gebhart/patrepeval huggingface dataset:
Laboratory costs and utilization: guidelines for efficient use of laboratory technology. (1985)

The practice of laboratory medicine now plays a major role in the delivery of health care. Under PPS, however, the laboratory has come under close scrutiny as one place where costs can be reduced. This article examines the use of continuous-flow and discrete analyzers in the chemistry laboratory and provides guidelines for determining which analyzer is most appropriate for a given organization.
Protection against Leishmania major infection in genetically susceptible BALB/c mice by gp63 delivered orally in attenuated Salmonella typhimurium (AroA- AroD-). (1995)

The gene encoding the Leishmania major (L. major) promastigote surface glycoprotein, gp63, was introduced into the Salmonella typhimurium (S. typhimurium) aroA- aroD- live oral vaccine strain BRD509 and expressed under the control of a constitutive tac promoter in plasmid pKK233-2. This construct (GID101) expressed gp63 in vitro and was used to immunize highly susceptible BALB/c mice by the oral route. The plasmid was relatively stably inherited by bacteria growing or persisting in the mesenteric lymph nodes of immunized mice. Mice immunized with GID101 developed significant resistance against a challenge infection with L. major compared to controls immunized with BRD509 alone. Spleen and lymph node cells from immunized mice developed a strong in vitro proliferative T-cell response to killed or live L. major. The activated T cells secreted interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) which was abrogated by treatment with anti-CD4 but not with anti-CD8 antibody. The cells did not produce detectable levels of interleukin-4 (IL-4). The immunized mice also produced significant amounts of leishmanial specific IgG2a antibody but did not develop delayed-type hypersensitivity (DTH) to live parasites. No IgG1 antibody was detected. These data therefore demonstrate that gp63 gene delivered orally by a vaccine strain of S. typhimurium can preferentially induce the development of Th-1 subset of CD4+ T cells and protective immunity in the highly susceptible BALB/c mice.
Epigenetics and parental effects (2010)

Parental effects are a major source of phenotypic plasticity and may influence offspring phenotype in concert with environmental demands. Studies of "environmental epigenetics" suggest that (1) DNA methylation states are variable and that both demethylation and remethylation occur in post-mitotic cells, and (2) that remodeling of DNA methylation can occur in response to environmentally driven intracellular signaling pathways. Studies of mother-offspring interactions in rodents suggest that parental signals influence the DNA methylation, leading to stable changes in gene expression. If parental effects do indeed enhance the "match" between prevailing environmental demands and offspring phenotype, then the potential for variation in environmental conditions over time would suggest a mechanism that requires active maintenance across generations through parental signaling. We suggest that parental regulation of DNA methylation states is thus an ideal candidate mechanism for parental effects on phenotypic variation.
Phagocytic processing of exogenous particulate antigens by macrophages for presentation by class I MHC molecules. (1994)

Exogenous Ags that are processed in vacuolar endocytic compartments are generally presented by class II MHC molecules and not class I MHC (MHC-I) molecules, which conventionally present cytoplasmic or endogenous Ags. Accordingly, i.v. immunization of C57BL/6 mice with soluble OVA did not elicit a CD8 T cell response. However, i.v. immunization with OVA coupled to Latex particles (Latex-OVA) elicited an OVA-specific CD8 T cell response in vivo (particles from 59 to 2000 nm diameter were effective). In vitro, Latex-OVA was processed by H-2b macrophages and presented by Kb at least 100- to 1000-fold more efficiently than was soluble OVA. Inhibition of phagocytosis by cytochalasin D blocked the processing of Latex-OVA, whereas processing was not blocked by Brefeldin A. Latex-OVA was presented directly by H-2b macrophages or after "regurgitation" of processed OVA peptide from viable MHC-disparate macrophages for binding to surface Kb molecules on fixed H-2b macrophages. Peptide regurgitation was observed during processing of both Latex-OVA and Salmonella typhimurium 14028s that express an OVA fusion protein (Crl-OVA). However, the regurgitation pathway was less efficient than direct processing by viable H-2b macrophages. Thus, macrophages express an alternate pathway that allows MHC-I presentation of vacuolar exogenous particulate Ags, including inert synthetic particles without lipid membranes and intravacuolar bacteria. Peptides from these Ags are released from intracellular compartments to bind to surface MHC-I molecules, but peptide-MHC-I complexes also may be generated within intracellular compartments.
mRNA-based SARS-CoV-2 vaccine candidate CVnCoV induces high levels of virus-neutralising antibodies and mediates protection in rodents (2021)

mRNA technologies have recently proven clinical efficacy against coronavirus disease 2019 and are among the most promising technologies to address the current pandemic. Here, we show preclinical data for our clinical candidate CVnCoV, a lipid nanoparticle-encapsulated mRNA vaccine that encodes full-length, pre-fusion stabilised severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein. In contrast to previously published approaches, CVnCoV is exclusively composed of naturally occurring nucleotides. Immunisation with CVnCoV induced strong humoral responses with high titres of virus-neutralising antibodies and robust T-cell responses. CVnCoV vaccination protected hamsters from challenge with wild-type SARS-CoV-2, demonstrated by the absence of viral replication in the lungs. Hamsters vaccinated with a suboptimal dose of CVnCoV leading to breakthrough viral replication exhibited no evidence of vaccine-enhanced disease. Overall, data presented here provide evidence that CVnCoV represents a potent and safe vaccine candidate against SARS-CoV-2.
Impact of Eicosapentaenoic Acid Treatment on the Fibrous Cap Thickness in Patients with Coronary Atherosclerotic Plaque: An Optical Coherence Tomography Study (2014)

In the present study, the administration of EPA for eight months significantly increased the fibrous cap thickness in patients with coronary atherosclerotic plaque.
Analysis of binding properties between 20 kDa human growth hormone (hGH) and hGH receptor (hGHR): the binding affinity for hGHR extracellular domain and mode of receptor dimerization (1999)

It has recently been shown that 20 kDa human growth hormone (hGH) forms the 1:2 hGH:hGH receptor (hGHR) complex and expresses full agonistic activity, although it hardly forms the 1:1 GH:GHR complex as compared with 22 kDa hGH. To clarify this mechanism, we analyzed the mode of receptor dimerization of 20 kDa hGH using the intact form and mutants. Complex formation analysis between hGHR extracellular domain (hGHBP) and either site1 mutant (K157A) or site2 mutant (G105R) by gel-filtration showed that the site1 mutant apparently formed no 1:1 complex and that the site2 mutant formed only the 1:1 complex. Cell proliferation analysis revealed that the activity curve (vs ligand concentration) of 20 kDa hGH showed a bell-shaped pattern. This indicates that the receptor dimerization of 20 kDa hGH proceeds in a sequential manner. Based on this sequential binding we have produced a mathematical model for receptor dimerization as a function of [hGH], [hGHBP], K(d) values for the first hGHBP binding (K(d1)) and the second hGHBP binding (K(d2)). The result of 20 kDa hGH binding to (S201C) hGHBP immobilized on biosensor tip showed that the K(d1) value was 1. 6x10(-8) M. Adopting this value as a constant in the function described above, we have obtained calculative hGHR dimerization curves vs hGH concentration. Since the K(d2) value could not be experimentally determined, the curves were simulatively obtained with varied K(d2) values. The simulated curve pattern coincided with the experimental result of the cell proliferation in Ba/F3-hGHR when the value 2.5x10(-10) M was adopted as K(d2). In conclusion, although the affinity of 20 kDa hGH for the first hGHR binding is reduced to one-tenth, that for the second binding is increased ten-fold in comparison with those of 22 kDa hGH, indicating that 20 kDa hGH can be an effective hGH isoform in the presence of hGHBP.
The protein kinase Akt induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma lines. (2003)

Epithelial-mesenchymal transition (EMT) is an important process during development and oncogenesis by which epithelial cells acquire fibroblast-like properties and show reduced intercellular adhesion and increased motility. Squamous cell carcinoma lines engineered to express constitutively active Akt underwent EMT, characterized by down-regulation of the epithelial markers desmoplakin, E-cadherin, and beta-catenin and up-regulation of the mesenchymal marker vimentin. The cells lost epithelial cell morphology and acquired fibroblast-like properties. Additionally, E-cadherin was down-regulated transcriptionally. The cells expressing constitutively active Akt exhibited reduced cell-cell adhesion, increased motility on fibronectin-coated surfaces, and increased invasiveness in animals. AKT is activated in many human carcinomas, and the AKT-driven EMT may confer the motility required for tissue invasion and metastasis. These findings suggest that future therapies based on AKT inhibition may complement conventional treatments by controlling tumor cell invasion and metastasis.
In Vitro Epileptic Seizure Prediction Microsystem (2007)

The architecture and VLSI implementation of an epileptic seizure prediction microsystem are presented. The microsystem comprises a neural recording interface and a seizure prediction processor. The two functional blocks have been prototyped in a 0.35 <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">μ</i> CMOS technology and experimentally characterized. The integrated microsystem is validated in predicting the onsets of seizures off line in an in vitro epilepsy model of recurrent spontaneous seizures in the hippocampus of mice.
Mini-SMIFTS: an uncooled LWIR hyperspectral sensor (2004)

A long-wave infrared hyperspectral sensor using an interferometer and an uncooled microbolometer array camera was built and tested. The sensor showed signal to noise ratios near 200 for ambient temperature scenes with 33 wavenumber resolution at a frame rate of 50 Hz. Straightforward performance improvements in optics and reported detector performances suggest signal to noise ratios near 1000 at 10 wavenumber resolution should be achievable.
3-Nitrotyrosine in the proteins of human plasma determined by an ELISA method (1998)

The modification of tyrosine residues in proteins to 3-nitrotyrosine by peroxynitrite or other potential nitrating agents has been detected in biological systems that are subject to oxidative stress. A convenient semi-quantitative method has been developed to assay nitrated proteins in biological fluids and homogenates using a competitive ELISA developed in our laboratory. This assay selectivity detected 3-nitro-l-tyrosine residues in a variety of peroxynitrite-treated proteins (BSA, human serum albumin (HSA), alpha1-antiprotease inhibitor, pepsinogen and fibrinogen) and also in a nitrated peptide, but had a low affinity for free 3-nitro-L-tyrosine and 3-chloro-L-tyrosine. The IC50 values for the inhibition of antibody binding by different nitrated proteins were in the range 5-100 nM, suggesting that the antibody discriminated between nitrotyrosine residues in different environments. The presence of nitrotyrosine in plasma proteins was detected by Western blot analysis and quantified by the ELISA. A concentration of 0. 12+/-0.01 microM nitro-BSA equivalents was measured in the proteins of normal plasma which was increased in peroxynitrite-treated plasma and was elevated in inflammatory conditions. HSA and low-density lipoprotein (LDL) isolated from plasma contained 0.085+/-0.04 and 0. 03+/-0.006 nmol nitro-BSA equivalents/mg protein, respectively. Comparison of the level of nitration in peroxynitrite-treated HSA and LDL in the presence and absence of plasma indicates that nitration and presumably oxidation is inhibited by plasma antioxidants. The presence of nitrotyrosine in LDL is consistent with previous reports implicating peroxynitrite in the oxidative modification of lipoproteins and the presence of a low concentration of oxidized LDL in the blood.
T helper 1 response against Leishmania major in pregnant C57BL/6 mice increases implantation failure and fetal resorptions. Correlation with increased IFN-gamma and TNF and reduced IL-10 production by placental cells. (1996)

Maternal immune responses can influence fetal survival and several cytokines have harmful or protective effects on pregnancy. The Th1 cytokines IFN-gamma and IL-2 can cause fetal loss, whereas the Th2 cytokine IL-10 is protective. However, infections such as leishmaniasis show the opposite pattern: resistance is associated with the preferential mounting of a Th1 response, whereas a Th2 response exacerbates the disease. We therefore asked whether the curative Th1 response against Leishmania major in genetically resistant C57BL/6 mice, would compromise concurrent pregnancy. The number of resorptions as assessed by uterine scars was significantly increased in infected C57BL/6 mice and this was associated with a decreased production by placental cells of the Th2 cytokines IL-4 and IL-10 and increased production of IFN-gamma and TNF. Interestingly, the frequency of pregnancy failure before implantation in C57BL/6 mice was also substantially increased. In contrast to C57BL/6 mice, early infection did not reduce implantations in BALB/c mice that mount a Th2 anti-L. major response and succumb to infection. For both resorptions and implantations, there appeared to be a short period early in infection that was detrimental to pregnancy, followed by a period with lesser effects, and a later period that again induced higher resorptions or pre-implantation losses. These results suggest that a beneficial anti-parasite Th1 response can adversely affect pregnancy outcome. Furthermore, Th1 cytokines may be deleterious for not only placental maintenance but also preimplantation events.
Adhesion and Migration Are Differentially Regulated in Hematopoietic Progenitor Cells by Cytokines and Extracellular Matrix (1997)

The conditions that control the migratory status of hematopoietic progenitor cells on extracellular matrix (ECM) and that decide whether a cell migrates or adheres are incompletely understood. We analyzed the migratory behavior of murine hematopoietic progenitor cells factor-dependent-cell-paterson (FDCP)-mix and purified lin-Sca1+ bone marrow cells on ECM. We found that migration on fibronectin (Fn) or laminin (Lam) becomes dependent on beta1-integrins if a surface restraint force is introduced by tilting the ECM-coated culture vessels. Under these conditions, migration specifically occured on Fn and Lam, and was not detected on collagen IV-, hyaluronate-, or bovine serum albumin- coated surfaces. Migration depended on the continuous presence of hematopoietic cytokines interleukin-3 (IL-3), granulocyte colony-stimulating factor (G-CSF), macrophage-CSF (M-CSF), granulocyte-macrophage-CSF (GM-CSF), or stem cell factor (SCF), whereas other cytokines, such as IL-8, macrophage inflammatory protein-1alpha, macrophage-chemotactic and activating factor, and erythropoietin resulted in very little or no migratory response. IL-3 induced migration was synergistically enhanced by other CSFs, but was completely inhibited by addition of transforming growth factor-beta1. In contrast to firm local adhesion of previously cytokine depleted progenitors that was rapidly inducible within 1 hour after exposure to cytokines, preincubation on Fn matrix for 4 to 6 hours was required before cytokines could induce migration. A sudden increase of cytokine concentration reversibly inhibited migration and induced a fully adhesive state; this effect could be prolonged by consecutive stimulation with heterologous cytokines. Whereas cytokines activated resting progenitor cells to migrate on ECM, cell migration speed was regulated by Fn concentration. These results indicate that beta1-integrin-mediated progenitor cell adhesion and migration are differentially regulated by external stimuli and suggest that this regulation corresponds to different activation states of beta1-integrins in hematopoietic progenitor cells.
Structure of a gene coding for human HMG2 protein. (1992)

A human genomic library was screened with the pig thymus cDNA coding for chromosomal protein HMG2. A 4341-base pair fragment containing the entire gene encoding this protein was isolated and characterized. The HMG2 gene is 2665 base pairs long from the start site to the end of transcription and comprises 5 exons. The size of mRNA postulated from the exons is 1125 base pairs long, consistent with that obtained by Northern hybridization analysis. The canonical 5'-regulatory motifs, CCAAT, are present, while the TATA element is absent from the gene. Southern analysis suggested that HMG2 protein is encoded by a single or only a few genes of high homology. The primary structure of the human HMG2 protein consists of 208 amino acid residues, deduced from the coding region of the gene, is different from that of pig HMG2 in only two amino acids; one is exchanged and the other is missing. The amino acid sequences of two DNA binding domains, HMG-box, also recently found in several transcription factors, are completely homologous in human and pig HMG2. The present study, which is the first one on the isolation and characterization of complete gene coding for HMG2 protein, may be useful for evolutional and genomic analysis of the proteins containing the HMG-box sequences for DNA binding.
Structure of heptameric protective antigen bound to an anthrax toxin receptor: A role for receptor in pH-dependent pore formation (2004)

After binding to cellular receptors and proteolytic activation, the protective antigen component of anthrax toxin forms a heptameric prepore. The prepore later undergoes pH-dependent conversion to a pore, mediating translocation of the edema and lethal factors to the cytosol. We describe structures of the prepore (3.6 A) and a prepore:receptor complex (4.3 A) that reveal the location of pore-forming loops and an unexpected interaction of the receptor with the pore-forming domain. Lower pH is required for prepore-to-pore conversion in the presence of the receptor, indicating that this interaction regulates pH-dependent pore formation. We present an example of a receptor negatively regulating pH-dependent membrane insertion.
Heparin-induced Thrombocytopenia: Towards Consensus (1998)

Summary Heparin-induced thrombocytopenia (HIT) is a drug-induced, immunoglobulin-mediated thrombocytopenic disorder that is important for at least three reasons. First, it is a relatively common drug-induced immunohematologic adverse reaction. Second, it is frequently complicated by life- and limb-threatening thrombotic complications. And third, there remains uncertainty about the optimal treatment approach for these patients. Recently, there has emerged increasing consensus on such important issues as the frequency, pathogenesis, and diagnostic testing, which we will summarize here. Further, a greater appreciation of the activation of the coagulation pathways in this syndrome indicate a rationale to treatment approaches that emphasize thrombin inhibition (eg. danaparoid sodium; hirudin and its analogues).
Combinatorial antibody library from multiple sclerosis patients reveals antibodies that cross‐react with myelin basic protein and EBV antigen (2011)

Multiple sclerosis (MS) is a widespread neurodegenerative autoimmune disease with unknown etiology. It is increasingly evident that, together with pathogenic T cells, autoreactive B cells are among the major players in MS development. The analysis of myelin neuroantigen-specific antibody repertoires and their possible cross-reactivity against environmental antigens, including viral proteins, could shed light on the mechanism of MS induction and progression. A phage display library of single-chain variable fragments (scFvs) was constructed from blood lymphocytes of patients with MS as a potential source of representative MS autoantibodies. Structural alignment of 13 clones selected toward myelin basic protein (MBP), one of the major myelin antigens, showed high homology within variable regions with cerebrospinal fluid MS-associated antibodies as well as with antibodies toward Epstein-Barr latent membrane protein 1 (LMP1). Three scFv clones showed pronounced specificity to MBP fragments 65-92 and 130-156, similar to the serum MS antibodies. One of these clones, designated E2, in both scFv and full-size human antibody constructs, was shown to react with both MBP and LMP1 proteins in vitro, suggesting natural cross-reactivity. Thus, antibodies induced against LMP1 during Epstein-Barr virus infection might act as inflammatory trigger by reacting with MBP, suggesting molecular mimicry in the mechanism of MS pathogenesis.
Natural TTS Synthesis by Conditioning WaveNet on Mel Spectrogram Predictions (2017)

This paper describes Tacotron 2, a neural network architecture for speech synthesis directly from text. The system is composed of a recurrent sequence-to-sequence feature prediction network that maps character embeddings to mel-scale spectrograms, followed by a modified WaveNet model acting as a vocoder to synthesize timedomain waveforms from those spectrograms. Our model achieves a mean opinion score (MOS) of $4.53$ comparable to a MOS of $4.58$ for professionally recorded speech. To validate our design choices, we present ablation studies of key components of our system and evaluate the impact of using mel spectrograms as the input to WaveNet instead of linguistic, duration, and $F_0$ features. We further demonstrate that using a compact acoustic intermediate representation enables significant simplification of the WaveNet architecture.
Critical Time-Window for NO–cGMP-Dependent Long-Term Memory Formation after One-Trial Appetitive Conditioning (2002)

The nitric oxide (NO)-cGMP signaling pathway is implicated in an increasing number of experimental models of plasticity. Here, in a behavioral analysis using one-trial appetitive associative conditioning, we show that there is an obligatory requirement for this pathway in the formation of long-term memory (LTM). Moreover, we demonstrate that this requirement lasts for a critical period of approximately 5 hr after training. Specifically, we trained intact specimens of the snail Lymnaea stagnalis in a single conditioning trial using a conditioned stimulus, amyl-acetate, paired with a salient unconditioned stimulus, sucrose, for feeding. Long-term associative memory induced by a single associative trial was demonstrated at 24 hr and shown to last at least 14 d after training. Tests for LTM and its dependence on NO were performed routinely 24 hr after training. The critical period when NO was needed for memory formation was established by transiently depleting it from the animals at a series of time points after training by the injection of the NO-scavenger 2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl 3-oxide (PTIO). By blocking the activity of NO synthase and soluble guanylyl cyclase enzymes after training, we provided further evidence that LTM formation depends on an intact NO-cGMP pathway. An electrophysiological correlate of LTM was also blocked by PTIO, showing that the dependence of LTM on NO is amenable to analysis at the cellular level in vitro. This represents the first demonstration that associative memory formation after single-trial appetitive classical conditioning is dependent on an intact NO-cGMP signaling pathway.