julilili42/papers huggingface dataset:
Host-Pathogen Adhesion as the Basis of Innovative Diagnostics for Emerging Pathogens
2021-07-14

Infectious diseases are an existential health threat, potentiated by emerging and re-emerging viruses and increasing bacterial antibiotic resistance. Targeted treatment of infectious diseases requires precision diagnostics, especially in cases where broad-range therapeutics such as antibiotics fail. There is thus an increasing need for new approaches to develop sensitive and specific in vitro diagnostic (IVD) tests. Basic science and translational research are needed to identify key microbial molecules as diagnostic targets, to identify relevant host counterparts, and to use this knowledge in developing or improving IVD. In this regard, an overlooked feature is the capacity of pathogens to adhere specifically to host cells and tissues. The molecular entities relevant for pathogen–surface interaction are the so-called adhesins. Adhesins vary from protein compounds to (poly-)saccharides or lipid structures that interact with eukaryotic host cell matrix molecules and receptors. Such interactions co-define the specificity and sensitivity of a diagnostic test. Currently, adhesin-receptor binding is typically used in the pre-analytical phase of IVD tests, focusing on pathogen enrichment. Further exploration of adhesin–ligand interaction, supported by present high-throughput “omics” technologies, might stimulate a new generation of broadly applicable pathogen detection and characterization tools. This review describes recent results of novel structure-defining technologies allowing for detailed molecular analysis of adhesins, their receptors and complexes. Since the host ligands evolve slowly, the corresponding adhesin interaction is under selective pressure to maintain a constant receptor binding domain. IVD should exploit such conserved binding sites and, in particular, use the human ligand to enrich the pathogen. We provide an inventory of methods based on adhesion factors and pathogen attachment mechanisms, which can also be of relevance to currently emerging pathogens, including SARS-CoV-2, the causative agent of COVID-19.
Bonding Interface and Repairability of 3D-Printed Intraoral Splints: Shear Bond Strength to Current Polymers, with and without Ageing
2021-07-14

This in-vitro study investigates the bonding interfaces reached by the conditioning of a splint material additively manufactured by digital light processing (AM base) as well as the shear bond strength (SBS) of resins bonded to these surfaces (repair material). Therefore, the AM base was either stored in dry for 12 h or wet environment for 14 days to simulate ageing by intraoral wear. The dry and wet group was bonded after physical and/or chemical conditioning to cylinders made from polymethylmethacrylate or four novel polymers allowing splint modifications. Blasted and methylmethacrylate (MMA)-conditioned Polymethylmethacrylate (PMMA) bonded to PMMA acted as the gold standard. The surface profiles revealed highest differences of Ra towards the gold standard in AM base conditioned with other than MMA after sandblasting. The adhesively bonded repair materials of the wet AM base were further aged in wet environment for 14 days. The SBS of the gold standard (25.2 MPa and 25.6 MPa) was only reached by PMMA bonded to blasted and MMA-conditioned AM base after dry (22.7 MPa) and non-conditioned after wet storage (23 MPa). Four repair materials failed to reach the threshold of 5 MPa after dry storage and three after wet storage, respectively. Non-conditioned AM base revealed the highest risk for adhesive fractures when using other resins than PMMA.
Accuracy Evaluation of Additively and Subtractively Fabricated Palatal Plate Orthodontic Appliances for Newborns and Infants – An In-vitro Study
2021-07-14

Different approaches for digital workflows have already been presented for their use in palatal plates for newborns and infants. However, there is no evidence on the accuracy of CAD/CAM manufactured orthodontic appliances for this kind of application. This study evaluates trueness and precision provided by different CAM technologies and materials for these appliances. Samples of a standard palatal stimulation plate were manufactured using stereolithography (SLA), direct light processing (DLP) and subtractive manufacturing (SM). The effect of material (for SM) and layer thickness (for DLP) were also investigated. Specimens were digitized with a laboratory scanner (D2000, 3Shape) and analyzed with a 3D inspection software (Geomagic Control X, 3D systems). For quantitative analysis, differences between 3D datasets were measured using root mean square (RMS) error values for trueness and precision. For qualitative analysis, color maps were generated to detect locations of deviations within each sample. SM showed higher trueness and precision than AM technologies. Reducing layer thickness in DLP did not significantly increase accuracy, but prolonged manufacturing time. All materials and technologies met the clinically acceptable range and are appropriate for their use. DLP with 100&amp;micro;m layer thickness showed the highest efficiency, obtaining high trueness and precision within the lowest manufacturing time.
Crown outline analysis of the hominin upper third molar from the Megalopolis Basin, Peloponnese, Greece
2021-07-14

The left upper third molar from the Megalopolis Basin is enigmatic due to its problematic preservation and context. The Megalopolis molar is the only possible human fossil known to date from the Megalopolis Basin. It was found on the surface during geological surveys in 1962-63. Based on the faunal assemblage collected during the same survey, it was proposed to be of Middle Pleistocene age and possibly one of the oldest human fossils in Europe. However, its actual geological age is unknown. In the past, dental crown outline analysis has been successfully used to differentiate between hominin species and populations. We applied the method to upper third molars, attempting to shed light on the affinities of the Megalopolis specimen. Principal component analysis (PCA) of the crown outline shape grouped the Megalopolis molar with our Homo sapiens sample; however, the PCA in form space, including shape plus size, as well as Procrustes distances based on overall shape, grouped it with our Neanderthal comparative sample. We conclude that its most likely identification is as a member of the Neanderthal lineage. However, we urge further analyses with an increased fossil comparative sample to include representatives of Homo heidelbergensis, which is underrepresented in our study. The Megalopolis molar contributes to the scarce Pleistocene human fossil record of Greece and highlights the potential of the Megalopolis Basin for yielding further paleoanthropological finds.
Value of PET imaging for radiation therapy
2021-07-14

Abstract This comprehensive review written by experts in their field gives an overview on the current status of incorporating positron emission tomography (PET) into radiation treatment planning. Moreover, it highlights ongoing studies for treatment individualisation and per-treatment tumour response monitoring for various primary tumours. Novel tracers and image analysis methods are discussed. The authors believe this contribution to be of crucial value for experts in the field as well as for policy makers deciding on the reimbursement of this powerful imaging modality.
Modelling pre-modern flow distances of inland waterways – a GIS study in southern Germany
2021-07-14

&lt;p class="VARAbstract"&gt;Rivers form major traffic arteries in pre-modern Central Europe and accurate regional to supra-regional network models of inland navigation are crucial for economic history. However, navigation distances have hitherto been based on modern flow distances, which could be a significant source of error due to modern changes in flow distance and channel pattern. Here, we use a systematic comparison of vectorized old maps, which enlighten the fluvial landscape before most of the large-scale river engineering took place, and modern opensource geodata to deduce change ratios of flow distance and channel patterns. The river courses have been vectorised, edited and divided into comparable grid units. Based on the thalweg, meandering and braided/anabranching river sections have been identified and various ratios have been calculated in order to detect changes in length and channel patterns. Our large-scale analytical approach and Geographic Information System (GIS) workflow are transferable to other rivers in order to deduce change ratios on a European scale. The 19&lt;sup&gt;th&lt;/sup&gt; century flow distance is suitable to model pre-modern navigation distances. As a case study, we have used our approach to reconstruct changes of flow pattern, flow distance and subsequent changes in navigation distance and transportation time for the rivers Altmühl, Danube, Main, Regnitz, Rednitz, Franconian and Swabian Rezat (Southern Germany). The change ratio is rather heterogeneous with length and travel time changes of the main channel up to 24% and an extensive transformation of channel morphology in many river sections. Based on published travel time data, we have modelled the effect of our change ratios. Shipping between the commercial hubs Ulm and Regensburg, to give an example, was up to 5 days longer based on pre-modern distances. This is highly significant and underlines the necessity for river-specific correction values to model supra-regional networks of pre-modern inland waterways and navigation with higher precision.&lt;/p&gt;&lt;p&gt;Highlights:&lt;/p&gt;&lt;ul&gt;&lt;li&gt;&lt;p&gt;Systematic comparison of old maps and modern geodata to deduce river-specific length correction values to improve supra-regional network models of pre-modern inland navigation.&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Large-scale analytical approach and transferable GIS workflow for flow distance reconstruction with case studies in Southern Germany.&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Length changes of navigated fairways result in pre-modern period travel times up to 24% higher in corrected models.&lt;/p&gt;&lt;/li&gt;&lt;/ul&gt;
Advancing research on unconscious priming: When can scientists claim an indirect task advantage?
2021-07-15

Current literature holds that many cognitive functions can be performed outside consciousness. Evidence for this view comes from unconscious priming. In a typical experiment, visual stimuli are masked such that participants are close to chance performance when directly asked to which of two categories the stimuli belong. This close-to-zero sensitivity is seen as evidence that participants cannot consciously report the category of the masked stimuli. Nevertheless, the category of the masked stimuli can indirectly affect responses to other stimuli (e.g., reaction times or brain activity)-an effect called priming. The priming effect is seen as evidence for a higher sensitivity to the masked stimuli in the indirect responses as compared with the direct responses. Such an apparent difference in sensitivities is taken as evidence that processing occurred unconsciously. But we show that this "standard reasoning of unconscious priming" is flawed: Sensitivities are not properly compared, creating the wrong impression of a difference in sensitivities even if there is none. We describe the appropriate way to determine sensitivities, replicate the behavioral part of a landmark study, develop methods to estimate sensitivities from reported summary statistics of published studies, and use these methods to reanalyze 15 highly influential studies. Results show that the interpretations of many studies need to be changed and that a community effort is required to reassess the vast literature on unconscious priming. This process will allow scientists to learn more about the true boundary conditions of unconscious priming, thereby advancing the scientific understanding of consciousness. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
In vivo macromolecule signals in rat brain 1H‐MR spectra at 9.4T: Parametrization, spline baseline estimation, and T2 relaxation times
2021-07-15

Purpose Reliable detection and fitting of macromolecules (MM) are crucial for accurate quantification of brain short‐echo time (TE) 1 H‐MR spectra. An experimentally acquired single MM spectrum is commonly used. Higher spectral resolution at ultra‐high field (UHF) led to increased interest in using a parametrized MM spectrum together with flexible spline baselines to address unpredicted spectroscopic components. Herein, we aimed to: (1) implement an advanced methodological approach for post‐processing, fitting, and parametrization of 9.4T rat brain MM spectra; (2) assess the concomitant impact of the LCModel baseline and MM model (ie, single vs parametrized); and (3) estimate the apparent T 2 relaxation times for seven MM components. Methods A single inversion recovery sequence combined with advanced AMARES prior knowledge was used to eliminate the metabolite residuals, fit, and parametrize 10 MM components directly from 9.4T rat brain in vivo 1 H‐MR spectra at different TEs. Monte Carlo simulations were also used to assess the concomitant influence of parametrized MM and DKNTMN parameter in LCModel. Results A very stiff baseline (DKNTMN ≥ 1 ppm) in combination with a single MM spectrum led to deviations in metabolite concentrations. For some metabolites the parametrized MM showed deviations from the ground truth for all DKNTMN values. Adding prior knowledge on parametrized MM improved MM and metabolite quantification. The apparent T 2 ranged between 12 and 24 ms for seven MM peaks. Conclusion Moderate flexibility in the spline baseline was required for reliable quantification of real/experimental spectra based on in vivo and Monte Carlo data. Prior knowledge on parametrized MM improved MM and metabolite quantification.
A Regulator Based “Semi-Targeted” Approach to Activate Silent Biosynthetic Gene Clusters
2021-07-15

By culturing microorganisms under standard laboratory conditions, most biosynthetic gene clusters (BGCs) are not expressed, and thus, the products are not produced. To explore this biosynthetic potential, we developed a novel “semi-targeted” approach focusing on activating “silent” BGCs by concurrently introducing a group of regulator genes into streptomycetes of the Tübingen strain collection. We constructed integrative plasmids containing two classes of regulatory genes under the control of the constitutive promoter ermE*p (cluster situated regulators (CSR) and Streptomyces antibiotic regulatory proteins (SARPs)). These plasmids were introduced into Streptomyces sp. TÜ17, Streptomyces sp. TÜ10 and Streptomyces sp. TÜ102. Introduction of the CSRs-plasmid into strain S. sp. TÜ17 activated the production of mayamycin A. By using the individual regulator genes, we proved that Aur1P, was responsible for the activation. In strain S. sp. TÜ102, the introduction of the SARP-plasmid triggered the production of a chartreusin-like compound. Insertion of the CSRs-plasmid into strain S. sp. TÜ10 resulted in activating the warkmycin-BGC. In both recombinants, activation of the BGCs was only possible through the simultaneous expression of aur1PR3 and griR in S. sp. TÜ102 and aur1P and pntR in of S. sp. TÜ10.
A Novel Small Molecule Neurotrophin-3 Analogue Promotes Inner Ear Neurite Outgrowth and Synaptogenesis In vitro
2021-07-15

Sensorineural hearing loss is irreversible and is associated with the loss of spiral ganglion neurons (SGNs) and sensory hair cells within the inner ear. Improving spiral ganglion neuron (SGN) survival, neurite outgrowth, and synaptogenesis could lead to significant gains for hearing-impaired patients. There has therefore been intense interest in the use of neurotrophic factors in the inner ear to promote both survival of SGNs and re-wiring of sensory hair cells by surviving SGNs. Neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) represent the primary neurotrophins in the inner ear during development and throughout adulthood, and have demonstrated potential for SGN survival and neurite outgrowth. We have pioneered a hybrid molecule approach to maximize SGN stimulation in vivo , in which small molecule analogues of neurotrophins are linked to bisphosphonates, which in turn bind to cochlear bone. We have previously shown that a small molecule BDNF analogue coupled to risedronate binds to bone matrix and promotes SGN neurite outgrowth and synaptogenesis in vitro . Because NT-3 has been shown in a variety of contexts to have a greater regenerative capacity in the cochlea than BDNF, we sought to develop a similar approach for NT-3. 1Aa is a small molecule analogue of NT-3 that has been shown to activate cells through TrkC, the NT-3 receptor, although its activity on SGNs has not previously been described. Herein we describe the design and synthesis of 1Aa and a covalent conjugate of 1Aa with risedronate, Ris-1Aa. We demonstrate that both 1Aa and Ris-1Aa stimulate neurite outgrowth in SGN cultures at a significantly higher level compared to controls. Ris-1Aa maintained its neurotrophic activity when bound to hydroxyapatite, the primary mineral component of bone. Both 1Aa and Ris-1Aa promote significant synaptic regeneration in cochlear explant cultures, and both 1Aa and Ris-1Aa appear to act at least partly through TrkC. Our results provide the first evidence that a small molecule analogue of NT-3 can stimulate SGNs and promote regeneration of synapses between SGNs and inner hair cells. Our findings support the promise of hydroxyapatite-targeting bisphosphonate conjugation as a novel strategy to deliver neurotrophic agents to SGNs encased within cochlear bone.
Naïve, unenculturated chimpanzees fail to make and use flaked stone tools
2021-07-15

<ns4:p><ns4:bold>Background</ns4:bold>: Despite substantial research on early hominin lithic technologies, the learning mechanisms underlying flake manufacture and use are contested. To draw phylogenetic inferences on the potential cognitive processes underlying the acquisition of both of these abilities in early hominins, we investigated if and how one of our closest living relatives, chimpanzees (<ns4:italic>Pan troglodytes</ns4:italic>), could learn to make and use flakes.</ns4:p><ns4:p><ns4:bold>Methods</ns4:bold>: Across several experimental conditions, we tested eleven task-naïve chimpanzees (unenculturated n=8, unknown status n=3) from two independent populations for their abilities to spontaneously make and subsequently use flakes as well as to use flakes made by a human experimenter.</ns4:p><ns4:p><ns4:bold>Results</ns4:bold>: Despite the fact that the chimpanzees seemed to understand the requirements of the task, were sufficiently motivated and had ample opportunities to develop the target behaviours, none of the chimpanzees tested made or used flakes in any of the experimental conditions.</ns4:p><ns4:p><ns4:bold>Conclusions</ns4:bold>: These results differ from all previous ape flaking experiments, which found flake manufacture and use in bonobos and one orangutan. However, these earlier studies tested human-enculturated apes and provided test subjects with flake making and using demonstrations. The contrast between these earlier positive findings and our negative findings (despite using a much larger sample size) suggests that enculturation and/or demonstrations may be necessary for chimpanzees to acquire these abilities. The data obtained in this study are consistent with the hypothesis that flake manufacture and use might have evolved in the hominin lineage after the split between<ns4:italic>Homo</ns4:italic>and<ns4:italic>Pan</ns4:italic>7 million years ago, a scenario further supported by the initial lack of flaked stone tools in the archaeological record after this split. We discuss possible evolutionary scenarios for flake manufacture and use in both non-hominin and hominin lineages.</ns4:p>
Discovery of a Potent and Highly Isoform-Selective Inhibitor of the Neglected Ribosomal Protein S6 Kinase Beta 2 (S6K2)
2021-07-15

The ribosomal protein S6 kinase beta 2 (S6K2) is thought to play an important role in malignant cell proliferation but is understudied compared to its closely related isoform S6 kinase beta 1 (S6K1). To better understand the biological function of S6K2, chemical probes are needed but the high structural homology between S6K2 and S6K1 makes it challenging to selectively address S6K2 with small molecules. We were able to design the first potent and highly isoform-specific S6K2 inhibitor by merging a known S6K1-selective inhibitor with a covalent inhibitor known to engage a cysteine located in the hinge region in the fibroblast growth factor receptor kinase (FGFR) 4 via a nucleophilic aromatic substitution (SNAr) reaction. The title compound shows high selectivity over kinases with an equivalently positioned cysteine as well as in a larger kinase panel. Good stability towards glutathione indicated a non-promiscuous reactivity pattern. Thus, the title compound represents an important step towards a high-quality chemical probe to study S6K2-specific signalling.
Red, black, and white hearts: ‘heart’, ‘liver’, and ‘lungs’ in typological and areal perspective
2021-07-15

Abstract On the basis of a sample of 424 languages or dialects, this article provides a typological-comparative investigation of designations for three major internal organs of the torso, the ‘heart’, the ‘liver’, and the ‘lungs’. While colexification patterns are relatively unconstrained, the data show a skewing in morphologically complex terms: ‘heart’ and ‘liver’ often serve as head nouns in complex terms for ‘lungs’, but the reverse is rare. Another recurrent phenomenon is that two of the organs –sometimes ‘heart’ and ‘lungs’, but more frequently ‘liver’ and ‘lungs’– share their head noun, and are distinguished from one another by modifiers that refer to their most salient characteristics, as in Azerbaijani aɣ ǯiyær ‘white ǯiyær’ = ‘lungs’ and gara-ǯiyær ‘black-ǯiyær’ = ‘liver’. Having thus set the typological stage, I move on to discuss two different regions of the world in which such terms for ‘lungs’ and ‘liver’ have spread through language contact. This has happened in Eurasia, where the abovementioned pattern, which I call “explicitly dyadic”, was brought from Turkish to vernaculars of the Balkans and, most likely through Azerbaijani influence, to languages of the Southern Caucasus. Similar explicitly dyadic terms, but based on a head noun meaning ‘heart’, also occur in the Andes, where they appear to have spread from Quechuan to Barbacoan languages. The evidence not only shows that ‘liver’ and ‘lungs’ form a “semantic dyad” in which designations make use of “opposed characteristics” in different regions of the world, but also that such designations are salient and therefore prone to spread in language contact situations.
The Laschamps geomagnetic excursion recorded in continental sediments from southern Germany
2021-07-15

SUMMARY We present palaeo- and rock magnetic results from a well-dated, 21 m-thick, Late Pleistocene continental sedimentary section located in southern Germany. Rock magnetic measurements reveal a complex magnetic mineralogy dominated by low coercivity minerals likely related to single domain biogenic magnetite and biogenic or early diagenetic greigite. In the lower part of the section also detrital haematite is present. The stable remanence shows predominantly normal polarity with two marked deviations at ∼1280-1200 cm and at 886 cm profile depth. Whereas the lower excursion is well established by several samples and documented also by detrital haematite, the upper one is only represented by a single sample and revealed by magnetite and greigite. Using the radiocarbon-based age model for the section, the lower excursion yields an age of 42.8–41.3 ka cal BP and is interpreted to represent the Laschamps geomagnetic excursion. The increased abundance of greigite in the upper part of the section, especially in the sample responsible for the upper anomalous direction, renders the interpretation of an actual excursion problematic due to the reducing environment necessary for the greigite formation.