gebhart/patrepeval huggingface dataset:
Interferon regulatory factor 1 is a myeloid differentiation primary response gene induced by interleukin 6 and leukemia inhibitory factor: role in growth inhibition. (1991)

To better understand the immediate early genetic response of myeloid cells to terminal differentiation and growth inhibitory stimuli, we have recently isolated complementary DNA clones of myeloid differentiation primary response (MyD) genes, activated in the absence of protein synthesis in M1 myeloid precursor cells following induction for terminal differentiation and growth arrest by conditioned media of mouse lungs, a potent physiological source of hemopoietic differentiation inducers. In this study, it is shown that one particular MyD complementary DNA clone, expressed highly in normal precursor enriched bone marrow cells, encodes for interferon regulatory factor 1 (IRF-1), a positive transcription factor for expression of the beta-interferon (IFN-beta) gene. Using a clone of M1 cells inducible for terminal differentiation by both interleukin 6 (IL-6) and leukemia inhibitory factor (LIF), two multifunctional cytokines recently identified as physiological inducers of hemopoietic cell differentiation, it has been shown that IRF-1 expression is rapidly induced by IL-6 and LIF in the absence of protein synthesis and is followed by a later increase in the levels of IFN-beta mRNA, observed to be largely dependent on protein synthesis. Also, it is shown that the growth inhibition associated with IL-6 or LIF induced terminal differentiation could be partially abrogated via the use of IRF-1 antisense oligomers or IFN-beta antiserum. Taken together, these findings imply a regulatory cascade, where induction of terminal myeloid differentiation by IL-6 or LIF triggers the immediate early activation of IRF-1, leading to the later induction of IFN-beta, in turn playing an autocrine role in growth inhibition.
Clinical evaluation (phase I) of a combination of two human monoclonal antibodies to HBV: Safety and antiviral properties (2002)

Treatment of chronic hepatitis B virus (HBV) infection with interferon alfa and lamivudine is characterized by lack of viral clearance, loss of response, or emergence of drug-resistant mutants. Thus, new and multiple drug approaches are needed. We have developed two fully human monoclonal antibodies, directed against different epitopes of hepatitis B surface antigen (HBsAg) that bind to all major HBV subtypes. A phase I clinical study was conducted to evaluate the safety, tolerability, and efficacy of a mixture of these two monoclonal antibodies, HBV-AB(XTL). A total of 27 chronic HBV patients were enrolled. In part A of the study 15 patients in 5 cohorts received a single intravenous infusion of antibodies with doses ranging from 0.26 mg (260 IU) to 40 mg (40,000 IU). All patients completed 16 weeks of follow-up. In the second part of the study (part B), 12 patients in 4 cohorts received 4 weekly infusions of 10, 20, 40, or 80 mg each of HBV-AB(XTL) and were followed for 4 additional weeks. Administration of antibodies was well tolerated. Patients administered doses at an Ab:Ag molar ratio of 1:2 to 1:20 showed a rapid and significant decrease in HBsAg to undetectable levels, with a corresponding reduction of HBV-DNA levels. In part B, HBV-AB(XTL) induced a significant reduction in both HBsAg and HBV-DNA levels repeatedly after administration. In conclusion, these data suggest that HBV-AB(XTL) binds HBV particles and reduces serum viral titers and HBsAg levels. HBV-AB(XTL) could be combined with other monotherapies that are currently used to treat HBV carriers.
Supporting Email Workflow (2001)

As more people use e-mail at home or on the job, more people have come to experience the pain of e-mail that Denning first wrote about 20 years ago [3]. In this paper, we present data from a field study in our own company to add to the existing body of research about how people use e-mail. We then use these data and prior literature to outline a framework of the five main activities that we believe people use e-mail for. In particular, we focus on two activities that we believe have been under-studied: attending to the flow of messages they arrive, and doing &amp;quot;triage&amp;quot; on a body of new messages. In addition, we outline potential design directions for improving the e-mail experience, with a focus on e-mail clients that group messages and their replies together into threads. We present a prototype of such an interface as well as results from a lab study of the prototype.
Adoptive transfer of ex vivo immune-programmed NKT lymphocytes alleviates immune-mediated colitis (2003)

T lymphocyte-expressing natural killer (NK) cell markers (NKT cells) play a role in immune regulation. Our aim was to evaluate the in vivo effect of adoptive transfer of immune-programmed NKT cells. Colitis was induced in C57/B6 mice by 2,4,6-trinitrobenzenesulfonic acid. NKT, CD4, CD8 lymphocytes, and dendritic cells (DC) were prepared from spleens of naive mice, animals with colitis, and animals with colitis that were orally tolerized. Subsets of splenocytes, NKT, CD4, and CD8 and NKT+CD4, NKT+CD8, and NKT+DC lymphocytes were prepared. Assessment of the T helper cell type 1 (Th1)/Th2 cytokine secretion paradigm in vitro was performed before and following exposure to the antigen. Adoptive transfer of ex vivo immune-programmed lymphocytes from each group was performed into recipient mice, followed by colitis induction. Ex vivo exposure of NKT cells harvested from mice with colitis-to-colitis proteins [colitis-extracted proteins (CEP)] led to a Th2 cytokine shift. The interleukin (IL)-4/interferon-gamma (IFN-gamma) ratio increased for NKT harvested from colitis-harboring mice following exposure to CEP. Adoptive transfer of NKT lymphocytes harvested from colitis-harboring mice, which were ex vivo-educated, significantly alleviated experimental colitis in vivo. Intrahepatic NKT lymphocytes increased significantly in mice transplanted with NKT lymphocytes harvested from colitis-harboring donor mice, which were ex vivo-exposed to CEP, similar to mice transplanted with NKT lymphocytes harvested from tolerized donors. Exposure of NKT cells to the disease-target antigen induced a significant increase in the IL-4/IFN-gamma cytokine ratio. Adoptive transfer of a relatively small number of immune-programmed NKT cells induced a systemic Th1 to Th2-immune shift and alleviated immune-mediated colitis.
Rapamycin Potentiates Transforming Growth Factor β-Induced Growth Arrest in Nontransformed, Oncogene-Transformed, and Human Cancer Cells (2002)

Transforming growth factor beta (TGF-beta) induces cell cycle arrest of most nontransformed epithelial cell lines. In contrast, many human carcinomas are refractory to the growth-inhibitory effect of TGF-beta. TGF-beta overexpression inhibits tumorigenesis, and abolition of TGF-beta signaling accelerates tumorigenesis, suggesting that TGF-beta acts as a tumor suppressor in mouse models of cancer. A screen to identify agents that potentiate TGF-beta-induced growth arrest demonstrated that the potential anticancer agent rapamycin cooperated with TGF-beta to induce growth arrest in multiple cell lines. Rapamycin also augmented the ability of TGF-beta to inhibit the proliferation of E2F1-, c-Myc-, and (V12)H-Ras-transformed cells, even though these cells were insensitive to TGF-beta-mediated growth arrest in the absence of rapamycin. Rapamycin potentiation of TGF-beta-induced growth arrest could not be explained by increases in TGF-beta receptor levels or rapamycin-induced dissociation of FKBP12 from the TGF-beta type I receptor. Significantly, TGF-beta and rapamycin cooperated to induce growth inhibition of human carcinoma cells that are resistant to TGF-beta-induced growth arrest, and arrest correlated with a suppression of Cdk2 kinase activity. Inhibition of Cdk2 activity was associated with increased binding of p21 and p27 to Cdk2 and decreased phosphorylation of Cdk2 on Thr(160). Increased p21 and p27 binding to Cdk2 was accompanied by decreased p130, p107, and E2F4 binding to Cdk2. Together, these results indicate that rapamycin and TGF-beta cooperate to inhibit the proliferation of nontransformed cells and cancer cells by acting in concert to inhibit Cdk2 activity.
Inducible nuclear factor binding to the kappa B elements of the human immunodeficiency virus enhancer in T cells can be blocked by cyclosporin A in a signal-dependent manner (1990)

Cyclosporin A (CsA) is thought to exert its immunosuppressive effects by inhibiting the expression of a distinct set of lymphokine genes which are induced upon T-cell activation, among them the gene coding for interleukin-2. In addition, the activation of the human immunodeficiency virus (HIV) is partially suppressed. To better understand the molecular mechanisms underlying suppression by CsA, we have investigated the effects of this drug on transcription factors in T cells. Here we report that the formation of two distinct mitogen-inducible DNA-binding complexes, the kappa B complex within the HIV enhancer and the NFAT-1 complex within the interleukin-2 enhancer, is inhibited in the presence of CsA. The kappa B-binding activity with the HIV enhancer is inhibited only if it is activated via the mitogen phytohemagglutinin whereas phorbol myristate acetate-mediated activation is completely insensitive to the drug. This suggests a model in which functionally indistinguishable kappa B complexes can be activated via two separate pathways of signal transduction distinguishable by CsA.
Affective Communication through Air Jet Stimulation: Evidence from Event-Related Potentials (2018)

In this article, effectiveness of air jet stimulation in mediated emotional communication was investigated by assessing cross-modal influences of visual emotional expressions on tactile perception. Brain responses to combined visual faces and air jet stimuli were measured using event-related potentials; whereas, emotional responses were assessed using self-reported pleasantness of the tactile stimulation. ERP results reveal significant differences between the different facial expressions for the same tactile air-jet intensity in the somatosensory area. Moreover, participants’ pleasantness ratings suggest an effect of the visual stimulus on the difference tactile conditions that correspond to air jet stimulation intensities: low, medium, and high. These promising results provide evidence in the potential efficiency of this stimulation technique in activating skin receptors that play an important role in social and affective behaviors.
Optical transmission through metal films with a subwavelength hole array in the presence of a magnetic field (1999)

In a recent paper Ebbesen et al. [Nature (London) 391, 667 (1998)] reported on extraordinary optical transmission through periodic hole arrays in metallic films. They explain this by the coupling of light with surface plasmons. Continuing this idea, we have studied such systems in the presence of a static magnetic field. The problem is treated in the quasistatic limit, i.e., when the wavelength is larger than the hole sizes and the array period. We find that the frequency of the transmission peak depends strongly on both the magnitude and the direction of the applied in-plane magnetic field. The directional sensitivity results in a magneto-induced anisotropy of the optical properties of such systems, even for hole arrays with square or triangular symmetry.
Ru(phen)2dppz2+ Luminescence:  Dependence on DNA Sequences and Groove-Binding Agents (1998)

Emission of Delta-Ru(phen)(2)dppz(2+) bound to nucleic acid polymers of different sequence has been investigated by time-resolved luminescence spectroscopy and the effect of major and minor groove DNA binding agents on the luminescence profile of the complex evaluated. In the presence of a 1:1 mixture of poly d(AT) and poly d(GC), the excited-state decay of Delta-Ru(phen)(2)dppz(2+) can be described by a linear combination of the decay profiles in the presence of poly d(AT) and poly d(GC) independently. This analysis indicates that approximately 85% of the complexes are bound to poly d(AT) and that the metallointercalator preferentially occupies AT sites in mixed-sequence polymers such as calf thymus or T4 DNA. When rac-Ru(phen)(2)dppz(2+) bound to [d(5'-GAGTGCACTC-3')(2)] is titrated with the major groove intercalator Delta-alpha-[Rh[(R,R)-Me(2)trien]phi](3+), the ruthenium emission yield decreases while the absorbance of the pi-pi transition centered on the dppz ligand increases, until saturation behavior is observed at a 1:1 Rh/duplex ratio. These titrations indicate that Ru(phen)(2)dppz(2+) is displaced from the major groove by the rhodium complex. In contrast, for rac-Ru(phen)(2)dppz(2+) bound to poly d(AT), addition of the minor groove binding agent distamycin produces an increase in ruthenium emission which saturates at approximately 1 distamycin/5 bp, consistent with the double helix being able to accommodate major and minor groove binders simultaneously. Distamycin has no effect on the emission of Ru(phen)(2)dppz(2+) emission bound to poly d(GC). These photophysical studies establish a sequence preference in binding to DNA by Ru(phen)(2)dppz(2+) as well as providing support for the original assignment by NMR of ruthenium intercalation from the major groove side of the DNA helix.
Identification of a promiscuous T-cell epitope encoded by multiple members of the MAGE family. (1999)

One of the major limitations of tumor-specific vaccination is the generation of antigen-loss variants that are able to escape the immune response elicited by a monoantigenic peptide epitope. Here, we report the identification of a new HLA-B*3701-restricted epitope shared by four different members of the MAGE family. Peripheral blood lymphocytes isolated from a melanoma patient were stimulated in vitro with the autologous HLA-negative melanoma line transfected with autologous HLA B*3701 molecule. This protocol led to the induction of tumor-specific, B*3701-restricted CTLs specific for a peptide epitope encoded by codons 127-136 of the gene MAGE-1. The same epitope is also encoded by the homologous region of three other members of the MAGE family, MAGE-2, -3, and -6. Consistent with the notion that the peptide encoded by MAGE-1 codons 127-136 is, indeed, processed from the proteins encoded by all four MAGE family members, the CTLs were able to specifically recognize Cos-7 cells cotransfected with HLA-B*3701 and any of these MAGE genes. Moreover, the CTLs also recognized a MAGE-6-positive melanoma line transfected with the B*3701 molecule. These findings allow the inclusion of a new set of tumor patients into clinical cancer vaccination trials. Furthermore, they suggest that some promiscuous peptide epitopes shared by different members of the MAGE family might be less prone to escape the immune response by generation of MAGE antigen loss variants.
Epidermal Growth Factor and Fibroblast Growth Factor 2 Cause Proliferation of Ependymal Precursor Cells in the Adult Rat Spinal Cord In Vivo (2000)

We investigated the mitogenic effect of continuous intrathecal infusion of epidermal growth factor (EGF) or fibroblast growth factor 2 (FGF2) on ependymal precursor cells of the adult rat spinal cord in vivo. Either EGF, FGF2, EGF plus FGF2, or artificial cerebrospinal fluid (aCSF) was infused at a flow rate of 0.5 microl/h (15 ng/h of EGF or FGF2) for 3 or 14 days into the intrathecal space at T1 through a catheter attached to an osmotic minipump. To assess proliferation, the bromodeoxyuridine (BrdU) labeling index (LI) in the ependyma at T1 was calculated at 3 or 14 days. At 3 days there was no statistical difference in LI between these groups, but at 14 days the LI was significantly higher in the EGF plus FGF2 group (27.2% = 16.0%) than in the aCSF group (5.4% +/- 4.7%; p < 0.05). With EGF alone or FGF2 alone, the LI increases were not significantly different from the aCSF group. With EGF plus FGF2 for 14 days, some BrdU-positive cells in the ependyma also expressed nestin. These results suggest that the intrathecal infusion of EGF plus FGF2 has a mitogenic effect on precursor cells in the ependyma of the adult rat spinal cord.
Attenuation of Endothelium-Dependent Dilation of Pig Pulmonary Arterioles After Cardiopulmonary Bypass Is Prevented by Monoclonal Antibody to Complement C5a (1999)

We examined whether pulmonary endothelial dysfunction associated with cardiopulmonary bypass (CPB) may be mediated by complement C5a in pigs.Pigs were placed on normothermic CPB for 1 h with or without a previous administration of 1.6 mg/kg anti-C5a monoclonal antibody (MAb), then reperfused for 2 h. Pulmonary tissue myeloperoxidase activity was measured. Expression of nitric oxide synthase (NOS) was measured by reverse transcriptase polymerase chain reaction and Western blotting. Pulmonary arterioles approximately 100 [micro sign]m in diameter were preconstricted with the thromboxane analog U46619 1 [micro sign]M, and relaxation responses to adenosine diphosphate 10-9-10-4 M, substance P 10-12-10-6 M, and sodium nitroprusside 10-9-10-4 M were examined in vitro by videomicroscopy. Relaxation to the endothelium-dependent dilators adenosine diphosphate and substance P was attenuated after CPB; this attenuation was prevented by the previous administration of MAb. Relaxation to sodium nitroprusside was not affected by CPB. Neutrophil sequestration, as measured by MPO activity, increased after CPB, either with or without MAb. Transcription of NOS was unchanged by CPB, but translation of constitutive NOS was decreased after CPB, and this decrease was prevented by a previous administration of MAb. We conclude that pig pulmonary endothelial dysfunction associated with CPB may be mediated by C5a. The mechanism may involve changes in NOS translation. Implications: In pigs, pulmonary endothelial dysfunction may occur after cardiopulmonary bypass due to product(s) of complement activation. (Anesth Analg 1999;89:42-8)
Nucleotide chemistry. XX. Use of the azido group in the synthesis of 5'-terminal aminodeoxythymidine oligonucleotides (1975)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNucleotide chemistry. XX. Use of the azido group in the synthesis of 5'-terminal aminodeoxythymidine oligonucleotidesWilliam S. Mungall, Geoffrey L. Greene, George A. Heavner, and Robert L. LetsingerCite this: J. Org. Chem. 1975, 40, 11, 1659–1662Publication Date (Print):May 1, 1975Publication History Published online1 May 2002Published inissue 1 May 1975https://pubs.acs.org/doi/10.1021/jo00899a038https://doi.org/10.1021/jo00899a038research-articleACS PublicationsRequest reuse permissionsArticle Views853Altmetric-Citations118LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
PHYSIOLOGICAL IMPLICATIONS OF STEROL BIOSYNTHESIS IN YEAST (1995)

Fungi are among the most primitive organisms that synthesize sterols. The fungal sterol, ergosterol, is similar to animal sterol, cholesterol, but with significant structural differences. The genetics and biochemistry for most of the steps in sterol biosynthesis have been studied in the yeast, Saccharomyces cerevisiae. Yet, little is known of the precise physiological roles that sterols play in the cell. Work with strains that are auxotrophic for ergosterol has led to the prediction of at least four growth-dependent functions for sterols. Most of the antifungal compounds in medical and agricultural use affect some aspect of sterol synthesis or function. Extensive studies on the modes of action of those substances and research on the effects of altering sterol metabolism by sterol mutants are providing new insights into sterol functions in the cells. In addition, questioning why fungi require ergosterol rather than the simpler cholesterol provides heuristic impetus for further experimentation.
Irinotecan plus leucovorin-modulated 5-fluorouracil I.V. bolus every other week may be a suitable therapeutic option also for elderly patients with metastatic colorectal carcinoma (2003)

The aim of this study was to assess the safety and efficacy of biweekly irinotecan plus leucovorin-modulated 5-fluorouracil i.v. bolus in metastatic colorectal carcinoma according to the age of patients. For this purpose, we have analysed 108 patients randomly allocated to receive irinotecan 200 mg m(-2) i.v. (1-h infusion) on day 1, and L-leucovorin 250 mg m(-2) i.v. (1-h infusion) plus 5-fluorouracil 850 mg m(-2) i.v. bolus on day 2 every 2 weeks (IRIFAFU) in our previous SICOG 9801 trial. According to age, patients were retrospectively divided into three groups: younger (</=54 years, n=37), middle-aged (55-69 years, n=64), and elderly (>/=70 years, n=17). Apart from gender, pretreatment characteristics were well balanced across the three groups. WHO grade >/=3 neutropenia and diarrhoea affected on the whole 46 and 16 patients, respectively, without any significant difference according to age-grouping. Patients aged </=54 years stayed on therapy for a longer time (median 24 vs 14-15 weeks), and received more cycles (median 9 vs 7), than the older ones. Only one patient in the young group withdrew consent to therapy as opposed to four patients each in the aged and elderly one. Response rate was 38% for younger patients, 34% for aged, and 35% for the elderly ones. Median time to progression was 7.4, 8.0, and 5.3 months, and median survival time was 13.4, 15.3, and 13.9 months, respectively. We conclude that IRIFAFU given every other week may represent a suitable therapeutic option also for elderly patients with metastatic colorectal carcinoma.
Improved enzymaticin vitroreactions in the gapped duplex DNA approach to oligonucleotide-directed construction of mutations (1988)

Journal Article Improved enzymatic in vitro reactions in the gapped duplex DNA approach to oligonucleotide-directed construction of mutations Get access Wilfried Kramer, Wilfried Kramer Max-Planck-Institut für Biochemie, Abteilung ZellbiologieAm Klopferspitz 18a, D-8033 Martinsried bei München, FRG * Present address: Department of Genetics, 345 Mulford Hall, Berkeley, CA 94720, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar Andrea Ohmayer, Andrea Ohmayer Max-Planck-Institut für Biochemie, Abteilung ZellbiologieAm Klopferspitz 18a, D-8033 Martinsried bei München, FRG Search for other works by this author on: Oxford Academic PubMed Google Scholar Hans-Joachim Fritz Hans-Joachim Fritz Max-Planck-Institut für Biochemie, Abteilung ZellbiologieAm Klopferspitz 18a, D-8033 Martinsried bei München, FRG Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 16, Issue 14, 25 July 1988, Page 7207, https://doi.org/10.1093/nar/16.14.7207 Published: 25 July 1988 Article history Received: 23 March 1988 Published: 25 July 1988