bluuebunny/crossref_metadata_2025 huggingface dataset:
Kinder- und jugendpsychiatrische Versorgung 2019 in Österreich – Stufen der Versorgung, Ist-Stand und Ausblick
Authors: Fliedl Rainer , Ecker Berenike , Karwautz A.
Published: November 2020

Hintergrund

Kinder- und jugendpsychiatrische Störungen sind häufig, die Versorgung in Österreich ist erst im Aufbau.

Methoden

Wir untersuchten, ob sich die fachärztliche Versorgungslage seit Etablierung des Sonderfaches verbessert hat.

Ergebnisse

Es besteht weiter eine große Heterogenität der Versorgungslage zwischen den Bundesländern, Die Mangelfachregelung in der derzeitigen Form ist nicht ausreichend, um die Ausbildung im Sonderfach zu konsolidieren und eine Vollversorgung in absehbarer Zeit zu erreichen.

Conclusion

Es werden Anregungen erarbeitet, wie die Versorgungssituation in der Zukunft verbessert werden könnte.
On critical points of the relative fractional perimeter
Authors: Pagliardini Dayana , Malchiodi Andrea , Novaga Matteo
Published: November 2020

We study the localization of sets with constant nonlocal mean curvature and prescribed small volume in a bounded open set, proving that they are sufficiently close to critical points of a suitable nonlocal potential. We then consider the fractional perimeter in half-spaces. We prove existence of minimizers under fixed volume constraint, and we show some properties such as smoothness and rotational symmetry.
Structural Geology
Authors: Fossen Haakon
Published: November 2020

This market-leading textbook has been fully updated in response to extensive user feedback. It includes a new chapter on joints and veins, additional examples from around the world, stunning new field photos, and extended online resources with new animations and exercises. The book's practical emphasis, hugely popular in the first edition, features applications in the upper crust, including petroleum and groundwater geology, highlighting the importance of structural geology in exploration and exploitation of petroleum and water resources. Carefully designed full-colour illustrations work closely with the text to support student learning, and are supplemented with high-quality photos from around the world. Examples and parallels drawn from practical everyday situations engage students, and end-of chapter review questions help them to check their understanding. Updated e-learning modules are available online (www.cambridge.org/fossen2e) and further reinforce key topics using summaries, innovative animations to bring concepts to life, and additional examples and figures.
Randomized numerical linear algebra: Foundations and algorithms
Authors: Martinsson Per-Gunnar , Tropp Joel A.
Published: November 2020

This survey describes probabilistic algorithms for linear algebraic computations, such as factorizing matrices and solving linear systems. It focuses on techniques that have a proven track record for real-world problems. The paper treats both the theoretical foundations of the subject and practical computational issues.

Topics include norm estimation, matrix approximation by sampling, structured and unstructured random embeddings, linear regression problems, low-rank approximation, subspace iteration and Krylov methods, error estimation and adaptivity, interpolatory and CUR factorizations, Nyström approximation of positive semidefinite matrices, single-view (‘streaming’) algorithms, full rank-revealing factorizations, solvers for linear systems, and approximation of kernel matrices that arise in machine learning and in scientific computing.
On Phonosophy
Authors: Fields Ken
Published: November 2020

With phonosophy, we are investigating a platform to disembark from the vehicle of the long-travelled logos. The once organic and flowing aspects of Logos (Heraclitus) have all but succumbed to the current scientific, materialistic, mechanistic, quantitative and spatially centric epistemology of the last century – one or all of which perspectives define most of the serious theoretical and critical approaches to organised sound, sound art, music concrète, acousmatic and electroacoustic music in our time. Phonosophy will address that which goes beyond or parallel to the logos, or the logocentric. Adrienne Janus’s discussion of Jean-Luc Nancy’sListeningand the sonic turn looks for conditions of an epistemology based on ‘listening as a mode of attending’ to the resonances of sense, ‘where sense touches upon and resonates with all registers of sensual perception as well as intellectual perception … insofar as they resonate’. Suzanne Guerlac points to Bergson’s theory of real duration (durée réelle) that is the vital energy of animate experience and consciousness as opposed to the entropic energy (thermodynamic) of physics. Together these two overlapping discussions consist of the method (listening/sensing) and field (resonance/duration) of the phonosophic investigation.
Music Thinking Process: Unfolding the creation of the pieceRésonances manifestes
Authors: Gendron-Blais Hubert
Published: November 2020

Beyond the social and even the human, sound opens onto the intertwining of movements animating the lived experience. A sonic epistemology considers not only that the acoustic ecologies are enunciative of social relations and power dynamics, but also that they tell about the way reality is lived, experienced, organised: they areexpressive, in themselves. This means, for an epistemology of phonosophy, that every perception of a sound implies a conceptual movement, which carries a mental dimension that could become the material for another thinking practice, for a sophia. This article approaches music as thinking in itself: a thought of the sonic. This affirmation will be expanded through the contribution of process philosophy (Whitehead, Deleuze and Guattari, Manning, etc.), which allows a musical event to be considered as an ecology, produced by the encounter of a multiplicity of bodies (human, sonic, technological, etc.). The processes of capture of forces involved and the different techniques required to increase the expressive potentialities of the musical assemblage will be unfolded through the case of Résonances manifestes, a comprovised music piece based on a sound score composed of field recordings from autonomous demonstrations.
From Physical to Spiritual: Defining the practice of embodied sonic meditation
Authors: Wu Jiayue Cecilia
Published: November 2020

This article narrates my practice-based research in embodied sonic meditation, as a Digital Musical Instrument (DMI) designer, a vocalist, a composer, a media artist and a long-term meditation practitioner. I define the concept of ‘embodied sonic meditation’ in the context of electroacoustic sound art with the augmentation by music technology and human-centred design. I historically connect embodied sonic meditation to its roots in Tibetan Buddhism and several inspiring music compositional practices in the Western world from the second half of the twentieth century. I argue that physicality and spirituality are unified in an inseparable non-duality form, through sound, body and mind. I develop a methodology for embodied sonic meditation practice, built on fifteen design principles based on previous research in DMI design principles, neuroscience research in meditation, Csikszentmihalyi’s Flow Theory, and the criteria of efficiency, music subjectivity, affordance, culture constraints and meaning making. I then make reference to three proof-of-concept case studies that use a sensor-augmented body as an instrument to create sound and sonic awareness. I argue that embodied sonic meditation affords an opportunity for sound art to mediate cultures, improve people’s well-being, and better connect people to their inner peace and the outer world.
Swamp, Sound, Sign: Reflections on interspecies difference in compositional practice
Authors: Bertrand William
Published: November 2020

Soundscape composition and environmental sound art already imply critiques and negotiations of nature/culture divide and human/non-human difference. This article, along with the composition it frames, thinks through a vision of environmental sound art that completes a link between sonic practice and its object. As a project, it navigates human/animal difference through a sonic knowing which is founded on life’s shared constitution in signs. Sounds beyond spoken words, like the signs that dominate non-human life, are foundationally non-symbolic, and the ability of environmental sound art to resemble and evoke networks of icons and indices is in some respects a privileged position of electroacoustic music. The article presents a non-dualistic sonic thinking within the decentred perspective of the environment, which emerges as a plural product of its engagements and participants. A vision for soundscape composition is presented, along with a frame for its interpretation as sonic thought, or phonosophy.
Understanding Barriers to Transition From Pediatric to Adult Care Among Young Adults With Sickle Cell Disease to Develop a Transition Mentor Program
Authors: Viola Adrienne S. , Levonyan-Radloff Kristine , Drachtman Richard , Porter Jerlym , Savage Beth , Kaveney Amanda , Sridharan Ashwin , Delnevo Cristine D. , Coups Elliot J. , Devine Katie A.
Published: November 2020

Objective: Patients with sickle cell disease require lifelong comprehensive care, necessitating patient compliance with primary care appointments, specialty clinical visits, medications, transfusions, and regular health maintenance. As patients transition from pediatric care to adult care, they are at risk for lapses in care that can result in serious complications, making the period of transition a medically vulnerable time. The goal of this study was to use formative interviews to identify targets for a mentoring intervention to improve transition outcomes. Methods: Ten young adults preparing to transition and 10 young adults within 10 years of their transition (ages 18–30 years) completed a semistructured interview. Interviews were analyzed using template thematic analysis, with the Social-Ecological Model of Adolescent and Young Adult Readiness to Transition (SMART) framework as the a priori thematic framework. Results: Themes were consistent with the SMART framework components. Young adults identified self-advocacy, provider communication, and disease knowledge as important targets for intervention. Participants were receptive to having a medical student as a mentor and also viewed it as an opportunity to educate health professionals. Conclusions: The SMART framework and patient interviews were useful in designing a transition mentor program to meet the needs of patients with sickle cell disease. Future research will evaluate the feasibility of this program.

Implications for Impact Statement

This study describes the development of a transition mentor program for young adults with sickle cell disease informed by a formative needs assessment and the Social-Ecological Model of Adolescent and Young Adult Readiness to Transition framework. These methods are generalizable to future transition intervention development in pediatric psychology.
Macrophage-derived small extracellular vesicles promote biomimetic mineralized collagen-mediated endogenous bone regeneration
Authors: Liu Anqi , Jin Shanshan , Fu Cuicui , Cui Shengji , Zhang Ting , Zhu Lisha , Wang Yu , Shen Steve G. F. , Jiang Nan , Liu Yan
Published: November 2020

Macrophages play an important role in material-related immune responses and bone formation, but the functionality of macrophage-derived extracellular vesicles (EVs) in material-mediated bone regeneration is still unclear. Here, we evaluated intracellular communication through small extracellular vesicles (sEVs) and its effects on endogenous bone regeneration mediated by biomimetic intrafibrillarly mineralized collagen (IMC). After implantation in the bone defect area, IMC generated more neobone and recruited more mesenchymal stem cells (MSCs) than did extrafibrillarly mineralized collagen (EMC). More CD63+CD90+ and CD63+CD163+ cells were detected in the defect area in the IMC group than in the EMC group. To determine the functional roles of sEVs, extracellular vesicles from macrophages cultured on different mineralized collagen were isolated, and they showed no morphological differences. However, macrophage-derived sEVs in the IMC group showed an enhanced Young’s modulus and exerted beneficial effects on the osteogenic differentiation of bone marrow MSCs by increasing the expression of the osteoblastic differentiation markers BMP2, BGLAP, COL1, and OSX and calcium nodule formation. Mechanistically, sEVs from IMC-treated macrophages facilitated MSC osteogenesis through the BMP2/Smad5 pathway, and blocking sEV secretion with GW4869 significantly impaired MSC proliferative, immunomodulative and osteogenic potential. Taken together, these findings show that macrophage-derived sEVs may serve as an emerging functional tool in biomaterial-mediated endogenous bone regeneration.
Design of freeform geometries in a MEMS accelerometer with a mechanical motion preamplifier based on a genetic algorithm
Authors: Wang Chen , Song Xiaoxiao , Fang Weidong , Chen Fang , Zeimpekis Ioannis , Wang Yuan , Quan Aojie , Bai Jian , Liu Huafeng , Schropfer Gerold , Welham Chris , Kraft Michael
Published: November 2020

This paper describes a novel, semiautomated design methodology based on a genetic algorithm (GA) using freeform geometries for microelectromechanical systems (MEMS) devices. The proposed method can design MEMS devices comprising freeform geometries and optimize such MEMS devices to provide high sensitivity, large bandwidth, and large fabrication tolerances. The proposed method does not require much computation time or memory. The use of freeform geometries allows more degrees of freedom in the design process, improving the diversity and performance of MEMS devices. A MEMS accelerometer comprising a mechanical motion amplifier is presented to demonstrate the effectiveness of the design approach. Experimental results show an improvement in the product of sensitivity and bandwidth by 100% and a sensitivity improvement by 141% compared to the case of a device designed with conventional orthogonal shapes. Furthermore, excellent immunities to fabrication tolerance and parameter mismatch are achieved.
Gradient wettability induced by deterministically patterned nanostructures
Authors: Min Siyi , Li Shijie , Zhu Zhouyang , Li Wei , Tang Xin , Liang Chuwei , Wang Liqiu , Cheng Xing , Li Wen-Di
Published: November 2020

We report a large-scale surface with continuously varying wettability induced by ordered gradient nanostructures. The gradient pattern is generated from nonuniform interference lithography by utilizing the Gaussian-shaped intensity distribution of two coherent laser beams. We also develop a facile fabrication method to directly transfer a photoresist pattern into an ultraviolet (UV)-cured high-strength replication molding material, which eliminates the need for high-cost reactive ion etching and e-beam evaporation during the mold fabrication process. This facile mold is then used for the reproducible production of surfaces with gradient wettability using thermal-nanoimprint lithography (NIL). In addition, the wetting behavior of water droplets on the surface with the gradient nanostructures and therefore gradient wettability is investigated. A hybrid wetting model is proposed and theoretically captures the contact angle measurement results, shedding light on the wetting behavior of a liquid on structures patterned at the nanoscale.
Modular operation of microfluidic chips for highly parallelized cell culture and liquid dosing via a fluidic circuit board
Authors: Vollertsen A. R. , de Boer D. , Dekker S. , Wesselink B. A. M. , Haverkate R. , Rho H. S. , Boom R. J. , Skolimowski M. , Blom M. , Passier R. , van den Berg A. , van der Meer A. D. , Odijk M.
Published: November 2020

Microfluidic systems enable automated and highly parallelized cell culture with low volumes and defined liquid dosing. To achieve this, systems typically integrate all functions into a single, monolithic device as a “one size fits all” solution. However, this approach limits the end users’ (re)design flexibility and complicates the addition of new functions to the system. To address this challenge, we propose and demonstrate a modular and standardized plug-and-play fluidic circuit board (FCB) for operating microfluidic building blocks (MFBBs), whereby both the FCB and the MFBBs contain integrated valves. A single FCB can parallelize up to three MFBBs of the same design or operate MFBBs with entirely different architectures. The operation of the MFBBs through the FCB is fully automated and does not incur the cost of an extra external footprint. We use this modular platform to control three microfluidic large-scale integration (mLSI) MFBBs, each of which features 64 microchambers suitable for cell culturing with high spatiotemporal control. We show as a proof of principle that we can culture human umbilical vein endothelial cells (HUVECs) for multiple days in the chambers of this MFBB. Moreover, we also use the same FCB to control an MFBB for liquid dosing with a high dynamic range. Our results demonstrate that MFBBs with different designs can be controlled and combined on a single FCB. Our novel modular approach to operating an automated microfluidic system for parallelized cell culture will enable greater experimental flexibility and facilitate the cooperation of different chips from different labs.
Lkb1 suppresses amino acid-driven gluconeogenesis in the liver
Authors: Just Pierre-Alexandre , Charawi Sara , Denis Raphaël G. P. , Savall Mathilde , Traore Massiré , Foretz Marc , Bastu Sultan , Magassa Salimata , Senni Nadia , Sohier Pierre , Wursmer Maud , Vasseur-Cognet Mireille , Schmitt Alain , Le Gall Morgane , Leduc Marjorie , Guillonneau François , De Bandt Jean-Pascal , Mayeux Patrick , Romagnolo Béatrice , Luquet Serge , Bossard Pascale , Perret Christine
Published: November 2020

Excessive glucose production by the liver is a key factor in the hyperglycemia observed in type 2 diabetes mellitus (T2DM). Here, we highlight a novel role of liver kinase B1 (Lkb1) in this regulation. We show that mice with a hepatocyte-specific deletion of Lkb1 have higher levels of hepatic amino acid catabolism, driving gluconeogenesis. This effect is observed during both fasting and the postprandial period, identifying Lkb1 as a critical suppressor of postprandial hepatic gluconeogenesis. Hepatic Lkb1 deletion is associated with major changes in whole-body metabolism, leading to a lower lean body mass and, in the longer term, sarcopenia and cachexia, as a consequence of the diversion of amino acids to liver metabolism at the expense of muscle. Using genetic, proteomic and pharmacological approaches, we identify the aminotransferases and specifically Agxt as effectors of the suppressor function of Lkb1 in amino acid-driven gluconeogenesis.
Single cell RNA sequencing of human microglia uncovers a subset associated with Alzheimer’s disease
Authors: Olah Marta , Menon Vilas , Habib Naomi , Taga Mariko F. , Ma Yiyi , Yung Christina J. , Cimpean Maria , Khairallah Anthony , Coronas-Samano Guillermo , Sankowski Roman , Grün Dominic , Kroshilina Alexandra A. , Dionne Danielle , Sarkis Rani A. , Cosgrove Garth R. , Helgager Jeffrey , Golden Jeffrey A. , Pennell Page B. , Prinz Marco , Vonsattel Jean Paul G. , Teich Andrew F. , Schneider Julie A. , Bennett David A. , Regev Aviv , Elyaman Wassim , Bradshaw Elizabeth M. , De Jager Philip L.
Published: November 2020

The extent of microglial heterogeneity in humans remains a central yet poorly explored question in light of the development of therapies targeting this cell type. Here, we investigate the population structure of live microglia purified from human cerebral cortex samples obtained at autopsy and during neurosurgical procedures. Using single cell RNA sequencing, we find that some subsets are enriched for disease-related genes and RNA signatures. We confirm the presence of four of these microglial subpopulations histologically and illustrate the utility of our data by characterizing further microglial cluster 7, enriched for genes depleted in the cortex of individuals with Alzheimer’s disease (AD). Histologically, these cluster 7 microglia are reduced in frequency in AD tissue, and we validate this observation in an independent set of single nucleus data. Thus, our live human microglia identify a range of subtypes, and we prioritize one of these as being altered in AD.
High pressure synthesis of phosphine from the elements and the discovery of the missing (PH3)2H2 tile
Authors: Ceppatelli Matteo , Scelta Demetrio , Serrano-Ruiz Manuel , Dziubek Kamil , Garbarino Gaston , Jacobs Jeroen , Mezouar Mohamed , Bini Roberto , Peruzzini Maurizio
Published: November 2020

High pressure reactivity of phosphorus and hydrogen is relevant to fundamental chemistry, energy conversion and storage, and materials science. Here we report the synthesis of (PH3)2H2, a crystalline van der Waals (vdW) compound (I4cm) made of PH3and H2molecules, in a Diamond Anvil Cell by direct catalyst-free high pressure (1.2 GPa) and high temperature (T ≲ 1000 K) chemical reaction of black phosphorus and liquid hydrogen, followed by room T compression above 3.5 GPa. Group 15 elements were previously not known to form H2-containing vdW compounds of their molecular hydrides. The observation of (PH3)2H2, identified by synchrotron X-ray diffraction and vibrational spectroscopy (FTIR, Raman), therefore represents the discovery of a previously missing tile, specifically corresponding to P for pnictogens, in the ability of non-metallic elements to form such compounds. Significant chemical implications encompass reactivity of the elements under extreme conditions, with the observation of the P analogue of the Haber-Bosch reaction for N, fundamental bond theory, and predicted high pressure superconductivity in P-H systems.
Organo–organic and organo–mineral interfaces in soil at the nanometer scale
Authors: Possinger Angela R. , Zachman Michael J. , Enders Akio , Levin Barnaby D. A. , Muller David A. , Kourkoutis Lena F. , Lehmann Johannes
Published: November 2020

The capacity of soil as a carbon (C) sink is mediated by interactions between organic matter and mineral phases. However, previously proposed layered accumulation of organic matter within aggregate organo–mineral microstructures has not yet been confirmed by direct visualization at the necessary nanometer-scale spatial resolution. Here, we identify disordered micrometer-size organic phases rather than previously reported ordered gradients in C functional groups. Using cryo-electron microscopy with electron energy loss spectroscopy (EELS), we show organo–organic interfaces in contrast to exclusively organo–mineral interfaces. Single-digit nanometer-size layers of C forms were detected at the organo–organic interface, showing alkyl C and nitrogen (N) enrichment (by 4 and 7%, respectively). At the organo–mineral interface, 88% (72–92%) and 33% (16–53%) enrichment of N and oxidized C, respectively, indicate different stabilization processes than at organo–organic interfaces. However, N enrichment at both interface types points towards the importance of N-rich residues for greater C sequestration.
Asymmetric polyamide nanofilms with highly ordered nanovoids for water purification
Authors: Yuan Bingbing , Zhao Shengchao , Hu Ping , Cui Jiabao , Niu Q. Jason
Published: November 2020

Tailor-made structure and morphology are critical to the highly permeable and selective polyamide membranes used for water purification. Here we report an asymmetric polyamide nanofilm having a two-layer structure, in which the lower is a spherical polyamide dendrimer porous layer, and the upper is a polyamide dense layer with highly ordered nanovoids structure. The dendrimer porous layer was covalently assembled in situ on the surface of the polysulfone (PSF) support by a diazotization-coupling reaction, and then the asymmetric polyamide nanofilm with highly ordered hollow nanostrips structure was formed by interfacial polymerization (IP) thereon. Tuning the number of the spherical dendrimer porous layers and IP time enabled control of the nanostrips morphology in the polyamide nanofilm. The asymmetric polyamide membrane exhibits a water flux of 3.7−4.3 times that of the traditional monolayer polyamide membrane, showing an improved divalent salt rejection rate (more than 99%), which thus surpasses the upper bound line of the permeability−selectivity performance of the existing various structural polyamide membranes. We estimate that this work might inspire the preparation of highly permeable and selective reverse osmosis (RO), organic solvent nanofiltration (OSNF) and pervaporation (PV) membranes.
BETs inhibition attenuates oxidative stress and preserves muscle integrity in Duchenne muscular dystrophy
Authors: Segatto Marco , Szokoll Roberta , Fittipaldi Raffaella , Bottino Cinzia , Nevi Lorenzo , Mamchaoui Kamel , Filippakopoulos Panagis , Caretti Giuseppina
Published: November 2020

Duchenne muscular dystrophy (DMD) affects 1 in 3500 live male births. To date, there is no effective cure for DMD, and the identification of novel molecular targets involved in disease progression is important to design more effective treatments and therapies to alleviate DMD symptoms. Here, we show that protein levels of the Bromodomain and extra-terminal domain (BET) protein BRD4 are significantly increased in the muscle of the mouse model of DMD, the mdx mouse, and that pharmacological inhibition of the BET proteins has a beneficial outcome, tempering oxidative stress and muscle damage. Alterations in reactive oxygen species (ROS) metabolism are an early event in DMD onset and they are tightly linked to inflammation, fibrosis, and necrosis in skeletal muscle. By restoring ROS metabolism, BET inhibition ameliorates these hallmarks of the dystrophic muscle, translating to a beneficial effect on muscle function. BRD4 direct association to chromatin regulatory regions of the NADPH oxidase subunits increases in the mdx muscle and JQ1 administration reduces BRD4 and BRD2 recruitment at these regions. JQ1 treatment reduces NADPH subunit transcript levels in mdx muscles, isolated myofibers and DMD immortalized myoblasts. Our data highlight novel functions of the BET proteins in dystrophic skeletal muscle and suggest that BET inhibitors may ameliorate the pathophysiology of DMD.
muscat detects subpopulation-specific state transitions from multi-sample multi-condition single-cell transcriptomics data
Authors: Crowell Helena L. , Soneson Charlotte , Germain Pierre-Luc , Calini Daniela , Collin Ludovic , Raposo Catarina , Malhotra Dheeraj , Robinson Mark D.
Published: November 2020

Single-cell RNA sequencing (scRNA-seq) has become an empowering technology to profile the transcriptomes of individual cells on a large scale. Early analyses of differential expression have aimed at identifying differences between subpopulations to identify subpopulation markers. More generally, such methods compare expression levels across sets of cells, thus leading to cross-condition analyses. Given the emergence of replicated multi-condition scRNA-seq datasets, an area of increasing focus is making sample-level inferences, termed here as differential state analysis; however, it is not clear which statistical framework best handles this situation. Here, we surveyed methods to perform cross-condition differential state analyses, including cell-level mixed models and methods based on aggregated pseudobulk data. To evaluate method performance, we developed a flexible simulation that mimics multi-sample scRNA-seq data. We analyzed scRNA-seq data from mouse cortex cells to uncover subpopulation-specific responses to lipopolysaccharide treatment, and provide robust tools for multi-condition analysis within themuscatR package.
Visible-light photoredox-catalyzed C–O bond cleavage of diaryl ethers by acridinium photocatalysts at room temperature
Authors: Tan Fang-Fang , He Xiao-Ya , Tian Wan-Fa , Li Yang
Published: November 2020

Cleavage of C–O bonds in lignin can afford the renewable aryl sources for fine chemicals. However, the high bond energies of these C–O bonds, especially the 4-O-5-type diaryl ether C–O bonds (~314 kJ/mol) make the cleavage very challenging. Here, we report visible-light photoredox-catalyzed C–O bond cleavage of diaryl ethers by an acidolysis with an aryl carboxylic acid and a following one-pot hydrolysis. Two molecules of phenols are obtained from one molecule of diaryl ether at room temperature. The aryl carboxylic acid used for the acidolysis can be recovered. The key to success of the acidolysis is merging visible-light photoredox catalysis using an acridinium photocatalyst and Lewis acid catalysis using Cu(TMHD)2. Preliminary mechanistic studies indicate that the catalytic cycle occurs via a rare selective electrophilic attack of the generated aryl carboxylic radical on the electron-rich aryl ring of the diphenyl ether. This transformation is applied to a gram-scale reaction and the model of 4-O-5 lignin linkages.
Neoadjuvant FLOT versus SOX phase II randomized clinical trial for patients with locally advanced gastric cancer
Authors: Sah Birendra Kumar , Zhang Benyan , Zhang Huan , Li Jian , Yuan Fei , Ma Tao , Shi Min , Xu Wei , Zhu Zhenglun , Liu Wentao , Yan Chao , Li Chen , Liu Bingya , Yan Min , Zhu Zhenggang
Published: November 2020

Neoadjuvant chemotherapy with docetaxel, oxaliplatin, fluorouracil, and leucovorin (FLOT regimen) has shown promising results in terms of pathological response and survival rate in patients with locally advanced resectable gastric cancer (LAGC). However, tegafur gimeracil oteracil potassium capsule (S-1) plus oxaliplatin (SOX regimen) is the preferred chemotherapy regimen in Eastern countries. Here, we conduct an open label, two-arm, phase II randomized interventional clinical trial (Dragon III; ClinicalTrials.gov: NCT03636893) to evaluate the safety and efficacy of both regimens. Patients with LAGC are randomly assigned to receive either 4 cycles of the neoadjuvant FLOT regimen (40 patients) or 3 cycles of the SOX regimen (34 patients) before gastrectomy. The primary endpoint is the comparison of complete (TRG1a) or subtotal (TRG1b) tumor regression grading in the primary tumor. There are no significant differences in adverse effects or postoperative morbidity and mortality between the two groups. No significant differences in the proportion of tumor regression grading between the FLOT group and the SOX group are found. Complete or subtotal TRG is 20.0% in the FLOT group versus 32.4% in the SOX group. Therefore, our study does not find statistically significant differences between neoadjuvant FLOT and SOX regimens for the primary outcomes reported here in locally advanced gastric cancer.
Direct binding of TFEα opens DNA binding cleft of RNA polymerase
Authors: Jun Sung-Hoon , Hyun Jaekyung , Cha Jeong Seok , Kim Hoyoung , Bartlett Michael S. , Cho Hyun-Soo , Murakami Katsuhiko S.
Published: November 2020

Opening of the DNA binding cleft of cellular RNA polymerase (RNAP) is necessary for transcription initiation but the underlying molecular mechanism is not known. Here, we report on the cryo-electron microscopy structures of the RNAP, RNAP-TFEα binary, and RNAP-TFEα-promoter DNA ternary complexes from archaea, Thermococcus kodakarensis (Tko). The structures reveal that TFEα bridges the RNAP clamp and stalk domains to open the DNA binding cleft. Positioning of promoter DNA into the cleft closes it while maintaining the TFEα interactions with the RNAP mobile modules. The structures and photo-crosslinking results also suggest that the conserved aromatic residue in the extended winged-helix domain of TFEα interacts with promoter DNA to stabilize the transcription bubble. This study provides a structural basis for the functions of TFEα and elucidates the mechanism by which the DNA binding cleft is opened during transcription initiation in the stalk-containing RNAPs, including archaeal and eukaryotic RNAPs.
Data-science ready, multisite, human diffusion MRI white-matter-tract statistics
Authors: Lerma-Usabiaga Garikoitz , Mukherjee Pratik , Perry Michael L. , Wandell Brian A.
Published: November 2020

The white matter tracts in the living human brain are critical for healthy function, and the diffusion MRI measured in these tracts is correlated with diverse behavioral measures. The technical skills required to analyze diffusion MRI data are complex: data acquisition requires MRI sequence development and acquisition expertise, analyzing raw-data into meaningful summary statistics requires computational neuroimaging and neuroanatomy expertise. The human white matter study field will advance faster if the tract summaries are available in plain data-science-ready format for non-diffusion MRI experts, such as statisticians, computer graphic researchers or data scientists in general. Here, we share a curated and processed dataset from three different MRI centers in a format that is data-science ready. The multisite data we share include measures of within and between MRI center variation in white-matter-tract diffusion measurements. Along with the dataset description and summary statistics, we describe the state-of-the-art computational system that guarantees reproducibility and provenance from the original scanner output.
Immunoinformatic design of a COVID-19 subunit vaccine using entire structural immunogenic epitopes of SARS-CoV-2
Authors: Behmard Esmaeil , Soleymani Bijan , Najafi Ali , Barzegari Ebrahim
Published: November 2020

Coronavirus disease 2019 (COVID-19) is an acute pneumonic disease, with no prophylactic or specific therapeutical solution. Effective and rapid countermeasure against the spread of the disease’s associated virus, SARS-CoV-2, requires to incorporate the computational approach. In this study, we employed various immunoinformatics tools to design a multi-epitope vaccine polypeptide with the highest potential for activating the human immune system against SARS-CoV-2. The initial epitope set was extracted from the whole set of viral structural proteins. Potential non-toxic and non-allergenic T-cell and B-cell binding and cytokine inducing epitopes were then identified through a priori prediction. Selected epitopes were bound to each other with appropriate linkers, followed by appending a suitable adjuvant to increase the immunogenicity of the vaccine polypeptide. Molecular modelling of the 3D structure of the vaccine construct, docking, molecular dynamics simulations and free energy calculations confirmed that the vaccine peptide had high affinity for Toll-like receptor 3 binding, and that the vaccine-receptor complex was highly stable. As our vaccine polypeptide design captures the advantages of structural epitopes and simultaneously integrates precautions to avoid relevant side effects, it is suggested to be promising for elicitation of an effective and safe immune response against SARS-CoV-2 in vivo.
Impact of osmotic stress on the phosphorylation and subcellular location of Listeria monocytogenes stressosome proteins
Authors: Dessaux Charlotte , Guerreiro Duarte N. , Pucciarelli M. Graciela , O’Byrne Conor P. , García-del Portillo Francisco
Published: November 2020

Listeria monocytogenes responds to environmental stress using a supra-macromolecular complex, the stressosome, to activate the stress sigma factor SigB. The stressosome structure, inferred from in vitro-assembled complexes, consists of the core proteins RsbR (here renamed RsbR1) and RsbS and, the kinase RsbT. The active complex is proposed to be tethered to the membrane and to support RsbR1/RsbS phosphorylation by RsbT and the subsequent release of RsbT following signal perception. Here, we show in actively-growing cells that L. monocytogenes RsbR1 and RsbS localize mostly in the cytosol in a fully phosphorylated state regardless of osmotic stress. RsbT however distributes between cytosolic and membrane-associated pools. The kinase activity of RsbT on RsbR1/RsbS and its requirement for maximal SigB activation in response to osmotic stress were demonstrated in vivo. Cytosolic RsbR1 interacts with RsbT, while this interaction diminishes at the membrane when RsbR1 paralogues (RsbR2, RsbR3 and RsbL) are present. Altogether, the data support a model in which phosphorylated RsbR1/RsbS may sustain basal SigB activity in unstressed cells, probably assuring a rapid increase in such activity in response to stress. Our findings also suggest that in vivo the active RsbR1-RsbS-RsbT complex forms only transiently and that membrane-associated RsbR1 paralogues could modulate its assembly.
Cage bedding modifies metabolic and gut microbiota profiles in mouse studies applying dietary restriction
Authors: Gregor A. , Fragner L. , Trajanoski S. , Li W. , Sun X. , Weckwerth W. , König J. , Duszka K.
Published: November 2020

Experiments involving food restriction are common practice in metabolic research. Under fasted conditions, mice supplement their diet with cage bedding. We aimed at identifying metabolic and microbiota-related parameters affected by the bedding type. We exposed mice housed with wooden, cellulose, or corncob cage beddings to ad libitum feeding, caloric restriction (CR), or over-night (ON) fasting. Additionally, two subgroups of the ON fast group were kept without any bedding or on a metal grid preventing coprophagy. Mice under CR supplemented their diet substantially with bedding; however, the amount varied depending on the kind of bedding. Bedding-related changes in body weight loss, fat loss, cecum size, stomach weight, fecal output, blood ghrelin levels as well as a response to glucose oral tolerance test were recorded. As fiber is fermented by the gut bacteria, the type of bedding affects gut bacteria and fecal metabolites composition of CR mice. CR wood and cellulose groups showed distinct cecal metabolite and microbiome profiles when compared to the CR corncob group. While all ad libitum fed animal groups share similar profiles. We show that restriction-related additional intake of bedding-derived fiber modulates multiple physiological parameters. Therefore, the previous rodent studies on CR, report the combined effect of CR and increased fiber consumption.
Real-time synthesis and detection of plasmonic metal (Au, Ag) nanoparticles under monochromatic X-ray nano-tomography
Authors: Bharti Amardeep , Chae Keun Hwa , Goyal Navdeep
Published: November 2020

Plasmonic nanostructures are of immense interest of research due to its widespread applications in microelectronics, photonics, and biotechnology, because of its size and shape-dependent localized surface plasmon resonance response. The great efforts have been constructed by physicists, chemists, and material scientists to deliver optimized reaction protocol to tailor the size and shape of nanostructures. Real-time characterization emerges out as a versatile tool in perspective to the optimization of synthesis parameters. Moreover, in the past decades, radiation-induced reduction of metallic-salt to nanoparticles dominates over the conventional direct chemical reduction process which overcomes the production of secondary products and yields ultra-high quality and pure nanostructures. Here we show, the real-time/in-situ synthesis and detection of plasmonic (Au andAg) nanoparticles using single synchrotron monochromatic 6.7 keV X-rays based Nano-Tomography beamline. The real-time X-ray nano-tomography of plasmonic nanostructures has been first-time successfully achieved at such a low-energy that would be leading to the possibility of these experiments at laboratory-based sources. In-situ optical imaging confirms the radiolysis of water molecule resulting in the production of$$e_{aq}^-,\,OH^\bullet ,$$eaq-,OH∙,and$$O_2^-$$O2-under X-ray irradiation. The obtained particle-size and size-distribution by X-ray tomography are in good agreement to TEM results. The effect of different chemical environment media on the particle-size has also been studied. This work provides the protocol to precisely control the size of nanostructures and to synthesize the ultrahigh-purity grade monodisperse nanoparticles that would definitely enhance the phase-contrast in cancer bio-imaging and plasmonic photovoltaic application.
Delay time of waves performing Lévy walks in 1D random media
Authors: Razo-López L. A. , Fernández-Marín A. A. , Méndez-Bermúdez J. A. , Sánchez-Dehesa J. , Gopar V. A.
Published: November 2020

The time that waves spend inside 1D random media with the possibility of performing Lévy walks is experimentally and theoretically studied. The dynamics of quantum and classical wave diffusion has been investigated in canonical disordered systems via the delay time. We show that a wide class of disorder—Lévy disorder—leads to strong random fluctuations of the delay time; nevertheless, some statistical properties such as the tail of the distribution and the average of the delay time are insensitive to Lévy walks. Our results reveal a universal character of wave propagation that goes beyond standard Brownian wave-diffusion.
The hydrogen-bond configuration modulates the energy transfer efficiency in helical protein nanotubes
Authors: He Jinlong , Zhang Lin , Liu Ling
Published: November 2020

As fundamental building blocks of proteins, helices take different forms including the 310-, α-, and π-helices that feature distinct H-bond networks. The H-bond connectivity is shown to modulate energy transfer efficiency in protein helical structures.
Solvent manipulation of the pre-reduction metal–ligand complex and particle-ligand binding for controlled synthesis of Pd nanoparticles
Authors: Li Wenhui , Taylor Michael G. , Bayerl Dylan , Mozaffari Saeed , Dixit Mudit , Ivanov Sergei , Seifert Soenke , Lee Byeongdu , Shanaiah Narasimhamurthy , Lu Yubing , Kovarik Libor , Mpourmpakis Giannis , Karim Ayman M.
Published: November 2020

Understanding how to control the nucleation and growth rates is crucial for designing nanoparticles with specific sizes and shapes.
The effects of silver nanoparticles biosynthesized using fig and olive extracts on cutaneousleishmaniasis-induced inflammation in female balb/c mice
Authors: Almayouf Mina A. , El-khadragy Manal , Awad Manal A. , Alolayan Ebtesam M.
Published: November 2020

Leishmaniasis is a group of infectious and noncontagious severe parasitic diseases, caused by protozoans of the Leishmania genus. Natural products characterize a rich source of prospective chemical entities for the development of new effective drugs for neglected diseases. Scientific evaluation of medicinal plants has made it possible to use some metabolites from flavonoids and polyphenols compounds for the treatment of parasitic diseases. Therefore, we aimed in the present study to evaluate the protective effect of silver nanoparticles (Ag-NPs) biosynthesized using Fig and Olive extracts (NFO) against Cutaneous leishmaniasis in female Balb/c mice. A total of 70 mice were used and divided into seven groups. Treatment was initiated when local lesions were apparent, we found that Fig and Olive extracts were found to be a good source for the synthesis of (Ag-NPs), their formation was confirmed by color change and stability in solution. Nanoparticles biosynthesized using Fig and Olive extracts induced a reduction in the average size of cutaneous leishmaniasis lesions compared with the untreated mice. Moreover, nanoparticles treatment decreased oxidative stress (LPO, NO), down-regulation gene expression levels (TNF-α, IL-1β, and BAX), and this antileishmanial activity of nanoparticles was associated with enhanced antioxidant enzyme activities. In addition, histopathological evaluation proved the antileishmanial activity of nanoparticles compared with the positive control.

Therefore, we aimed in the present study to evaluate the protective effect of silver nanoparticles biosynthesized using Fig and Olive extracts against cutaneous lesions induced by Leishmania major infection through their anti-inflammatory, antioxidant activities, and faster clinical efficacy than standard pentavalent antimonial treatment.
Growth, mortality and yield of Sarotherodon melanotheron melanotheron (Rüppell, 1852) in the Lake Nokoué and Porto-Novo Lagoon complex Benin, West Africa
Authors: Lederoun Djiman , Amoussou Gildas , Baglo Imaculé S. , Adjibogoun Hermann , Vodougnon Hamil , Moreau Jacques , Lalèyè Philippe A.
Published: November 2020

The study evaluated some population parameters of Sarotherodon melanotheron melanotheron within a lagoon complex in southern Benin: Lake Nokoué and Porto-Novo Lagoon. Data on the total length, total weight, and sex were recorded monthly between January and December 2015 for 1,745 specimens captured by local fishermen. The asymptotic length L∞ was estimated at 24.68 cm. The growth rate K was 0.86. The total, natural, and fishing mortalities were estimated at 2.46, 1.71, and 0.75 y−1, respectively. The size at first sexual maturity was 8.9 and 9.2 cm, respectively, for males andfemales. The size at first capture was estimated at 9.2 cm, which indicates that fish spawn at least once before capture. The current exploitation rate of 0.31 remains below the maximum exploitation rate Emax which was 0.604 but was equal to the exploitation rate retaining 50% of the biomass of the stock (E0.5 = 0.324). This suggests that the stock of S. m. melanotheron is not overexploited in the complex. However, it is recommended that the actual rate of exploitation be kept as it is to ensure a sustainable management of these fish populations.
Aktuelle Entwicklungen im Bereich Antibiotic Stewardship
Authors: Kern Winfried V. , Horn Stephan , Fink Geertje
Published: November 2020

Was ist neu?

Antibiotikaverbrauch in Deutschland In Deutschland wurden in den letzten Jahren sowohl im Krankenhausbereich als auch im ambulanten Setting immer weniger Fluorchinolone verordnet. Auch der Verbrauch der Cephalosporine ging etwas zurück.

Renaissance von Aminoglykosiden? Die inzwischen relativ seltenen Substanzen können aufgrund einer recht guten Resistenzlage bei Harnwegsinfektionen als geeignete Alternative – allerdings nur parenteral – eingesetzt werden. Bei akuten schweren Infektionen ist eine einmalige Gabe, z. B. von Tobramycin, initial zusätzlich zu einem geeigneten Betalactam ebenfalls eine Option, aber keine klare Empfehlung.

Antibiotikaeinsatz in der Hämatologie/Onkologie Bei Fieber und Neutropenie gilt nach wie vor die initiale empirische Gabe von Piperacillin-Tazobactam oder einem pseudomonasaktiven Carbapenem als Standard. Diese Betalactame sollten mit verlängerter Infusionsdauer, z. B. über 4 h, verabreicht werden. Linezolid ist ein Reservemedikament und sollte auch bei hämatoonkologischen Patienten nicht empirisch, sondern nur in der gezielten Therapie verwendet werden.

Penicillinallergie Die anamnestische Angabe einer Penicillinallergie sollte durch genaues Hinterfragen differenziert werden. Patienten können so bezüglich ihres Risikos für allergische Reaktionen gruppiert werden – oft besteht kein oder ein sehr geringes Risiko bei einer (erneuten) Behandlung mit Penicillinderivaten. Niedrigrisikopatienten dürfen ohne weitergehende allergologische Untersuchungen reexponiert werden.
[99mTc]Tc-PSMA-I&S: Anwendung zur Radioguided Surgery beim rezidivierten Prostatakarzinom
Authors: Maurer Tobias , Knipper Sophie , Heck Matthias M. , Horn Thomas , Berliner Christoph , Köhler Daniel , Krönke Markus , Rauscher Isabel , Eiber Matthias
Published: November 2020

Durch die verbesserte Detektionsrate hat sich die PSMA PET in den letzten Jahren zunehmend als bildgebende Standarduntersuchung beim biochemischen Rezidiv eines Prostatakarzinoms etabliert. Im Falle einer limitierten regionären lymphogenen Metastasierung in der PSMA PET rückt gegenwärtig eine chirurgische Resektion im Rahmen einer Salvage-Lymphadenektomie vermehrt in den Fokus. Um hierbei die intraoperative Detektion und somit eine sichere Resektion zu erleichtern, können neue PSMA-gerichtete Radioliganden (z. B. [99 mTc]Tc-PSMA-I&S, imaging&surgery) im Rahmen einer PSMA-radioguided surgery zum Einsatz kommen. Im vorliegenden Beitrag sollen der Ablauf, Ergebnisse sowie zukünftige Entwicklungen der Salvage-Lymphadenektomie mittels PSMA-radioguided surgery vorgestellt werden.