gebhart/patrepeval huggingface dataset:
1,10-Phenanthroline Inhibits Glycosylphosphatidylinositol Anchoring by Preventing Phosphoethanolamine Addition to Glycosylphosphatidylinositol Anchor Precursors (2001)

The glycosylphosphatidylinositol (GPI) moiety is widely used to anchor a functionally diverse group of proteins to the plasma membrane of eukaryotes. In mammals, the predominant glycan structure of the GPI anchor consists of EthN-P-Man-Man-(EthN-P)Man-GlcN attached to an inositol phospholipid. In a smaller percentage of anchors analyzed to date, a third P-EthN group linked to the middle mannosyl residue was found. The transfer of the three P-EthN groups present in the GPI glycan core is likely to be carried out by three different GPI-phosphoethanolamine transferases (GPI-PETs). Here we report that 1,10-phenanthroline (PNT), a commonly used inhibitor of metalloproteases, is a novel inhibitor of GPI anchor synthesis. Addition of PNT to cells caused the accumulation of GPI anchor intermediates that are substrates for GPI-PETs, suggesting that these enzymes are the targets of PNT. ZnCl(2) blocked the effect of PNT, a known Zn chelator, and Zn itself was able to stimulate the GPI anchor synthesis, indicating that this cation is likely to be required for GPI-PET activity. PNT acutely inhibited the synthesis of GPI-anchored proteins, but the synthesis was rapidly restored once the inhibitor was washed out. Therefore, PNT will be a useful tool to study the metabolism and trafficking of GPI anchor intermediates by providing a switch to turn the pathway on and off.
Peripheral burst of tumor-specific cytotoxic T lymphocytes and infiltration of metastatic lesions by memory CD8+ T cells in melanoma patients receiving interleukin 12. (2000)

Systemic effects on T-cell-mediated antitumor immunity, on expression of T-cell adhesion/homing receptors, and on the promotion of T-cell infiltration of neoplastic tissue may represent key steps for the efficacy of immunological therapies of cancer. In this study, we investigated whether these processes can be promoted by s.c. administration of low-dose (0.5 microg/kg) recombinant human interleukin-12 (rHuIL-12) to metastatic melanoma patients. A striking burst of HLA-restricted CTL precursors (CTLp) directed to autologous tumor was documented in peripheral blood by a high-efficiency limiting dilution analysis technique within a few days after rHuIL-12 injection. A similar burst in peripheral CTLp frequency was observed even when looking at response to a single tumor-derived peptide, as documented by an increase in Melan-A/Mart-1(27-35)-specific CTLp in two HLA-A*0201+ patients by limiting dilution analysis and by staining peripheral blood lymphocytes (PBLs) with HLA-A*0201-melanoma antigen-A/melanoma antigen recognized by T cells (Melan-A/Mart)-1 tetrameric complexes. The CTLp burst was associated, in PBLs, with enhanced expression of T-cell adhesion/homing receptors CD11a/CD18, CD49d, CD44, and with increased proportion of cutaneous lymphocyte antigen (CLA)-positive T cells. This was matched by a marked increase, in serum, of soluble forms of the endothelial cell adhesion molecules E-selectin, vascular cell adhesion molecules (VCAM)-1 and intercellular adhesion molecules (ICAM)-1. Infiltration of neoplastic tissue by CDS+ T cells with a memory and cytolytic phenotype was found by immunohistochemistry in eight of eight posttreatment metastatic lesions but not in five of five pretreatment metastatic lesions from three patients. Increased tumor necrosis and/or fibrosis were also found in several posttherapy lesions of two of three patients in comparison with pretherapy metastases. These results provide the first evidence that rHuIL-12 can boost the frequency of circulating antitumor CTLp in tumor patients, enhances expression of ligand receptor pairs contributing to the lymphocyte function-associated antigen-1/ICAM-1, very late antigen-4/VCAM-1, and CLA/E-selectin adhesion pathways, and promotes infiltration of neoplastic lesions by CD8+ memory T cells in a clinical setting.
Reconstitution of power transformer's residual flux with CVT's measurement during its de-energization (2010)

Power transformer's de-energization leaves the transformer core in a state of magnetization, called residual flux. The presence of this residual flux may induce inrush current which can cause damages on the equipments and system disturbances. In recent years, studies on power transformer's controlled switching have been carried out to reduce this effect. The purpose of this paper is to emphasize the calculation of residual flux with CVT (Capacitive Voltage Transformer) measurement, using EMTP, during the de-energization of no loaded power transformer. Measuring and integrating directly the CVT's voltage output may provide a false flux value.
Structure of the Tetramerization Domain of Measles Virus Phosphoprotein (2013)

The atomic structure of the stable tetramerization domain of the measles virus phosphoprotein shows a tight four-stranded coiled coil. Although at first sight similar to the tetramerization domain of the Sendai virus phosphoprotein, which has a hydrophilic interface, the measles virus domain has kinked helices that have a strongly hydrophobic interface and it lacks the additional N-terminal three helical bundles linking the long helices.
REPERFUSION INJURY AFTER LIVER PRESERVATION FOR TRANSPLANTATION (1997)

Preservation injury remains an obstacle to greater utilization of liver transplantation therapy. Livers can be preserved a maximum of 24 h in University of Wisconsin solution. After longer times, reperfusion precipitates endothelial cell killing and activation of Kupffer cells (liver macrophages). Together, Kupffer cell activation and endothelial cell killing cause microcirculatory disturbances, leukocyte and platelet adhesion, and a systemic inflammatory response after graft implantation. Down-regulation of Kupffer cells with calcium blockers or pentoxifylline improves graft survival, whereas priming with lipopolysaccharide or alcohol worsens survival. Flushing grafts after storage with Carolina rinse solution containing antioxidants, adenosine, calcium blocker, energy substrates, and glycine at pH 6.5 decreases endothelial cell killing, reduces Kupffer cell activation, and improves graft survival. Understanding of the roles of different cells in storage/reperfusion injury forms the basis for strategies to prolong organ storage, improve graft function, and reduce failure of fatty grafts from alcoholic donors.
Identification of RIP metallopeptidase RseP at Target Receptor for the Leaderless Bacteriocin Ej97, and the Presumptive Involvement of the Ecs ABC transporter in medium Resistance (2014)

In a recent study on the leaderless and Lactococcus-specific bacteriocin LsbB, the results implied that LsbB utilizes a zinc-dependent metallopeptidase YvjB from the M50 superfamily as receptor for target recognition and subsequent killing of other lactococcal bacteria. \nBased on this evidence, another study was initiated which elucidated a conserved motif near the C-terminal of LsbB, proving to be crucial for its activity. The work also revealed that several other leaderless bacteriocins, including Ej97, K1 and EntQ, all share this conserved motif with LsbB, suggesting that they target the same receptor. Despite this similarity, these bacteriocins display a significantly broader inhibition spectrum than LsbB.\nFor this thesis, it was initially affirmed that Ej97 and K1 exhibit a wide inhibition spectrum relative to LsbB, followed by generation of approximately 80 spontaneous mutants resistant to Ej97, K1 or EntQ. These mutants belonged to pediococcal, enterococcal and lactococcal strains. The homologous genes of the LsbB receptor (rseP) were identified in order to be sequenced and analyzed in all the collected mutants. Severe mutations inflicting premature termination of RseP were in many cases revealed. This suggests that these RseP proteins which are closely related to the LsbB receptor also serve as docking molecules in other bacterial species for LsbB-like bacteriocins. They are however unable to function as receptor for LsbB.\nStill, a large proportion of the mutants did not hold mutations within the putative RseP receptor. Phenotypic microtiter assays were performed to investigate Ej97 resistance levels. It became evident that the degree of resistance generally diverged into two levels – one very high indicating absolute resistance, and a lower level but still significantly higher than in the wild type. Interestingly, the mutants with the highest resistance level coincided with the presence of dysfunctional RseP.\nConcluding the work for this thesis, whole genome sequencing of 40 mutants was carried out to identify possible reasons for the resistance observed in mutants with intact RseP and lower level of resistance. Variant detection provided clear indications of components from the Ecs ABC-transporter being involved. After this revelation it was noticed that previous studies on non-bacteriocin systems have indicated a connection between EcsAB and RseP in other species. Future work will examine how these genes are interrelated in conferring bacteriocin resistance.
Fibronectin appears at the site of corneal stromal wound in rabbits (1981)

Fibronectin (FN) is present both in plasma and in extracellular matrix, and is postulated to be involved in wound healing. The appearance of FN was investigated in the wounded rabbit cornea after corneal stroma was injured with a sharp knife or after lamellar keratoplasty was performed. An indirect immunofluorescence technique was employed to detect the presence of FN. Normal, unwounded rabbit cornea showed an intensive fluorescence at Descemet's membrane. Strong specific fluorescence was observed at the edge of a stromal wound and beneath the sliding epithelial cells after non-perforating incisions. These could be detected as early as 3 hours after injury. The fluorescence became the strongest at 6 hours, and and then gradually decreased in its intensity, disappearing by about 7 days when epithelial cells entirely filled the stromal wound. In case of lamellar keratoplasty, FN was detected at the interface of the graft and the recipient cornea. These results suggest that FN plays an important role in the stromal wound healing.
CD40 expression by human monocytes: regulation by cytokines and activation of monocytes by the ligand for CD40. (1993)

CD40 is a member of the tumor necrosis factor (TNF) receptor family of cell surface proteins and was originally described as a B cell restricted antigen. Treatment of primary human monocytes with granulocyte/macrophage colony-stimulating factor (GM-CSF), interleukin 3 (IL-3), or interferon gamma (IFN-gamma) resulted in the induction of CD40 mRNA and enhancement of cell surface protein expression. CD40 was found to mediate monocyte adhesion to cells expressing recombinant CD40 ligand. CD40 ligand-transfected cells provided a potent costimulus for monocyte TNF-alpha and IL-6 production in the presence of GM-CSF, IL-3, or IFN-gamma, and enhanced IL-8 production stimulated by GM-CSF or IL-3. In addition, CD40 ligand-transfected cells acting in the absence of a costimulus induced monocytes to become tumoricidal against a human melanoma cell target. Collectively, these data indicate that CD40 ligand is pleiotropic with potent biological activity on monocytes.
Mutation analysis of the putative tumor suppressor gene PTEN/MMAC1 in primary breast carcinomas. (1997)

A novel gene was identified recently at chromosome 10q23, named PTEN or MMAC1, and based on several criteria it was designated as a potential human tumor suppressor gene. Loss of heterozygosity affecting this region of 10q is observed in several cancer types, especially glioblastoma, and inactivating mutations of the PTEN/MMAC1 gene are found in some of these cancers as well as cell lines and xenografts. Breast cancer is among the tumor types in which mutations are documented, and germline mutations of the gene appear to be responsible for the rare autosomal dominant familial cancer syndrome known as Cowden disease, which includes breast cancer among its clinical features. To further determine the role that PTEN/MMAC1 mutations may play in breast tumorigenesis, the entire coding region was screened for mutations in 54 unselected primary breast cancers. Two mutations were identified, a somatic 2-bp deletion in an apparently sporadic breast cancer, and a germ-line 4-bp deletion in a breast cancer patient with a clinical history consistent with Cowden disease. These data indicate that somatic mutations of PTEN/ MMAC1 occur in only a small fraction of primary breast cancers and confirm the role of this gene in the etiology of Cowden disease. Evidence is also presented suggesting that numerous polymorphisms and missense variants exist in the PTEN/MMAC1 transcript.
Biosynthetic Polydeoxynucleotides as Direct Templates for Polypeptide Synthesis (1968)

Abstract Homopolydeoxynucleotides containing pyrimidine bases, and random copolydeoxynucleotides of purines and pyrimidines or pyrimidines only, have been found to stimulate directly the incorporation of amino acids into acid-insoluble material in a neomycin-modified, cell-free system from Escherichia coli. In contrast, homopolydeoxynucleotides and random copolydeoxynucleotides containing only purine bases show no messenger activity in this system. Purine-containing triplets are read when the copolymer has a purine to pyrimidine ratio of 1:1, but not when this ratio is 2:1. The extent of amino acid incorporation with the active polydeoxynucleotide messengers is similar to that obtained with the ribose analogues, and the amino acids incorporated under the direction of the polyribo- and polydeoxyribonucleotide analogues are identical. No misreading of polydeoxynucleotide templates has been observed.
Akt/Protein Kinase B Isoforms Are Differentially Regulated by Epidermal Growth Factor Stimulation (2000)

Overexpression of epidermal growth factor receptor (EGFR) in certain cancers is well established. There is growing evidence that epidermal growth factor (EGF) activates Akt/protein kinase B (PKB) in a phosphoinositide 3-OH kinase (PI3K)-dependent manner, but it is not yet clear which Akt isoforms are involved in this signal transduction pathway. We investigated the functional regulation of three Akt isoforms, Akt1/PKBalpha, Akt2/PKBbeta, and Akt3/PKBgamma, in esophageal cancer cells where EGFR is frequently overexpressed. Upon EGF simulation, phosphorylation of Akt1 at the Ser-473 residue was remarkably induced. This result was corroborated by in vitro Akt kinase assays using glycogen synthase kinase 3beta as the substrate. PI3K inhibitors, wortmannin or LY294002, significantly blocked the Akt kinase activity induced by EGF. Akt2 activity was evaluated by electrophoretic mobility shift assays. Robust activation of Akt2 by EGF was observed in some cell lines in a PI3K-dependent manner. EGF-induced Akt3 activation was demonstrated by Ser-472 phosphorylation of Akt3 but in a restrictive fashion. In aggregate, EGF-mediated activation of Akt isoforms is overlapping and distinctive. The mechanism by which EGFR recruits the PI3K/Akt pathway was in part differentially regulated at the level of Ras but independent of heterodimerization of EGFR with either ErbB2 or ErbB3 based upon functional dissection of pathways in esophageal cancer cell lines.
A 5-GHz CMOS transceiver for IEEE 802.11a wireless LAN systems (2002)

A 5-GHz transceiver comprising the RF and analog circuits of an IEEE 802.11a-compliant WLAN has been integrated in a 0.25-/spl mu/m CMOS technology. The IC has 22-dBm maximum transmitted power, 8-dB overall receive-chain noise figure and -112-dBc/Hz synthesizer phase noise at 1-MHz frequency offset.
Antiparasitic and antiproliferative effects of indoleamine 2,3-dioxygenase enzyme expression in human fibroblasts (1994)

Studies were carried out to evaluate the proposed role of indoleamine 2,3-dioxygenase (INDO) induction in the antimicrobial and antiproliferative effects of gamma interferon (IFN-gamma) in human fibroblasts. The INDO cDNA coding region was cloned in the pMEP4 expression vector, containing the metallothionein (MTII) promoter in the sense (+ve) or the antisense (-ve) orientation. Human fibroblasts (GM637) stably transfected with the sense construct expressed INDO activity after treatment with CdCl2 or ZnSO4, but cells transfected with the antisense construct did not. The growth of Chlamydia psittaci was strongly inhibited in INDO +ve cells but not in INDO -ve cells after treatment with Cd2+ or Zn2+. The inhibition correlated with the level of INDO activity induced and could be reversed by the addition of excess tryptophan to the medium. The growth of Toxoplasma gondii was also strongly inhibited in INDO +ve cells but not in INDO -ve cells after treatment with Cd2+. Expression of Cd(2+)-induced INDO activity also inhibited thymidine incorporation and led to cytotoxicity in INDO +ve cells but not in INDO -ve cells. Thus, the induction of INDO activity by IFN-gamma may be an important factor in the antimicrobial and antiproliferative effects of IFN-gamma in human fibroblasts.
p300/CBP proteins: HATs for transcriptional bridges and scaffolds (2001)

p300/CBP transcriptional co-activator proteins play a central role in co-ordinating and integrating multiple signal-dependent events with the transcription apparatus, allowing the appropriate level of gene activity to occur in response to diverse physiological cues that influence, for example, proliferation, differentiation and apoptosis. p300/CBP activity can be under aberrant control in human disease, particularly in cancer, which may inactivate a p300/CBP tumour-suppressor-like activity. The transcription regulating-properties of p300 and CBP appear to be exerted through multiple mechanisms. They act as protein bridges, thereby connecting different sequence-specific transcription factors to the transcription apparatus. Providing a protein scaffold upon which to build a multicomponent transcriptional regulatory complex is likely to be an important feature of p300/CBP control. Another key property is the presence of histone acetyltransferase (HAT) activity, which endows p300/CBP with the capacity to influence chromatin activity by modulating nucleosomal histones. Other proteins, including the p53 tumour suppressor, are targets for acetylation by p300/CBP. With the current intense level of research activity, p300/CBP will continue to be in the limelight and, we can be confident, yield new and important information on fundamental processes involved in transcriptional control.
UV generation by frequency quadrupling of a Yb-doped fiber amplifier (1998)

The pulsed output of a Yb-doped fiber amplifier was frequency doubled and quadrupled to generate visible and UV radiation. When pumped with 150-200 mW at 980 nm and seeded at 1064 nm, the amplifier produced an average power of 90 mW at 1064 nm, 45 mW at 532 nm, and 1.4 mW at 266 nm. These results indicate that frequency-converted fiber lasers and amplifiers will be able to replace conventional tunable UV sources (e,g,, frequency-converted dye lasers) in a number of applications.
The immunopathology of experimental allergic encephalomyelitis. I. Quantitative analysis of inflammatory cells in situ. (1984)

Acute experimental allergic encephalomyelitis (EAE) is a T cell-mediated, neurologic disease that is under immunogenetic control. We systematically analyzed the quantity and distribution of T cells, B cells, and macrophages in the central nervous system (CNS) of susceptible and resistant guinea (GP) with a panel of seven monoclonal antibodies by using the avidin-biotin complex (ABC) immunoperoxidase technique and alpha-naphthyl-butyrate esterase (ANBE) staining. Adult EAE-susceptible strain 13 GP immunized with isogeneic spinal cord homogenate (SC) or with myelin basic protein (MBP) developed clinical signs (paralysis, weight loss, etc.) in 2 to 3 wk. T cells were present in all CNS inflammatory foci and comprised 44% of the perivascular mononuclear cells. T cells diffusely infiltrated the neuropil away from inflammatory cell aggregates. These T cells were judged to be extravascular by the lack of an associated identifiable vessel in counter-stained sections, and by their persistence following exhaustive perfusion of the brains. In routine sections, mononuclear cells could be detected only in perivascular aggregates. IgM+ B cells comprised 9% of the perivascular infiltrates and did not diffusely infiltrate the parenchyma. ANBE+ macrophages comprised the remaining 47% of the identified perivascular cells. SC- and MBP-immunized GP showed equivalent numbers of inflammatory foci, T cells, and macrophages, but SC-immunized GP had more IgM+ cells in the meninges and choroid plexus (p less than 0.001, p less than 0.02, respectively). Virtually all cells in perivascular locations were Ia+. Ia+ mononuclear cells were also present in the neuropil. EAE-resistant strain 2 GP immunized with SC developed no clinical signs. These GP had fewer perivascular foci than strain 13 GP but, when present, the cellular composition, including the density of diffuse parenchymal T cell infiltrates, was indistinguishable. Significantly fewer parenchymal mononuclear cells in the strain 2 GP, however, displayed Ia, both in perivascular and diffuse infiltrates (p less than 0.001). We conclude that T cell migration into the CNS parenchyma is a characteristic feature of acute EAE in the GP, but that T cells can occur in this pattern without clinical signs of disease. The two features that distinguish susceptible and resistant strains were the frequency of perivascular infiltrates and the expression of Ia on parenchymal mononuclear cells, which probably reflects their enhanced immunologic activation in situ.
Epilepsy (partial). (2011)

In this systematic review we present information relating to the effectiveness and safety of the following interventions: antiepileptic drugs after a single seizure; monotherapy for partial epilepsy using carbamazepine, gabapentin, lamotrigine, levetiracetam, phenobarbital, phenytoin, sodium valproate, or topiramate; addition of second-line drugs for drug-resistant partial epilepsy (allopurinol, eslicarbazepine, gabapentin, lacosamide, lamotrigine, levetiracetam, losigamone, oxcarbazepine, retigabine, tiagabine, topiramate, vigabatrin, or zonisamide); antiepileptic drug withdrawal for people with partial or generalised epilepsy who are in remission; behavioural and psychological treatments for partial or generalised epilepsy (biofeedback, cognitive behavioural therapy (CBT), educational programmes, family counselling, relaxation therapy (alone or plus behavioural modification therapy, yoga); and surgery for drug-resistant temporal lobe epilepsy ( lesionectomy, temporal lobectomy, vagus nerve stimulation as adjunctive therapy).
CD4+FoxP3+ regulatory T cells gradually accumulate in gliomas during tumor growth and efficiently suppress antiglioma immune responses in vivo (2007)

The suppressive activity of regulatory T cells (Treg) has been implicated as an important factor limiting immune mediated destruction of tumor cells. However, not much is known about the presence and function of Treg within tumors. Here we show in a syngeneic murine glioma model a time-dependent accumulation of CD4+FoxP3+ Treg in brain tumors. Further analysis revealed a time-dependent upregulation of CD25, CTLA-4, GITR and CXCR4 on intratumoral CD4+FoxP3+ Treg during tumor growth. Moreover, freshly isolated intratumoral Treg were highly suppressive when tested directly ex vivo. Treatment with anti-CD25 monoclonal antibodies (mAbs) significantly reduced the number of these highly suppressive CD4+FoxP3+ cells within the growing tumor and provoked a CD4 and CD8 T cell dependent destruction of the glioma cells. Combining Treg depletion with administration of blocking CTLA-4 mAbs further boosted glioma-specific CD4+ and CD8+ effector T cells as well as antiglioma IgG2a antibody titers resulting in complete tumor eradication without any signs of autoimmunity. These data illustrate that intratumoral accumulation and activation of CD4+FoxP3+ Treg act as a dominant immune escape mechanism for gliomas and underline the importance of controlling tumor-infiltrating Treg in glioma immunotherapy.