gebhart/patrepeval huggingface dataset:
Lack of effect of nitroglycerin on the transmural variation of tissue pH during fixed coronary stenosis. (1983)

A new MpH-measuring system was used to investigate the mechanism of action of intravenous NTG on pacing-induced myocardial ischemia during critical stenosis. In ten anesthetized open-chest dogs, two MpH electrodes were placed in a segment supplied by the CCA, one superficial and one deep. Atrial pacing at a rate 50 beats/min higher than baseline was instituted for a period of 10 min (Pacing I). Critical stenosis was then applied to the CCA. Three more similar periods of atrial pacing were instituted during critical stenosis. Pacing II was without any intervention, Pacing III was after the intravenous administration of a bolus of NTG, and Pacing IV was after the intravenous administration of NTG + A. NTG (metamarinol) during critical stenosis and atrial pacing did not alter preload and did not reduce afterload more than critical stenosis and atrial pacing alone. It did not significantly alter flow in the CCA measured by an electromagnetic flow meter. Consequently, the magnitude of fall in both endo- and epicardial MpH during critical stenosis and atrial pacing was no different with or without the administration of NTG. That under these conditions NTG failed to reduce the degree of myocardial ischemia suggests that the beneficial effects of NTG during fixed critical stenosis are determined primarily by its ability to reduce the determinants of myocardial oxygen demand, and not by a direct effect on the ischemic myocardium per se. The study also demonstrates for the first time a significant transmural gradient in MpH in the canine heart, even in the normal resting state.
Polyethylene glycol treatment after traumatic brain injury reduces β‐amyloid precursor protein accumulation in degenerating axons (2006)

Polyethylene glycol (PEG; 2,000 MW; 30% v/v) is a nontoxic molecule that can be injected intravenously and possesses well-documented neuroprotective properties in the spinal cord of the guinea pig. Recent studies have shown that intravenous PEG can also enter the rat brain parenchyma after injury and repair cellular membrane damage in the region of the corpus callosum. Disrupted anterograde axonal transport and resulting beta-amyloid precursor protein (APP) accumulation are byproducts of traumatic axonal injury (TAI) in the brain. APP accumulation indicates axonal degeneration as a result of axotomy, a detriment that can lead to cell death. In this study, we show that PEG treatment can eliminate APP accumulation in specific brain areas of rats receiving TAI. Six areas of the brain were analyzed: the medial cortex, hippocampus, lateral cortex, thalamus, medial lemniscus, and medial longitudinal fasciculus. Increased APP expression after injury was abolished in the thalamus and reduced in the medial longitudinal fasciculus by PEG treatment. In all remaining areas except for the lateral cortex, APP expression was not increased between injured and uninjured brains, indicating that damage was undetected in those brain areas in this study.
Mannose Receptor Targeting of Tumor Antigen pmel17 to Human Dendritic Cells Directs Anti-Melanoma T Cell Responses via Multiple HLA Molecules (2004)

Targeting recycling endocytic receptors with specific Abs provides a means for introducing a variety of tumor-associated Ags into human dendritic cells (DCs), culminating in their efficient presentation to T cells. We have generated a human mAb (B11) against the mannose receptor that is rapidly internalized by DCs through receptor-mediated endocytosis. By genetically linking the melanoma Ag, pmel17, to Ab B11, we obtained the fully human fusion protein, B11-pmel17. Treatment of DCs with B11-pmel17 resulted in the presentation of pmel17 in the context of HLA class I and class II molecules. Thus, potent pmel17-specific T cells were cytotoxic toward gp100(+) HLA-matched melanoma targets, but not HLA-mismatched melanoma or gp100(-) nonmelanoma tumor lines. Importantly, competitive inhibition of lysis of an otherwise susceptible melanoma cell line by cold targets pulsed with known gp100 CD8 T cell epitopes as well as a dose-dependent proliferative response to Th epitopes demonstrates that DCs can process targeted Ag for activation of cytotoxic as well as helper arms of the immune response. Thus, the specific targeting of soluble exogenous tumor Ag to the DC mannose receptor directly contributes to the generation of multiple HLA-restricted Ag-specific T cell responses.
Magnetic transducers in biosensors and bioassays (1999)

In affinity biosensor technology, antibodies are employed as the recognition element in close conjunction with a transducer. Much work has been put into developing effective transducers, and a number of technologies exist. In this review various works that we have found significant to the field of magnetic transducers in bioanalysis have been critically studied in order to describe the status and development of magnetic measurements in biosensors and bioassays. Our group has previously suggested that magnetic transducers in combination with magnetically labelled antibodies may be used in this context and this so-called magneto immunoassay (MIA) technique will be dealt with in some detail.
High resolution melting analysis for the detection of EMS induced mutations in wheat Sbella genes (2011)

TILLING has successfully been used to generate novel alleles for SBEIIa genes known to control amylose content in wheat. Single and double null SBEIIa genotypes have been found to show a significant increase in amylose content.
Pure Lipopolysaccharide or Synthetic Lipid A Induces Activation of p21Ras in Primary Macrophages through a Pathway Dependent on Src Family Kinases and PI3K (2005)

Recognition of bacterial LPS by macrophages plays a critical role in host defense against infection by Gram-negative bacteria. However, when not tightly regulated, the macrophage's response to LPS can induce severe disease and septic shock. Although LPS triggers the activation of multiple signaling pathways in macrophages, it was unclear whether these include activation of the p21Ras GTPases. We report that p21Ras is rapidly and transiently activated in murine primary macrophages stimulated with an ultra-pure preparation of LPS or with synthetic lipid A. The molecular basis of this activation was investigated using a pharmacological approach. LPS-induced activation of p21Ras was inhibited in the presence of PP2, LY294002, or wortmannin, suggesting that it depends on the activity of one or more members of the Src kinase family and the subsequent activation of PI3K. In that pharmacological inhibitors of PI3K inhibited LPS-induced activation of p21Ras, but not activation of ERK, we concluded that LPS-induced activation of ERK occurs through a pathway that is not dependent on the activation of p21Ras.
Mussel-Inspired Adhesives and Coatings (2011)

Mussels attach to solid surfaces in the sea. Their adhesion must be rapid, strong, and tough, or else they will be dislodged and dashed to pieces by the next incoming wave. Given the dearth of synthetic adhesives for wet polar surfaces, much effort has been directed to characterizing and mimicking essential features of the adhesive chemistry practiced by mussels. Studies of these organisms have uncovered important adaptive strategies that help to circumvent the high dielectric and solvation properties of water that typically frustrate adhesion. In a chemical vein, the adhesive proteins of mussels are heavily decorated with Dopa, a catecholic functionality. Various synthetic polymers have been functionalized with catechols to provide diverse adhesive, sealant, coating, and anchoring properties, particularly for critical biomedical applications.
Precordial Vibrations Provide Noninvasive Detection of Early-Stage Hemorrhage (2013)

Graded lower-body negative pressure was used to create a hemodynamic response similar to hemorrhage. Echocardiogram measurements showed a maximal reduction of 32.4% in stroke volume. Analysis of systolic time intervals, such as pre-ejection period and left ventricular ejection time (LVET), derived from a seismocardiogram (SCG), were demonstrated to be more sensitive in detection of early-stage hemorrhage compared with pulse pressure, heart rate, and the amplitude features extracted from SCG. In particular, the LVET and pre-ejection period/LVET features, extracted from SCG, were significantly different between, and correlated with, the different stages of lower-body negative pressure (r = 0.9 and 0.88, P < 0.05), for 32 subjects. These results suggest a portable, cost-effective solution for identification of mild or moderate hemorrhage using accelerometers.
Spectral linewidth preservation in parametric frequency combs seeded by dual pumps (2012)

We demonstrate new technique for generation of programmable-pitch, wideband frequency combs with low phase noise. The comb generation was achieved using cavity-less, multistage mixer driven by two tunable continuous-wave pump seeds. The approach relies on phase-correlated continuous-wave pumps in order to cancel spectral linewidth broadening inherent to parametric comb generation. Parametric combs with over 200-nm bandwidth were obtained and characterized with respect to phase noise scaling to demonstrate linewidth preservation over 100 generated tones.
Tumor Growth Inhibition with Cetuximab and Chemotherapy in Non–Small Cell Lung Cancer Xenografts Expressing Wild-type and Mutated Epidermal Growth Factor Receptor (2007)

Cetuximab showed antitumor activity in NSCLC models expressing wt and mutated EGFR. Combination treatments increased the efficacy of cetuximab, which may be important for the management of patients with chemorefractory NSCLC.
Preliminary criteria for clinical remission for select categories of juvenile idiopathic arthritis. (2004)

Using consensus formation techniques, we formulated preliminary criteria for inactive disease and clinical remission on and off medication for use in select categories of JIA. Retrospective validation is in progress; prospective validation will follow. Future efforts will include other categories of JIA.
Bevacizumab reduces tumor targeting of antiepidermal growth factor and anti‐insulin‐like growth factor 1 receptor antibodies (2013)

Bevacizumab (antivascular endothelial growth factor [anti-VEGF]) and cetuximab (antiepidermal growth factor receptor [anti-EGFR]) are approved antibodies for treatment of cancer. However, in advanced colorectal cancer, the combination fails to improve survival. As the reason for the lack of activity is unknown, our study aims to determine the effect of bevacizumab on targeting of anti-EGFR and insulin-like growth factor 1 receptor (IGF-1R) antibodies in tumors with single-photon emission computed tomography (SPECT)/CT imaging. Mice with subcutaneous EGFR and IGF-1R-expressing SUM149 xenografts received a single dose of bevacizumab (10 mg/kg) or saline. After 4 days, mice were injected with radiolabeled cetuximab or R1507, an anti-IGF-1R antibody. A control group received a radiolabeled irrelevant IgG (hLL2). Three days later, SPECT/CT images were acquired and mice were dissected to determine the concentration of antibodies in the tissues. Tumors were analyzed immunohistochemically to determine vascular density (CD34), VEGF, EGFR and IGF-1R expression. SPECT/CT imaging revealed that bevacizumab treatment significantly reduced tumor targeting of radiolabeled cetuximab by 40% from 33.1 ± 1.1 %ID/g to 19.8 ± 5.7 %ID/g (p = 0.009) for untreated and bevacizumab-treated tumors, respectively. A similar effect was found for (111) In-R1507: tumor targeting of R1507 decreased by 35%. No significant differences in tumor uptake were observed in mice that received an irrelevant IgG. Uptake in normal organs was not altered by bevacizumab. Immunohistochemical analysis showed that vascular density decreased with 43%, whereas EGFR and IGF-1R expression was unaltered. In conclusion, bevacizumab treatment significantly reduces tumor targeting of anti-EGFR and anti-IGF-1R antibodies. This emphasizes the importance of timing and sequencing of bevacizumab in combination with other antibodies.
Comparison of functional fitness outcomes in experienced and inexperienced older adults after 16-week tai chi program. (2014)

Tai chi appears to be an optimal mode of physical activity for older adults regardless of previous experience with tai chi.
The gene for the rat heat-shock cognate, hsc70, can suppress oncogene-mediated transformation. (1992)

In cells transformed by mutant mouse p53 plus ras, the former protein is found to be complexed with the heat-shock protein cognate hsc70. To determine whether hsc70 can directly affect neoplastic transformation, nonestablished rat embryo fibroblasts (REF) were transfected with rat genomic hsc70 DNA in conjunction with various oncogenes. We report here that the hsc70 gene could efficiently suppress focus induction by mutant p53 plus ras, as well as by myc plus ras. No inhibitory effect of hsc70 was detectable in assays monitoring the ability of REF to be immortalized by mutant p53, arguing against a nonspecific deleterious effect of the hsc70 genomic clone on REF survival and proliferation. Lines generated in the presence of the hsc70 plasmid produced augmented levels of hsc70. Plasmids encoding only short NH2-terminal fragments of hsc70 could also, in some cases, partially reduce oncogene-mediated focus formation. However, a maximal inhibitory effect required the production of a functional hsc70 protein. The data presented here raise the possibility that hsc70 may be directly involved in the modulation of oncogene-mediated transformation.
Performance issues and error analysis in an open-domain question answering system (2003)

This paper presents an in-depth analysis of a state-of-the-art Question Answering system. Several scenarios are examined: (1) the performance of each module in a serial baseline system, (2) the impact of feedbacks and the insertion of a logic prover, and (3) the impact of various retrieval strategies and lexical resources. The main conclusion is that the overall performance depends on the depth of natural language processing resources and the tools used for answer finding.
A new polymorphic probe which defines the region of chromosome 19 containing the myotonic dystrophy locus. (1990)

The region of human chromosome 19 which includes the myotonic dystrophy locus (DM) has recently been redefined by the tight linkage between it and the gene for muscle-specific creatine kinase (CKMM), which lies just proximal to DM. Utilizing human/hamster hybrid cell lines containing defined breakpoints within this region, we have assigned a number of new probes close to DM. Two of these probes, p134B and p134C, were isolated from a single cosmid clone (D19S51) and detect the same BglI RFLP; p134C detects an additional RFLP with the enzyme PstI. Analysis of these probes in the Centre d'Etude du Polymorphisme Humain families demonstrates tight linkage with a number of markers known to be proximal to DM. A two-point lod score of 6.34 at theta = .025 demonstrates the linkage of this probe to DM. Analysis of a DM individual previously shown to be recombinant for other tightly linked markers indicates that p134C is distal to DM. This result indicates that both the new probe and the existing group of proximal probes including CKMM and ERCC1 probably flank DM and define the genetic interval into which this mutation maps.
Consequences of N-Acylation on Structure and Membrane Binding Properties of Dermaseptin Derivative K4-S4-(1-13) (2006)

Acyl conjugation to antimicrobial peptides is known to enhance antimicrobial properties. Here, we investigated the consequences of aminolauryl (NC(12)) conjugation to the dermaseptin derivative K(4)-S4-(1-13) (P) on binding properties to bilayer models mimicking bacterial plasma membrane, which is often cited as the ultimate site of action. Isothermal titration calorimetry revealed that acylation was responsible for enhancing the binding affinity of NC(12)-P compared with P (K = 13 x 10(5) and 1.5 x 10(5) m(-1), respectively). Surface plasmon resonance measurements confirmed the isothermal titration calorimetry results (K(app) = 12.6 x 10(5) and 1.53 x 10(5) m(-1), respectively) and further indicated that enhanced adhesion affinity (K(adhesion) = 3 x 10(5) and 1 x 10(5) m(-1), respectively) was coupled to enhanced tendency to insert within the bilayer (K(insertion) = 4.5 and 1.5, respectively). To gain insight into the molecular basis for these observations, we investigated the three-dimensional structures in the presence of dodecylphosphocholine using NMR. The ensemble of NMR-calculated structures (backbone root mean square deviation <0.6 A) showed that the acyl moiety was responsible for a significant molecular reorganization, possibly affecting the electrostatic potential distribution in NC(12)-P relative to that of P. The combined data present compelling evidence in support of the hypothesis that N-acylation affects antimicrobial properties by modifying the secondary structure of the peptide in a manner that facilitates contact with the membrane and consequently increases its disruption.
NEW APPROACHES TO DONOR CROSSMATCHING AND SUCCESSFUL TRANSPLANTATION OF HIGHLY SENSITIZED PATIENTS1,2 (1983)

A class I HLA molecule may bear not only a private or unique determinant, but a shared, yet discrete, public epitope. These public determinants occur with a much higher frequency in the random donor population than the associated private determinants--and thus, are encountered more often in random donor blood transfusions and in renal transplantation. Sera from highly sensitized dialysis patients have been reported to contain a restricted number of antibodies to public determinants rather than a diverse array of antibodies directed against the private HLA-AB epitopes. As detailed in this report, comprehensive serum analysis of the public antibodies in highly sensitized transplant candidates has optimized identification of potential crossmatch-compatible donors and has avoided needless crossmatches. During the past two years, the incidence of renal transplantation from cadaveric donors to highly sensitized recipients has doubled at this institution. At 10-25 months following transplantation, 70% of these allografts are functioning. Private HLA class I antigen incompatibility was not a barometer for exclusion in the final donor crossmatch of these highly sensitized recipients. Furthermore, positive donor T cell crossmatches with sera obtained more than six months prior to transplantation may not represent an impediment to successful transplantation. We conclude that the approach of detailed antibody analysis can result in an improved outlook for successful transplantation of more dialysis patients who are highly sensitized to the class I HLA alloantigens.
Transcutaneous Immunization with Combined Cholera Toxin and CpG Adjuvant Protects againstChlamydia muridarumGenital Tract Infection (2004)

ABSTRACT Chlamydia trachomatis is a pathogen of the genital tract and ocular epithelium. Infection is established by the binding of the metabolically inert elementary body (EB) to epithelial cells. These are taken up by endocytosis into a membrane-bound vesicle termed an inclusion. The inclusion avoids fusion with host lysosomes, and the EBs differentiate into the metabolically active reticulate body (RB), which replicates by binary fission within the protected environment of the inclusion. During the extracellular EB stage of the C. trachomatis life cycle, antibody present in genital tract or ocular secretions can inhibit infection both in vivo and in tissue culture. The RB, residing within the intracellular inclusion, is not accessible to antibody, and resolution of infection at this stage requires a cell-mediated immune response mediated by gamma interferon-secreting Th1 cells. Thus, an ideal vaccine to protect against C. trachomatis genital tract infection should induce both antibody (immunoglobulin A [IgA] and IgG) responses in mucosal secretions to prevent infection by chlamydial EB and a strong Th1 response to limit ascending infection to the uterus and fallopian tubes. In the present study we show that transcutaneous immunization with major outer membrane protein (MOMP) in combination with both cholera toxin and CpG oligodeoxynucleotides elicits MOMP-specific IgG and IgA in vaginal and uterine lavage fluid, MOMP-specific IgG in serum, and gamma interferon-secreting T cells in reproductive tract-draining caudal and lumbar lymph nodes. This immunization protocol resulted in enhanced clearance of C. muridarum ( C. trachomatis , mouse pneumonitis strain) following intravaginal challenge of BALB/c mice.
Human infection with Trypanosoma cruzi induces parasite antigen-specific cytotoxic T lymphocyte responses. (1998)

Experimental models of Chagas' disease, an infection caused by the intracellular protozoan Trypanosoma cruzi, have demonstrated the crucial immunoprotective role played by CD8(+) T lymphocytes. These cells dominate inflammatory foci in parasitized tissues and their elimination from mice leads to uncontrolled parasite replication and subsequent death of the infected host. A trypomastigote surface antigen, TSA-1, and two amastigote surface molecules, ASP-1 and ASP-2, were recently identified as targets of CD8(+) cytotoxic T lymphocytes (CTL) in T. cruzi-infected mice. Until now, however, there was no evidence for the development of parasite-specific CTL in T. cruzi-infected humans. In this study, human CTL specific for TSA-1-, ASP-1-, and ASP-2-derived peptides were detected in the peripheral blood mononuclear cells from 21 of 24 HLA-A2(+) T. cruzi-infected patients. CTL recognition was antigen specific, A2-restricted, and CD8(+) T cell-dependent. Demonstration of human CTL against T. cruzi and against target molecules identified using the murine model provides important information for the optimal design and evaluation of vaccines to prevent or ameliorate Chagas' disease.
Effectiveness of Clinician-selected Electronic Information Resources for Answering Primary Care Physicians' Information Needs (2006)

For the primary care physicians studied, electronic information resources of choice did not always provide support for finding correct answers to simulated clinical questions and in some instances, individual resources may have contributed to an initially correct answer becoming incorrect.
Peptides Naturally Presented by MHC Class I Molecules (1993)

MHC class I molecules are peptide receptors of stringent specificity which however still allow millions of different ligands. This is achieved by the following specificity characteristics summarized as allele specific peptide motifs: Peptides are of defined length, depending on the class I allele (either 8 or 9 residues; exceptions have been observed). Typically, 2 of the 8 or 9 positions are anchors that can only be occupied by a single amino acid residue, or by residues with closely related side chains. Location and characteristics of anchors vary with class I alleles. The C terminus of the peptide ligands is frequently an aliphatic or charged residue. Such allele-specific class I peptide ligand motifs, known so far for H-2Kd, Kb, Kk, Kkm1, Db, HLA-A*0201, A*0205, and B*2705, are useful to predict natural T cell epitopes. The latter can be determined by extraction from cells recognized by the T cell of interest. It is not known how the class I ligands are produced in the cell, although speculative models exist. The peptide specificity of class I molecules and experimental evidence indicate that T cells are tolerant to only a small fraction of the expressed genomic sequences and are not tolerant to the remainder. The function of class I molecules is to present a collection of self-peptide samples at the cell surface for surveillance by T cells.