gebhart/patrepeval huggingface dataset:
How Autocatalysis Accelerates Drug Release from PLGA-Based Microparticles:  A Quantitative Treatment (2005)

The major aim of this study was to better understand the importance of autocatalysis in poly(lactic-co-glycolic acid) (PLGA)-based microparticles used as controlled drug delivery systems. Upon contact with biological fluids, PLGA is degraded into shorter chain alcohols and acids. An accumulation of the latter can lead to significant drops in micro-pH and subsequent accelerated polymer degradation. The system size, determining the diffusion path lengths, plays a crucial role for the occurrence/absence of autocatalytic effects. Using an oil-in-water solvent-extraction/evaporation process, different-sized drug-free and drug-loaded, PLGA-based microparticles were prepared and physicochemically characterized (SEM, DSC, SEC, optical microscopy, and UV-spectrophotometry) before and upon exposure to simulated biological fluids. Based on these experimental results, an adequate mathematical theory was developed describing the dominating mass transfer processes and chemical reactions. Importantly, a quantitative relationship could be established between the dimension of the device and the resulting drug release patterns, taking the effects of autocatalysis into account.
NF-κB activation in human breast cancer specimens and its role in cell proliferation and apoptosis (2004)

Lack of molecular targets in estrogen receptor-negative (ER-negative) breast cancer is a major therapeutic hurdle. We studied NF-kappa B activation in human breast tumors and in carcinoma cell lines. Activated NF-kappa B was detected predominantly in ER-negative vs. ER-positive breast tumors and mostly in ER-negative and ErbB2-positive tumors (86%). These in vivo results demonstrate association of activated NF-kappa B with a subgroup of human breast tumors and are consistent with previously reported in vitro observations using similar classes of human breast cancer cell lines. Finding such an association suggested functional and biological significance. Immunofluorescence demonstrated increased nuclear p65, a component of the active NF-kappa B complex, in cytokeratin 19 (CK19)-positive epithelial cells of ER-negative/ErbB2-positive tumor samples. In contrast, nuclear NF-kappa B was detected mostly in stroma of ER-negative and ErbB2-negative tumors, suggesting a role of activated NF-kappa B in intercellular signaling between epithelial and stromal cells in this type of breast cancers. To elucidate roles of activated NF-kappa B, we used an ER-negative and ErbB2-positive human breast tumor cell line (SKBr3). The polypeptide heregulin beta1 stimulated, and herceptin, the anti-ErbB2 antibody, inhibited, NF-kappa B activation in SKBr3 cells. The NF-kappa B essential modulator (NEMO)-binding domain (NBD) peptide, an established selective inhibitor of I kappa B-kinase (IKK), blocked heregulin-mediated activation of NF-kappa B and cell proliferation, and simultaneously induced apoptosis only in proliferating and not resting cells. These results substantiate the hypothesis that certain breast cancer cells rely on NF-kappa B for aberrant cell proliferation and simultaneously avoid apoptosis, thus implicating activated NF-kappa B as a therapeutic target for distinctive subclasses of ER-negative breast cancers.
A comparison of the influence of breast-feeding and bottle-feeding on the fatty acid composition of the erythrocytes (1979)

The proportion of long-chain polyunsaturated derivatives of linoleic and linolenic acids in the erythrocyte lipids of infants fed a cow's milk formula was lower than in breast-fed infants. Although th formula provided only 0.55% of the total energy as linoleic acid, essential fatty acid deficiency was not detected; the triene:tetraene ratio was 0.09.
Efficient and Persistent Splice Switching by Systemically Delivered LNA Oligonucleotides in Mice (2006)

Locked nucleic acid (LNA) oligomers were found to be very effective in their ability to modulate alternative splicing in vivo in transgenic mice that ubiquitously express a modified EGFP pre-mRNA containing an aberrantly spliced beta-globin intron (IVS2-654). Following intraperitoneal injections, the splice-switching oligonucleotide LNA SSO-654 targeted to the aberrant 5' splice site in EGFP-654 pre-mRNA corrected aberrant splicing and increased production of repaired EGFP mRNA mainly in the liver, colon, and small intestine. Little or no effect was detected in heart, lung, or kidney, the organ where most of the oligonucleotide was distributed after four consecutive daily injections. In the liver, LNA SSO-654 had an EC(50) of 3 mg/kg, approximately 17-fold more potent than its 2'-O-methyl congener. Moreover, in the liver, colon, and small intestine oral doses of 50 mg/kg resulted in detectable levels of splice switching. The effects of four daily injections at 25 mg/kg persisted for up to 29 days but did not result in liver toxicity. The results indicate that the LNA backbone confers sequence- and organ-specific functional biodistribution of the oligonucleotides and that these potent compounds have the potential to be safe and long-acting modulators of diseases treatable by splicing manipulation.
Avocado Seeds: Extraction Optimization and Possible Use as Antioxidant in Food (2014)

Consumption of avocado (Persea americana Mill) has increased worldwide in recent years. Part of this food (skin and seed) is lost during processing. However, a high proportion of bioactive substances, such as polyphenols, remain in this residue. The primary objective of this study was to model the extraction of polyphenols from the avocado pits. In addition, a further objective was to use the extract obtained to evaluate the protective power against oxidation in food systems, as for instance oil in water emulsions and meat products. Moreover, the possible synergy between the extracts and egg albumin in the emulsions is discussed. In Response Surface Method (RSM), the variables used are: temperature, time and ethanol concentration. The results are the total polyphenols content (TPC) and the antiradical power measured by Oxygen Radical Antioxidant Capacity (ORAC). In emulsions, the primary oxidation, by Peroxide Value and in fat meat the secondary oxidation, by TBARS (Thiobarbituric acid reactive substances), were analyzed. The RSM model has an R² of 94.69 for TPC and 96.7 for ORAC. In emulsions, the inhibition of the oxidation is about 30% for pure extracts and 60% for the combination of extracts with egg albumin. In the meat burger oxidation, the formation of TBARS is avoided by 90%.
Purification and biochemical characterization of non-myristoylated recombinant pp60c-src kinase (1992)

To obtain sufficient material for the biochemical and biophysical study of pp60c-src, we have utilized a recombinant pp60c-src baculovirus lacking the myristoylation site at codon 2. On infection of Sf9 cells, this virus produced large amounts of soluble non-myristoylated pp60c-src. The use of non-myristoylated pp60c-src (1) increases production of pp60c-src compared with the wild-type protein, (2) facilitates purification, (3) yields a stable product and (4) allows biochemical studies in the absence of detergents. Up to 20 mg of pp60c-src of greater than 95% purity has been purified from 6 litres of Sf9 cells grown in a bioreactor. One major and multiple minor forms of pp60c-src were separated by Mono Q f.p.l.c. Isoelectric focusing of purified pp60c-src species revealed heterogeneity, some of which could be attributed to differences in the tyrosine phosphorylation state of the enzyme. Kinetic analysis of non-myristoylated pp60c-src kinase in the presence of Mg2+ gave Km values for angiotensin II and ATP of 2 mM and 30 microM respectively and a Vmax. of 620 nmol/min per mg. The kinetic constants and metal ion preferences of a number of copolymers and peptide substrates have been compared. Polylysine and poly(GLAT), which was not phosphorylated by the pp60c-src kinase, dramatically activated autophosphorylation of Tyr-416, suggesting a conformation modulation of pp60c-src by charged polymers. This finding implies that Tyr-527 dephosphorylation is not sufficient for full activation of pp60c-src in vitro.
Comparison of experimental and theoretical fast ion slowing-down times in DIII-D (1988)

Short deuterium beam pulses are injected into the D III–D tokamak to study the variation of beam slowingdown time with temperature and density. The slowing-down time is inferred from the rate of decay of the d(d,n)3He neutron emission. To within ∼30%, the results are consistent with Sivukhin's classical theory. The short beam pulses,are also useful for measurements of the central deuterium density.
Inhibitors of glycolic acid oxidase. 4-Substituted 3-hydroxy-1H-pyrrole-2,5-dione derivatives (1983)

An extensive series of novel 4-substituted 3-hydroxy-1H-pyrrole-2,5-dione derivatives has been prepared and studied as inhibitors of glycolic acid oxidase (GAO). Compounds possessing large lipophilic 4-substituents are, in general, potent, competitive inhibitors of porcine liver GAO in vitro. Methylation of the nitrogen or the 3-hydroxy substituent reduced potency dramatically, indicating the requirement for the two acidic functions on the 1H-pyrrole-2,5-dione nucleus. In rat liver perfusion studies, with three representative compounds, concentration-dependent inhibition of the conversion of [1-14C]glycolate to [14C]oxalate was observed. Chronic oral administration to ethylene glycol fed rats of the 4-(4'-bromo[1,1'-biphenyl]-4-yl) derivative (83) was shown to effect a significant reduction in urinary oxalate levels over a 58-day period.
Snapshot of the Genome of the Pseudo-T-Even Bacteriophage RB49 (2002)

RB49 is a virulent bacteriophage that infects Escherichia coli. Its virion morphology is indistinguishable from the well-known T-even phage T4, but DNA hybridization indicated that it was phylogenetically distant from T4 and thus it was classified as a pseudo-T-even phage. To further characterize RB49, we randomly sequenced small fragments corresponding to about 20% of the approximately 170-kb genome. Most of these nucleotide sequences lacked sufficient homology to T4 to be detected in an NCBI BlastN analysis. However, when translated, about 70% of them encoded proteins with homology to T4 proteins. Among these sequences were the numerous components of the virion and the phage DNA replication apparatus. Mapping the RB49 genes revealed that many of them had the same relative order found in the T4 genome. The complete nucleotide sequence was determined for the two regions of RB49 genome that contain most of the genes involved in DNA replication. This sequencing revealed that RB49 has homologues of all the essential T4 replication genes, but, as expected, their sequences diverged considerably from their T4 homologues. Many of the nonessential T4 genes are absent from RB49 and have been replaced by unknown sequences. The intergenic sequences of RB49 are less conserved than the coding sequences, and in at least some cases, RB49 has evolved alternative regulatory strategies. For example, an analysis of transcription in RB49 revealed a simpler pattern of regulation than in T4, with only two, rather than three, classes of temporally controlled promoters. These results indicate that RB49 and T4 have diverged substantially from their last common ancestor. The different T4-type phages appear to contain a set of common genes that can be exploited differently, by means of plasticity in the regulatory sequences and the precise choice of a large group of facultative genes.
Antigen Presentation for the Generation of Binding Molecules (2012)

In the last few decades, several new methods have been established to isolate full antibodies and fragments thereof, some even using alternative scaffolds from in vivo and in vitro sources. These methods encompass robust techniques including immunization and hybridoma technology or phage display and also more laborious and novel approaches including ribosome display or B-cell immortalization. All methodologies are dependent upon proper antigen presentation for isolation, screening, and further characterization of the selected binding molecules. Here, antigens are classes of molecules including soluble or membrane proteins, part or domains thereof (extracellular domains of GPCRs), peptides, carbohydrates, and small-molecular-weight moieties. Presentation of the antigen in a functional state or perhaps even mimicking the intended application is crucial for successful isolation of useful binding molecules. Moreover, it is also necessary to consider the expression host and any posttranslational modifications of target proteins. The increasing demand to target more complex antigens, for instance, receptors and ion channels, is leading to the development of alternative procedures to present these proteins appropriately, for example by the use of virus-like particles and DNA immunization. This chapter describes in general approaches for the preparation of different forms of immunogens including synthetic peptides, proteins, cell-based antigens for immunization and in vitro display systems and in detail the preparation of a soluble protein as antigen.
SYSTEMIC INFLAMMATORY RESPONSE SYNDROME (SIRS), MULTIPLE ORGAN DYSFUNCTION SYNDROME (MODS), MULTIPLE ORGAN FAILURE (MOF) (1998)

The problems of inflammation and infection leading to organ dysfunction and failure continue to be the major problems after injury and operations and with intensive care for many diseases and problems. When SIRS goes to MODS and MOF, the mortality becomes high, ranging from 30-80% depending on the number of failed organs. In spite of this, there have been recent exciting discoveries and contributions to patient care. A reasonable question then is, are we making progress and if so, can we document it? Are the incidence and mortality of MOF decreasing? The literature comparing care over some years suggests a decrease in ICU mortality in patients with severe organ failure, a decrease in elective surgical mortality, and improvement in the results of care and outcome for trauma patients. Review of problems occurring in sick and injured patients indicates that certain problems are decreasing in frequency, such as renal failure and ARDS after trauma, stress gastrointestinal bleeding, and abdominal abscesses, and these should improve outcome. There are a number of exciting therapies that help certain patients but not everyone. These controversies challenge us to focus on where and when there are positive benefits. Risk factors for MOF are addressed to focus on early intervention. The possibilities of multiple therapeutic agents are described. Finally, we describe and emphasize our recommendation to strive to prevent MODS and SIRS.
Low Serum Insulin-Like Growth Factor I Is Associated With Increased Risk of Ischemic Heart Disease (2002)

Individuals without IHD but with low circulating IGF-I levels and high IGFBP-3 levels have significantly increased risk of developing IHD during a 15-year follow-up period. Our findings suggest that IGF-I may be involved in the pathogenesis of IHD.
Steroidal Glycoside Cholesterol Absorption Inhibitors (1997)

We have explored the use of steroidal glycosides as cholesterol absorption inhibitors which act through an unknown mechanism. The lead for this program was tigogenin cellobioside (1, tiqueside) which is a weak inhibitor (ED50 = 60 mg/kg) as measured in an acute hamster cholesterol absorption assay. Modification of the steroid portion of the molecule led to the discovery of 11-ketotigogenin cellobioside (5, pamaqueside) which has an ED50 of 2 mg/kg. Replacement of the cellobiose with other sugars failed to provide more potent analogs. However, large improvements in potency were realized through modification of the hydroxyl groups on the cellobiose. This strategy ultimately led to the 4", 6"-bis[(2-fluorophenyl)carbamoyl]-beta-D-cellobiosyl derivative of 11-ketotigogenin (51) with an ED50 of 0.025 mg/kg in the hamster assay, as well as the corresponding hecogenin analog 64 (ED50 = 0.07 mg/kg).
Increased levels of the chemokines GROalpha and MCP-1 in sputum samples from patients with COPD (2002)

These results suggest that GROalpha and MCP-1 are involved in the migration of inflammatory cells, thus contributing to the inflammatory load associated with COPD.
Role of 4-aminobutyrate aminotransferase in the arginine metabolism of Pseudomonas aeruginosa (1976)

4-Aminobutyrate aminotransferase (GABAT) from Pseudomonas aeruginosa was purified 64-fold to apparent electrophoretic homogeneity from cells grown with 4-aminobutyrate as the only source of carbon and nitrogen. Purified GABAT catalyzed the transamination of 4-aminobutyrate, N2-acetyl-L-ornithine, L-ornithine, putrescine, L-lysine, and cadaverine with 2-oxoglutarate (listed in order of decreasing activity). The enzyme is induced in cells grown on 4-guanidinobutyrate, 4-aminobutyrate, or putrescine as the only carbon and nitrogen source. Cells grown on arginine or on glutamate contained low levels of the enzyme. The regulation of the synthesis of GABAT as well as the properties of the mutant with an inactive N2-acetyl-L-ornithin 5-aminotransferase suggest that GABAT functions in the biosynthesis of arginine by convertine N2-acetyl-L-glutamate 5-semialdehyde to N2-acetyl-Lornithine as well as in catabolic reactions during growth on putrescine or 4-guanidinobutyrate but not during growth on arginine.
MECHANISMS AND BIOLOGICAL EFFECTS OF MISMATCH REPAIR (1991)

INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. .. . ... . . . . . . . . . . . . . . . . . . . . . . . . . ..... . . . . . . . . . . . . . . . . 229 LONG-PATCH MISMATCH CORRECTION . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... . . . 231 Specificity of Methyl-Directed Mismatch Repair in E. coli.. . ...... . . . ..... . .. . .... . . . . . . 231 Initiation of the Methyl-Directed Reaction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233 The Excision Reaction in Methyl-Directed Repair . . . . . . . . .... . . . . . . . . . . . . . . . . . . . ... . . . . 235 Methyl-Directed Repair and Replication Fidelity . . . . ....... . . ..... . . . . . . . . . . . . . . . . .. . 238 mutHLSU Gene Products and the Recombination Heteroduplex..... . . . . . . . . . . . . . . . . . . 239 Long-Patch. Strand-Specific Mismatch Repair in Eukaryotic Cells . . . . . .. .. . . . . . . . . . . . . 241 SHORT-PATCH MISMATCH REPAIR. . . . . . . . . . . . . . . . . . . . . . . ... ....... ......... 243 VSP Mismatch Correction in E. coli 243 MutY-Dependent G-A->G'C Mismatch Repair in E. coli . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 244 ReeF-Dependent Resolution of Heteroduplex DNA in E. coli ... . .. . . . . . .. . . . . . ........ 246 G-T->G' C Short-Patch Repair in Mammalian Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246
Laser Therapy in Acute Stroke Treatment (2008)

Recent development of near infrared light therapy (NILT) as an acute stroke treatment is promising. In various preclinical animal stroke models, NILT has been shown to be effective in improving long-term stroke outcome. More importantly, NILT has a long postischemic therapeutic window that has not been previously observed in other treatment modalities. The preliminary efficacy and safety of NILT in acute stroke patients were demonstrated in the recently published phase II NeuroThera Effectiveness and Safety Trial (NEST-1). If confirmed by the NEST-II trial, NILT will revolutionize acute stroke management as ut has a long time window (possible 24 hr) for therapy. Moreover, understanding the mechanisms of action of NILT will provide a new therapeutic target for future drug or device development.
Corrugated Photoactive Thin Films for Flexible Strain Sensor (2018)

In this study, a flexible strain sensor is devised using corrugated poly(3-hexylthiophene) (P3HT) thin film. In the previous studies, the P3HT-based photoactive thin film was shown to generate direct current (DC) under broadband light, and the generated DC voltage varied with applied tensile strain. Yet, the mechanical resiliency and strain sensing range of the P3HT-based thin film strain sensor were limited due to relatively more brittle thin film constituent&amp;mdash;poly(3,4-ethylenedioxythiophene)-polystyrene(sulfonate) (PEDOT:PSS) conductive thin film as a bottom electrode. To address this issue, it is aimed to design mechanically resilient strain sensor using corrugated thin film constituents. Buckling is induced to form corrugation in the thin films by applying pre-strain to the substrate, where the thin films are deposited, and releasing the pre-strain afterwards. It is known that corrugated thin film constituents exhibit different optical and electronic properties from non-corrugated ones. Therefore, to optimize design of the flexible strain sensor, it was studied to understand how the applied pre-strain and thickness of the PEDOT:PSS thin film affect the optical and electrical properties. Also, pre-strain effect on light absorptivity of the corrugated P3HT-based thin films was studied. In addition, strain effect was investigated on the optical and electrical properties of the corrugated thin film constituents. Finally, flexible strain sensors are fabricated by following the design guideline, which is suggested from the studies on the corrugated thin film constituents, and DC voltage strain sensing capability was validated. As a result, flexible strain sensor exhibited tensile strain sensing range up to 5% at frequency up to 15 Hz with maximum gage factor ~7.
A wideband speech and audio codec at 16/24/32 kbit/s using hybrid ACELP/TCX techniques (2003)

A hybrid ACELP/TCX algorithm for coding speech and music signals at 16, 24, and 32 kbit/s is presented. The algorithm switches between algebraic code excited linear prediction (ACELP) and transform coded excitation (TCX) modes on a 20-ms frame basis. Applying TCX on 20 ms frames improved the quality for music signals. Special care was taken to alleviate the switching artifacts between the two modes resulting in a transparent switching process. Subjective test results showed that for speech signals, the performance at 16, 24, and 32 kbit/s, is equivalent to G.722 at 48, 56, and 64 kbit/s, respectively. For music signals, the quality at 24 kbit/s was found equivalent to G.722 at 56 kbit/s. However, at 16 kbit/s, the quality for music was slightly lower than G.722 at 48 kbit/s.