julilili42/papers huggingface dataset:
Characterization, Stability, and In Vivo Efficacy Studies of Recombinant Human CNTF and Its Permeation into the Neural Retina in Ex Vivo Organotypic Retinal Explant Culture Models
2020-06-30

Ciliary neurotrophic factor (CNTF) is one of the most studied neuroprotective agents with acknowledged potential in treating diseases of the posterior eye segment. Although its efficacy and mechanisms of action in the retina have been studied extensively, it is still not comprehensively understood which retinal cells mediate the therapeutic effects of CNTF. As with therapeutic proteins in general, it is poorly elucidated whether exogenous CNTF administered into the vitreous can enter and distribute into the retina and hence reach potentially responsive target cells. Here, we have characterized our purified recombinant human CNTF (rhCNTF), studied the protein’s in vitro bioactivity in a cell-based assay, and evaluated the thermodynamic and oligomeric status of the protein during storage. Biological activity of rhCNTF was further evaluated in vivo in an animal model of retinal degeneration. The retinal penetration and distribution of rhCNTF after 24 h was studied utilizing two ex vivo retina models. Based on our characterization findings, our rhCNTF is correctly folded and biologically active. Moreover, based on initial screening and subsequent follow-up, we identified two buffers in which rhCNTF retains its stability during storage. Whereas rhCNTF did not show photoreceptor preservative effect or improve the function of photoreceptors in vivo, this could possibly be due to the used disease model or the short duration of action with a single intravitreal injection of rhCNTF. On the other hand, the lack of in vivo efficacy was shown to not be due to distribution limitations; permeation into the retina was observed in both retinal explant models as in 24 h rhCNTF penetrated the inner limiting membrane, and being mostly observed in the ganglion cell layer, distributed to different layers of the neural retina. As rhCNTF can reach deeper retinal layers, in general, having direct effects on resident CNTF-responsive target cells is plausible.
Deuteron EDM induced by CP-violating couplings of pseudoscalar mesons
2020-06-30

We analyze contributions to the electric dipole (EDM) and Schiff (SFM)\\nmoments of deuteron induced by the CP-violating three-pseudoscalar meson\\ncouplings using phenomenological Lagrangian approach involving nucleons and\\npseudoscalar mesons . Deuteron is considered as a\\nproton-neutron bound state and its properties are defined by one- and two-body\\nforces. One-body forces correspond to a picture there proton and neutron are\\nquasi free constituents of deuteron and their contribution to the deuteron EDM\\n(dEDM) is simply the sum of proton and neutron EDMs. Two-body forces in\\ndeuteron are induced by one-meson exchange between nucleons. They produce a\\ncontribution to the dEDM, which is estimated using corresponding potential\\napproach. From numerical analysis of nucleon and deuteron EDMs we derive\\nstringent limits on CP-violating hadronic couplings and parameter.\\nWe showed that proposed measurements of proton and deuteron EDMs at level of\\n by the Store Ring EDM and JEDI Collaborations will provide more\\nstringent upper limits on the CP violating parameters.\\n
Antibodies to the Muscarinic Acetylcholine Receptor M3 in Primary Biliary Cholangitis Inhibit Receptor Function on Cholangiocytes
2020-06-30

<b>Background and Aims:</b> In primary biliary cholangitis (PBC), antibodies to a peptide of the muscarinic acetylcholine receptor 3 (mAChR3) have been described. Since the mAChR3 is expressed on cholangiocytes and mAChR3-signaling is involved in the pathogenesis of chronic inflammatory biliary diseases, we wanted to investigate whether anti-mAChR3-antibodies influence the function of the receptor and the proliferative response of cholangiocytes. <b>Methods:</b> Immunoglobulins were isolated by ammonium sulfate precipitation using sera from patients with PBC (<i>n</i> = 63) and with other chronic liver disorders (<i>n</i> = 150). All immunoglobulins were analyzed by a luminometric assay using Chinese hamster ovary (CHO) cells overexpressing the mAChR3 and cholangiocytes (TFK-1-cells) expressing the receptor constitutively. Cell proliferation was measured by <sup>3</sup>H-thymidine assay. PBC patients were also analyzed in the follow-up. <b>Results:</b> Antibodies inhibiting the mAChR3 were found in 49 and 79% of PBC patients using CHO-cells or TFK-1-cells, respectively, but only in up to 26% of controls (<i>p</i> < 0.01). Stimulatory antibodies were hardly detected. Antibody reactivity only marginally changed during the course of the disease, independently of the choice of treatment (ursodeoxycholic acid, immunosuppressive therapy, or no medication). There was no correlation with laboratory, clinical or histological parameters, but the antibodies were more frequently found in PBC patients with a benign course (96%) than in patients with active disease progressing to late stages within 10 years (57%; <i>p</i> < 0.01). Proliferation of cells was not influenced by immunoglobulins from PBC-patients. <b>Conclusion:</b> Sera from patients with PBC contain inhibitory antibodies to the mAChR3 on cholangiocytes (TFK-1 cells) without influencing TFK-1-cell proliferation. These antibodies were predominantly observed in patients with non-progressing PBC.
Digital Documentation of the Saite Tombs in Saqqara
2020-06-30

This paper focuses on the digital documentation techniques employed in the recording of a number of Saite-Persian sarcophagus-tombs in the necropolis of Saqqara (Egypt). In this paper, we discus pros and cons of different three-dimensional technologies for the documentation of a vast site as well as the process of ongoing excavation. We then delve into a discussion of the results and benefits of the employed techniques, particularly understanding the complex spatial relationships of archaeological features both aboveground and underground. Furthermore, we explain how we derive precise scaled and ortho-rectified images of all inscribed walls and objects from the recorded 3D-information in order to produce digital facsimiles. The 3D approach gives us the opportunity to create an exact digital copy of the site, and to record all stages of the excavation. The produced 3D models can be used in various virtual environments in order to give researchers and the general public the possibility to visit and to examine the site from a distance. Also, it is important to note that this paper presents a sustainable long-term data-archiving strategy, since saving the digitally-born data for future generations is an integral part of our Saqqara Saite Tombs Project.
Cytotoxicity Burst? Differentiating Specific from Nonspecific Effects in Tox21 in Vitro Reporter Gene Assays
2020-07-01

The specificity analysis for measured <i>in vitro</i> effects identified whether a cytotoxicity burst had likely occurred. The SR-analysis not only prevented false positives, but it may also serve as measure for relative effect potency and can be used for quantitative <i>in vitro-in vivo</i> extrapolation and risk assessment of chemicals. https://doi.org/10.1289/EHP6664.
The epidemiology of dengue outbreaks in 2016 and 2017 in Ouagadougou, Burkina Faso
2020-07-01

BACKGROUND: Dengue is prevalent in as many as 128 countries with more than 100 million clinical episodes reported annually and four billion people estimated to be at risk. While dengue fever is systematically diagnosed in large parts of Asia and South America, the disease burden in Africa is less well investigated. This report describes two consecutive dengue outbreaks in Ouagadougou, Burkina Faso in 2016 and 2017. METHODS: Blood samples of febrile patients received at Schiphra laboratory in Ouagadougou, Burkina Faso, were screened for dengue infection using SD Bioline Dengue Duo rapid diagnostic test kits (Standard Diagnostics, Suwon, Republic of Korea). RESULTS: A total of 1,397 and 1,882 cases were reported by a single laboratory in 2016 and 2017, respectively. Most cases were at least 15 years of age and the results corroborated reports from WHO indicating the circulation of three dengue virus serotypes in Burkina Faso. CONCLUSION: This study complements data from other, simultaneously conducted surveillance efforts, and indicates that the dengue disease burden might be underestimated in sub-Saharan African nations. Dengue surveillance should be enhanced in African settings to determine the burden more accurately, and accelerated efforts towards a dengue vaccine should be put in place.
Reprogramming Acetogenic Bacteria with CRISPR-Targeted Base Editing via Deamination
2020-07-01

Acetogenic bacteria are rising in popularity as chassis microbes for biotechnology due to their capability of converting inorganic one-carbon (C1) gases to organic chemicals. To fully uncover the potential of acetogenic bacteria, synthetic biology tools are imperative to either engineer designed functions or to interrogate the physiology. Here, we report a genome-editing tool at a one-nucleotide resolution, namely base editing, for acetogenic bacteria based on CRISPR-targeted deamination. This tool combines nuclease deactivated Cas9 with activation-induced cytidine deaminase to enable cytosine-to-thymine substitution without DNA cleavage, homology-directed repair, and donor DNA, which are generally the bottlenecks for applying conventional CRISPR-Cas systems in bacteria. We designed and validated a modularized base-editing tool in the model acetogenic bacterium <i>Clostridium ljungdahlii</i>. The editing principles were investigated, and an <i>in-silico</i> analysis revealed the capability of base editing across the genome and the potential for off-target events. Moreover, genes related to acetate and ethanol production were disrupted individually by installing premature STOP codons to reprogram carbon flux toward improved acetate production. This resulted in engineered <i>C. ljungdahlii</i> strains with the desired phenotypes and stable genotypes. Our base-editing tool promotes the application and research in acetogenic bacteria and provides a blueprint to upgrade CRISPR-Cas-based genome editing in bacteria in general.
The craniomandibular anatomy of the early archosauriformEuparkeria capensisand the dawn of the archosaur skull
2020-07-01

Archosauria (birds, crocodilians and their extinct relatives) form a major part of terrestrial ecosystems today, with over 10 000 living species, and came to dominate the land for most of the Mesozoic (over 150 Myr) after radiating following the Permian–Triassic extinction. The archosaur skull has been essential to this diversification, itself diversified into myriad forms. The archosauriform Euparkeria capensis from the Middle Triassic (Anisian) of South Africa has been of great interest since its initial description in 1913, because its anatomy shed light on the origins and early evolution of crown Archosauria and potentially approached that of the archosaur common ancestor. Euparkeria has been widely used as an outgroup in phylogenetic analyses and when investigating patterns of trait evolution among archosaurs. Although described monographically in 1965, subsequent years have seen great advances in the understanding of early archosaurs and in imaging techniques. Here, the cranium and mandible of Euparkeria are fully redescribed and documented using all fossil material and computed tomographic data. Details previously unclear are fully described, including vomerine dentition, the epiptergoid, number of premaxillary teeth and palatal arrangement. A new diagnosis and cranial and braincase reconstruction is provided, and an anatomical network analysis is performed on the skull of Euparkeria and compared with other amniotes. The modular composition of the cranium suggests a flexible skull well adapted to feeding on agile food, but with a clear tendency towards more carnivorous behaviour, placing the taxon at the interface between ancestral diapsid and crown archosaur ecomorphology, corresponding to increases in brain size, visual sensitivity, upright locomotion and metabolism around this point in archosauriform evolution. The skull of Euparkeria epitomizes a major evolutionary transition, and places crown archosaur morphology in an evolutionary context.
Testing General Relativity with the Stellar-mass Black Hole in LMC X-1 Using the Continuum-fitting Method
2020-07-01

Abstract The iron-line and continuum-fitting methods are currently the two leading techniques for measuring black-hole spins with electromagnetic radiation. They can be naturally extended for probing the spacetime geometry around black holes and testing general relativity in the strong field regime. In the past couple of years, there has been significant work to use the iron-line method to test the nature of black holes. Here we use the continuum-fitting method and we show its capability of constraining the spacetime geometry around black holes by analyzing 17 Rossi X-ray Timing Explorer data of the X-ray binary LMC X-1.
X-ray reflection spectroscopy with Kaluza–Klein black holes
2020-07-01

Abstract Kaluza–Klein theory is a popular alternative theory of gravity, with both non-rotating and rotating black hole solutions known. This allows for the possibility that the theory could be observationally tested. We present a model which calculates the reflection spectrum of a black hole accretion disk system, where the black hole is described by a rotating solution of the Kaluza–Klein theory. We also use this model to analyze X-ray data from the stella-mass black hole in GRS 1915+105 and provide constraints on the free parameters of the Kaluza–Klein black holes.
Surgical management of submacular hemorrhage due to n-AMD: a comparison of three surgical methods
2020-07-01

Abstract Background To compare and assess the efficacy of three surgical methods for the treatment of acute submacular hemorrhage (ASH): pneumatic displacement with C2F6, in combination with intravitreal injection of bevacizumab and rtPA, pars plana vitrectomy (PPV) with intravitreal injection of gas (C2F6), bevacizumab and subretinal injection of recombinant tissue plasminogen activator (rtPA), pars plana vitrectomy (PPV) with intravitreal injection of gas (C2F6), bevacizumab and intravitreal injection of recombinant tissue plasminogen activator (rtPA). Methods The study included 85 patients with ASH. In the group without PPV (A), patients were treated with intravitreal injection of C2F6, bevacizumab and rtPA. In the second and third group, patients underwent a PPV, intravitreal injection of bevacizumab, pneumatic displacement with C2F6 and a subretinal (B) or intravitreal (C) injection of recombinant tissue plasminogen activator (rt PA). Results In group A, mean BCVA increased from preop logMAR 1.41 to 1.05, in group B from 1.46 to 1.28 and in group C from 1.63 to 1.33. In group A, CFT changed from 764 ± 340 μm at time point 0 to 246 ± 153 μm at time point 1, in group B from 987 ± 441 μm to 294 ± 166 μm and in group C from 642 ± 322 μm to 418 ± 364 μm. Patients had an average of 5 injections after surgery. Conclusion Our study demonstrates that the three methods are equally effective in improving the morphology and the BCVA of patients with ASH.
The First Inherited Retinal Disease Registry in Iran: Research Protocol and Results of a Pilot Study
2020-07-01

Background: To describe the protocol for developing a national inherited retinal disease (IRD) registry in Iran and present its initial report. Methods: This community-based participatory research was approved by the Ministry of Health and Medical Education of Iran in 2016. To provide the minimum data set (MDS), several focus group meetings were held. The final MDS was handed over to an engineering team to develop a web-based software. In the pilot phase, the software was set up in two referral centers in Iran. Final IRD diagnosis was made based on clinical manifestations and genetic findings. Ultimately, patient registration was done based on all clinical and non-clinical manifestations. Results: Initially, a total of 151 data elements were approved with Delphi technique. The registry software went live at www. IRDReg.org based on DHIS2 open source license agreement since February 2016. So far, a total of 1001 patients have been registered with a mean age of 32.41±15.60 years (range, 3 months to 74 years). The majority of the registered patients had retinitis pigmentosa (42%, 95% CI: 38.9% to 45%). Genetic testing was done for approximately 20% of the registered individuals. Conclusion: Our study shows successful web-based software design and data collection as a proof of concept for the first IRD registry in Iran. Multicenter integration of the IRD registry in medical centers throughout the country is well underway as planned. These data will assist researchers to rapidly access information about the distribution and genetic patterns of this disease.
Stable W isotope evidence for redistribution of homogeneous 182W anomalies in SW Greenland
2020-07-01

We present the first high precision stable tungsten isotope data for a comprehensive Eoarchean rock suite from the Isua region of SW Greenland with the aim to reconstruct the sources and processes that controlled the inventory of W in Eoarchean time and to place constraints on the origin of 182 W anomalies in Eoarchean rocks.When compared to modern igneous rocks, the observed range of δ 186/184 W in the Eoarchean rocks is substantially larger, ranging from -0.072 to þ0.249 ‰.But unlike in modern igneous rocks, we find no co-variation of δ 186/184 W with other geochemical parameters.Multiple stage mobilisation and re-enrichment of W by metasomatic fluids entirely obscured pristine geochemical signals.However, our results illustrate the potential of applying stable W isotopes as geochemical tracer for alteration effects on primary 182 W signatures.Despite secondary alteration and the large variation in δ 186/184 W the excesses in 182 W that were previously observed in the same rock samples appear to be unaffected by alteration arguing that the excesses were most likely initially uniform in the whole Eoarchean assemblage of SW Greenland.
Detecting and Quantifying Ataxia-Related Motor Impairments in Rodents Using Markerless Motion Tracking With Deep Neural Networks
2020-07-01

In this study we evaluate the application of video-based markerless motion tracking based on deep neural networks for the analysis of ataxia-specific movement abnormalities in rodent models of cerebellar ataxia. Based on a small amount (<100) of manually labeled video frames, markerless motion tracking enabled the extraction of movement trajectories and parameters characterizing ataxia-specific movement abnormalities. In the first experiment, we analyzed videos of 6 shaker and 4 wildtype rats and were able to reproduce thê5 Hz tremor frequency in the shaker rat without the usage of a force plate. In the second experiment, we investigated a spinocerebellar ataxia type 3 (SCA3) mouse model (6 mice aged 3 months and 3 mice aged 9 months) in a beam-balancing task. By establishing a parameter for the assessment of rhythmicity of gait (RoG), we not only found a significantly higher RoG in wildtype mice compared to affected SCA3 mice aged 9 months, but were also able to reveal a significantly lower than typical RoG in SCA3 mice aged 3 months which exhibit no abnormalities in visual inspection. These prototypical results suggest the capability of the presented methods for the application in upcoming therapeutic intervention trials to identify subtle changes in movement behavior.
Missing Carbodiimide and Oxide Carbodiimide of Scandium: Sc2(CN2)3 and Sc2O2(CN2)
2020-07-01

The new scandium(III) carbodiimides Sc 2 (CN 2 ) 3 and Sc 2 O 2 (CN 2 ) were prepared by solid‐state metathesis reactions between Li 2 (CN 2 ) and ScCl 3 and, regarding Sc 2 O 2 (CN 2 ), Sc 2 O 3 was added. The X‐ray powder diffraction pattern refinements lead to a trigonal‐rhombohedral ( R 3 c ) crystal system for Sc 2 (CN 2 ) 3 and to an orthorhombic ( Immm ) crystal system for Sc 2 O 2 (CN 2 ). The structure of Sc 2 (CN 2 ) 3 is isotypic to the well‐known rare earth carbodiimides RE 2 (CN 2 ) 3 with the smaller cations RE = Tm, Yb, and Lu, whereas Sc 2 O 2 (CN 2 ) is not isotypic to the known RE 2 O 2 (CN 2 ) (RE = Y, La, Ce–Gd, except Pm) compounds. Both crystal structures are represented by layered arrangements of scandium, respectively scandium and oxide, alternating with carbodiimide layers.
Reliability of the Oswestry-Bristol Classification for trochlear dysplasia
2020-07-01

Aims The Oswestry-Bristol Classification (OBC) was recently described as an MRI-based classification tool for the femoral trochlear. The authors demonstrated better inter- and intraobserver agreement compared to the Dejour classification. As the OBC could potentially provide a very useful MRI-based grading system for trochlear dysplasia, it was the aim to determine the inter- and intraobserver reliability of the classification system from the perspective of the non-founder. Methods Two orthopaedic surgeons independently assessed 50 MRI scans for trochlear dysplasia and classified each according to the OBC. Both observers repeated the assessments after six weeks. The inter- and intraobserver agreement was determined using Cohen’s kappa statistic and S-statistic nominal and linear weights. Results The OBC with grading into four different trochlear forms showed excellent inter- and intraobserver agreement with a mean kappa of 0.78. Conclusion The OBC is a simple MRI-based classification system with high inter- and intraobserver reliability. It could present a useful tool for grading the severity of trochlear dysplasia in daily practice. Cite this article: Bone Joint Open 2020;1-7:355–358.
Dermatofluoroscopy diagnostics in different pigmented skin lesions: Strengths and weaknesses
2020-07-01

Summary Background The melanin fluorescence of skin lesions is measurable with two‐photon excitation, a process termed dermatofluoroscopy, which has shown a shift from the green spectra in benign melanocytic lesions to the red spectra in melanoma. This study addressed the question as to which kind of pigmented lesions can be correctly diagnosed as melanin‐bearing malignant tumors. Methods 476 pigmented lesions including 101 cutaneous melanomas were analyzed with dermatofluoroscopy, measuring the melanin fluorescence in a grid‐like fashion with a separation of measurement points of 0.2 mm. The results of the dermatofluoroscopy are presented as a diagnostic score with a cut‐off score of ≥ 28 for the diagnosis of melanin‐bearing malignant tumors, and were compared to the gold standard of histopathology. Results A highly significant difference (p &lt; 0.0001) between the diagnostic scores of different skin tumors was found. Dermatofluoroscopy scores showed the highest sensitivity for melanomas (92.1 %). Interestingly, most pigmented basal cell carcinomas (BCCs, 88.9 %) were diagnosed as melanin‐bearing malignant tumors. A higher sensitivity for the correct diagnosis was observed in older patients (≥ 53 years, p = 0.003), in patients with skin tanning (p = 0.025), and in patients with freckles during childhood (p = 0.046). Conclusions Two‐photon fluorescence is an innovative technique for the diagnosis of pigmented skin lesions, and shows a high sensitivity for detection of melanomas and pigmented BCCs.
Nonleptonic Decays of Doubly Charmed Baryons
2020-07-01

We have made calculation of the W-exchange contribution to the nonleptonic two-body decays of the doubly charmed baryons and . The W-exchange contributions appear in addition to the factorizable tree graph contributions and are not suppressed in general. We make use of the covariant confined quark model to calculate the tree graph as well as the W-exchange contribution. We calculate helicity amplitudes and quantitatively compare the tree graph and W-exchange contributions.