julilili42/papers huggingface dataset:
Two distinct age groups of melilitites, foidites, and basanites from the southern Central European Volcanic Province reflect lithospheric heterogeneity
2022-12-04

Abstract Petrographic observations and in situ U–Pb ages of melilitites, foidites, basanites, phonolites, and trachytes from the southern part of the Central European Volcanic Province (CEVP) and related plutonic inclusions therein reveal two distinct age groups separated by a gap of ~ 20 Myr. A late Cretaceous to early Eocene group (~ 73–47 Ma; Taunus, Lower Main plain, Odenwald and Kraichgau area, Bonndorfer Graben and Freiburger Bucht area, Vosges and Pfälzerwald) is characterized by nephelinites and basanites mostly devoid of melilite and perovskite, and by rare haüynites, and trachytes. In contrast, a late Oligocene to late Miocene group (~ 27–9 Ma; Lorraine, southern Upper Rhine Graben, Urach, Hegau area) is dominated by melilitites, melilite-bearing nephelinites (both carrying perovskite), and phonolites. Both magmatic episodes are related to domal topographic uplift, erosion, and formation of major angular unconformities in the Upper Rhine Graben, suggesting an association with dynamic topography interrupted by phases of subsidence (or abatements of uplift). The investigated rocks in the southern CEVP (south of a line Eifel–Vogelsberg–Rhön–Heldburg), except for the Kaiserstuhl volcanic complex, mostly comprise small and isolated occurrences or monogenetic volcanic fields, whereas the northern CEVP is dominated by large volcanic complexes and dyke swarms, which are mostly SiO 2 -saturated to weakly SiO 2 -undersaturated. In the northern CEVP, evidence of spatially varying but recurrent volcanic activity exists since the Eocene, lacking the distinct 20 Myr gap as documented from the southern CEVP. While the temporal and spatial distribution of volcanism are a result of the Cretaceous to Miocene tectonic evolution in Central Europe, further studies are needed to explain the petrographic differences between the two age groups in the south.
Modal and Amodal Cognition: An Overarching Principle in Various Domains of Psychology
2022-12-04

Accounting for how the human mind represents the internal and external world is a crucial feature of many theories of human cognition. Central to this question is the distinction between modal as opposed to amodal representational formats. It has often been assumed that one but not both of these two types of representations underlies processing in specific domains of cognition (e.g., perception, mental imagery, and language). However, in this paper we suggest that both formats play a major role in most cognitive domains. We believe that a comprehensive theory of cognition requires a solid understanding of these representational formats and their functional roles within and across different domains of cognition, the developmental trajectory of these representational formats, and their role in dysfunctional behavior. Here we sketch such an overarching perspective that brings together research from diverse subdisciplines of psychology on modal and amodal representational formats so as to unravel their functional principles and their interactions.
Maintaining Order in Revolutionary Times—The Political Practices of a Mercantile Elite in the Rhineland, 1770–1830
2022-12-04

This chapter examines the political practices of the mercantile elite of the German Duchy of Berg as a process of political negotiation, in which both sides relied heavily on tried and tested forms of political interchange, namely petitions and delegations. The Duchy of Berg was a small territory, yet as a proto-industrial hotspot it was economically important in the Holy Roman Empire. This commercial success not only formed the backbone for the self-esteem of the mercantile classes driving the industries but also inspired most of their political activism. Despite all the political changes around them, this enabled them to maintain their status and to salvage some of their privileges well into the nineteenth century. As the chapter demonstrates, both administrators as well as the wider population relied heavily on the elites to help domesticate the new.
High-Dose Cytarabine and Autologous Stem-Cell Transplantation in Mantle Cell Lymphoma: Long-Term Follow-Up of the Randomized Mantle Cell Lymphoma Younger Trial of the European Mantle Cell Lymphoma Network
2022-12-05

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. In 2004, the European Mantle Cell Lymphoma (MCL) Network initiated the randomized open-label, phase III MCL Younger trial for first-line treatment of patients with advanced-stage MCL, age &lt; 66 years, comparing an alternating rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone/rituximab plus dexamethasone, high-dose cytarabine, and cisplatin (R-CHOP/R-DHAP) induction followed by high-dose cytarabine-containing myeloablative radiochemotherapy conditioning and autologous peripheral blood stem-cell transplantation (R-DHAP arm) to R-CHOP with standard myeloablative radiochemotherapy and autologous stem-cell transplantation (R-CHOP arm). After a median follow-up of 10.6 years, the time to treatment failure was still significantly improved in the R-DHAP versus R-CHOP arms (medians 8.4 v 3.9 years, 5-/10-year rates 64%/46% v 41%/25%, P = .038, hazard ratio, 0.59). Median overall survival (OS) was not reached in the R-DHAP arm versus 11.3 years in R-CHOP arm (5-/10-year rates, 76%/60% v 69%/55%, P = .12). The unadjusted OS hazard ratios (0.80 [95% CI, 0.61 to 1.06], P = .12) reached significance when adjusted for Mantle Cell Lymphoma International Prognostic Index (MIPI) and MIPI + Ki-67 (MIPI-c) (0.74; 95% CI, 0.56 to 0.98; P = .038 and .60; 95% CI, 0.41 to 0.87; P = .0066). The incidence of secondary hematologic malignancies tended to be higher in the R-DHAP arm (4.5% v 1.4% at 10 years). With mature long-term data, we confirm the previously observed substantially prolonged time to treatment failure and, for the first time to our knowledge, show an improvement of OS. Some patients with MCL may be cured.
A rare loss-of-function genetic mutation suggest a role of dermcidin deficiency in hidradenitis suppurativa pathogenesis
2022-12-05

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a multifactorial aetiology that involves a strict interplay between genetic factors, immune dysregulation and lifestyle. Familial forms represent around 40% of total HS cases and show an autosomal dominant mode of inheritance of the disease. In this study, we conducted a whole-exome sequence analysis on an Italian family of 4 members encompassing a vertical transmission of HS. Focusing on rare damaging variants, we identified a rare insertion of one nucleotide (c.225dupA:p.A76Sfs*21) in the DCD gene encoding for the antimicrobial peptide dermcidin (DCD) that was shared by the proband, his affected father and his 11-years old daughter. Since several transcriptome studies have shown a significantly decreased expression of DCD in HS skin, we hypothesised that the identified frameshift insertion was a loss-of-function mutation that might be associated with HS susceptibility in this family. We thus confirmed by mass spectrometry that DCD levels were diminished in the affected members and showed that the antimicrobial activity of a synthetic DCD peptide resulting from the frameshift mutation was impaired. In order to define the consequences related to a decrease in DCD activity, skin microbiome analyses of different body sites were performed by comparing DCD mutant and wild type samples, and results highlighted significant differences between the groins of mutated and wild type groups. Starting from genetic analysis conducted on an HS family, our findings showed, confirming previous transcriptome results, the potential role of the antimicrobial DCD peptide as an actor playing a crucial part in the etio-pathogenesis of HS and in the maintenance of the skin’s physiological microbiome composition; so, we can hypothesise that DCD could be used as a novel target for personalised therapeutic approach.
Estimating the perceived dimension of psychophysical stimuli using triplet accuracy and hypothesis testing
2022-12-05

Vision researchers are interested in mapping complex physical stimuli to perceptual dimensions. Such a mapping can be constructed using multidimensional psychophysical scaling or ordinal embedding methods. Both methods infer coordinates that agree as much as possible with the observer's judgments so that perceived similarity corresponds with distance in the inferred space. However, a fundamental problem of all methods that construct scalings in multiple dimensions is that the inferred representation can only reflect perception if the scale has the correct dimension. Here we propose a statistical procedure to overcome this limitation. The critical elements of our procedure are i) measuring the scale's quality by the number of correctly predicted triplets and ii) performing a statistical test to assess if adding another dimension to the scale improves triplet accuracy significantly. We validate our procedure through extensive simulations. In addition, we study the properties and limitations of our procedure using "real" data from various behavioral datasets from psychophysical experiments. We conclude that our procedure can reliably identify (a lower bound on) the number of perceptual dimensions for a given dataset.
Pharmacokinetics, absorption, distribution, metabolism and excretion of the MEK inhibitor zapnometinib in rats
2022-12-05

Zapnometinib is a MEK inhibitor currently under clinical development for the treatment of COVID-19 and influenza. Zapnometinib has both antiviral and immunomodulatory effects. Information concerning the absorption, distribution, metabolism, and excretion of the compound following single oral doses of 30 mg/kg [ 14 C]-zapnometinib to rats was required to support pharmacology and toxicology studies in animals and clinical studies in man. As part of the development and safety assessment of this substance, zapnometinib was radioactively labeled and used for the investigation of time-dependent plasma concentrations, the rates and routes of excretion, the extent and time-course of compound distribution in body tissues, the metabolite profiles in plasma, urine and feces and the chemical nature of its metabolites. The present study reveals a rapid but low absorption of zapnometinib from the gastrointestinal tract, with more than 90% of the compound being excreted within 48 h, mainly via feces. Whole body autoradiography confirms that zapnometinib was rapidly and widely distributed, with greatest concentrations in the circulatory and visceral tissues. Maximum plasma and tissue concentrations occurred between two and 8 h post dose. Penetration into the brain was low, and elimination from most tissues almost complete after 168 h. Metabolic profiles showed that the main clearance routes were metabolism via oxidative reactions and glucuronidation. These results further strengthen the knowledge of zapnometinib with respect to the clinical development of the drug.
Land use intensification results in abrupt transitions between contrasting grassland states
2022-12-05

Understanding whether land use intensification causes regime shifts is of key importance for management, particularly if these shifts are associated with thresholds separating different ecosystem states and with hysteretic dynamics. Here we use a unique, long-term grassland database to identify thresholds in the response of 16 ecosystem functions and the diversities of 21 taxa to land use intensity. We show that aboveground diversity (5 of 10 taxa), shoot biomass and soil N retention showed threshold responses to land use intensity, i.e., abrupt changes between extensively and intensively managed grasslands. Time-series analysis revealed that ecosystem functions showed hysteresis around the threshold, while diversity did not. Shifting back to the functioning seen in extensively managed grasslands may therefore require larger reductions in land use intensity than shifting to the high intensity state. Identifying such thresholds along land use gradients is critical to prevent ecosystem degradation and conserve biodiversity and ecosystem functions.
Abdominal and Peripheral Tissue Oxygen Supply during Selective Lower Body Perfusion for the Surgical Repair of Congenital Heart Disease: A Pilot Study
2022-12-05

Background: Lower body perfusion (LBP) may be a strategy for maintaining organ perfusion during congenital heart disease surgery. It is hypothesized that renal and lower limb oxygen supply during LBP is superior to off-pump surgery and comparable to that of a standard cardiopulmonary bypass (CPB). Methods: in this prospective single-center study, patients aged &lt;1 year were recruited if they were scheduled for a correction of aortic arch anomalies using antegrade cerebral perfusion and LBP (group 1), a repair of coarctation during aortic cross-clamping (group 2), or surgery under whole-body CPB (group 3). Renal (prefix “r”) and peripheral (prefix “p”) oxygen saturation (SO2), hemoglobin amount (Hb), blood velocity (Velo), and blood flow (Flow) were measured noninvasively. Results: A total of 23 patients were included (group 1, n = 9; group 2, n = 5; group 3, n = 9). Compared to the baseline values, rSO2 and pSO2 decreased significantly in group 2 compared to groups 1 and 3. Conversely, rHB significantly increased in group 2 compared to groups 1 and 3, reflecting abdominal venous stasis. Compared to group 3, group 1 showed a significantly lower pFlow during CPB; however, rFlow, pFlow, and pVelo did not differ. Conclusion: according to these observations, LBP results in an improved renal oxygen supply compared to off-pump surgery and may prove to be a promising alternative to conventional CPB.
The bittersweet lesson: data-rich models narrow the behavioural gap to human vision
2022-12-05

A major obstacle to understanding human visual object recognition is our lack of behaviourally faithful models. Even the best models based on deep learning classifiers strikingly deviate from human perception in many ways. To study this deviation in more detail, we collected a massive set of human psychophysical classification data under highly controlled conditions (17 datasets, 85K trials across 90 observers). We made this data publicly available as an open-sourced Python toolkit and behavioural benchmark called "model-vs-human", which we use for investigating the very latest generation of models. Generally, in terms of robustness, standard machine vision models make much more errors on distorted images, and in terms of image-level consistency, they make very different errors than humans. Excitingly, however, a number of recent models make substantial progress towards closing this behavioural gap: "simply" training models on large-scale datasets (between one and three orders of magnitude larger than standard ImageNet) is sufficient to, first, reach or surpass human-level distortion robustness and, second, to improve image-level error consistency between models and humans. This is significant given that none of those models is particularly biologically faithful on the implementational level, and in fact, large-scale training appears much more effective than, e.g., biologically-motivated self-supervised learning. In the light of these findings, it is hard to avoid drawing parallels to the "bitter lesson" formulated by Rich Sutton, who argued that "building in how we think we think does not work in the long run" - and ultimately, scale would be all that matters. While human-level distortion robustness and improved behavioural consistency with human decisions through large-scale training is certainly a sweet surprise, this leaves us with a nagging question: Should we, perhaps, worry less about biologically faithful implementations and more about the algorithmic similarities between human and machine vision induced by training on large-scale datasets?
Vergleichende Entwicklungsgeschichte — A Festschrift on the occasion of the 80th birthday of Prof. Dr. Wolfgang Maier, Tübingen
2022-12-05

Following the traditional and holistic concept of Vergleichende Entwicklungsgeschichte , Wolfgang Maier studied different aspects of vertebrate morphology, including dentition, the locomotor apparatus, nasal and ear regions. His work comprises investigations on pre- to postnatal stages of extant species as well as fossils and is mainly based on histological serial sections, but also on μCT data in recent years. This resulted in an integrative research agenda on the evolutionary biology of mammals and other vertebrates. Most of his studies are designed around the interrelationship of ontogenetic and functional adaptations and evolutionary transformations. The present collection in Vertebrate Zoology collates a series of research articles related to and in honor of Wolfgang Maier’s work. Invited colleagues of Maier provide current insights to their own research, in many cases inspired by his scholarship, ranging from mammalian to reptilian and fish comparative anatomy. In total, this volume contains 19 publications. They apply modern and traditional techniques to investigate the diversity of biological form. In so doing, they integrate traditional conceptual frameworks from the earliest days of morphological research more than two centuries ago.
Estimating the perceived dimensionality of psychophysical stimuli using a triplet accuracy and hypothesis testing procedure
2022-12-05

In vision research we are often interested in understanding the mapping of complex physical stimuli to their perceptual dimensions. This mapping can be explored experimentally with multi-dimensional psychophysical scaling. One fruitful approach is the combination of triplet comparison judgments, asking if stimulus A or B is more similar to C, together with ordinal embedding methods. Ordinal embedding infers a point representation such that the distances in the inferred, internal perceptual space agree with the observer’s judgments. One fundamental problem of psychophysical scaling in multiple dimensions is, however, that the inferred representation only reflects perception if it has the correct dimensionality. Unfortunately, the methods to derive the “correct” dimensionality were thus far not satisfactory for noisy, behavioural data (e.g. no clear “knee” in the stress-by-dimension graph of multi-dimensional scaling). Here we propose a statistical procedure inspired by model selection to choose the dimensionality: Dimensionality can be tuned to prevent both under- and overfitting. The key elements are, first, measuring the scale’s quality by the number of correctly predicted triplets (cross-validated triplet accuracy). Second, performing a statistical test to assess if adding another dimension improves triplet accuracy significantly. In order to validate this procedure we simulated noisy and sparse judgments and assessed how reliably the ground-truth dimensionality could be identified. Even for high noise levels we are able to identify a lower-bound estimate of the perceived dimensions. Furthermore, we studied the properties and limitations of our procedure using a variety of behavioural datasets from psychophysical experiments. We conclude that our procedure is a robust tool in the exploration of new perceptual spaces and is able to help identify a lower bound on the number of perceptual dimensions for a given dataset. The identified dimensions and the resulting representation can then be related to perceptual processes in order to explore human vision.
Meta’s Oversight Board and Beyond – Corporations as Interpreters and Adjudicators of International Human Rights
2022-12-05

Abstract Social media platform corporations such as Meta (Facebook), Twitter, etc. find themselves in a position of having to interpret international human rights norms, in particular Article 19 of the International Covenant on Civil and Political Rights ( ICCPR ) (freedom of expression). Millions or even billions of content moderation decisions need to be taken on the platforms each day that affect users’ human rights interests. Since content moderation is integral to the technical and commercial set-up of these platforms, corporate decision-making vis-à-vis human rights and thus corporate interpretation of international human rights norms is inevitable. Yet, corporations are flawed interpreters. Whereas they act, like a court or tribunal, as triadic decision-makers, they, unlike a court or tribunal, do not share the neutrality, impartiality and independence of the latter. In particular, they are responsible to their shareholders and they pursue commercial interests when moderating content. This article grapples with the theoretical and doctrinal implications of flawed but inevitable corporate human rights interpretation. Taking the early practice of the Oversight Board, a body established by Meta, Inc. (Facebook), in order to tackle the “hard cases” of content moderation as a case study, the pitfalls and challenges of corporate human rights interpretation become apparent. In the end, I submit a few suggestions in order to remedy what seems to be here to stay with us at least for as long as an important part of public discourse is channelled through social media platforms.
Cis-regulatory evolution of the potassium channel genekcnj13during pigment pattern diversification inDaniofish
2022-12-05

Abstract Teleost fish of the genus Danio are excellent models to study the genetic and cellular bases of pigment pattern variation in vertebrates. The two sister species Danio rerio and Danio aesculapii show divergent patterns of horizontal stripes and vertical bars that are partly caused by the evolution of the potassium channel gene kcnj13 . In D. rerio, kcnj13 is required in melanophores for interactions with xanthophores and iridophores, which cause location-specific pigment cell shapes and thereby influence colour pattern and contrast. Here, we show that cis-regulatory rather than protein coding changes underlie kcnj13 evolution between the two species. D. aesculapii express lower kcnj13 levels and exhibit low-contrast patterns similar to D. rerio mutants. Our results suggest that homotypic and heterotypic interactions between the pigment cells and their shapes diverged between species by quantitative changes in kcnj13 expression during pigment pattern diversification.