gebhart/patrepeval huggingface dataset:
Tumor necrosis factor alpha: a costimulator for cytotoxic cell differentiation. (1991)

Large granular lymphocytes (LGL) can be activated by interleukin-2 (IL-2) into lymphokine-activated killers (LAK). Tumor Necrosis factor alpha was found to act synergistically with very low concentrations of IL-2 which were ineffective by themselves in inducing LAK activity. We demonstrate that the failure of low doses of IL-2 to induce LAK generation was related to their incapacity to induce TNF production by LGL. When specific antibodies against TNF were added to the culture, the differentiation of LGL into LAK effectors by optimal concentrations of IL-2 in our system was partially inhibited suggesting that TNF may be a physiologic mediator in the sequential activation stages of LGL into LAK effectors. We have also investigated the functional interaction between IL-2 and TNF on the generation of alloreactive CTL. Using primary mixed cultures of lymphocytes from a MHC-recombinant sibling identical for MHC class II antigens and displaying MHC class I disparity, our data indicate that addition of exogenous TNF at the sensitizing phase of the primary mixed lymphocyte reaction did not result in CTL activation. However, when simultaneously added with IL-2, TNF could promote an optimal induction of cytotoxic T cell generation. The TNF property to potentiate the cytotoxic function appears to involve an enhancement of IL-2 induced serine esterase activity suggesting that TNF may affect some components of the cellular lytic machinery. In conclusion the data presented here are most consistent with the suggestion that TNF could increase the IL-2 signaling efficiency or potentiate activation signaling involved in the acquisition of lytic competence by cytotoxic T cells.
Structurally and Functionally Distinct Ca2+ Binding Sites in the γ‐Carboxyglutamic Acid‐Containing Domain of Factor VIIa (1995)

The structural and functional effects of Ca2+ binding to vitamin-K-dependent coagulation factor VIIa were investigated. Conformational changes with a midpoint around 0.7 mM Ca2+ quenched the intrinsic protein fluorescence of a fragment of factor VIIa comprising only the light chain and this coincided with an increase in factor VIIa amidolytic activity in the absence of tissue factor. Ca2+ binding to sites in factor VIIa and in the fragment with an apparent dissociation constant of 1.3-1.4 mM induced binding to phospholipids. A similar Ca2+ dependency was not observed with factor VIIa lacking the N-terminal 38 or 44 residues of the light chain and the observed effects could thus be attributed to gamma-carboxyglutamic-acid-dependent Ca2+ binding. Mg2+ appeared to bind to the site(s) of relatively higher affinity since, although it was less efficient than Ca2+, it stimulated the amidolytic activity and induced quenching of the intrinsic fluorescence. In contrast, Mg2+ did not induce expression of the phospholipid-interactive structure. The binding properties of two monoclonal antibodies that recognized epitopes in the gamma-carboxy-glutamic-acid-rich domain of factor VIIa corroborated the occurrence of two Ca(2+)-induced, sequential structural changes and only one of the antibodies recognized the Mg(2+)-induced structure. Thus Ca2+ binding to the gamma-carboxyglutamic-acid-containing domain appeared to result in at least two distinct structural transitions with different functional consequences. The two (sets of) sites responsible for the observed effects could be distinguished based upon differences in Ca2+ affinity and metal ion selectivity. The interaction between factor VIIa and tissue factor was monitored by means of a direct binding assay and an amidolytic assay. In both systems, half-maximal Ca2+ enhancement was observed at 0.25 mM. This coincided with a Ca(2+)-induced conformational change in factor VIIa associated with fluorescence quenching. The same effect on amidolytic activity was observed with the two N-terminally truncated forms of factor VIIa and it is presumably mediated by Ca2+ binding to a site located in the serine protease part.
ChemInform Abstract: Combinatorial Chemistry, High‐Speed Screening and Catalysis (2000)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Effect of treatment with a cationic antiviral compound on acute infection with bovine viral diarrhea virus. (2013)

Bovine viral diarrhea virus (BVDV) is a widespread bovine pathogen capable of causing disease affecting multiple body systems. Previous studies have shown 2-(2-benzimidazolyl)-5-[4-(2-imidazolino)phenyl]furan dihydrochloride (DB772) effectively prevents BVDV infection in cell culture. The aim of this project was to assess the efficacy of DB772 for the prevention of acute BVDV infection. Four calves seronegative to BVDV were treated with DB772 and another 4 calves were treated with diluent only on the same dosing schedule. Each calf was subsequently challenged intranasally with BVDV. Virus was isolated consistently from untreated calves on days 4 to 8, while treated calves remained negative by virus isolation during this period. Azotemia was exhibited by all treated calves on day 4 resulting in the euthanasia of 1 calf on day 10 and the death of another on day 13. Virus was isolated from the 2 remaining treated calves on day 14 or 21. On day 21, both remaining treated calves and all 4 untreated calves had anti-BVDV antibody titers > 1:2048. This pilot study indicates that DB772 temporarily prevented acute disease due to BVDV, but carries a significant concern of renal toxicity.
Physiology of Micturition (2017)

Micturition describes a dynamic process that alternates between phases of storage and expulsion of urine stored in the urinary bladder. The storage phase typically extends for hours, whereas the expulsion phase lasts for a few seconds. Reciprocal contraction and relaxation of smooth muscle in the bladder and urethra is required for these two phases of different duration to happen, which is accomplished by the complex interactions among smooth muscle, connective tissue, urothelium, and supportive structures with innervation. The relay of afferent input from the bladder to the neural circuitry in the brainstem, in particular the periaqueductal gray (pag) and the pontine micturition center (pmc), switches on the periodic transformation of the lower urinary tract from the mode of bladder filling to voiding [1–3] (figure 23.1). The volitional control over this dynamic process is lacking in infants, but is gained through learning by the age of 5 in most individuals. The micturition in both sexes is influenced by neural, biomechanical, biochemical, and morphologic properties of the bladder and urethra, as well as the hormonal influences and unique pelvic and perineal anatomy [4].
Design and Synthesis of BODIPY-Cored Near IR-emitting Lipophilic and Water-Soluble Dendritic Platforms (2017)

Capitalizing on our experience in constructing branched and dendritic monomers with functionalizable aromatic moiety at the focal point and various terminal groups, we prepared lipophilic and water-soluble dendrimers with BODIPY fluorophore in the core, emitting in the green and near IR spectral regions. The dendrimers, incorporating aliphatic tails, exhibited excellent fluorescence properties in apolar organic solvents, while those with the triethylenglycol-based tails were highly fluorescent in polar organic solvents as well. The water solubility induced by the terminal hexaethyleneglycol tails enables fluorescence of the dyes also in aqueous media. The phenolic hydroxyls in the molecules enable attachment of linkers for prospective conjugation of additional units.
Localization by Fusing a Group of Fingerprints via Multiple Antennas in Indoor Environment (2016)

Most existing fingerprints-based indoor localization approaches are based on some single fingerprints, such as received signal strength (RSS), channel impulse response (CIR), and signal subspace. However, the localization accuracy obtained by the single fingerprint approach is rather susceptible to the changing environment, multi-path, and non-line-of-sight (NLOS) propagation. Furthermore, building the fingerprints is a very time consuming process. In this paper, we propose a novel localization framework by Fusing A Group Of fingerprinTs (FAGOT) via multiple antennas for the indoor environment. We first build a GrOup Of Fingerprints (GOOF), which includes five different fingerprints, namely, RSS, covariance matrix, signal subspace, fractional low order moment, and fourth-order cumulant, which are obtained by different transformations of the received signals from multiple antennas in the offline stage. Then, we design a parallel GOOF multiple classifiers based on AdaBoost (GOOF-AdaBoost) to train each of these fingerprints in parallel as five strong multiple classifiers. In the online stage, we input the corresponding transformations of the real measurements into these strong classifiers to obtain independent decisions. Finally, we propose an efficient combination fusion algorithm, namely, MUltiple Classifiers mUltiple Samples (MUCUS) fusion algorithm to improve the accuracy of localization by combining the predictions of multiple classifiers with different samples. As compared with the single fingerprint approaches, the prediction probability of our proposed approach is improved significantly. The process for building fingerprints can also be reduced drastically. We demonstrate the feasibility and performance of the proposed algorithm through extensive simulations as well as via real experimental data using a Universal Software Radio Peripheral (USRP) platform with four antennas.
Intracellular functions of RNA-binding protein, Musashi1, in stem and cancer cells (2020)

RNA-binding protein, musashi1 (MSI1), is a main protein in asymmetric cell division of the sensory organ precursor cells, whereas its expression is reported to be upregulated in cancers. This protein is a critical element in proliferation of stem and cancer stem cells, which acts through Wnt and Notch signaling pathways. Moreover, MSI1 modulates malignancy and chemoresistance of lung cancer cells via activating the Akt signaling. Due to the main role of MSI1 in metastasis and cancer development, MSI1 would be an appropriate candidate for cancer therapy. Downregulation of MSI1 inhibits proliferation of cancer stem cells and reduces the growth of solid tumors in several cancers. On the other hand, MSI1 expression is regulated by microRNAs in such a way that several different tumor suppressor miRNAs negatively regulate oncogenic MSI1 and inhibit migration and tumor metastasis. The aim of this review is summarizing the role of MSI1 in stem cell proliferation and cancer promotion.
Toward a Multiplexed Serotyping Immunoassay for Foot-and-Mouth Disease Virus (2007)

Initial results demonstrating the feasibility of a multiplexed liquid array immunoassay for foot-and-mouth disease viral antigen detection and simultaneous serotype differentiation are presented. Serotype-specific antibodies from rabbit and guinea pig hyperimmunesera were isolated and prepared for use in a multiplexed, bead-based assay. The performance of all of the available antibodies as both capture and detector reagents was evaluated in the multiplexed system to establish a combination exhibiting the highest homotypic responses and lowest heterotypic reactions. The multiplexed assay was evaluated against inactivated cell culture supernatant samples of the same subtype as the virus used to raise the capture and detector antibodies. Distinct serotype differentiation was observed, except in the case of serotype SAT1. Subsequently, cell culture supernatant samples from a larger pool of viral subtypes were analyzed. Distinct serotype differentiation was obtained when analyzing cell culture supernatant samples from viral serotypes C, Asia, and SAT3, irrespective of the subtype. However, limitations of the current antibody pairs were realized in some inconclusive results obtained when analyzing samples from a broader range of O, A, and SAT2 subtypes. The results obtained in this initial study will be used to further optimize the assay using polyvalent or monoclonal antibodies and move toward the analysis of clinical samples.
ChemInform Abstract: TOTAL SYNTHESIS OF PROSTAGLANDIN‐F2α, AND THE 9‐O‐BENZYL DERIVATIVES OF PROSTAGLANDINS‐F2α, ‐F1α, ‐D2, AND ‐D1 (1981)

Abstract Ausgehend von‐dem Bicycloheptenon (I) wird über den Bromhydrinether (II) das tricyclische Keton (III) synthetisiert und mit dem Organocuprat (IV) zu dem Bicycloheptanon (V) umgesetzt.Baeyer‐Villiger Oxidation von (V) gibt die Lactone (VI) , deren Gemisch bei der Hydrid‐Reduktion die Hydroxyaldehyde (VII) und die Lactole (VIII) liefert.
Developments In Spirituality Among Youth In Australia And Other Western Societies (2010)

This chapter presents a profile, based on recent research, of the changing patterns of religion and spirituality among young people in Australia. The term 'spirituality', long used for the personal, practical dimension of traditional religion, has now acquired the much broader sense of 'whatever inspires someone'. The chapter examines topics such as traditional religions among youth, alternative spiritualities and spirituality and social involvement comparing recent Australian findings with those from other Western countries, especially Britain, Canada and the US. It explores research findings on youth's response to the alternative religions and alternative spiritual beliefs. The chapter also deals with religions which promote social involvement and beneficent concern for others. Keywords: Australian youth; social involvement; spiritual movements; traditional religious beliefs; Western countries
Abstract 2853: Co-delivery of antigen-encoding mRNA and signal 2/3 mRNAs to PBMCs by Cell Squeeze® technology generates SQZ™ eAPCs that prime CD8+T cells in a humanized mouse model (2022)

Abstract Antigen-specific CD8+ T cells are critical for mounting an effective immune response against tumors. Generation of antigen-specific T cells require interactions with multiple signals produced by antigen presenting cells (APCs). These signals are comprised of three components: (signal 1) the peptide-MHC complex binding to the T cell receptor, (signal 2) costimulatory molecules on the surface of APCs, and (signal 3) inflammatory cytokines binding to cognate receptors on T cells. To engineer all major cell subsets of human peripheral blood mononuclear cells (PBMCs) to become enhanced APCs (eAPCs), we used Cell Squeeze® technology to deliver multiple mRNAs encoding for non-self-antigens (signal 1), CD86 (signal 2), and/or membrane-bound cytokines (signal 3). The signal 3 molecules, membrane-bound IL-12 (mbIL-12) and membrane-bound IL-2 (mbIL-2), are chimeric proteins designed to increase the localized concentration of the cytokines at the immune synapse and limit off-target effects. Flow cytometry confirmed translation of delivered signal 2/3 mRNAs by all major subsets within PBMCs: T cells, B cells, NK cells, and monocytes. The potency of these SQZ™ eAPCs was assessed in vitro by culturing the eAPCs with antigen-specific T cells for multiple days before measuring the functionality of antigen-specific T cells via intracellular cytokine staining or ELISA. Using this approach, we demonstrate that Cell Squeeze® co-delivery of antigen mRNA and signal 2/3 mRNAs significantly enhances CD8+ T cell responses to a variety of antigens, including CMV pp65, Influenza M1, HPV16 E6, and HPV16 E7. Furthermore, we demonstrate that SQZ™ eAPCs drive significant expansion of antigen-specific CD8+ T cells in a humanized mouse model. Thus, we demonstrate that Cell Squeeze® can deliver multiple mRNAs encoding for signals 1, 2, and 3 to human PBMCs and has the potential to generate enhanced APCs that drive strong CD8+ T cell responses against multiple antigens. The versatility of this approach has the potential to enable rapid exchange of mRNA to encode for other antigens or T cell activation signals. Citation Format: Michael F. Maloney, Emrah Ilker Ozay, Katarina Blagovic, Carolyne Smith, Andrea A. Silva, Amber Martin, Sanjana Manja, Madhav Upadhyay, Lindsay J. Moore, Ryan Stagg, Henry Mack, Christine Trumpfheller, Pablo Umana, Armon Sharei, Howard Bernstein, Scott M. Loughhead. Co-delivery of antigen-encoding mRNA and signal 2/3 mRNAs to PBMCs by Cell Squeeze® technology generates SQZ™ eAPCs that prime CD8+T cells in a humanized mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2853.
Clutter locus equation for more general linear array orientation (2011)

The clutter locus is an important concept in space-time adaptive processing (STAP) for ground moving target indicator (GMTI) radar systems. The clutter locus defines the expected ground clutter location in the angle-Doppler domain. Typically in literature, the clutter locus is presented as a line, or even a set of ellipsoids, under certain assumptions about the geometry of the array. Most often, the array is assumed to be in the horizontal plane containing the velocity vector. This paper will give a more general 3-dimensional interpretation of the clutter locus for a general linear array orientation.
Eutectic Composition of a Chiral Mixture Containing a Racemic Compound (2005)

The enantioseparation process is of great interest to the pharmaceutical industry since more than 50% of the pharmaceutically active ingredients are known to be chiral and one enantiomer is usually preferred over the racemic mixture. Crystallization is widely used as the final step to reject the enantiomeric impurity from a mixture. Yet, a fundamental guidance on developing a purification procedure for systems forming racemic compounds (which account for more than 90% of all chiral systems) is not available. In this work, it is shown that the enantiomeric excess (ee) of the eutectic point is the key information needed to assess the feasibility of a crystallization process and to predict the purity and the yield of the product. In a dilute solution, the eutectic ee is determined solely by a eutectic constant (Keu), a new parameter introduced in this paper. Keu is defined as the ratio of the activity of the major enantiomer to that of the minor enantiomer. A eutectic constant equation was derived from the basics of thermodynamics, and for the first time, it was shown that the Keu is independent of solvent if no solvates are formed but varies with temperature. With an understanding of how the eutectic ee changes with solvent and temperature, the time and material required in developing a crystallization procedure for ee enhancement can be dramatically reduced. This theory was supported by experimental data, and its application was demonstrated on a system of pharmaceutical interest.
Mitochondrial NADH Fluorescence Is Enhanced by Complex I Binding (2008)

Mitochondrial NADH fluorescence has been a useful tool in evaluating mitochondrial energetics both in vitro and in vivo. Mitochondrial NADH fluorescence is enhanced several-fold in the matrix through extended fluorescence lifetimes (EFL). However, the actual binding sites responsible for NADH EFL are unknown. We tested the hypothesis that NADH binding to Complex I is a significant source of mitochondrial NADH fluorescence enhancement. To test this hypothesis, the effect of Complex I binding on NADH fluorescence efficiency was evaluated in purified protein, and in native gels of the entire porcine heart mitochondria proteome. To avoid the oxidation of NADH in these preparations, we conducted the binding experiments under anoxic conditions in a specially designed apparatus. Purified intact Complex I enhanced NADH fluorescence in native gels approximately 10-fold. However, no enhancement was detected in denatured individual Complex I subunit proteins. In the Clear and Ghost native gels of the entire mitochondrial proteome, NADH fluorescence enhancement was localized to regions where NADH oxidation occurred in the presence of oxygen. Inhibitor and mass spectroscopy studies revealed that the fluorescence enhancement was specific to Complex I proteins. No fluorescence enhancement was detected for MDH or other dehydrogenases in this assay system, at physiological mole fractions of the matrix proteins. These data suggest that NADH associated with Complex I significantly contributes to the overall mitochondrial NADH fluorescence signal and provides an explanation for the well established close correlation of mitochondrial NADH fluorescence and the metabolic state.
XIRL: Cross-embodiment Inverse Reinforcement Learning (2021)

We investigate the visual cross-embodiment imitation setting, in which agents learn policies from videos of other agents (such as humans) demonstrating the same task, but with stark differences in their embodiments -- shape, actions, end-effector dynamics, etc. In this work, we demonstrate that it is possible to automatically discover and learn vision-based reward functions from cross-embodiment demonstration videos that are robust to these differences. Specifically, we present a self-supervised method for Cross-embodiment Inverse Reinforcement Learning (XIRL) that leverages temporal cycle-consistency constraints to learn deep visual embeddings that capture task progression from offline videos of demonstrations across multiple expert agents, each performing the same task differently due to embodiment differences. Prior to our work, producing rewards from self-supervised embeddings typically required alignment with a reference trajectory, which may be difficult to acquire under stark embodiment differences. We show empirically that if the embeddings are aware of task progress, simply taking the negative distance between the current state and goal state in the learned embedding space is useful as a reward for training policies with reinforcement learning. We find our learned reward function not only works for embodiments seen during training, but also generalizes to entirely new embodiments. Additionally, when transferring real-world human demonstrations to a simulated robot, we find that XIRL is more sample efficient than current best methods. Qualitative results, code, and datasets are available at https://x-irl.github.io
Antimicrobial andUVprotective chitosan/lignin multilayer nanocoating with immobilized silver nanoparticles (2023)

Abstract Poor antimicrobial activity and lack of protection against UV irradiation are weaknesses of cotton textiles. In an attempt to impart superior antimicrobial and UV‐protective properties to cotton, layer‐by‐layer deposition of chitosan and magnesium lignosulfonate, and in situ synthesis of silver (Ag) nanoparticles (NPs), was performed. Lignin, in a chitosan/lignin multilayer, simultaneously acts as a UV protective macromolecule and natural reducing and stabilizing agent, allowing formation of Ag NPs. Four bilayers of this coating is sufficient for fabrication of a chitosan/lignin/Ag‐NP textile nanocomposite treatment with 50+ UV protection. 100% reduction of Gram‐negative bacteria Escherichia coli , gram‐positive bacteria Staphylococcus aureus, and yeast Candida albicans can be achieved with a 12‐bilayer coating, when 20 mM silver nitrate solution and sodium borohydride are applied. On the other hand, four bilayers impregnated with Ag NPs, using 10 mM silver nitrate solution, provides sufficient antimicrobial activity independent of an added reducing agent. This treatment exhibits no inhibition of human keratinocyte cells growth on the skin, indicating low cytotoxicity.