gebhart/patrepeval huggingface dataset:
Selective replication and oncolysis in p53 mutant tumors with ONYX-015, an E1B-55kD gene-deleted adenovirus, in patients with advanced head and neck cancer: a phase II trial. (2000)

ONYX-015 is an E1B-55kDa gene-deleted adenovirus engineered to selectively replicate in and lyse p53-deficient cancer cells. To evaluate the selectivity of ONYX-015 replication and cytopathic effects for the first time in humans, we carried out a Phase II clinical testing of intratumoral and peritumoral ONYX-015 injection in 37 patients with recurrent head and neck carcinoma. Patients received ONYX-015 at a daily dose of 1 x 10(10) plaque-forming units (pfu) via intratumoral injection for 5 days during week 1 of each 3-week cycle (n = 30; cohort A), or 1 x 10(10) pfu twice a day for 10 days during weeks 1 and 2 of each 3-week cycle. Posttreatment biopsies documented selective ONYX-015 presence and/or replication in the tumor tissue of 7 of 11 patients biopsied on days 5-14, but not in immediately adjacent normal tissue (0 of 11 patients; P = 0.01). Tissue destruction was also highly selective; significant tumor regression (>50%) occurred in 21% of evaluable patients, whereas no toxicity to injected normal peritumoral tissues was demonstrated. p53 mutant tumors were significantly more likely to undergo ONYX-015-induced necrosis (7 of 12) than were p53 wild-type tumors (0 of 7; P = 0.017). High neutralizing antibody titers did not prevent infection and/or replication within tumors. ONYX-015 is the first genetically engineered replication-competent virus to demonstrate selective intratumoral replication and necrosis in patients. This agent demonstrates the promise of replication-selective viruses as a novel therapeutic platform against cancer.
Temporal genetic program following B-cell receptor cross-linking: altered balance between proliferation and death in healthy and malignant B cells (2007)

Gene expression in cells is a dynamic process but is usually examined at a single time point. We used gene expression profiling over time to build temporal models of gene transcription after B-cell receptor (BCR) signaling in healthy and malignant B cells and chose this as a model since BCR cross-linking induces both cell proliferation and apoptosis, with increased apoptosis in chronic lymphocytic leukemia (CLL) compared to healthy B cells. To determine the basis for this, we examined the global temporal gene expression profile for BCR stimulation and developed a linear combination method to summarize the effect of BCR simulation over all the time points for all patients. Functional learning identified common early events in healthy B cells and CLL cells. Although healthy and malignant B cells share a common genetic pattern early after BCR signaling, a specific genetic program is engaged by the malignant cells at later time points after BCR stimulation. These findings identify the molecular basis for the different functional consequences of BCR cross-linking in healthy and malignant B cells. Analysis of gene expression profiling over time may be used to identify genes that might be rational targets to perturb these pathways.
Recent Developments in Paper-Based Microfluidic Devices (2014)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTRecent Developments in Paper-Based Microfluidic DevicesDavid M. Cate†, Jaclyn A. Adkins‡, Jaruwan Mettakoonpitak‡, and Charles S. Henry*†‡View Author Information† Department of Biomedical Engineering, Colorado State University, Fort Collins, Colorado 80523, United States‡ Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, United States*E-mail: [email protected]. Phone: +1-970-491-2852.Cite this: Anal. Chem. 2015, 87, 1, 19–41Publication Date (Web):November 6, 2014Publication History Published online21 November 2014Published inissue 6 January 2015https://pubs.acs.org/doi/10.1021/ac503968phttps://doi.org/10.1021/ac503968preview-articleACS PublicationsCopyright © 2014 American Chemical SocietyRequest reuse permissionsArticle Views23852Altmetric-Citations980LEARN 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 SUBJECTS:Electrodes,Hydrophobicity,Inkjet printing,Manufacturing,Reagents Get e-Alerts
Behavioral effects of centrally administered arginine vasopressin in the rat fetus. (1994)

Arginine8 vasopressin (AVP) was administered to rat fetuses on Embryonic Day 20 via intracisternal (IC), intrahemispheric (IH), or intrathecal (IT) injection. The IC administration of AVP promoted a 4-fold increase in motor activity, including the uncommon patterns of mouthing, licking, and facial wiping. The IH injection of AVP had little effect on fetal behavior, but IT injection resulted in pronounced increases in fetal activity, including mouthing, licking, and wiping. The IT administration of a V1 antagonist blocked AVP effects, whereas IH injection potentiated AVP-induced changes in fetal behavior. The IC blockade of V1 receptors suppressed facial wiping to a chemosensory fluid (lemon) and reduced oral grasping of an artificial nipple, whereas IH injection of the V1 antagonist promoted facial wiping responses and increased grasping of the nipple. These data suggest that AVP may play a role in the development of responsiveness to stimuli encountered in the context of suckling.
Effect of Intermittent Cyclical Etidronate Therapy on Bone Mass and Fracture Rate in Women with Postmenopausal Osteoporosis (1990)

STORE, TOMMY; THAMSBORG, GORM; STEINICHE, TORBEN; GENANT, HARRY K.; SØRENSEN, OLE HELMER Author Information
Modification and transfer into an embryonal carcinoma cell line of a 360-kilobase human-derived yeast artificial chromosome. (1990)

A neomycin resistance cassette was integrated into the human-derived insert of a 360-kilobase yeast artificial chromosome (YAC) by targeting homologous recombination to Alu repeat sequences. The modified YAC was transferred into an embryonal carcinoma cell line by using polyethylene glycol-mediated spheroplast fusion. A single copy of the human sequence was introduced intact and stably maintained in the absence of selection for over 40 generations. A substantial portion of the yeast genome was retained in hybrids in addition to the YAC. Hybrid cells containing the YAC retained the ability to differentiate when treated with retinoic acid. This approach provides a powerful tool for in vitro analysis because it can be used to modify any human DNA cloned as a YAC and to transfer large fragments of DNA intact into cultured mammalian cells, thereby facilitating functional studies of genes in the context of extensive flanking DNA sequences.
Estrogen Receptors α and β Form Heterodimers on DNA (1997)

The estrogen receptor (ER) is expressed in two forms, ERalpha and ERbeta. Here we show that ERalpha and ERbeta, expressed both in vitro and in vivo, form heterodimers which bind to DNA with an affinity (Kd of approximately 2 nM) similar to that of ERalpha and greater than that of ERbeta homodimers. Mutation analysis of the hormone binding domain of ERalpha suggests that the dimerization interface required to form heterodimers with ERbeta is very similar but not identical to that required for homodimer formation. The heterodimer, like the homodimers, are capable of binding the steroid receptor coactivator-1 when bound to DNA and stimulating transcription of a reporter gene in transfected cells. Given the relative expression of ERalpha and ERbeta in tissues and the difference in DNA binding activity between ERalpha/ERbeta heterodimers and ERbeta it seems likely that the heterodimer is functionally active in a subset of target cells.
Lipopolysaccharide (LPS)-binding protein accelerates the binding of LPS to CD14. (1994)

CD14 is a 55-kD protein found as a glycosylphosphatidylinositol (GPI)-anchored protein on the surface of monocytes, macrophages, and polymorphonuclear leukocytes, and as a soluble protein in the blood. Both forms of CD14 participate in the serum-dependent responses of cells to bacterial lipopolysaccharide (LPS). While CD14 has been described as a receptor for complexes of LPS with LPS-binding protein (LBP), there has been no direct evidence showing whether a ternary complex of LPS, LBP, and CD14 is formed, or whether CD14 binds LPS directly. Using nondenaturing polyacrylamide gel electrophoresis (native PAGE), we show that recombinant soluble CD14 (rsCD14) binds LPS in the absence of LBP or other proteins. Binding of LPS to CD14 is stable and of low stoichiometry (one or two molecules of LPS per rsCD14). Recombinant LBP (rLBP) does not form detectable ternary complexes with rsCD14 and LPS, but it does accelerate the binding of LPS to rsCD14. rLBP facilitates the interaction of LPS with rsCD14 at substoichiometric concentrations, suggesting that LBP functions catalytically, as a lipid transfer protein. Complexes of LPS and rsCD14 formed in the absence of LBP or other serum proteins strongly stimulate integrin function on PMN and expression of E-selectin on endothelial cells, demonstrating that LBP is not necessary for CD14-dependent stimulation of cells. These results suggest that CD14 acts as a soluble and cell surface receptor for LPS, and that LBP may function primarily to accelerate the binding of LPS to CD14.
A Nyquist-rate pixel-level ADC for CMOS image sensors (1999)

A multichannel bit-serial (MCBS) analog-to-digital converter (ADC) is presented. The ADC is ideally suited to pixel-level implementation in a CMOS image sensor. The ADC uses successive comparisons to output one bit at a time simultaneously from all pixels. It is implemented using a 1-bit comparator/latch pair per pixel or per group of neighboring pixels, and a digital-to-analog-converter/controller shared by all pixels. The comparator/latch pair operates at very slow speeds and can be implemented using simple robust circuits. The ADCs can be fully tested by applying electrical signals without any optics or light sources. A CMOS 320/spl times/256 sensor using the MCBS ADC is described. The chip measures 4.14/spl times/5.16 mm/sup 2/. It achieves 10/spl times/10 /spl mu/m/sup 2/ pixel size at 28% fill factor in 0.35 /spl mu/m CMOS technology. Each 2/spl times/2 pixel block shares an ADC. The pixel block circuit comprises 18 transistors. It operates in subthreshold to maximize gain and minimize power consumption. The power consumed by the sensor array is 20 mW at 30 frames/s. The measured integral nonlinearity is 2.3 LSB, and differential nonlinearity is 1.2 LSB at eight bits of resolution. The standard deviation of the gain and offset fixed pattern noise due to the ADC are 0.24 and 0.2%, respectively.
Electroinitiated polymerization of acrylamide in acetonitrile medium (1988)

Abstract The electroinitiated polymerization of acrylamide (AA) has been studied in acetonitrile medium using tetrabutylammonium perchlorate (TBAP) as the electrolyte. Split‐cell experiments showed that the polymer formation takes place both in the anode and the cathode compartments. The polymer yield depends on several factors such as the magnitude of the current flow, the duration of the electrolysis, the monomer concentration, the electrolyte concentration, the temperature of the solution, presence or absence of air, and finally whether or not the cell content was stirred. The current exponent of the polymerization was 0.28 with a reaction rate constant of 1.06 reaction % per hour. The IR and NMR spectra of the polymers suggest that the anodic polymer is polyacrylamide and the cathodic polymer is poly‐β‐alanine (CH 2 CH 2 CONH). Based on the experimental results, a radical mechanism for the anodic polymerization and an anionic mechanism for the cathodic polymerization have been proposed.
Phase II study of carboxyamidotriazole in patients with advanced renal cell carcinoma refractory to immunotherapy (2005)

Patients in trials of second-line therapy appear to have a better prognosis than previously considered, in part because they are eligible for another clinical trial. CAI was found to have little to no effect on the natural history of progressive RCC.
The Multifunctional Calcium/Calmodulin-Dependent Protein Kinase: From Form to Function (1995)

The regulation of cellular function by hormones and extracellular molecules, which bind to cell surface receptors, is initiated by signal transduction mech­ anisms at the plasma membrane that lead to the generation of intracellular signals, or second messengers. These second messengers interact with specific target molecules to initiate a cascade of biochemical events leading to a change in cellular function. A variety of intracellular second messengers, including divalent metals, phospholipid metabolites, and cyclic nucleotides, are known to be generated in response to extracellular stimuli. Calcium acts as an intra­ cellular second messenger in species as diverse as yeast to humans and is involved in cellular processes ranging from contraction to secretion to gene expression. Elevation of cytosolic calcium can occur by influx via regulated ion channels and transporters, or by release from intracellular stores via recep­ tor-generated second messengers (Figure 1). Cells contain a number of intra­ cellular calcium-binding proteins, and in most cell types, the major calcium­ binding protein is calmodulin (44, 91), an -17 kDa, heat-stable protein that binds four calcium ions with an overall high affinity of -1 11 M. This complex of 4(Ca)-calmodulin activates downstream targets. Although the importance of calcium as an intracellular messenger has been long recognized, identifica-
Real-Time Quantitative PCR Detection of Four Human Bocaviruses (2010)

Human bocavirus (HBoV) was discovered in 2005 and is associated with respiratory tract symptoms in young children. Three additional members of the genus Bocavirus, HBoV2, -3, and -4, were discovered recently from fecal specimens, and early results indicate an association between HBoV2 and gastrointestinal disease. In this study, we present an undifferentiating multiplex real-time quantitative PCR assay for the detection of these novel viruses. Differentiation of the individual bocavirus species can be subsequently achieved with corresponding singleplex PCRs or by sequencing. Both multiplex and singleplex assays were consistently able to detect ≤10 copies of HBoV1 to -4 plasmid templates/reaction, with dynamic quantification ranges of 8 logs and 97% to 102% average reaction efficiencies. These new assays were used to screen stool samples from 250 Finnish patients (median age, 40 years) that had been sent for diagnosis of gastrointestinal infection. Four patients (1.6%; median age, 1.1 years) were reproducibly positive for HBoV2, and one patient (0.4%; 18 years of age) was reproducibly positive for HBoV3. The viral DNA loads varied from <10(3) to 10(9) copies/ml of stool extract. None of the stool samples harbored HBoV1 or HBoV4. The highly conserved sequence of the hydrolysis probe used in this assay may provide a flexible future platform for the quantification of additional, hitherto-unknown human bocaviruses that might later be discovered. Our results support earlier findings that HBoV2 is a relatively common pathogen in the stools of diarrheic young children, yet does not often occur in the stools of adults.
Emerging viral diseases of fish and shrimp (2010)

The rise of aquaculture has been one of the most profound changes in global food production of the past 100 years. Driven by population growth, rising demand for seafood and a levelling of production from capture fisheries, the practice of farming aquatic animals has expanded rapidly to become a major global industry. Aquaculture is now integral to the economies of many countries. It has provided employment and been a major driver of socio-economic development in poor rural and coastal communities, particularly in Asia, and has relieved pressure on the sustainability of the natural harvest from our rivers, lakes and oceans. However, the rapid growth of aquaculture has also been the source of anthropogenic change on a massive scale. Aquatic animals have been displaced from their natural environment, cultured in high density, exposed to environmental stress, provided artificial or unnatural feeds, and a prolific global trade has developed in both live aquatic animals and their products. At the same time, over-exploitation of fisheries and anthropogenic stress on aquatic ecosystems has placed pressure on wild fish populations. Not surprisingly, the consequence has been the emergence and spread of an increasing array of new diseases. This review examines the rise and characteristics of aquaculture, the major viral pathogens of fish and shrimp and their impacts, and the particular characteristics of disease emergence in an aquatic, rather than terrestrial, context. It also considers the potential for future disease emergence in aquatic animals as aquaculture continues to expand and faces the challenges presented by climate change.
Regulatory roles of ganglioside GQ1b in neuronal cell differentiation of mouse embryonic stem cells (2011)

Gangliosides play an important role in neuronal differentiation processes. The regulation of ganglioside levels is related to the induction of neuronal cell differentiation. In this study, the ST8Sia5 gene was transfected into mESCs and then differentiated into neuronal cells. Interestingly, ST8Sia5 gene transfected mESCs expressed GQ1b by HPTLC and immunofluorescence analysis. To investigate the effects of GQ1b over-expression in neurogenesis, neuronal cells were differentiated from GQ1b expressing mESCs in the presence of retinoic acid. In GQ1b expressing mESCs, increased EBs formation was observed. After 4 days, EBs were co-localized with GQ1b and nestin, and GFAP. Moreover, GQ1b co-localized with MAP-2 expressing cells in GQ1b expressing mESCs in 7-day-old EBs. Furthermore, GQ1b expressing mESCs increased the ERK1/2 MAP kinase pathway. These results suggest that the ST8Sia5 gene increases ganglioside GQ1b and improves neuronal differentiation via the ERK1/2 MAP kinase pathway.
Resistance to root‐knot nematode in tomato roots expressing a nematicidal Bacillus thuringiensis crystal protein (2007)

Our laboratory has demonstrated previously that Bacillus thuringiensis (Bt) crystal (Cry) proteins present in the Cry5 and Cry6 subclades intoxicate free-living nematodes. In this study, we tested whether the expression of nematicidal Cry6A in transgenic plants provided protection against plant-parasitic nematodes. As bacterial codon usage is incompatible with expression in plants, two different codon-modified cry6A genes were synthesized for expression in plants. One was designed by maintaining codon diversity whilst removing codons not common in plants, and the other was designed by selecting the optimal codon for each amino acid based on the Arabidopsis genome. Both versions of the cry6A gene, driven by the constitutive cauliflower mosaic virus 35S promoter, were introduced into tomato roots via Agrobacterium rhizogenes. Although both were found to express Cry6A protein, the codon diversity gene generated superior expression. These Cry6A-expressing roots were then challenged with root-knot nematode, Meloidogyne incognita. Three different infection parameters were compared between Cry6A-expressing roots and control roots transformed with empty vector or green fluorescent protein (GFP). These data demonstrated that M. incognita was able to ingest the 54-kDa Cry6A, and that Cry6A intoxicated the parasitic nematode, as indicated by a decrease in progeny production of up to fourfold. These results indicate, for the first time, that a Bt Cry protein can confer plant resistance to an endoparasitic nematode, and that Cry proteins have the potential to control plant-parasitic nematodes in transgenic plants.
Genetic Therapeutic Approaches for Duchenne Muscular Dystrophy (2012)

Despite an expansive wealth of research following the discovery of the DMD gene 25 years ago, there is still no curative treatment for Duchenne muscular dystrophy. However, there are currently many promising lines of research, including cell-based therapies and pharmacological reagents to upregulate dystrophin via readthrough of nonsense mutations or by upregulation of the dystrophin homolog utrophin. Here we review genetic-based therapeutic strategies aimed at the amelioration of the DMD phenotype. These include the reintroduction of a copy of the DMD gene into an affected tissue by means of a viral vector; correction of the mutated DMD transcript by antisense oligonucleotide-induced exon skipping to restore the open reading frame; and direct modification of the DMD gene at a chromosomal level through genome editing. All these approaches are discussed in terms of the more recent advances, and the hurdles to be overcome if a comprehensive and effective treatment for DMD is to be found. These hurdles include the need to target all musculature of the body. Therefore any potential treatment would need to be administered systemically. In addition, any treatment needs to have a long-term effect, with the possibility of readministration, while avoiding any potentially detrimental immune response to the vector or transgene.
Characterization of an Intrinsically Fluorescent Gonadotropin-Releasing Hormone Receptor and Effects of Ligand Binding on Receptor Lateral Diffusion (1999)

The GnRH receptor (GnRHR) is a G protein-coupled receptor expressed by gonadotropes in the anterior pituitary gland.In the past several years, much has been learned about the structure-function relationships that exist in this receptor with regard to ligand binding and signal transduction.However, the lack of specific antibodies has precluded any analyses of the behavior of the unbound form of this receptor.We have constructed a functional GnRHR in which enhanced green fluorescent protein is fused to the carboxyl-terminus of the murine GnRHR.This fusion receptor was expressed diffusely throughout the cell, with approximately 38% of the fusion receptors colocalized with a plasma membrane marker in the gonadotropederived T3 cell line, and approximately 82% of the fusion receptors colocalized with a membrane marker in Chinese hamster ovary cells.Furthermore, the fusion receptor displayed a K d of 0.8 nM for iodinated des-Gly 10 ,D-Ala-6 -GnRH N-ethyl amide in Chinese hamster ovary cells, which was similar to the K d of the native GnRHR ex-