gebhart/patrepeval huggingface dataset:
Thalidomide: Emerging Role in Cancer Medicine (2002)

Thalidomide--removed from widespread clinical use by 1962 because of severe teratogenicity--has antiangiogenic and immunomodulatory effects, including the inhibition of tumor necrosis alpha factor. It has now returned to practice as an effective oral agent in the management of various disease states including erythema nodosum leprosum, for which it was approved by the U.S. Food and Drug Administration in 1998, and more recently certain malignancies, including multiple myeloma. Although thalidomide's mechanism of action remains incompletely understood, considerable insight has been generated by extensive preclinical studies in multiple myeloma. Moreover, clinical trials have confirmed benefit in relapsed disease, and the role of thalidomide in treating newly diagnosed patients is currently under study. Its use in other tumors is under evaluation, with promise in renal cell carcinoma, prostate cancer, glioma, and Kaposi's sarcoma. Activity has also been demonstrated in chronic graft-versus-host disease and in symptom relief as part of palliative care.
Quantitative evaluation of liver-specific promoters from retroviral vectors after in vivo transduction of hepatocytes (1994)

Hepatic gene therapy could be used to treat a number of inherited blood diseases such as hemophilia or thrombophilia. Although liver-directed retroviral transduction can result in long-term gene expression in vivo, the low level of protein production has limited its clinical application. We reasoned that the insertion of liver-specific promoters into retroviral vectors would increase gene expression in vivo. The 347- bp human alpha 1-antitrypsin (hAAT), the 810-bp murine albumin (mAIb), the 490-bp rat phosphoenolpyruvate carboxykinase (rPECK), and the 596- bp rat liver fatty acid binding protein promoters were inserted into a Moloney murine leukemia retroviral backbone containing the hAAT reporter gene. Vectors that produced appropriately sized RNA and hAAT protein in vitro were tested in vivo by transducing regenerating rat livers. Long-term serum expression of the hAAT reporter gene was normalized to retroviral transduction efficiency as determined by using a polymerase chain reaction-based assay of genomic DNA from transduced rat livers. The hAAT, mAIb, and rPEPCK promoters were, respectively, 35- , 8-, and 0.02-fold as strong as the previously studied constitutive Pol-II promoter. We conclude that the hAAT promoter resulted in the highest expression from a retroviral vector and may result in therapeutically significant expression of other clinically significant blood proteins.
Homology-Directed Recombination for Enhanced Engineering of Chimeric Antigen Receptor T Cells (2017)

Gene editing by homology-directed recombination (HDR) can be used to couple delivery of a therapeutic gene cassette with targeted genomic modifications to generate engineered human T cells with clinically useful profiles. Here, we explore the functionality of therapeutic cassettes delivered by these means and test the flexibility of this approach to clinically relevant alleles. Because CCR5-negative T cells are resistant to HIV-1 infection, CCR5-negative anti-CD19 chimeric antigen receptor (CAR) T cells could be used to treat patients with HIV-associated B cell malignancies. We show that targeted delivery of an anti-CD19 CAR cassette to the <i>CCR5</i> locus using a recombinant AAV homology template and an engineered megaTAL nuclease results in T cells that are functionally equivalent, in both in vitro and in vivo tumor models, to CAR T cells generated by random integration using lentiviral delivery. With the goal of developing off-the-shelf CAR T cell therapies, we next targeted CARs to the T cell receptor alpha constant (<i>TRAC</i>) locus by HDR, producing TCR-negative anti-CD19 CAR and anti-B cell maturation antigen (BCMA) CAR T cells. These novel cell products exhibited in vitro cytolytic activity against both tumor cell lines and primary cell targets. Our combined results indicate that high-efficiency HDR delivery of therapeutic genes may provide a flexible and robust method that can extend the clinical utility of cell therapeutics.
“HETEROGENIZING” HOMOGENEOUS CATALYSTS (1974)

Abstract For many years, it has been customary to classify catalysts as “homogeneous” or “heterogeneous.” The former commonly operate through the formation of “intermediate compounds,” and the latter, by adsorption of the reactants on the catalyst surface. The line between the two is a fine one, for the distinction between adsorption and compound formation is not at all clear, and seems to be becoming less and less clear as we learn more about adsorption. In recent years, several writers [l-7] have stressed the point that there is a good deal of overlap between homogeneous and heterogeneous catalysis. Experimental evidence supporting this point of view is accumulating, and while we are not prepared to say that there is no distinction, we can say with certainty that many homogeneous catalysts can be converted into heterogeneous ones, retaining the advantages of great activity and selectivity inherent in homogeneity and, at the same time, assuming the ready recovery which is the great advantage of heterogenity. In practice, of course, the matter is not quite that simple, for other factors must be considered. On the whole, however, many advantages have been found in the use of heterogenized homogeneous catalysts.
Modulation of Rho GTPase activity alleviates chondroitin sulfate proteoglycan‐dependent inhibition of neurite extension (2004)

The central nervous system (CNS) fails to regenerate after injury. A glial scar forms at the injury site, contributing to regenerative failure partly resulting from the chondroitin sulfate proteoglycans (CSPGs) in the glial scar. The family of Rho GTPases, which includes Cdc42, Rac1, and RhoA, is involved in growth cone dynamics. Although the response of neural cells to the inactivation of Rho when contacting myelin-related substrates, or CSPG, has been investigated, Rac1's and Cdc42's abilities to modulate CSPG-dependent inhibition have yet to be explored. In this study, a stripe assay was utilized to examine the effects of modulating all three Rho GTPases on neurite extension across inhibitory CSPG lanes. Alternating laminin (LN) and CSPG lanes were created and NG108-15 cells and E9 chick dorsal root ganglia (DRGs) were cultured on the lanes. By using the protein delivery agent Chariot, the neuronal response to exposure of constitutively active (CA) and dominant negative (DN) mutants of the Rho GTPases, along with the bacterial toxin C3, was determined by quantifying the percentage ratio of neurites crossing the CSPG lanes. CA-Cdc42, CA-Rac1, and C3 transferase significantly increased the number of neurites crossing into the CSPG lanes compared with the negative controls for both the NG108-15 cells and the E9 chick DRGs. We also show that these mutant proteins require the delivery vehicle, Chariot, to enter the neurons and affect neurite extension. Therefore, activation of Cdc42 and Rac, as well as inhibition of Rho, helps overcome the CSPG-dependent inhibition of neurite extension.
Carrier frequency offset estimation for OFDM-based WLANs (2001)

We present an efficient carrier frequency offset (CFO) estimation algorithm for the orthogonal frequency-division multiplexing (OFDM)-based wireless local area networks (WLANs). The packet preamble information we use is based on the high rate WLAN standards adopted by the IEEE 802.11 standardization group. Numerical results are presented to demonstrate the effectiveness of the proposed algorithm.
Combining advanced lithographic techniques and self-assembly of thin films of diblock copolymers to produce templates for nanofabrication (2000)

A technique to create templates for nanofabrication using thin films of diblock copolymers is discussed and demonstrated. Advanced lithographic techniques are used to create chemically patterned surfaces that manipulate the wetting behavior of diblock copolymer films and to guide the spatial microphase separation of the block copolymer domains. Guided microphase separation has great potential for application of block copolymer films in nanofabrication because of perpendicular orientation of the domains to the substrate and macroscopic perfection in the ordering of copolymer domains. Lithography allows for registration of the domains with the substrate for creating addressable arrays. Experimental implementation of the technique is demonstrated using extreme ultraviolet interferometric lithography, self-assembled monolayers of octadecyltrichlorosilane as imaging layers, and the self-assembly of films of symmetric poly(styrene-b-methyl methacrylate).
Properties of regular polygons of coupled microring resonators (2007)

The resonant properties of a closed and symmetric cyclic array of N coupled microring resonators (coupled-microring resonator regular N-gon) are for the first time determined analytically by applying the transfer matrix approach and Floquet theorem for periodic propagation in cylindrically symmetric structures. By solving the corresponding eigenvalue problem with the field amplitudes in the rings as eigenvectors, it is shown that, for even or odd N, this photonic molecule possesses 1 + N/2 or 1+N resonant frequencies, respectively. The condition for resonances is found to be identical to the familiar dispersion equation of the infinite coupled-microring resonator waveguide with a discrete wave vector. This result reveals the so far latent connection between the two optical structures and is based on the fact that, for a regular polygon, the field transfer matrix over two successive rings is independent of the polygon vertex angle. The properties of the resonant modes are discussed in detail using the illustration of Brillouin band diagrams. Finally, the practical application of a channel-dropping filter based on polygons with an even number of rings is also analyzed.
Digestibility of selected carbohydrates by anaerobic bacteria (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDigestibility of selected carbohydrates by anaerobic bacteriaAdam W. Mazur, M. Joseph. Mohlenkamp, George. Hiler, Tracy D. Wilkins, and Roger L. Van TassellCite this: J. Agric. Food Chem. 1993, 41, 11, 1925–1930Publication Date (Print):November 1, 1993Publication History Published online1 May 2002Published inissue 1 November 1993https://pubs.acs.org/doi/10.1021/jf00035a022https://doi.org/10.1021/jf00035a022research-articleACS PublicationsRequest reuse permissionsArticle Views121Altmetric-Citations5LEARN 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
Highly Sensitive Fluorescence Probes for Nitric Oxide Based on Boron Dipyrromethene ChromophoreRational Design of Potentially Useful Bioimaging Fluorescence Probe (2004)

Boron dipyrromethene (BODIPY) is known to have a high quantum yield (phi) of fluorescence in aqueous solution but has not been utilized much for biological applications, compared to fluorescein. We developed 8-(3,4-diaminophenyl)-2,6-bis(2-carboxyethyl)-4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene (DAMBO-P(H)), based on the BODIPY chromophore, as a highly sensitive fluorescence probe for nitric oxide (NO). DAMBO-P(H) had a low phi value of 0.002, whereas its triazole derivative (DAMBO-P(H)-T), the product of the reaction of DAMBO-P(H) with NO, fluoresced strongly (phi = 0.74). The change of the fluorescence intensity was found to be controlled by an intramolecular photoinduced electron transfer (PeT) mechanism. The strategy for development of DAMBO-P(H) was as follows: (1) in order to design a highly sensitive probe of NO, the reactivity of o-phenylenediamine derivatives as NO-reactive moieties was examined using 4,5-diaminofluorescein (DAF-2, a widely used NO fluorescence probe), (2) in order to avoid pH-dependency of the fluorescence intensity, the PeT process was controlled by modulating the spectroscopic and electrochemical properties of BODIPY chromophores according to the Rehm-Weller equation based on measurement of excitation energies of chromophores, ground-state reduction potentials of PeT acceptors (BODIPYs), and calculation of the HOMO energy level of the PeT donor (o-phenylenediamine moiety) at the B3LYP/6-31G level, (3) in order to avoid quenching of fluorescence by stacking of the probes and to obtain probes suitable for biological applications, hydrophilic functional groups were introduced. This strategy should be applicable for the rational design of other novel and potentially useful bioimaging fluorescence probes.
77 GHz high-isolation coplanar transmit-receive switch using InGaAs/InP PIN diodes (2002)

InP-based InGaAs PIN millimeter-wave diodes were used to design and fabricate monolithic integrated transmit-receive switches for W-band automotive applications. Coplanar-waveguide InGaAs PIN diode technology with reduced parasitics was employed for fabricating MMICs and yielded switches with high isolation and low insertion loss as shown by the performance of W-band single-pole double-throw switches. 77 GHz SPDT switches demonstrated less than 1.35 dB insertion loss, more than 43 dB input-to-output isolation, and more than 30 dB output-to-output crosstalk. W-band on-wafer large-signal characterization revealed no degradation of performance when the input power was increased to the maximum available level of +11 dBm.
Maize transformation technology development for commercial event generation (2014)

Maize is an important food and feed crop in many countries. It is also one of the most important target crops for the application of biotechnology. Currently, there are more biotech traits available on the market in maize than in any other crop. Generation of transgenic events is a crucial step in the development of biotech traits. For commercial applications, a high throughput transformation system producing a large number of high quality events in an elite genetic background is highly desirable. There has been tremendous progress in Agrobacterium-mediated maize transformation since the publication of the Ishida et al. (1996) paper and the technology has been widely adopted for transgenic event production by many labs around the world. We will review general efforts in establishing efficient maize transformation technologies useful for transgenic event production in trait research and development. The review will also discuss transformation systems used for generating commercial maize trait events currently on the market. As the number of traits is increasing steadily and two or more modes of action are used to control key pests, new tools are needed to efficiently transform vectors containing multiple trait genes. We will review general guidelines for assembling binary vectors for commercial transformation. Approaches to increase transformation efficiency and gene expression of large gene stack vectors will be discussed. Finally, recent studies of targeted genome modification and transgene insertion using different site-directed nuclease technologies will be reviewed.
Efferent synaptic connections of grafted dopaminergic neurons reinnervating the host neostriatum: a tyrosine hydroxylase immunocytochemical study (1985)

In adult rats with a unilateral 6-hydroxydopamine-induced destruction of the nigrostriatal dopamine (DA) pathway, grafts of embryonic substantia nigra can establish a new dopaminergic terminal fiber plexus in the previously denervated neostriatum and compensate for some of the behavioral deficits induced by the nigrostriatal lesion. In the present study the synaptic connections of the ingrowing DA fibers from the graft were analyzed ultrastructurally, using immunocytochemical localization of tyrosine hydroxylase (TH), in animals whose lesion-induced motor asymmetry had been completely compensated for by the nigral grafts. In two of the animals, horseradish peroxidase-wheatgerm agglutinin conjugate was injected into the graft in order to trace possible reciprocal afferent connections to the graft from the host striatum. TH-immunoreactive axons from the graft were seen to make abundant symmetric synapses with neuronal elements in the host neostriatum. Between 85 and 90% of these synapses were on dendritic shafts and spines, and the rest were on neuronal perikarya. Two principal targets were identified: dendrites of spiny neurons, the majority of which are likely to be striatal projection neurons; and the cell bodies of giant neurons, most (or perhaps all) of which are known to be cholinergic interneurons. The synapses made on dendritic spines, which constituted about 40% of all TH-positive synapses formed by the TH-positive neurons in the graft, resembled those seen in normal animals, both in that they made contacts with spine necks and in that they invariably were associated with an asymmetric TH-negative synapse contacting the spine head. The innervation of the giant cell perikarya, which constituted about 6% of all TH-positive synapses found, was strikingly abnormal in that the graft-derived TH-positive fibers formed dense pericellular "baskets" selectively around the giant cell bodies. Such arrangements were never seen in the normal striatum, nor did they occur in the intact contralateral striatum in the grafted animals. It is proposed that this apparent dopaminergic hyperinnervation from the graft could provide a powerful inhibition of the cholinergic interneurons in the reinnervated host striatum, and that such an inhibitory mechanism could assist in the graft-induced functional recovery by potentiating the functional effects of DA synapses terminating on the spiny efferent neurons. This dual innervation may thus help to explain why restoration of only a small proportion of the striatal DA innervation by the graft is sufficient to induce complete compensation of, e.g., motor asymmetry in the lesioned rats.(ABSTRACT TRUNCATED AT 400 WORDS)
Self‐processing 2A‐polyproteins – a system for co‐ordinate expression of multiple proteins in transgenic plants (1999)

Achieving co-ordinate, high-level and stable expression of multiple transgenes in plants is currently difficult. Expression levels are notoriously variable and influenced by factors that act independently on transgenes at different genetic loci. Instability of expression due to loss, re-arrangement or silencing of transgenes may occur, and is exacerbated by increasing numbers of transgenic loci and repeated use of homologous sequences. Even linking two or more genes within a T-DNA does not necessarily result in co-ordinate expression. Linking proteins in a single open reading frame--a polyprotein--is a strategy for co-ordinate expression used by many viruses. After translation, polyproteins are processed into constituent polypeptides, usually by proteinases encoded within the polyprotein itself. However, in foot-and-mouth disease virus (FMDV), a sequence (2A) of just 16-20 amino acids appears to have the unique capability to mediate cleavage at its own C-terminus by an apparently enzyme-independent, novel type of reaction. This sequence can also mediate cleavage in a heterologous protein context in a range of eukaryotic expression systems. We have constructed a plasmid in which the 2A sequence is inserted between the reporter genes chloramphenicol acetyltransferase (CAT) and beta-glucuronidase (GUS), maintaining a single open reading frame. Here we report that expression of this construct in wheatgerm lysate and transgenic plants results in efficient cleavage of the polyprotein and co-ordinate expression of active CAT and GUS. Self-processing polyproteins using the FMDV 2A sequence could therefore provide a system for ensuring co-ordinated, stable expression of multiple introduced proteins in plant cells.
Universal Multiplex PCR: a novel method of simultaneous amplification of multiple DNA fragments (2012)

UM-PCR greatly improves the universality of multiplex PCR. UM-PCR could rapidly detect the genetic purity of maize seeds. In addition, it could be applied in other areas, such as analysis of polymorphisms, quantitative assays and identifications of species.
Hyperphagia: Current concepts and future directions proceedings of the 2nd international conference on hyperphagia (2014)

This report documents the full scope of important topics reviewed at a comprehensive international meeting devoted to the topic of hyperphagia and identifies key areas for future funding and research.
The Repair of Potentially Lethal Damage in X-irradiated Cultures of Normal and Ataxia Telangiectasia Human Fibroblasts (1981)

The repair of potentially lethal damage (PLD) after X-rays was studied in plateau phase cultures of nine normal and five ataxia telangiectasia (AT) strains of human fibroblasts. In the normal strains PLD repair was complete after 6 hours of post-irradiation incubation. There were differences in the form of the survival curves of normal strains after maximum PLD repair but the extent of post-irradiation recovery was similar in all strains. In contrast all AT strains were almost completely deficient in PLD repair even when post-irradiation incubation was extended to 18 or 24 hours. The relevance of the PLD repair-deficiency in cultured AT strains to in vivo radiotherapeutic observations in AT patients is briefly discussed.
Isolation of human immunodeficiency virus-related simian immunodeficiency viruses from African green monkeys. (1989)

We have isolated lentivirus strains that are related to the human immunodeficiency virus (HIV) from African green monkeys (Cercopithecus aethiops; AGM). Although immunologically related, these SIVagm are clearly distinct from other simian immunodeficiency virus (SIV) isolates, including isolates from Macaca mulatta (SIVmac) or even from other AGM. The SIVagm strains described in this communication grow well in a limited number of human T-lymphoma lines. Virus density, morphology, and reverse transcriptase activity are characteristic of the lentivirus group. SIVagm exhibits the following pattern of major virus proteins: p18, p28, gp45, p64, gp140. They appear to bind to the target cell via the CD4 or its primate analogue. Four virus isolates have already been molecularly cloned for detailed genomic analysis and within this SIV agm group they exhibit the genomic variability that is typical of lentiviruses. AGMs infected with this virus apparently remain healthy and therefore SIVagm not only provides a virus model for vaccine studies but also allows investigation of the defense mechanisms (immunological and others) that keep the AGMs healthy. Furthermore, precise genomic analysis of these and other SIV strains will lead to a better understanding of the evolution and pathogenicity of human lentiviruses like HIV.
ChemInform Abstract: The Mid‐IR Spectrum of OCCCS: High‐Resolution Fourier‐Transform Measurements. (1991)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.