gebhart/patrepeval huggingface dataset:
Treatment with isotretinoin inhibits lipofuscin accumulation in a mouse model of recessive Stargardt's macular degeneration (2003)

Recessive Stargardt's macular degeneration is an inherited blinding disease of children caused by mutations in the ABCR gene. The primary pathologic defect in Stargardt's disease is accumulation of toxic lipofuscin pigments such as N-retinylidene-N-retinylethanolamine (A2E) in cells of the retinal pigment epithelium. This accumulation appears to be responsible for the photoreceptor death and severe visual loss in Stargardt's patients. Here, we tested a therapeutic strategy to inhibit lipofuscin accumulation in a mouse model of recessive Stargardt's disease. Isotretinoin (Accutane) has been shown to slow the synthesis of 11-cis-retinaldehyde and regeneration of rhodopsin by inhibiting 11-cis-retinol dehydrogenase in the visual cycle. Light activation of rhodopsin results in its release of all-trans-retinaldehyde, which constitutes the first reactant in A2E biosynthesis. Accordingly, we tested the effects of isotretinoin on lipofuscin accumulation in abcr(-/-) knockout mice. Isotretinoin blocked the formation of A2E biochemically and the accumulation of lipofuscin pigments by electron microscopy. We observed no significant visual loss in treated abcr(-/-) mice by electroretinography. Isotretinoin also blocked the slower, age-dependent accumulation of lipofuscin in wild-type mice. These results corroborate the proposed mechanism of A2E biogenesis. Further, they suggest that treatment with isotretinoin may inhibit lipofuscin accumulation and thus delay the onset of visual loss in Stargardt's patients. Finally, the results suggest that isotretinoin may be an effective treatment for other forms of retinal or macular degeneration associated with lipofuscin accumulation.
Nuclear pore localization and nucleocytoplasmic transport of eIF-5A: evidence for direct interaction with the export receptor CRM1 (1999)

Eukaryotic initiation factor 5A (eIF-5A) is the only cellular protein known to contain the unusual amino acid hypusine. The exact in vivo function of eIF-5A, however, is to date unknown. The finding that eIF-5A is an essential cofactor of the human immunodeficiency virus type 1 (HIV-1) Rev RNA transport factor suggested that eIF-5A is part of a specific nuclear export pathway. In this study we used indirect immunofluorescence and immunogold electron microscopy to demonstrate that eIF-5A accumulates at nuclear pore-associated intranuclear filaments in mammalian cells and Xenopus oocytes. We are able to show that eIF-5A interacts with the general nuclear export receptor, CRM1. Furthermore, microinjection studies in somatic cells revealed that eIF-5A is transported from the nucleus to the cytoplasm, and that this nuclear export is blocked by leptomycin B. Our data demonstrate that eIF-5A is a nucleocytoplasmic shuttle protein.
Purification, localization, and expression of human intestinal alkaline sphingomyelinase (2003)

Sphingomyelin (SM) metabolism in the gut may have an impact on colon cancer development. In this study, we purified alkaline sphingomyelinase (alk-SMase) from human intestinal content, and studied its location in the mucosa, expression in colon cancer, and function on colon cancer cells. The enzyme was purified by a series of chromatographies. The molecular mass of the enzyme is 60 kDa, optimal pH is 8.5, and isoelectric point is 6.6. Under optimal conditions, 1 mg of the enzyme hydrolyzed 11 mM SM per hour. The properties of the enzyme are similar to those of rat intestinal alk-SMase but not to those of bacterial neutral SMase. Immunogold electronmicroscopy identified the enzyme on the microvillar membrane in endosome-like structures and in the Golgi complexes of human enterocytes. The expression and the activity of the enzyme were decreased in parallel in human colon cancer tissues compared with the adjacent normal tissue. The enzyme inhibited DNA biosynthesis and cell proliferation dose dependently and caused a reduction of SM in HT29 cells. Intestinal alk-SMase is localized in the enterocytes, down-regulated in human colon cancer, and may have antiproliferative effects on colon cancer cells.
Recent development of fiber optic sensors for perimeter security (2001)

Outdoors fiber optic disturbance sensors are, now used for perimeter security and were presented at Carnahan Conference in London in 1995 by I.R. Hawkes and Griffiths. The fibre optic interferometer sensor in a Sagnac loop configuration has also been known as a product of Mason and Manson Company since 1994. This paper describes the investigation results of the new generation of the fiber optic perimeter sensor in the Sagnac loop configuration. The paper shows construction of the fiber optic sensor and how it uses currently available technologies to ensure both excellent detection properties and intruder recognition. This sensor gives extremely low false alarm rate. The details of the new hardware components and the test results from an initial field installation are described. Comparison of the sensor performance with the above-mentioned monitoring sensors indicates the advantages of this new sensor technology.
Gut microbiota: next frontier in understanding human health and development of biotherapeutics (2011)

The gut microbiota is a remarkable asset for human health. As a key element in the development and prevention of specific diseases, its study has yielded a new field of promising biotherapeutics. This review provides comprehensive and updated knowledge of the human gut microbiota, its implications in health and disease, and the potentials and limitations of its modification by currently available biotherapeutics to treat, prevent and/or restore human health, and future directions. Homeostasis of the gut microbiota maintains various functions which are vital to the maintenance of human health. Disruption of the intestinal ecosystem equilibrium (gut dysbiosis) is associated with a plethora of human diseases, including autoimmune and allergic diseases, colorectal cancer, metabolic diseases, and bacterial infections. Relevant underlying mechanisms by which specific intestinal bacteria populations might trigger the development of disease in susceptible hosts are being explored across the globe. Beneficial modulation of the gut microbiota using biotherapeutics, such as prebiotics, probiotics, and antibiotics, may favor health-promoting populations of bacteria and can be exploited in development of biotherapeutics. Other technologies, such as development of human gut models, bacterial screening, and delivery formulations eg, microencapsulated probiotics, may contribute significantly in the near future. Therefore, the human gut microbiota is a legitimate therapeutic target to treat and/or prevent various diseases. Development of a clear understanding of the technologies needed to exploit the gut microbiota is urgently required.
Overview of Newer Glucocorticosteroid Preparations for Inflammatory Bowel Disease (1990)

Because the glucocorticosteroid receptor seems to be uniform in the human body, there is currently no support for a possibility of separating the therapeutic and adverse glucocorticosteroid actions at the receptor level. However, based on a new generation of glucocorticosteroids characterized by a high first pass metabolism in the liver, it seems possible today co reach a more selective topical therapy of inflammatory bowel disease. The properties of three new glucocorticosteroids are presented: the highly potent budesonide, fluticasone propionate and tixocortol pivalate - the latter with only low topical potency. Their properties can be exemplified by budesonide, which is currently the best documented compound. The topical potency of budesonide is 200 and 15 times higher than chose of hydrocortisone and prednisolone, respectively. This means that there is a high potential for anti-inflammatory and immunosuppressive actions on rectal and bowel mucosa. The compound is metabolically stable in the bowel compartment, which allows full retention of glucocorticosteroid activity in the target organ. However, when absorbed and distributed to the liver, there is a 90% first pass hepatic metabolism co metabolites of very low potency. This suggests that after topical application to rectal or bowel mucosa, glucocorticosteroid activity in the systemic circulation is low. This is in contrast to prednisolone, which has a hepatic first pass metabolism of just 20%.
Evidence that the 42- and 40-amino acid forms of amyloid β protein are generated from the β-amyloid precursor protein by different protease activities (1996)

Cerebral deposition of the amyloid beta protein (A beta) is an early and invariant feature of Alzheimer disease (AD). Whereas the 40-amino acid form of A beta (A beta 40) accounts for approximately 90% of all A beta normally released from cells, it appears to contribute only to later phases of the pathology. In contrast, the longer more amyloidogenic 42-residue form (A beta 42), accounting for only approximately 10% of secreted A beta, is deposited in the earliest phase of AD and remains the major constituent of most amyloid plaques throughout the disease. Moreover, its levels have been shown to be increased in all known forms of early-onset familial AD. Thus, inhibition of A beta 42 production is a prime therapeutic goal. The same protease, gamma-secretase, is assumed to generate the C termini of both A beta 40 and A beta 42. Herein, we analyze the effect of the compound MDL 28170, previously suggested to inhibit gamma-secretase, on beta-amyloid precursor protein processing. By immunoprecipitating conditioned medium of different cell lines with various A beta 40- and A beta 42-specific antibodies, we demonstrate a much stronger inhibition of the gamma-secretase cleavage at residue 40 than of that at residue 42. These data suggest that different proteases generate the A beta 40 and A beta 42 C termini. Further, they raise the possibility of identifying compounds that do not interfere with general beta-amyloid precursor protein metabolism, including A beta 40 production, but specifically block the generation of the pathogenic A beta 42 peptide.
Therapeutic synergy of trimetrexate (CI-898) in combination with doxorubicin, vincristine, cytoxan, 6-thioguanine, cisplatin, or 5-fluorouracil against intraperitoneally implanted P388 leukemia. (1987)

In order to support planning of clinical trials of trimetrexate (CI-898) in combination chemotherapy regimens, several studies were carried out to determine the potential for therapeutic synergy between CI-898 and several clinically proven agents including doxorubicin, cytoxan, FUra, 6-thioguanine (6-TG), vincristine, methotrexate, and cisplatin. F1 hybrid mice bearing either early or advanced stage P388 leukemia were treated with either the single agents or with various combination regimens and observed for lifespan. These studies demonstrated a high degree of therapeutic synergism between CI-898 and doxorubicin, cytoxan, and 6-TG. Combinations of CI-898 with FUra, vincristine, and cisplatin also produced enhanced tumor cell kill, although the results were less dramatic than those mentioned above. The host toxicities of CI-898 and methotrexate were synergistic and appeared to negate any potential therapeutic benefit of the combination. The synergistic effect of the doxorubicin, vincristine, and cytoxan combinations may have been due to a lack of overlapping host toxicities, but the synergy observed with 6-TG was obtained in spite of synergistic host toxicity.
Viral DNA carried by human immunodeficiency virus type 1 virions (1992)

A fundamental step in the replication of retroviruses is the reverse transcription of the viral RNA genome into a double-stranded DNA provirus. Retroviruses are believed to carry genomic information only as RNA, and synthesis of DNA is thought to start only after virus entry into the infected cell. We report here that infectious mature human immunodeficiency virus type 1 virions contain viral DNA of heterogeneous size. This heterogeneity seems to result from random stops of reverse transcription during minus- and plus-strand synthesis. The DNA carried by human immunodeficiency virus type 1 virions presumably originates from reverse transcription which takes place prior to or during formation of the mature virus particle.
The Synthesis of Some Lipophilic Tetradentate Ligands for Use in the Formation of Metal-Linked Polymers (1994)

Two lipophilic tetradentate ligands, 5,5'-di-t-butyl- and 5,5'-dihexyl-2,2'-bipyrimidine, were prepared via either Ullmann or nickel(0)-promoted reactions in low but useful yields. Approaches towards the synthesis of lipophilic ligands based on 2,2'-biimidazole, namely 4,4',5,5'-tetrabutyl-2,2'-biimidazole (from decane-4,5-dione) and various 4,4',5,5'-tetra( arylamino )- 2,2'-biimidazoles (from 4,4',5,5'-tetrabromo-2,2'-biimidazole and arylamines), and a 2,2'- bibenzimidazole , 5,5',6,6?-tetra( octyloxy )-2,2'-bibenzimidazole (from N,N'- bis [4,5-di( octyloxy )-2-nitrophenyl] oxamide ), were uniformly unsuccessful for preparing the 2,2'-biheteroaryl compounds.
A Strain-Promoted [3 + 2] Azide−Alkyne Cycloaddition for Covalent Modification of Biomolecules in Living Systems [J. Am. Chem. Soc. 2004, 126, 15046−15047]. (2005)

ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionNEXTORIGINAL ARTICLEThis notice is a correctionA Strain-Promoted [3 + 2] Azide−Alkyne Cycloaddition for Covalent Modification of Biomolecules in Living Systems [J. Am. Chem. Soc. 2004, 126, 15046−15047].Nicholas J. Agard, Jennifer A. Prescher, and Carolyn R. BertozziCite this: J. Am. Chem. Soc. 2005, 127, 31, 11196Publication Date (Web):July 13, 2005Publication History Published online13 July 2005Published inissue 1 August 2005https://pubs.acs.org/doi/10.1021/ja059912xhttps://doi.org/10.1021/ja059912xcorrectionACS PublicationsCopyright © 2005 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views7636Altmetric-Citations45LEARN 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 PDF (12 KB) Get e-Alertsclose Get e-Alerts
Concept Mask: Large-Scale Segmentation from Semantic Concepts (2018)

Existing works on semantic segmentation typically consider a small number of labels, ranging from tens to a few hundreds. With a large number of labels, training and evaluation of such task become extremely challenging due to correlation between labels and lack of datasets with complete annotations. We formulate semantic segmentation as a problem of image segmentation given a semantic concept, and propose a novel system which can potentially handle an unlimited number of concepts, including objects, parts, stuff, and attributes. We achieve this using a weakly and semi-supervised framework leveraging multiple datasets with different levels of supervision. We first train a deep neural network on a 6M stock image dataset with only image-level labels to learn visual-semantic embedding on 18K concepts. Then, we refine and extend the embedding network to predict an attention map, using a curated dataset with bounding box annotations on 750 concepts. Finally, we train an attention-driven class agnostic segmentation network using an 80-category fully annotated dataset. We perform extensive experiments to validate that the proposed system performs competitively to the state of the art on fully supervised concepts, and is capable of producing accurate segmentations for weakly learned and unseen concepts.
Current Patents Related to Bacillus thuringiensis Insecticidal Crystal Proteins (2009)

This work categorizes a number of patents related to Bacillus thuringiensis insecticidal crystal proteins. The patents are classified into groups according to the type of toxins appearing in the claims. The purpose of the summary is to promote the application of B. thuringiensis insecticidal crystal proteins and the development of patentable technologies.
A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1 (2006)

To molecularly define high-risk disease, we performed microarray analysis on tumor cells from 532 newly diagnosed patients with multiple myeloma (MM) treated on 2 separate protocols. Using log-rank tests of expression quartiles, 70 genes, 30% mapping to chromosome 1 (P < .001), were linked to early disease-related death. Importantly, most up-regulated genes mapped to chromosome 1q, and down-regulated genes mapped to chromosome 1p. The ratio of mean expression levels of up-regulated to down-regulated genes defined a high-risk score present in 13% of patients with shorter durations of complete remission, event-free survival, and overall survival (training set: hazard ratio [HR], 5.16; P < .001; test cohort: HR, 4.75; P < .001). The high-risk score also was an independent predictor of outcome endpoints in multivariate analysis (P < .001) that included the International Staging System and high-risk translocations. In a comparison of paired baseline and relapse samples, the high-risk score frequency rose to 76% at relapse and predicted short postrelapse survival (P < .05). Multivariate discriminant analysis revealed that a 17-gene subset could predict outcome as well as the 70-gene model. Our data suggest that altered transcriptional regulation of genes mapping to chromosome 1 may contribute to disease progression, and that expression profiling can be used to identify high-risk disease and guide therapeutic interventions.
SIV DNA vaccine co‐administered with IL‐12 expression plasmid enhances CD8 SIV cellular immune responses in cynomolgus macaques (2005)

Current evidence suggests that a strong induced CD8 human immunodeficiency virus type 1 (HIV-1)-specific cell mediated immune response may be an important aspect of an HIV vaccine. The response rates and the magnitude of the CTL responses induced by current DNA vaccines in humans need to be improved and cellular immune responses to DNA vaccines can be enhanced in mice by co-delivering DNA plasmids expressing immune modulators. Two reported to work well in the mouse systems are interleukin (IL)-12 and CD40L. We sought to compare these molecular adjuvants in a primate model system. The cDNA for macaque IL-12 and CD40L were cloned into DNA vectors. Groups of cynomolgus macaques were immunized with 2 mg of plasmid expressing SIVgag alone or in combination with either IL-12 or CD40L. CD40L did not appear to enhance the cellular immune response to SIVgag antigen. However, more robust results were observed in animals co-injected with the IL-12 molecular adjuvant. The IL-12 expanded antigen-specific IFN-gamma positive effector cells as well as granzyme B production. The vaccine immune responses contained both a CD8 component as well a CD4 component. The adjuvanted DNA vaccines illustrate that IL-12 enhances a CD8 vaccine immune response, however, different cellular profiles.
SIDES (2006)

This paper presents a design case study of SIDES: Shared Interfaces to Develop Effective Social Skills. SIDES is a tool designed to help adolescents with Asperger's Syndrome practice effective group work skills using a four-player cooperative computer game that runs on tabletop technology. We present the design process and evaluation of SIDES conducted over six months with a middle school social group therapy class. Our findings indicate that cooperative tabletop computer games are a motivating and supportive tool for facilitating effective group work among our target population and reveal several design lessons to inform the development of similar systems.
Cistrons encoding Escherichia coli heat-labile toxin (1979)

The structure and products of the two cistrons encoding the Escherichia coli heat-labile toxin (LT) were studied. The LT deoxyribonucleic acid (DNA) region had been isolated as part of a DNA fragment from the plasmid P307, and this fragment was joined to the cloning vector pBR313. Deletion mutations of various lengths were introduced into the LT DNA region and into the adjacent DNA sequences. Analysis of the deletions indicated that the maximum size of the LT DNA region was 1.2 x 10(6) daltons. Two proteins of 11,500 daltons and 25,500 daltons had been shown to be encoded by the LT DNA region. The functions of these LT gene products were investigated. The 11,500-dalton protein had an adsorption activity for Y-1 adrenal cells, and this protein was shown to form aggregates of four or five monomers. The 25,500-dalton protein was shown to have an adenylate cyclase-activating activity. The two cistrons encoding for each of the LT proteins have been located on a genetic map of the LT DNA region. Both cistrons are probably transcribed from the same promoter.
Observation of a dynamic wetting process using Laser‐Doppler velocimetry (1989)

Abstract The purpose of this study is to observe the dynamic wetting process of a slide coater flow ( Ca = 0.16; Re = 14.4; St = 0.0142; Δ eP = 2.5), using a specially‐developed Laser‐Doppler measuring technique. The measurements, carried out with glycerol solutions, reveal that the observed contact line is apparent and that a thin air film is entrained between the web and the liquid surface. The liquid is accelerated along the lower free surface and attains approximately 50% of the web velocity at the apparent contact line. Downstream from the apparent contact line, the liquid is further accelerated along the air film to the web velocity at the real contact line. The apparent contact angle increases with the capillary number Ca and air entrainment occurs at Ca = 0.25.
Involvement of phage T5 tail proteins and contact sites between the outer and inner membrane of Escherichia coli in phage T5 DNA injection. (1992)

The penetration of phage T5 DNA into the Escherichia coli envelope takes place through ion channels (Boulanger, P., and Letellier, L. (1992) J. Biol. Chem. 267, 3168-3172). To identify putative phage protein(s) involved in the formation of these channels, E. coli cells were infected at 37 degrees C with radioactively labeled phage and their envelopes were fractionated. After a flotation gradient, proteins belonging to the phage tail were recovered both in fractions containing the contact sites between the inner and outer membranes and in the outer membrane. The electrophoretic banding pattern of phage proteins indicates that the contact sites were enriched in the protein pb2. Moreover, infected cells were significantly enriched in contact sites as compared to intact cells. There was no enrichment of contact sites and very little radioactivity was found in this fraction and in the outer membrane when the cells were infected at 4 degrees C (i.e. under conditions where the phage does not inject its DNA). These results suggest that both contact sites and pb2 may play a central role in the translocation of phage T5 DNA.