gebhart/patrepeval huggingface dataset:
Magnetization transfer: theory and clinical applications in neuroradiology. (1994)

Magnetization transfer, a new technique for improving image contrast in magnetic resonance (MR) imaging, is based on application of off-resonance radio-frequency pulses and observing their effects on MR images, as well as measuring the signal intensity with and without application of the pulses (ie, magnetization transfer ratio [MTR]). MTRs can be used to detect changes in the structural status of brain parenchyma that may or may not be visible with standard MR techniques. Use of MTRs may allow subcategorization of multiple sclerosis lesions into those with very low MTR (demyelinated lesions) and slightly decreased MTR (edematous lesions). In cases of wallerian degeneration, use of MTRs appears to allow reliable detection of changes undetectable with MR imaging or even light microscopy. In cases of infection with human immunodeficiency virus, MTRs seem to indicate that the macromolecular structure of white matter remains intact until relatively late in the course of disease. In cases of metastatic disease, MTRs of brain lesions indicate structural changes beyond the extent of the lesions seen on standard MR images. These findings may be due to chronic edema, myelin loss, and perhaps previous undetected tumor. In addition to being a new method of providing contrast, the magnetization transfer technique enables semi-quantitative, reproducible characterization of tissue and pathologic entities, which could substantially improve the specificity of MR imaging.
Regulation of Apoptotic Protease Activating Factor-1 Oligomerization and Apoptosis by the WD-40 Repeat Region (1999)

Apoptotic protease activating factor-1 (Apaf-1) has been identified as a proximal activator of caspase-9 in cell death pathways that trigger mitochondrial damage and cytochrome c release. The mechanism of Apaf-1 action is unclear but has been proposed to involve the clustering of caspase-9 molecules, thereby facilitating autoprocessing of adjacent zymogens. Here we show that Apaf-1 can dimerize via the CED-4 homologous and linker domains of the molecule providing a means by which Apaf-1 can promote the clustering of caspase-9 and facilitate its activation. Apaf-1 dimerization was repressed by the C-terminal half of the molecule, which contains multiple WD-40 repeats, but this repression was overcome in the presence of cytochrome c and dATP. Removal of the WD-40 repeat region resulted in a constitutively active Apaf-1 that exhibited greater cytotoxicity in transient transfection assays when compared with full-length Apaf-1. These data suggest a mechanism for Apaf-1 function and reveal an important regulatory role for the WD-40 repeat region.
Single-chain Fv radioimmunotargeting. (1996)

The availability of engineered antibody species has catalyzed new developments in radioimmunotargeting. This chapter summarized recent studies of single-chain Fv (sFv) proteins, which are minimal antibody binding sites engineered as single polypeptide chains. The single-chain Fv can be as small as 26 kDa monomers or may be engineered as larger fusion proteins designed to self-associate into dimeric or multimeric species. They typically exhibit rapid clearance that results in high targeting specificity within a matter of hours. We have compared different modes of administration to allow further manipulation of their biodistribution and targeting properties. Results of the present study comparing intravenous (i.v.) and intraperitoneal (i.p.) administration show comparable long-term retention in circulation, but the i.v. route showed an initially high peak blood level while i.p. injection did not. As with a single sFv dose, repeated bolus injections of sFv attained high target-to-background ratios, whereas continuous sFv infusion reached a steady state level of free sFv in blood and kidney that exceeded that in tumor xenografts. We observed improved localization of radioiodinated sFv in tumor xenografts if the radioiodine label resisted dehalogenation from the protein, which was accomplished, for example, through conjugation of a para-131I-benzoyl group to Iysyl epsilon-amino groups of the protein. Modification of the sFv by genetic incorporation of a cysteinyl peptide (to form sFv') provided a chelation site for radiometals that simplified incorporation of 99mTc with the opportunity for improved diagnostic imaging in cancer and other diseases. Therapeutic applications of sFv radioimmunotargeting could rely on sFv' complexed to 186Re or 188Re. Engineering sFv of sFv' with increased antigen-binding affinity and appropriately manipulating their mode of administration should promote sustained tumor retention conducive to clinically useful therapeutic indices.
Expression, Exon-Intron Organization, and Chromosome Mapping of the Human Sodium Iodide Symporter (1997)

The active iodide uptake of the thyroid gland in humans is mediated by the human sodium iodide symporter (hNIS). In this report, we show that hNIS expression was detected primarily in thyroid tissue, but also in breast, colon, and ovary tissues. Expression of hNIS is greatly reduced in thyroid tumors compared to normal thyroid tissue. Among tumor tissues, hNIS expression appears to be variable, consistent with the variable response to radioiodide treatment observed for thyroid carcinomas. The coding region of hNIS is interrupted by 14 introns, and the nucleotide sequence of each exon-intron junction is reported. Using this information, an alternatively spliced form of hNIS was identified. Finally, the chromosome location of the hNIS gene was mapped to chromosome 19p.
Molecular characterization of porcine respiratory coronavirus isolates with varying pathogenicity (1994)

Three new isolates of porcine respiratory coronavirus (PRCV) were isolated and characterized. Two of the PRCV isolates, AR310 and LEPP, were shown to produce moderate interstitial pneumonia, whereas the third PRCV isolate, IA1894, was only mildly pathogenic in five-week-old specific pathogen free pigs. The previously described PRCV isolate ISU-1, a mildly pathogenic PRCV isolate, was also included in this study. These PRCV isolates with varying pathogenicity provided an opportunity to determine if there are certain genes that correlate with virulence, as the genes 3 and 3-1 have been hypothesized to be virulence determinants for transmissible gastroenteritis virus (TGEV) isolates. Using Northern blot analysis, the numbers and sizes of the subgenomic mRNAs produced by the PRCV isolates in infected swine testicular cells were shown to vary. The PRCV isolates all had a mRNA 2 that was smaller than the mRNA 2 of TGEV. The PRCV isolates AR310 and LEPP both had two mRNA species that comigrated with the mRNAs 3 and 3-1 of TGEV. The PRCV isolate IA1894 had only mRNA 3 present, whereas the PRCV isolate ISU-1 had only mRNA 3-1 present. Nucleotide sequence analysis revealed that the PRCV isolates AR310 and LEPP both had identical S gene deletions of 621 nucleotides. The PRCV isolates IA1894 and ISU-1 had S gene deletions of 678 and 681 nucleotides, respectively. The 3 gene of the PRCV isolates AR310 and LEPP was predicted to yield a protein of 72 amino acids, the same size as that of the virulent Miller strain of TGEV. The 3a gene of the PRCV isolate IA1894 was predicted to yield a truncated protein of 53 amino acids due to a 23 nucleotide deletion in 3a gene. The CTAAAC leader-RNA-binding site and ATG start codon for the 3 gene of the PRCV isolate ISU-1 was removed due to a 168 nucleotide deletion. The fact that the PRCV isolates AR310 and LEPP were more pathogenic than the PRCV isolate IA1894 indicates that the presence of an intact gene 3 may be important in determining the pathogenicity of PRCV isolates.
Cloning and characterization of a maize pollen-specific calcium-dependent calmodulin-independent protein kinase. (1994)

A calcium-dependent calmodulin-independent protein kinase (CDPK) has been cloned from maize (Zea mays). The sequence predicts a 550-amino acid (predicted molecular mass is 60 kDa) protein with two major functional domains: an N-terminal catalytic domain highly homologous to protein kinases and a C-terminal domain resembling calmodulins. Northern analysis shows that the expression of the maize CDPK gene is pollen specific and that its transcription is restricted to late stages of pollen development. Western blots reveal a major abundance of CDPK protein at the stage of pollen germination. In vitro germination and pollen tube growth are impaired upon addition of a calmodulin antagonist (calmidazolium), CDPK inhibitors (W-7), and antisense oligonucleotides directed against CDPK mRNA. These observations indicate that the function of the pollen-specific maize CDPK protein is required for germination and pollen tube growth.
IL-6 Induces Target Cell Resistance to HIV-Specific Cytotoxic Lysis (1995)

Interleukin-6 (IL-6) is a pleiotropic cytokine with multiple immunomodulatory functions. Although IL-6 enhances cytotoxic effector cell function in vitro, we report the paradoxical effect of IL-6-induced resistance of target cells to lysis by cytotoxic T lymphocytes (CTL). The CTL system employed autologous, Epstein-Barr virus-transformed B lymphoblastoid target cells infected with vaccinia virus vectors carrying the envelope gene from the human immunodeficiency virus (HIV). Effector cells were fresh peripheral blood mononuclear cells from HIV+ individuals. Resistance was induced by exposing B cell line targets to exogenous IL-6, or via an autocrine pathway in which IL-6 was secreted by the target cells themselves. The IL-6 effect was dose dependent and reversible by antibody to IL-6. A large proportion of B cell lines from HIV+ individuals produced IL-6, and the lysis of HIV envelope-expressing B cell targets was inversely proportional to the amounts of IL-6 produced by the cell lines. These findings have significance for the utility and interpretation of CTL assays as in vitro correlates of T cell competence and may be significant in vivo in situations such as HIV infection where IL-6 production is increased.
Mouse models of autism spectrum disorders: The challenge for behavioral genetics (2006)

Autism is a severe neurodevelopmental disorder, which typically emerges early in childhood. The core symptoms of autism include deficits in social interaction, impaired communication, and aberrant repetitive behavior, including self-injury. Despite the strong genetic component for the disease, most cases of autism have not been linked to mutations in a specific gene, and the etiology of the disorder has yet to be established. At the present time, there is no generally accepted therapeutic strategy to treat the core symptoms of autism, and there remains a critical need for appropriate animal models and relevant behavioral assays to promote the understanding and treatment of the clinical syndrome. Challenges for the development of valid mouse models include complex genetic interactions underlying the high heritability of the disease in humans, diagnosis based on deficits in social interaction and communication, and the lack of confirmatory neuropathological markers to provide validation for genetic models of the disorder. Research focusing on genes that mediate social behavior in mice may help identify neural circuitry essential for normal social interaction, and lead to novel genetic animal models of the autism behavioral phenotype.
5-HT6 RECEPTORS (1999)

s of the First Congress of the Behavioral Pharmacology Society and the European Behavioural Pharmacology Society: PDF Only
Preferential Adsorption of a “Kinked” DNA to a Neutral Curved Surface:  Comparisons to and Implications for Nonspecific DNA−Protein Interactions (1996)

We have examined the adsorption of different DNA sequences to mercaptoethanol-capped CdS quantum dots, ∼40 Å diameter, as a minimalist model for nonspecific protein−DNA interactions, and compared these results to what we have previously found for Cd2+-surface-rich dots of the same size (Mahtab, R.; Rogers, J. P.; Murphy, C. J. J. Am. Chem. Soc. 1995, 117, 9099). We find that neutralization of the surface leads to no detectable binding, based on our luminescence assay, for “straight” and A-tract oligonucleotides, while a crystallographically “kinked” sequence does still bind, but by a factor of 4 less than that observed for a divalent metal ion-rich surface. The binding constants for both surfaces are within the range of nonspecific protein−DNA interactions. The kinetics of binding are also monitored and are compared to nonspecific protein−DNA interactions for large DNA fragments. Issues of biopolymer static bending vs flexibility are also addressed with fluorescence resonance energy transfer experiments.
P1‐235: TOMM40 “523” Genotype Affects Age of Alzheimer's Disease Onset Differentially by Race (2011)

The TOMM40 gene encodes the translocase of the outer mitochondrial membrane pore subunit, and is in linkage disequilibrium with APOE. The length of a poly-T variant (“523”) within intron 6 of TOMM40 has been shown to predict the age of onset of late onset Alzheimer's Disease (LOAD). We present new data using Kaplan Meier (KM) survival curves showing the effect of “523” on LOAD within a large, well-characterized sample followed annually for up to five years. The Bryan ADRC Memory Health and Aging study is comprised of a diverse group of residents from the local community (28% African-American; AfrAmer) all of whom were independent in their daily function at baseline. They were visited in the home or in the clinic annually and evaluated on a number of measures including a neuropsychological test battery, health history, behavioral functional assessments, and neurological evaluation. Using a sample of n = 438 participants, cognitively normal at baseline, we produced empirical survival curves to estimate age-specific proportions of participants surviving for TOMM40 “523” genotypes based on poly-T length. Individuals were followed over time until death, dementia onset, including probable or possible AD, or their last visit. A total of 106 individuals were diagnosed with dementia at a mean age of 78 (SD 8.0) years. KM curves show an effect (p < 0.0001, log rank test) of “523” genotype on age of LOAD onset, with age at 50% affected ranging from 75 to 94 years and a 3-5 year separation between curves. Ethnicity has an effect (p = 0.004) on LOAD onset whereas gender and years of education were not statistically-significant covariates. Limiting analysis to individuals with the APOE 3 /3 genotype (n = 199) showed a significant effect (p < 0.02) of “523” on LOAD onset. “523” genotypes define characteristic age of onset curves for LOAD which provide additional temporal resolution to curves based on APOE genotype. Results suggest that the age of onset in AfrAmer in this cohort is earlier, across all “523” genotypes, however this needs to be studied further as there were few AfrAmer in the sample.
Stress sensing performance using mechanoluminescence of SrAl2O4:Eu (SAOE) and SrAl2O4:Eu, Dy (SAOED) under mechanical loadings (2013)

In this paper, the stress sensing performance of two well-known mechanoluminescence (ML) sensing materials, (1) SrAl2O4:Eu (SAOE) and (2) SrAl2O4:Eu, Dy (SAOED), has been experimentally studied. Under the same input loadings and strain rates, changes of the light intensity have been characterized in terms of sensitivity, repeatability and linearity. Effects of the strain rate on the light intensity changes have also been investigated for both ML sensing materials. SAOED appears to perform better as an ML stress sensor than SAOE because it shows higher sensitivity and no saturation of light during the loading history. Although SAOE showed saturation of light emissions, its initial sensitivity to loading was higher than that of SAOED. Therefore, SAOE appears to be more suitable for sensors for monitoring dynamic active cracks.
Molecular imaging with endogenous substances (2003)

Dynamic nuclear polarization has enabled hyperpolarization of nuclei such as 13C and 15N in endogenous substances. The resulting high nuclear polarization makes it possible to perform subsecond 13C MRI. By using the dynamic nuclear polarization hyperpolarization technique, 10% polarization was obtained in an aqueous solution of 100 mM 13C-labeled urea, ready for injection. The in vivo T1 relaxation time of 13C in the urea solution was determined to 20 +/- 2 s. Due to the long relaxation time, it is possible to use the hyperpolarized substance for medical imaging. A series of high-resolution ( approximately 1-mm) magnetic resonance images were acquired, each with a scan time of 240 ms, 0-5 s after an i.v. injection of the hyperpolarized aqueous [13C]urea solution in a rat. The results show that it is possible to perform 13C angiography with a signal-to-noise ratio of approximately 275 in approximately 0.25 s. Perfusion studies with endogenous substances may allow higher spatial and/or temporal resolution than is possible with current proton imaging techniques.
Desensitization of myocardial beta-adrenergic receptors during cardiopulmonary bypass. Evidence for early uncoupling and late downregulation. (1991)

These data suggest that myocardial beta AR desensitization does occur during CPB in healthy, nonischemic canine myocardium and that this pattern is reversed 30 minutes after discontinuation of CPB. In addition, a slower process of beta AR downregulation persists after discontinuation of CPB. Because successful weaning from CPB is a critical process during myocardial surgery, these findings have potentially important implications in the management of such patients.
Keratocan is Expressed by Osteoblasts and Can Modulate Osteogenic Differentiation (2011)

Keratocan is an extracellular matrix protein that belongs to the small leucine-rich proteoglycan family that also includes lumican, biglycan, decorin, mimecan, and fibromodulin. Members of this family are known to play a role in regulating cellular processes such as proliferation and modulation of osteoprogenitor lineage differentiation. The aims of this study were to evaluate the expression pattern of the keratocan within the osteoprogenitor lineage and to assess its role in regulating osteoblast maturation and function. Results from gene expression analyses of cells at different maturation stages within the osteoblast lineage indicate that keratocan is differentially expressed by osteoblasts and shows little or no expression by osteocytes. During primary osteoblast cultures, high keratocan mRNA expression was observed on day 14, whereas lower expression was detected at days 7 and 21. To assess the effects of keratocan on osteoprogenitor cell differentiation, we evaluated primary calvarial cell cultures from keratocan-deficient mice. The mineralization of calvarial osteoblast cultures derived from keratocan null (Kera-/-) mice was lower than in wild-type osteoblast cultures. Furthermore, analysis of RNA derived from Kera-/- calvarial cell cultures showed a reduction in the mature osteoblast differentiation markers, that is, bone sialoprotein and osteocalcin. In addition, we have evaluated the bone formation in keratocan-deficient mice. Histomorphometric analysis indicated that homozygous knockout mice have significantly decreased rates of bone formation and mineral apposition. Taken together, our results demonstrate the expression of keratocan by osteoblast lineage cells and its ability to modulate osteoblast function.
Identification of phosphorylation sites in proteins by nanospray quadrupole ion trap mass spectrometry (2000)

A method is described for identifying serine phosphorylation sites in proteins, based on conventional (32)P labeling followed by electrophoretic separation, 'in-gel' digestion with a protease, peptide extraction, reversed-phase high-performance liquid chromatographic separation and collection and off-line analysis of the radioactive fractions by nanospray ion trap mass spectrometry. The method was successfully applied to the identification of three phosphorylation sites in two proteins which were subjected to in vitro phosphorylation under physiological conditions. Different combinations of the various scanning modes of the ion trap, including high-resolution, multiple subfragmentation (or MS(n)) and fast scan analysis, were employed to identify the phosphopeptides, determine their sequence and localize the exact site of phosphorylation. 'Blind' fragmentation using fast scans was used to analyze a phosphopeptide which was undetectable in other scanning modes. The sequence, phosphorylation site and double cysteine modification of the potassium adduct of a peptide containing 35 residues were also determined by multiple fragmentation. The results not only support the validity of the proposed method for routine identification of phosphorylation sites, but also demonstrate the exceptional capability of off-line ion trap mass spectrometry in combination with nanospray ionization for performing very detailed studies on the structure of peptides.
Affinity electrophoresis with monoclonal antibodies (1987)

Abstract Affinity electrophoresis was applied to the study of binding of monoclonal antibodies (MoAb's) with their respective antigens. The MoAb's may be either mixed with the antigen in an application well or incorporated into the agarose gel. The first approach is more convenient for studying high affinity MoAb's, while MoAb's with low affinity might be more efficiently studied in the second system. Our conditions for affinity electrophoresis do not imply nor necessitate immobilization of either an antigen or MoAb and are most suitable for studies of MoAb's reacting with antigens of alpha mobility demonstrated in experiments with MoAb's against human alpha‐fetoprotein (AFP). Both AFP‐MoAb and AFP‐MoAb‐AFP complexes were observed during electrophoresis. The identity of these complexes was confirmed by their reaction both with polyclonal antibodies against mouse immunoglobulins and against human AFP. The molecular weight of complexes was determined by gel filtration. Affinity electrophoresis was less convenient for studies of MoAb's reacting with antigens of gamma mobility at pH 8.6. Nevertheless, MoAb's against carcinomembryonic antigen, human IgG and human IgA did bind with their respective antigens under the conditions of affinity electrophoresis. The binding of MoAb's with these antigens during affinity electrophoresis was confirmed by demonstration of mouse immunoglobulins in the precipitates formed by reaction of the studied antigens with polyclonal antibodies. Our results point out the suitability of affinity electrophoresis for studies of MoAb's.
Trajectory determination for vibration-free motions of a flexible-joint robot (2005)

Acceleration profiles are developed for a two-link flexible-joint robot. These profiles generate point-to-point motion without residual vibration The command signals are derived using a minimum-energy performance index and solving the corresponding two-point boundary-value problem. By considering the full nonlinear dynamic model, this method determines input profiles that ensure minimum vibration when natural frequencies vary during the move.
A novel scheme combining interleaving technique with cipher in Rayleigh fading channels (2002)

This paper presents a novel scheme which consists of an interleaving technique and cipher simultaneously. The principle of the cipher lies in the random interleaving depth. The results of simulation show that the scheme can decrease the average interleaving delay compared to the conventional interleaving method at the same BER.