gebhart/patrepeval huggingface dataset:
EBV replicon vector system enhances transgene expressionin vivo: applications to cancer gene therapy (2001)

The EBV replicon vector appears useful for cancer gene therapy. Analysis of the transgene in tumors suggests that the EBV replicon system may be responsible for efficient transcription but not retention of the transgene.
Precipitating Factors of Headache. A Prospective Study in a National Control‐Matched Survey in Migraineurs and Nonmigraineurs (1999)

Prospective studies of precipitating factors in migraine are rare. Mig Access is a national control-matched survey conducted to evaluate the access of migraineurs to health care in France. This study allowed us to screen prospectively some precipitating factors of headache in migraineurs and in nonmigraineurs. Three hundred eighty-five migraineurs (group 1) and 313 nonmigraineurs (group 2) kept a diary for a 3-month period (a total of 35,805 day in group 1 and 29,109 days in group 2). Precipitating factors were reported for each headache period. Headache intensity was self-assessed during each headache period using a visual analog scale of 0 to 100. Headache was reported on 4274 days (12%) in group 1 and on 602 days (2%) in group 2. Headache intensity was greater in group 1 (39 +/- 20 versus 32 +/- 19, P < .05). The most frequent precipitating factors (reported at least once by more than 10% of subjects [range 18% to 80%] in both groups) were fatigue and/or sleep, stress, food and/or drinks, menstruation, heat/cold/weather, and infections in both groups. All these factors except infections were reported to cause headache more frequently in migraineurs than in nonmigraineurs. Mean intensity of headache related to fatigue and/or sleep, stress, food and/or drinks, hot/cold weather, and menstruation varied from 37 to 43 in migraineurs and from 29 to 35 in nonmigraineurs. Headache with the highest mean intensity was due to infections in the two groups (47 +/- 20 in group 1, 45 +/- 23 in group 2). Our results support that endogenous factors are the most frequent triggers of headache in migraineurs. The most frequent precipitating factors of headache appear identical in migraineurs and in nonmigraineurs. Our results suggest that similar triggers could precipitate headache of different type in these two populations.
PS1-11: Specimen Collection Within the Cancer Research Network: A Critical Appraisal (2010)

Methods: As part of a CRN pilot project, focus groups were conducted with Kaiser Permanente Colorado members in 2009 to determine individual perspectives and public opinion about the importance and value of family history, DTC genetic testing, and DTC advertising and other media representations of DTC genetic tests. Focus groups were conducted by concordant population groups: General population KPCO members, members who self-identify as African American, members who self-identify as Hispanic/Latino, women with a recent referral for BRCA1/2 testing, KPCO primary care providers, and KPCO specialty care providers. Results: Results on focus group demographics, media use, trust in information, and most trusted information sources are presented. Additional results include coding focus group transcripts for value and polarity (positive/negative) of opinion on family history and genetic testing. Additional coding for how different population groups frame opinion on the issue (progressive, deterministic, caution) include results on whether frames are similar or different across population groups. Finally, information on the impact of media presentations on member opinion and decision-making were assessed. Conclusions: Individual opinions about the value of family history and genetic testing for disease risk vary greatly. Salience of themes related to genetic testing and DTC genetic tests specifically may vary across concordant population groups.
Inhibition of Arg-Gly-Asp (RGD)-mediated cell adhesion to osteopontin by a monoclonal antibody against osteopontin. (1994)

Osteopontin (OPN), a secreted phosphoprotein, has been implicated in various biological phenomena (e.g. bone development, sepsis, tumor progression, and metastasis). Its role in any context is poorly understood. OPN contains a conserved Gly-Arg-Gly-Asp-Ser (GRGDS) sequence, and binds to cells via integrin-mediated mechanisms. Using recombinant human osteopontin-glutathione S-transferase fusion protein and our improved hybridoma fusion partner (Sp2/mIL6), we raised murine monoclonal antibodies against osteopontin. We characterized two antibodies that recognize not only recombinant but also native human osteopontin. These antibodies do not cross-react with mouse osteopontin (recombinant protein or that secreted by ras-transformed NIH 3T3 cells), or bovine bone osteopontin, suggesting that they recognize epitopes unique to human OPN. One antibody specifically inhibited adhesion of MDA-MB-435 human breast cancer cells and ras-transformed NIH 3T3 cells to human osteopontin. This antibody failed to recognize osteopontin cleaved by thrombin, which cleaves adjacent to the cell binding domain. We previously showed that thrombin cleavage reduces osteopontin cell binding activity. Thus we postulate that this monoclonal antibody recognizes and interferes with the function of the RGD/thrombin cleavage region of human OPN.
Microencapsulation of recombinant cells: a new delivery system for gene therapy (1993)

The therapeutic potential of somatic gene therapy has been extensively investigated in recent years, yet its slow progression into the clinical setting can be attributed to problems associated with the inability to achieve efficient gene transfers, to obtain sustained level of expression of the transfected gene, and the necessity to avoid immunorejection after transplantation. Here we report on an alternate strategy in gene therapy that overcomes all three problems by immunoisolating genetically modified cells in a biocompatible membrane, thereby introducing a system that can provide sustained delivery of the desired gene product. As a model, mouse fibroblasts transformed with the human growth hormone gene (Ltk‐GH) were encapsulated with an alginate‐poly‐L‐lysinealginate membrane. Long‐term in vitro studies showed that the encapsulation of the cells was physiologically compatible with growth and survival of the cells. Furthermore, there was a unique pattern of secretion of the human protein by the encapsulated cells: there was a phase of steady increase in the secretion of the human growth hormone by each cell, followed by a plateau phase. The most convincing evidence of the feasibility of this strategy was provided by the in vivo study: Balb‐c mice transplanted with encapsulated Ltk‐GH cells had detectable serum levels of human growth hormone (hGH) for the duration of the study (115 days). Moreover, encapsulated cells recovered from a recipient 1 year after the transplantation continued to secrete high levels of hGH in culture.—Tai, I. T., Sun, A. M. Microencapsulation of recombinant cells: a new delivery system for gene therapy. FASEB J. 7: 1061‐1069; 1993.
Frequent deletions and mutations of the beta-catenin gene are associated with overexpression of cyclin D1 and fibronectin and poorly differentiated histology in childhood hepatoblastoma. (2001)

Hepatoblastoma (HBL) is the most common malignant liver tumor in young children. Recent reports have shown that the beta-catenin gene was frequently mutated or deleted in HBLS: To elucidate the role of beta-catenin abnormalities in HBLs, we searched for mutations of beta-catenin and APC as well as expression of the target genes, cyclin D1, c-myc, and fibronectin, in 68 primary HBLS: The mutation analysis revealed that 44 (65%) tumors carried missense mutations or deletions of beta-catenin, all of which were somatic and targeted to the exon 3 encoding the amino acid residues involved in its degradation. However, no loss of function mutation of the APC gene was detected by the yeast functional assay. Of interest, beta-catenin mutation was significantly correlated with overexpression of the target genes, cyclin D1 and fibronectin, but not with that of c-myc in HBLs as measured by quantitative real-time reverse transcription-PCR. The immunohistochemical studies in 15 HBLs demonstrated that the nuclear/cytoplasmic accumulation of beta-catenin was positive in 13 tumors, 9 of which had the deletion or mutation of the gene. The significant correlation between the beta-catenin gene abnormality and the positive staining of cyclin D1 was also confirmed. Furthermore, the nuclear accumulation of beta-catenin was strongly associated with the poorly differentiated tumor cell components as well as with the positive staining of cyclin D1 within the tumor. Thus, our present results suggested that the gain of function mutation of beta-catenin played a crucial role in the malignant progression of HBL in vivo.
Loss of CD20 expression in relapsed lymphomas after rituximab therapy (2003)

The response rate at relapse to rituximab in prior responders B-cell non-Hodgkin's lymphoma (NHL) patients is below 50%. Loss of CD20 expression after rituximab therapy may explain this secondary resistance. However, the frequency of CD20 negative relapses cannot be assessed since most patients that relapsed after rituximab therapy have not been re-biopsied. Here, we present two patients with CD20 positive low grade B-cell NHL that lost the cell surface and cytoplasmic expression at relapse after rituximab therapy. Our findings suggest that confirmation of CD20 expression on the malignant B cells is required whenever rituximab therapy is considered.
Regulation of B-Cell Activation by Complement Receptors and Fc Receptors (2005)

In addition to producing autoantibodies, B cells act as critical antigen presenting cells in autoimmune disease. Tight regulation of B-cell activity is required to ensure humoral immunity against pathogens, on the one hand, and to avoid detrimental autoreactivity, on the other. Activation of B cells is mediated through cross-binding of the B-cell antigen receptor (BCR) and is greatly enhanced by co-engagement of complement receptor type 2 (CD21, CR2) and its signaling element, CD19. Feedback inhibition of B-cell activity is mediated by the binding of IgG antibodies to Fc?RIIB (CD32). The extent to which the individual receptors are engaged depends on the context in which antigen is encountered, be it as antigen alone, as complement-opsonized antigen, or as antigen complexed with IgM or IgG antibodies. Both over-expression of CD19 and deficiency of elements centrally involved in negative signaling, e.g. Fc?RIIB and Lyn, lead to autoimmune disease in mice. Upon formation of complementactivating ICs with natural or disease-associated antibodies, self-antigen binds to B cells via CD21 and CD35 (CR1) and induces proliferation of self-reactive B cells and CD4+ T cells. Here, we review the role of BCR, CD21/ CD19 and Fc?RIIB in regulating B-cell activity in immune and autoimmune responses.
CRISPR ‐Cas Systems for the Study of Immune Function (2016)

Abstract The ability to manipulate genomes has provided a wealth of knowledge about the structure and function of the immune system. For decades, genome manipulation has relied on transgenesis and homologous recombination to introduce or excise genetic material. The recent development of targetable DNA (deoxyribonucleic acid)‐modifying enzymes that allow the precise modification of any given locus within genomes of all species has transformed the way genome editing and engineering are performed. These targetable enzymes, in particular the clustered regularly interspaced palindromic repeats–CRISPR‐associated (CRISPR‐Cas) systems, have made it more accessible to generate genetically modified organisms in laboratories. In addition to genome editing and engineering, CRISPR‐Cas systems have been adapted to regulate gene expression, visualise genomic loci as well as RNA (ribonucleic acid) transcripts and modify DNA and DNA‐interacting protein markings. Key Concepts Forward and reverse genetics have played a key role in identifying genes involved in the development and function of the immune system. CRISPR‐Cas/Cpf1 systems for genome editing use short RNA molecules to direct an endonuclease (Cas9 or Cpf1) to virtually any location within the genome and introduce DNA double‐strand breaks (DSBs). The newly introduced DNA DSBs trigger DNA repair pathways and facilitate the introduction of random or engineered mutations. Four pathways are involved in the repair of DNA DSBs; of them, the nonhomologous end joining (NHEJ) and homologous recombination (HR) are the most prominent. Repair via the NHEJ pathway is error prone and can result in the random insertion or deletion of genetic material (indels). Repair via the HR pathway is error free and uses the sister chromatid as a template. The HR pathway can be taken over by providing a repair template [homology‐directed repair (HDR) template] containing engineered mutations. These HDR templates can be used to introduce specific genetic modifications or repair disease‐causing mutations. In addition, CRISPR‐Cas9 systems have been adapted to stimulate or repress gene expression, visualise chromosomal regions, modify DNA and DNA‐binding protein marking and track RNA molecules. CRISPR‐Cas systems have been used to identify genes involved in the development and function of the immune system, ranging from innate to adaptive immunity as well as to model human diseases.
Complete inhibition of rhabdomyosarcoma xenograft growth and neovascularization requires blockade of both tumor and host vascular endothelial growth factor. (2000)

Growth of the human rhabdomyosarcoma A673 cell line in nude mice is substantially reduced but not completely suppressed after systemic administration of the antihuman vascular endothelial growth factor (VEGF) monoclonal antibody (Mab) A.4.6.1. Potentially, such escape might be attributable to incomplete local penetration of the antibody because of a diffusion barrier associated with tumor growth. Alternatively, it might reflect a compensatory up-regulation of murine VEGF, produced by the stroma of the host, or of other angiogenic factor genes. To test these potential mechanisms, systemic administration of Mab A.4.6.1, was performed in conjunction with intratumoral administration of an irrelevant antibody, an antihuman VEGF Fab or mFlt(1-3)-IgG that neutralizes both human and murine VEGF. Tumor growth in the systemic-plus-intratumoral anti-VEGF group was not different from that in the systemic anti-VEGF-plus-intratumoral-control antibody group, arguing against the possibility that bioavailability is the factor that limits the antitumor efficacy of Mab A.4.6.1. However, intratumoral mFlt(l-3)-IgG administration dramatically enhanced the activity of systemic anti-VEGF Mab and resulted in complete suppression of tumor growth, which indicated that host VEGF significantly contributes to tumor growth. Systemic administration of mFlt(1-3)-IgG alone replicated these findings. Histological analysis of residual tumor tissues revealed an almost complete absence of host-derived vasculature and massive tumor-cell necrosis in the mFlt(1-3)-IgG groups. Such extensive necrotic areas were not present in the other groups. Real-time reverse transcription-PCR analysis of total RNA derived from tumor tissues indicated strong up-regulation of both human and murine VEGF as well as other genes regulated by hypoxia. Our findings emphasize the need to completely block VEGF for maximal inhibition of tumor growth.
The structure and functions of the adenovirus early region 1 proteins (1987)

Research Article| January 01 1987 The structure and functions of the adenovirus early region 1 proteins R J A Grand R J A Grand Search for other works by this author on: This Site PubMed Google Scholar Biochem J (1987) 241 (1): 25–38. https://doi.org/10.1042/bj2410025 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share MailTo Twitter LinkedIn Cite Icon Cite Get Permissions Citation R J A Grand; The structure and functions of the adenovirus early region 1 proteins. Biochem J 1 January 1987; 241 (1): 25–38. doi: https://doi.org/10.1042/bj2410025 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Journal Search Advanced Search This content is only available as a PDF. © 1987 London: The Biochemical Society1987 Article PDF first page preview Close Modal You do not currently have access to this content.
Polymer electrophosphorescence devices with high power conversion efficiencies (2004)

We demonstrate efficient single-layer polymer phosphorescent light-emitting devices based on a green-emitting iridium complex and a polymer host co-doped with electron-transporting and hole-transporting molecules. These devices can be operated at relatively low voltages, resulting in a power conversion efficiency of up to 24 lm/W at luminous efficiencies exceeding 30 cd/A. The overall performances of these devices suggest that efficient electrophosphorescent devices with acceptable operating voltages can be achieved in very simple device structures fabricated by spin coating.
Milking microalga Dunaliella salina for β‐carotene production in two‐phase bioreactors (2004)

A new method was developed for production of beta-carotene from Dunaliella salina. Cells were grown in low light intensity and then transferred to a production bioreactor illuminated at a higher light intensity. It was a two-phase bioreactor consisting of an aqueous and a biocompatible organic phase. Mixing of the cells and extraction were performed by recirculation of the organic phase. Two experiments were performed. In the first experiment, bioreactors were operated at two different solvent recirculation rates of 150 and 200 mL min(-1). The beta-carotene extraction rate increased significantly at the higher recirculation rate, without exerting any influence on cell number and viability. A second experiment was carried out at a recirculation rate (200 mL min(-1)) appropriate for the study of long-term production of beta-carotene. The results show that D. salina at high light intensity remained viable for a long period (>47 days) in the presence of a biocompatible organic phase; however, cell growth was very slow. beta-Carotene could be continuously extracted to the organic phase; the cells continued to produce beta-carotene and the extracted molecules were continuously reproduced. As a result, beta-carotene was continuously removed ("milked") from the cells. beta-Carotene extraction efficiency in this system was >55%, and productivity was 2.45 mg m(-2) day(-1), much higher than that of commercial plants.
The MyLifeBits lifetime store (2003)

Storage trends have brought us to the point where it is affordable to keep a complete digital record of one's life, and capture methods are multiplying. To experiment with a lifetime store, we are digitizing everything possible from Gordon Bell's life. The MyLifeBits system is designed to store and manage a lifetime's worth of data. MyLifeBits enables the capture of web pages, telephone, radio and television. This demonstration highlights the application of typed links and database features to make a lifetime store something that is truly useful.
Effect Sizes for Interpreting Changes in Health Status (1989)

Health status measures are being used with increasing frequency in clinical research. Up to now the emphasis has been on the reliability and validity of these measures. Less attention has been given to the sensitivity of these measures for detecting clinical change. As health status measures are applied more frequently in the clinical setting, we need a useful way to estimate and communicate whether particular changes in health status are clinically relevant. This report considers effect sizes as a useful way to interpret changes in health status. Effect sizes are defined as the mean change found in a variable divided by the standard deviation of that variable. Effect sizes are used to translate "the before and after changes" in a "one group" situation into a standard unit of measurement that will provide a clearer understanding of health status results. The utility of effect sizes is demonstrated from four different perspectives using three health status data sets derived from arthritis populations administered the Arthritis Impact Measurement Scales (AIMS). The first perspective shows how general and instrument-specific benchmarks can be developed and how they can be used to translate the meaning of clinical change. The second perspective shows how effect sizes can be used to compare traditional clinical measures with health status measures in a standard clinical drug trial. The third application demonstrates the use of effect sizes when comparing two drugs tested in separate drug trials and shows how they can facilitate this type of comparison. Finally, our health status results show how effect sizes can supplement standard statistical testing to give a more complete and clinically relevant picture of health status change. We conclude that effect sizes are an important tool that will facilitate the use and interpretation of health status measures in clinical research in arthritis and other chronic diseases.
The p53 activation domain binds the TATA box-binding polypeptide in Holo-TFIID, and a neighboring p53 domain inhibits transcription. (1993)

Antioncogene product p53 is a transcriptional transactivator. To investigate how p53 stimulates transcription, we examined the interaction of p53 with general transcription factors in vitro. We found that p53 binds directly to the human TATA box-binding polypeptide (TBP). We also observed a direct interaction between p53 and purified holo-TFIID, a complex composed of TBP and a group of TBP-associated polypeptides known as TAFs. The p53 binding domain on TBP was mapped to the conserved region of TBP, including residues 220 to 271. The TBP binding domain on p53 was mapped to the p53 activation domain between residues 20 and 57. To analyze the significance of the p53-TBP interaction in p53 transactivation, we compared the ability of Gal4-p53 fusion proteins to bind to TBP in vitro and to activate transcription in transient transfection assays. Fusion proteins which bound to TBP activated transcription, and those that did not bind to TBP did not activate transcription to a detectable level, suggesting that a direct interaction between TBP and p53 is required for p53 transactivation. We also found that inclusion of residues 93 to 160 of p53 in a Gal4-p53 fusion repressed transcriptional activation 100-fold. Consequently, this region of p53 inhibits transcriptional activation by the minimal p53 activation domain. Highest levels of activation were observed with sequences 1 to 92 of p53 fused to Gal4, even though this construct bound to TBP in vitro with an affinity similar to that of other Gal4-p53 fusion proteins. We conclude that TBP binding is necessary for p53 transcriptional activation and that p53 sequences outside the TBP binding domain modulate the level of activation.