gebhart/patrepeval huggingface dataset:
A method for profiling classes of plant hormones and their metabolites using liquid chromatography‐electrospray ionization tandem mass spectrometry: an analysis of hormone regulation of thermodormancy of lettuce (Lactuca sativa L.) seeds (2003)

A highly selective and sensitive method for the simultaneous analysis of several plant hormones and their metabolites is described. The method combines high-performance liquid chromatography (HPLC) with positive and negative electrospray ionization-tandem mass spectrometry (ESI-MS/MS) to quantify a broad range of chemically and structurally diverse compounds. The addition of deuterium-labeled analogs for these compounds prior to sample extraction permits accurate quantification by multiple reaction monitoring (MRM). Endogenous levels of abscisic acid (ABA), abscisic acid glucose ester (ABA-GE), 7'-hydroxy-abscisic acid (7'-OH-ABA), phaseic acid (PA), dihydrophaseic acid (DPA), indole-3-acetic acid (IAA), indole-3-aspartate (IAAsp), zeatin (Z), zeatin riboside (ZR), isopentenyladenine (2iP), isopentenyladenosine (IPA), and gibberellins (GA)1, GA3, GA4, and GA7 were determined simultaneously in a single run. Detection limits ranged from 0.682 fmol for Z to 1.53 pmol for ABA. The method was applied to the analysis of plant hormones and hormonal metabolites associated with seed dormancy and germination in lettuce (Lactuca sativa L. cv. Grand Rapids), using extracts from only 50 to 100 mg DW of seed. Thermodormancy was induced by incubating seeds at 33 degrees C instead of 23 degrees C. Germinating seeds transiently accumulated high levels of ABA-GE. In contrast, thermodormant seeds transiently accumulated high levels of DPA after 7 days at 33 degrees C. GA1 and GA3 were detected during germination, and levels of GA1 increased during early post-germinative growth. After several days of incubation, thermodormant seeds exhibited a striking transient accumulation of IAA, which did not occur in seeds germinating at 23 degrees C. We conclude that hormone metabolism in thermodormant seeds is surprisingly active and is significantly different from that of germinating seeds.
Abstinence Symptomatology and Psychiatric Diagnosis in Cocaine Abusers (1986)

Abstinence symptoms and psychiatric diagnoses were evaluated in 30 chronic cocaine abusers. Structured diagnostic interviews were done within an experimental design intended to maximize differentiation of enduring symptoms from symptoms linked to binges of cocaine use. Longitudinal evaluations showed a three-phase sequence of post-cocaine abuse abstinence symptoms. Over half the sample also met criteria for ed 3 DSM-III, axis I psychiatric disorders. The findings present specific implications for treatment design.
Antibiotic resistance and biofilm tolerance: a combined threat in the treatment of chronic infections (2018)

Since the introduction of antibiotics into human medicine in the 1940's, antibiotic resistance has emerged at an alarming rate and is now a major threat to public health. This problem is amplified by pathogenic bacteria existing most commonly in biofilm form, creating additional bacterial tolerance to antimicrobial agents. Biofilm is now considered to be a primary cause of chronic infection, and antibiotic-resistant bacteria are prevalent in biofilm form. In particular, chronic non-healing wounds commonly harbour complex polymicrobial, pathogenic biofilm that is tolerant to systemic and topical antimicrobial therapy. Antibiotic stewardship programmes have emerged globally to improve antibiotic prescribing practices, and to curb the emergence and spread of bacterial resistance. In this regard, new antimicrobial strategies must be considered, one of which is to use antibiofilm/antimicrobial combinations to disrupt biofilm, thereby facilitating effectiveness of antimicrobial agents, and reducing the opportunity for antibiotic resistance gene transfer within biofilm. This strategy is being considered in several clinical conditions, one of which is chronic non-healing wounds, where antibiotics are used excessively and often indiscriminately. A combination antibiofilm/antimicrobial wound dressing has been shown to facilitate healing in previously biofilm-impaired non-healing wounds. This approach must be considered as part of antibiotic stewardship programmes to reduce the usage and implications of antibiotic therapy, and improve outcomes associated with chronic infections.
Direct Synthesis of Imides from Dicarboxylic Acids using Microwaves (1999)

1,4- and 1,5-dicarboxylic acids, when treated with amines in a domestic microwave oven, afford good yields of the corresponding imides.
Subcellular localization and secretion of activity-dependent neuroprotective protein in astrocytes (2004)

Activity-dependent neuroprotective protein (ADNP, approximately 123562.8 Da), is synthesized in astrocytes and expression of ADNP mRNA is regulated by the neuroprotective peptide vasoactive intestinal peptide (VIP). The gene that encodes ADNP is conserved in human, rat and mouse, and contains a homeobox domain profile that includes a nuclear-export signal and a nuclear-localization signal. ADNP is essential for embryonic brain development, and NAP, an eight-amino acid peptide that is derived from ADNP, confers potent neuroprotection. Here, we investigate the subcellular localization of ADNP through cell fractionation, gel electrophoresis, immunoblotting and immunocytochemistry using alpha-CNAP, an antibody directed to the neuroprotective NAP fragment that constitutes part of an N-terminal epitope of ADNP. Recombinant ADNP was used as a competitive ligand to measure antibody specificity. ADNP-like immunoreactivity was found in the nuclear cell fraction of astrocytes and in the cytoplasm. In the cytoplasm, ADNP-like immunoreactivity colocalized with tubulin-like immunoreactivity and with microtubular structures, but not with actin microfilaments. Because microtubules are key components of developing neurons and brain, possible interaction between tubulin and ADNP might indicate a functional correlate to the role of ADNP in the brain. In addition, ADNP-like immunoreactivity in the extracellular milieu of astrocytes increased by approximately 1.4 fold after incubation of the astrocytes with VIP. VIP is known to cause astrocytes to secrete neuroprotective/neurotrophic factors, and we suggest that ADNP constitutes part of this VIP-stimulated protective milieu.
Targeting tumor-associated macrophages as a novel strategy against breast cancer (2006)

Tumor-associated macrophages (TAMs) are associated with tumor progression and metastasis. Here, we demonstrate for the first time that legumain, a member of the asparaginyl endopeptidase family functioning as a stress protein, overexpressed by TAMs, provides an ideal target molecule. In fact, a legumain-based DNA vaccine served as a tool to prove this point, as it induced a robust CD8+ T cell response against TAMs, which dramatically reduced their density in tumor tissues and resulted in a marked decrease in proangiogenic factors released by TAMs such as TGF-beta, TNF-alpha, MMP-9, and VEGF. This, in turn, led to a suppression of both tumor angiogenesis and tumor growth and metastasis. Importantly, the success of this strategy was demonstrated in murine models of metastatic breast, colon, and non-small cell lung cancers, where 75% of vaccinated mice survived lethal tumor cell challenges and 62% were completely free of metastases. In conclusion, decreasing the number of TAMs in the tumor stroma effectively altered the tumor microenvironment involved in tumor angiogenesis and progression to markedly suppress tumor growth and metastasis. Gaining better insights into the mechanisms required for an effective intervention in tumor growth and metastasis may ultimately lead to new therapeutic targets and better anticancer strategies.
Influenza a (H1N1) Virus Resistance to Cyanovirin-N Arises Naturally during Adaptation to Mice and by Passage in Cell Culture in the Presence of the Inhibitor (2007)

Influenza A/New Caledonia/20/99 (H1N1) virus was studied for development of resistance to cyanovirin-N (CVN). CVN neutralizes virus infectivity by binding to specific high-mannose oligosaccharides on the viral haemagglutinin 1 (HA1) subunit. During virus adaptation to mice in the absence of CVN treatment the virus became resistant to CVN (CVN-MR virus), as did virus passaged in cell culture in the presence of CVN (CVN-R virus). The CVN-R virus possessed a single amino acid change at position 94a (Asn94aAsp) of HA1 that eliminated this glycosylation site. The CVN-MR virus at mouse passage 7 was a mixture of clones, consisting of a single mutation (Asp225Gly) and double mutations (Asn63Ser+Asp225Gly or Asn94a+Asp225Gly), eliminating glycosylation sites. CVN did not bind well to the CVN-R and CVN-MR viruses. Propagating these viruses in cells treated with 1 mM deoxymannojirimycin (dMJ, mannosidase inhibitor) increased sensitivity to CVN, suggesting that glycans attached at other sites on HA1 that typically are not high-mannosidic became so due to dMJ treatment. Further evaluation showed that the Asp225Gly mutant virus was sensitive to the inhibitor and did not kill mice or induce weight loss. The CVN-R virus was also avirulent to mice. The double-mutant CVN-MR viruses were resistant to CVN and caused deaths and severe weight loss in mice. CVN-R virus subjected to mouse adaptation acquired the 225 mutation and a lethal phenotype. Thus, the 225 mutation in the HA receptor-binding site in combination with a loss of glycan at Asn (63 or 94a) are important for mouse adaptation in this virus. The mutations reported here causing resistance to CVN are consistent with its known mode of action.
Video Coding Standards: H.261, H.263 and H.26L (2002)

Chapter Five describes the ITU H.261, H.263 and H.26L standards for video coding: Brief overview of the H.261 standard The H.263 standard; the baseline CODEC; comparison with the core MPEG-4 Visual CODEC The H.263 optional coding modes; H.263 profiles; H.263+ and H.263++ The emerging H.26L standard; description of the H.26L coding tools and test model Comparison of the performance of the main video coding standards.
Current Trends in the Development of Nitric Oxide Donors (1999)

Nitric oxide (NO) is an important messenger molecule involved in many pathological and physiological processes within the mammalian body. Exogenous NO sources constitute a powerful way to supplement NO when the body can not generate enough for normal biological functions. In this article, general aspects on NO and NO donors are reviewed. Major focus is placed on recent developments of novel NO donors, NO releasing device(s) as well as innovative improvements to current NO donors. Finally, an outlook on future NO donor development is provided.
Modes and patterns of self-mutilation in persons with Lesch–Nyhan disease (2003)

Lesch-Nyhan disease (LND) is a rare X-linked recessive genetic disorder associated with cognitive impairment, choreoathetosis, hyperuricemia, and the hallmark symptom of severe and involuntary self-mutilation. This study examines data gathered from a survey of 64 families in the USA and abroad regarding the self-injury of their family members who have LND. The individuals with LND ranged in age from 1 to 40 years (mean 16 years 7 months, SD 11 years 2 months) and, with the exception of one, were males. The most common initial mode of self-mutilation, and the most frequently cited past or current behavior, was biting of lips and/or fingers. Other behaviors, in order of frequency, included head banging, extension of arms when being wheeled through doorways, tipping of wheelchairs, eye-poking, fingers in wheelchair spokes, and rubbing behaviors. Hierarchical cluster analysis identified patterns of association among the types of self-mutilation. Modes of self-mutilation in which external surfaces (such as a wheelchair component) served as instruments of self-injury tended to co-occur, as did biting of lips and fingers.
Production of Cell Lines Secreting TAT Fusion Proteins (2004)

Transduction of proteins and other macromolecules constitutes a potent technology to analyze cell functions and to achieve therapeutic interventions. In general, fusion proteins with protein transduction domains, such as TAT, are produced in a bacterial expression system. Here we describe the generation of a mammalian expression vector coding for TAT-EGFP fusion protein. Transfection of CHO-K1 cells by this vector and subsequent selection by Zeocin resulted in cell lines that express and secrete EGFP, a variant of the green fluorescent protein GFP. The ultimate cell line was produced by first cloning the stable integrants and subsequent selection of EGFP-expressing cells by flow cytometric sorting. In the resulting cell line approximately 98% of cells express EGFP. Using the same methodology, we generated cell lines that express DsRed fluorescent protein. The advantages of using such a mammalian expression system include the ease of generating TAT fusion proteins and the potential for sustained production of such proteins in vitro and, potentially, in vivo.
Introduction: The Space of Options (2009)

Abstract In this chapter, the author first presents a standard taxonomy of the major alternative positions about color ontology. The distinction between color realism and color irrealism is explored. Several difficulties with the Standard Taxonomy are discussed including some directions in which one might proceed to refine the characterization of the options. The distinction between relationalist and non-relationalist accounts of color is then illustrated. The author argues that this distinction is useful in understanding the space of alternative views on color ontology because it crystallizes a central set of issues that divides the accounts, and does so while sidestepping problems that plague the Standard Taxonomy. Further, an alternative Refined Taxonomy of positions on color ontology is then provided as a useful way to clarify the relationship of color relationalism to other views.
Biokinetic Analysis of Ubiquitin C-Terminal Hydrolase-L1 (UCH-L1) in Severe Traumatic Brain Injury Patient Biofluids (2011)

Ubiquitin C-terminal hydrolase-L1 (UCH-L1) is a neuron-specific enzyme that has been identified as a potential biomarker of traumatic brain injury (TBI). The study objectives were to determine UCH-L1 exposure and kinetic metrics, determine correlations between biofluids, and assess outcome correlations in severe TBI patients. Data were analyzed from a prospective, multicenter study of severe TBI (Glasgow Coma Scale [GCS] score ≤ 8). Cerebrospinal fluid (CSF) and serum data from samples taken every 6 h after injury were analyzed by enzyme-linked immunosorbent assay (ELISA). UCH-L1 CSF and serum data from 59 patients were used to determine biofluid correlations. Serum samples from 86 patients and CSF from 59 patients were used to determine outcome correlations. Exposure and kinetic metrics were evaluated acutely and up to 7 days post-injury and compared to mortality at 3 months. There were significant correlations between UCH-L1 CSF and serum median concentrations (r(s)=0.59, p<0.001), AUC (r(s)=0.3, p=0.027), Tmax (r(s)=0.68, p<0.001), and MRT (r(s)=0.65, p<0.001). Outcome analysis showed significant increases in median serum AUC (2016 versus 265 ng/mL*min, p=0.006), and Cmax (2 versus 0.4 ng/mL, p=0.003), and a shorter Tmax (8 versus 19 h, p=0.04) in those who died versus those who survived, respectively. In the first 24 h after injury, there was a statistically significant acute increase in CSF and serum median Cmax((0-24h)) in those who died. This study shows a significant correlation between UCH-L1 CSF and serum median concentrations and biokinetics in severe TBI patients, and relationships with clinical outcome were detected.
High-pressure sorption of carbon dioxide in solvent-cast poly(methyl methacrylate) and poly(ethyl methacrylate) films (1981)

Carbon dioxide sorption isotherms in poly(methyl methacrylate) (PMMA) and poly(ethyl methacrylate) (PEMA) are reported for pressures up to 20 atm. Temperatures between 35 and 80°C were studied for PMMA and temperatures between 30 and 55°C were studied for PEMA. Typical dual mode sorption isotherms concave to the pressure axis were observed in all cases. The measured Langmuir sorption capacities of both polymers extrapolated to zero at the glass transition (Tg) consistent with the behavior of other glassy polymer/gas systems. Sorption enthalpies for CO2 in the Henry's law mode for PMMA and PEMA are in the same range (−2 to −4 kcal/mole) as has been reported for a variety of other glassy polymers such as poly(ethylene terephthalate), polycarbonate, and polyacrylonitrile. Some of the data suggest that postcasting treatment of the PEMA films left a small amount of residual solvent in the film. the presence of the trace residual solvent during quenching from the rubbery to the glassy state after annealing appears to cause a dilation of the Langmuir capacity and an alteration in the apparent Langmuir affinity constant of the PEMA film. These results suggest the possibility of tailoring physical properties of glassy polymers such as sorptivity, permeability, impact strength, and craze resistance by doping small amounts of selected residuals into polymers prior to quenching to the glassy state from the rubbery state.
Cause-effect relation between hyperfibrinogenemia and vascular disease (2003)

Elevated plasma levels of fibrinogen are associated with the presence of cardiovascular disease, but it is controversial whether elevated fibrinogen causally imparts an increased risk, and as such is a true modifier of cardiovascular disease, or is merely associated with disease. By investigating a transgenic mouse model of hyperfibrinogenemia, we show that elevated plasma fibrinogen concentration (1) elicits augmented fibrin deposition in specific organs, (2) interacts with an independent modifier of hemostatic activity to regulate fibrin turnover/deposition, (3) exacerbates neointimal hyperplasia in an experimental model of stasis-induced vascular remodeling, yet (4) may suppress thrombin generation in response to a procoagulant challenge. These findings provide direct experimental evidence that hyperfibrinogenemia is more than a by-product of cardiovascular disease and may function independently or interactively to modulate the severity and/or progression of vascular disease.
Light-induced metastable defects in hydrogenated amorphous silicon: A systematic study (1985)

We study the magnitude of metastable light-induced changes in undoped hydrogenated amorphous silicon (the Staebler-Wronski effect) with electron-spin-resonance and photoconductivity measurements. The influence of the following parameters is investigated in a systematic way: sample thickness, impurity content, illumination time, light intensity, photon energy, and illumination and annealing temperatures. The experimental results can be explained quantitatively by a model based on the nonradiative recombination of photoexcited carriers as the defect-creating step. In the framework of this model, the Staebler-Wronski effect is an intrinsic, self-limiting bulk process, characterized by a strongly sublinear dependence on the total light exposure of a sample. The experimental results suggest that the metastable changes are caused by recombination-induced breaking of weak Si--Si bonds, rather than by trapping of excess carriers in already existing defects. Hydrogen could be involved in the microscopic mechanism as a stabilizing element. The main metastable defect created by prolonged illumination is the silicon dangling bond. An analysis of the annealing behavior shows that a broad distribution of metastable dangling bonds exists, characterized by a variation of the energy barrier separating the metastable state from the stable ground state between 0.9 and 1.3 eV.
Recurrent or Refractory High-Grade Gliomas Treated by Convection-Enhanced Delivery of a TGFβ2-Targeting RNA Therapeutic: A Post-Hoc Analysis with Long-Term Follow-Up (2019)

<i>Background</i>. OT101 is a first-in-class RNA therapeutic designed to abrogate the immunosuppressive actions of transforming growth factor beta 2 (TGFβ2). Here, we report our post-hoc analysis of the single-agent activity of OT101 in adult patients with recurrent and/or refractory (<i>R/R</i>) high-grade gliomas. <i>Methods</i>. In a Phase 2 clinical trial (ClinicalTrials.gov, NCT00431561), OT101 was administered to 89 <i>R/R</i> high-grade glioma (HGG) (anaplastic astrocytoma/AA: 27; glioblastoma multiforme/GBM: 62) patients with an intratumoral catheter using a convection enhanced delivery (CED) system. Seventy-seven patients (efficacy population; GBM: 51; AA: 26) received at least the intended minimum number of four OT101 treatment cycles. Response determinations were based on central review of magnetic resonance imaging (MRI) scans according to the McDonald criteria. Standard statistical methods were applied for the analysis of data. <i>Findings</i>. Nineteen patients had a complete response (CR) or partial response (PR) following a slow but robust size reduction of their target lesions (median time for 90% reduction of the baseline tumor volume = 11.7 months, range: 4.9-57.7 months). The mean log reduction of the tumor volume was 2.2 ± 0.4 (median = 1.4: range: 0.4-4.5) logs. In addition, seven patients had a stable disease (SD) lasting ≥6 months. For the combined group of 26 AA/GBM patients with favorable responses, the median progression-free survival (PFS) of 1109 days and overall survival (OS) of 1280 days were significantly better than the median PFS (<i>p</i> < 0.00001) and OS (<i>p</i> < 0.00001) of the non-responders among the 89 patients or the 77-patient efficacy population. <i>Conclusion</i>. Intratumorally administered OT101 exhibits clinically meaningful single-agent activity and induces durable CR/PR/SD in <i>R/R</i> HGG patients.
Mesenchymal stem cell derived extracellular vesicles: promising immunomodulators against autoimmune, autoinflammatory disorders and SARS-CoV-2 infection (2020)

Discovery of novel and broad-acting immunomodulators is of critical importance for the prevention and treatment of disorders occurring due to overexuberant immune responseincluding SARS-CoV-2 triggered cytokine storm leading to lung pathology and mortality during the ongoing viral pandemic. Mesenchymal stem/stromal cells (MSCs), highly regarded for their regenerative capacities, also possessesremarkable immunoregulatory functions affecting all types of innate and adaptive immune cells. Owing to that, MSCs have been heavily investigated in clinic for the treatment of autoimmune and inflammatory diseases along with transplant rejection. Extensive research in the last decaderevealed that MSCs carry out most of their functions through paracrine factors which are soluble mediators and extracellular vesicles (EVs). EVs, including exosomes and microvesicles, are an efficient way of intercellular communication due to their unique ability to carry biological messages such as transcription factors, growth factors, cytokines, mRNAs and miRNAs over long distances. EVs originate through direct budding of the cell membrane or the endosomal secretion pathway and they consist of the cytosolic and membrane components of their parent cell. Therefore, they are able to mimic the characteristics of the parent cell, affecting the target cells upon binding or internalization. EVs secreted by MSCs are emerging as a cell-free alternative to MSC-based therapies. MSC EVs are being tested in preclinical and clinical settings where they exhibit exceptional immunosuppressivecapacity. They regulate the migration, proliferation, activation and polarization of various immune cells, promoting a tolerogenic immune response while inhibiting inflammatory response. Being as effective immunomodulators as their parent cells, MSC EVs are also preferable over MSC-based therapies due to their lower risk of immunogenicity, tumorigenicity and overall superior safety. In this review, we present the outcomes of preclinical and clinical studies utilizing MSC EVs as therapeutic agents for the treatment of a wide variety of immunological disorders.