gebhart/patrepeval huggingface dataset:
Dietary clay in the chemoprevention of aflatoxin-induced disease (1999)

Aflatoxins are harmful by-products of mold growth and, though invisible to the naked eye, are potentially fatal. The aflatoxin problem is long-standing and inextricable. Concerns about the aflatoxins originate from the strong implications of their involvement in disease and death in humans and animals, yet scientists and clinicians are still seeking ways to effectively deal with these dangerous and elusive chemicals. Safe, practical, and effective strategies for the detoxification of aflatoxin-contaminated food and feed are highly desirable. A simple and effective approach to the chemoprevention of aflatoxicosis has been to diminish or block exposure to aflatoxins via the inclusion of HSCAS clay in the diet. HSCAS clay acts as an aflatoxin enterosorbent that tightly and selectively binds these poisons in the gastrointestinal tract of animals, decreasing their bioavailability and associated toxicities. Further studies to delineate the molecular mechanisms of action have shown that the dicarbonyl system of aflatoxin is essential for tight binding by HSCAS. In these studies, adsorption data was fitted to multiple isotherm equations including the Langmuir, multi-Langmuir, general Freundlich, Langmuir-Freundlich, Toth and various transforms. Information derived included: the Gibbs standard free energy change of adsorption, enthalpy of adsorption, capacity, affinity, and heterogeneity coefficient. Computer modeling was also utilized to provide additional structural information and insight into the mechanism. Evidence suggests that aflatoxins may react at multiple sites on HSCAS particles, especially the interlayer region, but also at edges and basal surfaces. Since clay and zeolitic minerals comprise a broad family of functionally diverse chemicals, there may be significant hidden risks associated with their indiscriminate inclusion in the diet. All aflatoxin binding agents should be rigorously tested, paying particular attention to their effectiveness and safety in aflatoxin-sensitive animals and their potential for interactions with critical nutrients.
Automatic activity estimation based on object behaviour signature (2010)

Automatic estimation of human activities is a topic widely studied. However the process becomes difficult when we want to estimate activities from a video stream, because human activities are dynamic and complex. Furthermore, we have to take into account the amount of information that images provide, since it makes the modelling and estimation activities a hard work. In this paper we propose a method for activity estimation based on object behavior. Objects are located in a delimited observation area and their handling is recorded with a video camera. Activity estimation can be done automatically by analyzing the video sequences. The proposed method is called "signature recognition" because it considers a space-time signature of the behaviour of objects that are used in particular activities (e.g. patients' care in a healthcare environment for elder people with restricted mobility). A pulse is produced when an object appears in or disappears of the observation area. This means there is a change from zero to one or vice versa. These changes are produced by the identification of the objects with a bank of nonlinear correlation filters. Each object is processed independently and produces its own pulses; hence we are able to recognize several objects with different patterns at the same time. The method is applied to estimate three healthcare-related activities of elder people with restricted mobility.
The Radiotoxicity of Iodine-125 in Mammalian Cells: II. A Comparative Study on Cell Survival and Cytogenetic Responses to 125 IUdR, 131 IUdR, and 3 HTdR (1976)

P. C. Chan, E. Lisco, H. Lisco, S. J. Adelstein, The Radiotoxicity of Iodine-125 in Mammalian Cells: II. A Comparative Study on Cell Survival and Cytogenetic Responses to 125 IUdR, ${}^{131}{\rm IUdR}$, and ${}^{3}{\rm HTdR}$, Radiation Research, Vol. 67, No. 2 (Aug., 1976), pp. 332-343
Spatial–temporal imaging of bacterial infection and antibiotic response in intact animals (2001)

We describe imaging the luminance of green fluorescent protein (GFP)-expressing bacteria from outside intact infected animals. This simple, nonintrusive technique can show in great detail the spatial-temporal behavior of the infectious process. The bacteria, expressing the GFP, are sufficiently bright as to be clearly visible from outside the infected animal and recorded with simple equipment. Introduced bacteria were observed in several mouse organs including the peritoneal cavity, stomach, small intestine, and colon. Instantaneous real-time images of the infectious process were acquired by using a color charge-coupled device video camera by simply illuminating mice at 490 nm. Most techniques for imaging the interior of intact animals may require the administration of exogenous substrates, anesthesia, or contrasting substances and require very long data collection times. In contrast, the whole-body fluorescence imaging described here is fast and requires no extraneous agents. The progress of Escherichia coli-GFP through the mouse gastrointestinal tract after gavage was followed in real-time by whole-body imaging. Bacteria, seen first in the stomach, migrated into the small intestine and subsequently into the colon, an observation confirmed by intravital direct imaging. An i.p. infection was established by i.p. injection of E. coli-GFP. The development of infection over 6 h and its regression after kanamycin treatment were visualized by whole-body imaging. This imaging technology affords a powerful approach to visualizing the infection process, determining the tissue specificity of infection, and the spatial migration of the infectious agents.
Partial loss of presenilins causes seborrheic keratosis and autoimmune disease in mice (2004)

Presenilin (PS1) and (PS2) are the centers of gamma-secretase that release Abeta from APP in Alzheimer's disease (AD). They cleave signaling proteins like Notch and downregulate beta-catenin to modulate Wnt signaling. Inactivation of PS1 or PS1 and PS2 causes a prenatally lethal 'Notch phenotype,' which has hampered investigation of PS function in adulthood seriously. We have thus turned towards PS1+/-PS2-/- mice which carry the most severe reduction of PS alleles compatible with survival, to analyze the consequences of impaired PS function especially in adulthood. In these 'partial deficient' mice, PS1 protein concentration is considerably lowered, functionally reflected by reduced gamma-secretase activity and impaired beta-catenin downregulation. Their phenotype is normal up to approximately 6 months, when the majority of the mice develop an autoimmune disease characterized by dermatitis, glomerulonephritis, keratitis and vasculitis, as seen in human systemic lupus erythematosus. Besides B-cell dominated infiltrates, we observe a hypergammaglobulinemia with immune complex deposits in several tissues, high-titer nuclear autoantibodies and an increased CD4+/CD8+ ratio. The mice further develop a benign skin hyperplasia similar to human seborrheic keratosis as opposed to malignant keratocarcinomata observed in skin-specific PS1 'full' knockouts. A partial reduction of PS function in PS1+/-PS2-/- mice causes a novel phenotype in adulthood unrelated to the developmental defects of full knockouts. As PS1+/-PS2+/- mice remain healthy, this points towards a sharply defined minimum of PS function. Skin and immune system appear to be especially sensitive targets of impaired PS function and may need careful monitoring if gamma-secretase inhibitors are envisaged for treating AD.
Antigenic Analyses of Sugi Basic Protein by Monoclonal Antibodies: II. Detection of Immunoreactive Fragments in Enzyme-cleaved <i>Cry j l</i> (1992)

The 4 anti-Cry j I mAbs showing an epitope specificity different from each other, 046, 029, 026 and 027, were selected to analyze the structure of the antigenic determinant for each mAb on a Cry j I molecule. Immunoreactive fragments in enzyme-cleaved Cry j I were detected by means of the adsorption on the mAb column and of the binding to the mAbs on Elisa. The mAb 026 was found to be reactive to the fragments containing a Cry j I N-terminal region obtained by V8 protease or pepsin digestion, but not to those by lysylendopeptidase digestion. The mAb 027 was found to be capable of binding to the fragments containing a linear structure of Asn-Ala-Gly-Val-Leu-Thr-Cys-Ser-Leu-Ser-Lys, which were generated by V8 protease, lysylendopeptidase or pepsin digestion. Furthermore, the synthetic peptide Asn-Ala-Gly-Val-Leu-Thr-Cys-Ser- Leu-Ser-Lys-Arg could bind to 027, but not to 026, and could inhibit the binding of 027 to Cry j I or to its immunoreactive fragments. No fragments capable of reacting to the mAbs 046 and 029 could be found in this study, suggesting that 046 and 029 recognize a conformationally constituted epitope of Cry j I molecule which is destroyed by enzymatic cleavage. The epitope recognized by the mAbs 027 or 026 was found to be located in conformationally hidden parts of the molecule which was exposed to react to the mAbs only after the physicochemical or enzymatic treatment.
'Long Distance Sequencer' Method; a Novel Strategy for Large DNA Sequencing Projects (1996)

Every DNA sequencing project involves two steps: (i) making suitable templates for all the regions to be sequenced; and (ii) running sequencing reactions and electrophoresis. The latter step can be automated by use of workstations and autosequencers. The former step requires careful experimental design and laborious DNA manipulations such as the construction of nested deletion mutants (1). This is often the limiting step in large sequencing projects. The 'shot-gun' method eliminates this complicated DNA manipulations (1), but many recombinant clones must be sequenced because of the random nature of this procedure. Here we describe a novel sequencing technique that utilizes recent advances in amplification of long DNA fragments by PCR (2). This systematic method requires minimal amount of starting DNA and eliminates complicated steps for template preparation. We have successfully used this method to determine the sequence of a cosmid insert and the genomic structure of the transforming growth factor type II receptor gene (5).
Potent Modification of Low Density Lipoprotein by Group X Secretory Phospholipase A2 Is Linked to Macrophage Foam Cell Formation (2002)

The deposition of cholesterol ester within foam cells of the artery wall is fundamental to the pathogenesis of atherosclerosis. Modifications of low density lipoprotein (LDL), such as oxidation, are prerequisite events for the formation of foam cells. We demonstrate here that group X secretory phospholipase A2 (sPLA2-X) may be involved in this process. sPLA2-X was found to induce potent hydrolysis of phosphatidylcholine in LDL leading to the production of large amounts of unsaturated fatty acids and lysophosphatidylcholine (lyso-PC), which contrasted with little, if any, lipolytic modification of LDL by the classic types of group IB and IIA secretory PLA2s. Treatment with sPLA2-X caused an increase in the negative charge of LDL with little modification of apolipoprotein B (apoB) in contrast to the excessive aggregation and fragmentation of apoB in oxidized LDL. The sPLA2-X-modified LDL was efficiently incorporated into macrophages to induce the accumulation of cellular cholesterol ester and the formation of non-membrane-bound lipid droplets in the cytoplasm, whereas the extensive accumulation of multilayered structures was found in the cytoplasm in oxidized LDL-treated macrophages. Immunohistochemical analysis revealed marked expression of sPLA2-X in foam cell lesions in the arterial intima of high fat-fed apolipoprotein E-deficient mice. These findings suggest that modification of LDL by sPLA2-X in the arterial vessels is one of the mechanisms responsible for the generation of atherogenic lipoprotein particles as well as the production of various lipid mediators, including unsaturated fatty acids and lyso-PC.
Radiolabeled HER-2 binding affibody molecules for tumor targeting : preclinical studies. (2006)

Conventional cancer treatment based on radiotherapy or chemotherapy affects all dividing cells. By directing the therapy specifically to the tumor cells, normal cells can be spared. Tumor targeting molecules carrying a cytotoxic moiety is then an attractive approach. In this thesis, an affibody molecule with high affinity for the protein HER-2, that is strongly associated with aggressive forms of breast cancer, was selected. After radiolabeling with 125I, the affibody molecule, in monovalent and bivalent form, was tested in vitro in HER-2 overexpressing tumor cells and in transplanted tumors in mice. It was shown that the HER-2 targeting affibody molecule bound its target in a specific manner, both in vitro and in vivo. The small size of the affibody molecule resulted in fast clearance through the kidneys. An impressive tumor-to-blood ratio of 10 eight hours post injection was achieved and the tumors could easily be visualized in a gamma camera. The biologic effects of the bivalent affibody molecule and a monovalent affinity maturated version was measured and compared with the effects of the monoclonal antibody trastuzumab. It was found that although all molecules target the same protein, the effects differed greatly. The affibody molecule was also labeled with the alpha-emitting radionuclide 211At. Specific decrease in survival was seen in HER-2 overexpressing cells receiving the 211At labeled affibody molecule. The sensitivity to the treatment differed between cell lines, probably as a result of differences between the cell lines in internalization and nuclear size. The 211At labeled affibody molecules were also tested in vivo, where stability of the 211At label was a problem. To circumvent this problem, more stable conjugation chemistry was tested, as well as strategies to prevent uptake of released 211At by normal organs. This thesis describes the selection and optimization of affibody molecules for medical use for the first time.
Effect of hydroxyl group configuration in hydroxyethylamine dipeptide isosteres on HIV protease inhibition. Evidence for multiple binding modes (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEffect of hydroxyl group configuration in hydroxyethylamine dipeptide isosteres on HIV protease inhibition. Evidence for multiple binding modesDaniel H. Rich, Chong Qing Sun, J. V. N. Vara Prasad, Ahammadunny Pathiasseril, Mihaly V. Toth, Garland R. Marshall, Michael Clare, Richard A. Mueller, and Kathryn HousemanCite this: J. Med. Chem. 1991, 34, 3, 1222–1225Publication Date (Print):March 1, 1991Publication History Published online1 May 2002Published inissue 1 March 1991https://pubs.acs.org/doi/10.1021/jm00107a049https://doi.org/10.1021/jm00107a049research-articleACS PublicationsRequest reuse permissionsArticle Views557Altmetric-Citations124LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Impact of the NSW Young Offenders Act (1997) on likelihood of custodial order, The (2013)

Aim: The aim of this study was to determine whether the introduction of the Young Offenders Act had any impact on (a) the probability that a young offender will receive a custodial order 1; and (b) the time taken to receive a first custodial order. These two custodial outcomes were compared for Indigenous and non-Indigenous young people. Method: The rates of a custodial order prior to and following the introduction of the Young Offenders Act were compared using a frailty model with Gompertz distribution. The times taken to receive the first custodial order prior to, and following the introduction of the Young Offenders Act were compared using the asymptotic failure rate of ever receiving a custodial order. Results: The results show that while Indigenous young people are more likely to receive a custodial order as a juvenile (hazard ratio of 1.4) compared to non-Indigenous young people, the risk of receiving a custodial order fell for both groups after the introduction of the YOA (hazard ratio of 0.63). The results show that, after the introduction of the YOA, the risks of receiving a custodial order for both Indigenous and non-Indigenous young people dropped by 17.5 per cent and 16.3 per cent respectively. For Indigenous young people, 10 per cent of the pre-YOA cohort received a custodial order within 17 months of first proven court appearance, whereas after the YOA commenced this took 21 months. For the non-Indigenous young people, 10 per cent of the pre-YOA cohort received a custodial order within 36 months whereas after the YOA commenced this took 57 months. Conclusion: The results suggest the YOA has been effective in diverting young people from custody (including Indigenous young people). The likelihood of ever ending up in custody reduced and the time taken to receive a custodial order after the first proven court appearance lengthened for both indigenous and non-indigenous young people after the introduction of the YOA.
Isolation and Characterization of the B-Cell Marker CD20 (2005)

The integral membrane protein CD20 has been identified as an important therapeutic target in the treatment of non-Hodgkin's lymphoma (NHL). CD20 binding of many antibodies including the therapeutic antibody, rituximab, has been shown to be critically dependent upon the conformation of a loop structure between the third and fourth helical transmembrane regions. In this work, human and murine CD20 proteins expressed in Escherichia coli are shown to be localized with the cell membrane and are purified in nondenaturing detergent solutions. The purified human and murine CD20 proteins have a substantial helical structure as measured by circular dichroism spectroscopy. Only small changes in the secondary structure are observed following the reduction of CD20, with the addition of SDS, or after heating. The rituximab antibody is shown to bind to purified human CD20 with nanomolar affinity. Rituximab binding is abolished by reduction and alkylation of CD20, with data consistent with the proposed antibody epitope being within the disulfide-bonded loop formed between cysteine residues 167 and 183. Disulfide-bond-dependent antibody binding is partially recovered following reoxidation of reduced CD20. Antibody binding is unaffected by mutations of cysteines proposed to be in the intracellular domain of CD20. The affinities of intact rituximab and its Fab fragment to the isolated and purified CD20 are similar to the observed affinity of rituximab Fab for CD20 on the surface of B cells. However, the intact rituximab antibody shows much higher affinity for CD20 on B cells. This suggests that B cells display CD20 in such a way that allows for marked avidity effects to be observed, perhaps through cross-linking of CD20 monomers into lipid rafts, which limits receptor diffusion in the membrane. Such cross-linking may play a role in partitioning CD20 into lipid rafts and in enhancing antibody-dependent B-cell depletion activities of rituximab and other therapeutic anti-CD20 antibodies.
Genotypic analysis of N-ethyl-N-nitrosourea-induced mutations by Taq I restriction fragment length polymorphism/polymerase chain reaction in the c-H-ras1 gene. (1992)

In genotypic mutation analysis DNA sequence changes are determined without the in vivo or in vitro selection of phenotypically altered cells. We have studied the induction of base-pair changes by N-ethyl-N-nitrosourea in Taq I endonuclease recognition site 2508-2511 (TCGA) of the c-H-ras1 gene in human fibroblasts by the restriction fragment length polymorphism/polymerase chain reaction (RFLP/PCR) method. This site contains the four bases, and all 12 possible single base-pair changes can be monitored. The transition of guanine to adenine at position 2510 was the major mutation detected by lambda plaque oligonucleotide hybridization and quantitative sequence analysis of the RFLP/PCR products. It involves the G residue of the CpG sequence of the coding strand. Data calibration with an internal mutant standard indicates that absolute frequencies for this transition lie in the range of 4-12 x 10(-7). The present study documents the capacity of the RFLP/PCR approach to measure mutagen-induced base-pair changes in a specific gene sequence without the selection of a phenotypically altered cell.
Salmonella typhimurium Encodes an SdiA Homolog, a Putative Quorum Sensor of the LuxR Family, That Regulates Genes on the Virulence Plasmid (1998)

Quorum sensing is a phenomenon in which bacteria sense and respond to their own population density by releasing and sensing pheromones. In gram-negative bacteria, quorum sensing is often performed by the LuxR family of transcriptional regulators, which affect phenotypes as diverse as conjugation, bioluminescence, and virulence gene expression. The gene encoding one LuxR family member, named sdiA (suppressor of cell division inhibition), is present in the Escherichia coli genome. In this report, we have cloned the Salmonella typhimurium homolog of SdiA and performed a systematic screen for sdiA-regulated genes. A 4.4-kb fragment encoding the S. typhimurium sdiA gene was sequenced and found to encode the 3' end of YecC (homologous to amino acid transporters of the ABC family), all of SdiA and SirA (Salmonella invasion regulator), and the 5' end of UvrC. This gene organization is conserved between E. coli and S. typhimurium. We determined that the S. typhimurium sdiA gene was able to weakly complement the E. coli sdiA gene for activation of ftsQAZ at promoter 2 and for suppression of filamentation caused by an ftsZ(Ts) allele. To better understand the function of sdiA in S. typhimurium, we screened 10,000 random lacZY transcriptional fusions (MudJ transposon mutations) for regulation by sdiA. Ten positively regulated fusions were isolated. Seven of the fusions were within an apparent operon containing ORF8, ORF9, rck (resistance to complement killing), and ORF11 of the S. typhimurium virulence plasmid. The three ORFs have now been named srgA, srgB, and srgC (for sdiA-regulated gene), respectively. The DNA sequence adjacent to the remaining three fusions shared no similarity with previously described genes.