gebhart/patrepeval huggingface dataset:
SFK–STAT Pathway: An Alternative and Important Way to Malignancies (2006)

Signal transducers and activators of transcription (STAT) proteins play a crucial role in mediating signals from a diverse spectrum of cytokine receptors. STAT is thought to be activated by JAK family kinases (JFK) in many cytokine receptor signal pathways; however, recent studies have demonstrated an alternative pathway to activate STAT by Src family kinases (SFK) in growth factor receptor signal. We also observed STAT5 phosphorylation by Lyn, a member of SFK, in our two recent studies. We introduce these studies and review the literature of STAT activation by SFK and aberrant activation of STAT by oncogenic signals.
Erb:YAG and Hol:YAG laser ablation of meniscus and intervertebral discs (1992)

Erb:YAG and Hol:YAG laser ablation rates of fibrocartilage and nucleus pulposus were measured in vitro simulating clinical conditions. After ablation macroscopic and microscopic appearance of the ablation site was investigated. Hol:YAG and Erb:YAG laser mean ablation rates increased almost linearly with rising energies, showing higher total ablation rates for the Hol:YAG laser due to its higher achievable energy density. At comparable energy densities the Erb:YAG laser appears to be more effective with respect to the corresponding ablation rates. Consequently, the ablational threshold proved to be lower for the Erb:YAG laser. Whereas during Hol:YAG laser ablation, some smoke formation and considerable tissue shrinking occurred, these effects could not be observed during Erb:YAG laser ablation. Consequently macroscopic and microscopic inspection showed some thermal damage after Hol:YAG and only minimal alterations after Erb:YAG laser ablation. Adjacent thermal damage was determined and proved to be lower for the Erb:YAG laser. In our opinion the characteristics of each laser system provide certain advantages for special clinical indications.
The cytoplasmic domain of CD8 beta regulates Lck kinase activation and CD8 T cell development. (1998)

Previous studies have shown that CD8 beta plays a role in both enhancing CD8 alpha-associated Lck kinase activity and promoting the development of CD8-lineage T cells. To examine the role of this enhancement in the maturation of CD8-lineage cells, we assessed CD8 alpha-associated Lck kinase activity in both T cell hybridomas and thymocytes of mice expressing CD8 beta mutations known to impair CD8 T cell development. Lack of CD8 beta expression or expression of a cytoplasmic domain-deleted CD8 beta resulted in a severalfold reduction in CD8 alpha-associated Lck kinase activity compared with that observed with cells expressing wild-type CD8 beta chain. This analysis indicated a critical role for the cytoplasmic domain of CD8 beta in the regulation of CD8 alpha-associated Lck activity. Decreased CD8 alpha-associated Lck activity observed with the various CD8 beta mutations also correlated with diminished in vivo cellular tyrosine phosphorylation. In addition, analysis of CD8 beta mutant mice (CD8 beta-/- or cytoplasmic domain-deleted CD8 beta transgenic) indicated that the degree of reduction in CD8 alpha-associated Lck activity associated with each mutation correlated with the severity of developmental impairment. These results support the importance of CD8 beta-mediated enhancement of CD8 alpha-associated Lck kinase activity in the differentiation of CD8 single-positive thymocytes.
Arylcholine Carbonates and Aryl-3,3-dimethyl-1-butyl Carbonates as Inhibitors and Inactivators of Acetylcholinesterase (1991)

Five novel carbonates, designed as suicide (mechanism-based) inhibitors of acetylcholinesterase, were synthesized and evaluated against the enzyme in vitro and screened for insecticidal activity. The design strategy of inhibition was based on the isosteric relationship of carbonates to the ester of the natural substrate acetylcholine, and on the release of electrophilic quinone methides or alpha-chloroketones at the active site after enzymatic carbonate hydrolysis. Most compounds were inhibitory in vitro, with good specificity for acetylcholinesterase. Some showed modest insecticidal activity. Results of kinetic studies on one analog were consistent with mechanism-based inhibition.
Imiquimod (1999)

The imidazoquinoline, imiquimod, is a low molecular weight, synthetic immune response modifier that is used for the treatment of external genital and perianal warts. It is formulated in a 5% vanishing cream as Aldara. This self-applied therapy has shown good efficacy and safety in the treatment of external genital and perianal warts caused by human papillomavirus (HPV) infection. The antiviral mechanism of action of this compound is unlike any other approved antiviral therapy in that it induces the production of antiviral cytokines and cytokines that enhance cellular immunity believed to be necessary for the control or elimination of HPV infection. Imiquimod does not exert its antiviral effects directly on virus-infected cells. Treatment with imiquimod results in resolution of wart tissue and reduction of viral burden. Post-marketing trials using imiquimod demonstrated that patients who experience complete clearance of either new or recalcitrant warts tend to remain clear for longer periods as compared to other treatment modalities. Preclinical data demonstrate in vitro and in vivo that imiquimod directly induces antiviral and immunomodulating cytokines from monocytes, macrophages and dendritic cells. These immunomodulating cytokines have been shown to potentiate Th1 immunity. Self-application, good tolerability, a unique mechanism of action and a relatively high sustained clearance rate combine to make imiquimod a cost-effective first-line therapy for external genital warts and an appropriate second-line therapy when other treatments are unsuccessful. In small-scale studies requiring replication, imiquimod has also been shown to be effective in the treatment of non-HVP-related skin infections and some dermal neoplasias.
Identification of a Cyclin-cdk2 Recognition Motif Present in Substrates and p21-Like Cyclin-Dependent Kinase Inhibitors (1996)

Understanding how cyclin-cdk complexes recognize their substrates is a central problem in cell cycle biology. We identified an E2F1-derived eight-residue peptide which blocked the binding of cyclin A and E-cdk2 complexes to E2F1 and p21. Short peptides spanning similar sequences in p107, p130, and p21-like cdk inhibitors likewise bound to cyclin A-cdk2 and cyclin E-cdk2. In addition, these peptides promoted formation of stable cyclin A-cdk2 complexes in vitro but inhibited the phosphorylation of the retinoblastoma protein by cyclin A- but not cyclin B-associated kinases. Mutation of the cyclin-cdk2 binding motifs in p107 and E2F1 likewise prevented their phosphorylation by cyclin A-associated kinases in vitro. The cdk inhibitor p21 was found to contain two functional copies of this recognition motif, as determined by in vitro kinase binding/inhibition assays and in vivo growth suppression assays. Thus, these studies have identified a cyclin A- and E-cdk2 substrate recognition motif. Furthermore, these data suggest that p21-like cdk inhibitors function, at least in part, by blocking the interaction of substrates with cyclin-cdk2 complexes.
Soluble fumarate reductase isoenzymes from Saccharomyces cerevisiae are required for anaerobic growth (1998)

In Saccharomyces cerevisiae, the cytosolic and promitochondrial isoenzymes of fumarate reductase are encoded by the FRDS and OSM1 genes, respectively. The product of the OSM1 gene is reported to be required for growth in hypertonic medium. Simultaneous disruption of the FRDS and OSM1 genes resulted in the inability of the yeasts to grow anaerobically on glucose as a carbon source, and disruption of the OSM1 gene caused poor growth under anaerobic conditions. However, the disruption of both the FRDS and/or OSM1 genes had no effect on aerobic growth or growth under hypertonic conditions. These results suggest that the fumarate reductase isoenzymes in Saccharomyces cerevisiae are essential for anaerobic growth but not for growth under hypertonic conditions.
The E mu-myc transgenic mouse. A model for high-incidence spontaneous lymphoma and leukemia of early B cells. (1988)

Mice transgenic for a c-myc gene driven by the IgH enhancer (E mu-myc) were shown to almost invariably develop lymphomas, 90% succumbing in the first 5 mo of life. The tumors typically presented as rapidly progressive lymphadenopathy with thymic involvement and were highly malignant by transplantation assay. Morphologically, they were lymphoblastic lymphomas, usually accompanied by lymphoid leukemia and granulocytosis, and were distinct from the tumors that arose much later in 37% of nontransgenic mice of the same (C57BL/6 x SJL)F2 genetic background. Cell-surface markers on 31 E mu-myc tumors identified 52% as pre-B lymphomas, 29% as mixed pre-B and B lymphomas, and 19% as B lymphomas. The tumors appeared to arise at random from a population of pre-B cells expanded by constitutive expression of the myc transgene. A majority of the animals initiated malignancy at the rate of 17% per week. The rate at which the cycling, benign pre-B cells spontaneously convert to malignancy was estimated to about 10(-10) per cell per generation. A transient leukocytosis identified in young E mu-myc mice was developed into a rapid assay for inheritance of the transgene.
Spatiotemporal increases in epidermal growth factor receptors following peripheral nerve injury (1992)

Non-neuronal cells of peripheral nerve respond to axonal injury with a series of cellular changes that facilitate neuronal regeneration. To characterize the potential role of the epidermal growth factor (EGF) family of proteins in this response, we monitored the expression of EGF receptor mRNA and protein in the injured rat sciatic nerve. EGF receptor mRNA is synthesized in both primary cultured fibroblasts and Schwann cells, and Schwann cells express EGF receptor-like immunoreactivity. In situ hybridization and immunocytochemistry revealed that EGF receptor mRNA and protein are expressed in Schwann cells and fibroblasts of the sciatic nerve in vivo, and that receptor levels increase following nerve injury. Thirty-six hours postlesion, EGF receptors were expressed in gradients along the nerve both proximal and distal to the lesion, with the highest levels localized adjacent to the transection site. By 72 hr, receptor levels were maintained in a gradient in the proximal segment, but were uniformly increased throughout the portions of the distal segment that were analyzed. These changes were similar to those observed for low-affinity NGF receptor mRNA and protein, with transection causing increased expression in both Schwann cells and fibroblasts. Northern blots confirmed that primary cultured fibroblasts express low-affinity NGF receptor mRNA. To determine whether spatiotemporal gradients were a general characteristic of the nerve injury response, we monitored expression of the mRNA encoding the major myelin protein P0. Levels of P0 mRNA decreased initially in cells immediately adjacent to the transection site and, by 72 hr, were uniformly decreased throughout the distal segment. These data suggest that members of the EGF family of proteins may play a role in the peripheral nerve response to injury, and demonstrate a generalized gradient of cellular responses that commence at the transection site and progress distally in the nerve in the absence of intact axons.
Short‐term effects of magnetic sacral dermatome stimulation for idiopathic slow transit constipation: Sham‐controlled, cross‐over pilot study (2006)

Sacral dermatome stimulation may offer potential for therapeutic benefit for a subset of patients with idiopathic slow transit constipation, particularly constipated patients with rectal hyposensation or hindgut dysfunction.
A Diversity of Antibody Epitopes Can Induce Signaling through the Erythropoietin Receptor (2010)

Stimulation of red cell production through agonism of the erythropoietin receptor (EpoR) has historically been accomplished through administration of erythropoietin (EPO), the native ligand. The short half-life of EPO has led to the development of a variety of other agonists, including antibodies. It is of considerable interest to understand how these agents might activate the EpoR and whether or not it is important to bind in a manner similar to the native ligand. The binding epitopes of a panel of eight agonistic, single-chain antibody (scFv-Fc) constructs were determined through scanning alanine mutagenesis as well as more limited arginine mutagenesis of the receptor. It was found that while some of these constructs bound to receptor epitopes shared by the ligand, others bound in completely unique ways. The use of a panel of agonists and scanning mutagenesis can define the critical binding regions for signaling; in the case of the EpoR, these regions were remarkably broad.
Epidermal growth factor and keratinocyte growth factor differentially regulate epidermal migration, growth, and differentiation (2000)

Various growth factors such as epidermal growth factor and keratinocyte growth factor have been reported to promote wound closure and epidermal regeneration. In the present study epidermis reconstructed on de-epidermized dermis was used to investigate the effects of epidermal growth factor and keratinocyte growth factor on keratinocyte proliferation, migration and differentiation. Our results show that epidermal growth factor supplemented cultures share many of the features which are observed during regeneration of wounded epidermis: a thickening of the entire epidermis, an enhanced rate of proliferation and migration, and an increase in keratin 6, keratin 16, skin-derived antileukoproteinase, involucrin and transglutaminase 1 expression. The increase in transglutaminase 1 protein is accompanied by an increase in the amount of active transglutaminase 1 enzyme. Surprisingly no increase in keratin 17 is observed. Prolonging the culture period for more than two weeks results in rapid senescence and aging of the cultures. In contrast, keratinocyte growth factor supplemented cultures have a tissue architecture that is similar to healthy native epidermis and remains unchanged for at least 4 weeks of air-exposure. The rate of proliferation and the expression of keratins 6, 16 and 17, skin-derived antileukoproteinase, involucrin and transglutaminase 1 is similar to that found in healthy epidermis and furthermore keratinocyte migration does not occur. When the culture medium is supplemented with a combination of keratinocyte growth factor and a low concentration of epidermal growth factor, skin-derived antileukoproteinase, involucrin and keratins 6, 16 and 17 expression is similar to that found in cultures supplemented with keratinocyte growth factor alone and in healthy epidermis. Only high transglutaminase 1 expression remains similar to that observed in cultures supplemented with epidermal growth factor alone. Our results show that the regulation of keratinocyte growth, migration and differentiation depends on the availability of these growth factors. Epidermal growth factor may play a dominant early role in wound healing by stimulating keratinocyte proliferation and migration while keratinocyte growth factor may play a role later in the repair process by stabilizing epidermal turnover and barrier function.
A dicarbazole–triazine hybrid bipolar host material for highly efficient green phosphorescent OLEDs (2012)

A novel bipolar host material 9-(4,6-diphenyl-1,3,5-triazin-2-yl)-9′-phenyl-3,3′-bicarbazole (CzT) comprising a dicarbazole donor linking to an electron deficient 1,3,5-triazine acceptor was synthesized and characterized. The molecular design of CzT allows the spatial separation of HOMO and LUMO on the donor and acceptor moieties, respectively, giving sufficient triplet energy (2.67 eV) together with promising physical properties and morphological stability (Tg = 134 °C). This tailor-made material was used as a host for an efficient yellowish-green iridium complex, bis(o-tolylpyrimidinato-N,C2′)Ir(III)acetylacetonate [(TPm)2Ir(acac)]; the as-fabricated phosphorescent OLEDs (PHOLEDs) demonstrated high performance, with maximum efficiencies of 20.0% (75.7 cd A−1 and 71.3 lm W−1) and 20.1% (76.3 cd A−1 and 72.7 lm W−1) achieved in trilayer and bilayer device architectures, respectively. The efficiency of the trilayer device can sustain ∼20% over a wide brightness range from 102 to 103cd m−2 due to the more effective confinement of emissive excitons within the emitting layer.
Solvent Microextraction into a Single Drop (1996)

An analytical technique is described which combines solvent extraction with gas chromatographic (GC) analysis in a simple and inexpensive apparatus involving very little solvent consumption. A small drop (8 μL) of a water-immiscible organic solvent, containing an internal standard, is located at the end of a Teflon rod which is immersed in a stirred aqueous sample solution. After the solution has been stirred for a prescribed period of time, the probe is withdrawn from the aqueous solution, and the organic phase is sampled with a microsyringe and injected into the GC for quantification. The observed rate of solvent extraction is in good agreement with a convective-diffusive kinetic model. Analytically, the relative standard deviation of the method is 1.7% for a 5.00-min extraction of the analyte 4-methylacetophenone into n-octane.
Extended lapped transforms: properties, applications, and fast algorithms (1992)

The family of lapped orthogonal transforms is extended to include basis functions of arbitrary length. Within this new family, the extended lapped transform (ELT) is introduced, as a generalization of the previously reported modulated lapped transform (MLT). Design techniques and fast algorithms for the ELT are presented, as well as examples that demonstrate the good performance of the ELT in signal coding applications. Therefore, the ELT is a promising substitute for traditional block transforms in transform coding systems, and also a good substitute for less efficient filter banks in subband coding systems.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Pneumococcal Vaccine After 15 Years of Use (1994)

IN A recent Commentary, Hirschmann and Lipsky 1 reviewed pneumococcal vaccine after 15 years of use in United Following their evaluation of prospective vaccine trials, retrospective studies, and projections of vaccine effectiveness, they stated that no conclusive evidence has yet emerged that pneumococcal vaccine is effective in any group in United States. In their judgment, the evidence justifies not vaccinating immunocompromised or elderly populations with pneumococcal vaccine. While most observers would agree that available evidence on clinical effectiveness of pneumococcal vaccination is incomplete, evidence has been subject of ongoing critical review by several expert groups, including Advisory Committee on Immunization Practices, 2 American College of Physicians/ Infectious Diseases Society of America Task Force on Adult Immunization, 3 National Advisory Committee on Immunization in Canada, 4 and a Technical Advisory Group to World Health Organization Regional Office for Europe. 5
[Clinical value of positron emission tomography (PET) in oncologic questions: results of an interdisciplinary consensus conference. Schirmerreschaft der Deutschen Gesellschaft for Nuklearmedizin]. (1996)

Metabolic imaging of PET provides for many principle advantages compared to conventional anatomically based cross sectional imaging. For routine use in oncology a detailed assessment of specific efficiency of PET is indicated.
Vagus nerve stimulation therapy for partial-onset seizures (1998)

<b>Objective:</b> The purpose of this multicenter, add-on, double-blind, randomized, active-control study was to compare the efficacy and safety of presumably therapeutic (high) vagus nerve stimulation with less (low) stimulation. <b>Background:</b> Chronic intermittent left vagus nerve stimulation has been shown in animal models and in preliminary clinical trials to suppress the occurrence of seizures. <b>Methods:</b> Patients had at least six partial-onset seizures over 30 days involving complex partial or secondarily generalized seizures. Concurrent antiepileptic drugs were unaltered. After a 3-month baseline, patients were surgically implanted with stimulating leads coiled around the left vagus nerve and connected to an infraclavicular subcutaneous programmable pacemaker-like generator. After randomization, device initiation, and a 2-week ramp-up period, patients were assessed for seizure counts and safety over 3 months. The primary efficacy variable was the percentage change in total seizure frequency compared with baseline. <b>Results:</b> Patients receiving high stimulation (94 patients, ages 13 to 54 years) had an average 28% reduction in total seizure frequency compared with a 15% reduction in the low stimulation group (102 patients, ages 15 to 60 year; <i>p</i> = 0.04). The high-stimulation group also had greater improvements on global evaluation scores, as rated by a blinded interviewer and the patient. High stimulation was associated with more voice alteration and dyspnea. No changes in physiologic indicators of gastric, cardiac, or pulmonary functions occurred. <b>Conclusions:</b> Vagus nerve stimulation is an effective and safe adjunctive treatment for patients with refractory partial-onset seizures. It represents the advent of a new, nonpharmacologic treatment for epilepsy.
A southeastern cancer study group phase I/II trial with vaccinia melanoma oncolysates (1986)

Vaccinia melanoma oncolysates (VMO) were tested in a Southeastern Cancer Study Group (SECSG) Phase I/II trial. Forty-eight patients with high-risk Stage I or pathologic Stage II disease were placed on study at six different dose levels and two different treatment regimens. Patients were monitored for toxicity to the VMO after each injection. Patients' sera were tested for anti-human melanoma reactivity with the Staphylococcus Protein A (SpA) assay. Toxicity was minimal at all doses tested. In only 2 of 19 patients on delayed treatment did reactivity develop in the SpA assay by 6 months. However, 13 of 23 patients on immediate treatment showed reactivity, including 8 of 8 at the two highest doses. Since the VMO appears to be safe at all of the doses tested, and because of the immunogenicity of the VMO at the higher doses as demonstrated by the SpA assay, the 2-mg dose level, for immediate treatment, was chosen for use in future trials.
Vav binds to several SH2/SH3 containing proteins in activated lymphocytes. (1994)

In T lymphocytes, several proteins are rapidly phosphorylated on tyrosine after stimulation. In this study we examine the ability of tyrosine phosphorylated proteins from Jurkat T cells stimulated by CD2 or T cell receptor-CD3 to interact with the src homology 2 or src homology 3 domains from eight different proteins involved in signal transduction in lymphocytes: Vav, Shc, Nck, phosphatidylinositol-3-kinase, phospholipase C-gamma 1, Ras-GTPase activating protein, c-Crk and Grb2. Our data show that different SH2 domains have distinct patterns of binding to phosphotyrosine containing proteins. We show that Vav, a protein expressed only in hematopoietic cells that may have guanine nucleotide releasing factor activity, is able to interact with certain SH2-containing proteins depending on its tyrosine phosphorylation and with Grb2 in a manner independent of phosphorylation on tyrosine. Coimmunoprecipitation experiments support the idea of a trimolecular complex Shc-Grb2-Vav in vivo. These data suggest a central role played by Vav and provide insight in the complexity and specificity of protein-protein interactions in the signaling events in lymphocytes.