gebhart/patrepeval huggingface dataset:
Regression of established renal cell carcinoma in nude mice using lentivirus-transduced human T cells expressing a human anti-CAIX chimeric antigen receptor (2014)

Carbonic anhydrase IX (CAIX) is a tumor-associated antigen and marker of hypoxia that is overexpressed on > 90% of clear-cell type renal cell carcinoma (RCC) but not on neighboring normal kidney tissue. Here, we report on the construction of two chimeric antigen receptors (CARs) that utilize a carbonic anhydrase (CA) domain mapped, human single chain antibody (scFv G36) as a targeting moiety but differ in their capacity to provide costimulatory signaling for optimal T cell proliferation and tumor cell killing. The resulting anti-CAIX CARs were expressed on human primary T cells via lentivirus transduction. CAR-transduced T cells (CART cells) expressing second-generation G36-CD28-TCRζ exhibited more potent in vitro antitumor effects on CAIX(+) RCC cells than first-generation G36-CD8-TCRζ including cytotoxicity, cytokine secretion, proliferation, and clonal expansion. Adoptive G36-CD28-TCRζ CART cell therapy combined with high-dose interleukin (IL)-2 injection also lead to superior regression of established RCC in nude mice with evidence of tumor cell apoptosis and tissue necrosis. These results suggest that the fully human G36-CD28-TCRζ CARs should provide substantial improvements over first-generation mouse anti-CAIX CARs in clinical use through reduced human anti-mouse antibody responses against the targeting scFv and administration of lower doses of T cells during CART cell therapy of CAIX(+) RCC.
Androgen receptors in prostate cancer. (2002)

The androgen receptor (AR), a transcription factor that mediates the action of androgens in target tissues, is expressed in nearly all prostate cancers. Carcinoma of the prostate is the most frequently diagnosed neoplasm in men in industrialized countries. Palliative treatment for non-organ-confined prostate cancer aims to down-regulate the concentration of circulating androgen or to block the transcription activation function of the AR. AR function during endocrine therapy was studied in tumor cells LNCaP subjected to long-term steroid depletion; newly generated sublines could be stimulated by lower concentrations of androgen than parental cells and showed up-regulation of AR expression and activity as well as resistance to apoptosis. Androgenic hormones regulate the expression of key cell cycle regulators, cyclin-dependent kinase 2 and 4, and that of the cell cycle inhibitor p27. Inhibition of AR expression could be achieved by potential chemopreventive agents flufenamic acid, resveratrol, quercetin, polyunsaturated fatty acids and interleukin-1beta, and by the application of AR antisense oligonucleotides. In the clinical situation, AR gene amplification and point mutations were reported in patients with metastatic disease. These mutations generate receptors which could be activated by other steroid hormones and non-steroidal antiandrogens. In the absence of androgen, the AR could be activated by various growth-promoting (growth factors, epidermal growth factor receptor-related oncogene HER-2/neu) and pleiotropic (protein kinase A activators, interleukin-6) compounds as well as by inducers of differentiation (phenylbutyrate). AR function is modulated by a number of coactivators and corepressors. The three coactivators, TIF-2, SRC-1 and RAC3, are up-regulated in relapsed prostate cancer. New experimental therapies for prostate cancer are aimed to down-regulate AR expression and to overcome difficulties which occur because of the acquisition of agonistic properties of commonly used antiandrogens.
Silicon vapor phase epitaxial growth catalysis by the presence of germane (1990)

Experiments involving the epitaxial growth of GexSi1−x films by chemical vapor deposition have shown that the addition of germane greatly enhances the growth rate, compared to that seen with dichlorosilane alone. Careful analysis shows that the increase is not accounted for by summing the individual growth rates, but clearly indicates that the silicon growth rate is catalyzed. The magnitude of the effect increases at lower temperatures, with a two orders of magnitude increase seen at 625 °C.
Functional invadopodia formation through stabilization of the PDPN transcript by IMP-3 and cancer-stromal crosstalk for PDPN expression (2012)

We previously reported that insulin-like growth factor-II mRNA-binding protein-3 (IMP-3) depletion (IMP-3(Δ)) was shown to inhibit invadopodia formation and extracellular matrix degradation capacity in oral squamous cell carcinoma (OSCC) cells. In this study, we found that IMP-3(Δ) cells significantly downregulated the podoplanin (PDPN) level, which resulted in a loss of extracellular matrix degradation activity, although invadopodia was still thriving. From RNA in situ hybridization using a digoxigenin-labeled 3'UTR recognition probe of PDPN and reporter assay with 3'UTR of the PDPN gene cloned downstream from the luciferase reporter gene, we revealed that IMP-3 depletion was shown to be downregulated, which most probably lowered PDPN gene expression by reducing mRNA stabilization. In a xenograft model, PDPN depletion was the cause of a decrease in tumor volume and regional infiltration into nearby stroma. Taken together, transforming growth factor beta 1 increased PDPN expression, which potentiated cancer invasion through increased invadopodia formation and extracellular matrix degradation in the low invasive OSCC cell line. Reciprocally, interleukin-1 beta secreted by OSCC cells, stimulated transforming growth factor beta 1 secretion from stromal fibroblasts to induce PDPN expression in OSCC cells. In addition, a retrospective investigation of OSCC patients found that IMP-3 and PDPN expression significantly correlated with lymph node metastasis of OSCC patients. Moreover, co-expression of IMP-3 and PDPN were frequently detected both in primary and lymph nodes metastatic OSCC cells using immunohistochemical dual staining. Thus, the IMP-3-PDPN axis may be a sensitive target molecule in anti-invadopodia therapy for the treatment of metastatic cancers.
The RNA Tumor Viruses—Background and Foreground (1972)

The members of the RNA tumor virus (or leukovirus) group of animal viruses replicate via a DNA intermediate and transmit their information stably in cells as DNA. Although some of these viruses are capable of inducing neoplastic transformation, others are not. These viruses may be related to spontaneous neoplasia, but the relationship is that of analogy rather than etiology. The relationship of these viruses to human disease is unknown. Two models of spontaneous neoplasia that involve either activation of the information of a transforming RNA tumor virus or the creation of information for neoplastic transformation by recombination involving information transfer from RNA to DNA are being tested in model systems.
An Introduction to Computational Networks and the Computational Network Toolkit (2014)

We introduce computational network (CN), a unified framework for describing arbitrary learning machines, such as deep neural networks (DNNs), convolutional neural networks (CNNs), recurrent neural networks (RNNs), long short term memory (LSTM), logistic regression, and maximum entropy model, that can be illustrated as a series of computational steps. A CN is a directed graph in which each leaf node represents an input value or a parameter and each non-leaf node represents a matrix operation upon its children. We describe algorithms to carry out forward computation and gradient calculation in CN and introduce most popular computation node types used in a typical CN. We further introduce the computational network toolkit (CNTK), an implementation of CN that supports both GPU and CPU. We describe the architecture and the key components of the CNTK, the command line options to use CNTK, and the network definition and model editing language, and provide sample setups for acoustic model, language model, and spoken language understanding. We also describe the Argon speech recognition decoder as an example to integrate with CNTK.
Franz Link, Geschichte der Amerikanischen Erzählkunst von 1900 bis 1950 (Stuttgart: W. Kohlhammer, 1983, DM 39.80). Pp. 294. (1984)

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The Human Auricular Chondrocyte: Responses to Growth Factors (1993)

The first human auricular (elastic cartilage) chondrocyte cell culture model is presented. These chondrocytes, harvested from fresh human cadaver auricular cartilage, are easily grown in culture. They produce type II collagen and abundant alkaline phosphatase. Like growth plate chondrocytes, human auricular chondrocytes respond mitogenically to both transforming growth factor-beta and basic fibroblast growth factor by increasing proliferation twofold. The growth factors exert a synergistic effect on thymidine uptake in this model, with maximal stimulation occurring at the dose combination of basic fibroblast growth factor, 10 ng/mL, and transforming growth factor-beta, 3 ng/mL. Human nasal septal (hyaline cartilage) chondrocytes do not increase proliferation in response to these two growth factors. Human auricular chondrocytes also increase matrix production in response to transforming growth factor-beta, as indicated by increased proteoglycan production and increased collagen synthesis. The increased matrix production combined with increased proliferative rate elicited with transforming growth factor-beta and basic fibroblast growth factor indicates that human elastic cartilage chondrocytes harvested from the external ear are better suited for in vitro cartilage implant growth than human hyaline cartilage chondrocytes. Further biochemical and molecular biological characterization of the human auricular chondrocyte cell culture model is currently under way. Additional work is also under way to generate multilayer culture growth on absorbable frameworks, in the pursuit of the long-term goal of in vitro production of autogenous cartilage implants.
A new method to compute K-mer frequencies and its application to annotate large repetitive plant genomes (2008)

The Tallymer software was effective in a variety of applications to aid genome annotation in maize, despite limitations imposed by the relatively low coverage of sequence available. For more information on the software, see http://www.zbh.uni-hamburg.de/Tallymer.
The Aerobic and Anaerobic Microflora of the Gastric Remnant More than 15 Years after Billroth II Resection (1982)

The bacteriology of the gastric remnant contents was examined in 150 patients 15-20 years after Billroth II resection for duodenal ulcer disease. Samples of gastric contents were aspirated through a gastroscope, and aerobic and anaerobic microflora were cultured and analyzed semiquantitatively. All patients but one had bacterial growth, with a mean number of 6.8 strains per remnant. One third of the bacterial strains were anaerobic, and many of them had their normal habitat in the colon. The role played by bacteria of the gastric remnant in the etiology of mucosal pathology and gastric remnant disease is discussed.
Treatment of therapy-refractory B-lineage acute lymphoblastic leukemia with an apoptosis-inducing CD19-directed tyrosine kinase inhibitor. (1999)

Seven children and eight adults with CD19+ B-lineage acute lymphoblastic leukemia, as well as one adult with chronic lymphocytic leukemia, were treated with the CD19 receptor-directed tyrosine kinase inhibitor B43-Genistein. All patients had failed previous chemotherapy regimens, and six patients had relapsed after bone marrow transplantation. B43-Genistein was administered as a 1-hour i.v. infusion at 0.1-0.32 mg/kg/day dose levels for 10 consecutive days or 3 consecutive days weekly for a total of nine doses. B43-Genistein was well tolerated by all patients with no life-threatening side effects. There were six episodes of grade 2-3 fever, two of which were clearly drug related, one episode each of grade 3 myalgia, grade 2 sinus tachycardia, and grade 2 vascular leak syndrome. There was one durable complete remission and two transient responses. Pharmacokinetic analyses in 12 patients revealed a plasma half-life of 20 +/- 5 h, mean residence time of 24 +/- 5 h, and a systemic clearance rate of 20 +/- 3 ml/h/kg. Moderate levels of human antimouse antibody (HAMA) ranging from 20-87 ng/ml were detected in the day 28 blood samples from three of nine cases examined. Treatment of these three HAMA-positive patients with a second course of B43-Genistein did not yield measurable immunoconjugate levels in the plasma, indicating that the administered B43-Genistein molecules were rapidly cleared from circulation due to the HAMA. On the basis of its acceptable toxicity profile and its ability to elicit objective responses at nontoxic dose levels, B43-Genistein may provide the basis for an effective treatment strategy for B-lineage acute lymphoblastic leukemia patients who have failed standard therapy.
Staging of the pathophysiologic responses of the primate microvasculature to Escherichia coli and endotoxin: Examination of the elements of the compensated response and their links to the corresponding uncompensated lethal variants (2001)

This review concerns the primate microvascular endothelial response to inflammatory and hemostatic stress. Studies of the impact of inflammatory and hemostatic stress on this microvasculature have fallen into four categories. First, studies of pure hemostatic stress using factor Xa phospholipid vesicles showed that blockade of protein C as well as protein C plus tissue plasminogen activator produced a severe but transient consumptive and a lethal thrombotic coagulopathy, respectively. These studies showed that the protein C and fibrinolytic systems can work in tandem to regulate even a severe response if the endothelium is not rendered dysfunctional by metabolic or inflammatory factors. Second, studies of compensated (nonlethal) inflammatory stress using E. coli or endotoxin in baboon and human subjects showed that even under minimal stress in which there is no evidence of overt disseminated intravascular coagulation, injury of the endothelium and activation of neutrophils and hemostatic factors are closely associated. This showed that molecular markers of hemostatic activity could be used to detect microvascular endothelial stress (nonovert disseminated intravascular coagulation) in patients who are compensated but at risk. These studies also showed that the compensated response to inflammatory stress could exhibit two stages, each with its unique inflammatory and hemostatic response signature. The first is driven by vasoactive peptides, cytokines, and thrombin, followed 12 to 14 hrs later by a second stage driven by C-reactive protein/complement complexes, tissue factor, and plasminogen activator inhibitor 1 secondary to oxidative stress after reperfusion. Third, studies of uncompensated (lethal) inflammatory stress using E. coli showed that irreversible thrombosis of the microvasculature was not a link in the lethal chain of events even though inhibition of components of the protein C network (protein C and endothelial protein C receptor) converted compensated responses to sublethal E. coli into uncompensated lethal responses. Fourth, these studies also showed that there were variants of the lethal response ranging from capillary leak and shock to recurrent sustained inflammatory disorders. We believe that each of these variants arises from their sublethal counterparts, depending on underlying or modulating host factors operating at the time of challenge. Such underlying conditions range from preexisting microvascular ischemia, reperfusion, and oxidative stress to alteration or reprogramming of monocyte/macrophage responses (tolerance to hyperresponsiveness). Characterization of these underlying conditions in patients who are at risk should aid in identifying and optimizing management of these variants.
Bayesian update of dialogue state: A POMDP framework for spoken dialogue systems (2009)

This paper describes a statistically motivated framework for performing real-time dialogue state updates and policy learning in a spoken dialogue system. The framework is based on the partially observable Markov decision process (POMDP), which provides a well-founded, statistical model of spoken dialogue management. However, exact belief state updates in a POMDP model are computationally intractable so approximate methods must be used. This paper presents a tractable method based on the loopy belief propagation algorithm. Various simplifications are made, which improve the efficiency significantly compared to the original algorithm as well as compared to other POMDP-based dialogue state updating approaches. A second contribution of this paper is a method for learning in spoken dialogue systems which uses a component-based policy with the episodic Natural Actor Critic algorithm. The framework proposed in this paper was tested on both simulations and in a user trial. Both indicated that using Bayesian updates of the dialogue state significantly outperforms traditional definitions of the dialogue state. Policy learning worked effectively and the learned policy outperformed all others on simulations. In user trials the learned policy was also competitive, although its optimality was less conclusive. Overall, the Bayesian update of dialogue state framework was shown to be a feasible and effective approach to building real-world POMDP-based dialogue systems.
Role of Calcitonin Gene-Related Peptide in Inhibitory Neurotransmission to the Pig Bladder Neck (2011)

We studied the role of calcitonin gene-related peptide in nonadrenergic, noncholinergic neurotransmission to the pig bladder neck.We used immunohistochemical techniques to determine the distribution of calcitonin gene-related peptide immunoreactive fibers as well as organ baths for isometric force recording. We investigated relaxation due to endogenously released or exogenously applied calcitonin gene-related peptide in urothelium denuded phenylephrine precontracted strips treated with guanethidine, atropine and NG-nitro-L-arginine to block noradrenergic neurotransmission, muscarinic receptors and nitric oxide synthase, respectively.Rich calcitonin gene-related peptide immunoreactive innervation was found penetrating through the adventitia and distributed in the suburothelial and muscle layers. Numerous, variable size, varicose calcitonin gene-related peptide immunopositive terminals were seen close below the urothelium. In the muscle layer calcitonin gene-related peptide immunopositive nerves usually appeared as varicose terminals running along muscle fibers. Electrical field stimulation (2 to 16 Hz) and exogenous calcitonin gene-related peptide (0.1 nM to 0.3 μM) evoked frequency and concentration dependent relaxation, respectively. Nerve responses were potentiated by capsaicin, decreased by calcitonin gene-related peptide (8-37) and abolished by tetrodotoxin, capsaicin sensitive primary afferent blockers, calcitonin gene-related peptide receptors and neuronal voltage gated Na+ channels. Calcitonin gene-related peptide-induced relaxation was potentiated by the neuronal voltage gated Ca2+ channels blocker ω-conotoxin-GVIA and decreased by calcitonin gene-related peptide (8-37). Calcitonin gene-related peptide relaxation was not modified by blockade of endopeptidases, nitric oxide synthase, guanylyl cyclase and cyclooxygenase.Results suggest that calcitonin gene-related peptide is involved in the nonadrenergic, noncholinergic inhibitory neurotransmission of the pig bladder neck, producing relaxation through neuronal and muscle calcitonin gene-related peptide receptors. Nitric oxide/cyclic guanosine monophosphate and cyclooxygenase pathways do not seem to be involved in such responses.
Concentrations of galectin-3 in the sera of normal controls and cancer patients. (2000)

Galectin-3, a member of the beta-galactoside-binding animal lectins, has been implicated in tumor invasion and metastasis. Using an immunoligand assay, we assessed the circulating levels of galectin-3 in sera from cancer patients as well as from healthy controls. Low serum levels of galectin-3 were detected in healthy individuals (median, 62 ng/ml; range, 20-313 ng/ml; 95th percentile, 184.3 ng/ml). Compared with healthy individuals, galectin-3 serum levels in patients with breast, gastrointestinal, lung, or ovarian cancer, melanoma, and non-Hodgkin's lymphoma were significantly elevated (P = 0.014). Moreover, galectin-3 concentrations in sera from patients with metastatic disease were higher than in sera from patients with localized tumors. Maximum serum concentrations of galectin-3 (median, 320 ng/ml; range, 20-950 ng/ml) were found in patients with metastatic gastrointestinal carcinoma. These results suggest that circulating galectin-3 may play a role in tumor progression. The possibility of using this assay in early-stage cancer to predict metastasis should be studied.
Electrodeposition of Patterned CdSe Nanocrystal Films using Thermally Charged Nanocrystals (2002)

A dc electric field is used to attract charged CdSe nanocrystals in hexane to rapidly form very smooth, robust, large-area, several micron-thick films of equal thickness on both electrodes. This deposition on both electrodes implies there are both positively and negatively thermally charged dots, unlike conventional electrophoretic deposition. With patterned electrodes, controllable and locally selective assembly is achieved.
Neuropeptide Y mobilizes Ca2+ and inhibits adenylate cyclase in human erythroleukemia cells (1988)

Neuropeptide Y (NPY), a peptide often coreleased with catecholamines, appears to be an important component of the sympathetic nervous system, but little is known about the molecular basis of its action. We introduce here human erythroleukemia (HEL) cells as a new model system for studies of NPY action. NPY inhibited adenosine 3,5'-cyclic monophosphate (cAMP) accumulation in HEL cells with a 50% effective concentration (EC50) of 3 nM. Additionally NPY increased intracellular Ca2+, as assessed by fura-2 fluorescence, with a similar EC50. Pretreatment with pertussis toxin blocked both responses, suggesting the involvement of one or more G proteins. Chelating extracellular Ca2+ with EGTA did not reduce the Ca2+ signal, demonstrating mobilization from intracellular stores rather than influx. Experiments with various agents demonstrated that the Ca2+ mobilization was not secondary to lowering of cAMP levels, formation of arachidonic acid products, or Na+-H+ exchange. Ca2+ mobilization also did not appear to be associated with inositol phosphate generation. In conclusion, we demonstrate for the first time that NPY, in addition to inhibiting adenylate cyclase, also can elevate intracellular Ca2+. HEL cells should prove useful in further studies of the molecular basis of NPY action.
Excited states ofFe3+in GaN (1997)

We report a comprehensive photoluminescence excitation (PLE) investigation of the deep iron acceptor in hexagonal GaN. PLE spectra of the ${\mathrm{Fe}}^{3+}$ ${[}^{4}$ ${\mathrm{T}}_{1}$ (G)${\mathrm{\ensuremath{-}}}^{6}$ ${\mathrm{A}}_{1}$ (S)] luminescence in semi-insulating GaN samples reveal intracenter excitation processes via excited states of the ${\mathrm{Fe}}^{3+}$ center. Zero-phonon lines resolved around 2.01 and at 2.731 eV are attributed to the $^{6}$ ${\mathrm{A}}_{1}$ (S)${\mathrm{\ensuremath{-}}}^{4}$ ${\mathrm{T}}_{2}$ (G) and the $^{6}$ ${\mathrm{A}}_{1}$ (S)${\mathrm{\ensuremath{-}}}^{4}$ E(G) transition, respectively. A steplike excitation structure on the low-energy onset of the ${\mathrm{Fe}}^{3+\mathrm{/}2+}$ charge-transfer band is attributed to the formation of a (${\mathrm{Fe}}^{3+}$,e,h) complex at 2.888 eV. We estimate a binding energy of 280 meV locating the deep ${\mathrm{Fe}}^{3+\mathrm{/}2+}$ acceptor level 3.17 eV above the valence-band maximum. In n-type GaN samples the ${\mathrm{Fe}}^{3+}$ luminescence is excited by hole-transfer processes. The experimental results indicate that the internal reference rule fails for the GaN/GaAs heterostructure.