gebhart/patrepeval huggingface dataset:
Phase I clinical study with pharmacokinetic analysis of 2-beta-D-ribofuranosylthiazole-4-carboxamide (NSC 286193) administered as a five-day infusion. (1985)

A Phase I trial of 2-beta-D-ribofuranosylthiazole-4-carboxamide (NSC 286193, tiazofurin) was conducted using a 5-day continuous infusion schedule. Twenty-four patients with advanced cancer were entered on this trial. Dose levels ranged from 360 to 2350 mg/sq m/day for 5 days. Neurotoxicity was dose limiting and occurred in six patients. Neurotoxicity was expressed as confusion, lethargy, or obtundation and was associated with focal neurological deficits in four of six patients: hemiparesis, three; cortical blindness and bilateral upper extremity weakness, one. Neurotoxicity was not clearly dose related, occurring at 900 mg/sq m/day for 5 days (two patients), 1100 mg/sq m/day for 5 days (two patients), 1850 mg/sq m/day for 5 days, and 2350 mg/sq m/day for 5 days (one patient each). Other toxicities seen were myelosuppression, desquamation of palms and soles, malar erythema, and hyperpigmentation, stomatitis, chest pain, drug fever, and increased serum creatine phosphokinase. Administered drug [71.5 +/- 11.2% (SE)] was recovered intact in the urine within 24 h of administration. Terminal-phase mean harmonic half-life was 8.0 h. The unpredictable neurotoxicity seen following continuous infusion therapy with tiazofurin suggests that Phase II trials of this schedule are not indicated until better understanding of the biochemical effects of tiazofurin is achieved.
Computation of the structures of the phenyl and benzyl radicals with the UHF method (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTComputation of the structures of the phenyl and benzyl radicals with the UHF methodHendrik F. HamekaCite this: J. Org. Chem. 1987, 52, 22, 5025–5026Publication Date (Print):October 1, 1987Publication History Published online1 May 2002Published inissue 1 October 1987https://pubs.acs.org/doi/10.1021/jo00231a035https://doi.org/10.1021/jo00231a035research-articleACS PublicationsRequest reuse permissionsArticle Views209Altmetric-Citations12LEARN 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
Masitinib Antagonizes ATP-Binding Cassette Subfamily C Member 10–Mediated Paclitaxel Resistance: A Preclinical Study (2014)

Paclitaxel displays clinical activity against a wide variety of solid tumors. However, resistance to paclitaxel significantly attenuates the response to chemotherapy. The ABC transporter subfamily C member 10 (ABCC10), also known as multidrug resistance protein 7 (MRP7) efflux transporter, is a major mediator of paclitaxel resistance. In this study, we show that masitinib, a small molecule stem-cell growth factor receptor (c-Kit) tyrosine kinase inhibitor, at nontoxic concentrations, significantly attenuates paclitaxel resistance in HEK293 cells transfected with ABCC10. Our in vitro studies indicated that masitinib (2.5 μmol/L) enhanced the intracellular accumulation and decreased the efflux of paclitaxel by inhibiting the ABCC10 transport activity without altering the expression level of ABCC10 protein. Furthermore, masitinib, in combination with paclitaxel, significantly inhibited the growth of ABCC10-expressing tumors in nude athymic mice in vivo. Masitinib administration also resulted in a significant increase in the levels of paclitaxel in the plasma, tumors, and lungs compared with paclitaxel alone. In conclusion, the combination of paclitaxel and masitinib could serve as a novel and useful therapeutic strategy to reverse paclitaxel resistance mediated by ABCC10.
Antigenic Specificity of Benzo[a]pyrene-Induced Sarcomas2 (1964)

Tumors induced in C3H and C57BL mice by benzopyrene elicited isograft immune reactions to tumor-specific antigens. The antigenicity of primary tumors was higher than that of the same sarcomas after a series of transfers through isologous hosts. Apparently the progressive growth of transplants of primary tumors is determined by the antigenicity of the tumors. Sarcomas that did not take in normal hosts—such as grafts of early transplant generations—grew progressively when transplanted to animals exposed to total-body X irradiation, i.e., in immunologically suppressed animals. The decrease in antigenicity was not associated with a complete loss of the tumor antigens. Tumors that could no longer immunize animals were still susceptible to the immune response elicited by immunogenic grafts of earlier transplant generations. Each of the 2 sarcomas produced in a single animal by 2 simultaneous applications of the carcinogen had distinct antigenic specificity. Tumors produced in a single animal may differ from each other in (a) transplantability, (b) immunogenicity, and (c) antigenic specificity. The exposure of preimmunized animals to X irradiation, followed by test grafting, was most useful for the analysis of antigenic specificity of non-transplantable tumors. Experiments in which sarcomas, originating in C3H, were tested for antigenicity in (C3H × C57BL)F1 hybrids demonstrated that the lack of manifested immunological reactivity to certain tumors is due to the properties of the tumor cells themselves and not to the recipient animals.
Growth Inhibitory Effects of Interferon-β but Not Interferon-α on Human Glioma Cells: Correlation of Receptor Binding, 2′,5′-O1igoadenylate Synthetase and Protein Kinase Activity (1990)

The antiproliferative effects of human recombinant interferon-alpha (rIFN-alpha A) and interferon-beta (rIFN-beta ser) were assessed in vitro against seven human glioma cell lines. Further analysis of one of these lines (EFC-2) in response to rIFN-alpha A demonstrated a minimum growth inhibition by day 6 of treatment, whereas a 50% inhibition of cell growth was observed with a dose of 50 U/ml of IFN-beta ser. No significant growth inhibition was seen by rIFN-alpha A at doses up to 500 U/ml. Addition of rIFN-alpha A to rIFN-beta ser-treated EFC-2 cells neither suppressed nor augmented the antiproliferative response to IFN-beta ser. The binding of 125I-labeled rIFN-alpha A or 125I-labeled rIFN-beta ser to EFC-2 cells was inhibited competitively by increasing concentrations of either unlabeled rIFN-alpha A or rIFN-beta ser. This suggests that the cellular receptors for both rIFN-alpha A and rIFN-beta ser appear to be intact and appear to bind both agents equally. Furthermore, incubation of EFC-2 cells for 72 h with either rIFN-alpha A or rIFN-beta ser resulted in an increase in 2',5'-oligoadenylate (2-5A) synthetase activity 5-fold with rIFN-alpha A and 50-fold with rIFN-beta ser. Similarly, the 68-kD IFN-induced protein kinase was induced substantially with rIFN-beta ser but only slightly induced with rIFN-alpha A treatment. These results suggest that EFC-2 human glioma cells demonstrate a differential sensitivity in terms of growth inhibition to rIFN-beta ser and to rIFN-alpha A which appears to correlate with a differential induction of both intracellular 2-5A synthetase and protein kinase activity. These results cannot be explained solely on the basis of surface receptor binding of rIFN-alpha A and rIFN-beta ser. These data do suggest that, for human glioma cells in culture, type I IFN receptors may display a subtle architectural variation that allows equivalent binding of both IFN-alpha and IFN-beta ser, but allows an enhanced signal transduction and biological effect only after binding a specific IFN subtype.
Cellular Controlled Drone Experiment: Evaluation of Network Requirements (2015)

The cellular and drone technologies have advanced enough to be combined. The modern cellular technologies, especially the Long Term Evolution (LTE), have low latency and high bit rate. Hence, they are sufficient for controlling delay sensitive video enabled drones. Particularly fitting drone type for LTE control is a multicopter with its high payload and long flight time. This thesis briefs on the drones and LTE Quality Of Service (QoS), and explains how to construct an LTE drone.&#13;\n&#13;\nFirst, the background on the drones and LTE QoS is explained based on literature. Basic knowledge of LTE QoS is then amended with expert interviews describing the status of it in Finland. Next, a hands on project is executed to construct an LTE controlled drone. The LTE is then evaluated as a control method by comparing its performance to the traditional Radio Controller (RC). Finally, the feasibility of an LTE controlled drone is evaluated by performing example 3D LTE coverage measurements.&#13;\n&#13;\nIn this thesis, the LTE controlled drone it is proven to be achievable by constructing a working prototype. Next, the suitability of the LTE is observed to be equal to the traditional RC as a control link. Finally, in the 3D LTE coverage measurements, the LTE controlled drone is discovered to be feasible.
Analysis of Tn antigenicity with a panel of new IgM and IgG1 monoclonal antibodies raised against leukemic cells (2011)

CD175 or Tn antigen is a carbohydrate moiety of N-acetylgalactosamine (GalNAc)α1-O- linked to the residue of amino acid serine or threonine in a polypeptide chain. Despite the chemical simplicity of the Tn antigen, its antigenic structure is considered to be complex and the clear determinants of Tn antigenicity remain poorly understood. As a consequence, a broad variety of anti-Tn monoclonal antibodies (mAbs) have been generated. To further investigate the nature and complexity of the Tn antigen, we generated seven different anti-Tn mAbs of IgM and IgG classes raised against human Jurkat T cells, which are Tn-positive due to the low activity of T-synthase and mutation in specific chaperone Cosmc. The binding analysis of anti-Tn mAbs with the array of synthetic saccharides, glycopeptides and O-glycoproteins revealed unexpected differences in specificities of anti-Tn mAbs. IgM mAbs bound the terminal GalNAc residue of the Tn antigen irrespective of the peptide context or with low selectivity to the glycoproteins. In contrast, IgG mAbs recognized the Tn antigen in the context of a specific peptide motif. Particularly, JA3 mAb reacted to the GSPP or GSPAPP, and JA5 mAb recognized specifically the GSP motif (glycosylation sites are underlined). The major O-glycan carrier proteins CD43 and CD162 and isoforms of CD45 expressed on Jurkat cells were precipitated by anti-Tn mAbs with different affinities. In summary, our data suggest that Tn antigen-Ab binding capacity is determined by the peptide context of the Tn antigen, antigenic specificity of the Ab and class of the immunoglobulin. The newly generated anti-Tn IgG mAbs with the strong specificity to glycoprotein CD43 can be particularly interesting for the application in leukemia diagnostics and therapy.
The Combinations of Haemoglobin with Oxygen and with Carbon Monoxide. I (1913)

Research Article| October 01 1913 The Combinations of Haemoglobin with Oxygen and with Carbon Monoxide. I Archibald Vivian Hill Archibald Vivian Hill 1The Physiological Laboratory, Cambridge Search for other works by this author on: This Site PubMed Google Scholar Biochem J (1913) 7 (5): 471–480. https://doi.org/10.1042/bj0070471 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Cite Icon Cite Get Permissions Citation Archibald Vivian Hill; The Combinations of Haemoglobin with Oxygen and with Carbon Monoxide. I. Biochem J 1 October 1913; 7 (5): 471–480. doi: https://doi.org/10.1042/bj0070471 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. © 1913 CAMBRIDGE UNIVERSITY PRESS1913 Article PDF first page preview Close Modal You do not currently have access to this content.
Isolation and functional analysis of a human 70,000-dalton heat shock protein gene segment. (1985)

A human 70-kDa heat shock protein (hsp70) gene segment has been isolated. The segment contains 3.15 kilobase pairs (kbp) of 5' nontranscribed sequence, an RNA leader of 119 bp, and a protein-coding region of 741 bp. The human protein sequence shows a high degree of homology to hsp70 sequences from other species. Expression experiments in Xenopus oocytes and mammalian cells indicate that a region that includes only 105 bp of 5' nontranscribed sequence contains all elements required for the efficient heat-controlled expression of the human gene. Two adjacent identical sequence elements, which are partly homologous to the Drosophila "heat shock consensus" sequence, are located 57 to 76 bp upstream from the capping site. Interestingly, the capping site itself is flanked by inverted repeat sequences.
Apoptosis induced by an anti-epidermal growth factor receptor monoclonal antibody in a human colorectal carcinoma cell line and its delay by insulin. (1995)

Both EGF and insulin, or IGF, stimulate the growth of many cell types by activating receptors that contain tyrosine kinase activities. A monoclonal antibody (mAb 225) against the EGF receptor produced in this laboratory has been shown to competitively inhibit EGF binding and block activation of receptor tyrosine kinase. Here we report that a human colorectal carcinoma cell line, DiFi, which expresses high levels of EGF receptors on plasma membranes, can be induced to undergo G1 cell cycle arrest and programmed cell death (apoptosis) when cultured with mAb 225 at concentrations that saturate EGF receptors. Addition of IGF-1 or high concentrations of insulin can delay apoptosis induced by mAb 225, while the G1 arrest cannot be reversed by either IGF-1 or insulin. Insulin/IGF-1 cannot activate EGF receptor tyrosine kinase that has been inhibited by mAb 225. Moreover, an mAb against the IGF-1 receptor, which has little direct effect on DiFi cell growth, can block the capacity of insulin/IGF-1 to delay apoptosis induced by mAb 225, suggesting that the insulin/IGF-1-mediated delay of apoptosis is acting through the IGF-1 receptor. In contrast, insulin/IGF-1 cannot delay the apoptosis caused by the DNA damaging agent, cisplatin. The results indicate that EGF receptor activation is required both for cell cycle progression and for prevention of apoptosis in DiFi cells, and that a signal transduction pathway shared by receptors for insulin/IGF-1 and EGF may be involved in regulating apoptosis triggered by blockade of the EGF receptor.
Enhanced Engagement of CTLA-4 Induces Antigen-Specific CD4+CD25+Foxp3+ and CD4+CD25− TGF-β1+ Adaptive Regulatory T Cells (2007)

CTLA-4 is a critical negative regulator of T cell response and is instrumental in maintaining immunological tolerance. In this article, we report that enhanced selective engagement of CTLA-4 on T cells by Ag-presenting dendritic cells resulted in the induction of Ag-specific CD4(+)CD25(+)Foxp3(+) and CD4(+)CD25(-)TGF-beta1(+) adaptive Tregs. These cells were CD62L(low) and hyporesponsive to stimulation with cognate Ag but demonstrated a superior ability to suppress Ag-specific effector T cell response compared with their CD62L(high) counterparts. Importantly, treatment of mice with autoimmune thyroiditis using mouse thyroglobulin (mTg)-pulsed anti-CTLA-4 agonistic Ab-coated DCs, which results in a dominant engagement of CTLA-4 upon self-Ag presentation, not only suppressed thyroiditis but also prevented reemergence of the disease upon rechallenge with mTg. Further, the disease suppression was associated with significantly reduced mTg-specific T cell and Ab responses. Collectively, our results showed an important role for selective CTLA-4 signaling in the induction of adaptive Tregs and suggested that approaches that allow dominant CTLA-4 engagement concomitant with Ag-specific TCR ligation can be used for targeted therapy.
Downregulation of GLP-1 and GIP Receptor Expression by Hyperglycemia (2007)

Stimulation of insulin secretion by the incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) has been found to be diminished in type 2 diabetes. We hypothesized that this impairment is due to a defect at the receptor level induced by the diabetic state, particularly hyperglycemia. Gene expression of incretin receptors, GLP-1R and GIPR, were significantly decreased in islets of 90% pancreatectomized (Px) hyperglycemic rats, with recovery when glucose levels were normalized by phlorizin. Perifused islets isolated from hyperglycemic Px rats showed reduced insulin responses to GLP-1 and GIP. To examine the acute effect of hyperglycemia on incretin receptor expression, a hyperglycemic clamp study was performed for 96 h with reduction of GLP-1 receptor expression but increase in GIP receptor expression. Similar findings were found when islets were cultured at high glucose concentrations for 48 h. The reduction of GLP-1 receptor expression by high glucose was prevented by dominant-negative protein kinase C (PKC)alpha overexpression, whereas GLP-1 receptor expression was reduced with wild-type PKCalpha overexpression. Taken together, GLP-1 and GIP receptor expression is decreased with chronic hyperglycemia, and this decrease likely contributes to the impaired incretin effects found in diabetes.
A new algorithm for dynamic focusing of phased-array hyperthermia applicators through tissue inhomogeneities (1993)

A prototype needle hydrophone array for acoustic feedback during phased-array hyperthermia treatments was presented previously. The authors present a new algorithm for adaptive dynamic focusing of phased-array applicators in the presence of inhomogeneities. This algorithm uses measurements from a limited number of acoustic sensors such as those on the needle hydrophone array. The algorithm is based on a Taylor series expansion of the (measured) propagation operator from the array elements, in the vicinity of the implanted acoustic sensors. The authors show that the new algorithm does not require prior knowledge of the applicator geometry and that all parameters for correction terms can be measured directly at the sensor location. Experimental results of dynamic focusing based on the new algorithm are presented using a 1D cylindrical section phased-array prototype
EphB4 Overexpression in B16 Melanoma Cells Affects Arterial-Venous Patterning in Tumor Angiogenesis (2007)

EphB4 receptor and its ligand ephrinB2 play an important role in vascular development during embryogenesis. In blood vessels, ephrinB2 is expressed in arterial endothelial cells (EC) and mesenchymal supporting cells, whereas EphB4 is only expressed in venous ECs. Previously, we reported that OP9 stromal cells, which support the development of both arterial and venous ECs, in which EphB4 was overexpressed, could inhibit ephrinB2-positive (ephrinB2+) EC development in an embryonic tissue organ culture system. Although the EphB4 receptor is expressed in a variety of tumor cells, its exact function in regulating tumor progression has not been clearly shown. Here we found that overexpression of EphB4 in B16 melanoma cells suppressed tumor growth in a s.c. transplantation tumor model. Histologic examination of these tumors revealed that EphB4 overexpression in B16 cells selectively suppressed arterial ephrinB2+ EC development. By coculturing ephrinB2-expressing SV40-transformed mouse ECs (SVEC) with EphB4-overexpressing B16 cells, we found that EphB4 induced the apoptosis of SVECs. However, ephrinB2 did not induce the apoptosis of EphB4-overexpressing B16 cells. Based on results from these experiments, we concluded that EphB4 overexpression in B16 tumor cells suppresses the survival of arterial ECs in tumors by a reverse signaling via ephrinB2.
Long-term follow-up of cervical intraepithelial neoplasia treated with minimal conization by carbon dioxide laser (1997)

Minimal conization is a safe, effective treatment for CIN and early forms of microinvasive carcinoma. Invasive carcinoma can be detected early and should be treated without delay. The cumulative risk of developing new CIN is 3.02% at year 15 and there is no risk of sudden-onset invasive carcinoma following this procedure.
ERD'14 (2014)

In this paper we overview the 2014 Entity Recognition and Disambiguation Challenge (ERD'14), which took place from March to June 2014 and was summarized in a dedicated workshop at SIGIR 2014. The main goal of the ERD challenge was to promote research in recognition and disambiguation of entities in unstructured text. Unlike many past entity linking challenges, no mention segmentations were given to the participating systems for a given document. Participants were asked to implement a web service for their system to minimize human involvement during evaluation and to enable measuring the processing times. The challenge has attracted a lot of interest (over 100 teams registered, and 27 of those submitted final results). In this paper we cover the task definition, issues encountered during annotation, and provide a detailed analysis of all the participating systems. Specifically, we show how we adapted the pooling technique to address the difficulties of gathering annotations for the entity linking task. We also summarize the ERD workshop that followed the challenge, including the oral and poster presentations as well as the invited talks.
Characterization of revertant muscle fibers in Duchenne muscular dystrophy, using exon-specific monoclonal antibodies against dystrophin. (1995)

Most Duchenne muscular dystrophy (DMD) patients have genetic deletions or point mutations in the dystrophin gene that alter the reading frame of dystrophin mRNA. This causes early termination of translation, and no dystrophin (or, less commonly, a truncated N-terminal dystrophin fragment) is produced. In many DMD patients, however, a small proportion of muscle fibers show strong dystrophin staining, and these "revertant fibers" are thought to arise by a mechanism that restores the reading frame. Exon-specific monoclonal antibodies (mAbs) have now been used to determine, for the first time, which exons are removed, in order to correct the reading frame in individual muscle fibers. Thus, 15 revertant fibers in a DMD patient with a frameshift deletion of exon 45 were shown to correct the frameshift by the additional deletion of exon 44 (or perhaps exon 46 in some fibers) from the dystrophin mRNA, but not by larger deletions. This result was consistent with reverse transcription (RT)-PCR and sequencing of a minor dystrophin mRNA with an exon 43/46 junction in this biopsy. In a DMD patient with a frameshift deletion of exons 42 and 43, however, larger deletions than the minimum necessary were used to correct the frameshift. In this patient, who produces a half-size N-terminal dystrophin fragment in all fibers, we were able to show that the revertant dystrophin replaces the truncated dystrophin in revertant-fiber sarcolemma. The results are consistent with somatic mutations in revertant-fiber nuclei, which result in removal of additional exons from dystrophin mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)