bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kant’s Non-Positivistic Concept of Law
Authors: Alexy Robert 
Published: November 2019

AbstractThe main thesis of this article is that Kant’s concept of law is a non-positivistic one, notwithstanding the fact that his legal philosophy includes very strong positivistic elements. My argument takes as its point of departure the distinction of three elements, around which the debate between positivism and non-positivism turns: first, authoritative issuance, second, social efficacy, and, third, moral correctness. All positivistic theories are confined to the first two elements. As soon as a necessary connection between these first two elements and the third element, moral correctness, is established, the picture changes fundamentally. Positivism becomes non-positivism. There exist two kinds of connections between law and morality: classifying and qualifying connections. This distinction stems from different sorts of effects that moral defects give rise to. A classifying connection leads to the loss of legal validity, whereas a qualifying connection leads only to legal defectiveness. In Kant’s theory of law both connections are found. The qualifying connection is conspicuous throughout Kant’s theory of law, whereas the classifying connection, by contrast, is rare and well hidden. This will suffice to consider Kant as a representative of inclusive non-positivism.
The Legislative Authority
Authors: Newhouse M. E. 
Published: November 2019

AbstractThis article develops an account of the nature and limits of the state’s legislative authority that closely attends to the challenge of harmonizing Kant’s ethical and juridical theories. It clarifies some key Kantian concepts and terms, then explains the way in which the state’s three interlocking authorities – legislative, executive, and judicial – are metaphysically distinct and mutually dependent. It describes the emergence of the Kantian state and identifies the preconditions of its authority. Then it offers a metaphysical model of the Kantian state and uses it to argue that the activity of juridical lawgiving is an act of the omnilateral will itself. Legislative authority is limited in the sense that it does not include the capacity to create juridical laws that are conceptually incompatible with the idea of universal external freedom. I argue that my proposed account of the legislative authority is wholly consistent with that authority’s exclusive lawgiving capacity and does not threaten the possibility of ‘distributive justice’ – the legal finality that is the sine qua non of a civil condition.
Political Independence, Territorial Integrity and Private Law Analogies
Authors: Ripstein Arthur 
Published: November 2019

AbstractKant deploys analogies from private law in describing relations between states. I explore the relation between these analogies and the broader Kantian idea of the distinctively public nature of a rightful condition, in order to explain why states, understood as public things, stand in horizontal, private legal relations without themselves being private. I use this analysis to explore the international law analogues of the three titles of private right, explaining how territory differs from property, treaty from contract and the specific form of status relations between nations. I conclude with a brief discussion of the ongoing relevance of these horizontal relations.
Perfectionism in a Transdiagnostic Context
Authors: Maricuțoiu Laurențiu P. , Măgurean Silvia , Tulbure Bogdan Tudor 
Published: November 2019

Abstract. Despite recent claims that perfectionism is a transdiagnostic process, few studies have directly tested this hypothesis. We investigated the relationship between perfectionism measured by the Almost Perfect Scale-Revised (APS-R) and the Axis I psychopathology (affective and anxiety disorders) using a transdiagnostic approach. Adult participants ( N = 450, 78% females, Mage = 33 years) completed a series of online self-report measures of perfectionism, anxiety, and depression for this cross-sectional study. The results support a linear relationship between the Discrepancy subscale of APS-R and anxiety/affective psychopathology, while a non-linear relationship appeared between the High Standards subscale of APS-R and anxiety/affective psychopathology. Overall, we provided additional evidence for the transdiagnostic nature of perfectionism, as higher levels of perfectionistic concerns appear to be associated with higher number of clinical symptoms in multiple domains. The possible implications of the study are discussed.
Measuring Test Anxiety in Primary and Middle School	Children
Authors: Donolato Enrica , Marci Tatiana , Altoè Gianmarco , Mammarella Irene C. 
Published: November 2019

Abstract. The increasing use of tests to assess academic competences has been associated with higher levels of test anxiety (TA) in children, underlining the importance of identifying this emotional problem and sustain academic achievement. This study aimed to contribute to the extant literature on the assessment of TA by examining the psychometric properties of the Test Anxiety Questionnaire for Children (TAQ-C), in primary and middle school children. In Study 1 ( N = 123), we selected 24 items from a wider initial pool, dividing them into scales measuring Thoughts, Autonomic Reactions, Off-Task Behaviors, and Social Derogation, to develop the TAQ-C. In Study 2 ( N = 899), the psychometric properties of this set of scales were assessed in students attending primary and middle school. Analyses supported the bifactor latent structure of the TAQ-C, invariance across educational levels and gender, concurrent and convergent validity, and test–retest reliability. Overall, the TAQ-C is a promising tool for assessing TA in primary and middle school students. Implications and directions for future research are discussed.
Therapeutic targeting of the E3 ubiquitin ligase SKP2 in T-ALL
Authors: Rodriguez Sonia , Abundis Christina , Boccalatte Francesco , Mehrotra Purvi , Chiang Mark Y. , Yui Mary A. , Wang Lin , Zhang Huajia , Zollman Amy , Bonfim-Silva Ricardo , Kloetgen Andreas , Palmer Joycelynne , Sandusky George , Wunderlich Mark , Kaplan Mark H. , Mulloy James C. , Marcucci Guido , Aifantis Iannis , Cardoso Angelo A. , Carlesso Nadia 
Published: November 2019

AbstractTimed degradation of the cyclin-dependent kinase inhibitor p27Kip1 by the E3 ubiquitin ligase F-box protein SKP2 is critical for T-cell progression into cell cycle, coordinating proliferation and differentiation processes. SKP2 expression is regulated by mitogenic stimuli and by Notch signaling, a key pathway in T-cell development and in T-cell acute lymphoblastic leukemia (T-ALL); however, it is not known whether SKP2 plays a role in the development of T-ALL. Here, we determined that SKP2 function is relevant for T-ALL leukemogenesis, whereas is dispensable for T-cell development. Targeted inhibition of SKP2 by genetic deletion or pharmacological blockade markedly inhibited proliferation of human T-ALL cells in vitro and antagonized disease in vivo in murine and xenograft leukemia models, with little effect on normal tissues. We also demonstrate a novel feed forward feedback loop by which Notch and IL-7 signaling cooperatively converge on SKP2 induction and cell cycle activation. These studies show that the Notch/SKP2/p27Kip1 pathway plays a unique role in T-ALL development and provide a proof-of-concept for the use of SKP2 as a new therapeutic target in T-cell acute lymphoblastic leukemia (T-ALL).
Repression of transcription factor AP-2 alpha by PPARγ reveals a novel transcriptional circuit in basal-squamous bladder cancer
Authors: Yamashita Hironobu , Kawasawa Yuka I. , Shuman Lauren , Zheng Zongyu , Tran Truc , Walter Vonn , Warrick Joshua I. , Chen Guoli , Al-Ahmadie Hikmat , Kaag Matthew , Wong Pak Kin , Raman Jay D. , DeGraff David J. 
Published: November 2019

AbstractThe discovery of bladder cancer transcriptional subtypes provides an opportunity to identify high risk patients, and tailor disease management. Recent studies suggest tumor heterogeneity contributes to regional differences in molecular subtype within the tumor, as well as during progression and following treatment. Nonetheless, the transcriptional drivers of the aggressive basal-squamous subtype remain unidentified. As PPARɣ has been repeatedly implicated in the luminal subtype of bladder cancer, we hypothesized inactivation of this transcriptional master regulator during progression results in increased expression of basal-squamous specific transcription factors (TFs) which act to drive aggressive behavior. We initiated a pharmacologic and RNA-seq-based screen to identify PPARɣ-repressed, basal-squamous specific TFs. Hierarchical clustering of RNA-seq data following treatment of three human bladder cancer cells with a PPARɣ agonist identified a number of TFs regulated by PPARɣ activation, several of which are implicated in urothelial and squamous differentiation. One PPARɣ-repressed TF implicated in squamous differentiation identified is Transcription Factor Activating Protein 2 alpha (TFAP2A). We show TFAP2A and its paralog TFAP2C are overexpressed in basal-squamous bladder cancer and in squamous areas of cystectomy samples, and that overexpression is associated with increased lymph node metastasis and distant recurrence, respectively. Biochemical analysis confirmed the ability of PPARɣ activation to repress TFAP2A, while PPARɣ antagonist and PPARɣ siRNA knockdown studies indicate the requirement of a functional receptor. In vivo tissue recombination studies show TFAP2A and TFAP2C promote tumor growth in line with the aggressive nature of basal-squamous bladder cancer. Our findings suggest PPARɣ inactivation, as well as TFAP2A and TFAP2C overexpression cooperate with other TFs to promote the basal-squamous transition during tumor progression.
Identification of novel genetic variants predisposing to familial oral squamous cell carcinomas
Authors: Huang Yaping , Zhao Jizhi , Mao Guogen , Lee Grace Sanghee , Zhang Jia , Bi Lijun , Gu Liya , Chang Zhijie , Valentino Joseph , Li Guo-Min 
Published: November 2019

AbstractOral squamous cell carcinoma (OSCC) is a common subtype of head and neck squamous cell carcinoma (HNSCC), but the pathogenesis underlying familial OSCCs is unknown. Here, we analyzed whole-genome sequences of a family with autosomal dominant expression of oral tongue cancer and identified proto-oncogenesVAV2andIQGAP1as the primary factors responsible for oral cancer in the family. These two genes are also frequently mutated in sporadic OSCCs and HNSCCs. Functional analysis revealed that the detrimental variants target tumorigenesis-associated pathways, thus confirming that these novel genetic variants help to establish a predisposition to familial OSCC.
Global alteration of T-lymphocyte metabolism by PD-L1 checkpoint involves a block of de novo nucleoside phosphate synthesis
Authors: Palaskas Nicolaos Jay , Garcia Jacob David , Shirazi Roksana , Shin Daniel Sanghoon , Puig-Saus Cristina , Braas Daniel , Ribas Antoni , Graeber Thomas Glen 
Published: November 2019

AbstractMetabolic obstacles of the tumor microenvironment remain a challenge to T-cell-mediated cancer immunotherapies. To better understand the interplay of immune checkpoint signaling and immune metabolism, this study developed and used an optimized metabolite extraction protocol for non-adherent primary human T-cells, to broadly profile in vitro metabolic changes effected by PD-1 signaling by mass spectrometry-based metabolomics and isotopomer analysis. Inhibitory signaling reduced aerobic glycolysis and glutaminolysis. A general scarcity across the panel of metabolites measured supported widespread metabolic regulation by PD-1. Glucose carbon fate analysis supported tricarboxylic acid cycle reliance on pyruvate carboxylation, catabolic-state fluxes into acetyl-CoA and succinyl-CoA, and a block in de novo nucleoside phosphate synthesis that was accompanied by reduced mTORC1 signaling. Nonetheless, exogenous administration of nucleosides was not sufficient to ameliorate proliferation of T-cells in the context of multiple metabolic insufficiencies due to PD-L1 treatment. Carbon fate analysis did not support the use of primarily glucose-derived carbons to fuel fatty acid beta oxidation, in contrast to reports on T-memory cells. These findings add to our understanding of metabolic dysregulation by PD-1 signaling and inform the effort to rationally develop metabolic interventions coupled with immune-checkpoint blockade for increased treatment efficacy.
Invariant patterns of clonal succession determine specific clinical features of myelodysplastic syndromes
Authors: Nagata Yasunobu , Makishima Hideki , Kerr Cassandra M. , Przychodzen Bartlomiej P. , Aly Mai , Goyal Abhinav , Awada Hassan , Asad Mohammad Fahad , Kuzmanovic Teodora , Suzuki Hiromichi , Yoshizato Tetsuichi , Yoshida Kenichi , Chiba Kenichi , Tanaka Hiroko , Shiraishi Yuichi , Miyano Satoru , Mukherjee Sudipto , LaFramboise Thomas , Nazha Aziz , Sekeres Mikkael A. , Radivoyevitch Tomas , Haferlach Torsten , Ogawa Seishi , Maciejewski Jaroslaw P. 
Published: November 2019

AbstractMyelodysplastic syndromes (MDS) arise in older adults through stepwise acquisitions of multiple somatic mutations. Here, analyzing 1809 MDS patients, we infer clonal architecture by using a stringent, the single-cell sequencing validated PyClone bioanalytic pipeline, and assess the position of the mutations within the clonal architecture. All 3,971 mutations are grouped based on their rank in the deduced clonal hierarchy (dominant and secondary). We evaluated how they affect the resultant morphology, progression, survival and response to therapies. Mutations of SF3B1, U2AF1, and TP53 are more likely to be dominant, those of ASXL1, CBL, and KRAS are secondary. Among distinct combinations of dominant/secondary mutations we identified 37 significant relationships, of which 12 affect clinical phenotypes, 5 cooperatively associate with poor prognosis. They also predict response to hypomethylating therapies. The clonal hierarchy has distinct ranking and the resultant invariant combinations of dominant/secondary mutations yield novel insights into the specific clinical phenotype of MDS.
Digit-tracking as a new tactile interface for visual perception analysis
Authors: Lio Guillaume , Fadda Roberta , Doneddu Giuseppe , Duhamel Jean‐René , Sirigu Angela 
Published: November 2019

AbstractEye‐tracking is a valuable tool in cognitive science for measuring how visual processing resources are allocated during scene exploration. However, eye-tracking technology is largely confined to laboratory‐based settings, making it difficult to apply to large-scale studies. Here, we introduce a biologically‐inspired solution that involves presenting, on a touch‐sensitive interface, a Gaussian‐blurred image that is locally unblurred by sliding a finger over the display. Thus, the user’s finger movements provide a proxy for their eye movements and attention. We validated the method by showing strong correlations between attention maps obtained using finger-tracking vs. conventional optical eye‐tracking. Using neural networks trained to predict empirically‐derived attention maps, we established that identical high‐level features hierarchically drive explorations with either method. Finally, the diagnostic value of digit‐tracking was tested in autistic and brain‐damaged patients. Rapid yet robust measures afforded by this method open the way to large scale applications in research and clinical settings.
The in vivo ISGylome links ISG15 to metabolic pathways and autophagy upon Listeria monocytogenes infection
Authors: Zhang Yifeng , Thery Fabien , Wu Nicholas C. , Luhmann Emma K. , Dussurget Olivier , Foecke Mariko , Bredow Clara , Jiménez-Fernández Daniel , Leandro Kevin , Beling Antje , Knobeloch Klaus-Peter , Impens Francis , Cossart Pascale , Radoshevich Lilliana 
Published: November 2019

AbstractISG15 is an interferon-stimulated, ubiquitin-like protein, with anti-viral and anti-bacterial activity. Here, we map the endogenous in vivo ISGylome in the liver followingListeria monocytogenesinfection by combining murine models of reduced or enhanced ISGylation with quantitative proteomics. Our method identifies 930 ISG15 sites in 434 proteins and also detects changes in the host ubiquitylome. The ISGylated targets are enriched in proteins which alter cellular metabolic processes, including upstream modulators of the catabolic and antibacterial pathway of autophagy. Computational analysis of substrate structures reveals that a number of ISG15 modifications occur at catalytic sites or dimerization interfaces of enzymes. Finally, we demonstrate that animals and cells with enhanced ISGylation have increased basal and infection-induced autophagy through the modification of mTOR, WIPI2, AMBRA1, and RAB7. Taken together, these findings ascribe a role of ISGylation to temporally reprogram organismal metabolism following infection through direct modification of a subset of enzymes in the liver.
Gene gain and loss push prokaryotes beyond the homologous recombination barrier and accelerate genome sequence divergence
Authors: Iranzo Jaime , Wolf Yuri I. , Koonin Eugene V. , Sela Itamar 
Published: November 2019

AbstractBacterial and archaeal evolution involve extensive gene gain and loss. Thus, phylogenetic trees of prokaryotes can be constructed both by traditional sequence-based methods (gene trees) and by comparison of gene compositions (genome trees). Comparing the branch lengths in gene and genome trees with identical topologies for 34 clusters of closely related bacterial and archaeal genomes, we show here that terminal branches of gene trees are systematically compressed compared to those of genome trees. Thus, sequence evolution is delayed compared to genome evolution by gene gain and loss. The extent of this delay differs widely among bacteria and archaea. Mathematical modeling shows that the divergence delay can result from sequence homogenization by homologous recombination. The model explains how homologous recombination maintains the cohesiveness of the core genome of a species while allowing extensive gene gain and loss within the accessory genome. Once evolving genomes become isolated by barriers impeding homologous recombination, gene and genome evolution processes settle into parallel trajectories, and genomes diverge, resulting in speciation.
Zinc anode-compatible in-situ solid electrolyte interphase via cation solvation modulation
Authors: Qiu Huayu , Du Xiaofan , Zhao Jingwen , Wang Yantao , Ju Jiangwei , Chen Zheng , Hu Zhenglin , Yan Dongpeng , Zhou Xinhong , Cui Guanglei 
Published: November 2019

AbstractThe surface chemistry of solid electrolyte interphase is one of the critical factors that govern the cycling life of rechargeable batteries. However, this chemistry is less explored for zinc anodes, owing to their relatively high redox potential and limited choices in electrolyte. Here, we report the observation of a zinc fluoride-rich organic/inorganic hybrid solid electrolyte interphase on zinc anode, based on an acetamide-Zn(TFSI)2 eutectic electrolyte. A combination of experimental and modeling investigations reveals that the presence of anion-complexing zinc species with markedly lowered decomposition energies contributes to the in situ formation of an interphase. The as-protected anode enables reversible (~100% Coulombic efficiency) and dendrite-free zinc plating/stripping even at high areal capacities (>2.5 mAh cm‒2), endowed by the fast ion migration coupled with high mechanical strength of the protective interphase. With this interphasial design the assembled zinc batteries exhibit excellent cycling stability with negligible capacity loss at both low and high rates.
Multi-dimensional computational pipeline for large-scale deep screening of compound effect assessment: an in silico case study on ageing-related compounds
Authors: Gupta Vipul , Crudu Alina , Matsuoka Yukiko , Ghosh Samik , Rozot Roger , Marat Xavier , Jäger Sibylle , Kitano Hiroaki , Breton Lionel 
Published: November 2019

AbstractDesigning alternative approaches to efficiently screen chemicals on the efficacy landscape is a challenging yet indispensable task in the current compound profiling methods. Particularly, increasing regulatory restrictions underscore the need to develop advanced computational pipelines for efficacy assessment of chemical compounds as alternative means to reduce and/or replace in vivo experiments. Here, we present an innovative computational pipeline for large-scale assessment of chemical compounds by analysing and clustering chemical compounds on the basis of multiple dimensions—structural similarity, binding profiles and their network effects across pathways and molecular interaction maps—to generate testable hypotheses on the pharmacological landscapes as well as identify potential mechanisms of efficacy on phenomenological processes. Further, we elucidate the application of the pipeline on a screen of anti-ageing-related compounds to cluster the candidates based on their structure, docking profile and network effects on fundamental metabolic/molecular pathways associated with the cell vitality, highlighting emergent insights on compounds activities based on the multi-dimensional deep screen pipeline.
Monitored data on occupants’ presence and actions in an office building
Authors: Mahdavi Ardeshir , Berger Christiane , Tahmasebi Farhang , Schuss Matthias 
Published: November 2019

AbstractWithin a study, an open plan area and one closed office in a university building with a floor area of around 200 m2 were monitored. The present data set covers a period of one year (from 2013-01-01 to 2013-12-31). The collected data pertains to indoor environmental conditions (temperature, humidity) as well as plug loads and external factors (temperature, humidity, wind speed, and global irradiance) along with occupants’ presence and operation of windows and lights. The monitored data can be used for multiple purposes, including the development and validation of occupancy-related models.
X-ray Fokker–Planck equation for paraxial imaging
Authors: Paganin David M. , Morgan Kaye S. 
Published: November 2019

AbstractThe Fokker–Planck equation can be used in a partially-coherent imaging context to model the evolution of the intensity of a paraxial x-ray wave field with propagation. This forms a natural generalisation of the transport-of-intensity equation. The x-ray Fokker–Planck equation can simultaneously account for both propagation-based phase contrast, and the diffusive effects of sample-induced small-angle x-ray scattering, when forming an x-ray image of a thin sample. Two derivations are given for the Fokker–Planck equation associated with x-ray imaging, together with a Kramers–Moyal generalisation thereof. Both equations are underpinned by the concept of unresolved speckle due to unresolved sample micro-structure. These equations may be applied to the forward problem of modelling image formation in the presence of both coherent and diffusive energy transport. They may also be used to formulate associated inverse problems of retrieving the phase shifts due to a sample placed in an x-ray beam, together with the diffusive properties of the sample. The domain of applicability for the Fokker–Planck and Kramers–Moyal equations for paraxial imaging is at least as broad as that of the transport-of-intensity equation which they generalise, hence the technique is also expected to be useful for paraxial imaging using visible light, electrons and neutrons.