gebhart/patrepeval huggingface dataset:
Antibody responses to endemic coronaviruses modulate COVID-19 convalescent plasma functionality (2020)

COVID-19 convalescent plasma, particularly plasma with high-titer SARS-CoV-2 (CoV2) antibodies, has been successfully used for treatment of COVID-19. The functionality of convalescent plasma varies greatly, but the association of antibody epitope specificities with plasma functionality remains uncharacterized. We assessed antibody functionality and reactivities to peptides across the CoV2 and the four endemic human coronavirus (HCoV) genomes in 126 COVID-19 convalescent plasma donations. We found strong correlation between plasma functionality and polyclonal antibody targeting of CoV2 spike protein peptides. Antibody reactivity to many HCoV spike peptides also displayed strong correlation with plasma functionality, including pan-coronavirus cross-reactive epitopes located in a conserved region of the fusion peptide. After accounting for antibody cross-reactivity, we identified an association between greater alphacoronavirus NL63 antibody responses and development of highly neutralizing antibodies to SARS-CoV-2. We also found that plasma preferentially reactive to the CoV2 receptor binding domain (RBD), versus the betacoronavirus HKU1 RBD, had higher neutralizing titer. Finally, we developed a two-peptide serosignature that identifies plasma donations with high anti-S titer but that suffer from low neutralizing activity. These results suggest that analysis of coronavirus antibody fine specificities may be useful for selecting therapeutic plasma with desired functionalities.
Results of two consecutive treatment protocols in Polish children with acute lymphoblastic leukemia (2020)

The aim of the study was to retrospectively compare the effectiveness of the ALL IC-BFM 2002 and ALL IC-BFM 2009 protocols and the distribution of risk groups by the two protocols after minimal residual disease (MRD) measurement as well as its impact on survival. We reviewed the medical records of 3248 patients aged 1-18 years with newly diagnosed ALL who were treated in 14 hemato-oncological centers between 2002 and 2018 in Poland. The overall survival (OS) of 1872 children with ALL treated with the ALL IC 2002 protocol was 84% after 3 years, whereas the OS of 1376 children with ALL treated with the ALL IC 2009 protocol was 87% (P < 0.001). The corresponding event-free survival rates were 82% and 84% (P = 0.006). Our study shows that the ALL IC-BFM 2009 protocol improved the results of children with ALL compared to the ALL IC-BFM 2002 protocol in Poland. This analysis confirms that MRD marrow assessment on day 15 of treatment by FCM-MRD is an important predictive factor.
Novel One-Pot Vicinal Double C-Acylation of Styrenes and Methacrylates by Electroreduction (2003)

[reaction: see text] Electroreduction of styrenes or alkyl methacrylates in the presence of aliphatic acid anhydrides or N-acylimidazoles with an undivided cell equipped with zinc electrodes as the anode and the cathode brought about novel one-pot vicinal double C-acylation to afford the corresponding 1,4-diketones in satisfactory yields.
Variational Clustering: Leveraging Variational Autoencoders for Image\n Clustering (2020)

Recent advances in deep learning have shown their ability to learn strong\nfeature representations for images. The task of image clustering naturally\nrequires good feature representations to capture the distribution of the data\nand subsequently differentiate data points from one another. Often these two\naspects are dealt with independently and thus traditional feature learning\nalone does not suffice in partitioning the data meaningfully. Variational\nAutoencoders (VAEs) naturally lend themselves to learning data distributions in\na latent space. Since we wish to efficiently discriminate between different\nclusters in the data, we propose a method based on VAEs where we use a Gaussian\nMixture prior to help cluster the images accurately. We jointly learn the\nparameters of both the prior and the posterior distributions. Our method\nrepresents a true Gaussian Mixture VAE. This way, our method simultaneously\nlearns a prior that captures the latent distribution of the images and a\nposterior to help discriminate well between data points. We also propose a\nnovel reparametrization of the latent space consisting of a mixture of discrete\nand continuous variables. One key takeaway is that our method generalizes\nbetter across different datasets without using any pre-training or learnt\nmodels, unlike existing methods, allowing it to be trained from scratch in an\nend-to-end manner. We verify our efficacy and generalizability experimentally\nby achieving state-of-the-art results among unsupervised methods on a variety\nof datasets. To the best of our knowledge, we are the first to pursue image\nclustering using VAEs in a purely unsupervised manner on real image datasets.\n
Selective and Wash‐Resistant Fluorescent Dihydrocodeinone Derivatives Allow Single‐Molecule Imaging of μ‐Opioid Receptor Dimerization (2019)

μ-Opioid receptors (μ-ORs) play a critical role in the modulation of pain and mediate the effects of the most powerful analgesic drugs. Despite extensive efforts, it remains insufficiently understood how μ-ORs produce specific effects in living cells. We developed new fluorescent ligands based on the μ-OR antagonist E-p-nitrocinnamoylamino-dihydrocodeinone (CACO), that display high affinity, long residence time and pronounced selectivity. Using these ligands, we achieved single-molecule imaging of μ-ORs on the surface of living cells at physiological expression levels. Our results reveal a high heterogeneity in the diffusion of μ-ORs, with a relevant immobile fraction. Using a pair of fluorescent ligands of different color, we provide evidence that μ-ORs interact with each other to form short-lived homodimers on the plasma membrane. This approach provides a new strategy to investigate μ-OR pharmacology at single-molecule level.
Terpenoids from Chloranthus serratus and Their Anti-inflammatory Activities (2012)

Seven new terpenoids, including two sesquiterpene dimers (1, 2), two norditerpenoids (3, 4), and three sesquiterpenes (5-7), along with six known sesquiterpene dimers and four known sesquiterpenes were isolated from the whole plant of Chloranthus serratus. Their structures and relative configurations were elucidated on the basis of spectroscopic data analysis. The absolute configuration of 1 was determined by the CD exciton chirality method. These isolates were evaluated for their inhibitory effects on lipopolysaccharide-induced nitric oxide production in RAW264.7 cells. Compound 2 and two known compounds, shizukaols B and D, showed significant anti-inflammatory activities, with IC(50) values of 0.22, 0.15, and 7.22 μM, respectively.
Photonic encryption using all optical logic. (2003)

With the build-out of large transport networks utilizing optical technologies, more and more capacity is being made available. Innovations in Dense Wave Division Multiplexing (DWDM) and the elimination of optical-electrical-optical conversions have brought on advances in communication speeds as we move into 10 Gigabit Ethernet and above. Of course, there is a need to encrypt data on these optical links as the data traverses public and private network backbones. Unfortunately, as the communications infrastructure becomes increasingly optical, advances in encryption (done electronically) have failed to keep up. This project examines the use of optical logic for implementing encryption in the photonic domain to achieve the requisite encryption rates. In order to realize photonic encryption designs, technology developed for electrical logic circuits must be translated to the photonic regime. This paper examines two classes of all optical logic (SEED, gain competition) and how each discrete logic element can be interconnected and cascaded to form an optical circuit. Because there is no known software that can model these devices at a circuit level, the functionality of the SEED and gain competition devices in an optical circuit were modeled in PSpice. PSpice allows modeling of the macro characteristics of the devices in context of a logic element as opposed to device level computational modeling. By representing light intensity as voltage, 'black box' models are generated that accurately represent the intensity response and logic levels in both technologies. By modeling the behavior at the systems level, one can incorporate systems design tools and a simulation environment to aid in the overall functional design. Each black box model of the SEED or gain competition device takes certain parameters (reflectance, intensity, input response), and models the optical ripple and time delay characteristics. These 'black box' models are interconnected and cascaded in an encrypting/scrambling algorithm based on a study of candidate encryption algorithms. We found that a low gate count, cascadable encryption algorithm is most feasible given device and processing constraints. The modeling and simulation of optical designs using these components is proceeding in parallel with efforts to perfect the physical devices and their interconnect. We have applied these techniques to the development of a 'toy' algorithm that may pave the way for more robust optical algorithms. These design/modeling/simulation techniques are now ready to be applied to larger optical designs in advance of our ability to implement such systems in hardware.
Refining electromagnetic bias estimation [sea surface height measurement] (2003)

Sea surface height measurements using remote sensing instruments have become increasingly accurate as satellite altimetry technology has matured. Early satellite missions had altimetry errors on the order of tens of centimetres. As these errors have been eliminated, the electromagnetic (EM) bias has become increasingly significant. The latest satellite missions, TOPEX/Poseidon and Jason-1, have EM bias error budgets of 4.2 cm and 2.5 cm, respectively. The purpose of our research has been to investigate methods to reduce the EM bias estimation errors to the sub-cm level. Most current EM bias models create estimates from geophysical properties that can be measured remotely. Typically these parameters are wind speed and significant wave height. The current operational model for the TOPEX/Poseidon and Jason-1 satellite missions is of this type. The operational model uses nonparametric methods to improve the accuracy of the estimates. In addition to improving the bias estimates, the latest operational model has shown a stronger agreement between satellite and tower EM bias models. Combining nonparametric techniques with the wind speed and significant wave height has created the most accurate empirical models to date. However, the amount of variance in the bias requires new methods to improve bias estimates. We made a preliminary study based on the angular dependence of the EM bias. Theoretical scattering models indicate that the bias is dependent on incidence angle, which may allow improved operational correction of the bias using a wide-swath altimeter.
Immunogenicity and pre-clinical efficacy of an OMV-based SARS-CoV-2 vaccine (2023)

The vaccination campaign against SARS-CoV-2 relies on the world-wide availability of effective vaccines, with a potential need of 20 billion vaccine doses to fully vaccinate the world population. To reach this goal, the manufacturing and logistic processes should be affordable to all countries, irrespectively of economical and climatic conditions. Outer membrane vesicles (OMV) are bacterial-derived vesicles that can be engineered to incorporate heterologous antigens. Given the inherent adjuvanticity, such modified OMV can be used as vaccine to induce potent immune responses against the associated protein. Here we show that OMVs engineered to incorporate peptides derived from the receptor binding motif (RBM) of the spike protein from SARS-CoV-2 elicit an effective immune response in vaccinated mice, resulting in the production of neutralizing antibodies (nAbs). The immunity induced by the vaccine is sufficient to protect the animals from intranasal challenge with SARS-CoV-2, preventing both virus replication in the lungs and the pathology associated with virus infection. Furthermore, we show that OMVs can be effectively decorated with the RBM of the Omicron BA.1 variant and that such engineered OMVs induced nAbs against Omicron BA.1 and BA.5, as judged by pseudovirus infectivity assay. Importantly, we show that the RBM<sub>438-509</sub> ancestral-OMVs elicited antibodies which efficiently neutralized <i>in vitro</i> both the homologous ancestral strain, the Omicron BA.1 and BA.5 variants, suggesting its potential use as a pan SARS-CoV-2 vaccine. Altogether, given the convenience associated with ease of engineering, production and distribution, our results demonstrate that OMV-based SARS-CoV-2 vaccines can be a crucial addition to the vaccines currently available.
A stochastic model for Cu(InGa)(SeS)2 absorber growth during selenization/sulfization (2015)

The optical and electronic properties of Cu(InGa)(SeS) <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> absorbers are functions of the gallium and sulfur fractions, defined as the mole fractions Ga/(In+Ga) and S/(Se+S). During absorber growth, through-film composition gradients arise, and these gradients affect the photovoltaic performance of the solar cell. However, there has been little effort in quantitative prediction of the through-film composition. In this work, we present a stochastic model to simulate film growth during selenization and sulfization processes. Our goal is to predict the through-film composition of a Cu(InGa)(SeS) <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> absorber film, especially the gallium and sulfur gradients. Our model can predict the steep gradient in gallium that is observed during the selenization reaction and the gallium homogenization that occurs with the sulfurization reaction. Although the model requires a large number of parameters, we show how they can be estimated from simplifying assumptions and related to physical properties. We believe that this method is the first attempt to model explicitly the through-film composition of a Cu(InGa)(SeS) <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> produced via selenization.
Organolanthanide-Catalyzed Imine Hydrogenation. Scope, Selectivity, Mechanistic Observations, and Unusual Byproducts (1997)

In this paper we report the Cp‘2Ln/Me2SiCp‘‘2Ln-catalyzed (Cp‘ = η5-Me5C5; Cp‘‘ = η5-Me4C5) hydrogenation of acyclic imines to yield the corresponding amines. At 190 psi of H2, the observed turnover frequencies (h-1) (100:1 substrate:catalyst ratio, Cp‘2Ln, temperature (°C)) are (1) (N-benzylidene(methyl)amine, Ln = La, 50) 0.03; (Ln = Sm, 90) 1.0; (Ln = Sm + PhSiH3, 90) 2.2; (Ln = Lu, 90) 0.60; (2) (N-benzylideneaniline, Ln = Sm, 90) 0.10; (3) (N-benzylidene(trimethylsilyl)amine, Ln = Sm, 90) 0.40; (4) (N-(α-methylbenzylidene)(methyl)amine, Ln = Sm, 90) 0.20; (5) (N-(α-methylbenzylidene)(benzyl)amine, Ln = Sm, 90) 0.70. The stoichiometric reaction of N-benzylidene(methyl)amine with Cp‘2SmCH(SiMe3)2 or (Cp‘2SmH)2 yields an orthometalated Cp‘2Sm−substrate complex which undergoes either hydrogenolysis/hydrogenation or competing CN insertion of a second substrate molecule to yield a Cp‘2Sm-imine−amido complex with a seven-membered chelate ring. The stoichiometric reaction of 2-methyl-1-pyrroline with Cp‘2SmCH(SiMe3)2 or (Cp‘2SmH)2 yields a Cp‘2Sm-imine−amido complex in which two substrate molecules have been coupled to form a six-membered chelate ring (characterized by X-ray diffraction). The stoichiometric reaction of N-benzylidene(trimethylsilyl)amine with (Cp‘2SmH)2 yields a desilylated Cp‘2Sm-imine−amido complex with a four-membered Sm(NSiMe3)(CPh)NCHPh chelate ring (characterized by X-ray diffraction). Additional heating of this product under H2 yields S6-symmetric (Cp‘2SmCN)6, which contains an unusual chairlike 18-membered (SmCN)6 ring (characterized by X-ray diffraction).
Imbalanced Biphasic Electrical Stimulation: Muscle Tissue Damage (2005)

The effects of imbalanced biphasic stimulation were studied on cat skeletal muscle to determine if greater charge densities can be safely used than with balanced or monophasic stimulation. The results of the study indicate that imbalanced biphasic stimulation can be tolerated safely by tissue at or below a net dc current density of 35 μA/mm2 and not safely tolerated at or above a net dc current of 50 μA/mm2. Monophasic stimulation has been shown to be safe at or below net dc current levels of 10 μA/mm2 and in these studies we found it was not safe at or above net dc current levels of 20 μA/mm2. Stimuli were applied to muscles via coiled wire intramuscular electrodes using a regulated current source. Since the safe average current density was higher for imbalanced biphasic stimulation than for monophasic stimulation, this suggests that: (a) pH change is not the primary reaction causing tissue damage and (b) the damaging electrochemical process that takes place during a cathodic stimulation pulse can be reversed by an anodic pulse having substantially less charge than its companion cathodic pulse. We conclude that greater cathodic charge densities can be safely employed with imbalanced biphasic stimulation than with either monophasic stimulation or balanced charge biphasic stimulation.
[Done is done--and gone is gone. Sex reassignment is presently the best cure for transsexuals]. (2001)

Sweden was the first country to legislate on sex reassignment procedures in 1972. Patients with gender dysphoria are in Sweden referred to one of six university clinics specialised in the field; all surgery, however, is centralised to the Karolinska Hospital in Stockholm. The aetiological strivings regarding transsexualism have to date been inconclusive; however, several lines of evidence speak in favour of an early biological influence on gender identity. The vast majority of studies addressing outcome have provided convincing evidence for the benefit of sex reassignment surgery in carefully selected cases. The current article summarises the state of the art regarding work-up and treatment of transsexuals.
Identification of a Novel HIV-1 Inhibitor Targeting Vif-dependent Degradation of Human APOBEC3G Protein (2015)

APOBEC3G (A3G) is a cellular cytidine deaminase that restricts HIV-1 replication by inducing G-to-A hypermutation in viral DNA and by deamination-independent mechanisms. HIV-1 Vif binds to A3G, resulting in its degradation via the 26 S proteasome. Therefore, this interaction represents a potential therapeutic target. To identify compounds that inhibit interaction between A3G and HIV-1 Vif in a high throughput format, we developed a homogeneous time-resolved fluorescence resonance energy transfer assay. A 307,520 compound library from the NIH Molecular Libraries Small Molecule Repository was screened. Secondary screens to evaluate dose-response performance and off-target effects, cell-based assays to identify compounds that attenuate Vif-dependent degradation of A3G, and assays testing antiviral activity in peripheral blood mononuclear cells and T cells were employed. One compound, N.41, showed potent antiviral activity in A3G(+) but not in A3G(-) T cells and had an IC50 as low as 8.4 μM and a TC50 of >100 μM when tested against HIV-1Ba-L replication in peripheral blood mononuclear cells. N.41 inhibited the Vif-A3G interaction and increased cellular A3G levels and incorporation of A3G into virions, thereby attenuating virus infectivity in a Vif-dependent manner. N.41 activity was also species- and Vif-dependent. Preliminary structure-activity relationship studies suggest that a hydroxyl moiety located at a phenylamino group is critical for N.41 anti-HIV activity and identified N.41 analogs with better potency (IC50 as low as 4.2 μM). These findings identify a new lead compound that attenuates HIV replication by liberating A3G from Vif regulation and increasing its innate antiviral activity.
Multiple Gastrointestinal Stromal and Other Tumors Caused by Platelet-Derived Growth Factor Receptor α Gene Mutations: A Case Associated with a Germline V561D Defect (2007)

Multiple GISTs and other tumors may be caused by germline PDGFRA gene mutations; the V561D mutation can occur in the germline state and lead to a syndrome that should not be confused with other genetic conditions associated with a predisposition to NETs and other tumors. A number of chromosomal loci are likely to be involved in the PDGFRA V561D-dependent tumorigenesis, as shown by CGH and other DNA analyses.
Hsp70 chaperone blocks α-synuclein oligomer formation via a novel engagement mechanism (2021)

Overexpression and aggregation of α-synuclein (ASyn) are linked to the onset and pathology of Parkinson's disease and related synucleinopathies. Elevated levels of the stress-induced chaperone Hsp70 protect against ASyn misfolding and ASyn-driven neurodegeneration in cell and animal models, yet there is minimal mechanistic understanding of this important protective pathway. It is generally assumed that Hsp70 binds to ASyn using its canonical and promiscuous substrate-binding cleft to limit aggregation. Here we report that this activity is due to a novel and unexpected mode of Hsp70 action, involving neither ATP nor the typical substrate-binding cleft. We use novel ASyn oligomerization assays to show that Hsp70 directly blocks ASyn oligomerization, an early event in ASyn misfolding. Using truncations, mutations, and inhibitors, we confirm that Hsp70 interacts with ASyn via an as yet unidentified, noncanonical interaction site in the C-terminal domain. Finally, we report a biological role for a similar mode of action in H4 neuroglioma cells. Together, these findings suggest that new chemical approaches will be required to target the Hsp70-ASyn interaction in synucleinopathies. Such approaches are likely to be more specific than targeting Hsp70's canonical action. Additionally, these results raise the question of whether other misfolded proteins might also engage Hsp70 via the same noncanonical mechanism.
High optical power testing of physical contact connectors at 1550 nm (2001)

We have investigated the high optical power handling capability of standard SC PC and APC connectors using SMF-28TM fiber at powers of 1 and 3 W at 1550 nm. We will report results of short-term exposure tests of mated connector pairs prepared with various endface surface conditions.
Natural Products in the Prevention of Metabolic Diseases: Lessons Learned from the 20th KAST Frontier Scientists Workshop (2021)

The incidence of metabolic and chronic diseases including cancer, obesity, inflammation-related diseases sharply increased in the 21st century. Major underlying causes for these diseases are inflammation and oxidative stress. Accordingly, natural products and their bioactive components are obvious therapeutic agents for these diseases, given their antioxidant and anti-inflammatory properties. Research in this area has been significantly expanded to include chemical identification of these compounds using advanced analytical techniques, determining their mechanism of action, food fortification and supplement development, and enhancing their bioavailability and bioactivity using nanotechnology. These timely topics were discussed at the 20th Frontier Scientists Workshop sponsored by the Korean Academy of Science and Technology, held at the University of Hawaii at Manoa on 23 November 2019. Scientists from South Korea and the U.S. shared their recent research under the overarching theme of Bioactive Compounds, Nanoparticles, and Disease Prevention. This review summarizes presentations at the workshop to provide current knowledge of the role of natural products in the prevention and treatment of metabolic diseases.