gebhart/patrepeval huggingface dataset:
Conjugation of Folate via Gelonin Carbohydrate Residues Retains Ribosomal-inactivating Properties of the Toxin and Permits Targeting to Folate Receptor Positive Cells (2001)

Conjugation of folate to proteins permits receptor-mediated endocytosis via the folate receptor (FR) and delivery of the conjugate into the cytoplasm of cells. Since many cancers up-regulate the FR it has enabled the targeting of toxins to tumor cells resulting in specific cell death. However, current conjugation methods rely on chemistries that can affect certain catalytic subunits, such as the A-chain of the plant toxin gelonin. As a result many folate-targeted toxins are a compromise between receptor/ligand interaction and toxin activity. We describe the first example of folate conjugated to a protein via carbohydrate residues, using a novel SH-folate intermediate. The folate-gelonin conjugate retains over 99% of toxin activity in a cell-free translational assay compared with unmodified gelonin and is able to bind the FR at the same affinity as free folic acid (10(-10) m). Additionally, the conjugate exhibits prolonged inhibition of protein synthesis in FR positive cell lines in vitro. Folate linked to gelonin via amino conjugation exhibits the same affinity for FR as free folic acid but the toxin is 225-fold less active in a cell-free translational assay. The effect of different conjugation methods on toxin activity and the implications for folate targeting of other glycoproteins are discussed.
Radioimmunoimaging of Liver Metastases with PET Using a 64Cu-Labeled CEA Antibody in Transgenic Mice (2014)

We show here that the (64)Cu-DOTA-labeled M5A antibody imaged by PET can detect CEA positive liver metastases and is therefore a potential tool for staging cancer, stratifying the patients or radioimmunotherapy.
Up‐regulation of GAD65 and GAD67 in remaining hippocampal GABA neurons in a model of temporal lobe epilepsy (1999)

In the pilocarpine model of chronic limbic seizures, subpopulations of glutamic acid decarboxylase (GAD)-containing neurons within the hilus of the dentate gyrus and stratum oriens of the CA1 hippocampal region are vulnerable to seizure-induced damage. However, many γ-aminobutyric acid (GABA) neurons remain in these and other regions of the hippocampal formation. To determine whether long-term changes occur in the main metabolic pathway responsible for GABA synthesis in remaining GABA neurons, the levels of mRNA and protein labeling for the two forms of GAD (GAD65 and GAD67) were studied in pilocarpine-treated animals that had developed spontaneous seizures. Qualitative and semiquantitative analyses of nonradioactive in situ hybridization experiments demonstrated marked increases in the relative amounts of GAD65 and GAD67 mRNAs in remaining hippocampal GABA neurons. In addition, immunohistochemical studies demonstrated parallel increases in the intensity of terminal labeling for both GAD65 and GAD67 isoforms throughout the hippocampal formation. These increases were most striking for GAD65, the isoform of GAD that is particularly abundant in axon terminals. These findings demonstrate that, in a neuronal network that is capable of generating seizures, both GAD65 and GAD67 are up-regulated at the gene and protein levels in the remaining GABA neurons of the hippocampal formation. This study provides further evidence for the complexity of changes in the GABA system in this model of temporal lobe epilepsy. J. Comp. Neurol. 412:488–505, 1999. © 1999 Wiley-Liss, Inc.
Fibroblast Growth Factor 10-Fibroblast Growth Factor Receptor 2b Mediated Signaling Is Not Required for Adult Glandular Stomach Homeostasis (2012)

The signaling pathways that are essential for gastric organogenesis have been studied in some detail; however, those that regulate the maintenance of the gastric epithelium during adult homeostasis remain unclear. In this study, we investigated the role of Fibroblast growth factor 10 (FGF10) and its main receptor, Fibroblast growth factor receptor 2b (FGFR2b), in adult glandular stomach homeostasis. We first showed that mouse adult glandular stomach expressed Fgf10, its receptors, Fgfr1b and Fgfr2b, and most of the other FGFR2b ligands (Fgf1, Fgf7, Fgf22) except for Fgf3 and Fgf20. Fgf10 expression was mesenchymal whereas FGFR1 and FGFR2 expression were mostly epithelial. Studying double transgenic mice that allow inducible overexpression of Fgf10 in adult mice, we showed that Fgf10 overexpression in normal adult glandular stomach increased epithelial proliferation, drove mucous neck cell differentiation, and reduced parietal and chief cell differentiation. Although a similar phenotype can be associated with the development of metaplasia, we found that Fgf10 overexpression for a short duration does not cause metaplasia. Finally, investigating double transgenic mice that allow the expression of a soluble form of Fgfr2b, FGF10's main receptor, which acts as a dominant negative, we found no significant changes in gastric epithelial proliferation or differentiation in the mutants. Our work provides evidence, for the first time, that the FGF10-FGFR2b signaling pathway is not required for epithelial proliferation and differentiation during adult glandular stomach homeostasis.
A novel fluorescent tracer for real-time tracing of clay transport over soil surfaces (2016)

Clay is an important vector for the transport of pollutants in the environment, including nutrients, pesticides and metals; therefore, the fate of many chemicals in soil systems is closely linked to that of clay. Understanding the mechanisms responsible for clay transport has been hampered by the lack of a suitable tracer. Producing a tracer that accurately mimics clay transport is challenging, due to the small size of the particles and their unique physical properties. Here we describe the design and synthesis of a tracer using natural clay particles as a foundation, exploiting the natural ability of clay to sorb molecules to coat the clay with a thin layer of fluorophore. Application of the tracer has been demonstrated through the collection of real-time images of the tracer moving over the surface of a soil box during a rainfall event. These images allow, for the first time, clay to be tracked spatially and temporally without need to remove soil for analysis, thus resulting in minimal experimental artefacts. Custom written software has been used to extract high resolution data describing tracer movement and extent throughout the experiment.
American Roulette: The Effect of Reminders of Death on Support for George W. Bush in the 2004 Presidential Election (2005)

An experiment was conducted to assess the effect of a subtle reminder of death on voting intentions for the 2004 U.S. presidential election. On the basis of terror management theory and previous research, we hypothesized that a mortality salience induction would increase support for President George W. Bush and decrease support for Senator John Kerry. In late September 2004, following a mortality salience or control induction, registered voters were asked which candidate they intended to vote for. In accord with predictions, Senator John Kerry received substantially more votes than George Bush in the control condition, but Bush was favored over Kerry following a reminder of death, suggesting that President Bush's re‐election may have been facilitated by nonconscious concerns about mortality in the aftermath of September 11, 2001.
A bilingual VOYAGER system (1993)

This paper describes our initial efforts at porting the VOYAGER spoken language system to Japanese. In the process we have reorganized the structure of the system so that language dependent information is separated from the core engine as much as possible. For example, this information is encoded in tabular or rule-based form for the natural language understanding and generation components. The internal system manager, discourse and dialogue component, and database are all maintained in language transparent form. Once the generation component was ported, data were collected from 40 native speakers of Japanese using a wizard collection paradigm. A portion of these data was used to train the natural language and segment-based speech recognition components. The system obtained an overall understanding accuracy of 52% on the test data, which is similar to our earlier reported results for English [1].
A simple method for isolation of genomic DNA from fresh and dry leaves of Terminalia arjuna (Roxb.) Wight and Arnot (2007)

Current protocols for isolation of genomic DNA from Terminalia arjuna have their own limitations due to the presence of high content of gummy polysaccharides and polyphenols. DNA isolated by these protocols is contaminated with a yellowish, sticky and viscous matrix. In our modified DNA isolation method polysaccharides and polyphenols are removed prior to the precipitation of the DNA. Then the genomic DNA was precipitated using isopropanol. This protocol yielded a high molecular weight DNA isolated from fresh as well as dry leaves of T. arjuna , which was free from contamination and colour. Isolated DNA can be used for restriction digestion and PCR amplification. The main objective of the present protocol is to provide a simple method of isolation of DNA, using in house prepared reagents.
Clonal heterogeneity in colony stimulating factor production by murine T lymphocytes (1985)

A panel of 55 alloreactive murine T-lymphocyte clones was screened for the production of granulocyte-macrophage colony stimulating factor (GM-CSF), multilineage CSF (multi-CSF), human-active eosinophil CSF (human-active EO-CSF), and interleukin 2 (IL-2) in response to stimulation with the lectin concanavalin A. Many clones were also characterized for cytolytic specificity and expression of the T-cell antigen receptor-associated surface markers Lyt-2 and L3T4, which reflect their specificity for Class I (H-2K, H-2D) or Class II (H-2l, Mls) histocompatibility antigens, respectively. Eighty percent of the clones secreted detectable quantities of at least one of the four factors measured. Of the factor-producing clones, all appeared to secrete GM-CSF and half also secreted multi-CSF. A subpopulation of multi-CSF producers also released human-active EO-CSF. More than half of the factor-producing clones secreted detectable IL-2; whereas the IL-2-producing clones included some that did not secrete multi-CSF, IL-2 production was always associated with concomitant synthesis of GM-CSF. Comparison of the range and quantities of factors secreted by Lyt-2+ and L3T4+ clones indicated that more L3T4+ clones produced measurable titers of the four factors; on average, this group also secreted 10- to 100-fold higher titers of both the hemopoietic regulators and IL-2 than Lyt-2+ clones. Cells of the L3T4+ phenotype would therefore be expected to account for the majority of CSF and IL-2 secretion by polyclonal populations of activated T lymphocytes.
Exendin 4 Up-Regulates Expression of PDX 1 and Hastens Differentiation and Maturation of Human Fetal Pancreatic Cells (2002)

In addition to stimulating insulin secretion, glucagon-like peptide and its long-acting analog exendin 4 have been reported to increase beta-cell mass by both differentiation/neogenesis of precursor cells and enhanced replication of existing beta-cells. Here, we investigated the effect of exendin 4 in the growth and differentiation of beta-cells from undifferentiated precursors in islet-like cell clusters (ICCs) derived from human fetal pancreases. Our results show that the addition of exendin 4 to the culture media stimulates PDX 1 expression in ICCs as shown by immunofluorescence staining. The up-regulation of PDX 1 was not accompanied by changes in insulin expression because we did not find a significant difference in the number of insulin-positive cells in the exendin 4-treated ICCs, compared with controls. We also tested the effects of exendin 4 in the glucose-induced insulin secretion of human ICCs transplanted under the kidney capsule of athymic rats. In the exendin 4-treated rats (given ip during 10 d) 8 wk after the beginning of the treatment, insulin was released in response to glucose as detected by the measurement of circulating human C-peptide. In control (saline-treated) rats, the basal levels of human C-peptide did not change significantly after glucose stimulation. Thus, exendin 4 induces functional maturation of fetal beta-cells in response to glucose. In these rats, serial sections of the kidney-bearing grafts were examined histologically for insulin containing cells. We found a significant increase in beta-cell number, compared with the control rats. Overall, these results show that in vivo exendin 4 causes growth and differentiation of human fetal beta-cells from undifferentiated precursor cells. It also accelerates the functional maturation of fetal beta-cells as evidenced by their glucose-stimulated insulin secretion.
Safety and Efficacy of Buccal Dexmedetomidine for MRI Sedation in School-Aged Children (2019)

In a selected population of pediatric patients, buccal dexmedetomidine with or without midazolam provides adequate sedation for most MRI studies with few adverse effects, but given a failure rate of almost 20%, modifications to buccal dexmedetomidine dosing should be investigated.
CCR4 versus CCR10 in human cutaneous TH lymphocyte trafficking (2003)

The chemokine receptors (CCRs) CCR4 and CCR10, and the cutaneous lymphocyte antigen (CLA), have each been proposed as critical mediators of skin-specific TH lymphocyte homing in mice and humans. CLA initiates skin homing by mediating E-selectin-dependent tethering and rolling within cutaneous venules, but the specific roles of CCR4 and CCR10 are unclear. We have generated an antihuman CCR10 monoclonal antibody (mAb; 1B5) to illuminate the individual contributions of these molecules. This mAb allows us to compare CCR10, CCR4, and CLA expression within human TH populations. The mAb 1B5 recognizes functional CCR10 expression, as chemotactic responsiveness to cutaneous T-cell-attracting chemokine (CTACK)/CCL27 (a CCR10 ligand) parallels the staining of TH subsets. We find CCR10 expressed by only a minority (approximately 30%) of blood-borne, skin-homing (CLA+/CCR4+) TH cells. However, essentially all members of the relatively small "effector" (CLA+/CCR4+/CD27-/CCR7-) skin-homing TH population express CCR10. Most skin-infiltrating lymphocytes in allergic delayed-type hypersensitivity (DTH) and bacterial chancroid skin lesions express both CCR4 and CLA, but only about 10% express CCR10. This suggests for the 2 models of TH skin homing studied here that CCR10+ TH cells have no advantage over other CLA+/CCR4+ TH cells in homing to cutaneous sites. We conclude that the skin-homing TH compartment is itself divided into distinct subpopulations, the smaller of which expresses both CCR4 and CCR10, and the larger of which expresses only CCR4. Thus, CCR10 is unlikely to be necessary for cutaneous homing of TH cells in the models studied here. CCR10 may instead play a role in the movement of specialized "effector" cutaneous TH cells to and/or within epidermal microenvironments.
Material property estimation for tubes and arteries using ultrasound radiation force and analysis of propagating modes (2011)

Arterial elasticity has been proposed as an independent predictor of cardiovascular diseases and mortality. Identification of the different propagating modes in thin shells can be used to characterize the elastic properties. Ultrasound radiation force was used to generate local mechanical waves in the wall of a urethane tube or an excised pig carotid artery. The waves were tracked using pulse-echo ultrasound. A modal analysis using two-dimensional discrete fast Fourier transform was performed on the time-space signal. This allowed the visualization of different modes of propagation and characterization of dispersion curves for both structures. The urethane tube/artery was mounted in a metallic frame, embedded in tissue-mimicking gelatin, cannulated, and pressurized over a range of 10-100 mmHg. The k-space and the dispersion curves of the urethane tube showed one mode of propagation, with no effect of transmural pressure. Fitting of a Lamb wave model estimated Young's modulus in the urethane tube around 560 kPa. Young's modulus of the artery ranged from 72 to 134 kPa at 10 and 100 mmHg, respectively. The changes observed in the artery dispersion curves suggest that this methodology of exciting mechanical waves and characterizing the modes of propagation has potential for studying arterial elasticity.
Angiotensin II and the Endothelium (2005)

The initial view of the renin-angiotensin system focused on the role of angiotensin II as a hormone involved in blood pressure control, based on its role in renal salt and water regulation, as well as central nervous system (thirst) and vascular smooth muscle tone. Subsequent data showed a role for angiotensin II in long-term effects on cardiovascular structure, including cardiac hypertrophy and vascular remodeling. Importantly, recent human studies with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers have demonstrated exciting clinical benefits including decreases in incidence of stroke, diabetes, and end-stage renal disease that suggest important new mechanisms of action. In this review, we focus on new roles for the renin-angiotensin system in the endothelium based on the concepts of diverse signals and effects mediated by multiple angiotensin I- and angiotensin II-derived peptides, multiple angiotensin metabolizing enzymes, multiple receptors, and vascular bed-specific intracellular signals.
Fast algorithm for predicting the secondary structure of single-stranded RNA. (1980)

A computer method is presented for finding the most stable secondary structures in long single-stranded RNAs. It is 1-2 orders of magnitude faster than existing codes. The time required for its application increases as N3 for a chain N nucleotides long. As many as 1000 nucleotides can be searched in a single run. The approach is systematic and builds an optimal structure in a straightforward inductive procedure based on an exact mathematical algorithm. Two simple half-matrices are constructed and the best folded form is read directly from the second matrix by a simple back-tracking procedure. The program utilizes published values for base-pairing energies to compute one structure with the lowest free energy.
A prospective, randomized, double‐blind study comparing the efficacy of topical anesthetics in nasal endoscopy (2013)

In patients undergoing transnasal endoscopy, use of either 2% tetracaine or 4% lidocaine has similar effect. Tetracaine may be a better choice in older patients, however.
Virtual hardware for graphics applications using FPGAs (2002)

The suitability of FPGA devices for implementing graphics algorithms is analysed by a series of experiments. The performance of simple and complicated graphics algorithms on two kinds of FPGAs are compared with the performance of existing custom graphics chips and against general-purpose processors with specialised instruction sets. Various architectures for incorporating FPGA-based systems into graphics workstations are discussed. Finally, a new design method (based on virtual memory) is presented that exploits the dynamically reconfigurable nature of FPGAs.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
BCR-ABL tyrosine kinase is autophosphorylated or transphosphorylates P160 BCR on tyrosine predominantly within the first BCR exon. (1993)

The role of BCR gene sequences in Philadelphia (Ph) chromosome-positive leukemia is not well understood. Our previous studies demonstrated that P210 BCR-ABL co-precipitates with P160 BCR following immunoprecipitation with antibodies to the C-terminal domain of P160 BCR, sequences lacking in P210 BCR-ABL. We now report that tryptic peptides shared by both P160 BCR and P210 BCR-ABL are phosphorylated on tyrosine in vitro either when using immune complexes containing P160 BCR complexed to BCR-ABL or when P160 BCR is phosphorylated in trans by P210 BCR-ABL immune complexes from cells lacking functional P160 BCR. P185 BCR-ABL produced in a cell line derived from a Ph chromosome-positive acute lymphocytic leukemia patient also co-immunoprecipitated with P160 BCR. As with P210 BCR-ABL, P160 BCR tyrosine phosphopeptides were shared with P185 BCR-ABL, indicating that the major sites of tyrosine phosphorylation in vitro are contained within the first exon of P160 BCR. Similarly, BCR-ABL autophosphorylation was found to occur predominantly at tyrosines within BCR exon 1 sequences. These results raise the possibility that the activated ABL protein kinase of BCR-ABL proteins modulates the putative signal transduction activities of P160 BCR by tyrosine phosphorylation of exon 1 sequences.
THE IMPACT OF EARLY LIFE STRESS ON PSYCHOPHYSIOLOGICAL, PERSONALITY AND BEHAVIORAL MEASURES IN 740 NON-CLINICAL SUBJECTS (2005)

Early Life Stress (ELS) has been associated with a range of adverse outcomes in adults, including abnormalities in electrical brain activity [1], personality dimensions [40], increased vulnerability to substance abuse and depression [14]. The present study seeks to quantify these proposed effects in a large sample of non-clinical subjects. Data for the study was obtained from The Brain Resource International Database (six laboratories: two in USA, two in Europe, two in Australia). This study analyzed scalp electrophysiological data (EEG eyes open, closed and target auditory oddball data) and personality (NEO-FFI), history of addictive substance use and ELS) data that was acquired from 740 healthy volunteers. The ELS measures were collected via a self-report measure and covered a broad range of events from childhood sexual and physical abuse, to first-hand experience of traumatizing accidents and sustained domestic conflict [41]. Analysis of covariance, controlling for age and gender, compared EEG data from subjects exposed to ELS with those who were unexposed. ELS was associated with significantly decreased power across the EEG spectrum. The between group differences were strongest in the eyes closed paradigm, where subjects who experienced ELS showed significantly reduced beta (F1,405=12.37, p=.000), theta (F1,405=20.48, p=.000), alpha (F1,405=9.65, p=.002) and delta power (F1,450=36.22, p=.000). ELS exposed subjects also showed a significantly higher alpha peak frequency (F1,405=6.39, p=.012) in the eyes closed paradigm. Analysis of covariance on ERP components revealed that subjects who experienced ELS had significantly decreased N2 amplitude (F1,405=7.73, p=.006). Analyses of variance conducted on measures of personality revealed that subjects who experienced ELS had significantly higher levels of neuroticism (F1,264=13.39, p=.000) and openness (F1,264=17.11, p=.000), but lower levels of conscientiousness, than controls (F1,264=4.08, p=.044). The number of ELS events experienced was shown to be a significant predictor of scores on the DASS questionnaire [27], which rates subjects on symptoms of depression (F3,688=16.44, p=.000, R2=.07), anxiety (F3,688=14.32, p=.000, R2=.06) and stress (F3,688=20.02, p=.000, R2=.08). Each additional early life stressor was associated with an increase in these scores independent of age, gender and the type of stressor. Furthermore, the number of ELS experiences among smokers was also found to be a positive predictor of the nicotine dependency score (Faegstrom Test For Nicotine Dependence, [19]) (F3,104=10.99, p=.000, R2=.24), independent of age, gender and type of stressor. In conclusion, we highlight the impact of a history of ELS showed significant effects on brain function (EEG and ERP activity), personality dimensions and nicotine dependence.