gebhart/patrepeval huggingface dataset:
The Role of Factor XI in Thrombin Generation Induced by Low Concentrations of Tissue Factor (2001)

Thrombin generation has been studied in the plasma of severely factor XI deficient patients under conditions in which contact activation did not play a role. In platelet-rich as well as platelet-poor plasma, thrombin generation was dependent upon the presence of factor XI at tissue factor concentrations of between 1 and 20 pg/ml i.e. approximately 0.01 to 0.20% of the concentration normally present in the thromboplastin time determination. The requirement for factor XI is low; significant thrombin generation was seen at 1% factor XI; at 10%, thrombin formation was nearly normalised. A suspension of normal platelets in severely factor XI deficient plasma did not increase thrombin generation. This implies that there is no significant factor XI activity carried by normal platelets, although the presence of factor XI and factor XI inhibitors in platelets cannot be ruled out.
Stat Protein Transactivation Domains Recruit p300/CBP through Widely Divergent Sequences (1999)

The signal transduction and activator of transcription (Stat) gene family has been highly conserved throughout evolution. Gene duplication and divergence has produced 7 mammalian Stat genes, each of which mediates a distinct process. While some Stat proteins are activated by multiple cytokines, Stat2 is highly specific for responses to type I interferon. We have cloned mouse Stat2 and found that while its sequence was more divergent from its human homologue than any other mouse-human Stat pairs, it was fully functional even in human cells. Overall sequence identity was only 69%, compared with 85-99% similarity for other Stat genes, and several individual domains that still served similar or identical functions in both species were even less well conserved. The coiled-coil domain responsible for interaction with IRF9 was only 65% identical and yet mouse Stat2 interacted with either human or mouse IRF9; the carboxyl terminus was only 30% identical and yet both regions functioned as equal transactivation domains. Both mouse and human transactivation domains recruited the p300/CBP coactivator and were equally sensitive to inhibition by adenovirus E1A protein. Interestingly, the Stat3 carboxyl terminus also functioned as a transactivator capable of recruiting p300/CBP, as does the Stat1 protein, although with widely differing potencies. Yet these proteins share no sequence similarity with Stat2. These data demonstrate that highly diverged primary sequences can serve similar or identical functions, and that the minimal regions of similarity between human and mouse Stat2 may define the critical determinants for function.
Predicting Depth, Surface Normals and Semantic Labels with a Common Multi-scale Convolutional Architecture (2015)

In this paper we address three different computer vision tasks using a single basic architecture: depth prediction, surface normal estimation, and semantic labeling. We use a multiscale convolutional network that is able to adapt easily to each task using only small modifications, regressing from the input image to the output map directly. Our method progressively refines predictions using a sequence of scales, and captures many image details without any superpixels or low-level segmentation. We achieve state-of-the-art performance on benchmarks for all three tasks.
Classification of the thyroid nodules using support vector machines (2008)

Most of the thyroid nodules are heterogeneous with various internal components, which confuse many radiologists and physicians with their various echo patterns in thyroid nodules. A lot of texture extraction methods were used to characterize the thyroid nodules. Accordingly, the thyroid nodules could be classified by the corresponding textural features. In this paper, five support vector machines (SVM) were adopted to select the significant textural features and to classify the nodular lesions of thyroid. Experimental results showed the proposed method classifies the thyroid nodules correctly and efficiently. The comparison results demonstrated that the capability of feature selection of the proposed method was similar to the sequential floating forward selection (SFFS) method. However, the proposed method is faster than the SFFS method.
More than 1000 channel optical frequency chaingeneration from single supercontinuum source with 12.5 GHz channel spacing (2000)

More than 1000 optical frequency channels are generated with 12.5 GHz spacing from a single supercontinuum source. 600–700 channels for the wavelength range 1512–1580 nm are confirmed to offer SNRs and Q factors sufficient for multi-span 2.5 Gbit/s DWDM transmission.
Regulation of Promoter Activity of the APP Gene by Cytokines and Growth Factors (2002)

One of the major pathological hallmarks of Alzheimer's disease (AD) is the presence of brain depositions of senile plaques that are primarily composed of potentially toxic amyloid beta-peptide (Abeta), which is generated from a family of Abeta-containing precursor proteins (APP; 695-770 amino acids). The role of inflammatory cytokines and growth factors has been implicated in the pathogenesis of AD. Our goal is to study the effects of these factors on the regulation of APP gene expression. Here we compared APP promoter activity in the presence of different growth factors and cytokines such as brain-derived neurotrophic factor (BDNF), interleukin (IL-1), nerve growth factor (NGF), neurotrofin-3 (NT-3), transforming growth factor (TGF-beta1), and tumor necrosis factor (TNF-alpha1). PC12 neuronal cells, which were treated separately with these agents, were transfected with the construct containing either 190 bp APP proximal promoter region (-46 to 144 bp with respect to the transcription start site [+1]), 94 bp APP 5'-untranslated region (UTR, +50 to 144) or other 5'-UTR-deleted regions. Each construct was cloned upstream of a reporter chloramphenicol acetyl transferase gene (CAT). The treatment of PC12 cells with NGF stimulated reporter activity in all constructs tested. The treatment of cells with BDNF, NT3, TGF-beta1, or TNF-alpha stimulated reporter activity in a promoter/UTR-specific manner. Transfection with the complete -46 to 144 region retained the maximum stimulatory activity for any treatment tested in PC12 cells. These results suggest that the regulatory elements of the APP gene respond to the stimulation of different growth factors, cytokines, and interleukins. This is consistent with the effects of the different growth factors, cytokines, and interleukins on APP message and protein levels.
Human acid sphingomyelinase. Isolation, nucleotide sequence and expression of the full-length and alternatively spliced cDNAs (1991)

Two types of partial cDNAs encoding human acid sphingomyelinase (EC 3.1.4.12; ASM) were recently isolated from fibroblast and placental cDNA libraries (Quintern, L. E., Schuchman, E.H., Levran, O., Suchi. M., Ferlinz, K., Reinke, H., Sandhoff, K., and Desnick, R. J. (1989) EMBO J. 8, 2469-2473). The cDNA inserts had identical sequences with the exception of an internal region; type 1 cDNAs (representing approximately 90% of the ASM cDNAs isolated) had 172 in-frame base pairs (bp), which were replaced in the type 2 cDNAs by a 40-bp in-frame sequence. Northern hybridization and RNase protection studies indicated that both type 1 and 2 transcripts were approximately 2.5 kilobases; therefore, efforts were directed to isolate full-length type 1 and 2 cDNAs by screening human placental, testis, hepatoma, and retinal cDNA libraries. In addition to type 1 and 2 cDNAs, a new type of ASM cDNA (type 3), which did not contain the type 1- or 2-specific regions, was isolated and sequenced. The full-length type 1 and the reconstructed full-length type 2 and 3 cDNAs were transiently expressed in COS-1 cells. Only the full-length type 1 transcript encoded catalytically active human ASM, demonstrating its functional integrity. The 2347-bp full-length type 1 placental cDNA (pASM-1FL) had an 87-bp 5'-untranslated region, an 1890-bp open reading frame encoding 629 amino acids, and a 370-bp 3'-untranslated sequence. The predicted location of the signal peptide cleavage site was after alanine 46. Two base differences were identified in codons 322 and 506 and shown to be polymorphisms with the common alleles having frequencies of 0.6 and 0.7, respectively. To determine the genomic organization of the type 1, 2, and 3 sequences, a 1665-bp genomic region containing both the unique type 1 (172 bp) and type 2 (40 bp) sequences was amplified by the polymerase chain reaction and sequenced. The 172-bp sequence was exonic, flanked by 5'- and 3'-intronic sequences of 1052 and 229 bp, respectively. The 40-bp type 2 sequence was intronic, occurring at the 5' end of the 1052-bp intron due to the use of a cryptic 5' donor splice site, which deleted the entire 172-bp exon and both flanking intronic sequences. The type 3 cDNA resulted from an alternative splicing event, which excised the 172-bp exon. These studies demonstrate the occurrence of alternatively splicing of the ASM transcript, but the existence of only one functional mRNA.
Encyclopedia of Materials, Parts and Finishes (2002)

During the past two decades, higher processing temperatures, more efficient engines at higher temperatures, and the use of a vacuum environment have led to the development of a number of important processing, fabrication, and industrial techniques, resulting in new material forms including: matrix composites, nano- and functionally graded structure
Disabled Infectious Single-Cycle Herpes Simplex Virus as an Oncolytic Vector for Immunotherapy of Colorectal Cancer (1999)

New modalities of treatment for colorectal cancer are required to support and improve those currently available. One such approach is immunotherapy by transfer of immunostimulatory genes to tumor cells. Here, we report the use of a herpes simplex virus (HSV) vector that is capable of a single round of infection (disabled infectious single-cycle [DISC]-HSV) as a gene transfer vehicle for colorectal cancer. This vector has potential advantages over other vectors for cancer immunotherapy in that it lyses infected tumor cells. Infection with DISC-HSV inhibited tumor cell growth both in vitro and in vivo. In addition, DISC-HSV-mediated cell killing occurs by both apoptotic and necrotic mechanisms. A range of colorectal tumor cell lines could be rapidly transduced with DISC-HSV/lacZ (14-90% in 4 hr). Both tumor prevention and tumor therapy protocols showed clear antitumor effects with DISC-HSV/mGM-CSF. In the prophylactic approach, an infected/irradiated whole cell vaccine protected up to 80% of mice from rechallenge. In addition, intratumoral injection of established tumors with DISC-HSV/GM-CSF caused rejection in 40% of mice and generated some protection from subsequent rechallenge. In both cases, however, it is clear that a dominant therapeutic effect of the DISC-HSV vector derives from its oncolytic properties, irrespective of the transduced gene. As a prelude to taking these studies forward to human clinical trials, we demonstrate that tumor cells could be successfully grown from freshly obtained human colorectal cancer resections (within 1 week of surgery), were transduced with DISC-HSV/hGM-CSF, and secreted the cytokine. This study provides the preclinical basis for trials of immunotherapy of colorectal cancer using DISC-HSV.
Characterization of a membrane receptor for transforming growth factor-beta in normal rat kidney fibroblasts. (1984)

A procedure has been developed for the iodination of human transforming growth factor-beta (TGF-beta) with full retention of biological activity. Using the iodinated peptide, saturable receptors have been found for TGF-beta on normal rat kidney fibroblasts, a cell line that will grow in soft agar in the presence of TGFs but not in their absence. Scatchard analysis of the binding data showed a high affinity binding site (dissociation constant equal to 25 to 30 pM with approximately 17,000 receptors per cell). The receptor was specific for TGF-beta with epidermal growth factor, insulin, insulin-like growth factors I and II, platelet-derived growth factor, and TGF-alpha being unable to compete for the binding of 125I-TGF-beta to the receptor. The binding of TGF-beta was a time- and temperature-dependent process. At 37 degrees C, maximal binding was attained within 45 to 60 min after addition of 125I-TGF-beta followed by a rapid decline in cell-associated radioactivity due to degradation of the 125I-TGF-beta. As demonstrated using ammonium acetate, a compound known to inhibit lysosomal enzymes, this degradation was most likely due to the action of proteolytic enzymes found in the lysosome. At 0 degrees C, binding reached a plateau within 2 to 3 h and maintained this level with no apparent drop during the 4-h incubation period. The receptor could be down-regulated by TGF-beta, but not by epidermal growth factor, to approximately 50% of the level initially observed.
CD40–CD40L cross-talk integrates strong antigenic signals and microbial stimuli to induce development of IL-17-producing CD4 + T cells (2009)

IL-17-producing CD4(+) T cells have been recognized as key players in organ-related autoimmune disease; however, the parameters that govern their development are yet to be elucidated fully. By using both in vivo and in vitro systems, we have investigated the role of antigen dose, pathogen-associated molecular patterns, and CD40-CD40 ligand (CD40L) cross-talk in Th17 differentiation. We found that the strength of antigenic stimulation critically influenced the extent of Th17 differentiation, because high, but not low or intermediate, antigen concentrations led to IL-17 production. Strong antigenic stimulation of T cells up-regulated CD40L expression, which in concert with certain microbial stimuli (i.e., cytosine phosphate guanine, curdlan, and zymosan) synergistically increased dendritic cell (DC) IL-6 production and Th17 polarization. CD40-deficient DCs exhibited reduced cytokine release and failed to drive Th17 development in vitro. These results were confirmed in vivo where the absence of CD40-CD40L cross-talk was found to prevent the expansion of IL-17-producing cells and accordingly the development of experimental autoimmune encephalitis. Our data demonstrate that CD40-CD40L cross-talk is important for Th17 development by translating strong T cell receptor and microbial stimuli into IL-6 production.
Spin-polarized current induced switching in Co/Cu/Co pillars (2001)

We present experiments of magnetization reversal by spin injection performed on pillar-shaped Co/Cu/Co trilayers. The pillars (200×600 nm2) are fabricated by electron beam lithography and reactive ion etching. Our data for the magnetization reversal at a threshold current confirm previous results on similar pillars. In addition, we present another type of experiment that also clearly evidences the control of the magnetic configuration by the current intensity. Our interpretation is based on a version of the Slonczewski model in which the polarization of the current is calculated in the Valet–Fert model of the giant magnetoresistance with current applied perpendicular to plane.
An ATF/CREB binding motif is required for aberrant constitutive expression of the MHC class II DRα promoter and activation by SV4O T-antigen (1992)

Constitutive expression of major histocompatibility complex class II (MHC II) antigens normally occurs in B-lymphocytes and antigen presenting cells of the monocyte/macrophage lineage. However, many malignant tumours and transformed cells express these proteins aberrantly. We demonstrate here that the MHC II DR alpha promoter is constitutively active both in the SV40 large T antigen transformed cell line, COS, and in CV1 cells from which they are derived. As an approach to understanding the molecular mechanisms underlying aberrant DR alpha expression we have examined the cis- and trans-acting requirements for DR alpha transcription in these cell types. Electrophoretic mobility shift assays showed that the region immediately 3' to the X-box was bound by a member of the ATF/CREB family of transcription factors. Using deletions and point mutations in the DR alpha promoter we demonstrate that, in contrast to B-cells, the octamer motif and conserved X- and Y-boxes make only a minor contribution to promoter function while single point mutations in the ATF/CREB motif reduced transcription up to 20-fold. In addition, we show that the DR alpha promoter is activated by SV40 large T-antigen and that activation requires an intact ATF/CREB motif. Similar data were obtained using B16 melanoma cells. These results suggest that the ATF/CREB motif may be a target for transcription deregulation in several transformed cell types.
Single-agent CEP-701, a novel FLT3 inhibitor, shows biologic and clinical activity in patients with relapsed or refractory acute myeloid leukemia (2004)

Activating mutations of FMS-like tyrosine kinase 3 (FLT3) are present in approximately 30% of patients with de novo acute myeloid leukemia (AML) and are associated with lower cure rates from standard chemotherapy-based treatment. Targeting the mutation by inhibiting the tyrosine kinase activity of FLT3 is cytotoxic to cell lines and primary AML cells harboring FLT3 mutations. Successful FLT3 inhibition can also improve survival in mouse models of FLT3-activated leukemia. CEP-701 is an orally available, novel, receptor tyrosine kinase inhibitor that selectively inhibits FLT3 autophosphorylation. We undertook a phase 1/2 trial to determine the in vivo hematologic effects of single-agent CEP-701 as salvage treatment for patients with refractory, relapsed, or poor-risk AML expressing FLT3-activating mutations. Fourteen heavily pretreated AML patients were treated with CEP-701 at an initial dose of 60 mg orally twice daily. CEP-701-related toxicities were minimal. Five patients had clinical evidence of biologic activity and measurable clinical response, including significant reductions in bone marrow and peripheral blood blasts. Laboratory data confirmed that clinical responses correlated with sustained FLT3 inhibition to CEP-701. Our results show that FLT3 inhibition is associated with clinical activity in AML patients harboring FLT3-activating mutations and indicate that CEP-701 holds promise as a novel, molecularly targeted therapy for this disease.
Extensive homologies between the methylated nucleotide sequences in several vertebrate ribosomal ribonucleic acids (1978)

The methylated nucleotide sequences in the rRNA molecules of the following vertebrate cultured cells were compared: human (HeLa); hamster (BHK/C13); mouse (L); chick-embryo fibroblast; Xenopus laevis kidney. In each species the combined 18S, 28S and 5.8S molecules possess approx. 110-115 methyl groups, and the methylated oligonucleotides released after complete digestion of the rRNA by T1 ribonuclease encompass several hundred nucleotides. "Fingerprints" of the three mammalian methyl-labelled 18S rRNA species were qualitatively indistinguishable. "Fingerprints" of digests of 28S rRNA of hamster and mouse L-cells were extremely similar to those of HeLa cells, differing in one and three methylated oligonucleotides respectively. "Fingerprints" of methyl-labelled rRNA from chick and Xenopus strongly resembled those of mammals in most respects, but differed in several oligonucleotides in both 18S and 28S rRNA. At least some of the differences between "fingerprints" appear to be due to single base changes or to the presence or absence of methyl groups at particular points in the primary sequence. The findings strongly suggest that the methylated-nucleotide sequences are at least 95% homologous between the rRNA molecules of the two most distantly related vertebrates compared, man and Xenopus laevis.
A fast burst synchronization scheme for OFDM (2002)

This paper proposes a burst synchronization scheme with a short preamble signal for high data rate wireless LAN systems that use orthogonal frequency division multiplexing (OFDM). The proposed scheme, which consists of automatic frequency control (AFC) and symbol timing detection, enables us to shorten the preamble length to 1/4 that of a conventional one. Computer simulation results show that the degradation in required E/sub b//N/sub 0/ due to the synchronization scheme is less than 1 dB in a selective Rayleigh fading channel.
Atypical negative ALK FISH accompanied by immunohistochemistry positivity harbored various ALK rearrangements in NSCLC patients and respond to targeted therapy. (2016)

e20506 Background: Detection of ALK rearrangements in patients with non-small cell lung cancer (NSCLC) presents a significant technical challenge due to the existence of multiple translocation partners and break-points. Although fluorescence in situ hybridization (FISH) is the first FDA-approved method, there are some atypical negative FISH cases accompanied by immunohistochemistry (IHC) positivity and responded well to crizotinib treatment. Methods: 3128 NSCLCs were screened for ALK fusions through both FISH analysis and IHC assays with Ventana-D5F3 antibody. IHC results were scored with a binary scoring system. Fourteen cases with atypical negative FISH and positive IHC results were performed with targeted next-generation sequencing. Results: Among 3128 cases tested, 228 (7.3%) and 214 (6.8%) cases were ALK positive by IHC and FISH, respectively. Fourteen cases with atypical negative FISH all demonstrated IHC positivity. Two patients showed isolated 5’-side signal. Targeted next-generation sequencing analysis revealed two novel ALK partner genes, baculoviral inhibition of apoptosis protein repeat containing six (BIRC6) and Phosphatidylinositol Binding Clathrin Assembly Protein (PICALM). One patient showed isolated and attenuated 3’-red signal and demonstrated a novel translocation partner with CCAAT/Enhancer binding protein zeta (CEBPZ). Eight patients with fused signals and positive IHC demonstrated EML4-ALK fusions revealed by NGS and the relative abundance of fusion ranged from 7.26% to 37.8%. Besides, 3 patients with confirmed IHC positivity and negative FISH results did not exhibit any type of ALK fusions. Among them, 4 patients received crizotinib treatment and demonstrated partial responses at the end of follow-up. Conclusions: Our study showed that patients with atypical ALK FISH patterns, which are regarded as negative in the current criteria, could have positive results for IHC and also respond to ALK inhibitor therapy.
A flow cytometry technique for measuring chromosome-mediated gene transfer (2001)

The results indicate that IdUrd-labeled artificial chromosomes can be detected 24 h after transfection. This efficient, sensitive, high-throughput detection technique is being used to evaluate and optimize other transfer technologies (e.g., electroporation and sonoporation), different delivery reagents, and protocols in a variety of cells in vitro. This work represents the first step in utilizing artificial chromosomes as nonviral vectors for gene therapy.
A new photoiniferter/RAFT agent for ambient temperature rapid and well‐controlled radical polymerization (2008)

Abstract Phenacyl morpholine‐4‐dithiocarbamate is synthesized and characterized. Its capability to act as both a photoiniferter and reversible addition fragmentation chain transfer agent for the polymerization of styrene is examined. Polymerization carried out in bulk under ultra violet irradiation at above 300 nm at room temperature shows controlled free radical polymerization characteristics up to 50% conversions and produces well‐defined polymers with molecular weights close to those predicted from theory and relatively narrow poyldispersities ( M w / M n ∼ 1.30). End group determination and block copolymerization with methyl acrylate suggest that morpholino dithiocarbamate groups were attained at the end of the polymer. Photolysis and polymerization studies revealed that polymerization proceeds via both reversible termination and RAFT mechanisms. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 3387–3395, 2008