gebhart/patrepeval huggingface dataset:
Identification and biochemical characterization of a novel autotaxin isoform, ATX , with a four-amino acid deletion (2011)

Autotaxin (ATX) is lysophospholipase D, which converts lysophospholipids such as lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), a bioactive lipid mediator with multiple biological roles. ATX is present in high concentrations in various biological fluids and is responsible for LPA production in these fluids. The plasma ATX level is altered in some patho-physiological conditions. Three splicing isoforms of ATX have been reported so far (ATXα, β and γ). In this study, we identified and characterized ATXδ, a novel alternative splice variant of ATX, which has a four-amino acid deletion in the L2 linker region of ATXβ. ATXδ was found to be the second major isoform following ATXβ and fully active. ATXβ and ATXδ showed similar divalent cation sensitivity and cell motility-stimulating activity. ATXβ and ATXδ are present in wide range of organism from fish to mammals. Among them, only ATXδ was found in Gallus gallus and Xenopus laevis, suggesting the indispensable role of the isoform. ATXδ was expressed in various human tissues with different expression patterns from that of ATXβ. These results show that ATXδ is a second major ATX isoform sharing similar biochemical characters with the major isoform, ATXβ, and is a potential biomarker.
An area-efficient topology for VLSI implementation of Viterbi decoders and other shuffle-exchange type structures (1991)

A topology for single-chip implementation of computing structures based on shuffle-exchange (SE)-type interconnection networks is presented. The topology is suited for structures with a small number of processing elements (i.e. 32-128) whose area cannot be neglected compared to the area required for interconnection. The processing elements are implemented in pairs that are connected to form a ring. In this way three-quarters of the interconnections are between neighbors. The ring structure is laid out in two columns and the interconnection of nonneighbors is routed in the channel between the columns. The topology has been used in a VLSI implementation of the add-compare-select (ACS) module of a fully parallel K=7, R=1/2 Viterbi decoder. Both the floor-planning issues and some of the important algorithm and circuit-level aspects of this design are discussed. The chip has been designed and fabricated in a 2- mu m CMOS process using MOSIS-like simplified design rules. The chip operates at speeds up to 19 MHz under worst-case conditions (V/sub DD/=4.75 V and T/sub A/=70 degrees C). The core of the chip (excluding pad cells) is 7.8*5.1 mm/sup 2/ and contains approximately 50000 transistors. The interconnection network occupies 32% of the area.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Inhibition of viral replication reverses respiratory syncytial virus-induced NF-kappaB activation and interleukin-8 gene expression in A549 cells (1996)

Previous studies have demonstrated that respiratory syncytial virus (RSV) infection of airway epithelial cells results in the expression of a number of cytokines, such as interleukin-8 (IL-8), that are transcriptionally regulated by nuclear factor kappaB (NF-kappaB). In the studies reported here, we demonstrate that treatment of RSV-infected A549 cells with 100 microg of ribavirin (a viral replication inhibitor) per ml results in reversal of RSV-induced NF-kappaB activation, IL-8 mRNA expression, and IL-8 protein production in A549 cells. These data confirm that viral replication is a key step in RSV-induced NF-kappaB activation and IL-8 production.
Multifunctional Iridium Complexes Based on Carbazole Modules as Highly Efficient Electrophosphors (2007)

Since publication of their Communication, it has been brought to the authors' attention that the chemical structures of 1 and 2 shown in Scheme 1 were incorrectly drawn. The authors apologize for the oversight. The correct structures are shown below.1
Novel anti–B-cell maturation antigen antibody-drug conjugate (GSK2857916) selectively induces killing of multiple myeloma (2014)

B-cell maturation antigen (BCMA), highly expressed on malignant plasma cells in human multiple myeloma (MM), has not been effectively targeted with therapeutic monoclonal antibodies. We here show that BCMA is universally expressed on the MM cell surface and determine specific anti-MM activity of J6M0-mcMMAF (GSK2857916), a novel humanized and afucosylated antagonistic anti-BCMA antibody-drug conjugate via a noncleavable linker. J6M0-mcMMAF specifically blocks cell growth via G2/M arrest and induces caspase 3-dependent apoptosis in MM cells, alone and in coculture with bone marrow stromal cells or various effector cells. It strongly inhibits colony formation by MM cells while sparing surrounding BCMA-negative normal cells. J6M0-mcMMAF significantly induces effector cell-mediated lysis against allogeneic or autologous patient MM cells, with increased potency and efficacy compared with the wild-type J6M0 without Fc enhancement. The antibody-dependent cell-mediated cytotoxicity and apoptotic activity of J6M0-mcMMAF is further enhanced by lenalidomide. Importantly, J6M0-mcMMAF rapidly eliminates myeloma cells in subcutaneous and disseminated mouse models, and mice remain tumor-free up to 3.5 months. Furthermore, J6M0-mcMMAF recruits macrophages and mediates antibody-dependent cellular phagocytosis of MM cells. Together, these results demonstrate that GSK2857916 has potent and selective anti-MM activities via multiple cytotoxic mechanisms, providing a promising next-generation immunotherapeutic in this cancer.
Rate Control for H.264 with Two-Step Quantization Parameter Determination but Single-Pass Encoding (2006)

We present an efficient rate control strategy for H.264 in order to maximize the video quality by appropriately determining the quantization parameter (QP) for each macroblock. To break the chicken-and-egg dilemma resulting from QP-dependent rate-distortion optimization (RDO) in H.264, a preanalysis phase is conducted to gain the necessary source information, and then the coarse QP is decided for rate-distortion (RD) estimation. After motion estimation, we further refine the QP of each mode using the obtained actual standard deviation of motion-compensated residues. In the encoding process, RDO only performs once for each macroblock, thus one-pass, while QP determination is conducted twice. Therefore, the increase of computational complexity is small compared to that of the JM 9.3 software. Experimental results indicate that our rate control scheme with two-step QP determination but single-pass encoding not only effectively improves the average PSNR but also controls the target bit rates well.
Structurally Diverse Nitric Oxide-Releasing Poly(propylene imine) Dendrimers (2011)

Structurally diverse secondary amine-functionalized poly(propylene imine) (PPI) dendrimers capable of tunable nitric oxide (NO) release were synthesized in a straightforward, one-step manner using ring-opening or conjugate-addition reactions with propylene oxide (PO), styrene oxide (SO), acrylonitrile (ACN), poly(ethylene glycol) methyl ether acrylate (average Mn = 480) (PEG) or 1,2-epoxy-9-decene (ED). N-Diazeniumdiolate nitric oxide donors were formed on the resulting secondary amine-functionalized G2-G5 PPI dendrimers by reaction with NO gas in basic solution. The NO storage and release kinetics for the resulting dendritic scaffolds were diverse (0.9-3.8 μmol NO/mg totals and 0.3 to 4.9 h half lives), illustrating the importance of the exterior chemical modification (e.g., steric environments, hydrophobicity, etc.) on diazeniumdiolate stability/decomposition. Tunable NO release was demonstrated by combining two donor systems on the exterior of one macromolecular scaffold. Additionally, a mathematical model was developed that allows for the simulation of dual NO release kinetics using the NO release data from the two single NO donor systems. The approaches described herein extend the range and scope of NO-releasing macromolecular scaffolds by unlocking a series of materials for use as dopants in biomedical polymers or stand-alone therapeutics depending on the exterior modification.
Kdo2-Lipid A of Escherichia coli, a defined endotoxin that activates macrophages via TLR-4 (2006)

The LIPID MAPS Consortium (www.lipidmaps.org) is developing comprehensive procedures for identifying all lipids of the macrophage, following activation by endotoxin. The goal is to quantify temporal and spatial changes in lipids that occur with cellular metabolism and to develop bioinformatic approaches that establish dynamic lipid networks. To achieve these aims, an endotoxin of the highest possible analytical specification is crucial. We now report a large-scale preparation of 3-deoxy-D-manno-octulosonic acid (Kdo)(2)-Lipid A, a nearly homogeneous Re lipopolysaccharide (LPS) sub-structure with endotoxin activity equal to LPS. Kdo(2)-Lipid A was extracted from 2 kg cell paste of a heptose-deficient Escherichia coli mutant. It was purified by chromatography on silica, DEAE-cellulose, and C18 reverse-phase resin. Structure and purity were evaluated by electrospray ionization/mass spectrometry, liquid chromatography/mass spectrometry and (1)H-NMR. Its bioactivity was compared with LPS in RAW 264.7 cells and bone marrow macrophages from wild-type and toll-like receptor 4 (TLR-4)-deficient mice. Cytokine and eicosanoid production, in conjunction with gene expression profiling, were employed as readouts. Kdo(2)-Lipid A is comparable to LPS by these criteria. Its activity is reduced by >10(3) in cells from TLR-4-deficient mice. The purity of Kdo(2)-Lipid A should facilitate structural analysis of complexes with receptors like TLR-4/MD2.
Characterization of the promoter region of the human c-erbB-2 protooncogene. (1987)

Three overlapping genomic clones that contain the 5'-terminal portion of the human c-erbB-2 gene (ERBB2) were isolated. The promoter region was identified by nuclease S1 mapping with c-erbB-2 mRNA. Seven transcriptional start sites were identified. DNA sequence analysis showed that the promoter region contains a "TATA box" and a "CAAT box" about 30 and 80 base pairs (bp), respectively, upstream of the most downstream RNA initiation site. Two putative binding sites for transcription factor Sp1 were identified about 50 and 110 bp upstream of the CAAT box, and six GGA repeats were found between the CAAT box and the TATA box. This region had strong promoter activity when placed upstream of the bacterial chloramphenicol acetyltransferase gene and transfected into monkey CV-1 cells. These data indicate that the promoter of the human c-erbB-2 protooncogene is different from that of the protooncogene c-erbB-1 (epidermal growth factor receptor gene), which does not contain either a TATA box or a CAAT box. Comparison of the promoter sequences and activities of the two protooncogenes should be helpful in analysis of the regulatory mechanism of expression of their gene products, which are growth-factor receptors.
Activated microglia in cortex of mouse models of mucopolysaccharidoses I and IIIB (2003)

Alpha-N-acetylglucosaminidase deficiency (mucopolysaccharidosis IIIB, MPS IIIB) and alpha-l-iduronidase deficiency (MPS I) are heritable lysosomal storage diseases; neurodegeneration is prominent in MPS IIIB and in severe cases of MPS I. We have obtained morphologic and molecular evidence for the involvement of microglia in brain pathology of mouse models of the two diseases. In the cortex, a subset of microglia (sometimes perineuronal) consists of cells that are probably phagocytic; they have large storage vacuoles, react with MOMA-2 (monoclonal antibody against macrophages) and Griffonia simplicifolia isolectin IB(4), and stain intensely for the lysosomal proteins Lamp-1, Lamp-2, and cathepsin D as well as for G(M3) ganglioside. MOMA-2-positive cells appear at 1 and 6 months in MPS IIIB and MPS I mice, respectively, but though their number increases with age, they remain sparse. However, a profusion of cells carrying the macrophage CD68/macrosialin antigen appear in the cortex of both mouse models at 1 month. mRNA encoding CD68/macrosialin also increases at that time, as shown by microarray and Northern blot analyses. Ten other transcripts elevated in both mouse models are associated with macrophage functions, including complement C4, the three subunits of complement C1q, lysozyme M, cathepsins S and Z, cytochrome b558 small subunit, macrophage-specific protein 1, and DAP12. An increase in IFN-gamma and IFN-gamma receptor was observed by immunohistochemistry. These functional increases may represent activation of resident microglia, an influx and activation of blood monocytes, or both. They show an inflammatory component of brain disease in the two MPS, as is known for many neurodegenerative disorders.
Specific labeling of mouse brain membrane phospholipids with [20-3H]phorbol 12-p-azidobenzoate 13-benzoate, a photolabile phorbol ester. (1983)

As part of our effort to characterize receptors for the phorbol ester tumor promoters, a phorbol ester photoaffinity probe, [20-3H]phorbol 12-p-azidobenzoate 13-benzoate (PaBzBz), was synthesized. In the dark, PaBzBz bound reversibly to brain particulate fractions with a dissociation constant (Kd) of 0.81 +/- 0.09 x 10(-9) M. Specific binding of PaBzBz, at a concentration equal to its Kd, represented 85% of the total bound. At saturation, 24 +/- 5 pmol of PaBzBz were bound per mg of brain protein, a level similar to that observed with [20-3H]phorbol 12,13-dibutyrate. Under the conditions used (concentrations greater than the Kd for PaBzBz), irradiation caused 45% of the PaBzBz binding to become irreversible. Most of the binding (approximately equal to 60%), including most of the specific irreversible binding, was to phospholipid rather than to protein. Based on susceptibility to enzymatic digestion and on chromatographic mobility, the specifically labeled phospholipids were identified as phosphatidylserine, phosphatidylethanolamine, and phosphatidylethanolamine plasmalogen. Although the PaBzBz specifically labeled lipid, labeling was blocked by pretreatment of membranes at 100 degrees C for 5 min or by papain digestion. Therefore, it seems likely that the identified lipids are specifically associated with a protein receptor and are preferentially labeled either because of the location or reactivity of the nitrene generated on the photoaffinity probe.
Heteroduplex formation and mismatch repair of the "stuck" mutation during mating-type switching in Saccharomyces cerevisiae. (1991)

We sequenced two alleles of the MATa locus of Saccharomyces cerevisiae that reduce homothallic switching and confer viability to HO rad52 strains. Both the MATa-stk (J. E. Haber, W. T. Savage, S. M. Raposa, B. Weiffenbach, and L. B. Rowe, Proc. Natl. Acad. Sci. USA 77:2824-2828, 1980) and MATa-survivor (R. E. Malone and D. Hyman, Curr. Genet. 7:439-447, 1983) alleles result from a T----A base change at position Z11 of the MAT locus. These strains also contain identical base substitutions at HMRa, so that the mutation is reintroduced when MAT alpha switches to MATa. Mating-type switching in a MATa-stk strain relative to a MATa Z11T strain is reduced at least 50-fold but can be increased by expression of HO from a galactose-inducible promoter. We confirmed by Southern analysis that the Z11A mutation reduced the efficiency of double-strand break formation compared with the Z11T variant; the reduction was more severe in MAT alpha than in MATa. In MAT alpha, the Z11A mutation also creates a mat alpha 1 (sterile) mutation that distinguishes switches of MATa-stk to either MAT alpha or mat alpha 1-stk. Pedigree analysis of cells induced to switch in G1 showed that MATa-stk switched frequently (23% of the time) to produce one mat alpha 1-stk and one MAT alpha progeny. This postswitching segregation suggests that Z11 was often present in heteroduplex DNA that was not mismatch repaired. When mismatch repair was prevented by deletion of the PMS1 gene, there was an increase in the proportion of mat alpha 1-stk/MAT alpha sectors (59%) and in pairs of switched cells that both retained the stk mutation (27%). We conclude that at least one strand of DNA only 4 bp from the HO cut site is not degraded in most of the gene conversion events that accompany MAT switching.
The KAP1 Corepressor Functions To Coordinate the Assembly of De Novo HP1-Demarcated Microenvironments of Heterochromatin Required for KRAB Zinc Finger Protein-Mediated Transcriptional Repression (2006)

KAP1/TIF1beta is proposed to be a universal corepressor protein for the KRAB zinc finger protein (KRAB-zfp) superfamily of transcriptional repressors. To characterize the role of KAP1 and KAP1-interacting proteins in transcriptional repression, we investigated the regulation of stably integrated reporter transgenes by hormone-responsive KRAB and KAP1 repressor proteins. Here, we demonstrate that depletion of endogenous KAP1 levels by small interfering RNA (siRNA) significantly inhibited KRAB-mediated transcriptional repression of a chromatin template. Similarly, reduction in cellular levels of HP1alpha/beta/gamma and SETDB1 by siRNA attenuated KRAB-KAP1 repression. We also found that direct tethering of KAP1 to DNA was sufficient to repress transcription of an integrated transgene. This activity is absolutely dependent upon the interaction of KAP1 with HP1 and on an intact PHD finger and bromodomain of KAP1, suggesting that these domains function cooperatively in transcriptional corepression. The achievement of the repressed state by wild-type KAP1 involves decreased recruitment of RNA polymerase II, reduced levels of histone H3 K9 acetylation and H3K4 methylation, an increase in histone occupancy, enrichment of trimethyl histone H3K9, H3K36, and histone H4K20, and HP1 deposition at proximal regulatory sequences of the transgene. A KAP1 protein containing a mutation of the HP1 binding domain failed to induce any change in the histone modifications associated with DNA sequences of the transgene, implying that HP1-directed nuclear compartmentalization is required for transcriptional repression by the KRAB/KAP1 repression complex. The combination of these data suggests that KAP1 functions to coordinate activities that dynamically regulate changes in histone modifications and deposition of HP1 to establish a de novo microenvironment of heterochromatin, which is required for repression of gene transcription by KRAB-zfps.
RANDOMIZED TRIAL COMPARING CRYOPRESERVED CULTURED EPIDERMAL ALLOGRAFTS WITH TULLE-GRAS IN THE TREATMENT OF SPLIT-THICKNESS SKIN GRAFT DONOR SITES (1993)

Cultured epidermal allografts have been successfully used to treat a wide variety of skin defects ranging from burns to leg ulcers. Their postulated mechanism of action is through release of multiple cytokines that stimulate epithelialization from the wound periphery as well as from remnant epidermal appendages. A randomized, controlled clinical trial was undertaken to compare the efficacy of cryopreserved cultured allograft dressings (CCAD) with tulle-gras dressings in the treatment of split-skin graft donor sites. Five patients were enrolled in the study and in each patient, half of the donor site was allografted and the other half was treated with tulle-gras control. The mean time to complete healing was 6.2 days for CCAD compared with 9.6 days (p = 0.035) for the tulle-gras controls. Patient assessment of pain with dressing changes was also significantly lower at the CCAD-treated sites than at the control sites (p = 0.001). The results indicate that cultured allografts offer greater patient comfort and earlier maturation of regenerated skin.
Evaluating Clinical Accuracy of Systems for Self-Monitoring of Blood Glucose (1987)

Although the scientific literature contains numerous reports of the statistical accuracy of systems for self-monitoring of blood glucose (SMBG), most of these studies determine accuracy in ways that may not be clinically useful. We have developed an error grid analysis (EGA), which describes the clinical accuracy of SMBG systems over the entire range of blood glucose values, taking into account 1) the absolute value of the system-generated glucose value, 2) the absolute value of the reference blood glucose value, 3) the relative difference between these two values, and 4) the clinical significance of this difference. The EGA of accuracy of five different reflectance meters (Eyetone, Dextrometer, Glucometer I, Glucometer II, Memory Glucometer II), a visually interpretable glucose reagent strip (Glucostix), and filter-paper spot glucose determinations is presented. In addition, reanalyses of a laboratory comparison of three reflectance meters (Accucheck II, Glucometer II, Glucoscan 9000) and of two previously published studies comparing the accuracy of five different reflectance meters with EGA is described. EGA provides the practitioner and the researcher with a clinically meaningful method for evaluating the accuracy of blood glucose values generated with various monitoring systems and for analyzing the clinical implications of previously published data.
Haemophilia prophylaxis in young patients–a long‐term follow‐up (1997)

There is a growing international consensus haemophilic arthropathy can be prevented by administering early high-dose prophylaxis. The results of the present investigation strongly support this opinion.
Effective Suppression of Class I Major Histocompatibility Complex Expression by the US11 or ICP47 Genes Can Be Limited by Cell Type or Interferon- γ Exposure (2003)

An impediment encountered in many viral-based gene therapy clinical trials has been the rapid destruction of the transgene by the host's immune response. The processing and presentation of antigens through the class I major histocompatibility complex (MHC) pathway is the initial specific response to viral infection. Disruption of the class I MHC pathway by herpes simplex virus (HSV) or the human cytomegalovirus (HCMV) results in a decrease of the CD8(+) cytotoxic T lymphocyte (CTL) response and prolongs survival of infected cells in the host. Two viral immune suppression genes that interfere with the class I MHC presentation pathway, the HSV type I ICP47 gene and HCMV US11 gene, were cloned and each incorporated into a retroviral vector. HSV ICP47 and HCMV US11 transgenes were expressed in multiple cells lines and compared for their abilities to reduce antigen presentation on the cell surface by class I MHC. Retroviral supernatants were used to transduce human, canine, and rat cell lines. Fluorescence-activated cell sorter (FACS) analysis of US11- and ICP47-transduced cell lines demonstrated substantial reductions in class I MHC cell surface expression in most cell lines except in rodent cells where ICP47 is nonfunctional. The decrease in the level of class I MHC expression for ICP47 transduced cell lines ranged from 31-98% relative to negative controls. US11 decreased class I cell surface MHC by 67-96%. When both ICP47 and US11 are expressed in human cells, a further reduction of class I MHC was observed. Next, human A375 melanoma cells were tested to determine if the resulting reduction in cell surface class I MHC would reduce in vitro cytotoxicity by CTL. A375 cells expressing either ICP47 or US11 demonstrated a twofold to threefold reduction of specific lysis by primed CD8(+) CTL. These data clearly establish an ability to convey immune protection to human cells by viral genes. However, further analysis demonstrated that interferon (IFN)-gamma could reverse part or all of the downregulation of class I MHC induced by the ICP47 or US11 genes. The ICP47 and US11 genes, when expressed in target cells, decrease class I MHC presentation and as such might be used in strategies to create local immunosuppression against transgenes or allografts.