julilili42/papers huggingface dataset:
The Adhesion GPCR VLGR1/ADGRV1 Regulates the Ca2+ Homeostasis at Mitochondria-Associated ER Membranes
2022-09-07

The very large G protein-coupled receptor (VLGR1, ADGRV1) is the largest member of the adhesion GPCR family. Mutations in VLGR1 have been associated with the human Usher syndrome (USH), the most common form of inherited deaf-blindness as well as childhood absence epilepsy. VLGR1 was previously found as membrane–membrane adhesion complexes and focal adhesions. Affinity proteomics revealed that in the interactome of VLGR1, molecules are enriched that are associated with both the ER and mitochondria, as well as mitochondria-associated ER membranes (MAMs), a compartment at the contact sites of both organelles. We confirmed the interaction of VLGR1 with key proteins of MAMs by pull-down assays in vitro complemented by in situ proximity ligation assays in cells. Immunocytochemistry by light and electron microscopy demonstrated the localization of VLGR1 in MAMs. The absence of VLGR1 in tissues and cells derived from VLGR1-deficient mouse models resulted in alterations in the MAM architecture and in the dysregulation of the Ca2+ transient from ER to mitochondria. Our data demonstrate the molecular and functional interaction of VLGR1 with components in MAMs and point to an essential role of VLGR1 in the regulation of Ca2+ homeostasis, one of the key functions of MAMs.
Standardized procedure prevents perioperative and early complications in totally implantable venous-access ports—a complication analysis of more than 1000 TIVAP implantations
2022-09-07

Abstract Purpose Since their invention 40 years ago, totally implantable venous-access ports (TIVAPs) have become indispensable in cancer treatment. The aim of our study was to analyze complications under standardized operative and perioperative procedures and to identify risk factors for premature port catheter explantation. Methods A total of 1008 consecutive TIVAP implantations were studied for success rate, perioperative, early, and late complications. Surgical, clinical, and demographic factors were analyzed as potential risk factors for emergency port catheter explantation. Results Successful surgical TIVAP implantation was achieved in 1005/1008 (99.7%) cases. No intraoperative or perioperative complications occurred. A total of 32 early complications and 88 late complications were observed leading to explantation in 11/32 (34.4%) and 34/88 (38.6%) cases, respectively. The most common complications were infections in 4.7% followed by thrombosis in 3.6%. Parameters that correlated with unplanned TIVAP explantation were gender (port in situ: female 95% vs. male 91%, p = 0.01), underlying disease (breast cancer 97% vs. gastrointestinal 89%, p = 0.004), indication (chemotherapy 95% vs. combination of chemotherapy and parenteral nutrition 64%, p &lt; 0.0001), and type of complication (infection 13.4% vs. TIVAP-related complication 54% and thrombosis 95%, p &lt; 0.0001). Conclusion Standardized operative and perioperative TIVAP implantation procedures provide excellent results and low explantation rate.
Predicting fraction and algebra achievements online: A large‐scale longitudinal study using data from an online learning environment
2022-09-07

Abstract Background Mastering fractions seems among the most critical mathematical skills for students to acquire in school as fraction understanding significantly predicts later mathematic achievements, but also broader academic and vocational prospects. As such, identifying longitudinal predictors of fraction understanding (e.g., mastery of numbers and operations) is highly relevant. However, almost all existing studies identifying more basic numerical skills as predictors of fraction understanding rest on data acquired in face‐to‐face testing—mostly in classrooms. Objectives In this article, we evaluated whether results obtained in these previous studies generalized to data from the curriculum‐based online learning environment Bettermarks for mathematics used in schools in the Netherlands. Methods We considered data from more than 5000 students who solved over 1 million mathematical problem sets on basic mathematical skills, fractions, but also algebra. Results and Conclusions In line with previous findings, we found that fraction understanding was predicted significantly by more basic mathematical skills. Our analyses also indicated that algebra achievement was predicted significantly by fraction understanding beyond influences of more basic mathematical skills. Implications Together, these findings generalized previous results based on face‐to‐face testing to the context of data from online learning environments and thus, indicate that data from such large‐scale online learning environments may well qualify to provide significant insights into the hierarchical development of mathematical skills.
Interference based aberration-free chromatic stimulator for human myopia research
2022-09-07

Previous studies showed an impact of the light spectrum on ocular growth. It is unclear whether the eye reacts to the light chromaticity or to the defocus induced by the longitudinal chromatic aberration (LCA). This study investigated the influence of narrow-band aberration-free light on axial length as an indicator for eye growth. Using a laser-interference exposure setup, 18 healthy eyes were stimulated with aberration-free short-wavelength light (450 ± 5 nm), mid-wavelength light (550 ± 5 nm) and long-wavelength light (650 ± 5 nm) for 20 min. Axial length was measured before and after the exposure in the test eye and control eye. No statistically significant axial length changes from baseline were observed after exposure to narrow-band aberration-free light (all p &gt; 0.05). Axial length responses did not differ significantly between chromatic conditions or test and control eye (all p &gt; 0.05). The study suggests that light chromaticity does not present a signal for ocular growth under the tested conditions without the additional information of LCA-induced defocus.
Diagnostics of quantum-gate coherences via end-point-measurement statistics
2022-09-07

Quantum coherence is a central ingredient in quantum physics with several theoretical and technological ramifications. In this work we consider a figure of merit encoding the information on how the coherence generated on average by a quantum gate is affected by unitary errors (coherent noise sources). We provide numerical evidences that such information is well captured by the statistics of local energy measurements on the output states of the gate. These findings are then corroborated by experimental data taken in a quantum optics setting.
Synthesis of tryptophan-dehydrobutyrine diketopiperazine and biological activity of hangtaimycin and its co-metabolites
2022-09-07

An improved synthesis for tryptophan-dehydrobutyrine diketopiperazine (TDD), a co-metabolite of the hybrid polyketide/non-ribosomal peptide hangtaimycin, starting from ʟ-tryptophan is presented. Comparison to TDD isolated from the hangtaimycin producer Streptomyces spectabilis confirmed its S configuration. The X-ray structure of the racemate shows an interesting dimerisation through hydrogen bridges. The results from bioactivity testings of hangtaimycin, TDD and the hangtaimycin degradation product HTM 222 are given.
Body experience influences lexical-semantic knowledge of body parts in children with hemiplegic cerebral palsy
2022-09-07

Background Disorders in different levels of body representation (i.e., body schema, body structural description, and body image) are present in hemiplegic cerebral palsy (HCP). However, it remains unclear whether the body image develops from aspects of body schema and body structural description, and how this occurs in children with HCP. Objective and methods In a cross-sectional study, we investigated 53 children with HCP (mean age about 10 years) and 204 typically developing (TD) control children to qualitatively evaluate whether and how body schema (related sensorimotor experiences) and body structural description (related visuospatial experiences) affect the development of children’s body image and whether this development is delayed through HCP. Graph analysis was used to create a lexical-semantic map of body representation from data of a semantic word fluency task. Results Results indicated a similar qualitative pattern of influences of sensorimotor and visuospatial experiences on lexical-semantic knowledge of body parts, with a delayed developmental course in children with HCP compared to TD children. Conclusion These findings suggest that children’s body image seemed to be influenced by body schema and body structural descriptions as indicated by poorer lexical-semantic knowledge of body parts in children with HCP due to missing physical experiences of the affected body parts. This might imply that “body talk” may beneficially complement physical therapy for children with HCP to promote body image development.
Search for Dark Matter Annihilation Signals in the H.E.S.S. Inner Galaxy Survey
2022-09-08

The central region of the Milky Way is one of the foremost locations to look for dark matter (DM) signatures. We report the first results on a search for DM particle annihilation signals using new observations from an unprecedented -ray survey of the Galactic Center (GC) region, i.e., the Inner Galaxy Survey, at very high energies (≳100 GeV) performed with the H.E.S.S. array of five ground-based Cherenkov telescopes. No significant -ray excess is found in the search region of the 2014–2020 dataset and a profile likelihood ratio analysis is carried out to set exclusion limits on the annihilation cross section . Assuming Einasto and Navarro-Frenk-White (NFW) DM density profiles at the GC, these constraints are the strongest obtained so far in the TeV DM mass range. For the Einasto profile, the constraints reach values of 3.7×10 cm s for 1.5 TeV DM mass in the W W annihilation channel, and 1.2×10 cm s for 0.7 TeV DM mass in the annihilation channel. With the H.E.S.S. Inner Galaxy Survey, ground-based -ray observations thus probe values expected from thermal-relic annihilating TeV DM particles.
Limited diversity and QCA solution types: assumptions and their consequences
2022-09-08

Abstract Limited diversity is a term employed in the context of Ragin’s Qualitative Comparative Analysis (QCA), but it describes a phenomenon which is widespread in social contexts: cases are usually not distributed evenly across all the possible combinations of factors linked to some outcome. Instead, they are often clustered together. To deal with limited diversity, the three solution types parsimonious, intermediate, and complex (or conservative) solution have been proposed. There is an ongoing debate as to the merits of each solution type. This paper contributes to the debate by focussing on what the implications of choosing each solution type are. In making this choice, researchers have to make certain assumptions, and the paper discusses what these are and how they vary depending on which solution type is being implemented, drawing on invented examples and examples from published work to bring out the consequences of these assumptions. It concludes that it is not obvious that any one solution type is superior, certainly not to the degree that the others always have to be ruled out. They rely on different kinds of assumptions and models of causation. Thus, depending on the research situation, it may be helpful to analyse different scenarios, including one(s) where we assume that our initial assumptions are wrong. Ideally, researchers are able to take steps to reduce or eliminate limited diversity since none of the existing solution types are without problems. However, since this is not always possible, it is best to be aware of the consequences of choices.
Human-environmental interactions and seismic activity in a Late Bronze to Early Iron Age settlement center in the southeastern Caucasus
2022-09-08

Long-term human-environmental interactions in naturally fragile drylands are a focus of geomorphological and geoarchaeological research. Furthermore, many dryland societies were also affected by seismic activity. The semi-arid Shiraki Plain in the tectonically active southeastern Caucasus is currently covered by steppe and largely devoid of settlements. However, numerous Late Bronze to Early Iron Age city-type settlements suggest early state formation between ca. 3.2-2.5 ka that abruptly ended after that time. A paleolake was postulated for the lowest plain, and nearby pollen records suggest forest clearcutting of the upper altitudes under a more humid climate during the Late Bronze/Early Iron Ages. Furthermore, also an impact of earthquakes on regional Early Iron Age settlements was suggested. However, regional paleoenvironmental changes and paleoseismicity were not systematically studied so far. We combined geomorphological, sedimentological, chronological and paleoecological data with hydrological modelling to reconstruct regional Holocene paleoenvironmental changes, to identify natural and human causes and to study possible seismic events during the Late Bronze/Early Iron Ages. Our results show a balanced to negative Early to Mid-Holocene water balance probably caused by forested upper slopes. Hence, no lake but a pellic Vertisol developed in the lowest plain. Following, Late Bronze/Early Iron Age forest clear-cutting caused lake formation and the deposition of lacustrine sediments derived from soil erosion. Subsequently, regional aridification caused slow lake desiccation. Remains of freshwater fishes indicate that the lake potentially offered valuable ecosystem services for regional prehistoric societies even during the desiccation period. Finally, colluvial coverage of the lake sediments during the last centuries could have been linked with hydrological extremes during the Little Ice Age. Our study demonstrates that the Holocene hydrological balance of the Shiraki Plain was and is situated near a major hydrological threshold, making the landscape very sensitive to small-scale human or natural influences with severe consequences for local societies. Furthermore, seismites in the studied sediments do not indicate an influence of earthquakes on the main and late phases of Late Bronze/Early Iron Age settlement. Altogether, our study underlines the high value of multi-disciplinary approaches to investigate human-environmental interactions and paleoseismicity in drylands on millennial to centennial time scales.
Walking parameters of older adults from a lower back inertial measurement unit, a 6-year longitudinal observational study
2022-09-08

Gait changes during aging and differs between sexes. Inertial measurement units (IMUs) enable accurate quantitative evaluations of gait in ambulatory environments and in large populations. This study aims to provide IMU-based gait parameters’ values derived from a large longitudinal cohort study in older adults. We measured gait parameters, such as velocity, step length, time, variability, and asymmetry, from straight, self-paced 20-m walks in older adults (four visits: 715/1102/1017/957 participants) every second year over 6 years using an IMU at the lower back. Moreover, we calculated the associations of gait parameters with sex and age. Women showed lower gait speed, step length, step time, stride time, swing time, and stance time, compared to men. Longitudinal analyses suggest that these parameters are at least partly deteriorating within the assessment period of 2 years, especially in men and at an older age. Variability and asymmetry parameters show a less clear sex- and age-associated pattern. Altogether, our large longitudinal dataset provides the first sex-specific information on which parameters are particularly promising for the detection of age-related gait changes that can be extracted from an IMU on the lower back. This information may be helpful for future observational and treatment studies investigating sex and age-related effects on gait, as well as for studies investigating age-related diseases.
Vaccination completeness in children with rheumatic diseases: A longitudinal, observational multicenter cohort study in Switzerland
2022-09-08

Introduction Children with pediatric inflammatory rheumatic diseases (PRD) have an increased infection risk. Vaccinations are effective to avoid vaccine-preventable diseases. This study aimed to assess the vaccination completeness in Swiss PRD patients stratified by immunosuppressive treatment (IST). Materials and methods This multicenter observational cohort study of PRD patients was performed in Basel, Geneva, Lucerne, Lausanne, and Zurich in PRD patients aged &amp;lt; 18 years included in the Juvenile Inflammatory Rheumatism Cohort. Completeness was assessed for i) the overall vaccination status (Swiss national immunization program (NIP) and specific additional PRD-recommended vaccinations), ii) for all and each vaccination of the NIP at PRD diagnosis and reference date (RefD) and iii) all and each specific additional PRD-recommended vaccination at RefD. Completeness was assessed over the disease course and stratified by IST. Results Of 616 eligible patients, 234 children were analyzed. Of these, 147 (63%) were girls. Median age at PRD diagnosis was 6.5 years (IQR 2.9–10.3) and 10.9 years at RefD (6.9–14.3). The median follow-up since PRD diagnosis was 3 years (1.1–5.5). 120/234 children received IST. At RefD, overall vaccination completeness was 3.8% (9/234 children), completeness for the NIP vaccinations was 70.1% (164/234 children; IST 65%, no IST: 75.4%) and for all specific additional PRD-recommended vaccinations was 3.8% (9/234 children; IST 2.5%; no IST 5.3%). Vaccination completeness against pneumococcal disease, hepatitis B virus, and human papilloma virus (HPV) was 50.4, 20, 37.9%, respectively. In 25/35 children with negative varicella zoster virus history vaccination status was complete (IST: 94.4%, no IST: 47%). Annual non-live influenza vaccination was complete in 24.2% of children during IST; adherence decreased over the disease course. Discussion This study identified a low overall vaccination completeness in children with PRD. Particularly, the completeness of specific additional PRD-recommended vaccinations was low. If not performed early after PRD diagnosis, vaccination status remained frequently incomplete. Close collaboration between pediatrician and rheumatologist to improve vaccination completeness is essential. Exchange of vaccination records, standardized assessment of specific PRD-recommended vaccinations and those of the NIP, and annual reminder for influenza vaccination are crucial to improve vaccination completeness in this vulnerable pediatric population.
Cerebrovascular Gi Proteins Protect Against Brain Hypoperfusion and Collateral Failure in Cerebral Ischemia
2022-09-08

Abstract Cerebral hypoperfusion and vascular dysfunction are closely related to common risk factors for ischemic stroke such as hypertension, dyslipidemia, diabetes, and smoking. The role of inhibitory G protein-dependent receptor (G i PCR) signaling in regulating cerebrovascular functions remains largely elusive. We examined the importance of G i PCR signaling in cerebral blood flow (CBF) and its stability after sudden interruption using various in vivo high-resolution magnetic resonance imaging techniques. To this end, we induced a functional knockout of G i PCR signaling in the brain vasculature by injection of pertussis toxin (PTX). Our results show that PTX induced global brain hypoperfusion and microvascular collapse. When PTX-pretreated animals underwent transient unilateral occlusion of one common carotid artery, CBF was disrupted in the ipsilateral hemisphere resulting in the collapse of the cortically penetrating microvessels. In addition, pronounced stroke features in the affected brain regions appeared in both MRI and histological examination. Our findings suggest an impact of cerebrovascular G i PCR signaling in the maintenance of CBF, which may be useful for novel pharmacotherapeutic approaches to prevent and treat cerebrovascular dysfunction and stroke.
Variation of Proteolytic Cleavage Sites towards the N-Terminal End of the S2 Subunit of the Novel SARS-CoV-2 Omicron Sublineage BA.2.12.1
2022-09-08

The prevalence of novel SARS-CoV-2 variants is also accompanied by an increased turnover rate and additional cleavage sites at the positions necessary for priming the Spike (S) protein. Of these priming sites, the proteolytically sensitive polybasic sequence of the activation loop at the S1/S2 interface and the S2′ location within the S2 subunit of the S protein are cleaved by furin and TMPRSS2, which are important for the infection of the target cell. Neutrophils, migrating to the site of infection, secrete serine proteases to fight against pathogens. The serine proteases encompass neutrophil elastase (NE), proteinase 3 (PR3), and cathepsin G (CatG), which can hydrolyze the peptide bond adjacent to the S1/S2 interface. SARS-CoV-2 might take the opportunity to hijack proteases from an immune response to support viral entry to the cell. The region near S704L within the S2 subunit, a novel amino acid substitution of SARS-CoV-2 Omicron sublineage BA.2.12.1, is located close to the S1/S2 interface. We found that NE, PR3, and CatG digested the peptide within this region; however, the S704L amino acid substitution altered cleavage sites for PR3. In conclusion, such an amino acid substitution modifies S2 antigen processing and might further impact the major histocompatibility complex (MHC) binding and T cell activation.
Structural Basis for Inhibition of Mutant EGFR with Lazertinib (YH25448)
2022-09-08

Lazertinib (YH25448) is a novel third-generation tyrosine kinase inhibitor (TKI) developed as a treatment for EGFR mutant non-small cell lung cancer. To better understand lazertinib inhibition at the molecular level, we determined crystal structures of lazertinib in complex with both WT and mutant EGFR and compared its binding mode to that of structurally-related EGFR TKIs. We observe that lazertinib binds with the novel pyrazole moiety involved in hydrogen bonds and van der Waals interactions consistent with drug potency and T790M mutant selectivity. Biochemical assays and cell studies confirm that lazertinib effectively targets EGFR(L858R/T790M) and to a lesser extent against HER2 as consistent with an improved toxicity profile. The molecular basis for lazertinib inhibition of EGFR reported here highlights new strategies for structure-guided design of tyrosine kinase inhibitors.
Context matters during pick-and-place in VR: Impact on search and transport phases
2022-09-08

When considering external assistive systems for people with motor impairments, gaze has been shown to be a powerful tool as it is anticipatory to motor actions and is promising for understanding intentions of an individual even before the action. Up until now, the vast majority of studies investigating the coordinated eye and hand movement in a grasping task focused on single objects manipulation without placing them in a meaningful scene. Very little is known about the impact of the scene context on how we manipulate objects in an interactive task. In the present study, it was investigated how the scene context affects human object manipulation in a pick-and-place task in a realistic scenario implemented in VR. During the experiment, participants were instructed to find the target object in a room, pick it up, and transport it to a predefined final location. Thereafter, the impact of the scene context on different stages of the task was examined using head and hand movement, as well as eye tracking. As the main result, the scene context had a significant effect on the search and transport phases, but not on the reach phase of the task. The present work provides insights into the development of potential supporting intention predicting systems, revealing the dynamics of the pick-and-place task behavior once it is realized in a realistic context-rich scenario.