gebhart/patrepeval huggingface dataset:
Molecular confinement influences protein structure and enhances thermal protein stability (2001)

The sol-gel method of encapsulating proteins in a silica matrix was investigated as a potential experimental system for testing the effects of molecular confinement on the structure and stability of proteins. We demonstrate that silica entrapment (1) is fully compatible with structure analysis by circular dichroism, (2) allows conformational studies in contact with solvents that would otherwise promote aggregation in solution, and (3) generally enhances thermal protein stability. Lysozyme, alpha-lactalbumin, and metmyoglobin retained native-like solution structures following sol-gel encapsulation, but apomyoglobin was found to be largely unfolded within the silica matrix under control buffer conditions. The secondary structure of encapsulated apomyoglobin was unaltered by changes in pH and ionic strength of KCl. Intriguingly, the addition of other neutral salts resulted in an increase in the alpha-helical content of encapsulated apomyoglobin in accordance with the Hofmeister ion series. We hypothesize that protein conformation is influenced directly by the properties of confined water in the pores of the silica. Further work is needed to differentiate the steric effects of the silica matrix from the solvent effects of confined water on protein structure and to determine the extent to which this experimental system mimics the effects of crowding and confinement on the function of macromolecules in vivo.
Minimal oligosaccharide structures required for induction of immune responses against meningococcal immunotype L1, L2, and L3,7,9 lipopolysaccharides determined by using synthetic oligosaccharide-protein conjugates (1991)

The 12 types of meningococcal lipopolysaccharide (LPS) (immunotypes) contain immunotype-specific and cross-reactive epitopes situated on the oligosaccharide part of the LPS molecules. To identify useful cross-reactive epitopes and to determine minimal oligosaccharide structures required for the induction of an immune response against the most prevalent immunotypes, L1, L2, and L3,7,9, synthetic as well as native LPS-derived oligosaccharides were conjugated with tetanus toxoid. L3,7,9 phosphoethanolamine (PEA) group-containing oligosaccharide-tetanus toxoid conjugates evoked high immunoglobulin G (IgG) antibody levels in rabbits which were detected by an L2-, L3,7,9-, and, depending on the antiserum, L1-specific enzyme-linked immunosorbent assay (ELISA). Inhibition studies revealed that an identical antibody population was detected by L1 and L3,7,9 ELISA, indicating a similar tertiary structure of the inner core oligosaccharide of these two immunotypes. These antibodies recognize PEA group-containing epitopes present on the L1 and L3,7,9 LPS. An L2 PEA group-containing oligosaccharide-tetanus toxoid conjugate elicited L2- and L3,7,9-specific IgG antibodies, but in contrast with the L3,7,9 conjugates, no L1-specific IgG antibodies were evoked. These results indicate that L1 and L2 LPS do not contain cross-reactive epitopes, whereas both L2 and L3,7,9 LPS and L1 and L3,7,9 LPS possess common determinants. Three linear oligosaccharides and one branched oligosaccharide, representing partial structures of the inner core oligosacchardes of meningococcal LPS, were synthesized. Only the branched synthetic oligosaccharide-containing conjugate was able to induce and L1- and L3,7,9-specific immune response, whereas the linear oligosaccharide-protein conjugates evoked L2-specific immune responses. The branched oligosaccharide (beta-D-Glcp(1----4)-[L-alpha-D-Hepp(1----3)]-L-alpha-D-Hepp ) is therefore considered a minimal structure required for the induction of an immune response against L1 and L3,7,9 LPS and part of a cross-reactive epitope between these two immunotypes. For L2-specific immune responses, oligosaccharide structures terminating in beta-D-Glcp(1----4), alpha-D-GlcNAcp(1----2), or L-alpha-D-Hepp(1----5) are needed. The results suggest that it is possible to prepare an oligosaccharide structure with the ability to evoke an immune response against L1, L2, and L3,7,9 LPS. A feasible structure for such a "hybrid" oligosaccharide is discussed.
Toward memory-based reasoning (1986)

The intensive use of memory to recall specific episodes from the past—rather than rules—should be the foundation of machine reasoning.
Cloned DNA sequences complementary to mRNAs encoding precursors to the small subunit of ribulose-1,5-bisphosphate carboxylase and a chlorophyll a/b binding polypeptide (1981)

Double-stranded cDNA was synthesized from pea poly(A)-containing mRNA and inserted into the Pst I site of the bacterial plasmid pBR322 by the addition of synthetic oligonucleotide linkers. Bacterial colonies containing recombinant plasmids were detected by hybridization to partially purified mRNAs and further characterized by cell-free translation of hybridization-selected mRNAs. To confirm the identity of cDNA clones encoding chloroplast polypeptides, we incubated translation products derived from complementary mRNAs with intact chloroplasts in vitro. After uptake, precursor polypeptides were converted to their mature size and identified by fractionation of the chloroplast stroma and thylakoid membranes. By using these procedures, we have isolated and characterized cDNA clones encoding the two major cytoplasmically synthesized chloroplast proteins: the small subunit of ribulose-1,5-bisphosphate carboxylase and a constituent polypeptide (polypeptide 15) of the light-harvesting chlorophyll a/b-protein complex. Similarly, a third cDNA clone was isolated and shown to encode a 22,000-dalton thylakoid membrane polypeptide.
Therapeutic Hypothermia: Applications in Pediatric Cardiac Arrest (2009)

There is a rich history for the use of therapeutic hypothermia after cardiac arrest in neonatology and pediatrics. Laboratory reports date back to 1824 in experimental perinatal asphyxia. Similarly, clinical reports in pediatric cold water drowning victims represented key initiating work in the field. The application of therapeutic hypothermia in pediatric drowning victims represented some of the seminal clinical use of this modality in modern neurointensive care. Uncontrolled application (too deep and too long) and unique facets of asphyxial cardiac arrest in children (a very difficult insult to affect any benefit) likely combined to result in abandonment of therapeutic hypothermia in the mid to late 1980s. Important studies in perinatal medicine have built upon the landmark clinical trials in adults, and are once again bringing therapeutic hypothermia into standard care for pediatrics. Although more work is needed, particularly in the use of mild therapeutic hypothermia in children, there is a strong possibility that this important therapy will ultimately have broad applications after cardiac arrest and central nervous system (CNS) insults in the pediatric arena.
A New Target for Amyloid Beta Toxicity Validated by Standard and High-Throughput Electrophysiology (2010)

The MEA recording method utilized here is non-invasive, thus long term chronic measurements are possible and it does not require precise positioning of electrodes, thus it is ideal for functional screens. Even more significantly, we believe we have now identified a new target for drug development for AD based on functional toxicity of hippocampal neurons that could treat neurodegenerative diseases prior to the development of mild cognitive impairment.
High-efficiency in vivo gene transfer using intraarterial plasmid DNA injection following in vivo electroporation. (1996)

A novel method for high-efficiency and region- controlled in vivo gene transfer was developed by combining in vivo electroporation and intraarterial plasmid DNA injection. A mammalian expression plasmid for the Escherichia coli lacZ gene (driven with a SV40 early promoter) was injected into the internal carotid artery of rats whose brain tumors (from prior inoculation) had been electroporated between two electrodes. The lacZ gene was efficiently transferred and expressed in the tumor cell 3 days after plasmid injection. However, neither any gene transfers nor any elevated lacZ activity was detected in tissues outside the electrodes. The plasmid was not transferred without electroporation. Human monocyte chemoattractant protein-1 cDNA was also transferred by this method, and its long-lasting (3 weeks) expression was confirmed by using the Epstein-Barr virus episomal replicon system. The expressed monocyte chemoattractant protein-1 protein was functional, as evident by the presence of a large number of monocytes in tumor tissue. This method, electrogene therapy, which does not require viral genes or particles, allows genes to be transferred and expressed in desired organs or tissues, and it may lead to the development of a new type of highly effective gene therapy.
beta-Catenin regulates vascular endothelial growth factor expression in colon cancer. (2003)

To evaluate whether beta-catenin signaling has a role in the regulation of angiogenesis in colon cancer, a series of angiogenesis-related gene promoters was analyzed for beta-catenin/TCF binding sites. Strikingly, the gene promoter of human vascular endothelial growth factor (VEGF, or VEGF-A) contains seven consensus binding sites for beta-catenin/TCF. Analysis of laser capture microdissected human colon cancer tissue indicated a direct correlation between up-regulation of VEGF-A expression and adenomatous polyposis coli (APC) mutational status (activation of beta-catenin signaling) in primary tumors. In metastases, this correlation was not observed. Analysis by immunohistochemistry of intestinal polyps in mice heterozygous for the multiple intestinal neoplasia gene (Min/+) at 5 months revealed an increase and redistribution of VEGF-A in proximity to those cells expressing nuclear beta-catenin with a corresponding increase in vessel density. Transfection of normal colon epithelial cells with activated beta-catenin up-regulated levels of VEGF-A mRNA and protein by 250-300%. When colon cancer cells with elevated beta-catenin levels were treated with beta-catenin antisense oligodeoxynucleotides, VEGF-A expression was reduced by more than 50%. Taken together, our observations indicate a close link between beta-catenin signaling and the regulation of VEGF-A expression in colon cancer.
Inhibition of Tumorigenicity and Metastasis of Human Melanoma Cells by Anti-Cathepsin L Single Chain Variable Fragment (2004)

We demonstrated previously that the switch from nonmetastatic to highly metastatic phenotype of human melanoma cells is directly related to secretion of procathepsin L form. This cysteine proteinase was identified on the basis of its property to cleave human C3, the third component of complement. In an attempt to control procathepsin L secretion, we have recently generated an anti-cathepsin L single chain variable fragment (ScFv) from an anti-cathepsin L monoclonal antibody generated against recombinant cathepsin L. We herein selected clones stably transfected with this anti-cathepsin L ScFv and analyzed them for changes in tumor growth and metastasis. We show that in stably transfected clones, anti-cathepsin L ScFv strongly inhibited the secretion of procathepsin L without modifying the intracellular amount or processing pattern of cathepsin L forms. Confocal analysis demonstrated colocalization of endogenous cathepsin L and anti-cathepsin L ScFv. In addition, expression of this ScFv strongly inhibited generation of tumor and metastasis by these human melanoma clones in nude mice. In vivo, the anti-cathepsin L ScFv-transfected cells produced tumors with decreased vascularization (angiogenesis) concomitant with increased apoptosis of tumor cells. Matrigel assay also demonstrated that melanoma invasiveness was completely abolished. Thus, this is the first demonstration that anti-cathepsin L ScFv could be used to inhibit the tumorigenic and metastatic phenotype of human melanoma, depending on procathepsin L secretion, and could therefore be used as a molecular tool in a therapeutic cellular approach.
The ring opening metathesis polymerization of 7-oxabicyclo[2.2.1]hept-5-ene derivatives: a new acyclic polymeric ionophore (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe ring opening metathesis polymerization of 7-oxabicyclo[2.2.1]hept-5-ene derivatives: a new acyclic polymeric ionophoreBruce M. Novak and Robert H. GrubbsCite this: J. Am. Chem. Soc. 1988, 110, 3, 960–961Publication Date (Print):February 3, 1988Publication History Published online1 May 2002Published inissue 3 February 1988https://pubs.acs.org/doi/10.1021/ja00211a043https://doi.org/10.1021/ja00211a043research-articleACS PublicationsRequest reuse permissionsArticle Views1760Altmetric-Citations201LEARN 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
Neither backlash nor fad: The new men's studies (1993)

Although men's studies is no longer a novelty on college campuses, it can still raise some bewildered eyebrows and prompt a few explosive reactions. Recently, on a national computer bulletin board used by reference librarians, a request for journals, articles, and books “that analyze drama from a male/masculine perspective” touched off considerable crossfire among respondents. Beneath the hostilities, however, were serious questions and understandable confusions about the topic of men's studies. These concerns suggest that some clarifications concerning the new men's studies might be useful.
MicroRNAs Are Mediators of Androgen Action in Prostate and Muscle (2010)

Androgen receptor (AR) function is critical for the development of male reproductive organs, muscle, bone and other tissues. Functionally impaired AR results in androgen insensitivity syndrome (AIS). The interaction between AR and microRNA (miR) signaling pathways was examined to understand the role of miRs in AR function. Reduction of androgen levels in Sprague-Dawley rats by castration inhibited the expression of a large set of miRs in prostate and muscle, which was reversed by treatment of castrated rats with 3 mg/day dihydrotestosterone (DHT) or selective androgen receptor modulators. Knockout of the miR processing enzyme, DICER, in LNCaP prostate cancer cells or tissue specifically in mice inhibited AR function leading to AIS. Since the only function of miRs is to bind to 3' UTR and inhibit translation of target genes, androgens might induce miRs to inhibit repressors of AR function. In concordance, knock-down of DICER in LNCaP cells and in tissues in mice induced the expression of corepressors, NCoR and SMRT. These studies demonstrate a feedback loop between miRs, corepressors and AR and the imperative role of miRs in AR function in non-cancerous androgen-responsive tissues.
Diseño de un sistema borroso para la detección de intrusos (2001)

En los ultimos anos, debido al incremento en el uso de los ordenadores y la emergencia del comercio electronico, la deteccion de intrusos se ha convertido en una prioridad importante, pues no resulta tecnicamente factible construir un sistema invulnerable. La hipotesis de la investigacion es que la Logica Borrosa es capaz de producir mejores reglas que incrementen la flexibilidad y robusted de los sistemas de auditoria informatica. De hecho, los Sistemas Basados en Reglas Borrosas (SBRBs) han demostrado ser una herramienta muy efectiva para el diseno de Sistemas Inteligentes de Analisis de Datos para problemas de control, clasificacion, modelado etc., en aquellos contextos donde la informacion y/o los estan afectados de imprecision no probabilistica. De esta forma, el principal proposito del presente del trabajo consistira en elaborar un modelo de Sistema Experto Borroso aplicado a la Deteccion de Intrusos, para ello nuestra propuesta consiste en profundizar en los dos aspectos siguientes: el diseno de un SBRB y estudiar la adaptacion de estos modelos en mineria de datos relativos a la deteccion de intrusos.
Interleukin 24 (MDA-7/MOB-5) Signals through Two Heterodimeric Receptors, IL-22R1/IL-20R2 and IL-20R1/IL-20R2 (2002)

Interleukin 24 (IL-24) encodes a secreted protein that exhibits significant homology to the interleukin 10 (IL-10) family of cytokines. Here we show that the human IL-24 is secreted by activated peripheral blood mononuclear cells and is the ligand for two heterodimeric receptors, IL-22R1/IL-20R2 and IL-20R1/IL-20R2. The latter is also the receptor for IL-20. COS cells transfected with either IL-24 receptor heterodimers bind the ligand with similar saturation kinetics. IL-24 binding to either its endogenous receptors on human keratinocytes or to ectopically expressed receptors on baby hamster kidney cells leads to activation of the signal transducers and activators of transcription. Taken together, these results provide compelling evidence for IL-24 being the fourth member of IL-10 family of cytokines to which their specific receptors have been identified.
12. A New Class of Hybrid Adeno-Associated Viral Vectors with Non-Homologous ITRs Improves Directional Recombination and Dual-Vector Reconstitution of Large Transgenes (2004)

The relatively small package capacity (less than 5 kb) of adeno-associated virus vectors has been effectively doubled with the development of dual vector heterodimerization approaches. However, the efficiency of such dual vector systems is limited not only by the extent to which intermolecular recombination occurs between two independent vector genomes, but also by the directional bias required for successful transgene reconstitution following concatamerization. In the present study, we sought to evaluate the mechanisms by which ITR sequences mediate intermolecular recombination of AAV genomes with the goal of engineering more efficient vectors capable of reconstituting large transgenes delivered by a dual vector trans-splicing approach. To this end, we generated a novel AAV hybrid-ITR vector characterized by an AAV-2 and an AAV-5 ITR at either ends of the viral genome. This hybrid genome was efficiently packaged into either AAV-2 or AAV-5 capsids to generate infectious virions. Hybrid AV2:5 ITR viruses had a significantly reduced capacity to form circular intermediates in infected cells, as compared to homologous AV2:2 and AV5:5 ITR vectors, despite their similar capacity to express an encoded EGFP transgene. To examine whether the divergent ITR sequences contained within hybrid AV2:5 ITR vectors could direct intermolecular recombination in a head-to-tail fashion, we generated two hybrid ITR trans-splicing vectors (AV5:2LacZdonor and AV2:5LacZacceptor) for which each delivered one exon of a beta-galactosidase minigene flanked by donor and acceptor splice sequences. These hybrid trans-splicing vectors were compared to homologous AV5:5 and AV2:2 trans-splicing vector sets for their efficiency to reconstitute ?-galactosidase gene expression. Results from this comparison demonstrated that hybrid ITR dual vector sets had a significantly enhanced trans-splicing efficiency (6-10 fold, depending on the capsid serotype) as compared to homologous ITR vectors. Molecular studies of viral genome structure suggest that hybrid ITR vectors provide more efficient directional recombination due to an increased abundance of linear form genomes. These studies provide direct evidence for the importance of ITR sequences in directing intermolecular and intramolecular homologous recombination of AAV genomes. The use of hybrid ITR AAV vector genomes provide new strategies to manipulate viral genome conversion products and direct intermolecular recombination events required for efficient dual AAV vector reconstitution of transgene.
CW Laser Wavelength Modulation in Raman and Site Selection Fluorescence Spectroscopy (1976)

Raman and site selection fluorescence spectra are compared when these spectra have been measured with conventional fixed wavelength excitation and with modulated wavelength excitation. The samples were solutions of benzene and of chlorophyll. The modulated wavelength method records the differential spectra. Simple analysis of signal/noise ratios from these different experimental techniques show modulation methods can give improvements under particular conditions. These conditions are discussed.
The Effect of Changes in the Federal Disability Programs on State and Local General Assistance Programs (1985)

Since early 1981, there has been a large-scale removal of persons from the SSI and Social Security disability programs as a result of the Social Security Disability Amendments of 1980. This article reports on the findings of a national survey designed to determine whether the removal of persons from the federal disability programs had an impact on state and local General Assistance programs and the extent to which older recipients of General Assistance are in need of long-term income assistance for health and other reasons. Some states and jurisdictions have noticed an increase in applications as a result of federal cutoffs and tightened administrative policies which is an indicator that state and local programs are sensitive to changes in federal policies. Since General Assistance programs are serving persons terminated from federal disability programs and a significant number of older clients who are in need of long-term income assistance, this article suggests that consideration should be given to modifying the disability criteria for the SSI program, at least for older persons.
Mimicking Posttranslational Modifications of Proteins (2004)

Strategies for the synthesis of pure posttranslationally modified proteins or their mimics (for example, glycosylation or prenylation) have been recently developed. In his Perspective, [Davis][1] discusses how these strategies are allowing the creation of useful biomolecular probes and how they may offer a potential route to new protein pharmaceuticals.

 [1]: http://www.sciencemag.org/cgi/content/full/303/5657/480
Bacteriophage lambda cro mutations: effects on activity and intracellular degradation. (1986)

Following random mutagenesis of the bacteriophage lambda cro gene, we have isolated missense mutations that affect approximately half of the 66 residue positions of Cro. About two-thirds of the mutations change residues involved in the maintenance of Cro structure and stability. The corresponding mutant proteins are severely degraded in the cell but often have specific activities near that of wild-type Cro. The remaining mutations affect residues involved in DNA binding. These mutant proteins are present at moderately reduced intracellular levels, but their specific activities are much lower than that of wild type.