the foot was recorded at the tibialis anterior muscle before and after 5 days of treatment. For the supraspinal activity, 61-channel electroencephalogram evoked potentials (EPs) to the electrical stimulations were simultaneously recorded. Areas under curve (AUCs) of the EMG signals were analyzed. Latencies and AUCs were computed for the major EP peaks and brain source analysis was done. The NWR was decreased in venlafaxine arm (P = 0.02), but the EP parameters did not change. Oxycodone increased the AUC of the EP response (P = 0.04). Oxycodone also shifted the cingulate activity anteriorly in the mid-cingulate-operculum network (P < 0.01), and the cingulate activity was increased while the operculum activity was decreased (P = 0.02). Venlafaxine exerts its effects on the modulation of spinal nociceptive transmission, which may reflect changes in balance between descending inhibition and descending facilitation. Oxycodone, on the other hand, exerts its effects at the cortical level. This study sheds light on how opioids and SNRI drugs modify the human central nervous system and where their effects dominate.

Ellipsometric characterization of doped Ge0.95Sn0.05 films in the infrared range for plasmonic applications.

GeSn as a group-IV material opens up new possibilities for realizing photonic device concepts in Si-compatible fabrication processes. Here we present results of the ellipsometric characterization of highly p- and n-type doped Ge0.95Sn0.05 alloys deposited on Si substrates investigated in the wavelength range from 1 to 16 µm. We discuss the suitability of these films for integrated plasmonic applications in the infrared region.

Experimental Phase-Space Tomography of Semiconductor Laser Dynamics.

We perform phase-space tomography of semiconductor laser dynamics by simultaneous experimental determination of optical intensity, frequency, and population inversion with high temporal resolution. We apply this technique to a laser with delayed feedback, serving as prominent example for high-dimensional chaotic dynamics and as model system for fundamental investigations of complex systems. Our approach allows us to explore so far unidentified trajectories in phase space and identify the underlying physical mechanism.

Formation of polycyclic aromatic hydrocarbons from bimolecular reactions of phenyl radicals at high temperatures.

The self-reaction of the phenyl radical is one of the key reactions in combustion chemistry. Here we study this reaction in a high-temperature flow reactor by IR/UV ion dip spectroscopy, using free electron laser radiation as mid-infrared source. We identified several major reaction products based on their infrared spectra, among them indene, 1,2-dihydronaphthalene, naphthalene, biphenyl and para-terphenyl. Due to the structural sensitivity of the method, the reaction products were identified isomer-selectively. The work shows that the formation of indene and naphthalene, which was previously considered to be evidence for the HACA (hydrogen abstraction C2H2 addition) mechanism in the formation of polycyclic aromatic hydrocarbons and soot can also be understood in a phenyl addition model.

Assignment of high-lying bending mode levels in the threshold photoelectron spectrum of NH2: a comparison between pyrolysis and fluorine-atom abstraction radical sources.

In this manuscript we present threshold photoelectron spectra (TPES) of the amidogen radical, NH2, recorded at two vacuum ultraviolet synchrotron radiation beamlines, the DESIRS beamline of Synchrotron SOLEIL and the VUV beamline of the Swiss Light Source (SLS). Amidogen radicals were generated by two different methods, (a) H-atom abstraction of ammonia in a fluorine microwave discharge flow tube and (b) flash pyrolysis of methylhydrazine and diphenylmethylamine. Due to the large geometry change upon photoionization from the bent neutral molecule NH2 (X[combining tilde] (2)B1) to the quasi-linear cation NH2(+) (X[combining tilde] (3)B1), significant activity in the bending vibration υ2(+) of NH2(+) (X[combining tilde] (3)B1) is observed in the TPES. Transitions into a large number of υ2(+), Ka(+) levels of the cation are resolved.