julilili42/papers huggingface dataset:
Single depolymerizing and transport kinesins stabilize microtubule ends
2021-05-01

Abstract Microtubules are highly dynamic cellular filaments and an accurate control of their length is important for many intracellular processes like cell division. Among other factors, microtubule length is actively modulated by motors from the kinesin superfamily. For example, yeast kinesin‐8, Kip3, motors depolymerize microtubules by a cooperative, force‐ and length‐dependent mechanism. However, whether single motors can also depolymerize microtubules is unclear. Here, we measured how single kinesin motors influenced the stability of microtubules in an in vitro assay. Using label‐free interference reflection microscopy, we determined the spontaneous microtubule depolymerization rate of stabilized microtubules in the presence of kinesins. Surprisingly, we found that both single Kip3 and nondepolymerizing kinesin‐1 transport motors, used as a control, stabilized microtubules further. For Kip3, this behavior is contrary to the collective force‐dependent depolymerization activity of multiple motors. Because of the control measurement, the finding may hint at a more general stabilization mechanism. The complex, concentration‐dependent interaction with microtubule ends provides new insights into the molecular mechanism of kinesin‐8 and its regulatory function of microtubule length.
Update Breast Cancer 2021 Part 2 – Advanced Stages, Long-Term Consequences and Biomarkers
2021-05-01

Abstract This review summarises and discusses significant aspects of recently published studies on patient treatment in advanced breast cancer and on biomarkers in breast cancer. In recent years, a large number of drugs for all molecular subtypes have been developed up to phase III trials. With regard to immune checkpoint inhibitors in metastasised breast cancer, the recent discussion has centred on the best candidate for combined chemotherapy. The oral taxanes could become a new type of oral chemotherapies. There is a growing body of data on biomarkers for the use of CDK4/6 inhibitors, which could also signify further development for other molecular subtypes. New substances have been developed for metastatic HER2+ breast cancer that still result in good remission even after massive prior treatment and/or cerebral metastasis. Similarly, knowledge is growing about targeted therapies with antibody-drug conjugates (ADC) against Trop-2, which could bolster our therapeutic armoury in triple-negative breast cancer (TNBC). In addition, the clinical focus is on understanding how to maintain fertility after breast cancer treatment. Here, pooled analyses provide new insights.
Ocular Findings in Patients with COVID-19: Impact on Eye Banking [Letter]
2021-05-01

Lo&iuml;c Hamon, 1 Tarek Bayyoud, 2 Berthold Seitz 1 1Department of Ophthalmology, Saarland University Medical Center (UKS), Homburg/Saar, Germany; 2Department of Ophthalmology, University of T&uuml;bingen, T&uuml;bingen, GermanyCorrespondence: Lo&iuml;c HamonDepartment of Ophthalmology, Saarland University Medical Center (UKS), Kirrbergerstra&szlig;e 100, Bld. 22, Homburg/Saar, 66421, GermanyTel +49 1742169806Fax +49 68411622400Email loic.hamon@uks.eu&nbsp; &nbsp; View the original paper by Qu and colleagues
Basic physics course with MATLAB’s symbolic toolbox and live editor
2021-05-01

Abstract The course offers a compact presentation of the basic content of classical mechanics, quantum mechanics, interaction and chaos theory. In 26 MATLAB Live scripts, the basic physical laws are presented, and examples are solved. Since it is assumed that the reader already has basic knowledge of physics and mathematics, a more modern view of physics, mathematics and calculation can be chosen. The dynamic laws, uniform throughout the course, stem from the concepts of invariance and continuity. Throughout the course, ground vectors and metric are used instead of basis vectors. The use of symbolic computer software enables more complicated problems, vivid graphics, and lots of animation. Students like it because they are play-like. Even students who major in mathematics, computer science and similar subjects have gained a good understanding of the basic physical principles.
Interaction between mafic dike rocks and salt deposits in the Rhine Graben, southwest Germany
2021-05-01

ABSTRACT Dikes of primitive olivine melilitites and monchiquites intruded into an Oligocene (Rupelian) potash salt deposit near Buggingen (SW Germany). Ocelli and amygdules reveal distinct mineral assemblages depending on whether the dike rocks are in direct contact with the potash layer or with bituminous shales (Fish Shale). Samples in contact with the potash salt layer show roundish textures that contain smectite ± talc ± chlorite, calcite, and in cases anhydrite and halite, while those close to the bituminous shale mainly comprise smectite, calcite, zeolite group minerals, and analcime. No textural or mineralogical evidence for high-temperature (magmatic) interaction between the dike rocks and the evaporites was observed. This is presumably related to (1) a very low magmatic water activity in the magma, which prevented exsolution of aqueous fluids and appreciable dissolution of the salt, and (2) fast cooling of the magmas, inhibiting melting of the salt deposits and potential liquid mingling and/or assimilation processes. Halite formation in the dike rocks is, rather, related to later, post-magmatic hydrothermal fluids that previously interacted with the salt-rich host rocks. Alteration of the initially glassy groundmass to smectites and zeolites caused an enrichment of Na in the residual fluid, but halite saturation was not attained, as indicated by the absence of groundmass halite. Only fluid–rock interaction in millimeter-sized vugs caused halite precipitation via desiccation by swelling of previously formed clay minerals. Locally, the boron silicate datolite formed in pseudomorphs after olivine. Its precipitation was controlled by the Si and B supply provided by the breakdown of serpentine and smectite.
Linked machine learning classifiers improve species classification of fungi when using error-prone long-reads on extended metabarcodes
2021-05-01

ABSTRACT Background The increased usage of error-prone long-read sequencing for metabarcoding of fungi has not been matched with adequate public databases and concomitant analysis approaches. We address this gap and present a proof-of-concept study for classifying fungal taxa using linked machine learning classifiers. We demonstrate the capability of linked machine learning classifiers to accurately classify species and strains using real-world and simulated fungal ribosomal DNA datasets, including plant and human pathogens. We benchmark our new approach in comparison to current alignment and k-mer based methods based on synthetic mock communities. We also assess real world applications of species identification in complex unlabelled datasets. Results Our machine learning approach assigned individual nanopore long-read amplicon sequences to fungal species with high recall rates and low false positive rates. Importantly, our approach successfully distinguished between closely-related species and strains when individual read errors were higher than the genetic distance between individual taxa, which the alignment and k-mer methods could not do. The machine learning approach showed an ability to identify key species with high recall rates, even in complex samples of unknown species composition. Conclusions A proof of concept machine learning approach using a tree-descent approach on a decision tree of classifiers can identify known taxa with high accuracy, and precisely detect known target species from complex samples with high recall rates. We propose this approach is suitable for detecting the known knowns of pathogens or invasive species in any environment of mostly unknown composition, including agriculture and wild ecosystems.
A novel local impedance algorithm and contact force sensing to guide high power short duration radiofrequency ablation is efficient and safe for circumferential pulmonary vein isolation
2021-05-01

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Local impedance (LI) drop can predict sufficient lesion formation during radiofrequency ablation (RF). Recently, a novel ablation catheter technology able to measure LI and contact force has been made available for clinical use. High power short duration (HPSD) RF ablation has been shown to be feasible for atrial fibrillation (AF) ablation with short procedure time. We used LI drop and plateau formation to guide duration of 50 Watt RF power applications for circumferential pulmonary vein isolation (PVI). Methods Consecutive patients with indication for de novo AF ablation (n = 32, age 65 ± 10 years) with paroxysmal (n = 16) or persistent (n = 16) AF underwent ultra high density 3D mapping of the left atrium and catheter ablation. Thereafter, ipsilateral PV encircling with 50 Watt RF-applications targeting an interlesion distance of ≤ 6mm and a contact force of 10-30g was performed. Duration of HPSD RF application between 7-15s was guided by impedance drop &amp;gt;20 Ohm and plateau formation of LI. Further ablation strategy was left to the investigator’s discretion. Esophageal temperature measurement was performed using a three thermistor catheter with temperature cut off 39.0°C. In case of temperature rise or very near esophageal contact to the circumferential line, RF application time was shortened to 7s. Patients underwent adenosine testing after PVI. Previously we performed all types of AF ablation using an LI guided HPSD ablation without contact force measurement capability in 80 patients. Results Complete PVI was achieved in all pts with only 13.5 ± 4.3 min cumulative RF application duration and an ablation procedure duration of 46.5 ± 10.4 min with the novel LI measuring catheter. First-pass isolation of ipsilateral veins was achieved in 75% of circles. Recurrence of PV conduction during waiting period (20min) and adenosine testing occured in 25% of circles, and was reablated in most patients with a single spot of HPSD application. Using 94 ± 36 RF application per patient, mean maximum LI drop was 23.6 ± 4.0 Ohm. Reconnected fibers were associated with low LI drop due to instability of contact in most cases due to breathing in case of difficult sedation of the patients. No serious complications occurred in all 32 pts using HPSD with the novel contact force catheter design. Conclusion Guiding of HPSD RF ablation by LI is highly efficient and safe. A novel local impedance algorithm in combination with contact force sensing enable short PVI times with low early recurrence of PV conduction. Prediction of permanent lesions seems possible and the only limitation seems to be unstable RF catheter contact due patients breathing. Follow up have to be waited.
The Alchemist’s work: Ibn Arfaʿ Raʾs and the reception of his collection of alchemical poems Shudhūr al-dhahab
2021-05-01

Abstract In recent years, scholars have increasingly turned their attention to the social contexts of Islamic manuscripts related to the occult sciences. With regard to manuscripts dealing with Arabic alchemy, however, in-depth studies are still lacking. This article aims at shedding some light on the readers and owners of Arabic alchemical literature, focusing on Ibn Arfaʿ Raʾs, a Moroccan alchemist of the twelfth century, and his collection of poems entitled Shudhūr al-dhahab (“The Splinters of Gold”). In the centuries following Ibn Arfaʿ Raʾs’s death, his dīwān became a “bestseller” and was copied numerous times in many parts of the Islamicate world. The 94 extant manuscripts bear witness to this incredible success and allow us to take a closer look at the milieus in which this text circulated.
Alchemical stanzaic poetry (muwashshaḥ) by Ibn Arfaʿ Raʾs (fl. twelfth century)
2021-05-01

Abstract The twelfth-century alchemist Ibn Arfaʿ Raʾs is best known for his collection ( dīwān ) of alchemical poems entitled Shudhūr al-dhahab (“The Splinters of Gold”). However, he is also credited with other works, including stanzaic poetry ( muwashshaḥāt ) on alchemy. This paper presents the current state of the scholarship concerning life and works of Ibn Arfaʿ Raʾs, and then focuses on three strophic poems attributed to this alchemist. It includes first editions and English translations of all three poems, and argues that at least two of the poems are likely to have been authored by Ibn Arfaʿ Raʾs, while one is a literary imitation ( muʿāraḍa ) and therefore probably not a work of Ibn Arfaʿ Raʾs himself. Furthermore, the article discusses the literary features of the poems as well as their historical contexts and their – somewhat limited – reception. This also allows us to think of Ibn Arfaʿ Raʾs in a less regional Andalusī-Maghribī context, and consider if he perhaps moved east at some point of his life, which would explain the reception history of his poems, both those included in the dīwān and the muwashshaḥāt .
Trade in tasks: Revisiting the wage and employment effects of offshoring
2021-05-01

Abstract We examine conditions under which offshoring of labour tasks raises domestic wages and employment. Existing literature emphasizes that absorption of job displacement through intersectoral reallocation of factors is a key requirement for this outcome, mostly assuming full employment. We develop a model featuring a less benign environment that rules out such reallocation and allows for equilibrium unemployment due to costly search and matching. Assuming offshoring of both high‐skilled and low‐skilled labour tasks, we derive conditions under which offshoring benefits all workers in terms of both, wages and employment.
Tumor-exclusive peptides from shared and individual antigens in the HLA-ligandome of oropharyngeal squamous cell carcinoma
2021-05-01

Introduction Cancer-antigens are presented to the immune system via Human leucocyte antigens (HLA). The HLA-ligandome in oropharyngeal squamous cell carcinoma (OPSCC) has not been described previously.
P369 High prevalence of abdominal pain in Crohn’s Disease patients of the TRUST study cohort- Is there a connection to inflammatory activity?
2021-05-01

Abstract Background Pain is a debilitating symptom in many patients with Crohn’s disease (CD) both in flare and in remission [1]. However, pain is insufficiently understood and therefore often underrepresented in disease management [2]. Thus, it is of paramount importance to raise awareness for this common but insufficiently managed IBD symptom. With this analysis, we aimed to investigate (1) the prevalence of abdominal pain (AP) and (2) the correlation of AP with further parameters including inflammatory activity assessed by intestinal ultrasound (IUS), lab parameters and patient-well-being in CD patients of the TRUST study cohort. Methods We evaluated the prevalence of pain in 230 of 234 CD patients of the prospective, non-interventional, multi-centre TRUST study. At baseline, all patients were in clinical flare (Harvey-Bradshaw index (HBI) of≥7) and received treatment intensification. IUS parameters such as bowel wall thickness (BWT) and clinical data were assessed at baseline and after 3, 6, and 12 months. AP was analysed using the HBI subscore 2. To investigate the connection between AP and inflammation, AP was correlated with BWT and C-reactive protein (CRP). Results Based on the TRUST study, we found that 95.2% of patients in clinical flare experienced AP. AP was significantly reduced within 12 weeks after treatment intensification (p &amp;lt; 0.001) but 30% (n=69) to 48.3% (n=111) of patients still experienced AP at the subsequent visits (p(T1-T2) = 0.668; p(T2-T3) = 1.000) (figure 1). Of note, 35.6%-42.5% of patients with clinical response had a lasting pain experience (figure 2). AP positively correlated with poor well-being which is in line with previously published results [3]. We found a weak positive correlation between AP and inflammatory activity, represented by BWT (not shown), and between AP and CRP (table 1). Figure 1: Percentage of patients with mild, moderate or severe abdominal pain during the study. *Friedman test with post-hoc Wilcoxon tests. Figure 2: Percentage of patients with abdominal pain and clinical response (reduction of total HBI≥3 points) at the indicated visit Table 1: Spearmann rank correlations for abdominal pain vs. poor general well-being (as measured by the HBI subscore 1) and vs. CRP at baseline Conclusion Our results clearly demonstrate that more than 1/3 of CD patients suffers from AP despite treatment intensification and clinical improvement. We found a weak correlation between AP and markers of inflammatory activity suggesting the existence of a subgroup of patients with persistent pain experience even with IBD treatment. Our data emphasize the importance of adjuvant pain management in IBD. References
Detection of Fully Cleaved Gamma Subunit of the Epithelial Sodium Channel (γ‐ENaC) in Kidney Cortex of Healthy and Nephrotic Wild Type Mice
2021-05-01

Background and Objective The epithelial sodium channel (ENaC) located in the distal region of the nephron regulates body sodium homeostasis. It exhibits proteolytic posttranslational processing which leads to the removal of inhibitory peptide tracts and subsequent alterations in channel gating. Maximum channel activation and open probability occur at the proteolytic removal of the inhibitory tracts by serine proteases. Nephrotic Syndrome is thought to involve ENaC activation by full proteolysis of the gamma subunit and the detection of the expression of fully cleaved γ‐ENaC has been elusive in vivo. Methods Three‐month‐old wild‐type 129S1/SvImJ mice of both sexes were used for the experiment. Experimental nephrotic syndrome was induced by the use of doxorubicin. The mice were euthanized on days 4 and 8 and their kidneys were collected. Western blot analysis for γ‐ENaC was performed with 20 μg of kidney lysate per lane. Samples were deglycosylated using Peptide: N‐glycosidase F (PNGaseF). Subsequently, 20 μg of sample was loaded on an 8% polyacrylamide gel for electrophoresis. After transfer to nitrocellulose membranes, the blocked blots were incubated with the primary antibody against the γ‐ENaC subunit overnight at 4°C in a 1:1000 dilution. γ‐ENaC subunit was detected with a fluorescent secondary antibody labelled with IRDye 800CW. For loading control, total protein was measured using Revert Total Protein Stain. Anti‐γ‐ENaC was raised in rabbits against the C‐terminal amino acids 634–655 of γ‐ENaC (SPC‐405, Stressmaq). Results Western blot analysis from murine kidney cortex samples for γ‐ENaC revealed a band at 74 kDa and below this a blurry signal which extended until 64 kDa. Deglycosylation of the same samples using PNGaseF led to characteristic shifts of the migration pattern of γ‐ENaC subunit. The most significant change was obtained where the migration pattern changed with three separate bands arising at 74, 60 and 53 kDa. The molecular mass of the obtained bands approximated the expected mass calculated from the amino acid sequence suggesting that these bands at 74, 60 and 53 kDa represent full length, furin‐cleaved and fully cleaved γ‐ENaC, respectively. Kidneys from nephrotic mice displayed increased expression of fully cleaved γ‐ENaC in samples collected at day 8 after induction of nephrotic syndrome. Treatment of nephrotic mice with the serine protease inhibitor aprotinin normalized the expression of fully cleaved γ‐ENaC. Conclusion Deglycosylation leads to the detection of the expression of fully cleaved γ‐ENaC from kidney tissues. Nephrotic syndrome leads to increased expression of fully cleaved γ‐ENaC which might mediates sodium retention.
The alchemical symbols in the manuscripts of “The Mirror of Wonders” (Mirʾāt al-ʿajāʾib)
2021-05-01

Abstract “The Mirror of Wonders” ( Mirʾāt al-ʿajāʾib ) is an illustrated Arabic treatise about a mysterious mirror that displays different alchemical symbols. This work of unsettled authorship, which was composed between the 12th and 16th centuries, has got a rich manuscript tradition with more than 45 extant copies dating from the 16th to the 20th centuries, including translations into Turkish and Persian and various short versions of the text. They prove the remarkable popularity of “The Mirror of Wonders” throughout the Islamicate world, even in modern times. Most manuscripts contain a coloured illustration of the mirror and its symbols, with a large scope of variation in their visual design. The nine alchemical symbols of the mirror are: 1. The two figures embracing each other ( al-shakhṣān al-muʿtaniqān ); 2. The black circle ( al- dāʾira al-sawdāʾ ); 3. The palm of the hand ( al-kaff ); 4. The black raven ( al-ghurāb al-aswad ); 5. The eagle ( al-ʿuqāb ); 6. The sun ( al-shams ); 7. The snake ( al-thuʿbān ); 8. The nine crabs ( al-saraṭānāt al-tisʿa ) with the dog descending into the water ( al-kalb al-nāzil fī l-māʾ ) and 9. The nine circles ( al-dawāʾir al-tisʿa ). This paper presents the manuscript tradition of Mirʾāt al-ʿajāʾib and analyses the diverging imagery of the symbols and their meanings in the different manuscripts.
Detection of reduced diameter of nervus cochlearis in long term deaf patients quantified with semiautimatic 3 tesla MRI ZOOMIT sequence
2021-05-01

Beside audiological testing routine preoperative evaluation includes MRI scan of the neurocranium. This allows the evaluation of the morphology of the nerves in the inner ear canal. Earlier studies have shown that the diameter of the cochlear nerve can be used as prognostic marker for the auditory performance after cochlear implantation. In this study we used 3 tesla MRI ZOOMIT sequence together with semiautomatic analysis to determine the maximal area of the nerves in the inner ear canal. We therefore retrospectively analyzed 100 3 tesla MRI scans with ZOOMIT Sequence using our semiautomatic tool to measure area of cochlear, vestibular and facial nerve in the inner ear canal and correlated this with patient history and audiology testing. We evaluated 5 groups of patient with a length of deafness of more than 20 years (normakusis, 11-40 dB hearing loss (hl), 41-70 dB hl, 71-100 dB hl and complete deafness) and calculated the quotient of cochlear and facial nerve area. There was a significant difference between patients with normakusis (1.29 ± 0.15 mm2) and patients with hearing loss of more than 41 dB (1.03 ±0.16, 0.99 ± 0.07 und 0.88 ± 0.1 mm2). However there was no significant difference in patients with moderate hearing loss (11-40 dB). Therefor we could show that in long term deaf patients, the diameter of the cochlear nerve is decreasing the more severe the hearing loss is. Also, the maximal area of the facial nerve was not different between all groups. This tool can therefore be used prior to cochlea implantation to assess nerve diameter and possibly determine patients with nerve degeneration that will possibly not profit from cochlear implantation or vice versa.
Replication and Reproducibility in Primate Cognition Research
2021-05-02

Replication is an important tool used to test and develop scientific theories. Areas of biomedical and psychological research have experienced a replication crisis, in which many published findings failed to replicate. Following this, many other scientific disciplines have been interested in the robustness of their own findings. This chapter examines replication in primate cognitive studies. First, it discusses the frequency and success of replication studies in primate cognition and explores the challenges researchers face when designing and interpreting replication studies across the wide range of research designs used across the field. Next, it discusses the type of research that can probe the robustness of published findings, especially when replication studies are difficult to perform. The chapter concludes with a discussion of different roles that replication can have in primate cognition research.