gebhart/patrepeval huggingface dataset:
Role of cytokines in the modulation of nitric oxide production by cyclic AMP. (2001)

Enhanced levels of cyclic AMP (cAMP), resulting from stimulation of adenylyl cyclase through activation of distinct pharmacological receptor systems, have a remarkable impact on the activity of the immune system. Among other responses, production of nitric oxide (NO) is also affected. The effects of cAMP range from stimulation to inhibition (or no effect) of immune-stimulated biosynthesis of NO, with a preponderance of stimulatory interference. cAMP has been shown to be a potent, dual modulator of cytokine expression. It dose-dependently suppresses secretion of major NO up-regulatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). On the other hand, production of IL-10, which is known to regulate the inducible NO synthase (iNOS) activation in both a positive and negative direction, is inversely enhanced. It is suggested that the dual effects of cAMP on NO formation are likely to result from the differences in the concentration ratio of these cytokines. The value of this parameter depends on the type and concentration of cAMP-stable derivatives and cAMP-enhancing agents, such as prostaglandins, beta-adrenoceptor agonists, phosphodiesterase inhibitors, forskolin and cholera toxin. The cytokine ratio may be influenced by dynamically developing multiple down- and up-regulatory feedback circuits among cytokines, NO, and cAMP.
D11S287, a putative oncogene on chromosome 11q13, is amplified and expressed in squamous cell and mammary carcinomas and linked to BCL-1. (1991)

Approximately 15 to 20% of primary breast cancers and an even higher proportion of squamous cell carcinomas of the head and neck show amplification of DNA markers on band q13 of human chromosome 11. However, known genes within the amplified region, such as the FGF-related oncogenes INT-2 and HST-1, are very rarely expressed in these tumors. Here we show that another candidate oncogene, designated D11S287, implicated in the pathogenesis of parathyroid adenomas, is also amplified in breast cancers. Significantly, it is consistently coamplified with INT-2 and HST-1 in 36 out of 202 primary tumors, including one case in which the amplified unit did not encompass the translocation breakpoint marker BCL-1. This implies that D11S287 is on the same side of the breakpoint as INT-2, and pulsed-field gel electrophoresis indicates that D11S287 is less than 250 kb from the BCL-1 marker. Since D11S287 RNA was present at elevated levels in a group of tumors and cell lines in which the 11q13 region is amplified, it may be the key oncogene on this amplified unit, and could also be activated by BCL-1 translocations.
Mad acts downstream of Dpp receptors, revealing a differential requirement for dpp signaling in initiation and propagation of morphogenesis in the Drosophila eye (1996)

Decapentaplegic (Dpp), a member of the TGF-beta family of cytokines, has been implicated in many patterning processes in Drosophila, including the initial steps of pattern formation in the developing eye. We show that the Mothers against dpp (Mad) gene is required for dpp signaling during eye development. Clonal analysis demonstrates a cell-autonomous function for Mad and genetic interactions indicate that Mad is an essential component of the signal transduction pathway downstream of the Dpp receptors in responding cells. Mad-mediated dpp signaling is absolutely required for the initiation of the morphogenetic furrow in the eye, but has only a minor role in its subsequent propagation across the eye disc. We also present evidence for the repression of wingless transcription by dpp signaling.
Deformable registration of 4D computed tomography data (2006)

Four-dimensional radiotherapy requires deformable registration to track delivered dose across varying anatomical states. Deformable registration based on B-splines was implemented to register 4D computed tomography data to a reference respiratory phase. To assess registration performance, anatomical landmarks were selected across ten respiratory phases in five patients. These point landmarks were transformed according to global registration parameters between different respiratory phases. Registration uncertainties were computed by subtraction of transformed and reference landmark positions. The selection of appropriate registration masks to separate independently moving anatomical subunits is crucial to registration performance. The average registration error for five landmarks for each of five patients was 2.1 mm. This level of accuracy is acceptable for most radiotherapy applications.
High-performance polysilicon contacted shallow junctions formed by stacked-amorphous-silicon films (1992)

A high-performance polysilicon contacted shallow junction diode formed by using a stacked-amorphous-silicon (SAS) film as the diffusion source is reported. The diode exhibited a very low leakage current (<or=1 nA/cm/sup 2/ at -5 V), a very high breakdown voltage (>or=100 V), and a forward ideality factor m<or=1.05 over seven decades.<<ETX>>
Increasing CRISPR Efficiency and Measuring Its Specificity in HSPCs Using a Clinically Relevant System (2020)

Genome editing of human cluster of differentiation 34<sup>+</sup> (CD34<sup>+</sup>) hematopoietic stem and progenitor cells (HSPCs) holds great therapeutic potential. This study aimed to optimize on-target, <i>ex vivo</i> genome editing using the CRISPR-Cas9 system in CD34<sup>+</sup> HSPCs and to create a clear workflow for precise identification of off-target effects. Modified synthetic guide RNAs (gRNAs), either 2-part gRNA or single-guide RNA (sgRNA), were delivered to CD34<sup>+</sup> HSPCs as part of ribonucleoprotein (RNP) complexes, targeting therapeutically relevant genes. The addition of an Alt-R electroporation enhancer (EE), a short, single-stranded oligodeoxynucleotide (ssODN), significantly increased editing efficiency in CD34<sup>+</sup> HSPCs. Notably, similar editing improvement was observed when excess gRNA over Cas9 protein was used, providing a DNA-free alternative suitable for therapeutic applications. Furthermore, we demonstrated that sgRNA may be preferable over 2-part gRNA in a locus-specific manner. Finally, we present a clear experimental framework suitable for the unbiased identification of bona fide off-target sites by Genome-Wide, Unbiased Identification of Double-Strand Breaks (DSBs) Enabled by Sequencing (GUIDE-seq), as well as subsequent editing quantification in CD34<sup>+</sup> HSPCs using rhAmpSeq. These findings may facilitate the implementation of genome editing in CD34<sup>+</sup> HSPCs for research and therapy and can be adapted for other hematopoietic cells.
Activation of CD8+T lymphocytes through the T cell receptor turns on CD4 gene expression: Implications for HIV pathogenesis (1998)

T cell activation through the T cell receptor is necessary to achieve a specific and effective immune response. We report here that stimulation of CD8+ T cells through the T cell receptor complex leads to de novo expression of the CD4 antigen on the cell surface that results in susceptibility of CD8+ T cells to HIV infection. In addition, activation of peripheral blood mononuclear cells from HIV-infected individuals results in the appearance of double-positive CD4+/CD8+ T cells, which become infected by endogenous HIV. HIV DNA sequences could be detected in uncultured and sorted mature CD3+CD8+ T cells from HIV+ individuals. These results suggest a new mechanism by which HIV could attack the immune system and may help to explain the CD8+ T cell defects in AIDS patients.
Loss of receptors for transforming growth factor beta in human T-cell malignancies. (1994)

Ki-1 (CD30)+ cutaneous T-cell lymphomas CTCLs) are slowly progressive lymphomas in which initial spontaneous regression is often observed. To better understand the mechanisms of spontaneous regression and eventual tumor progression in Ki-1+ CTCLs, type beta transforming growth factor (TGF-beta)-mediated growth inhibition of clonally related cell lines derived from two time points, before and after tumor progression, was studied. TGF-beta 1 inhibited colony-forming efficiency (CFE) of a cell line (Mac-1) derived from clinically indolent Ki-1+ CTCLs but failed to inhibit CFE of Mac-2A and -2B cell lines from advanced CTCLs. To determine the basis for TGF-beta 1 resistance in advanced CTCL cells, we looked for possible defects in the expression of cell surface TGF-beta receptors. Mac-1 cells were found to express TGF-beta receptors I and II, which mediate growth inhibition, and the TGF-beta-binding proteoglycan betaglycan. In contrast, receptors I and II were not detected in CTCL lines Mac-2A and -2B even though these cell lines did express betaglycan. Various treatments that unmask or induce TGF-beta receptors in other cells failed to show evidence for these receptors in advanced CTCL cells. Loss of TGF-beta receptor expression in these cells correlated with a marked decrease in TGF-beta receptor II mRNA levels. Loss of cell surface TGF-beta receptors was also found in two of five other patients with T-cell lymphomas including the Sezary syndrome and a noncutaneous T-cell lymphoma, suggesting that loss of TGF-beta receptor expression may be a recurrent feature of human T-cell malignancies.
TEN YEARS' EXPERIENCE OF BONE MARROW TRANSPLANTATION FOR GAUCHER DISEASE (1995)

Six patients underwent allogeneic bone marrow transplantation (BMT) because of severe Gaucher disease. Their ages was from 2 to 9 years at the time of transplantation. The donors were 4 HLA-identical siblings, a father with one incompatible HLA antigen and an HLA-A, -B, and -DR-identical unrelated donor. Among the donors, three were heterozygous for glucocerebrosidase and three were healthy homozygotes. Four patients underwent total splenectomy and two patients partial splenectomy prior to transplantation. In the former group one patient developed pneumococcal meningitis. In the latter group transfusion requirements were increased. The parental graft was rejected, but 4 of 5 other patients have donor enzyme levels from 2 up to 11 years after BMT. Two patients became mixed chimeras with around 40% of donor erythrocyte markers for one and 80% for the other. One of these had low enzyme activity in his lymphocytes, but the clinical outcome is excellent. This case gives good hope for future trials with gene therapy in Gaucher disease. Glucosylceramide in plasma was within the normal range in all other patients with engraftment, but glucosylceramide in erythrocytes were in the upper normal range in the two chimeric patients with heterozygous donors. Glucosylceramide levels in the liver decreased markedly in the two patients where it was studied. Gaucher cells disappeared in the bone marrow and liver size normalized or decreased within two to three years after BMT. All patients with engraftment had a growth spurt. Skeletal kyphosis was unaffected by BMT in three patients and became apparent in one patient 8 years after BMT. The patients had a favorable psychological development after BMT, with an excellent IQ between 112 and 120 ten years after BMT in the longest survivor. The data suggest that in advanced Gaucher disease BMT still may be a treatment of choice if an HLA-identical related or unrelated donor is available.
Biphasic forearm vascular responses to intraarterial arginine vasopressin. (1989)

Forearm vascular responses to arginine vasopressin (AVP) infused into a brachial artery in a wide range of infusion rates (0.05-2.0 ng/kg per min) were examined in 20 young healthy volunteers. Intraarterial AVP at lower doses (0.05 and 0.1 ng/kg per min) caused forearm vasoconstriction, whereas AVP at a dose of 0.2 ng/kg per min or higher caused forearm vasodilatation. The maximal forearm vasoconstriction was induced at the venous plasma AVP level of 76.3 +/- 8.8 pg/ml. Forearm vasodilatation was associated with the venous plasma AVP level of 369 +/- 43 pg/ml or higher. Forearm vasodilatation was the result of the direct effect of AVP since forearm blood flow and vascular resistance in the contralateral arm did not change. We attempted to explore the mechanisms involved in AVP-induced direct vasodilatation. The treatment with indomethacin, 75 mg/d for 3 d, did not alter AVP-induced forearm vasodilatation. In contrast, intraarterial infusion of isoosmolar CaCl2 totally prevented AVP-induced forearm vasodilatation. Intra-arterial CaCl2 also markedly attenuated forearm vasodilatation induced by intraarterial sodium nitroprusside, but did not alter forearm vasodilatation induced by intraarterial isoproterenol. These results indicate that the direct vascular effects of intra-arterial AVP on the forearm vessels are biphasic, causing vasoconstriction at lower doses and vasodilatation at higher doses. The direct vasodilatation induced by intraarterial AVP at higher doses is not mediated by prostaglandins but may involve cGMP-related mechanisms.
Genome of Geobacter sulfurreducens: Metal Reduction in Subsurface Environments (2003)

The complete genome sequence of Geobacter sulfurreducens, a delta-proteobacterium, reveals unsuspected capabilities, including evidence of aerobic metabolism, one-carbon and complex carbon metabolism, motility, and chemotactic behavior. These characteristics, coupled with the possession of many two-component sensors and many c-type cytochromes, reveal an ability to create alternative, redundant, electron transport networks and offer insights into the process of metal ion reduction in subsurface environments. As well as playing roles in the global cycling of metals and carbon, this organism clearly has the potential for use in bioremediation of radioactive metals and in the generation of electricity.
β*, a UV-inducible Shorter Form of the β Subunit of DNA Polymerase III of Escherichia coli (1996)

Control elements located inside the coding sequence of dnaN, the gene encoding the beta subunit of DNA polymerase III holoenzyme, direct the synthesis of a shorter and UV-inducible form of the beta subunit (Skaliter, R., Paz-Elizur, T., and Livneh, Z. (1996) J. Biol. Chem. 271, 2278-2281, and Paz-Elizur, T., Skaliter, R., Blumenstein, S., and Livneh, Z. (1996) J. Biol. Chem. 271, 2282-2290). The protein, termed beta*, was overproduced using the phage T7 expression system, leading to its accumulation as inclusion bodies at 5-10% of the total cellular proteins. beta* was purified in denatured form, followed by refolding to yield a preparation > 95% pure. Denatured beta* had a molecular mass of 26 kDa and contained two isoforms when analyzed by two-dimensional gel electrophoresis. The major isoform had a pI of 5.45, and comigrated with cellular beta*. Size exclusion high performance liquid chromatography under nondenaturing conditions and chemical cross-linking experiments indicate that beta* is a homotrimer. DNA synthesis by DNA polymerase III* was stimulated up to 10-fold by beta*, primarily due to an increase in the processivity of polymerization. It is suggested that beta* functions as an alternative sliding DNA clamp in a process associated with DNA synthesis in UV-irradiated cells.
Evidence That the v- sis Gene Product Transforms by Interaction with the Receptor for Platelet-Derived Growth Factor (1985)

A scheme for partial purification of biologically active v-sis-coded protein from cells transformed with simian sarcoma virus (SSV) has made possible a functional comparison of the transforming protein with platelet-derived growth factor (PDGF). The SSV-transforming gene product is capable of specifically binding PDGF receptors, stimulating tyrosine phosphorylation of PDGF receptors, and inducing DNA synthesis in quiescent fibroblasts. Each of these activities was specifically inhibited by antibodies to different regions of the v-sis gene product. Moreover, viral infection of a variety of cell types revealed a strict correlation between those cells possessing PDGF receptors and those susceptible to transformation by SSV. These findings provide evidence that SSV-transforming activity is mediated by the interaction of a virus-coded mitogen with PDGF receptors.
<title>Knowledge-based object recognition and model generation</title> (1993)

We will present a new system for knowledge-based image analysis which exploits the benefits of object oriented programming. The knowledge base is built using a formal language for semantic nets, which are already successfully applied in an industrial project. The knowledge base is compiled into an image analysis program. Time consuming search in the knowledge base can thus be avoided. The system provides a general interface to pattern analysis techniques which are included in the generated program as specified by the user. The approach combines the advantages of a compiled program for a special purpose with the flexibility of a general knowledge base tool. The resulting program is used for the reconstruction of the 3D shape of industrial objects using stereo techniques. Images are taken from several viewpoints. Models of 3D objects are then created by an integration of the segmentation data.
Research on Method of Nonlinear Analog-Circuit Fault Diagnosis Based on HAAR Wavelet And BPNN (2003)

In this paper,a fault diagnosis method based on Haar wavelet and BP neural network for nonlinear analog circuit has been presented.The proposed method by using wavelet decomposition as a preprocessor of nonlinear analog circuit fault signal can drastically reduces the number of inputs and training and processing time of the neural network.After briefly introducing an improved BPNN which adpots momentum factor for preventing local convergency used for nonlinear analog-circuit fault diagnosis,the basic principle based on Haar wavelet decomposition that can extracts the fault feature from fault signal is discussed.
Internationalizing Domain Names in Applications (IDNA) (2003)

Until now, there has been no standard method for domain names to use characters outside the ASCII repertoire. This document defines internationalized domain names (IDNs) and a mechanism called Internationalizing Domain Names in Applications (IDNA) for handling them in a standard fashion. IDNs use characters drawn from a large repertoire (Unicode), but IDNA allows the non-ASCII characters to be represented using only the ASCII characters already allowed in so- called host names today. This backward-compatible representation is required in existing protocols like DNS, so that IDNs can be introduced with no changes to the existing infrastructure. IDNA is only meant for processing domain names, not free text.
Factor IXPortland: a nonsense mutation (CGA to TGA) resulting in hemophilia B. (1989)

Male siblings with severe hemophilia b were studied for the molecular defect responsible for their disorder. To define the precise DNA alteration, a 362-bp fragment in the first part of exon VIII of the factor IX gene was amplified and sequenced. A single-base-pair substitution of C----T at the nucleotide sequence 30875 was found which resulted in a nonsense mutation (TGA) and terminated the protein synthesis of factor IX at amino acid residue 252. The single-base change occurred as a classic CG dinucleotide alteration to TG (or CA), a common mechanism for point mutations in mammals.
Improving macrophage responses to therapeutic antibodies by molecular engineering of SIRPα variants (2013)

CD47 transduces inhibitory signals through signal-regulatory protein α (SIRPα), a plasma membrane receptor expressed by macrophages. Many cancers upregulate CD47 to evade immunosurveillance. We have recently engineered SIRPα variants that potently antagonize CD47 for use as anticancer immunotherapeutics. These high-affinity SIRPα variants synergize with antineoplastic antibodies by lowering the threshold for macrophage-mediated destruction of malignant cells.
A mixed-scale dense convolutional neural network for image analysis (2017)

Deep convolutional neural networks have been successfully applied to many image-processing problems in recent works. Popular network architectures often add additional operations and connections to the standard architecture to enable training deeper networks. To achieve accurate results in practice, a large number of trainable parameters are often required. Here, we introduce a network architecture based on using dilated convolutions to capture features at different image scales and densely connecting all feature maps with each other. The resulting architecture is able to achieve accurate results with relatively few parameters and consists of a single set of operations, making it easier to implement, train, and apply in practice, and automatically adapts to different problems. We compare results of the proposed network architecture with popular existing architectures for several segmentation problems, showing that the proposed architecture is able to achieve accurate results with fewer parameters, with a reduced risk of overfitting the training data.
Cloning and expression of a specific human 1,2-mannosidase that trims Man9GlcNAc2 to Man8GlcNAc2 isomer B during N-glycan biosynthesis (1999)

We report the isolation of a novel human cDNA encoding a type II membrane protein of 79.5 kDa with amino acid sequence similarity to Class I alpha 1,2-mannosidases. The catalytic domain of the enzyme was expressed as a secreted protein in Pichia pastoris. The recombinant enzyme removes a single mannose residue from Man9GlcNAc and [1H]-NMR analysis indicates that the only product is Man8GlcNAc isomer B, the form lacking the middle-arm terminal alpha 1,2-mannose. Calcium is required for enzyme activity and both 1-deoxymannojirimycin and kifunensine inhibit the human alpha 1,2-mannosidase. The properties and specificity of this human alpha 1,2-mannosidase are identical to the endoplasmic reticulum alpha 1,2-mannosidase from Saccharomyces cerevisiae and differ from those of previously cloned Golgi alpha 1,2-mannosidases that remove up to four mannose residues from Man9GlcNAc2 during N-glycan maturation. Northern blot analysis showed that all human tissues examined express variable amounts of a 3 kb transcript. This highly specific alpha 1,2-mannosidase is likely to be involved in glycoprotein quality control since there is increasing evidence that trimming of Man9GlcNAc2 to Man8GlcNAc2 isomer B in yeast cells is important to target misfolded glycoproteins for degradation.
Search for common antigenicities among twenty-five sarcomas induced by methylcholanthrene. (1970)

The possibility that antigenic specificities may be shared by sarcomas independently induced in mice by methylcholanthrene was explored in 25 tumors. Two modalities of the transplantation test for antigenicity, designated as “multiple challenge” and “multiple immunization,” were used. The first consisted of immunizing mice with one tumor (implantation and excision) and testing in them the rejection of the same and others when threshold cell doses were injected intradermally in different skin sites. It was observed that, while each one of the tumors was clearly rejected in mice immunized with the same tumor line, it grew regularly in mice immunized with each one of the other tumors and in controls. There appeared to be some instances of cross-immunization in a first screening of the 90 possible tests between 10 tumors, but no such cases could be reproduced for any pair of tumors. Therefore, we conclude that each of 10 tumors tested had a different antigenic type. Fifteen tumors were studied in multiple immunization experiments. These consisted of inducing immunity simultaneously with four tumors and challenging this immunity with a single, different one. No stable cross-protection was revealed in 13 out of 14 such tests. One tumor pool was selected, however, which cross-immunized against a different tumor in three out of three tests. It was investigated whether this pool might also protect against four other tumors, with negative results. This study shows the extreme rarity of either totally or partially shared antigenic components between methylcholanthrene-induced tumors, as demonstrated by rejection of tumor cell inocula.