gebhart/patrepeval huggingface dataset:
Increased molecular damage and heterogeneity as the basis of aging (2008)

Aging at the molecular level is characterized by the progressive accumulation of molecular damage. The sources of damage act randomly through environmental and metabolically generated free radicals, through spontaneous errors in biochemical reactions, and through nutritional components. However, damage to a macromolecule may depend on its structure, localization and interactions with other macromolecules. Damage to the maintenance and repair pathways comprising homeodynamic machinery leads to age-related failure of homeodynamics, increased molecular heterogeneity, altered cellular functioning, reduced stress tolerance, diseases and ultimate death. Novel approaches for testing and developing effective means of intervention, prevention and modulation of aging involve means to minimize the occurrence and accumulation of molecular damage. Mild stress-induced hormesis by physical, biological and nutritional methods, including hormetins, represents a promising strategy for achieving healthy aging and for preventing age-related diseases.
Kringle Domains of Human Angiostatin (1996)

Recently we have identified angiostatin, an endogenous angiogenesis inhibitor of 38 kDa which specifically blocks the growth of endothelial cells (O'Reilly, M. S., Holmgren, L., Shing, Y., Chen, C. , Rosenthal, R. A., Moses, M., Lane, W. S., Cao, Y., Sage, E. H., and Folkman, J. (1994) Cell 79, 315-328; Folkman, J. (1995) Nat. Med. 1, 27-31). Angiostatin was shown to represent an internal fragment of plasminogen containing the first four kringle structures. We now report on the inhibitory effects of individual or combined kringle structures of angiostatin on capillary endothelial cell proliferation. Recombinant kringle 1 and kringle 3 exhibit potent inhibitory activity with half-maximal concentrations (ED50) of 320 nM and 460 nM, respectively. Also, recombinant kringle 2 displays a significant inhibition, although decreased compared with both kringle 1 and kringle 3. In contrast, kringle 4 is an ineffective inhibitor of basic fibroblast growth factor-stimulated endothelial cell proliferation. Among the tandem kringle arrays, the recombinant kringle 2-3 fragment exerts inhibitory activity similar to kringle 2 alone. However, relative to kringle 2-3, a marked enhancement in inhibition is observed when individual kringle 2 and kringle 3 are added together to endothelial cells. This implies that it is necessary to open the cystine bridge between kringle 2 and kringle 3 to obtain the maximal inhibitory effect of kringle 2-3. An increased (<2-fold) inhibitory activity is observed for the kringle 1-3 fragment (ED50 = 70 nM) compared with kringle 1-4 (ED50 = 135 nM). These data indicate that the anti-proliferative activity of angiostatin on endothelial cells is shared by kringle 1, kringle 2, and kringle 3, but probably not by kringle 4 and that more potent inhibition results when kringle 4 is removed from angiostatin. Thus, in view of the variable lysine affinity of the homologous domains, it would appear that lysine binding capability does not correlate with the relative inhibitory effects of the kringle-containing constructs. However, as we also demonstrate, appropriate folding of kringle structures is essential for angiostatin to maintain its full anti-endothelial activity.
A new three dimensional IC fabrication technology, stacking thin film DUAL-CMOS layers (1991)

A novel 3-D IC has been developed in which electrical function blocks of thin-film dual-active-device-layer (DUAL) CMOS ICs are bonded cumulatively. In the DUAL-CMOS ICs, pMOSFETs are stacked on nMOSFETs by using a laser beam annealing technique. By mechano-chemical polishing, the IC substrates are thinned, and then joined together. Operation of function blocks such as an inverter and ring oscillator stacked in the 3-D IC is confirmed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Decarburization of Fe/C melts in a crucible: Effects of bath sulfur level and bath surface area (2004)

Experiments to investigate decarburization of Fe/C/S melts in a crucible were carried out. The effects of the concentration of sulfur and the surface area of bath open to reaction were investigated. Using controlled Fe/C melts, it was found that sulfur significantly retards the decarburization of Fe/C melts. The retardation reached its maximum for sulfur concentrations higher than 0.1%. Similar results were also obtained for melts of commercial type metal. Retardation was observed when either O 2 and/or CO 2 were used as a decarburizing gas. Sulfur in the melt did not react with the oxidizing gas during decarburization. It was also observed that the formation of droplets was enhanced by the presence of sulfur. Finally the effects of surface tension, known as the Marangoni effect, were clearly observed during experiments.
Magnetic Resonance Imaging of Hippocampal Subfields in Posttraumatic Stress Disorder (2010)

The findings indicate for the first time in humans that PTSD is associated with selective volume loss of the CA3/dentate gyrus subfields, consistent with animal studies, implying that chronic stress suppresses neurogenesis and dendritic branching in these structures.
Synthesis and transport applications of 3-aminobicyclo[3,2,1]octane-3-carboxylic acids (1983)

The isomeric 3-aminobicyclo[3.2.1]octane-3-carboxylic acids were synthesized and compared with the widely used (1R,2S,4S)-2-aminobicyclo[2.2.1]heptane-2-carboxylic acid as to specificity to the Na+-independent membrane transport system L of the Ehrlich ascites tumor cell and of the rat hepatoma cell line HTC. The presence of an additional methylene group in the ring system leads to an optically symmetrical amino acid, with the advantages that the product is devoid of isomeric contamination. Hence, optical resolution is not necessary to secure a homogeneous test substrate for discrimination of amino acid transport systems. Through its inhibitory action on the cellular uptake of known system-specific amino acids, the bicyclo[3.2.1]octane amino acid proved more reactive than the bicycloheptane analogue with the Na+-independent amino acid transport system of the test cells and not perceptibly reactive with the accompanying Na+-dependent systems. Recent evidence of the presence of a second component of Na+-independent amino acid transport, beyond system L, increases the importance of securing a variety of possibly discriminatory model substrates.
Putative Roles for Peptidylarginine Deiminases in COVID-19 (2020)

Peptidylarginine deiminases (PADs) are a family of calcium-regulated enzymes that are phylogenetically conserved and cause post-translational deimination/citrullination, contributing to protein moonlighting in health and disease. PADs are implicated in a range of inflammatory and autoimmune conditions, in the regulation of extracellular vesicle (EV) release, and their roles in infection and immunomodulation are known to some extent, including in viral infections. In the current study we describe putative roles for PADs in COVID-19, based on in silico analysis of BioProject transcriptome data (PRJNA615032 BioProject), including lung biopsies from healthy volunteers and SARS-CoV-2-infected patients, as well as SARS-CoV-2-infected, and mock human bronchial epithelial NHBE and adenocarcinoma alveolar basal epithelial A549 cell lines. In addition, BioProject Data PRJNA631753, analysing patients tissue biopsy data (n = 5), was utilised. We report a high individual variation observed for all PADI isozymes in the patients' tissue biopsies, including lung, in response to SARS-CoV-2 infection, while PADI2 and PADI4 mRNA showed most variability in lung tissue specifically. The other tissues assessed were heart, kidney, marrow, bowel, jejunum, skin and fat, which all varied with respect to mRNA levels for the different PADI isozymes. In vitro lung epithelial and adenocarcinoma alveolar cell models revealed that PADI1, PADI2 and PADI4 mRNA levels were elevated, but PADI3 and PADI6 mRNA levels were reduced in SARS-CoV-2-infected NHBE cells. In A549 cells, PADI2 mRNA was elevated, PADI3 and PADI6 mRNA was downregulated, and no effect was observed on the PADI4 or PADI6 mRNA levels in infected cells, compared with control mock cells. Our findings indicate a link between PADI expression changes, including modulation of PADI2 and PADI4, particularly in lung tissue, in response to SARS-CoV-2 infection. PADI isozyme 1-6 expression in other organ biopsies also reveals putative links to COVID-19 symptoms, including vascular, cardiac and cutaneous responses, kidney injury and stroke. KEGG and GO pathway analysis furthermore identified links between PADs and inflammatory pathways, in particular between PAD4 and viral infections, as well as identifying links for PADs with a range of comorbidities. The analysis presented here highlights roles for PADs in-host responses to SARS-CoV-2, and their potential as therapeutic targets in COVID-19.
IKK-1 and IKK-2: Cytokine-Activated IκB Kinases Essential for NF-κB Activation (1997)

Activation of the transcription factor nuclear factor kappa B (NF-kappaB) is controlled by sequential phosphorylation, ubiquitination, and degradation of its inhibitory subunit IkappaB. A large multiprotein complex, the IkappaB kinase (IKK) signalsome, was purified from HeLa cells and found to contain a cytokine-inducible IkappaB kinase activity that phosphorylates IkappaB-alpha and IkappaB-beta. Two components of the IKK signalsome, IKK-1 and IKK-2, were identified as closely related protein serine kinases containing leucine zipper and helix-loop-helix protein interaction motifs. Mutant versions of IKK-2 had pronounced effects on RelA nuclear translocation and NF-kappaB-dependent reporter activity, consistent with a critical role for the IKK kinases in the NF-kappaB signaling pathway.
Interaction of Sodium Dodecyl Sulfate with Polyethyleneimine:  Surfactant-Induced Polymer Solution Colloid Dispersion Transition (2003)

The binding isotherm of sodium dodecyl sulfate (SDS) on a hyperbranched polyethyleneimine (PEI) was determined by an equilibrium dialysis method. Dynamic light scattering, electrophoretic mobility, and coagulation kinetics measurements were also performed in order to monitor the changes in the charged nature and size of PEI/SDS complexes. The experimental binding isotherm shows that the SDS interacts with PEI in two different ways. In a first binding process, the dodecyl sulfate ions bind in monomer form to the protonated amine groups, which is accompanied by an increase of the pH. A quantitative model is presented to describe the relation between the surfactant binding and the pH change. Above a critical amount of the bound surfactant, the PEI/SDS complex molecules collapse and precipitate. After the collapse of the polyelectrolyte/surfactant molecules, the SDS adsorbs on the surface layer of the collapsed particles (causing a charge reversal). This means that the interaction of the SDS with PEI can be divided into different characteristic SDS concentration ranges. At low surfactant concentrations, the system is a thermodynamically stable solution of the polymer/surfactant complex molecules. Above this critical concentration, the system is an unstable colloid dispersion of the complex particles. At even higher surfactant concentrations, the system may be a kinetically stable dispersion of the PEI/SDS particles, depending on the method of preparation. It can be concluded that the observed mechanism of PEI−SDS interaction is different from the general characteristics of the oppositely charged linear polyelectrolytes and surfactants, where the precipitated complex dissolves in the excess surfactant due to a collective (micelle-like) polymer−surfactant interaction.
MORPHOLOGICAL VARIABILITIES OF THREE CLOSELY RELATED MATING GROUPS OF CLOSTERIUM EHRENBERGII MENEGHINI (CHLOROPHYTA) (1986)

The ranges of morphological variabilities in vegetative cells of three closely related mating groups of Closterium ehrenbergii Meneghini were statistically analyzed, having been grown under standard and uniform culture conditions, using Group A clones from Japan and Australia, Group B clones from Japan and Taiwan and Group H clones from Nepal. Significant differences in the morphological characters were not recognized between the two complementary mating types in any of the three groups. It has been shown that cells of Group A are smallest (mean width 50 μm and mean length 250 μm) and cells of Group B are largest (mean width 67 μm and mean length 404 μm), while cells of Group H are intermediate (mean width 57 μm and mean length 333 μm). There are considerable differences in the mean cell size between the three mating groups, although some intergrading clones were recognized. Degrees of the intergrading overlap were shown to be small between the sympatric groups (A and B) and large between the two pairs of allopatric groups (A and H & B and H). It has been shown that cells of Group A are shorter and much more curved than cells of the other two mating groups. Cells of Groups B and H are slender and less curved. It has also been shown that the ranges in cell size of each mating group are smaller than those currently accepted for C. ehrenbergii.
Regulation of Distinct Stages of Skeletal Muscle Differentiation by Mitogen-Activated Protein Kinases (1997)

The signal transduction pathway or pathways linking extracellular signals to myogenesis are poorly defined. Upon mitogen withdrawal from C2C12 myoblasts, the mitogen-activated protein kinase (MAPK) p42Erk2 is inactivated concomitant with up-regulation of muscle-specific genes. Overexpression of MAPK phosphatase-1 (MKP-1) inhibited p42Erk2 activity and was sufficient to relieve the inhibitory effects of mitogens on muscle-specific gene expression. Later during myogenesis, endogenous expression of MKP-1 decreased. MKP-1 overexpression during differentiation prevented myotube formation despite appropriate expression of myosin heavy chain. This indicates that muscle-specific gene expression is necessary but not sufficient to commit differentiated myocytes to myotubes and suggests a function for the MAPKs during the early and late stages of skeletal muscle differentiation.
Ring-Opening Metathesis Polymers for Biodetection and Signal Amplification: Synthesis and Self-Assembly (2010)

The ring-opening metathesis polymerization (ROMP) was used to develop a new class of block copolymers toward biological detection with signal amplification. For this, three classes of ROMP monomers were synthesized: (i) luminescent and electrochemiluminescent transition-metal-containing monomers, with ruthenium, osmium, and iridium bipyridine units, (ii) biologically compatible monomers and macromonomers containing oligothylene glycol units, and (iii) bioconjugatable monomers as well as monomers containing the biorecognition unit biotin. ROMP was used to efficiently combine these monomers into amphiphilic di- and triblock copolymers. Self-assembly of these block copolymers in aqueous media generates micellar spherical assemblies, which contain a large number of luminescent transition-metal centers in their core, a biocompatible and biologically inert protecting shell, and biological recognition units or bioconjugatable groups on their periphery. These micelles can act as luminescent markers for biological molecules with potential for signal amplification. In addition, the monomers and polymers reported here can serve as useful biologically enabled building blocks for a number of applications, including drug delivery and tissue engineering.
Smallpox vaccines for biodefense: need and feasibility (2008)

Smallpox, eradicated as a cause of natural disease through an intensive global effort in the later part of the 20th Century, has resurfaced as a possible agent of bioterrorism. For this reason, there is renewed interest in smallpox vaccines. Live vaccinia virus, an orthopoxvirus related to smallpox, has a long and successful clinical track record as an effective smallpox vaccine; however, its use is associated with uncommon yet serious adverse events. This has led to a surge of recent research into newer-generation smallpox vaccines with improved safety profiles and retained efficacy. This article will review the history of smallpox vaccines, assess the status of newer-generation vaccines and examine the overall risk-versus-benefit profile of smallpox vaccination.
심층의 시학 : 예이츠 시에 대한 융 (C. G. Jung) 적 실천 (2002)

C. G Jung`s analytical psychology is basically different from Freud`s psychoanalysis in that the former is in pursuit of causation of daily events and the latter heads for synchronity of pre-history. Accordingly, Freudian positions focus on subjective experiences of history, while Jungian positions center on objective experiences of myth as racial memory far away from history. In the sense Freud`s unconscious is concerned with dissatisfaction resulting from the conflicting relation between desire and real world, and Jung`s is associated with archetypal qualities to completeness of self. Thus Marxism is believed to be related to Freudian theories that external and real world forms motives of unconscious and Jungian theories, centering on internal and primordial world that makes up base of real world, communicate with occultism and alchemy. When we think of the relation between literature and Jungian theories, we often remind of the practices of archetypal criticism born from Northrop Frye. But the meanings of archetypes argued by Jung and Frye are very different in that the former points out that archetypes clinically serve to accomplish process of individuation through quest of collective unconscious, while the latter reveals that all symbols are literarily converged into universal archetypes, taking such conventional examples as river symbolizes death and rebirth and sun energy and father principle. Of course there are their common points that archetypes imply mythical elements having no relation with real world. In the sense the way that Jungian theories can be applied to literary text is to analyse the symbols as agents of archetypes revealed in Yeats` poetry and amplify our poetic imagination to the meanings of their origin, overcoming `epistemological obstacle` resulting from Lockian tabula rasa, while Fyre`s theories overly adhere to myths of hero that usually go through the trials of quest, initiation(separation, transformation, and return), and sacrificial scapegoat. In the view of Jungian theories, in 「The Lake Isle of Innisfree」, Innisfree means maternal space comforting poetic narrator for frustrated idea in the real world. In 「Tower」, poetic narrator longs for completeness of individuation or restoration of self going through transcendence and integration. In 「Lamentation of The Old Pensioner」, broken tree means both libidinal retrogression and restoration, so here we find spiritual sublimation of libido as revealed in my chair was nearest to the fire/ in every company. In 「Fergus and The Druid」, poetic narrator admires Druid symbolizing `wise man` as major archetype, since he wants to escape from his `persona` and to remove his characteristic mask. In 「When you are old」, beauty is favored as essential system rather than formal system meaning skin-deep modes. In 「Leda and The Swan」, the episode of swan reminding us of the mythic event of between Zeus and the queen of Sparta in Greek myth means greek tradition attacking and ruling over western society possibly displaced as Leda, so a shudder in the loins means the extension and acception of divinity.
A New Method for Mapping Discontinuous Antibody Epitopes to Reveal Structural Features of Proteins (2003)

Antibodies that bind to protein surfaces of interest can be used to report the three-dimensional structure of the protein as follows: Proteins are composed of linear polypeptide chains that fold together in complex spatial patterns to create the native protein structure. These folded structures form binding sites for antibodies. Antibody binding sites are typically "assembled" on the protein surface from segments that are far apart in the primary amino acid sequence of the target proteins. Short amino acid probe sequences that bind to the active region of each antibody can be used as witnesses to the antibody epitope surface and these probes can be efficiently selected from random sequence peptide libraries. This paper presents a new method to align these antibody epitopes to discontinuous regions of the one-dimensional amino acid sequence of a target protein. Such alignments of the epitopes indicate how segments of the protein sequence must be folded together in space and thus provide long-range constraints for solving the 3-D protein structure. This new antibody-based approach is applicable to the large fraction of proteins that are refractory to current approaches for structure determination and has the additional advantage of requiring very small amounts of the target protein. The binding site of an antibody is a surface, not just a continuous linear sequence, so the epitope mapping alignment problem is outside the scope of classical string alignment algorithms, such as Smith-Waterman. We formalize the alignment problem that is at the heart of this new approach, prove that the epitope mapping alignment problem is NP-complete, and give some initial results using a branch-and-bound algorithm to map two real-life cases. Initial results for two validation cases are presented for a graph-based protein surface neighbor mapping procedure that promises to provide additional spatial proximity information for the amino acid residues on the protein surface.
Alpha-Toxin Induces Programmed Cell Death of Human T cells, B cells, and Monocytes during USA300 Infection (2012)

This investigation examines the influence of alpha-toxin (Hla) during USA300 infection of human leukocytes. Survival of an USA300 isogenic deletion mutant of hla (USA300Δhla) in human blood was comparable to the parental wild-type strain and polymorphonuclear leukocyte (PMN) plasma membrane permeability caused by USA300 did not require Hla. Flow cytometry analysis of peripheral blood mononuclear cells (PBMCs) following infection by USA300, USA300Δhla, and USA300Δhla transformed with a plasmid over-expressing Hla (USA300Δhla Comp) demonstrated this toxin plays a significant role inducing plasma membrane permeability of CD14(+), CD3(+), and CD19(+) PBMCs. Rapid plasma membrane permeability independent of Hla was observed for PMNs, CD14(+) and CD19(+) PBMCs following intoxication with USA300 supernatant while the majority of CD3(+) PBMC plasma membrane permeability induced by USA300 required Hla. Addition of recombinant Hla to USA300Δhla supernatant rescued CD3(+) and CD19(+) PBMC plasma membrane permeability generated by USA300 supernatant. An observed delay in plasma membrane permeability caused by Hla in conjunction with Annexin V binding and ApoBrdU Tunel assays examining PBMCs intoxicated with recombinant Hla or infected with USA300, USA300Δhla, USA300Δhla Comp, and USA300ΔsaeR/S suggest Hla induces programmed cell death of monocytes, B cells, and T cells that results in plasma membrane permeability. Together these findings underscore the importance of Hla during S. aureus infection of human tissue and specifically demonstrate Hla activity during USA300 infection triggers programmed cell death of human monocytes, T cells and B cells that leads to plasma membrane permeability.
Robust and Practical Optical Fibers for Single Mode Operation with Core Diameters up to 170?m (2008)

All-glass leakage-channel-fibers with core up to ~170?m are demonstrated with substantial differential mode losses. No tight coils are needed for single-mode-operation, minimizing bend-induced mode reduction. Elimination of air-holes significantly enables ease of fabrication and use.