bluuebunny/crossref_metadata_2025_split huggingface dataset:
A way to thioacetate esters compatible with non-oxidative prebiotic conditions
Authors: Leqraa Naoual , Nicolet Yvain , Milet Anne , Vallée Yannick 
Published: September 2020

AbstractThe centrality of pyruvate oxidative decarboxylation into acetyl-CoA in current biochemistry is a strong argument for proposing that a similar reaction have been necessary for the development of an effective protometabolism on the primitive Earth. However, such a decarboxylation requires the use of an oxidant and a catalyst, today enzymatic. Based on the mechanisms of the pyruvate dehydrogenase complex and pyruvate-ferredoxin oxidoreductase, we propose that the initial mechanism involved disulfides and occurred via radicals. A first disulfide is obtained by reacting glyoxylate with hydrogen sulfide. It is then possible to produce a wide variety of other disulfides by exchange reactions. When reacted with pyruvate under UV light they give thioesters. This process requires no oxidant and is therefore compatible with what is known of the redox conditions of the early Earth. Neither does it require any catalyst. It could be the first way to acetyl thioesters, a way that was later improved by the introduction of catalysts, first minerals, then enzymes.
Repeatability and reproducibility of post-mortem central corneal thickness measurements using a portable optical coherence tomography system in humans: a prospective multicenter study
Authors: Napoli Pietro Emanuele , Nioi Matteo , Gabiati Letizia , Laurenzo Michela , De-Giorgio Fabio , Scorcia Vincenzo , Grassi Simone , d’Aloja Ernesto , Fossarello Maurizio 
Published: September 2020

AbstractTo assess the repeatability and reproducibility of post-mortem central corneal thickness (CCT) measurements made by the portable iVue spectra-domain (SD) optical coherence tomography OCT (Optovue Inc, Fremont, CA) system in humans, and to prospectively establish the time-course of CCT after death. In a prospective multicenter setting, CCT measurements were obtained from 58 human eyes at the following 16 time-points after death: immediately (within 2 h), and at each hour by the next 17 h. The range of CCT values for each subject was determined and longitudinal data were used to illustrate the variation in open and close eye mode. All measurements were made by two independent and well-trained examiners for session. Main outcome measures were intraclass correlation coefficients (ICC), repeatability and reproducibility coefficients, and coefficients of variation of the average central (0–2 mm). Overall, a total of 5,568 OCT measurements were performed by examiners. The repeatability coefficient varied from 0.3 to 1.7% and the reproducibility coefficient varied from 0.3 to 1.6% throughout the entire experimental time frame. Furthermore, the values of the different ICCs were also high during the different postmortem intervals, thus demonstrating the excellent repeatability and reproducibility of the present OCT approach. When CCT measurements were analyzed longitudinally, corneal thickness showed different behavior based on the open or close eye mode. The present study demonstrates that portable OCT imaging can be reliably used for corneal pachymetric measurements in supine subjects and during the post mortem period, i.e. without visual fixation and normal physiology/architecture of examined tissues.
Large-scale pan-cancer analysis reveals broad prognostic association between TGF-β ligands, not Hedgehog, and GLI1/2 expression in tumors
Authors: de Reyniès Aurélien , Javelaud Delphine , Elarouci Nabila , Marsaud Véronique , Gilbert Cristèle , Mauviel Alain 
Published: September 2020

AbstractGLI1 expression is broadly accepted as a marker of Hedgehog pathway activation in tumors. Efficacy of Hedgehog inhibitors is essentially limited to tumors bearing activating mutations of the pathway. GLI2, a critical Hedgehog effector, is necessary for GLI1 expression and is a direct transcriptional target of TGF-β/SMAD signaling. We examined the expression correlations of GLI1/2 with TGFB and HH genes in 152 distinct transcriptome datasets totaling over 23,500 patients and representing 37 types of neoplasms. Their prognostic value was measured in over 15,000 clinically annotated tumor samples from 26 tumor types. In most tumor types, GLI1 and GLI2 follow a similar pattern of expression and are equally correlated with HH and TGFB genes. However, GLI1/2 broadly share prognostic value with TGFB genes and a mesenchymal/EMT signature, not with HH genes. Our results provide a likely explanation for the frequent failure of anti-Hedgehog therapies in tumors, as they suggest a key role for TGF-β, not Hedgehog, ligands, in tumors with elevated GLI1/2-expression.
Chemical composition of material extractives influences microbial growth and dynamics on wetted wood materials
Authors: Zhao Dan , Cardona Cesar , Gottel Neil , Winton Valerie J. , Thomas Paul M. , Raba Daniel A. , Kelley Scott T. , Henry Christopher , Gilbert Jack A. , Stephens Brent 
Published: September 2020

AbstractThe impact of material chemical composition on microbial growth on building materials remains relatively poorly understood. We investigate the influence of the chemical composition of material extractives on microbial growth and community dynamics on 30 different wood species that were naturally inoculated, wetted, and held at high humidity for several weeks. Microbial growth was assessed by visual assessment and molecular sequencing. Unwetted material powders and microbial swab samples were analyzed using reverse phase liquid chromatography with tandem mass spectrometry. Different wood species demonstrated varying susceptibility to microbial growth after 3 weeks and visible coverage and fungal qPCR concentrations were correlated (R2 = 0.55). Aspergillaceae was most abundant across all samples; Meruliaceae was more prevalent on 8 materials with the highest visible microbial growth. A larger and more diverse set of compounds was detected from the wood shavings compared to the microbial swabs, indicating a complex and heterogeneous chemical composition within wood types. Several individual compounds putatively identified in wood samples showed statistically significant, near-monotonic associations with microbial growth, including C11H16O4, C18H34O4, and C6H15NO. A pilot experiment confirmed the inhibitory effects of dosing a sample of wood materials with varying concentrations of liquid C6H15NO (assuming it presented as Diethylethanolamine).
Rapid optimisation of fragments and hits to lead compounds from screening of crude reaction mixtures
Authors: Baker Lisa M. , Aimon Anthony , Murray James B. , Surgenor Allan E. , Matassova Natalia , Roughley Stephen D. , Collins Patrick M. , Krojer Tobias , von Delft Frank , Hubbard Roderick E. 
Published: September 2020

AbstractFragment based methods are now widely used to identify starting points in drug discovery and generation of tools for chemical biology. A significant challenge is optimization of these weak binding fragments to hit and lead compounds. We have developed an approach where individual reaction mixtures of analogues of hits can be evaluated without purification of the product. Here, we describe experiments to optimise the processes and then assess such mixtures in the high throughput crystal structure determination facility, XChem. Diffraction data for crystals of the proteins Hsp90 and PDHK2 soaked individually with 83 crude reaction mixtures are analysed manually or with the automated XChem procedures. The results of structural analysis are compared with binding measurements from other biophysical techniques. This approach can transform early hit to lead optimisation and the lessons learnt from this study provide a protocol that can be used by the community.
Enzymatic kinetic resolution of desmethylphosphinothricin indicates that phosphinic group is a bioisostere of carboxyl group
Authors: De Biase Daniela , Cappadocio Francesca , Pennacchietti Eugenia , Giovannercole Fabio , Coluccia Antonio , Vepsäläinen Jouko , Khomutov Alex 
Published: September 2020

AbstractEscherichia coli glutamate decarboxylase (EcGadB), a pyridoxal 5’-phosphate (PLP)-dependent enzyme, is highly specific for L-glutamate and was demonstrated to be effectively immobilised for the production of γ-aminobutyric acid (GABA), its decarboxylation product. Herein we show that EcGadB quantitatively decarboxylates the L-isomer of D,L-2-amino-4-(hydroxyphosphinyl)butyric acid (D,L-Glu-γ-PH), a phosphinic analogue of glutamate containing C-P-H bonds. This yields 3-aminopropylphosphinic acid (GABA-PH), a known GABAB receptor agonist and provides previously unknown D-Glu-γ-PH, allowing us to demonstrate that L-Glu-γ-PH, but not D-Glu-γ-PH, is responsible for D,L-Glu-γ-PH antibacterial activity. Furthermore, using GABase, a preparation of GABA-transaminase and succinic semialdehyde dehydrogenase, we show that GABA-PH is converted to 3-(hydroxyphosphinyl)propionic acid (Succinate-PH). Hence, PLP-dependent and NADP+-dependent enzymes are herein shown to recognise and metabolise phosphinic compounds, leaving unaffected the P-H bond. We therefore suggest that the phosphinic group is a bioisostere of the carboxyl group and the metabolic transformations of phosphinic compounds may offer a ground for prodrug design.
El Niño/Southern Oscillation response to low-latitude volcanic eruptions depends on ocean pre-conditions and eruption timing
Authors: Predybaylo Evgeniya , Stenchikov Georgiy , Wittenberg Andrew T. , Osipov Sergey 
Published: September 2020

AbstractProxy-based reconstructions of the past suggest that the Pacific ocean has often shown El Niño-like warming after low-latitude volcanic eruptions, while climate model simulations have suggested diverse responses. Here we present simulations from a coupled ocean–atmosphere model that illuminate the roles of ocean preconditioning, eruption magnitude and timing, and air–sea feedbacks in the El Niño/Southern Oscillation (ENSO) response to these eruptions. A deterministic component of the response, which dominates for boreal summer eruptions, leads to cooler tropical Pacific sea surface temperatures in the eruption year and El Niño-like warming the following year. A stochastic component is also important, especially for boreal winter eruptions. The simulated ENSO response depends nonlinearly on the eruption magnitude and the tropical Pacific conditions before the eruption. We conclude that adequate sampling is critical to accurately assess the ENSO responses in both models and observations.
Vertical GaN MISFET for chip‐on‐chip high speed laser driving applications
Authors: Bahat Treidel E. , Christopher H. , Hilt O. , Klehr A. , Ginolas A. , Liero A. , Würfl J. 
Published: September 2020

In this work, the authors developed vertical gallium nitride metal‐insulator‐semiconductor field‐effect transistors (GaN MISFETs) for direct chip‐on‐chip assembly with gallium arsenide‐based broad area distributed Bragg reflector diode laser. The intention of this work had been to provide a high‐speed driver solution having extremely small parasitic inductive loops. It is shown that devices manufactured on ammonothermal substrates have large conduction current density above 1.7 kA/cm2, specific on‐state resistance as low as 2.1 mΩ·cm2 and on‐state sheet resistance of 18.6 Ω·mm. It is further shown that scaling these devices to large gate periphery chips is possible. Finally, a low inductance vertical GaN MISFET on laser diode integration assembly is realised on an AlN ceramic board using a transistor chip with 142 mm gate width and 305 mΩ on‐state resistance. The arrangement enables 3.6 ns laser pulses at an emission wavelength at 904 nm and a peak optical power of 4 W.
OFDM joint communication–radar with leaky‐wave antennas
Authors: Steeg M. , Exner F. , Tebart J. , Czylwik A. , Stöhr A. 
Published: September 2020

In this Letter, the authors report on a 26 GHz joint communication–radar system. By exploiting the beam steering features of leaky‐wave antennas, angle‐of‐arrival estimation and multi‐user transmission are achieved. Furthermore, the Zadoff–Chu preamble of the OFDM waveform is used to provide a frequency‐modulated continuous‐wave radar signal. This way, the wide operational bandwidth is used for both, communications and radar, yielding high data throughput and precise user localisation. Experimentally, spectral‐efficient 16‐QAM multi‐user 5 × 4 Gbit/s communications and user localisation with an accuracy of about 2 cm and ±1.5° is demonstrated.
Wide locking range frequency tripler based on a dual‐band VCO
Authors: Zhou H.F. , Shum K.M. , Chan C.H. 
Published: September 2020

A wide locking range (LR) injection locked frequency tripler (ILFT) based on a dual‐band voltage controlled oscillator (VCO) is proposed in this Letter. By rationally designing the transformer parameters, the VCO can easily realise the adjacent dual‐band operating characteristics. The ILFT has dual LRs which can easily overlap each other at a fixed bias. A subharmonic signal is also injected through the transformer for frequency locking. A wide LR of 27.1% from 69 to 90.6 GHz at an injection power of 0 dBm is achieved whereas the tripler only consumes 5.88 mW under a 0.6 V supply voltage.
Compact wideband CMOS lumped‐element Wilkinson power divider with asymmetric negative capacitance circuit
Authors: Doan N.‐T. , Ngo T.‐B. , Yoon S.‐W. 
Published: September 2020

The authors developed a wideband on‐chip Wilkinson power divider (WPD) using lumped‐element transmission lines (LE TLs) with 2‐port negative capacitance (NCAP) circuits that provide the phase response with a positive slope and broadband port impedance. The bandwidth of the WPD was increased using the broadband quarter‐wavelength (λ /4) LE TLs with port‐matched NCAP circuits. The WPD was implemented in the Global Foundry 8SF 130‐nm RF CMOS IC technology. The size of the core chip is 1100 µm × 400 µm. The S‐parameter measurements showed an absolute bandwidth ranging between 0.76 and 1.6 GHz, and a fractional bandwidth of 71.2%. In the frequency range of the bandwidth, the insertion loss was 0.4–3.4 dB, with the isolation between the two output ports was >18 dB, and the noise figures were 11–12 dB. The input‐referred 1‐dB gain compression point at the frequency of 1 GHz was ‒6 dBm.
Giant planet formation at the pressure maxima of protoplanetary disks
Authors: Guilera Octavio Miguel , Sándor Zsolt , Ronco María Paula , Venturini Julia , Miller Bertolami Marcelo Miguel 
Published: September 2020

Context.Recent high-resolution observations of protoplanetary disks have revealed ring-like structures that can be associated to pressure maxima. Pressure maxima are known to be dust collectors and planet migration traps. The great majority of planet formation studies are based either on the pebble accretion model or on the planetesimal accretion model. However, recent studies proposed hybrid accretion of pebbles and planetesimals as a possible formation mechanism for Jupiter.Aims.We aim to study the full process of planet formation consisting of dust evolution, planetesimal formation, and planet growth at a pressure maximum in a protoplanetary disk.Methods.We compute, through numerical simulations, the gas and dust evolution in a protoplanetary disk, including dust growth, fragmentation, radial drift, and particle accumulation at a pressure maximum. The pressure maximum appears due to an assumed viscosity transition at the water ice line. We also consider the formation of planetesimals by streaming instability and the formation of a moon-size embryo that grows into a giant planet by the hybrid accretion of pebbles and planetesimals, all within the pressure maximum.Results.We find that the pressure maximum is an efficient collector of dust drifting inwards. The condition of planetesimal formation by streaming instability is fulfilled due to the large amount of dust accumulated at the pressure bump. Subsequently, a massive core is quickly formed (in ~104yr) by the accretion of pebbles. After the pebble isolation mass is reached, the growth of the core slowly continues by the accretion of planetesimals. The energy released by planetesimal accretion delays the onset of runaway gas accretion, allowing a gas giant to form after ~1 Myr of disk evolution. The pressure maximum also acts as a migration trap.Conclusions.Pressure maxima generated by a viscosity transition at the water ice line are preferential locations for dust traps, planetesimal formation by streaming instability, and planet migration traps. All these conditions allow the fast formation of a giant planet by the hybrid accretion of pebbles and planetesimals.
The role of small-scale surface motions in the transfer of twist to a solar jet from a remote stable flux rope
Authors: Joshi Reetika , Schmieder Brigitte , Aulanier Guillaume , Bommier Véronique , Chandra Ramesh 
Published: September 2020

Context. Jets often have a helical structure containing ejected plasma that is both hot and also cooler and denser than the corona. Various mechanisms have been proposed to explain how jets are triggered, primarily attributed to a magnetic reconnection between the emergence of magnetic flux and environment or that of twisted photospheric motions that bring the system into a state of instability.
Aims. Multi-wavelength observations of a twisted jet observed with the Atmospheric Imaging Assembly (AIA) onboard the Solar Dynamics Observatory and the Interface Region Imaging Spectrograph (IRIS) were used to understand how the twist was injected into the jet, thanks to the IRIS spectrographic slit fortuitously crossing the reconnection site at that time.
Methods. We followed the magnetic history of the active region based on the analysis of the Helioseismic and Magnetic Imager vector magnetic field computed with the UNNOFIT code. The nature and dynamics of the jet reconnection site are characterised by the IRIS spectra.
Results. This region is the result of the collapse of two emerging magnetic fluxes (EMFs) overlaid by arch filament systems that have been well-observed with AIA, IRIS, and the New Vacuum Solar Telescope in Hα. In the magnetic field maps, we found evidence of the pattern of a long sigmoidal flux rope (FR) along the polarity inversion line between the two EMFs, which is the site of the reconnection. Before the jet, an extension of the FR was present and a part of it was detached and formed a small bipole with a bald patch (BP) region, which dynamically became an X-current sheet over the dome of one EMF where the reconnection took place. At the time of the reconnection, the Mg II spectra exhibited a strong extension of the blue wing that is decreasing over a distance of 10 Mm (from −300 km s−1 to a few km s−1). This is the signature of the transfer of the twist to the jet.
Conclusions. A comparison with numerical magnetohydrodynamics simulations confirms the existence of the long FR. We conjecture that there is a transfer of twist to the jet during the extension of the FR to the reconnection site without FR eruption. The reconnection would start in the low atmosphere in the BP reconnection region and extend at an X-point along the current sheet formed above.
Perception of Inpatient Oncologic Rehabilitation in Children,
Adolescents and Young Adults Diagnosed with Cancer in
Switzerland
Authors: Otth Maria , Denzler Sibylle , Schmid Sibylle , Setz Birgitta , Scheinemann Katrin 
Published: September 2020

Abstract
Background Inpatient rehabilitation improves physical and psychosocial
performance in childhood cancer patients and their families. Two kinds of
inpatient rehabilitation are available in specialized institutions in Germany:
family-oriented rehabilitation or peer group-oriented rehabilitation for
adolescents and young adults (AYA). Our study aimed to find out what Swiss
childhood and AYA cancer patients and their families thought about the
rehabilitation programs in which they had participated.
Patients and methods We conducted a questionnaire-based, cross-sectional
study of Swiss childhood and AYA cancer patients and their families whose
inpatient rehabilitation stays were scheduled to take place in Germany between
May 2012 and March 2019. We analyzed the data descriptively and present our
findings in accordance with the STROBE statement.
Results Of the 57 eligible families contacted, 38 (67%)
responded. Most rated the rehabilitation stay as very good (68%) or good
(26%). Nearly all participants emphasized that these programs should be
available to all affected patients and their families. Most (80%)
thought the program gave them enough valuable information to enable them to cope
with daily life after the stay ended. Only one fifth (19%) of the
rehabilitation stays were fully funded by the health or disability
insurance.
Conclusion Participants expressed an overwhelmingly positive opinion
about the rehabilitation programs they attended. We are convinced that childhood
and AYA cancer patients and their families in Switzerland benefit from these
programs and encourage insurances to cover the costs.
Association of CEP72 rs924607 TT Genotype with Vincristine-induced
Peripheral Neuropathy Measured by Motor Nerve Conduction Studies
Authors: Kavčič Marko , Zečkanović Aida , Jazbec Janez , Debeljak Marusa 
Published: September 2020

IntroductionVincristine is at the core of many treatment protocols for childhood malignancies.
The major dose-limiting side effect is vincristine-induced peripheral neuropathy
(VIPN) which may cause morbidity and disrupt curative treatment. Several studies
have tried to identify pharmacogenetic biomarkers for susceptibility to
vincristine-induced toxicity (Egbelakin A et al., Pediatr Blood Cancer 2011;
56: 361–367. Aplenc R et al., Br J Haematol 2003; 122:
240–244. Diouf B et al., JAMA 2015; 313: 815–823. Zgheib NK
et al., Pharmacogenet Genomics, 2018; 28: 189–195. Gutierrez-Camino A
et al., Pharmacogenet Genomics 2016; 26: 100–102. Wright GE et al.,
Clin Pharmacol Ther 2019; 105: 402–410. Kayilioğlu H et
al., J Pediatr Hematol Oncol 2017; 39(6): 458–462). A major
limitation of these studies is that VIPN is difficult to measure objectively using
only clinical examination and clinical scales. This is especially true for children,
who are often unable to report or grade symptoms such as paresthesia, numbness, and
pain. Furthermore, some studies are questioning the validity of currently available
neuropathy grading scales (Postma TJ et al., Ann Oncol 1998; 9:
739–744). Our group recently showed that electrophysiological studies can be
used with great accuracy for early detection of VIPN (Kavcic M et al., J Pediatr
Hematol Oncol 2017; 39: 266–271). In the previous study, we found
that VIPN presents with primary axonal involvement and is more pronounced on motor
neurons (Kavcic M et al., J Pediatr Hematol Oncol 2017; 39:
266–271).