gebhart/patrepeval huggingface dataset:
Effect of dietary docosahexaenoic acid on desaturation and uptake in vivo of isotope‐labeled oleic, linoleic, and linolenic acids by male subjects (1999)

The effect of dietary docosahexaenoic acid (22:6n-3, DHA) on the metabolism of oleic, linoleic, and linolenic acids was investigated in male subjects (n = 6) confined to a metabolic unit and fed diets containing 6.5 or <0.1 g/d of DHA for 90 d. At the end of the diet period, the subjects were fed a mixture of deuterated triglycerides containing 18:1n-9[d6], 18:2n-6[d2], and 18:3n-3[d4]. Blood samples were drawn at 0, 2, 4, 6, 8, 12, 24, 48, and 72 h. Methyl esters of plasma total lipids, triglycerides, phospholipids, and cholesterol esters were analyzed by gas chromatography-mass spectrometry. Chylomicron triglyceride results show that the deuterated fatty acids were equally well absorbed and diet did not influence absorption. Compared to the low-DHA diet (LO-DHA), clearance of the labeled fatty acids from chylomicron triglycerides was modestly higher for subjects fed the high DHA diet (HI-DHA). DHA supplementation significantly reduced the concentrations of most n-6[d2] and n-3[d4] long-chain fatty acid (LCFA) metabolites in plasma lipids. Accumulation of 20:5n-3[d4] and 22:6n-3[d4] was depressed by 76 and 88%, respectively. Accumulations of 20:3n-6[d2] and 20:4n-6[d2] were both decreased by 72%. No effect of diet was observed on acyltransferase selectivity or on uptake and clearance of 18:1n-9[d6], 18:2n-6[d2], and 18:3n-3[d4]. The results indicate that accumulation of n-3 LCFA metabolites synthesized from 18:3n-3 in typical U.S. diets would be reduced from about 120 to 30 mg/d by supplementation with 6.5 g/d of DHA. Accumulation of n-6 LCFA metabolites synthesized from 18:2n-6 in U.S. diets is estimated to be reduced from about 800 to 180 mg/d. This decrease is two to three times the amount of n-6 LCFA in a typical U.S. diet. These results support the hypothesis that health benefits associated with DHA supplementation are the combined result of reduced accretion of n-6 LCFA metabolites and an increase in n-3 LCFA levels in tissue lipids.
Stability of Self-Assembled Polymeric Micelles in Serum (2011)

The stability of polymeric nanoparticles in serum is critical to their use in drug delivery where dilution after intravenous injection often results in nanoparticle disassembly and drug unloading; however, few investigate this in biologically relevant media. To gain greater insight into nanoparticle stability in blood, the stability of self-assembled polymeric micelles of poly(d,l-lactide-co-2-methyl-2-carboxytrimethylene carbonate)-g-poly(ethylene glycol), P(LA-co-TMCC)-g-PEG, were tested in both serum and individual serum protein solutions. By encapsulating Förster resonance energy transfer pairs and following their release by fluorescence, these micelles demonstrated excellent thermodynamic and kinetic stability in the presence of serum. Further analyses by fast protein liquid chromatography and dynamic light scattering confirmed these data. Moreover, these micelles are compatible with red blood cells, as shown by a hemolysis assay. The stability and compatibility demonstrated in blood suggest that these micelles may be stable in vivo, which is critical for intravenous drug delivery applications. This comprehensive approach to understanding micelle stability and compatibility is broadly applicable.
Advances in welding science and technology (1995)

Over the years, welding has been more of an art than a science, but in the last few decades major advances have taken place in welding science and technology. With the development of new methodologies at the crossroads of basic and applied sciences, enormous opportunities and potential exist to develop a science-based design of composition, structure, and properties of welds with intelligent control and automation of the welding processes. In the last several decades, welding has evolved as an interdisciplinary activity requiring synthesis of knowledge from various disciplines and incorporating the most advanced tools of various basic applied sciences. A series of international conferences and other publications have covered the issues, current trends and directions in welding science and technology. In the last few decades, major progress has been made in (i) understanding physical processes in welding, (ii) characterization of microstructure and properties, and (iii) intelligent control and automation of welding. This paper describes some of these developments.
Coupling of Mitotic Chromosome Tethering and Replication Competence in Epstein-Barr Virus-Based Plasmids (2001)

The Epstein-Barr virus (EBV) replicates once per cell cycle and segregates with high efficiency yet does not encode the enzymes needed for DNA replication or the proteins required to contact mitotic spindles. The virus-encoded EBNA-1 (EBV nuclear antigen 1) and latent replication origin (oriP) are required for both replication and segregation. We developed a sensitive and specific fluorescent labeling strategy to analyze the interactions of both EBNA-1 with viral episomes and viral episomes with host chromosomes. This enabled investigation of the hypothesis that replication and chromosome tethering are linked through the EBNA-1 protein. We show that deleting EBNA-1 or oriP disrupts mitotic chromosome tethering but removing the dyad symmetry element of oriP does not. Microscopic and biochemical approaches demonstrated that an EBNA-1 mutant lacking residues 16 to 372 bound to oriP plasmids but did not support their mitotic chromosome association and that the mutant lost the ability of wild-type EBNA-1 to associate with interphase chromatin. Importantly, the transient-replication abilities of various mutant forms of EBV plasmids, including the mutant form with the EBNA-1 internal deletion, correlated directly with their chromosome-tethering abilities. These data lead us to propose that EBNA-1 recruits oriP-containing plasmids into chromatin subdomains in interphase nuclei to both engage the host replication machinery and enable the plasmids to adhere to host chromosomes to increase their segregation efficiency.
Phase‐structure transitions of the elastin polypentapeptide–water system within the framework of composition–temperature studies (1985)

Abstract The temperature dependence of the composition of coacervate and equilibrium phases is examined for the polypentapeptide of elastin ( L ‐Val 1 ‐ L ‐Pro 2 ‐Gly 3 ‐ L ‐Val 4 ‐Gly 5 ) n in water. This provides for the development of a phase diagram. CD data is presented that provides information on associated polypeptide structure changes that, when added to previous CD, nmr, and dielectric relaxation data at lower water composition, allow construction of a phase‐structure diagram of the polypentapeptide–water system. The molecular‐weight dependence of phase change (coacervation) is included. The volume–composition studies as a function of temperature also provide temperature coefficients of expansion and of composition important in analyzing the mechanism of elasticity.
Controlled Growth of Si Nanowire Arrays for Device Integration (2005)

Silicon nanowires were synthesized, in a controlled manner, for their practical integration into devices. Gold colloids were used for nanowire synthesis by the vapor-liquid-solid growth mechanism. Using SiCl4 as the precursor gas in a chemical vapor deposition system, nanowire arrays were grown vertically aligned with respect to the substrate. By manipulating the colloid deposition on the substrate, highly controlled growth of aligned silicon nanowires was achieved. Nanowire arrays were synthesized with narrow size distributions dictated by the seeding colloids and with average diameters down to 39 nm. The density of wire growth was successfully varied from approximately 0.1-1.8 wires/microm2. Patterned deposition of the colloids led to confinement of the vertical nanowire growth to selected regions. In addition, Si nanowires were grown directly into microchannels to demonstrate the flexibility of the deposition technique. By controlling various aspects of nanowire growth, these methods will enable their efficient and economical incorporation into devices.
Pneumatic capillary gun for ballistic delivery of microparticles (2005)

A pneumatic gun for ballistic delivery of microparticles to soft targets is proposed and demonstrated. The particles are accelerated by a high-speed flow of helium in a capillary tube. Vacuum suction applied to a concentric larger diameter tube is used to divert substantially all of the flow of helium from the gun nozzle, thereby preventing the gas from hitting and damaging the target. Speed of ejection of micron-sized gold particles from the gun nozzle, and their depth of penetration into agarose gels are reported.
Pathophysiology of Sickle Cell Disease (2018)

Since the discovery of sickle cell disease (SCD) in 1910, enormous strides have been made in the elucidation of the pathogenesis of its protean complications, which has inspired recent advances in targeted molecular therapies. In SCD, a single amino acid substitution in the β-globin chain leads to polymerization of mutant hemoglobin S, impairing erythrocyte rheology and survival. Clinically, erythrocyte abnormalities in SCD manifest in hemolytic anemia and cycles of microvascular vaso-occlusion leading to end-organ ischemia-reperfusion injury and infarction. Vaso-occlusive events and intravascular hemolysis promote inflammation and redox instability that lead to progressive small- and large-vessel vasculopathy. Based on current evidence, the pathobiology of SCD is considered to be a vicious cycle of four major processes, all the subject of active study and novel therapeutic targeting: ( a) hemoglobin S polymerization, ( b) impaired biorheology and increased adhesion-mediated vaso-occlusion, ( c) hemolysis-mediated endothelial dysfunction, and ( d) concerted activation of sterile inflammation (Toll-like receptor 4- and inflammasome-dependent innate immune pathways). These molecular, cellular, and biophysical processes synergize to promote acute and chronic pain and end-organ injury and failure in SCD. This review provides an exhaustive overview of the current understanding of the molecular pathophysiology of SCD, how this pathophysiology contributes to complications of the central nervous and cardiopulmonary systems, and how this knowledge is being harnessed to develop current and potential therapies.
Enhanced Skin Permeation of Sex Hormones with Novel Topical Spray Vehicles (1998)

The feasibility of using some novel topical spray vehicles for enhanced transdermal delivery of the sex hormones, testosterone (Tes), estradiol (E2), progesterone (Prog), and norethindrone acetate (NA) has been investigated. The new penetration enhancers, padimate O (PadO) and octyl salicylate (OSal) were used and compared with laurocapram (AZ) and oleic acid (OA). A finite dose (5 microL/cm2) of each vehicle was applied to either shed snake skin or swine skin in vitro, and the amount penetrated was measured with flow-through diffusion cells. Partitioning into swine skin was determined after an exposure time of 1 min. Rapid partitioning of Tes and PadO into swine skin occurred after 1 min with 70% and 60% of the applied dose, respectively, remaining in the skin after the unabsorbed dose was removed by rinsing with absolute ethanol. The cumulative amount at 24 h (Q24 h) of Tes penetrating across the snake skin was significantly enhanced (p < 0.05) up to 6-fold for OSal, 3-fold for OA and AZ, and 2-fold for PadO compared to control. Using PadO or AZ, the Q24 h ranged from three- to thirteen-fold over control (p < 0.05) for E2, Prog, and NA. Extrapolation of these data to predict what would happen in humans suggests that it should be possible to deliver clinically relevant amounts of sex hormones in this manner with once daily dosing.
Kindred S thyroid hormone receptor is an active and constitutive silencer and a repressor for thyroid hormone and retinoic acid responses. (1992)

Mutations in the gene encoding the human thyroid hormone receptor beta (hTR beta) have been associated with generalized thyroid hormone resistance (GTHR). However, the molecular basis by which the receptor mutants cause the clinical symptoms is largely unknown. We show here that the beta form of the human receptor possesses, in addition to hormone-dependent activation, the ability to repress basal-level activity of a target promoter. This silencing function is localized in the carboxyl-terminal part of the receptor and can be transferred to a heterologous DNA binding domain. This mode of silencing is therefore distinct from inhibition by competition with activator proteins on DNA. We show that two receptor mutants isolated from patients with GTHR are impaired in transcriptional activation but fully retain the silencing function, which enforces dominant negative regulation by the receptor. Interestingly, the kindred S receptor (hTR delta 332) acts as a constitutive repressor with a strong silencing ability similar to that of the v-erbA oncogene product. We also provide evidence for distinct transcriptional regulatory properties of both proteins. Finally, we show that both thyroid hormone- and retinoic acid-responsive genes are potentially repressed to generate the clinical manifestations of the GTHR syndrome. Our findings suggest that silencing plays an important role in the phenotypic expression of the symptoms in patients with GTHR.
A statistical model for multidimensional irreversible electroporation cell death in tissue (2010)

In this work we introduce a new methodology for evaluation of tissue ablation by IRE using statistical models of cell death. We believe that the use of a statistical model rather than a deterministic model for IRE cell death will improve the accuracy of treatment planning for cancer treatment with IRE.
Lipofuscin accumulation, abnormal electrophysiology, and photoreceptor degeneration in mutant ELOVL4 transgenic mice: A model for macular degeneration (2005)

Macular degeneration is a heterogeneous group of disorders characterized by photoreceptor degeneration and atrophy of the retinal pigment epithelium (RPE) in the central retina. An autosomal dominant form of Stargardt macular degeneration (STGD) is caused by mutations in ELOVL4, which is predicted to encode an enzyme involved in the elongation of long-chain fatty acids. We generated transgenic mice expressing a mutant form of human ELOVL4 that causes STGD. In these mice, we show that accumulation by the RPE of undigested phagosomes and lipofuscin, including the fluorophore, 2-[2,6-dimethyl-8-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E,7E-octatetraenyl]-1-(2-hyydroxyethyl)-4-[4-methyl-6-(2,6,6,-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E-hexatrienyl]-pyridinium (A2E) is followed by RPE atrophy. Subsequently, photoreceptor degeneration occurs in the central retina in a pattern closely resembling that of human STGD and age-related macular degeneration. The ELOVL4 transgenic mice thus provide a good model for both STGD and dry age-related macular degeneration, and represent a valuable tool for studies on therapeutic intervention in these forms of blindness.
Machine Learning Methods for Predicting HLA-Peptide Binding Activity (2015)

As major histocompatibility complexes in humans, the human leukocyte antigens (HLAs) have important functions to present antigen peptides onto T-cell receptors for immunological recognition and responses. Interpreting and predicting HLA-peptide binding are important to study T-cell epitopes, immune reactions, and the mechanisms of adverse drug reactions. We review different types of machine learning methods and tools that have been used for HLA-peptide binding prediction. We also summarize the descriptors based on which the HLA-peptide binding prediction models have been constructed and discuss the limitation and challenges of the current methods. Lastly, we give a future perspective on the HLA-peptide binding prediction method based on network analysis.
Effects of Oral Folic Acid Supplementation on Endothelial Function in Familial Hypercholesterolemia (1999)

These data demonstrate that oral supplementation of folic acid can improve endothelial function in patients with increased risk of atherosclerotic disease due to hypercholesterolemia, without changes in plasma lipids.
A Unified Nomenclature System for the Insect Olfactory Coreceptor (2011)

We propose a revised nomenclature for the insect olfactory coreceptor variously named ‘‘Or83b,’’ ‘‘Or1,’’ ‘‘Or2,’’ and ‘‘Or7.’’ This gene appears to be functionally orthologous across all insects and serves as a chaperoning coreceptor for the odor- and pheromone-specific subunits of the insect
Multipotential differentiation of adipose tissue-derived stem cells (2005)

Tissue engineering offers considerable promise in the repair or replacement of diseased and/or damaged tissues. The cellular component of this regenerative approach will play a key role in bringing these tissue engineered constructs from the laboratory bench to the clinical bedside. However, the ideal source of cells still remains unclear and may differ depending upon the application. Current research for many applications is focused on the use of adult stem cells. The properties of adult stem cells that make them well-suited for regenerative medicine are (1) ease of harvest for autologous transplantation, (2) high proliferation rates for ex vivo expansion and (3) multilineage differentiation capacity. This review will highlight the use of adipose tissue as a reservoir of adult stem cells and draw conclusions based upon comparisons with bone marrow stromal cells.
A comparison of glucagon and glucose in prehospital hypoglycaemia. (1997)

Intravenous glucose is the treatment of choice in prehospital hypoglycaemia but glucagon should also be available for intramuscular use when intravenous access is not possible.
Chemoenzymatic Conjugation of Toxic Payloads to the Globally Conserved N-Glycan of Native mAbs Provides Homogeneous and Highly Efficacious Antibody–Drug Conjugates (2015)

A robust, generally applicable, nongenetic technology is presented to convert monoclonal antibodies into stable and homogeneous ADCs. Starting from a native (nonengineered) mAb, a chemoenzymatic protocol allows for the highly controlled attachment of any given payload to the N-glycan residing at asparagine-297, based on a two-stage process: first, enzymatic remodeling (trimming and tagging with azide), followed by ligation of the payload based on copper-free click chemistry. The technology, termed GlycoConnect, is applicable to any IgG isotype irrespective of glycosylation profile. Application to trastuzumab and maytansine, both components of the marketed ADC Kadcyla, demonstrate a favorable in vitro and in vivo efficacy for GlycoConnect ADC. Moreover, the superiority of the native glycan as attachment site was demonstrated by in vivo comparison to a range of trastuzumab-based glycosylation mutants. A side-by-side comparison of the copper-free click probes bicyclononyne (BCN) and a dibenzoannulated cyclooctyne (DBCO) showed a surprising difference in conjugation efficiency in favor of BCN, which could be even further enhanced by introduction of electron-withdrawing fluoride substitutions onto the azide. The resulting mAb-conjugates were in all cases found to be highly stable, which in combination with the demonstrated efficacy warrants ADCs with a superior therapeutic index.
The Sorcerer's Apprentice Guide to Fault Attacks. (2004)

The effect of faults on electronic systems has been studied since the 1970s when it was noticed that radioactive particles caused errors in chips. This led to further research on the effect of charged particles on silicon, motivated by the aerospace industry who was becoming concerned about the effect of faults in airborn electronic systems. Since then various mechanisms for fault creation and propagation have been discovered and researched. This paper covers the various methods that can be used to induce faults in semiconductors and exploit such errors maliciously. Several examples of attacks stemming from the exploiting of faults are explained. Finally a series of countermeasures to thwart these attacks are described.
Parthenogenetic Stem Cells in Nonhuman Primates (2002)

Parthenogenesis is the process by which an egg can develop into an embryo in the absence of sperm. This process has been characterized to some extent in nonhuman primates ([1][1], [2][2]); however, to date, no primate parthenogenetic embryonic stem (ES) cell lines have been derived. Although
Mechanisms of endothelial senescence (2008)

When endothelial cells from different vascular beds are grown in culture they show a limited capacity to divide, eventually entering into a permanent and phenotypically distinctive non-dividing state referred to as 'replicative senescence'. Replicative senescence is thought to result from progressive shortening of telomeric DNA and consequent telomere dysfunction. More recently, it has been realised that senescence can also be induced by a variety of insults, including those causing intracellular oxidative stress. In this report, we review evidence for the occurrence of endothelial cell senescence in vivo. We will also examine the causes, mechanisms and regulation of this process as they emerge from our studies in cell culture, focusing in particular on the roles of oxidative stress, telomerase, growth factors and nitric oxide.
The ubiquitously expressed Syp phosphatase interacts with c-kit and Grb2 in hematopoietic cells. (1994)

The c-kit proto-oncogene encodes a transmembrane tyrosine kinase receptor, which is important for the normal development of hematopoietic cells, melanoblasts, and germ cells. Autophosphorylation of c-kit receptor on tyrosine creates binding sites for cellular src homology 2 (SH2)-containing signaling molecules. The discovery of phosphotyrosine phosphatases that contain SH2 domains suggests roles for these molecules in growth factor signaling pathways. We found that Syp, a phosphotyrosine phosphatase widely expressed in all the tissues in mammals, associates with c-kit receptor after activation with its ligand, steel factor, in the factor-dependent cell line, M07e. Both NH2-terminal and COOH-terminal SH2 domains of Syp, made as glutathione S-transferase fusion proteins, were able to bind to the activated c-kit receptor in vitro. Furthermore, Syp became marginally phosphorylated on tyrosine upon c-kit receptor activation, and tyrosine-phosphorylated Syp was found to be complexed with Grb2 in steel factor-stimulated M07e cells. Direct binding between Syp and Grb2 was also observed in vitro. Last, Ras and Raf interacts in vitro as a result of steel factor-stimulated Ras activation. These results suggest that Syp may be an important signaling component downstream of the c-kit receptor and involved in activation of the Ras signaling pathway in hematopoietic cells.