julilili42/papers huggingface dataset:
Deformation between the highly oblique Yakutat–North American plate boundary and the Eastern Denali fault
2021-10-27

Abstract This study investigates the spatial and temporal pattern of rock exhumation inboard of the highly oblique Yakutat–North American plate boundary. We aim to quantify how far deformation is transferred inboard of the Fairweather transform plate boundary and across the Eastern Denali fault. We present new detrital apatite and zircon fission track data from 27 modern drainages collected on both sides of the Eastern Denali fault and from the Alsek and Tatshenshini River catchments that drain the mountainous region between the Fairweather fault and the Eastern Denali fault. By integrating our data with published bedrock and detrital geochronology and thermochronology, we show that exhumation reaches much farther inboard (&amp;gt;100 km) of the Fairweather fault than farther north in the St. Elias syntaxial region (&amp;lt;30 km). This suggests that the entire corridor between the Fairweather and Eastern Denali faults exhumed since mid-Miocene time. The Eastern Denali fault appears to be the backstop, and late Cenozoic exhumation northeast of the fault is very limited.
Video analysis to examine Kepler’s laws of planetary motion
2021-10-27

Video motion analysis allows tracing trajectories of objects in motion and is an established method in physics education. Tablet computers, with their integrated cameras, offer the opportunity to both record and analyze dynamic motions during experiments on a single device. This enables students to work without transitioning the data between camera and computer, but with ubiquitously available applications on mobile devices. This article describes a model experiment to examine Kepler’s laws of motion using tablet computers with a video analysis application.
Increasing the Reach of the Submental Artery Island Flap Using the Y-V Pedicle Lengthening Technique: Video and Technical Considerations
2021-10-27

Summary: This article and instructional video detail a step-by-step approach to performing the Y-V venous pedicle lengthening technique, which can be used to increase the reach of the submental artery island flap by up to 5 cm, permitting reconstruction of soft-tissue defects of the middle and upper thirds of the face. This technique can also be used to maximize advancement of many common flaps around the body, including the medial plantar and lateral arm flaps.
Solons Fr. 12 G.-P.2(= 9 W.2): ein Textvorschlag
2021-10-27

Abstract This paper proposes a new conjecture for Solon fr. 12 G.-P. 2 (= 9 W. 2 ). In this, as in other poems, Solon shows a clear desire to present himself as an expert in the political milieu and to serve as a guide for the community of Athens. The politician’s penetrating gaze, his far-sighted νόος, is able to grasp in nuce the development of political dynamics which, if they prevail, could mean the ruin of the city as a whole. Solon frames his νόος as an indispensable tool for the analysis of the city and its optimal and timely planning. To a secular conception of the νόος, which is the essential characteristic of the excellent politician, is added a traditional one that considers the νόος as a gift of Apollo. In this way, Solon appears as a politically engaged poet of the πόλις who mediates between the fighting factions and tries to work for the good of the community.
Who Knows what Mary Knew? An Experimental Study
2021-10-27

Who Knows what Mary Knew? An Experimental Study Abstract This paper reports the results of an experimental philosophy study of intuitions among members of the general US population regarding a version of Frank Jackson’s famous ‘Mary in the black and white room’ thought experiment. A large majority of respondents (82.1%, significantly above chance) reported having the intuition which is critical to the thought experiment, i.e., that Mary does not know what it is like to see red before she actually sees red. The intuition was pervasive across demographic groups.
Oxidative Stress and Energy Metabolism in the Brain: Midlife as a Turning Point
2021-10-28

Neural tissue is one of the main oxygen consumers in the mammalian body, and a plentitude of metabolic as well as signaling processes within the brain is accompanied by the generation of reactive oxygen (ROS) and nitrogen (RNS) species. Besides the important signaling roles, both ROS and RNS can damage/modify the self-derived cellular components thus promoting neuroinflammation and oxidative stress. While previously, the latter processes were thought to progress linearly with age, newer data point to midlife as a critical turning point. Here, we describe (i) the main pathways leading to ROS/RNS generation within the brain, (ii) the main defense systems for their neutralization and (iii) summarize the recent literature about considerable changes in the energy/ROS homeostasis as well as activation state of the brain’s immune system at midlife. Finally, we discuss the role of calorie restriction as a readily available and cost-efficient antiaging and antioxidant lifestyle intervention.
The incretin/glucagon system as a target for pharmacotherapy of obesity
2021-10-28

Summary Obesity is a chronic, multifactorial, relapsing disease. Despite multicomponent lifestyle interventions, including pharmacotherapy, maintaining bodyweight loss is challenging for many people. The pathophysiology of obesity is complex, and currently approved pharmacotherapies only target a few of the many pathways involved; thus, single‐targeting agents have limited efficacy. Proglucagon‐derived peptides, glucagon, and the incretin hormones glucagon‐like peptide‐1 (GLP‐1) and glucose‐dependent insulinotropic polypeptide (GIP), represent attractive targets for managing obesity and metabolic disorders because they may have direct roles in multiple mechanisms including satiety, energy homeostasis, and lipolytic activity. Unimolecular dual and triple agonists targeting glucagon and incretin hormone receptors have been shown to promote bodyweight loss, lower glucose levels, and reduce food intake in animal models of obesity. Multiple dual receptor agonists are in clinical development for the treatment of obesity, including GLP‐1/GIP and GLP‐1/glucagon receptor agonists. The extent to which glucagon contributes to treatment effects remains to be understood, but it may promote bodyweight loss by reducing food intake, while concomitant GLP‐1 receptor agonism ensures normal glucose control. Further research is required to fully understand the molecular mechanisms of action and metabolic effects of both dual and triple receptor agonists.
Resolving the “muddle in the middle”: The case for Homo bodoensis sp. nov.
2021-10-28

Abstract Recent developments in the field of palaeoanthropology necessitate the suppression of two hominin taxa and the introduction of a new species of hominins to help resolve the current nebulous state of Middle Pleistocene (Chibanian) hominin taxonomy. In particular, the poorly defined and variably understood hominin taxa Homo heidelbergensis (both sensu stricto and sensu lato ) and Homo rhodesiensis need to be abandoned as they fail to reflect the full range of hominin variability in the Middle Pleistocene. Instead, we propose: (1) introduction of a new taxon, Homo bodoensis sp. nov., as an early Middle Pleistocene ancestor of the Homo sapiens lineage, with a pan‐African distribution that extends into the eastern Mediterranean (Southeast Europe and the Levant); (2) that many of the fossils from Western Europe (e.g. Sima de los Huesos) currently assigned to H . heidelbergensis s.s. be reassigned to Homo neanderthalensis to reflect the early appearance of Neanderthal derived traits in the Middle Pleistocene in the region; and (3) that the Middle Pleistocene Asian fossils, particularly from China, likely represent a different lineage altogether.
Stereodivergent Nitrocyclopropane Formation during Biosynthesis of Belactosins and Hormaomycins
2021-10-28

Belactosins and hormaomycins are peptide natural products containing 3-(2-aminocyclopropyl)alanine and 3-(2-nitrocyclopropyl)alanine residues, respectively, with opposite stereoconfigurations of the cyclopropane ring. Herein we demonstrate that the heme oxygenase-like enzymes BelK and HrmI catalyze the N-oxygenation of l-lysine to generate 6-nitronorleucine. The nonheme iron enzymes BelL and HrmJ then cyclize the nitroalkane moiety to the nitrocyclopropane ring with the desired stereochemistry found in the corresponding natural products. We also show that both cyclopropanases remove the 4-<i>proS</i>-H of 6-nitronorleucine during the cyclization, establishing the inversion and retention of the configuration at C4 during the BelL and HrmJ reactions, respectively. This study reveals the unique strategy for stereocontrolled cyclopropane synthesis in nature.
Empirical audit and review and an assessment of evidentiary value in research on the psychological consequences of scarcity
2021-10-28

Empirical audit and review is an approach to assessing the evidentiary value of a research area. It involves identifying a topic and selecting a cross-section of studies for replication. We apply the method to research on the psychological consequences of scarcity. Starting with the papers citing a seminal publication in the field, we conducted replications of 20 studies that evaluate the role of scarcity priming in pain sensitivity, resource allocation, materialism, and many other domains. There was considerable variability in the replicability, with some strong successes and other undeniable failures. Empirical audit and review does not attempt to assign an overall replication rate for a heterogeneous field, but rather facilitates researchers seeking to incorporate strength of evidence as they refine theories and plan new investigations in the research area. This method allows for an integration of qualitative and quantitative approaches to review and enables the growth of a cumulative science.
Dravet Variant SCN1AA1783V Impairs Interneuron Firing Predominantly by Altered Channel Activation
2021-10-28

Dravet syndrome (DS) is a developmental epileptic encephalopathy mainly caused by functional Na V 1.1 haploinsufficiency in inhibitory interneurons. Recently, a new conditional mouse model expressing the recurrent human p.(Ala1783Val) missense variant has become available. In this study, we provided an electrophysiological characterization of this variant in tsA201 cells, revealing both altered voltage-dependence of activation and slow inactivation without reduced sodium peak current density. Based on these data, simulated interneuron (IN) firing properties in a conductance-based single-compartment model suggested surprisingly similar firing deficits for Na V 1.1 A1783V and full haploinsufficiency as caused by heterozygous truncation variants. Impaired Na V 1.1 A1783V channel activation was predicted to have a significantly larger impact on channel function than altered slow inactivation and is therefore proposed as the main mechanism underlying IN dysfunction. The computational model was validated in cortical organotypic slice cultures derived from conditional Scn1a A 1783 V mice. Pan-neuronal activation of the p.Ala1783V in vitro confirmed a predicted IN firing deficit and revealed an accompanying reduction of interneuronal input resistance while demonstrating normal excitability of pyramidal neurons. Altered input resistance was fed back into the model for further refinement. Taken together these data demonstrate that primary loss of function (LOF) gating properties accompanied by altered membrane characteristics may match effects of full haploinsufficiency on the neuronal level despite maintaining physiological peak current density, thereby causing DS.
Effect of Oxidized LDL on Platelet Shape, Spreading, and Migration Investigated with Deep Learning Platelet Morphometry
2021-10-28

Platelets are functionally versatile blood cells involved in thrombosis, hemostasis, atherosclerosis, and immune response. Platelet interaction with the immediate microenvironment in blood, vasculature, and tissues alters platelet morphology. The quantification of platelet morphodynamics by geometrical parameters (morphometry) can provide important insights into how platelets sense and respond to stimulatory cues in their vicinity. However, the extraction of platelet shapes from phase contrast microscopy images by conventional image processing is difficult. Here, we used a convolutional neural network (CNN) to develop a deep-learning-based approach for the unbiased extraction of information on platelet morphodynamics by phase contrast microscopy. We then investigated the effect of normal and oxidized low-density lipoproteins (LDL, oxLDL) on platelet morphodynamics, spreading, and haptotactic migration. Exposure of platelets to oxLDL led to a decreased spreading area and rate on fibrinogen, accompanied by increased formation of filopodia and impaired formation of lamellipodia. Haptotactic platelet migration was affected by both LDL and oxLDL in terms of decreased migration velocity and reduced directional persistence. Our results demonstrate the use of deep learning in investigating platelet morphodynamics and reveal differential effects of LDL and oxLDL on platelet morphology and platelet–matrix interaction.
The Role of Vegan Diets in Lipotoxicity-induced Beta-cell Dysfunction in Type-2-Diabetes: A Narrative Review.
2021-10-28

Type-2-diabetes is considered the new plague of the current century and its incidence and prevalence are rapidly increasing. Chronic insulin resistance and a progressive decline in beta-cell function are discussed as the root causes of type-2-diabetes. Both are associated with obesity and prolonged exposure to pathologically elevated concentrations of circulating free fatty acid (FFA) levels in the blood. Fatty acid derivatives may interfere with beta-cell function and ultimately lead to their death through lipoapoptosis. The harmful effects of chronically elevated FFA levels on glucose homeostasis and non-adipose tissues are generally referred to as lipotoxicity. Pancreatic beta-cells appear to be particularly vulnerable, and both dietary fat quantity and quality may impact their function. Diets high in saturated fat are especially harmful to beta-cells while (poly-)unsaturated fatty acids (PUFA) are associated with beta-cell protective effects. Therefore, this narrative review suggests that a dietary modification toward a low-fat vegan diet might help to prevent or reduce lipotoxicity-induced beta-cell dysfunction. By cutting the oversupply of saturated fat and reducing total calorie intake, and by improving both body weight and glycemic control, low-fat vegan diets may reduce the likelihood of lipotoxic events to occur. In light of the accumulating evidence that lipotoxic events are tightly coupled to excess glucose levels, improved glycemic parameters appear to be of utmost importance. These mechanisms are likely to contribute complementarily to improved beta-cell function in individuals with type-2-diabetes who choose a low-fat vegan diet. Physicians must consider these findings when counseling patients on lifestyle modifications and healthy nutrition.
Maternal eating disorder severity is associated with increased latency of foetal auditory event‐related brain responses
2021-10-28

Abstract Objective Maternal eating disorders (EDs) are associated with adverse pregnancy and child outcomes. There is limited research investigating the influence of maternal EDs on foetal brain development. Method Using foetal magnetoencephalography (fMEG), an auditory sequence was presented for 10 min to assess brain response latencies in foetuses of mothers with ( n = 12) and without ( n = 11) a history of anorexia nervosa (AN) in the third trimester of pregnancy. ED history and severity were assessed using the structured clinical expert interview eating disorder examination (EDE) and the self‐report questionnaire EDE‐Q. Results Foetuses of mothers with AN showed delayed foetal brain responses to auditory stimulation compared to foetuses of control women. Self‐reported ED symptom severity explained 34% of variance in foetal brain response latencies in the AN group. Conclusions ED pathology was strongly associated with foetal brain response latencies in the third trimester with longer latencies in foetuses of women with a history of AN reporting more ED symptoms. Follow‐up on the children is pivotal to investigate if fMEG outcomes are associated with later child development.
An efficient single‐cell based method for linking human T cell phenotype to T cell receptor sequence and specificity
2021-10-28

Abstract Single‐cell antigen‐receptor gene amplification and sequencing platforms have been used to characterize T cell receptor (TCR) repertoires but typically fail to generate paired full‐length gene products for direct expression cloning and do not enable linking this data to cell phenotype information. To overcome these limitations, we established a high‐throughput platform for the quantitative and qualitative analysis of human TCR repertoires that provides insights into the clonal and functional composition of human CD4 + and CD8 + αβ T cells at the molecular and cellular level. The strategy is a powerful tool to qualitatively assess differences between antigen receptors of phenotypically defined αβ T cell subsets, e.g. in immune responses to cancer, vaccination, or infection, and in autoimmune diseases.
Individualized Proteogenomics Reveals the Mutational Landscape of Melanoma Patients in Response to Immunotherapy
2021-10-28

Immune checkpoint inhibitors are used to restore or augment antitumor immune responses and show great promise in the treatment of melanoma and other types of cancers. However, only a small percentage of patients are fully responsive to immune checkpoint inhibition, mostly due to tumor heterogeneity and primary resistance to therapy. Both of these features are largely driven by the accumulation of patient-specific mutations, pointing to the need for personalized approaches in diagnostics and immunotherapy. Proteogenomics integrates patient-specific genomic and proteomic data to study cancer development, tumor heterogeneity and resistance mechanisms. Using this approach, we characterized the mutational landscape of four clinical melanoma patients. This enabled the quantification of hundreds of sample-specific amino acid variants, among them many that were previously not reported in melanoma. Changes in abundance at the protein and phosphorylation site levels revealed patient-specific over-represented pathways, notably linked to melanoma development (MAPK1 activation) or immunotherapy (NLRP1 inflammasome). Personalized data integration resulted in the prediction of protein drug targets, such as the drugs vandetanib and bosutinib, which were experimentally validated and led to a reduction in the viability of tumor cells. Our study emphasizes the potential of proteogenomic approaches to study personalized mutational landscapes, signaling networks and therapy options.
Synthesis and Properties of the Octaboron Cluster Series hypercloso‐B8Cl8, the Radical Anion hypercloso‐[B8Cl8].− and the Dianion closo‐[B8Cl8]2−
2021-10-28

Abstract The synthesis, spectroscopic data, redox properties of B 8 Cl 8 , [B 8 Cl 8 ] .− , and [B 8 Cl 8 ] 2− , and the single‐crystal X‐ray structure analysis of [Ph 4 P] + 2 [B 8 Cl 8 ] 2− ⋅ CH 3 CN are described. Temperature‐dependent 11 B NMR measurements and theoretical studies (DFT) concerning the fluxional behavior of [B 8 Cl 8 ] 2− will be discussed. – B 8 Cl 8 reacts with reductants like iodide to the intense purple colored radical anion [B 8 Cl 8 ] .− which is formed as well from B 8 Cl 8 by traces of water. The colorless dianion closo‐ [B 8 Cl 8 ] 2− is obtained by the reaction of B 8 Cl 8 or [B 8 Cl 8 ] .− with iodide. The single‐crystal X‐ray structure analysis of [Ph 4 P] + 2 [B 8 Cl 8 ] 2− confirms the dodecahedral D 2d structure of [B 8 Cl 8 ] 2− . The 11 B NMR spectra of [B 8 Cl 8 ] 2− solutions show only one broad signal even at low temperatures due to the fast fluctuation of the [B 8 Cl 8 ] 2− polyhedron. The energy of the C 2v structure isomer of [B 8 Cl 8 ] 2− was calculated by DFT methods to be only 0.6 kcal/mol higher in energy than the D 2d form, and the activation barrier for the D 2d to C 2v transformation is predicted to be about 0.9 kcal/mol.
Chronic stroke sensorimotor impairment is related to smaller hippocampal volumes: An ENIGMA analysis
2021-10-28

Abstract Persistent sensorimotor impairments after stroke can negatively impact quality of life. The hippocampus is involved in sensorimotor behavior but has not been widely studied within the context of post-stroke upper limb sensorimotor impairment. The hippocampus is vulnerable to secondary degeneration after stroke, and damage to this region could further weaken sensorimotor circuits, leading to greater chronic sensorimotor impairment. The purpose of this study was to investigate the cross-sectional association between non-lesioned hippocampal volume and upper limb sensorimotor impairment in people with chronic stroke. We hypothesized that smaller ipsilesional hippocampal volumes would be associated with worse upper-limb sensorimotor impairment. Cross-sectional T1-weighted brain MRIs were pooled from 357 participants at the chronic stage after stroke (&gt;180 days post-stroke) compiled from 18 research cohorts worldwide in the ENIGMA Stroke Recovery Working Group (age: median = 61 years, interquartile range = 18, range = 23-93; 135 women and 222 men). Sensorimotor impairment was estimated from the Fugl-Meyer Assessment of Upper Extremity scores. Robust mixed-effects linear models were used to test associations between post-stroke sensorimotor impairment and hippocampal volumes (ipsilesional and contralesional separately; Bonferroni-corrected, p - value &lt; 0.025), controlling for age, sex, lesion volume, and lesioned hemisphere. We also performed an exploratory analysis to test whether sex differences influence the relationship between sensorimotor impairment and hippocampal volume. Upper limb sensorimotor impairment was positively associated with ipsilesional ( p = 0.005; d = 0.33) but not contralesional ( p = 0.96; d = 0.01) hippocampal volume, such that impairment was worse for participants with smaller ipsilesional hippocampal volume. This association remained significant independent of lesion volume or other covariates ( p = 0.001; d = 0.36). Evidence indicates an interaction between sensorimotor impairment and sex for both ipsilesional ( p = 0.008; d = −0.29) and contralesional ( p = 0.006; d = −0.30) hippocampal volumes, whereby women showed progressively worsening sensorimotor impairment with smaller hippocampal volumes compared to men. The present study has identified a novel association between chronic post-stroke sensorimotor impairment and ipsilesional, but not contralesional, hippocampal volume. This finding was not due to lesion size and may be stronger in women. We also provide supporting evidence that smaller hippocampal volume post-stroke is likely a consequence of ipsilesional damage, which could provide a link between vascular disease and other disorders, such as dementia.