gebhart/patrepeval huggingface dataset:
Improved efficacy of gefitinib therapy in phospho-Akt positive patients with advanced non-small cell lung cancer (2004)

3004 Background: At the present time there is no reliable and identifiable marker that would help to identify those patients who are more likely to respond to gefitinib therapy. In some of the patients with NSCLC, EGFR may be the critical pathway signalling tumor growth. It is possible that responding patients are those in whom cell survival is maintained by activated EGFR-dependent pathways and in whom these pathways are suppressed by gefitinib. We investigated whether the evaluation of the Ras/raf/MAPK and the PI3K-AKT pathways before starting gefitinib therapy could help in identifying responding patients. This trial has been designed in order to possibly correlate Phospho-AKT/Phospho-MAPK status and gefitinib activity in terms of Response Rate (RR) and Time to Progression (TTP). Methods: Consecutive patients with NSCLC progressing or relapsing with standard therapy received gefitinib at a daily dose of 250 mg given until disease progression, unacceptable toxicity or refusal. Tumor tissue specimens obtained at the time of primary diagnosis were collected to determine P-AKT/P-MAPK status by immunohistochemistry. Results: One hundred-six NSCLC patients were enrolled onto the study in three Italian Institutions, and 103 were evaluable for P-AKT/P-MAPK status. P-AKT was positive in 51 (49.5%) and negative in 52 (50.5%) patients. P-MAPK resulted positive (2+/3+) in 23 (22.3%) and negative (0/1+) in 80 (77.7%). P-AKT positive status resulted significantly related to female gender (P<0.001), smoking history (P<0.05), and bronchioloalveolar histology (P<0.05). Compared to the P-AKT negative group, P-AKT positive patients had better RR (26.1% versus 3.9%, P=0.003), disease control rate (60.9% versus 23.5%, P<0.001), and significantly longer TTP (5.5 versus 2.8 months, P=0.004). No difference was observed in patients P-MAPK 0/1+ versus 2+/3 in terms of RR, disease control rate and TTP. Multivariate analysis confirmed that P-AKT positive status resulted in a significant reduction of disease progression risk (HR: 0.66, CI 95%:0.40–1.10). Conclusions: Gefitinib therapy resulted more active in P-AKT positive patients. No significant financial relationships to disclose.
Delivery systems for inhaled nitric oxide. (1997)

From a practical standpoint, technical issues related to NO delivery are as important as therapeutic issues. The benefits can be appreciated only if a reliable delivery system is used. Further, hazards and toxicity may be more problematic with an unreliable delivery system. It is incumbent on clinicians using inhaled NO to ensure that the delivery system is safe and reliable.
A Two-Gene Expression Ratio of Homeobox 13 and Interleukin-17B Receptor for Prediction of Recurrence and Survival in Women Receiving Adjuvant Tamoxifen (2006)

A high HOXB13/IL-17BR expression ratio is associated with increased relapse and death in patients with resected node-negative, ER-positive breast cancer treated with tamoxifen and may identify patients in whom alternative therapies should be studied.
Zur Bildung makrocyclischer B-N-Verbindungen / About the Formation of Macrocyclic B-N-Compounds (1978)

By the reaction of 2-alkyl-4,6-dichloro-1,3,5-trimethylborazines with bis(trimethylsilyl)amine and pyrolysis of the products in vacuo, macrocyclic polyborazines consisting of NH-bridged borazine rings are obtained. Besides pentacyclic systems (of four borazine rings) which have been isolated, a hexacyclic compound formed by five borazines was detected in a mass spectrum
Expression pattern of S100 calcium‐binding proteins in human tumors (1996)

The S100 Ca2+-binding proteins recently became of major interest because of their differential expression in neoplastic tissues, their involvement in metastatic processes, and the clustered organization of at least 10 S100 genes on human chromosome 1q21, a region frequently rearranged in several tumors. As a first attempt towards a specific and differentiated immunohistochemical classification of human tumors, we produced, purified and characterized a number of human recombinant S100 proteins and raised specific polyclonal antibodies. Their distinct cellular and intracellular localization was examined by immunohistochemical methods in normal and cancerogenic human tissues and cell lines. S100A1 and S100A2 can be detected in a few normal tissues only, whereas S100A4, S100A6, and S100B are expressed at higher levels in cancer tissues. In the future, these S100 antibodies will potentially be of great value in cancer diagnosis and therapy. © 1996 Wiley-Liss, Inc.
Photoactivation of toxin conjugates (1992)

A novel photocleavable protein cross-linking reagent has been used for conjugation of the ribosome-inactivating protein pokeweed antiviral protein from seeds of Phytolacca americana (PAP-S), with either the monoclonal antibody 5E9 directed against the human transferrin-receptor or the B-chain of ricin that binds to cell-surface oligosaccharides bearing terminal D-galactose residues. When irradiated with near-UV light (350 nm), the linker of these conjugates undergoes photolytic degradation, resulting in the release of native toxin that is fully functional. The cytotoxicities of these 5E9-PAP-S and ricin B-chain-PAP-S conjugates for HeLa cells could be enhanced by irradiating the cells with light after they had internalized the conjugates.
Identification of an endo- -N-acetylglucosaminidase gene in Caenorhabditis elegans and its expression in Escherichia coli (2002)

We report the identification, molecular cloning, and characterization of an endo-beta-N-acetylglucosaminidase from the nematode Caenorhabditis elegans. A search of the C. elegans genome database revealed the existence of a gene exhibiting 34% identity to Mucor hiemalis (a fungus) endo-beta-N-acetylglucosaminidase (Endo-M). Actually, the C. elegans extract contained endo-beta-N-acetylglucosaminidase activity. The putative cDNA for the C. elegans endo-beta-N-acetylglucosaminidase (Endo-CE) was amplified by polymerase chain reaction from the Uni-ZAP XR library, cloned, and sequenced. The recombinant Endo-CE expressed in Escherichia coli exhibited substrate specificity mainly for high-mannose type oligosaccharides. Man(8)GlcNAc(2) was the best substrate for Endo-CE, and Man(3)GlcNAc(2) was also hydrolyzed. Biantennary complex type oligosaccharides were poor substrates, and triantennary complex substrates were not hydrolyzed. Its substrate specificity was similar to those of Endo-M and endo-beta-N-acetylglucosaminidase from hen oviduct. Endo-CE was confirmed to exhibit transglycosylation activity, as seen for some microbial endo-beta-N-acetylglucosaminidases. This is the first report of the molecular cloning of an endo-beta-N-acetylglucosaminidase gene from a multicellular organism, which shows the possibility of using this well-characterized nematode as a model system for elucidating the role of this enzyme.
Effect of composition on the dielectric properties of hydrogels for biomedical applications (2010)

The effect of composition on the dielectric properties of hydrogels for biomedical applications is experimentally investigated. The hydrogels, containing hydroxyethylcellulose (HEC), are characterized by means of the impedance spectroscopy technique. The real and imaginary parts of the electrical impedance of the hydrogels are determined for several concentrations of HEC, and of KCl, dissolved in it, for the frequency range of interest for biomedical applications. The results are compared with those corresponding to depurated water. The equivalent conductivity of the hydrogels is evaluated by performing measurements on samples of different thicknesses. With the limit of a small concentration of salt (≤ 6%), the dependence of the electrical conductivity of the hydrogel on the salt concentration is linear.
Infantile Colic: Crying Time Reduction With a Whey Hydrolysate: A Double-Blind, Randomized, Placebo-Controlled Trial (2000)

An extensively hydrolyzed whey formula is effective in reducing the duration of crying in a primary care setting.
CD4+/CD25+ Regulatory Cells Inhibit Activation of Tumor-Primed CD4+ T Cells with IFN-γ-Dependent Antiangiogenic Activity, as well as Long-Lasting Tumor Immunity Elicited by Peptide Vaccination (2003)

CD25(+) regulatory T (T reg) cells suppress the activation/proliferation of other CD4(+) or CD8(+) T cells in vitro. Also, down-regulation of CD25(+) T reg cells enhance antitumor immune responses. In this study, we show that depletion of CD25(+) T reg cells allows the host to induce both CD4(+) and CD8(+) antitumoral responses following tumor challenge. Simultaneous depletion of CD25(+) and CD8(+) cells, as well as adoptive transfer experiments, revealed that tumor-specific CD4(+) T cells, which emerged in the absence of CD25(+) T reg cells, were able to reject CT26 colon cancer cells, a MHC class II-negative tumor. The antitumoral effect mediated by CD4(+) T cells was dependent on IFN-gamma production, which exerted a potent antiangiogenic activity. The capacity of the host to mount this antitumor response is lost once the number of CD25(+) T reg cells is restored over time. However, CD25(+) T reg cell depletion before immunization with AH1 (a cytotoxic T cell determinant from CT26 tumor cells) permits the induction of a long-lasting antitumoral immune response, not observed if immunization is conducted in the presence of regulatory cells. A study of the effect of different levels of depletion of CD25(+) T reg cells before immunization with the peptide AH1 alone, or in combination with a Th determinant, unraveled that Th cells play an important role in overcoming the suppressive effect of CD25(+) T reg on the induction of long-lasting cellular immune responses.
Speech Segment Durations Produced by Healthy and Asthmatic Subjects (1988)

Speech segment durations of various lengths were measured to study the effect of asthma. Subjects produced 5 min of conversation and a monologue and counted at a rate of two numbers per second at two loudness levels. The number of syllables per breath was determined for all tasks. Average sound pressure level, individual segments such as voice onset time, word duration, pause time, and total duration of the activity were compared between groups for the counting tasks. Results revealed that asthmatic speakers met the sound level requirements of loud counting and generally produced speech segment durations similar to healthy subjects. Asthmatic subjects increased pause time between speech segments, produced fewer syllables per breath, and spent a larger percentage of time in nonspeech ventilatory activity than the healthy subjects, presumably to meet metabolic needs.
Identification of Bacillus subtilis genes for septum placement and shape determination (1992)

The Bacillus subtilis divIVB1 mutation causes aberrant positioning of the septum during cell division, resulting in the formation of small, anucleate cells known as minicells. We report the cloning of the wild-type allele of divIVB1 and show that the mutation lies within a stretch of DNA containing two open reading frames whose predicted products are in part homologous to the products of the Escherichia coli minicell genes minC and minD. Just upstream of minC and minD, and in the same orientation, are three genes whose products are homologous to the products of the E. coli shape-determining genes mreB, mreC, and mreD. The B. subtilis mreB, mreC, and mreD genes are the site of a conditional mutation (rodB1) that causes the production of aberrantly shaped cells under restrictive conditions. Northern (RNA) hybridization experiments and disruption experiments based on the use of integrational plasmids indicate that the mre and min genes constitute a five-cistron operon. The possible involvement of min gene products in the switch from medial to polar placement of the septum during sporulation is discussed.
P-selectin mediates the adhesion of sickle erythrocytes to the endothelium (2001)

The adherence of sickle red blood cells (RBCs) to the vascular endothelium may contribute to painful vaso-occlusion in sickle cell disease. Sickle cell adherence involves several receptor-mediated processes and may be potentiated by the up-regulated expression of adhesion molecules on activated endothelial cells. Recent results showed that thrombin rapidly increases the adhesivity of endothelial cells for sickle erythrocytes. The current report presents the first evidence for the novel adhesion of normal and, to a greater extent, sickle RBCs to endothelial P-selectin. Studies of the possible interaction of erythrocytes with P-selectin revealed that either P-selectin blocking monoclonal antibodies or sialyl Lewis tetrasaccharide inhibits the enhanced adherence of normal and sickle cells to thrombin-treated endothelial cells. Both RBC types also adhere to immobilized recombinant P-selectin. Pretreating erythrocytes with sialidase reduces their adherence to activated endothelial cells and to immobilized recombinant P-selectin. Herein the first evidence is presented for the binding of normal or sickle erythrocytes to P-selectin. This novel finding suggests that P-selectin inhibition be considered as a potential approach to therapy for the treatment of painful vaso-occlusion in sickle cell disease.
Recombinant anti-erbB2 immunotoxins containing Pseudomonas exotoxin. (1992)

Immunotoxins were made using five different murine monoclonal antibodies to the human erbB2 gene product and LysPE40, a 40-kDa recombinant form of Pseudomonas exotoxin (PE) lacking its cell-binding domain. All five conjugates were specifically cytotoxic to cancer cell lines overexpressing erbB2 protein. The most active conjugate was e23-LysPE40, generated by chemical crosslinking of anti-erbB2 monoclonal antibody e23 to LysPE40. In addition, a recombinant immunotoxin, e23(Fv)PE40, was constructed that consists of the light-chain variable domain of e23 connected through a peptide linker to its heavy-chain variable domain, which in turn is fused to PE40. The recombinant protein was made in Escherichia coli, purified to near homogeneity, and shown to selectively kill cells expressing the erbB2 protooncogene. To improve the cytotoxic activity of e23(Fv)PE40, PE40 was replaced with a variant, PE38KDEL, in which the carboxyl end of PE is changed from Arg-Glu-Asp-Leu-Lys to Lys-Asp-Glu-Leu and amino acids 365-380 of PE are deleted. The e23(Fv)PE38KDEL protein inhibits the growth of tumors formed by the human gastric cancer cell line N87 in immunodeficient mice.
Impact of Type 2 Diabetes Mellitus on Sympathetic Neural Mechanisms in Hypertension (2003)

Patients with EHT+DM2, EHT, or DM2 had central sympathetic hyperactivity, although plasma insulin levels were raised only in EHT+DM2 and DM2. The combination of EHT and DM2 resulted in the greatest sympathetic hyperactivity and level of plasma insulin, and this hyperactivity could constitute a mechanism for the increased risks of this condition.
The time consuming nature of phenylketonuria: A cross-sectional study investigating time burden and costs of phenylketonuria in the Netherlands (2013)

Management of PKU is associated with a considerable time burden for both caregivers of children with PKU and adult patients. Caregivers of PKU-affected children reported a significantly higher time burden than adult patients. The OOPC of caregivers and patients was mainly driven by the expenditure on low protein food.
Diversity of Alkane Hydroxylase Systems in the Environment (2003)

The first step in the aerobic degradation of alkanes by bacteria, yeasts, and fungi is catalyzed by oxygenases. These enzymes, which introduce oxygen atoms derived from molecular oxygen into the alkane substrate, play an important role in oil bioremediation and in the cometabolic degradation of compounds such as trichloroethylene and fuel oxygenates. In addition, they are useful biocatalysts and important models for a difficult chemical reaction: the regio- and stereospecific activation of C-H bonds. Several unrelated enzyme classes catalyze the oxidation of alkanes. Alkane-degrading yeast strains contain multiple alkane hydroxylases belonging to the P450 superfamily, while many bacteria contain enzymes related to the Pseudomonas putida GPo1 membrane-bound alkane hydroxylase system. Short-chain alkanes are probably oxidized by alkane hydroxylases related to the soluble and particulate methane monooxygenases. Only the membrane-bound enzymes have been studied with respect to their prevalence in environments such as soils or aquifers.
Fully integrated CMOS phase-locked loop with 15 to 240 MHz locking range and ±50 ps jitter (1995)

A fully integrated phase-locked loop (PLL) in a digital 0.5 /spl mu/m CMOS technology is described. The PLL has a locking range of 15 to 240 MHz. The static phase error is less than 1100 ps with a peak-to-peak jitter of /spl plusmn/50 ps at a 100 MHz output frequency. The PLL has a resistorless architecture achieved by the implementation of feedforward current injection into the current controlled oscillator.
The Prostacyclin Analog Beraprost Sodium Ameliorates Characteristics of Metabolic Syndrome in Obese Zucker (Fatty) Rats (2010)

BPS suppressed the pathogenesis and development of diabetes and its complication, nephropathy, which was presumably accompanied by improving glucose intolerance and insulin resistance in obese Zucker rats.
Mechanism of Inhibition of Vaccinia DNA Topoisomerase by Novobiocin and Coumermycin (1996)

Vaccinia DNA topoisomerase, a eukaryotic type I enzyme, has unique pharmacological properties, including sensitivity to the coumarin drugs novobiocin and coumermycin, which are classical inhibitors of DNA gyrase, a type II enzyme. Whereas coumarins inhibit gyrase by binding the GyrB subunit and thereby blocking the ATP-binding site, they inhibit vaccinia topoisomerase by binding to the protein and blocking the interaction of enzyme with DNA. Noncovalent DNA binding and single-turnover DNA cleavage by topoisomerase are inhibited with K1 values of 10-25 microM for coumermycin and 350 microM for novobiocin. Spectroscopic and fluorescence measurements of drug binding t enzyme indicate a single binding site on vaccinia topoisomerase for coumermycin (KD = 27 +/- 5 microM) and two classes of binding sites for novobiocin, one tight site (KD1 = 20 +/- 5 microM) and several weak sites (KD2 = 513 +/- 125 microM; n = 4.9 +/- 0.7). Addition of a stoichiometric amount of DNA to a performed coumermycin-topoisomerase complex quantitatively displaces the drug, indicating that coumermycin binding and DNA binding to topoisomerase are mutually exclusive. A simple interpretation is that the site of drug binding coincides or overlaps with the DNA-binding site on the topoisomerase. Both novobiocin and coumermycin alter the susceptibility of vaccinia topoisomerase to proteolysis with either chymotrypsin or trypsin; similar effects occur when topoisomerase binds to duplex DNA.
Wrapping Things up about Virus RNA Replication (2005)

All single-stranded 'positive-sense' RNA viruses that infect mammalian, insect or plant cells rearrange internal cellular membranes to provide an environment facilitating virus replication. A striking feature of these unique membrane structures is the induction of 70-100 nm vesicles (either free within the cytoplasm, associated with other induced vesicles or bound within a surrounding membrane) harbouring the viral replication complex (RC). Although similar in appearance, the cellular composition of these vesicles appears to vary for different viruses, implying different organelle origins for the intracellular sites of viral RNA replication. Genetic analysis has revealed that induction of these membrane structures can be attributed to a particular viral gene product, usually a non-structural protein. This review will highlight our current knowledge of the formation and composition of virus RCs and describe some of the similarities and differences in RNA-membrane interactions observed between the virus families Flaviviridae and Picornaviridae.
Design Engineering of a Bioartificial Renal Tubule Cell Therapy Device (1999)

The use of a bioartificial renal tubule device composed of renal proximal tubule cells grown within a hollow fiber cartridge is a first step in engineering a bioartificial kidney to provide more complete replacement therapy of renal function than is available today. In this study, the feasibility of two designs for a tubule device were investigated: one with cells grown on microcarrier beads densely packed within the extracapillary space of a hollow fiber cartridge, and the other with cells grown as a confluent monolayer within the hollow fibers themselves. First, the oxygen requirements of porcine renal proximal tubule cells were determined, both attached to microcarriers and in suspension and compared to that of proximal tubule segments. The basal rate of cell respiration was found to be 2.29 +/- 0.53 nmol O2/10(6) cells/min for our cultured proximal tubule cells in suspension and no significant difference was seen with attached cells. Proximal tubule segments displayed significantly higher respiratory rates. Cells were also found to be responsive in the presence of mitochondrial inhibitors or uncouplers, and their respiratory rates remained constant, despite multiple passaging. The resultant cell oxygen consumption parameter was used in models describing oxygen concentration profiles within the two device configurations. From these models, it was found that cells within our proposed device designs could theoretically be sustained and remain viable, with respect to oxygen limitations. Finally, flow visualization studies were performed to assess fluid flow distribution and determine optimal device configuration and geometry to decrease areas of low or stagnant flow.
An overview of the Specialist Advisory Committee on Antimicrobial Resistance (SACAR) (2007)

In 1969, the Swann Committee reported that there was a significant problem with regard to antimicrobial (mis)use in both human and veterinary practice and recommended that the UK Government establish a committee that should have overall responsibility for the whole field of antimicrobial use. This view was reiterated in 1997-8 by the House of Lords Science and Technology Committee, under the Chairmanship of Lord Soulsby of Swaffham Prior. In 2001 such a group, the Specialist Advisory Committee on Antimicrobial Resistance (SACAR), was finally launched. SACAR encompassed representatives from human and veterinary medicine and involved many branches of public health, pharmacy, nursing, bacteriology and virology. It met three times a year and has advised ministers and the Chief Medical Officer on current and emerging problems by providing expert advice to inform local and national policy on antimicrobial resistance. This Supplement provides an overview of the work of SACAR and its Subgroups.
Cleavage of nascent reovirus mRNA by localized activation of the 2'-5'-oligoadenylate-dependent endoribonuclease (1984)

Addition of cell extracts prepared from untreated or interferon-treated cells reduced the yield of reovirus RNA synthesized in transcription reactions with purified virions. The reduction observed with the extract of interferon-treated cells was greater than that observed with the extract of untreated cells. The yield of reovirus RNA could be restored to the level obtained without addition of cell extracts by carrying out transcription either in the presence of an inhibitor of 2'-5'-oligoadenylate (2-5A) synthesis, 2'-dATP, or in the presence of the 3'-methyl analog of 5'-monophosphate 2-5A, which inhibits the 2-5A-dependent endoribonuclease. This enzyme was activated in a localized way since neither mRNA added to transcription reactions containing the extract of interferon-treated cells nor rRNA was appreciably degraded, whereas accumulation of reovirus mRNA was drastically inhibited. These findings provide evidence for an antiviral role of the 2-5A synthetase/endoribonuclease system, which preferentially cleaves nascent viral RNA.