Exploring Inflammation and Stress as Biological Correlates of Symptoms in Children With Advanced Cancer: A Longitudinal Feasibility Study.

Background: Few studies have examined biomarkers of stress and inflammation as underlying mechanisms of symptoms in adolescents and young adults with cancer. This study determined the feasibility of collecting blood and saliva samples across time, described the range and distribution of biomarkers, and explored the association of biomarkers with symptom adverse events (AEs). Method: This longitudinal, prospective repeated-measures single-site feasibility study recruited N = 10 children (M = 12.5 years) receiving treatment for advanced cancer. Symptom AE data and inflammation (cytokines and C-reactive protein) and physiologic response to stress (salivary cortisol and salivary alpha-amylase) biomarker levels were collected at three time points. Descriptive statistics were used to examine feasibility and acceptability and to summarize symptom AE, stress, and inflammatory biomarker data. A linear regression model was used to determine cortisol diurnal slopes. The relationship between symptom and inflammatory biomarker data was explored and Hedges's g statistic was used to determine its effect size. Results: Participants provided 83% of saliva samples (n = 199/240) and 185 samples were sufficient to be analyzed. Nurses collected 97% (n = 29/30) of blood samples. Participants reported the saliva collection instructions, kits, and reminders were clear and helpful. Insomnia, pain, fatigue, and anxiety demonstrated the most medium and large negative effects with inflammatory markers. Symptom AEs demonstrated the highest number of medium and large negative effects with interleukin-8 and tumor necrosis factor-alpha (-0.53 to -2.00). Discussion: The results indicate longitudinal concurrent collection of symptom and biomarker data is feasible and inflammatory and stress biomarkers merit consideration for inclusion in future studies.

Evidence of superconducting Fermi arcs.

An essential ingredient for the production of Majorana fermions for use in quantum computing is topological superconductivity1,2. As bulk topological superconductors remain elusive, the most promising approaches exploit proximity-induced superconductivity3, making systems fragile and difficult to realize4-7. Due to their intrinsic topology8, Weyl semimetals are also potential candidates1,2, but have always been connected with bulk superconductivity, leaving the possibility of intrinsic superconductivity of their topological surface states, the Fermi arcs, practically without attention, even from the theory side. Here, by means of angle-resolved photoemission spectroscopy and ab initio calculations, we identify topological Fermi arcs on two opposing surfaces of the non-centrosymmetric Weyl material trigonal PtBi2 (ref. 9). We show these states become superconducting at temperatures around 10 K. Remarkably, the corresponding coherence peaks appear as the strongest and sharpest excitations ever detected by photoemission from solids. Our findings indicate that superconductivity in PtBi2 can occur exclusively at the surface, rendering it a possible platform to host Majorana modes in intrinsically topological superconductor-normal metal-superconductor Josephson junctions.

Development of non-sedating antischistosomal benzodiazepines.

The neglected tropical disease schistosomiasis infects over 200 million people worldwide and is treated with just one broad spectrum antiparasitic drug (praziquantel). Alternative drugs are needed in the event of emerging praziquantel resistance or treatment failure. One promising lead that has shown efficacy in animal models and a human clinical trial is the benzodiazepine meclonazepam, discovered by Roche in the 1970's. Meclonazepam was not brought to market because of dose-limiting sedative side effects. However, the human target of meclonazepam that causes sedation (GABAARs) are not orthologous to the parasite targets that cause worm death. Therefore, we were interested in whether the structure of meclonazepam could be modified to produce antiparasitic benzodiazepines that do not cause host sedation. We synthesized 18 meclonazepam derivatives with modifications at different positions on the benzodiazepine ring system and tested them for in vitro antiparasitic activity. This identified five compounds that progressed to in vivo screening in a murine model, two of which cured parasite infections with comparable potency to meclonazepam. When these two compounds were administered to mice that were run on the rotarod test, both were less sedating than meclonazepam. These findings demonstrate the proof of concept that meclonazepam analogs can be designed with an improved therapeutic index, and point to the C3 position of the benzodiazepine ring system as a logical site for further structure-activity exploration to further optimize this chemical series.

Tunable positions of Weyl nodes via magnetism and pressure in the ferromagnetic Weyl semimetal CeAlSi.

The noncentrosymmetric ferromagnetic Weyl semimetal CeAlSi with simultaneous space-inversion and time-reversal symmetry breaking provides a unique platform for exploring novel topological states. Here, by employing multiple experimental techniques, we demonstrate that ferromagnetism and pressure can serve as efficient parameters to tune the positions of Weyl nodes in CeAlSi. At ambient pressure, a magnetism-facilitated anomalous Hall/Nernst effect (AHE/ANE) is uncovered. Angle-resolved photoemission spectroscopy (ARPES) measurements demonstrated that the Weyl nodes with opposite chirality are moving away from each other upon entering the ferromagnetic phase. Under pressure, by tracing the pressure evolution of AHE and band structure, we demonstrate that pressure could also serve as a pivotal knob to tune the positions of Weyl nodes. Moreover, multiple pressure-induced phase transitions are also revealed. These findings indicate that CeAlSi provides a unique and tunable platform for exploring exotic topological physics and electron correlations, as well as catering to potential applications, such as spintronics.

Exploring protein-protein interactions and oligomerization state of pulmonary surfactant protein C (SP-C) through FRET and fluorescence self-quenching.

Pulmonary surfactant (PS) is a lipid-protein complex that forms films reducing surface tension at the alveolar air-liquid interface. Surfactant protein C (SP-C) plays a key role in rearranging the lipids at the PS surface layers during breathing. The N-terminal segment of SP-C, a lipopeptide of 35 amino acids, contains two palmitoylated cysteines, which affect the stability and structure of the molecule. The C-terminal region comprises a transmembrane α-helix that contains a ALLMG motif, supposedly analogous to a well-studied dimerization motif in glycophorin A. Previous studies have demonstrated the potential interaction between SP-C molecules using approaches such as Bimolecular Complementation assays or computational simulations. In this work, the oligomerization state of SP-C in membrane systems has been studied using fluorescence spectroscopy techniques. We have performed self-quenching and FRET assays to analyze dimerization of native palmitoylated SP-C and a non-palmitoylated recombinant version of SP-C (rSP-C) using fluorescently labeled versions of either protein reconstituted in different lipid systems mimicking pulmonary surfactant environments. Our results reveal that doubly palmitoylated native SP-C remains primarily monomeric. In contrast, non-palmitoylated recombinant SP-C exhibits dimerization, potentiated at high concentrations, especially in membranes with lipid phase separation. Therefore, palmitoylation could play a crucial role in stabilizing the monomeric α-helical conformation of SP-C. Depalmitoylation, high protein densities as a consequence of membrane compartmentalization, and other factors may all lead to the formation of protein dimers and higher-order oligomers, which could have functional implications under certain pathological conditions and contribute to membrane transformations associated with surfactant metabolism and alveolar homeostasis.

Development of Three-Layered Composite Color Converters for White LEDs Based on the Epitaxial Structures of YAG:Ce, TbAG:Ce and LuAG:Ce Garnets.

This work was dedicated to the development of novel types of composite phosphor converters of white LED, based on the epitaxial structures containing Y3Al5O12:Ce (YAG:Ce) and Tb3Al5O12:Ce (TbAG:Ce) single crystalline films, steeply grown, using the liquid-phase epitaxy method, onto LuAG:Ce single crystal substrates. The influence of Ce3+ concentration in the LuAG:Ce substrate, as well as the thickness of the subsequent YAG:Ce and TbAG:Ce films, on the luminescence and photoconversion properties of the three-layered composite converters were investigated. Compared to its traditional YAG:Ce counterpart, the developed composite converter demonstrates broadened emission bands, due to the compensation of the cyan-green dip by the additional LuAG:Ce substrate luminescence, along with yellow-orange luminescence from the YAG:Ce and TbAG:Ce films. Such a combination of emission bands from various crystalline garnet compounds allows the production of a wide emission spectrum of WLEDs. In turn, the variation in the thickness and activator concentration in each part of the composite converter allows the production of almost any shade from green to orange emission on the chromaticity diagram.

Single Crystalline Films of Ce3+-Doped Y3MgxSiyAl5-x-yO12 Garnets: Crystallization, Optical, and Photocurrent Properties.

This research focuses on LPE growth, and the examination of the optical and photovoltaic properties of single crystalline film (SCF) phosphors based on Ce3+-doped Y3MgxSiyAl5-x-yO12 garnets with Mg and Si contents in x = 0-0.345 and y = 0-0.31 ranges. The absorbance, luminescence, scintillation, and photocurrent properties of Y3MgxSiyAl5-x-yO12:Ce SCFs were examined in comparison with Y3Al5O12:Ce (YAG:Ce) counterpart. Especially prepared YAG:Ce SCFs with a low (x, y < 0.1) concentration of Mg2+ and Mg2+-Si4+ codopants also showed a photocurrent that increased with rising Mg2+ and Si4+ concentrations. Mg2+ excess was systematically present in as-grown Y3MgxSiyAl5-x-yO12:Ce SCFs. The as-grown SCFs of these garnets under the excitation of α-particles had a low light yield (LY) and a fast scintillation response with a decay time in the ns range due to producing the Ce4+ ions as compensators for the Mg2+ excess. The Ce4+ dopant recharged to the Ce3+ state after SCF annealing at T > 1000 °C in a reducing atmosphere (95%N2 + 5%H2). Annealed SCF samples exhibited an LY of around 42% and similar scintillation decay kinetics to those of the YAG:Ce SCF counterpart. The photoluminescence studies of Y3MgxSiyAl5-x-yO12:Ce SCFs provide evidence for Ce3+ multicenter formation and the presence of an energy transfer between various Ce3+ multicenters. The Ce3+ multicenters possessed variable crystal field strengths in the nonequivalent dodecahedral sites of the garnet host due to the substitution of the octahedral positions by Mg2+ and the tetrahedral positions by Si4+. In comparison with YAG:Ce SCF, the Ce3+ luminescence spectra of Y3MgxSiyAl5-x-yO12:Ce SCFs greatly expanded in the red region. Using these beneficial trends of changes in the optical and photocurrent properties of Y3MgxSiyAl5-x-yO12:Ce garnets as a result of Mg2+ and Si4+ alloying, a new generation of SCF converters for white LEDs, photovoltaics, and scintillators could be developed.

An Update on Eukaryotic Viruses Revived from Ancient Permafrost.

One quarter of the Northern hemisphere is underlain by permanently frozen ground, referred to as permafrost. Due to climate warming, irreversibly thawing permafrost is releasing organic matter frozen for up to a million years, most of which decomposes into carbon dioxide and methane, further enhancing the greenhouse effect. Part of this organic matter also consists of revived cellular microbes (prokaryotes, unicellular eukaryotes) as well as viruses that have remained dormant since prehistorical times. While the literature abounds on descriptions of the rich and diverse prokaryotic microbiomes found in permafrost, no additional report about "live" viruses have been published since the two original studies describing pithovirus (in 2014) and mollivirus (in 2015). This wrongly suggests that such occurrences are rare and that "zombie viruses" are not a public health threat. To restore an appreciation closer to reality, we report the preliminary characterizations of 13 new viruses isolated from seven different ancient Siberian permafrost samples, one from the Lena river and one from Kamchatka cryosol. As expected from the host specificity imposed by our protocol, these viruses belong to five different clades infecting Acanthamoeba spp. but not previously revived from permafrost: Pandoravirus, Cedratvirus, Megavirus, and Pacmanvirus, in addition to a new Pithovirus strain.

Ferromagnetic Layers in a Topological Insulator (Bi,Sb)2Te3 Crystal Doped with Mn.

Magnetic topological insulators (MTIs) have recently become a subject of poignant interest; among them, Z2 topological insulators with magnetic moment ordering caused by embedded magnetic atoms attract special attention. In such systems, the case of magnetic anisotropy perpendicular to the surface that holds a topologically nontrivial surface state is the most intriguing one. Such materials demonstrate the quantum anomalous Hall effect, which manifests itself as chiral edge conduction channels that can be manipulated by switching the polarization of magnetic domains. In the present paper, we uncover the atomic structure of the bulk and the surface of Mn0.06Sb1.22Bi0.78Te3.06 in conjunction with its electronic and magnetic properties; this material is characterized by naturally formed ferromagnetic layers inside the insulating matrix, where the Fermi level is tuned to the bulk band gap. We found that in such mixed crystals septuple layers (SLs) of Mn(Bi,Sb)2Te4 form structures that feature three SLs, each of which is separated by two or three (Bi,Sb)2Te3 quintuple layers (QLs); such a structure possesses ferromagnetic properties. The surface obtained by cleavage includes terraces with different terminations. Manganese atoms preferentially occupy the central positions in the SLs and in a very small proportion can appear in the QLs, as indirectly indicated by a reshaped Dirac cone.

Luminescent Carbon Dots from Wet Olive Pomace: Structural Insights, Photophysical Properties and Cytotoxicity.

Carbon nanomaterials endowed with significant luminescence have been synthesized for the first time from an abundant, highly localized waste, the wet pomace (WP), a semi-solid by-product of industrial olive oil production. Synthetic efforts were undertaken to outshine the photoluminescence (PL) of carbon nanoparticles through a systematic search of the best reaction conditions to convert the waste biomass, mainly consisting in holocellulose, lignin and proteins, into carbon dots (CDs) by hydrothermal carbonization processes. Blue-emitting CDs with high fluorescence quantum yields were obtained. Using a comprehensive set of spectroscopic tools (FTIR, Raman, XPS, and 1H/13C NMR) in combination with steady-state and time-resolved fluorescence spectroscopy, a rational depiction of WP-CDs structures and their PL properties was reached. WP-CDs show the up-conversion of PL capabilities and negligible cytotoxicity against two mammalian cell lines (L929 and HeLa). Both properties are excellent indicators for their prospective application in biological imaging, biosensing, and dynamic therapies driven by light.

Quantification of phosphatides in sunflower oils using a potentiometric e-tongue.

Consisting of two fatty acyl groups, phospholipids are a vital part of vegetable oils and the source of essential fatty acids. Moreover, phospholipids influence oxidative and flavor stability and color evolution of vegetable oils, and their quantification has a significant role in the quality assessment of oils. In this study, we proposed a new highly efficient, affordable, environmentally friendly, and simple approach for the evaluation of phospholipid concentrations based on potentiometric multisensor systems coupled with chemometric data processing. Support vector machines, partial least squares, and multiple linear regressions were used to predict phosphatide concentrations based on potentiometric multisensor system responses. Application of multivariate regression tools yielded the following root mean square errors of prediction: 0.005 mg/100 g of oil in the range 0.0-59.4 mg/100 g for refined oils; 0.008 mg/100 g in the range 0.0-100 mg/100 g for low phosphatide oils and 0.24 mg/100 g in the range 100-2270 mg/100 g for high phosphatide oils. This approach can be considered as a rapid and straightforward method to quantify the phosphatides in sunflower oils.

Electronic structure and low-temperature thermoelectric transport of TiCoSb single crystals.

Band structure engineering has a strong beneficial impact on thermoelectric performance, where theoretical methods dominate the investigation of electronic structures. Here, we use angle-resolved photoemission spectroscopy (ARPES) to analyze the electronic structure and report on the thermoelectric transport properties of half-Heusler TiCoSb high-quality single crystals. High degeneracy of the valence bands at the L and Γ band maximum points was observed, which provides a band-convergence scenario for the thermoelectric performance of TiCoSb. Previous efforts have shown how crystallographic defects play an important role in TiCoSb transport properties, while the intrinsic properties remain elusive. Using hard X-ray photoelectron spectroscopy (HAXPES), we discard the presence of interstitial defects that could induce in-gap states near the valence band in our crystals. Contrary to polycrystalline reports, intrinsic TiCoSb exhibits p-type transport, albeit defects still affect the carrier concentration. In two initially identical p-type TiCoSb crystal batches, distinct metallic and semiconductive behaviors were found owing to defects not noticeable by elemental analysis. A varying Seebeck effective mass is consistent with the change at the Fermi level within this band convergence picture. This report tackles the direct investigation of the electronic structure of TiCoSb and reveals new insights and the strong impact of point defects on the optimization of thermoelectric properties.

Fermi surface tomography.

Fermi surfaces are essential for predicting, characterizing and controlling the properties of crystalline metals and semiconductors. Angle-resolved photoemission spectroscopy (ARPES) is the only technique directly probing the Fermi surface by measuring the Fermi momenta (kF) from energy- and angular distribution of photoelectrons dislodged by monochromatic light. Existing apparatus is able to determine a number of kF -vectors simultaneously, but direct high-resolution 3D Fermi surface mapping remains problematic. As a result, no such datasets exist, strongly limiting our knowledge about the Fermi surfaces. Here we show that using a simpler instrumentation it is possible to perform 3D-mapping within a very short time interval and with very high resolution. We present the first detailed experimental 3D Fermi surface as well as other experimental results featuring advantages of our technique. In combination with various light sources our methodology and instrumentation offer new opportunities for high-resolution ARPES in the physical and life sciences.

Direct Spectroscopic Evidence of Magnetic Proximity Effect in MoS2 Monolayer on Graphene/Co.

A magnetic field modifies optical properties and provides valley splitting in a molybdenum disulfide (MoS2) monolayer. Here we demonstrate a scalable approach to the epitaxial synthesis of MoS2 monolayer on a magnetic graphene/Co system. Using spin- and angle-resolved photoemission spectroscopy we observe a magnetic proximity effect that causes a 20 meV spin-splitting at the Γ̅ point and canting of spins at the K̅ point in the valence band toward the in-plane direction of cobalt magnetization. Our density functional theory calculations reveal that the in-plane spin component at K̅ is localized on Co atoms in the valence band, while in the conduction band it is localized on the MoS2 layer. The calculations also predict a 16 meV spin-splitting at the Γ̅ point and 8 meV K̅-K'¯ valley asymmetry for an out-of-plane magnetization. These findings suggest control over optical transitions in MoS2 via Co magnetization. Our estimations show that the magnetic proximity effect is equivalent to the action of the magnetic field as large as 100 T.

Emergence of Fermi arcs due to magnetic splitting in an antiferromagnet.

The Fermi surface plays an important role in controlling the electronic, transport and thermodynamic properties of materials. As the Fermi surface consists of closed contours in the momentum space for well-defined energy bands, disconnected sections known as Fermi arcs can be signatures of unusual electronic states, such as a pseudogap1. Another way to obtain Fermi arcs is to break either the time-reversal symmetry2 or the inversion symmetry3 of a three-dimensional Dirac semimetal, which results in formation of pairs of Weyl nodes that have opposite chirality4, and their projections are connected by Fermi arcs at the bulk boundary3,5-12. Here, we present experimental evidence that pairs of hole- and electron-like Fermi arcs emerge below the Neel temperature (TN) in the antiferromagnetic state of cubic NdBi due to a new magnetic splitting effect. The observed magnetic splitting is unusual, as it creates bands of opposing curvature, which change with temperature and follow the antiferromagnetic order parameter. This is different from previous theoretically considered13,14 and experimentally reported cases15,16 of magnetic splitting, such as traditional Zeeman and Rashba, in which the curvature of the bands is preserved. Therefore, our findings demonstrate a type of magnetic band splitting in the presence of a long-range antiferromagnetic order that is not readily explained by existing theoretical ideas.

Charge-Density-Wave-Induced Peak-Dip-Hump Structure and the Multiband Superconductivity in a Kagome Superconductor CsV_{3}Sb_{5}.

The entanglement of charge density wave (CDW), superconductivity, and topologically nontrivial electronic structure has recently been discovered in the kagome metal AV_{3}Sb_{5} (A=K, Rb, Cs) family. With high-resolution angle-resolved photoemission spectroscopy, we study the electronic properties of CDW and superconductivity in CsV_{3}Sb_{5}. The spectra around K[over ¯] is found to exhibit a peak-dip-hump structure associated with two separate branches of dispersion, demonstrating the isotropic CDW gap opening below E_{F}. The peak-dip-hump line shape is contributed by linearly dispersive Dirac bands in the lower branch and a dispersionless flat band close to E_{F} in the upper branch. The electronic instability via Fermi surface nesting could play a role in determining these CDW-related features. The superconducting gap of ∼0.4 meV is observed on both the electron band around Γ[over ¯] and the flat band around K[over ¯], implying the multiband superconductivity. The finite density of states at E_{F} in the CDW phase is most likely in favor of the emergence of multiband superconductivity, particularly the enhanced density of states associated with the flat band. Our results not only shed light on the controversial origin of the CDW, but also offer insights into the relationship between CDW and superconductivity.

High-Quality Graphene Using Boudouard Reaction.

Following the game-changing high-pressure CO (HiPco) process that established the first facile route toward large-scale production of single-walled carbon nanotubes, CO synthesis of cm-sized graphene crystals of ultra-high purity grown during tens of minutes is proposed. The Boudouard reaction serves for the first time to produce individual monolayer structures on the surface of a metal catalyst, thereby providing a chemical vapor deposition technique free from molecular and atomic hydrogen as well as vacuum conditions. This approach facilitates inhibition of the graphene nucleation from the CO/CO2 mixture and maintains a high growth rate of graphene seeds reaching large-scale monocrystals. Unique features of the Boudouard reaction coupled with CO-driven catalyst engineering ensure not only suppression of the second layer growth but also provide a simple and reliable technique for surface cleaning. Aside from being a novel carbon source, carbon monoxide ensures peculiar modification of catalyst and in general opens avenues for breakthrough graphene-catalyst composite production.

Interaction Features of Sodium Oleate and Oxyethylated Phosphoric Acid Esters with the Apatite Surface.

Apatite ores are the most important phosphate materials used for the agricultural and livestock chemical production. With the global demand for phosphorous compounds, apatite and other phosphorus-bearing ores are being depleted. The main method of apatite ore enrichment at the moment is the flotation process, the efficiency of which depends on complex heterogeneous processes occurring at the boundary of three phases ("liquid-gas", "solid-liquid", and "solid-gas"). Significant influence on the process have the flotation modes and composition of the reagent mixture, which provide a synergistic effect. The purpose of this work was to investigate the reasons for the synergism of surfactants used in apatite ore flotation with fatty acid-based collectors. The object of the study is a monomineral fraction of apatite, separated from the apatite-nepheline ore of Khibiny deposits. In the course of the work, it was found that the mixture of sodium oleate and phospholane PE65 has a synergistic effect on the mineral surface of apatite during foam flotation. The ratio of reagents was determined at which the maximum synergistic effect was observed.

Metagenomic survey of the microbiome of ancient Siberian permafrost and modern Kamchatkan cryosols.

In the context of global warming, the melting of Arctic permafrost raises the threat of a reemergence of microorganisms some of which were shown to remain viable in ancient frozen soils for up to half a million years. In order to evaluate this risk, it is of interest to acquire a better knowledge of the composition of the microbial communities found in this understudied environment. Here, we present a metagenomic analysis of 12 soil samples from Russian Arctic and subarctic pristine areas: Chukotka, Yakutia and Kamchatka, including nine permafrost samples collected at various depths. These large datasets (9.2 × 1011 total bp) were assembled (525 313 contigs > 5 kb), their encoded protein contents predicted, and then used to perform taxonomical assignments of bacterial, archaeal and eukaryotic organisms, as well as DNA viruses. The various samples exhibited variable DNA contents and highly diverse taxonomic profiles showing no obvious relationship with their locations, depths or deposit ages. Bacteria represented the largely dominant DNA fraction (95%) in all samples, followed by archaea (3.2%), surprisingly little eukaryotes (0.5%), and viruses (0.4%). Although no common taxonomic pattern was identified, the samples shared unexpected high frequencies of ß-lactamase genes, almost 0.9 copy/bacterial genome. In addition to known environmental threats, the particularly intense warming of the Arctic might thus enhance the spread of bacterial antibiotic resistances, today's major challenge in public health. ß-Lactamases were also observed at high frequency in other types of soils, suggesting their general role in the regulation of bacterial populations.