gebhart/patrepeval huggingface dataset:
In Vivo Positron Emission Tomography (PET) Imaging with an αvβ6 Specific Peptide Radiolabeled using 18F-“Click” Chemistry: Evaluation and Comparison with the Corresponding 4-[18F]Fluorobenzoyl- and 2-[18F]Fluoropropionyl-Peptides (2008)

Numerous radiolabeled peptides have been utilized for in vivo imaging of a variety of cell surface receptors. For applications in PET using [(18)F]fluorine, peptides are radiolabeled via a prosthetic group approach. We previously developed solution-phase (18)F-"click" radiolabeling and solid-phase radiolabeling using 4-[(18)F]fluorobenzoic and 2-[(18)F]fluoropropionic acids. Here we compare the three different radiolabeling approaches and report the effects on PET imaging and pharmacokinetics. The prosthetic groups did have an effect; metabolites with significantly different polarities were observed.
L-lyxose metabolism employs the L-rhamnose pathway in mutant cells of Escherichia coli adapted to grow on L-lyxose (1991)

Escherichia coli cannot grow on L-lyxose, a pentose analog of the 6-deoxyhexose L-rhamnose, which supports the growth of this and other enteric bacteria. L-Rhamnose is metabolized in E. coli by a system that consists of a rhamnose permease, rhamnose isomerase, rhamnulose kinase, and rhamnulose-1-phosphate aldolase, which yields the degradation products dihydroxyacetone phosphate and L-lactaldehyde. This aldehyde is oxidized to L-lactate by lactaldehyde dehydrogenase. All enzymes of the rhamnose system were found to be inducible not only by L-rhamnose but also by L-lyxose. L-Lyxose competed with L-rhamnose for the rhamnose transport system, and purified rhamnose isomerase catalyzed the conversion of L-lyxose into L-xylulose. However, rhamnulose kinase did not phosphorylate L-xylulose sufficiently to support the growth of wild-type E. coli on L-lyxose. Mutants able to grow on L-lyxose were analyzed and found to have a mutated rhamnulose kinase which phosphorylated L-xylulose as efficiently as the wild-type enzyme phosphorylated L-rhamnulose. Thus, the mutated kinase, mapped in the rha locus, enabled the growth of the mutant cells on L-lyxose. The glycolaldehyde generated in the cleavage of L-xylulose 1-phosphate by the rhamnulose-1-phosphate aldolase was oxidized by lactaldehyde dehydrogenase to glycolate, a compound normally utilized by E. coli.
Stretch-induced programmed myocyte cell death. (1995)

To determine the effects of loading on active and passive tensions, programmed cell death, superoxide anion formation, the expression of Fas on myocytes, and side-to-side slippage of myocytes, papillary muscles were exposed to 7-8 and 50 mN/mm2 and these parameters were measured over a 3-h period. Overstretching produced a 21- and a 2.4-fold increase in apoptotic myocyte and nonmyocyte cell death, respectively. Concurrently, the generation of reactive oxygen species increased 2.4-fold and the number of myocytes labeled by Fas protein 21-fold. Moreover, a 15% decrease in the number of myocytes included in the thickness of the papillary muscle was found in combination with a 7% decrease in sarcomere length and the inability of muscles to maintain stable levels of passive and active tensions. The addition of the NO-releasing drug, C87-3754, prevented superoxide anion formation, programmed cell death, and the alterations in active and passive tensions with time of overloaded papillary muscles. In conclusion, overstretching appears to be coupled with oxidant stress, expression of Fas, programmed cell death, architectural rearrangement of myocytes, and impairment in force development of the myocardium.
Primary structure of the "hinge" region of human IgG3. Probable quadruplication of a 15-amino acid residue basic unit. (1977)

The middle part of the heavy chain of IgG3 (hinge region) which covalently links the two gamma3 chains to each other, is about 4 times larger than the same region in the three other human IgG subclasses. This is probably due to a quadruplication of a 45-nucleotide DNA segment resulting in a gamma3 hinge region which is 62 amino acid residues long and consists of an NH2-terminal 17-residue segment followed by a 15-residue segment which is identically and consecutively repeated three times. The NH2-terminal 17-residue segment shows 70% homology with the repetitive 15-residue segment and appears to be the result of a small insertion and several point mutations of the same 45-nucleotide DNA stretch. Since this unit of repetition shows 60 to 70% homology with the hinge of the other IgG subclasses, it may represent the primitive IgG hinge.
Combined transfection with EBV-specific epitopes and HLA-A2 genes is more effective than separate transfection in promoting CTL lysis against nasopharyngeal carcinoma. (2004)

To augment specific cytotoxic T lymphocyte (CTL) lysis is a promising strategy for cancer therapy. In this study, we examined the boosting effect of CTLs upon autologous lymphoblastoid B cell lines (LCLs) transfected with diverse plasmids, to explore the possible CTL-based immunotherapy of nasopharyngeal carcinoma (NPC). FCM analysis displayed rather high ratio (>30%) of successfully transfected LCLs by utilizing the DMRIE-C kit. CTL assays demonstrated that substantially higher ratio of CTL specific lysis was observed upon the LCLs transfected with both expression vectors encoding EBV-specific epitopes and their presentation molecule HLA-A2, in contrast with those transfected separately. By transfecting the vector encoding HLA-A2 alone, only the LCLs of HLA-A2(+) donors elicited markedly higher CTL lysis. CTL assays also showed that there existed no marked differences upon transfection by either different vectors (pcDNA3, pNGVL3 or pNGVL3-hFlex), or different EBV-derived peptides (LMP(2)Pep1 or LMP(2)Pep2), or with or without the doubled DNA sequence encoding peptides. This study indicated a promising immunotherapy strategy on NPC through boosting and eliciting the EBV-specific CTL activation by transferring vectors encoding both EBV-specific epitopes and their presentation molecule HLA-A2 into autologous LCL, the presentation cells of MHC/peptide tetrameric complex.
The Scaffold/Matrix Attachment Region Binding Protein hnRNP-U (SAF-A) Is Directly Bound to Chromosomal DNA in Vivo:  A Chemical Cross-Linking Study (1997)

The protein heterogeneous nuclear ribonucleoprotein U (hnRNP-U, also known as scaffold attachment factor A, SAF-A) is an abundant component of hnRNP particles and of the nuclear matrix. Previous experiments have demonstrated that, in vitro, hnRNP-U specifically binds to scaffold/matrix attachment (S/MAR) region DNA elements and could thus be involved in higher order chromatin structure. In this paper we report on the use of chemical cross-linking to investigate whether the protein is also bound to DNA in vivo, which is a prerequisite for its presumed function in chromatin loop formation. We have improved published methods for cross-linking proteins to DNA with the aim to minimize unspecific fixation and possible contamination with RNA binding proteins. Our protocol is based on a limited cross-linking of living human cells with formaldehyde, followed by the purification of DNA/protein complexes by two consecutive cesium chloride density gradient centrifugations. Analysis of the protein constituents of these complexes shows a specific subset of cross-linked proteins with the histones as major components. By western blotting, we demonstrate that hnRNP-U is efficiently cross-linked to DNA under experimental conditions that yield DNA/protein complexes with a buoyant density equivalent to that of native chromatin. Dimethylsulfate cross-linking and limited protease digestion of the complexes was used to establish that hnRNP-U is bound directly to DNA and not via cross-linking to other proteins. This is the first direct demonstration of the in vivo DNA binding of a S/MAR specific protein and suggests a structural role of hnRNP-U in chromatin organization.
Sox17 is indispensable for acquisition and maintenance of arterial identity (2013)

The functional diversity of the arterial and venous endothelia is regulated through a complex system of signalling pathways and downstream transcription factors. Here we report that the transcription factor Sox17, which is known as a regulator of endoderm and hemopoietic differentiation, is selectively expressed in arteries, and not in veins, in the mouse embryo and in mouse postnatal retina and adult. Endothelial cell-specific inactivation of Sox17 in the mouse embryo is accompanied by a lack of arterial differentiation and vascular remodelling that results in embryo death in utero. In mouse postnatal retina, abrogation of Sox17 expression in endothelial cells leads to strong vascular hypersprouting, loss of arterial identity and large arteriovenous malformations. Mechanistically, Sox17 acts upstream of the Notch system and downstream of the canonical Wnt system. These data introduce Sox17 as a component of the complex signalling network that orchestrates arterial/venous specification.
A New Member of the Leucine Zipper Class of Proteins that Binds to the HLA DRα Promoter (1990)

Several mutants derived from transformed human B cell lines are defective in expressing major histocompatibility complex (MHC) class II genes. The failure to express a class II gene in at least one such mutant line has been mapped to the MHC class II X box, a conserved transcriptional element in the promoter region. A complementary DNA encoding a DNA-binding protein (human X box binding protein, hXBP-1) whose target is the human DR alpha X box and the 3' flanking region has now been cloned. This complementary DNA encoded a protein with structural similarities to the c-jun proto-oncogene product, and its target sequence was closely related to the palindromic target sequence of c-jun. Mutation of the hXBP-1 DNA target sequence decreased DR alpha promoter activity in vivo. These studies suggest that the hXBP-1 protein acts as a transcription factor in B cells.
On the analysis and fast implementation of oversampled modulated filter banks (2000)

Oversampled modulated filter banks (OSFBs) play an important role in reducing the computational cost of numerically intensive problems. The concern of this paper is an efficient implementation of the OSFB itself. The proposed method is based on a polyphase description to remove redundancies in the filter operations. Using OSFBs that are modulated from a prototyep filter, a factorisation can be obtained which depends on the filter coefficients the prototype filter and the modulating transform only. Based on a state-space representation of this polyphase factorisation, signal flow graphs can be obtained by minor modifications, which allow us a very simple and efficient implementation of OSFBs. A comparison to existing methods is drawn.
A Simplified Risk Score for Predicting Postoperative Nausea and Vomiting (1999)

The risk scores derived from one center proved valid in the other and could be simplified without significant loss of discriminating power. Therefore, it appears that this risk score has broad applicability in predicting PONV in adult patients undergoing inhalational anesthesia for various types of surgery. For patients with at least two out of these four identified predictors a prophylactic antiemetic strategy should be considered.
Prognostic Value of Placental Growth Factor in Patients With Acute Chest Pain (2004)

Plasma PlGF levels may be an independent biomarker of adverse outcome in patients with suspected ACS. A single initial measurement of plasma PlGF appears to extend the predictive and prognostic information gained from traditional inflammatory markers.
Downregulation of Urokinase-Type and Tissue-Type Plasminogen Activators in a Rabbit Model of Renal Ischemia/Reperfusion (2002)

Urokinase-type and tissue-type plasminogen activators (uPA, tPA) are key enzymes for starting the plasminogen system, which plays important roles in various physiological and pathological conditions. In order to examine the gene regulation in rabbit pathophysiological models we attempted to clone full-length cDNAs encoding uPA and tPA from kidney extracts of rabbit (Oryctolagus cuniculus) by reverse transcription-polymerase chain reaction and rapid amplification of cDNA ends. The cloned rabbit uPA and tPA cDNAs were 2,350 and 2,561 bp in length, respectively, and the basic molecular structures predicted from the cDNAs were well-conserved compared with human uPA and tPA. In a rabbit model of renal ischemia/reperfusion (I/R), the expression of uPA and tPA mRNAs was down-regulated and that of their physiological inhibitor, type 1 plasminogen activator inhibitor, mRNA was up-regulated in ischemic kidney compared to non-ischemic kidney. In addition, fibrinolytic activity in ischemic kidney was lower than that in non-ischemic kidney. It is suggested that repression of fibrinolysis in the kidneys in rabbit I/R may contribute to the progression of renal damage in the model.
Sacral nerve stimulation for fecal incontinence (2011)

sacral nerve stimulation is a simple technique that improves Wexner scores in a statistically significant manner with a low complications rate.
Limits of Predictive Models Using Microarray Data for Breast Cancer Clinical Treatment Outcome (2005)

Data from microarray studies have been used to develop predictive models for treatment outcome in breast cancer, such as a recently proposed predictive model for antiestrogen response after tamoxifen treatment that was based on the expression ratio of two genes. We attempted to validate this model on an independent cohort of 58 patients with resectable estrogen receptor-positive breast cancer. We measured expression of the genes HOXB13 and IL17BR with real time-quantitative polymerase chain reaction and assessed the association between their expression and outcome by use of univariate logistic regression, area under the receiver-operating-characteristic curve (AUC), a two-sample t test, and a Mann-Whitney test. We also applied standard supervised methods to the original microarray dataset and to another independent dataset from similar patients to estimate the classification accuracy obtainable by using more than two genes in a microarray-based predictive model. We could not validate the performance of the two-gene predictor on our cohort of samples (relation between outcome and the following genes estimated by logistic regression: for HOXB13, odds ratio [OR] = 1.04, 95% confidence interval [CI] = 0.92 to 1.16, P = .54; for IL17BR, OR = 0.69, 95% CI = 0.40 to 1.20, P = .18; and for HOXB13/IL17BR, OR = 1.30, 95% CI = 0.88 to 1.93, P = .18). Similar results were obtained with the AUC, a two-sample two-sided t test, and a Mann-Whitney test. In addition, estimates of classification accuracies applied to two independent microarray datasets highlighted the poor performance of treatment-response predictive models that can be achieved with the sample sizes of patients and informative genes to date.
Different amino acid substitutions at the same position in the nucleotide-binding site of aspartate transcarbamoylase have diverse effects on the allosteric properties of the enzyme. (1991)

Site-directed mutagenesis was used to determine how the allosteric properties of aspartate transcarbamoylase (ATCase) are affected by amino acid replacements in the nucleotide binding region of the regulatory polypeptide chains. Amino acid substitutions were made for both Lys-60 and Lys-94 in the regulatory chain since those residues have been implicated by x-ray diffraction studies, chemical modification experiments, and site-directed mutagenesis as playing a role in binding CTP and ATP. Lys-60 was replaced by His, Arg, Gln, and Ala, and Lys-94 was changed to His. These mutant forms of ATCase exhibit bewildering changes in the allosteric properties compared to the wild-type enzyme as well as altered affinities for the nucleotide effectors. The enzyme containing His-60 lacks both homotropic and heterotropic effects and exhibits no detectable binding of nucleotides. In contrast, the holoenzymes containing either Gln-60 or Arg-60 retain both homotropic and heterotropic effects. Replacement of Lys-60 by Ala yields a derivative exhibiting altered heterotropic effects involving insensitivity to CTP and activation by ATP. The mutant enzyme containing His-94 in place of Lys exhibits cooperativity with reduced affinity for nucleotides. The multiple substitutions at Lys-60 in the nucleotide binding region of the regulatory chains of ATCase demonstrate that different amino acids in the same location can alter indirectly the delicate balance of interactions responsible for the allosteric properties of ATCase. The studies show that it is hazardous and frequently unwarranted from single amino acid replacements of a specific residue to attribute to that residue the properties observed for the wild-type enzyme.
Time-Dependent Behavior of Block Polyelectrolyte Micelles in Aqueous Media Studied by Potentiometric Titrations, QELS and Fluorometry (2000)

Block polyelectrolyte samples containing long hydrophobic blocks, e.g., polystyrene, and long polyelectrolyte blocks, e.g., poly(methacrylic acid), do not dissolve in aqueous media. However, multimolecular micelles consisting of compact polystyrene cores and polyelectrolyte shells may be prepared by dialysis from organic solvent−water mixtures into aqueous buffers. Polystyrene cores are kinetically frozen in water and the behavior of the micellar systems is determined by the polyelectrolyte behavior of the shell. Poly(methacrylic acid) does not represent a typical polyelectrolyte. Due to the presence of a strongly hydrophobic methyl group in each repeating unit, its behavior more resembles that of a polysoap. In aqueous micellar systems, poly(methacrylic acid) chains form a fairly compact hydrophobic layer close to the core/shell interface. In our recent works, we have found that the state of the inner part of the shell responds rather slowly to shock changes in the bulk pH and the ionic strength of the solution. In this work, we use a combination of potentiometry, QELS, and fluorometry to study the time-dependent behavior of polyelectrolyte micellar shells.
cycloSal Phosphates as Chemical Trojan Horses for Intracellular Nucleotide and Glycosylmonophosphate Delivery — Chemistry Meets Biology (2005)

Abstract Pronucleotides represent a promising alternative to improve the biological activity of nucleoside analogs in antiviral and cancer chemotherapy. In addition, pronucleotides are valuable tools for studies regarding the nucleoside/nucleotide metabolism. The aim is to achieve nucleotide delivery into cells and thereby bypass limitations during intracellular formation of nucleotides from their nucleoside precursors. The cyclo Sal approach is one of several conceptually different pronucleotide systems known but is the only approach in which a pronucleotide is cleaved successfully by simple but selective chemical hydrolysis. The basic concept, chemistry, different structural modifications, and their effects on the antiviral potency of the cyclo Sal d4TMP triesters are briefly discussed first. Then, the application of the approach to various biologically active nucleoside analogs against different targets is summarized. In the second part, the results of a conceptual extension of the cyclo Sal approach are presented: once cyclo Sal pronucleotides have passed the membrane, they should be trapped inside the cells after an enzyme‐catalyzed process and then release the nucleotide. Finally, results are summarized that demonstrate that the cyclo Sal approach is not restricted to the delivery of bioactive nucleotides but is also applicable to the intracellular delivery of hexose‐1‐phosphates. Chemical synthesis, biophysical studies, and biological evaluation will be discussed in combination throughout this paper to demonstrate the strength of the cyclo Sal approach. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2006)
Targeting of ganglioside GD2 monoclonal antibody to neuroblastoma. (1987)

The biodistribution of 3F8, and IgG3 murine monoclonal antibody (MoAb) specific for the disialoganglioside GD2, was studied in nude mice xenografted with human neuroblastoma (NB). 3F8 conjugated to radioactive iodine and injected intravenously localized selectively to seven human NB when compared with Ewing's sarcoma and Hela cell xenograft controls. Uptake in NB was shown to be specific for MoAb 3F8 when contrasted with pooled mouse IgG or irrelevant IgG3 MoAb controls. Both small (50 mg) and large tumors greater than 2 g) showed radiolocalization. The percent injected dose uptake per gram tumor ranged from 8 to 50% and was inversely correlated with tumor size. Optimal tumor to normal tissue ratios were reached by 24-48 hr. There was no abnormal uptake in the reticuloendothelial system and the MoAb did not cross the blood-brain barrier. Based on the kinetics of the amount of radioactivity deposited in tissues, the relative radiation dose to normal organs was estimated to be 1% to 20% of the tumor dose. The MoAb 3F8 is useful for targeting radioactivity to human NB in vivo and the nude mice xenograft model may allow optimization of parameters that influence such biodistribution.
Intercellular adhesion molecule-2, a second counter-receptor for CD11a/CD18 (leukocyte function-associated antigen-1), provides a costimulatory signal for T-cell receptor-initiated activation of human T cells (1992)

Activation of T cells often requires both activation signals delivered by ligation of the TCR and those resulting from costimulatory interactions between certain T cell surface accessory molecules and their respective counter-receptors on APC. CD11a/CD18 complex on T cells modulate the activation of T cells by interacting with its counter-receptors intracellular adhesion molecule (ICAM-1) (CD54) and/or ICAM-2 on the surface of APC. The costimulatory ability of ICAM-1 has been demonstrated. Using a soluble ICAM-2 Ig fusion protein (receptor globulin, Rg) we demonstrate the costimulatory effect of ICAM-2 during the activation of CD4+ T cells. When coimmobilized with anti-TCR-1 mAb ICAM-2 Rg induced vigorous proliferative response of CD4+ T cells. This costimulatory effect of ICAM-2 was dependent on its coimmobilization with mAb directed at the CD3/TCR complex but not those directed at CD2 or CD28. Both resting as well as Ag-primed CD4+ T cells responded to the costimulatory effects of ICAM-2. The addition of mAb directed at the CD11a or CD18 molecules almost completely inhibited the responses to ICAM-2 Rg. These results are consistent with the role of CD11a/CD18 complex as a receptor for ICAM-2 mediating its costimulatory effects. Stimulation of T cells with coimmobilized anti-TCR-1 and ICAM-2 resulted in the induction of IL-2R (CD25), and anti-Tac (CD25) mAb inhibited this response suggesting the contribution of endogenously synthesized IL-2 during this stimulation. These results demonstrate that like its homologue ICAM-1, ICAM-2 also exerts a strong costimulatory effect during the TCR-initiated activation of T cells. The costimulatory effects generated by the CD11a/CD18:ICAM-2 interaction may be critical during the initiation of T cell activation by ICAM-1low APC.
Sphingosine-1-phosphate effects on guinea pig atrial myocytes: Alterations in action potentials and K+ currents (2006)

I(K(S-1-P)) is carried by weakly inwardly-rectifying K+ channels that are the same as those activated by ACh. This K+ current can markedly shorten APD in guinea pig atrial myocytes. This effect would be expected to increase the incidence of atrial rhythm disturbances.