gebhart/patrepeval huggingface dataset:
Expression cloning of a human IL-12 receptor component. A new member of the cytokine receptor superfamily with strong homology to gp130. (1994)

A cDNA encoding a human IL-12R subunit was isolated by expression cloning. This subunit is a 662 amino acid type I transmembrane protein with an extracellular domain of 516 amino acids and a cytoplasmic domain of 91 amino acids. It is a member of the hemopoietin receptor superfamily and is most closely related over its entire length to gp130 and the receptors for granulocyte-CSF (G-CSF) and leukemia-inhibitory factor. When expressed in COS cells, this IL-12R subunit binds both human and murine IL-12 with an apparent affinity of 2 to 5 nM. The transfected COS cells express both monomers and disulfide-linked dimers or oligomers of the IL-12R subunit on their surface. However, unlike the IL-6-induced dimerization of gp130, the oligomerization of the IL-12R subunit is not dependent on binding of IL-12. Only the IL-12R subunit dimers/oligomers but not the monomers bind IL-12 with an affinity of 2 to 5 nM. A polyclonal antiserum raised against this receptor subunit specifically inhibits IL-12-induced proliferation of PHA-activated PBMC. The data are consistent with the hypotheses that 1) a dimer/oligomer of the cloned IL-12R subunit (IL-12R-beta) represents the low affinity IL-12 binding site identified on human lymphoblasts, 2) the cloned receptor subunit is involved in IL-12 signal transduction, and 3) an additional, as of yet unidentified subunit is required to generate a high affinity IL-12R complex.
Isolation of Flower-inducing and Flower-inhibitory Factors from Aphid Honeydew (1974)

The aphid Dactynotus ambrosiae Thomas has been allowed to feed on vegetative or flowering plants of the short-day plant Xanthium strumarium L., and the honeydew which they produce is extracted and tested for an effect on flowering using the long-day plant Lemna gibba L., strain G3 for the bioassay. One zone of flower-inducing activity and at least two zones of flower-inhibitory activity are consistently obtained from the honeydew extracts. The levels of flower-inducing and flower-inhibitory activity are not demonstrably different in vegetative and flowering honeydew. The honeydew extracts are inactive on Xanthium but do give some flower induction with the short-day plant Lemna perpusilla Torr., strain 6746. The flower-inducing activity is clearly of plant origin and is present in the phloem since the same active material can be obtained from vegetative or flowering Xanthium by methanol extraction, and honeydew produced by aphids feeding on a chemically defined synthetic diet is completely without flower-inducing activity. This is the first report of successful flower induction in the long-day plant L. gibba G3 by some means other than long-day treatment.
Beyond trastuzumab: novel therapeutic strategies in HER2-positive metastatic breast cancer (2012)

The use of trastuzumab, a monoclonal antibody that targets the human epidermal growth factor receptor 2 (HER2) alteration present in 25 to 30% of breast cancers, has been associated with improved survival outcomes in both the adjuvant and metastatic settings. However, despite the robust clinical efficacy of trastuzumab in HER2-positive metastatic breast cancer (MBC), primary and secondary resistance remains a clinical challenge. Although lapatinib has demonstrated modest activity in this setting, trials reported to date have yet to demonstrate improvements in overall survival with its use. Novel therapeutic strategies to circumvent trastuzumab resistance are warranted, and agents targeting the HER, vascular endothelial growth factor, heat shock protein 90, phosphoinositide 3 kinase/Akt/mammalian target of rapamycin, and insulin-like growth factor-1 receptor pathways represent rational approaches in the management of HER2-positive disease. In this review, early-phase and emerging trial data surrounding the use of these promising agents in HER2-positive MBC will be discussed.
Liposomes Containing Lipid A Serve as an Adjuvant for Induction of Antibody and Cytotoxic T-Cell Responses against RTS,S Malaria Antigen (1998)

Encapsulation of soluble protein antigens in liposomes was previously shown to result in processing of antigen via the major histocompatibility complex class I pathway, as evidenced by costaining of the trans-Golgi region of murine bone marrow-derived macrophages (BMs) by fluorophore-labeled liposomal antigen and by a trans-Golgi-specific fluorescent lipid. Evidence is presented here that free or liposome-encapsulated RTS,S, a particulate malaria antigen consisting of hepatitis B particles coexpressed with epitopes from the Plasmodium falciparum circumsporozoite protein, also was localized in the trans-Golgi after incubation with BMs, suggesting processing by the class I pathway. An in vivo cytotoxic T-lymphocyte (CTL) response was detected, however, only after immunization with RTS,S encapsulated in liposomes containing lipid A and not after immunization with free RTS,S or with RTS,S encapsulated in liposomes lacking lipid A. Therefore, intracellular delivery of antigen containing CTL epitopes to the Golgi of BMs does not necessarily result in a CTL response in vivo unless an additional adjuvant, such as liposomes containing lipid A, is utilized. Encapsulation of RTS,S in liposomes containing monophosphoryl lipid A (MPL) resulted in a dose-dependent enhancement of the NANP-specific immunoglobulin G (IgG) antibody response compared to that of free RTS,S. The IgG1 and IgG2a subclasses predominated after immunization with RTS,S encapsulated in liposomes containing MPL. These results demonstrate that encapsulation of a lipid-containing particulate antigen, such as RTS, S, in liposomes containing lipid A can enhance both humoral and cellular immune responses.
ANTI-CD25 THERAPY REVEALS THE REDUNDANCY OF THE INTRAGRAFT CYTOKINE NETWORK AFTER CLINICAL HEART TRANSPLANTATION1 (1999)

After heart transplantation, high numbers of IL-15- and CD68-positive cells infiltrate the graft. This phenomenon is independent of the rejection status. IL-15 remains present during blockade of the IL-2/IL-2R pathway by anti-CD25 monoclonal antibodies, and it may participate in T cell-dependent donor-directed immune responses, thereby explaining the occurrence of rejection in the absence of IL-2.
Vitamin A and Retinoids in Health and Disease (1984)

NIGHT blindness was recognized as a disease entity in ancient Egypt. Moreover, literature dating from ancient times to the early 20th century contains comments that appear to indicate recognition of the existence of a dietary substance necessary for night vision. In 1913 McCollum and Davis1 reported that an essential lipid-soluble substance in certain foods promoted growth in rats. They later called this substance "Fat Soluble A," to distinguish it from essential water-soluble nutrients ("Water Soluble B"). Further studies by a number of investigators showed that "Fat Soluble A" (later named vitamin A) not only maintained growth but was capable of . . .
Isolation of anti-T cell receptor scFv mutants by yeast surface display (1997)

Yeast surface display and sorting by flow cytometry have been used to isolate mutants of an scFv that is specific for the Vbeta8 region of the T cell receptor. Selection was based on equilibrium binding by two fluorescently labeled probes, a soluble Vbeta8 domain and an antibody to the c-myc epitope tag present at the carboxy-terminus of the scFv. The mutants that were selected in this screen included a scFv with threefold increased affinity for the Vbeta8 and scFv clones that were bound with reduced affinities by the anti-c-myc antibody. The latter finding indicates that the yeast display system may be used to map conformational epitopes, which cannot be revealed by standard peptide screens. Equilibrium antigen binding constants were estimated within the surface display format, allowing screening of isolated mutants without necessitating subcloning and soluble expression. Only a relatively small library of yeast cells (3 x 10[5]) displaying randomly mutagenized scFv was screened to identify these mutants, indicating that this system will provide a powerful tool for engineering the binding properties of eucaryotic secreted and cell surface proteins.
Investigation of Speech Separation as a Front-End for Noise Robust Speech Recognition (2014)

Recently, supervised classification has been shown to work well for the task of speech separation. We perform an in-depth evaluation of such techniques as a front-end for noise-robust automatic speech recognition (ASR). The proposed separation front-end consists of two stages. The first stage removes additive noise via time-frequency masking. The second stage addresses channel mismatch and the distortions introduced by the first stage; a non-linear function is learned that maps the masked spectral features to their clean counterpart. Results show that the proposed front-end substantially improves ASR performance when the acoustic models are trained in clean conditions. We also propose a diagonal feature discriminant linear regression (dFDLR) adaptation that can be performed on a per-utterance basis for ASR systems employing deep neural networks and HMM. Results show that dFDLR consistently improves performance in all test conditions. Surprisingly, the best average results are obtained when dFDLR is applied to models trained using noisy log-Mel spectral features from the multi-condition training set. With no channel mismatch, the best results are obtained when the proposed speech separation front-end is used along with multi-condition training using log-Mel features followed by dFDLR adaptation. Both these results are among the best on the Aurora-4 dataset.
'Atom-interchange Manipulation' using Non-contact Atomic Force Microscopy (2005)

We demonstrate a novel atom manipulation method of ‘Atom-interchange manipulation’ using non-contact atomic force microscopy (NC-AFM). Previously, methods of lateral atom manipulation are performed by manipulating single atoms or molecules adsorbed on metallic surfaces, but in this paper the atom-interchange manipulation is performed by interchanging two different atom species embedded in semiconductor surface layers. We use a Sn/Ge(111)-c(2×8) surface for the Atom-interchange manipulation, where some Ge adatoms are substituted by Sn adatoms. Although the diffusion rate of Sn adatoms is very low at room temperature, the atom interchange between selected Sn adatom and Ge adatom can be controlled by the NC-AFM tip. ‘Atom inlay’, that is, artificial atomic patterns formed from embedded Sn atoms in the plane of the Ge surface, is created at room temperature by rearranging configuration of two kind of atom species on the surface. This paper describes our first experiment of the atom assembly using AFM.
Application of beta-1,3-glucan to prevent shipping fever in imported heifers. (1994)

Particulated beta-1,3-glucan from Saccharomyces cerevisiae was evaluated to prevent shipping fever in imported heifers during the 15 days following their arrival to Cuba. Seventy seven animals received a single subcutaneous dose (5 mg/kg body weight) during the first 12 h following their arrival, whereas 44 served as untreated controls. Clinical symptoms were observed in 3 treated and 19 untreated animals (p < 0.001). One untreated heifer died. These observations confirm the usefulness of beta-1,3-glucan to prevent shipping fever.
Sorbitol-MacConkey medium for detection of Escherichia coli O157:H7 associated with hemorrhagic colitis (1986)

Escherichia coli serotype O157:H7 is a recently recognized human pathogen associated with hemorrhagic colitis. Unlike most E. coli strains, E. coli O157:H7 does not ferment sorbitol. Therefore, the efficacy of MacConkey agar containing sorbitol (SMAC medium) instead of lactose as a differential medium for the detection of E. coli O157:H7 in stool cultures was determined in comparison with MacConkey agar. The relative frequency of non-sorbitol-fermenting (NSF) organisms other than E. coli O157:H7 in feces was low at 10 to 20% (95% confidence limits), and NSF organisms also occurred mostly in small numbers. In a field trial involving over 1,000 diarrheal stools, E. coli O157:H7 was isolated from 18 stools, all of which were from patients with bloody diarrhea. In every instance, the growth of E. coli O157:H7 on SMAC medium was heavy and occurred in almost pure culture as colorless NSF colonies in contrast to fecal flora, which are mostly sorbitol fermenting and hence appear pink on this medium, whereas on MacConkey agar cultures, the growth of E. coli O157:H7 was indistinguishable from fecal flora. SMAC medium permitted ready recognition of E. coli O157:H7 in stool cultures. Detection of E. coli O157:H7 on SMAC medium had a sensitivity of 100%, a specificity of 85%, and an accuracy of 86%. SMAC medium stool culture is a simple, inexpensive, rapid, and reliable means of detecting E. coli O157:H7, and we recommend routine use of SMAC medium especially for culturing bloody stools.
Ovalbumin is synthesized in mouse cells transformed with the natural chicken ovalbumin gene. (1980)

The entire chicken ovalbumin gene, accompanied by genomic DNA sequences flanking both termini of the gene and three copies of the herpes simplex virus thymidine kinase gene, has been cloned in plasmid pBR322. This recombinant plasmid was linearized and used to transform thymidine kinase-deficient mouse cells. Thymidine kinase-positive transformants were selected by their ability to grow in the hypoxanthin/aminopterin/thymidine (HAT) medium. The entire ovalbumin gene integrated into high molecular weight DNA within all the transformants and retained its original sequence organization. In all of the transformants examined, a protein identified as chicken ovalbumin by immunoreactivity was detected within the cells. It is estimated that between 1000 and 100,000 molecules of chicken ovalbumin were produced per mouse cell in each of these transformants. Our results demonstrate that the mouse cellular machinery can be utilized to accurately express genetic information encoded in a cloned gene from a different eukaryotic organism into its specific protein product.
Evaluation of the temperature stability of AlGaN/GaN heterostructure FETs (1999)

Temperature stress experiments up to 800/spl deg/C have been applied to AlGaN/GaN FET's grown by MOVPE on sapphire and their individual technological building blocks. It was found that the temperature limit is given by the irreversible degradation of the intrinsic active heterostructure material itself during operation above 600/spl deg/C. The irreversible degradation was observed for both unconnected and electrically operated devices during temperature stress.
Yield loss attributable to neck‐rot of rice caused byPyricularia oryzaeCav. in Cote d'lvoire (1990)

Abstract Neck‐rot disease caused by Pyricularia oryzae is one of the most devastating diseases limiting rice production. Grain yield losses attributable to the disease were established in two locations (Bouake and Tombokro) in Cote d'lvoire using two different methods. First, by suppressing the activity of the pathogen using fungicides and comparing the grain yield of treated and untreated varieties; secondly, by comparing the yield of rice varieties with varying susceptibility levels to neck‐rot but of the same yield potential and duration. Yield losses ranging from 0.5% to 58.5% and 32.1% to 59.2% were obtained from the first and second methods, respectively. Yields varied with the variety and the fungicide used. Although the two methods are valid, the latter looks more economical, with less energy and time consumed. Keywords: Neck‐rotyield lossrice Notes Present address: Department of Biological Sciences, Faculty of Science, Ogun State University, PMB 2002, Ago‐lwoye, Ogun State, Nigeria.
Autophagy-mediated reentry of Francisella tularensis into the endocytic compartment after cytoplasmic replication (2006)

Intracellular bacterial pathogens evade the bactericidal functions of mammalian cells by physical escape from their phagosome and replication into the cytoplasm or through the modulation of phagosome maturation and biogenesis of a membrane-bound replicative organelle. Here, we detail in murine primary macrophages the intracellular life cycle of Francisella tularensis, a highly infectious bacterium that survives and replicates within mammalian cells. After transient interactions with the endocytic pathway, bacteria escaped from their phagosome by 1 h after infection and underwent replication in the cytoplasm from 4 to 20 h after infection. Unexpectedly, the majority of bacteria were subsequently found to be enclosed within large, juxtanuclear, LAMP-1-positive vacuoles called Francisella-containing vacuoles (FCVs). FCV formation required intracytoplasmic replication of bacteria. Using electron and fluorescence microscopy, we observed that the FCVs contained morphologically intact bacteria, despite fusing with lysosomes. FCVs are multimembranous structures that accumulate monodansylcadaverine and display the autophagy-specific protein LC3 on their membrane. Formation of FCVs was significantly inhibited by 3-methyladenine, confirming a role for the autophagic pathway in the biogenesis of these organelles. Taken together, our results demonstrate that, via autophagy, F. tularensis reenters the endocytic pathway after cytoplasmic replication, a process thus far undescribed for intracellular pathogens.
Functional analysis of the two Arabidopsis homologues of Toc34, a component of the chloroplast protein import apparatus† (2000)

Two Arabidopsis Toc34 homologues, atToc34 and atToc33, components of the chloroplast protein import machinery located in the outer envelope membrane, were recently isolated. Both proteins insert into the outer envelope, are supposed to bind GTP and to interact with Toc75 as demonstrated by in vitro import assays. We studied the expression of the two genes by RNA gel blot analysis, promoter-GUS plants and in situ hybridisations as well as immunoblot analysis. The atToc34 and atToc33 genes are expressed in green as well as non-green tissues and are developmentally regulated. Despite these similarities, however, the two Arabidopsis Toc34 homologues are differentially expressed in various plant organs. To gain more insight into the in vivo function of both proteins, antisense plants were created. While antisense plants of atToc33 are characterized by a pale yellowish phenotype, antisense plants of atToc34 show a weaker phenotype. Protein interaction studies using an in vitro translated precursor protein and heterologously expressed atToc34 and atToc33 proteins showed a direct GTP-dependent interaction, but demonstrated different affinities of the two atToc proteins towards the precursor protein. Thus, our results indicate a more specialized function for both atToc34 and atToc33, suggesting specificity for certain imported precursor proteins.
Permanent photowritten optical gratings in irradiated silicate glasses (1992)

We show that permanent optical gratings can be photowritten into simple silicate glasses by exposure to interfering beams of an Ar-ion laser after the glass has been treated by x rays. Gratings with index modulations as large as Deltan = 10(-5) can be formed in less than a minute by exposure to write beams with intensities of the order of 50 W/cm(2).
Acid-Labile Cys-Protecting Groups for the Fmoc/tBu Strategy: Filling the Gap (2012)

To address the existing gap in the current set of acid-labile Cys-protecting groups for the Fmoc/tBu strategy, diverse Fmoc-Cys(PG)-OH derivatives were prepared and incorporated into a model tripeptide to study their stability against TFA. S-Dpm proved to be compatible with the commonly used S-Trt group and was applied for the regioselecive construction of disulfide bonds.
SPARC expression and prognostic value in non-small cell lung cancer (2012)

Secreted protein, acidic and rich in cysteine (SPARC) is expressed in numerous types of tumors and is suggested to have prognostic value. Moreover, because of its strong affinity for albumin, and hence albumin-bound drugs, SPARC has increasingly become a focus for research. In this study, we aimed to determine SPARC expression in patients with non-small cell lung cancer (NSCLC) and investigate the association of SPARC with disease prognosis. Tissue microarrays were constructed with specimens from 105 patients with NSCLC treated at Sun Yat-sen University Cancer Center, and immunohistochemical analysis was performed on these tissue microarrays to assess SPARC expression. Our results showed that SPARC expression status did not significantly relate with age, gender, and tumor stage. However, SPARC was expressed more frequently in squamous cell carcinoma than in adenocarcinoma (75% vs. 43.5%, P = 0.004). Patients with smoking history had higher SPARC expression than non-smokers (68.2% vs. 33.3%, P = 0.002). In both univariate and multivariate analyses, SPARC was a prognostic factor of overall survival (HR = 0.32; 95% CI: 0.16-0.65) but not disease-free survival. Our study indicates that SPARC expression is higher in squamous cell carcinoma than in adenocarcinoma in NSCLC. Most notably, SPARC can be used as a prognostic factor for NSCLC.
Novel Benzimidazole Inhibitors Bind to a Unique Site in the Kinesin Spindle Protein Motor Domain (2010)

Affinity selection-mass spectrometry (AS-MS) screening of kinesin spindle protein (KSP) followed by enzyme inhibition studies and temperature-dependent circular dichroism (TdCD) characterization was utilized to identify a series of benzimidazole compounds. This series also binds in the presence of Ispinesib, a known anticancer KSP inhibitor in phase I/II clinical trials for breast cancer. TdCD and AS-MS analyses support simultaneous binding implying existence of a novel non-Ispinesib binding pocket within KSP. Additional TdCD analyses demonstrate direct binding of these compounds to Ispinesib-resistant mutants (D130V, A133D, and A133D + D130V double mutant), further strengthening the hypothesis that the compounds bind to a distinct binding pocket. Also importantly, binding to this pocket causes uncompetitive inhibition of KSP ATPase activity. The uncompetitive inhibition with respect to ATP is also confirmed by the requirement of nucleotide for binding of the compounds. After preliminary affinity optimization, the benzimidazole series exhibited distinctive antimitotic activity as evidenced by blockade of bipolar spindle formation and appearance of monoasters. Cancer cell growth inhibition was also demonstrated either as a single agent or in combination with Ispinesib. The combination was additive as predicted by the binding studies using TdCD and AS-MS analyses. The available data support the existence of a KSP inhibitory site hitherto unknown in the literature. The data also suggest that targeting this novel site could be a productive strategy for eluding Ispinesib-resistant tumors. Finally, AS-MS and TdCD techniques are general in scope and may enable screening other targets in the presence of known drugs, clinical candidates, or tool compounds that bind to the protein of interest in an effort to identify potency-enhancing small molecules that increase efficacy and impede resistance in combination therapy.