gebhart/patrepeval huggingface dataset:
Generation of Destabilized Green Fluorescent Protein as a Transcription Reporter (1998)

The green fluorescent protein (GFP) is a widely used reporter in gene expression and protein localization studies. GFP is a stable protein; this property allows its accumulation and easy detection in cells. However, this stability also limits its application in studies that require rapid reporter turnover. We created a destabilized GFP for use in such studies by fusing amino acids 422-461 of the degradation domain of mouse ornithine decarboxylase (MODC) to the C-terminal end of an enhanced variant of GFP (EGFP). The fusion protein, unlike EGFP, was unstable in the presence of cycloheximide and had a fluorescence half-life of 2 h. Western blot analysis indicated that the fluorescence decay of EGFP-MODC-(422-461) was correlated with degradation of the fusion protein. We mutated key amino acids in the PEST sequence of EGFP-MODC-(422-461) and identified several mutants with variable half-lives. The suitability of destabilized EGFP as a transcription reporter was tested by linking it to NFkappaB binding sequences and monitoring tumor necrosis factor alpha-mediated NFkappaB activation. We obtained time course induction and dose response kinetics similar to secreted alkaline phosphatase obtained in transfected cells. This result did not occur when unmodified EGFP was used as the reporter. Because of its autofluorescence, destabilized EGFP can be used to directly correlate gene induction with biochemical change, such as NFkappaB translocation to the nucleus.
Interaction of Dbf4, the Cdc7 Protein Kinase Regulatory Subunit, with Yeast Replication Origins in Vivo (1994)

DNA replication in the budding yeast Saccharomyces cerevisiae initiates from origins of specific DNA sequences during S phase. A screen based on two- and one-hybrid approaches demonstrates that the product of the DBF4 gene interacts with yeast replication origins in vivo. The Dbf4 protein interacts with and positively regulates the activity of the Cdc7 protein kinase, which is required for entry into S phase in the yeast mitotic cell cycle. The analysis described here suggests a model in which one function of Dbf4 may be to recruit the Cdc7 protein kinase to initiation complexes.
Expression of inducible nitric oxide synthase (iNOS/NOS II) in the vestibule of guinea pigs after the application of cisplatin (2000)

It is well known that the anti-cancer drug cisplatin has an ototoxic property; however, the details are not yet evident. In this study, the expression of inducible nitric oxide synthase (INOS/NOS II) in the vestibule of guinea pigs after i.p. injections of cisplatin was examined immunohistochemically. Three days after the injection of cisplatin (10 mg/kg) or placebo, animals were sacrificed. Then the temporal bones were removed and subjected to Immunohistochemical studies for iNOS. In the cisplatin group, INOS was detectable, whereas the tissue in the control group was negative for iNOS. The vestibule, the wall of blood vessels and the vestibular ganglion cells showed immunoreactivity for iNOS. It is known that INOS catalyzes an inadequate quantity of NO under pathological conditions. Increased NO levels lead to inner ear dysfunction. Therefore, our results indicate that iNOS could also mediate the vestibulo-toxicity of cisplatin.
ChemInform Abstract: Reactions of Furo(3,2‐b)pyrroles and Their Benzo(b) Analogues. (1988)

Abstract Treatment of the ethoxycarbonylfuropyrroles (I) with acetic anhydride (II) yields the N‐acetyl derivatives (III), whereas the corresponding carboxylic acids (VIII) react with (II) under decarboxylation to give (IX) and dimerization, forming the pyrazinedione (Xb).
Preliminary Evaluation of an Aqueous Wax Emulsion for Controlled-Release Coating (1998)

The purpose of this work was to evaluate the use of an aqueous carnauba wax emulsion (Primafresh HS, Johnson Wax) in a spray-coating process. This involved assessing the effectiveness of the wax in sustaining the release of the drug, theophylline. Second, the process by which the drug was released from the wax-coated pellets was modeled. Finally, a method to determine the optimum blend of pellets with different wax thicknesses, in order to yield a zero-order release profile of the drug, was addressed. Nonpareil pellets were loaded with theophylline using a novel powder coating technique. These drug-loaded pellets were then coated with different levels of carnauba wax in a 6-in. diameter Plexiglas fluid bed with a 3.5-in. diameter Wurster partition. Drug release was measured using a spin-filter dissolution device. The study resulted in continuous carnauba wax coatings which showed sustained drug release profile characteristics typical of a barrier-type, diffusion-controlled system. The effect of varying wax thickness on the release profiles was investigated. It was observed that very high wax loadings would be required to achieve long sustained-release times. The diffusion model, developed to predict the release of the drug, showed good agreement with the experimental data. However, the data exhibited an initial lag-time for drug release which could not be predicted a priori based on the wax coating thickness. A method of mixing pellets with different wax thicknesses was proposed as a way to approximate zero-order release.
Inertial fusion science and technology for the next century (1999)

This paper reviews the leading edge of the basic and applied science and technology that use high-intensity facilities and looks at what opportunities lie ahead. The more than 15,000 experiments on the Nova laser since 1985 and many thousands more on other laser, particle beam, and pulsed power facilities around the world have established the new laboratory field of high-energy-density plasma physics and have furthered development of inertial fusion. New capabilities such as those provided by high-brightness femtosecond lasers have enabled the study of matter in conditions previously unachievable on earth. These experiments, along with advanced calculations now practical because of the progress in computing capability, have established the specifications for the National Ignition Facility and Laser MegaJoule and have enhanced new scientific fields such as laboratory astrophysics. Science and technology developed in inertial fusion have found near-term commercial use, have enabled steady progress toward the goal of fusion ignition and gain in the laboratory, and have opened up new fields of study for the 21st century.
The 4+1 View Model of architecture (1995)

The 4+1 View Model organizes a description of a software architecture using five concurrent views, each of which addresses a specific set of concerns. Architects capture their design decisions in four views and use the fifth view to illustrate and validate them. The logical view describes the design's object model when an object-oriented design method is used. To design an application that is very data driven, you can use an alternative approach to develop some other form of logical view, such as an entity-relationship diagram. The process view describes the design's concurrency and synchronization aspects. The physical view describes the mapping of the software onto the hardware and reflects its distributed aspect. The development view describes the software's static organization in its development environment.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Iron chelator, exopolysaccharide and protease production in Staphylococcus epidermidis: a comparative study of the effects of specific growth rate in biofilm and planktonic culture (1994)

The growth rate of Staphylococcus epidermidis was controlled for populations growing as a biofilm and perfused with supplemented, simple-salts medium. Production of iron chelators, extracellular protease and exopolysaccharide (EPS) by these populations was assessed as a function of specific growth rate and compared to that by planktonic populations grown in the same medium within a chemostat. Perfused biofilms increased their iron chelator and protease production with increasing growth rate. Chemostat populations decreased their production of iron chelators with increasing growth rate, whilst showing much enhanced production of proteases at intermediate growth rates (mu 0.15-0.25 h-1). Production of iron chelator and protease was generally 2-50 times higher by biofilms than by planktonic populations. EPS production was low and relatively unaffected by growth rate for the chemostat cultures (about 0.2 micrograms per unit cell mass) but high for the attached biofilms, particularly at slow growth rates (about 4 micrograms per unit cell mass). EPS production within the biofilms decreased markedly with increasing growth rate. At growth rates of 0.35 h-1 and above, the levels of EPS for biofilms and planktonic populations were equivalent. The results of this study clearly indicate that growth as a biofilm markedly influences extracellular virulence factor production by S. epidermidis.
Pilot Study of a 213Bismuth-Labeled Anti-CD45 mAb as a Novel Nonmyeloablative Conditioning for DLA-Haploidentical Littermate Hematopoietic Transplantation (2010)

The results suggest that nonmyeloablative conditioning with (213)Bi-labeled anti-CD45 mAb could be applicable to major histocompatibility haploidentical HCT without excessive nonhematologic regimen-related toxicity.
Improved delivery of Cas9 protein/gRNA complexes using lipofectamine CRISPRMAX (2016)

Lipofectamine CRISPRMAX was characterized as the best lipid nanoparticles for the delivery of Cas9 RNPs into a variety of mammalian cell lines, including mouse ES cells and iPSCs.
Evaluation of Buprenorphine CEDIA Assay versus GC-MS and ELISA using Urine Samples from Patients in Substitution Treatment (2005)

As buprenorphine becomes more clinically used in heroin substitution treatment, there is an increasing need for methods suitable for high-volume screening. In this study, a new immunochemical test based on CEDIA technology was evaluated for the use in clinical urine drug testing. The method was compared with an existing ELISA method and a gas chromatography-mass spectrometry (GC-MS) method on urine specimens from patients in heroin substitution treatment. The precision of the CEDIA assay was < 9% both within- and between-day at levels at and above the cutoff limit of 5 microg/L. The concordance in qualitative results with an existing ELISA method was 96.8%. The CEDIA measuring range was extended by diluting urine samples 100-fold with saline, and the results agreed well (slope of regression line was 1.09, r(2) = 0.968) with GC-MS. The sensitivity of CEDIA in detecting authentic specimen containing buprenorphine at levels >or= 5 microg/L was 99.5%. Cross-reactivity causing false-positive response was discovered in patients receiving prescribed dihydrocodeine. The urine concentration of total buprenorphine in urine from patients prescribed daily doses between 0.2 and 24 mg ranged from 0.5 to 2900 microg/L. The concentration of the metabolite norbuprenorphine was usually higher, and the median ratio of buprenorphine to norbuprenorphine was 0.23 (95% were below 1). We conclude that the CEDIA assay is suitable for application in high-volume screening of buprenorphine for urine drug testing.
Arabidopsis metacaspase 2d is a positive mediator of cell death induced during biotic and abiotic stresses (2011)

Cysteine proteases such as caspases play important roles in programmed cell death (PCD) of metazoans. Plant metacaspases (MCPs), a family of cysteine proteases structurally related to caspases, have been hypothesized to be ancestors of metazoan caspases, despite their different substrate specificity. Arabidopsis thaliana contains six type II MCP genes (AtMCP2a-f). Whether and how these individual members are involved in controlling PCD in plants remains largely unknown. Here we investigated the function and regulation of AtMCP2d, the predominant and constitutively expressed member of type II MCPs, in stress-inducible PCD. Two AtMCP2d mutants (mcp2d-1 and mcp2d-3) exhibited reduced sensitivity to PCD-inducing mycotoxin fumonisin B1 as well as oxidative stress inducers, whereas AtMCP2d over-expressors were more sensitive to these agents, and exhibited accelerated cell-death progression. We found that AtMCP2d exclusively localizes to the cytosol, and its accumulation and self-processing patterns were age-dependent in leaves. Importantly, active proteolytic processing of AtMCP2d proteins dependent on its catalytic activity was observed in mature leaves during mycotoxin-induced cell death. We also found that mcp2d-1 leaves exhibited reduced cell death in response to Pseudomonas syringae carrying avirulent gene avrRpt2, and that self-processing of AtMCP2d was also detected in wild-type leaves in response to this pathogen. Furthermore, increases in processed AtMCP2d proteins were found to correlate with conditional cell-death induction in two lesion-mimic mutants (cpr22 and ssi4) that exhibit spontaneous cell-death phenotypes. Taken together, our data strongly suggest that AtMCP2d plays a positive regulatory role in biotic and abiotic stress-induced PCD.
A rapid and sensitive bioassay for the simultaneous measurement of multiple bone morphogenetic proteins. Identification and quantification of BMP4, BMP6 and BMP9 in bovine and human serum (2009)

The assay is rapid (<48 hours) and can be used to simultaneously measure isoform specific and total BMP activity in complex solutions.
Role of 3'UTR in the regulation of neurotrophic factors BDNF and GDNF (2014)

Neurotrophic factors such as brain¬-derived neurotrophic factor (BDNF) and glial cell line¬¬¬-derived neurotrophic factor (GDNF) are a family of proteins which play an important role inside and outside central nervous system. While precise regulation of BDNF and GDNF levels in time and space in an organism is crucial in determining the biological outcome, mechanisms involved in controlling their levels are not fully understood. \n\nMessenger RNAs (mRNAs) play a critical role in gene expression by conveying genetic information from DNA to protein synthesis. 3ʹ untranslated region (3ʹUTR) is a part of mRNA sequence which regulates gene expression by binding to microRNAs (miRs), RNA-binding proteins (RBPs) and other trans-acting factors. \n\nIn this thesis, we investigated the 3ʹUTR mediated regulation of BDNF and GDNF. We demonstrate the presence of regulatory elements in the 3ʹUTR of BDNF and GDNF and, show that BDNF is regulated by four different miRs, namely miR-1, miR-10b, miR-155 and miR-191 and, RBP tristetraprolin (TTP) in different cell lines. Further, we show that GDNF is regulated by multiple miRs in cell lines and identify binding sites for miR-146a and miR-96 in the GDNF 3ʹUTR. Finally, we demonstrate that replacement of GDNF 3ʹUTR in mice with a 3ʹUTR with reduced responsiveness to negative regulators including miRs leads to elevated level of endogenous GDNF mRNA and protein in various organs with profound biological effects including in the brain dopamine system function in mice. We conclude that 3ʹUTR mediated regulation of BDNF and GDNF is biologically important and propose that 3ʹUTR replacement is an informative way to study gene function in vivo.
The Synthesis and Chelation Chemistry of DOTA−Peptide Conjugates (2007)

Metal complexes of DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid)-peptide conjugates are increasingly used as targeted imaging and therapeutic radiopharmaceuticals and MRI contrast agents. This review covers the bifunctional derivatives of DOTA, the solution and solid-phase synthesis of DOTA-peptide conjugates, their coordination and chelation chemistry, and the biomedical applications of various DOTA-peptide conjugate metal complexes.
Gene therapy of cancer through restoration of tumor-suppressor functions? (1992)

The tools and concepts of gene therapy are being applied to the development of effective new treatments for human cancer. Most human cancers are associated with multiple interacting and cooperating mutations in protooncogenes and tumor suppressor genes. In several model systems, some features of the tumor phenotype can be suppressed in vitro through the restoration of expression of tumor suppressor genes such as Rb and p53. Before this phenomenon can serve as the basis for gene therapy of cancer, many conceptual and technical problems must be solved. Because such genetically modified cells continue to contain and express other mutations, it is important to determine the mechanisms and frequency of reversion to the tumor phenotype. To be clinically useful, highly efficient and targeted gene delivery vectors must be developed. The experimental evidence for tumor suppression by restored gene expression and the pivotal role played by tumor suppressor genes in the regulation of cell replication suggests that restored expression of some tumor suppressor genes in some tumor cells will eventually play a role in cancer gene therapy.
Introduction: From Monumental Fragments to Fragmented Monumentalism (2013)

The author of "Sent to a Young Lady" was fed up with modish headwear; that much is obvious. Such weariness was understandable in the 1820s when one simply could not avoid the Grecian vogue that had saturated English fashion, art, architecture, poetry and political discourse. Moreover, with respect to clothing trends, the author here rightly associates Greek and French influences and, in doing so, he touches on a central controversy of English Hellenism. Although baneful to England in most every way during and after the Waterloo era, France always remained at the vanguard of international taste, and the fact that England's sartorial neoclassicism owed much to the French empire style led some English commentators to view the Grecian craze as decidedly unpatriotic. Still, many subscribers to The Lady's Monthly Museum would have owned various items of clothing à la Grecque and no amount of balladry on bonnets could deter them from the look. In fact, Frenchified dress à la Grecque had gained much publicity over the years in the magazine's own fashion pages, where the promotion of Grecian draping and Sappho-Knot hairstyles overwhelmed any dissension.KeywordsRomantic PeriodGreek LanguageWoman WriterEnglish PoetryGreek WomanThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Synthetic nanopores with fixed charges: An electrodiffusion model for ionic transport (2003)

Synthetic nanopores with fixed charges exhibit ionic equilibrium and transport properties that resemble those displayed by biological ion channels. We present an electrodiffusion model based on the Nernst-Planck flux equations, which allows for a qualitative description of the steady state ionic transport through a nanopore when the membrane fixed charges and all mobile carriers (including the water ions) are properly taken into account. In particular, we study the current-voltage curve, the electrical conductance, the reversal potential (a measure of the nanopore ionic selectivity), as well as the flux inhibition by protons and divalent cations in the nanopore. The model clearly shows how the changes in the ionization state of the fixed charges with pH and salt concentration dictate the electrical properties of the nanopore. The agreement between the model predictions and previous experimental data allows us to identify which are the main characteristics that permit a simple description of this complex system.
Self-Complementary AAV9 Gene Delivery Partially Corrects Pathology Associated with Juvenile Neuronal Ceroid Lipofuscinosis (CLN3) (2016)

Juvenile neuronal ceroid lipofuscinosis (JNCL) is a fatal lysosomal storage disease caused by CLN3 mutations. We explored a gene delivery approach using two self-complementary adeno-associated virus 9 (scAAV9) constructs to address CLN3 dosage effects using the methyl-CpG-binding protein 2 (MeCP2) and β-actin promoters. hCLN3 levels were elevated 3- to 8-fold in Cln3(Δex7/8) mice receiving scAAV9/β-actin-hCLN3 versus scAAV9/MeCP2-hCLN3 after a single systemic injection. However, only scAAV9/MeCP2-hCLN3 corrected motor deficits and attenuated glial activation and lysosomal pathology. This may reflect preferential promoter usage because transgene expression with scAAV9/MeCP2-green fluorescent protein (GFP) was primarily in neurons, whereas scAAV9/β-actin-GFP drove transgene expression in astrocytes. This is the first demonstration of systemic delivery for CLN3 using scAAV9 and highlights the importance of promoter selection for disease modification in juvenile animals.
Proteolytic Actuation of Nanoparticle Self‐Assembly (2006)

Schlafender Riese: Anorganische Nanopartikel in Ruheform, die durch Proteolyse zur Selbstorganisation in Nanostrukturen mit stärkeren magnetischen Eigenschaften aktiviert werden, wurden synthetisiert. Das Binden komplementärer Fe3O4-Nanopartikel wird durch das Anbinden inhibierender Polymere blockiert, die durch an der Krebszelleninvasion und der Metastase beteiligte Proteasen entfernt werden können.
Tri-functional T cell receptor antigen coupler (Tri-TAC): a novel method to direct T cells against tumors (2014)

Meeting abstracts Engineering T cells with chimeric antigen receptors (CARs) is proving to be an effective method for directing T cells to attack tumors in an MHC-independent manner. Current generation CARs aim to recapitulate T cell signaling by incorporating modular functional components of the
Dendrimer‐Entrapped Gold Nanoparticles as a Platform for Cancer‐Cell Targeting and Imaging (2007)

We present a general approach for the targeting and imaging of cancer cells using dendrimer-entrapped gold nanoparticles (Au DENPs). Au DENPs were found to be able to covalently link with targeting and imaging ligands for subsequent cancer-cell targeting and imaging. The Au DENPs linked with defined numbers of folic acid (FA) and fluorescein isothiocyanate (FI) molecules are water soluble, stable, and biocompatible. In vitro studies show that the FA- and FI-modified Au DENPs can specifically bind to KB cells (a human epithelial carcinoma cell line) that overexpress high-affinity folate receptors and they are internalized dominantly into lysosomes of target cells within 2 h. These findings demonstrate that Au DENPs may serve as a general platform for cancer imaging and therapeutics.
Efficient compression and application of deterministic patterns in a logic BIST architecture (2003)

We present a novel method to efficiently generate, compress and apply test patterns in a logic BIST architecture. Patterns are generated by a modified automatic test pattern generator (ATPG) and are encoded as linear feedback shift register (LFSR) initial values (seeds); one or more patterns can be encoded into a single LFSR seed. During test application, seeds are loaded into the LFSR with no cycle overhead. The method presented achieves reductions of at least 100x in test data and 10x in tester cycles compared to deterministic ATPG while maintaining complete fault coverage, as confirmed by experimental results on industrial designs.