gebhart/patrepeval huggingface dataset:
B-type receptor for platelet-derived growth factor mediates a chemotactic response by means of ligand-induced activation of the receptor protein-tyrosine kinase. (1990)

Porcine aorta endothelial cells are devoid of receptors for platelet-derived growth factor (PDGF). We have transfected such cells with cDNA for the PDGF B-type receptor, both the wild-type receptor and a mutant form of the receptor (K634A), in which the putative nucleotide-binding lysine of the protein-tyrosine domain has been changed to alanine. Immunoprecipitation studies of metabolically labeled cells showed that both types of receptors were synthesized and processed to the mature form of Mr 190,000. In cells expressing the wild-type receptor, PDGF-BB, the natural ligand for the B-type receptor, induced membrane ruffling and reorganization of actin. Such a response has previously been seen in cells expressing the natural PDGF B-type receptor in response to PDGF-BB. No such effect was induced in nontransfected cells or in cells expressing the K634A mutant receptor. PDGF was also shown to be chemotactic for cells expressing the wild-type receptor, whereas no chemotactic response was elicited in control cells or in cells expressing the K634A mutant receptor. Our study thus provides formal evidence that the PDGF B-type receptor mediates a motility response including actin reorganization and chemotaxis. Furthermore, the results establish a role for the receptor-associated protein-tyrosine kinase in the transduction of the chemotactic signal.
STUDIES IN THE ADAPTATION OF AN ARTIFICIAL FOOD TO HUMAN MILK (1915)

Introduction by H. J. Gerstenberger In 1910, the physiologist, Friedenthal 1 again picked up the threads which led to the ideal set up by the pediatrist Biedert a generation ago; namely, to the production of an artificial milk similar in all its important characteristics to the best food for the human infant, namely, breast milk. By not getting the results that it had expected from mixtures which took into consideration the quantities of protein, lactose, and fat in human milk, the pediatric world became discouraged and considered the production of an artificial human milk that would give good practical results a hopeless task. Friedenthal gathered courage for another attempt for the solution of this important and interesting problem from the fact that the salt content and the physical-chemical characteristics of human milk had been entirely neglected, and also from the conviction that these were important, if not the most important
Dynamical diffraction explanation of the anomalous transmission of light through metallic gratings (2002)

In this paper, it is pointed out that the light transmission anomalies observed for thin-film metallic gratings can be explained entirely in terms of dynamical diffraction theory. Surface plasmons are an intrinsic component of the diffracted wave field and, as such, play no independent causal role in the anomalies, as has been implied by others. The dynamical scattering matrix for the Bloch-wave modes of the diffracted photon wave field (E, H) is derived for a three-dimensionally periodic medium with arbitrary dielectric constant. A new theoretical treatment and numerical results are presented for a one-dimensional array of slits. In model metallic slit arrays, with negative dielectric constant, 100% and 0% transmission is possible at different wavelengths in the zero-order beam. In slit arrays, both propagating and evanescent modes (traditional surface plasmons) are strongly excited at both the peak and the minimum transmission conditions.
Durable Molecular Remissions in Chronic Lymphocytic Leukemia Treated With CD19-Specific Chimeric Antigen Receptor–Modified T Cells After Failure of Ibrutinib (2017)

Purpose We evaluated the safety and feasibility of anti-CD19 chimeric antigen receptor-modified T (CAR-T) cell therapy in patients with chronic lymphocytic leukemia (CLL) who had previously received ibrutinib. Methods Twenty-four patients with CLL received lymphodepleting chemotherapy and anti-CD19 CAR-T cells at one of three dose levels (2 × 10<sup>5</sup>, 2 × 10<sup>6</sup>, or 2 × 10<sup>7</sup> CAR-T cells/kg). Nineteen patients experienced disease progression while receiving ibrutinib, three were ibrutinib intolerant, and two did not experience progression while receiving ibrutinib. Six patients were venetoclax refractory, and 23 had a complex karyotype and/or 17p deletion. Results Four weeks after CAR-T cell infusion, the overall response rate (complete response [CR] and/or partial response [PR]) by International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria was 71% (17 of 24). Twenty patients (83%) developed cytokine release syndrome, and eight (33%) developed neurotoxicity, which was reversible in all but one patient with a fatal outcome. Twenty of 24 patients received cyclophosphamide and fludarabine lymphodepletion and CD19 CAR-T cells at or below the maximum tolerated dose (≤ 2 × 10<sup>6</sup> CAR-T cells/kg). In 19 of these patients who were restaged, the overall response rate by IWCLL imaging criteria 4 weeks after infusion was 74% (CR, 4/19, 21%; PR, 10/19, 53%), and 15/17 patients (88%) with marrow disease before CAR-T cells had no disease by flow cytometry after CAR-T cells. Twelve of these patients underwent deep IGH sequencing, and seven (58%) had no malignant IGH sequences detected in marrow. Absence of the malignant IGH clone in marrow of patients with CLL who responded by IWCLL criteria was associated with 100% progression-free survival and overall survival (median 6.6 months follow-up) after CAR-T cell immunotherapy. The progression-free survival was similar in patients with lymph node PR or CR by IWCLL criteria. Conclusion CD19 CAR-T cells are highly effective in high-risk patients with CLL after they experience treatment failure with ibrutinib therapy.
Precision genome editing using synthesis-dependent repair of Cas9-induced DNA breaks (2017)

The RNA-guided DNA endonuclease Cas9 has emerged as a powerful tool for genome engineering. Cas9 creates targeted double-stranded breaks (DSBs) in the genome. Knockin of specific mutations (precision genome editing) requires homology-directed repair (HDR) of the DSB by synthetic donor DNAs containing the desired edits, but HDR has been reported to be variably efficient. Here, we report that linear DNAs (single and double stranded) engage in a high-efficiency HDR mechanism that requires only ∼35 nucleotides of homology with the targeted locus to introduce edits ranging from 1 to 1,000 nucleotides. We demonstrate the utility of linear donors by introducing fluorescent protein tags in human cells and mouse embryos using PCR fragments. We find that repair is local, polarity sensitive, and prone to template switching, characteristics that are consistent with gene conversion by synthesis-dependent strand annealing. Our findings enable rational design of synthetic donor DNAs for efficient genome editing.
The performance of screening tests for ovarian cancer: results of a systematic review (1998)

Ultrasound and multimodal screening can detect ovarian cancer in asymptomatic women, but there is currently no evidence on whether screening improves outcome for women in any risk group. On-going randomised controlled trials should establish the magnitude of any benefit of screening. The low prevalence of ovarian cancer in the population, and its rate of progression, may limit the potential cost-effectiveness of screening.
On type systems for object-oriented database programming languages (2002)

The concept of an object-oriented database programming language (OODBPL) is appealing because it has the potential of combining the advantages of object orientation and database programming to yield a powerful and universal programming language design. A uniform and consistent combination of object orientation and database programming, however, is not straightforward. Since one of the main components of an object-oriented programming language is its type system, one of the first problems that arises during an OODBPL design is related to the development of a uniform, consistent, and theoretically sound type system that is sufficiently expressive to satisfy the combined needs of object orientation and database programming.The purpose of this article is to answer two questions: "What are the requirements that a modern type system for an object-oriented database programming language should satisfy?" and "Are there any type systems developed to-date that satisfy these requirements?". In order to answer the first question, we compile the set of requirements that an OODBPL type system should satisfy. We then use this set of requirements to evaluate more than 30 existing type systems. The result of this extensive analysis shows that while each of the requirements is satisfied by at least one type system, no type system satisfies all of them. It also enables identification of the mechanisms that lie behind the strengths and weaknesses of the current type systems.
POLARIMETRIC SAR CALIBRATION VALIDATION FOR ALOS/PALSAR IN MONGOLIA (2007)

The Japanese remote sensing satellite ALOS/PALSAR was launched successfully in January 2006. We are carrying out polarimetric calibration of the PALSAR sensor, which has the full-polarimetric function of L-band SAR. We set corner reflectors in Ulaanbaatar in May and August 2006, and the acquired data was used to confirm the polarimetric calibration coefficients, which will be used for the data products. In addition, the acquired polarimetric SAR data will provide new possibility in remote sensing. Since this is the world first satellite borne full-polarimetric SAR system. Full-polarimetric SAR data acquired over Mongolia show some interesting features. Temporal changes can be clearly detected, and also the data can be used for estimation of terrain slope.
Peptide‐pulsed dendritic cells induce tumoricidal cytotoxic T lymphocytes from healthy donors against stably HLA‐A*0201‐binding peptides from the Melan‐A/MART‐1 self antigen (1996)

The melanoma antigen Melan-A/MART-1 was screened for the presence of potential HLA-A*0201-binding cytotoxic T lymphocytes (CTL) epitopes. The immunodominant nonamer epitope AAGIGILTV demonstrated weak binding to T2 but a significant half-life of binding to HLA-A*0201 in contrast to the decamer EAAGIGILTV. In addition to the immunodominant CTL epitope, we describe two peptides, GILTVILGV and ALMDKSLHV, that display stable binding to HLA-A*0201. Using cultured autologous dendritic cells pulsed with these peptides, CTL lines were induced from peripheral blood lymphocytes that displayed reactivity with HLA-A2+, Melan-A/MART-1+ melanoma cells. CTL reactivity against the immunodominant epitope could be induced with the nonamer epitope alone, but not with the decamer variant. CTL clones generated from an (EAAGIGILTV + AAGIGILTV)-induced CTL line recognize the appropriate melanoma cells and normal melanocytes. Upon further characterization of one of these CTL clones, it was found to be of surprisingly high affinity considering that it is directed against a self antigen. This study demonstrates that immunogenic peptides can be selected based on stability (half-life) of peptide/HLA binding. In addition, cultured DC were found to efficiently induce CTL responses in vitro against such selected peptides, and some of these CTL were capable of recognizing endogenously processed antigen.
The Development and Verification of TIPS: An Expert System to Forecast Thunderstorm Occurrence (1993)

A rule-based expert system has been developed to assist military weather forecasters in the prediction of thunderstorms. The knowledge base used by the Thunderstorm Intelligence Prediction System (TIPS) was built by using meteorological principles associated with convective activity. The goal of TIPS is to provide a generalized system that can be used at any geographical location. TIPS was evaluated during the spring and summer months of 1990 for several locations across the United States. Thunderstorm forecasts were derived using 1200 UTC, atmospheric sounding data, and a single forecaster input value. Verification results show that TIPS can assist the weather forecaster in predicting thunderstorm occurrence.
GAVEL - a new tool for genetic algorithm visualization (2001)

This paper surveys the state of the art in evolutionary algorithm visualization and describes a new tool called GAVEL. It provides a means to examine in a genetic algorithm (GA) how crossover and mutation operations assembled the final result, where each of the alleles came from, and a way to trace the history of user-selected sets of alleles. A visualization tool of this kind can be very useful in choosing operators and parameters and in analyzing how and, indeed, whether or not a GA works. We describe the new tool and illustrate some of the benefits that can be gained from using it with reference to three different problems: a timetabling problem, a job-shop scheduling problem, and Goldberg and Horn's long-path problem. We also compare the tool to other available visualization tools, pointing out those features which are novel and identifying complementary features in other tools.
Aldehyde Syntheses. Study of the preparation of 9,10-anthracenedicarboxaldehyde (1979)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAldehyde Syntheses. Study of the preparation of 9,10-anthracenedicarboxaldehydeYang-I Lin, S. A. Lang Jr., Christina M. Seifert, R. G. Child, G. O. Morton, and P. F. FabioCite this: J. Org. Chem. 1979, 44, 25, 4701–4703Publication Date (Print):December 1, 1979Publication History Published online1 May 2002Published inissue 1 December 1979https://pubs.acs.org/doi/10.1021/jo00393a050https://doi.org/10.1021/jo00393a050research-articleACS PublicationsRequest reuse permissionsArticle Views890Altmetric-Citations22LEARN 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
Management of cellular energy by the AMP‐activated protein kinase system (2003)

The AMP-activated protein kinase is a sensor of cellular energy status that is found in all eukaryotic cells. It is activated by rising AMP and falling ATP by a complex mechanism that results in an ultrasensitive response. The functions of the different domains on the three subunits of the alphabetagamma heterotrimer are slowly being unravelled, and a recent development has been the identification of a glycogen-binding domain on the beta subunit. Along with findings that high cellular glycogen represses kinase activation, this suggests that the system may be a sensor of glycogen content as well as of AMP and ATP. New insights have been obtained into the sequence and structural features by which the kinase recognises its downstream target proteins, and these are discussed. Once activated by depletion of cellular energy reserves, the kinase switches on ATP-producing catabolic pathways and switches off ATP-consuming processes, both via direct phosphorylation of regulatory proteins and via indirect effects on gene expression. A survey of the range of downstream targets for this important signalling pathway is presented.
CCAAT Box Enhancer Binding Protein α (C/EBP-α) Stimulates B Element-mediated Transcription in Transfected Cells (1996)

A construct comprising three tandemly repeated copies of the kappaB element from the interleukin-8 gene linked to chloramphenicol acetyltransferase (CAT) (3xNF-kappaBCAT) was transcriptionally activated in normal human FS-4 fibroblasts by co-transfection with expression vectors for NF-kappaB p50, p65, or p52. Unexpectedly, a significant activation of 3xNF-kappaBCAT was also seen upon its co-transfection with the expression vector for CCAAT box enhancer binding protein alpha (C/EBP-alpha) (but not C/EBP-beta or C/EBP-delta). Stimulation by C/EBP-alpha required some other factor(s) present in FS-4 cells because no transcriptional activation of 3xNF-kappaBCAT was seen after co-transfection with C/EBP-alpha in F9 mouse embryonic carcinoma cells, known to be deficient in several transcription factors. To determine whether transcriptional activation was the result of interaction with one of the major NF-kappaB proteins, we co-transfected C/EBP-alpha with NF-kappaB p50, p65, p50 + p65, or p52 into F9 or FS-4 cells. No cooperative interaction was seen; in fact, C/EBP- alpha reduced p65-stimulated transcription, especially in F9 cells. Electrophoretic mobility shift assay with a kappaB probe revealed that the addition of recombinant C/EBP-alpha protein to nuclear extracts from untreated FS-4 cells resulted in the appearance of four bands. Only one of these bands was supershifted by antibody to p50, whereas antibodies to p65 or other NF-kappaB proteins had no effect. Our findings show that C/EBP-alpha may cause activation of some kappaB element-containing genes lacking C/EBP binding sites.
Biomarker evidence of DNA oxidation in lung cancer patients: association of urinary 8‐hydroxy‐2′‐deoxyguanosine excretion with radiotherapy, chemotherapy, and response to treatment (1997)

Ratios of urinary 8-hydroxy-2'-deoxyguanosine to urinary creatinine (8-OHdG/creatinine) have been considered as a good biological indicator of DNA oxidation. Urinary 8-OHdG/creatinine levels of lung cancer patients were evaluated by enzyme-linked immunosorbent assay using a monoclonal antibody N45.1 during radiotherapy and chemotherapy. An increase in urinary 8-OHdG/creatinine was found in non-small-cell carcinoma (non-SCC) patients during the course of radiotherapy. SCC patients showed higher levels of urinary 8-OHdG/creatinine than the controls. Furthermore, SCC patients with complete or partial response to the chemotherapy showed a significant decrease in urinary 8-OHdG/creatinine while patients with no change or progressive disease showed an increase.
Glucocorticoid receptor and protein/RNA synthesis-dependent mechanisms underlie the control of synaptic plasticity by stress (1998)

Learning and memory are exquisitely sensitive to behavioral stress, but the underlying mechanisms are still poorly understood. Because activity-dependent persistent changes in synaptic strength are believed to mediate memory processes in brain areas such as the hippocampus we have examined the means by which stress affects synaptic plasticity in the CA1 region of the hippocampus of anesthetized rats. Inescapable behavioral stress (placement on an elevated platform for 30 min) switched the direction of plasticity, favoring low frequency stimulation-induced decreases in synaptic transmission (long-term depression, LTD), and opposing the induction of long-term potentiation by high frequency stimulation. We have discovered that glucocorticoid receptor activation mediates these effects of stress on LTD and long-term potentiation in a protein synthesis-dependent manner because they were prevented by the glucocorticoid receptor antagonist RU 38486 and the protein synthesis inhibitor emetine. Consistent with this, the ability of exogenously applied corticosterone in non-stressed rats to mimic the effects of stress on synaptic plasticity was also blocked by these agents. The enablement of low frequency stimulation-induced LTD by both stress and exogenous corticosterone was also blocked by the transcription inhibitor actinomycin D. Thus, naturally occurring synaptic plasticity is liable to be reversed in stressful situations via glucocorticoid receptor activation and mechanisms dependent on the synthesis of new protein and RNA. This indicates that the modulation of hippocampus-mediated learning by acute inescapable stress requires glucocorticoid receptor-dependent initiation of transcription and translation.
Qualitative and quantitative assessment of meningococcal antigens to evaluate the potential strain coverage of protein-based vaccines (2010)

A unique multicomponent vaccine against serogroup B meningococci incorporates the novel genome-derived proteins fHbp, NHBA, and NadA that may vary in sequence and level of expression. Measuring the effectiveness of such vaccines, using the accepted correlate of protection against invasive meningococcal disease, could require performing the serum bactericidal assay (SBA) against many diverse strains for each geographic region. This approach is impractical, especially for infants, where serum volumes are very limited. To address this, we developed the meningococcal antigen typing system (MATS) by combining a unique vaccine antigen-specific ELISA, which detects qualitative and quantitative differences in antigens, with PorA genotyping information. The ELISA correlates with killing of strains by SBA and measures both immunologic cross-reactivity and quantity of the antigens NHBA, NadA, and fHbp. We found that strains exceeding a threshold value in the ELISA for any of the three vaccine antigens had ≥80% probability of being killed by immune serum in the SBA. Strains positive for two or more antigens had a 96% probability of being killed. Inclusion of multiple different antigens in the vaccine improves breadth of coverage and prevents loss of coverage if one antigen mutates or is lost. The finding that a simple and high-throughput assay correlates with bactericidal activity is a milestone in meningococcal vaccine development. This assay allows typing of large panels of strains and prediction of coverage of protein-based meningococcal vaccines. Similar assays may be used for protein-based vaccines against other bacteria.
RVLM and raphe differentially regulate sympathetic outflows to splanchnic and brown adipose tissue (1999)

To determine whether neurons in the rostral raphe pallidus (RPa) specifically control the sympathetic nerve activity to brown adipose tissue (BAT SNA), thereby regulating adipocyte metabolism and BAT thermogenesis, the responses in BAT SNA to disinhibition of RPa neurons and to disinhibition of neurons in the vasomotor region of the rostral ventrolateral medulla (RVLM) were compared with those in splanchnic (Spl) SNA, which primarily regulates visceral vasoconstriction. In urethan-chloralose-anesthetized ventilated rats, both acute hypothermia and microinjection of bicuculline into RPa produced significantly larger increases in BAT SNA (542 and 1,949% of control) than in Spl SNA (19 and 24% of control). The enhanced burst discharge in BAT SNA was not coherent with that in Spl SNA or with the arterial pressure (AP) at any frequency except the central respiratory frequency. Microinjections of bicuculline into RVLM evoked increases in Spl SNA (86% of control) and AP (32 mmHg), but reduced BAT SNA to low, normothermic levels. Microinjections of muscimol into RVLM reduced Spl SNA (-82% of control) and AP (-59 mmHg), but did not prevent the increase in BAT SNA after disinhibition of RPa neurons. These results indicate that the neural networks generating BAT SNA in response to disinhibition of RPa neurons are independent of those generating basal Spl SNA and support a model in which sympathetic outflow to tissues involved in thermoregulation and metabolism is regulated by central pathways, including neurons in RPa, that are distinct from those involved in the sympathetic control of the cardiovascular system.