julilili42/papers huggingface dataset:
Coupled otolith and foraminifera oxygen and carbon stable isotopes evidence paleoceanographic changes and fish metabolic responses
2022-10-06

Capturing the mechanisms leading to the local extirpation of a species in deep-time is a challenge. Combining stable oxygen and carbon isotopic analyses on benthic and planktonic foraminifera and the otoliths of pelagic and benthic fish species, we reveal here the paleoceanographic regime shifts changes that took place in the Eastern Mediterranean from 7.2 to 6.5 Ma, in the precursor phase to the Messinian Salinity Crisis, and discuss the fishes’ response to these events. The step-wise restriction of the Mediterranean–Atlantic gateway impacted the Mediterranean fishes’ metabolisms, particularly those dwelling in the sea bottom. An important shift in the Mediterranean paleoceanographic conditions took place between 6.951 and 6.882 Ma, from predominantly temperature to salinity control, which was probably related to stratification of the water column. A regime shift at 6.814 Ma due to change in the influx amount, source and/or preservation of organic matter led a pelagic–benthic decoupling of the fish fauna. The oxygen isotopic composition of the benthic fish otoliths expresses higher salinity of the lower part of the water column at that time, and is accompanied by a rapid increase and then drop in the carbon isotopic compositions of the otoliths (which is metabolic rate proxy) of the benthic fish, ultimately leading to the local extirpation of the species. Overall, our results confirm that otolith stable oxygen and carbon isotopes are promising proxies for paleoceanographic studies and, when combined with those of foraminifera, can reveal changes in the life history and migration patterns of teleost fishes in deep time.
Report on 2207.09375v1
2022-10-06

The CRESST experiment observes an unexplained excess of events at low energies.In the current CRESST-III data-taking campaign we are operating detector modules with different designs to narrow down the possible explanations.In this work, we show first observations
B7-H3-targeting Fc-optimized antibody for induction of NK cell reactivity against sarcoma
2022-10-07

Natural killer (NK) cells largely contribute to antibody-dependent cellular cytotoxicity (ADCC), a central factor for success of monoclonal antibodies (mAbs) treatment of cancer. The B7 family member B7-H3 (CD276) recently receives intense interest as a novel promising target antigen for immunotherapy. B7-H3 is highly expressed in many tumor entities, whereas expression on healthy tissues is rather limited. We here studied expression of B7-H3 in sarcoma, and found substantial levels to be expressed in various bone and soft-tissue sarcoma subtypes. To date, only few immunotherapeutic options for treatment of sarcomas that are limited to a minority of patients are available. We here used a B7-H3 mAb to generate chimeric mAbs containing either a wildtype Fc-part (8H8_WT) or a variant Fc part with amino-acid substitutions (S239D/I332E) to increase affinity for CD16 expressing NK cells (8H8_SDIE). In comparative studies we found that 8H8_SDIE triggers profound NK cell functions such as activation, degranulation, secretion of IFNγ and release of NK effector molecules, resulting in potent lysis of different sarcoma cells and primary sarcoma cells derived from patients. Our findings emphasize the potential of 8H8_SDIE as novel compound for treatment of sarcomas, particularly since B7-H3 is expressed in bone and soft-tissue sarcoma independent of their subtype.
An update on environment-induced pulmonary edema – “When the lungs leak under water and in thin air”
2022-10-07

Acute pulmonary edema is a serious condition that may occur as a result of increased hydrostatic forces within the lung microvasculature or increased microvascular permeability. Heart failure or other cardiac or renal disease are common causes of cardiogenic pulmonary edema. However, pulmonary edema may even occur in young and healthy individuals when exposed to extreme environments, such as immersion in water or at high altitude. Immersion pulmonary edema (IPE) and high-altitude pulmonary edema (HAPE) share some morphological and clinical characteristics; however, their underlying mechanisms may be different. An emerging understanding of IPE indicates that an increase in pulmonary artery and capillary pressures caused by substantial redistribution of venous blood from the extremities to the chest, in combination with stimuli aggravating the effects of water immersion, such as exercise and cold temperature, play an important role, distinct from hypoxia-induced vasoconstriction in high altitude pulmonary edema. This review aims at a current perspective on both IPE and HAPE, providing a comparative view of clinical presentation and pathophysiology. A particular emphasis will be on recent advances in understanding of the pathophysiology and occurrence of IPE with a future perspective on remaining research needs.
The ataxia-linked E1081Q mutation affects the sub-plasma membrane Ca2+-microdomains by tuning PMCA3 activity
2022-10-07

Abstract Calcium concentration must be finely tuned in all eukaryotic cells to ensure the correct performance of its signalling function. Neuronal activity is exquisitely dependent on the control of Ca 2+ homeostasis: its alterations ultimately play a pivotal role in the origin and progression of many neurodegenerative processes. A complex toolkit of Ca 2+ pumps and exchangers maintains the fluctuation of cytosolic Ca 2+ concentration within the appropriate threshold. Two ubiquitous (isoforms 1 and 4) and two neuronally enriched (isoforms 2 and 3) of the plasma membrane Ca 2+ ATPase (PMCA pump) selectively regulate cytosolic Ca 2+ transients by shaping the sub-plasma membrane (PM) microdomains. In humans, genetic mutations in ATP2B1, ATP2B2 and ATP2B3 gene have been linked with hearing loss, cerebellar ataxia and global neurodevelopmental delay: all of them were found to impair pump activity. Here we report three additional mutations in ATP2B3 gene corresponding to E1081Q, R1133Q and R696H amino acids substitution, respectively. Among them, the novel missense mutation (E1081Q) immediately upstream the C-terminal calmodulin-binding domain (CaM-BD) of the PMCA3 protein was present in two patients originating from two distinct families. Our biochemical and molecular studies on PMCA3 E1081Q mutant have revealed a splicing variant-dependent effect of the mutation in shaping the sub-PM [Ca 2+ ]. The E1081Q substitution in the full-length b variant abolished the capacity of the pump to reduce [Ca 2+ ] in the sub-PM microdomain (in line with the previously described ataxia-related PMCA mutations negatively affecting Ca 2+ pumping activity), while, surprisingly, its introduction in the truncated a variant selectively increased Ca 2+ extrusion activity in the sub-PM Ca 2+ microdomains. These results highlight the importance to set a precise threshold of [Ca 2+ ] by fine-tuning the sub-PM microdomains and the different contribution of the PMCA splice variants in this regulation.
Convergent evolution of plant pattern recognition receptors sensing cysteine-rich patterns from three microbial kingdoms
2022-10-07

Abstract The Arabidopsis thaliana receptor-like protein RLP30 contributes to immunity against the fungal pathogen Sclerotinia sclerotiorum . Here we identified the RLP30-ligand as a small cysteine-rich protein (SCP) that occurs in many fungi and oomycetes and is also recognized by the Nicotiana benthamiana RLP RE02. However, RLP30 and RE02 share little sequence similarity and respond to different parts of the native/folded protein. Interestingly, some Brassicaceae other than Arabidopsis also respond to a linear SCP peptide, suggesting that SCP is an eminent immune target that led to the convergent evolution of distinct immune receptors in plants. Surprisingly, RLP30 shows a second ligand specificity for a SCP-nonhomologous protein secreted by bacterial Pseudomonads. RLP30 expression in N. tabacum resulted in lower susceptibility to bacterial, fungal and oomycete pathogens, thus demonstrating that detection of immunogenic patterns by Arabidopsis RLP30 is involved in defense against pathogens from three microbial kingdoms.
Gallium Methylene in the Pocket
2022-10-07

Adduct complexes Ga6(μ-CH2)9(DMAP)3(THF) and Ga8(μ-CH2)12(PEt3)x (x = 4 and 6) could be obtained upon crystallization of Ga8(CH2)12 from THF/DMAP (hard Lewis bases) and PEt3 (soft Lewis base), respectively. Mixed methyl/methylene {Ga4} species with either bridging aryloxy, thiophenolato, or arylamido ligands were accessible via the treatment of Ga8(CH2)12 with phenols (HOC6H2Me3-2,4,6 and HOC6H3Me2-2,6), thiophenol HSC6H2Me3-2,4,6, and anilines (H2NC6H2Me3-2,4,6 and H2NC6H3Me2-2,6). Such tetrametallic complexes Ga4(μ2-CH2)2(CH3)4(μ2-XAr)4 (X = O, S, NH) are isostructural, displaying an adamantane-like core structure. The sterically more demanding phenol HOC6H3tBu2-2,6 afforded the {Ga5} cluster Ga5(μ2-CH2)6(OC6H3tBu2-2,6)3(THF)2 with the gallium centers exclusively bridged by methylene groups. Treatment of Ga8(CH2)12 with other protic substrates HOR/H2NR′, including HOCH2tBu, HOSi(OtBu)3, H2NC6H3iPr2-2,6, and H2NSiPh3 point to a pronounced stereoelectronic dependency and intricacy of such transformations but provided helpful information about potential side products such as [(CH3)2Ga(μ-X)]2 (X = OR, HNR′) and reaction intermediates. Efficient methylene → imido transformations using Ga8(CH2)12/aniline mixtures could not be implemented.
An Inquiry into the Semantic Transparency and Productivity of German Particle Verbs and Derivational Affixation
2022-10-07

This study addresses the relation between morphological productivity and semantic transparency. Us- ing distributional semantics, we compare German word formation with particles with derivational word formation. We observed that derivational suffixes, but not particles, tend to make strong independent semantic contributions to their carrier words. In two-dimensional t-SNE maps, complex words show clus- tering by affix, but not by particle. Furthermore, the semantic vectors of suffixed words are predictable from their base words with higher accuracy than is possible for particle verbs. This holds irrespective of whether the semantic vectors of complex words are predicted using a generalization of the FRACCS model, or whether a more recent, and more precise, additive model (CosClassAvg) is used. For particle verbs, but not affixed verbs, a greater semantic similarity within the set of complex words correlated negatively with the number of types. Only for particle verbs, a greater number of types predicted a reduced probability of unseen types. Considered jointly, the particle verbs are characterized by quan- titative properties that are very similar to those observed for Mandarin compounds. We propose that particle verbs, just as compounds, primarily serve the onomasiological function of labeling, resulting in highly distinct semantic vectors for particle verbs. By contrast, derivational affixation groups complex words closely together in semantic space while maintaining strong and consistent semantic relations with the base words. This enables these words to serve not only as labels, but also allows them to be used for syntactic recategorization.
Capturing clinical progression in multisystemic genetic ataxias: lessons from a prospective study of 884 patients with autosomal recessive or early-onset ataxia
2022-10-07

Abstract Objective The Scale for the Assessment and Rating of Ataxia (SARA) is the most widely applied clinical outcome assessment (COA) for genetic ataxias, but presents metrological and regulatory challenges. To facilitate trial planning, we characterize its responsiveness (including subitem-level relations to ataxia severity and patient-focused outcomes) across a large number of ataxias, and provide first natural history data for several of them. Methods Subitem-level correlation- and distribution-based analysis of 1637 SARA assessments in 884 patients with autosomal-recessive/early-onset ataxia (370 with 2-8 longitudinal assessments), complemented by linear mixed-effects modeling to estimate progression and sample sizes. Results While SARA subitem responsiveness varied between ataxia severities, gait / stance showed a robust granular linear scaling across the broadest range (SARA&lt;25). Responsiveness was diminished by incomplete sub-scale use at intermediate or upper levels, non-transitions (“static periods”), and fluctuating decreases/increases. All subitems -except nose-finger -showed moderate-to-strong correlations to activities of daily living, indicating that metric properties -not content validity-limit SARA responsiveness. SARA captured mild-to-moderate progression in many genotypes, e.g., SYNE1-ataxia: 0.55 points/year, AOA2: 1.14, POLG-ataxia: 1.56; but no change in others (ARSACS, COQ8A-ataxia). While sensitivity to change was optimal in mild ataxia (SARA≤10), it substantially deteriorated in advanced ataxia (SARA&gt;25; 2.7-fold sample size). Use of a novel rank-optimized SARA without subitems finger-chase and nose-finger reduces sample sizes by 20-25%. Interpretation This study comprehensively characterizes COA properties and annualized changes of the SARA across and within a large number of ataxias. It suggests specific approaches for optimizing its responsiveness that might facilitate regulatory qualification and trial design.
Unified and standardized mass spectrometry data processing in Python using spectrum_utils
2022-10-07

Abstract spectrum_utils is a Python package for mass spectrometry data processing and visualization. Since its introduction, spectrum_utils has grown into a fundamental software solution that powers various applications in proteomics and metabolomics, ranging from spectrum preprocessing prior to spectrum identification and machine learning applications, to spectrum plotting from online data repositories, and assisting data analysis tasks for dozens of other projects. Here we present updates to spectrum_utils, which include new functionality to integrate mass spectrometry community data standards, enhanced mass spectral data processing, and unified mass spectral data visualization in Python. spectrum_utils is freely available as open source at https://github.com/bittremieux/spectrum_utils .
Nitrate leaching and its implication for Fe and As mobility in a Southeast Asian aquifer
2022-10-07

Abstract The drinking water quality of millions of people in South and Southeast Asia is at risk due to arsenic (As) contamination of groundwater and insufficient access to water treatment facilities. Intensive use of nitrogen (N) fertilizer increases the possibility of nitrate (NO 3 - ) leaching into aquifers, yet very little is known about how the N cycle will interact with and affect the iron (Fe) and As mobility in aquifers. We hypothesized that input of NO 3 - into highly methanogenic aquifers can stimulate nitrate-dependent anaerobic methane oxidation (N-DAMO) and subsequently help to remove NO 3 - and decrease CH 4 emission. We, therefore, investigated the effects of N input into aquifers and its effect on Fe and As mobility, by running a set of microcosm experiments using aquifer sediment from Van Phuc, Vietnam supplemented with 15 NO 3 - and 13 CH 4 . Additionally, we assessed the effect of N-DAMO by inoculating the sediment with two different N-DAMO enrichment cultures (N-DAMO(O) and N-DAMO(V)). We found that native microbial communities and both N-DAMO enrichments could efficiently consume nearly 5 mM NO 3 - in 5 days. In an uninoculated setup, NO 3 - was preferentially used over Fe(III) as electron acceptor and consequently inhibited Fe(III) reduction and As mobilization. The addition of N-DAMO(O) and N-DAMO(V) enrichment cultures led to substantial Fe(III) reduction followed by the release of Fe 2+ (0.190±0.002 mM and 0.350±0.007 mM, respectively) and buildup of sedimentary Fe(II) (11.20±0.20 mM and 10.91±0.47 mM, respectively) at the end of the experiment (day 64). Only in the N-DAMO(O) inoculated setup, As was mobilized (27.1±10.8 μg/L), while in the setup inoculated with N-DAMO(V) a significant amount of Mn (24.15±0.41 mg/L) was released to the water. Methane oxidation and 13 CO 2 formation were observed only in the inoculated setups, suggesting that the native microbial community did not have sufficient potential for N-DAMO. An increase of NH 4 + implied that dissimilatory nitrate reduction to ammonium (DNRA) took place in both inoculated setups. The archaeal community in all treatments was dominated by Ca . Methanoperedens while the bacterial community consisted largely of various denitrifiers. Overall, our results suggest that input of N fertilizers to the aquifer decreases As mobility and that CH 4 cannot serve as an electron donor for the native NO 3 - reducing community. Graphical abstract
Environment-aware Optimization of Track-to-Track Fusion for Collective Perception
2022-10-08

Correct and complete perception is key for autonomous vehicles to plan safe maneuvers. Especially under harsh weather conditions the use of sensing capabilities from other road users via vehicle-to-everything (V2X) communication can contribute to more complete perception. However, information from other road users may contain additional uncertainties and lead to less accurate perception. Additionally, attackers may use the V2X channel to transmit malicious data. For building an accurate environmental model an autonomous vehicle needs as precise information as possible. To tackle the problems of additional uncertainties within collective perception we propose a methodology to check perceived information for its trustworthiness and validity. This is achieved by evaluating the perception capabilities of a holistic perception pipeline and checking collectively transmitted information for consistency. The proposed approach is evaluated under varying environmental conditions on a simulated highway scenario.
The START domain potentiates HD-ZIPIII transcriptional activity
2022-10-08

Abstract HD-ZIPIII transcription factors (TFs) were repeatedly deployed over 725 million years of evolution to regulate central developmental innovations. The START domain of this pivotal class of developmental regulators was recognized over twenty years ago, but its putative ligands and functional contributions remain unknown. Here, we demonstrate that the START domain promotes HD-ZIPIII TF homodimerization and increases transcriptional potency. Effects on transcriptional output can be ported onto heterologous TFs, consistent with principles of evolution via domain capture. We also show the START domain binds several species of phospholipids, and that mutations in conserved residues predicted to affect either ligand binding, or its downstream readout, abolish HD-ZIPIII DNA-binding competence. Our data present a model in which the START domain potentiates transcriptional activity and uses ligand-induced conformational change to render HD-ZIPIII dimers competent to bind DNA. These findings resolve a long-standing mystery in plant development and highlight the flexible and diverse regulatory potential coded within this widely distributed evolutionary module.
Certification as dysplasia unit and its impact on large loop electrosurgical excision (LEEP)
2022-10-08

Abstract Purpose This study evaluates the overall treatment indicators and outcomes of patients who underwent loop electrosurgical excision procedure (LEEP) at the Department of Women’s Health Tübingen and the impact of certification as a dysplasia unit on treatment quality. Methods Retrospective data analysis of 1596 patients from 2013 to 2018 who underwent LEEP excision at the Department of Women’s Health Tübingen. Data of cytology, colposcopy, biopsy, LEEP histology, repeat LEEP histology and general characteristics were collected and analyzed descriptively. Results 85.4% (1364) of patients had CIN 2 + and 14.6% (232) had CIN 1 or normal findings on LEEP histology. The proportion of CIN 2 + excisions increased significantly from 82.4% in 2013 to 89% in 2018. The concordance of HSIL biopsy and LEEP histology was 89.1% in 2013 and 92.6% in 2018. In 2018, more biopsies and colposcopies were performed before excision. Complete resection (R0) was achieved in 88.3% of all excisions. R0 rates in patients with CIN 3 increased in 2014–2017 compared to 2013, resulting in fewer Re-LEEP excisions and hysterectomies. Conclusion Certification as a dysplasia unit and the associated requirements have improved the diagnostic quality for patients with cervical dysplasia undergoing LEEP. This was demonstrated by several treatment indicators such as the number of colposcopies and biopsies and treatment outcomes such as an increased proportion of CIN 2 + excisions and R0 resections.
Esters from castor oil functionalized with aromatic amines as a potential lubricant
2022-10-09

Abstract Vegetable oils are very promising alternatives to fossil lubricants due to their abundance, low cost, excellent performance, and environmental friendliness. Due to its multifunctional structure, castor oil is an excellent precursor in the synthesis of new biolubricants. However, it showed poor thermal‐oxidative stability and a higher pour point. This study used castor oil fatty acids prepared by transesterification (EHRO), epoxidation (TEPO), and oxirane ring opening with the aromatic amines aniline (ANIL) and p ‐anisidine (ANIS). The chemical structure of these oils was verified by 1 H and 13 C NMR analysis, and mass spectrometry. Measurements show that the presence of an aromatic amine increases the viscosity resulting in 172 (ANIL) and 199 (ANIS) cSt at 40°C, but reduces viscosity index to 16 and 1, respectively. In addition, the amine groups can scavenge radicals increasing their thermal and oxidative stability. These products do not oxidize copper, and tribological analysis reveals that ANIS has the lowest torque with wear equivalent to commercial mineral lubricant NH‐140.
The promise of a model-based psychiatry: building computational models of mental ill health
2022-10-10

Computational models have great potential to revolutionise psychiatry research and clinical practice. These models are now used across multiple subfields, including computational psychiatry and precision psychiatry. Their goals vary from understanding mechanisms underlying disorders to deriving reliable classification and personalised predictions. Rapid growth of new tools and data sources (eg, digital data, gamification, and social media) requires an understanding of the constraints and advantages of different modelling approaches in psychiatry. In this Series paper, we take a critical look at the range of computational models that are used in psychiatry and evaluate their advantages and disadvantages for different purposes and data sources. We describe mechanism-driven and mechanism-agnostic computational models and discuss how interpretability of models is crucial for clinical translation. Based on these evaluations, we provide recommendations on how to build computational models that are clinically useful.