gebhart/patrepeval huggingface dataset:
Mutation of an Active Site Residue in Escherichia coli Uracil-DNA Glycosylase:  Effect on DNA Binding, Uracil Inhibition and Catalysis (1999)

The role of the conserved histidine-187 located in the leucine intercalation loop of Escherichia coli uracil-DNA glycosylase (Ung) was investigated. Using site-directed mutagenesis, an Ung H187D mutant protein was created, overproduced, purified to apparent homogeneity, and characterized in comparison to wild-type Ung. The properties of Ung H187D differed from Ung with respect to specific activity, substrate specificity, DNA binding, pH optimum, and inhibition by uracil analogues. Ung H187D exhibited a 55000-fold lower specific activity and a shift in pH optimum from pH 8.0 to 7.0. Under reaction conditions optimal for wild-type Ung (pH 8.0), the substrate preference of Ung H187D on defined single- and double-stranded oligonucleotides (25-mers) containing a site-specific uracil target was U/G-25-mer > U-25-mer > U/A-25-mer. However, Ung H187D processed these same DNA substrates at comparable rates at pH 7.0 and the activity was stimulated approximately 3-fold relative to the U-25-mer substrate. Ung H187D was less susceptible than Ung to inhibition by uracil, 6-amino uracil, and 5-fluorouracil. Using UV-catalyzed protein/DNA cross-linking to measure DNA binding affinity, the efficiency of Ung H187D binding to thymine-, uracil-, and apyrimidinic-site-containing DNA was (dT20) = (dT19-U) >/= (dT19-AP). Comparative analysis of the biochemical properties and the X-ray crystallographic structures of Ung and Ung H187D [Putnam, C. D., Shroyer, M. J. N., Lundquist, A. J., Mol, C. D., Arvai, A. S., Mosbaugh, D. W., and Tainer, J. A. (1999) J. Mol. Biol. 287, 331-346] provided insight regarding the role of His-187 in the catalytic mechanism of glycosylic bond cleavage. A novel mechanism is proposed wherein the developing negative charge on the uracil ring and concomitant polarization of the N1-C1' bond is sustained by resonance effects and hydrogen bonding involving the imidazole side chain of His-187.
Resin bonding using an all‐etch or self‐etch adhesive to enamel after carbamide peroxide and/or CPP‐ACP treatment (2007)

These findings suggest the shear bond strength of resin to enamel using a self-etching priming adhesive may be affected if the enamel is treated with a bleaching agent or CPP-ACP.
Why Do So Many Cancer Patients Fail to Respond to Interferon Therapy? (1996)

Since their first use in the clinic some 25 years ago, interferons (IFNs) have become accepted therapy in a range of cancer forms. However, although in some patients they induce remission, in the great majority they are of no benefit or, at best, lead only to minor improvements. This review considers possible reasons for these failures.
Mechanisms of the antitumoral effect of lipid A (2002)

Bacterial lipopolysaccharide (LPS) and its active component, lipid A, have been used either alone or as adjuvant in therapeutic anticancer vaccines. Lipid A induces various transcription factors via intracellular signaling cascades initiated by their receptor CD14-TLR4. These events lead to the synthesis of cytokines, which either have direct cytotoxic effect or stimulate the immune system. Their antitumoral effect has been demonstrated in animal models as well as clinical trials. Studies in animal models showed that their antitumoral effect relies mostly on the generation of an effective immune response. In humans, the antitumoral effect was correlated with an antibody response and cell-mediated cytotoxicity. So far, some encouraging results have been achieved in phase I and II clinical trials with regards to response and stabilization of the disease, but an expansion of the studies and trials is needed to find the best conditions for their clinical application.
Autostereoscopic displays and computer graphics (2005)

Autostereoscopic displays present a three-dimensional image to a viewer without the need for glasses or other encumbering viewing aids. Three classes of autostereoscopic displays are described: reimaging displays, volumetric displays, and parallax displays. Reimaging displays reproject an existing three-dimensional object to a new location or depth. Volumetric displays illuminate points in a spatial volume. Parallax displays emit directionally-varying image information into the viewing zone. Parallax displays are the most common autostereoscopic displays and are most compatible with computer graphics. Different display technologies of the three types are described. Computer graphics techniques useful for three-dimensional image generation are outlined.
siRNA Delivery In Vivo (2005)

Inhibition of gene expression at the mRNA levels can be accomplished by several methods, including ribozymes, DNAzymes, and small interfering RNAs (siRNAs) (1–3). This is now driven predominantly by siRNAs, as they are not technically demanding as traditional antisense and ribozyme technologies (4,5). The success of siRNAs as therapeutics, however, is largely dependent on the development of a delivery vehicle that can efficiently deliver them in vivo.
Mechanism of antibody-independent activation of the first component of complement (C1) on retrovirus membranes (1980)

Murine leukemia viruses activate human C1 in the absence of specific antibody. Such activation requires the binding of C1 to the viral surface through two subcomponents, C1q and C1s. This conclusion is based on the following results. (1) Isolated human C1q and C1s bind the same membrane protein on virions. (2) Binding one subcomponent is independent of the other. (3) Only dimeric C1s binds, whereas monomeric C1s, prepared by dissociation with ethylenediaminetetraacetate (EDTA), has no affinity for the virus. (4) The activated C1s dimer, C1s, does not attach to the virus. (5) Saturation of C1s binding sites on the viral surface does not prevent binding of macromolecular C1, but such bound C1 is not activated. (6) No exchange occurs between C1s bound to the viral membrane and C1s contained in C1, which in turn is attached via C1q to the same virus. Therefore activation occurs only when both C1q and C1s in the same C1 complex in contact with the viral activator. Human C1r has no affinity for the virus nor does guinea pig C1s. The latter result explains why guinea pig serum does not function in antibody-independent virolysis.
EV charging algorithm implementation with user price preference (2015)

In this paper, we propose and implement a smart Electric Vehicle (EV) charging algorithm to control the EV charging infrastructures according to users' price preferences. Charging boxes, equipped with bi-directional communication devices and smart meters, can be remotely monitored by the proposed charging algorithm applied to EV control center and mobile app. On the server side, ARIMA model is utilized to fit historical charging load data and perform day-ahead prediction. A pricing strategy with energy bidding policy is proposed and implemented to generate a charging price list to be broadcasted to EV users through mobile app. On the user side, EV drivers can submit their price preferences and daily travel schedules to negotiate with Control Center to consume the expected energy and minimize charging cost simultaneously. The proposed algorithm is tested and validated through the experimental implementations in UCLA parking lots.
Cysteine Scanning Mutagenesis at 40 of 76 Positions in Villin Headpiece Maps the F-Actin Binding Site and Structural Features of the Domain (1996)

Villin headpiece, the 76 amino acid, C-terminal domain of villin, is one of the two F-actin binding sites in villin necessary for F-actin bundling activity. Expression and study of recombinant headpiece revealed the domain to be remarkably thermostable (Tm = 74 degrees C) for a non-disulfide-bonded domain. Forty independent point mutations to cysteine of headpiece have been purified and tested for their actin binding activity, cysteine reactivity, and thermal stability. These assays identify two segments of headpiece, near amino acids 38 and 70 of headpiece, in which mutations to cysteine significantly disrupt cosedimentation of headpiece with F-actin. Assay of the thermal stability of these mutants and assay of the reactivity of the introduced cysteine show that these amino acids are mutations at the protein surface that do not perturb the overall structure of the domain. The actin binding mutants are replacements to cysteine of Lys38, Glu39, Lys65, Lys70, Lys71, Leu75, and Phe76 of headpiece. We propose that these discontinuous segments of charged amino acids define the F-actin binding contacts of the headpiece domain. The assay of mutants for effects on the thermal stability of helical structure as well as the assay of reactivity of the introduced sulfhydryl group identify candidate positions that are involved in the stabilizing core and internal structure of the domain. The cysteine scanning mutagenesis also identifies an amino-terminal subdomain (Val1-Leu35) and a predominantly helical carboxy-terminal subdomain (Pro36-Phe76).
Prevention of cell death induced by tumor necrosis factor alpha in LNCaP cells by overexpression of sulfated glycoprotein-2 (clusterin). (1995)

Sulfated glycoprotein-2 (SGP-2) expression has been associated with programmed cell death in the prostate, but its exact role remains unclear. The present study was carried out in an attempt to establish the function of SGP-2 in programmed cell death using tumor necrosis factor (TNF) alpha-induced cytotoxicity in LNCaP cells as the model system. LNCaP is an androgen-sensitive, human prostatic cancer cell line that responds to TNF in culture by undergoing programmed cell death, as determined by the loss of cell number, failure to exclude trypan blue, detection of DNA fragmentation, and increased release of previously incorporated [3H]thymidine. Immunocytochemical staining for SGP-2 was weak but evident in LNCaP cells. Following treatment with TNF alpha, there was a time-dependent increase in SGP-2 staining, the intensity of which peaked at 2 h and declined thereafter. SGP-2 staining in LNCaP cells was undetectable prior to the onset of DNA fragmentation at 6 h of TNF treatment. This observation indicated that TNF-induced cell death in LNCaP cells was characterized by an initial transient elevation of SGP-2, followed by a period of SGP-2 depletion that preceded cell death. Transfection of LNCaP with a 21-base oligonucleotide antisense to SGP-2 resulted in a significant increase in cell death that was sequence specific and was accompanied by a reduction in SGP-2 biosynthesis. These findings supported the concept that SGP-2 depletion, rather than its expression, was associated with cell death. Finally, stable transfection and subsequent overexpression of SGP-2 in LNCaP cells resulted in resistance to the cytotoxic effect of TNF. These results have provided evidence to indicate that SGP-2 plays a role in the protection of TNF-induced cell death in LNCaP cells.
Intranasal Dexmedetomidine as a Sedative for Pediatric Procedural Sedation (2017)

IN dexmedetomidine may be used for non-invasive pediatric procedural sedation. Subjects receiving IN dexmedetomidine had a similar rate of observed events/interventions as the subjects receiving non-dexmedetomidine sedation, with the exception of sleeping time. Also, patients sedated with IN dexmedetomidine had longer time to discharge, procedure time, and total admit time in comparison to other forms of sedation.
Voltage-Gated Sodium Channels and Hyperalgesia (2004)

Physiological and pharmacological evidence both have demonstrated a critical role for voltage-gated sodium channels (VGSCs) in many types of chronic pain syndromes because these channels play a fundamental role in the excitability of neurons in the central and peripheral nervous systems. Alterations in function of these channels appear to be intimately linked to hyperexcitability of neurons. Many types of pain appear to reflect neuronal hyperexcitability, and importantly, use-dependent sodium channel blockers are effective in the treatment of many types of chronic pain. This review focuses on the role of VGSCs in the hyperexcitability of sensory primary afferent neurons and their contribution to the inflammatory or neuropathic pain states. The discrete localization of the tetrodotoxin (TTX)-resistant channels, in particular NaV1.8, in the peripheral nerves may provide a novel opportunity for the development of a drug targeted at these channels to achieve efficacious pain relief with an acceptable safety profile.
Mechanistic aspects of the opposing effects of monoclonal antibodies to the ERBB2 receptor on tumor growth. (1991)

The ERBB2 (also called HER2, neu, and c-erbB-2) gene product, which encodes a growth factor receptor, was implicated in the malignancy of human adenocarcinomas. An antibody directed to the rat oncogenic receptor has been previously shown to have an antitumor effect in model systems. In an attempt to extend this observation to the protooncogenic human receptor and also to understand the underlying mechanism, we generated a panel of monoclonal antibodies specific to the extracellular portion of the ERBB2 protein. The effects of the antibodies on tumor growth were compared with their cellular and biochemical actions in vitro. Surprisingly, opposing in vivo effects were observed: although some antibodies almost completely inhibited the growth in athymic mice of transfected murine fibroblasts that overexpress Erbb-2, other antibodies either accelerated tumor growth or resulted in intermediate responses. When tested on cultured human breast carcinoma cells or ERBB2 transfectants, the tumor-stimulatory antibody was found to induce significant elevation of tyrosine phosphorylation of the ERBB2 protein. In contrast, only partial correlation was observed between the capacity to restrict tumor growth and the effects of the antibodies on receptor degradation and cellular proliferation in vitro. This suggests that the antitumor antibodies affect both receptor function and host-tumor interactions. Our results may help establish experimental criteria for the selection of specific antibodies for use either alone or in conjunction with other molecules as pharmacological antitumor agents.
Effect of cyanocobalamin and p-toluic acid on the fatty acid composition of Schizochytrium limacinum (Thraustochytriaceae, Labyrinthulomycota) (2005)

Changes in the fatty acid composition of docosahexaenoic acid (DHA)-producing Schizochytrium limacinum SR21 were investigated. The addition of cyanocobalamin, which is an active component of vitamin B12, decreased the content of odd-chain fatty acids such as pentadecanoic acid (C15:0) and heptadecanoic acid (C17:0). Cyanocobalamin may upregulate the cobalamindependent methylmalonyl-CoA mutase, which converts propionic acid to succinic acid, thereby decreasing the content of odd-chain fatty acids. The addition of p-toluic acid resulted in a decrease in docosapentaenoic acid (DPA, 22:5n-6) content and an increase in eicosapentaenoic acid (EPA, 20:5n-3) content in a dose-dependent manner. Two additional peaks of fatty acids, characterized as Δ4,7,10,14-eicosatetraenoic acid (20:4n-7) and Δ4,7,10,14- docosatetraenoic acid (22:4n-9), were detected.
WINTER SURVIVAL OF NORTHERN PINTAILS IN THE MIDDLE RIO GRANDE VALLEY, NEW MEXICO (2007)

In response to continued low population numbers of Northern Pintail (Anas acuta) in North America and to increase knowledge of the geographic variation in pintail survival rates, we estimated 126-day (27 October–2 March) survival for male and female pintails wintering in the Middle Rio Grande Valley, New Mexico, during 2001–2002 (SY1) and 2002–2003 (SY2). Sixty-nine adult male and female pintails were marked with radio-transmitters and tracked throughout the study period. Weekly relocation data in relation to study year, sex, time (week), body condition at capture, and hunting seasons were modeled using the known-fate procedure in Program MARK. Year, sex, time, and body condition covariates did not improve model performance in estimating survival, so we used the most parsimonious model to produce an overall winter survival estimate of 0.597 ± 0.077 (95% C.I. = 0.442–0.735). Weekly survival estimates did not differ between hunting and nonhunting seasons. Male and female point estimates did not differ (χ12 = 0.209, P = 0.65). Our adult female survival estimate of 0.639 ± 0.117 (95% C.I. = 0.396–0.827) was 5.5%–28.6% lower than published estimates for adult female pintails in 5 other geographic regions. No winter survival estimates for males in other geographic regions were available for direct comparison with our study. Although relatively small sample sizes may have contributed to the lack of statistical differences in weekly survival between years, sexes, and hunting seasons, as well as to the lack of influence of body condition, relatively abundant water and food resources and absence of hunting in a refuge setting contributed to consistent survival probabilities. Because our low survival estimates, relative to other geographic regions, cannot be attributed to hunting, we postulate that natural causes of mortality play a larger role in pintail survival in our study region than in other wintering regions.
Effect of cultural factors on cellulase activity and protein production by Aspergillus terreus (1981)

Abstract Protein production by Aspergillus terreus GN1 grown on 1.0% alkali‐treated bagasse was studied under various cultural conditions. The maximum biomass protein content of 20.1% and protein recovery of 11.2% was obtained with an initial pH of 4.0, with 1/5 (v/v) inoculum in continuously shaken cultures grown for seven days. Protein content of the alkali‐treated bagasse was 3.0%. Highest crude protein percent also corresponded with highest carboxymethyl cellulase and filter paper enzyme activities.
Trop-2-targeting tetrakis-ranpirnase has potent antitumor activity against triple-negative breast cancer (2014)

A new class of immunoRNases was generated with enhanced potency for targeted therapy of cancer. The promising results from (Rap)2-E1-(Rap)2 and (Rap)2-E1*-(Rap)2 support their further investigation as a potential treatment option for TNBC and other Trop-2-expressing cancers.
Contact Allergens from Surfactants. Atmospheric Oxidation of Polyoxyethylene Alcohols, Formation of Ethoxylated Aldehydes, and Their Allergenic Activity (1998)

Ethoxylated surfactants are susceptible to oxidation upon air exposure. We have previously studied the rate of peroxidation and formaldehyde formation in the chemically well-defined ethoxylated alcohol C12H25(OCH2CH2)5OH. Formaldehyde is a common cause of contact allergy. The aim of the present study was to identify other oxidation products that could be formed upon air exposure of the ethoxylated alcohol and to determine their allergenic activity. It was shown that air oxidation of C12H25(OCH2CH2)5OH gave all the theoretically possible aldehydes of the general formula C12H25(OCH2CH2)nOCH2CHO (n = 0-4) and that the major oxidation product was C12H25(OCH2CH2)4OCH2CHO, dodecyltetraoxyethyleneoxyacetaldehyde. The structure elucidation and synthesis of these aldehydes are here presented for the first time. The major aldehyde was shown to be a contact allergen with the same sensitizing capacity as that of formaldehyde. A dose-response relationship was observed in the sensitization studies. The allergens were formed from the surfactant itself and the skin reactions cannot be explained due to any impurities that may be present in a technical quality of the surfactant. Cases of allergic contact dermatits to ethoxylated surfactants have been reported. To avoid the formation of allergenic oxidation products it is important to control the conditions for storage, handling, and transportation of ethoxylated surfactants.
The Bruton's tyrosine kinase gene is expressed throughout B cell differentiation, from early precursor B cell stages preceding immunoglobulin gene rearrangement up to mature B cell stages (1993)

X-linked agammaglobulinemia (XLA) is an immunodeficiency disease in man, resulting from an arrest in early B cell differentiation. The gene defective in XLA has recently been identified and encodes a cytoplasmic protein tyrosine kinase, named Bruton's tyrosine kinase (btk), essential for cell differentiation and proliferation at the transition from pre-B to later B cell stages. In this study we investigated btk expression by Northern blotting experiments in a series of human (precursor-) B cell lines, acute lymphoblastic leukemias and plasmacytomas. btk was found to be already expressed in very early stages of B cell differentiation, even prior to immunoglobulin (Ig) heavy (H) or light (L) chain gene rearrangements. Transcripts were also detected at the pre-B cell stage and in mature B cells, irrespective of the Ig H chain class expressed. Approximately at the transition from mature B cells to plasma cells, expression of the btk gene is down-regulated. In addition, the btk gene was found to be expressed in myeloid cell lines and acute myeloid leukemias. btk expression in myeloid cells is probably not a prerequisite for myeloid differentiation, since myeloid cells in XLA patients seem not to be affected. No btk expression was found in T-lineage cells. The btk expression profile, i.e. from early precursor-B cell stages preceding Ig rearrangement up to mature B cells, supports the hypothesis that the XLA defect resides in a critical step of B cell development which is independent of the Ig gene recombination machinery.
The Fashionable Bush (2009)

The Australian bush needs a makeover to entice people to it, and presenting positive images of rural areas is a starting point, writes Bernard Salt.
cDNA cloning and disruption of the major vault protein alpha gene (mvpA) in Dictyostelium discoideum (1993)

Vaults are large cytoplasmic ribonucleoprotein particles found in nearly all eukaryotic cells. Dictyostelium vaults contain two major proteins, MVP alpha (94.2 kDa) and MVP beta (approximately 92 kDa). Using an anti-rat vault antibody, we screened a Dictyostelium cDNA expression library and isolated a 2.8-kilobase pair clone that contained a single full-length reading frame. The identity of the clone was established by the presence of a predicted 20-amino acid sequence identical to that found in a peptide sequenced from purified MVP alpha. We have disrupted the single copy gene using homologous recombination and have demonstrated a loss of MVP alpha. Although the cells still produce MVP beta, they do not contain characteristic vault particles, suggesting that MVP alpha is required for normal vault structure. These cells should be a valuable tool for elucidating the function of vaults.
Inflammatory Markers and Sleep Disturbance in Major Depression (2005)

These findings support the hypothesis that sleep disturbance is associated with elevated levels of the inflammatory markers IL-6 and sICAM. This relationship was not accounted for by other confounding factors such as age and body weight. These findings suggest that the elevations in inflammatory markers found in depressive subjects may be partially the result of disturbances of sleep initiation found in this population.