gebhart/patrepeval huggingface dataset:
Definition of an Immunogenic Region Within the Ovarian Tumor Antigen Stratum Corneum Chymotryptic Enzyme (2005)

The 110-139 region of SCCE incorporates multiple CD8+ CTL and CD4+ helper T cell epitopes, and represents an attractive target antigen for immunotherapy of ovarian cancer.
A New Approach to Simultaneously Quantify Both TCR α- and β-Chain Diversity after Adoptive Immunotherapy (2012)

DTEA can rapidly and sensitively track changes in TCRVα and Vβ gene usages in T-cell pools following immune interventions, such as adoptive T-cell transfer, and may also be used to assess impact of vaccination or reconstitution of T-cell compartment after hematopoietic stem cell transplantation.
Decreased atherosclerosis in CX3CR1–/– mice reveals a role for fractalkine in atherogenesis (2003)

The hallmark of early atherosclerosis is the accumulation of lipid-laden macrophages in the subendothelial space. Circulating monocytes are the precursors of these "foam cells," and recent evidence suggests that chemokines play important roles in directing monocyte migration from the blood to the vessel wall. Fractalkine (FK) is a structurally unusual chemokine that can act either as a soluble chemotactic factor or as a transmembrane-anchored adhesion receptor for circulating leukocytes. A polymorphism in the FK receptor, CX(3)CR1, has been linked to a decrease in the incidence of coronary artery disease. To determine whether FK is critically involved in atherogenesis, we deleted the gene for CX(3)CR1 and crossed these mice into the apoE(-/-) background. Here we report that FK is robustly expressed in lesional smooth muscle cells, but not macrophages, in apoE(-/-) mice on a high-fat diet. CX(3)CR1(-/-) mice have a significant reduction in macrophage recruitment to the vessel wall and decreased atherosclerotic lesion formation. Taken together, these data provide strong evidence that FK plays a key role in atherogenesis.
Long-Term Treatment of Lasofoxifene Preserves Bone Mass and Bone Strength and Does Not Adversely Affect the Uterus in Ovariectomized Rats (2004)

The purpose of this study was to determine the long-term effects of lasofoxifene, a new selective estrogen receptor modulator, on bone mass, bone strength, and reproductive tissues in ovariectomized (OVX) rats. Sprague Dawley female rats at 3.5 months of age were OVX and treated orally with lasofoxifene (60, 150, or 300 microg/kg x d) for 52 wk. The urinary deoxypyridinoline/creatinine ratio was significantly lower in all lasofoxifene-treated OVX rats compared with OVX controls at wk 26. Peripheral quantitative computerized tomography analysis of proximal tibial metaphysis showed that the significant loss in trabecular content and density induced by OVX was significantly prevented by lasofoxifene treatment. Proximal tibial and lumber vertebral trabecular bone histomorphometric analysis showed that all doses of lasofoxifene significantly reduced OVX-induced bone loss by decreasing bone resorption and bone turnover. The ultimate strength, energy, and toughness of the fourth lumbar vertebral body in OVX rats treated with all doses of lasofoxifene were significantly higher compared with those in OVX controls, and did not differ significantly from those in sham controls. Uterine weight in OVX rats treated with lasofoxifene was slightly, but significantly, higher when compared with that in OVX controls, but was still much less than that in sham controls. No abnormal finding associated with lasofoxifene was observed with uterine histology examination. In summary, long-term treatment with lasofoxifene preserves bone mass and bone strength and does not adversely affect the uterus in OVX rats. These data suggest that lasofoxifene is an effective antiosteoporosis agent, and its efficacy and safety can be maintained over an extended period of time.
Cyclophilin D as a Drug Target (2003)

The mitochondrial permeability transition (MPT) plays an important role in damage-induced cell death, and agents inhibiting the MPT may have a therapeutic potential for treating human conditions such as ischemia/reperfusion injury, trauma, and neurodegenerative diseases. The mitochondrial matrix protein, cyclophilin D (CYP D), a member of a family of highly homologous peptidylprolyl cis-trans isomerases (PPIases), plays a decisive role in MPT, being an integral constituent of the MPT pore. Other putative MPT pore proteins include the adenine nucleotide translocator (ANT) and the voltage-dependent anion channel (VDAC). In an alternative model, the MPT pore is formed by clusters of misfolded membrane proteins outlining aqueous channels that are regulated by CYP D and other chaperone-like proteins. Like cyclophilin A (CYP A) and other cyclophilin family members, CYP D is targeted by the immunosuppressant cyclosporin A (CsA). CsA is cytoprotective in many cellular and animal models, but protection may result from either inhibition of the MPT through an interaction with CYP D or inhibition of calcineurin-mediated dephosphorylation of BAD through an interaction with CYP A. The relevance of MPT inhibition by CsA for its cytoprotective effects is well documented in many cellular models. Mechanisms of action in vivo are more difficult to define, and accordingly the evidence is as yet less compelling in in vivo animal models of ischemia/reperfusion injury, trauma and neurodegenerative diseases. Notwithstanding, CYP D is a drug target of high interest. Structural considerations suggest feasibility of designing CYP D ligands without immunosuppressant properties. This is highly desirable, since they have the potential of being useful therapeutic agents in a variety of disease states. It might be a tougher challenge to obtain compounds specific for CYP D vs. other cyclophilins, and/or of small molecular weight, allowing brain penetration to make them suitable for treating neurodegenerative diseases.
Aurora Sheds Light on Head and Neck Squamous Cell Carcinoma (2006)

The retrospective study by Reiter et al. in this issue of Clinical Cancer Research ([1][1]) provides further support to the growing body of evidence that Aurora A kinase is an important player in cancer. It also identifies a potential new prognostic marker and drug target for head and neck squamous
RESTORING LONG SPAN EDENTULOUS ARCH WITH FIXED DENTAL PROSTHESIS A CONSERVATIVE APPROACH (2018)

This report describes the case of a 48-year-old female patient who wanted to replace her missing teeth. Edentulous arch span was long so a 4 unit fixed movable resin bonded fixed partial denture [RBFPD] was planed. Ceka preci vertix extracoronal attachment was used to provide non rigid connection between minor and major retainer. RBFDPs are a conservative tooth replacement option that requires minimum tooth preparation and retention by a resin cement to etched enamel. This case report highlights the use of modified non-rigid connector which allows relative movement between abutment teeth and therefore a reduced stress on the bonding interface of resin bonded prosthesis. It is proposed that the use of modified non-rigid connectors that allow independent movement between the abutment teeth during function is responsible for the long term clinical success of fixed-movable RBFDPs.
REGULATION OF T CELL FATE BY NOTCH (1999)

The transmembrane receptor Notch participates in diverse cell fate decisions throughout embryonic development. Notch receptors and their ligands are expressed in the mammalian thymus, raising the possibility that Notch could regulate T cell fate decisions. Expression of a constitutively activated form of Notch in developing thymocytes causes thymocytes normally destined for the CD4 lineage to adopt the CD8 lineage instead. This suggests that Notch activity normally acts to direct CD4+CD8+ precursors to the CD8 lineage. The choice between CD4 and CD8 T cell fates is also controlled by MHC recognition during positive selection, implying that recognition of class I or II MHC might regulate Notch signaling. Possible models for the regulation of Notch by MHC recognition during CD4 versus CD8 lineage determination are discussed.
Differential expression of pleiotrophin and midkine in advanced neuroblastomas. (1995)

Pleiotrophin (PTN) and midkine (MK) are members of a new family of neurotrophic factors whose expression is developmentally regulated. PTN also transforms NIH 3T3 cells, and MK is mitogenic to certain cell lines. Neuroblastomas are tumors derived from neural crest cells, and recent studies have revealed that the biology of these tumors is at least partly regulated by neurotrophic factors and their receptors. To examine the expression of PTN and MK in neuroblastoma, we analyzed their mRNA expression in 72 primary neuroblastomas and 11 neuroblastoma cell lines as well as other tissues and cell lines. PTN is highly expressed in favorable neuroblastomas (stages I, II, and IV-S, n = 44), whereas it is expressed at a significantly lower level in advanced tumors (stages III and IV, n = 28, P = 0.003). PTN is not expressed in either aggressive neuroblastomas with N-myc amplification or in neuroblastoma cell lines. Moreover, the expression pattern of PTN was similar to that of TRK-A, the high affinity receptor for nerve growth factor, in that it is correlated with a favorable prognosis (P < 0.004). In contrast, MK is highly expressed in almost all primary neuroblastomas and cell lines and showed no correlation with disease stage or N-myc amplification. These results suggest that differential expression of PTN and MK may have an important role in regulating growth and differentiation of neuroblastomas.
Parvalbumin fast‐spiking interneurons are selectively altered by paediatric traumatic brain injury (2018)

Paediatric traumatic brain injury (TBI) is a leading cause of death and disability in children. Traditionally, ongoing neurodevelopment and neuroplasticity have been considered to confer children with an advantage following TBI. However, recent findings indicate that the paediatric brain may be more sensitive to brain injury. Inhibitory interneurons are essential for proper cortical function and are implicated in the pathophysiology of TBI, yet few studies have directly investigated TBI-induced changes to interneurons themselves. Accordingly, in the present study, we examine how inhibitory neurons are altered following controlled cortical impact (CCI) in juvenile mice with targeted Cre-dependent fluorescence labelling of interneurons (Vgat:Cre/Ai9 and PV:Cre/Ai6). Although CCI failed to alter the number of excitatory neurons or somatostatin-expressing interneurons in the peri-injury zone, it significantly decreased the density of parvalbumin (PV) immunoreactive cells by 71%. However, PV:Cre/Ai6 mice subjected to CCI showed a lower extent of fluorescence labelled cell loss. PV interneurons are predominantly of a fast-spiking (FS) phenotype and, when recorded electrophysiologically from the peri-injury zone, exhibited intrinsic properties similar to those of control neurons. Synaptically, CCI induced a decrease in inhibitory drive onto FS interneurons combined with an increase in the strength of excitatory events. The results of the present study indicate that CCI induced both a loss of PV interneurons and an even greater loss of PV expression. This suggests caution is required when interpreting changes in PV immunoreactivity alone as direct evidence of interneuronal loss. Furthermore, in contrast to reports in adults, TBI in the paediatric brain selectively alters PV-FS interneurons, primarily resulting in a loss of interneuronal inhibition.
OPIOID RECEPTOR SIGNALLING MECHANISMS (1999)

1. Three pharmacological types of opioid receptors, mu, delta and kappa, and their corresponding genes have been identified. Although other types of opioid receptors have been suggested, their existence has not been established unequivocally. A fourth opioid receptor, ORL1, which is genetically closely related to the others, has also been isolated. ORL1 responds to the endogenous agonist nociceptin (orphanin FQ) and displays a pharmacological profile that differs greatly from mu, delta and kappa receptors. 2. All opioid receptors mediate many of their cellular effects via activation of heterotrimeric G-proteins. The mu, delta and kappa receptors are all capable of interacting with the pertussis toxin-sensitive G-protein alpha-subunits Gi1, Gi2, Gi3, Go1, Go2 and the pertussis toxin-insensitive Gz and G16. None of the opioid receptors interacts substantially with Gs and mu receptors do not activate Gq, G11, G12, G13, or G14. 3. Differential coupling of different opioid receptors to most types of G-proteins is marginal. The mu, delta and kappa receptors appear to preferentially activate Go and Gi2 over other pertussis toxin-sensitive G-proteins, although there is evidence that mu receptors show some preference for Gi3. delta Receptors couple more efficiently to G16 than do mu or kappa receptors. 4. There is some evidence that opioid receptors, particularly mu and ORL1 receptors, can also couple to cellular effectors in a G-protein-independent manner. 5. In general, the consequences of activation of any of the opioid receptors in a given cell type depend more on the profile (stoichiometry) of the G-proteins and effectors expressed than on the type of opioid receptor present in the cell. Notions that different types of opioid receptors intrinsically couple preferentially to one type of effector rather than another should, therefore, be discarded.
The gangliosides (1964)

The results of recent studies on the complexities of gangliosides from brain, spleen, and erythrocyte stroma are described, and ganglioside nomenclature is discussed. A description of the chemistry and methods of estimation of component groups (sialic acids, hexosamine and hexoses, fatty acids, and sphingosine bases) is followed by an account of the detailed investigation of isolated mono-, di-, and trisialogangliosides. Methods for the isolation of gangliosides from tissues and for their analysis are critically reviewed, and reference to the physiology of gangliosides is made.
Tumor necrosis factor alpha inhibits signaling from the insulin receptor. (1994)

Insulin resistance is a common problem associated with infections and cancer and, most importantly, is the central component of non-insulin-dependent diabetes mellitus. We have recently shown that tumor necrosis factor (TNF) alpha is a key mediator of insulin resistance in animal models of non-insulin-dependent diabetes mellitus. Here, we investigate how TNF-alpha interferes with insulin action. Chronic exposure of adipocytes to low concentrations of TNF-alpha strongly inhibits insulin-stimulated glucose uptake. Concurrently, TNF-alpha treatment causes a moderate decrease in the insulin-stimulated autophosphorylation of the insulin receptor (IR) and a dramatic decrease in the phosphorylation of IR substrate 1, the major substrate of the IR in vivo. The IR isolated from TNF-alpha-treated cells is also defective in the ability to autophosphorylate and phosphorylate IR substrate 1 in vitro. These results show that TNF-alpha directly interferes with the signaling of insulin through its receptor and consequently blocks biological actions of insulin.
A Single Point Mutation Controls the Cholesterol Dependence of Semliki Forest Virus Entry and Exit (1998)

Membrane fusion and budding are key steps in the life cycle of all enveloped viruses. Semliki Forest virus (SFV) is an enveloped alphavirus that requires cellular membrane cholesterol for both membrane fusion and efficient exit of progeny virus from infected cells. We selected an SFV mutant, srf-3, that was strikingly independent of cholesterol for growth. This phenotype was conferred by a single amino acid change in the E1 spike protein subunit, proline 226 to serine, that increased the cholesterol independence of both srf-3 fusion and exit. The srf-3 mutant emphasizes the relationship between the role of cholesterol in membrane fusion and virus exit, and most significantly, identifies a novel spike protein region involved in the virus cholesterol requirement.
A High-Level Query Language for Events (2006)

Nowadays events are omnipresent and exchanged as messages over networks. Characteristic for applications involving advanced (or complex) event processing is the need to (1) utilize data contained in the events, (2) detect patterns made up of multiple events (so-called composite events), (3) reason about temporal and causal relationships of events, (4) accumulate events for negation and data aggregation. This article describes a high-level language approach for expressing queries to events. Its foundations are: embedding of a query language for XML and other Web data formats, support for rule-based reasoning, and a complete coverage of the four dimensions mentioned above
Identification of the guanine nucleotide dissociation stimulator for Ral as a putative effector molecule of R-ras, H-ras, K-ras, and Rap. (1994)

To identify proteins that bind to the Ras-related protein R-ras we performed a yeast two-hybrid cDNA library screen. Several clones were obtained encoding the C-terminal region of the guanine nucleotide dissociation stimulator for Ral (RalGDS). The R-ras-binding domain of RalGDS (RalGDS-RBD) is distinct from the conserved catalytic exchange factor regions. Using the two-hybrid system, we show that RalGDS-RBD interacts with H-ras, K-ras, and Rap, and with active but not with inactive point mutants of these Ras-like GTPases. Moreover, using purified proteins, we demonstrate the direct GTP-dependent interaction of the Ras-like GTPases with RalGDS-RBD and full-length RalGDS in vitro. Furthermore, we show that RalGDS-RBD and the Ras-binding domain of Raf-1 compete for binding to the Ras-like GTPases. These data indicate that RalGDS is a putative effector molecule for R-ras, H-ras, K-ras, and Rap.
Transcriptional regulation of flhDC by QseBC and σ 28 (FliA) in enterohaemorrhagic Escherichia coli (2005)

Enterohaemorrhagic Escherichia coli (EHEC) serotype O157:H7, the causative agent of haemorrhagic colitis, has been shown to utilize a cell-to-cell signalling system to regulate gene expression. We have previously reported that the quorum sensing E. coli regulators B and C (QseBC) may act as a two-component system in EHEC to transcriptionally regulate the expression of flagella and motility through flhDC, the master regulator of flagella and motility genes. Here, we performed deletion analyses using the flhDC promoter in order to determine the minimal promoter regions necessary for QseBC transcriptional activation. We also performed electrophoretic mobility shift assays, competition experiments and DNaseI footprints, which suggest that QseB directly binds the flhDC promoter at high- and low-affinity binding sites. These analyses have allowed us to determine the potential consensus sequence to which QseB binds in order to regulate transcription. Additionally, we mapped the transcriptional start site of flhDC responsive to QseBC, leading to the identification of a conserved FliA (sigma28) consensus sequence. These results suggest that FliA (sigma28), a class 2 flagellar gene, may be aiding in the transcriptional initiation of class 1 genes (flhDC) in EHEC. In order to further characterize the role of FliA (sigma28) in transcription of the flhDC promoter, we constructed a fliA isogenic mutant in EHEC. The flhDC::lacZ transcriptional fusion showed decreased activity in the fliA mutant compared with wild-type and complemented strains. Taken together, these results indicate that transcriptional initiation at the flhDC promoter by QseBC appears to be complex and dependent on the presence of FliA (sigma28).
Nonadrenergic inhibitory nervous system in human airways (1976)

Human airways, from the middle of the trachea to the distal bronchi, were studied in vitro for the presence of inhibitory nerves. The tissue was obtained from operations and from recent autopsies. Electrical field stimulation of the tissues demonstrated cholinergic, excitatory nerves and their effect was blocked by atropine. Field stimulation of the tissues, in the presence of atropine, relaxed the smooth muscle even when the muscle was contracted by histamine. The field stimulation-induced relaxation was neither blocked nor modified by adrenergic blocking agents. Maximum relaxation of the bronchial muscle was obtained with a pulse duration of 1-2 ms, 70 V, and frequencies of 20 Hz and greater. The tracheal smooth muscle showed 85% of maximal relaxation with a frequency of 10 Hz. Tetrodotoxin, blocked the field stimulation-induced relaxation for pulse durations of 2 ms; this indicated that nerves were being stimulated. The airway system shows some of the characteristics of the nonadrenergic inhibitory system in the gastrointestinal tract and of the system reported in the guinea pig trachealis muscle. No evidence of adrenergic inhibitory fibers was found in the bronchial muscle with either pharmacological or histochemical techniques. These findings suggest that the nonadrenergic inhibitory system is the principal inhibitory system for the smooth muscle of human airways. We suggest that a defect in the airway system, such as that shown in the gastrointestinal tract, may be an explanation for the hyperreactive airways of asthma and chronic bronchitis.
Fractionation of human lymphocytes with plant lectins. II. Lens culinaris lectin and wheat germ agglutinin identify distinct lymphocyte subclasses. (1979)

We have fractionated human peripheral blood lymphocytes (PBL) into distinct subclasses based upon differential adherence to the plant lectins wheat germ agglutinin (WGA) and Lens culinaris lectin (lentil-PHA), derivatized to gelatin surfaces in plastic tubes and Petri dishes. Fifteen to forty percent of PBL were adherent to WGA-derivatized gelatin. Binding studies with 125 I-WGA showed that, compared to unfractionated PBL which bound 31.9 × 10 6 WGA molecules/cell, adherent cells bound more (44.1 × 10 6 molecules/cell), and nonadherent cells bound less (20.4 × 10 6 molecules/cell) WGA. By contrast, there were no differences among these groups for binding of other plant lectins. When lentil-PHA-derivatized gelatin was used, 25 to 50% of PBL were adherent, and, as previously reported, adherent cells bound approximately 4 times as many lentil-PHA molecules as nonadherent cells, whereas there were no differences in binding of other lectins. Sequential fractionation studies indicated that the WGA- and lentil-PHA-selected subclasses were separate groups. The percentage of T and B lymphocytes and macrophages did not differ among the subclasses. WGA-selected and lentil-PHA-selected lymphocyte subpopulations responded differently to stimulation in vitro by a panel of plant mitogens. Human PBL contain a spectrum of cell subclasses with different lectin-binding capacities. These subclasses are functionally unique.
Intracellular Delivery of a Tat-eGFP Fusion Protein into Muscle Cells (2001)

The Tat protein from HIV-1, when fused with heterologous proteins or peptides, can traverse biological membranes in a process called “protein transduction,” delivering its cargo into cells. A Tat-eGFP fusion protein was purified from bacteria to study the transduction kinetics of Tat fusion proteins into cultured myoblasts and in the muscle tissue. Correctly folded Tat-eGFP reaches a maximum intracellular level in nearly 30 min, while its endogenous fluorescence is first detected only after 14 h. The nuclear localization signal from the basic domain of Tat was not sufficient to confer nuclear localization to Tat-eGFP, suggesting that the nuclear import pathway used by the exogenously added Tat-eGFP might be sensitive to the folding state of eGFP. In mice, the direct delivery to the muscle tissue using subcutaneous injections or the intra-arterial pathway led to few positive fibers in the muscle periphery or surrounding the blood vessels. Muscles injected with Tat-eGFP showed intense labeling of the extracellular matrix (ECM), suggesting that, although Tat fusion proteins can transduce muscle fibers, their binding by components of the ECM surrounding myofibers could interfere with the intracellular transduction process.