bluuebunny/crossref_metadata_2025 huggingface dataset:
Toll-like receptor 7 deficiency suppresses type 1 diabetes development by modulating B-cell differentiation and function
Authors: Huang Juan , Peng Jian , Pearson James Alexander , Efthimiou Georgios , Hu Youjia , Tai Ningwen , Xing Yanpeng , Zhang Luyao , Gu Jianlei , Jiang Jianping , Zhao Hongyu , Zhou Zhiguang , Wong F. Susan , Wen Li
Published: January 2021

Innate immunity mediated by Toll-like receptors (TLRs), which can recognize pathogen molecular patterns, plays a critical role in type 1 diabetes development. TLR7 is a pattern recognition receptor that senses single-stranded RNAs from viruses and host tissue cells; however, its role in type 1 diabetes development remains unclear. In our study, we discovered that Tlr7-deficient (Tlr7−/−) nonobese diabetic (NOD) mice, a model of human type 1 diabetes, exhibited a significantly delayed onset and reduced incidence of type 1 diabetes compared with Tlr7-sufficient (Tlr7+/+) NOD mice. Mechanistic investigations showed that Tlr7 deficiency significantly altered B-cell differentiation and immunoglobulin production. Moreover, Tlr7−/− NOD B cells were found to suppress diabetogenic CD4+ T-cell responses and protect immunodeficient NOD mice from developing diabetes induced by diabetogenic T cells. In addition, we found that Tlr7 deficiency suppressed the antigen-presenting functions of B cells and inhibited cytotoxic CD8+ T-cell activation by downregulating the expression of both nonclassical and classical MHC class I (MHC-I) molecules on B cells. Our data suggest that TLR7 contributes to type 1 diabetes development by regulating B-cell functions and subsequent interactions with T cells. Therefore, therapeutically targeting TLR7 may prove beneficial for disease protection.
Double viral vector technology for selective manipulation of neural pathways with higher level of efficiency and safety
Authors: Koshimizu Yoshinori , Isa Kaoru , Kobayashi Kenta , Isa Tadashi
Published: January 2021

Pathway-selective gene delivery would be critical for future gene therapy against neuropsychiatric disorders, traumatic neuronal injuries, or neurodegenerative diseases, because the impaired functions depend on neural circuits affected by the insults. Pathway-selective gene delivery can be achieved by double viral vector techniques, which combine an injection of a retrograde transport viral vector into the projection area of the target neurons and that of an anterograde viral vector into their somas. In this study, we tested the efficiency of gene delivery with different combinations of viral vectors to the pathway extending from the ventral tegmental area (VTA) to the cortical motor regions in rats, considered to be critical in the promotion of motor recovery from neural injuries. It was found that retrograde recombinant adeno-associated virus 2-retro (rAAV2reto) combined with anterograde AAVDJ (type2/type4/type5/type8/type9/avian/bovine/caprine chimera) exhibited the highest transduction efficiency in the short term (3–6 weeks) but high toxicity in the long term (3 months). In contrast, the same rAAV2reto combined with anterograde AAV5 displayed moderate transduction efficiency in the short term but low toxicity in the long term. These data suggest that the combination of anterograde AAV5 and retrograde rAAV2retro is suitable for safe and efficient gene delivery to the VTA-cortical pathway.
Validation of an IFN-gamma ELISpot assay to measure cellular immune responses against viral antigens in non-human primates
Authors: Yang Fan , Patton Kathryn , Kasprzyk Theresa , Long Brian , Gupta Soumi , Zoog Stephen J. , Tracy Kristin , Vettermann Christian
Published: January 2021

Adeno-Associated Virus (AAV)-based gene therapy vectors are in development for many inherited human disorders. In nonclinical studies, cellular immune responses mediated by cytotoxic T cells may target vector-transduced cells, which could impact safety and efficacy. Here, we describe the bioanalytical validation of an interferon-gamma (IFN-γ)-based Enzyme-Linked Immunospot (ELISpot) assay for measuring T cell responses against viral antigens in cynomolgus monkeys. Since ELISpots performed with antigen-derived peptides offer a universal assay format, method performance characteristics were validated using widely available peripheral blood mononuclear cells (PBMCs) responsive to cytomegalovirus peptides. The limit of detection and confirmatory cut point were established using statistical methods; precision, specificity, and linearity were confirmed. Monkey PBMCs from an AAV5 gene therapy study were then analyzed, using peptide pools spanning the vector capsid and transgene product. AAV5-specific T cell responses were detected only in 2 of 18 monkeys at Day 28, but not at Day 13 and 56 after vector administration, with no correlation to liver enzyme elevations or transgene expression levels. No transgene product-specific T cell responses occurred. In conclusion, while viral peptide-specific IFN-γ ELISpots can be successfully validated for monkey PBMCs, monitoring peripheral T cell responses in non-clinical AAV5 gene therapy studies was of limited value to interpret safety or efficacy.
Multi-atom quasiparticle scattering interference for superconductor energy-gap symmetry determination
Authors: Sharma Rahul , Kreisel Andreas , Sulangi Miguel Antonio , Böker Jakob , Kostin Andrey , Allan Milan P. , Eisaki H. , Böhmer Anna E. , Canfield Paul C. , Eremin Ilya , Séamus Davis J. C. , Hirschfeld P. J. , Sprau Peter O.
Published: January 2021

Complete theoretical understanding of the most complex superconductors requires a detailed knowledge of the symmetry of the superconducting energy-gap $${\mathrm{{\Delta}}}_{\mathbf{k}}^\alpha$$

Δ

k

α

, for all momenta k on the Fermi surface of every band α. While there are a variety of techniques for determining $$|{\mathrm{{\Delta}}}_{\mathbf{k}}^\alpha |$$

∣

Δ

k

α

∣

, no general method existed to measure the signed values of $${\mathrm{{\Delta}}}_{\mathbf{k}}^\alpha$$

Δ

k

α

. Recently, however, a technique based on phase-resolved visualization of superconducting quasiparticle interference (QPI) patterns, centered on a single non-magnetic impurity atom, was introduced. In principle, energy-resolved and phase-resolved Fourier analysis of these images identifies wavevectors connecting all k-space regions where $${\mathrm{{\Delta}}}_{\mathbf{k}}^\alpha$$

Δ

k

α

has the same or opposite sign. But use of a single isolated impurity atom, from whose precise location the spatial phase of the scattering interference pattern must be measured, is technically difficult. Here we introduce a generalization of this approach for use with multiple impurity atoms, and demonstrate its validity by comparing the $${\mathrm{{\Delta}}}_{\mathbf{k}}^\alpha$$

Δ

k

α

it generates to the $${\mathrm{{\Delta}}}_{\mathbf{k}}^\alpha$$

Δ

k

α

determined from single-atom scattering in FeSe where s± energy-gap symmetry is established. Finally, to exemplify utility, we use the multi-atom technique on LiFeAs and find scattering interference between the hole-like and electron-like pockets as predicted for $${\mathrm{{\Delta}}}_{\mathbf{k}}^\alpha$$

Δ

k

α

of opposite sign.
The traded water footprint of global energy from 2010 to 2018
Authors: Chini Christopher M. , Peer Rebecca A. M.
Published: January 2021

The energy-water nexus describes the requirement of water-for-energy and energy-for-water. The consumption of water in the production and generation of energy resources is also deemed virtual water. Pairing the virtual water estimates for energy with international trade data creates a virtual water trade network, facilitating analysis of global water resources management. In this database, we identify the virtual water footprints for the trade of eleven different energy commodities including fossil fuels, biomass, and electricity. Additionally, we provide the necessary scripts for downloading and pairing trade data with the virtual water footprints to create a virtual water trade network. The resulting database contains country-to-country virtual water trade from 2010–2018, broken down by commodity. The purpose of this data descriptor is to provide detailed methods and validation of the dataset beyond the complementary research publication. The resulting database provides opportunities to understand global energy-related water demands and advance future global water resources research.
Opioid use may be associated with postoperative complications in myotonic dystrophy type 1 with high-grade muscular impairment
Authors: Kim Chan-Sik , Park Jin-Mo , Park Donghwi , Kim Doo-Hwan , Park Jin-Sung
Published: January 2021

Individuals with myotonic dystrophy type 1 (DM1) reportedly have a higher risk of postoperative complications than those without DM1; however, factors related to perioperative complications in DM1 patients remain unclear. We aimed to identify the risk factors that may be associated with postoperative complications in DM1 patients. We reviewed medical records of 256 patients with DM1 from 1998 to 2018, among whom 42 (16.4%) had previously undergone 51 surgeries under general and regional anaesthesia. Among the 42 patients, 11 (21.5%) had 13 postoperative complications including respiratory complications, sustained hypotension, wound infection and dehiscence, artery thrombosis and occlusion, and delayed recovery from anaesthesia. There were significant inter-group differences between the non-complicated and complicated groups considering the following parameters: high-grade (≥ 3) muscular impairment rating scale (MIRS), extubation time, postoperative opioid use, and hospital length of stay. Furthermore, univariate analysis revealed that an MIRS score ≥ 3 (odds ratio [OR] 9.346, confidence interval [CI] 1.761–49.595, p = 0.009) and postoperative opioid use (OR 8.000, CI 1.772–36.127, p = 0.007) were the only statistically significant factors. Therefore, clinicians should be cautious in administering opioids, particularly in patients with a high-grade MIRS score during the perioperative period.
Mortality in neonates with giant omphalocele subjected to a surgical technique in Barranquilla, Colombia from 1994 to 2019
Authors: Barrios-Sanjuanelo Alexander , Abelló-Munarriz Cristóbal , Cardona-Arias Jaiberth Antonio
Published: January 2021

No studies of the efficacy and safety of surgical techniques for the primary closure of giant omphalocele have been performed in Colombia. To determine the mortality rate and factors associated with mortality in neonates with giant omphalocele subjected to the surgical technique of early closure with a surgical silo described by Abello in Barranquilla, Colombia from 1994 to 2019. Retrospective cohort study of 30 neonates diagnosed with giant omphalocele and subjected to early closure of the defect. Medical history data were collected, information bias was controlled for, and descriptive statistical analysis was performed using Fisher’s exact test and the Mann–Whitney U test in SPSS 25.0. Of the patients in the cohort, 36.7% presented technique-related complications, 56.7% developed sepsis, 23.3% had low birth weight, 26.7% were preterm births, 43.3% had other malformations, 26.7% had congenital heart defects, and 13.3% presented pulmonary hypertension. The mean hospital stay was 26 days. The mortality rate was 16.7%; it was significantly higher among patients with other malformations, congenital heart defects, pentalogy of Cantrell and pulmonary hypertension. The Abello technique for the treatment of giant omphalocele showed a high neonatal survival rate and a low rate of procedure-related complications. The main factors associated with the death of neonatal patients were the presence of other malformations, congenital heart defect, pentalogy of Cantrell and pulmonary hypertension.
Facial recognition technology can expose political orientation from naturalistic facial images
Authors: Kosinski Michal
Published: January 2021

Ubiquitous facial recognition technology can expose individuals’ political orientation, as faces of liberals and conservatives consistently differ. A facial recognition algorithm was applied to naturalistic images of 1,085,795 individuals to predict their political orientation by comparing their similarity to faces of liberal and conservative others. Political orientation was correctly classified in 72% of liberal–conservative face pairs, remarkably better than chance (50%), human accuracy (55%), or one afforded by a 100-item personality questionnaire (66%). Accuracy was similar across countries (the U.S., Canada, and the UK), environments (Facebook and dating websites), and when comparing faces across samples. Accuracy remained high (69%) even when controlling for age, gender, and ethnicity. Given the widespread use of facial recognition, our findings have critical implications for the protection of privacy and civil liberties.
Changing patterns in aerosol vertical distribution over South and East Asia
Authors: Ratnam M. Venkat , Prasad P. , Raj S. T. Akhil , Raman M. Roja , Basha Ghouse
Published: January 2021

Changing patterns in aerosol concentrations over the Asian region is well documented with a concurrent increase over India and a marked reduction over China. However, aerosol vertical distribution in the changing climate is not fully understood. By combining long-term satellite observations from MODIS and CALIOP, here we show rapid changes in the aerosol vertical distribution over the South and East Asia covering India and China. A statistically significant decreasing (increasing) trend in the boundary layer (free troposphere) aerosol concentrations is noticed over India. ERA-Interim reanalysis model suggests that this increase in free tropospheric aerosol concentrations are due to the lifting of boundary layer pollutants through an increase in convection (and vertical velocity) in a changing climate. In contrast, a consistent decreasing trend is observed over China irrespective of the altitude. Interestingly, a decreasing trend in Aerosol Optical Depth is observed over the northwest India and we relate this to an observed increase in precipitation leading to increase in the vegetation. It is also found that long-term oscillations like QBO, ENSO and solar cycle significantly affect the aerosol concentrations. Thus, it is prudent to conclude that background meteorology and dynamics play an important role in changing patterns of aerosol vertical distribution.
Continuity of the Middle Stone Age into the Holocene
Authors: Scerri Eleanor M. L. , Niang Khady , Candy Ian , Blinkhorn James , Mills William , Cerasoni Jacopo N. , Bateman Mark D. , Crowther Alison , Groucutt Huw S.
Published: January 2021

The African Middle Stone Age (MSA, typically considered to span ca. 300–30 thousand years ago [ka]), represents our species’ first and longest lasting cultural phase. Although the MSA to Later Stone Age (LSA) transition is known to have had a degree of spatial and temporal variability, recent studies have implied that in some regions, the MSA persisted well beyond 30 ka. Here we report two new sites in Senegal that date the end of the MSA to around 11 ka, the youngest yet documented MSA in Africa. This shows that this cultural phase persisted into the Holocene. These results highlight significant spatial and temporal cultural variability in the African Late Pleistocene, consistent with genomic and palaeoanthropological hypotheses that significant, long-standing inter-group cultural differences shaped the later stages of human evolution in Africa.
Association between long-range temporal correlations in intrinsic EEG activity and subjective sense of identity
Authors: Sugimura Kazumi , Iwasa Yasuhiro , Kobayashi Ryota , Honda Tatsuru , Hashimoto Junya , Kashihara Shiho , Zhu Jianhong , Yamamoto Kazuki , Kawahara Tsuyoshi , Anno Mayo , Nakagawa Risa , Hatano Kai , Nakao Takashi
Published: January 2021

The long-range temporal correlation (LRTC) in resting-state intrinsic brain activity is known to be associated with temporal behavioral patterns, including decision making based on internal criteria such as self-knowledge. However, the association between the neuronal LRTC and the subjective sense of identity remains to be explored; in other words, whether our subjective sense of consistent self across time relates to the temporal consistency of neural activity. The present study examined the relationship between the LRTC of resting-state scalp electroencephalography (EEG) and a subjective sense of identity measured by the Erikson Psychosocial Stage Inventory (EPSI). Consistent with our prediction based on previous studies of neuronal-behavioral relationships, the frontocentral alpha LRTC correlated negatively with identity confusion. Moreover, from the descriptive analyses, centroparietal beta LRTC showed negative correlations with identity confusion, and frontal theta LRTC showed positive relationships with identity synthesis. These results suggest that more temporal consistency (reversely, less random noise) in intrinsic brain activity is associated with less confused and better-synthesized identity. Our data provide further evidence that the LRTC of intrinsic brain activity might serve as a noise suppression mechanism at the psychological level.
Crystal structure of a thermophilic fungal cyanase and its implications on the catalytic mechanism for bioremediation
Authors: Ranjan Bibhuti , Choi Philip H. , Pillai Santhosh , Permaul Kugenthiren , Tong Liang , Singh Suren
Published: January 2021

Cyanase catalyzes the bicarbonate-dependent degradation of cyanate to produce ammonia and carbon dioxide, and ammonia is a considerable alternative nitrogen source. Strikingly, the cyanase from the thermophilic fungus Thermomyces lanuginosus (Tl-Cyn) has the highest catalytic efficiency reported among these enzymes. However, its molecular mechanism of action is not clearly understood, because currently there is no structural information available on fungal cyanases. Here we report the crystal structure of Tl-Cyn in complex with inhibitors malonate and formate at 2.2 Å resolution. The structure reveals extensive interactions at the subunit interfaces in a dimer, and a decamer is formed by a pentamer of these dimers. Our biochemical, kinetic and mutagenesis studies confirm the structural observations on the complex and provide further insights into its catalytic mechanism and inhibition. The structure has also aided the creation of a mutant enzyme with enhanced catalytic activity, and such enzymes may have the potential for biotechnological applications, including biotransformation and bioremediation. Moreover, other fungal cyanases with potentially high catalytic activity could also be predicted based on the Tl-Cyn structure, as the active site region among fungal cyanases are highly conserved.
Mechanism understanding in cryo atomic layer etching of SiO2 based upon C4F8 physisorption
Authors: Antoun G. , Tillocher T. , Lefaucheux P. , Faguet J. , Maekawa K. , Dussart R.
Published: January 2021

Cryogenic Atomic Layer Etching (cryo-ALE) of SiO2based on alternating a C4F8molecule physisorption step and an argon plasma step, has been enhanced thanks to a better understanding of the mechanism. First, we used Quadrupole Mass spectrometry (QMS) and spectroscopic ellipsometry analyses to evaluate the residence time of physisorbed C4F8molecules versus temperature and pressure on SiO2surface. QMS monitoring of the SiF4etching by-product also enabled to follow the self-limiting etching behavior. Finally, a SiO2cryo-ALE process was proposed at a temperature of − 90 °C resulting in a very linear etch over 150 cycles and an Etch amount Per Cycle as low as 0.13 nm/cycle.
Environmentally friendly Pd(II) recovery from spent automotive catalysts using resins impregnated with a pincer-type extractant
Authors: Yamada Manabu , Kimura Shun , Rajiv Gandhi Muniyappan , Shibayama Atsushi
Published: January 2021

Extractant-impregnated resins have potential for recovering platinum group metals selectively and efficiently. Herein, 1,3-bis(2-(octylthio)propan-2-yl)benzene (1), a pincer-type extractant, was impregnated in Amberlite XAD-7 resin (1-EIR), and the batch Pd(II) sorption conditions, including impregnated amount, shaking time, Pd(II) concentration, HCl concentration, and Pd(II) desorption reagents, were optimized. The maximum Pd(II) sorption capacity of 1-EIR was 49 mg g−1 after 24 h in a 700 ppm Pd(II) solution. Over 20 adsorption–desorption cycles, 1-EIR showed good reusability, with a sorption percentage (S%) of > 92%. However, not all Pd(II) was desorbed from 1-EIR. Complete Pd(II) collection was achieved by combining desorption with flaking of the Pd–extractant complex from Pd(II)-loaded 1-EIR by Soxhlet extraction, as ~ 13 mg g−1 remained after the 20th adsorption–desorption cycle by absorptiometric method. The sorption mechanism was elucidated based on the Langmuir isotherm model, thermodynamic parameters, and sorption kinetics. Pd(II) sorption by 1-EIR was spontaneous and endothermic, and the sorption kinetics followed a pseudo-second-order model. Notably, 1-EIR also exhibited high selectivity for Pd(II) from a simulated mixed metal solution and a spent automotive catalyst leachate (S% = 98% and > 99%, respectively). Thus, this extractant-impregnated system is promising for selective Pd(II) recovery from spent automotive catalysts and other secondary resources.
Specification of the patterning of a ductal tree during branching morphogenesis of the submandibular gland
Authors: Walker Janice L. , Wang Weihao , Lin Edith , Romisher Alison , Bouchie Meghan P. , Bleaken Brigid , Menko A. Sue , Kukuruzinska Maria A.
Published: January 2021

The development of ductal structures during branching morphogenesis relies on signals that specify ductal progenitors to set up a pattern for the ductal network. Here, we identify cellular asymmetries defined by the F-actin cytoskeleton and the cell adhesion protein ZO-1 as the earliest determinants of duct specification in the embryonic submandibular gland (SMG). Apical polarity protein aPKCζ is then recruited to the sites of asymmetry in a ZO-1-dependent manner and collaborates with ROCK signaling to set up apical-basal polarity of ductal progenitors and further define the path of duct specification. Moreover, the motor protein myosin IIB, a mediator of mechanical force transmission along actin filaments, becomes localized to vertices linking the apical domains of multiple ductal epithelial cells during the formation of ductal lumens and drives duct maturation. These studies identify cytoskeletal, junctional and polarity proteins as the early determinants of duct specification and the patterning of a ductal tree during branching morphogenesis of the SMG.
Strontium isotope evidence for a trade network between southeastern Arabia and India during Antiquity
Authors: Ryan Saskia E. , Dabrowski Vladimir , Dapoigny Arnaud , Gauthier Caroline , Douville Eric , Tengberg Margareta , Kerfant Céline , Mouton Michel , Desormeau Xavier , Zazzo Antoine , Bouchaud Charlène
Published: January 2021

Cotton (Gossypium sp.), a plant of tropical and sub-tropical origin, appeared at several sites on the Arabian Peninsula at the end of the 1st mill. BCE-beginning of the 1st mill. CE. Its spread into this non-native, arid environment is emblematic of the trade dynamics that took place at this pivotal point in human history. Due to its geographical location, the Arabian Peninsula is connected to both the Indian and African trading spheres, making it complex to reconstruct the trans-continental trajectories of plant diffusion into and across Arabia in Antiquity. Key questions remain pertaining to: (1) provenance, i.e. are plant remains of local or imported origin and (2) the precise timing of cotton arrival and spread. The ancient site of Mleiha, located in modern-day United Arab Emirates, is a rare and significant case where rich archaeobotanical remains dating to the Late Pre-Islamic period (2nd–3rd c. CE), including cotton seeds and fabrics, have been preserved in a burned-down fortified building. To better understand the initial trade and/or production of cotton in this region, strontium isotopes of leached, charred cotton remains are used as a powerful tracer and the results indicate that the earliest cotton finds did not originate from the Oman Peninsula, but were more likely sourced from further afield, with the north-western coast of India being an isotopically compatible provenance. Identifying the presence of such imported cotton textiles and seeds in southeastern Arabia is significant as it is representative of the early diffusion of the crop in the region, later to be grown extensively in local oases.
Nanostructural deformation of high-stiffness spruce wood under tension
Authors: Thomas Lynne H. , Altaner Clemens M. , Forsyth V. Trevor , Mossou Estelle , Kennedy Craig J. , Martel Anne , Jarvis Michael C.
Published: January 2021

Conifer wood is an exceptionally stiff and strong material when its cellulose microfibrils are well aligned. However, it is not well understood how the polymer components cellulose, hemicelluloses and lignin co-operate to resist tensile stress in wood. From X-ray scattering, neutron scattering and spectroscopic data, collected under tension and processed by novel methods, the ordered, disordered and hemicellulose-coated cellulose components comprising each microfibril were shown to stretch together and demonstrated concerted, viscous stress relaxation facilitated by water. Different cellulose microfibrils did not all stretch to the same degree. Attempts were made to distinguish between microfibrils showing large and small elongation but these domains were shown to be similar with respect to orientation, crystalline disorder, hydration and the presence of bound xylan. These observations are consistent with a major stress transfer process between microfibrils being shear at interfaces in direct, hydrogen-bonded contact, as demonstrated by small-angle neutron scattering. If stress were transmitted between microfibrils by bridging hemicelluloses these might have been expected to show divergent stretching and relaxation behaviour, which was not observed. However lignin and hemicellulosic glucomannans may contribute to stress transfer on a larger length scale between microfibril bundles (macrofibrils).
Transformer neural network for protein-specific de novo drug generation as a machine translation problem
Authors: Grechishnikova Daria
Published: January 2021

Drug discovery for a protein target is a very laborious, long and costly process. Machine learning approaches and, in particular, deep generative networks can substantially reduce development time and costs. However, the majority of methods imply prior knowledge of protein binders, their physicochemical characteristics or the three-dimensional structure of the protein. The method proposed in this work generates novel molecules with predicted ability to bind a target protein by relying on its amino acid sequence only. We consider target-specific de novo drug design as a translational problem between the amino acid “language” and simplified molecular input line entry system representation of the molecule. To tackle this problem, we apply Transformer neural network architecture, a state-of-the-art approach in sequence transduction tasks. Transformer is based on a self-attention technique, which allows the capture of long-range dependencies between items in sequence. The model generates realistic diverse compounds with structural novelty. The computed physicochemical properties and common metrics used in drug discovery fall within the plausible drug-like range of values.
A novel human ex vivo skin model to study early local responses to burn injuries
Authors: Hofmann Elisabeth , Fink Julia , Eberl Anita , Prugger Eva-Maria , Kolb Dagmar , Luze Hanna , Schwingenschuh Simon , Birngruber Thomas , Magnes Christoph , Mautner Selma I. , Kamolz Lars-Peter , Kotzbeck Petra
Published: January 2021

Burn injuries initiate numerous processes such as heat shock response, inflammation and tissue regeneration. Reliable burn models are needed to elucidate the exact sequence of local events to be able to better predict when local inflammation triggers systemic inflammatory processes. In contrast to other ex vivo skin culture approaches, we used fresh abdominal skin explants to introduce contact burn injuries. Histological and ultrastructural analyses confirmed a partial-thickness burn pathology. Gene expression patterns and cytokine production profiles of key mediators of the local inflammation, heat shock response, and tissue regeneration were analyzed for 24 h after burn injury. We found significantly increased expression of factors involved in tissue regeneration and inflammation soon after burn injury. To investigate purely inflammation-mediated reactions we injected lipopolysaccharide into the dermis. In comparison to burn injury, lipopolysaccharide injection initiated an inflammatory response while expression patterns of heat shock and tissue regeneration genes were unaffected for the duration of the experiment. This novel ex vivo human skin model is suitable to study the local, early responses to skin injuries such as burns while maintaining an intact overall tissue structure and it gives valuable insights into local mechanisms at the very beginning of the wound healing process after burn injuries.
Double-high in palmitic and oleic acids accumulation in a non-model green microalga, Messastrum gracile SE-MC4 under nitrate-repletion and -starvation cultivations
Authors: Wan Afifudeen Che-Lah , Loh Saw Hong , Aziz Ahmad , Takahashi Kazutaka , Effendy Abd Wahid Mohd , Cha Thye San
Published: January 2021

Bioprospecting for biodiesel potential in microalgae primarily involves a few model species of microalgae and rarely on non-model microalgae species. Therefore, the present study determined changes in physiology, oil accumulation, fatty acid composition and biodiesel properties of a non-model microalga Messastrum gracile SE-MC4 in response to 12 continuous days of nitrate-starve (NS) and nitrate-replete (NR) conditions respectively. Under NS, the highest oil content (57.9%) was achieved despite reductions in chlorophyll content, biomass productivity and lipid productivity. However, under both NS and NR, palmitic acid and oleic acid remained as dominant fatty acids thus suggesting high potential of M. gracile for biodiesel feedstock consideration. Biodiesel properties analysis returned high values of cetane number (CN 61.9–64.4) and degree of unsaturation (DU 45.3–57.4) in both treatments. The current findings show the possibility of a non-model microalga to inherit superior ability over model species in oil accumulation for biodiesel development.
A framework to identify structured behavioral patterns within rodent spatial trajectories
Authors: Donnarumma Francesco , Prevete Roberto , Maisto Domenico , Fuscone Simone , Irvine Emily M. , van der Meer Matthijs A. A. , Kemere Caleb , Pezzulo Giovanni
Published: January 2021

Animal behavior is highly structured. Yet, structured behavioral patterns—or “statistical ethograms”—are not immediately apparent from the full spatiotemporal data that behavioral scientists usually collect. Here, we introduce a framework to quantitatively characterize rodent behavior during spatial (e.g., maze) navigation, in terms of movement building blocks ormotor primitives. The hypothesis that we pursue is that rodent behavior is characterized by a small number of motor primitives, which are combined over time to produce open-ended movements. We assume motor primitives to be organized in terms of two sparsity principles: each movement is controlled using a limited subset of motor primitives (sparse superposition) and each primitive is active only for time-limited, time-contiguous portions of movements (sparse activity). We formalize this hypothesis using a sparse dictionary learning method, which we use to extract motor primitives from rodent position and velocity data collected during spatial navigation, and successively to reconstruct past trajectories and predict novel ones. Three main results validate our approach. First, rodent behavioral trajectories are robustly reconstructed from incomplete data, performing better than approaches based on standard dimensionality reduction methods, such as principal component analysis, or single sparsity. Second, the motor primitives extracted during one experimental session generalize and afford the accurate reconstruction of rodent behavior across successive experimental sessions in the same or in modified mazes. Third, in our approach the number of motor primitives associated with each maze correlates with independent measures of maze complexity, hence showing that our formalism is sensitive to essential aspects of task structure. The framework introduced here can be used by behavioral scientists and neuroscientists as an aid for behavioral and neural data analysis. Indeed, the extracted motor primitives enable the quantitative characterization of the complexity and similarity between different mazes and behavioral patterns across multiple trials (i.e., habit formation). We provide example uses of this computational framework, showing how it can be used to identify behavioural effects of maze complexity, analyze stereotyped behavior, classify behavioral choices and predict place and grid cell displacement in novel environments.
Lies, Gosh Darn Lies, and not enough good statistics: why epidemic model parameter estimation fails
Authors: Platt Daniel E. , Parida Laxmi , Zalloua Pierre
Published: January 2021

We sought to investigate whether epidemiological parameters that define epidemic models could be determined from the epidemic trajectory of infections, recovery, and hospitalizations prior to peak, and also to evaluate the comparability of data between jurisdictions reporting their statistics. We found that, analytically, the pre-peak growth of an epidemic underdetermines the model variates, and that the rate limiting variables are dominated by the exponentially expanding eigenmode of their equations. The variates quickly converge to the ratio of eigenvector components of the positive growth mode, which determines the doubling time. Without a sound epidemiological study framework, measurements of infection rates and other parameters are highly corrupted by uneven testing rates, uneven counting, and under reporting of relevant values. We argue that structured experiments must be performed to estimate these parameters in order to perform genetic association studies, or to construct viable models accurately predicting critical quantities such as hospitalization loads.
Fusing the single-excitation subspace with $${\mathbb C}^{2^n}$$
Authors: Geller Michael R.
Published: January 2021

There is a tremendous interest in developing practical applications for noisy intermediate-scale quantum processors without the overhead required by full error correction. Near-term quantum information processing is especially challenging within the standard gate model, as algorithms quickly lose fidelity as the problem size and circuit depth grow. This has lead to a number of non-gate-model approaches such as analog quantum simulation and quantum annealing. These come with specific hardware requirements that are different than that of a universal gate-based quantum computer. We have previously proposed an approach called the single-excitation subspace (SES) method, which uses a complete graph of superconducting qubits with tunable coupling. Without error correction the SES method is not scalable, but it offers several algorithmic components with constant depth, which is highly desirable for near-term use. The challenge of the SES method is that it requires a physical qubit for every basis state in the computer’s Hilbert space. This imposes exponentially large resource costs for algorithms using registers of ancillary qubits, as each ancilla would double the required graph size. Here we show how to circumvent this doubling by leaving the SES and fusing it with a multi-ancilla Hilbert space. Specifically, we implement the tensor product of an SES register holding “data” with one or more ancilla qubits, which are able to independently control arbitrary $$n\!\times \!n$$

n

×

n

unitary operations on the data in a constant number of steps. This enables a hybrid form of quantum computation where fast SES operations are performed on the data, traditional logic gates and measurements are performed on the ancillas, and controlled-unitaries act between. As example applications, we give ancilla-assisted SES implementations of quantum phase estimation and the quantum linear system solver of Harrow, Hassidim, and Lloyd.
Therapeutic efficacy of repetitive transcranial magnetic stimulation in an animal model of Alzheimer’s disease
Authors: Choung Jin Seung , Kim Jong Moon , Ko Myoung-Hwan , Cho Dong Sik , Kim MinYoung
Published: January 2021

Previous studies on repetitive transcranial magnetic stimulation (rTMS) suggested potential neurorestorative properties in Alzheimer’s disease (AD). This study aimed to investigate therapeutic effects of rTMS on an AD mouse model at high and low frequencies. The subject mice were allocated into the AD model group (AD induced by intracerebroventricular amyloid beta 42 oligomer [Aβ42] injection) and the saline-injected control group. Each group was subdivided according to rTMS treatment: high frequency (20 Hz), low frequency (1 Hz), and not rTMS-treated. Behavioural assessments with Y-maze test and novel object recognition task were performed; the results indicated cognition recovery by both the frequencies of rTMS after treatment in the AD model (Ps < 0.01). Tendency of further effects by high frequency compared to low frequency rTMS was also shown in Y-maze test. Neurotransmitter assay showed increment in dopamine concentration and upregulation of dopamine-receptor 4 (DR4) by rTMS in AD mice with higher response by high frequency stimulation (Ps < 0.05). Only high-frequency rTMS induced an elevation of brain-derived neurotrophic factor (BDNF) levels and enhanced the expression of Nestin and NeuN in the brain tissue (Ps < 0.05). Under in vitro conditions, Aβ42 incubated mouse hippocampal cell showed an increase in dopamine levels and BDNF by application of high-frequency rTMS treatment. In conclusion, rTMS might have a potential therapeutic effect on AD, and it seems to be related with dopaminergic activation. High frequency of stimulation seems to induce higher efficacy than that induced by low frequency, with elevated expressions of DR4 gene and neurogenic proteins.
Cystoscopic hydrodistention characteristics provide clinical and long-term prognostic features of interstitial cystitis after treatment
Authors: Yu Wan-Ru , Jhang Jia-Fong , Ho Han-Chen , Jiang Yuan-Hong , Lee Cheng-Ling , Hsu Yung-Hsiang , Kuo Hann-Chorng
Published: January 2021

To evaluate the correlations of clinical symptoms, urodynamic parameters, and long-term treatment outcomes with different findings of cystoscopic hydrodistention (HD) in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). This retrospective analysis of 486 patients with IC/BPS investigated baseline clinical symptoms, disease duration, medical comorbidities, urodynamic findings, cystoscopic characteristics [including maximal bladder capacity (MBC) and the presence of glomerulations and Hunner’s lesions], and outcomes according to the five IC/BPS HD subtypes based on the glomerulation grade, MBC, and the presence of Hunner’s lesions. Receiver operation characteristic analysis identified an optimal cutoff value of MBC ≥ 760 ml as a predictor of satisfactory outcomes. Glomerulation grade and MBC were significantly correlated (r =  − 0.403, P < 0.001), and both were significantly associated with IC Symptom Index scores. The rate of satisfactory outcomes was better for the patients with low glomerulation grade and MBC ≥ 760 ml (64.2%), and significantly worse for those with Hunner’s lesions (36.8%); no significant differences were noted among the other groups. The results suggested that IC/BPS patients can be classified into the following three distinct subgroups: (1) those with low glomerulation grade and MBC ≥ 760 ml; (2) those with low glomerulation grade and MBC < 760 ml, or with high glomerulation grade regardless of MBC; and (3) those with Hunner’s lesions. The results showed that three IC/BPS subgroups had distinct bladder characteristics and treatment outcomes. The patients with high MBC and low glomerulation grade after HD had more medical comorbidities but a significantly higher rate of satisfactory treatment outcome.

IRB: 105-25-B.
Giant persistent photoconductivity in monolayer MoS2 field-effect transistors
Authors: George A. , Fistul M. V. , Gruenewald M. , Kaiser D. , Lehnert T. , Mupparapu R. , Neumann C. , Hübner U. , Schaal M. , Masurkar N. , Arava L. M. R. , Staude I. , Kaiser U. , Fritz T. , Turchanin A.
Published: January 2021

Monolayer transition metal dichalcogenides (TMD) have numerous potential applications in ultrathin electronics and photonics. The exposure of TMD-based devices to light generates photo-carriers resulting in an enhanced conductivity, which can be effectively used, e.g., in photodetectors. If the photo-enhanced conductivity persists after removal of the irradiation, the effect is known as persistent photoconductivity (PPC). Here we show that ultraviolet light (λ = 365 nm) exposure induces an extremely long-living giant PPC (GPPC) in monolayer MoS2 (ML-MoS2) field-effect transistors (FET) with a time constant of ~30 days. Furthermore, this effect leads to a large enhancement of the conductivity up to a factor of 107. In contrast to previous studies in which the origin of the PPC was attributed to extrinsic reasons such as trapped charges in the substrate or adsorbates, we show that the GPPC arises mainly from the intrinsic properties of ML-MoS2 such as lattice defects that induce a large number of localized states in the forbidden gap. This finding is supported by a detailed experimental and theoretical study of the electric transport in TMD based FETs as well as by characterization of ML-MoS2 with scanning tunneling spectroscopy, high-resolution transmission electron microscopy, and photoluminescence measurements. The obtained results provide a basis for the defect-based engineering of the electronic and optical properties of TMDs for device applications.
3D bioprinting dermal-like structures using species-specific ulvan
Authors: Chen Xifang , Yue Zhilian , Winberg Pia C. , Lou Yan-Ru , Beirne Stephen , Wallace Gordon G.
Published: January 2021

3D cellularized structures revealing dermal-like properties have been successfully printed using bioinks based on the sulfated polysaccharide ulvan from Australian green seaweed.
Caffeine vehiculation into alpha-zirconium phosphate: a multifunctional intercalation product and its application for modified topical release
Authors: Bastianini M. , Sisani M. , Petracci A. , Di Guida I. , Faffa C. , Cardellini F.
Published: January 2021

Zirconium phosphate is able to intercalate basic molecules and it is an effective drug carrier that can be used to project slow release for topical applications.
Synthesis of high molar extinction coefficient push–pull tricyanofuran-based disperse dyes: Biological activity and dyeing performance
Authors: Aldalbahi Ali , Periyasami Govindasami , Alrehaili Abdulaziz
Published: January 2021

Novel push–pull tricyanofuran-based disperse dyes demonstrated high extinction coefficient, good antimicrobial performance and high colorfastness on polyester fibers.
Recent advances of oxyfluorides for nonlinear optical applications
Authors: Bai Shuo , Wang Dan , Liu Hongkun , Wang Ying
Published: January 2021

Oxyfluorides exhibit rich crystal structures that provide a new perspective for designing new NLO materials.
Design of unique porous carbons with double support structure: toward overall performance by employing bidirectional anchoring strategy
Authors: Liu Yujing , Zhao Chengyao , Liu Qi , Zhou Xin , Liu Zhongqiu , You Jinmao , Ying Anguo
Published: January 2021

We propose a unique bidirectional anchoring strategy to develop porous carbons with double support structure, which eliminates the dead volume and represents an enhanced overall performance. This is a significant innovation in performance optimization for hard carbon.
Tunable dual-emission luminescence from Cu(i)-cluster-based MOFs for multi-stimuli responsive materials
Authors: Zhao Yunfang , Yu Muxin , Liu Caiping , Li Shengchang , Li Zhijia , Jiang Feilong , Chen Lian , Hong Maochun
Published: January 2021

Through filling guest molecules in cages, two Cu(i)-cluster-based MOFs with distinct luminescence at room temperature were obtained. They show multi-stimuli responses to VOCs, temperature and nitro-compounds.
Reversible data encryption–decryption using a pH stimuli-responsive hydrogel
Authors: Wen Hongjing , Zeng Xianzhi , Xu Xiaoxuan , Li Wanyi , Xie Fei , Xiong Zhong , Song Shichao , Wang Bin , Li Xiangping , Cao Yaoyu
Published: January 2021

Unprecedented data manipulation employed using a pH-stimuli responsive hydrogel was developed to achieve reversible data encryption–decryption.
Dust moments: towards a new modeling of the galactic dust emission for CMBB-modes analysis
Authors: Mangilli A. , Aumont J. , Rotti A. , Boulanger F. , Chluba J. , Ghosh T. , Montier L.
Published: January 2021

The characterization of the spectral energy distribution (SED) of dust emission has become a critical issue in the quest for primordialB-modes. The dust SED is often approximated by a modified black body (MBB) emission law but the extent to which this is accurate is unclear. This paper addresses this question, expanding the dust SED at the power spectrum level. The expansion is performed by means of moments around the MBB law, related to derivatives with respect to the dust spectral index. We present the mathematical formalism and apply it to simulations andPlancktotal intensity data, from 143 to 857 GHz, because no polarized data are yet available that provide the required sensitivity to perform this analysis. With simulations, we demonstrate the ability of high-order moments to account for spatial variations in MBB parameters. Neglecting these moments leads to poor fits and a bias in the recovered dust spectral index. We identify the main moments that are required to fit thePlanckdata. The comparison with simulations helps us to disentangle the respective contributions from dust and the cosmic infrared background to the high-order moments, but the simulations give an insufficient description of the actualPlanckdata. Extending our model to cosmic microwave backgroundB-mode analyses within a simplified framework, we find that ignoring the dust SED distortions, or trying to model them with a single decorrelation parameter, could lead to biases that are larger than the targeted sensitivity for the next generation of CMBB-mode experiments.