bluuebunny/crossref_metadata_2025_split 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

AbstractAssessments 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

AbstractSelf-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

AbstractActivating 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

AbstractMucosal-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

AbstractWhile 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

AbstractInstallation 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

AbstractMetabolic 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

AbstractThermoelectric 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

AbstractPoised 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

AbstractNeuro-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

AbstractConformational 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

AbstractPhoton 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

AbstractHealth 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

AbstractPlants 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

AbstractAttosecond 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

AbstractBanana, 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.