gebhart/patrepeval huggingface dataset:
Recent progress in soft lithography (2005)

The future of nanoscience and nanotechnology depends critically on techniques for micro- and nanofabrication. An emerging set of methods, known collectively as soft lithography, uses elastomeric stamps, molds, and conformable photomasks for patterning two- and three-dimensional structures with minimum feature sizes deep into the nanometer regime. The powerful patterning capabilities of these techniques together with their experimental simplicity make them useful for a wide range of applications. This article reviews recent progress in the field of soft lithography, with a focus on trends in research and steps toward commercialization.
Reservoir Connectivity: Definitions, Examples, and Strategies (2007)

Reservoir connectivity, and its inverse, compartmentalization,&lt;br&gt;is a critical area of petroleum industry research and business&lt;br&gt;application. However, significant differences in how it is&lt;br&gt;defined, measured, and modeled exist among companies. For&lt;br&gt;some, connectivity is defined relative to an entity such as a&lt;br&gt;well or set of perforations in a reservoir. Others prefer&lt;br&gt;reservoir connectivity indexes, using a set of often&lt;br&gt;subjectively defined criteria to gauge how problematic a field&lt;br&gt;will be to develop or exploit.
Association of Inhalation Toxicologists (AIT) Working Party Recommendation for Standard Delivered Dose Calculation and Expression in Non-Clinical Aerosol Inhalation Toxicology Studies with Pharmaceuticals (2008)

There are many ways in which the dose can be expressed in inhalation toxicology studies. This can lead to confusion when comparing results from studies performed in different laboratories. A working party of the Association of Inhalation Toxicologists has reviewed this subject in detail and has collected data from 10 inhalation laboratories and used these data to determine a new algorithm for the calculation of Respiratory Minute Volume (RMV), one of the most important factors in the calculation of delivered dose. The recommendations of the working party for regulatory inhalation toxicology studies with pharmaceuticals are as follows: 1. The dose should be reported as the delivered dose calculated according to the formula: DD = C x RMV x D(xIF)/BW, where DD = delivered dose (mg/Kg); C = concentration of substance in air (mg/L); RMV =respiratory minute volume or the volume of air inhaled in one minute (L/min); D = duration of exposure (min); IF = proportion by weight of particles that are inhalable by the test species, the inhalable fraction (inclusion of this parameter is not essential provided that the aerosol has reasonable respirability for the intended species. If it is included, the way in which it is determined should be clearly stated); BW = bodyweight (Kg). 2. The RMV for mice, rats, dogs and cynomolgus monkeys should be calculated according to the formula:RMV(L/min) = 0.608 x BW(Kg)(0.852). 3. If deposited dose or the amount of material actually retained inthe respiratory tract is presented as supplementary information,the way in which it is calculated should be clearly stated.4. Dose should always be presented in mg/Kg but may also bepresented in other ways, such as mg/unit body surface area, as supplementary information.
The epidermal growth factor tyrosine kinase inhibitor AG1478 and erlotinib reverse ABCG2-mediated drug resistance (2009)

ABCG2 is an important member of ATP-binding cassette (ABC) transporter shown to confer drug resistance in cancer cells. Recent studies show that an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), gefitinib, is able to modulate the function of ABCG2 and reverse ABCG2-mediated multidrug resistance (MDR) in cancer cells. Additionally, ABCG2 expression has been shown to impact treatment efficacy and development of side-effects in patients receiving gefitinib. However, it is unclear whether other EGFR TKIs interact with ABCG2 in a similar manner. In the present study, we investigated the interaction of two other EGFR TKIs, AG1478 and erlotinib, with ABCG2. Our data show that AG1478 and erlotinib potently sensitized drug-resistant cells overexpressing either wild-type or mutated ABCG2 to the ABCG2 substrate anti-cancer drugs flavopiridol and mitoxantrone. Neither AG1478 nor erlotinib sensitized ABCG2-overexpressing cells to drugs that are not substrates of ABCG2 nor did they impact drug sensitivity of parental cells. Furthermore, AG1478 and erlotinib were able to significantly enhance the intracellular accumulation of mitoxantrone in cells expressing either wild-type or mutated ABCG2. Additionally, they did not alter the protein expression of ABCG2 in the ABCG2-overexpressing cells. Taken together, we conclude that AG1478 and erlotinib potently reverse ABCG2-mediated MDR through directly inhibiting the drug efflux function of ABCG2 in the ABCG2-overexpressing cells. These results will be useful in the development of novel and more effective EGFR TKIs as well as the development of combinational chemotherapeutic strategies.
Blockade of the epidermal growth factor receptor tyrosine kinase suppresses tumorigenesis in MMTV/Neu + MMTV/TGF-α bigenic mice (2000)

Overexpression of ErbB-2/Neu has been causally associated with mammary epithelial transformation. Here we report that blockade of the epidermal growth factor receptor (EGFR) kinase with AG-1478 markedly delays breast tumor formation in mouse mammary tumor virus (MMTV)/Neu + MMTV/transforming growth factor alpha bigenic mice. This delay was associated with inhibition of EGFR and Neu signaling, reduction of cyclin-dependent kinase 2 (Cdk2) and mitogen-activated protein kinase (MAPK) activities and cyclin D1, and an increase in the levels of the Cdk inhibitor p27(Kip1). In addition, BrdUrd incorporation into tumor cell nuclei was prevented with no signs of tumor cell apoptosis. These observations prompted us to investigate the stability of p27. Recombinant p27 was degraded rapidly in vitro by untreated but not by AG-1478-treated tumor lysates. Proteasome depletion of the tumor lysates, addition of the specific MEK1/2 inhibitor U-0126, or a T187A mutation in recombinant p27 all prevented p27 degradation. Cdk2 and MAPK precipitates from untreated tumor lysates phosphorylated recombinant wild-type p27 but not the T187A mutant in vitro. Cdk2 and MAPK precipitates from AG-1478-treated tumors were unable to phosphorylate p27 in vitro. These data suggest that increased signaling by ErbB receptors up-regulates MAPK activity, which, in turn, phosphorylates and destabilizes p27, thus contributing to dysregulated cell cycle progression.
Tandem Reflectron Time-of-Flight Mass Spectrometer Utilizing Photodissociation (1995)

A tandem time-of-flight (TOF) mass spectrometer has been designed to obtain complete MS/MS spectra from compounds eluting from a gas chromatograph. This application requires high spectral generation rate, unit mass resolution for both precursor selection and product spectra, and efficient ion utilization. These objectives are achieved by reflectron TOF mass separation in both stages and laser photoinduced dissociation as the ion fragmentation method. Careful timing of the laser pulse relative to ion extraction allows ions of a single m/z value up to m/z 1000 to be photodissociated while ions with adjacent m/z values are essentially unaffected. The convergent foci of the ion packet and laser pulse results in ion fragmentation efficiencies as high as 79%. An ion gate prevents the nonselected precursor ions from convoluting the product spectra. Product spectra can be generated at the maximum laser repetition rate (currently 200 Hz). To achieve unit mass resolution for all product m/z values simultaneously, a novel reflectron was designed for the second TOF stage.
Inhibitory Feedback Loop Between Tolerogenic Dendritic Cells and Regulatory T Cells in Transplant Tolerance (2003)

An active role of T regulatory cells (Treg) and tolerogenic dendritic cells (Tol-DC) is believed important for the induction and maintenance of transplantation tolerance. However, interactions between these cells remain unclear. We induced donor-specific tolerance in a fully MHC-mismatched murine model of cardiac transplantation by simultaneously targeting T cell and DC function using anti-CD45RB mAb and LF 15-0195, a novel analog of the antirejection drug 15-deoxyspergualin, respectively. Increases in splenic Treg and Tol-DC were observed in tolerant recipients as assessed by an increase in CD4(+)CD25(+) T cells and DC with immature phenotype. Both these cell types exerted suppressive effects in MLR. Tol-DC purified from tolerant recipients incubated with naive T cells induced the generation/expansion of CD4(+)CD25(+) Treg. Furthermore, incubation of Treg isolated from tolerant recipients with DC progenitors resulted in the generation of DC with Tol-DC phenotype. Treg and Tol-DC generated in vitro were functional based on their suppressive activity in vitro. These results are consistent with the notion that tolerance induction is associated with a self-maintaining regulatory loop in which Tol-DC induce the generation of Treg from naive T cells and Treg programs the generation of Tol-DC from DC progenitors.
Regulation of plant growth by cytokinin (2001)

Cytokinins are a class of plant-specific hormones that play a central role during the cell cycle and influence numerous developmental programs. Because of the lack of biosynthetic and signaling mutants, the regulatory roles of cytokinins are not well understood. We genetically engineered cytokinin oxidase expression in transgenic tobacco plants to reduce their endogenous cytokinin content. Cytokinin-deficient plants developed stunted shoots with smaller apical meristems. The plastochrone was prolonged, and leaf cell production was only 3-4% that of wild type, indicating an absolute requirement of cytokinins for leaf growth. In contrast, root meristems of transgenic plants were enlarged and gave rise to faster growing and more branched roots. These results suggest that cytokinins are an important regulatory factor of plant meristem activity and morphogenesis, with opposing roles in shoots and roots.
The Ser96Ala variant in histidine-rich calcium-binding protein is associated with life-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy (2008)

The Ser96Ala genetic variant of HRC is associated with life-threatening ventricular arrhythmias in idiopathic DCM and may serve as an independent predictor of susceptibility to arrhythmogenesis in the setting of DCM.
Reconsidering targeted toxins to eliminate HIV infection: You gotta have HAART (1998)

The success of highly active anti-retroviral therapy (HAART) has inspired new concepts for eliminating HIV from infected individuals. A major obstacle is the persistence of long-lived reservoirs of latently infected cells that might become activated at some time after cessation of therapy. We propose that, in the context of treatment strategies to deliberately activate and eliminate these reservoirs, hybrid toxins targeted to kill HIV-infected cells be reconsidered in combination with HAART. Such combinations might also prove valuable in protocols aimed at preventing mother-to-child transmission and establishment of infection immediately after exposure to HIV. We suggest experimental approaches in vitro and in animal models to test various issues related to safety and efficacy of this concept.
Analysis of Assembly of Synthetic Antibody Fragments: Expression of Functional scFv with Predefined Specificity (1997)

In this work, we have investigated parameters important for the assembly of synthetic genes encoding antibody fragments. These genes are constructed from a set of overlapping single-stranded oligonucleotides (primers), which are assembled into a gene sequence in a one-step process using PCR. Using the Oligo program, we made a detailed analysis of wanted and unwanted interactions between these primers; both the stability of hairpin structures of homodimers and of heterodimers were examined. The Oligo program could be used to identify unwanted interactions of high stability, and the present study suggests that if the stabilities of the unwanted interactions are kept to 25%-50% of the designed interactions, a successful assembly of synthetic genes can occur.
Cytogenetics on released DNA fibers. (1997)

DNA fibers can be released from cell suspensions and frozen tissue and can be used as a template for hybridization with multiple differently labeled probes. Simultaneous hybridization with 5-10 adjacent or partly overlapping probes generates a highly specific "color barcode" for individual DNA segments. Rearrangements in this barcode can be easily detected and mapped. The resolution of DNA fiber FISH is between 2 and 500kb. In mixing experiments of cell lines with different structural abnormalities, we found a sensitivity of approximately 10%. We applied DNA fiber FISH for detection of t(11;14) in mantle cell lymphoma (MCL) and immunoglobulin (Ig) class switching in hairy cell leukemia (HCL). Using a barcode for the Ig and BCL-1 loci at 14q32 and 11q13, we detected and mapped a t(11;14) breakpoint in 35 of 36 MCL. In 5 cases complex mono-allelic rearrangements at both sides of the cyclin D1 gene were identified. In 13 HCL with phenotypic evidence of Ig class switching, including 2 cases with solely IgD, fiber FISH revealed concordant Ig class switch deletions. In most cases both alleles were affected. These results indicate that DNA fiber FISH is a very powerful method to detect and map structural DNA alterations.
Comparisons of Disease and Nonbattle Injury Incidence across Various Military Operations (1995)

Daily rates of disease and nonbattle injury (DNBI) incidence were analyzed and compared for four ground operations: Okinawa, Korea, Vietnam, and the Falklands. Average daily DNBI admission rates among operations ranged from 0.99 per 1,000 strength to 4.03 for combat troops. Average daily admission rates for support troops ranged from 0.71 to 1.15. Among combat troops, between 26 and 38% of DNBI presentations were of a nature that precluded returns to their unit due to a medical transfer; among support troops, less than 17% were not returned to their units due to transfers.
Interleukin-6 signals activating junB and TIS11 gene transcription in a B-cell hybridoma. (1991)

The events in interleukin-6 (IL-6) signal transduction leading to primary response gene activation were analyzed in murine B-cell hybridoma and plasmacytoma cells which require IL-6 for growth. IL-6 stimulation of IL-6-deprived cells resulted in the rapid and transient tyrosine phosphorylation of a 160-kDa cellular protein (p160). This was followed by the highly selective induction of two primary response genes, junB/AP-1 transcription factor and TIS11. junB and TIS11 inductions were unaffected by cycloheximide, suggesting that posttranslational modifications accounted for their activation. Activation of junB and TIS11 transcription required rapid tyrosine kinase activity as well as a different protein kinase activity sensitive to the potent kinase inhibitor, H7, and activated following p160 tyrosine phosphorylation. This H7-sensitive kinase appears to be distinct from any well-characterized protein kinase-second messenger system. On the basis of these findings, we propose that IL-6-induced signal transduction proceeds through a novel protein kinase cascade which activates junB and TIS11 gene transcription.
Chondroitin Sulfate Synthase-2 (2003)

Chondroitin sulfate is found in a variety of tissues as proteoglycans and consists of repeating disaccharide units of N-acetylgalactosamine and glucuronic acid residues with sulfate residues at various places. We found a novel human gene (GenBank accession number AB086063) that possesses a sequence homologous with the human chondroitin sulfate glucuronyltransferase gene which we recently cloned and characterized. The full-length open reading frame encodes a typical type II membrane protein comprising 775 amino acids. The protein had a domain containing beta 3-glycosyltransferase motif but lacked a typical beta 4-glycosyltransferase motif, which is the same as chondroitin sulfate glucuronyltransferase, whereas chondroitin synthase had both domains. The putative catalytic domain was expressed in COS-7 cells as a soluble enzyme. Surprisingly, both glucuronyltransferase and N-acetylgalactosaminyltransferase activities were observed when chondroitin, chondroitin sulfate, and their oligosaccharides were used as the acceptor substrates. The reaction products were identified to have the linkage of GlcUA beta 1-3GalNAc and GalNAc beta 1-4GlcUA at the non-reducing terminus of chondroitin for glucuronyltransferase activity and N-acetylgalactosaminyltransferase activity, respectively. Quantitative real time PCR analysis revealed that the transcripts were ubiquitously expressed in various human tissues but highly expressed in the pancreas, ovary, placenta, small intestine, and stomach. These results indicate that this enzyme could synthesize chondroitin sulfate chains as a chondroitin sulfate synthase that has both glucuronyltransferase and N-acetylgalactosaminyltransferase activities. Sequence analysis based on three-dimensional structure revealed the presence of not typical but significant beta 4-glycosyltransferase architecture.
Evolution of interleukin-18 binding proteins and interleukin-1 receptor, type II proteins (2005)

Interleukin-18 (IL-18) is one of the pivotal cytokines controlling the defense mechanism called inflammation. As a first step to develop proteins for controlling the IL-18 level, we initiated a study of IL-18-binding proteins (IL-18BPs). Twenty-four IL-18BP family members, 11 from vertebrates and 13 from chordopoxviruses, were picked from the NCBI database. Eight of these vertebrate IL-18BPs and two of the chordopoxvirus IL18-BPs were identified here and characterized as new members of the IL-18BP family. Their IL-18 binding domains were aligned and the distribution of highly conserved critical amino acid residues was analyzed and used to construct a phylogenetic tree. From this tree it was inferred that at least two independent events created two different ancestral viral IL-18BP genes by retroposition of IL-18BP genes from the vertebrate lineage. These two events are estimated to have occurred after an ancient mammalian IL-18BP gene diverged from birds, and before the mammalian IL-18BP gene diverged into human, ungulate and rodent IL-18BP genes. Moreover, our results suggest that IL-18BP and interleukin-1 receptor, type II (IL-1R2) had a common ancestral gene and diverged from the ancestral gene into IL-18BP and IL-1R2 genes in the fish period.
Donor blood perfusion improves myocardial recovery after heart transplantation. (1997)

Perfusion of donor blood improved the ability to wean off bypass after 4 hours of storage. Blood perfusion permitted persistent myocardial metabolism during the ischemic period, which led to improved functional recovery. Harvesting donor blood for subsequent perfusion during prolonged storage may improve the results of orthotopic heart transplantation and allow for more distant procurement of donor organs.
Maxillary and Mandibular Osteosyntheses with PLGA and P(L/DL)LA Implants: A 5-Year Inpatient Biocompatibility and Degradation Experience (2006)

Both copolymers showed reliable biocompatibility and disintegration. Overall, 6 percent clinically apparent foreign body reactions were controlled conservatively and by local curettage; 85:15 PLGA degraded within 12 months and 70:30 P(L/DL)LA within 24 months, leaving powdering residual granules. Burr holes reossified 12 months later.
Mu class glutathione S‐transferase mRNA isoform expression in acute lymphoblastic leukaemia (2002)

Glutathione S-transferases (GSTs) are implicated in cytotoxic drug resistance in leukaemia. In a previous study, expression of mu class GST (GSTM) was associated with poor prognosis in childhood acute lymphoblastic leukaemia (ALL), however, that study did not differentiate between individual GSTM isoforms. This study, therefore, investigated individual GSTM isoform expression in ALL blasts at the mRNA level. Leukaemic blasts from 21 children with ALL were studied. Interindividual variation in the pattern of GSTM mRNA isoform expression was demonstrated. GSTM2 transcript was expressed in all patients in contradistinction to GSTM5, which was not detected in any sample. GSTM3 and GSTM4 expression varied between individuals, with GSTM3 expressed in 62% and GSTM4 in 24% of patients. Lymphoblast expression of GSTM3 was positively related to good prognosis whereas expression of GSTM4 was not related to clinical outcome in this small cohort. No relationship was demonstrated with established indicators of prognosis, including sex, age, immunophenotype and presenting white cell count. The results suggest that expression of GSTM3 may play a role in determining prognosis in childhood ALL and could provide more information for accurate stratification of treatment. Further studies are required to determine whether there is a causal relationship between GSTM3 expression and clinical outcome.
Prefrontal deficits in attention and inhibitory control with aging (1997)

Event-related potentials and behavioral measures were obtained from young and elderly subjects while they performed two different auditory delayed match-to-sample tasks. In each experiment, subjects had to indicate whether an initial and a subsequent test sound were identical in two different conditions: one filled with distracting tone pips and one with no distractors. Electrophysiologically, elderly subjects had reduced attention-related activity over frontal regions. In addition, the distracting stimuli elicited an enhanced primary auditory evoked response in the elderly. The percentage of perseverative errors on the Wisconsin card sorting test, a putative measure of frontal lobe function, was positively correlated with the amplitude of the primary auditory evoked response in elderly subjects. Behaviorally, elderly subjects were impaired by distractors at long but not short delays. Taken together, these results suggest that increased distractibility and impaired sustained attention with aging may be due to altered prefrontal cortex function. These data support the loss of prefrontal suppression over the primary auditory regions with aging.