bluuebunny/crossref_metadata_2025 huggingface dataset:
Standard assessments of climate forecast skill can be misleading
Authors: Risbey James S. , Squire Dougal T. , Black Amanda S. , DelSole Timothy , Lepore Chiara , Matear Richard J. , Monselesan Didier P. , Moore Thomas S. , Richardson Doug , Schepen Andrew , Tippett Michael K. , Tozer Carly R.
Published: July 2021

Assessments of climate forecast skill depend on choices made by the assessor. In this perspective, we use forecasts of the El Niño-Southern-Oscillation to outline the impact of bias-correction on skill. Many assessments of skill from hindcasts (past forecasts) are probably overestimates of attainable forecast skill because the hindcasts are informed by observations over the period assessed that would not be available to real forecasts. Differences between hindcast and forecast skill result from changes in model biases from the period used to form forecast anomalies to the period over which the forecast is made. The relative skill rankings of models can change between hindcast and forecast systems because different models have different changes in bias across periods.
Self-rechargeable cardiac pacemaker system with triboelectric nanogenerators
Authors: Ryu Hanjun , Park Hyun-moon , Kim Moo-Kang , Kim Bosung , Myoung Hyoun Seok , Kim Tae Yun , Yoon Hong-Joon , Kwak Sung Soo , Kim Jihye , Hwang Tae Ho , Choi Eue-Keun , Kim Sang-Woo
Published: July 2021

Self-powered implantable devices have the potential to extend device operation time inside the body and reduce the necessity for high-risk repeated surgery. Without the technological innovation of in vivo energy harvesters driven by biomechanical energy, energy harvesters are insufficient and inconvenient to power titanium-packaged implantable medical devices. Here, we report on a commercial coin battery-sized high-performance inertia-driven triboelectric nanogenerator (I-TENG) based on body motion and gravity. We demonstrate that the enclosed five-stacked I-TENG converts mechanical energy into electricity at 4.9 μW/cm3 (root-mean-square output). In a preclinical test, we show that the device successfully harvests energy using real-time output voltage data monitored via Bluetooth and demonstrate the ability to charge a lithium-ion battery. Furthermore, we successfully integrate a cardiac pacemaker with the I-TENG, and confirm the ventricle pacing and sensing operation mode of the self-rechargeable cardiac pacemaker system. This proof-of-concept device may lead to the development of new self-rechargeable implantable medical devices.
Biochemical and functional characterization of mutant KRAS epitopes validates this oncoprotein for immunological targeting
Authors: Bear Adham S. , Blanchard Tatiana , Cesare Joseph , Ford Michael J. , Richman Lee P. , Xu Chong , Baroja Miren L. , McCuaig Sarah , Costeas Christina , Gabunia Khatuna , Scholler John , Posey Avery D. , O’Hara Mark H. , Smole Anze , Powell Daniel J. , Garcia Benjamin A. , Vonderheide Robert H. , Linette Gerald P. , Carreno Beatriz M.
Published: July 2021

Activating RAS missense mutations are among the most prevalent genomic alterations observed in human cancers and drive oncogenesis in the three most lethal tumor types. Emerging evidence suggests mutant KRAS (mKRAS) may be targeted immunologically, but mKRAS epitopes remain poorly defined. Here we employ a multi-omics approach to characterize HLA class I-restricted mKRAS epitopes. We provide proteomic evidence of mKRAS epitope processing and presentation by high prevalence HLA class I alleles. Select epitopes are immunogenic enabling mKRAS-specific TCRαβ isolation. TCR transfer to primary CD8+ T cells confers cytotoxicity against mKRAS tumor cell lines independent of histologic origin, and the kinetics of lytic activity correlates with mKRAS peptide-HLA class I complex abundance. Adoptive transfer of mKRAS-TCR engineered CD8+ T cells leads to tumor eradication in a xenograft model of metastatic lung cancer. This study validates mKRAS peptides as bona fide epitopes facilitating the development of immune therapies targeting this oncoprotein.
Francisella tularensis induces Th1 like MAIT cells conferring protection against systemic and local infection
Authors: Zhao Zhe , Wang Huimeng , Shi Mai , Zhu Tianyuan , Pediongco Troi , Lim Xin Yi , Meehan Bronwyn S. , Nelson Adam G. , Fairlie David P. , Mak Jeffrey Y. W. , Eckle Sidonia B. G. , de Lima Moreira Marcela , Tumpach Carolin , Bramhall Michael , Williams Cameron G. , Lee Hyun Jae , Haque Ashraful , Evrard Maximilien , Rossjohn Jamie , McCluskey James , Corbett Alexandra J. , Chen Zhenjun
Published: July 2021

Mucosal-associated Invariant T (MAIT) cells are recognized for their antibacterial functions. The protective capacity of MAIT cells has been demonstrated in murine models of local infection, including in the lungs. Here we show that during systemic infection of mice with Francisella tularensis live vaccine strain results in evident MAIT cell expansion in the liver, lungs, kidney and spleen and peripheral blood. The responding MAIT cells manifest a polarised Th1-like MAIT-1 phenotype, including transcription factor and cytokine profile, and confer a critical role in controlling bacterial load. Post resolution of the primary infection, the expanded MAIT cells form stable memory-like MAIT-1 cell populations, suggesting a basis for vaccination. Indeed, a systemic vaccination with synthetic antigen 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil in combination with CpG adjuvant similarly boosts MAIT cells, and results in enhanced protection against both systemic and local infections with different bacteria. Our study highlights the potential utility of targeting MAIT cells to combat a range of bacterial pathogens.
Selective targeting of ligand-dependent and -independent signaling by GPCR conformation-specific anti-US28 intrabodies
Authors: De Groof Timo W. M. , Bergkamp Nick D. , Heukers Raimond , Giap Truc , Bebelman Maarten P. , Goeij-de Haas Richard , Piersma Sander R. , Jimenez Connie R. , Garcia K. Christopher , Ploegh Hidde L. , Siderius Marco , Smit Martine J.
Published: July 2021

While various GPCRs, including US28, display constitutive, ligand-independent activity, it remains to be established whether ligand-dependent and -independent active conformations differ and can be selectively modulated. Previously, the agonist-bound conformation of US28 was stabilized and its structure was solved using the anti-US28 nanobody Nb7. Here we report the recognition of the constitutively active, apo-conformation of US28 by another nanobody VUN103. While the Nb7 intrabody selectively inhibits ligand-induced signaling, the VUN103 intrabody blocks constitutive signaling, indicating the existence of distinct US28 conformational states. By displacing Gαq protein, VUN103 prevents US28 signaling and reduces tumor spheroids growth. Overall, nanobodies specific for distinct GPCR conformational states, i.e. apo- and agonist-bound, can selectively target and discern functional consequences of ligand-dependent versus independent signaling.
Organozinc pivalates for cobalt-catalyzed difluoroalkylarylation of alkenes
Authors: Cheng Xinyi , Liu Xingchen , Wang Shengchun , Hu Ying , Hu Binjing , Lei Aiwen , Li Jie
Published: July 2021

Installation of fluorine into pharmaceutically relevant molecules plays a vital role in their properties of biology or medicinal chemistry. Direct difunctionalization of alkenes and 1,3-dienes to achieve fluorinated compounds through transition-metal catalysis is challenging, due to the facile β-H elimination from the Csp3‒[M] intermediate. Here we report a cobalt-catalyzed regioselective difluoroalkylarylation of both activated and unactivated alkenes with solid arylzinc pivalates and difluoroalkyl bromides through a cascade Csp3‒Csp3/Csp3‒Csp2bond formation under mild reaction conditions. Indeed, a wide range of functional groups on difluoroalkyl bromides, olefins, 1,3-dienes as well as (hetero)arylzinc pivalates are well tolerated by the cobalt-catalyst, thus furnishing three-component coupling products in good yields and with high regio- and diastereoselectivity. Kinetic experiments comparing arylzinc pivalates and conventional arylzinc halides highlight the unique reactivity of these organozinc pivalates. Mechanistic studies strongly support that the reaction involves direct halogen atom abstraction via single electron transfer to difluoroalkyl bromides from the in situ formed cobalt(I) species, thus realizing a Co(I)/Co(II)/Co(III) catalytic cycle.
Glucose limitation activates AMPK coupled SENP1-Sirt3 signalling in mitochondria for T cell memory development
Authors: He Jianli , Shangguan Xun , Zhou Wei , Cao Ying , Zheng Quan , Tu Jun , Hu Gaolei , Liang Zi , Jiang Cen , Deng Liufu , Wang Shengdian , Yang Wen , Zuo Yong , Ma Jiao , Cai Rong , Chen Yalan , Fan Qiuju , Dong Baijun , Xue Wei , Tan Hongsheng , Qi Yitao , Gu Jianmin , Su Bing , Eugene Chin Y. , Chen Guoqiang , Wang Qi , Wang Tianshi , Cheng Jinke
Published: July 2021

Metabolic programming and mitochondrial dynamics along with T cell differentiation affect T cell fate and memory development; however, how to control metabolic reprogramming and mitochondrial dynamics in T cell memory development is unclear. Here, we provide evidence that the SUMO protease SENP1 promotes T cell memory development via Sirt3 deSUMOylation. SENP1-Sirt3 signalling augments the deacetylase activity of Sirt3, promoting both OXPHOS and mitochondrial fusion. Mechanistically, SENP1 activates Sirt3 deacetylase activity in T cell mitochondria, leading to reduction of the acetylation of mitochondrial metalloprotease YME1L1. Consequently, deacetylation of YME1L1 suppresses its activity on OPA1 cleavage to facilitate mitochondrial fusion, which results in T cell survival and promotes T cell memory development. We also show that the glycolytic intermediate fructose-1,6-bisphosphate (FBP) as a negative regulator suppresses AMPK-mediated activation of the SENP1-Sirt3 axis and reduces memory development. Moreover, glucose limitation reduces FBP production and activates AMPK during T cell memory development. These data show that glucose limitation activates AMPK and the subsequent SENP1-Sirt3 signalling for T cell memory development.
Observation of nuclear-spin Seebeck effect
Authors: Kikkawa T. , Reitz D. , Ito H. , Makiuchi T. , Sugimoto T. , Tsunekawa K. , Daimon S. , Oyanagi K. , Ramos R. , Takahashi S. , Shiomi Y. , Tserkovnyak Y. , Saitoh E.
Published: July 2021

Thermoelectric effects have been applied to power generators and temperature sensors that convert waste heat into electricity. The effects, however, have been limited to electrons to occur, and inevitably disappear at low temperatures due to electronic entropy quenching. Here, we report thermoelectric generation caused by nuclear spins in a solid: nuclear-spin Seebeck effect. The sample is a magnetically ordered material MnCO3 having a large nuclear spin (I = 5/2) of 55Mn nuclei and strong hyperfine coupling, with a Pt contact. In the system, we observe low-temperature thermoelectric signals down to 100 mK due to nuclear-spin excitation. Our theoretical calculation in which interfacial Korringa process is taken into consideration quantitatively reproduces the results. The nuclear thermoelectric effect demonstrated here offers a way for exploring thermoelectric science and technologies at ultralow temperatures.
The chromatin, topological and regulatory properties of pluripotency-associated poised enhancers are conserved in vivo
Authors: Crispatzu Giuliano , Rehimi Rizwan , Pachano Tomas , Bleckwehl Tore , Cruz-Molina Sara , Xiao Cally , Mahabir Esther , Bazzi Hisham , Rada-Iglesias Alvaro
Published: July 2021

Poised enhancers (PEs) represent a genetically distinct set of distal regulatory elements that control the expression of major developmental genes. Before becoming activated in differentiating cells, PEs are already bookmarked in pluripotent cells with unique chromatin and topological features that could contribute to their privileged regulatory properties. However, since PEs were originally characterized in embryonic stem cells (ESC), it is currently unknown whether PEs are functionally conserved in vivo. Here, we show that the chromatin and 3D structural features of PEs are conserved among mouse pluripotent cells both in vitro and in vivo. We also uncovered that the interactions between PEs and their target genes are globally controlled by the combined action of Polycomb, Trithorax and architectural proteins. Moreover, distal regulatory sequences located close to developmental genes and displaying the typical genetic (i.e. CpG islands) and chromatin (i.e. high accessibility and H3K27me3 levels) features of PEs are commonly found across vertebrates. These putative PEs show high sequence conservation within specific vertebrate clades, with only a few being evolutionary conserved across all vertebrates. Lastly, by genetically disrupting PEs in mouse and chicken embryos, we demonstrate that these regulatory elements play essential roles during the induction of major developmental genes in vivo.
Empirical assessment and comparison of neuro-evolutionary methods for the automatic off-line design of robot swarms
Authors: Hasselmann Ken , Ligot Antoine , Ruddick Julian , Birattari Mauro
Published: July 2021

Neuro-evolution is an appealing approach to generating collective behaviors for robot swarms. In its typical application, known as off-line automatic design, the neural networks controlling the robots are optimized in simulation. It is understood that the so-called reality gap, the unavoidable differences between simulation and reality, typically causes neural network to be less effective on real robots than what is predicted by simulation. In this paper, we present an empirical study on the extent to which the reality gap impacts the most popular and advanced neuro-evolutionary methods for the off-line design of robot swarms. The results show that the neural networks produced by the methods under analysis performed well in simulation, but not in real-robot experiments. Further, the ranking that could be observed in simulation between the methods eventually disappeared. We find compelling evidence that real-robot experiments are needed to reliably assess the performance of neuro-evolutionary methods and that the robustness to the reality gap is the main issue to be addressed to advance the application of neuro-evolution to robot swarms.
Correlation of membrane protein conformational and functional dynamics
Authors: Sanganna Gari Raghavendar Reddy , Montalvo‐Acosta Joel José , Heath George R. , Jiang Yining , Gao Xiaolong , Nimigean Crina M. , Chipot Christophe , Scheuring Simon
Published: July 2021

Conformational changes in ion channels lead to gating of an ion-conductive pore. Ion flux has been measured with high temporal resolution by single-channel electrophysiology for decades. However, correlation between functional and conformational dynamics remained difficult, lacking experimental techniques to monitor sub-millisecond conformational changes. Here, we use the outer membrane protein G (OmpG) as a model system where loop-6 opens and closes the β-barrel pore like a lid in a pH-dependent manner. Functionally, single-channel electrophysiology shows that while closed states are favored at acidic pH and open states are favored at physiological pH, both states coexist and rapidly interchange in all conditions. Using HS-AFM height spectroscopy (HS-AFM-HS), we monitor sub-millisecond loop-6 conformational dynamics, and compare them to the functional dynamics from single-channel recordings, while MD simulations provide atomistic details and energy landscapes of the pH-dependent loop-6 fluctuations. HS-AFM-HS offers new opportunities to analyze conformational dynamics at timescales of domain and loop fluctuations.
Six-photon upconverted excitation energy lock-in for ultraviolet-C enhancement
Authors: Su Qianqian , Wei Han-Lin , Liu Yachong , Chen Chaohao , Guan Ming , Wang Shuai , Su Yan , Wang Haifang , Chen Zhigang , Jin Dayong
Published: July 2021

Photon upconversion of near-infrared (NIR) irradiation into ultraviolet-C (UVC) emission offers many exciting opportunities for drug release in deep tissues, photodynamic therapy, solid-state lasing, energy storage, and photocatalysis. However, NIR-to-UVC upconversion remains a daunting challenge due to low quantum efficiency. Here, we report an unusual six-photon upconversion process in Gd3+/Tm3+-codoped nanoparticles following a heterogeneous core-multishell architecture. This design efficiently suppresses energy consumption induced by interior energy traps, maximizes cascade sensitizations of the NIR excitation, and promotes upconverted UVC emission from high-lying excited states. We realized the intense six-photon-upconverted UV emissions at 253 nm under 808 nm excitation. This work provides insight into mechanistic understanding of the upconversion process within the heterogeneous architecture, while offering exciting opportunities for developing nanoscale UVC emitters that can be remotely controlled through deep tissues upon NIR illumination.
Consensus statement on the role of health systems in advancing the long-term well-being of people living with HIV
Authors: Lazarus Jeffrey V. , Safreed-Harmon Kelly , Kamarulzaman Adeeba , Anderson Jane , Leite Ricardo Baptista , Behrens Georg , Bekker Linda-Gail , Bhagani Sanjay , Brown Darren , Brown Graham , Buchbinder Susan , Caceres Carlos , Cahn Pedro E. , Carrieri Patrizia , Caswell Georgina , Cooke Graham S. , Monforte Antonella d’Arminio , Dedes Nikos , del Amo Julia , Elliott Richard , El-Sadr Wafaa M. , Fuster-Ruiz de Apodaca María José , Guaraldi Giovanni , Hallett Tim , Harding Richard , Hellard Margaret , Jaffar Shabbar , Kall Meaghan , Klein Marina , Lewin Sharon R. , Mayer Ken , Pérez-Molina Jose A. , Moraa Doreen , Naniche Denise , Nash Denis , Noori Teymur , Pozniak Anton , Rajasuriar Reena , Reiss Peter , Rizk Nesrine , Rockstroh Jürgen , Romero Diana , Sabin Caroline , Serwadda David , Waters Laura
Published: July 2021

Health systems have improved their abilities to identify, diagnose, treat and, increasingly, achieve viral suppression among people living with HIV (PLHIV). Despite these advances, a higher burden of multimorbidity and poorer health-related quality of life are reported by many PLHIV in comparison to people without HIV. Stigma and discrimination further exacerbate these poor outcomes. A global multidisciplinary group of HIV experts developed a consensus statement identifying key issues that health systems must address in order to move beyond the HIV field’s longtime emphasis on viral suppression to instead deliver integrated, person-centered healthcare for PLHIV throughout their lives.
Induced plasticity alters responses to conspecific interactions in seedlings of a perennial grass
Authors: Foxx Alicia J.
Published: July 2021

Plants can interact with different individuals in their lifetime which may lead to plastic response that affect performance. If conspecific interactions are altered through previous plastic responses that could affect stabilizing niche mechanisms, in which conspecifics compete more intensely to promote diversity and coexistence. Here, I show interactions between Pascopyrum smithii and conspecifics resulted in largely canalized traits, whereas P. smithii with an invasive grass, Bromus tectorum resulted in plastic responses for root mass (p = 0.02), shoot mass (p < 0.0001), root mass fraction (p = 0.003) and plant height (p < 0.0001). A subset of individuals transplanted from these two interaction treatments which were moved with new, same aged conspecifics showed that previous interactions led to differing trait relationships: increases in the number of leaves for the interspecific-induced plants were related to increases in non-focal leaf production, whereas increases in the number of leaves for the intraspecific-induced plants were related to decreases in the non-focal plants (R2 = 0.52, p = 0.006). These results suggest that previous intraspecific interactions intensify conspecific competition and stabilize subsequent interactions with conspecifics by imposing greater competition, and that invasive-interspecific interactions can weaken stabilizing niche mechanisms, thus negatively influencing species coexistence.
Vacuum ultraviolet coherent undulator radiation from attosecond electron bunches
Authors: Brunetti Enrico , van der Geer Bas , de Loos Marieke , Dewhurst Kay A. , Kornaszewski Andrzej , Maitrallain Antoine , Muratori Bruno D. , Owen Hywel L. , Wiggins S. Mark , Jaroszynski Dino A.
Published: July 2021

Attosecond duration relativistic electron bunches travelling through an undulator can generate brilliant coherent radiation in the visible to vacuum ultraviolet spectral range. We present comprehensive numerical simulations to study the properties of coherent emission for a wide range of electron energies and bunch durations, including space-charge effects. These demonstrate that electron bunches with r.m.s. duration of 50 as, nominal charge of 0.1 pC and energy range of 100–250 MeV produce $$10^9$$

10
9

coherent photons per pulse in the 100–600 nm wavelength range. We show that this can be enhanced substantially by self-compressing negatively chirped 100 pC bunches in the undulator to produce $$10^{14}$$

10
14

coherent photons with pulse duration of 0.5–3 fs.
Decoding the molecular mechanism of parthenocarpy in Musa spp. through protein–protein interaction network
Authors: Backiyarani Suthanthiram , Sasikala Rajendran , Sharmiladevi Simeon , Uma Subbaraya
Published: July 2021

Banana, one of the most important staple fruit among global consumers is highly sterile owing to natural parthenocarpy. Identification of genetic factors responsible for parthenocarpy would facilitate the conventional breeders to improve the seeded accessions. We have constructed Protein–protein interaction (PPI) network through mining differentially expressed genes and the genes used for transgenic studies with respect to parthenocarpy. Based on the topological and pathway enrichment analysis of proteins in PPI network, 12 candidate genes were shortlisted. By further validating these candidate genes in seeded and seedless accession ofMusaspp. we put forwardMaAGL8, MaMADS16,MaGH3.8,MaMADS29, MaRGA1,MaEXPA1,MaGID1C,MaHK2andMaBAM1as possible target genes in the study of natural parthenocarpy. In contrary, expression profile ofMaACLB-2andMaZEPis anticipated to highlight the difference in artificially induced and natural parthenocarpy. By exploring the PPI of validated genes from the network, we postulated a putative pathway that bring insights into the significance of cytokinin mediated CLAVATA(CLV)–WUSHEL(WUS) signaling pathway in addition to gibberellin mediated auxin signaling in parthenocarpy. Our analysis is the first attempt to identify candidate genes and to hypothesize a putative mechanism that bridges the gaps in understanding natural parthenocarpy through PPI network.
Growth arrest and DNA damage-inducible proteins (GADD45) in psoriasis
Authors: Rodríguez-Jiménez Pedro , Fernández-Messina Lola , Ovejero-Benito María C. , Chicharro Pablo , Vera-Tomé Paula , Vara Alicia , Cibrian Danay , Martínez-Fleta Pedro , Jiménez-Fernández María , Sánchez-García Inés , Llamas-Velasco Mar , Abad-Santos Francisco , Sánchez-Madrid Francisco , Dauden Esteban , de la Fuente Hortensia
Published: July 2021

The interplay between T cells, dendritic cells and keratinocytes is crucial for the development and maintenance of inflammation in psoriasis. GADD45 proteins mediate DNA repair in different cells including keratinocytes. In the immune system, GADD45a and GADD45b regulate the function and activation of both T lymphocytes and dendritic cells and GADD45a links DNA repair and epigenetic regulation through its demethylase activity. Here, we analyzed the expression of GADD45a and GADD45b in the skin, dendritic cells and circulating T cells in a cohort of psoriasis patients and their regulation by inflammatory signals. Thirty patients (17 male/13 female) with plaque psoriasis and 15 controls subjects (7 male/8 female), were enrolled. Psoriasis patients exhibited a lower expression of GADD45a at the epidermis but a higher expression in dermal infiltrating T cells in lesional skin. The expression of GADD45a and GADD45b was also higher in peripheral T cells from psoriasis patients, although no differences were observed in p38 activation. The expression and methylation state of the GADD45a target UCHL1 were evaluated, revealing a hypermethylation of its promoter in lesional skin compared to controls. Furthermore, reduced levels of GADD45a correlated with a lower expression UCHL1 in lesional skin. We propose that the demethylase function of GADD45a may account for its pleiotropic effects, and the complex and heterogeneous pattern of expression observed in psoriatic disease.
Novel competition test for food rewards reveals stable dominance status in adult male rats
Authors: Costa Diana F. , Moita Marta A. , Márquez Cristina
Published: July 2021

Social hierarchy is a potent modulator of behavior, that is typically established through overt agonistic interactions between individuals in the group. Once established, social ranks are maintained through subtler interactions allowing the redirection of energy away from agonistic interactions towards other needs. The available tasks for assessing social rank in rats allow the study of the mechanisms by which social hierarches are formed in early phases but fail to assess the maintenance of established hierarchies between stable pairs of animals, which might rely on distinct neurobiological mechanisms. Here we present and validate a novel trial-based dominancy assay, the modified Food Competition test, where established social hierarchies can be identified in the home cage of non-food deprived pairs of male rats. In this task, we introduce a small conflict in the home cage, where access to a new feeder containing palatable pellets can only be gained by one animal at a time. We found that this subtle conflict triggered asymmetric social interactions and resulted in higher consumption of food by one of the animals in the pair, which reliably predicted hierarchy in other tests. Our findings reveal stable dominance status in pair-housed rats and provide a novel tool for the evaluation of established social hierarchies, the modified Food Competition test, that is robust and easy to implement.
Mitochondrial energetics with transmembrane electrostatically localized protons: do we have a thermotrophic feature?
Authors: Lee James Weifu
Published: July 2021

Transmembrane electrostatically localized protons (TELP) theory has been recently recognized as an important addition over the classic Mitchell’s chemiosmosis; thus, the proton motive force (pmf) is largely contributed from TELP near the membrane. As an extension to this theory, a novel phenomenon of mitochondrial thermotrophic function is now characterized by biophysical analyses of pmf in relation to the TELP concentrations at the liquid-membrane interface. This leads to the conclusion that the oxidative phosphorylation also utilizes environmental heat energy associated with the thermal kinetic energy (kBT) of TELP in mitochondria. The local pmf is now calculated to be in a range from 300 to 340 mV while the classic pmf (which underestimates the total pmf) is in a range from 60 to 210 mV in relation to a range of membrane potentials from 50 to 200 mV. Depending on TELP concentrations in mitochondria, this thermotrophic function raises pmf significantly by a factor of 2.6 to sixfold over the classic pmf. Therefore, mitochondria are capable of effectively utilizing the environmental heat energy with TELP for the synthesis of ATP, i.e., it can lock heat energy into the chemical form of energy for cellular functions.
Multi-view convolutional neural networks for automated ocular structure and tumor segmentation in retinoblastoma
Authors: Strijbis Victor I. J. , de Bloeme Christiaan M. , Jansen Robin W. , Kebiri Hamza , Nguyen Huu-Giao , de Jong Marcus C. , Moll Annette C. , Bach-Cuadra Merixtell , de Graaf Pim , Steenwijk Martijn D.
Published: July 2021

In retinoblastoma, accurate segmentation of ocular structure and tumor tissue is important when working towards personalized treatment. This retrospective study serves to evaluate the performance of multi-view convolutional neural networks (MV-CNNs) for automated eye and tumor segmentation on MRI in retinoblastoma patients. Forty retinoblastoma and 20 healthy-eyes from 30 patients were included in a train/test (N = 29 retinoblastoma-, 17 healthy-eyes) and independent validation (N = 11 retinoblastoma-, 3 healthy-eyes) set. Imaging was done using 3.0 T Fast Imaging Employing Steady-state Acquisition (FIESTA), T2-weighted and contrast-enhanced T1-weighted sequences. Sclera, vitreous humour, lens, retinal detachment and tumor were manually delineated on FIESTA images to serve as a reference standard. Volumetric and spatial performance were assessed by calculating intra-class correlation (ICC) and dice similarity coefficient (DSC). Additionally, the effects of multi-scale, sequences and data augmentation were explored. Optimal performance was obtained by using a three-level pyramid MV-CNN with FIESTA, T2 and T1c sequences and data augmentation. Eye and tumor volumetric ICC were 0.997 and 0.996, respectively. Median [Interquartile range] DSC for eye, sclera, vitreous, lens, retinal detachment and tumor were 0.965 [0.950–0.975], 0.847 [0.782–0.893], 0.975 [0.930–0.986], 0.909 [0.847–0.951], 0.828 [0.458–0.962] and 0.914 [0.852–0.958], respectively. MV-CNN can be used to obtain accurate ocular structure and tumor segmentations in retinoblastoma.
Tumor microenvironment-adjusted prognostic implications of the KRAS mutation subtype in patients with stage III colorectal cancer treated with adjuvant FOLFOX
Authors: Park Hye Eun , Yoo Seung-Yeon , Cho Nam-Yun , Bae Jeong Mo , Han Sae-Won , Lee Hye Seung , Park Kyu Joo , Kim Tae-You , Kang Gyeong Hoon
Published: July 2021

Several studies have reported that the prognostic effect of KRAS mutations on colorectal cancers (CRCs) varies depending on the type of mutation. Considering the effect of KRAS mutations on tumor microenvironment, we analyzed the prognostic significance of KRAS mutation types after adjusting for the tumor-infiltrating lymphocytes (TIL) and tumor-stromal percentage (TSP) statuses. In two independent cohorts, KRAS mutations were analyzed by Sanger sequencing and/or next-generation sequencing. TIL density and the TSP were quantified from whole-slide immunohistochemical images. KRAS-mutant CRCs were divided into three subgroups (G12D/V, other codon 12 mutations and codon 13 mutations) to examine their differential effect on TIL density, the TSP and recurrence-free survival (RFS). Among the KRAS mutations, only the G12D/V subgroups showed significantly less TIL infiltration than the wild-type CRCs. According to survival analysis, G12D/V mutations were associated with short RFS; codon 13 mutations showed discordant trends in the two cohorts, and other codon 12 mutations showed no significant association. Multivariate analysis further supported the prognostic value of G12D/V mutations. This result is not only consistent with a recent study suggesting the immunosuppressive effect of mutant KRAS but also provides insight into the type-specific prognostic effect of KRAS mutations.
The Yangian relations of Heisenberg spin chain model
Authors: Du Guijiao , Xue Kang , Zhou Chengcheng
Published: July 2021

In this paper, we investigate the Yangian relations of Heisenberg spin chain systems. Firstly, we consider the closed XXZ spin chain model, through the Heisenberg spin XXZ model, we found the Hamiltonians for one kind system of three adjacent partial particles interaction systems. The model’s constitution rules of energy levels and energy states which expand from the few-particle system to multi-particle system have good regularity. In this system, we found Yangian’s law and illustrate it through graphs. Secondly, we further consider the closed XXZ spin chain’s generalization of other three neighboring particles interaction systems from few-particle system to multi-particle system. Finally, we also discussed the laws of the three adjacent particles system of some models, they are the XXZ model with twist boundary condition, the open XXZ spin chain model and the XXZ model containing the next neighbor. In addition, not only XXZ model, XXX model, XY model and Ising model, but the relevant laws of spin-1 systems of these models were also discussed, they have similar rules to the XXZ model. Through calculation and research, the eigensystems of these models all have good Yangian and constitution laws.
Novel genetic variants associated with brain functional networks in 18,445 adults from the UK Biobank
Authors: Foo Heidi , Thalamuthu Anbupalam , Jiang Jiyang , Koch Forrest C. , Mather Karen A. , Wen Wei , Sachdev Perminder S.
Published: July 2021

Here, we investigated the genetics of weighted functional brain network graph theory measures from 18,445 participants of the UK Biobank (44–80 years). The eighteen measures studied showed low heritability (mean h2SNP = 0.12) and were highly genetically correlated. One genome-wide significant locus was associated with strength of somatomotor and limbic networks. These intergenic variants were located near the PAX8 gene on chromosome 2. Gene-based analyses identified five significantly associated genes for five of the network measures, which have been implicated in sleep duration, neuronal differentiation/development, cancer, and susceptibility to neurodegenerative diseases. Further analysis found that somatomotor network strength was phenotypically associated with sleep duration and insomnia. Single nucleotide polymorphism (SNP) and gene level associations with functional network measures were identified, which may help uncover novel biological pathways relevant to human brain functional network integrity and related disorders that affect it.
Trajectories in glycated hemoglobin and body mass index in children and adolescents with diabetes using the common data model
Authors: Lee Yun Jeong , Yoo Sooyoung , Yi Soyoung , Kim Seok , Lee Chunggak , Cho Jihoon , Ahn Soyeon , Choi Sunkyu , Hwang Hee , Lee Young Ah , Shin Choong Ho , Yoon Hyung-Jin , Kim Kwangsoo , Song Eunhye , Choi Jin Ho , Yoo Han Wook , Kim Young-Hak , Oh Ji Seon , Kang Eun-Ae , Baek Ga Kyoung , Kim Jae Hyun
Published: July 2021

We evaluated trajectories of glycated hemoglobin (HbA1c) levels and body mass index z-scores (BMIz) for 5 years after diagnosis among Korean children and adolescents with type 1 diabetes (T1D) or type 2 diabetes (T2D) using the common data model. From the de-identified database of three hospitals, 889 patients < 15 years of age diagnosed with T1D or T2D (393 boys, 664 T1D patients) were enrolled. Diagnosis was defined as first exposure to antidiabetic drug at each center. Compared with T2D patients, T1D patients had lower BMIz at diagnosis (− 0.4 ± 1.2 vs. 1.5 ± 1.4, p < 0.001) and 3 months (− 0.1 ± 1.0 vs. 1.5 ± 1.5, p < 0.001), and higher HbA1c levels at diagnosis (10.0 ± 2.6% vs. 9.5 ± 2.7%, p < 0.01). After 3 months, HbA1c levels reached a nadir of 7.6% and 6.5% in T1D and T2D patients, respectively, followed by progressive increases; only 10.4% of T1D and 29.7% of T2D patients achieved the recommended HbA1c target (< 7.0%) at 60 months. T1D patients showed consistent increases in BMIz; T2D patients showed no significant change in BMIz during follow-up. Peri-pubertal girls with T1D had higher HbA1c and BMIz values. Achieving optimal glycemic control and preventing obesity should be emphasized in pediatric diabetes care.
High coverage COVID-19 mRNA vaccination rapidly controls SARS-CoV-2 transmission in long-term care facilities
Authors: De Salazar Pablo M. , Link Nicholas B. , Lamarca Karuna , Santillana Mauricio
Published: July 2021

Background

Residents of Long-Term Care Facilities (LTCFs) represent a major share of COVID-19 deaths worldwide. Measuring the vaccine effectiveness among the most vulnerable in these settings is essential to monitor and improve mitigation strategies.

Methods

We evaluate the early effect of the administration of BNT162b2-mRNA vaccine to individuals older than 64 years residing in LTCFs in Catalonia, Spain. We monitor all the SARS-CoV-2 documented infections and deaths among LTCFs residents once more than 70% of them were fully vaccinated (February–March 2021). We develop a modeling framework based on the relationship between community and LTCFs transmission during the pre-vaccination period (July–December 2020). We compute the total reduction in SARS-CoV-2 documented infections and deaths among residents of LTCFs over time, as well as the reduction in the detected transmission for all the LTCFs. We compare the true observations with the counterfactual predictions.

Results

We estimate that once more than 70% of the LTCFs population are fully vaccinated, 74% (58–81%, 90% CI) of COVID-19 deaths and 75% (36–86%, 90% CI) of all expected documented infections among LTCFs residents are prevented. Further, detectable transmission among LTCFs residents is reduced up to 90% (76–93%, 90% CI) relative to that expected given transmission in the community.

Conclusions

Our findings provide evidence that high-coverage vaccination is the most effective intervention to prevent SARS-CoV-2 transmission and death among LTCFs residents. Widespread vaccination could be a feasible avenue to control the COVID-19 pandemic conditional on key factors such as vaccine escape, roll out and coverage.
An electrochemical immunosensor based on reduced graphene oxide/multiwalled carbon nanotubes/thionine/gold nanoparticle nanocomposites for the sensitive testing of follicle-stimulating hormone
Authors: Fan Yan , Guo Yaohua , Shi Shengyu , Ma Junshuang
Published: July 2021

An electrochemical immunosensor based on rGO/MWCNTs/Thi/AuNP nanocomposites for the sensitive testing of FSH.
Ferrous ions doped layered double hydroxide: smart 2D nanotheranostic platform with imaging-guided synergistic chemo/photothermal therapy for breast cancer
Authors: Guo Zhenhu , Xie Wensheng , Lu Jingsong , Guo Xiaoxiao , Chi Yongjie , Wang Dan , Takuya Nonaka , Xu Wanling , Ye Jielin , Liu Xiangyan , Gu Zi , Xu Benhua , Wu Hong , Zhao Lingyun
Published: July 2021

Fe-Doped Mg–Al layer double hydroxide NPs were endowed with enhanced photo-induced ability and T2-weighted MR effect for cancer theranostic application.
An “AND”-logic-gate-based fluorescent probe with dual reactive sites for monitoring extracellular methylglyoxal level changes of activated macrophages
Authors: Wang Wenli , Chen Junwei , Ma Huijuan , Xing Wanjin , Lv Nan , Zhang Baoning , Xu Huan , Wang Wei , Lou Kaiyan
Published: July 2021

An “AND”-logic-gate-based fluorescent probe with reversible guanidino and irreversible o-phenylenediamino reactive sites for monitoring extracellular methylglyoxal levels upon macrophage activation.
Sensitive imaging of tumors using a nitroreductase-activated fluorescence probe in the NIR-II window
Authors: Zhang Xiaofan , Li Xiaohua , Shi Wen , Ma Huimin
Published: July 2021

We develop a nitroreductase-activated NIR-II fluorescence probe, which can emit fluorescence in the range of 900–1300 nm, and achieve the accurate delineation of tumor margins through deep penetration.
Identification of beryllium fluoride complexes in mechanically distorted gels using quadrupolar split 9Be NMR spectra resolved with solution-state selective cross-polarization
Authors: Romanenko Konstantin , Elliott Stuart J. , Shubin Aleksandr A. , Kuchel Philip W.
Published: July 2021

Uniformly anisotropic media afforded by hydrogels are exploited in analytical (structure elucidation) nuclear magnetic resonance (NMR) spectroscopy, and in studies of mechanosensitive biophysical and biochemical properties of living cells.
Robustness and accuracy improvement of data processing with 2D neural networks for transient absorption dynamics
Authors: Zhao Ruixuan , Wu Daxin , Wen Jiao , Zhang Qi , Zhang Guanglei , Li Jiebo
Published: July 2021

A robust method is developed to solve time-dependent differential equations, which is potentially applicable for transient absorption data processing.
Mechanistic understanding of methane-to-methanol conversion on graphene-stabilized single-atom iron centers
Authors: Hong Sungil , Mpourmpakis Giannis
Published: July 2021

DFT calculations and kinetic modeling elucidate solvent effects and complex mechanisms for the room-temperature methane-to-methanol conversion on an FeN4/graphene catalyst.
Selectivity of the Lindlar catalyst in alkyne semi-hydrogenation: a direct liquid-phase adsorption study
Authors: Cherkasov Nikolay , Murzin Dmitry Yu. , Catlow C. Richard A. , Chutia Arunabhiram
Published: July 2021

Pd catalysts contain active sites that strongly adsorb alkyne and alkene molecules. The presence of the latter, alkene sites, defines the low semi-hydrogenation selectivity.
Copper niobate nanowires boosted by a N, S co-doped carbon coating for superior lithium storage
Authors: Cai Xinhao , Yan Huihui , Yang Zhengwei , Li Wenru , Yu Haoxiang , Yan Lei , Zhang Liyuan , Shui Miao , Cui Yanhua , Shu Jie
Published: July 2021

N, S co-doped carbon layer boosts the kinetic properties of Cu2Nb34O87 nanowires as anode host for lithium-ion batteries.
Spin transition triggered by desorption of crystal solvents for a two-dimensional cobalt(ii) complex with hydrogen bonding
Authors: Kanetomo Takuya , Inokuma Kiwamu , Naoi Yuya , Enomoto Masaya
Published: July 2021

[Co(5tpybNOH)2](BPh4)2 has a two-dimensional structure and showed irreversible structural/spin changes by the removal of crystal solvents.
The effect of legacy gold mining on methylmercury cycling and microbial community structure in northern freshwater lakes
Authors: Aždajić Mija , Yumvihoze Emmanuel , Blais Jules M. , Poulain Alexandre J.
Published: July 2021

Historical smelting pollution gradient at Giant Mine (Yellowknife, NWT, Canada) affects rate of methylmercury production in sediments and final methylmercury concentrations in water columns of nearby lakes.
Carbon-based electrodes for perovskite solar cells
Authors: Que Meidan , Zhang Boyue , Chen Jin , Yin Xingtian , Yun Sining
Published: July 2021

The cost-effective processability and high stability of carbon-based perovskite solar cells (C-PSCs) have shown great potential to positively devote to the development of large-scale production processes.
Will the chemical probes please stand up?
Authors: Škuta Ctibor , Southan Christopher , Bartůněk Petr
Published: July 2021

This study provides a comprehensive and comparative overview of probe sources, structures and targets. The analysis encompasses 4466 chemical probe candidates supported by evidence of specific binding to 796 human proteins.
Turbulence enhanced ferroelectric-nanocrystal-based photocatalysis in urchin-like TiO2/BaTiO3 microspheres for hydrogen evolution
Authors: Li Haidong , Song Yanyan , Zhang Jiyun , He Jiating
Published: July 2021

The coupling effect of two types of piezoelectric potential in the presence of BaTiO3 nanocubes and optical properties of TiO2 nanowires of the urchin-like TiO2/BaTiO3 hybrid structure enhance the photocatalytic H2 generation.
Dimeric Mn(ii), Co(ii), Ni(ii) and Cu(ii) complexes of a common carboxylate-appended (2-pyridyl)alkylamine ligand: structure, magnetism and DFT study
Authors: Manda Munirathnam , Arora Himanshu , Sengupta Arunava , Kant Shashi , Lloret Francesc , Mukherjee Rabindranath
Published: July 2021

Weak anti- (1) and ferro-magnetic (2–4) interactions are observed in [MII2(L3)2(S)2]2+(Mn 1, Co 2, Ni 3) (S = MeOH) and Cu 4 (S = none).
In situ synthesis of Co–B-doped porous carbon through laser thermal reduction for an efficient oxygen reduction reaction
Authors: Liu Junbo , Zhang Wenzhuo , Chen Guangyi , Tao Shengyang
Published: July 2021

High dispersibility Co/B–C catalysts are prepared by laser thermal reduction on boron phenolic resin, exhibiting an efficient ORR electrocatalytic activity.
Unraveling the electron transfer rates of highly crystalline carbon nanowires with surface oxides
Authors: Deng Jufeng , Liu Chong , Madou Marc
Published: July 2021

In this work, we demonstrate the carbon microstructure transformation from low crystalline glassy carbon to crystalline micro-structure and unravel the electron transfer rates of highly crystalline carbon nanowires with surface oxides.
Phosphorus modulation of a mesoporous rhodium film for enhanced nitrogen electroreduction
Authors: Wang Ziqiang , Tian Wenjing , Yu Hongjie , Zhou Tongqing , Wang Peng , Xu You , Li Xiaonian , Wang Liang , Wang Hongjing
Published: July 2021

A phosphorus modulated mesoporous Rh film on Ni foam has been synthesized for an electrochemical nitrogen reduction reaction with predominant electrocatalytic performance.
Construction of a thermoreversible chemical crosslinking network – a new exploration for the efficient reusability of commercial rubber
Authors: Wang Xiaoping , Wu Haijian , Liang Dong , Gong Yuzhu
Published: July 2021

A thermoreversible rubber DSBR was prepared via a reaction between a nitroxide-based crosslinker and commercial styrene–butadiene rubber. Impressive recoveries of mechanical properties of DSBR were achieved for the alkoxyamine crosslinking network.
Use of artificial cells as drug carriers
Authors: Emir Diltemiz Sibel , Tavafoghi Maryam , de Barros Natan Roberto , Kanada Masamitsu , Heinämäki Jyrki , Contag Christopher , Seidlits Stephanie K. , Ashammakhi Nureddin
Published: July 2021

Cells are the fundamental functional units of biological systems and mimicking their size, function and complexity is a primary goal in the development of new therapeutic strategies.
Intermolecular interactions between β-cyclodextrin and water
Authors: Guo Tianxiang , Kong Lingfeng , Xu Junpeng , Geng Yuhan , Zhang Runan , Pan Yuanfeng , Xiao Huining
Published: July 2021

This study focused on demonstrating the intermolecular interactions between β-cyclodextrin and water, with the aim to better understand the transfer of small molecules to β-cyclodextrin.
π-Conjugated organosilanes at the nexus of single-molecule electronics and imaging
Authors: Pham Lan D. , Nguyen Nhien Q. , Hight Matthew O. , Su Timothy A.
Published: July 2021

This article explores the fundamental σ-π orbital interactions that underlie the physical properties of conjugated organosilane molecular materials in single-molecule electronics and single-molecule imaging.
The Need for Increased Study of Infants and Toddlers Later Diagnosed With Childhood Apraxia of Speech
Authors: Overby Megan , Highman Chantelle
Published: July 2021

Purpose

This article examines the need for increased research into the prelinguistic trajectory of childhood apraxia of speech (CAS). We discuss the significant gains made in the early identification of disorders such as autism spectrum disorder, fragile X syndrome, and Rett syndrome that have resulted through the study of early (i.e., prelinguistic) developmental behaviors of infants and toddlers at risk for these disorders. We suggest that notable gains in understanding CAS could be made by increasing investigative focus on infants and toddlers later diagnosed with CAS or who are at risk for it (i.e., have an older sibling diagnosed with the disorder).

Conclusions

Currently, there are few studies to guide clinical decision making for infants and toddlers who may have CAS. To address this gap, we present a call to action with recommendations for researchers and clinicians. We recommend more retrospective investigative designs be conducted, inclusive of retrospective parent questionnaires and retrospective home video analysis, as well as prospective longitudinal studies of at-risk infants. We suggest that studies not be limited to exploring an affected infant's vocal output, but that efforts be made to acquire a broad view of an affected infant's early developmental trajectory (e.g., social skills, eye gaze, and imitative skills). A more comprehensive understanding of CAS will guide clinicians not only in identification of the disorder but will inform treatment decisions as well.