bluuebunny/crossref_metadata_2025 huggingface dataset:
Highly Enhanced Curie Temperature in Ga‐Implanted Fe3GeTe2 van der Waals Material
Authors: Yang Mengmeng , Li Qian , Chopdekar Rajesh V. , Stan Camelia , Cabrini Stefano , Choi Jun Woo , Wang Sheng , Wang Tianye , Gao Nan , Scholl Andreas , Tamura Nobumichi , Hwang Chanyong , Wang Feng , Qiu Ziqiang
Published: February 2020

Among many efforts in the research of van der Waals (vdW) magnetic materials, increasing the Curie temperature above room temperature has been at the center of research in developing spintronics technology using vdW materials. Here an effective and reliable method of increasing the Curie temperature of ferromagnetic Fe3GeTe2 vdW materials by Ga implantation is reported. It is found that implanting Ga into Fe3GeTe2 by the amount of 10−3 Ga Å−3 could greatly enhance the Fe3GeTe2 Curie temperature by almost 100%. Spatially resolved microdiffraction and element‐resolved X‐ray absorption spectroscopy show little changes in the Fe3GeTe2 crystal structure and Fe valence state. In addition, the Ga implantation changes the Fe3GeTe2 magnetization from out‐of‐plane direction at low temperature to in‐plane direction at high temperature. The result opens a new opportunity for tailoring the magnetic properties of vdW materials beyond room temperature.
“Novel Dextrin‐Cysteine Schiff Base: A Highly Efficient Sensor for Mercury Ions in Aqueous Environment”
Authors: Mondal Barun , Banerjee Shankha , Ray Jagabandhu , Jana Subinoy , Senapati Sanjib , Tripathy Tridib
Published: February 2020

We report a highly sensitive electrochemical and fluorescence sensor for the detection of toxic environmental pollutant Hg2+ ions by using a novel dextrin‐cysteine‐Schiff base (DCS). The sensor is developed by the periodate oxidation of dextrin followed by Schiff base formation with an amino acid, cysteine. The new characterized DCS is used as an efficient and selective sensor for the detection of Hg2+ ions in aqueous solution both by electrochemical and fluorescence quenching process. The detection limit (LOD) by the electrochemical method is 0.74 nM which is much lower than that by the fluorometric detection, where LOD value is found to be 40.93 μM. The Schiff base/glassy carbon electrode (DCS/GCE) shows an excellent selectivity towards Hg2+ ions compare to other environmentally relevant ions where almost nil current response is observed. The DCS/GCE also exhibits remarkable sensing of Hg2+ in real water samples such as river and tap water. The electrochemical sensing of Hg2+ by DCS is found to be superior to that of fluorescence sensing.
FeCl3‐Mediated Boc Deprotection: Mild Facile Boc‐Chemistry in Solution and on Resin
Authors: Giri Rajat S. , Roy Sayanta , Dolai Gobinda , Manne Srinivasa R. , Mandal Bhubaneswar
Published: February 2020

A mild, practical, and straight forward method for Boc deprotection and its use in peptide synthesis both in solution and on solid support is presented. Boc protecting group is removed from the N‐terminal amino acid of the amino acid and the peptide using environment‐friendly cost‐effective Lewis acid, FeCl3. The deprotected amino group undergoes C−N bond formation with the next Boc‐protected amino acid in the presence of a suitable coupling reagent and base. A library of di‐ to tetrapeptides is synthesized with moderate to good yield from standard and nonstandard Boc‐protected amino acids in solution. Most importantly, this protocol can be used for the solid‐phase peptide synthesis (SPPS) using Boc‐protected amino acids on the acid‐sensitive Rink amide resin, which is usually used for Fmoc chemistry. This protocol thus allows practicing Boc chemistry in a greener manner, and on‐demand switching from Fmoc to Boc chemistry and vice‐versa while synthesizing one oligopeptide on the same resin. The inherent orthogonality of Fmoc and Boc chemistry allows facile synthesis of branched and cyclized peptides on the resin as well.
Visualizing Transparent 2D Sheets by Fluorescence Quenching Microscopy
Authors: Kong Zhizhi , Daab Matthias , Yano Hitomi , Huang Haiyue , Breu Josef , Sasaki Takayoshi , Nguyen SonBinh T. , Huang Jiaxing
Published: February 2020

The high‐contrast optical imaging of nearly transparent 2D materials such as clays and some oxide sheets has been an outstanding challenge; yet there is a critical research capability needed in the synthesis and processing of these materials, which show promise in a number of applications including barrier coatings, membranes, and composites. Using delaminated silicate clay and titania sheets as model systems, here it is shown that these weakly quenching, nearly transparent 2D sheets can be readily imaged by fluorescence quenching microscopy (FQM) based on a new mechanism. When these sheets are deposited on strongly quenching substrates, including doped silicon wafers and metals or indium tin oxide‐coated glass slides, they can act as a “spacer” to reduce the degree of quenching of the dye layer by the substrate, appearing as highly visible bright sheets against a dark background. This new FQM strategy can visualize dielectric 2D materials with high contrast and layer resolutions comparable to scanning electron microscopy and atomic force microscopy. When different 2D materials are co‐deposited, FQM not only differentiates them readily based on their quenching capabilities, but also can resolve their vertical stacking sequence based on the contrast of their overlapped areas.
Numerische Modellierung des Kraft‐Verformungsverhaltens vorgespannter Schrauben in L‐Flanschverbindungen
Authors: Wegener Filip , Schwarz Mathias , Glienke Ralf , Marten Frithjof , Seidel Marc
Published: February 2020

Stahlrohrtürme von Windenergieanlagen sind schwingungsanfällige Tragstrukturen, welche infolge des Anlagenbetriebs wechselnden Beanspruchungen ausgesetzt sind. Dem Ermüdungsfestigkeitsnachweis für den Turm kommt daher eine große Bedeutung zu. Ein neuralgischer Punkt innerhalb der Turmstruktur sind in der Regel die Ringflanschverbindungen, welche die einzelnen Turmsektionen mittels vorgespannter Schrauben miteinander verbinden. In Bezug auf die Ermüdungsfestigkeit dieser Verbindung ist die Sicherstellung einer ausreichend hohen Schraubenvorspannung dabei entscheidend. Für eine realitätsnahe Vorhersage der verbleibenden Vorspannkraft in einer Flanschverbindung nach einer Überbeanspruchung ist eine präzise Erfassung des plastischen Verformungsverhaltens der Schraube‐Mutter‐Verbindung wichtig. In dem vorliegenden Beitrag wird ein numerischer Ansatz zur Vorhersage des Vorspannkraftverlusts von zentrisch und exzentrisch vorgespannten Schraubenverbindungen infolge von hohen Einzellasten vorgestellt, welcher durch Versuche verifiziert wird.
The role of freshwater bioacoustics in ecological research
Authors: Greenhalgh Jack A. , Genner Martin J. , Jones Gareth , Desjonquères Camille
Published: February 2020

Conventional methodologies used to estimate biodiversity in freshwater ecosystems can be nonselective and invasive, sometimes leading to capture and potential injury of vulnerable species. Therefore, interest in noninvasive surveying techniques is growing among freshwater ecologists. Passive acoustic monitoring, the noninvasive recording of environmental sounds, has been shown to effectively survey biota in terrestrial and marine ecosystems. However, knowledge of the sounds produced by freshwater species is relatively scarce. Furthermore, little is known about the representation of different freshwater taxonomic groups and habitat types within the literature. Here we present results of a systematic review of research literature on freshwater bioacoustics and identify promising areas of future research. The review showed that fish are the focal taxonomic group in 44% of published studies and were studied primarily in laboratory aquaria and lotic habitats. By contrast, lentic habitats and other taxonomic groups have received relatively little research interest. It is particularly striking that arthropods are only represented by 26% of studies, despite their significant contributions to freshwater soundscapes. This indicates a mismatch between the representation of taxonomic groups within the freshwater bioacoustic literature and their relative acoustic contribution to natural freshwater soundscapes. In addition, the review indicates an ongoing shift from behavioral studies, often with focus on a single taxonomic group, towards field‐based studies using ecoacoustic approaches. On the basis of this review we suggest that future freshwater bioacoustics research should focus on passive acoustic monitoring and arthropod sound, which would likely yield novel insights into freshwater ecosystem function and condition.

This article is categorized under:

Water and Life > Nature of Freshwater Ecosystems

Water and Life > Conservation, Management, and Awareness

Water and Life > Methods
Covert symmetries in the neutrino mass matrix
Authors: Björkeroth Fredrik , Di Luzio Luca , Mescia Federico , Nardi Enrico
Published: February 2020

Abstract

The flavour neutrino puzzle is often addressed by considering neutrino mass matrices m with a certain number of vanishing entries (mij = 0 for some values of the indices), since a reduction in the number of free parameters increases the predictive power. Symmetries that can enforce textures zero can also enforce a more general type of conditions f(mij) = 0 with f some function of the matrix elements mij. In this case m can have all entries non-vanishing with no reduction in its predictive power. We classify all generation-dependent U(1) symmetries which, in the presence of two leptonic Higgs doublets, can reduce the number of independent high-energy parameters of type-I seesaw to the minimum number compatible with non-vanishing neutrino mixings and CP violation. These symmetries are broken above the scale where the effective operator is generated and can thus remain covert, in the sense that no explicit evidence of the symmetry can be read off the neutrino mass matrix, and different symmetries can give rise to the same low-energy structure. We find that only two cases are viable: one yields a structure with two zero-textures already considered in the literature, the other has no zero-textures and has never been considered before. It predicts normal ordering, a lightest neutrino mass ∼ 10 meV, a Dirac phase δ ∼ $$ \frac{3\pi }{2} $$

3
π

2

and definite values for the Majorana phases.
Birational geometry of moduli spaces of stable objects on Enriques surfaces
Authors: Beckmann Thorsten
Published: February 2020

Using wall-crossing for K3 surfaces, we establish birational equivalence of moduli spaces of stable objects on generic Enriques surfaces for different stability conditions. As an application, we prove in the case of a Mukai vector of odd rank that they are birational to Hilbert schemes. The argument makes use of a new Chow-theoretic result, showing that moduli spaces on an Enriques surface give rise to constant cycle subvarieties of the moduli spaces of the covering K3.
Interplay Between Loewner and Dirichlet Energies via Conformal Welding and Flow-Lines
Authors: Viklund Fredrik , Wang Yilin
Published: February 2020

The Loewner energy of a Jordan curve is the Dirichlet energy of its Loewner driving term. It is finite if and only if the curve is a Weil–Petersson quasicircle. In this paper, we describe cutting and welding operations on finite Dirichlet energy functions defined in the plane, allowing expression of the Loewner energy in terms of Dirichlet energy dissipation. We show that the Loewner energy of a unit vector field flow-line is equal to the Dirichlet energy of the harmonically extended winding. We also give an identity involving a complex-valued function of finite Dirichlet energy that expresses the welding and flow-line identities simultaneously. As applications, we prove that arclength isometric welding of two domains is sub-additive in the energy, and that the energy of equipotentials in a simply connected domain is monotone. Our main identities can be viewed as action functional analogs of both the welding and flow-line couplings of Schramm–Loewner evolution curves with the Gaussian free field.
Optimal isoperimetric inequalities for surfaces in any codimension in Cartan-Hadamard manifolds
Authors: Schulze Felix
Published: February 2020

Let$$(M^n,g)$$(Mn,g)be simply connected, complete, with non-positive sectional curvatures, and$$\Sigma $$Σa 2-dimensional closed integral current (or flat chain mod 2) with compact support inM. LetSbe an area minimising integral 3-current (resp. flat chain mod 2) such that$$\partial S = \Sigma $$∂S=Σ. We use a weak mean curvature flow, obtained via elliptic regularisation, starting from$$\Sigma $$Σ, to show that S satisfies the optimal Euclidean isoperimetric inequality:$$ 6 \sqrt{\pi }\, \mathbf {M}[S] \le (\mathbf {M}[\Sigma ])^{3/2} $$6πM[S]≤(M[Σ])3/2. We also obtain an optimal estimate in case the sectional curvatures of M are bounded from above by$$-\kappa < 0$$-κ<0and characterise the case of equality. The proof follows from an almost monotonicity of a suitable isoperimetric difference along the approximating flows in one dimension higher and an optimal estimate for the Willmore energy of a 2-dimensional integral varifold with first variation summable in$$L^2$$L2.
Ein Botaniker in der Papiergeschichte: Offene und geschlossene Kooperationen in den Wissenschaften um 1900
Authors: Musil-Gutsch Josephine , Nickelsen Kärin
Published: February 2020

Die Studie analysiert die Dynamik wissenschaftlicher Kooperation zwischen Natur- und Geisteswissenschaften an einem Beispiel aus der historischen Papierforschung in Wien um 1900. Im Mittelpunkt steht der Wiener Pflanzenphysiologe Julius Wiesner (1838–1916), der ab 1884 (und bis 1911) mittelalterliche Papiermanuskripte unter dem Mikroskop prüfte. Dies erfolgte in produktiver Zusammenarbeit mit Paläographen, Archäologen und Orientalisten (Josef Karabacek, Marc Aurel Stein, Rudolf Hoernle). Der Aufsatz untersucht, warum dies gelang und wie die Zusammenarbeit sich entwickelte. Wir unterscheiden dabei zwei Formen der Kooperation: Während Wiesner anfangs nur reaktiv zuarbeitete, in einer „geschlossenen Kooperation“, trat er später in „offene Kooperationen“ ein, in der beide Parteien die Fragen definieren und geeignete Methoden entwickeln. Diese Form der Kooperation erwies sich als besonders erfolgreich – zugleich war sie besonders anspruchsvoll, denn neben fachlicher Expertise erforderte sie erhebliche „Integrationsexpertise“ (Andersen 2016). Dies wurde begünstigt durch die lokale Konstellation in einer Umbruchphase der historischen Hilfswissenschaften. Wiesner konnte seine Kenntnisse der technischen Mikroskopie einbringen und gewann ein genuines Interesse an den historischen Fragen, während die Geisteswissenschaftler bereit waren, sich naturwissenschaftlichen Verfahren gegenüber zu öffnen und Wiesner letztlich als Papierhistoriker eigenen Rechts anzuerkennen.
T1-Weighted Intensity Increase After a Single Administration of a Linear Gadolinium-Based Contrast Agent in Multiple Sclerosis
Authors: Grahl S. , Bussas M. , Pongratz V. , Kirschke J. S. , Zimmer C. , Berthele A. , Hemmer B. , Mühlau M.
Published: February 2020

Purpose

Through analysis of T1-weighted (T1w) images this study investigated gadolinium (Gd) deposition in the brain after administration of a linear (gadopentetic acid) and a cyclic (gadoteric acid) gadolinium-based contrast agent (GBCA) in patients with multiple sclerosis (MS), a disorder frequently requiring magnetic resonance imaging (MRI) scans over years.

Methods

A total of 3233 T1w images (unenhanced with respect to the same scanning session) of 881 MS patients were retrospectively analyzed. After spatial normalization and intensity scaling using a sphere within the pons, differences of all pairs of subsequent scans were calculated and attributed to either linear (n = 2718) or cyclic (n = 385) or no GBCA (n = 130) according to the first scan. Regional analyses were performed, focusing on the dentate nucleus, and whole brain analyses. By 1‑sample t‑tests, signal intensity increases within conditions were searched for; conditions were compared by 2‑sample t‑tests. Furthermore, recent hypotheses on the reversibility of GBCA deposition were tested.

Results

In the dentate nucleus, a significant increase was observed only after administration of linear GBCA even after a single GBCA administration. This increase differed significantly (p < 0.001) from the other conditions (cyclic and no GBCA). Whole brain analyses revealed T1w signal increases only after administration of linear GBCA within two regions, the dentate nucleus and globus pallidus. Additional analyses did not indicate any decline of Gd deposition in the brain.

Conclusion

The data point towards Gd deposition in the brain after administration of linear GBCA even after a single administration.
Efficacy of a certified modular ultrasound curriculum
Authors: Tomasi R. , Stark K. , Scheiermann P.
Published: February 2020

Background

In recent years, ultrasound (US) has become more incorporated into anesthesia and intensive care medicine. The German Anesthesia Society established a modular curriculum to teach US skills. Until now, the efficacy of this modular curriculum has not been validated.

Objective

The main objective of this study was to determine whether there is an increase of knowledge and of psychomotor skills for the trainees in this curriculum.

Material and methods

After ethical committee approval, 41 anesthesia physicians were enrolled. To determine the increase of knowledge and of practical skills theoretical and practical tests performed were evaluated before and after two different US courses.

Results

Comparing before and after course tests, the participants showed significant improvement in theoretical multiple choice tests (p = 0.008). Regarding psychomotor skills following course 1, the trainees improved significantly in the time needed to perform the two practical tests (p = 0.03), but not in the performance of the test. Better needle visualization during simulated US-guided vessel puncture (p = 0.52) and better identification of the anatomical structures in the axillary region (p = 0.56) could not be achieved.

Conclusion

This study shows that although this US course curriculum has positively enhanced the trainees’ theoretical knowledge of US practice, it does not enhance the practical application of that theoretical knowledge. To improve this curriculum, a supervised clinically practical training should follow the course.
Ist die Fachrichtung assoziiert mit der Selbstsicherheit im Umgang mit rationaler Antibiotikaverordnung?
Authors: Schneider F. , Schulz C. M. , May M. , Schneider G. , Jacob M. , Mutlak H. , Pawlik M. , Zoller M. , Kretzschmar M. , Koch C. , Kees M. G. , Burger M. , Lebentrau S. , Novotny A. , Hübler M. , Koch T. , Heim M.
Published: February 2020

Hintergrund

Vor dem Hintergrund einer stetig zunehmenden Gesundheitsgefährdung durch multiresistente Erreger spielt neben der Bevölkerungsaufklärung, der Fachkenntnis und der Fortbildung der Ärztinnen und Ärzte auch deren Selbstsicherheit eine Schlüsselrolle in der klinischen Entscheidungsfindung.

Ziel der Arbeit

Die Analyse soll den Einfluss der Fachrichtung auf Unterschiede der Selbstsicherheit im Umgang mit Antibiotika und in der Selbsteinschätzung des eigenen Wissens untersuchen.

Methodik

Im Jahr 2015 wurden 1061 Ärztinnen und Ärzte der Fachrichtungen Innere Medizin, Allgemeinchirurgie, Gynäkologie und Urologie mithilfe des MR2 (Multiinstitutional Reconnaissance of practice with MultiResistant bacteria)-Surveys über ihre Einstellung und ihr Wissen zu Antibiotika und multiresistenten Erregern befragt. Ein ähnlicher Fragebogen wurde 2017 an 1268 Ärzte der Anästhesiologie versendet. Es wurden vier Fragen zur eigenen Sicherheit in der Anwendung von Antibiotika und elf Fragen zur Einschätzung des eigenen Wissens über multiresistente Erreger und rationale Antibiotikatherapie ausgewertet. Der Einfluss der Fachrichtung auf diese Items wurde mittels einer logistischen Regressionsanalyse, eines „chi square tests“ und des Kruskal-Wallis-Tests untersucht.

Ergebnisse

Die Rücklaufquoten betrugen 43 % (456/1061) und 56 % (705/1268). Im Jahr vor der Umfrage haben 44 % der Nicht-Anästhesisten und 57 % der Anästhesisten keine Fortbildung zu Inhalten des Antibiotic Stewardships besucht. Im Hinblick auf die Selbstsicherheit im Umgang mit Antibiotika zeigten sich Anästhesisten (Mittelwert ± Standardabweichung: 2,53±0,54) signifikant unsicherer als ihre Kollegen (Innere Medizin: 3,10±0,50; Chirurgie: 2,97±0,44; Gynäkologie: 3,12±0,42; Urologie: 3,15±0,44); dies gilt sowohl für die nicht-adjustierten (alle p<0,001), als auch die adjustierten Vergleiche. Ähnliche Ergebnisse zeigten sich für die Selbsteinschätzung des eigenen Wissens. Facharztstatus und der Besuch von infektiologischen Fortbildungen waren signifikant mit einem besseren Selbstbewusstsein als auch einer höheren Selbsteinschätzung des eigenen Wissens assoziiert.

Schlussfolgerungen

Anästhesisten zeigten eine signifikant geringere Selbstsicherheit im Umgang mit Antibiotika als ihre Kollegen aus anderen Fachrichtungen. Fortbildungen zur rationalen Verordnung von Antibiotika waren mit einer höheren Handlungssicherheit assoziiert, so dass eine Verankerung in den jeweiligen Weiterbildungsinhalten zu diskutieren ist.
Early childhood and adolescent risk factors for psychotic depression in a general population birth cohort sample
Authors: Nietola Miika , Huovinen Hanna , Heiskala Anni , Nordström Tanja , Miettunen Jouko , Korkeila Jyrki , Jääskeläinen Erika
Published: February 2020

Background and purpose

In the group of severe mental disorders, psychotic depression (PD) is essentially under-researched. Knowledge about the risk factors is scarce and this applies especially to early risk factors. Our aim was to study early childhood and adolescent risk factors of PD in a representative birth cohort sample with a follow-up of up to 50 years.

Methods

The study was carried out using the Northern Finland Birth Cohort 1966 (NFBC 1966). We used non-psychotic depression (NPD) (n = 746), schizophrenia (SZ) (n = 195), psychotic bipolar disorder (PBD) (n = 27), other psychoses (PNOS) (n = 136) and healthy controls (HC) (n = 8200) as comparison groups for PD (n = 58). We analysed several potential early risk factors from time of birth until the age of 16 years.

Results

The main finding was that parents’ psychiatric illness [HR 3.59 (1.84–7.04)] was a risk factor and a high sports grade in school was a protective factor [HR 0.29 (0.11–0.73)] for PD also after adjusting for covariates in the multivariate Cox regression model. Parental psychotic illness was an especially strong risk factor for PD. The PD subjects had a parent with psychiatric illness significantly more often (p < 0.05) than NPD subjects. Differences between PD and other disorder groups were otherwise small.

Conclusions

A low sports grade in school may be a risk factor for PD. Psychiatric illnesses, especially psychoses, are common in the parents of PD subjects. A surprisingly low number of statistically significant risk factors may have resulted from the size of the PD sample and the underlying heterogeneity of the etiology of PD.
Characterizing sustainability in discrete time
Authors: Asheim Geir B. , Mitra Tapan
Published: February 2020

We examine the investment rule that must be satisfied by an efficient and egalitarian path in a discrete-time version of the Dasgupta–Heal–Solow model of capital accumulation and resource depletion. In the discrete-time model, competitive valuation of net investments in terms of early and late pricing differs. We redefine Hartwick’s rule to require zero value of net investments at a valuation rule intermediate between these two. Using this definition, we show that along an efficient and egalitarian path, Hartwick’s rule is followed in all time periods. We thereby establish the converse of Hartwick’s result in discrete time, and we do so under weaker assumptions than those in the existing literature on how output varies as a function of capital and resource use. Our redefinition of Hartwick’s rule follows naturally if discrete time is viewed as providing information at discrete points in time of an underlying continuous-time process.
MOG encephalomyelitis: distinct clinical, MRI and CSF features in patients with longitudinal extensive transverse myelitis as first clinical presentation
Authors: Loos Julia , Pfeuffer Steffen , Pape Katrin , Ruck Tobias , Luessi Felix , Spreer Annette , Zipp Frauke , Meuth Sven G. , Bittner Stefan
Published: February 2020

Background

Based on clinical, immunological and histopathological evidence, MOG-IgG-associated encephalomyelitis (MOG-EM) has emerged as a distinct disease entity different from multiple sclerosis (MS) and aquaporin-4-antibody-positive neuromyelitis optica spectrum disorder (NMOSD). MOG-EM is associated with a broader clinical phenotype including optic neuritis, myelitis, brainstem lesions and acute disseminated encephalomyelitis with a substantial clinical and radiological overlap to other demyelinating CNS disorders.

Objective

To evaluate common clinical, MRI and CSF findings, as well as therapy responses in patients with longitudinal extensive transverse myelitis (LETM) as initial clinical presentation of MOG-EM.

Methods

After excluding patients with a known diagnosis of MS, we identified 153 patients with myelitis of which 7 fulfilled the inclusion criteria and were investigated for MRI, CSF and clinical parameters.

Results

Patients with LETM as first clinical presentation of MOG-EM display similar characteristics, namely a lack of gadolinium-enhancement in spinal cord MRI, marked pleocytosis, negative oligoclonal bands, a previous history of infections/vaccinations and response to antibody-depleting treatments for acute attacks and long-term treatment.

Conclusions

We identify common pathological findings in patients with LETM as first clinical presentation of MOG-EM which distinguishes it from other forms of LETM and should lead to testing for MOG-IgG in these cases.
Restoration of MARCK enhances chemosensitivity in cancer
Authors: Wenzel Tim , Büch Thomas , Urban Nicole , Weirauch Ulrike , Schierle Katrin , Aigner Achim , Schaefer Michael , Kalwa Hermann
Published: February 2020

Purpose

Increased ATP-binding-cassette (ABC) transporter activity is a major cause of chemotherapy resistance in cancer. The ABC transporter family member ABCB1 is often overexpressed in colorectal cancer (CRC). Phosphatidylinositol-4,5-bisphosphat (PI(4,5)P2)-dependent pathways are involved in the regulation of ABCB1 function. The protein Myristoylated Alanine-Rich C-Kinase Substrate (MARCKS) is a pivotal regulator of PI(4,5)P2 and inactivated in many CRC cancers via genetic deletion or hyperphosphorylation. Therefore, MARCKS may critically impact ABCB1.

Methods

CRC samples as well as CRC cell lines were tested for a connection between MARCKS and ABCB1 via immunofluorescence and Western-blot analysis. ABCB1 function was studied via calcein influx assay under treatment with known ABCB1 inhibitors (verapamil, tariquidar) as well as the kinase inhibitor bosutinib. ABCB1 internalization and MARCKS translocation was analyzed via confocal microscopy exploiting the endocytosis inhibitors chlorpromazine and dynasore. Abundance of PI(4,5)P2 was monitored by intramolecular fluorescence resonance energy transfer (FRET). Reproductive cell survival was studied via colorimetric WST-1 and clonogenic assays in combination with exposure to the chemotherapeutics doxorubicin and 5-fuorouracil (5-FU).

Results

We found increased ABCB1 expression in MARCKS negative CRC patient tumor samples and established CRC cell lines. Mechanistically, the reconstitution of MARCKS function via recombinant expression or the pharmacological inhibition of MARCKS phosphorylation led to a substantial decrease in ABCB1 activity. In CRC cells, bosutinib treatment resulted in a MARCKS translocation from the cytosol to the plasma membrane, while simultaneously, ABCB1 was relocated to intracellular compartments. Inhibition of MARCKS phosphorylation via bosutinib rendered cells more sensitive to the chemotherapeutics doxorubicin and 5-FU.

Conclusions

Cells devoid of MARCKS function showed incomplete ABCB1 internalization, leading to higher ABCB1 activity enhancing chemoresistance. Vice versa our data suggest the prevention of MARCKS inhibition by reversing hyperphosphorylation or genomic restoration after deletion as two promising approaches to overcome tumor cell resistance towards chemotherapeutic ABCB1 substrates.
Two novel cases further expand the phenotype of TOR1AIP1-associated nuclear envelopathies
Authors: Lessel Ivana , Chen Mei-Jan , Lüttgen Sabine , Arndt Florian , Fuchs Sigrid , Meien Stefanie , Thiele Holger , Jones Julie R. , Shaw Brandon R. , Crossman David K. , Nürnberg Peter , Korf Bruce R. , Kubisch Christian , Lessel Davor
Published: February 2020

Biallelic variants in TOR1AIP1, encoding the integral nuclear membrane protein LAP1 (lamina-associated polypeptide 1) with two functional isoforms LAP1B and LAP1C, have initially been linked to muscular dystrophies with variable cardiac and neurological impairment. Furthermore, a recurrent homozygous nonsense alteration, resulting in loss of both LAP1 isoforms, was identified in seven likely related individuals affected by multisystem anomalies with progeroid-like appearance and lethality within the 1st decade of life. Here, we have identified compound heterozygosity in TOR1AIP1 affecting both LAP1 isoforms in two unrelated individuals affected by congenital bilateral hearing loss, ventricular septal defect, bilateral cataracts, mild to moderate developmental delay, microcephaly, mandibular hypoplasia, short stature, progressive muscular atrophy, joint contractures and severe chronic heart failure, with much longer survival. Cellular characterization of primary fibroblasts of one affected individual revealed absence of both LAP1B and LAP1C, constitutively low lamin A/C levels, aberrant nuclear morphology including nuclear cytoplasmic channels, and premature senescence, comparable to findings in other progeroid forms of nuclear envelopathies. We additionally observed an abnormal activation of the extracellular signal-regulated kinase 1/2 (ERK 1/2). Ectopic expression of wild-type TOR1AIP1 mitigated these cellular phenotypes, providing further evidence for the causal role of identified genetic variants. Altogether, we thus further expand the TOR1AIP1-associated phenotype by identifying individuals with biallelic loss-of-function variants who survived beyond the 1st decade of life and reveal novel molecular consequences underlying the TOR1AIP1-associated disorders.
Comparison of suicide risk and other outcomes among boys and girls who self-harm
Authors: Ohlis Anna , Bjureberg Johan , Lichtenstein Paul , D’Onofrio Brian M. , Fruzzetti Alan E. , Cederlöf Martin , Hellner Clara
Published: February 2020

Little is known about sex differences in outcomes of self-harm, and there are inconclusive results concerning the association between sex, self-harm, and suicide attempts. The aim of this study was to explore sex differences in outcomes of self-harm in adolescence. In this cohort study, all individuals (0–17 years) enrolled at the child- and adolescent mental health services (CAMHS) in Stockholm between 2001 and 2015 (N = 110,072) were followed in national registers from their last contact with the CAMHS, until end of 2015. Exposure was self-harm as reason for contact, outcome measures were: alcohol-/substance use disorder, psychiatric hospitalization, non-violent or violent crime, and suicide. Differences in outcomes rates between exposed versus unexposed males, and exposed versus unexposed females, were examined using Cox regressions, expressed as hazard ratios (HR) with 95% confidence intervals (CI). Median follow-up time was 5.8 years (Q1: 2.3 years; Q3: 9.7 years). Self-harm was documented in 2.2% (N = 1241) males and 8.7% (4716) females. Exposed individuals had higher HR for all outcomes as compared with unexposed individuals of their own sex. Exposed females had more pronounced risk for drug use disorder (HR 11.2; 95% CI 9.9–12.7) compared with exposed males (HR 6.5, 95% 5.2–8.0). Both males and females who had engaged in self-harm had elevated risks for future suicide. Adjusting for socio-economic status and age at start of follow-up only marginally affected the associations. Females and males with self-harm had similarly elevated risk for suicide, and self-harm was also an important risk marker for other adverse outcomes within both sexes.
Bayesian Beauty
Authors: Milano Silvia
Published: February 2020

The Sleeping Beauty problem has attracted considerable attention in the literature as a paradigmatic example of how self-locating uncertainty creates problems for the Bayesian principles of Conditionalization and Reflection. Furthermore, it is also thought to raise serious issues for diachronic Dutch Book arguments. I show that, contrary to what is commonly accepted, it is possible to represent the Sleeping Beauty problem within a standard Bayesian framework. Once the problem is correctly represented, the ‘thirder’ solution satisfies standard rationality principles, vindicating why it is not vulnerable to diachronic Dutch Book arguments. Moreover, the diachronic Dutch Books against the ‘halfer’ solutions fail to undermine the standard arguments for Conditionalization. The main upshot that emerges from my discussion is that the disagreement between different solutions does not challenge the applicability of Bayesian reasoning to centered settings, nor the commitment to Conditionalization, but is instead an instance of the familiar problem of choosing the priors.
Development of a Non-destructive Testing Method for Assessing Thermal Status of District Heating Pipes
Authors: Lidén H. P. , Adl-Zarrabi B.
Published: February 2020

Pre-insulated district heating (DH) pipes have been in use for more than 40 years. The thermal performance of these pipes decreases over time as a result of thermal and mechanical aging, which leads to higher heat energy losses. A non-destructive method based on a cooling method is under development for assessing the thermal performance of a DH network. The method utilizes the copper wire, which is already embedded in the polyurethane insulation for detection of water leakage, as a sensor for measuring the temperature at the position of the copper wire. The method involves a shutdown of a selected part of a network for less than 2 h and evaluating the cooling process by measuring the supply pipe temperature and the temperature of the copper wire. The method was applied in a DH network during heating season. The thermal conductivity calculated by the method [0.027 W/(m K)] was in good agreement with the reference value [0.026 W/(m K)]. The cooling of the network can be measured at a valve or at other more easily accessible steel parts. It was also shown that the method is applicable for DH networks without a copper wire. However, a temperature measurement is needed on the casing pipe.
A genome-wide association study on medulloblastoma
Authors:   The Cefalo Study Group, Dahlin Anna M. , Wibom Carl , Andersson Ulrika , Bybjerg-Grauholm Jonas , Deltour Isabelle , Hougaard David M. , Scheurer Michael E. , Lau Ching C. , McKean-Cowdin Roberta , Kennedy Rebekah J. , Hung Long T. , Yee Janis , Margol Ashley S. , Barrington-Trimis Jessica , Gauderman W. James , Feychting Maria , Schüz Joachim , Röösli Martin , Kjaerheim Kristina , Januszkiewicz-Lewandowska Danuta , Fichna Marta , Nowak Jerzy , Searles Nielsen Susan , Asgharzadeh Shahab , Mirabello Lisa , Hjalmars Ulf , Melin Beatrice
Published: February 2020

Introduction

Medulloblastoma is a malignant embryonal tumor of the cerebellum that occurs predominantly in children. To find germline genetic variants associated with medulloblastoma risk, we conducted a genome-wide association study (GWAS) including 244 medulloblastoma cases and 247 control subjects from Sweden and Denmark.

Methods

Genotyping was performed using Illumina BeadChips, and untyped variants were imputed using IMPUTE2.

Results

Fifty-nine variants in 11 loci were associated with increased medulloblastoma risk (p < 1 × 10–5), but none were statistically significant after adjusting for multiple testing (p < 5 × 10–8). Thirteen of these variants were genotyped, whereas 46 were imputed. Genotyped variants were further investigated in a validation study comprising 249 medulloblastoma cases and 629 control subjects. In the validation study, rs78021424 (18p11.23, PTPRM) was associated with medulloblastoma risk with OR in the same direction as in the discovery cohort (ORT = 1.59, pvalidation = 0.02). We also selected seven medulloblastoma predisposition genes for investigation using a candidate gene approach: APC, BRCA2, PALB2, PTCH1, SUFU, TP53, and GPR161. The strongest evidence for association was found for rs201458864 (PALB2, ORT = 3.76, p = 3.2 × 10–4) and rs79036813 (PTCH1, ORA = 0.42, p = 2.6 × 10–3).

Conclusion

The results of this study, including a novel potential medulloblastoma risk loci at 18p11.23, are suggestive but need further validation in independent cohorts.
Measurement of EHD Friction at Very High Contact Pressures
Authors: Zhang Jie , Spikes Hugh
Published: February 2020

EHD friction curves have been measured up to very high pressure (pmean = 5 GPa, pmax = 7.5 GPa) using a newly developed, rolling-sliding, ball on disc machine, the ETM. Six base fluids have been studied, spanning the API base oil categories Group I to Group V. At high pressures, thermal effects become substantial even at quite modest slide-roll ratios, and these must be considered when analysing friction measurements in terms of the underlying rheological properties of the oils. By comparing measurements from steel/steel and WC/WC ball and disc combinations with very different thermal conductivities, the use of thermal correction to derive isothermal friction curves has been validated. At relatively low pressures (mean pressure = 1 GPa), there are substantial differences between the EHD friction properties of the various API Group base oils, but as pressure is raised these diminish and the EHD friction coefficients of all the Groups approach a similar maximum value at a given temperature. EHD friction continues to be quite strongly temperature dependent even at very high pressure. As pressure is increased, EHD friction curves become progressively steeper, so that friction coefficients at very low slide-roll ratios (1 to 2% SRR) become several times greater at high than at low pressure. This has important practical implications for the efficiency of rolling element bearings at high pressures since these components normally operate in this SRR range. There is no evidence of any of the base oils reaching a limiting shear stress over the whole pressure and temperature range studied. Instead, shear stress continues to increase with log(strain rate) in accord with the Eyring-activated flow model up to very high pressures.
At what carbon price forest cutting should stop
Authors: Pukkala Timo
Published: February 2020

The carbon sink of boreal forests can be increased by paying forest landowners for carbon sequestration and taxing carbon releases. The aim of the study was to analyze the effect of carbon pricing on optimal forest management when forests are managed for maximal discounted benefits from timber production and carbon payments. A 0.5% random sample of all private forest stands of Finland was used in the analyses (48,842 stands). Calculations were performed for a 100-year time horizon. It was assumed that the carbon balance (difference between sequestrated carbon and released carbon) in the forest (trees and soil) or the carbon balance of forestry (trees, soil and wood-based products) was subsidized (positive balance) or taxed (negative balance) by 0, 50, 100 or 150 € t−1, corresponding to CO2 prices of 0, 13.6, 27.3 or 40.9 € t−1, respectively. The results showed that paying forest landowners 150 € t−1 of carbon sequestrated in forests would lead to the cessation of all cuttings everywhere in Finland for at least 100 years. In the northern part of the country, a carbon price of 100 € t−1 would be enough to make the no-cutting management economically optimal. A low carbon price had the highest relative impact (value of increased sequestration divided by the cost of carbon payments). The benefit/cost ratio of carbon subsidies was higher in the northern part of boreal zone than in the southern parts. Subsidizing within-forest carbon sequestration by 50 € t−1 would increase the carbon sequestration of Finnish forestry by 50%, ranging from 36% (south Finland) to 116% (north Finland). A payment of 100 € t−1 or more would increase carbon sequestration by 70%, which is nearly the maximum possible increase that can be obtained by carbon subsidies.
Understanding Computational Costs of Cellular-Level Brain Tissue Simulations Through Analytical Performance Models
Authors: Cremonesi Francesco , Schürmann Felix
Published: February 2020

Computational modeling and simulation have become essential tools in the quest to better understand the brain’s makeup and to decipher the causal interrelations of its components. The breadth of biochemical and biophysical processes and structures in the brain has led to the development of a large variety of model abstractions and specialized tools, often times requiring high performance computing resources for their timely execution. What has been missing so far was an in-depth analysis of the complexity of the computational kernels, hindering a systematic approach to identifying bottlenecks of algorithms and hardware. If whole brain models are to be achieved on emerging computer generations, models and simulation engines will have to be carefully co-designed for the intrinsic hardware tradeoffs. For the first time, we present a systematic exploration based on analytic performance modeling. We base our analysis on three in silico models, chosen as representative examples of the most widely employed modeling abstractions: current-based point neurons, conductance-based point neurons and conductance-based detailed neurons. We identify that the synaptic modeling formalism, i.e. current or conductance-based representation, and not the level of morphological detail, is the most significant factor in determining the properties of memory bandwidth saturation and shared-memory scaling of in silico models. Even though general purpose computing has, until now, largely been able to deliver high performance, we find that for all types of abstractions, network latency and memory bandwidth will become severe bottlenecks as the number of neurons to be simulated grows. By adapting and extending a performance modeling approach, we deliver a first characterization of the performance landscape of brain tissue simulations, allowing us to pinpoint current bottlenecks for state-of-the-art in silico models, and make projections for future hardware and software requirements.
Improving Prediction of Favourable Outcome After 6 Months in Patients with Severe Traumatic Brain Injury Using Physiological Cerebral Parameters in a Multivariable Logistic Regression Model
Authors: Bennis Frank C. , Teeuwen Bibi , Zeiler Frederick A. , Elting Jan Willem , van der Naalt Joukje , Bonizzi Pietro , Delhaas Tammo , Aries Marcel J.
Published: February 2020

Background/Objective

Current severe traumatic brain injury (TBI) outcome prediction models calculate the chance of unfavourable outcome after 6 months based on parameters measured at admission. We aimed to improve current models with the addition of continuously measured neuromonitoring data within the first 24 h after intensive care unit neuromonitoring.

Methods

Forty-five severe TBI patients with intracranial pressure/cerebral perfusion pressure monitoring from two teaching hospitals covering the period May 2012 to January 2019 were analysed. Fourteen high-frequency physiological parameters were selected over multiple time periods after the start of neuromonitoring (0–6 h, 0–12 h, 0–18 h, 0–24 h). Besides systemic physiological parameters and extended Corticosteroid Randomisation after Significant Head Injury (CRASH) score, we added estimates of (dynamic) cerebral volume, cerebral compliance and cerebrovascular pressure reactivity indices to the model. A logistic regression model was trained for each time period on selected parameters to predict outcome after 6 months. The parameters were selected using forward feature selection. Each model was validated by leave-one-out cross-validation.

Results

A logistic regression model using CRASH as the sole parameter resulted in an area under the curve (AUC) of 0.76. For each time period, an increased AUC was found using up to 5 additional parameters. The highest AUC (0.90) was found for the 0–6 h period using 5 parameters that describe mean arterial blood pressure and physiological cerebral indices.

Conclusions

Current TBI outcome prediction models can be improved by the addition of neuromonitoring bedside parameters measured continuously within the first 24 h after the start of neuromonitoring. As these factors might be modifiable by treatment during the admission, testing in a larger (multicenter) data set is warranted.
Sedimentation in a Rifted Basin: Insights from the Proterozoic Rajgarh Siliciclastics, Delhi Supergroup, Northeastern Rajasthan
Authors: Khanam Sadia , Quasim M. A. , Ahmad A. H. M. , Ghosh Sumit K.
Published: February 2020

The fining upward sequence of Proterozoic Rajgarh Formation mainly consists of feldspathic sandstone, quartzarenite, bands of shale and have a restricted lateral extent with variable palaeoflow pattern. Eight major lithofacies identified from this succession collectively indicate fluvial to marginal marine depositional set up. The Rajgarh quartzose to feldspatho-quartzose siliciclastics are fine- to coarse grained, poorly- to moderately sorted derived from a stable continental block provenance that deposited in a fault bounded graben. The deposition of the Rajgarh siliciclastics can be best explained by short transportation, high relief and fast sedimentation in rapidly subsiding fault-bounded basin and indicate radial slope and source located in the Dausa uplift in the east and banded gneissic complex (BGC) in the south and southeast.
Potential Use of Airborne Hyperspectral AVIRIS-NG Data for Mapping Proterozoic Metasediments in Banswara, India
Authors: Rani Komal , Guha Arindam , Kumar K. Vinod , Bhattacharya Bimal Kumar , Pradeep B.
Published: February 2020

Airborne Visible InfraRed Imaging Spectrometer – Next Generation (AVIRIS-NG) data with high spectral and spatial resolutions are used for mapping metasediments in parts of Banswara district, Rajasthan, India. The AVIRIS–NG image spectra of major metasedimentary rocks were compared with their respective laboratory spectra to identify few diagnostic spectral features or absorption features of the rocks. These spectral features were translated from laboratory to image and consistently present in the image spectra of these rocks across the area. After ensuring the persistency of absorption features from sample to image pixels, three AVIRIS – NG based spectral indices is proposed to delineate calcareous (dolomite), siliceous (quartzite) and argillaceous (phyllite) metasedimentary rocks. The index image composite was compared with the reference lithological map of Geological Survey of India and also was validated in the field. The study demonstrates the efficiency of AVIRIS – NG data for mapping metasedimentary units from the Aravalli Supergroup that are known to host strata bound mineral deposits.