Distilling coarse-grained representations of molecular electronic structure with continuously gated message passing.

Bottom-up methods for coarse-grained (CG) molecular modeling are critically needed to establish rigorous links between atomistic reference data and reduced molecular representations. For a target molecule, the ideal reduced CG representation is a function of both the conformational ensemble of the system and the target physical observable(s) to be reproduced at the CG resolution. However, there is an absence of algorithms for selecting CG representations of molecules from which complex properties, including molecular electronic structure, can be accurately modeled. We introduce continuously gated message passing (CGMP), a graph neural network (GNN) method for atomically decomposing molecular electronic structure sampled over conformational ensembles. CGMP integrates 3D-invariant GNNs and a novel gated message passing system to continuously reduce the atomic degrees of freedom accessible for electronic predictions, resulting in a one-shot importance ranking of atoms contributing to a target molecular property. Moreover, CGMP provides the first approach by which to quantify the degeneracy of "good" CG representations conditioned on specific prediction targets, facilitating the development of more transferable CG representations. We further show how CGMP can be used to highlight multiatom correlations, illuminating a path to developing CG electronic Hamiltonians in terms of interpretable collective variables for arbitrarily complex molecules.

Bypassing backmapping: Coarse-grained electronic property distributions using heteroscedastic Gaussian processes.

We employ deep kernel learning electronic coarse-graining (DKL-ECG) with approximate Gaussian processes as a flexible and scalable framework for learning heteroscedastic electronic property distributions as a smooth function of coarse-grained (CG) configuration. The appropriateness of the Gaussian prior on predictive CG property distributions is justified as a function of CG model resolution by examining the statistics of target distributions. The certainties of predictive CG distributions are shown to be limited by CG model resolution with DKL-ECG predictive noise converging to the intrinsic physical noise induced by the CG mapping operator for multiple chemistries. Further analysis of the resolution dependence of learned CG property distributions allows for the identification of CG mapping operators that capture CG degrees of freedom with strong electron-phonon coupling. We further demonstrate the ability to construct the exact quantum chemical valence electronic density of states (EDOS), including behavior in the tails of the EDOS, from an entirely CG model by combining iterative Boltzmann inversion and DKL-ECG. DKL-ECG provides a means of learning CG distributions of all-atom properties that are traditionally "lost" in CG model development, introducing a promising methodological alternative to backmapping algorithms commonly employed to recover all-atom property distributions from CG simulations.

Threshold-dependent iodine imaging and spectral separation in a whole-body photon-counting CT system.

OBJECTIVE: To evaluate the dual-energy (DE) performance and spectral separation with respect to iodine imaging in a photon-counting CT (PCCT) and compare it to dual-source CT (DSCT) DE imaging. METHODS: A semi-anthropomorphic phantom extendable with fat rings equipped with iodine vials is measured in an experimental PCCT. The system comprises a PC detector with two energy bins (20 keV, T) and (T, eU) with threshold T and tube voltage U. Measurements using the PCCT are performed at all available tube voltages (80 to 140 kV) and threshold settings (50-90 keV). Further measurements are performed using a conventional energy-integrating DSCT. Spectral separation is quantified as the relative contrast media ratio R between the energy bins and low/high images. Image noise and dose-normalized contrast-to-noise ratio (CNRD) are evaluated in resulting iodine images. All results are validated in a post-mortem angiography study. RESULTS: R of the PC detector varies between 1.2 and 2.6 and increases with higher thresholds and higher tube voltage. Reference R of the EI DSCT is found as 2.20 on average overall phantoms. Maximum CNRD in iodine images is found for T = 60/65/70/70 keV for 80/100/120/140 kV. The highest CNRD of the PCCT is obtained using 140 kV and is decreasing with decreasing tube voltage. All results could be confirmed in the post-mortem angiography study. CONCLUSION: Intrinsically acquired DE data are able to provide iodine images similar to conventional DSCT. However, PCCT thresholds should be chosen with respect to tube voltage to maximize image quality in retrospectively derived image sets. KEY POINTS: • Photon-counting CT allows for the computation of iodine images with similar quality compared to conventional dual-source dual-energy CT. • Thresholds should be chosen as a function of the tube voltage to maximize iodine contrast-to-noise ratio in derived image sets. • Image quality of retrospectively computed image sets can be maximized using optimized threshold settings.

Laboratory confirmation of C60(+) as the carrier of two diffuse interstellar bands.

The diffuse interstellar bands are absorption lines seen towards reddened stars. None of the molecules responsible for these bands have been conclusively identified. Two bands at 9,632 ångströms and 9,577 ångströms were reported in 1994, and were suggested to arise from C60(+) molecules (ref. 3), on the basis of the proximity of these wavelengths to the absorption bands of C60(+) measured in a neon matrix. Confirmation of this assignment requires the gas-phase spectrum of C60(+). Here we report laboratory spectroscopy of C60(+) in the gas phase, cooled to 5.8 kelvin. The absorption spectrum has maxima at 9,632.7 ± 0.1 ångströms and 9,577.5 ± 0.1 ångströms, and the full widths at half-maximum of these bands are 2.2 ± 0.2 ångströms and 2.5 ± 0.2 ångströms, respectively. We conclude that we have positively identified the diffuse interstellar bands at 9,632 ångströms and 9,577 ångströms as arising from C60(+) in the interstellar medium.

Coccygectomy for coccygodynia: a cohort study with a long-term follow-up of up to 29 years.

PURPOSE: We aim to critically review the effectiveness and safety of coccygectomy with special regard to long-term outcomes. METHODS: Coccygectomy was performed in our clinic in 38 patients between 1990 and 2019. All these patients (32 females vs. 6 males) have failed to respond to conservative treatment for at least 6 months prior to surgery. All patients were available for follow-up after mean 12,3 years (2 months to 29 years, 11 patients had a minimum FUP of 24 years). We evaluated all patients clinically and radiologically. RESULTS: Nineteen patients reported traumatic and 17 patients reported idiopathic onset of their symptoms; one patient had clinical symptoms after childbirth and another patient had coccygodynia after extensive low back surgery. 36 of our 38 patients were free of pain at least 6 months after surgery and had good or excellent clinical results according to the VAS which improved from 6.37 (SD 1.08) preoperatively to 0.68 (SD 0.99) at the recent follow-up. Two patients showed an ODI > 22 at the recent follow-up (24 and 28) and 32 had an ODI equal or under 4. There was no statistical significant difference in terms of clinical outcome between the different radiological types of the coccyx. Postoperative complications were rare: 1 superficial infection and one re-operation 6 months after initial surgery due to an pre-existing exostosis which had not been removed at the index surgery; no neurological complications and no major bleeding occurred. No patient had recurrent onset of coccygodynia. 37 out of 38 patients would have coccygectomy again. CONCLUSIONS: Coccygectomy is a safe treatment option in patients with coccygodynia and shows excellent long-term results. We recommend to perform coccygectomy if patients fail to respond to conservative treatment for 6 months. LEVEL OF EVIDENCE: IV.

[Infiltration of the skull by dedifferentiated cutaneous leiomyosarcoma]. / Infiltration der Schädelkalotte durch ein dedifferenziertes kutanes Leiomyosarkom.

We present a brief report of an 81-year-old man with a pretreated leiomyosarcoma of the skull. Histologically the diagnosis of a dedifferentiated cutaneous leiomyosarcoma with an infiltration of the skull was confirmed. In an interdisciplinary approach together with the University Clinic for Neurosurgery, complete removal of the tumour was performed. Cutaneous leiomyosarcoma are rare tumors of the skin and typically present as slowly growing erythematosus nodes. Because of the risk of metastatic spread, complete micrographically confirmed resection is necessary.

First-principles comparative study of perfect and defective CsPbX3 (X = Br, I) crystals.

First principles Density Functional Theory (DFT) hybrid functional PBESOL0 calculations of the atomic and electronic structure of perfect CsPbI3, CsPbBr3 and CsPbCl3 crystals, as well as defective CsPbI3 and CsPbBr3 crystals are performed and discussed. For the perfect structure, decomposition energy into binary compounds (CsX and PbX2) is calculated, and a stability trend of the form CsPbBr3 > CsPbI3 > CsPbCl3 is found. In addition, calculations of the temperature-dependent heat capacity are performed and shown to be in good agreement with experimental data. As far as the defect structure is considered, it is shown that interstitial halide atoms in CsPbBr3 do not tend to form di-halide dumbbells Br2- while such dimers are energetically favoured in CsPbI3, analogous to the well-known H-centers in alkali halides. In the case of CsPbBr3, a loose trimer configuration (Br32-) seems to be energetically preferred. The effects of crystalline symmetry and covalency are discussed, alongside the role of defects in recombination processes.

Adipose-tissue-derived therapeutic cells in their natural environment as an autologous cell therapy strategy: the microtissue-stromal vascular fraction.

The prerequisite for a successful clinical use of autologous adipose-tissue-derived cells is the highest possible regenerative potential of the applied cell population, the stromal vascular fraction (SVF). Current isolation methods depend on high enzyme concentration, lysis buffer, long incubation steps and mechanical stress, resulting in single cell dissociation. The aim of the study was to limit cell manipulation and obtain a derivative comprising therapeutic cells (microtissue-SVF) without dissociation from their natural extracellular matrix, by employing a gentle good manufacturing practice (GMP)-grade isolation. The microtissue-SVF yielded larger numbers of viable cells as compared to the improved standard-SVF, both with low enzyme concentration and minimal dead cell content. It comprised stromal tissue compounds (collagen, glycosaminoglycans, fibroblasts), capillaries and vessel structures (CD31+, smooth muscle actin+). A broad range of cell types was identified by surface-marker characterisation, including mesenchymal, haematopoietic, pericytic, blood and lymphatic vascular and epithelial cells. Subpopulations such as supra-adventitial adipose-derived stromal/stem cells and endothelial progenitor cells were significantly more abundant in the microtissue-SVF, corroborated by significantly higher potency for angiogenic tube-like structure formation in vitro. The microtissue-SVF showed the characteristic phenotype and tri-lineage mesenchymal differentiation potential in vitro and an immunomodulatory and pro-angiogenic secretome. In vivo implantation of the microtissue-SVF combined with fat demonstrated successful graft integration in nude mice. The present study demonstrated a fast and gentle isolation by minor manipulation of liposuction material, achieving a therapeutically relevant cell population with high vascularisation potential and immunomodulatory properties still embedded in a fraction of its original matrix.

Risk factors associated with 30-day mortality for out-of-center ECMO support: experience from the newly launched ECMO retrieval service.

Out-of-hospital extracorporeal membrane oxygenation (ECMO) implantation and ECMO transport have become a growing field useful for emergent treatment of heart or lung failure with increasing number of centers launching such service. This study was designed to present risk factors predicting 30-day mortality for patients receiving ECMO support in a newly launched ECMO retrieval service. From 01/2015 till 01/2017 28 consecutive patients received ECMO support in peripheral hospitals using a miniaturized portable Cardiohelp System® (Maquet, Rastatt Germany) for heart, lung or heart/lung failure as a bridge-to-decision as a part of our newly launched ECMO retrieval service. Outcomes and predictors for 30-day mortality were presented. The mean age was 56 ± 15 (maximum 78) years. The mean ECMO support duration was 97 ± 100 h, whereas 11 patients (40%) were weaned off support and discharged from hospital. Presence of hemolysis (p = 0.041), renal failure (p = 0.016), lower platelet count before ECMO implantation (p = 0.001), and higher lactate 24 h after initiation of support (p = 0.006) were factors associated with 30-day mortality. Initial success of an ECMO retrieval service depends on logistic organization and clinical management. Taking into consideration highly deleterious effects of hemodynamic malperfusion of end organs, rapid initiation of ECMO support is a vital factor for survival. This is highlighted by predictive factors of early mortality that are associated with peripheral organ failure or complications.

The oxidation kinetics of thin nickel films between 250 and 500 °C.

The oxidation kinetics of thin polycrystalline Ni films is of fundamental interest as well as being relevant for potential applications. It was investigated between 250 and 500 °C for 10-150 nm thick films. Even for the thinnest films, oxidation was found to be diffusion controlled. The high density of grain boundaries in the formed NiO layer leads to a tracer diffusion coefficient that is higher than reported in the literature, indicating accelerated Ni diffusion along the grain boundaries. Cr segregation to the bottom interface in doped-NiO films hindered the acceleration of the oxidation of thin films.

Use of site symmetry in supercell models of defective crystals: polarons in CeO2.

In supercell calculations of defective crystals, it is common to place a point defect or vacancy in the atomic position with the highest possible point symmetry. Then, the initial atomic structure is often arbitrary distorted before its optimization, which searches for the total energy minimum. In this paper, we suggest an alternative approach to the application of supercell models and show that it is necessary to preliminarily analyze the site symmetry of the split Wyckoff positions of the perfect crystal supercell atoms (which will be substituted or removed in defective crystals) and then perform supercell calculations with point defects for different possible site symmetries, to find the energetically most favorable defect configuration, which does not necessarily correspond to the highest site symmetry. Using CeO2 as an example, it is demonstrated that this use of the site symmetry of the removed oxygen atoms in the supercells with vacancies allows us to obtain all the possible atomic and magnetic polaron configurations, and predict which vacancy positions correspond to the lowest formation energies associated with small polarons. We give a simple symmetry based explanation for the existence of controversies in the literature on the nature of the oxygen vacancies in CeO2. In particular, the experimentally observed small polaron formation could arise for oxygen vacancies with the lowest Cs site symmetry, which exist in 3 × 3 × 3 and larger supercells. The results of first principles calculations using a linear combination of atomic orbitals and hybrid exchange-correlation functionals are compared with those from previous studies, obtained using a widely used DFT+U approach.

Perspective: C60+ and laboratory spectroscopy related to diffuse interstellar bands.

In the last 30 years, our research has focused on laboratory measurements of the electronic spectra of organic radicals and ions. Many of the species investigated were selected based on their potential astrophysical relevance, particularly in connection with the identification of appealing candidate molecules for the diffuse interstellar absorptions. Notably, carbon chains and derivatives containing hydrogen and nitrogen atoms in their neutral and ionic forms were studied. These data could be obtained after developing appropriate techniques to record spectra at low temperatures relevant to the interstellar medium. The measurement of gas phase laboratory spectra has enabled direct comparisons with astronomical data to be made and though many species were found to have electronic transitions in the visible where the majority of diffuse bands are observed, none of the absorptions matched the prominent interstellar features. In 2015, however, the first carrier molecule was identified: C60+. This was achieved after the measurement of the electronic spectrum of C60+-He at 6K in a radiofrequency ion trap.

Expression of the autoantigen TRIM33/TIF1γ in skin and muscle of patients with dermatomyositis is upregulated, together with markers of cellular stress.

Dermatomyositis (DM) is an autoimmune disorder associated with a dysregulation of immune homeostasis of both the innate and adaptive immune system. Earlier data suggested that these two arms of the immune system interconnect in DM. In the current study, we analysed the association of autoantigen expression [adaptive system components: Mi2, transcriptional intermediary factor (TIF)1γ, small ubiquitin-like modifier 1 activating enzyme subunit (SAE)1, melanoma differentiation-associated protein (MDA)5] with markers of cellular stress (innate system components: MxA, p53) in skin and muscle (immunohistology and gene expression data, respectively). We found that distinctive self-antigens of DM were elevated in both skin and muscle tissue. In particular, TIF1γ expression was seen in autoimmune diseases including DM, but not in other inflammatory skin disorders. This upregulation was closely associated with p53 expression and type I interferon-regulated inflammation, suggesting that upregulation of autoantigens in the skin and muscle of patients with DM might be driven by cellular stress. Better understanding of these mechanisms could pave the way for new therapeutic concepts focusing on stress reduction.

Electronic Spectra of Protonated Fluoranthene in a Neon Matrix and Gas Phase at 10 K.

Four electronic systems with origin bands at 759.5, 559.3, 476.3, and 385.5 nm are detected in a 6 K neon matrix following deposition of mass-selected protonated fluoranthene C16H11(+) produced from a reaction of neutral vapor and ethanol in a hot-cathode ion source. Two cationic isomers are identified as the carriers of these band systems. The 559.3, 476.3, and 385.5 nm absorptions are assigned to 4,3,2 (1)A' ← X (1)A' transitions of isomer E(+) (γ-) and the 2 (1)A' ← X (1)A' system at 759.5 nm is of isomer C(+) (α-) of protonated fluoranthene on the basis of theoretical predictions. The electronic spectrum of E(+) was also recorded in the gas phase using a resonant 1 + 1 two-photon excitation-dissociation technique in an ion trap at vibrational and rotational temperatures of 10 K. The 3,2 (1)A' ← X (1)A' transitions have origin band maxima at 558.28 ± 0.01 and 474.92 ± 0.01 nm. Both the 2 (1)A' and 3 (1)A' excited states have a distinct vibrational pattern with lifetimes on the order of 1 ps.

[Skin diseases due to systemic vasculitides and vasculopathies]. / Hauterkrankungen durch systemische Vaskulitiden und Vaskulopathien.

Vasculitis and vasculopathy are two distinct disease entities. Each entity comprises a large number of heterogeneous diseases, which can occur alone or associated with autoimmune, infectious or neoplastic diseases. The terms vasculitis and vasculopathy are often falsely used synonymously. A vasculitis initially causes inflammation of the vessel walls that may result in a secondary occlusion. In contrast, a vasculopathy is a primary occlusion of the vascular lumen, which is followed by inflammation after ischemia and ulceration. In most patients the distinction can be made based on the clinical presentation. A clear clinical diagnosis is then followed by targeted serological, histological and imaging procedures to confirm the clinical diagnosis. On this basis a well-founded treatment can be initiated. In the presence of vasculitis an anti-inflammatory therapy is indicated, whereas in the case of vasculopathy, removal of the vascular occlusion is the main focus. This article provides an overview of the various diseases and addresses the pathogenetic and clinical characteristics used to differentiate the individual disease entities. It also provides an insight into the therapy options and prophylaxis.

[Civilian blast injuries: an underestimated problem? : Results of a retrospective analysis of the TraumaRegister DGU®]. / Zivile Explosionstraumata - ein unterschätztes Problem? : Ergebnisse einer retrospektiven Analyse aus dem TraumaRegister DGU®.

BACKGROUND: Blast injuries are a rare cause of potentially life-threatening injuries in Germany. During the past 30 years such injuries were seldom the cause of mass casualties, therefore, knowledge and skills in dealing with this type of injury are not very extensive. MATERIAL AND METHODS: A retrospective identification of all patients in the TraumaRegister DGU® of the German Trauma Society (TR-DGU) who sustained blast injuries between January 1993 and November 2012 was carried out. The study involved a descriptive characterization of the collective as well as three additional collectives. The arithmetic mean, standard deviation and 95 % confidence interval of the arithmetic mean for different demographic parameters and figures for prehospital and in-hospital settings were calculated. A computation of prognostic scores, such as the Revised Injury Severity Classification (RISC) and the updated version RISC II (TR-DGU-Project-ID 2012-035) was performed. RESULTS: A total of 137 patients with blast injuries could be identified in the dataset of the TR-DGU. Of the patients 90 % were male and 43 % were transported by the helicopter emergency service (HEMS) to the various trauma centres. The severely injured collective with a mean injury severity scale (ISS) of 18.0 (ISS ≥ 16 = 52 %) had stable vital signs. In none of the cases was it necessary to perform on-site emergency surgery but a very high proportion of patients (59 %) had to be surgically treated before admittance to the intensive care unit (ICU). Of the patients 27 % had severe soft tissue injuries with an Abbreviated Injury Scale (AIS) ≥ 3 and 90 % of these injuries were burns. The 24 h in-hospital fatality was very low (3 %) but the stay in the ICU tended to be longer than for other types of injury (mean 5.5 ventilation days and 10.7 days in the intensive care unit). Organ failure occurred in 36 % of the cases, multiorgan failure in 29 % and septic events in 14 %. Of the patients 16 % were transferred to another hospital during the first 48 h. The RISC and the updated RISC II tended to underestimate the severity of injuries and mortality (10.2 % vs. 6.8 % and 10.7 % vs. 7.5 %, respectively) and the trauma associated severe hemorrhage (TASH) score underestimated the probability for transfusion of more than 10 units of packed red blood cells (5.0 % vs. 12.5 %). CONCLUSION: This article generates several hypotheses, which should be confirmed with additional investigations. Until then it has to be concluded that patients who suffer from accidental blast injuries in the civilian setting (excluding military operations and terrorist attacks) show a combination of classical severe trauma with blunt and penetrating injuries and additionally a high proportion of severe burns (combined thermomechanical injury). They stay longer in the ICU than other trauma patients and suffer more complications, such as sepsis and multiorgan failure. Established scores, such as RISC, RISC II and TASH tend to underestimate the severity of the underlying trauma.

Quantitative ultrasonometry during pregnancy and lactation: a longitudinal study.

UNLABELLED: This study describes bone mass changes during pregnancy and lactation measured by a special ultrasound method. Pregnant women showed a decrease of bone mass followed by a stable bone mass while breast-feeding afterwards. Later in life, there is a recovery of bone mass loss. INTRODUCTION: The aim of this study was to evaluate bone changes during pregnancy using the radiation-free method of quantitative ultrasonometry (QUS). METHODS: One hundred twenty-five pregnant women who underwent prenatal care were included in this study. Ultrasound measurement of the calcaneus was performed in each trimester and then 6 weeks, 3 months, and 1 year postpartum. The calcaneal QUS measurements were carried out using the Achilles plus device (GE/Lunar Corporation, Madison, WI). Three ultrasound variables were measured: speed of sound (SOS, m/s), broadband ultrasound attenuation (BUA, dB/MHz), and the "stiffness index" (expressed as the percentage of the mean value in young adults). SOS and BUA raw data result in the t-score and z-score. RESULTS: A complete panel of six measurements was acquired over the time period in 101 patients (80.8%). Forty-two percent of the included patients were primipara, while 58% had given birth to at least one child (47%) previously. There was a statistically significant change of the t-score (tv = 2.14, p = 0.035) and the stiffness index (tv = 2.46, p = 0.016) from the second to the third trimester, followed by a plateau during lactation. Interestingly, the t-score remained stable during lactation, regardless of the duration of lactation (<3 months, 3-6 months, and >6 months). CONCLUSIONS: Young primiparas who had a sedentary adolescence were at the highest risk of bone loss during pregnancy. Bone loss that occurred during pregnancy was typically recovered later on, based on unknown molecular and biochemical mechanisms that must be elucidated with further studies.

Gas-phase electronic transitions of C17H12N⁺ at 15 K.

The electronic spectrum of C17H12N(+), phenanthrene with a side chain, was measured in the gas phase at a vibrational and rotational temperature of ∼15 K in an ion trap using a resonant multiphoton dissociation technique. The C17H12N(+) structure was produced in a chemical ionization source and identified by a comparison with theoretical calculations of stable structures and excitation energies. The (3), (2), (1) (1)A ← X (1)A electronic transitions of this nitrogen-containing aromatic species with 30 atoms have origin band maxima at 23,586 ± 1 cm(-1), 16,120 ± 50 cm(-1), and 14,519 ± 30 cm(-1). Distinct vibrational structure in the (3) (1)A state is observed, and assignments are made. Astronomical aspects are considered.

[Gastrointestinal stromal tumours (GIST)--development in pathology, surgery and medical therapy. Developed during the 10th German GIST-meeting, Göttingen]. / Gastrointestinale Stromatumoren (GIST)--Neues zu Pathologie, Chirurgie und medikamentöser Therapie. Erarbeitet im Rahmen des 10. Deutschen GIST-Treffens, Göttingen.

The first description of ligand-independent activating mutations in the KIT gene, which encodes the tyrosine-kinase KIT, greatly improved our understanding of gastrointestinal stromal tumour (GIST) biology. The therapeutic success in GIST has made tyrosine kinase inhibitors a "paradigm of targeted therapy". Deciphering resistance mechanisms in GIST has had implications for many other kinase-driven cancers. To exchange current knowledge within the field of GIST, the German GIST Meeting has taken place for now 10 years, traditionally in Göttingen. Subjects discussed include clinical diagnostics, pathology, surgery, and medical therapy. The following presentation gives an overview of the last meeting held in December 2013, including distinctive features in GIST and current data on the different topics.

[Obstetrical care in myotonic dystrophy type 1 (Steinert disease)]. / Schwangerschaftsbetreuung bei Myotoner Muskeldystrophie Curschmann Steinert.

In 1909 the neurologist Dr. Hans Steinert was the first to describe the most common of all neural-muscular diseases: Mytotonic Dystrophy Curschmann Steinert. Up to today this disease is seldom published particularly in obstetrics. This is a case report of a 23-year-old patient. Following extensive interdisciplinary diagnostic a successful caesarian delivery of a healthy boy was performed in the 39(th) week of pregnancy without any complications.