bluuebunny/crossref_metadata_2025 huggingface dataset:
A FN-MdV pathway and its role in cerebellar multimodular control of sensorimotor behavior
Authors: Wang Xiaolu , Yu Si-yang , Ren Zhong , De Zeeuw Chris I. , Gao Zhenyu
Published: November 2020

The cerebellum is crucial for various associative sensorimotor behaviors. Delay eyeblink conditioning (DEC) depends on the simplex lobule-interposed nucleus (IN) pathway, yet it is unclear how other cerebellar modules cooperate during this task. Here, we demonstrate the contribution of the vermis-fastigial nucleus (FN) pathway in controlling DEC. We found that task-related modulations in vermal Purkinje cells and FN neurons predict conditioned responses (CRs). Coactivation of the FN and the IN allows for the generation of proper motor commands for CRs, but only FN output fine-tunes unconditioned responses. The vermis-FN pathway launches its signal via the contralateral ventral medullary reticular nucleus, which converges with the command from the simplex-IN pathway onto facial motor neurons. We propose that the IN pathway specifically drives CRs, whereas the FN pathway modulates the amplitudes of eyelid closure during DEC. Thus, associative sensorimotor task optimization requires synergistic modulation of different olivocerebellar modules each provide unique contributions.
Genetic requirements and transcriptomics of Helicobacter pylori biofilm formation on abiotic and biotic surfaces
Authors: Hathroubi Skander , Hu Shuai , Ottemann Karen M.
Published: November 2020

Biofilm growth is a widespread mechanism that protects bacteria against harsh environments, antimicrobials, and immune responses. These types of conditions challenge chronic colonizers such as Helicobacter pylori but it is not fully understood how H. pylori biofilm growth is defined and its impact on H. pylori survival. To provide insights into H. pylori biofilm growth properties, we characterized biofilm formation on abiotic and biotic surfaces, identified genes required for biofilm formation, and defined the biofilm-associated gene expression of the laboratory model H. pylori strain G27. We report that H. pylori G27 forms biofilms with a high biomass and complex flagella-filled 3D structures on both plastic and gastric epithelial cells. Using a screen for biofilm-defective mutants and transcriptomics, we discovered that biofilm cells demonstrated lower transcripts for TCA cycle enzymes but higher ones for flagellar formation, two type four secretion systems, hydrogenase, and acetone metabolism. We confirmed that biofilm formation requires flagella, hydrogenase, and acetone metabolism on both abiotic and biotic surfaces. Altogether, these data suggest that H. pylori is capable of adjusting its phenotype when grown as biofilm, changing its metabolism, and re-shaping flagella, typically locomotion organelles, into adhesive structures.
Machine learning the Hubbard U parameter in DFT+U using Bayesian optimization
Authors: Yu Maituo , Yang Shuyang , Wu Chunzhi , Marom Noa
Published: November 2020

Within density functional theory (DFT), adding a Hubbard U correction can mitigate some of the deficiencies of local and semi-local exchange-correlation functionals, while maintaining computational efficiency. However, the accuracy of DFT+U largely depends on the chosen Hubbard U values. We propose an approach to determining the optimal U parameters for a given material by machine learning. The Bayesian optimization (BO) algorithm is used with an objective function formulated to reproduce the band structures produced by more accurate hybrid functionals. This approach is demonstrated for transition metal oxides, europium chalcogenides, and narrow-gap semiconductors. The band structures obtained using the BO U values are in agreement with hybrid functional results. Additionally, comparison to the linear response (LR) approach to determining U demonstrates that the BO method is superior.
Environmental flexibility does not explain metabolic robustness
Authors: Libiseller-Egger Julian , Coltman Benjamin Luke , Gerstl Matthias P. , Zanghellini Jürgen
Published: November 2020

Cells show remarkable resilience against genetic and environmental perturbations. However, its evolutionary origin remains obscure. In order to leverage methods of systems biology for examining cellular robustness, a computationally accessible way of quantification is needed. Here, we present an unbiased metric of structural robustness in genome-scale metabolic models based on concepts prevalent in reliability engineering and fault analysis. The probability of failure (PoF) is defined as the (weighted) portion of all possible combinations of loss-of-function mutations that disable network functionality. It can be exactly determined if all essential reactions, synthetic lethal pairs of reactions, synthetic lethal triplets of reactions etc. are known. In theory, these minimal cut sets (MCSs) can be calculated for any network, but for large models the problem remains computationally intractable. Herein, we demonstrate that even at the genome scale only the lowest-cardinality MCSs are required to efficiently approximate the PoF with reasonable accuracy. Building on an improved theoretical understanding, we analysed the robustness of 489 E. coli, Shigella, Salmonella, and fungal genome-scale metabolic models (GSMMs). In contrast to the popular “congruence theory”, which explains the origin of genetic robustness as a byproduct of selection for environmental flexibility, we found no correlation between network robustness and the diversity of growth-supporting environments. On the contrary, our analysis indicates that amino acid synthesis rather than carbon metabolism dominates metabolic robustness.
Real-world longitudinal data collected from the SleepHealth mobile app study
Authors: Deering Sean , Pratap Abhishek , Suver Christine , Borelli A. Joseph , Amdur Adam , Headapohl Will , Stepnowsky Carl J.
Published: November 2020

Conducting biomedical research using smartphones is a novel approach to studying health and disease that is only beginning to be meaningfully explored. Gathering large-scale, real-world data to track disease manifestation and long-term trajectory in this manner is quite practical and largely untapped. Researchers can assess large study cohorts using surveys and sensor-based activities that can be interspersed with participants’ daily routines. In addition, this approach offers a medium for researchers to collect contextual and environmental data via device-based sensors, data aggregator frameworks, and connected wearable devices. The main aim of the SleepHealth Mobile App Study (SHMAS) was to gain a better understanding of the relationship between sleep habits and daytime functioning utilizing a novel digital health approach. Secondary goals included assessing the feasibility of a fully-remote approach to obtaining clinical characteristics of participants, evaluating data validity, and examining user retention patterns and data-sharing preferences. Here, we provide a description of data collected from 7,250 participants living in the United States who chose to share their data broadly with the study team and qualified researchers worldwide.
Pharmacological characterisation of novel adenosine A3 receptor antagonists
Authors: Barkan Kerry , Lagarias Panagiotis , Stampelou Margarita , Stamatis Dimitrios , Hoare Sam , Safitri Dewi , Klotz Karl-Norbert , Vrontaki Eleni , Kolocouris Antonios , Ladds Graham
Published: November 2020

The adenosine A3 receptor (A3R) belongs to a family of four adenosine receptor (AR) subtypes which all play distinct roles throughout the body. A3R antagonists have been described as potential treatments for numerous diseases including asthma. Given the similarity between (adenosine receptors) orthosteric binding sites, obtaining highly selective antagonists is a challenging but critical task. Here we screen 39 potential A3R, antagonists using agonist-induced inhibition of cAMP. Positive hits were assessed for AR subtype selectivity through cAMP accumulation assays. The antagonist affinity was determined using Schild analysis (pA2 values) and fluorescent ligand binding. Structure–activity relationship investigations revealed that loss of the 3-(dichlorophenyl)-isoxazolyl moiety or the aromatic nitrogen heterocycle with nitrogen at α-position to the carbon of carboximidamide group significantly attenuated K18 antagonistic potency. Mutagenic studies supported by molecular dynamic simulations combined with Molecular Mechanics—Poisson Boltzmann Surface Area calculations identified the residues important for binding in the A3R orthosteric site. We demonstrate that K18, which contains a 3-(dichlorophenyl)-isoxazole group connected through carbonyloxycarboximidamide fragment with a 1,3-thiazole ring, is a specific A3R (< 1 µM) competitive antagonist. Finally, we introduce a model that enables estimates of the equilibrium binding affinity for rapidly disassociating compounds from real-time fluorescent ligand-binding studies. These results demonstrate the pharmacological characterisation of a selective competitive A3R antagonist and the description of its orthosteric binding mode. Our findings may provide new insights for drug discovery.
Comparison of global end-diastolic volume index derived from jugular and femoral indicator injection: a prospective observational study in patients equipped with both a PiCCO-2 and an EV-1000-device
Authors: Herner Alexander , Heilmaier Markus , Mayr Ulrich , Schmid Roland M. , Huber Wolfgang
Published: November 2020

Transpulmonary thermodilution (TPTD)-derived global end-diastolic volume index (GEDVI) is a static marker of preload which better predicted volume responsiveness compared to filling pressures in several studies. GEDVI can be generated with at least two devices: PiCCO and EV-1000. Several studies showed that uncorrected indicator injection into a femoral central venous catheter (CVC) results in a significant overestimation of GEDVI by the PiCCO-device. Therefore, the most recent PiCCO-algorithm corrects for femoral indicator injection. However, there are no systematic data on the impact of femoral indicator injection for the EV-1000 device. Furthermore, the correction algorithm of the PiCCO is poorly validated. Therefore, we prospectively analyzed 14 datasets from 10 patients with TPTD-monitoring undergoing central venous catheter (CVC)- and arterial line exchange. PiCCO was replaced by EV-1000, femoral CVCs were replaced by jugular/subclavian CVCs and vice-versa. For PiCCO, jugular and femoral indicator injection derived GEDVI was comparable when the correct information about femoral catheter site was given (p = 0.251). By contrast, GEDVI derived from femoral indicator injection using the EV-1000 was obviously not corrected and was substantially higher than jugular GEDVI measured by the EV-1000 (846 ± 250 vs. 712 ± 227 ml/m2; p = 0.001). Furthermore, measurements of GEDVI were not comparable between PiCCO and EV-1000 even in case of jugular indicator injection (p = 0.003). This is most probably due to different indexations of the raw value GEDV. EV-1000 could not be recommended to measure GEDVI in case of a femoral CVC. Furthermore, different indexations used by EV-1000 and PiCCO should be considered even in case of a jugular CVC when comparing GEDVI derived from PiCCO and EV-1000.
Variation in microparasite free-living survival and indirect transmission can modulate the intensity of emerging outbreaks
Authors: Ogbunugafor C. Brandon , Miller-Dickson Miles D. , Meszaros Victor A. , Gomez Lourdes M. , Murillo Anarina L. , Scarpino Samuel V.
Published: November 2020

Variation in free-living microparasite survival can have a meaningful impact on the ecological dynamics of established and emerging infectious diseases. Nevertheless, resolving the importance of indirect and environmental transmission in the ecology of epidemics remains a persistent challenge. It requires accurately measuring the free-living survival of pathogens across reservoirs of various kinds and quantifying the extent to which interaction between hosts and reservoirs generates new infections. These questions are especially salient for emerging pathogens, where sparse and noisy data can obfuscate the relative contribution of different infection routes. In this study, we develop a mechanistic, mathematical model that permits both direct (host-to-host) and indirect (environmental) transmission and then fit this model to empirical data from 17 countries affected by an emerging virus (SARS-CoV-2). From an ecological perspective, our model highlights the potential for environmental transmission to drive complex, nonlinear dynamics during infectious disease outbreaks. Summarizing, we propose that fitting alternative models with indirect transmission to real outbreak data from SARS-CoV-2 can be useful, as it highlights that indirect mechanisms may play an underappreciated role in the dynamics of infectious diseases, with implications for public health.
MCPIP1 reduces HBV-RNA by targeting its epsilon structure
Authors: Li Yingfang , Que Lusheng , Fukano Kento , Koura Miki , Kitamura Kouichi , Zheng Xin , Kato Takanobu , Aly Hussein Hassan , Watashi Koichi , Tsukuda Senko , Aizaki Hideki , Watanabe Noriyuki , Sato Yuko , Suzuki Tadaki , Suzuki Hiroshi I. , Hosomichi Kazuyoshi , Kurachi Makoto , Wakae Kousho , Muramatsu Masamichi
Published: November 2020

Hepatitis B virus (HBV) is the major causative factor of chronic viral hepatitis, liver cirrhosis, and hepatocellular carcinoma. We previously demonstrated that a proinflammatory cytokine IL-1β reduced the level of HBV RNA. However, the mechanism underlying IL-1β-mediated viral RNA reduction remains incompletely understood. In this study, we report that immune regulator Monocyte chemotactic protein-1-induced protein 1 (MCPIP1) can reduce HBV RNA in hepatocytes. MCPIP1 expression level was higher in the liver tissue of HBV-infected patients and mice. Overexpression of MCPIP1 decreased HBV RNA, whereas ablating MCPIP1 in vitro enhanced HBV production. The domains responsible for RNase activity or oligomerization, were required for MCPIP1-mediated viral RNA reduction. The epsilon structure of HBV RNA was important for its antiviral activity and cleaved by MCPIP1 in the cell-free system. Lastly, knocking out MCPIP1 attenuated the anti-HBV effect of IL-1β, suggesting that MCPIP1 is required for IL-1β-mediated HBV RNA reduction. Overall, these results suggest that MCPIP1 may be involved in the antiviral effect downstream of IL-1β.
Electronic structure with direct diagonalization on a D-wave quantum annealer
Authors: Teplukhin Alexander , Kendrick Brian K. , Tretiak Sergei , Dub Pavel A.
Published: November 2020

Quantum chemistry is regarded to be one of the first disciplines that will be revolutionized by quantum computing. Although universal quantum computers of practical scale may be years away, various approaches are currently being pursued to solve quantum chemistry problems on near-term gate-based quantum computers and quantum annealers by developing the appropriate algorithm and software base. This work implements the general Quantum Annealer Eigensolver (QAE) algorithm to solve the molecular electronic Hamiltonian eigenvalue-eigenvector problem on a D-Wave 2000Q quantum annealer. The approach is based on the matrix formulation, efficiently uses qubit resources based on a power-of-two encoding scheme and is hardware-dominant relying on only one classically optimized parameter. We demonstrate the use of D-Wave hardware for obtaining ground and excited electronic states across a variety of small molecular systems. The approach can be adapted for use by a vast majority of electronic structure methods currently implemented in conventional quantum-chemical packages. The results of this work will encourage further development of software such as qbsolv which has promising applications in emerging quantum information processing hardware and has expectation to address large and complex optimization problems intractable for classical computers.
Dated phylogeny suggests early Neolithic origin of Sino-Tibetan languages
Authors: Zhang Hanzhi , Ji Ting , Pagel Mark , Mace Ruth
Published: November 2020

An accurate reconstruction of Sino-Tibetan language evolution would greatly advance our understanding of East Asian population history. Two recent phylogenetic studies attempted to do so but several of their conclusions are different from each other. Here we reconstruct the phylogeny of the Sino-Tibetan language family, using Bayesian computational methods applied to a larger and linguistically more diverse sample. Our results confirm previous work in finding that the ancestral Sino-Tibetans first split into Sinitic and Tibeto-Burman clades, and support the existence of key internal relationships. But we find that the initial divergence of this group occurred earlier than previously suggested, at approximately 8000 years before the present, coinciding with the onset of millet-based agriculture and significant environmental changes in the Yellow River region. Our findings illustrate that key aspects of phylogenetic history can be replicated in this complex language family, and calls for a more nuanced understanding of the first Sino-Tibetan speakers in relation to the “early farming dispersal” theory of language evolution.
A recursive bifurcation model for early forecasting of COVID-19 virus spread in South Korea and Germany
Authors: Shen Julia
Published: November 2020

Early forecasting of COVID-19 virus spread is crucial to decision making on lockdown or closure of cities, states or countries. In this paper we design a recursive bifurcation model for analyzing COVID-19 virus spread in different countries. The bifurcation facilitates recursive processing of infected population through linear least-squares fitting. In addition, a nonlinear least-squares fitting procedure is utilized to predict the future values of infected populations. Numerical results on the data from two countries (South Korea and Germany) indicate the effectiveness of our approach, compared to a logistic growth model and a Richards model in the context of early forecast. The limitation of our approach and future research are also mentioned at the end of this paper.
GHG displacement factors of harvested wood products: the myth of substitution
Authors: Leturcq Philippe
Published: November 2020

A common idea is that substituting wood for fossil fuels and energy intensive materials is a better strategy in mitigating climate change than storing more carbon in forests. This opinion remains highly questionable for at least two reasons. Firstly, the carbon footprints of wood-products are underestimated as far as the “biomass carbon neutrality” assumption is involved in their determination, as it is often the case. When taking into account the forest carbon dynamics consecutive to wood harvest, and the limited lifetime of products, these carbon footprints are time-dependent and their presumed values under the carbon neutrality assumption are achieved only in steady-state conditions. Secondly, even if carbon footprints are correctly assessed, the benefit of substitutions is overestimated when all or parts of the wood products are supposed to replace non-wood products whatever the market conditions. Indeed, substitutions are effective only if an increase in wood product consumption implies verifiably a global reduction in non-wood productions. When these flaws in the evaluation of wood substitution effects are avoided, one must conclude that increased harvesting and wood utilization may be counter-productive for climate change mitigation objectives, especially when wood is used as a fuel.
Rab6 regulates recycling and retrograde trafficking of MR1 molecules
Authors: Huber Megan E. , Kurapova Regina , Heisler Chelsea M. , Karamooz Elham , Tafesse Fikadu G. , Harriff Melanie J.
Published: November 2020

Mucosal-associated invariant T (MAIT) cells are an innate-like T cell subset important in the early response to bacterial and viral lung pathogens. MAIT cells recognize bacterial small molecule metabolites presented on the Class I-like molecule MR1. As with other Class I and Class II molecules, MR1 can likely sample ligands in the intracellular environment through multiple cellular pathways. Rab6, a small GTPase that regulates a number of endosomal trafficking pathways including retrograde transport to the trans-Golgi network (TGN), is involved in the presentation of ligands fromMycobacterium tuberculosis(Mtb) to MAIT cells. The Rab6-mediated trafficking pathway contains endosomal compartments that share features with the Mtb intracellular compartment. Using inducible expression of MR1, this study demonstrates that Rab6 regulates the recycling of MR1 molecules from the cell surface through endosomal trafficking compartments to the TGN. This Rab6-dependent pool of recycled MR1, which is available for reloading with ligands from bacterial pathogens like Mtb, may be important for early recognition of infected cells by MAIT cells in the lung.
2D single crystal Bragg-dip mapping by time-of-flight energy-resolved neutron imaging on IMAT@ISIS
Authors: Strickland Joel , Tassenberg Karl , Sheppard Gareth , Nenchev Bogdan , Perry Sam , Li Jun , Dong Hongbiao , Burca Genoveva , Kelleher Joe , Irwin Steve
Published: November 2020

The cold neutron imaging and diffraction instrument IMAT, at the second target station of the pulsed neutron and muon source ISIS, is used to investigate bulk mosaicity within as-cast single crystal CMSX-4 and CMSX-10 Ni-base superalloys. Within this study, neutron transmission spectrum is recorded by each pixel within the microchannel plate image detector. The movement of the lowest transmission wavelength within a specified Bragg-dip for each pixel is tracked. The resultant Bragg-dip shifting has enabled crystallographic orientation mapping of bulk single crystal specimens with good spatial resolution. The total acquisition time required to collect sufficient statistics for each test is ~ 3 h. In this work, the influence of a change in bulk solidification conditions on the variation in single crystal mosaicity was investigated. Misorientation of the (001) crystallographic plane has been visualised and a new spiral twisting solidification phenomena observed. This proof of concept work establishes time-of-flight energy-resolved neutron imaging as a fundamental characterisation tool for understanding and visualising mosaicity within metallic single crystals and provides the foundation for post-mortem deduction of the shape of the solid/liquid isotherm.
Spin-coated $$\hbox {Cu}_2\hbox {ZnSnS}_{4}$$ solar cells: A study on the transformation from ink to film
Authors: Engberg Sara , Martinho Filipe , Gansukh Mungunshagai , Protti Alexander , Küngas Rainer , Stamate Eugen , Hansen Ole , Canulescu Stela , Schou Jørgen
Published: November 2020

In this paper, we study the DMSO/thiourea/chloride salt system for synthesis of pure-sulfide$$\hbox {Cu}_2\hbox {ZnSnS}_{4}$$Cu2ZnSnS4(CZTS) thin-film solar cells under ambient conditions. We map out the ink constituents and determine the effect of mixing time and filtering. The thermal behavior of the ink is analyzed, and we find that more than 90% of the solvent has evaporated at$$250\,^{\circ }\hbox {C}$$250∘C. However, chloride and sulfoxide species are released continually until$$500\,^{\circ }\hbox {C}$$500∘C, suggesting the advantage of a higher pre-annealing temperature, which is also commonly observed in the spin-coating routines in literature. Another advantage of a higher pre-annealing temperature is that the worm-like pattern in the spin-coated film can be avoided. We hypothesize that this pattern forms as a result of hydrodynamics within the film as it dries, and it causes micro-inhomogeneities in film morphology. Devices were completed in order to finally evaluate the effect of varying thermal exposure during pre-annealing. Contrary to the previous observations, a lower pre-annealing temperature of$$250\,^{\circ }\hbox {C}$$250∘Cresults in the best device efficiency of 4.65%, which to the best of our knowledge is the highest efficiency obtained for a pure-sulfide kesterite made with DMSO. Lower thermal exposure during pre-annealing results in larger grains and a thicker$$\hbox {MoS}_2$$MoS2layer at the CZTS/Mo interface. Devices completed at higher pre-annealing temperatures display the existence of either a Cu-S secondary phase or an incomplete sulfurization with smaller grains and a fine-grain layer at the back interface.
Pathological findings in the endometrium after microwave endometrial ablation
Authors: Nakayama Kentaro , Razia Sultana , Ishibashi Tomoka , Ishikawa Masako , Yamashita Hitomi , Nakamura Kohei , Sawada Kiyoka , Yoshimura Yuki , Tatsumi Nagisa , Kurose Sonomi , Minamoto Toshiko , Iida Kouji , Ishikawa Noriyoshi , Kyo Satoru
Published: November 2020

The acceptance of MEA in Japan is well demand due to its outstanding effectiveness and safety. Infrequently, a repeat MEA or hysterectomy is needed for recurrent menorrhagia in case of failure ablation. The reasons of recurrent menorrhagia subsequent MEA treatment are unclear. The objective of current study is to identify the possible causes of menorrhagia repetition following MEA, together with the observation of histological changes in the endometrium due to this treatment compared with normal cycling endometrial tissue. A total of 170 patients, 8 (4.7%) of them carried out hysterectomy after 16.8 months (range, 2–29 months) of MEA treatment. Normal (n = 47) and MEA (n = 8) treated paraffin embedded endometrial tissue were prepared for hematoxylin and eosin (H&E) and immunostaining study to recognize the histological changes in the endometrium as a result of MEA treatment. The histological features observed increased tubal metaplasia (TM) including negative expression of the estrogen receptor (ER) and progesterone receptor (PR) in the endometrium subsequent MEA treatment. Increased TM together with the absence of ER and PR expression might be a reasonable explanation for repetition menorrhagia in cases of failure ablation. Further study is required to clarify the molecular mechanisms of tubal metaplasia and the expression loss of hormone receptor in the endometrium as a result of MEA treatment. Current studies propose that low dose estrogen-progestin may not be effective with recurrent menorrhagia patient’s due to the inadequacy of hormone receptor expression in the endometrium following MEA.
Effects of dietary n-3-PUFA supplementation, post-insemination plane of nutrition and pregnancy status on the endometrial transcriptome of beef heifers
Authors: Surlis Carla , Cormican Paul , Waters Sinead M. , Lonergan Patrick , Keogh Kate , Doyle David N. , Kenny David A.
Published: November 2020

Supplementation of cattle diets with n-3-polyunsaturated fatty acids (PUFA) can improve reproductive efficiency. Conversely, short-term fluctuations in feed supply can impact pregnancy establishment. The objectives of this study were to examine the effects of (1) dietary supplementation with n-3-PUFA and (2) post-insemination plane of nutrition on the endometrial transcriptome. Beef crossbred heifers were offered concentrate based diets fortified with n-3-PUFA (PUFA; n = 32) or not (CONT; n = 28) for 30 days prior to breeding at a synchronised oestrous. Following artificial insemination, heifers were allocated within treatment to either a high or low plane of nutrition. Heifers were maintained on these diets for 16 days following which endometrial tissue was harvested at slaughter for subsequent RNAseq analysis. The influence of pregnancy status on the endomentrial transcriptome, within each dietary treatment group, was also examined. Post-insemination diet affected (P < 0.05) the endometrial transcriptome. Specifically, within n-3-PUFA-supplemented heifers, genes involved in embryonic development and mTOR signalling pathways, important in pregnancy establishment, were identified as differentially expressed. Results indicate that dietary supplementation of cattle diets with n-3-PUFA may have a positive effect on the expression of key fertility-related genes and pathways, during the critical window of maternal recognition of pregnancy, particularly where animals are underfed.
Steering complex networks toward desired dynamics
Authors: Gutiérrez Ricardo , Materassi Massimo , Focardi Stefano , Boccaletti Stefano
Published: November 2020

We consider networks of dynamical units that evolve in time according to different laws, and are coupled to each other in highly irregular ways. Studying how to steer the dynamics of such systems towards a desired evolution is of great practical interest in many areas of science, as well as providing insight into the interplay between network structure and dynamical behavior. We propose a pinning protocol for imposing specific dynamic evolutions compatible with the equations of motion on a networked system. The method does not impose any restrictions on the local dynamics, which may vary from node to node, nor on the interactions between nodes, which may adopt in principle any nonlinear mathematical form and be represented by weighted, directed or undirected links. We first explore our method on small synthetic networks of chaotic oscillators, which allows us to unveil a correlation between the ordered sequence of pinned nodes and their topological influence in the network. We then consider a 12-species trophic web network, which is a model of a mammalian food web. By pinning a relatively small number of species, one can make the system abandon its spontaneous evolution from its (typically uncontrolled) initial state towards a target dynamics, or periodically control it so as to make the populations evolve within stipulated bounds. The relevance of these findings for environment management and conservation is discussed.
Relationship between tendon structure, stiffness, gait patterns and patient reported outcomes during the early stages of recovery after an Achilles tendon rupture
Authors: Laurent Didier , Walsh Lorcan , Muaremi Amir , Beckmann Nicolau , Weber Eckhard , Chaperon Frederique , Haber Harry , Goldhahn Joerg , Klauser Andrea Sabine , Blauth Michael , Schieker Matthias
Published: November 2020

After an Achilles tendon (AT) injury, the decision to return to full weightbearing for the practice of sports or strenuous activities is based on clinical features only. In this study, tendon stiffness and foot plantar pressure, as objective quantitative measures that could potentially inform clinical decision making, were repeatedly measured in 15 patients until 3 months after the AT rupture by using shear wave elastography (SWE) and wearable insoles, respectively. Meanwhile, patient reported outcomes assessing the impact on physical activity were evaluated using the Achilles Tendon Total Rupture Score (ATRS). At week-2 post-injury, stiffness of the injured tendon varied from 6.00 ± 1.62 m/s (mean ± SD) close to the rupture to 8.91 ± 2.29 m/s when measured more distally. While near complete recovery was observed in distal and middle regions at week-8, the shear wave velocity in the proximal region recovered to only 65% of the contralateral value at week-12. In a parallel pre-clinical study, the tendon stiffness measured in vivo by SWE in a rat model was found to be strongly correlated with ex vivo values of the Young’s modulus, which attests to the adequacy of SWE for these measures. The insole derived assessment of the plantar pressure distribution during walking showed slight sub-optimal function of the affected foot at week-12, while the ATRS score recovered to a level of 59 ± 16. Significant correlations found between tendon stiffness, insole variables and distinct ATRS activities, suggest clinical relevance of tendon stiffness and foot plantar pressure measurements. These results illustrate how an alteration of the AT structure can impact daily activities of affected patients and show how digital biomarkers can track recovery in function over time.
A VCP modulator, KUS121, as a promising therapeutic agent for post-traumatic osteoarthritis
Authors: Saito Motoo , Nishitani Kohei , Ikeda Hanako O. , Yoshida Shigeo , Iwai Sachiko , Ji Xiang , Nakahata Akihiro , Ito Akira , Nakamura Shinichiro , Kuriyama Shinichi , Yoshitomi Hiroyuki , Murata Koichi , Aoyama Tomoki , Ito Hiromu , Kuroki Hiroshi , Kakizuka Akira , Matsuda Shuichi
Published: November 2020

Post-traumatic osteoarthritis (PTOA) is a major cause which hinders patients from the recovery after intra-articular injuries or surgeries. Currently, no effective treatment is available. In this study, we showed that inhibition of the acute stage chondrocyte death is a promising strategy to mitigate the development of PTOA. Namely, we examined efficacies of Kyoto University Substance (KUS) 121, a valosin-containing protein modulator, for PTOA as well as its therapeutic mechanisms. In vivo, in a rat PTOA model by cyclic compressive loading, intra-articular treatments of KUS121 significantly improved the modified Mankin scores and reduced damaged-cartilage volumes, as compared to vehicle treatment. Moreover, KUS121 markedly reduced the numbers of TUNEL-, CHOP-, MMP-13-, and ADAMTS-5-positive chondrocytes in the damaged knees. In vitro, KUS121 rescued human articular chondrocytes from tunicamycin-induced cell death, in both monolayer culture and cartilage explants. It also significantly downregulated the protein or gene expression of ER stress markers, proinflammatory cytokines, and extracellular-matrix-degrading enzymes induced by tunicamycin or IL-1β. Collectively, these results demonstrated that KUS121 protected chondrocytes from cell death through the inhibition of excessive ER stress. Therefore, KUS121 would be a new, promising therapeutic agent with a protective effect on the progression of PTOA.
Non-linear association between admission temperature and neonatal mortality in a low-resource setting
Authors: Cavallin Francesco , Calgaro Serena , Brugnolaro Valentina , Wingi Olivier Manzungu , Muhelo Arlindo Rosario , Da Dalt Liviana , Pizzol Damiano , Putoto Giovanni , Trevisanuto Daniele
Published: November 2020

Both neonatal hypothermia and hyperthermia represent important risk factors for neonatal mortality, but information on mortality risk across a full range of neonatal temperatures is lacking in low-resource settings. We evaluated the association between neonatal mortality and a full range of admission temperatures in a low-resource setting. This retrospective observational study was conducted at Beira Central Hospital, Mozambique. The relationship between admission temperature and mortality was evaluated using multivariable analyses with temperature modeled as non-linear term. Among 2098 neonates admitted to the Special Care Unit between January–December 2017, admission temperature was available in 1344 neonates (64%) who were included in the analysis. A non-linear association between mortality rate and temperature was identified. Mortality rate decreased from 84% at 32 °C to 64% at 34.6 °C (− 8% per °C), to 41% at 36 °C (− 16% per °C), to 26% to 36.6 °C (− 25% per °C) and to 22% at 38.3 °C (− 2% per °C), then increased to 40% at 41 °C (+ 7% per °C). Mortality rate was estimated to be at minimum at admission temperature of 37.5 °C. In conclusions, the non-linear relationship highlighted different mortality risks across a full range of neonatal temperatures in a low-resource setting. Admission temperature was not recorded in one third of neonates.
Changes of protein levels in human urine reflect the dysregulation of signaling pathways of chronic kidney disease and its complications
Authors: Hao Yiming , Reyes Luis Tanon , Morris Robert , Xu Yifeng , Wang Yiqin , Cheng Feng
Published: November 2020

The increasing prevalence of chronic kidney disease (CKD) seriously is threatening human health and overall quality of life. The discovery of biomarkers of pathogenesis of CKD and the associated complications are very important for CDK diagnosis and treatment. In this paper, urine protein biomarkers were investigated because urine sample collection is convenient and non-invasive. We analyzed the protein concentrations in the urine of CKD patients and extracted abnormal protein signals comparing with the healthy control groups. The enriched signaling pathways that may characterize CKD pathology were identified from these proteins. We applied surface-enhanced laser desorption and ionization time of flight mass spectrometry technology to detect different protein peaks in urine samples from patients with CKD and healthy controls. We searched the proteins corresponding to protein peaks through the UniProt database and identified the signaling pathways of CKD and its complications by using the NIH DAVID database. 42 low abundance proteins and 46 high abundance proteins in the urine samples from CKD patients were found by comparing with healthy controls. Seven KEGG pathways related to CKD and its complications were identified from the regulated proteins. These pathways included chemokine signaling pathway, cytokine–cytokine receptor interaction, oxidative phosphorylation, cardiac muscle contraction, Alzheimer’s disease, Parkinson's disease, and salivary secretion. In CKD stages 2, 3, 4, and 5, five proteins showed significantly differential abundances. The differential protein signals and regulated signaling pathways will provide new insight for the pathogenesis of CKD and its complications. These altered proteins may also be used as novel biomarkers for the noninvasive and convenient diagnosis methods of CKD and its complications through urine testing in the future.
A new spin crossover FeII coordination environment in a two-fold interpenetrated 3-D Hofmann-type framework material
Authors: Ahmed Manan , Xie Zixi , Thoonen Shannon , Hua Carol , Kepert Cameron J. , Price Jason R. , Neville Suzanne M.
Published: November 2020

Spin-crossover is observed for the first time in a FeII(py)3(NC⋯)3 coordination environment which arises in a two-fold interpenetrated 3-D Hofmann-like framework.
Tuning the transition barrier of H2 dissociation in the hydrogenation of CO2 to formic acid on Ti-doped Sn2O4 clusters
Authors: Sarma Plaban J. , Dowerah Dikshita , Gour Nand K. , Logsdail Andrew J. , Catlow C. Richard A. , Deka Ramesh Ch.
Published: November 2020

Schematic representation of Ti-doping on a pure Sn2O4 cluster for the hydrogenation of CO2 to HCOOH via a hydride pathway.
The interaction of defects in a mayenite structure
Authors: Shkerin Sergey N. , Ulyanova Ekaterina S. , Naumov Sergey V. , Shmakov Aleksandr N. , Tolkacheva Anna S.
Published: November 2020

A relatively small variation in the oxygen partial pressure at high temperature leads to the appearance of differences in Ca12Al14O33 structure.
Studying the mechanism of phase separation in aqueous solutions of globular proteins via molecular dynamics computer simulations
Authors: Brudar Sandi , Gujt Jure , Spohr Eckhard , Hribar-Lee Barbara
Published: November 2020

Proteins are the most abundant biomacromolecules in living cells, where they perform vital roles in virtually every biological process.
Two derivatives of phenylpyridyl-fused boroles with contrasting electronic properties: decreasing and enhancing the electron accepting ability
Authors: He Jiang , Rauch Florian , Krummenacher Ivo , Braunschweig Holger , Finze Maik , Marder Todd B.
Published: November 2020

The pyridyl groups of two phenylpyridyl-fused boroles were transformed into an electron-rich dihydropyridine moiety or an even more electron-deficient N-methylpyridinium cation, leading to contrasting electronic properties.
A valence tautomeric cobalt–dioxolene complex with an anchoring group for prospective chemical grafting to metal oxides
Authors: Mörtel Max , Seller Michael , Heinemann Frank W. , Khusniyarov Marat M.
Published: November 2020

A valence tautomeric cobalt–dioxolene complex featuring a protected anchoring group has been synthesized and its thermal switchability has been confirmed.
The co-effect of ampicillin and multi-walled carbon nanotubes on activated sludge in sequencing batch reactors: microbial status, microbial community structure and ARGs propagation
Authors: Zhou Wenlin , Wang Yan , Wang Min , Qian Binghong , Li Li , Gao Baoyu
Published: November 2020

The co-occurrences of ampicillin and multi-walled carbon nanotubes showed a lower cytotoxicity to activated sludge compared to individual ones, but enhanced the relative abundances of antibiotic resistance genes.
High n-3 fatty acids counteract hyperglycemia-induced insulin resistance in fat-1 miceviapre-adipocyte NLRP3 inflammasome inhibition
Authors: Yu Qingyao , Wang Tiantian , Wang Feng , Yang Yong , He Canxia , Yang Wenge , Zhang JinJie , Zou Zuquan
Published: November 2020

Hyperglycemia induces TXNIP expression and triggers NLRP3 inflammasome-dependent IL-1β secretion, which is counteracted by n-3 PUFAs such as DHA through the PI3K/Akt pathway-mediated downregulation of TXNIP in adipose pre-adipocytes.
Online simultaneous determination of H2O and KCl in potash with LIBS coupled to convolutional and back-propagation neural networks
Authors: Zou Long , Sun Chen , Wu Mengting , Zhang Yuqing , Yue Zengqi , Xu Weijie , Shabbir Sahar , Chen Fengye , Liu Bin , Liu Wenhui , Yu Jin
Published: November 2020

H2O and KCl concentrations in potash have been precisely determined using LIBS online detection coupled with machine learning data processing.
Determination of thallium(iii) ions by oxidative hydrolysis of rhodamine–hydroxamate
Authors: Yoo Jae Hoon , Lee Yu Jeong , Lee Kang Min , Choi Myung Gil , Park Tae Jung , Chang Suk-Kyu
Published: November 2020

A colorimetric and turn-on type fluorescence Tl3+ signaling probe for the early screening of elevated urinary thallium levels in acute poisoning cases using a readily available smartphone was developed.
Energy band alignment at the heterointerface between a nanostructured TiO2 layer and Au22(SG)18 clusters: relevance to metal-cluster-sensitized solar cells
Authors: Larina Liudmila L. , Omelianovych Oleksii , Dao Van-Duong , Pyo Kyunglim , Lee Dongil , Choi Ho-Suk
Published: November 2020

XPS study of the electronic structure of the Au22(SG)18 clusters and their interface with TiO2 reveals that tailoring of the electronic band structure at the interface can be exploited to increase the efficiency of metal-cluster-sensitized solar cells.
Self-template-derived ZnCo2O4 porous microspheres decorated by Ag nanoparticles and their selective detection of formaldehyde
Authors: Qin Qixuan , Li Yuliang , Bu Weiyi , Meng Lingling , Chuai Xiaohong , Zhou Zhijie , Hu Changhua
Published: November 2020

ZnCo2O4 porous microspheres were successfully synthesized through a facile one-step solvent method using polyethylene glycol 1000 as a self-assembly template and subsequent annealing.
Synthesis and charge transfer characteristics of a ruthenium–acetylide complex
Authors: Kuhrt Robert , Ho Po-Yuen , Hantusch Martin , Lissel Franziska , Blacque Olivier , Knupfer Martin , Büchner Bernd
Published: November 2020

A newly synthesised ruthenium–acetylide complex is characterised by various methods and its charge transfer to the acceptor F6TCNNQ is studied by optical and photoelectron spectroscopy.
Facile synthesis of multi-type carbon doped and modified nano-TiO2 for enhanced visible-light photocatalysis
Authors: Li Jianing , Wang Junzhong , Liu Juming , Li Yan , Ma Huiyan , Yang Jucai , Zhang Qiancheng
Published: November 2020

The synergistic modification of nano-TiO2 by multi-type carbon species results in excellent and stable visible-light photocatalytic degradation activity.
Consistent inclusion of continuum solvation in energy decomposition analysis: theory and application to molecular CO2 reduction catalysts
Authors: Mao Yuezhi , Loipersberger Matthias , Kron Kareesa J. , Derrick Jeffrey S. , Chang Christopher J. , Sharada Shaama Mallikarjun , Head-Gordon Martin
Published: November 2020

Extension of ALMO-EDA to include contributions from continuum solvent and application to electro- and photochemical CO2 reduction catalysts.
Rh(i)-catalyzed stereoselective desymmetrization of prochiral cyclohexadienones via highly exo-selective Huisgen-type [3 + 2] cycloaddition
Authors: Gollapelli Krishna Kumar , Patil Vaibhav B. , Vinaykumar Allam , Chegondi Rambabu
Published: November 2020

A Rh(i)-catalyzed highly stereoselective desymmetrization of 2-alkynylbenzaldehyde-tethered cyclohexadienones triggered by intramolecular Huisgen-type [3 + 2] cycloaddition has been developed.
Mechanism of inhibition of SARS-CoV-2 Mpro by N3 peptidyl Michael acceptor explained by QM/MM simulations and design of new derivatives with tunable chemical reactivity
Authors: Arafet Kemel , Serrano-Aparicio Natalia , Lodola Alessio , Mulholland Adrian J. , González Florenci V. , Świderek Katarzyna , Moliner Vicent
Published: November 2020

QM/MM simulations identify the mechanism of reaction of N3, a covalent peptidyl inhibitor of SARS-CoV-2 main protease. Modelling of two novel proposed compounds, B1 and B2, suggests that reversibility of covalent inhibition could be tailored.
Magnetorheological fluids based on core–shell carbonyl iron particles modified by various organosilanes: synthesis, stability and performance
Authors: Ronzova Alena , Sedlacik Michal , Cvek Martin
Published: November 2020

Implications of the organosilane-coated particles on the utility properties of MR fluids.
Metal chalcogenide-associated catalysts enabling CO2 electroreduction to produce low-carbon fuels for energy storage and emission reduction: catalyst structure, morphology, performance, and mechanism
Authors: Shao Xiaolin , Zhang Xurui , Liu Yuyu , Qiao Jinli , Zhou Xiao-Dong , Xu Nengneng , Malcombe Jamie L. , Yi Jin , Zhang Jiujun
Published: November 2020

Electrochemical reduction of CO2 (ERCO2) to low-carbon fuels/chemicals can simultaneously realize storage of electrical energy in the form of chemicals and alleviate environmental deterioration.
PROTEIN l-ISOASPARTYL METHYLTRANSFERASE (PIMT) in plants: regulations and functions
Authors: Kamble Nitin Uttam , Majee Manoj
Published: November 2020

Proteins are essential molecules that carry out key functions in a cell. However, as a result of aging or stressful environments, the protein undergoes a range of spontaneous covalent modifications, including the formation of abnormal l-isoaspartyl residues from aspartyl or asparaginyl residues, which can disrupt the protein's inherent structure and function. PROTEIN l-ISOASPARTYL METHYLTRANSFERASE (PIMT: EC 2.1.1.77), an evolutionarily conserved ancient protein repairing enzyme (PRE), converts such abnormal l-isoaspartyl residues to normal l-aspartyl residues and re-establishes the protein's native structure and function. Although originally discovered in animals as a PRE, PIMT emerged as a key PRE in plants, particularly in seeds, in which PIMT plays a predominant role in preserving seed vigor and viability for prolonged periods of time. Interestingly, higher plants encode a second PIMT (PIMT2) protein which possesses a unique N-terminal extension, and exhibits several distinct features and far more complexity than non-plant PIMTs. Recent studies indicate that the role of PIMT is not restricted to preserving seed vigor and longevity but is also implicated in enhancing the growth and survivability of plants under stressful environments. Furthermore, expression studies indicate the tantalizing possibility that PIMT is involved in various physiological processes apart from its role in seed vigor, longevity and plant's survivability under abiotic stress. This review article particularly describes new insights and emerging interest in all facets of this enzyme in plants along with a concise comparative overview on isoAsp formation, and the role and regulation of PIMTs across evolutionary diverse species. Additionally, recent methods and their challenges in identifying isoaspartyl containing proteins (PIMT substrates) are highlighted.