gebhart/patrepeval huggingface dataset:
New observations on antigenic diversification of RNA viruses. Antigenic variation is not dependent on immune selection (1993)

Recent results have revealed novel features in the process of antigenic diversification of FMDV. (i) Antigenic variation is not necessarily the result of immune selection. (ii) Single, critical amino acid replacements may either have a minor effect on antigenic specificity or cause a drastic antigenic change affecting many epitopes on an antigenic site. (iii) The effect of such a critical replacement may be suppressed by additional substitutions at neighbouring sites. (iv) Antigenic diversification does not necessarily involve net accumulation of amino acid substitutions over time. We review evidence that some of these features apply also to other riboviruses and retroviruses. A model is proposed to relate antigenic variation without immune selection to the quasispecies structure of RNA virus populations.
Immunotherapy with OX40L‐Fc or anti‐CTLA‐4 enhances local tissue responses and killing of Leishmania donovani (2004)

Enhancing granuloma development and effector function, but without inducing the pathology associated with excess granulomatous inflammation, poses a major challenge for immunotherapeutic intervention against diseases such as visceral leishmaniasis (VL). Here, we demonstrate that a chimeric fusion protein (OX40L-Fc) which stimulates T cells through OX40 and a monoclonal antibody which blocks CTLA-4, an inhibitory receptor on T cells, both enhanced the rate of granuloma maturation, CD4(+) T cell proliferation, and killing of Leishmania. Costimulation-based therapy induced no adverse fibrotic or necrotic reactions, and had no significant effect on the levels of endogenous anti-inflammatory cytokines (IL-10 and TGF-beta). Furthermore, both OX40L-Fc and anti-CTLA4 could be co-administered with conventional anti-leishmanial drugs. Until now, enhancing T cell immunity by the manipulation of costimulatory pathways has only received serious attention for cancer immunotherapy, but our data provide a compelling argument for the evaluation of this approach in human VL and other infectious diseases.
A technique for error estimation of linewidth and damping parameters extracted from ferromagnetic resonance measurements (2015)

Ferromagnetic resonance (FMR) characterization, using a vector network analyzer (VNA), is widely used to determine anisotropy, g-factor, and Gilbert damping parameter of magnetic thin films, but results are typically reported without calculation of the measurement accuracy. We present a method of processing VNA-FMR measurements to determine both the value and confidence interval of these properties. The discussion is presented using FMR data obtained from stacks of MgO/CoFeB/Ta/CoFeB/MgO with varying CoFeB thickness. Measured S-parameters are de-embedded, drift corrected, fit to a Lorentzian curve, and analyzed to produce a confidence interval. A method of plotting the results of the Lorentzian fitting such that fitting errors or measurement drift can be visually analyzed is shown.
High numerical aperture Fourier ptychography: principle, implementation and characterization (2015)

Fourier ptychography (FP) utilizes illumination control and computational post-processing to increase the resolution of bright-field microscopes. In effect, FP extends the fixed numerical aperture (NA) of an objective lens to form a larger synthetic system NA. Here, we build an FP microscope (FPM) using a 40X 0.75NA objective lens to synthesize a system NA of 1.45. This system achieved a two-slit resolution of 335 nm at a wavelength of 632 nm. This resolution closely adheres to theoretical prediction and is comparable to the measured resolution (315 nm) associated with a standard, commercially available 1.25 NA oil immersion microscope. Our work indicates that Fourier ptychography is an attractive method to improve the resolution-versus-NA performance, increase the working distance, and enlarge the field-of-view of high-resolution bright-field microscopes by employing lower NA objectives.
SegFlow: Joint Learning for Video Object Segmentation and Optical Flow (2017)

This paper proposes an end-to-end trainable network, SegFlow, for simultaneously predicting pixel-wise object segmentation and optical flow in videos. The proposed SegFlow has two branches where useful information of object segmentation and optical flow is propagated bidirectionally in a unified framework. The segmentation branch is based on a fully convolutional network, which has been proved effective in image segmentation task, and the optical flow branch takes advantage of the FlowNet model. The unified framework is trained iteratively offline to learn a generic notion, and fine-tuned online for specific objects. Extensive experiments on both the video object segmentation and optical flow datasets demonstrate that introducing optical flow improves the performance of segmentation and vice versa, against the state-of-the-art algorithms.
A New Highly Selective Metabotropic Excitatory Amino Acid Agonist:  2-Amino-4-(3-hydroxy-5-methylisoxazol-4-yl)butyric Acid (1996)

The homologous series of acidic amino acids, ranging from aspartic acid (1) to 2-aminosuberic acid (5), and the corresponding series of 3-isoxazolol bioisosteres of these amino acids, ranging from (RS)-2-amino-2-(3-hydroxy-5-methylisoxazol-4-yl)acetic acid (AMAA, 6) to (RS)-2-amino-6-(3-hydroxy-5-methylisoxazol-4-yl)hexanoic acid (10), were tested as ligands for metabotropic excitatory amino acid receptors (mGlu1 alpha, mGlu2, mGlu4a, and mGlu6). Whereas AMAA (6) and (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propinoic acid (AMPA, 7) are potent and highly selective agonists at N-methyl-D-aspartic acid (NMDA) and AMPA receptors, respectively, the higher homologue of AMPA (7), (RS)-2-amino-4-(3-hydroxy-5-methylisoxazol-4-yl)butyric acid (homo-AMPA, 8), is inactive at ionotropic excitatory amino acid receptors. Homo-AMPA (8), which is a 3-isoxazolol bioisostere of 2-aminoadipic acid (3), was, however, shown to be a specific and rather potent agonist at mGlu6, approximately 4 times weaker than the nonselective excitatory amino acid receptor agonist (S)-glutamic acid. 2-Aminoadipic acid (3), which shows a complex excitatory amino acid synaptic pharmacology, was an agonist at mGlu6 as well as mGlu2. AMPA (7) and the higher homologue of homo-AMPA (8), (RS)-2-amino-5-(3-hydroxy-5-methylisoxazol-4-yl)pentanoic acid (9), showed relatively weak agonist effects at mGlu6. It is concluded that homo-AMPA (8) is likely to be a useful tool for studies of the pharmacology and physiological role of mGlu6. We describe a new versatile synthesis of this homologue of AMPA and the synthesis of compound 10.
The Unresponsiveness of Lipid Metabolism in Canine Mesenteric Adipose Tissue to Biogenic Amines and to Sympathetic Nerve Stimulation (1969)

Abstract The net release or uptake of glycerol and free fatty acids by adipose tissue in perfused mesentery of dogs was determined a) during stimulation of the superior mesenteric nerves and b) following intra‐arterial injection of noradrenaline, 5‐hydroxytryptamine, histamine and compound 48/80. Nerve stimulation had no observable effect on lipolysis, a finding which is in contrast to previously reported results from subcutaneous adipose tissue. Moreover, in order to evoke lipolysis, noradrenaline and histamine had to be administered in amounts over 10 times higher than required for subcutaneous adipose tissue. Compound 48/80, a mast cell‐depleting agent, and 5‐hydroxytryptamine did not increase lipolysis. It is concluded that mesenteric adipose tissue may not be influenced by the same agents for lipolysis as subcutaneous adipose tissue from the same species.
Chemotaxis Inhibitory Protein of Staphylococcus aureus Binds Specifically to the C5a and Formylated Peptide Receptor (2004)

Chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS) is an exoprotein produced by several strains of S. aureus, and a potent inhibitor of neutrophil and monocyte chemotaxis toward C5a and formylated peptides like fMLP. These chemoattractants act on their target cells by binding and activating the C5aR and formylated peptide receptor (FPR), respectively. In the present report, we examined the mechanism by which CHIPS affects both of these receptors. We showed that CHIPS blocked binding of anti-C5aR mAb and formylated peptide to human neutrophils as efficiently at temperatures of 0 and 37 degrees C, implying that it is independent of signal transducing systems. This was confirmed by showing that CHIPS acts completely independently of ATP. Additionally, CHIPS was not internalized upon binding to neutrophils. Furthermore, we showed that CHIPS binds specifically to the C5aR and FPR expressed on U937 cells. This binding was functional in blocking C5a- and fMLP-induced calcium mobilization in these cell lines. These results suggest that CHIPS binds directly to the C5aR and FPR, thereby preventing the natural ligands from activating these receptors. The apparent K(d) values of CHIPS for the C5aR and FPR were 1.1 +/- 0.2 nM and 35.4 +/- 7.7 nM, respectively. Moreover, after screening a wide variety of other G protein-coupled receptors, CHIPS was found to affect exclusively the C5aR and FPR. This selectivity and high-affinity binding with potent antagonistic effects makes CHIPS a promising lead for the development of new anti-inflammatory compounds for diseases in which damage by neutrophils plays a key role.
GITR-Dependent Regulation of 4-1BB Expression: Implications for T Cell Memory and Anti–4-1BB–Induced Pathology (2013)

The TNFR family member 4-1BB plays a key role in the survival of activated and memory CD8 T cells. However, the mechanisms that regulate 4-1BB re-expression on memory CD8 T cells after Ag clearance are unknown. In unimmunized mice, ∼10% of CD8 CD44(hi) memory T cells in the bone marrow (BM) and liver express 4-1BB, with minimal 4-1BB expression in spleen and lymph node. IL-2, IL-15, and IL-7 are collectively dispensable for 4-1BB expression on the memory CD8 T cells. Rather, T cell-intrinsic glucocorticoid-induced TNFR-related protein (GITR) contributes to 4-1BB expression on CD8 T cells upon their entry into the BM or liver. Consistent with its role in regulation of 4-1BB, GITR is required on memory CD8 T cells for their persistence in vivo. These findings reveal site-specific effects of the BM and liver microenvironment on CD8 memory T cells. Previous work has demonstrated that 4-1BB agonists given to unimmunized mice induce splenomegaly, hepatitis, and other immune system anomalies. Moreover, severe liver pathology has been observed in a subset of anti-4-1BB-treated melanoma patients. Remarkably, the absence of GITR in mice almost completely abrogates cellular expansions, splenomegaly, and liver inflammation associated with anti-4-1BB agonist treatment of unimmunized mice. In contrast, lack of CD8 T cells selectively improves liver pathology, but not splenomegaly in the mice. Thus, the regulation of 4-1BB expression by GITR on CD8 T cells, as well as on other cells, contributes to the pathological effects of anti-4-1BB in unimmunized mice.
Large scale infrared imaging of tissue micro arrays (TMAs) using a tunable Quantum Cascade Laser (QCL) based microscope (2014)

Chemical imaging in the field of vibrational spectroscopy is developing into a promising tool to complement digital histopathology. Applications include screening of biopsy tissue via automated recognition of tissue/cell type and disease state based on the chemical information from the spectrum. For integration into clinical practice, data acquisition needs to be speeded up to implement a rack based system where specimens are rapidly imaged to compete with current visible scanners where 100's of slides can be scanned overnight. Current Fourier transform infrared (FTIR) imaging with focal plane array (FPA) detectors are currently the state-of-the-art instrumentation for infrared absorption chemical imaging, however recent development in broadly tunable lasers in the mid-IR range is considered the most promising potential candidate for next generation microscopes. In this paper we test a prototype quantum cascade laser (QCL) based spectral imaging microscope with a focus on discrete frequency chemical imaging. We demonstrate how a protein chemical image of the amide I band (1655 cm(-1)) of a 2 × 2.4 cm(2) breast tissue microarray (TMA) containing over 200 cores can be measured in 9 min. This result indicates that applications requiring chemical images from a few key wavelengths would be ideally served by laser-based microscopes.
Impact of nutrition on pancreatic exocrine and endocrine secretion in ruminants: a review (1992)

Because of the unique features of the ruminant digestive system, variations in diet composition and intake produce dramatic changes in ruminal fermentation. Optimizing nutritional management requires an understanding of how these variations and changes influence digestion and metabolism. Although the pancreas plays a central role in digestion and subsequent nutrient metabolism, relatively little is known about pancreatic adaptation to nutritional changes in the ruminant. Increasing starch intake has been suggested to increase pancreatic alpha-amylase; however, recent work suggests that dietary energy per se may drive these changes, and interactions with other nutrients, such as protein, may exist. Studies describing the influence of altered protein and lipid intakes on pancreatic adaptation in ruminants are lacking. Pancreatic secretion of both insulin and glucagon respond to the intravenous infusion of VFA in a dramatic fashion; however, feeding studies suggest that the influence of VFA on insulin and glucagon may be more subtle. Interactions exist between stimulatory signals and physiological state, such as lactation. Assessment of pancreatic endocrine secretion is further complicated by a variable removal of insulin and glucagon by hepatic tissues. These studies point out that pancreatic hormone secretion is controlled by integrated and complex mechanisms. Studies of these controlling mechanisms should consider the entire array to more fully understand hormone secretion.
Fibrinogen Signal Transduction as a Mediator and Therapeutic Target in Inflammation:Lessons from Multiple Sclerosis (2007)

The blood protein fibrinogen as a ligand for integrin and non-integrin receptors functions as the molecular nexus of coagulation, inflammation and immunity. Studies in animal models and in human disease have demonstrated that extravascular fibrinogen that is deposited in tissues upon vascular rupture is not merely a marker, but a mediator of diseases with an inflammatory component, such as rheumatoid arthritis, multiple sclerosis, sepsis, myocardial infarction and bacterial infection. The present article focuses on the recent discoveries of specific cellular targets and receptors for fibrinogen within tissues that have extended the role of fibrinogen from a coagulation factor to a regulator of inflammation and immunity. Fibrinogen has the potential for selective drug targeting that would target its proinflammatory properties without affecting its beneficial effects in hemostasis, since it interacts with different receptors to mediate blood coagulation and inflammation. Strategies to target receptors for fibrinogen and fibrin within the tissue microenvironment could reveal selective and disease-specific agents for therapeutic intervention in a variety of human diseases associated with fibrin deposition.
Immune Response of Hepatitis B Vaccine Among Persons With Diabetes (2012)

In October 2011, the Advisory Committee on Immunization Practices (ACIP) recommended hepatitis B vaccination for adults with diabetes in the United States (1). Serosurvey data from the 1999–2010 National Health and Nutrition Examination Survey found that noninstitutionalized adults aged ≥18 years with diabetes have an increased seroprevalence of past or current hepatitis B virus (HBV) infection (1). Outbreaks of hepatitis B in elderly persons with diabetes in long-term care facilities have been linked to diabetes care procedures (including blood glucose monitoring), with likely vehicles for transmission including spring-loaded finger-stick devices used on multiple patients and blood glucose testing meters that were not cleaned between uses on different patients.

In the U.S., hepatitis B vaccination is routinely recommended for infants, children, and adolescents. It also is recommended for adults at increased risk of HBV infection, including persons with end-stage renal disease or chronic liver disease, health care personnel, injection-drug users, and men who have sex with men (2–4). A hepatitis B vaccination series results in protection in a high proportion (>95%) of infants, children, and young adults (5). As with other vaccines, the efficacy of the hepatitis B vaccine progressively declines with advancing age, as well as with the presence of obesity and other comorbid conditions (6–12). Results of studies of the hepatitis B vaccine among persons with diabetes generally follow these patterns (13,14).

Primary hepatitis B vaccination usually consists of 3 (or 4) doses of 10 or 20 µg of recombinant hepatitis B surface antigen (HBsAg) protein administered intramuscularly into the deltoid muscle on a 0-, 1-, and 6-month schedule (Table 1). Alternative schedules are U.S.-approved for routine vaccination for specific ages and vaccine formulations, and they elicit dose-specific and final rates of seroprotection similar to those obtained on a 0-, 1-, and …
Multifocal High Grade Prostatic Intraepithelial Neoplasia is a Risk Factor for Subsequent Prostate Cancer (2010)

Multifocal and bilateral disease are adverse features of high grade prostatic intraepithelial neoplasia that significantly increase the risk of prostate cancer despite adjusting for other clinical indicators such as prostate specific antigen and abnormal digital rectal examination.
Human immunodeficiency virus type 1 Vpr induces apoptosis following cell cycle arrest (1997)

The human immunodeficiency virus type 1 (HIV-1) vpr gene encodes a protein which induces arrest of cells in the G2 phase of the cell cycle. Here, we demonstrate that following the arrest of cells in G2, Vpr induces apoptosis in human fibroblasts, T cells, and primary peripheral blood lymphocytes. Analysis of various mutations in the vpr gene revealed that the extent of Vpr-induced G2 arrest correlated with the levels of apoptosis. However, the alleviation of Vpr-induced G2 arrest by treatment with the drug pentoxifylline did not abrogate apoptosis. Together these studies indicate that induction of G2 arrest, but not necessarily continued arrest in G2, was required for Vpr-induced apoptosis to occur. Finally, Vpr-induced G2 arrest has previously been correlated with inactivation of the Cdc2 kinase. Some models of apoptosis have demonstrated a requirement for active Cdc2 kinase for apoptosis to occur. Here we show that accumulation of the hypophosphorylated or active form of the Cdc2 kinase is not required for Vpr-induced apoptosis. These studies indicate that Vpr is capable of inducing apoptosis, and we propose that both the initial arrest of cells and subsequent apoptosis may contribute to CD4 cell depletion in HIV-1 disease.
Nucleotide sequence of transforming human c-siscDNA clones with homology to platelet-derived growth factor (1985)

Three c-sis cDNA clones were obtained from polyadenylated RNA of a human T-cell lymphotropic virus (HTLV) type I transformed cell line. Two clones, designated pSM-1 and pSM-2, have cDNA inserts of 2498 and 2509 base pairs (bp), respectively, excluding the sizes of the guanylate tails, and the polyadenylate tracts. These clones are shorter than the estimated size of the c-sis mRNA of 4200 bp. Both of these clones can transform NIH 3T3 cells. The third clone, designated pSM-3 has a cDNA insert of 1421 bp and lacks transforming activity. The sequence of clone pSM-1 reveals a single long open reading frame (nucleotides 118-840) encoding chain A of platelet-derived growth factor, and two segments with homology to v-sis (nucleotides 182-871 and 1021-1325). Sequence homology is noted in the 3' untranslated region to the corresponding regions of the beta 1 interferon (IFN), human and murine beta-nerve growth factor (NGF), human interleukin 2 (IL2) genes, and tubulin pseudogenes. However, no typical AATAAA polyadenylation signal is present. An alternating (dCdA)n X (dGdT)n sequence is present in the 3' flanking cellular sequences similar to those in the corresponding position of the human proenkephalin gene, in the first intron of the gamma-IFN gene, and the second intron of the beta-NGF gene.
Dopa dimer (1968)

Y. Omote, Y. Fujinuma and N. Sugiyama, Chem. Commun. (London), 1968, 190a DOI: 10.1039/C1968000190A
3‐Hydroxyacyl‐CoA dehydrogenase and short chain 3‐hydroxyacyl‐CoA dehydrogenase in human health and disease (2005)

3-Hydroxyacyl-CoA dehydrogenase (HAD) functions in mitochondrial fatty acid beta-oxidation by catalyzing the oxidation of straight chain 3-hydroxyacyl-CoAs. HAD has a preference for medium chain substrates, whereas short chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD) acts on a wide spectrum of substrates, including steroids, cholic acids, and fatty acids, with a preference for short chain methyl-branched acyl-CoAs. Therefore, HAD should not be referred to as SCHAD. SCHAD is not a member of the HAD family, but instead, belongs to the short chain dehydrogenase/reductase superfamily. Previously reported cases of SCHAD deficiency are due to an inherited HAD deficiency. SCHAD, also known as 17beta-hydroxysteroid dehydrogenase type 10, is important in brain development and aging. Abnormal levels of SCHAD in certain brain regions may contribute to the pathogenesis of some neural disorders. The human SCHAD gene and its protein product, SCHAD, are potential targets for intervention in conditions, such as Alzheimer's disease, Parkinson's disease, and an X-linked mental retardation, that may arise from the impaired degradation of branched chain fatty acid and isoleucine.
Lutein/Zeaxanthin for the Treatment of Age-Related Cataract (2013)

clinicaltrials.gov Identifier: NCT00345176.
Homology requirements for recombination in Escherichia coli. (1985)

The DNA sequence homology required for recombination in Escherichia coli has been determined by measuring the recombination frequency between insulin DNA in a miniplasmid pi VX and a homologous sequence in a bacteriophage lambda vector. A minimum of approximately equal to 20 base pairs in a completely homologous segment is required for significant recombination. There is an exponential increase in the frequency of recombination when the length of homologous DNA is increased from 20 base pairs to 74 base pairs and an apparently linear increase with longer DNA segments. Mismatches within a homologous segment can dramatically decrease the frequency of recombination. Thus, the process of recombination is sensitive to the length of precisely base-paired segments between recombining homologues.