gebhart/patrepeval huggingface dataset:
Identification of Thioaptamer Ligand against E-Selectin: Potential Application for Inflamed Vasculature Targeting (2010)

Active targeting of a drug carrier to a specific target site is crucial to provide a safe and efficient delivery of therapeutics and imaging contrast agents. E-selectin expression is induced on the endothelial cell surface of vessels in response to inflammatory stimuli but is absent in the normal vessels. Thus, E-selectin is an attractive molecular target, and high affinity ligands for E-selectin could be powerful tools for the delivery of therapeutics and/or imaging agents to inflamed vessels. In this study, we identified a thiophosphate modified aptamer (thioaptamer, TA) against E-selectin (ESTA-1) by employing a two-step selection strategy: a recombinant protein-based TA binding selection from a combinatorial library followed by a cell-based TA binding selection using E-selectin expressing human microvascular endothelial cells. ESTA-1 selectively bound to E-selectin with nanomolar binding affinity (K(D) = 47 nM) while exhibiting minimal cross reactivity to P- and L-selectin. Furthermore, ESTA-1 binding to E-selectin on the endothelial cells markedly antagonized the adhesion (over 75% inhibition) of sLe(x) positive HL-60 cells at nanomolar concentration. ESTA-1 also bound specifically to the inflamed tumor-associated vasculature of human carcinomas derived from breast, ovarian, and skin but not to normal organs, and this binding was highly associated with the E-selectin expression level. Similarly, intravenously injected ESTA-1 demonstrated distinct binding to the tumor vasculature in a breast cancer xenograft model. Together, our data substantiates the discovery of a thioaptamer (ESTA-1) that binds to E-selectin with high affinity and specificity, thereby highlighting the potential application of ESTA-1 for E-selectin targeted delivery.
Organization and evolution of immunoglobulin VH gene subgroups. (1982)

The organization and evolution of immunoglobulin variable region genes was studied by comparing human and mouse heavy chain variable region (VH) genes. We show that a VH gene subgroup constitutes a physically linked multigene family separated from another VH subgroup. We mapped the VHIII gene subgroup to be 3' to the VHII gene subgroup based on deletion of VH genes after V-D-J rearrangement. The results indicate that the human VHIII gene subgroup underwent a significant gene expansion as compared to the mouse VHIII subgroup. Amino acid sequence data indicate that human VHIII genes correspond to only a small subset of mouse VHIII genes. Human VHIII genes contain a shorter intron and are two codons shorter than most BALB/c mouse VHIII genes. The nature of nucleotide substitutions between VH genes within a species (human) is similar to that between genes of different species (human/mouse). Both contain approximately 50% silent substitutions.
PC9, A New Actor in Autosomal Dominant Hypercholesterolemia (2005)

First named Narc-1 (Neural apoptosis regulated convertase 1), PC9 is the ninth member of the family of proprotein convertases. This newly identified human subtilase contributes to cholesterol homeostasis and mutations in its gene, PCSK9 (Proprotein Convertase Subtilisin/Kexin type 9), are responsible for Autosomal Dominant Hypercholesterolemia. This is the first example of a dominant disease associated with a defect in a member of the convertase family. Hypercholesterolemia is a main risk factor of atherosclerosis and its vascular complications. In the general population, about 1 person out of 20 presents high plasma LDL-cholesterol. In particular, familial forms with autosomal dominant transmission affect about 1 person out of 500. Until recently, mutations in only two genes were associated with the disease: the LDLR gene encoding a transmembrane receptor implicated in endocytosis and degradation of circulating LDL, and the APOB gene encoding the main ligand of this receptor present at LDL surface. Pathophysiology of these two main forms of the disease has been extensively studied and is well understood. In 1999, two teams simultaneously published hypercholesterolemic families presenting neither LDLR nor APOB defects and, in 2003, a third major gene involved in Autosomal Dominant Hypercholesterolemia, PCSK9, was identified. To date, no substrate of PC9 has been found except itself. The purpose of the present review is to compile all reported data and current knowledge on PC9 and hypotheses of its role in cholesterol homeostasis and in pathophysiology of hypercholesterolemia. Keywords: Autosomal Dominant Hypercholesterolemia, PCSK9, PC9, Narc-1, proprotein convertase, LDL receptor, SREBP, VLDL
Using iRT, a normalized retention time for more targeted measurement of peptides (2012)

Multiple reaction monitoring (MRM) has recently become the method of choice for targeted quantitative measurement of proteins using mass spectrometry. The method, however, is limited in the number of peptides that can be measured in one run. This number can be markedly increased by scheduling the acquisition if the accurate retention time (RT) of each peptide is known. Here we present iRT, an empirically derived dimensionless peptide-specific value that allows for highly accurate RT prediction. The iRT of a peptide is a fixed number relative to a standard set of reference iRT-peptides that can be transferred across laboratories and chromatographic systems. We show that iRT facilitates the setup of multiplexed experiments with acquisition windows more than four times smaller compared to in silico RT predictions resulting in improved quantification accuracy. iRTs can be determined by any laboratory and shared transparently. The iRT concept has been implemented in Skyline, the most widely used software for MRM experiments.
Robot kinematics learning computations using polynomial neural networks (2002)

The group method of data handling (GMDH), a data analysis technique for identification of nonlinear complex systems, is a feature-based mapping neural network. It is also an example of a polynomial neural network (PNN). The PNN can be trained to interpolate an unknown function by observing few samples. The PNN, a major type of neural network used in airborne combat applications is used to interpolate robot forward and inverse kinematics computations (FKC and IKC). The FKC and IKC are used, respectively, to find the mapping from the joint space to the Cartesian space and to find the mapping from the Cartesian space to joint space. A PPN simulation software package has been developed for solving both FKC and IKC. The simulation is performed in a two-degree-of-freedom manipulator. The solutions of the FKC and IKC networks are compared with the analytic equations. The PNN learns successfully the indicated path. The simulation results show that the PNN can interpolate the indicated path with better than 99.87% accuracy when the PNN network has been trained on 361 data pairs. The approach can be expanded to six-degree-of-freedom manipulators. Detailed GMDH algorithms for constructing the PNN kinematics models are discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
THE FATTY ACID AND STEROL COMPOSITION OF FIVE MARINE DINOFLAGELLATES (1999)

The fatty acid and sterol compositions of five species of marine dinoflagellates ( Scrippsiella sp. Symbiodinium microadriaticum Freud, Gymnodinium sp., Gymnodinium sanguineum Hirasaki, and Fragilidium sp.) are reported. All contained the major fatty acids that are considered common in dinoflagellates, but the proportions were quite variable, and some species contained low contents of some polyunsaturated fatty acids. Concentration ranges for the major fatty acids were: 16:0 (9.0%–24.8%), 18:4(n‐3) (2.5%–11.5%), 18:5(n‐3) (7.0%–43.1%), 20:5(n‐3) (EPA) (1.8%–20.9%), and 22:6(n‐3) (DHA) (9.9%– 26.3%). Small amounts of novel very‐long‐chain highly unsaturated C 28 fatty acids occurred in all species. Each dinoflagellate contained a complex mixture of 4‐methyl sterols and 4‐desmethyl sterols. Four species contained cholesterol, although the amounts were highly variable (from 0.2% of total sterols in Scrippsiella sp. to 45.6% in Fragilidium sp.). All but G. sanguineum contained the 4‐methyl sterol dinosterol, and all species contained sterols lacking a double bond in the ring system (i.e. stanols); in Scrippsiella sp. cholestanol composed 24.3% of the total sterols. Other common features of the 4‐methylsterol profiles were the presence of 23,24‐dimethyl alkylation and unsaturation at Δ 22 in the side chain. In Scrippsiella sp., four steroidal ketones were identified: cholestanone, dinosterone, 4α,23,24‐trimethyl‐5α‐cholest‐8(14)‐en‐3‐one, and dinostanone. The structures of these corresponded to the major sterols in this species, suggesting that the sterols and steroidal ketones are biosynthetically linked. Steroidal ketones were not detected in the other species. Although fatty acid profiles can be used to distinguish among algal classes, they were not useful for differentiating among dinoflagellate species. In contrast, whereas some taxonomic groupings of dinoflagellates display similar sterol patterns, others, such as the gymnodinoids studied here, clearly do not. The combination of fatty acid, sterol, and steroidal ketone profiles may be useful complementary chemotaxonomic tools for distinguishing morphologically similar species. The identification of steroidal ketones supports earlier suggestions that certain dinoflagellates might be a significant source of such components in marine environments.
Tapasin-Mediated Retention and Optimization of Peptide Ligands During the Assembly of Class I Molecules (2000)

The murine class I H-2Kb molecule achieves high level surface expression in tapasin-deficient 721.220 human cells. Compared with their behavior in wild-type cells, Kb molecules expressed on 721.220 cells are more receptive to exogenous peptide, undergo more rapid surface decay, and fail to form macromolecular peptide loading complexes. As a result, they are rapidly transported to the cell surface, reflecting a failure of endoplasmic reticulum retention mechanisms in the absence of loading complex formation. Despite the failure of Kb molecules to colocalize to the TAP and their rapid egress to the cell surface, Kb is still capable of presenting TAP-dependent peptides in the absence of tapasin. Furthermore, pool sequencing of peptides eluted from these molecules revealed strict conservation of their canonical H-2Kb-binding motif. There was a reduction in the total recovery of peptides associated with Kb molecules purified from the surface of tapasin-deficient cells. Comparison of the peptides bound to Kb in the presence and absence of tapasin revealed considerable overlap in peptide repertoire. These results indicate that in the absence of an interaction with tapasin, Kb molecules fail to assemble with calreticulin and TAP, yet they are still capable of acquiring a diverse array of peptides. However, a significant proportion of these peptides appear to be suboptimal, resulting in reduced cell surface stability of Kb complexes. Taken together, the findings indicate that tapasin plays an essential role in the formation of the class I loading complex, which retains class I heterodimers in the endoplasmic reticulum until optimal ligand selection is completed.
Silicon photovoltaic cells in TPV conversion (1979)

An experimental and theoretical investigation of thermophotovoltaic (TPV) energy conversion using silicon photovoltaic cells has been performed. These cells are intended for use in a proposed solar-electric system that, in concept, uses concentrating mirrors focused on a TPV converter that operates at high power density and high efficiency. Within the TPV converter, the concentrated sunlight heats a refractory radiator. Photovoltaic cells face the radiator, receive incandescent radiation from it, and convert this radiation into electricity. A previously developed numerical model of TPV conversion and a TPV test facility were used to test TPV cells and correlate the results with theory. The important cell parameters have been identified and investigated. The accuracy of the TPV model has been verified. Continued processing and TPV cell design development has taken the measured energy conversion efficiencies from 14 to 26 percent during the report period. Using parameters that are now thought reasonable, the TPV model predicts that mature TPV cells will have efficiencies around 43 percent.
In Vivo Assembly of the τ-Complex of the DNA Polymerase III Holoenzyme Expressed from a Five-Gene Artificial Operon (1996)

A plasmid was constructed that encodes all five subunits of the Escherichia coli tau-complex on a single artificially constructed operon under the control of an inducible promoter. The proteins tau, delta, delta , chi, and psi overproduced from this artificial operon assemble efficiently in vivo, providing an efficient source of homogeneous tau-complex. The gamma subunit is a truncated form of tau that is produced by a translational frameshift. When protein expression was induced in bacterial strains containing the outer membrane protein T (OmpT) protease, tau was proteolyzed after lysis to a gamma-like protein, gammaP, and a peptide, C-tau, corresponding to the C terminus of tau. N-terminal sequencing of C-tau revealed a cleavage site between two lysines at positions 429 and 430 of tau. The deduced sequence of gammaP is, therefore, only two amino acids shorter than natural gamma. The proteolysis by OmpT was also shown directly by using purified OmpT and tau-complex in an in vitro reaction. A gammaP-complex and a mixed tau-gammaP-complex were purified from ompT+ cells. When the tau-complex proteins were overexpressed in ompT- bacteria, intact tau-complex lacking gammaP could be purified.
Fertilization and early embryology: Time-course of oocyte activation, pronucleus formation and cleavage in human oocytes fertilized by intracytoplasmic sperm injection (1994)

Knowledge of the timing of the stages of fertilization in humans is still limited because the time of gamete fusion is not known when pre-ovulatory or in-vitro matured cumulus-enclosed oocytes are inseminated. We therefore studied the morphological nuclear changes in 14 patients' oocytes by means of light microscopic observation at 2, 4, 6, 8, 16, 18 and at 20 h after intracytoplasmic single sperm injection (ICSI). A total of 144 metaphase II oocytes were injected with the spermatozoa of the patients' partners. Out of the 134 oocytes that survived the injection, 93 displayed two pronuclei in the course of the observation period (69%). Out of the 93 normally fertilized oocytes, 21 extruded the second polar body at 2 h after micro-injection (23%) and 63 oocytes at 4 h (68%). Pronuclei appeared as early as 6 h after ICSI in 16 normally fertilized oocytes (17%). At 8 h, 75 (80%) oocytes had two visible pronuclei, at 16 h 92 (99%), at 18 h 76 (82%) and at 20 h 63 (68%). In 24 oocytes (26%) the appearance of pronuclei was asynchronous, while the disappearance of the pronuclei was always synchronous, except in one oocyte. Nine of the 134 successfully injected oocytes showed three equal-sized pronuclei (6.7%). Four of the nine multi-pronucleated oocytes did not extrude the second polar body at all, while the time sequence of appearance of pronuclei was similar to that of the normally fertilized oocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Platelet Activating Factor and Thromboxane B2Production After Cardiopulmonary Bypass (1997)

Platelet-activating factor (PAF) is believed to have a central role in the pathogenesis of ischemia-reperfusion injury. The purpose of this study was to investigate the relationships among production of PAF, thromboxane B2 (T alpha B2), and cardiopulmonary sequelae in patients undergoing coronary artery bypass graft surgery (CABGS). Venous blood from nine patients (eight men, one woman) undergoing scheduled CABGS, was sampled from central venous catheters before anesthetic induction, pre-cardiopulmonary bypass (CPB), 10 and 30 minutes post-CPB, 10 and 30 minutes post-aortic declamping, and 120 minutes and 24 hours after the conclusion of CPB. Plasma levels of PAF and T alpha B2 were determined by radioimmunoassay kits (Amersham Canada Ltd.). PAF and T alpha B2 were significantly different between high-risk patients (group I; Canadian Cardiovascular Society class 3-4; n = 4) and low-risk patients (group II; Canadian Cardiovascular Society class 2; n = 5): group I PAF = 960 pg/mL, group II PAF = 159 pg/mL (P = 0.0029); group I T alpha B2 = 320 pg/mL, group II T alpha B2 = 229 pg/mL (P = 0.0262). Group I PAF was significantly greater than group II PAF: before CPB = 825 pg/mL (group I), 138 pg/mL (group II); during initiation of CPB = 1600-2015 pg/mL (group I), 158-200 pg/mL (group II) (P = 0.0143). Correlations between duration of CPB and peak PAF (r = 0.7049, P = 0.0339), peak PAF level, and time to extubation (r = 0.8863, P = 0.0079) were significant. PAF levels were different in patients requiring postoperative epinephrine (2124 +/- 700 pg/mL) or dopamine (667 +/- 266 pg/mL) (P = 0.0042). The production of PAF is determined by preoperative patient characteristics and duration of CPB. Increased levels of PAF in patients with unstable angina, left main coronary artery disease, or recent myocardial infarction are associated with the need for increased inotropy and prolonged ventilatory support following CABGS. The degree of PAF production during CPB may be a factor in postoperative instability in high-risk patients.
Intracellular distribution of microinjected antisense oligonucleotides. (1991)

Antisense oligomers constitute an attractive class of specific tools for genetic analysis and for potential therapeutic applications. Targets with different cellular locations have been described, such as mRNA translation initiation sites, pre-mRNA splicing sites, or the genes themselves. However the mechanism(s) of action and the intracellular distribution of antisense oligomers remain poorly understood. Antisense oligomers conjugated with various fluorochromes or with BrdUrd were microinjected into the cytoplasm of somatic cells, and their cellular distribution was monitored by fluorescence microscopy in fixed and nonfixed cells. A fast translocation in the nuclei and a concentration on nuclear structures were observed whatever probe was used. Nuclear transport occurs by diffusion since it is not affected by depletion of the intracellular ATP pool, temperature, or excess unlabeled oligomer. Accumulation of the oligomers in the nuclei essentially takes place on a set of proteins preferentially extracted between 0.2 M and 0.4 M NaCl as revealed by crosslinking of photosensitive oligomers. The relationship between nuclear location of antisense oligomers and their mechanism of action remains to be ascertained and could be of major interest in the design of more efficient antisense molecules.
Cytokine Reduction in the Treatment of Joint Conditions (1994)

The destruction of joints caused by rheumatoid arthritis and osteoarthritis is characterized by an imbalance of enzyme catalysed cartilage breakdown and regeneration. A complex cytokine network perpetuates joint conditions by direct regulation of metalloproteases, by indirect recruitment of cells that secrete degradative enzymes, and by inhibition of reparative processes. The destructive action of cytokines such as interleukin-1, interleukin-6 and tumour necrosis factor-alpha can be modulated at multiple points associated either with cytokine production or with cytokine action. Potential agents for cytokine reduction include selective anti-cytokine antibodies, anticytokine receptor antibodies, cytokine receptor antagonist proteins, and soluble and chimeric cytokine receptor molecules. Pharmacologic regulation of IL-1 and TNFalpha remain primary targets for treatment of arthritis, and results of early clinical trials are promising. However, the results of long-term clinical trials will be required to support the value of anti-cytokine therapy in treatment of arthritis.
Cytokine quantitation: technologies and applications (2007)

Assessment of cytokines in body fluids, cells or tissues provides important information in understanding of disease process and designing treatment strategies. Today, wide range of cytokine assays are available, including; measurement of levels of cytokines (direct) or cytokine soluble receptor levels (indirect) in body fluids or cellular supernatants (immunoassays and cytokine bioassays), measurement of cytokines produced by population of cells (multiparametric flow cytometry, magnetic beads based quantitation of cytokine producing cells, mRNA based assays), measurement of cytokines produced by single cells (Enzyme-linked immunospot (ELISPOT), Intra-cytoplasmic cytokine staining (ICC), mRNA based assays) and detection of cytokines in tissues (immunostaining). Improved understanding of cytokine interactions has led to a consensus that simultaneous assessment of many cytokines in a biological sample provides more comprehensive information rather than assessing a single cytokine. Thus, technologies that measure one cytokine at a time are being gradually replaced by multiplex-type formats (DNA and protein microarrays).
Effect of oxygen pressure on the orthorhombic-tetragonal transition in the high-temperature superconductorYBa2Cu3Ox (1988)

High-resolution in situ x-ray-diffraction measurements were made of the lattice constants of ${\mathrm{YBa}}_{2}$${\mathrm{Cu}}_{3}$${\mathrm{O}}_{\mathrm{x}}$ as it was heated and cooled through the orthorhombic-tetragonal transition at a series of ${\mathrm{O}}_{2}$ pressures. The transition is sharp, continuous, and reversible in temperature and pressure. As ${\mathrm{O}}_{2}$ pressure is reduced from 1.0 to 0.005 atm, the transition temperature falls from 676\ifmmode\pm\else\textpm\fi{}5 \ifmmode^\circ\else\textdegree\fi{}C to 521\ifmmode\pm\else\textpm\fi{}10 \ifmmode^\circ\else\textdegree\fi{}C while oxygen content at the transition falls from 6.66\ifmmode\pm\else\textpm\fi{}0.01 to 6.59\ifmmode\pm\else\textpm\fi{}0.02. Dilation along the c axis is observed as oxygen is removed. Under helium, an irreversible but time-dependent orthorhombic-to-tetragonal transition occurs during heating.
Towards an understanding of decision complexity in IT configuration (2007)

In previous work we laid out an approach to quantifying configuration complexity [3]. In that earlier work, we explicitly focused on complexity as experienced by expert systems managers, and thus looked at straight-line configuration procedures, ignoring the complexity faced by non-experts as they have to decide what configuration steps to follow. Decision complexity is the complexity faced by a non-expert system administrator---the person providing IT support in a small-business environment, who is confronted by decisions during the configuration process, and is a measure of how easy or hard it is to identify the appropriate sequence of configuration actions to perform in order to achieve a specified configuration goal. To identify spots of high decisionmaking complexity, we need a model of decision complexity for configuring and operating computing systems. This paper extends previous work on models and metrics for IT configuration complexity by adding the concept of decision complexity. As the first step towards a complete model of decision complexity, we describe an extensive user study of decision making in a carefully-mapped analogous domain (route planning), and illustrate how the results of that study suggest an initial model of decision complexity applicable to IT configuration. The model identifies the key factors affecting decision complexity and highlights several interesting results, including the fact that decision complexity has significantly different impacts on user-perceived difficulty than on objective measures like time and error rate. We also describe some of the implications of our decision complexity model for system designers seeking to automate the decision-making and reduce the configuration complexity of their systems.