gebhart/patrepeval huggingface dataset:
Molecular mechanisms underlying IGF‐I‐induced attenuation of the growth‐inhibitory activity of trastuzumab (Herceptin) on SKBR3 breast cancer cells (2003)

The clinical usefulness of trastuzumab (Herceptin; Genentech, San Francisco, CA) in breast cancer treatment is limited by the rapid development of resistance. We previously reported that IGF-I signaling confers resistance to the growth-inhibitory actions of trastuzumab in a model system, but the underlying molecular mechanism remains unknown. We used SKBR3/neo cells (expressing few IGF-I receptors) and SKBR3/IGF-IR cells (overexpressing IGF-I receptor) as our experimental model. IGF-I antagonized the trastuzumab-induced increase in the level of the Cdk inhibitor p27(Kip1). This resulted in decreased association of p27(Kip1) with Cdk2, restoration of Cdk2 activity and attenuation of cell-cycle arrest in G(1) phase, all of which had been induced by trastuzumab treatment in SKBR3/IGF-IR cells. We also found that the decrease in p27(Kip1) induced by IGF-I was accompanied by an increase in expression of Skp2, which is a ubiquitin ligase for p27(Kip1), and by increased Skp2 association with p27(Kip1). A specific proteasome inhibitor (LLnL) completely blocked the ability of IGF-I to reduce the p27(Kip1) protein level, while IGF-I increased p27(Kip1) ubiquitination. This suggests that the action of IGF-I in conferring resistance to trastuzumab involves targeting of p27(Kip1) to the ubiquitin/proteasome degradation machinery. Finally, specific inhibitors of MAPK and PI3K suggest that the IGF-I-mediated reduction in p27(Kip1) protein level by increased degradation predominantly involves the PI3K pathway. Our results provide an example of resistance to an antineoplastic therapy that targets one tyrosine kinase receptor by increased signal transduction through an alternative pathway in a complex regulatory network.
Preventing cervical cancer (2008)

Three federal programs with the potential to reduce cervical cancer incidence, morbidity, and mortality, especially among underserved populations, are administered by the Centers for Disease Control and Prevention (CDC): the National Breast and Cervical Cancer Early Detection Program (NBCCEDP), the Vaccines for Children (VFC) Program, and the Section 317 immunization grant program. The NBCCEDP provides breast and cervical cancer screening and diagnostic services to uninsured and underinsured women. The VFC program and the Section 317 immunization grant program provide vaccines, including human papillomavirus (HPV) vaccine, to targeted populations at no cost for these vaccines. This article describes the programs, their histories, populations served, services offered, and roles in preventing cervical cancer through HPV vaccination and cervical cancer screening. Potential long-term reduction in healthcare costs resulting from HPV vaccination is also discussed. As an example of an initiative to vaccinate uninsured women aged 19-26 years through a cancer services program, a state-based effort that was recently launched in New York, is highlighted.
Multi-Prototype Vector-Space Models of Word Meaning (2010)

Current vector-space models of lexical seman-tics create a single “prototype ” vector to rep-resent the meaning of a word. However, due to lexical ambiguity, encoding word mean-ing with a single vector is problematic. This paper presents a method that uses cluster-ing to produce multiple “sense-specific ” vec-tors for each word. This approach provides a context-dependent vector representation of word meaning that naturally accommodates homonymy and polysemy. Experimental com-parisons to human judgements of semantic similarity for both isolated words as well as words in sentential contexts demonstrate the superiority of this approach over both proto-type and exemplar based vector-space models. 1
Bayesian Basecalling for DNA Sequence Analysis Using Hidden Markov Models (2007)

It has been shown that electropherograms of DNA sequences can be modeled with hidden Markov models. Basecalling, the procedure that determines the sequence of bases from the given eletropherogram, can then be performed using the Viterbi algorithm. A training step is required prior to basecalling in order to estimate the HMM parameters. In this paper, we propose a Bayesian approach which employs the Markov chain Monte Carlo (MCMC) method to perform basecalling. Such an approach not only allows one to naturally encode the prior biological knowledge into the basecalling algorithm, it also exploits both the training data and the basecalling data in estimating the HMM parameters, leading to more accurate estimates. Using the recently sequenced genome of the organism Legionella pneumophila we show that the MCMC basecaller outperforms the state-of-the-art basecalling algorithm in terms of total errors while requiring much less training than other proposed statistical basecallers.
Accelerating 3D convolution using graphics hardware (1999)

Many volume filtering operations used for image enhancement, data processing or feature detection can be written in terms of three-dimensional convolutions. It is not possible to yield interactive frame rates on todays hardware when applying such convolutions on volume data using software filter routines. As modern graphics workstations have the ability to render two-dimensional convoluted images to the frame buffer, this feature can be used to accelerate the process significantly. This way generic 3D convolution can be added as a powerful tool in interactive volume visualization toolkits.
Hypertension and proteinuria: a class-effect of antiangiogenic therapies (2008)

Antiangiogenic therapy has now become a cornerstone in the treatment of several solid tumor cancers. Those drugs present with a renal toxicity profile manifesting as proteinuria and hypertension, often reported in the literature to be linked to bevacizumab, a monoclonal antibody targeted at the circulating vascular endothelial growth factor (VEGF). However, there is evidence that those side effects are most probably related to the pharmacological action of those drugs: the inhibition of the VEGF pathway. Thus, they may occur with any antiangiogenic therapy, either those acting on circulating VEGF (bevacizumab or VEGF-trap), or those acting on VEGF receptor(s) (sunitinib, sorafenib, or axitinib). Clinicians should thus be aware of such a 'class effect' to appropriately monitor and treat their patients, regardless of which antiangiogenic drug is used.
Glucose refractoriness of β-cells from fed fa/fa rats is ameliorated by nonesterified fatty acids (1999)

The aim of this study was to characterize the glucose responsiveness of individual beta-cells from fa/fa rats under ad libitum feeding conditions. Enlarged intact islets from fed fa/fa rats had a compressed insulin response curve to glucose compared with smaller islets. Size-sorted islets from obese rats yielded beta-cells whose glucose responsiveness was assessed by reverse hemolytic plaque assay to determine whether glucose refractoriness was caused by a decreased number of responsive cells or output per cell. In addition, the effects of palmitic acid on glucose-stimulated insulin secretion were assessed because of evidence that nonesterified fatty acids have acute beneficial effects. Two- to threefold more beta-cells from >250 microm diameter (large) islets than <125 microm diameter (small) or lean islets responded to low glucose. Increasing the glucose (8.3-16.5 mM) induced a >10-fold increase in recruitment of active cells from small islets, compared with only a 2.6-fold increase in large islets. This refractoriness was partially reversed by preincubation of the cells in low glucose for 2 h. In addition, secretion per cell of the large islet beta-cell population was significantly reduced compared with lean beta-cells, so that the overall response capacity of large but not small islet beta-cells was significantly reduced at high glucose. Therefore, continued near-normal function of the beta-cells from small islets of fa/fa rats seems crucial for glucose responsiveness. Incubation of beta-cells from large islets with palmitic acid normalized the secretory capacity to glucose mainly by increasing recruitment and secondarily by increasing secretion per cell. In conclusion, these studies demonstrate refractoriness to glucose of beta-cells from large islets of fa/fa rats under ad libitum feeding conditions. When acutely exposed to nonesterified fatty acids, islets from fa/fa rats have a potentiated insulin response despite chronic elevation of plasma lipids in vivo.
Nervous System-Specific Expression of a Novel Serine Protease: Regulation in the Adult Rat Spinal Cord by Excitotoxic Injury (1997)

A full-length cDNA clone of a previously unidentified serine protease, myelencephalon-specific protease (MSP), has been isolated by using a PCR cloning strategy and has been shown to be expressed in a nervous system and spinal cord-specific pattern. Sequence analysis demonstrated that MSP is most similar in sequence to neuropsin, trypsin, and tissue kallikrein and is predicted to have trypsin-like substrate specificity. MSP mRNA was found to be approximately 10-fold greater in the CNS of the rat and human, as compared with most peripheral tissues, and within the CNS was found to be highest by a factor of four in the medulla oblongata and spinal cord. Levels of mRNA encoding tissue plasminogen activator (tPA) also were elevated in the spinal cord but were more widespread in peripheral tissues as compared with MSP. In the adult rat lumbosacral spinal cord, in situ localization of MSP mRNA demonstrated 2-fold higher levels in the white, as compared with the gray, matter. MSP mRNA expression was shown to increase 3-fold in the white matter and 1.5-fold in the gray laminae at 72 hr after intraperitoneal injection of the AMPA/kainate glutamate receptor-specific agonist, kainic acid (KA). MSP mRNA remained elevated in the ventral gray matter, including expression associated with the motor neurons of lamina IX, at 7 d after the initial excitotoxic insult. Together, these observations indicate that MSP is in a position to play a fundamental role in normal homeostasis and in the response of the spinal cord to injury.
Sustained protective rabies neutralizing antibody titers after administration of cationic lipid-formulated pDNA vaccine. (2006)

Published data indicate that formulation of pDNA with cationic lipids could greatly enhance the response to a pDNA vaccine in larger mammals. The present work tested the influence of several pDNA:cationic lipid formulations on rabies neutralizing titers. Plasmid expressing Rabies G protein (CVS strain) was evaluated in vivo for ability to elicit neutralizing titers. pDNA:DMRIE-DOPE formulated at two DNA:cationic lipid molar ratios was compared in mice to a Vaxfectin-pDNA formulation. Mouse data indicate that Vaxfectin is more effective than DMRIE-DOPE in eliciting neutralizing titers. In addition, the ratio of pDNA to DMRIE-DOPE can also affect neutralizing titers. Our data show that sustained neutralizing titers (120 days) can be obtained after a single administration of DMRIE-DOPE-formulated pDNA in rabbits.
Prevalence of sarcopenia in Germany and the corresponding effect of osteoarthritis in females 70 years and older living in the community: results of the FORMoSA study (2015)

The prevalence of sarcopenia in CD German females 70 years+ is relatively low. However, participants with OA at the hip or lower limbs were at increased risk for sarcopenia.
Restricted usage of T‐cell receptor α‐chain variable region (TCRAV) and T‐cell receptor β‐chain variable region (TCRBV) repertoires after human allogeneic haematopoietic transplantation (2000)

We analysed T-cell receptor alpha-chain variable region (TCRAV) and T-cell receptor beta-chain variable region (TCRBV) repertoires in peripheral blood mononuclear cells (PBMCs) from 34 recipients of allogeneic bone marrow transplantation (allo-BMT), seven of allogeneic peripheral blood stem cell transplantation and 19 of autologous peripheral blood stem cell transplantation using the quantitative microplate hybridization assay. TCR usage skewed at an early period (6-7 weeks) after BMT. The change was more apparent in allogeneic recipients than in autologous recipients. In particular, a predominant increase was detected in the frequency of VA1-4 (26%, 11 of 41 recipients), VA3-1 (32%) and VB24-1 (28%). Interestingly, acidic amino acid residues frequently followed the arginine residue in complementarity-determining region 3 of BV24S1. We further examined the extent of skew using samples obtained at serial time points after transplantation. The normalization of skewed repertoires occurred over a long period of time (> 8 years). There was a significant difference in the rate of normalization of skewed TCR repertoires between adult and child recipients (P < 0.05). The results suggest that these T cells may have expanded in response to allogeneic antigens, such as miHA (minor histocompatibility antigen), and that altered repertoires are eventually normalized by T-cell regeneration via a thymic-dependent pathway in children.
A deletion map of the WAGR region on chromosome 11. (1989)

The WAGR (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation) region has been assigned to chromosome 11p13 on the basis of overlapping constitutional deletions found in affected individuals. We have utilized 31 DNA probes which map to the WAGR deletion region, together with six reference loci and 13 WAGR-related deletions, to subdivide this area into 16 intervals. Specific intervals have been correlated with phenotypic features, leading to the identification of individual subregions for the aniridia and Wilms tumor loci. Delineation, by specific probes, of multiple intervals above and below the critical region and of five intervals within the overlap area provides a framework map for molecular characterization of WAGR gene loci and of deletion boundary regions.
Optimal power deposition in hyperthermia. I. The treatment goal: The ideal temperature distribution: the role of large blood vessels (1991)

AbstractImproved hyperthermia heating systems that have flexibility in their deposition patterns are becoming available commercially, and even more flexible systems are being developed in research laboratories. To best use these devices one must determine how to deposit the power optimally, for which one needs a clear thermal treatment goal including an ideal temperature distribution. This paper presents definitions for these quantities, and theoretically investigates the relative effects of thermal conduction and blood convection cooling on them. It is shown that both cooling mechanisms can be important clinically, and that the presence of 'large' blood vessels can have a major impact on the optimal power deposition patterns. In particular, an ideal heating system would deposit enough power both outside the treatment volume in order to preheat the incoming blood to the desired treatment temperature, and at the treatment volume boundary in order to overcome thermal conduction effects. The degree to which any heating system can approach the ideal temperature distribution is shown to be strongly influenced by the size and shape of its power deposition field, i.e. its conformability, or ability to conform to the boundary of the desired treatment volume.
ATP-coupled transport of vesicular stomatitis virus G protein between the endoplasmic reticulum and the Golgi. (1986)

The temperature and ATP dependence of transport of the vesicular stomatitis virus strain ts045 G protein from the endoplasmic reticulum (ER) to an early Golgi compartment containing mannosidase I was studied in the mutant Chinese hamster ovary cell clone 15B. Appearance of G protein containing the Man5GlcNAc2 oligosaccharide species occurred after a shift to the permissive temperature with a lag period of 5 min and without detectable formation of the intermediate Man7GlcNAc2 and Man6GlcNAc2 species. Two biochemically distinct transport steps were detected during transport from the ER to the Golgi. An initial step is temperature sensitive, thermoreversible, and requires a high threshold of cellular ATP for maximal rate of transport (80% of the normal cellular ATP pool). Export from the ER is inhibited at 65% of the normal cellular ATP pool. Prolonged incubation at reduced levels of cellular ATP or at the restrictive temperature resulted in the accumulation of G protein in either the Man8GlcNAc2 species or the Man7GlcNAc2 and Man6GlcNAc2 species, respectively. Reversal of the temperature-sensitive block is ATP coupled. A second step is insensitive to incubation at the restrictive temperature and proceeds efficiently when the cellular ATP pool is reduced to 20% of the control. G protein accumulates at this intermediate step during prolonged incubation at 15 degrees C. The data suggest a functional division of processes required for transport of protein between the ER and Golgi compartments. The two steps may reflect the export (budding) and delivery (fusion) of proteins through vesicular trafficking between the ER and Golgi.
[Value of MN/CAIX in the diagnosis of renal cell carcinoma]. (2012)

MN/CAIX is specifically overexpressed in RCC, especially in clear cell RCC, suggesting its potential in the diagnosis and prognostic and therapeutic evaluation of RCC.
Informing the design of collaborative virtual environments (1997)

This paper addresses the design of Collaborative Virtual Environments (CVEs). More specifically, it considers key design issues concerning the use of either real world 'facsimile' representations or more abstracted means of delivering CVEs. We suggest that the use of ethnographic studies of the context-of-use of the CVE under development is a useful means of informing these design issues in contrast to more in-principle means of drawing conclusions. This approach is illustrated by informing the development of a virtual environment from and ethnographic study of work.
Decreased neutrophil L-selectin expression in patients with systemic inflammatory response syndrome. (1996)

The loss of L-selectin may be partly responsible for reduced neutrophil exudation to extravascular sites in patients with SIRS.
Glucuronidation of 3-O-methylnoradrenaline, harmalol and some related compounds (1968)

1. The following compounds were glucuronidated in the presence of UDP-glucuronic acid and a microsomal preparation made from guinea-pig liver: (14)C-labelled 3-O-methyladrenaline, 3-O-methylnoradrenaline, 3-methoxytyramine and 4-hydroxy-3-methoxyphenethanol, as well as unlabelled harmalol and harmol. 2. [(14)C]Homovanillic (4-hydroxy-3-methoxyphenylacetic) acid was not a substrate for the microsomal glucuronyltransferase. 3. The K(m) values for harmalol and harmol were 0.69x10(-4)m and 0.50x10(-4)m respectively. 4. The K(m) values for UDP-glucuronic acid, in the presence of (14)C-labelled 3-O-methylnoradrenaline, harmalol and harmol as aglycones, were 0.57x10(-4)m, 0.44x10(-4)m and 2.20x10(-4)m respectively. 5. Mg(2+) added at 2.5-10mm activated glucuronyltransferase, with harmalol as substrate. Concentrations above 10mm inhibited the enzymic activity. 6. The overall, or net, transglucuronidating activity of microsomal preparations of the liver, with harmalol as substrate, was greatest for guinea pig, and very much lower for rabbit, mouse and rat.
Phase II trial of imiquimod and HPV therapeutic vaccination in patients with vulval intraepithelial neoplasia (2010)

The therapeutic effect of treatment depends on the differential immune response of responders and non-responders with affect locally and systemically.
Templos de civilização: a implantação da escola primária graduada no Estado de São Paulo (1890-1910) (1999)

A partir de 1890, entre as várias medidas de reforma da instrução pública no Estado de São Paulo, foram criados os então chamados Grupos Escolares que viriam a provocar profundas modificações no sistema educacional brasileiro através de inovações nas práticas de ensino.Baseada nas experiências de países europeus e principalmente dos Estados Unidos, esta iniciativa fazia parte de um projeto mais amplo pretendido pelo recém-instituído regime republicano.Através de transformações profundas nos objetivos, na concepção educacional e na organização da escola, pretendia-se atingir a universalização do ensino e alinhar a nação, no que dizia respeito a um projeto educacional, com as propostas avançadas de outros países, nos quais esta experiência já era uma realidade.A implantação desta nova forma de escola provocou um entusiasmo na sociedade da época pois, além de satisfazer a necessidade de novas vagas escolares, dava resposta a um anseio de modernidade que identificava a democratização do ensino com a prosperidade do país.Os idealizadores das reformas educacionais acreditavam que seria imprescindível a renovação do ensino primário para atingir a pretendida reforma social.Esse é o tema do livro Templos de civilização, no qual a autora, Rosa Fátima de Souza, analisa a estrutura e a forma da escola primária criada no estado de São Paulo pelo projeto educacional republicano.Através do conceito de representações culturais observados em Roger Chartier, Rosa Fátima reconstrói a institucionalização de um modelo que, através da introdução de diversas inovações na escola primária, marcou uma nova realidade no Brasil, ajudando a legitimar o recém-inaugurado regime republicano
A simple protocol for the automation of DNA cycle sequencing reactions and polymerase chain reactions (1992)

Automated DNA sequencing methods using robotic workstations have been previously reported, however it is often an arduous task to import these technologies into a laboratory. We describe protocols making use of a Beckman Biomek 1000 robotic workstation to prepare polymerase chain reactions (PCRs) and "cycle sequencing" reactions to be performed in a Perkin Elmer Cetus System 9600 thermocycler. The combination of these two instruments allows a high throughput of PCR and DNA sequencing reactions. The programs described are freely available via anonymous file transfer protocol (FTP).
Interaction of omeprazole with DNA in rat tissues (1992)

There has been concern recently over the possible genotoxicity of omeprazole, a potent inhibitor of gastric acid secretion in humans. In order to investigate its possible DNA binding activity in vivo, 14C-labelled omeprazole was administered to male PVG rats, 8-10 weeks old, orally by gavage at a dose of 30 mg/kg. At various times after treatment, animals were killed and DNA isolated from the fundic and antral regions of the glandular stomach, and from the duodenum, ileum and colon. Scintillation counting of the DNA samples revealed a reproducible association of 14C that was not extractable with organic solvents and could not be removed from the DNA by column cartridge chromatography. DNA samples were digested enzymically to deoxyribonucleosides and analysed by reversed-phase high performance liquid chromatography (HPLC). With DNA from each tissue, most of the radioactivity eluted in a peak that was chromatographically distinct from normal nucleosides and from omeprazole itself. Chromatography following partial digestion of DNA gave rise to the same radioactivity elution profiles, whilst chromatography on hydroxyapatite resulted in retention of most of the radioactivity on the column using conditions under which DNA was eluted. These findings suggest either the formation in rat tissues of chemically-labile covalent omeprazole-DNA adducts or, more likely, a strong non-covalent interaction. The apparent DNA binding occurs rapidly in vivo and is short-lived, the maximum levels of radioactive incorporation (equivalent of up to 36 pmol omeprazole/mg DNA) occurring at 0.5 h in fundus, 0.5-1 h in antrum, 1 h in duodenum, 2 h in ileum and at 4-8 h in colon.