gebhart/patrepeval huggingface dataset:
Intravenous Injection of a Lentiviral Vector Encoding NY-ESO-1 Induces an Effective CTL Response (2004)

Lentiviral vectors can efficiently transduce a variety of nondividing cells, including APCs. We assessed the immunogenicity of a lentiviral vector encoding the melanoma Ag NY-ESO-1 in HLA-A2 transgenic mice. Direct i.v. injection of NY-ESO-1 lentivirus induced NY-ESO-1(157-165)-specific CD8(+) cells, detected ex vivo with an A2/H-2K(b) chimeric class I tetramer. These NY-ESO-1(157-165)-specific CD8(+) cells could be expanded by boosting with an NY-ESO-1 vaccinia virus and could kill NY-ESO-1(157-165) peptide-pulsed targets in vivo. Such direct lentiviral vector injection was similar in potency to the injection of in vitro-transduced dendritic cells (DC). In addition, human monocyte-derived DC transduced by the NY-ESO-1 lentivirus stimulated an NY-ESO-1(157-165)-specific specific CTL clone. These data suggest that direct lentiviral transduction of DC in vivo might provide a powerful immunotherapeutic strategy.
Cognitive Effects of Antipsychotic Drugs in First-Episode Schizophrenia and Schizophreniform Disorder: A Randomized, Open-Label Clinical Trial (EUFEST) (2009)

Treatment with antipsychotic medication is associated with moderate improvement in the cognitive test performance of patients who have schizophreniform disorder or who are in their first episode of schizophrenia. The magnitude of improvement does not differ between treatment with haloperidol and treatment with second-generation antipsychotics. Moreover, cognitive improvement is weakly related to symptom change.
Self-Assembled Peptide Amphiphile Nanofibers Conjugated to MRI Contrast Agents (2004)

Self-assembled peptide amphiphile nanofibers have been investigated for their potential use as in vivo scaffolds for tissue engineering and drug delivery applications. We report here the synthesis of magnetic resonance (MR) active peptide amphiphile molecules that self-assemble into spherical and fiber-like nanostructures, enhancing T(1) relaxation time. This new class of MR contrast agents can potentially be used to combine high-resolution three-dimensional MR fate mapping of tissue-engineered scaffolds with targeting of specific cellular receptors.
Retinoid X receptor-specific retinoids inhibit the ability of retinoic acid receptor-specific retinoids to increase the level of insulin-like growth factor binding protein-3 in human ectocervical epithelial cells. (1996)

The hormones derived from vitamin A and related synthetic ligands (retinoids) are important regulators of differentiation and development and have been shown to be therapeutically useful in the treatment of cervical cancer. All-trans-retinoic acid exerts its effects by activation of retinoic acid receptor (RAR) and retinoid X receptor (RXR) heterodimers. These heterodimers bind to the retinoic acid response elements of target genes to regulate gene expression. RXR ligands act through RXR homodimers to regulate gene expression. In the present study, we describe the effects of RAR- and RXR-specific ligands on the regulation of insulin-like growth factor binding protein-3 (IGFBP-3) production and cell proliferation in human ectocervical epithelial (ECE) cell lines. Treatment of ECE16-1 cells with a RAR-specific ligand (TTNPB) or a ligand that interacts with both RAR and RXR receptors (9-cis-retinoic acid) increases IGFBP-3 levels and suppresses cell proliferation. In contrast, RXR-specific ligands (AGN191701, SR11217, and SR11237) do not regulate proliferation and slightly suppress the IGFBP-3 level. Cotreatment with increasing concentrations (0.01-1000nm) of RXR-specific ligand antagonizes the growth suppressive and IGFB-3-increasing effects of 1000 nM TTNPB. Similar results are observed in two other ECE cell lines, ECE16-D1 and ECE16-D2. These results indicate that RXR-specific ligands can antagonize RAR responses in these cell lines and suggest that a RAR-specific retinoid may be superior to one with mixed RAR/RXR binding activity for inhibiting cervical cancer cell proliferation. Moreover, the antagonism of RAR-dependent responses by RXR-specific ligands is consistent with a squelching model in which the RXR-specific ligand drives formation of RXR/RXR homodimers at the expense of the more active RAR/RXR heterodimers.
Dissipation-induced geometric phase for an atom trapped in an optical cavity (2012)

I present a feasible scheme to investigate the geometric phase for an atom trapped in an optical cavity induced by the effective decay process due to cavity-photon loss. The cavity mode, together with the external driving fields, acts as the engineered environment of the atom. When the parameters of the reservoir are adiabatically and cyclically changed, the system initially in the nontrivial dark state of the effective Lindblad operator undergoes a cyclic evolution and acquires a geometric phase. The geometric phase can be observed with the atomic-Ramsey-interference oscillation in the decoherence-free subspace.
PDE5 Inhibitors: In Vitro and In Vivo Pharmacological Profile (2009)

PDE5 inhibitors have been clearly established as first-line therapy for the treatment of erectile dysfunction (ED). Three PDE5 inhibitors--sildenafil (Viagra), vardenafil (Levitra) and tadalafil (Cialis)--are currently approved by the FDA and the EMEA for use in ED, whereas sildenafil is also marketed under a different proprietary name (Revatio) for the treatment of pulmonary arterial hypertension (PAH). A forth PDE5 inhibitor, udenafil (Zydena), is currently marketed. In the present review the molecular basis and the mechanism of action of PDE5 inhibitors is discussed. In addition experimental and clinical data concerning their effects on different tissues, organs and systems is systematically reviewed and their possible beneficial action in numerous disorders is presented.
New solid state photomultiplier (1995)

The physical properties of a new high-sensitive photodetector developed on the base of Avalanche heterostructures with Negative Feedback (ANF) are considered. The main difference between such a structure and a conventional avalanche photodiode (APD) is non- stationarity of the electrical field strength in an avalanche region caused by the feedback. It is shown that when the non-stationarity is manifested at amplification of a single photocarrier, it changes radically the main characteristics of the avalanche process. A qualitative physical model of ANF process and the results of numerical simulation and experiments are presented. They exhibit an ability of ANF-based device to provide a unique for solid state photosensor a combination of low noise, high gain and low response time. It is also shown that at the same time the negative feedback enables an avalanche device to be manufactured in multi-element design without serious difficulties. The experimental distribution of gain resulting from single- electron-initiated avalanche events was obtained on a SiC-Si ANF heterostructure, and confirmed the main model predictions. The results, illustrating the process of a few-photon light pulse registration are also presented. The opportunities of ANF-based devices further development are discussed.
Long-Term IgG Response to Porcine Neu5Gc Antigens without Transmission of PERV in Burn Patients Treated with Porcine Skin Xenografts (2013)

Acellular materials of xenogenic origin are used worldwide as xenografts, and phase I trials of viable pig pancreatic islets are currently being performed. However, limited information is available on transmission of porcine endogenous retrovirus (PERV) after xenotransplantation and on the long-term immune response of recipients to xenoantigens. We analyzed the blood of burn patients who had received living pig-skin dressings for up to 8 wk for the presence of PERV as well as for the level and nature of their long term (maximum, 34 y) immune response against pig Ags. Although no evidence of PERV genomic material or anti-PERV Ab response was found, we observed a moderate increase in anti-αGal Abs and a high and sustained anti-non-αGal IgG response in those patients. Abs against the nonhuman sialic acid Neu5Gc constituted the anti-non-αGal response with the recognition pattern on a sialoglycan array differing from that of burn patients treated without pig skin. These data suggest that anti-Neu5Gc Abs represent a barrier for long-term acceptance of porcine xenografts. Because anti-Neu5Gc Abs can promote chronic inflammation, the long-term safety of living and acellular pig tissue implants in recipients warrants further evaluation.
Switching between executive and default mode networks in posttraumatic stress disorder: alterations in functional connectivity (2010)

The different patterns of connectivity imply significant group differences with task-induced switches (i.e., engaging and disengaging the default mode network and the central-executive network).
Water-induced accelerated ion diffusion: voltammetric studies in 1-methyl-3-[2,6-(S)-dimethylocten-2-yl]imidazolium tetrafluoroborate, 1-butyl-3-methylimidazolium tetrafluoroborate and hexafluorophosphate ionic liquids (2000)

The electrochemical properties of the room temperature ionic liquids 1-butyl-3-methylimidazolium tetrafluoroborate (BMIM+BF4−), 1-butyl-3-methylimidazolium hexafluorophosphate (BMIM+PF6−) and 1-methyl-3-[2,6-(S)-dimethylocten-2-yl]imidazolium tetrafluoroborate (MDIM+BF4−) as solvents have been studied using micro-samples, with a volume of 10 μL, of the ionic liquids under vacuum conditions and under conditions with controlled gas and moisture supplies. The impact of water—absorbed into the ionic liquid in a controlled manner from the gas phase—on the voltammetry of dissolved redox systems and on the accessible potential window of the ionic liquids was investigated. The diffusion coefficients for three representative redox systems, the oxidation of neutral N,N,N′,N′-tetramethyl-p-phenylenediamine (TMPD), the reduction of cationic methyl viologen (MV2+) and reduction of anionic hexacyanoferrate(III), Fe(CN)63−, have been determined as a function of the water content of the ionic liquids. Water is shown to have a much more dramatic acceleration effect on the diffusion of the ionic compounds compared to its effect on neutral species in ionic liquids. A model based on nanoscale structural features of wet ionic liquid materials is proposed. The novel methodology, which employs redox-active compounds dissolved or partitioned in microdroplets of ionic liquid, uses conditions suitable for the study of ionic liquids for applications in electrochemical gas phase reactors and gas sensor systems.
Bioorganic & Medicinal Chemistry Letters (1995)

abstract Protein tyrosine phosphatases (PTPs) are cysteine-dependent enzymes that play a central role in cell sig-naling. Organic hydroperoxides cause thiol-reversible, oxidative inactivation of PTP1B in a manner thatmirrors the endogenous signaling agent hydrogen peroxide. 2008 Elsevier Ltd. All rights reserved. Protein tyrosine phosphatases (PTPs) are cysteine-dependentenzymes that catalyze the hydrolytic removal of phosphate groupsfrom tyrosine residues in proteins (Scheme 1). 1–3 Thus, PTPs, inconcert with protein tyrosine kinases, play a central role in cell sig-naling by regulating the phosphorylation status and, in turn, thefunctional properties of target proteins in various signal transduc-tion pathways. 4,5 The cellular activity of some PTPs is regulated by hydrogen per-oxide (H 2 O 2 ) that is produced as a second messenger in response toextracellular stimuli such as insulin, epidermal growth factor, andplatelet-derived growth factor. 6–9 H 2 O 2 inactivates PTPs via oxida-tion of the active site cysteine thiol residue to a sulfenic acid.
OCT elastography: imaging microscopic deformation and strain of tissue (1998)

Optical coherence tomography (OCT) has been applied to the study of the microscopic deformation of biological tissue under compressive stress. We describe the hardware and theory of operation of an OCT elastography system that measures internal displacements as small as a few micrometers by using 2D cross-correlation speckle tracking. Results obtained from gelatin scattering models, pork meat, and intact skin suggest possible medical applications of the technique.
Gp96 and its different expression in breast carcinomas. (2008)

The aim of our work was to determine the expression of glycoprotein 96 (gp96; glucose-regulated protein 94 - GRP94) in 69 samples of breast carcinoma. Enzyme immunohistochemical method was chosen for the detection of gp96 protein and its expression was compared in breast cancer cells versus normal breast cells. We found higher expression of gp96 protein in breast carcinoma cells and low or no expression in normal breast cells. Furthermore, we demonstrate first time, that ductal invasive breast carcinomas showed higher expression of gp96 than lobular invasive breast carcinomas.
Abstract 3962: SGN-LIV1A: a development stage antibody drug-conjugate targeting LIV-1 for the treatment of metastatic breast cancer. (2013)

Abstract LIV-1, also known as SLC39A6 or ZIP6, is a member of the zinc transporter family and was first identified as an estrogen-inducible gene in breast cancer derived cell lines. LIV-1, as a downstream target of STAT3, promotes the epithelial to mesenchymal transition that is important in the malignant progression to metastasis. Consistent with its role in cancer, we determined by immunohistochemical (IHC) analysis that LIV-1 is expressed in subtypes of metastatic breast cancers (ER+/HER2-, HER2+ and triple negative). In healthy human tissues, LIV-1 expression is limited to four hormonally-regulated organs. The broad expression of LIV-1 in metastatic breast cancer in combination with the limited expression in vital organs makes LIV-1 an excellent target for an antibody-drug conjugate (ADC). SGN-LIV1A is an ADC consisting of a humanized anti-LIV-1 mAb conjugated to the microtubule-disrupting agent, monomethyl auristatin E, via a protease-cleavable linker. In vitro, SGN-LIV1A shows target specific internalization and cytotoxic activity against a breast cancer cell line. In vivo studies also demonstrate antitumor activity of SGN-LIV1A in preclinical xenograft models with significant delay of tumor growth compared to control groups. These findings support further evaluation and development of SGN-LIVA as a therapeutic for the treatment of metastatic breast cancer. Citation Format: Django Sussman, Leia M. Smith, Martha E. Anderson, Steve Duniho, Joshua H. Hunter, Heather Kostner, Jamie B. Miyamoto, Albina Nesterova, Lori Westendorf, Heather A. Van Epps, Nancy Whiting, Dennis R. Benjamin. SGN-LIV1A: a development stage antibody drug-conjugate targeting LIV-1 for the treatment of metastatic breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3962. doi:10.1158/1538-7445.AM2013-3962
Crystal structure of the von Willebrand factor A domain of human capillary morphogenesis protein 2: An anthrax toxin receptor (2004)

Anthrax toxin is released from Bacillus anthracis as three monomeric proteins, which assemble into toxic complexes at the surface of receptor-bearing host cells. One of the proteins, protective antigen (PA), binds to receptors and orchestrates the delivery of the other two (the lethal and edema factors) into the cytosol. PA has been shown to bind to two cellular receptors: anthrax toxin receptor/tumor endothelial marker 8 and capillary morphogenesis protein 2 (CMG2). Both are type 1 membrane proteins that include an approximately 200-aa extracellular von Willebrand factor A (VWA) domain with a metal ion-dependent adhesion site (MIDAS) motif. The anthrax toxin receptor/tumor endothelial marker 8 and CMG2 VWA domains share approximately 60% amino acid identity and bind PA directly in a metal-dependent manner. Here, we report the crystal structure of the CMG2 VWA domain, with and without its intramolecular disulfide bond, to 1.5 and 1.8 A, respectively. Both structures contain a carboxylate ligand-mimetic bound at the MIDAS and appear as open conformations when compared with the VWA domains from alpha-integrins. The CMG2 structures provide a template to begin probing the high-affinity CMG2-PA interaction (200 pM) and may facilitate understanding of toxin assembly/internalization and the development of new anthrax treatments. The structural data also allow molecular interpretation of known CMG2 VWA domain mutations linked to the genetic disorders, juvenile hyaline fibromatosis, and infantile systemic hyalinosis.
A systematic review of ovarian cancer and fear of recurrence (2015)

This review demonstrates that FCR is prevalent in the ovarian cancer population. Moreover, cancer recurrence fears are not adequately assessed or treated. More information is needed on the factors that may be related to women's fears about recurrence of ovarian cancer. In addition, a validated measure of FCR among ovarian cancer patients as well as a treatment intervention are needed.
An improved PCR-mutagenesis strategy for two-site mutagenesis or sequence swapping between related genes (1998)

The QuikChangeTM protocol is one of the simplest and fastest methods for site-directed mutagenesis, but introduces mutations at only one site at a time, and requires two HPLC-purified complementary oligonucleotides. Here, we describe that this method can be used with non-overlapping oligonucleotides. By doing this, two separate sites can be mutagenised simultaneously, or money can be saved by using a second 'standard' oligonucleotide. By a further modification, we have also used the QuikChangeTM approach to exchange DNA sequences between closely related genes.
Screening for new mutations in the LDL receptor gene in seven French familial hypercholesterolemia families by the single strand conformation polymorphism method (1992)

To investigate the molecular basis of familial hypercholesterolemia (FH) in France, we applied the single strand conformation polymorphism (SSCP) method to the promoter region and the 18 exons of the low density lipoprotein receptor (LDLR) gene. Seven probands, 4 heterozygotes, 2 compound heterozygotes, and 1 homozygote, belonging to FH families were tested. In all cases, previous genetic analysis and/or LDL receptor fibroblast assay had shown that the disease was due to defects in the LDLR gene. Out of the nine mutations expected, one nonsense mutation in exon 2 and six missense mutations were identified in exons 3, 6, 8, 11, and 15. Two of the latter were found in exon 6. In each family, cosegregation of the base substitution and the disease was observed. Ninety-five control subjects were screened for the presence of the six missense mutations. None was detected, implying that the mutations identified are deleterious. Our results indicate that the SSCP analysis of amplified genomic DNA fragments can be successfully used to rapidly screen mutation containing exons in large genes. Furthermore, all these mutations are newly described and demonstrate heterogeneity of LDLR gene mutations responsible for FH in the French population, as in other reported Caucasian populations.
Expression of p27kip1 in prostatic adenocarcinoma. (1998)

p27kip1 (p27) protein is an inhibitor of cyclin and cyclin-dependent kinase complexes and prevents progression of cells from G1 to the S phase of the cell cycle. p27 might have tumor suppressor activity, and decreased p27 expression is associated with aggressive tumor behavior in several human malignancies. The object of this study was to evaluate p27 expression in prostatic adenocarcinoma treated by radical prostatectomy and to assess its association with numerous morphologic and clinical features. One hundred thirty-eight prostatic adenocarcinomas were evaluated for p27 expression by quantifying nuclear immunohistochemical staining. p27 expression was tested for association with patient age, family history of prostate cancer, preoperative serum prostate-specific antigen level, Gleason score, extraprostatic extension, seminal vesicle involvement, lymph node metastases, tumor-node-metastasis stage, DNA ploidy by flow cytometric analysis, and subclinical biochemical failure. p27 expression was analyzed as a continuous variable, and we also classified the tumors as low expressors (< 50% of cells p27 positive) or high expressors (> 50% of cells p27 positive) for comparison. Patients with adenocarcinomas that exhibited low p27 expression had higher mean Gleason scores than did high expressors (7 vs. 6.2, respectively; P = .002). Low p27 expression correlated with positive surgical margins (P = .05), seminal vesicle involvement (P = .007), lymph node metastasis (P = .03), and aneuploid cancers (P = .003), but it did not correlate with subclinical biochemical failure. p27 expression correlated with a number of prognostic morphologic features in prostatic adenocarcinoma, and the evaluation of p27 expression might provide additional prognostic information.
Feedforward—an alternative approach to amplifier linearization (1974)

Feedforward has largely been ignored as a circuit technique since feedback was introduced in the 1920s. Modern amplifiers can benefit from the application of feedforward as well as feedback and the principle can be applied to both h.f. and X-band amplifiers. The basic principles of feedforward are described and both equations and design curves are included. Two variants of the basic feedforward arrangement are also described. One is arranged for power conservation while the other uses two identical amplifiers at full power to give a more linear output than that available from either separately. The results of these different feedforward arrangements using a pair of proprietary 30 W h.f. amplifiers are included.
GAIP, GIPC and Gαi3 are Concentrated in Endocytic Compartments of Proximal Tubule Cells (2002)

Megalin is the most abundant endocytic receptor in the proximal tubule epithelium (PTE), where it is concentrated in clathrin-coated pits (CCPs) and vesicles in the brush border region. The heterotrimeric G protein alpha subunit, Galphai3, has also been localized to the brush border region of PTE. By immunofluorescence GIPC and GAIP, components of G protein-mediated signaling pathways, are also concentrated in the brush border region of PTE and are present in megalin-expressing cell lines. By cell fractionation, these signaling molecules cosediment with megalin in brush border and microvillar fractions. GAIP is found by immunoelectron microscopy in CCPs, and GIPC is found in CCPs and apical tubules of endocytic compartments in the renal brush border. In precipitation assays, GST-GIPC specifically binds megalin. The concentration of Galphai3, GIPC, and GAIP with megalin in endocytic compartments of the proximal tubule, where extensive endocytosis occurs, and the interaction between GIPC and the cytoplasmic tail of megalin suggest a model whereby G protein-mediated signaling may regulate megalin's endocytic function and/or trafficking.
A knowledge-based configurator that supports sales, engineering, and manufacturing at AT&T Network Systems (1993)

PROSE is a knowledge-based configurator platform for telecommunications products. Its outstanding feature is a product knowledge base written in C-classIC, a frame-based knowledge representation system in the KL-ONE family of languages. It is one of the first successful products using a KL-ONE style language. Unlike previous configurator applications, the PROSE knowledge base is in a purely declarative form that provides developers with the ability to add knowledge quickly and consistently. The PROSE architecture is general and is not tied to any specific telecommunications product. As such, it is being reused to develop configurators for several different products. Finally, PROSE not only generates configurations from just a few high-level parameters, but it can also verify configurations produced manually by customers, engineers, or salespeople. The same product knowledge, encoded in C-classIC, supports both the generation and the verification of product configurations.