gebhart/patrepeval huggingface dataset:
The effects of oxytetracycline on the intestinalEscherichia coliflora of newly weaned pigs (1985)

Four recently weaned pigs were dosed orally with oxytetracycline. This caused a rapid increase in the incidence of tetracycline resistance (TcR) among Escherichia coli isolates from the faecal flora. The isolates were differentiated further on the basis of O-serogroup, biotype and resistance pattern. There was no evidence that the administration of the antibiotic selected for a few TcR clones, but rather a relatively large number of TcR strains were identified during the dosing period. Using selective isolation media a proportion of these strains were demonstrated in the minority faecal Esch. coli flora before dosing, while the remainder were recognized for the first time after dosing commenced. The incidence of TcR among Esch. coli isolates also increased after weaning in other pigs which were not dosed with oxytetracycline or any other antibacterial agent. In a proportion of these animals this increase was associated with the dominance of a TcR enteropathogenic serotype (0149:K 91, K 88a, c) in the faecal Esch. coli flora which was probably ingested in small numbers before weaning. The source of other TcR strains was probably the environment in which each pig was placed after weaning.
Clinical and Preclinical Rationale for CGRP‐Receptor Antagonists in the Treatment of Migraine (2008)

Calcitonin gene-related peptide (CGRP) is linked to migraine and other primary headache disorders. It is found in every location described in migraine genesis and processing, including meninges, trigeminal ganglion, trigeminocervical complex, brainstem nuclei, and cortex. It is released in animal models following stimulation of the CNS similar to that seen in migraine, and triptans inhibit this release. Injection of CGRP into migraineurs results in delayed headache similar to migraine. Elevation of CGRP occurs during migraine, resolving following migraine-specific treatment. Finally, and most importantly, CGRP receptor antagonists terminate migraine with efficacy similar to triptans. Both intravenous olcegepant (BIBN 4096 BS) and oral telcagepant (MK-0974) have been effective, safe, and well tolerated in phase I and II studies. Telcagepant is currently in phase III trials, and preliminary results are favorable. The potential for a migraine-specific medication without vasoconstrictive or vascular side effects is enormous. CGRP receptor blockade may also have applications in other pathologic and pain syndromes.
Endogenous Nerve Growth Factor Regulates Collagen Expression and Bladder Hypertrophy through Akt and MAPK Pathways during Cystitis (2009)

Type I collagen forms the main constituent of the extracellular matrix in visceral organs. We reported here that cyclophosphamide (CYP)-induced cystitis significantly increased the production of type I collagen in the inflamed bladder leading to increases in the bladder weight and the thickness of the bladder wall. The endogenous nerve growth factor (NGF) in the urinary bladder regulated type I collagen expression because the neutralizing NGF antibody attenuated cystitis-induced type I collagen up-regulation in the inflamed bladder. Neutralizing NGF antibody also subsequently reversed cystitis-induced increases in bladder weight. Further studies on the intermediate signaling pathways mediating NGF-induced type I collagen expression in the inflamed bladder during cystitis revealed that Akt, JNK, and ERK1/2 activities were increased in the inflamed bladder, whereas p38 MAPK remained unchanged. Suppression of endogenous NGF level with neutralizing NGF antibody significantly blocked the increased activity of Akt, JNK, and ERK1/2 in the inflamed bladder during cystitis. These results indicate that endogenous NGF plays an important role in the activation of Akt and MAPK in the urinary bladder and in bladder hypertrophy during cystitis.
Ins and Outs of Dendritic Cells (2006)

Dendritic cells (DC) are professional antigen-presenting cells which are strategically positioned at the boundaries between the inner and the outside world, in this way bridging innate and adaptive immunity. DC can initiate T cell responses against microbial pathogens and tumors due to their capacity to stimulate naïve T cells. The development of DC occurs in distinct stages. DC precursors develop in the bone marrow and home to a large variety of tissues. Immature DC capture antigen (Ag) and, following proinflammatory signals, migrate to the lymphoid organs where, after maturation, they present captured Ag to naïve T cells, thereby inducing differentiation of naïve T cells into effector T cells. An important cognate event in the development of cell-mediated immunity is the interaction between CD40 and CD40 ligand. Ligation of CD40 on DC by its ligand results in maturation of the DC. In addition to CD40 ligand (expressed by activated Th cells), inflammatory cytokines, bacterial components or Ag-Ab immune complexes can induce maturation of DC. Maturation of DC is crucial for the priming of efficient T cell responses and is characterized by a decreased Ag processing capacity, an increased cell surface expression of MHC and costimulatory molecules, and rearrangement of cytoskeleton, adhesion molecules, and cytokine receptors. Mature DC migrate from peripheral tissues to secondary lymphoid organs, where T cell priming occurs. DC are not only critical in initiating T cell immunity, they also play a role in the induction of T cell tolerance and the regulation of the type of T cell response that is induced. Here we give an overview of the dendritic cell system.
Finding New Drug Targets for the Treatment of Migraine Attacks (2009)

No new preventive drugs specific to migraine have appeared for the last 20 years and existing acute therapies need improvement. Unfortunately, no animal models can predict the efficacy of new therapies for migraine. Because migraine attacks are fully reversible and can be aborted by therapy, the headache- or migraine-provoking property of naturally occurring signalling molecules can be tested in a human model. This model has predicted efficacy of nitric oxide synthase inhibition and calcitonin gene-related peptide receptor blockade. The pharmaceutical industry should pay more attention to human models, although methods are different from normal target validation.
Suppression of pro-metastasis phenotypes expression in malignant pleural mesothelioma by the PI3K inhibitor LY294002 or the MEK inhibitor UO126. (2006)

The selective MEK or PI3K kinase inhibitors are equally effective in down-regulating the expression of pro-metastasis phenotypes, suggesting that MEK or PI3K are appropriate targets for the development of molecular therapeutics for malignant pleural mesothelioma.
Cluster and Principal Component Analysis of Human Glioblastoma Multiforme (GBM) Tumor Proteome. (2014)

2D gel electrophoresis is the core of proteomics which permitted the separation of thousands of proteins. High resolution 2DE can resolve up to 5,000 proteins simultaneously. Using cluster analysis, we can also form groups of related variables, similar to what is practiced in factor analysis.
Analysis of leptin signalling in hematopoietic cells using an adapted MAPPIT strategy (2006)

The adipocyte-secreted hormone leptin participates in the regulation of hematopoiesis and enhances proliferation of hematopoietic cells. We used an adaptation of the MAPPIT mammalian two-hybrid method to study leptin signalling in a hematopoietic setting. We confirmed the known interactions of suppressor of cytokine signalling 3 (SOCS3) and STAT5 with the Y985 and Y1077 motifs of the leptin receptor, respectively. We also provide evidence for novel interactions at the Y1077 motif, including phospholipase C gamma and several members of the SOCS protein family, further underscoring the important role of the Y1077 motif in leptin signalling.
Adenoviral-Mediated Thymidine Kinase Gene Transfer into the Primate Brain Followed by Systemic Ganciclovir: Pathologic, Radiologic, and Molecular Studies (1996)

Transduction of experimental gliomas with the herpes simplex virus thymidine kinase gene (HSV-tk) using a replication-defective adenoviral vector (ADV/RSV-tk) confers sensitivity to ganciclovir (GCV) leading to tumor destruction and prolonged host survival in rodents. To determine treatment tolerance prior to clinical trials, we conducted toxicity studies in 6 adult baboons (Papio sp.). The animals received intracerebral injections of either a high dose of ADV/RSV-tk [1.5 x 10(9) plaque-forming units (pfu)] with or without GCV, or a low dose of ADV/RSV-tk (7.5 x 10(7) pfu) with GCV. The low dose corresponded to the anticipated therapeutic dose; the high dose was expected to be toxic. Magnetic resonance imaging (MRI) of the brain was obtained before treatment and at 3 and 6 weeks after treatment. Animals receiving the high-dose vector and GCV either died or became moribund and required euthanasia during the first 8 days of treatment. Necropsies revealed cavities of coagulative necrosis at the injection sites. Animals receiving only the high-dose vector were clinically normal; however, lesions were detected with MRI at the injection sites corresponding to cystic cavities at necropsy. Animals receiving the low-dose vector and GCV were clinically normal, exhibited small MRI abnormalities, and, although no gross lesions were present at necropsy, microscopic foci of necrosis were present. The vector sequence was detected by polymerase chain reaction (PCR) at the injection sites and in non-adjacent central nervous system tissue in all animals. Recombinant DNA sequence was detected outside of the nervous system in some animals, and persisted up to 6 weeks. The viral vector injections stimulated the production of neutralizing antibodies in the animals. No shedding of the vector was found in urine, feces, or serum 7 days after intracerebral injection. This study suggests that further investigations including clinical toxicity trials of this form of brain tumor therapy are warranted.
Contribution of MT1-MMP and of human laminin-5 γ2 chain degradation to mammary epithelial cell migration (2001)

Membrane-type matrix metalloproteinase 1 (MT1-MMP) is a membrane-anchored matrix metalloproteinase (MMP) that is frequently associated with processes involving tissue remodelling and cell migration. We have examined MT1-MMP expression and subcellular distribution as a function of MCF10A mammary epithelial cell migration using an in vitro outgrowth migration assay. Stronger expression of MT1-MMP was observed at the mRNA and at the protein level in cells at the periphery of the outgrowth. As shown by videomicroscopy, these cells were involved in an orientated cell migration, in contrast to stationary cells distant from the periphery. Furthermore, MT1-MMP was mainly distributed in lamellipodia of migratory cells, as well as at their basal surface in contact with the substrate. Laminin-5 (Ln-5), a recently described substrate for MT1-MMP, was deposited preferentially in the matrix by migratory cells. Fragments of the gamma2 subunit of Ln-5 were also identified in migratory cultures of MCF10A cells, attesting to its proteolytic degradation. These fragments corresponded in size to those we observed after incubation of purified human Ln-5 with the recombinant catalytic domain of human MT1-MMP. We also show that anti-Ln5 blocking antibodies, MMP inhibitors (BB94 and TIMP-2) and MT1-MMP antisense oligonucleotides significantly decreased MCF10A cell migration. Taken together, these observations demonstrate that MT1-MMP is spatially and temporally regulated during MCF10A cell migration, and suggest that MT1-MMP-mediated pericellular proteolysis of Ln-5 gamma2 chain could contribute to this process.
Tri-component Diels–Alder polymerized dendrimer glass exhibiting large, thermally stable, electro-optic activity (2007)

A novel, thermally curable, tri-component organic glass for electro-optic applications was designed and synthesized. The system employed the Diels–Alder cycloaddition reaction to effect efficient cross-linking. The first component was a dendrimer containing multiple electro-optic chromophore substituents surrounded by an outer periphery possessing diene functionality. The second was a furan-protected, bis-dienophile electro-optic chromophore, introduced in order to function as a nonlinear optically-active cross-linking agent. The initial glass-transition temperature of the material was tuned by the addition of the third component, an optically-inert, maleimide-based dienophile cross-linking agent. Tuning of this mixture allowed optimum poling temperature to coincide with optimum thermal conditions for promotion of the Diels–Alder cross-linking reaction. The electro-optic properties of the material were evaluated in real-time, using a reflection-based single-beam ellipsometry apparatus that was modified to perform in situ signal monitoring. The high electro-optic activity observed (r33 of 150 pm V−1), was thermally stable up to 130 °C (a 48 °C improvement over similar uncross-linked materials). After processing, materials were insoluble in acetone, retained 90% of their original r33 after 15 months at room temperature, and performed well in accelerated operational testing at 85 °C in air.
(Section A: Molecular, Structural, and Cellular Biology of Drug Transporters) Mammalian Nucleoside Transporters (2004)

Nucleoside transporters mediate cellular uptake of physiologic nucleosides for nucleic acid synthesis in the salvage pathways in many cell types. These transporters also play an important role in in vivo disposition and intracellular targeting of many nucleoside analogs used in anticancer and antiviral drug therapy. In mammalian cells, there are two major nucleoside transporter gene families: the equilibrative nucleoside transporters (ENTs) and the concentrative nucleoside transporters (CNTs). The ENTs are facilitated carrier proteins and the CNTs are Na(+)-dependent secondary active transporters. Recent molecular cloning of a number of ENT and CNT transporters has greatly advanced our understanding of the molecular and cellular mechanisms by which nucleosides and nucleoside analogs are transported across biological membranes. In this manuscript, we review the structure, function, tissue distribution, and cellular localization of various cloned mammalian nucleoside transporters. Information on transporter interaction with various nucleoside drugs and analogs is presented. Current knowledge on the regulation of nucleoside transporters in various cell types and tissues is reviewed. The therapeutic significance of nucleoside transporters is discussed along with emerging data from recent clinical studies.
Using Nitrile-Derivatized Amino Acids as Infrared Probes of Local Environment (2002)

It is well-known that the C=N stretching vibration in acetonitrile is sensitive to solvent. Therefore, we proposed in this contribution to use this vibrational mode to report local environment of a particular amino acid in proteins or local environmental changes upon binding or folding. We have studied the solvent-induced frequency shift of two nitrile-derivatized amino acids, which are, AlaCN and PheCN, in H(2)O and tetrahydrofuran (THF), respectively. Here, THF was used to approximate a protein's hydrophobic interior because of its low dielectric constant. As expected, the C=N stretching vibrations of both AlaCN and PheCN shift as much as approximately 10 cm(-1) toward higher frequency when THF was replaced with H2O, indicative of the sensitivity of this vibration to solvation. To further test the utility of nitrile-derivatized amino acids as probes of the environment within a peptide, we have studied the binding between calmodulin (CaM) and a peptide from the CaM binding domain of skeletal muscle myosin light chain kinase (MLCK(579-595)), which contains a single PheCN. MLCK(579-595) binds to CaM in a helical conformation. When the PheCN was substituted on the polar side of the helix, which was partially exposed to water, the C=N stretching vibration is similar to that of PheCN in water. In constrast, when PheCN is introduced at a site that becomes buried in the interior of the protein, the C=N stretch is similar to that of PheCN in THF. Together, these results suggest that the C=N stretching vibration of nitrile-derivatized amino acids can indeed be used as local internal environmental markers, especially for protein conformational studies.
Antiviral Activity of Limitin against Encephalomyocarditis Virus, Herpes Simplex Virus, and Mouse Hepatitis Virus: Diverse Requirements by Limitin and Alpha Interferon for Interferon Regulatory Factor 1 (2003)

Limitin has sequence homology with alpha interferon (IFN-alpha) and IFN-beta and utilizes the IFN-alpha/beta receptor. However, it has no influence on the proliferation of normal myeloid and erythroid progenitors. In this study, we show that limitin has antiviral activity in vitro as well as in vivo. Limitin inhibited not only cytopathic effects in encephalomyocarditis virus- or herpes simplex virus (HSV) type 1-infected L929 cells, but also plaque formation in mouse hepatitis virus (MHV) type 2-infected DBT cells. In addition, administration of limitin to mice suppressed MHV-induced hepatitis and HSV-induced death. The antiviral activity may be mediated in part by 2',5'-oligoadenylate synthetase, RNA-dependent protein kinase, and Mx protein, which inhibit viral replication or degrade viral components, because limitin induced their mRNA expression and enzyme activity. While limitin has antiviral activity as strong as that of IFN-alpha in vitro (the concentration that provided 50% inhibition of cytopathic effect is approximately 30 pg/ml), IFN regulatory factor 1 (IRF-1) dependencies for induction of an antiviral state were different for limitin and IFN-alpha. In IRF-1-deficient fibroblasts, a higher concentration of limitin than of IFN-alpha was required for the induction of antiviral activity and the transcription of proteins from IFN-stimulated response element. The unique signals and the fewer properties of myelosuppression suggest that a human homolog of limitin may be used as a new antiviral drug.
Perturbed-Chain SAFT:  An Equation of State Based on a Perturbation Theory for Chain Molecules (2001)

A modified SAFT equation of state is developed by applying the perturbation theory of Barker and Henderson to a hard-chain reference fluid. With conventional one-fluid mixing rules, the equation of state is applicable to mixtures of small spherical molecules such as gases, nonspherical solvents, and chainlike polymers. The three pure-component parameters required for nonassociating molecules were identified for 78 substances by correlating vapor pressures and liquid volumes. The equation of state gives good fits to these properties and agrees well with caloric properties. When applied to vapor−liquid equilibria of mixtures, the equation of state shows substantial predictive capabilities and good precision for correlating mixtures. Comparisons to the SAFT version of Huang and Radosz reveal a clear improvement of the proposed model. A brief comparison with the Peng−Robinson model is also given for vapor−liquid equilibria of binary systems, confirming the good performance of the suggested equation of state. The applicability of the proposed model to polymer systems was demonstrated for high-pressure liquid−liquid equilibria of a polyethylene mixture. The pure-component parameters of polyethylene were obtained by extrapolating pure-component parameters of the n-alkane series to high molecular weights.
Differential recruitment of CD63 and Rab7-interacting-lysosomal-protein to phagosomes containingMycobacterium tuberculosisin macrophages (2010)

M.tb is an intracellular pathogen which survives within the phagosomes of host macrophages by inhibiting their fusion with lysosomes. Here, it has been demonstrated that a lysosomal glycoprotein, CD63, is recruited to the majority of M.tb phagosomes, while RILP shows limited localization. This is consistent with the author's findings that CD63, but not RILP, is recruited to the phagosomes in macrophages expressing the dominant negative form of Rab7. These results suggest that M.tb phagosomes selectively fuse with endosomes and lysosomes to escape killing activity while acquiring nutrients.
Camelid Heavy-Chain Variable Domains Provide Efficient Combining Sites to Haptens (2000)

Camelids can produce antibodies devoid of light chains and CH1 domains (Hamers-Casterman, C. et al. (1993) Nature 363, 446−448). Camelid heavy-chain variable domains (VHH) have high affinities for protein antigens and the structures of two of these complexes have been determined (Desmyter, A. et al. (1996) Nature Struc. Biol. 3, 803−811; Decanniere, K. et al. (1999) Structure 7, 361−370). However, the small size of these VHHs and their monomeric nature bring into question their capacity to bind haptens. Here, we have successfully raised llama antibodies against the hapten azo-dye Reactive Red (RR6) and determined the crystal structure of the complex between a dimer of this hapten and a VHH fragment. The surface of interaction between the VHH and the dimeric hapten is large, with an area of ca. 300 Å2; this correlates well with the low-dissociation constant of 22 nM measured for the monomer. The VHH fragment provides an efficient combining site to the RR6, using its three CDR loops. In particular, CDR1 provides a strong interaction to the hapten through two histidine residues bound to its copper atoms. VHH fragments might, therefore, prove to be valuable tools for selecting, removing, or capturing haptens. They are likely to play a role in biotechnology extending beyond protein recognition alone.
Molecular Genetic Changes Found in Human Lung Cancer and Its Precursor Lesions (1994)

Lung cancer is the most common cancer killer of men and women in the United States. Current treatment options lead to cure in only 10%, a rate that has not altered in more than a decade (Minna 1992). Lung cancers frequently metastasize and are seldom diagnosed at an early curative stage. In contrast, lung cancer is largely preventable by stopping carcinogen exposure from cigarette smoke. Although it is highly desirable to stop all cigarette smoking, it is also realistic to target antismoking and chemoprevention efforts to those persons with the highest risk of developing lung cancer. Because a large fraction of lung cancers develop in former cigarette smokers, it first may be most practical to target these efforts to exsmokers, who for many years will still have a significantly increased risk of developing lung cancer.
Vision-based guidance of an agriculture tractor (1987)

The ordered structure of agricultural row crops can provide useful guidance information for tractor control. A description of research for coupling a machine vision system and a solid-state camera to derive vehicle guidance parameters for a tractor is presented. Image segmentation is enhanced by optical filtering and controlling light intensity to the image sensor. An analysis of camera location and steering errors that can be determined from the row crops is determined by simulating the geometric relationships between the crop canopy and the image plane.