gebhart/patrepeval huggingface dataset:
Highly Stable Trimers Formed by Human Immunodeficiency Virus Type 1 Envelope Glycoproteins Fused with the Trimeric Motif of T4 Bacteriophage Fibritin (2002)

The envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) function as a trimer composed of three gp120 exterior glycoproteins and three gp41 transmembrane proteins. Soluble gp140 glycoproteins composed of the uncleaved ectodomains of gp120 and gp41 form unstable, heterogeneous oligomers, but soluble gp140 trimers can be stabilized by fusion with a C-terminal, trimeric GCN4 motif (X. Yang et al., J. Virol. 74:5716-5725, 2000). To understand the influence of the C-terminal trimerization domain on the properties of soluble HIV-1 envelope glycoprotein trimers, uncleaved, soluble gp140 glycoproteins were stabilized by fusion with another trimeric motif derived from T4 bacteriophage fibritin. The fibritin construct was more stable to heat and reducing conditions than the GCN4 construct. Both GCN4- and fibritin-stabilized soluble gp140 glycoproteins exhibited patterns of neutralizing and nonneutralizing antibody binding expected for the functional envelope glycoprotein spike. Of note, two potently neutralizing antibodies, immunoglobulin G1b12 and 2G12, exhibited the greatest recognition of the stabilized, soluble trimers, relative to recognition of the gp120 monomer. The observed similarities between the GCN4 and fibritin constructs indicate that the HIV-1 envelope glycoprotein ectodomains dictate many of the antigenic and structural features of these fusion proteins. The melting temperatures and ligand recognition properties of the GCN4- and fibritin-stabilized soluble gp140 glycoproteins suggest that these molecules assume conformations distinct from that of the fusion-active, six-helix bundle.
The α1domain of HLA-G1 and HLA-G2 inhibits cytotoxicity induced by natural killer cells: Is HLA-G the public ligand for natural killer cell inhibitory receptors? (1997)

We have investigated the protective role of the membrane-bound HLA-G1 and HLA-G2 isoforms against natural killer (NK) cell cytotoxicity. For this purpose, HLA-G1 and HLA-G2 cDNAs were transfected into the HLA class I-negative human K562 cell line, a known reference target for NK lysis. The HLA-G1 protein, encoded by a full-length mRNA, presents a structure similar to that of classical HLA class I antigens. The HLA-G2 protein, deduced from an alternatively spliced transcript, consists of the alpha1 domain linked to the alpha3 domain. In this study we demonstrate that (i) HLA-G2 is present at the cell surface as a truncated class I molecule associated with beta2-microglobulin; (ii) NK cytolysis, observed in peripheral blood mononuclear cells and in polyclonal CD3(-) CD16(+) CD56(+) NK cells obtained from 20 donors, is inhibited by both HLA-G1 and HLA-G2; this HLA-G-mediated inhibition is reversed by blocking HLA-G with a specific mAb; this led us to the conjecture that HLA-G is the public ligand for NK inhibitory receptors (NKIR) present in all individuals; (iii) the alpha1 domain common to HLA-G1 and HLA-G2 could mediate this protection from NK lysis; and (iv) when transfected into the K562 cell line, both HLA-G1 and HLA-G2 abolish lysis by the T cell leukemia NK-like YT2C2 clone due to interaction between the HLA-G isoform on the target cell surface and a membrane receptor on YT2C2. Because NKIR1 and NKIR2, known to interact with HLA-G, were undetectable on YT2C2, we conclude that a yet-unknown specific receptor for HLA-G1 and HLA-G2 is present on these cells.
Multiple mechanisms for the activation of human platelet aggregation by Staphylococcus aureus: roles for the clumping factors ClfA and ClfB, the serine–aspartate repeat protein SdrE and protein A (2002)

The ability of Staphylococcus aureus cells to induce platelet aggregation has long been recognized. However, despite several attempts to identify the mechanisms involved in this interaction, the nature of the bacterial receptors required remains poorly understood. Using genetic manipulation, this study for the first time provides clear evidence that several S. aureus surface proteins participate in the inter-action with platelets. Mutants of S. aureus strain Newman lacking one or more surface proteins were tested for their ability to stimulate platelet aggregation. This approach was complemented by the expression of a number of candidate proteins in the non-aggregating Gram-positive bacterium Lacto-coccus lactis. S. aureus-induced aggregation was monophasic and was dependent on the platelet receptor GPIIb/IIIa. The fibrinogen-binding proteins, clumping factors A and B and the serine-aspartate repeat protein SdrE could each induce aggregation when expressed in L. lactis. Although protein A expressed in L. lactis was not capable of inducing aggregation independently, it enhanced the aggregation response when expressed on the surface of S. aureus. Thus, S. aureus has multiple mechanisms for stimulating platelet aggregation. Such functional redundancy suggests that this phenomenon may be important in the pathogenesis of invasive diseases such as infective endocarditis.
Plasma soluble vascular endothelial growth factor receptor-1 concentration is elevated prior to the clinical diagnosis of pre-eclampsia (2005)

Plasma sVEGFR-1 concentration is elevated in pre-eclampsia prior to the clinical diagnosis of the disease. This elevation began 6-10 weeks prior to the clinical manifestations, and the increase was more pronounced at 2-5 weeks before the diagnosis, as well as at clinical presentation. Furthermore, in early-onset pre-eclampsia, plasma concentration ofsVEGFR-1 is elevated earlier than the late-onset disease.
ASSESSMENT OF MUSCARINIC AND NICOTINIC ACETYLCHOLINE RECEPTOR EXPRESSION IN PRIMITIVE NEUROECTODERMAL TUMOR/EWING FAMILY OF TUMOR AND DESMOPLASTIC SMALL ROUND CELL TUMOR: AN IMMUNOHISTOCHEMICAL AND WESTERN BLOT STUDY OF TISSUE MICROARRAY AND CELL LINES (2008)

The primitive neuroectodermal tumor (PNET)/Ewing family of tumors (EFT) and desmoplastic small round cell tumor (DSRCT) portend a grave prognosis. Ongoing research in similar neurocrest-derived neoplasms has implicated both the muscarinic acetylcholine receptor (mAChR) and nicotinic acetylcholine receptor (nAChR) in the pathogenesis of these neoplasms. Acetylcholine has been reported to impart a modulatory effect on chemotaxis and proliferation, an effect ameliorated by anticholinergic drugs. The aim of our study is to characterize the pattern of expression of mAChR and nAChR in PNET/EFT and DSRCT, in hopes of discovering a potential target for therapeutic improvements. We examined 34 cases of PNET/EFT and 2 DSRCT retrospectively by immunohistochemical studies. We found that AChRs are overexpressed in a significant number of PNET/EFT and DSRCT. The Western blot analysis of 3 human Ewing sarcoma cell lines confirms the presence of AChRs. Future studies are planned to confirm these results as well as to investigate their potential therapeutic implications.
Viral and Nonviral Uses of Imiquimod: A Review (2004)

Imiquimod has been shown to be a safe and effective treatment for a variety of skin conditions.
Unsupervised Machine Learning with Independent Component Analysis to Identify Areas of Progression in Glaucomatous Visual Fields (2005)

The vB-ICA-mm can quantitatively identify progression in eyes with glaucoma by evaluating change in one or more patterns of the visual field loss while other areas or patterns remain stable. This may enable each eye to contribute to the determination of whether change is caused by true progression or by variability.
Cholinergic neurotransmission in human corpus cavernosum. I. Responses of isolated tissue (1988)

To investigate the role of cholinergic neurotransmission in erection, human penile corpus cavernosum tissue was studied. Electrical stimulation of strips of corpus cavernosum suspended in an organ chamber induced contractions and relaxations that were blocked by tetrodotoxin. The contractions also were blocked by bretylium and prazosin. Norepinephrine and phenylephrine contracted the isolated strips and this response was prevented by prazosin. Electrical stimulation-induced relaxations were enhanced by bretylium and physostigmine and partially blocked by atropine. The effect of atropine, but not that of physostigmine, was prevented by bretylium. Corporal strips contracted with norepinephrine relaxed to acetylcholine; this effect was blocked by atropine and enhanced by physostigmine. Strips lacking endothelium contracted normally with norepinephrine, but the relaxation caused by acetylcholine was virtually abolished. Thus endothelium lining the lacunar spaces within human corpus cavernosum is required for the relaxation caused by exogenous acetylcholine. There may be three neurotransmitter effector systems that control corpus cavernosum smooth muscle tone: adrenergic (excitatory), cholinergic (inhibitory), and nonadrenergic noncholinergic (inhibitory). Cholinergic nerves do not dilate or constrict directly the smooth muscle but may modulate other neuroeffector systems and/or the endothelium.
VEGF-A Induces Angiogenesis, Arteriogenesis, Lymphangiogenesis, and Vascular Malformations (2002)

The mature vasculature develops initially from thetwin processes of vasculogenesis (de novo formation ofblood vessels from primitive precursors) and angiogenesis (formation of new blood vessels from preexisting vessels) (Folkman and D'Amore 1996; Beck and D'Amore1997; Folkman 1997; Hanahan 1997; Risau 1997; Galeand Yancopoulos 1999). The resulting blood vessels thatcome to supply normal adult tissues are distributed at regular and closely spaced intervals and are organized into ahierarchy of elastic and muscular arteries, arterioles, capillaries, post-capillary venules, and small and large veins.Each of these vessel types has a characteristic size andstructure that allow it to perform specialized functions.Thus, muscular arteries and arterioles regulate pressure;capillaries are the major site of molecular exchange; andvenules and small veins are the primary vascular segments responsive to inflammation, whether humoral(plasma extravasation initiated by histamine, VEGF-A,etc.) or cellular (inflammatory cell extravasation)...
Lipid-Based Nanocarriers for CNS-Targeted Drug Delivery (2011)

Nanotechnology exerts an increasing impact on the development of more effective tools for the diagnosis and treatment of human diseases. This applies in particular to central nervous system (CNS) disorders. Development of therapeutics for CNS is, in fact, one of the most challenging areas in drug development, mainly due to the presence of the blood-brain barrier (BBB) which separates the blood from the cerebral parenchyma thus limiting the brain uptake of the vast majority of neurotherapeutic agents. Among the several strategies which have been developed over the last years in order to overcome this problem, nanotechnology-based approaches have gained increasing attention as the most promising strategies for CNS targeted drug delivery. Nanocarriers offer several advantages such as the possibility to maintain drug levels in a therapeutically desirable range, as well as the increase of half-lives, solubility, stability and permeability of drugs. Furthermore, the system can be designed in such a way as to release the drug in a controlled way or in a triggered way. This review focuses on lipid-based nanocarriers and more specifically on liposomes, lipid-core micelles, and lipid nanocapsules, and provides an update on their composition and use, including recent patents in the field.
Saccharomyces cerevisiae BUR6Encodes a DRAP1/NC2α Homolog That Has both Positive and Negative Roles in Transcription In Vivo (1997)

BUR3 and BUR6 were identified previously by selecting for mutations that increase transcription from an upstream activating sequence (UAS)-less promoter in Saccharomyces cerevisiae. The bur3-1 and bur6-1 mutations are recessive, increase transcription from a suc2 delta uas allele, and cause other mutant phenotypes, suggesting that Bur3p and Bur6p function as general repressors of the basal transcriptional machinery. The molecular cloning and characterization of BUR3 and BUR6 are presented here. BUR3 is identical to MOT1, a previously characterized essential gene that encodes an ATP-dependent inhibitor of the TATA box-binding protein. Cloning and nucleotide sequence analysis reveals that BUR6 encodes a homolog of DRAP1 (also called NC2alpha), a mammalian repressor of basal transcription. Strains that contain a bur6 null allele are viable but grow extremely poorly, demonstrating that BUR6 is critical for normal cell growth in yeast. The Bur6p histone fold domain is required for function; an extensive nonoverlapping set of deletion alleles throughout the histone fold domain impairs BUR6 function in vivo, whereas mutations in the amino- and carboxy-terminal tails have no detectable effect. BUR6 and BUR3/MOT1 have different functions depending on promoter context: although the bur3-1 and bur6-1 mutations increase transcription from delta uas promoters, they result in reduced transcription from the wild-type GAL1 and GAL10 promoters. This transcriptional defect is due to the inability of the GAL10 UAS to function in bur6-1 strains. The similar phenotypes of bur6 and bur3 (mot1) mutations suggest that Bur6p and Mot1p have related, but not identical, functions in modulating the activity of the general transcription machinery in vivo.
56. The extent of dissociation of salts in water. Part VI. Some calcium salts of organic acids (1938)

The first page of this article is displayed as the abstract.
Plasma membrane associated transcription of cytoplasmic DNA (2012)

Cytoplasmic membrane-associated DNA (cmDNA) is a species of DNA that attaches to the plasma membrane and has physical and chemical properties that differ from those of bulk chromosomal and mitochondrial DNAs. Here, we used deep sequencing to analyze cmDNA and showed that satellite DNAs consisting of both of simple (CCATT)(N) repeats from the pericentromere regions of the chromosomes and 171-bp α-satellite repeat sequences from centromeres were highly enriched. Importantly, we found there is a special cytoplasmic membrane-associated transcription system in which DNA-dependent RNA polymerase II, which colocalizes with template cmDNA at the plasma membrane, can transcribe the membrane-associated 171-bp α-satellite repeat sequences into RNA. Analysis of phosphorylation patterns indicated that the RNA polymerase II in the plasma membrane is in a different chemical state from its nuclear counterpart.
Morbidity at Bone Graft Donor Sites (1989)

A review of the medical records of 239 patients with 243 autogenous bone grafts was undertaken to document the morbidity at the donor sites. The overall major complication rate was 8.6%. Major complications included infection (2.5%), prolonged wound drainage (0.8%), large hematomas (3.3%), reoperation (3.8%), pain greater than 6 months (2.5%), sensory loss (1.2%), and unsightly scars. Minor complications (20.6%) included superficial infection, minor wound problems, temporary sensory loss, and mild or resolving pain. There was a much higher complication rate (17.9% major) if the incision used for the surgery was also the same incision used to harvest the bone graft.
The DXD motif is required for GM2 synthase activity but is not critical for nucleotide binding (2001)

We tested the importance of the aspartate-any residue-aspartate (DXD) motif for the enzymatic activity and nucleotide binding capacity of the Golgi glycosyltransferase GM2 synthase. We prepared point mutations of the motif, which is found in the sequence 352-VLWVDDDFV, and analyzed cells that stably expressed the mutated proteins. Whereas the folding of the mutated proteins was not seriously disrupted as judged by assembly into homodimers, Golgi localization, and secretion of a soluble form of the enzyme, exchange of the highly conserved aspartic acid residues at position 356 or 358 with alanine or asparagine reduced enzyme activity to background levels. In contrast, the D356E and D357N mutations retained weak activity, while the activity of V352A and W354A mutants was 167% and 24% that of wild-type enzyme, respectively. Despite the major effect of the DXD motif on enzymatic activity, nucleotide binding was not altered in the triple mutant D356N/D357N/D358N as revealed by binding to UDP-beads and labeling with the photoaffinity reagent, P(3)-(4-azidoanilido)uridine 5'-triphosphate (AAUTP). In summary, rather than being critical for nucleotide binding, this motif may function during catalysis in GM2 synthase, as has been proposed elsewhere for the SpsA glycosyltransferase based on its crystal structure.
Induction of WAF1/CIP1 by a p53-independent pathway. (1994)

The p53-inducible gene WAF1/CIP1 encodes a M(r) 21,000 protein (p21) that has been shown to arrest cell growth by inhibition of cyclin-dependent kinases. Induction of WAF1/CIP1 in cells undergoing p53-dependent G1 arrest or apoptosis supports the idea that WAF1/CIP1 is a critical downstream effector of p53. In the present study, we used embryonic fibroblasts from p53 "knock-out" mice to demonstrate p53-independent induction of WAF1/CIP1. We show that serum or individual growth factors such as platelet-derived growth factor, fibroblast growth factor, and epidermal growth factor but not insulin are able to induce WAF1/CIP1 in quiescent p53-deficient cells as well as in normal cells. The kinetics of this transient induction, which is enhanced by cycloheximide, demonstrates that WAF1/CIP1 is an immediate-early gene the transcript of which reaches a peak at approximately 2 h following serum or growth factor stimulation. On the other hand, DNA damage elicited by gamma-irradiation induces WAF1/CIP1 in normal human and mouse fibroblasts but does not affect WAF1/CIP1 expression in p53-deficient cells. These results suggest the existence of two separate pathways for the induction of WAF1/CIP1, a p53-dependent one activated by DNA damage and a p53-independent one activated by mitogens at the entry into the cell cycle. The possible function of p21 at this early stage is discussed.
Noninvasive measurement of fluorophore concentration in turbid media with a simple fluorescence/reflectance ratio technique (2001)

Measurement of the concentration of fluorescent compounds in turbid media is difficult because the absorption and multiple scattering of excitation and emission of light has a large effect on the detected fluorescence. For surface measurements with optical fibers we demonstrate by experiments and numerical simulation that this effect can be minimized by measurement of the fluorescence at one source-detector distance, the diffusely reflected excitation light at a second distance, and with the ratio of these two signals as an indicator of fluorophore concentration. For optical properties typical of soft tissue in the red and the near infrared the optimum performance is obtained by measurement of fluorescence at 0.65 mm and reflectance at 1.35 mm. This choice reduces the rms error in fluorophore concentration to 14.6% over a wide range of absorption and scattering coefficients.
A technique for producing epitaxial films on reuseable substrates (1980)

Using a new technique, which we have named the CLEFT process (cleavage of lateral epitaxial films for transfer), we have grown single-crystal GaAs films by vapor phase epitaxy (VPE) on reusable GaAs substrates. A carbonized photoresist mask with narrow, widely spaced stripe openings is first deposited on a (110) GaAs substrate. Epitaxial growth initiated within the openings, followed by lateral growth over the mask, produces a continuous single-crystal GaAs film. The upper surface of the film is bonded to a glass substrate, and the film is then cleaved from the GaAs substrate, leaving the surface of the latter in condition for repeating the procedure. The same GaAs substrate has been used for successive growth of four GaAs films, each about 4 cm2, ranging in thickness from 5 to 10 μm. The electrical properties of a CLEFT film were found comparable to those of conventional VPE layers. The CLEFT process should also be applicable to other semiconductors.
Neuroprotective Role of Nanoparticles Against Alzheimer';s Disease (2016)

This review summarizes our recent findings on the protective roles of redox nanoparticles both in vitro and in vivo. In addition, vital role of nanoparticles employed to encapsulate natural compounds such as curcumin and metal chelators has been summarized. We warrant further studies in animal models using these protective nanoparticles.
Pomegranate juice flavonoids inhibit low-density lipoprotein oxidation and cardiovascular diseases: studies in atherosclerotic mice and in humans. (2002)

The beneficial health effects attributed to the consumption of fruit and vegetables are related, at least in part, to their antioxidant activity. Of special interest is the inverse relationship between the intake of dietary nutrients rich in polyphenols and cardiovascular diseases. This effect is attributed to polyphenols' ability to inhibit low-density lipoprotein (LDL) oxidation, macrophage foam cell formation and atherosclerosis. Pomegranate polyphenols can protect LDL against cell-mediated oxidation via two pathways, including either direct interaction of the polyphenols with the lipoprotein and/or an indirect effect through accumulation of polyphenols in arterial macrophages. Pomegranate polyphenols were shown to reduce the capacity of macrophages to oxidatively modify LDL, due to their interaction with LDL to inhibit its oxidation by scavenging reactive oxygen species and reactive nitrogen species and also due to accumulation of polyphenols in arterial macrophages; hence, the inhibition of macrophage lipid peroxidation and the formation of lipid peroxide-rich macrophages. Furthermore, pomegranate polyphenols increase serum paraoxonase activity, resulting in the hydrolysis of lipid peroxides in oxidized lipoproteins and in atherosclerotic lesions. These antioxidative and antiatherogenic effects of pomegranate polyphenols were demonstrated in vitro, as well as in vivo in humans and in atherosclerotic apolipoprotein E deficient mice. Dietary supplementation of polyphenol-rich pomegranate juice to atherosclerotic mice significantly inhibited the development of atherosclerotic lesions and this may be attributed to the protection of LDL against oxidation.
CD4+CD25+ Immunoregulatory T Cells Suppress Polyclonal T Cell Activation In Vitro by Inhibiting Interleukin 2 Production (1998)

Peripheral tolerance may be maintained by a population of regulatory/suppressor T cells that prevent the activation of autoreactive T cells recognizing tissue-specific antigens. We have previously shown that CD4+CD25+ T cells represent a unique population of suppressor T cells that can prevent both the initiation of organ-specific autoimmune disease after day 3 thymectomy and the effector function of cloned autoantigen-specific CD4+ T cells. To analyze the mechanism of action of these cells, we established an in vitro model system that mimics the function of these cells in vivo. Purified CD4+CD25+ cells failed to proliferate after stimulation with interleukin (IL)-2 alone or stimulation through the T cell receptor (TCR). When cocultured with CD4+CD25- cells, the CD4+CD25+ cells markedly suppressed proliferation by specifically inhibiting the production of IL-2. The inhibition was not cytokine mediated, was dependent on cell contact between the regulatory cells and the responders, and required activation of the suppressors via the TCR. Inhibition could be overcome by the addition to the cultures of IL-2 or anti-CD28, suggesting that the CD4+CD25+ cells may function by blocking the delivery of a costimulatory signal. Induction of CD25 expression on CD25- T cells in vitro or in vivo did not result in the generation of suppressor activity. Collectively, these data support the concept that the CD4+CD25+ T cells in normal mice may represent a distinct lineage of "professional" suppressor cells.