gebhart/patrepeval huggingface dataset:
Mobility and Persistence of Metolachlor and Aldicarb in Field Lysimeters (1988)

Abstract The mobility and persistence of metolachlor [2‐chloro‐ N ‐(2‐ethyl‐6‐methylphenyl)‐ N ‐(2‐methoxy‐1‐methylethyl)acetamide], a herbicide, and aldicarb [2‐methyl‐2‐(methylthio)propanaldehyde O ‐(methylcarbamoyl) oxime], an insecticide, were studied using field lysimeters containing 15 cm (diam.) by 70 cm (length) cores of Plainfield sand (mixed, mesic Typic Udipsamments). One‐half of the cores received only rainfall, while the remainder received rainfall plus simulated 50.8‐mm rainfalls on the second and eighth days after treatment, followed by simulated irrigation for the duration of the study. Metolachlor exhibited limited mobility, except in the supplementary watering treatment, in which there was rapid transport of some herbicide 40 cm down the core, with accompanying traces in the effluent. Metolachlor half‐life was in the 3‐ to 4‐wk range. Aldicarb rapidly converted to its sulfoxide [2‐methyl‐2‐(methylsulfinyl)propanal O ‐(methylamino)carbonyl oxime] and sulfone [2‐methyl‐2‐(methylsulfonyl)propanal O ‐(methylamino)carbonyl oxime] (50% in 3–5 d). Under normal rainfall, about 9% of the applied aldicarb leached out of the soil cores as sulfoxide or sulfone. In cores receiving supplementary watering, up to 64% of applied aldicarb appeared in the effluent principally as sulfoxide or sulfone.
A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure (2006)

Diverse forms of injury and stress evoke a hypertrophic growth response in adult cardiac myocytes, which is characterized by an increase in cell size, enhanced protein synthesis, assembly of sarcomeres, and reactivation of fetal genes, often culminating in heart failure and sudden death. Given the emerging roles of microRNAs (miRNAs) in modulation of cellular phenotypes, we searched for miRNAs that were regulated during cardiac hypertrophy and heart failure. We describe >12 miRNAs that are up- or down-regulated in cardiac tissue from mice in response to transverse aortic constriction or expression of activated calcineurin, stimuli that induce pathological cardiac remodeling. Many of these miRNAs were similarly regulated in failing human hearts. Forced overexpression of stress-inducible miRNAs was sufficient to induce hypertrophy in cultured cardiomyocytes. Similarly, cardiac overexpression of miR-195, which was up-regulated during cardiac hypertrophy, resulted in pathological cardiac growth and heart failure in transgenic mice. These findings reveal an important role for specific miRNAs in the control of hypertrophic growth and chamber remodeling of the heart in response to pathological signaling and point to miRNAs as potential therapeutic targets in heart disease.
Epidermal Growth Factor (EGF)-induced Generation of Hydrogen Peroxide (1997)

Recent evidence indicates that reactive oxygen species (ROS) may function as intracellular messengers in receptor signaling pathways. The possible role of ROS in epidermal growth factor (EGF) signaling was therefore investigated. Stimulation of A431 human epidermoid carcinoma cells with EGF resulted in a transient increase in the intracellular concentration of ROS, measured with the oxidation-sensitive fluorescent probe 2',7'-dichlorofluorescin diacetate and laser-scanning confocal microscopy. The predominant ROS produced appeared to be H2O2, because the EGF-induced increase in fluorescence was completely abolished by incorporation of catalase into the cells by electroporation. The elimination of H2O2 by catalase also inhibited the EGF-induced tyrosine phosphorylation of various cellular proteins including the EGF receptor and phospholipase C-gamma1. The dependence of H2O2 production on the intrinsic tyrosine kinase activity of the EGF receptor and the autophosphorylation sites located in its COOH-terminal tail was investigated. EGF failed to induce H2O2 generation in cells expressing a kinase-inactive EGF receptor. However, normal H2O2 generation was observed in cells expressing a mutant receptor from which the 126 COOH-terminal amino acids had been deleted to remove four (out of the total of five) autophosphorylation sites. These results suggest that EGF-induced H2O2 formation requires the kinase activity but probably not the autophosphorylation sites of the EGF receptor and that inhibition of protein tyrosine phosphatase activity by H2O2 may be required for EGF-induced protein tyrosine phosphorylation to be manifested.
Identification of a binding site on human FGF-2 for fibrinogen (2003)

Endothelial cell adhesive interactions are mediated by both fibrinogen and fibrin, and growth is stimulated by fibroblast growth factor 2 (FGF-2). We have shown previously that FGF-2 binds specifically and with high affinity to fibrinogen and fibrin and that fibrinogen potentiates the proliferative capacity of FGF-2 and also protects it from proteolytic degradation. To further characterize this interaction we have performed FGF-2 mutagenesis to identify the interactive site. Because FGF-1 has a similar structure to FGF-2 but does not bind to fibrinogen, we used a strategy of cassette and site-directed mutagenesis, exchanging residues from FGF-1 and FGF-2 and correlating structural changes with fibrinogen binding. Two cassette interchange mutants, 2212 and 2211, contained either the third cassette or both the third and fourth cassettes from FGF-1, and neither exhibited any affinity for fibrinogen. Exchange of 5 residues (Phe95, Ser100, Asn102, Arg107, and Arg109) from FGF-2 into the corresponding sites in the third cassette of FGF-1 imparted high-affinity binding with apparent dissociation constants (Kd) of 5.3 nM and 8.6 nM, respectively, compared with 1.3 nM for wild-type FGF-2. We conclude that these 5 residues define a high-affinity binding site in FGF-2 for fibrinogen.
Constitutive Expression of Fas (Apo-1/CD95) Ligand on Multiple Myeloma Cells: A Potential Mechanism of Tumor-Induced Suppression of Immune Surveillance (1997)

The Fas (Apo-1/CD95) ligand (FasL) plays a central role in the elimination of target cells by effector T lymphocytes and in the suppression of cellular immune responses against nonmalignant and malignant cells. We show the expression of FasL on the surface of neoplastic plasma cells. We provide evidence that the FasL is functionally active because five of five neoplastic plasma cell lines tested killed CEM-C7H2 T-acute lymphoblastic leukemia (T-ALL) cells. The effect was mediated via the Fas (Apo-1/CD95) receptor molecule because blocking of Fas on the target cells or the FasL on the tumor cells by receptor- and ligand-specific monoclonal antibodies (MoAbs), respectively, protected T cells from being killed by myeloma cells. In addition, overexpression of the cowpox virus protein CrmA, a molecule with inhibitory potential on caspase-1 and caspase-8, specifically involved in Fas-induced signaling, protected T cells from being destroyed by the neoplastic cells or the agonistic anti-Fas MoAb. The potential of the malignant plasma cells to extinguish target T cells was independent of their own sensitivity to the agonistic anti-Fas MoAb, and FasL-positive (FasL+) CEM-C7H2 T cells were incapable of killing myeloma cells. Our results suggest that tumor cell–induced suppression of the immune system may be exerted via the FasL active on malignant plasma cells. Furthermore, loss of Fas expression or insensitivity to the agonistic anti-Fas MoAb do not seem to be prerequisites for myeloma cells to defeat T cells via Fas/FasL interaction.
Modeling the Regulatory Mechanisms by Which NLRX1 Modulates Innate Immune Responses to Helicobacter pylori Infection (2015)

Helicobacter pylori colonizes half of the world's population as the dominant member of the gastric microbiota resulting in a lifelong chronic infection. Host responses toward the bacterium can result in asymptomatic, pathogenic or even favorable health outcomes; however, mechanisms underlying the dual role of H. pylori as a commensal versus pathogenic organism are not well characterized. Recent evidence suggests mononuclear phagocytes are largely involved in shaping dominant immunity during infection mediating the balance between host tolerance and succumbing to overt disease. We combined computational modeling, bioinformatics and experimental validation in order to investigate interactions between macrophages and intracellular H. pylori. Global transcriptomic analysis on bone marrow-derived macrophages (BMDM) in a gentamycin protection assay at six time points unveiled the presence of three sequential host response waves: an early transient regulatory gene module followed by sustained and late effector responses. Kinetic behaviors of pattern recognition receptors (PRRs) are linked to differential expression of spatiotemporal response waves and function to induce effector immunity through extracellular and intracellular detection of H. pylori. We report that bacterial interaction with the host intracellular environment caused significant suppression of regulatory NLRC3 and NLRX1 in a pattern inverse to early regulatory responses. To further delineate complex immune responses and pathway crosstalk between effector and regulatory PRRs, we built a computational model calibrated using time-series RNAseq data. Our validated computational hypotheses are that: 1) NLRX1 expression regulates bacterial burden in macrophages; and 2) early host response cytokines down-regulate NLRX1 expression through a negative feedback circuit. This paper applies modeling approaches to characterize the regulatory role of NLRX1 in mechanisms of host tolerance employed by macrophages to respond to and/or to co-exist with intracellular H. pylori.
Developmental appearance of thrombospondin in neonatal mouse skeletal muscle. (1991)

Immunocytochemical localization of the adhesive glycoprotein thrombospondin made in comparison with other components of extracellular matrices shows its sequential appearance in the mouse muscle endomysium during postnatal development. Thrombospondin, absent at birth, in contrast to laminin, type IV collagen and fibronectin, is progressively detected during the first month of neonatal life in the whole muscle extracellular matrix. Immunoblotting of thrombospondin showed the appearance 14 days after birth of a band migrating at 180 kDa corresponding to thrombospondin. A fragment of thrombospondin at 110 kDa was already present at birth, as was also a lower molecular mass band at 70 kDa. Another band at 50 kDa also appeared during development in muscle extracts. Clonal muscle cells in culture were able to synthesize thrombospondin but only at the myotube stage, since little thrombospondin was detected at the myoblast stage. These data show a development regulation of thrombospondin expression in muscle which correlates with muscle differentiation.
Ternary Neural Networks with Fine-Grained Quantization (2017)

We propose a novel fine-grained quantization (FGQ) method to ternarize pre-trained full precision models, while also constraining activations to 8 and 4-bits. Using this method, we demonstrate a minimal loss in classification accuracy on state-of-the-art topologies without additional training. We provide an improved theoretical formulation that forms the basis for a higher quality solution using FGQ. Our method involves ternarizing the original weight tensor in groups of $N$ weights. Using $N=4$, we achieve Top-1 accuracy within $3.7\%$ and $4.2\%$ of the baseline full precision result for Resnet-101 and Resnet-50 respectively, while eliminating $75\%$ of all multiplications. These results enable a full 8/4-bit inference pipeline, with best-reported accuracy using ternary weights on ImageNet dataset, with a potential of $9\times$ improvement in performance. Also, for smaller networks like AlexNet, FGQ achieves state-of-the-art results. We further study the impact of group size on both performance and accuracy. With a group size of $N=64$, we eliminate $\approx99\%$ of the multiplications; however, this introduces a noticeable drop in accuracy, which necessitates fine tuning the parameters at lower precision. We address this by fine-tuning Resnet-50 with 8-bit activations and ternary weights at $N=64$, improving the Top-1 accuracy to within $4\%$ of the full precision result with $&lt;30\%$ additional training overhead. Our final quantized model can run on a full 8-bit compute pipeline using 2-bit weights and has the potential of up to $15\times$ improvement in performance compared to baseline full-precision models.
Phase I Trial of an Alhydrogel Adjuvanted Hepatitis B Core Virus-Like Particle Containing Epitopes of Plasmodium falciparum Circumsporozoite Protein (2008)

ClinicalTrials.gov NCT00587249.
Synthesis of mycolic acid biosurfactants and their physical and surface‐active properties (2005)

Abstract Five mycolic acids [2‐alkyl‐3‐hydroxy FA: R 1 C * (OH)C * HR 2 COOH] were synthesized using acyl chlorides with alkyl chains of different lengths (total carbon numbers of mycolic acids, 12, 16, 20, 24, 36). The relationship between the chemical structures of the mycolic acids and their surface‐active properties was determined. The acids were synthesized in three steps: (i) dimerization of acyl chloride into alkyl ketene dimer, (ii) selective reduction of C=C to C‐C by hydrogenation, and (iii) β‐lactone ring cleavage under alkaline conditions. The yields of C 12 ‐, C 16 ‐, C 20 ‐, C 24 ‐, and C 36 ‐mycolic acid were 72, 73, 73, 73, and 73%, respectively. The critical micelle concentrations (CMC) of C 12 ‐, C 16 ‐, and C 20 ‐mycolic acid were 2.2×10 −4 , 1.36×10 −4 , and 7.4×10 −5 M, respectively. As the carbon number increased, the surface tension at the CMC value was also lower; the values for C 12 ‐, C 16 ‐ and C 20 ‐mycolic acid were 46.54, 43.59, and 41.57 dyn/cm, respectively. The emulsifying activities of mycolic acids were determined for n ‐tetradecane, n ‐hexadecane, cyclohexane, and diesel oil. The results showed that C 12 ‐mycolic acid was the best emulsifier for diesel oil, C 16 ‐mycolic acid was the best emulsifier for n ‐tetradecane and n ‐hexadecane, and C 20 ‐mycolic acid was the best emulsifier for cyclohexane. This study showed that mycolic acids having, surface‐active properties can be chemically synthesized for potential applications in the detergent/cleaning material industries, for example, in oil spill cleanup, oil recovery, textiles, pharmaceuticals, and cosmetics.
Early dihydrofolate reductase gene amplification events in CHO cells usually occur on the same chromosome arm as the original locus. (1989)

We used fluorescence in situ hybridization to examine the products of early DNA sequence amplification events in CHO cells. Nine independent populations of cells were selected for resistance to 0.4 microM methotrexate (MTX), and mitotic chromosome spreads were hybridized to a mixture of cloned cosmids representing approximately 273 kb of contiguous DNA sequence from the dihydrofolate reductase (DHFR) locus. Of the nine populations, eight contain cells that have amplified the DHFR domain. Cells in the remaining population displayed only the two single-copy loci on chromosomes 2 and Z2. Of the eight amplificants, one carries amplified DHFR genes on chromosome 2, six on chromosome Z2, and one on an unidentified chromosome. Some cultures carry additional amplified genes on other chromosomes, probably resulting from bridge/breakage/fusion cycles or translocations. In six of the eight amplificants, both single-copy parental loci are detected at their original positions, and amplicon clusters are situated at least 50 megabases (Mb) away on the same chromosome arm, often at the termini. Amplification occurred at or close to the original site of the DHFR gene in only one population. Our results are not consistent with models in which initial amplification events occur by over-replication of the parental locus followed by recombination in loco. Because amplified DHFR sequences occur most often on the same chromosome arm as the parental DHFR gene but at a considerable distance from it, our results are most compatible with either sister chromatid exchange between widely separated sites or with a form of conservative intrachromosomal duplication analogous to transposition in bacteria.
The fascia of the limbs and back – a review (2008)

Although fasciae have long interested clinicians in a multitude of different clinical and paramedical disciplines, there have been few attempts to unite the ensuing diverse literature into a single review. The current article gives an anatomical perspective that extends from the gross to the molecular level. For expediency, it deals only with fascia in the limbs and back. Particular focus is directed towards deep fascia and thus consideration is given to structures such as the fascia lata, thoracolumbar fascia, plantar and palmar fascia, along with regional specializations of deep fascia such as retinacula and fibrous pulleys. However, equal emphasis is placed on general aspects of fascial structure and function, including its innervation and cellular composition. Among the many functions of fascia considered in detail are its ectoskeletal role (as a soft tissue skeleton for muscle attachments), its importance for creating osteofascial compartments for muscles, encouraging venous return in the lower limb, dissipating stress concentration at entheses and acting as a protective sheet for underlying structures. Emphasis is placed on recognizing the continuity of fascia between regions and appreciating its key role in coordinating muscular activity and acting as a body-wide proprioceptive organ. Such considerations far outweigh the significance of viewing fascia in a regional context alone.
2-methoxyestradiol-induced caspase-3 activation and apoptosis occurs through G2/M arrest dependent and independent pathways in gastric carcinoma cells (2001)

These results suggest that the 2-Me-induced apoptosis of gastric carcinoma cells by DNA fragmentation accompanied caspase activation. Elevation of free radicals was associated with G(2)/M-cycle arrest. The induction of G(2)/M-cycle arrest is not a prerequisite for caspase activation.
A Novel Family of Cys-Cys, His-Cys Zinc Finger Transcription Factors Expressed in Developing Nervous System and Pituitary Gland (1996)

A screen designed to identify proteins that specifically bind to retinoic acid response elements resulted in the identification of a rat cDNA encoding a novel protein containing six Cys-Cys, His-Cys zinc fingers. This gene is expressed in a restricted fashion exhibiting distinct temporal and spatial patterns in the developing nervous system, primarily brain, spinal cord, sensory ganglia, retina, and nasal epithelia, as well as in the pituitary, and is referred to as neural zinc finger factor 1 (NZF-1). NZF-1 binds specifically to a cis-regulatory element of the beta-retinoic acid receptor (RAR beta) gene, as well as to other related DNA elements, including two in the upstream enhancer region of the mouse Pit-1 gene. In heterologous cells, NZF-1 activates transcription from promoters containing specific binding sequences and can synergize with other factors, such as Pit-1, to regulate gene expression. These results suggest that NZF-1 may exert regulatory roles in the developing and mature nervous system and in the pituitary gland. Identification of a second mouse gene highly homologous to NZF-1, encoded by a distinct genomic locus, reveals a dispersed gene family encoding proteins containing Cys-Cys, His-Cys motifs.
Einleitung (1998)

Der vorliegende Forschungsbericht stellt die Ergebnisse des im September 1996 von der Landesanstalt für Rundfunk Nordrhein-Westfalen (LfR) ausgeschriebenen Projektes „Medienbezogene Problemwahrnehmungen von Erzieherinnen im Kindergarten“ dar1. Im Rahmen dieses Projektes waren gemäß Ausschreibungstext im Hinblick auf die im Titel angerissene Problemstellung insbesondere die folgenden Leitfragen zu beantworten:
The evolution of lymph node assessment in breast cancer (2008)

Lymph node evaluation remains integral in the management of breast cancer for prognostic and therapeutic purposes. The introduction of sentinel lymph node biopsy has revolutionized axillary surgery, presenting new challenges relating to clinical implications and quality which will be reviewed in this article.
Characterization of recombinant human farnesyl-protein transferase: Cloning, expression, farnesyl diphosphate binding, and functional homology with yeast prenyl-protein transferases (1993)

We have isolated cDNAs encoding the alpha and beta subunits of human farnesyl-protein transferase (FPTase). The proteins encoded by these two cDNAs are 93-95% identical to the corresponding subunits of bovine and rat FPTase and show regions of homology with proteins encoded by Saccharomyces cerevisiae prenyl-protein transferase genes. Human FPTase expressed in Escherichia coli from a translationally coupled operon had kinetic properties similar to those of FPTase isolated from bovine brain. Examination of farnesyl diphosphate binding indicated that while neither individual subunit was capable of isoprenoid binding, a radiolabeled farnesyl diphosphate analog could be specifically photo-cross-linked to the beta subunit of FPTase holoenzyme. To further analyze subunit structure-function and to detect functional similarities with yeast prenyl-protein transferases (FPTase and two geranylgeranyl-protein transferases), amino acid changes homologous to those found in mutant yeast prenyl-protein transferase subunits were made in the subunits of human FPTase. Substitutions in either the alpha or beta subunits that decrease the activity of yeast prenyl-protein transferases were also observed to impair human FPTase. Kinetic analyses showed that these mutant human FPTases have Km and kcat values that are altered with respect to wild-type human FPTase.
Synthesis and Evaluation of Substituted 4‐Alkoxy‐2‐aminopyridines as Novel Neuropeptide Y1 Receptor Antagonists. (2004)

Abstract For Abstract see ChemInform Abstract in Full Text.
Tiplaxtinin impairs nutritionally induced obesity in mice (2006)

To investigate the effect of tiplaxtinin, designed as a synthetic inhibitor of plasminogen activator inhibitor-1 (PAI-1), on obesity, male C57Bl/6 mice (13-14 weeks old) were kept on a high-fat diet (20.1 kJ/g) for four weeks without or with addition of tiplaxtinin (PAI-039) at a dose of 2 mg/g food. At the time of sacrifice, body weights were significantly lower in the inhibitor-treated mice (p < 0.0005). The weights of the isolated subcutaneous and gonadal fat deposits were also significantly lower (both p < 0.0005), associated with adipocyte hypotrophy. Inhibitor-treated adipose tissues displayed similar blood vessel size, but a higher blood vessel density. Fasting glucose and insulin levels, as well as glucose-tolerance tests were not significantly affected by the inhibitor treatment, whereas plasma triglyceride levels were significantly reduced (p = 0.02) and LDL-cholesterol levels significantly enhanced (p = 0.0002). Insulin-tolerance tests revealed significantly lower glucose levels at the end of the test in the inhibitor treated mice (p = 0.03). Thus, in this model of diet-induced obesity in mice administration of tiplaxtinin resulted in impaired adipose tissue development.