gebhart/patrepeval huggingface dataset:
Igg-, Igm- And Iga-Rheumatoid Factors In Healthy Adults And Rheumatoid Patients Determined By An Indirect Immunofluoroscence Method (1979)

Sera from 173 healthy adults and 55 rheumatoid patients were studied for IgG-, IgM- and IgA-rheumatoid factors (RFs) by a modification of Este's indirect immunofluorescence method. Rabbit IgG bound to smeared sheep red cells was used as antigen. With each serum tested a smear of non-sensitized cells was used as control antigen. Anti-IgG of the sera studied, binding to the antigen, was demonstrated by fluorescein-conjugated anti-sera, monospecific for γ, μ and α chains, and not containing antibodies to sheep erythrocytes or rabbit IgG. Positive reactions were obtained with IgG as antigen, but not with the F(ab′)2 fragment. The sera tested were treated with dithiothreitol before they were assayed for IgG-RF, in order to abolish false-positive reactions due to IgM-RF activity. The detection limit for IgM-RF was 1 IU per ml. IgM-RF titres of 9 occurred in 7% of healthy adults and 73% of rheumatoid patients, titres ⩾18 in 3.5% and 67% respectively. IgG-RF titres of 9 occurred in 9% of healthy adults, 21% of seronegative and 24% of seropositive rheumatoid patients. Titres of 18 occurred in 3% of healthy adults and in 14% of seronegative rheumatoid patients. Titres of ⩾18 occurred in 22% of seropositive rheumatoid patients. IgG-RF was correlated with an involvement of more than 20 joints. IgA-RF was found in 83% of seropositive, 11% of seronegative rheumatoid patients and in none of the healthy adults (serum dilution 1: 9).
Machine Learning of Generic and User-Focused Summarization (1998)

A key problem in text summarization is finding a salience function which determines what information in the source should be included in the summary. This paper describes the use of machine learning on a training corpus of documents and their abstracts to discover salience functions which describe what combination of features is optimal for a given summarization task. The method addresses both "generic" and user-focused summaries.
Degradation and beyond: Control of androgen receptor activity by the proteasome system (2006)

The androgen receptor (AR) is a transcription factor belonging to the family of nuclear receptors which mediates the action of androgens in the development of urogenital structures. AR expression is regulated post-translationally by the ubiquitin/proteasome system. This regulation involves more complex mechanisms than typical degradation. The ubiquitin/proteasome system may regulate AR via mechanisms that do not engage in receptor turnover. Given the critical role of AR in sexual development, this complex regulation is especially important. Deregulation of AR signalling may be a causal factor in prostate cancer development. AR is the main target in prostate cancer therapies. Due to the critical role of the ubiquitin/proteasome system in AR regulation, current research suggests that targeting AR degradation is a promising approach.
Effects of Mitochondrial Gene Deletion on Tumorigenicity of Metastatic Melanoma: Reassessing the Warburg Effect (2010)

Metabolic flexibility is a hallmark of cancer. Although many tumors preferentially use glycolysis in the presence of oxygen for bioenergetic purposes (Warburg effect), the effects of glycolytic metabolism on tumor metastasis have not been investigated. We have employed an extreme model of glycolytic metabolism to investigate the ability of metastatic B16 mouse melanoma cells to grow as primary subcutaneous tumors and to form lung tumors when injected intravenously into syngeneic and immunocompromised mice. Mitochondrial gene-knockout B16rho degrees cells showed delayed subcutaneous tumor growth and, surprisingly, failed to form lung tumors. The results suggest that mitochondrial reactive oxygen species (ROS) may be required for tumor metastasis.
Influence of mutations in tissue factor on the fine specificity of macromolecular substrate activation (1997)

The C-terminal fibronectin-type-III-like module of the tissue factor (TF) extracellular domain plays a requisite role in the activation of macromolecular substrates by factor VIIa (VIIa) in complex with TF. Unlike the mutations Lys165-->Ala, Lys166-->Ala in TF, which prevent efficient proteolysis of factor X, we found that the coagulant defect of a site-specific Trp158-->Arg, Ser160-->Gly replacement mutant of TF is largely attributable to the inability of TF to efficiently support the activation of the bound zymogen VII to the active protease VIIa. Binding studies demonstrated comparable affinity of binding of VIIa or VII by wild-type TF and TF(R158G160). In comparison with wild-type TF, the catalytic efficiency of factor X activation was reduced 56-fold with TF(A165A166) as the cofactor, but only 3.5-fold with TF(R165G160). The activation of VII bound to TF by factor Xa or VIIa was reduced 2-fold in the presence of TF(R158G160) and 7-8-fold with TF(A165A166). This suggests that the molecular recognition of VII in complex with TF by the enzymes TF-VIIa and factor Xa are similar. Generation of factor IXa by TF(R158G160)-VIIa was unaltered, but reduced 2-fold with TF(A165A166). In addition, the mutations affected the cleavage of the two scissile bonds of factor IX differently, providing further support for the idea that the cofactor, TF, influences the fine specificity of activation of macromolecular substrates by the TF-VIIa complex.
A First-in-Human Study To Assess the Safety and Pharmacokinetics of Monoclonal Antibodies against Human Cytomegalovirus in Healthy Volunteers (2016)

Human cytomegalovirus (HCMV) can cause significant disease in immunocompromised patients and treatment options are limited by toxicities. CSJ148 is a combination of two anti-HCMV human monoclonal antibodies (LJP538 and LJP539) that bind to and inhibit the function of viral HCMV glycoprotein B (gB) and the pentameric complex, consisting of glycoproteins gH, gL, UL128, UL130, and UL131. Here, we evaluated the safety, tolerability, and pharmacokinetics of a single intravenous dose of LJP538 or LJP539 or their combination in healthy volunteers. Adverse events and laboratory abnormalities occurred sporadically with similar incidence between antibody and placebo groups and without any apparent relationship to dose. No subject who received antibody developed a hypersensitivity, infusion-related reaction or anti-drug antibodies. After intravenous administration, both LJP538 and LJP539 demonstrated typical human IgG1 pharmacokinetic properties, with slow clearances, limited volumes of distribution, and long terminal half-lives. The pharmacokinetic parameters were linear and dose proportional for both antibodies across the 50-fold range of doses evaluated in the study. There was no apparent impact on pharmacokinetics when the antibodies were administered alone or in combination. CSJ148 and the individual monoclonal antibodies were safe and well tolerated, with pharmacokinetics as expected for human immunoglobulin.
Colorization using optimization (2004)

Colorization is a computer-assisted process of adding color to a monochrome image or movie. The process typically involves segmenting images into regions and tracking these regions across image sequences. Neither of these tasks can be performed reliably in practice; consequently, colorization requires considerable user intervention and remains a tedious, time-consuming, and expensive task.In this paper we present a simple colorization method that requires neither precise image segmentation, nor accurate region tracking. Our method is based on a simple premise; neighboring pixels in space-time that have similar intensities should have similar colors. We formalize this premise using a quadratic cost function and obtain an optimization problem that can be solved efficiently using standard techniques. In our approach an artist only needs to annotate the image with a few color scribbles, and the indicated colors are automatically propagated in both space and time to produce a fully colorized image or sequence. We demonstrate that high quality colorizations of stills and movie clips may be obtained from a relatively modest amount of user input.
Users' perception of relevance of spoken documents (2000)

We present the results of a study of user's perception of relevance of documents. The aim is to study experimentally how users' perception varies depending on the form that retrieved documents are presented. Documents retrieved in response to a query are presented to users in a variety of ways, from full text to a machine spoken query-biased automatically-generated summary, and the difference in users' perception of relevance is studied. The experimental results suggest that the effectiveness of advanced multimedia Information Retrieval applications may be affected by the low level of users' perception of relevance of retrieved documents.
Friedreich Ataxia: Neuropathology Revised (2013)

Friedreich ataxia is an autosomal recessive disorder that affects children and young adults. The mutation consists of a homozygous guanine-adenine-adenine trinucleotide repeat expansion that causes deficiency of frataxin, a small nuclear genome-encoded mitochondrial protein. Low frataxin levels lead to insufficient biosynthesis of iron-sulfur clusters that are required for mitochondrial electron transport and assembly of functional aconitase, and iron dysmetabolism of the entire cell. This review of the neuropathology of Friedreich ataxia stresses the critical role of hypoplasia and superimposed atrophy of dorsal root ganglia. Progressive destruction of dorsal root ganglia accounts for thinning of dorsal roots, degeneration of dorsal columns, transsynaptic atrophy of nerve cells in Clarke column and dorsal spinocerebellar fibers, atrophy of gracile and cuneate nuclei, and neuropathy of sensory nerves. The lesion of the dentate nucleus consists of progressive and selective atrophy of large glutamatergic neurons and grumose degeneration of corticonuclear synaptic terminals that contain γ-aminobutyric acid (GABA). Small GABA-ergic neurons and their projection fibers in the dentato-olivary tract survive. Atrophy of Betz cells and corticospinal tracts constitute a second intrinsic CNS lesion. In light of the selective vulnerability of organs and tissues to systemic frataxin deficiency, many questions about the pathogenesis of Friedreich ataxia remain.
An Activated Sulfonylating Agent That Undergoes General Base-Catalyzed Hydrolysis by Amines in Preference to Aminolysis (2008)

Activated sulfonyl derivatives, similar to acyl ones, usually undergo aminolysis with amines in water as nucleophilic attack by the amine is preferred to hydrolysis. However, despite being active sulfonyl derivatives, four-membered heterocyclic sulfonamides, beta-sultams, do not undergo aminolysis in aqueous solution but preferentially react to give hydrolysis products only. The rate of the reaction of beta-sultams in buffered solutions of simple primary amines shows a first-order dependence on amine concentrations attributed to general base-catalyzed hydrolysis by the amine. Even N-benzyl-4,4-dimethyl-3-oxo-beta-sultam, which is both a beta-sultam and a beta-lactam, undergoes hydrolysis at the sulfonyl center rather than aminolysis at either the sulfonyl or acyl center. The solvent kinetic isotope effects (SKIE, k(H(2)O)/k(D(2)O)) for the amine-catalyzed hydrolyses are 1.4 and 1.9 for the hydrolysis of N-benzoyl-beta-sultam and N-benzyl-4,4-dimethyl-3-oxo-beta-sultam, respectively, compatible with a general base-catalyzed mechanism. The amine-catalyzed hydrolysis gives a Bronsted beta value of +0.9 for both N-benzoyl beta-sultam and N-benzyl-4,4-dimethyl-3-oxo-beta-sultam, indicating that the general base amine is almost fully protonated in the transition state. A general base-catalyzed mechanism for hydrolysis rather than nucleophilic attack was also deduced for the reaction of N-benzyl-4,4-dimethyl-3-oxo-beta-sultam with carboxylate anions based on a SKIE of 1.7-1.9 and rate constants which fit the Bronsted plot for amines. In contrast to acyl transfer reactions, those for sulfonyl transfer appear to show an inverse reactivity-selectivity relationshipthe most active compounds being the most selective. The lack of reactivity of beta-sultams toward amine nucleophiles appears to be related to the mechanism of ring opening of beta-sultams with a decreased reactivity toward amines relative to hydroxide ion, probably related to the expulsion of the relatively poor leaving group amide anion.
Intragenic anaplastic lymphoma kinase (ALK) rearrangements: Translocations as a novel mechanism of ALK activation in neuroblastoma tumors (2014)

Anaplastic lymphoma kinase (ALK) has been demonstrated to be deregulated in sporadic as well as in familiar cases of neuroblastoma (NB). Whereas ALK-fusion proteins are common in lymphoma and lung cancer, there are few reports of ALK rearrangements in NB indicating that ALK mainly exerts its oncogenic capacity via activating mutations and/or overexpression in this tumor type. In this study, 332 NB tumors and 13 cell lines were screened by high resolution single nucleotide polymorphism microarray. Gain of 2p was detected in 23% (60/332) of primary tumors and 46% (6/13) of cell lines, while breakpoints at the ALK locus were detected in four primary tumors and two cell lines. These were further analyzed by next generation sequencing and a targeted enrichment approach. Samples with both ALK and MYCN amplification displayed complex genomic rearrangements with multiple breakpoints within the amplicon. None of the translocations characterized in primary NB tumors are likely to result in a chimeric protein. However, immunohistochemical analysis reveals high levels of phosphorylated ALK in these samples despite lack of initial exons, possibly due to alternative transcription initiation sites. Both ALK proteins predicted to arise from such alterations and from the abnormal ALK exon 4-11 deletion observed in the CLB-BAR cell line show strong activation of downstream targets STAT3 and extracellular signal-regulated kinase (ERK) when expressed in PC12 cells. Taken together, our data indicate a novel, although rare, mechanism of ALK activation with implications for NB tumorigenesis.
A dynamic lithium-ion battery model considering the effects of temperature and capacity fading (2009)

Battery models capture the characteristics of real-life batteries, and can be used to predict their behavior under various operating conditions. In this paper, a dynamic model of lithium-ion battery has been developed with MATLAB/Simulink <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">reg</sup> in order to investigate the output characteristics of lithium-ion batteries. Dynamic simulations are carried out, including the observation of the changes in battery terminal output voltage under different charging/discharging, temperature and cycling conditions, and the simulation results are compared with the results obtained from several recent studies. The simulation studies are presented for manifesting that the model is effective and operational.
Low‐dose doxycycline therapy: Effect on gingival and crevicular fluid collagenase activity in humans (1990)

Tetracyclines are now recognized to have non-antimicrobial properties with therapeutic potential--for example, these agents can inhibit pathologic collagenolysis by blocking mammalian collagenases and other matrix-degrading metalloproteinases. In the current study, adult human subjects with moderate chronic periodontitis were administered specially formulated capsules of doxycycline, containing lower-than-usual amounts of this semi-synthetic tetracycline, on a daily basis for 2 weeks prior to a full-thickness flap procedure; control subjects were administered placebo capsules. The gingiva excised during this surgical procedure were extracted, the extracts partially purified and analyzed for collagenase activity using [3H-methyl] collagen as substrate and the techniques of SDS-PAGE/fluorography or liquid scintillation spectrometry. In the absence of any drug pre-treatment, or after a 2-wk regimen of placebo capsules, the gingival extracts exhibited pathologically-excessive mammalian collagenase activity. The 2-wk regimen of low-dose doxycycline capsules reduced this activity by approximately 60-80% (p less than 0.05 and less than 0.01, respectively); in vitro exposure of the gingival extract to doxycycline also inhibited its collagenase activity. Collagenase activity in the crevicular fluid of periodontal pockets of an additional group of subjects was also significantly reduced, as was the severity of inflammation at the same gingival sites. The results suggest that a regimen of low-dose doxycycline capsules may provide a safe (other studies indicate that this regimen may not induce tetracycline resistance in the subgingival plaque) and effective adjunct to instrumentation therapy in the management of pathologic collagenolysis in the periodontal patient. However, further studies are necessary to confirm this hypothesis.
História da cidade e do urbanismo no Brasil: reflexões sobre a produção recente (2004)

Texto apresentado ao II Seminário de História da Cidade e do Urbanismo, realizado\nem 1993 em Salvador, e publicado em 1998
Control of globin gene transcription by erythropoietin in erythroblasts from friend virus-infected mice. (1985)

Splenic erythroblasts of mice infected with the anemia-inducing strain of Friend virus can be isolated in large numbers with less than 5% contamination with other cell types. In short-term culture, the isolated cells will initiate globin synthesis and undergo other aspects of terminal differentiation only if erythropoietin (EP) is added to the medium. An early effect of the hormone on these cells is stimulation of total RNA synthesis. EP also causes initiation of transcription of the beta-globin genes after a lag period of 4 to 6 h. By 6 h, the transcription rate of beta-globin RNA is enhanced threefold, and by 12 h, it is nearly maximal at ca. 20 times the level of control cells which received no EP. Transcription rates of alpha and beta-globin genes are approximately equal to each other throughout the period of terminal differentiation. In the splenic erythroblasts, the chromatin structure in the vicinity of the beta-major globin gene was analyzed with two nucleases during these transcription rate changes. No S1 nuclease-hypersensitive site is detectable near the gene. The beta-major gene is quite sensitive to DNase I in comparison with the albumin gene; however, the level of sensitivity is the same before EP addition as it is during maximal gene transcription after EP addition. Also, a hypersensitive site near the 5' cap site of the beta-major gene is quantitatively equivalent both before and after EP addition. Analysis of cytosine methylation at two sites upstream from the gene showed no changes upon induction of beta-globin gene transcription by EP. Thus, the initiation of beta-globin transcription by EP appears to be at some step after chromatin structural alteration such as synthesis, release, or activation of a specific transcription initiation factor.
Vaccination with autologous endothelium inhibits angiogenesis and metastasis of colon cancer through autoimmunity (2004)

Overcoming immune tolerance of tumor angiogenesis should be useful for adjuvant therapy of cancer. We hypothesized that vaccination with autologous endothelium would induce an autoimmune response targeting tumor angiogenesis. To test this concept, we immunized BALB/c mice with a vaccine of glutaraldehyde-fixed murine hepatic sinusoidal endothelial cells (HSEs) in a lung metastasis model of Colon-26 cancer. Vaccination with autologous HSEs induced both preventive and therapeutic anti-tumor immunity that significantly inhibited the development of metastases. ELISA revealed an immunoglobulin response involving IgM and IgG subclasses. These antibodies had a strong affinity for antigens of both murine and human endothelium, and lyzed endothelial cells in the CDC assay. Flow-cytometry and chromium-release cytotoxicity assay revealed a specific CTL response against endothelial cells, which were lyzed in an effector: target ratio-dependent manner. Neither antibodies nor CTLs reacted with Colon-26. The effect of autologous HSEs was more pronounced than that of xenogeneic human umbilical vein endothelial cells (HUVECs), which were tested in the same experimental setting. Our results suggest that vaccination with autologous endothelium can overcome peripheral tolerance of self-angiogenic antigens and therefore should be useful for adjuvant immunotherapy of cancer.
Epidemiology and natural history of atopic diseases (2015)

The atopic diseases - atopic dermatitis, asthma, and hay fever - pose a great burden to the individual and society, not least, since these diseases have reached epidemic proportions during the past decades in industrialized and, more recently, in developing countries. Whereas the prevalence of the atopic diseases now seems to have reached a plateau in many Western countries, they are still on the increase in the developing world. This emphasizes continuing research aimed at identifying the causes, risk factors, and natural history of these diseases. Herein, the fundamental aspects of the natural history and epidemiology of the atopic diseases are reviewed.
Intrinsic Signaling Functions of the β4 Integrin Intracellular Domain (2007)

A key issue regarding the role of alpha6beta4 in cancer biology is the mechanism by which this integrin exerts its profound effects on intracellular signaling, including growth factor-mediated signaling. One approach is to evaluate the intrinsic signaling capacity of the unique beta4 intracellular domain in the absence of contributions from the alpha6 subunit and tetraspanins and to assess the ability of growth factor receptor signaling to cooperate with this domain. Here, we generated a chimeric receptor composed of the TrkB extracellular domain and the beta4 transmembrane and intracellular domains. Expression of this chimeric receptor in beta4-null cancer cells enabled us to assess the signaling potential of the beta4 intracellular domain alone or in response to dimerization using brain-derived neurotrophic factor, the ligand for TrkB. Dimerization of the beta4 intracellular domain results in the binding and activation of the tyrosine phosphatase SHP-2 and the activation of Src, events that also occur upon ligation of intact alpha6beta4. In contrast to alpha6beta4 signaling, however, dimerization of the chimeric receptor does not activate either Akt or Erk1/2. Growth factor stimulation induces tyrosine phosphorylation of the chimeric receptor but does not enhance its binding to SHP-2. The chimeric receptor is unable to amplify growth factor-mediated activation of Akt and Erk1/2, and growth factor-stimulated migration. Collectively, these data indicate that the beta4 intracellular domain has some intrinsic signaling potential, but it cannot mimic the full signaling capacity of alpha6beta4. These data also question the putative role of the beta4 intracellular domain as an "adaptor" for growth factor receptor signaling.