gebhart/patrepeval huggingface dataset:
The full-length E6 protein of human papillomavirus type 16 has transforming and trans-activating activities and cooperates with E7 to immortalize keratinocytes in culture (1991)

The wild-type E6 and E7 genes of human papillomavirus type 16 (HPV16) can cooperate to immortalize normal human keratinocytes in culture. The E6 open reading frame of HPV16 and other HPV types highly associated with cervical cancer has the potential of encoding both full-length E6 and two truncated E6* proteins, the latter being generated via splicing within the E6 open reading frame portion of the E6-E7 polycistronic transcript. Those types, such as HPV6, that are infrequently associated with cervical carcinoma lack the splice site and encode only a full-length E6. We have now found that, in addition to cooperating with E7 to immortalize keratinocytes, HPV16 E6 can induce anchorage-independent growth in NIH 3T3 cells and trans-activate the adenovirus E2 promoter. HPV6 E6 was also able to trans-activate the adenovirus E2 promoter, although it was inactive in both cell transformation assays. An HPV16 splice site mutant which expressed only the full-length HPV16 E6 was active in all three assays, indicating that the E6* proteins are not required for these activities. The plasmid which encodes the E6* proteins was inactive and did not potentiate the activity of the HPV16 splice site mutant. The mutation that prevented splicing in E6-E7 mRNA severely reduced the level of E7 protein and increased E6 protein. Taken together, the results suggest that the primary function of the splice within E6 is to facilitate the translation of E7 and reduce translation of full-length E6, rather than to generate biologically active E6* proteins.
Whispering-gallery-mode-resonator-stabilized narrow-linewidth fiber loop laser (2009)

We demonstrate a narrow-line fiber loop laser using erbium-doped fiber as the gain material, stabilized by using a microsphere as a transmissive frequency selective element. Stable lasing with a linewidth of 170 kHz is observed, limited by the experimental spectral resolution. A linear increase in output power and a redshift of the lasing mode were also observed with increasing pump power. Its potential applications are discussed.
A therapeutic human IgG4 monoclonal antibody that depletes target cells in humans (1996)

It is traditionally held that human IgG4 MoAbs should not deplete target cells in vivo, as this isotype is inactive in a number of in vitro assays that measure effector function. We have previously challenged this dogma, and the current study was designed to investigate the in vivo biological effects in humans of a MoAb of human IgG4 isotype. Nine patients with refractory rheumatoid arthritis (RA) fulfilling ARA criteria, and one with ankylosing spondylitis (AS) received a human IgG4 Campath-1 MoAb (with specificity against the pan-lymphocyte antigen CD52) as part of a two-stage therapeutic protocol. In stage 1, patients received a single dose of this MoAb. Stage 2, starting 48 h later, comprised a 5-day course of a human IgG1 Campath-1 MoAb with identical V-region (CAMPATH-1H), as previously used in the management of RA patients. The intervening 48 h provided a window of opportunity to monitor the biological effects of the IgG4 MoAb for comparison with the IgG1. The two MoAbs were also compared for in vitro biological activity. IgG4 depleted peripheral blood lymphocytes (PBL), albeit less efficiently than IgG1. It produced a first-dose reaction of similar intensity, although associated circulating tumour necrosis factor-alpha (TNF-alpha) levels were lower. TNF-alpha release from whole blood in vitro was also greater with the IgG1 MoAb. The study design did not permit conclusions to be drawn regarding therapeutic efficacy of the IgG4 MoAb. In summary, a human IgG4 Campath-1 MoAb depletes target cells in vivo. Importantly, this study demonstrates for the first time in humans that in vitro assays may not predict the in vivo effector function of therapeutic MoAbs.
Hyaluronan as an Immune Regulator in Human Diseases (2011)

Accumulation and turnover of extracellular matrix components are the hallmarks of tissue injury. Fragmented hyaluronan stimulates the expression of inflammatory genes by a variety of immune cells at the injury site. Hyaluronan binds to a number of cell surface proteins on various cell types. Hyaluronan fragments signal through both Toll-like receptor (TLR) 4 and TLR2 as well as CD44 to stimulate inflammatory genes in inflammatory cells. Hyaluronan is also present on the cell surface of epithelial cells and provides protection against tissue damage from the environment by interacting with TLR2 and TLR4. Hyaluronan and hyaluronan-binding proteins regulate inflammation, tissue injury, and repair through regulating inflammatory cell recruitment, release of inflammatory cytokines, and cell migration. This review focuses on the role of hyaluronan as an immune regulator in human diseases.
Synthesis of acyclic and dehydroaspartic acid analogs of Ac-Asp-Glu-OH and their inhibition of rat brain N-acetylated .alpha.-linked acidic dipeptidase (NAALA dipeptidase) (1990)

The following structural and conformationally constrained analogues of Ac-Asp-Glu-OH (1) were synthesized: Ac-Glu-Glu-OH (2), Ac-D-Asp-Glu-OH (3), Ac-Glu-Asp-OH (4), Ac-Asp-Asp-OH (5), Ac-Asp-3-aminohexanedioic acid (6), Ac-3-amino-3-(carboxymethyl)propanoyl-Glu-OH (7), N-succinyl-Glu-OH (8), N-maleyl-Glu-OH (9), N-fumaryl-Glu-OH (10), and Ac-delta ZAsp-Glu-OH (11). These analogues were evaluated for their ability to inhibit the hydrolysis of Ac-Asp-[3,4-3H]-Glu-OH by N-acetylated alpha-linked acidic dipeptidase (NAALA dipeptidase) in order to gain some insight into the structural requirements for the inhibition of this enzyme. Analogues 4-6 and 9 were very weak inhibitors of NAALA dipeptidase (Ki greater than 40 microM), while 2, 3, and 7 with Ki values ranging from 3.2-8.5 microM showed intermediate inhibitory activity. The most active inhibitors of NAALA dipeptidase were compounds 8, 10, and 11 with Ki values of 0.9, 0.4, and 1.4 microM, respectively. These results suggest that the relative spacing between the side chain carboxyl and the alpha-carboxyl group of the C-terminal residue may be important for binding to the active site of the enzyme. They also indicate that the chi 1 torsional angle for the aspartyl residue is in the vicinity of 0 degrees.
Long-Range Ordering of Diblock Copolymers Induced by Droplet Pinning (2003)

The directed self-assembly of diblock copolymers offers unique routes for the design and fabrication of well-ordered arrays of nanoscopic structures. However, generating arrays with long-range order and few defects has been a difficult goal to achieve without extended thermal annealing processes. Here, a simple, one-step route, based on the flow of a solution within a droplet pinned to a surface coupled with solvent evaporation, is shown where highly oriented, ordered arrays of nanoscopic cylindrical domains of a block copolymer can be produced over large distances (tens of microns). Hexagonal arrays of the cylindrical domains of block copolymers are shown to orient parallel to the film surface and in the direction of an evaporation-induced flow, producing morphologies with very long-range order. This solution casting process, that naturally couples two orthogonal fields, is easily transferable to blade- and dip-coating processes that are routinely used to prepare thin films. Thus, a simple route is shown, by which the barrier to long-range order in arrays of nanoscopic elements can be overcome, providing valuable insight for designing addressable media.
Polysulfobetaine-Grafted Surfaces as Environmentally Benign Ultralow Fouling Marine Coatings (2009)

Coatings based on polysulfobetaine polymers are being developed as environmentally benign, fouling-resistant marine coatings. Poly(sulfobetaine methacrylate) (polySBMA) brushes were grafted onto glass surfaces using surface-initiated atom transfer radical polymerization (ATRP). The settlement, growth, and attachment strength of marine algae were investigated on polySBMA-coated surfaces. Results showed that few spores of the green marine alga, Ulva, settled (attached) on the polySMBA surfaces, and the adhesion strength of both spores and sporelings (young plants) was low. Diatoms were also mostly unable to adhere to the polySMBA surfaces. Assays demonstrated that SBMA polymers in solution were not toxic. The data are discussed in terms of the interfacial properties presented by the polySMBA surfaces. Zwitterionic polymers and coatings exhibit great advantages for their effectiveness to resist marine fouling while being environmentally benign and are promising as ultralow fouling marine coatings.
Acceleration of thrombolysis with a high-dose transthrombus bolus technique. (1989)

The rate of complication and the time necessary to achieve thrombolysis remain major disadvantages of regional thrombolytic therapy. By lacing the entire length of arterial or arterial bypass graft occlusions in the lower extremities of 49 patients with one of two different bolus doses of urokinase (mean, 52,000 International U in 35 infusions = low-dose group [28 patients]; mean, 230,000 U in 23 infusions = high-dose group [21 patients]) prior to identical continuous infusions, it was possible to demonstrate a decrease in the time needed to complete thrombolysis from 33.6 hours in the low-dose group to 10.4 hours in the high-dose group (P less than .001). The total urokinase dose necessary for successful thrombolysis was also significantly less in the high-dose group (P less than .001). The major complication rate was 22.9% in the low-dose group and 8.7% in the high-dose group, although the difference was not statistically significant. The use of urokinase and a high-dose transthrombus bolus injection technique significantly accelerates thrombolysis, decreases the total urokinase dose needed, and may lower the major complication rate.
Homomeric interactions between type II transforming growth factor-beta receptors. (1994)

Transforming growth factor-beta (TGF-beta) binds with high affinity to three cell-surface receptors. Both type I and II receptors are transmembrane serine/threonine kinases and thought to mediate TGF-beta responses by forming a heteromeric complex in the presence of TGF-beta. We investigated whether the type II receptors form a homomeric complex in the presence or absence of ligand. Double immunoprecipitation analyses were performed using lysates from metabolically labeled cells cotransfected with differentially epitope-tagged type II receptors. We demonstrate that the type II receptors can form a homomeric complex even in the absence of their ligand, TGF-beta. This pre-existing type II receptor complex has the ability to bind TGF-beta. Moreover, in addition to the extracellular and transmembrane domains, the cytoplasmic portions of the receptors are also able to interact with each other, indicating that multiple contact points are involved in the formation of the homomeric type II receptor complex. Our results suggest a novel mechanism of complex formation and receptor activation of the serine/threonine kinase receptor family.
The interaction of C5 with C3b in free solution: a sufficient condition for cleavage by a fluid phase C3/C5 convertase. (1980)

We have measured the interactions of C3b with C5 in free solution under conditions that favor detecting weak binding interactions (high C3b and low C5 concentrations and low ionic strength). When a mixture of 125I-C5 (2 X 10(-8) M) and unlabeled C3b (3.8 x 10(-5) M) was ultracentrifuged in a sucrose gradient, virtually all of the C5 sedimented to the position of a 13 to 14S complex. In contrast, a sedimentation rate for C5 of 9S was obtained in the absence of C3b. The ability to bind C5 was observed to be a property of C3b since native C3 was unable to bind C5. It was also found that beta 1H by itself could inhibit the binding of C5 to cell-bound C3b. From inhibition studies, we estimate that the association constant for the C3b-C5 interaction is on the order of 2 x 10(6) M-1 in a low ionic strength buffer (mu = 0.06) and 5-fold weaker at physiologic ionic strength. C5 bound to C3b in free solution was cleaved by nephritic factor-stabilized fluid phase C3bB. C5 activation did not occur on omitting C3b. We conclude that the ability to bind C5 is a property of C3b molecules whether surface bound or in free solution and that when C5 is bound in either fashion, it can be cleaved by a fluid phase C3/C5 convertase.
CD164-A Novel Sialomucin on CD34 + Cells (2000)

Hematopoiesis in adult bone marrow is a tightly regulated process involving interactions between cytokine and adhesion receptors on hematopoietic progenitor cells and their cognate ligands in the immediate microenvironment. These interactions control hematopoietic stem cell self-renewal, quiescence, commitment and migration. Recently, sialomucins have assumed some importance in hematopoiesis, with six of these receptors, CD34, PSGL-1, CD43, PCLP, CD45RA and CD164, having been identified on primitive hematopoietic precursor cells and/or their associated stromal/endothelial elements. This article reviews the cloning, expression and function of the recently identified sialomucin, CD164, which is highly expressed by primitive hematopoietic progenitor cells. The CD164 receptor is implicated in mediating or regulating hematopoietic precursor cell adhesion to stroma, and may serve as a potent negative regulator of hematopoietic progenitor cell proliferation.
Application of brassinolide mitigates saline stress of certain metabolites of sorghum grown in Karaikal (2012)

Effect of brassinolide on the metabolite contents (free proline, soluble proteins and RNA) of two sorghum varieties (‘CSH-5’ and ‘CSH-6’) grown in two saline experimental sites of Karaikal viz. Varchikudy and Mallavur, was studied. Brassinolide application resulted in substantial elevated levels of free proline, soluble proteins and RNA of the two varieties of sorghum plants grown in two saline experimental sites of Karaikal. The study revealed that brassinolide was more effective in more saline site –II (Mallavur) than less saline site –I (Varchikudy) thus indicating its ability to counteract the negative impact of saline stress.
Protein Kinase C Plays a Key Role in Cellular Senescence Programs of Human Normal Diploid Cells (2009)

In the present study, we clarified that transforming growth factor beta (TGF-beta) induces cellular senescence in human normal diploid cells, TIG-1, and identified protein kinase Cs (PKCs) as downstream mediators of TGF-beta-induced cellular senescence. Among PKCs, we showed that PKC-delta induced cellular senescence in TIG-1 cells and was activated in replicatively and prematurely senescent TIG-1 cells. The causative role of PKC-delta in cellular senescence programs was demonstrated using a kinase negative PKC-delta and small interfering RNA against PKC-delta. Furthermore, PKC-delta was shown to function in human telomerase reverse transcriptase (hTERT) gene repression. These results indicate that PKC-delta plays a key role in cellular senescence programs, and suggest that the induction of senescence and hTERT repression are coordinately regulated by PKC-delta.
Prevention of ischemia‐induced cardiac Sudden death by n−3 polyunsaturated fatty acids in dogs (1997)

The objective of this study was to obtain functional information associated with the prevention by n-3 polyunsaturated fatty acids (PUFA) of ischemia-induced fatal cardiac ventricular arrhythmias in the intact, conscious, exercising dog. Thirteen dogs susceptible to ischemia-induced ventricular fibrillation were prepared surgically by ligation of their anterior descending left coronary artery and placement of an inflatable cuff around their left circumflex artery. After 4 wk of recovery, exercise-plus-ischemia tests were performed without and then with an intravenous infusion of an emulsion of free n-3 PUFA just prior to occluding the left circumflex artery while the animals were running on a treadmill. One week later the exercise-plus-ischemia test was repeated but with a control infusion replacing the emulsion of n-3 PUFA. The infusion of the free n-3 PUFA in quantities of 1.0 to 10 g prevented ventricular fibrillation in 10 of the 13 dogs tested (P < 0.005), apparently without esterification of the PUFA into membrane phospholipids. The antiarrhythmic effect of the n-3 PUFA was associated with slowing of the heart rate, shortening of the QT-interval (electrical action potential duration), reduction of left ventricular systolic pressure, and prolongation of the electrocardiographic atrial-ventricular conduction time (P-R interval). These effects are comparable with those we have reported in studies with cultured neonatal rat cardiac myocytes.
A simple and efficient algorithm for gene selection using sparse logistic regression (2003)

Supplementary material is available at the site http://guppy.mpe.nus.edu.sg/~mpessk/SparseLOGREG.shtml
Serum amyloid A protein enhances the activity of secretory non-pancreatic phospholipase A2 (1995)

The acute-phase proteins serum amyloid A protein (SAA) and secretory phospholipase A2 (sPLA2) are simultaneously expressed during inflammatory conditions. SAA associates with high-density lipoprotein (HDL) altering its physicochemical composition. We found that purified acute-phase SAA, but not the constitutive form, markedly enhances the lipolytic activity of sPLA2 in a dose-related manner with phosphatidylcholine/lysophosphatidylcholine or phosphatidylethanolamine/lysophosphatidylethanolamine liposomal substrates. Normal HDL was found to reduce activity of sPLA2 in a dose-dependent manner, but when acute-phase HDL containing 27% SAA was tested, it enhanced sPLA2 activity. Immunopurified monospecific antibodies against SAA completely abolished the enhancing activity of SAA and acute-phase HDL. Given the central role of HDL in lipoprotein metabolism, the interaction between HDL, SAA and sPLA2 may account for changes detected in lipoprotein metabolism during the acute phase.
Post-transcriptional Regulation of Erythropoietin mRNA Stability by Erythropoietin mRNA-binding Protein (1997)

We have previously identified a sequence in the 3'-untranslated region (3'-UTR) of erythropoietin (Epo) mRNA which binds a protein(s), erythropoietin mRNA-binding protein (ERBP). A mutant lacking the ERBP binding site (EpoM) was generated. Hep3B cells were stably transfected with a wild-type Epo (EpoWT) cDNA or EpoM cDNA construct located downstream of a promoter of cytomegalovirus. Following inhibition of transcription, the half-lives of EpoWT and EpoM mRNAs were 7 h and 2.5 h in normoxia, respectively. The EpoM mRNA half-life remained unchanged in hypoxia. EpoWT mRNA half-life increased approximately 40% in response to a 6-h hypoxic pre-exposure and an additional approximately 50% when pre-exposed to 12 h hypoxia. The steady-state level of EpoWT mRNA was 4-fold that of EpoM mRNA reflecting the difference in mRNA decay rates in normoxia. The Epo protein level expressed from exogenous EpoM was unchanged in both normoxia and hypoxia. In contrast, the Epo protein level expressed from exogenous EpoWT increased 50% in hypoxia when compared with normoxia. These observations were further supported by chimeric chloramphenicol acetyltransferase and Epo-3'-UTR constructs. We have demonstrated that Epo mRNA stability was modulated in normoxia and further by hypoxia, therefore, providing evidence that Epo is regulated at the post-transcriptional level through ERBP complex formation.
Inadequate Interleukin 2 Production (1984)

We studied the production of the two major mediators of cellular immune responses, Interleukin 1 (IL-1) and Interleukin 2 (IL-2), by the peripheral blood mononuclear cells of 23 burn patients (16 men, seven women, mean age 48.9 years) compared with 23 matched controls (16 men, seven women, mean age 46.7 years). Serial measurements were made of IL-1 production by adherent mononuclear cells after stimulation with lipopolysaccharide and of IL-2 production by lymphocytes after stimulation with phytohemagglutinin (PHA). Eighty determinations of IL-2 production by lymphocytes from 12 patients with greater than 30% body surface area burn revealed a mean IL-2 production of 0.71 u as compared with a mean of 1.23 u for patients with less than 30% burns (p = 0.04). Patients with greater than 30% body surface area burns had significantly reduced IL-2 production (p less than or equal to 0.05) until 60 days after injury, whereas those with smaller burns had reduced IL-2 production only at 20-29 and 30-39 days postburn. Nine burn patients with systemic sepsis showed significantly lower IL-2 production (p = 0.03) at 10-29 days postburn than nonseptic patients, and significantly less IL-2 production during septic episodes. Eight patients with greater than 50% suppression of lymphocyte response to PHA produced less IL-2 (0.4 u) than patients with less than 50% suppression, (1.07 u, p = 0.004). IL-1 production was significantly elevated as compared with controls (4.45 u vs. 3.6 u, p = 0.05) early after injury, but was subsequently within the normal range regardless of burn size. The percentage of circulating helper T-lymphocytes, the principal source of IL-2, was also reduced, although this did not always correlate with IL-2 production, which remained depressed after recovery of the helper T-cell population. These results indicate that failure to produce IL-2, a powerful mediator of cellular immune responses, is an important mechanism underlying the defective cell mediated immunity seen in burn patients.
Elucidating and Minimizing the Loss by Recombinant Vaccinia Virus of Human Immunodeficiency Virus Gene Expression Resulting from Spontaneous Mutations and Positive Selection (2009)

While characterizing modified vaccinia virus recombinants (rMVAs) containing human immunodeficiency virus env and gag-pol genes, we detected nonexpressing mutants by immunostaining individual plaques. In many cases, the numbers of mutants increased during successive passages, indicating strong selection pressure. This phenomenon provided an opportunity to investigate the formation of spontaneous mutations in vaccinia virus, which encodes its own cytoplasmic replication system, and a challenge to reduce the occurrence of mutations for vaccine production. Analysis of virus from individual plaques indicated that loss of expression was due to frameshift mutations, mostly by addition or deletion of a single nucleotide in runs of four to six Gs or Cs, and large deletions that included MVA DNA flanking the recombinant gene. Interruption of the runs of Gs and Cs by silent codon alterations and moving the recombinant gene to a site between essential, highly conserved MVA genes eliminated or reduced frameshifts and viable deletion mutants, respectively. The rapidity at which nonexpressing mutants accumulated depended on the individual env and gag-pol genes and their suppressive effects on virus replication. Both the extracellular and transmembrane domains contributed to the selection of nonexpressing Env mutants. Stability of an unstable Env was improved by swapping external or transmembrane domains with a more stable Env. Most dramatically, removal of the transmembrane and cytoplasmic domains stabilized even the most highly unstable Env. Understanding the causes of instability and taking preemptive actions will facilitate the development of rMVA and other poxviruses as human and veterinary recombinant vaccines.