bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pedestrian orientation dynamics from high-fidelity measurements
Authors: Willems Joris , Corbetta Alessandro , Menkovski Vlado , Toschi Federico 
Published: July 2020

AbstractWe investigate in real-life conditions and with very high accuracy the dynamics of body rotation, or yawing, of walking pedestrians—a highly complex task due to the wide variety in shapes, postures and walking gestures. We propose a novel measurement method based on a deep neural architecture that we train on the basis of generic physical properties of the motion of pedestrians. Specifically, we leverage on the strong statistical correlation between individual velocity and body orientation: the velocity direction is typically orthogonal with respect to the shoulder line. We make the reasonable assumption that this approximation, although instantaneously slightly imperfect, is correct on average. This enables us to use velocity data as training labels for a highly-accurate point-estimator of individual orientation, that we can train with no dedicated annotation labor. We discuss the measurement accuracy and show the error scaling, both on synthetic and real-life data: we show that our method is capable of estimating orientation with an error as low as $$7.5^\circ$$7.5∘. This tool opens up new possibilities in the studies of human crowd dynamics where orientation is key. By analyzing the dynamics of body rotation in real-life conditions, we show that the instantaneous velocity direction can be described by the combination of orientation and a random delay, where randomness is provided by an Ornstein–Uhlenbeck process centered on an average delay of $$100\,\hbox {ms}$$100ms. Quantifying these dynamics could have only been possible thanks to a tool as precise as that proposed.
Blood residence time to assess significance of coronary artery stenosis
Authors: Hashemi Javad , Rai Shesh , Ghafghazi Shahab , Berson R. Eric 
Published: July 2020

AbstractCoronary artery stenosis is a narrowing of coronary lumen space caused by an atherosclerotic lesion. Fractional flow reserve (FFR) is the gold standard metric to assess physiological significance of coronary stenosis, but requires an invasive procedure. Computational modeling in conjunction with patient-specific imaging demonstrates formation of regions of recirculatory flow distal to a stenosis, increasing mean blood residence time relative to uninhibited flow. A new computational parameter, mean blood residence time (BloodRT), was computed for 100 coronary artery segments for which FFR was known. A threshold for BloodRT was determined to assess the physiological significance of a stenosis, analogous to diagnostic threshold for FFR. Model sensitivity and specificity of BloodRT for diagnosis of hemodynamically significant coronary stenosis was 98% and 96% respectively, compared with FFR. When applied to clinical practice, this could potentially allow practicing cardiologists to accurately assess the severity of coronary stenosis without resorting to invasive techniques.
Prediction of age at onset in Parkinson’s disease using objective specific neuroimaging genetics based on a sparse canonical correlation analysis
Authors: Won Ji Hye , Kim Mansu , Youn Jinyoung , Park Hyunjin 
Published: July 2020

AbstractThe age at onset (AAO) is an important determinant in Parkinson’s disease (PD). Neuroimaging genetics is suitable for studying AAO in PD as it jointly analyzes imaging and genetics. We aimed to identify features associated with AAO in PD by applying the objective-specific neuroimaging genetics approach and constructing an AAO prediction model. Our objective-specific neuroimaging genetics extended the sparse canonical correlation analysis by an additional data type related to the target task to investigate possible associations of the imaging–genetic, genetic–target, and imaging–target pairs simultaneously. The identified imaging, genetic, and combined features were used to construct analytical models to predict the AAO in a nested five-fold cross-validation. We compared our approach with those from two feature selection approaches where only associations of imaging–target and genetic–target were explored. Using only imaging features, AAO prediction was accurate in all methods. Using only genetic features, the results from other methods were worse or unstable compared to our model. Using both imaging and genetic features, our proposed model predicted the AAO well (r = 0.5486). Our findings could have significant impacts on the characterization of prodromal PD and contribute to diagnosing PD early because genetic features could be measured accurately from birth.
Upregulated TNF/Eiger signaling mediates stem cell recovery and tissue homeostasis during nutrient resupply in Drosophila testis
Authors: Chang Yi Chieh , Tu Hsin , Huang To-Wei , Xu Bo-Wen , Pi Haiwei 
Published: July 2020

AbstractStem cell activity and cell differentiation is robustly influenced by the nutrient availability in the gonads. The signal that connects nutrient availability to gonadal stem cell activity remains largely unknown. In this study, we show that tumor necrosis factor Eiger (Egr) is upregulated in testicular smooth muscles as a response to prolonged protein starvation in Drosophila testis. While Egr is not essential for starvation-induced changes in germline and somatic stem cell numbers, Egr and its receptor Grindelwald influence the recovery dynamics of somatic cyst stem cells (CySCs) upon protein refeeding. Moreover, Egr is also involved in the refeeding-induced, ectopic expression of the CySC self-renewal protein and the accumulation of early germ cells. Egr primarily acts through the Jun N-terminal kinase (JNK) signaling in Drosophila. We show that inhibition of JNK signaling in cyst cells suppresses the refeeding-induced abnormality in both somatic and germ cells. In conclusion, our study reveals both beneficial and detrimental effects of Egr upregulation in the recovery of stem cells and spermatogenesis from prolonged protein starvation.
The discovery of a new antibody for BRIL-fused GPCR structure determination
Authors: Miyagi Hikaru , Asada Hidetsugu , Suzuki Michihiko , Takahashi Yuichi , Yasunaga Mai , Suno Chiyo , Iwata So , Saito Jun-ichi 
Published: July 2020

AbstractG-protein-coupled receptors (GPCRs)—the largest family of cell-surface membrane proteins—mediate the intracellular signal transduction of many external ligands. Thus, GPCRs have become important drug targets. X-ray crystal structures of GPCRs are very useful for structure-based drug design (SBDD). Herein, we produced a new antibody (SRP2070) targeting the thermostabilised apocytochrome b562 from Escherichia coli M7W/H102I/R106L (BRIL). We found that a fragment of this antibody (SRP2070Fab) facilitated the crystallisation of the BRIL-tagged, ligand bound GPCRs, 5HT1B and AT2R. Furthermore, the electron densities of the ligands were resolved, suggesting that SPR2070Fab is versatile and adaptable for GPCR SBDD. We anticipate that this new tool will significantly accelerate structure determination of other GPCRs and the design of small molecular drugs targeting them.
Disparate survival of late-stage male oropharyngeal cancer in Appalachia
Authors: Papenberg Brenen W. , Allen Jessica L. , Markwell Steven M. , Interval Erik T. , Montague Phillip A. , Johnson Christopher J. , Weed Scott A. 
Published: July 2020

AbstractThe United States Appalachian region harbors a higher cancer burden than the rest of the nation, with disparate incidence of head and neck squamous cell carcinomas (HNSCC), including oral cavity and pharynx (OC/P) cancers. Whether elevated HNSCC incidence generates survival disparities within Appalachia is unknown. To address this, HNSCC survival data for 259,737 tumors from the North American Association for Central Cancer Registries 2007–2013 cohort were evaluated, with age-adjusted relative survival (RS) calculated based on staging, race, sex, and Appalachian residence. Tobacco use, a primary HNSCC risk factor, was evaluated through the Behavioral Risk Factor Surveillance System from Appalachian states. Decreased OC/P RS was found in stage IV Appalachian white males within a subset of states. The survival disparity was confined to human papillomavirus (HPV)-associated oropharyngeal cancers, specifically the oropharynx subsite. This correlated with significantly higher smoking and male smokeless tobacco use in most Appalachian disparity states. Lower survival of Appalachian males with advanced-stage HPV-associated oropharyngeal cancers suggests pervasive tobacco consumption likely generates more aggressive tumors at HPV-associated oropharynx subsites than national averages. Comprehensive tobacco and HPV status should therefore be evaluated prior to considering treatment de-intensification regimens for HPV-associated oropharyngeal cancers in populations with high tobacco consumption.
Identifying hotspots of invasive alien terrestrial vertebrates in Europe to assist transboundary prevention and control
Authors: Polaina Ester , Pärt Tomas , Recio Mariano R. 
Published: July 2020

AbstractThis study aims to identify environmentally suitable areas for 15 of the most harmful invasive alien terrestrial vertebrates (IATV) in Europe in a transparent and replicable way. We used species distribution models and publicly-available data from GBIF to predict environmental suitability and to identify hotspots of IATV accounting for knowledge gaps in their distributions. To deal with the ecological particularities of invasive species, we followed a hierarchical approach to estimate the global climatic suitability for each species and incorporated this information into refined environmental suitability models within Europe. Combined predictions on environmental suitability identified potential areas of IATV concentrations or hotspots. Uncertainty of predictions identified regions requiring further survey efforts for species detection. Around 14% of Europe comprised potential hotspots of IATV richness, mainly located in northern France, UK, Belgium and the Netherlands. IATV coldspots covered ~ 9% of Europe, including southern Sweden and Finland, and northern Germany. Most of Europe (~ 77% area) comprised uncertain suitability predictions, likely caused by a lack of data. Priorities on prevention and control should focus on potential hotspots where harmful impacts might concentrate. Promoting the collection of presence data within data-deficient areas is encouraged as a core strategy against IATVs.
Jamming, fragility and pinning phenomena in superconducting vortex systems
Authors: Reichhardt Charles , Reichhardt Cynthia J. O. 
Published: July 2020

AbstractWe examine driven superconducting vortices interacting with quenched disorder under a sequence of perpendicular drive pulses. As a function of disorder strength, we find four types of behavior distinguished by the presence or absence of memory effects. The fragile and jammed states exhibit memory, while the elastic and pinning dominated regimes do not. In the fragile regime, the system organizes into a pinned state during the first pulse, flows during the second perpendicular pulse, and then returns to a pinned state during the third pulse which is parallel to the first pulse. This behavior is the hallmark of the fragility proposed for jamming in particulate matter. For stronger disorder, we observe a robust jamming state with memory where the system reaches a pinned or reduced flow state during the perpendicular drive pulse, similar to the shear jamming of granular systems. We show signatures of the different states in the spatial vortex configurations, and find that memory effects arise from coexisting elastic and pinned components of the vortex assembly. The sequential perpendicular driving protocol we propose for distinguishing fragile, jammed, and pinned phases should be general to the broader class of driven interacting particles in the presence of quenched disorder.
Crystals reveal magma convection and melt transport in dyke-fed eruptions
Authors: Albert Helena , Larrea Patricia , Costa Fidel , Widom Elisabeth , Siebe Claus 
Published: July 2020

AbstractThe processes and ranges of intensive variables that control magma transport and dyke propagation through the crust are poorly understood. Here we show that textural and compositional data of olivine crystals (Mg/Fe, Ni and P) from the tephra of the first months of Paricutin volcano monogenetic eruption (Mexico, 1943–1952) record fast growth and large temperature and oxygen fugacity gradients. We interpret that these gradients are due to convective magma transport in a propagating dyke to the Earth’s surface in less than a few days. The shortest time we have obtained is 0.1 day, and more than 50% of the calculated timescales are < 2 days for the earliest erupted tephra, which implies magma ascent rates of about 0.1 and 1 m s−1. The olivine zoning patterns change with the eruptive stratigraphy, and record a transition towards a more steady magma flow before the transition from explosive to effusive dynamics. Our results can inform numerical and experimental analogue models of dyke propagation, and thus facilitate a better understanding of the seismicity and other precursors of dyke-fed eruptions.
Determination of the most effective design for the measurement of photosynthetic light-response curves for planted Larix olgensis trees
Authors: Liu Qiang , Jia Weiwei , Li Fengri 
Published: July 2020

AbstractA photosynthetic light-response (PLR) curve is a mathematical description of a single biochemical process and has been widely applied in many eco-physiological models. To date, many PLR measurement designs have been suggested, although their differences have rarely been explored, and the most effective design has not been determined. In this study, we measured three types of PLR curves (High, Middle and Low) from planted Larix olgensis trees by setting 31 photosynthetically active radiation (PAR) gradients. More than 530 million designs with different combinations of PAR gradients from 5 to 30 measured points were conducted to fit each of the three types of PLR curves. The influence of different PLR measurement designs on the goodness of fit of the PLR curves and the accuracy of the estimated photosynthetic indicators were analysed, and the optimal design was determined. The results showed that the measurement designs with fewer PAR gradients generally resulted in worse predicted accuracy for the photosynthetic indicators. However, the accuracy increased and remained stable when more than ten measurement points were used for the PAR gradients. The mean percent error (M%E) of the estimated maximum net photosynthetic rate (Pmax) and dark respiratory rate (Rd) for the designs with less than ten measurement points were, on average, 16.4 times and 20.1 times greater than those for the designs with more than ten measurement points. For a single tree, a unique PLR curve design generally reduced the accuracy of the predicted photosynthetic indicators. Thus, three optimal measurement designs were provided for the three PLR curve types, in which the root mean square error (RMSE) values reduced by an average of 8.3% and the coefficient of determination (R2) values increased by 0.3%. The optimal design for the High PLR curve type should shift more towards high-intensity PAR values, which is in contrast to the optimal design for the Low PLR curve type, which should shift more towards low-intensity PAR values.
Alternative splicing of flowering time gene FT is associated with halving of time to flowering in coconut
Authors: Xia Wei , Liu Rui , Zhang Jun , Mason Annaliese S. , Li Zhiying , Gong Shufang , Zhong Yazhu , Dou Yajing , Sun Xiwei , Fan Haikuo , Xiao Yong 
Published: July 2020

AbstractCoconut palm has two distinct types—“tall” and “dwarf”—which differ morphologically. Tall coconut varieties need 8–10 years to start flowering, while dwarf coconut varieties only require 3–5 years. We compared seedling and reproductive stage transcriptomes for both coconut types to determine potential molecular mechanisms underlying control of flowering time in coconut. Several key genes in the photoperiod pathway were differentially expressed between seedling and reproductive leaf samples in both tall and dwarf coconut. These genes included suppressor of overexpression of constans (SOC1), flowering locus T (FT), and Apetala 1 (AP1). Alternative splicing analysis of genes in the photoperiod pathway further revealed that the FT gene produces different transcripts in tall compared to dwarf coconut. The shorter alternative splice variant of FT [which included a 6 bp deletion, alternative 3′ splicing sites (A3SS)] was found to be exclusively present in dwarf coconut varieties but absent in most tall coconut varieties. Our results provide a valuable information resource as well as suggesting a probable mechanism for differentiation of flowering time onset in coconut, providing a target for future breeding work in accelerating time to flowering in this crop species.
Twenty-four-hour versus clinic blood pressure levels as predictors of long-term cardiovascular and renal disease outcomes among African Americans
Authors: Kidambi Srividya , Wang Tao , Chelius Thomas , Nunuk Irene , Agarwal Priyanka , Laud Purushottam , Mattson David , Cowley Allen W. , Liang Mingyu , Kotchen Theodore 
Published: July 2020

AbstractIn Caucasian and Asian populations, evidence suggests that 24-h blood pressures (BP) are more predictive of long-term cardiovascular events than clinic BP. However, few long-term studies have evaluated the predictive value of 24-h BP phenotypes (24-h, daytime, nighttime) among African Americans (AA). The purpose of this study is to evaluate the added value of 24-h BP phenotypes compared to clinic BP in predicting the subsequent fatal and non-fatal cardiovascular/renal disease events in AA subjects. AA subjects (n = 270) were initially studied between 1994 and 2006 and standardized clinic BP measurements were obtained during screening procedures for a 3-day inpatient clinical study during which 24-h BP measurements were obtained. To assess the subsequent incidence of cardiovascular and renal disease events, follow-up information was obtained and confirmed by review of paper and electronic medical records between 2015 and 2017. During a mean follow-up of 14 ± 4 years, 50 subjects had one or more fatal or non-fatal cardiovascular/renal disease events. After adjustment for covariates, clinic systolic and diastolic BP were strongly associated with cardiovascular/renal disease events and all-cause mortality (p < 0.0001). Twenty-four-hour BP phenotypes conferred a small incremental advantage over clinic BP in predicting cardiovascular/renal events, which was limited to making a difference of one predicted event in 250–1,000 predictions depending on the 24-h BP phenotype. Nocturnal BP was no more predictive than the other 24-h BP phenotypes. In AA, 24-h BP monitoring provides limited added value as a predictor of cardiovascular/renal disease events. Larger studies are needed in AA to confirm these findings.
Munc18-1 induces conformational changes of syntaxin-1 in multiple intermediates for SNARE assembly
Authors: Lee Sanghwa , Shin Jonghyeok , Jung Younghun , Son Heyjin , Shin Jaeil , Jeong Cherlhyun , Kweon Dae-Hyuk , Shin Yeon-Kyun 
Published: July 2020

AbstractIn neuronal exocytosis, SNARE assembly into a stable four-helix bundle drives membrane fusion. Previous studies have revealed that the SM protein Munc18-1 plays a critical role for precise SNARE assembly with the help of Munc13-1, but the underlying mechanism remains unclear. Here, we used single-molecule FRET assays with a nanodisc membrane reconstitution system to investigate the conformational dynamics of SNARE/Munc18-1 complexes in multiple intermediate steps towards the SNARE complex. We found that single Munc18-1 proteins induce the closed conformation of syntaxin-1 not only in the free syntaxin-1 but also in the t-SNARE (syntaxin-1/SNAP-25) complex. These results implicate that Munc18-1 may act as a gatekeeper for both binary and ternary SNARE complex formation by locking the syntaxin-1 in a cleft of Munc18-1. Furthermore, the kinetic analysis of the opening/closing transition reveals that the closed syntaxin-1 in the syntaxin-1/SNAP-25/Munc18-1 complex is less stable than that in the closed syntaxin-1/Munc18-1 complex, which is manifested by the infrequent closing transition, indicating that the conformational equilibrium of the ternary complex is biased toward the open conformation of syntaxin-1 compared with the binary complex.
The effect of the VKORC1 promoter variant on warfarin responsiveness in the Saudi WArfarin Pharmacogenetic (SWAP) cohort
Authors: Al Ammari Maha , AlBalwi Mohammed , Sultana Khizra , Alabdulkareem Ibrahim B. , Almuzzaini Bader , Almakhlafi Nada S. , Aldrees Mohammed , Alghamdi Jahad 
Published: July 2020

AbstractWarfarin is a frequently prescribed oral anticoagulant with a narrow therapeutic index, requiring careful dosing and monitoring. However, patients respond with significant inter-individual variability in terms of the dose and responsiveness of warfarin, attributed to genetic polymorphisms within the genes responsible for the pharmacokinetics and pharmacodynamics of warfarin. Extensive warfarin pharmacogenetic studies have been conducted, including studies resulting in genotype-guided dosing guidelines, but few large scale studies have been conducted with the Saudi population. In this study, we report the study design and baseline characteristics of the Saudi WArfarin Pharmacogenomics (SWAP) cohort, as well as the association of the VKORC1 promoter variants with the warfarin dose and the time to a stable INR. In the 936 Saudi patients recruited in the SWAP study, the minor allele C of rs9923231 was significantly associated with a 8.45 mg higher weekly warfarin dose (p value = 4.0 × 10–46), as well as with a significant delay in achieving a stable INR level. The addition of the rs9923231 status to the model, containing all the significant clinical variables, doubled the warfarin dose explained variance to 31%. The SWAP cohort represents a valuable resource for future research with the objective of identifying rare and prevalent genetic variants, which can be incorporated in personalized anticoagulation therapy for the Saudi population.
Mitochondrial dysfunction impairs osteogenesis, increases osteoclast activity, and accelerates age related bone loss
Authors: Dobson Philip F. , Dennis Ella P. , Hipps Daniel , Reeve Amy , Laude Alex , Bradshaw Carla , Stamp Craig , Smith Anna , Deehan David J. , Turnbull Doug M. , Greaves Laura C. 
Published: July 2020

AbstractThe pathogenesis of declining bone mineral density, a universal feature of ageing, is not fully understood. Somatic mitochondrial DNA (mtDNA) mutations accumulate with age in human tissues and mounting evidence suggests that they may be integral to the ageing process. To explore the potential effects of mtDNA mutations on bone biology, we compared bone microarchitecture and turnover in an ageing series of wild type mice with that of the PolgAmut/mut mitochondrial DNA ‘mutator’ mouse. In vivo analyses showed an age-related loss of bone in both groups of mice; however, it was significantly accelerated in the PolgAmut/mut mice. This accelerated rate of bone loss is associated with significantly reduced bone formation rate, reduced osteoblast population densities, increased osteoclast population densities, and mitochondrial respiratory chain deficiency in osteoblasts and osteoclasts in PolgAmut/mut mice compared with wild-type mice. In vitro assays demonstrated severely impaired mineralised matrix formation and increased osteoclast resorption by PolgAmut/mut cells. Finally, application of an exercise intervention to a subset of PolgAmut/mut mice showed no effect on bone mass or mineralised matrix formation in vitro. Our data demonstrate that mitochondrial dysfunction, a universal feature of human ageing, impairs osteogenesis and is associated with accelerated bone loss.