gebhart/patrepeval huggingface dataset:
Effects of Added Lipids on Digestibility and Nitrogen Balance in Oiled Common Murres (Uria aalge) and Western Grebes (Aechmophorus occidentalis) Fed Four Formulations of a Critical Care Diet (2017)

Nutritional support is a primary therapy administered to oiled animals during responses to oil spills, but data informing nutritional decision-making during events are limited. In this study, 44 common murres ( Uria aalge ) and 6 Western grebes ( Aechmophorus occidentalis ), naturally oiled by oceanic seeps off the coast of Ventura and Santa Barbara Counties, CA, USA, were assigned to 1 of 4 groups fed diets with varying levels (6.8% [no added oil], 11%, and 20%) and types (salmon, corn) of oil added to a partially purified basal diet. Birds used in the study ranged from extremely emaciated to thin body condition (62%-80% wild bird mean body mass). Acid-insoluble ash was used as an indigestible dietary marker to quantify nitrogen retention, apparent nitrogen digestibility, nitrogen-corrected apparent metabolizable energy, energy digestibility, fat retention, fat digestibility, and estimated fat excretion. Fat excretion is important in these species because once birds have been cleaned they are at risk of plumage recontamination from excreted fat during care. Lower fat diets resulted in lower fat excretion but higher nitrogen retention, higher apparent nitrogen digestibility, and higher apparent metabolizable energy. Decreases in nitrogen retention were significantly related to increases in fat excretion. Regardless of diet, energy digestibility significantly declined with declines in body mass, suggesting severity of emaciation reduced a birds' ability to extract energy from food. Energy digestibility was highest in the 11% (low) salmon oil diet; hence, this diet had the highest effective energy content despite a lower gross kcal/kg diet. Diets fed during oil spills historically have had high fat concentrations to provide maximum caloric support. Results of this study suggest that lower fat diets may be more efficacious for nutritionally depleted seabirds. This study provides valuable data to guide clinical decision making regarding nutritional support during oil spills and other mass stranding events.
Adaptive Image Transmission (1997)

. This paper presents an image transmission control mechanism which -- in contrast to existing systems -- adapts dynamically to the capabilities of the client display as well as to the available transmission bandwidth. This mechanism is based on existing image compression algorithms whose strengths and weaknesses are summarised. For JPEG image compression, the predictability of the compression ratio depending on image content and compressor parameterization are discussed. An experimental image transmission system is presented which shows the feasibility of adaptive image transmission. Keywords: Adaptive image transmission, Image compression, Image quality, Image compressor configuration 1 Introduction Globally distributed information spaces (e.g., the WWW) make extensive use of images, which, however, demand high bandwidth when transmitted over the network. This problem gets even harder when using mobile computers and wireless data transmission. To decrease the bandwidth demands of ...
Salivary Mucins Protect Surfaces from Colonization by Cariogenic Bacteria (2014)

Understanding how the body's natural defenses function to protect the oral cavity from the myriad of bacteria that colonize its surfaces is an ongoing topic of research that can lead to breakthroughs in treatment and prevention. One key defense mechanism on all moist epithelial linings, such as the mouth, gastrointestinal tract, and lungs, is a layer of thick, well-hydrated mucus. The main gel-forming components of mucus are mucins, large glycoproteins that play a key role in host defense. This study focuses on elucidating the connection between MUC5B salivary mucins and dental caries, one of the most common oral diseases. Dental caries is predominantly caused by Streptococcus mutans attachment and biofilm formation on the tooth surface. Once S. mutans attaches to the tooth, it produces organic acids as metabolic by-products that dissolve tooth enamel, leading to cavity formation. We utilize CFU counts and fluorescence microscopy to quantitatively show that S. mutans attachment and biofilm formation are most robust in the presence of sucrose and that aqueous solutions of purified human MUC5B protect surfaces by acting as an antibiofouling agent in the presence of sucrose. In addition, we find that MUC5B does not alter S. mutans growth and decreases surface attachment and biofilm formation by maintaining S. mutans in the planktonic form. These insights point to the importance of salivary mucins in oral health and lead to a better understanding of how MUC5B could play a role in cavity prevention or diagnosis.
Different Mechanisms of Hydroxylation Site Selection by Liver and Kidney Cytochrome P450 Species (CYP27 and CYP24) Involved in Vitamin D Metabolism (1995)

A series of homologated 1 alpha-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 molecules with one to three extra carbons in the side chain were used to examine the substrate preferences and hydroxylation site selection mechanisms of the liver vitamin D3-25-hydroxylase (CYP27) and the target cell 25-hydroxyvitamin D3-24-hydroxylase (CYP24). Cultured and transfected cell models, used as sources of these hydroxylases, gave 23-, 24-, 25-, and 27-hydroxylated metabolites which were identified by their high performance liquid chromatography and GC-MS characteristics. Lengthening the side chain is tolerated by each cytochrome P450 isoform such that 25-hydroxylation or 24-hydroxylation continues to occur at the same rate as in the native side chain, while the site of hydroxylation remains the same for the liver enzyme in that CYP27 continues to hydroxylate at C-25 and C-27 (minor) despite the two-carbon-atom extension. Somewhat surprising is the finding that C-24 and C-23 (minor) hydroxylations also do not change as the side chain is extended by as much as three carbons. We conclude that CYP24 must be directed to its hydroxylation site(s) by the distance of carbon 24 from the vitamin D ring structure and not as in CYP27 by the distance of the hydroxylation site from the end of the side chain.
Circulating cell-free DNA-based epigenetic assay can detect early breast cancer (2016)

Circulating cell-free DNA (cfDNA) has recently been recognized as a resource for biomarkers of cancer progression, treatment response, and drug resistance. However, few have demonstrated the usefulness of cfDNA for early detection of cancer. Although aberrant DNA methylation in cfDNA has been reported for more than a decade, its diagnostic accuracy remains unsatisfactory for cancer screening. Thus, the aim of the present study was to develop a highly sensitive cfDNA-based system for detection of primary breast cancer (BC) using epigenetic biomarkers and digital PCR technology. Array-based genome-wide DNA methylation analysis was performed using 56 microdissected breast tissue specimens, 34 cell lines, and 29 blood samples from healthy volunteers (HVs). Epigenetic markers for BC detection were selected, and a droplet digital methylation-specific PCR (ddMSP) panel with the selected markers was established. The detection model was constructed by support vector machine and evaluated using cfDNA samples. The methylation array analysis identified 12 novel epigenetic markers (JAK3, RASGRF1, CPXM1, SHF, DNM3, CAV2, HOXA10, B3GNT5, ST3GAL6, DACH1, P2RX3, and chr8:23572595) for detecting BC. We also selected four internal control markers (CREM, GLYATL3, ELMOD3, and KLF9) that were identified as infrequently altered genes using a public database. A ddMSP panel using these 16 markers was developed and detection models were constructed with a training dataset containing cfDNA samples from 80 HVs and 87 cancer patients. The best detection model adopted four methylation markers (RASGRF1, CPXM1, HOXA10, and DACH1) and two parameters (cfDNA concentration and the mean of 12 methylation markers), and, and was validated in an independent dataset of 53 HVs and 58 BC patients. The area under the receiver operating characteristic curve for cancer-normal discrimination was 0.916 and 0.876 in the training and validation dataset, respectively. The sensitivity and the specificity of the model was 0.862 (stages 0-I 0.846, IIA 0.862, IIB-III 0.818, metastatic BC 0.935) and 0.827, respectively. Our epigenetic-marker-based system distinguished BC patients from HVs with high accuracy. As detection of early BC using this system was comparable with that of mammography screening, this system would be beneficial as an optional method of screening for BC.
A potent specific pure antiestrogen with clinical potential. (1991)

Previous studies from this laboratory have described a series of 7 alpha-alkylamide analogues of estradiol with pure antiestrogenic activity, exemplified by ICI 164,384. A new compound, 7 alpha-[9-(4,4,5,5,5-pentafluoropentylsulfinyl)nonyl]estra-1,3,5(10 )- triene-3,17 beta-diol (ICI 182,780) has now been identified which has significantly increased antiestrogenic potency and retains pure estrogen antagonist activity. The antiuterotrophic potency of ICI 182,780 in the immature rat was more than 10-fold greater than that of ICI 164,384 (50% effective doses of 0.06 and 0.9 mg/kg, respectively). This order of magnitude increase of in vivo potency was also reflected, in part, by intrinsic activity at the estrogen receptor. The relative binding affinities of ICI 182,780 and ICI 164,384 were 0.89 and 0.19, respectively, compared with that of estradiol (1.0). Similarly, the in vitro growth-inhibitory potency of ICI 182,780 exceeded that of ICI 164,384 in MCF-7 human breast cancer cells, where 50% inhibitory concentrations of 0.29 and 1.3 nM, respectively, were recorded. ICI 182,780 was a more effective inhibitor of MCF-7 growth than 4'-hydroxytamoxifen, producing an 80% reduction of cell number under conditions where 4'-hydroxytamoxifen achieved a maximum of 50% inhibition. This increased efficacy was reflected by a greater reduction of the proportion of cells engaged in DNA synthesis in ICI 182,780-treated cell cultures compared with tamoxifen-treated cells. Sustained antiestrogenic effects, following a single parenteral dose of ICI 182,780 in oil suspension, were apparent in both rats and pigtail monkeys. In vivo, antitumor activity of ICI 182,780 was demonstrated with xenografts of MCF-7 and Br10 human breast cancers in nude mice. A single injection of ICI 182,780 provided antitumor efficacy equivalent to that of daily tamoxifen treatment for at least 4 weeks. The properties of ICI 182,780 identify this pure antiestrogen as a prime candidate with which to evaluate the potential therapeutic benefits of complete estrogen withdrawal in endocrine-responsive human breast cancer.
Aridicins, novel glycopeptide antibiotics. II. Isolation and characterization. (1985)

A new antibacterial antibiotic complex, aridicin, was produced by a new genus, Kibdelosporangium aridum (SK&F-AAD-216). The individual factors, aridicins A, B and C, were isolated from the fermentation broth by an Amberlite XAD-7 resin extraction and purified by preparative reversed phase HPLC. The aridicins were found to be novel members of the glycopeptide class of antibiotics as exemplified by ristocetin and vancomycin, based on chemical and spectroscopic data, their molecular weights as determined by FAB mass spectrometry (1,786, 1,800 and 1,814), the detection of actinoidinic acid in their acid hydrolysates, and detailed TLC and HPLC comparisons with representative members of this class.
Lag-1 sparing in the attentional blink: Benefits and costs of integrating two events into a single episode (2005)

When people monitor a visual stream of rapidly presented stimuli for two targets (T1 and T2), they often miss T2 if it falls into a time window of about half a second after T1 onset--the attentional blink. However, if T2 immediately follows T1, performance is often reported being as good as that at long lags--the so-called Lag-1 sparing effect. Two experiments investigated the mechanisms underlying this effect. Experiment 1 showed that, at Lag 1, requiring subjects to correctly report both identity and temporal order of targets produces relatively good performance on T2 but relatively bad performance on T1. Experiment 2 confirmed that subjects often confuse target order at short lags, especially if the two targets are equally easy to discriminate. Results suggest that, if two targets appear in close succession, they compete for attentional resources. If the two competitors are of unequal strength the stronger one is more likely to win and be reported at the expense of the other. If the two are equally strong, however, they will often be integrated into the same attentional episode and thus get both access to attentional resources. But this comes with a cost, as it eliminates information about the targets' temporal order.
A translational approach for limb vascular delivery of the micro-dystrophin gene without high volume or high pressure for treatment of Duchenne muscular dystrophy (2007)

These studies demonstrate regional vascular gene delivery with AAV serotype(s) in mouse and non-human primate at doses, pressures and volumes applicable for clinical trials in children with DMD.
Onset of changes in glucose transport across ocular barriers in streptozotocin-induced diabetes. (1984)

In a previous study, measurements were made of facilitated and passive transport of glucose, using [3H]-3-O-methyl-D-glucose and [14C]-L-glucose, respectively, across blood-aqueous and blood-vitreous barriers in long-term streptozotocin-diabetic rats. It was found that passive transport was increased, while facilitated transport was decreased, possibly due to saturation of the transport system. The present study examines the appearance of these changes in glucose transport at various times following streptozotocin (STZ) injection. Passive transport, as indicated by the L-glucose rate constant, began to increase at about 10 days following induction of diabetes, stabilized at the elevated rates at 50-60 days and persisted during the 170-day period of observation. Rate constants for [3H]-3-O-methyl-D-glucose transport decreased within 1 day following induction of diabetes. Prevention of hyperglycemia by insulin treatment upon onset of diabetes prevented the latter changes ruling out a direct effect of STZ. Glucose infusion into normal rats produced a similar decrease in 3-O-methylglucose transport constants suggesting that hyperglycemia was responsible for the early decrease in facilitated transport found in the diabetic rats. It is speculated that increased passive transport of glucose may reflect an early loss in ocular barrier integrity. The later decrease in carrier facilitated transport cannot be explained by hyperglycemia alone and, thus, a loss in carrier function is suggested. Despite a decrease in facilitated transport, absolute glucose entry rates are increased in the diabetic due to elevated plasma glucose, which serves as an inward driving force, due to the significantly increased entry of glucose by the passive route.
Maltodextrin‐binding proteins from diverse bacteria and archaea are potent solubility enhancers (2003)

Escherichia coli maltose-binding protein (MBP) is frequently used as an affinity tag to facilitate the purification of recombinant proteins. An important additional attribute of MBP is its remarkable ability to enhance the solubility of its fusion partners. MBPs are present in a wide variety of microorganisms including both mesophilic and thermophilic bacteria and archaea. In the present study, we compared the ability of MBPs from six diverse microorganisms (E. coli, Pyrococcus furiosus, Thermococcus litoralis, Vibrio cholerae, Thermotoga maritima, and Yersinia pestis) to promote the solubility of eight different aggregation-prone proteins in E. coli. In contrast to glutathione S-transferase (GST), all of these MBPs proved to be effective solubility enhancers and some of them were even more potent solubilizing agents than E. coli MBP.
Mono‐, di‐ and trimeric binding of a bis‐netropsin to DNA (1995)

An unusual 3:1 stoichiometry for complex formation between an elongated bis-netropsin compound and its binding site on DNA has been observed. Circular dichroism measurements distinguish two types of complexes formed between this bis-netropsin and poly[d(A-T)].poly[d(A-T)]. The first type is characterized by a 1:1 saturating ratio of bound molecules per ten base pairs. Formation of the second type results from the cooperative binding of two additional bis-netropsin molecules to the first type of complex. In contrast to these results observed for binding to the alternating polynucleotide, only the 1:1 type of complex is formed when this ligand binds to the homopolymer poly(dA).poly(dT).
An implantable guide-screw system for brain tumor studies in small animals (2000)

The guide-screw system allows a large number of animals to be rapidly and reproducibly engrafted and for intratumoral treatments to be accurately delivered into established xenografts.
Changes in Extracellular Polysaccharides During Cold Acclimation of Cultured Pear Cells (1986)

Abstract Suspension-cultured pear ( Pyrus communis ‘Bartlett’) cells cold-acclimated during exposure to 2°C. Cold acclimation was accompanied by changes in soluble extracellular polysaccharides and in the deposition of callose in the cell wall. Release of a relatively small neutral polysaccharide into culture medium was increased at 2°. However, low temperature decreased the extracellular accumulation of a larger molecular weight ( M r ) pectic polysaccharide. The reduced amount of pectic polysaccharide may have been the result of both a low-temperature-enhanced degradation of existing polysaccharide and an inhibition of new synthesis or secretion. The effect of low temperature on callose deposition was observed using an aniline blue fluorescent staining procedure. Pear cells held at 2° showed far more intense staining than those at 22°, indicating increased deposition of callose or other β-1,3-glucans at the cell surface during cold acclimation.
Stability and expression of bacterial genes in replicating geminivirus vectors in plants (1989)

Bacterial beta-glucuronidase (gus) and neomycin phosphotransferase (neo) genes were introduced into coat protein replacement vectors based on DNA A of tomato golden mosaic virus (TGMV). Recombinant gus and neo vectors up to 1.1 kbp larger than DNA A were shown to replicate stably in transgenic plants containing partial dimers (master copies) of the vectors integrated into their chromosomal DNA in the absence of DNA B. Beta-glucuronidase and neomycin phosphotransferase activities in independently transformed plants were proportional to the copy number of the double-stranded forms of the vector. Deletion analysis has shown that an essential part of the TGMV coat protein promoter, including a TATA box, lies within 76 nt upstream of the initiation codon of the gene. An increase in expression of a neo gene was obtained by replacing this 76 nt sequence by an 800 nt sequence containing a cauliflower mosaic virus 35S RNA promoter with no effect on the ability of the vector to replicate or on its stability in transgenic plants. Systemic infection of plants by agroinoculation with TGMV vectors larger than DNA A in the presence of DNA B resulted in deletions in the vector DNA in some, but not all, plants. Possible reasons for vector instability in systemically infected plants, and vector stability in transgenic plants containing master copies of the vector, are discussed.
Studies on the inhibitory mechanism of iodonium compounds with special reference to neutrophil NADPH oxidase (1993)

Diphenyleneiodonium (DPI) and its analogues have been previously shown to react via a radical mechanism whereby an electron is abstracted from a nucleophile to form a radical, which then adds back to the nucleophile to form covalent adducts [Banks (1966) Chem. Rev. 66, 243-266]. We propose that the inhibition of neutrophil NADPH oxidase by DPI occurs via a similar mechanism. A reduced redox centre in the oxidase could serve as electron donor to DPI, and inhibition would occur after direct phenylation of the redox cofactor, or of adjacent amino acid groups by the DPI radical. In the absence of an activatory stimulus, human neutrophil NADPH-oxidase was not inhibited by DPI. The Ki for time-dependent inhibition by DPI of human neutrophil membrane NADPH oxidase was found to be 5.6 microM. Inhibitory potency of DPI was shown to be directly related to rate of enzyme turnover, indicating the need for a reduced redox centre. Adducts were formed between photoreduced flavin (FAD or FMN) and inhibitor (DPI or diphenyliodonium). These were separated by h.p.l.c. and characterized by absorbance spectroscopy, 1H-n.m.r. and fast-atom-bombardment m.s. and found to have properties consistent with substituted 4a,5-dihydroflavins. After incubation of pig neutrophil membranes with DPI, the quantity of recoverable intact flavin was greatly diminished when NADPH was present to initiate oxidase turnover, indicating that the flavin may be the site of DPI activation. These results may provide a common mechanism of action for iodonium compounds as inhibitors of other flavoenzymes.
PTBP1-Mediated Alternative Splicing Regulates the Inflammatory Secretome and the Pro-tumorigenic Effects of Senescent Cells (2018)

Oncogene-induced senescence is a potent tumor-suppressive response. Paradoxically, senescence also induces an inflammatory secretome that promotes carcinogenesis and age-related pathologies. Consequently, the senescence-associated secretory phenotype (SASP) is a potential therapeutic target. Here, we describe an RNAi screen for SASP regulators. We identified 50 druggable targets whose knockdown suppresses the inflammatory secretome and differentially affects other SASP components. Among the screen candidates was PTBP1. PTBP1 regulates the alternative splicing of genes involved in intracellular trafficking, such as EXOC7, to control the SASP. Inhibition of PTBP1 prevents the pro-tumorigenic effects of the SASP and impairs immune surveillance without increasing the risk of tumorigenesis. In conclusion, our study identifies SASP inhibition as a powerful and safe therapy against inflammation-driven cancer.
Caspases in Cell Death, Inflammation, and Pyroptosis (2020)

Caspases are a family of conserved cysteine proteases that play key roles in programmed cell death and inflammation. In multicellular organisms, caspases are activated via macromolecular signaling complexes that bring inactive procaspases together and promote their proximity-induced autoactivation and proteolytic processing. Activation of caspases ultimately results in programmed execution of cell death, and the nature of this cell death is determined by the specific caspases involved. Pioneering new research has unraveled distinct roles and cross talk of caspases in the regulation of programmed cell death, inflammation, and innate immune responses. In-depth understanding of these mechanisms is essential to foster the development of precise therapeutic targets to treat autoinflammatory disorders, infectious diseases, and cancer. This review focuses on mechanisms governing caspase activation and programmed cell death with special emphasis on the recent progress in caspase cross talk and caspase-driven gasdermin D-induced pyroptosis.