gebhart/patrepeval huggingface dataset:
The prevalence of atopic dermatitis beyond childhood: A systematic review and meta‐analysis of longitudinal studies (2017)

The prevalence of AD in longitudinal birth cohort studies is similar in childhood and adolescence/early adulthood.
A Polymer Electrolyte‐Based Rechargeable Lithium/Oxygen Battery (1996)

A novel rechargeable battery is reported. It comprises a conductive organic polymer electrolyte membrane sandwiched by a thin Li metal foil anode, and a thin carbon composite electrode on which oxygen, the electroactive cathode material, accessed from the environment, is reduced during discharge to generate electric power. It features an all solid state design in which electrode and electrolyte layers are laminated to form a 200 to 300 μm thick battery cell. The overall cell reaction during discharge appears to be . It has an open‐circuit voltage of about 3 V, and a load voltage that spans between 2 and 2.8 V depending upon the load resistance. The cell can be recharged with good coulombic efficiency using a cobalt phthalocyanine catalyzed carbon electrode.
Potentiation of radiation‐induced regrowth delay by isosorbide dinitrate in FSaII murine tumors (2002)

Oxygen deficiency in tumors reduces the efficacy of nonsurgical treatment modalities such as conventional radiotherapy and chemotherapy. Since tumor perfusion is directly affected by the vascular resistance to flow of vessels feeding the tumor, vasodilator drugs might be a way to increase tumor blood flow and oxygenation. The effects of nitric oxide (NO) donor administration on tumor oxygenation, perfusion and radiation sensitivity were studied in the FSaII tumor model. Local tumor oxygenation was measured using electron paramagnetic resonance oximetry and a fiberoptic probe, OxyLite. We concomitantly measured the modulation of tumor blood flow by laser Doppler flowmetry. We determined FSaII tumor regrowth delay after isosorbide dinitrate administration and irradiation compared to carbogen breathing before irradiation and with X-rays alone. Administration of the NO donor improved the FSaII tumor pO(2) concomitant with an increase in tumor blood flow. We also demonstrated an increase in FSaII tumor radiation sensitivity after isosorbide dinitrate administration, which was similar to the effect of carbogen breathing in the same tumor model. Administration of isosorbide dinitrate could be considered in terms of improvement in tumor blood flow and a possible concomitant increase in accessibility of chemosensitizing agents to the tumor, particularly in terms of modification of the tumor response to irradiation.
Interaction Profiles of Protein Kinase−Inhibitor Complexes and Their Application to Virtual Screening (2004)

A major challenge facing structure-based drug discovery efforts is how to leverage the massive amount of experimental (X-ray and NMR) and virtual structural information generated from drug discovery projects. Many important drug targets have large numbers of protein-inhibitor complexes, necessitating tools to compare and contrast their similarities and differences. This information would be valuable for understanding potency and selectivity of inhibitors and could be used to define target constraints to assist virtual screening. We describe a profile-based approach that enables us to capture the conservation of interactions between a set of protein-ligand receptor complexes. The use of profiles provides a sensitive means to compare multiple inhibitors binding to a drug target. We demonstrate the utility of profile-based analysis of small molecule complexes from the protein-kinase family to identify similarities and differences in binding of ATP, p38, and CDK2 compounds to kinases and how these profiles can be applied to differentiate the selectivity of these inhibitors. Importantly, our virtual screening results demonstrate superior enrichment of kinase inhibitors using profile-based methods relative to traditional scoring functions. Interaction-based analysis should provide a valuable tool for understanding inhibitor binding to other important drug targets.
High Glucose-induced O-GlcNAcylated Carbohydrate Response Element-binding Protein (ChREBP) Mediates Mesangial Cell Lipogenesis and Fibrosis (2014)

Carbohydrate response element-binding protein (ChREBP) is a transcription factor responsible for carbohydrate metabolism in the liver. However, the role of ChREBP in diabetic nephropathy has not been elucidated. Thus, we investigated the role of ChREBP in mesangial cells in diabetic nephropathy. Treatment with 25 mM glucose (high glucose; HG) increased cellular O-GlcNAc and O-GlcNAcylated ChREBP in mesangial cells compared with normal 5.5 mM glucose. O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenylcarbamate (PUGNAc), a drug that increases O-GlcNAc, augmented the expression of ChREBP targets, whereas DON, a drug that decreases O-GlcNAc and O-GlcNAcase overexpression, mitigated the increase with HG. O-GlcNAc augmented the protein stability, transcriptional activity, and nuclear translocation of ChREBP. HG treatment also stimulated lipid accumulation and the contents of triglyceride and cholesterol in mesangial cells. In addition, HG triggered expression of hypoxia-inducible factor 1-α, vascular endothelial growth factor, and extracellular matrix components related to nephrosclerosis. The ChREBP mutant, W130A, did not exhibit HG-induced lipid accumulation and fibrotic proteins, suggesting that the Trp-130 residue in the MCR3 domain is important in the development of glomerulosclerosis. O-GlcNAcylated ChREBP was elevated in mesangium cells of streptozotocin-induced diabetic rats. In conclusion, HG increased the O-GlcNAcylated ChREBP level, which resulted in lipid accumulation and up-regulation of fibrotic proteins in mesangial cells. These effects may lead mesangial cells to an ultimately pathological state.
Existent proliferative responses of peripheral blood mononuclear cells from healthy donors and ovarian cancer patients to HER-2 peptides. (1997)

Identifying target antigens for tumor-reactive T cells is important for understanding the mechanisms of tumor escape and developing novel anticancer therapies. To date, mainly CTL responses from tumor infiltrating associated lymphocytes (TIL/TAL) to peptide antigens have been investigated in ovarian cancer. In the present study, the ability of self-peptides derived from HER-2/neu proto-oncogene product (HER-2) to stimulate proliferation of PBMC from healthy donors and ovarian cancer patients has been assessed. Peptide sequences from HER-2 containing anchors for major human MHC-class II molecules have been identified. These peptides induced proliferative and cytokine responses at higher frequency in healthy donors than ovarian cancer patients. Four HER-2 peptides corresponding to positions: 396-406, 474-487, 777-789, and 884-899 were able to stimulate proliferation of a larger number of healthy donors than three other distinct HER-2 peptides 449-464, 975-987 and 1086-1098. The pattern of responses of twenty five ovarian cancer patients was different from that in healthy donors. T cell lines were developed by stimulation with peptides from PBMC of an ovarian cancer patient who showed a stable response to all four HER-2 peptides for over six months. Each T cell line was different in its ability to secrete IFN-gamma and IL-10. These results demonstrate (a) that self-peptides from HER-2 can stimulate expansion of T cells in both healthy donors and ovarian cancer patients, and (b) the ability of different peptides to stimulate secretion of different cytokines from lymphocytes of ovarian cancer patients. These results may be important for understanding the mechanisms of tolerance and autoimmunity in human cancers.
Salmonella typhimurium secreted invasion determinants are homologous to Shigella lpa proteins (1995)

Salmonella typhimurium secreted proteins (Ssp) were previously implicated in epithelial cell invasion. Here we describe four genes (SspB, sspC, sspD, and sspA), located between spaT and prgH, which encode proteins of 63, 42, 36, and 87 kDa, respectively. These Ssp are homologous to Shigella flexneri secreted proteins IpaB, IpaC, IpaD and IpaA. A non-invasive mutant with a transposon insertion in sspC lacks Ssp of 87, 42 and 36 kDa. Complementation and analyses show that sspC and sspD encode the 42 and the 36 kDa Ssp, while the 87 kDa Ssp is encoded by sspA. sspC and sspD, but not sspA, are required for invasion. Amino-terminal sequencing shows that SspC and SspA are secreted without amino-terminal processing. We further demonstrate that Ssp secretion requires proteins encoded by prgHIJK, homologous to the Shigella Ipa secretion system, since SspA is abundantly secreted by wild-type bacteria but is completely retained within the cellular fraction of a prgHIJK mutant. A precipitate containing abundant SspC and three other major Ssp of 63, 59 and 22 kDa was isolated from culture supernatants of wild-type bacteria. These data indicate that major secreted invasion determinants of S. typhimurium are structurally and functionally homolgous to S. flexneri Ipa proteins.
Electrostatic shielding of a test charge in a non-neutral plasma (1971)

The electrostatic shielding of a test electron embedded in a magnetically confined pure electron gas column is investigated. For rigid-rotor equilibria with nearly uniform density in the column interior, it is shown that the shielding length is the local electron Debye length for the case that the test electron is at rest relative to the mean motion of the column.
Possible involvement of peptidylprolyl isomerase Pin1 in rheumatoid arthritis (2010)

The peptidylprolyl isomerase Pin1 is over-expressed in some human diseases including malignancies and chronic inflammatory diseases, this suggests that it contributes to the constitutive activation of certain intracellular signaling pathways that promote cell proliferation and cell invasion. Here, we investigate the possible role of Pin1 in rheumatoid arthritis (RA). Pin1 expression was immunohistochemically analyzed in synovial tissue (ST) obtained from patients with RA and osteoarthritis (OA). To investigate the correlation between Pin1 and motility and proliferation of synovial cells, Pin1 localization was immunohistochemically compared with matrix metalloproteinase (MMP)-1, MMP-3, and proliferating cell nuclear antigen (PCNA). Double immunofluorescent staining for Pin1 and p65 was performed to determine whether Pin1 is involved in nuclear factor κB (NF-κB) activation in RA-ST. Results showed Pin1 expression was significantly higher in RA-ST than in OA-ST. The expression of MMP-1, MMP-3, and PCNA was also significantly elevated in RA-ST. Double immunofluorescent staining revealed colocalization of Pin1 and p65 in the nuclei of RA-ST. These results suggest that Pin1 may be involved in the pathogenesis of RA binding with p65 to activate the proteins MMP-1, MMP-3, and PCNA. Therefore, Pin1 may play a pivotal role in the pathogenesis of RA.
Reporter gene assays for algal-derived toxins (1999)

We have modified the cell-based directed cytotoxicity assay for sodium channel and calcium channel active phycotoxins using a c-fos-luciferase reporter gene construct. In this report we describe the conceptual basis to the development of reporter gene assays for algal-derived toxins and summarize both published and unpublished data using this method. N2A mouse neuroblastoma cells, which express voltage-dependent sodium channels, were stably transfected with the reporter gene c-fos-luc, which contains the firefly luciferase gene under the transcriptional regulation of the human c-fos response element. The characteristics of the N2A reporter gene assay were determined by dose response with brevetoxin and ciguatoxin. Brevetoxin-1 and ciguatoxin-1 induced c-fos-luc with an EC50 of 4.6 and 3.0 ng ml(-1), respectively. Saxitoxin caused a concentration-dependent inhibition of brevetoxin-1 induction of c-fos-luc with an EC50 of 3.5 ng ml(-1). GH4C1 rat pituitary cells, which lack voltage-dependent sodium channels but express voltage-dependent calcium channels, were also stably transfected with the c-fos-luc. GH4C1 cells expressing c-fos-luciferase were responsive to maitotoxin (1 ng ml(-1)) and a putative toxin produced by Pfiesteria piscicida. Although reporter gene assays are not designed to replace existing detection methods used to measure toxin activity in seafood, they do provide a valuable means to screen algal cultures for toxin activity, to conduct assay-guided fractionation and to characterize pharmacologic properties of algal toxins.
Fluorescence Self-Quenching from Reporter Dyes Informs on the Structural Properties of Amyloid Clusters Formed in Vitro and in Cells (2016)

The characterization of the aggregation kinetics of protein amyloids and the structural properties of the ensuing aggregates are vital in the study of the pathogenesis of many neurodegenerative diseases and the discovery of therapeutic targets. In this article, we show that the fluorescence lifetime of synthetic dyes covalently attached to amyloid proteins informs on the structural properties of amyloid clusters formed both in vitro and in cells. We demonstrate that the mechanism behind such a "lifetime sensor" of protein aggregation is based on fluorescence self-quenching and that it offers a good dynamic range to report on various stages of aggregation without significantly perturbing the process under investigation. We show that the sensor informs on the structural density of amyloid clusters in a high-throughput and quantitative manner and in these aspects the sensor outperforms super-resolution imaging techniques. We demonstrate the power and speed of the method, offering capabilities, for example, in therapeutic screenings that monitor biological self-assembly. We investigate the mechanism and advantages of the lifetime sensor in studies of the K18 protein fragment of the Alzheimer's disease related protein tau and its amyloid aggregates formed in vitro. Finally, we demonstrate the sensor in the study of aggregates of polyglutamine protein, a model used in studies related to Huntington's disease, by performing correlative fluorescence lifetime imaging microscopy and structured-illumination microscopy experiments in cells.
Phenotypic characterization of the archaebacterial genus Sulfolobus: comparison of five wild-type strains (1989)

Though amenable to routine manipulation and a popular subject of molecular genetic and biochemical studies on archaebacteria, the genus Sulfolobus has remained poorly described in phenotypic terms. To delineate their physiological capabilities and diversity, five laboratory strains, including type strains of the described species Sulfolobus acidocaldarius and S. solfataricus, were compared with respect to a variety of growth and biochemical parameters, including component profile of the surface-layer cell wall, inhibitors of growth, growth rate as a function of temperature and pH, and compounds used as sole sources of carbon or nitrogen. Motility and photoregulated production of an orange pigment were detected in all five strains tested. The results provide new criteria for distinguishing Sulfolobus strains as well as potential tools for the physiological and genetic manipulation of these extreme thermophiles.
Magnetic resonance spectroscopy (MRS) can identify painful lumbar discs and may facilitate improved clinical outcomes of lumbar surgeries for discogenic pain (2019)

MRS correlates with PD and may support improved surgical outcomes for CLBP patients. Noninvasive MRS is a potentially valuable approach to clarifying pain mechanisms and designing CLBP therapies that are customized to the patient. These slides can be retrieved under Electronic Supplementary Material.
New ionic organic compounds containing a linear tris(imidazolium) core and their thermotropic liquid crystal behaviour (2013)

Abstract Imidazolium-containing thermotropic ionic liquid crystals (TILCs) are of interest because of their structural similarity to imidazolium-based ionic liquids (ILs), allowing them to exhibit some IL-like properties in addition to the LC order. More imidazolium units are important for increasing the IL character; however, the effect of multiple imidazolium units on LC behaviour is not well known. Most reported imidazolium TILCs contain one imidazolium unit; only a handful containing multiple imidazolium units is known. The only examples of TILCs with multiple imidazolium units sequentially linked with a flexible spacer are based on an alkyl- or oligo(ethylene oxide)-bridged bis(imidazolium) core with an n-alkyl tail at each end. Herein, a series of 10 new symmetric compounds containing three hexyl-bridged imidazolium bromide units as the core and two terminal n-alkyl chains was synthesised and analysed. Thermotropic LC phases were generally not observed for homologues with even-numbered tails less than 16 carbons. However, after initial annealing, the homologues containing 16-, 18- and 20-carbon tails, all form a smectic A phase in the 25–137°C range, with the latter two also forming a higher-order smectic phase. This indicates that with sufficiently long n-alkyl tails to counterbalance the poly(ion) core, these tris(imidazolium) salts can exhibit thermotropic mesomorphism. Keywords: tris(imidazolium) saltsthermotropic ionic liquid crystalssmectic A phasehigher-order smectic phase Acknowledgements Primary financial support for this research from the National Science Foundation (DMR-0820579) is gratefully acknowledged. Support for M.R.S. in the form of matching funds from the University of Colorado Graduate School is also gratefully acknowledged. We also thank M. Springer for performing the Spartan computational molecular modelling and Dr. N. D. Urban for ionic column chromatography purification of some of the prepared compounds.
Imaging profiles of light intensity in the near field: applications to phase-shift photolithography (1998)

We describe a method of imaging the intensity profiles of light in near-field lithographic experiments directly by using a sensitive photoresist. This technique was applied to a detailed study of the irradiance distribution in the optical near field with contact-mode photolithography carried out by use of elastomeric phase masks. The experimental patterns in the photoresist determined by scanning electron microscopy and atomic force microscopy were compared with the corresponding theoretical profiles of intensity calculated by use of a simple scalar analysis; the two correlate well. This comparison makes it possible to improve the theoretical models of irradiance distribution in the near field. Analysis of the images highlights issues in the experimental design, provides a means for the optimization of this technique, and extends its application to the successful fabrication of test structures with linewidths of ~50 nm.
Using glutamate homeostasis as a target for treating addictive disorders (2010)

Well-developed cellular mechanisms exist to preserve glutamate homeostasis and regulate extrasynaptic glutamate levels. Accumulating evidence indicates that disruptions in glutamate homeostasis are associated with addictive disorders. The disruptions in glutamate concentrations observed after prolonged exposure to drugs of abuse are associated with changes in the function and activity of several key components within the homeostatic control mechanism, including the cystine/glutamate exchanger xc(-) and the glial glutamate transporter, EAAT2/GLT-1. Changes in the balance between synaptic and extrasynaptic glutamate levels in turn influence signaling through presynaptic and postsynaptic glutamate receptors, and thus affect synaptic plasticity and circuit-level activity. In this review, we describe the evidence for impaired glutamate homeostasis as a critical mediator of long-term drug-seeking behaviors, how chronic neuroadaptations in xc(-) and the glutamate transporter, GLT-1, mediate a disruption in glutamate homeostasis, and how targeting these components restores glutamate levels and inhibits drug-seeking behaviors.
New Approaches to Magnetic Resonance Imaging of Intervertebral Discs, Tendons, Ligaments, and Menisci (2002)

This review article discusses new magnetic resonance techniques for imaging collagen containing structures such as intervertebral discs, tendons, and ligaments. The semisolid collagen in tendons and ligaments is not normally demonstrable with magnetic resonance imaging but may be visualized with magic angle imaging and other techniques. This allows these structures to be studied with methods used for other tissues and organs. The ordered nature of collagen provides a directional signature for the tissues that may be of diagnostic value. Solute transport in these avascular or partially avascular structures can be observed with gadolinium chelates. The time scale of this process is much slower than for other tissues of the body. Solid state imaging techniques applied in applied in material sciences may provide other new approaches to diagnosis of disease in these structures.
Counteracting muscle wasting in aging and neuromuscular diseases: the critical role of IGF-1 (2009)

Most muscle pathologies are characterized by the progressive loss of muscle tissue due to chronic degeneration combined with the inability of regeneration machinery to replace the damaged muscle. These pathological changes, known as muscle wasting, can be attributed to the activation of several proteolytic systems, such as calpain, ubiquitin-proteasome and caspases, and to the alteration in muscle growth factors. Among them, insulin-like growth factor-1 (IGF-1) has been implicated in the control of skeletal muscle growth, differentiation, survival, and regeneration and has been considered a promising therapeutic agent in staving off the advance of muscle weakness. Here we review the molecular basis of muscle wasting associated with diseases, such as sarcopenia, muscular dystrophy and Amyotrophic Lateral Sclerosis, and discuss the potential therapeutic role of local IGF-1 isoforms in muscle aging and diseases.
Effects of Family History of Alcohol Dependence on the Subjective Response to Alcohol Using the Intravenous Alcohol Clamp (2013)

Results from this study showed that healthy individuals responded to an IV alcohol challenge in a dose-related manner; however, there were no significant differences on subjective response, or on EtOH-induced impairment of coordination or cognition, between individuals with a positive FH for alcoholism and those with a negative FH. Results suggest that FH may not be a specific enough marker of risk, particularly in individuals who are beyond the age where alcohol use disorders often develop.
The effect of electroporation pulses on functioning of the heart (2008)

Electrochemotherapy is an effective antitumor treatment currently applied to cutaneous and subcutaneous tumors. Electrochemotherapy of tumors located close to the heart could lead to adverse effects, especially if electroporation pulses were delivered within the vulnerable period of the heart or if they coincided with arrhythmias of some types. We examined the influence of electroporation pulses on functioning of the heart of human patients by analyzing the electrocardiogram. We found no pathological morphological changes in the electrocardiogram; however, we demonstrated a transient RR interval decrease after application of electroporation pulses. Although no adverse effects due to electroporation have been reported so far, the probability for complications could increase in treatment of internal tumors, in tumor ablation by irreversible electroporation, and when using pulses of longer durations. We evaluated the performance of our algorithm for synchronization of electroporation pulse delivery with electrocardiogram. The application of this algorithm in clinical electroporation would increase the level of safety for the patient and suitability of electroporation for use in anatomical locations presently not accessible to existing electroporation devices and electrodes.