gebhart/patrepeval huggingface dataset:
Stromal CD38 regulates outgrowth of primary melanoma and generation of spontaneous metastasis (2018)

The outgrowth of primary melanoma, the deadliest skin cancer, and generation of metastasis is supported by the tumor microenvironment (TME) which includes non-cancerous cells. Since the TME plays an important role in melanoma pathogenesis, its targeting is a promising therapeutic approach. Thus, it is important to identify proteins in the melanoma TME that may serve as therapeutic targets. Here we show that the nicotinamide adenine dinucleotide glycohydrolase CD38 is a suitable target for this purpose. Loss of CD38 in the TME as well as inhibition of its enzymatic activity restrained outgrowth of primary melanoma generated by two transplantable models of melanoma, B16F10 and Ret-mCherry-sorted (RMS) melanoma cells. Pathological analysis indicated that loss of CD38 increased cell death and reduced the amount of cancer-associated fibroblasts (CAFs) and blood vessels. Importantly, in addition to inhibiting outgrowth of primary melanoma tumors, loss of CD38 also inhibited spontaneous occurrence of RMS pulmonary and brain metastasis. The underlying mechanism may involve, at least in the brain, inhibition of metastasis expansion, since loss of CD38 inhibited the outgrowth of B16F10 and RMS brain tumors that were generated by direct intracranial implantation. Collectively, our results suggest that targeting CD38 in the melanoma TME provides a new therapeutic approach for melanoma treatment.
Use of Human Adenovirus-based Vectors for Antigen Expression in Animals (1989)

An infectious recombinant human adenovirus type 5 (Ad5) vector, AdG12, which carries the glycoprotein gene of vesicular stomatitis virus (VSV) and expresses that gene in cultured HeLa cells was used to examine the host range of insert expression by human Ad vectors. The VSV glycoprotein was expressed in bovine, canine and murine cells when infected with AdG12 in culture. These cell lines are respectively permissive, non-permissive and semi-permissive for human Ad5 replication. Administration of the AdG12 vector to calves, piglets or dogs by either the subcutaneous or oral route resulted in the production of high titres of neutralizing antibodies to VSV. Mice injected intraperitoneally with the vector produced neutralizing antibodies and were protected against subsequent intravenous challenge with normally lethal doses of VSV. This work demonstrates the utility of human adenoviral vectors for antigen expression in a number of non-human cell lines and for the induction of an immune response to the delivered antigen in a number of species.
Automatic tracking of region of interest in neurosurgical video (2005)

In this paper, we present a new method to automatically detect a region of interest (ROI) within video frames for remote monitoring of neurosurgery. This method is based on an object tracking technique combined with an automatic shape analysis. By defining the ROI, this method produces a smooth and convex emphasis region within which surgical procedures are performed. A large bandwidth budget is assigned within the ROI to archive high-fidelity Internet transmission. Outside the ROI, a small bandwidth budget is allocated to efficiently utilize the bandwidth resource in Internet connection.
A Saccharomyces cerevisiae homolog of the human adrenoleukodystrophy transporter is a heterodimer of two half ATP-binding cassette transporters. (1996)

The adrenoleukodystrophy protein (ALDP) and the 70-kDa peroxisomal membrane protein (PMP70) are half ATP-binding cassette (ABC) transporters in the human peroxisome membrane. ALDP and PMP70 share sequence homology and both are implicated in genetic diseases. PXA1 and YKL741 are Saccharomyces cerevisiae genes that encode homologs of ALDP and PMP70. Pxa1p, a putative ortholog of ALDP, is involved in peroxisomal beta-oxidation of fatty acids while YKL741 is an open reading frame found by the yeast genome sequencing project. Here we designate YKL741 as PXA2 and show that its protein product, Pxa2p, like Pxa1p, is associated with peroxisomes but not required for their assembly. Yeast strains carrying gene disruption of PXA1, PXA2, or both have similar and, in the case of the latter, nonadditive phenotypes. We also find that the stability of Pxa1p, but not Pxa2p, is markedly reduced in the absence of the other. Finally, we find that Pxa1p and Pxa2p coimmuno-precipitate. These genetic and physical data suggest that Pxa1p and Pxa2p heterodimerize to form a complete peroxisomal ABC transporter involved in fatty acid beta-oxidation. This result predicts the presence of similar heterodimeric ABC transporters in the mammalian peroxisome membrane.
Synthesis and Structure–Activity Relationship Studies of Small Molecule Disruptors of EWS-FLI1 Interactions in Ewing’s Sarcoma (2014)

EWS-FLI1 is an oncogenic fusion protein implicated in the development of Ewing's sarcoma family tumors (ESFT). Using our previously reported lead compound 2 (YK-4-279), we designed and synthesized a focused library of analogues. The functional inhibition of the analogues was measured by an EWS-FLI1/NR0B1 reporter luciferase assay and a paired cell screening approach measuring effects on growth inhibition for human cells containing EWS-FLI1 (TC32 and TC71) and control PANC1 cell lines devoid of the oncoprotein. Our data revealed that substitution of electron donating groups at the para-position on the phenyl ring was the most favorable for inhibition of EWS-FLI1 by analogs of 2. Compound 9u (with a dimethylamino substitution) was the most active inhibitor with GI50 = 0.26 ± 0.1 μM. Further, a correlation of growth inhibition (EWS-FLI1 expressing TC32 cells) and the luciferase reporter activity was established (R(2) = 0.84). Finally, we designed and synthesized a biotinylated analogue and determined the binding affinity for recombinant EWS-FLI1 (Kd = 4.8 ± 2.6 μM).
Genetic and Structural Evidence for Antigen Selection of Anti-DNA Antibodies (1994)

The primary structure of anti-DNA antibodies is highly diverse, a result of different germline variable (V) gene use, different combinations of immunoglobulin gene segments, peculiar heavy chain complementarity determining region 3 (H-CDR3) segments, and somatic mutations. Nevertheless, tertiary structure predictions reveal common features that yield information about likely contact sites in the anti-DNA combining site. That these contacts are involved with DNA binding is supported by recurrent features of a newly compiled set of homology groups of 13 variable regions of heavy chains (VH) and 11 variable regions of light chains (VL), characteristic pattern of somatic mutations, and the results of site-directed mutagenesis. The role of antigen in the etiology of the autoimmune response is viewed in light of recent data on overlaps between anti-DNA and anti-nucleic acid binding protein specificities.
Initiation of Plant Disease Resistance by Physical Interaction of AvrPto and Pto Kinase (1996)

Resistance to bacterial speck disease in tomato occurs when the Pto kinase in the plant responds to expression of the avirulence gene avrPto in the Pseudomonas pathogen. Transient expression of an avrPto transgene in plant cells containing Pto elicited a defense response. In the yeast two-hybrid system, the Pto kinase physically interacted with AvrPto. Alterations of AvrPto or Pto that disrupted the interaction in yeast also abolished disease resistance in plants. The physical interaction of AvrPto and Pto provides an explanation of gene-for-gene specificity in bacterial speck disease resistance.
RESPONSE OF HUMAN INTERVERTEBRAL DISC CELLS TO IL-1 (2003)

Objective and Background : This study investigated the effects of IL-1 on human intervertebral disc cells (IVD). IL-1 has been implicated in the degradation of IVD, in particular the up-regulation of Matrix Metalloproteinases (MMPs) and the down regulation of proteoglycan synthesis. However very little is known of the effects of IL-1 on human IVD cells. Here, we have investigated the effects of both IL-1 α and IL-1 β on nucleus pulposus (NP) and Annulus fibrosus (AF) cells isolated from human degenerate IVD. Methods : Human IVD tissue was obtained from disc replacement surgery and separated into NP and AF tissue, cells were cultured within an alginate bead system for 5 weeks before treatment with IL-1 α and IL-1 β for 48 hours. Following treatment, RNA was extracted and Real time RT-PCR was performed to investigate gene expression of IL-1 gene family, matrix proteins and degrading enzymes MMPs and ADAMTS. Results : Interleukin 1 α showed a more potent response than IL-1 β and in addition NP cells were more sensitive than AF cells. In summary, IL-1 showed a positive feedback loop causing an up-regulation of α and β genes. IL-1 Ra was also up-regulated but to a lesser extent than IL-1 α and IL-1 β. A negative feedback loop was seen with inhibition of the IL-1 receptor gene upon treatment with IL-1. MMPs and ADAMTS showed up-regulation upon treatment with IL-1. In addition IL-1 down regulated the matrix protein’s collagen type II and Aggrecan. Conclusions : This study demonstrates that IL-1 causes up-regulation in discal cells of the major degrading enzymes involved in discal degeneration, and a down regulation of the major matrix components within the IVD. Suggesting that IL-1 plays a major in process of discal degeneration.
Methods for the Selective Oxidation of Cellulose: Preparation of 2,3-Dicarboxycellulose and 6-Carboxycellulose (1998)

Three methods for the selective oxidation of cellulose are described. The classical method consists of consecutive oxidation with sodium periodate, leading to 2,3-dialdehyde cellulose and sodium chlorite, giving 2,3-dicarboxy cellulose. This material, which is obtained in high yield and has a high carboxylate content (7.6 mmol COONa/g; 90% of the theoretical value), has a very good calcium sequestering capacity. The second method is by oxidation of the substrate, dissolved in concentrated phosphoric acid with nitrite/nitrate, leading to the selective oxidation of the substrate at the 6-position of the glucose unit. Generally, the yields are higher than 80%, and the degree of oxidation is 80-90%. However, the reaction is not completely specific, since some oxidation at the secondary hydroxylic groups occurs. Borohydride reduction of the product restores the diol configuration and also β-elimination is avoided and thereby depolymerization. Oxidation with sodium hypochlorite and bromide as a catalyst and TEMPO as a mediator appears also to be applicable to cellulose. Selectivity of oxidation at the 6-CH2OH group is somewhat lower than that obtained earlier for glucans like starch and pullulan. Products with a degree of oxidation of 80% are obtained in 90% yield or higher.
Promiscuous Coupling at Receptor-Gα Fusion Proteins (2003)

Fusion proteins between heptahelical receptors (GPCR) and G protein alpha-subunits show enhanced signaling efficiency in transfected cells. This is believed to be the result of molecular proximity, because the interaction between linked modules of one protein chain, if not constrained by structure, should be strongly favored compared with the same in which partners react as free species. To test this assumption we made a series of fusion proteins (type 1 and 4 opioid receptors with G(o) and beta(2) adrenergic and dopamine 1 receptors with G(sL)) and some mutated analogs carrying different tags and defective GPCR or Galpha subunits. Using cotransfection experiments with readout protocols able to distinguish activation at fused and non-fused alpha-subunits, we found that both the GPCR and the Galpha limb of one fusion protein can freely interact with non-fused proteins and the tethered partners of a neighboring fusion complex. Moreover, a bulky polyanionic inhibitor can suppress with identical potency receptor-Galpha interaction, either when occurring between latched domains of a fused system or separate elements of distinct molecules, indicating that the binding surfaces are equally accessible in both cases. These data demonstrate that there is no entropy drive from the linked condition of fusion proteins and suggest that their signaling may result from the GPCR of one complex interacting with the alpha-subunit of another. Moreover, the enhanced coupling efficiency commonly observed for fusion proteins is not due to the receptor tether, but to the transmembrane helix that anchors Galpha to the membrane.
Neogenin inhibits HJV secretion and regulates BMP-induced hepcidin expression and iron homeostasis (2010)

Neogenin, a deleted in colorectal cancer (DCC) family member, has been identified as a receptor for the neuronal axon guidance cues netrins and repulsive guidance molecules repulsive guidance molecules (RGM). RGMc, also called hemojuvelin (HJV), is essential for iron homeostasis. Here we provide evidence that neogenin plays a critical role in iron homeostasis by regulation of HJV secretion and bone morphogenetic protein (BMP) signaling. Livers of neogenin mutant mice exhibit iron overload, low levels of hepcidin, and reduced BMP signaling. Mutant hepatocytes in vitro show impaired BMP2 induction of Smad1/5/8 phosphorylation and hepcidin expression. Neogenin is expressed in liver cells in a reciprocal pattern to that of hepcidin, suggesting that neogenin functions in a cell nonautonomous manner. Further studies demonstrate that neogenin may stabilize HJV, a glycosylphosphatidylinositol-anchored protein that interacts with neogenin and suppresses its secretion. Taken together, our results lead the hypothesis that neogenin regulates iron homeostasis via inhibiting secretion of HJV, an inhibitor of BMP signaling, to enhance BMP signaling and hepcidin expression. These results reveal a novel mechanism underlying neogenin regulation of HJV-BMP signaling.
Improved radioimmunotherapeutic efficacy of an anticarcinoma monoclonal antibody (131I-CC49) when given in combination with gamma-interferon. (1993)

The moderately differentiated human colon tumor cell line, HT-29, constitutively expresses low levels of the high molecular weight mucin, tumor-associated glycoprotein 72 (TAG-72), and the M(r) 180,000 carcinoembryonic antigen (CEA) when grown as s.c. tumors in athymic mice. We report that the in vivo administration of gamma-interferon (IFN-gamma) resulted in a time- and dose-dependent increase in both TAG-72 and CEA expression in the HT-29 tumors. Immunohistochemical staining revealed a more homogeneous TAG-72-positive tumor cell population after IFN-gamma. Furthermore, both anti-TAG-72 and anti-CEA monoclonal antibodies (MAbs) showed enhanced localization to the HT-29 tumors in mice treated with IFN-gamma. Using that experimental model, subsequent studies presented evidence showing that the combination of IFN-gamma with 131I-CC49, an anti-TAG-72 MAb, resulted in a statistically significant improvement in therapeutic efficacy when compared with 131I-CC49 alone. For example, treatment with 300 microCi of 131I-CC49 initially suppressed HT-29 tumor growth; however, that reduction in tumor growth was transient as evidenced by the emergence of additional tumor growth at later time points. In contrast, an 8-day treatment with IFN-gamma in combination with 300 microCi 131I-CC49 resulted in sustained suppression of HT-29 tumor growth. Thus, IFN-gamma in vivo can substantially increase the TAG-72 expression in human colon tumor xenografts which leads to an increased tumor localization of anti-TAG-72 MAbs and seems to be responsible for the enhanced antitumor effects when IFN-gamma was combined with 131I-CC49. The results provide further evidence for including a biological response modifier, such as IFN-gamma, which can increase the expression of specific tumor antigens (i.e., TAG-72 and CEA) subsequently leading to a dramatic improvement in the antitumor efficacy of a radionuclide-conjugated MAb.
A novel cell technology using N-doped GeSbTe films for phase change RAM (2004)

The Ge/sub 2/Sb/sub 2/Te/sub 5/ (GST) thin film is well known to play a critical role in PRAM (Phase Change Random Access Memory). Through device simulation, we found that high-resistive GST is indispensable to minimize the writing current of PRAM. For the first time, we tried to increase the GST resistivity by doping nitrogen. Doping nitrogen to GST successfully reduced writing current. Also, the cell endurance has been enhanced with grain growth suppression effect of dopant nitrogen.
Treatment of Inherited Homocystinurias (2012)

Inherited homocystinurias, have in common, accumulation of homocysteine with subsequent neurotoxicity; they also encompass two distinctive clinical entities: classical homocystinuria due to cystathionine β-synthase (CBS) deficiency and the rare inborn errors of cobalamin and folate metabolism. In the latter group, remethylation disorders of homocysteine to methionine (chiefly CblC defect and 5,10-methylenetetrahydrofolate reductase [MTHFR] deficiency) are by far the most frequently encountered situations. The natural history of CBS deficiency is relatively well known and described. Similarly, clinical presentations of remethylation defects are becoming better recognized and reported. Conversely, few data are available regarding treatment of these disorders, especially for remethylation defects. In this review, after an overview of the metabolic pathophysiology and the clinical features of inherited homocystinurias due to CBS deficiency, CblC defect, and MTHFR deficiency, we focus on present and prospective therapeutic approaches.
Immunization and Antibody Response in the Newborn Infant (1965)

THE pediatrician, general practitioner and public-health officer are concerned with early, safe, effective protection against diseases that can be prevented by the use of vaccines. The earliest time that adequate active immunization can be accomplished in infants is very difficult to determine, and in fact not finally decided for any of the immunizing agents commonly used in infancy,1 2 3 4 5 although the basic processes involved in immunology are being pursued. Previous studies6,7 showed that children at three weeks of age can be effectively immunized against pertussis, tetanus and diphtheria. These studies demonstrated that protective levels of antibody responses could be obtained . . .
Runoff responses to afforestation in a watershed of the Loess Plateau, China (2003)

Afforestation has been suggested as a means of improving soil and water conservation in north-western China, especially on the Loess Plateau. Understanding of the hydrological responses to afforestation will help us develop sustainable watershed management strategies. A study was conducted during the period of 1956 to 1980 to evaluate runoff responses to afforestation in a watershed on the Loess Plateau with an area of 1·15 km2, using a paired watershed approach. Deciduous trees, including locust (locusta L.), apricot (praecox L.) and elm (ulmus L.), were planted on about 80% of a treated watershed, while a natural grassland watershed remained unchanged. It was estimated that cumulative runoff yield in the treated watershed was reduced by 32% as a result of afforestation. A significant trend was also observed that shows annual runoff reduction increases with the age of the trees planted. Reduction in monthly runoff occurred mainly from June to September, which was ascribed to greater rainfall and utilization by trees during this period. Afforestation also resulted in reduction in the volume and peak flow of storm runoff events in the treated watershed with greater reduction in peak flow. Copyright © 2003 John Wiley & Sons, Ltd.
Fibroblast growth factor promotes survival of dissociated hippocampal neurons and enhances neurite extension. (1986)

Basic fibroblast growth factor (FGF) has been found to increase neuronal survival and neurite extension in a highly purified population of fetal rat hippocampal neurons under well-defined serum-free cell culture conditions. In the presence of FGF, neuronal survival after 7 days in culture on a simple plastic substrate is increased 4-fold, to 54% of the initial population. Survival is increased 2-fold to 40% on polyornithine-laminin. When FGF was bound to plastic or heparin substrates, neurite outgrowth was significantly increased to lengths comparable to those seen with laminin; however, FGF produced no further increase in neurite outgrowth on laminin. Half-maximal survival was observed at FGF concentrations of about 15 pg/ml (1 pM); half-maximal process outgrowth occurred at about 375 pg/ml (20 pM). The responsive cells were identified as neurons by their labeling with tetanus toxin and by antibodies to neurofilaments and to the neuron-specific enolase. Astrocytes, identified by the presence of glial fibrillary acidic protein, constituted about 10% of cells present at 1 week both in the presence and in the absence of FGF. These results strongly suggest that, in addition to its known mitogenic effects on nonneuronal cells, FGF possesses neurotrophic activity for hippocampal neurons.
Tumor Antigens (1992)

This review solidifies a new concept that common and rare types of human cancers harbor a variety of tumor-specific mutant proteins that may be recognized as tumor-specific antigens. These mutant proteins are encoded by oncogenes or suppressor genes that have undergone structural mutations resulting from point mutations, chromosomal translocations, internal deletions and viral insertional mutagenesis; several of these changes result in fusion proteins. While there is no evidence that immunosurveillance against these mutant proteins can prevent the development of primary cancers without prior immunization of the host, such tumor-specific molecules might be important for diagnosis and as targets for specific immunotherapy once the cancer has developed or even as targets for preventive cancer vaccines. Evidence further supports the notion that cytolytic or helper T cells are exquisitely selective in recognizing intracellular mutant proteins, and tumor-specific T cell clones presently available may become useful for identifying previously unrecognized tumor-specific mutations. Many tumor-specific mutant proteins clearly play a causative role in the establishment of malignant behavior, whereas other carcinogen-induced changes have at least immunological relevance. In any case strong evidence in mouse and man indicates that a single malignant cell can express multiple independent antigenic target sites. Such multiplicity may allow a multi-pronged immune attack that substantially decreases the chance of tumor escape. Future work must explore whether immune responses to tumor-specific mutant proteins can lead to immunological tumor rejection and explore the possibility of chemically engineering tumor mutant peptides to be highly immunogenic, even in hosts that have previously failed to respond to the tumor.
Early Involvement of the Phosphatidylinositol 3-Kinase/Akt Pathway in Lung Cancer Progression (2004)

Signaling through the phosphatidylinositol 3-kinase (PI3-kinase) pathway has been associated with lung tumorigenesis. We examined the association between gene copy number of the PI3-kinase catalytic subunit alpha (PIK3CA) and phosphorylated Akt expression in invasive and preinvasive lung cancers. We sought to determine at what stage of tumor development gene copy number increase or phosphorylated Akt overexpression might affect tumor development. We assessed PIK3CA gene copy number by fluorescence in situ hybridization and expression of phosphorylated Akt by immunohistochemistry in 242 invasive and 43 preinvasive lung cancers and correlated our findings with clinical outcome. The PIK3CA was amplified in 70% of squamous carcinomas, 38% of large cell carcinomas, 19% of adenocarcinomas, and 67% of small cell lung cancers. Phosphorylated Akt overexpression was frequently observed, and strongly so in 12 to 17% of lung cancers depending on nuclear or cytoplasmic localization. Neither PIK3CA gene copy number nor phosphorylated Akt protein expression had prognostic significance. In preinvasive lesions, amplification of the PIK3CA and overexpression of phosphorylated Akt were associated with severe dysplasia and each other. These observations suggest frequent and early involvement of the PI3-kinase pathway in lung cancer.