gebhart/patrepeval huggingface dataset:
Comparison of Rabbit and Mouse Models for Persistence Analysis of Plasmid-Based Vaccines (2006)

Experiments were conducted with a cationic lipid-formulated pDNA vaccine (VCL-AB01) to evaluate the models used to determine biodistribution, persistence and the potential for integration (into genomic DNA) of plasmid DNA-based vaccines. Mice were injected with a high-dose volume of 50 microL unilaterally containing approximately 1.33 x 10(13) plasmid copy numbers (PCN) or a low-dose volume of 20 microL bilaterally ( approximately 5.3 x 10(12) PCN). Rabbits were injected bilaterally with a 0.5 mL ( approximately 1.33 x 10(14) PCN) volume. Injection site muscle tissue was harvested two days, one month, and two months postinjection for the low-dose murine and rabbit models and two days and two months postinjection for the high-dose murine model. Total DNA was extracted and analyzed by real-time quantitative PCR for sequences specific to the injected pDNA. The geometric mean PCN/microg of total DNA from the high and low dose models were compared to determine if injection volume impacts clearance and/or persistence. Results from these studies showed that PCN clearance over two months was similar in mice injected with 20 microL and rabbits injected with 0.5 mL, but PCN clearance was slower in mice injected with similar PCN in 50 microL (1.33 x 10(13) PCN) compared to 20 microL (5.3 x 10(12) PCN). Persistence at two months in the rabbit and low-dose murine models was comparable, with geometric mean of 5.22 x 10(3) PCN/microg of total DNA for the low-dose volume murine model and 2.81 x 10(3)/microg DNA for the rabbit model. Interanimal variability in persistence was not impacted by dose volume.
Mechanisms and therapeutic advances in the management of endocrine-resistant breast cancer (2014)

The estrogen receptor (ER) pathway plays a critical role in breast cancer development and progression. Endocrine therapy targeting estrogen action is the most important systemic therapy for ER positive breast cancer. However its efficacy is limited by intrinsic and acquired resistance. Mechanisms responsible for endocrine resistance include deregulation of the ER pathway itself, including loss of ER expression, post-translational modification of ER, deregulation of ER co-activators; increased receptor tyrosine kinase signaling leading to activation of various intracellular pathways involved in signal transduction, proliferation and cell survival, including growth factor receptor tyrosine kinases human epidermal growth factor receptor-2, epidermal growth factor receptor, PI3K/AKT/mammalian target of rapamycin (mTOR), Mitogen activated kinase (MAPK)/ERK, fibroblast growth factor receptor, insulin-like growth factor-1 receptor; alterations in cell cycle and apoptotic machinery; Epigenetic modification including dysregulation of DNA methylation, histone modification, and nucleosome remodeling; and altered expression of specific microRNAs. Functional genomics has helped us identify a catalog of genetic and epigenetic alterations that may be exploited as potential therapeutic targets and biomarkers of response. New treatment combinations targeting ER and such oncogenic signaling pathways which block the crosstalk between these pathways have been proven effective in preclinical models. Results of recent clinical studies suggest that subsets of patients benefit from the combination of inhibitor targeting certain oncogenic signaling pathway with endocrine therapy. Especially, inhibition of the mTOR signaling pathway, a key component implicated in mediating multiple signaling cascades, offers a promising approach to restore sensitivity to endocrine therapy in breast cancer. We systematically reviewed important publications cited in PubMed, recent abstracts from ASCO annual meetings and San Antonio Breast Cancer Symposium, and relevant trials registered at ClinicalTrials.gov. We present the molecular mechanisms contributing to endocrine resistance, in particular focusing on the biological rationale for the clinical development of novel targeted agents in endocrine resistant breast cancer. We summarize clinical trials utilizing novel strategies to overcome therapeutic resistance, highlighting the need to better identify the appropriate patients whose diseases are most likely to benefit from these specific strategies.
Developmentally Regulated Expression of mRNA for Neurotrophin High‐Affinity (trk) Receptors within Chick Trigeminal Sensory Neurons (1995)

To investigate the distribution of neurons within the developing trigeminal sensory system which express mRNA for each of the three known high-affinity neurotrophin receptors (trk, trkB and trkC), we have performed in situ hybridization histochemistry on serial sections through the trigeminal ganglion and trigeminal mesencephalic nucleus at various ages of development using specific antisense oligonucleotide probes. We show that trkC mRNA is first expressed in the chicken embryo at stage 13, in presumptive neurons prior to the formation of the ganglion, that trkB mRNA labelling is initially observed within peripheral neurons slightly later, at stage 19, and that trk mRNA expression is not detectable until around embryonic day 3.5 (stage 21/22). The neurons which exhibit mRNA labelling for each of the high-affinity receptors occupy discrete regions within the ganglion, indicating that the ganglion comprises distinct neuronal subpopulations, each of which has a different capacity to respond to the different neurotrophins. Neurons which express trk mRNA are confined to the proximal region of the ganglion, whereas those which express trkB mRNA and trkC mRNA are located in two distinct regions within the distal aspect and also within the trigeminal mesencephalic nucleus. From the estimation of the number of neurons which exhibit labelling between embryonic days 9 and 18, we determined that the expression of mRNA for the high-affinity receptors changes during embryonic development of the ganglion. This is consistent with the observed differences in the response to neurotrophins in vitro.
Isolation and Structure Elucidation of the Major Simmondsin Analogs in Jojoba Meal by Two-Dimensional NMR Spectroscopy (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIsolation and Structure Elucidation of the Major Simmondsin Analogs in Jojoba Meal by Two-Dimensional NMR SpectroscopyM. Van Boven, P. Daenens, M. M. Cokelaere, and G. JanssenCite this: J. Agric. Food Chem. 1994, 42, 12, 2684–2687Publication Date (Print):December 1, 1994Publication History Published online1 May 2002Published inissue 1 December 1994https://pubs.acs.org/doi/10.1021/jf00048a007https://doi.org/10.1021/jf00048a007research-articleACS PublicationsRequest reuse permissionsArticle Views78Altmetric-Citations9LEARN 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
Treating Agitation With Dexmedetomidine in the ICU (2009)

Patients in the intensive care unit frequently experience delirium, anxiety, and agitation, with a variety of treatments used. This article discusses the role of an alpha-adrenoceptor agonist, dexmedetomidine, and its clinical relevance and advantages for the agitated patient.
Reversible Charging of CdSe Nanocrystals in a Simple Solid-State Device (2002)

The reversible charging of multiple layers of nanocrystals (NCs) at room temperature has been achieved by using a simple, solid-state device. This reversible charging leads to the possibility of using NCs in optical modulators and in tunable fluorescent or photochromic displays. These structures should also allow systematic studies of the photophysics of charged NCs. The Figure shows the schematic diagram of the NC charging device.
Noninvasive determination of the arterial input function of an anticancer drug from dynamic PET scans using the population approach (1999)

For the application of a kinetic model to PET data, it is generally necessary to obtain the arterial input function (AIF). It was the aim of the present study to introduce a method suitable for the determination of the AIF of a substance that undergoes biochemical transformation from noisy PET data: the population approach. F-18 labeled 5-fluorouracil (5-[18F]FU) was administered i.v. to eight patients suffering from liver metastases of colorectal carcinoma. Radioactivity concentrations in liver and aorta were dynamically measured with PET over 120 min. Pharmacokinetic analysis was carried out by applying a five-compartment model to individual activity-time data for the eight patients or to the mean activity-time data among the eight patients. The mean values of all parameters describing 5-FU transport and catabolism, i.e., volumes of distribution and clearances, as well as interindividual coefficients of variation (CV) were calculated according to both approaches. With our model, we were able to separate the concentration-time course of 5-FU in plasma, i.e., the AIF, from that of its major catabolite alpha-fluoro-beta-alanine (FBAL). As far as the mean parameter estimates are concerned, the differences between both approaches are not significant. For the liver data, the CV's are almost the same for both approaches. For the parameters concerning the aorta, however, there is a decrease in the CV's by using the population approach. For example, the CV of the central distribution volume of 5-FU was 30% for the individual approach and 18% for the population approach. With the population approach, it is possible to determine the AIF of drugs that undergo metabolic conversion, such as anticancer drugs, from the abdominal aorta visualized on PET images. The population approach helps to overcome noise in individual data. Since no measurements are needed in addition to the PET examination, the suggested method helps to reduce risk and pain for the patients as well as cost and thus facilitates large scale patient studies.
Comparative expression of different antibody formats in mammalian cells and Pichia pastoris (2007)

Generation of recombinant antibody fragments has been advanced by phage display technology but their broad use in biochemical or analytical applications is often hindered by their univalence. For enhancement of functional affinity and overall applicability, the fusion of scFvs (single-chain variable fragments) to IgG constant domains has become an attractive approach. In order to evaluate characteristics and expression behaviour of different IgG-analogous antibody formats, we fused an scFv to different portions of the heavy chain constant region of human IgG1. Two types of antibodies, an scFv-C(H)2-3 antibody and an scFv-C(H)1-3 antibody, a new intermediate with retained C(H)1 domain, were generated with or without an affinity tag for purification. Additionally, the scFv was reconverted into the heterotetrameric IgG molecule. To allow a reliable comparison of expression behaviours of different antibodies, we established vector systems that allow isogenetic and efficient expression of the recombinant antibodies based on site-specific recombination. Upon recombinant expression in mammalian cells and the methylotrophic yeast Pichia pastoris, disulfide-linked and glycosylated oligomers were obtained. Establishment of isogenetic cell lines revealed that the presence of the C(H)1 domain is not critical for secretion efficiency. Reactivity of the different constructs with antigen and Fc receptors was verified by ELISA, surface plasmon resonance approaches, as well as FACS analysis of HEK-293 cells (human embryonic kidney cells) stably transfected with human FcgammaRI (high-affinity IgG receptor) (CD64). In summary, the results obtained provide evidence for comparable behaviour of the different antibody formats and the vectors for isogenetic expression will contribute to a broader application of phage display-derived antibodies.
Images+Weather: Collection, Validation, and Refinement (2015)

The time and location that an image is captured in-directly defines the appearance of the scene. However, for outdoor scenes, the more directly relevant variables that affect image appearance are the scene structure, lo-cal weather conditions, and the position of the sun. In this paper, we present a large dataset of archived time-lapse imagery with associated geo-location and weather annota-tions collected from multiple sources. Through validation via crowdsourcing, we estimate the reliability of this auto-matically gathered data. We use this dataset to investigate the value of direct geo-temporal context for the problem of predicting the scene appearance and show that explicitly incorporating the sun position and weather variables sig-nificantly reduces reconstruction error. 1.
Protein kinase C activity and hexamethylenebisacetamide-induced erythroleukemia cell differentiation. (1987)

Hexamethylenebisacetamide (HMBA) is a potent inducer of murine erythroleukemia (MEL) cell differentiation. The mechanism of action of HMBA is not known. In this study we provide evidence that protein kinase C has a role in inducer-mediated MEL cell differentiation: (i) HMBA induces the formation of a soluble, proteolytically activated form of protein kinase C that is catalytically active in the absence of Ca2+ and phospholipid; (ii) the protease inhibitor leupeptin blocks formation of this activated form of the kinase and inhibits HMBA-induced MEL cell hemoglobin accumulation; (iii) phorbol 12-myristate 13-acetate (PMA) inhibits HMBA-induced MEL differentiation and causes depletion of total protein kinase C activity; (iv) MEL cells depleted in protein kinase C activity by culture with PMA are resistant to induction by HMBA; (v) upon removal of PMA, restoration of MEL cell sensitivity to HMBA is correlated with reaccumulation of protein kinase C activity; and (vi) MEL cells grown to density arrest are both depleted of protein kinase C activity and resistant to HMBA. Together, these results suggest that HMBA-mediated MEL cell differentiation involves a protein kinase C-related mechanism and the proteolytically activated form of the kinase, which does not require Ca2+ or phospholipid for its catalytic activity.
Self-written waveguide in methylene blue sensitized poly(vinyl alcohol)/acrylamide photopolymer material (2008)

We report the observation of a self-written waveguide inside a bulk methylene blue sensitized poly/vinyl alcohol)/acrylamide photopolymer material. Light from a low power He-Ne laser is focused into the material, and the evolution of the beam is monitored. The refractive index of the material is modulated in the region of high intensity due to photobleaching and photopolymerization effects occurring in the material. As a result, the beam propagates through the medium without any diffraction effects.
Program restructuring for virtual memory (1971)

Our general experience so far has shown the display of a virtual memory use pattern to be a good diagnostic tool. The automatic sector reordering technique brings noticeable improvements in paging performance where there is room for improvement, reducing the necessary working space (for a given number of exceptions) by as much as one-third to one-half. We have worked entirely in the environment of a simple hierarchy of main memory and a uniform speed replacement memory, with all replacement blocks having the same size. We have found that the reordering process, assuming a page size of 4K bytes, also produces improvements on pages of 8K and 2K bytes with the improvements favoring the doubled page size over the halved. This is consistent with a tendency we have noticed in the programs we have examined for better packed memory to favor larger page sizes. But the page size for clustering bears a direct relationship to the program sectors themselves. It has not proved effective to cluster at the physical page size when the average sector size is half as large or more. The optimal page size for a program depends on (besides physical I/O timings) complicated patterns in the use of virtual memory, about which very little is known.
Escaping Antiangiogenic Therapy: Strategies Employed by Cancer Cells (2016)

Tumor angiogenesis is widely recognized as one of the "hallmarks of cancer". Consequently, during the last decades the development and testing of commercial angiogenic inhibitors has been a central focus for both basic and clinical cancer research. While antiangiogenic drugs are now incorporated into standard clinical practice, as with all cancer therapies, tumors can eventually become resistant by employing a variety of strategies to receive nutrients and oxygen in the event of therapeutic assault. Herein, we concentrate and review in detail three of the principal mechanisms of antiangiogenic therapy escape: (1) upregulation of compensatory/alternative pathways for angiogenesis; (2) vasculogenic mimicry; and (3) vessel co-option. We suggest that an understanding of how a cancer cell adapts to antiangiogenic therapy may also parallel the mechanisms employed in the bourgeoning tumor and isolated metastatic cells delivering responsible for residual disease. Finally, we speculate on strategies to adapt antiangiogenic therapy for future clinical uses.
Experimental bacterial endocarditis. II. Survival of a bacteria in endocardial vegetations. (1972)

A method has been developed for assessing metabolic activity of bacteria in the vegetations of bacterial endocarditis using a labelled metabolite and autoradiography. Evidence provided by this technique suggests that there are different degrees of activity between superficial and more deeply placed bacterial colonies, and that variations in activity also exist within a single group of organisms. The possible relevance of these findings to the antibiotic therapy of endocarditis is discussed.
A universal method to produce in vitro transcripts with homogeneous 3' ends (2002)

A method is described that allows a general drawback of in vitro transcription assays to be overcome: RNA polymerases tend to add extra nucleotides to the RNA 3' end that are not encoded in the linearized DNA template. Furthermore, these polymerases show a considerable rate of premature termination close to the RNA's 3' end. These features lead to a decreased yield of full-length transcripts and often make it difficult to determine and isolate the correctly transcribed full-length RNA. The hammerhead ribozyme is frequently used in cis to cleave off these extra nucleotides. However, the upstream sequence requirements of this ribozyme restrict its general usability. In contrast, the hepatitis delta virus ribozyme has no such requirements and can therefore be applied to any RNA sequence in cis. Due to the catalytic activity of the ribozyme, the desired transcript is released as an RNA molecule with a homogeneous 3' end. The resulting 2',3'-cyclo-phosphate group of the released RNA can be easily and efficiently removed by T4 polynucleotide kinase treatment. The presented method can be applied for virtually any sequence to be transcribed and is therefore superior to other ribozyme strategies, suggesting possible applications in every field where transcripts with homogeneous 3' ends are required.
T‐Helper Epitopes on Human Nicotinic Acetylcholine Receptor in Myasthenia Gravisa (1993)

The synthesis of AChR antibodies requires intervention of AChR-specific Th cells. Because of the paucity of anti-AChR Th cells in the blood of myasthenia gravis (MG) patients, direct studies of these autoimmune cells in the blood are seldom possible. Propagation in vitro of anti-AChR T cells from MG patients by cycles of stimulation with AChR antigens selectively enriches and expands the autoimmune T-cell clones, allowing investigation of their function and epitope specificity. Torpedo electroplax AChR was initially used for propagation of anti-AChR T-cell lines. Those studies demonstrated the feasibility of in vitro propagation of AChR-specific T cells. These are bona fide CD4+ Th cells, which stimulate production in vitro of anti-AChR antibodies by B cells of myasthenic patients and recognize equally well denatured and native AChR, suggesting the usefulness of synthetic human AChR sequences as antigens for propagation of the autoimmune Th cells. We used pools of overlapping synthetic peptides, corresponding to the complete sequences of the human AChR alpha-, beta-, gamma-, and delta-subunits, to propagate AChR-specific Th cells from the blood of MG patients. The AChR sequence regions forming epitopes recognized by the autoimmune T cells were determined by challenging the lines with individual synthetic peptides, 20 residues long, screening the AChR subunit sequences. Although each line had an individual pattern of epitope recognition--as expected from their different HLA-DR haplotype--some peptides were recognized by most of all the CD4+ T-cell lines, irrespective of their DR haplotype. The existence of immunodominant regions of the AChR sequence was verified by investigating the response of unselected CD4+ cells from the blood of a relatively large number of MG patients to the individual peptides screening the human alpha-, gamma-, and delta-subunit sequences. Those studies confirmed that each patient has an individual pattern of peptide recognition. The studies also identified a large number of T epitopes of the human AChR and verified the existence of sequence regions immunodominant for T-helper sensitization, because a limited number of sequence regions, including all those immunodominant for the T-helper lines, were recognized by most patients. Anti-AChR CD4+ T lines could be propagated from some healthy controls only for a brief period of time. They recognized AChR sequences poorly, suggesting a low affinity of their T-cell receptors for the corresponding AChR epitopes.(ABSTRACT TRUNCATED AT 400 WORDS)