gebhart/patrepeval huggingface dataset:
Amino-terminal alteration of the HLA-A*0201-restricted human immunodeficiency virus pol peptide increases complex stability and in vitro immunogenicity. (1995)

Initial studies suggested that major histocompatibility complex class I-restricted viral epitopes could be predicted by the presence of particular residues termed anchors. However, recent studies showed that nonanchor positions of the epitopes are also significant for class I binding and recognition by cytotoxic T lymphocytes (CTLs). We investigated if changing nonanchor amino acids could increase class I affinity, complex stability, and T-cell recognition of a natural viral epitope. This concept was tested by using the HLA-A 0201-restricted human immunodeficiency virus type 1 epitope from reverse transcriptase (pol). Position 1 (P1) amino acid substitutions were emphasized because P1 alterations may not alter the T-cell receptor interaction. The peptide with the P1 substitution of tyrosine for isoleucine (I1Y) showed a binding affinity for HLA-A 0201 similar to that of the wild-type pol peptide in a cell lysate assembly assay. Surprisingly, I1Y significantly increased the HLA-A 0201-peptide complex stability at the cell surface. I1Y sensitized HLA-A 0201-expressing target cells for wild-type pol-specific CTL lysis as well as wild-type pol. Peripheral blood lymphocytes from three HLA-A2 HIV-seropositive individuals were stimulated in vitro with I1Y and wild-type pol. I1Y stimulated a higher wild-type pol-specific CTL response than wild-type pol in all three donors. Thus, I1Y may be an "improved" epitope for use as a CTL-based human immunodeficiency virus vaccine component. The design of improved epitopes has important ramifications for prophylaxis and therapeutic vaccine development.
A method to confer Protein L binding ability to any antibody fragment (2015)

Recombinant antibody single-chain variable fragments (scFv) are difficult to purify homogeneously from a protein complex mixture. The most effective, specific and fastest method of purification is an affinity chromatography on Protein L (PpL) matrix. This protein is a multi-domain bacterial surface protein that is able to interact with conformational patterns on kappa light chains. It mainly recognizes amino acid residues located at the VL FR1 and some residues in the variable and constant (CL) domain. Not all kappa chains are recognized, however, and the lack of CL can reduce the interaction. From a scFv composed of IGKV10-94 according to IMGT®, it is possible, with several mutations, to transfer the motif from the IGKV12-46 naturally recognized by the PpL, and, with the single mutation T8P, to confer PpL recognition with a higher affinity. A second mutation S24R greatly improves the affinity, in particular by modifying the dissociation rate (kd). The equilibrium dissociation constant (KD) was measured at 7.2 10(-11) M by surface plasmon resonance. It was possible to confer PpL recognition to all kappa chains. This protein interaction can be modulated according to the characteristics of scFv (e.g., stability) and their use with conjugated PpL. This work could be extrapolated to recombinant monoclonal antibodies, and offers an alternative for protein A purification and detection.
The Stem of Vesicular Stomatitis Virus G Can Be Replaced With the HIV-1 Env Membrane-Proximal External Region Without Loss of G Function or Membrane-Proximal External Region Antigenic Properties (2014)

The structure of the HIV-1 envelope membrane-proximal external region (MPER) is influenced by its association with the lipid bilayer on the surface of virus particles and infected cells. To develop a replicating vaccine vector displaying MPER sequences in association with membrane, Env epitopes recognized by the broadly neutralizing antibodies 2F5, 4E10, or both were grafted into the membrane-proximal stem region of the vesicular stomatitis virus (VSV) glycoprotein (G). VSV encoding functional G-MPER chimeras based on G from the Indiana or New Jersey serotype propagated efficiently, although grafting of both epitopes (G-2F5-4E10) modestly reduced replication and resulted in the acquisition of one to two adaptive mutations in the grafted MPER sequence. Monoclonal antibodies 2F5 and 4E10 efficiently neutralized VSV G-MPER vectors and bound to virus particles in solution, indicating that the epitopes were accessible in the preattachment form of the G-MPER chimeras. Overall, our results showed that the HIV Env MPER could functionally substitute for the VSV G-stem region implying that both perform similar functions even though they are from unrelated viruses. Furthermore, we found that the MPER sequence grafts induced low but detectable MPER-specific antibody responses in rabbits vaccinated with live VSV, although additional vector and immunogen modifications or use of a heterologous prime-boost vaccination regimen will be required to increase the magnitude of the immune response.
High-resolution spectral self-interference fluorescence microscopy (2002)

We present a new method of fluorescence imaging, which yields nm-scale axial height determination and ~15 nm axial resolution. The method uses the unique spectral signature of the fluorescent emission intensity well above a reflecting surface to determine vertical position unambiguously. We have demonstrated axial height determination with nm sensitivity by resolving the height difference of fluorescein directly on the surface or on top of streptavidin. While different positions of fluorophores of different color are determined independently with nm precision, resolving the position of two fluorophores of the same color is a more convoluted problem due to the finite spectral emission widow of the fluorophores. Hence, for physically close (<&lambda;/2) fluorophores, it is necessary to collect multiple spectra by independently scanning an excitation standing wave in order to deconvolute the contribution to the spectral pattern from different heights. Moving the excitation standing wave successively enhances or suppresses excitation from different parts of the height distribution, changing the spectral content. This way two fluorophores of the same color can be resolved to better than 20 nm. Design aspects of the dielectric stack for independent excitation wave scanning and limits of deconvolution for an arbitrary height distribution will be discussed.
Growth and Differentiation in the Hemopoietic System (1987)

Hemopoiesis is regulated by a complex series of interactions, including interactions among hemopoietic cells themselves, hemopoietic cells and the extracellular matrix, hemopoietic cells and marrow stromal cells, and hemopoietic cells and growth factors. In vitro culture systems have allowed a reductionist approach to the solution of these various problems and have facilitated experiments at the mechanistic level. The hemopoietic system is organized hierarchically with multipotential self-renewing stem cells, committed progenitor cells, and mature cells. The various stimuli necessary for growth and development of these cells are rapidly being elucidated. The nature of commitment (or differentiation) remains an enigma, but model systems have been developed in which various aspects of this problem can be investigated. In this respect, growth and differentiation factors obviously have a major role to play. Now that many of these factors have been molecularly cloned (and pure target cell populations are available) their role in vivo and their mode of action can be examined.
The Role of Mesoprefrontal Dopamine Neurons in Stress (1996)

While several catecholaminergic systems are activated by stressful stimuli, the mesoprefrontal dopamine (DA) system appears to be particularly vulnerable to stress. Low intensity stressors that do not produce detectable effects in most ascending catecholaminergic systems activate mesoprefrontal DA neurons. Mesoprefrontal DA neurons are unique in that they lack or have decreased densities of specific autoreceptors affecting autoregulatory capabilities, which could contribute to the fact that mesoprefrontal DA neurons exhibit increased rates of burst firing and DA turnover relative to other midbrain dopaminergic projections. In addition, mesoprefrontal DA neurons are uniquely modulated by a number of chemically distinct afferent influences including gamma-aminobutyric acid (GABA), serotonin, excitatory amino acid, substance P, opiate, and noradrenergic systems. Any or all of these factors could contribute to the selective activation of mesoprefrontal DA neurons following exposure to low intensity stressors. The present review summarizes the possible mechanisms by which mesoprefrontal DA neurons are preferentially activated by stress. The operational significance of this unique neurochemical response to stress is discussed in terms of a possible coping versus anxiety function. Also discussed are the ramifications of a dysfunction of this system with respect to stress-related or exacerbated disorders such as post-traumatic stress disorder and schizophrenia.
Anti-Inflammatory Effects of IKK Inhibitor XII, Thymulin, and Fat-Soluble Antioxidants in LPS-Treated Mice (2014)

The present study was designed to compare the anti-inflammatory effects of several agents applied in vivo, namely, a synthetic inhibitor of the NF-κB cascade, fat-soluble antioxidants, and the thymic peptide thymulin. Cytokine response in LPS-treated mice was analysed in tandem with the following parameters: the synthesis of inducible forms of the heat shock proteins HSP72 and HSP90α; activity of the NF-κB and SAPK/JNK signalling pathways; and TLR4 expression. Inflammation-bearing Balb/c male mice were pretreated with an inhibitor of IKK-α/β kinases (IKK Inhibitor XII); with thymulin; with dietary coenzyme Q9, α-tocopherol, and β-carotene; or with combinations of the inhibitor and peptide or antioxidants. Comparable anti-inflammatory effects were observed in inflammation-bearing mice treated separately with thymulin or with dietary antioxidants administered daily for two weeks before LPS treatment. When LPS-injected mice were treated with the inhibitor and antioxidants together, neither plasma cytokines, signal proteins, nor heat shock proteins recovered more efficiently than when mice were treated with these agents separately. In contrast to antioxidant diet, the thymulin was shown to increase the effect of IKK Inhibitor XII in preventing IKK activation in LPS-treated mice.
Altered hepatic lymphocyte subpopulations in obesity-related murine fatty livers: Potential mechanism for sensitization to liver damage (2000)

Although obesity-related fatty livers are vulnerable to damage from endotoxin, the mechanisms involved remain obscure. The purpose of this study was to determine if immunologic priming might be involved by determining if fatty livers resemble normal livers that have been sensitized to endotoxin damage by Propionibacterium acnes infection. The latter induces interleukin (IL)-12 and -18, causing a selective reduction of CD4+NK T cells, diminished IL-4 production, deficient production of T-helper type 2 (Th-2) cytokines (e.g., IL-10), and excessive production of Th-1 cytokines (e.g., interferon gamma [IFN-gamma]). Liver and spleen lymphocyte populations and hepatic cytokine production were compared in genetically obese, ob/ob mice (a model for obesity-related fatty liver) and lean mice. Obese mice have a selective reduction of hepatic CD4+NK T cells. Serum IL-18 is also increased basally, and the hepatic mRNA levels of IL-18 and -12 are greater after endotoxin challenge. Thus, up-regulation of IL-18 and IL-12 in fatty livers may reduce hepatic CD4+NK T cells. In addition, mononuclear cells from fatty livers have decreased expression of the adhesion molecule, leukocyte factor antigen-1 (LFA-1), which is necessary for the hepatic accumulation of CD4+NK T cells. Consistent with reduced numbers of hepatic CD4+NK T cells, mononuclear cells from fatty livers produce less IL-4. Furthermore, after endotoxin treatment, hepatic induction of IL-10 is inhibited, while that of IFN-gamma is enhanced. Thus, fatty livers have inherent immunologic alterations that may predispose them to damage from endotoxin and other insults that induce a proinflammatory cytokine response.
Therapeutic Angiogenesis With Recombinant Fibroblast Growth Factor-2 Improves Stress and Rest Myocardial Perfusion Abnormalities in Patients With Severe Symptomatic Chronic Coronary Artery Disease (2000)

These preliminary data suggest that the administration of rFGF-2 to patients with advanced coronary disease resulted in an attenuation of stress-induced ischemia and an improvement in resting myocardial perfusion; these findings are consistent with a favorable effect of therapeutic angiogenesis.
Legionella pneumophila feoABPromotes Ferrous Iron Uptake and Intracellular Infection (2002)

In order to determine the role of ferrous iron transport in Legionella pathogenesis, we identified and mutated the feoB gene in virulent Legionella pneumophila strain 130b. As it is in Escherichia coli, the L. pneumophila feoB gene was contained within a putative feoAB operon. L. pneumophila feoB insertion mutants exhibited decreased ferrous but not ferric iron uptake compared to the wild type. Growth on standard buffered charcoal yeast extract agar or buffered yeast extract broth was unaffected by the loss of L. pneumophila FeoB. However, the L. pneumophila feoB mutant had a reduced ability to grow on buffered charcoal yeast extract agar with a reduced amount of its usual iron supplementation, a phenotype that could be complemented by the addition of feoB in trans. In unsupplemented buffered yeast extract broth, the feoB mutant also had a growth defect, which was further exacerbated by the addition of the ferrous iron chelator, 2,2'-dipyridyl. The feoB mutant was also 2.5 logs more resistant to streptonigrin than wild-type 130b, confirming its decreased ability to acquire iron during extracellular growth. Decreased replication of the feoB mutant was noted within iron-depleted Hartmannella vermiformis amoebae and human U937 cell macrophages. The reduced intracellular infectivity of the feoB mutant was complemented by the introduction of a plasmid containing feoAB. The L. pneumophila feoB gene conferred a modest growth advantage for the wild type over the mutant in a competition assay within the lungs of A/J mice. Taken together, these results indicate that L. pneumophila FeoB is a ferrous iron transporter that is important for extracellular and intracellular growth, especially in iron-limited environments. These data represent the first evidence for the importance of ferrous iron transport for intracellular replication by a human pathogen.
Imaging transcriptional regulation of p53-dependent genes with positron emission tomography in vivo (2001)

A noninvasive method for molecular imaging of the activity of different signal transduction pathways and the expression of different genes in vivo would be of considerable value. It would aid in understanding the role specific genes and signal transduction pathways have in various diseases, and could elucidate temporal dynamics and regulation at different stages of disease and during various therapeutic interventions. We developed and assessed a method for monitoring the transcriptional activation of endogenous genes by positron-emission tomography (PET) imaging. The HSV1-tk/GFP (TKGFP) dual reporter gene was used to monitor transcriptional activation of p53-dependent genes. A retrovirus bearing the Cis-p53/TKGFP reporter system was constructed in which the TKGFP reporter gene was placed under control of an artificial cis-acting p53-specific enhancer. U87 glioma and SaOS-2 osteosarcoma cells were transduced with this retrovirus and used to establish xenografts in rats. We demonstrated that DNA damage-induced up-regulation of p53 transcriptional activity correlated with the expression of p53-dependent downstream genes, such as p21, in U87 (wild-type p53), but not in SaOS-2 osteosarcoma (p53 -/-) cells. We showed that PET, with [(124)I]FIAU (2'-fluoro-2'-deoxy-1-beta-d-arabinofuranosyl-5-[(124)I]iodouracil) and the Cis-p53TKGFP reporter system, is sufficiently sensitive to image the transcriptional regulation of genes in the p53 signal transduction pathway. These imaging results were confirmed by independent measurements of p53 activity and the expression levels of downstream genes (e.g., p21) by using conventional molecular-biological assays. PET imaging of p53 transcriptional activity in tumor xenografts by using the Cis-p53TKGFP reporter system may be useful in assessing novel therapeutic approaches.
Pemphigus and pemphigoid as paradigms of organ-specific, autoantibody-mediated diseases. (1989)

The blistering skin diseases pemphigus and pemphigoid can be considered paradigms of antibody-mediated, organ-specific autoimmune diseases. These diseases not only demonstrate mechanisms whereby autoantibodies can mediate tissue dam- age, but are also examples ofhow autoantibodies from patients can be used as tools to further our understanding ofthe molec- ular structure of normal tissue. In this Perspectives article, I will briefly describe the clinical, histologic, and immunopatho- logic features of these diseases. I will then discuss in more detail the newer data regarding the pathophysiology of these diseases, as well as the molecules defined by the autoantibodies from these patients.
Phenolic P2/P3 Core Motif as Thrombin Inhibitors — Design, Synthesis, and X‐Ray Co‐Crystal Structure. (2006)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
<title>Genosensors: microfabricated devices for automated DNA sequence analysis</title> (1993)

A new technology is introduced for developing potentially low cost, high throughput DNA sequence analysis. This approach utilizes novel bioelectronic genosensor devices to rapidly detect hybridization events across a DNA probe array. Detection of DNA probe/target hybridization has been achieved by two electronic methods. The first method utilizes a permittivity chip which interrogates the miniature test fixtures with a low voltage alternating electric field. The second method, which is the emphasis of this paper, utilizes a charge- coupled device (CCD) to detect the hybridization of appropriately tagged (radioisotope, fluorescent, or chemiluminescent labels) target DNA to an array of DNA probes immobilized above the pixels. Such direct electronic-biologic coupling is shown to provide a tenfold sensitivity improvement over conventional lens-based detection systems.
Possible Mechanism of Miltefosine-Mediated Death of Leishmania donovani (2004)

Miltefosine causes leishmanial death, but the possible mechanism(s) of action is not known. The mode of action of miltefosine was investigated in vitro in Leishmania donovani promastigotes as well as in extra- and intracellular amastigotes. Here, we demonstrate that miltefosine induces apoptosis-like death in L. donovani based on observed phenomena such as nuclear DNA condensation, DNA fragmentation with accompanying ladder formation, and in situ labeling of DNA fragments by the terminal deoxyribonucleotidyltransferase-mediated dUTP-biotin nick end labeling method. Understanding of miltefosine-mediated death will facilitate the design of new therapeutic strategies against Leishmania parasites.
Fundamental Reaction Pathways and Free-Energy Barriers for Ester Hydrolysis of Intracellular Second-Messenger 3‘,5‘-Cyclic Nucleotide (2004)

We have performed a series of first-principles electronic structure calculations to study competing reaction pathways and the corresponding free-energy barriers for the ester hydrolysis of intracellular second-messenger adenosine 3‘,5‘-cyclic monophosphate (cAMP) and related phosphodiesters including trimethylene phosphate (TMP). Reaction coordinate calculations show three fundamental reaction pathways for the ester hydrolysis, including (A) attack of a hydroxide ion at the P atom of the phosphate anion (an SN2 process without a pentacoordinated phosphorus intermediate), (B) direct attack of a water molecule at the P atom of the anion (a three-step process), and (C) direct attack of a water molecule at the P atom of the neutral ester molecule (a two-step process). The calculated energy results show that for the reactions in the gas phase the free-energy barrier for pathway A is the highest and the barrier for the rate-controlling step of pathway C is the lowest. However, for the reactions in aqueous solution, the free-energy barrier calculated for pathway A becomes the lowest, and the two main hydrolysis pathways are A and B. We also have demonstrated how the pKa of the ester and the pH of the reaction solution affect the relative contributions of different hydrolysis pathways to the total hydrolysis rate. Reaction pathway A should be dominant for the cAMP hydrolysis in neutral aqueous solution. However, the relative contribution of pathway A to the total hydrolysis rate should decrease with decreasing pH of the solution. For pH < ∼3.7, the contribution of pathway B is larger. For pH > ∼3.7, the contribution of pathway A is larger. The reliability of our theoretical predictions is supported by the excellent agreement of the calculated free-energy barrier with available experimental data for the hydrolysis of TMP in solution.
Oxidation Characteristics of Pure Hydrocarbons (1942)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOxidation Characteristics of Pure HydrocarbonsR. G. Larsen, R. E. Thorpe, and F. A. ArmfieldCite this: Ind. Eng. Chem. 1942, 34, 2, 183–193Publication Date (Print):February 1, 1942Publication History Published online1 May 2002Published inissue 1 February 1942https://pubs.acs.org/doi/10.1021/ie50386a012https://doi.org/10.1021/ie50386a012research-articleACS PublicationsRequest reuse permissionsArticle Views255Altmetric-Citations68LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options Get e-Alerts