julilili42/papers huggingface dataset:
A TOR (target of rapamycin) and nutritional phosphoproteome of fission yeast reveals novel targets in networks conserved in humans
2021-04-01

Fluctuations in TOR, AMPK and MAP-kinase signalling maintain cellular homeostasis and coordinate growth and division with environmental context. We have applied quantitative, SILAC mass spectrometry to map TOR and nutrient-controlled signalling in the fission yeast Schizosaccharomyces pombe . Phosphorylation levels at more than 1000 sites were altered following nitrogen stress or Torin1 inhibition of the TORC1 and TORC2 networks that comprise TOR signalling. One hundred and thirty of these sites were regulated by both perturbations, and the majority of these (119) new targets have not previously been linked to either nutritional or TOR control in either yeasts or humans. Elimination of AMPK inhibition of TORC1, by removal of AMPK α ( ssp2::ura4 + ), identified phosphosites where nitrogen stress-induced changes were independent of TOR control. Using a yeast strain with an ATP analogue-sensitized Cdc2 kinase, we excluded sites that were changed as an indirect consequence of mitotic control modulation by nitrogen stress or TOR signalling. Nutritional control of gene expression was reflected in multiple targets in RNA metabolism, while significant modulation of actin cytoskeletal components points to adaptations in morphogenesis and cell integrity networks. Reduced phosphorylation of the MAPKK Byr1, at a site whose human equivalent controls docking between MEK and ERK, prevented sexual differentiation when resources were sparse but not eliminated.
The geography and development of language isolates
2021-04-01

This contribution theorizes the historical dynamics of so-called language isolates, languages which cannot be demonstrated to belong to any known language family. On the basis of a qualitative review of how isolates, language families or their branches lost territory to other languages through time, I develop a simple model for the genesis of isolates as a function of proximity to major geographical barriers, and pit it against an alternative view that sees them as one manifestation of linguistic diversity generally. Using a variety of statistical techniques, I test both accounts quantitatively against a worldwide dataset of language locations and distances to geographical barriers, and find support for the position that views language isolates as one manifestation of linguistic diversity generally. However, I caution that different processes which are not necessarily mutually exclusive may have shaped the present-day distribution of language isolates. These may form elements of a broader theory of language isolates in particular and language diversity in general.
Glucagon's Metabolic Action in Health and Disease
2021-04-01

Abstract Discovered almost simultaneously with insulin, glucagon is a pleiotropic hormone with metabolic action that goes far beyond its classical role to increase blood glucose. Albeit best known for its ability to directly act on the liver to increase de novo glucose production and to inhibit glycogen breakdown, glucagon lowers body weight by decreasing food intake and by increasing metabolic rate. Glucagon further promotes lipolysis and lipid oxidation and has positive chronotropic and inotropic effects in the heart. Interestingly, recent decades have witnessed a remarkable renaissance of glucagon's biology with the acknowledgment that glucagon has pharmacological value beyond its classical use as rescue medication to treat severe hypoglycemia. In this article, we summarize the multifaceted nature of glucagon with a special focus on its hepatic action and discuss the pharmacological potential of either agonizing or antagonizing the glucagon receptor for health and disease. © 2021 American Physiological Society. Compr Physiol 11:1759‐1783, 2021.
Broad Linguistic Complexity Analysis for Greek Readability Classification.
2021-04-01

This paper explores the linguistic complexity of Greek textbooks as a readability classification task. We analyze textbook corpora for different school subjects and textbooks for Greek as a Second Language, covering a very wide spectrum of school age groups and proficiency levels. A broad range of quantifiable linguistic complexity features (lexical, morphological and syntactic) are extracted and calculated. Conducting experiments with different feature subsets, we show that the different linguistic dimensions contribute orthogonal information, each contributing towards the highest result achieved using all linguistic feature subsets. A readability classifier trained on this basis reaches a classification accuracy of 88.16% for the Greek as a Second Language corpus. To investigate the generalizability of the classification models, we also perform cross-corpus evaluations. We show that the model trained on the most varied text collection (for Greek as a school subject) generalizes best. In addition to advancing the state of the art for Greek readability analysis, the paper also contributes insights on the role of different feature sets and training setups for generalizable readability classification.
Replication of Previous Findings? Comparing Gray Matter Volumes in Transgender Individuals with Gender Incongruence and Cisgender Individuals
2021-04-01

The brain structural changes related to gender incongruence (GI) are still poorly understood. Previous studies comparing gray matter volumes (GMV) between cisgender and transgender individuals with GI revealed conflicting results. Leveraging a comprehensive sample of transmen (n = 33), transwomen (n = 33), cismen (n = 24), and ciswomen (n = 25), we employ a region-of-interest (ROI) approach to examine the most frequently reported brain regions showing GMV differences between trans- and cisgender individuals. The primary aim is to replicate previous findings and identify anatomical regions which differ between transgender individuals with GI and cisgender individuals. On the basis of a comprehensive literature search, we selected a set of ROIs (thalamus, putamen, cerebellum, angular gyrus, precentral gyrus) for which differences between cis- and transgender groups have been previously observed. The putamen was the only region showing significant GMV differences between cis- and transgender, across previous studies and the present study. We observed increased GMV in the putamen for transwomen compared to both transmen and ciswomen and for all transgender participants compared to all cisgender participants. Such a pattern of neuroanatomical differences corroborates the large majority of previous studies. This potential replication of previous findings and the known involvement of the putamen in cognitive processes related to body representations and the creation of the own body image indicate the relevance of this region for GI and its potential as a structural biomarker for GI.
An Fc-Optimized CD133 Antibody for Induction of NK Cell Reactivity against B Cell Acute Lymphoblastic Leukemia
2021-04-01

In recent decades, antibody-dependent cellular cytotoxicity (ADCC)-inducing monoclonal antibodies (mAbs) have revolutionized cancer immunotherapy, and Fc engineering strategies have been utilized to further improve efficacy. A promising option is to enhance the affinity of an antibody’s Fc-part to the Fc-receptor CD16 by altering the amino acid sequence. Herein, we characterized an S239D/I332E-modified CD133 mAb termed 293C3-SDIE for treatment of B cell acute lymphoblastic leukemia (B-ALL). Flow cytometric analysis revealed CD133 expression on B-ALL cell lines and leukemic cells of 50% (14 of 28) B-ALL patients. 293C3-SDIE potently induced NK cell reactivity against the B-ALL cell lines SEM and RS4;11, as well as leukemic cells of B-ALL patients in a target antigen-dependent manner, as revealed by analysis of NK cell activation, degranulation, and cytotoxicity. Of note, CD133 expression did not correlate with BCR-ABL, CD19, CD20, or CD22, which are presently used as therapeutic targets in B-ALL, which revealed CD133 as an independent target for B-ALL treatment. Increased CD133 expression was also observed in MLL-AF4-rearranged B-ALL, indicating that 293C3-SDIE may constitute a particularly suitable treatment option in this hard-to-treat subpopulation. Taken together, our results identify 293C3-SDIE as a promising therapeutic agent for the treatment of B-ALL.
Update Breast Cancer 2020 Part 5 – Moving Therapies From Advanced to Early Breast Cancer Patients
2021-04-01

Abstract In recent years, significant progress has been made in new therapeutic approaches to breast cancer, particularly in patients with HER2-positive and HER2-negative/hormone receptor-positive (HR+) breast cancer. In the case of HER2-positive tumours, these approaches have included, in particular, treatment with pertuzumab, T-DM1, neratinib and, soon, also tucatinib and trastuzumab deruxtecan (neither of which has yet been authorised in Europe). In patients with HER2−/HR+ breast cancer, CDK4/6 inhibitors and the PIK3CA inhibitor alpelisib are of particular importance. Further novel therapies, such as Akt kinase inhibitors and oral SERDs (selective estrogen receptor down regulators), are already being investigated in ongoing clinical trials. These therapeutic agents are not only being introduced into curative, (neo-)adjuvant therapeutic settings for HER2-positive tumours; a first favourable study on abemaciclib as an adjuvant therapy has now also been published. In patients with triple-negative breast cancer, after many years of negative study results with the Trop-2 antibody drug conjugate (ADC) sacituzumab govitecan, a randomised study has been published that may represent a significant therapeutic advance. This review describes the latest developments in breast cancer subsequent to the ESMO Congress 2020.
Investigating the 1930s Kohl-Larsen collection from the Lake Eyasi Basin, Tanzania
2021-04-01

Since more than 80 years, the University of Tübingen hosts the archaeological collections excavated by Margit and Ludwig Kohl-Larsen between 1934 and 1939 in modern-day Tanzania. Despite the great scientific relevance of these collections, most of them were never published on an international scale and were thus unavailable for the broader Africanist archaeological community. In the light of new excavations around Lake Eyasi, conducted jointly by the Universities of Dar es Salaam and Tübingen and the Senckenberg Gesellschaft für Naturforschung, we decided to undertake a new inventory of the Kohl-Larsen collection, to analyze the assemblages using state of the art methods, link them with new excavation data and make them internationally available. As a first step, here we want to introduce the project by reporting on some preliminary observations from Njarasa Cave. Ultimately this research will help to create a coherent reconstruction of human cultural change and behavioral adaptions over the last ~200.000 years in this important archaeological landscape.
Environmental Earth Sciences Progress Report 2020 and Outlook 2021
2021-04-01

Abstract The present editorial 2020 continues the series of status reports in Environmental Earth Sciences (EES) in previous years 2017 and 2019 (Kolditz et al. in Environ Earth Sci 77: 8, 2018, Kolditz et al. in Environ Earth Sci 79: 11, 2020). The year 2020 coming to an end was heavily influenced by the COVID-19 pandemic affecting all areas of life including research work and, therefore, scientific publishing as well (“Introduction”). One bright spot which shows longevity of journals that produce a quality product is that Environmental Earth Sciences (EES) is celebrating its 45th anniversary of publication. To this extent EES continues the tradition to honor the most cited papers contributing to the 2020 Impact Factor (IF) (“Highly and most cited topics”) and provide information on the current status of EES as well as an outlook to 2021 (“Progress report”)
Vegetation and climate effects on soil production, chemical weathering, and physical erosion rates
2021-04-01

Abstract. Weathering of bedrock to produce regolith is essential for sustaining life on Earth and global biogeochemical cycles. The rate of this process is influenced not only by tectonics, but also by climate and biota. Here we investigate these interactions with new observations of soil production, chemical weathering, and physical erosion rates from the large climate and vegetation gradient of the Chilean Coastal Cordillera (26° to 38° S). These findings are compared to a global compilation of published data from similar settings. The four Chilean study areas span (from North to South): arid (Pan de Azúcar), semi-arid (Santa Gracia), mediterranean (La Campana) and temperate humid (Nahuelbuta) climate zones. We test the hypotheses that: 1) soil production as well as chemical weathering rates increase with increasing mean annual precipitation; 2) physical erosion rates stabilize as vegetation cover increases; and 3) the contribution of chemical weathering to total denudation is constant over the climate gradient.We find observed soil production rates range from ~7 to 290 t/(km2 yr) and are lowest in the sparsely vegetated and arid North, increase southward toward the vegetated mediterranean climate, and then decrease further South in the temperate humid zone. This trend is discussed and compared with global data from similar catchments underlain by granitic lithologies. Calculated chemical weathering rates range from zero in the arid North to a high value of 211 t/(km2 yr) in the mediterranean zone. Chemical weathering rates are comparable in the semi-arid and temperate humid zones (~20 t/(km2 yr). Physical erosion rates are low in the arid zone (~11 t/(km2 yr)) and increase towards the South (~ 40 t/(km2 yr)). Combined total chemical weathering and physical erosion rates indicate that denudation rates are lowest in the arid North and highest in the Mediterranean climate zone. The contribution of chemical weathering to total denudation rates increases and then decreases with increasing mean annual precipitation from North to South. The observation that the calculated chemical weathering rates in the southernmost location, with the highest mean annual precipitation and the highest chemical index of alteration, are not the highest of all four study areas is found to be consistent with the global data analysis.
Does Phototherapy Promote Wound Healing? Limitations of Blue Light Irradiation.
2021-04-01

Blue light reduces keratinocyte proliferation and migration at high doses and therefore could negatively affect wound healing. Available irradiation devices for possible use in wound therapy should be critically scrutinized and evaluated with in vitro methods prior to clinical use.
Consistency Proof for Multi-time Schrödinger Equations with Particle Creation and Ultraviolet Cut-Off
2021-04-01

Abstract For multi-time wave functions, which naturally arise as the relativistic particle-position representation of the quantum state vector, the analog of the Schrödinger equation consists of several equations, one for each time variable. This leads to the question of how to prove the consistency of such a system of PDEs. The question becomes more difficult for theories with particle creation, as then different sectors of the wave function have different numbers of time variables. Petrat and Tumulka (2014) gave an example of such a model and a non-rigorous argument for its consistency. We give here a rigorous version of the argument after introducing an ultraviolet cut-off into the creation and annihilation terms of the multi-time evolution equations. These equations form an infinite system of coupled PDEs; they are based on the Dirac equation but are not fully relativistic (in part because of the cut-off). We prove the existence and uniqueness of a smooth solution to this system for every initial wave function from a certain class that corresponds to a dense subspace in the appropriate Hilbert space.
Universal Gene Correction Approaches for β-hemoglobinopathies Using CRISPR-Cas9 and Adeno-Associated Virus Serotype 6 Donor Templates
2021-04-01

Mutations in the human <i>β-globin</i> gene are the cause of β-hemoglobinopathies, one of the most common inherited single-gene blood disorders in the world. Novel therapeutic approaches are based on lentiviral vectors (LVs) or CRISPR-Cas9-mediated gene disruption to express adult hemoglobin (HbA), or to reactivate the completely functional fetal hemoglobin, respectively. Nonetheless, LVs present a risk of insertional mutagenesis, while gene-disrupting transcription factors (BCL11A, KLF1) involved in the fetal-to-adult hemoglobin switch might generate dysregulation of other cellular processes. Therefore, universal gene addition/correction approaches combining CRISPR-Cas9 and homology directed repair (HDR) by delivering a DNA repair template through adeno-associated virus could mitigate the limitations of both lentiviral gene transfer and gene disruption strategies, ensuring targeted integration and controlled transgene expression. In this study, we attained high rates of gene addition (up to 12%) and gene correction (up to 38%) in hematopoietic stem and progenitor cells from healthy donors without any cell sorting/enrichment or the application of HDR enhancers. Furthermore, these approaches were tested in heterozygous (β<sup>0</sup>/β<sup>+</sup>) and homozygous (β<sup>0</sup>/β<sup>0</sup>, β<sup>+</sup>/β<sup>+</sup>) β-thalassemia patients, achieving a significant increase in HbA and demonstrating the universal therapeutic potential of this study for the treatment of β-hemoglobinopathies.
Solid‐State Synthesis of (Ph4P)MI3 (M=Eu2+, Sr2+, Sn2+) and Investigation of Photoluminescence Properties of Green Emitting Phosphor
2021-04-01

Abstract This work reports a solid‐state preparation of hybrid tetraphenylphosphonium (Ph 4 P + ) compounds (Ph 4 P)MI 3 (M=Eu 2+ , Sr 2+ and Sn 2+ ). The new materials (Ph 4 P)EuI 3 and (Ph 4 P)SrI 3 are found to crystallize isotypically in the trigonal space group , where Eu 2+ and Sr 2+ ions exhibit similarly two different crystallographic positions and occupy the centers of trigonal antiprismatic sites. The corresponding compound (Ph 4 P)SnI 3 was accordingly prepared by solid‐state reaction to yield yellow crystals which crystallize in a monoclinic structure ( P 2 1 / c ). The luminescent properties of (Ph 4 P)EuI 3 were investigated and the results revealed that Eu 2+ displays an intensive green band emission peaked at 536 nm. The radiative decay time determined upon excitation at 536 nm is 508 ns.
Mesalazine Suppresses Proinflammatory Cytokines in Patients with Acute Anterior Uveitis Independently of HLA-B27
2021-04-01

Here we show that mesalazine (5-ASA) inhibits the transcription of proinflammatory and (ER) stress associated cytokines and markers, independently of the HLA-B27 status. Results show the similarities of both AAU types but do not decipher the mechanism why the HLA-B27 status determines the therapeutic response to mesalazine in AAU.
Molluscs of the Genus Glycymeris from Vogelherd Cave near Niederstotzingen (Lonetal, Southwestern Germany)
2021-04-01

The site of Vogelherd in the Lone Valley of southwestern Germany has become world famous for its many unique artworks made from mammoth ivory, personal ornaments, flute fragments, lithic artifacts, and antler and bone artifacts. In the study below, the molluscs from Vogelherd are presented, offering us new insights on the mobility and social behavior of Aurignacian groups in the Lone Valley. Some of the mollusc finds come from the 1931 excavation of Gustav Riek; however, most of them were uncovered during the later re-excavations of the site between 2005 and 2012. In order to provide context for these finds, we compare the molluscs from Vogelherd with those from across Central Europe. The identifiable fragments from Vogelherd belong to the genus Glycymeris. The Glycymeris molluscs originated from the Mainz Basin. This determination makes it possible to reconstruct one of the farthest long-distance connections known for the Upper Paleolithic in Germany. In addition to the Glycymeris finds, we present a tool that was also made from a mollusc. This mollusc-tool, coming from the excavation of 1931 and attributed to the Aurignacian, is a unique find for this time period of southern Germany. With this piece, along with microscopic examinations and discussions of the Glycymeris molluscs, we present a wide range of possible uses for these finds. For example, we discuss the possible use of the molluscs as ochre containers. To test this, we used EDX-analysis and a raster electron microscope. We compare the Glycymeris molluscs of Vogelherd with those from Gravettian and Magdalenian contexts at Hohle Fels, Geißenklösterle, Petersfels, and Gnirshöhle, and we provide a list of all sites from Germany, Switzerland, Eastern France, and Belgium with Glycymeris finds. We use size comparisons to show differences as well among the Glycymeris finds of Vogelherd and other Upper Paleolithic sites in southwestern Germany. In conclusion, we demonstrate that the Glycymeris molluscs of Vogelherd best fit into the Aurignacian, and we provide other Aurignacian sites that contained similar finds. By discussing other long-distance connections in the Aurignacian of southern Germany, it becomes evident that Glycymeris molluscs are not specific only to the Swabian Aurignacian.
The quandary of diagnosing mathematical difficulties in a generally low performing population
2021-04-01

ABSTRACT. Brazilian students’ mathematical achievement was repeatedly observed to fall below average levels of mathematical attainment in international studies such as PISA. Objective: In this article, we argue that this general low level of mathematical attainment may interfere with the diagnosis of developmental dyscalculia when a psychometric criterion is used establishing an arbitrary cut-off (e.g., performance&lt;percentile 10) may result in misleading diagnoses. Methods: Therefore, the present study evaluated the performance of 706 Brazilian school children from 3rd to 5th grades on basic arithmetic operations addition, subtraction, and multiplication. Results: In line with PISA results, children presented difficulties in all arithmetic operations investigated. Even after five years of formal schooling, less than half of 5th graders performed perfectly on simple addition, subtraction, or multiplication problems. Conclusions: As such, these data substantiate the argument that the sole use of a psychometric criterion might not be sensible to diagnose dyscalculia in the context of a generally low performing population, such as Brazilian children of our sample. When the majority of children perform poorly on the task at hand, it is hard to distinguish atypical from typical numerical development. As such, other diagnostic approaches, such as Response to Intervention, might be more suitable in such a context.