gebhart/patrepeval huggingface dataset:
Two roles for CD4 cells in the control of the generation of cytotoxic T lymphocytes (1991)

The generation of CTL against Qa-1 Ag in C57BL/6 (B6) (Qa-1b) and B6.Tlaa (Qa-1a) congenic strains requires in vivo priming with the Qa-1 alloantigen together with a helper Ag, such as H-Y. The primed precursors obtained from these female mice generate Qa-1-specific CTL activity upon culture in vitro. Although the presence of the H-Y helper Ag is not required for the in vitro sensitization, no response occurs in the absence of CD4 cells. Addition of unprimed B6.Tlaa CD4 cells from Qa-1 incompatible radiation bone marrow chimeras (B6.Tlaa----B6), that are presumably tolerant to Qa-1b, provide helper activity for Qa-1b-specific CTL. This indicates that although CD4 cells are obligatory for the Qa-1 response, they need not be specific for alloantigens on the APC to generate helper activity in in vitro cultures. Addition of unirradiated B6 CD8-depleted spleen cells to CD4-depleted B6.Tlaa anti-B6 cultures in the presence of either B6.Tlaa CD4 cells or rIL-2 prevents the generation of Qa-1 specific CTL. This inhibition is not due to an anti-idiotypic Ts cell since B6.Tlaa----B6 chimeric cells do not suppress an anti-Qa-1b response. Rather, this finding is consistent with that of a veto cell mechanism. To determine whether CD4 cells themselves exhibit veto activity, highly purified CD4 populations were tested for their ability to inhibit the generation of Qa-1-specific CTL. CD4 cells precultured for 2 to 3 days with Con A and rIL-2 specifically inhibit CTL activity whereas resting cells do not, similar to that noted for CD8 veto cells. The relative efficiency of activated CD4 cells is greater than that of resting NK cells but is less than that of activated CD8 or NK cells. Thus, CD4 cells not only provide helper activity for CTL precursors, but also act as veto cells to prevent the generation of CTL activity.
Rake cursor (2009)

We investigate the use of two concurrent input channels to perform a pointing task. The first channel is the traditional mouse input device whereas the second one is the gaze position. The rake cursor interaction technique combines a grid of cursors controlled by the mouse and the selection of the active cursor by the gaze. A controlled experiment shows that rake cursor pointing drastically outperforms mouse-only pointing and also significantly outperforms the state of the art of pointing techniques mixing gaze and mouse input. A theory explaining the improvement is proposed: the global difficulty of a task is split between those two channels, and the sub-tasks could partly be performed concurrently.
Kunitz-Type Proteinase Inhibitors Derived by Limited Proteolysis of the Inter-α-Trypsin Inhibitor, IX. Isolation and Characterization of the Inhibitory Parts of Inter-α-Trypsin Inhibitors From Several Mammalian Sera (1983)

The inhibitory parts of inter-alpha-trypsin inhibitor-like proteins from several mammalian sera (sheep, goat, horse, donkey, pig, rabbit, rat and dog) were released by limited proteolysis with trypsin and were isolated by reversible binding to immobilized trypsin. The inhibitors are very similar with respect to their stability in acids, molecular masses and amino-acid compositions. They are different, however, in their inhibitory properties. In view of the known covalent structures of the inhibitory parts of the human and bovine inhibitors, homologous covalent structures consisting of two tandem Kunitz-type domains are suggested also for the isolated inhibitors. Bovine trypsin, bovine chymotrypsin and porcine plasmin are inhibited by all investigated inhibitors, most likely via their C-terminal domain. The inhibitors from horse, donkey, rabbit, rat and dog serum interact also with elastase from human polymorphonuclear granulocytes, those from sheep, goat and pig serum inhibit in addition porcine pancreatic elastase and bovine chymotrypsin via their N-terminal Kunitz-type domain. It is supposed that the amino-acid residue in position P1 of the N-terminal Kunitz-type domain is responsible for the characteristic inhibitory properties of each inhibitor.
Podocin, a raft-associated component of the glomerular slit diaphragm, interacts with CD2AP and nephrin (2001)

NPHS2 was recently identified as a gene whose mutations cause autosomal recessive steroid-resistant nephrotic syndrome. Its product, podocin, is a new member of the stomatin family, which consists of hairpin-like integral membrane proteins with intracellular NH2- and COOH-termini. Podocin is expressed in glomerular podocytes, but its subcellular distribution and interaction with other proteins are unknown. Here we show, by immunoelectron microscopy, that podocin localizes to the podocyte foot process membrane, at the insertion site of the slit diaphragm. Podocin accumulates in an oligomeric form in lipid rafts of the slit diaphragm. Moreover, GST pull-down experiments reveal that podocin associates via its COOH-terminal domain with CD2AP, a cytoplasmic binding partner of nephrin, and with nephrin itself. That podocin interacts with CD2AP and nephrin in vivo is shown by coimmunoprecipitation of these proteins from glomerular extracts. Furthermore, in vitro studies reveal direct interaction of podocin and CD2AP. Hence, as with the erythrocyte lipid raft protein stomatin, podocin is present in high-order oligomers and may serve a scaffolding function. We postulate that podocin serves in the structural organization of the slit diaphragm and the regulation of its filtration function.
The fibroblast growth factor receptor, FGFR3, forms gradients of intact and degraded protein across the growth plate of developing bovine ribs (2002)

Point mutations in the human fibroblast growth factor (FGF) receptor 3 gene (Fgfr3) produce a constitutively active receptor, which disrupts chondrocyte differentiation in the growth plate and results in skeletal dysplasias with severe shortening of the limbs. Alternative splicing of the Fgfr3 transcript gives rise to two isoforms, IIIc and IIIb, which vary in their specificity for FGF ligands. We examined the expression of these FGFR3 isoforms in the bovine fetal rib growth plate to determine whether levels of FGFR3 expression are zone-related. Transcripts for both Fgfr3 isoforms are expressed in rib growth plate, with maximum expression in the hypertrophic region and the least expression in the reserve zone. Fgfr3 IIIc is the predominant isoform in the growth plate. Western-blot analysis revealed the presence of full-length FGFR3 (135 kDa) for both isoforms in the reserve zone, a major 98 kDa fragment in all zones and smaller fragments primarily in the hypertrophic zone. Immunostaining localized FGFR3 to the pericellular region of reserve chondrocytes and to the extracellular matrix in the hypertrophic zone. These results suggest that the transmembrane form of FGFR3 increasingly undergoes proteolytic cleavage towards the hypertrophic zone to produce an extracellular-domain fragment of FGFR3, which is present in large amounts in the matrix of hypertrophic cells. These findings suggest a proteolytic regulatory mechanism for FGFR3, whereby Fgfr3 fragments could control availability of FGF for the intact receptor, and by which proteolysis could inactivate the receptor.
Comparative Evaluation of Combined Cycles and Gas Turbine Systems With Water Injection, Steam Injection, and Recuperation (1995)

Combined cycles have gained widespread acceptance as the most efficient utilization of the gas turbine for power generation, particularly for large plants. A variety of alternatives to the combined cycle that recover exhaust gas heat for re-use within the gas turbine engine have been proposed and some have been commercially successful in small to medium plants. Most notable have been the steam-injected, high-pressure aeroderivatives in sizes up to about 50 MW. Many permutations and combinations of water injection, steam injection, and recuperation, with or without intercooling, have been shown to offer the potential for efficiency improvements in certain ranges of gas turbine cycle design parameters. A detailed, general model that represents the gas turbine with turbine cooling has been developed. The model is intended for use in cycle analysis applications. Suitable choice of a few technology description parameters enables the model to represent accurately the performance of actual gas turbine engines of different technology classes. The model is applied to compute the performance of combined cycles as well as that of three alternatives. These include the simple cycle, the steam-injected cycle, and the dual-recuperated intercooled aftercooled steam-injected cycle (DRIASI cycle). The comparisons are based on state-of-the-art gas turbine technology and cycle parameters in four classes: large industrial (123–158 MW), medium industrial (38–60 MW), aeroderivatives (21–41 MW), and small industrial (4–6 MW). The combined cycle’s main design parameters for each size range are in the present work selected for computational purposes to conform with practical constraints. For the small systems, the proposed development of the gas turbine cycle, the DRIASI cycle, are found to provide efficiencies comparable or superior to combined cycles, and superior to steam-injected cycles. For the medium systems, combined cycles provide the highest efficiencies but can be challenged by the DRIASI cycle. For the largest systems, the combined cycle was found to be superior to all of the alternative gas turbine based cycles considered in this study.
Human T lymphocytes recognize a peptide of single point-mutated, oncogenic ras proteins. (1991)

P21ras proteins are thought to play an important role in cell proliferation and differentiation. Single nucleotide mutations in the encoding cellular proto-oncogenes often result in p21ras proteins with transforming activity. Such activated ras oncogenes have been demonstrated in a variety of human malignancies and also in preneoplastic changes. Using a synthetic peptide corresponding to amino acids 5-16 of mutated p21ras proteins with an exchange of the normal glycine at position 12 by valine, it is shown here that human CD4+ T cells specifically recognize the mutated protein sequence and can be generated as antigen-specific T lymphocyte lines. The fact that these T lines did not crossreact to the sequence of normal p21ras proteins offers new perspectives for specific immunotherapy of human malignancies and even precancerous lesions.
Identification of 9 Genes Differentially Expressed in Head and Neck Squamous Cell Carcinoma (2003)

Using differential display and microarray analysis, we have identified and confirmed the differential expression of 9 genes in HNSCC. Work is in progress to determine the biological significance of these genes and their potential as biomarkers or targets for therapy.
Symposium Summary (2016)

Developing inhaled drugs requires knowledge of lung anatomy, cell biology, respiratory physiology, particle physics, and some plumbing. Although dose makes the poison, in the context of an inhaled drug, the "dose" is not easily defined. This lack of clarity around dose poses issues and challenges in the design of inhalation toxicology programs. To better understand dose, the influence of ventilation is discussed as are the perturbations in pulmonary function observed with inhalation exposure that can affect dose. Methods for determining inhaled drug deposition to arrive at an estimate of lung dose are examined. Equally important to understanding dose are the techniques used to deliver aerosols to animals. With a better understanding of dose and inhalation exposure, species-specific histopathologic lesions, both common background and toxicologically significant lesions, are reviewed. Finally, insight into how regulators synthesize and evaluate these complex findings to assess clinical safety risks is presented.
Effect of foreign N‐terminal residues on the conformational stability of human lysozyme (1999)

To minutely understand the effect of foreign N-terminal residues on the conformational stability of human lysozyme, five mutant proteins were constructed: two had Met or Ala in place of the N-terminal Lys residue (K1M and K1A, respectively), and others had one additional residue, Met, Gly or Pro, to the N-terminal Lys residue (Met(-1), Gly(-1) and Pro(-1), respectively). The thermodynamic parameters for denaturation of these mutant proteins were examined by differential scanning calorimetry and were compared with that of the wild-type protein. Three mutants with the extra residue were significantly destabilized: the changes in unfolding Gibbs energy (DeltaDeltaG) were -9.1 to -12.2 kJ.mol-1. However, the stability of two single substitutions at the N-terminal slightly decreased; the DeltaDeltaG values were only -0.5 to -2.5 kJ.mol-1. The results indicate that human lysozyme is destabilized by an expanded N-terminal residue. The crystal structural analyses of K1M, K1A and Gly(-1) revealed that the introduction of a residue at the N-terminal of human lysozyme caused the destruction of hydrogen bond networks with ordered water molecules, resulting in the destabilization of the protein.
Recombinant human cachectin/tumor necrosis factor but not interleukin-1 alpha downregulates lipoprotein lipase gene expression at the transcriptional level in mouse 3T3-L1 adipocytes. (1988)

Lipoprotein lipase (LPL) is synthesized primarily in muscle and adipose tissue and by hydrolyzing triglycerides in chylomicrons and very low density lipoprotein allows uptake of the resultant free fatty acids by these tissues. This report describes the cloning of the mouse LPL gene from which probes were derived to study the regulation of LPL synthesis in the 3T3-L1 adipocyte cell culture system. Preconfluent 3T3-L1 preadipocytes had very small amounts of LPL mRNA (less than 1 pg/micrograms of RNA). At confluency, LPL mRNA levels increased to 5 to 15 pg/micrograms of RNA. After insulin and dexamethasone were added, LPL activity and mRNA levels rose in parallel. Peak mRNA levels were reached within 4 to 10 days, achieving LPL mRNA concentrations of 150 to 500 pg/micrograms of RNA. This represents a 15- to 50-fold increase over confluent cells. Two cytokines known to diminish adipose tissue LPL activity were studied to see how their effects were regulated. Recombinant human cachectin/tumor necrosis factor diminished both LPL activity and LPL mRNA levels. The effect on LPL activity compared with mRNA levels was quicker, at a lower dose, and more complete (95 versus 75% maximum effect). The effect of recombinant human cachectin tumor necrosis factor on LPL mRNA levels was shown by nuclear run-on experiments to be exerted transcriptionally. It was also independent of new protein synthesis. Recombinant human interleukin-1 alpha diminished only LPL activity but not mRNA levels. This study suggests that during times of stress, cytokines secreted by activated macrophages can alter energy balance by affecting transcriptional and posttranscriptional processes in adipocytes.
Pure antiestrogens as a new therapy for breast cancer. (1997)

Tamoxifen is the endocrine therapy of choice for all stages of breast cancer. However, the drug cannot be considered to be a cure as drug resistance will eventually develop. The resistance can take two forms: either the loss of estrogen receptor or the selection of estrogen receptor positive disease that is tamoxifen stimulated for growth. Laboratory studies have demonstrated that tamoxifen-stimulated MCF-7 breast tumors can develop in athymic mice. A number of pure (nonestrogenic) antiestrogens have been discovered that can either be administered by injection (e.g., ICI 182,780) or orally (e.g., EM-800). In preliminary clinical studies, the compound ICI 182,780 (Faslodex) has been shown to be an effective second-line therapy after tamoxifen failure. The goal of future clinical studies is to evaluate the therapeutic efficacy and patient acceptability of aromatase inhibitors (postmenopausal estrogen withdrawal), and injectable or oral pure antiestrogens after the failure of long-term tamoxifen therapy. Clearly, the primary purpose for the treatment of advanced breast cancer is to control disease growth; nevertheless, an evaluation of the effect of new agents on bones and lipids is required before pure antiestrogens could be considered for adjuvant therapy.
Macaw Feathers Help Preserve Wild Populations (1988)

Parrot feathers have been used for centuries for ornamentation by natives throughout South and Central America. In Panama , scarlet macaws (Ara m.acao)- a species now classified as endangered and placed on Appendix I of CITES- are traditionally captured to obtain feathers used in local folk dances in the central part of the country. However, the increasing popularity of the dance in which the feathers are used has greatly increased the demand. Capture of macaws, including the Buffon 's (Ara ambigua), also the less rare blue and yellow (A. ararauna) and green-winged (A. chloroptera), has increased. Most of these must be killed for their feathers as few are held in captivity in the region .
Human Parainfluenza Virus Induces a Type-Specific Protective Immune Response (1990)

Induction of type-specific and cross-protective immune responses against human parainfluenza viruses have been investigated. The envelope glycoproteins HN (76 kDa) and F0 (62 kDa) from parainfluenza type 2 virus were selectively solubilized with octylglucoside. Detergent-soluble envelope glycoproteins were used as vaccine antigens for intranasal immunization of hamsters. The immunized animals showed complete protection from challenge infection with prototype live virus but failed to demonstrate a significant level of protection against either human parainfluenza type 1 or type 3 virus. The sera and bronchial lavages of immunized animals also showed type-specific neutralizing antibodies. A similar type-specific protective immune response was also noted after primary infection with live virus. The results indicate that a multivalent parainfluenza virus vaccine is probably required for protection against natural infection.
Microfabricated Reference Electrodes and their Biosensing Applications (2010)

Over the past two decades, there has been an increasing trend towards miniaturization of both biological and chemical sensors and their integration with miniaturized sample pre-processing and analysis systems. These miniaturized lab-on-chip devices have several functional advantages including low cost, their ability to analyze smaller samples, faster analysis time, suitability for automation, and increased reliability and repeatability. Electrical based sensing methods that transduce biological or chemical signals into the electrical domain are a dominant part of the lab-on-chip devices. A vital part of any electrochemical sensing system is the reference electrode, which is a probe that is capable of measuring the potential on the solution side of an electrochemical interface. Research on miniaturization of this crucial component and analysis of the parameters that affect its performance, stability and lifetime, is sparse. In this paper, we present the basic electrochemistry and thermodynamics of these reference electrodes and illustrate the uses of reference electrodes in electrochemical and biological measurements. Different electrochemical systems that are used as reference electrodes will be presented, and an overview of some contemporary advances in electrode miniaturization and their performance will be provided.
Targeting Dendritic Cells in vivo for Cancer Therapy (2012)

Monoclonal antibodies that recognize cell surface molecules have been used deliver antigenic cargo to dendritic cells (DC) for induction of immune responses. The encouraging anti-tumor immunity elicited using this immunization strategy suggests its suitability for clinical trials. This review discusses the complex network of DC, the functional specialization of DC subsets, the immunological outcomes of targeting different DC subsets and their cell surface receptors, and the requirements for the induction of effective anti-tumor CD4 and CD8 T cell responses that can recognize tumor-specific antigens. Finally, we review preclinical experiments and the progress toward targeting human DC in vivo.
PRMT5 dimethylates R30 of the p65 subunit to activate NF-κB (2013)

The ubiquitous inducible transcription factor NF-κB plays central roles in immune and inflammatory responses and in tumorigenesis. Complex posttranslational modifications of the p65 subunit (RelA) are a major aspect of the extremely flexible regulation of NF-κB activity. Although phosphorylation, acetylation, ubiquitination, and lysine methylation of NF-κB have been well described, arginine methylation has not yet been found. We now report that, in response to IL-1β, the p65 subunit of NF-κB is dimethylated on arginine 30 (R30) by protein-arginine methyltransferase 5 (PRMT5). Expression of the R30A and R30K mutants of p65 substantially decreased the ability of NF-κB to bind to κB elements and to drive gene expression. A model in which dimethyl R30 is placed into the crystal structure of p65 predicts new van der Waals contacts that stabilize intraprotein interactions and indirectly increase the affinity of p65 for DNA. PRMT5 was the only arginine methyltransferase that coprecipitated with p65, and its overexpression increased NF-κB activity, whereas PRMT5 knockdown had the opposite effect. Microarray analysis revealed that ∼85% of the NF-κB-inducible genes that are down-regulated by the R30A mutation are similarly down-regulated by knocking PRMT5 down. Many cytokine and chemokine genes are among these, and conditioned media from cells expressing the R30A mutant of p65 had much less NF-κB-inducing activity than media from cells expressing the wild-type protein. PRMT5 is overexpressed in many types of cancer, often to a striking degree, indicating that high levels of this enzyme may promote tumorigenesis, at least in part by facilitating NF-κB-induced gene expression.
The azygos vein pathway: an overview from anatomical variations to pathological changes (2014)

The azygos venous system represents an accessory venous pathway supplying an important collateral circulation between the superior and inferior vena cava. The aim of this article is to revise the wide spectrum of changes ranging from normal to pathological conditions involving the azygos system. Teaching points • The azygos vein is a collateral venous pathway, becoming a vital shunt if major pathways of venous return are obstructed. • In azygos continuation, the azygos vein becomes significantly enlarged due to inferior vena cava interruption. • Fibrosing mediastinitis is an underestimated acquired disorder. • Fibrosing mediastinitis induces a variable engorgement of collateral veins. • Fibrosing mediastinitis leads to superior vena cava syndrome.
The Role of Graft-derived Dendritic Leukocytes in the Rejection of Vascularized Organ Allografts (1990)

Dendritic cells isolated from lymphoid tissues are potent stimulators of primary allogeneic T-cell responses in vitro and in vivo. Similar major histocompatibility complex class II-bearing dendritic-shaped leukocytes are contained within transplanted organs and these are thought to be important passenger leukocytes that trigger rejection. Recent findings on the migration, phenotype, and function of cardiac dendritic leukocytes (DLs) are reviewed. After transplantation donor DLs migrate rapidly from mouse cardiac allografts into the recipients's spleens. Within the spleens donor DLs, associate with recipient CD4+ T cells. Isolated cardiac DLs, like lymphoid dendritic cells, are potent stimulators of T-cell proliferation in vitro. This suggests that DLs function as passenger leukocytes by migrating from grafts into the lymphoid tissues of the recipient and that sensitization to vascularized organ allografts may occur centrally within lymphoid tissues rather than peripherally in the graft itself.