gebhart/patrepeval huggingface dataset:
Membrane‐bound fatty acid desaturases are inserted co‐translationally into the ER and contain different ER retrieval motifs at their carboxy termini (2003)

Fatty acid desaturases (FADs) play a prominent role in plant lipid metabolism and are located in various subcellular compartments, including the endoplasmic reticulum (ER). To investigate the biogenesis of ER-localized membrane-bound FADs, we characterized the mechanisms responsible for insertion of Arabidopsis FAD2 and Brassica FAD3 into ER membranes and determined the molecular signals that maintain their ER residency. Using in vitro transcription/translation reactions with ER-derived microsomes, we show that both FAD2 and FAD3 are efficiently integrated into membranes by a co-translational, translocon-mediated pathway. We also demonstrate that while the C-terminus of FAD3 (-KSKIN) contains a functional prototypic dilysine ER retrieval motif, FAD2 contains a novel C-terminal aromatic amino acid-containing sequence (-YNNKL) that is both necessary and sufficient for maintaining localization in the ER. Co-expression of a membrane-bound reporter protein containing the FAD2 C-terminus with a dominant-negative mutant of ADP-ribosylation factor (Arf)1 abolished transient localization of the reporter protein in the Golgi, indicating that the FAD2 peptide signal acts as an ER retrieval motif. Mutational analysis of the FAD2 ER retrieval signal revealed a sequence-specific motif consisting of Phi-X-X-K/R/D/E-Phi-COOH, where -Phi- are large hydrophobic amino acid residues. Interestingly, this aromatic motif was present in a variety of other known and putative ER membrane proteins, including cytochrome P450 and the peroxisomal biogenesis factor Pex10p. Taken together, these data describe the insertion and retrieval mechanisms of FADs and define a new ER localization signal in plants that is responsible for the retrieval of escaped membrane proteins back to the ER.
Communications Reduction of Acetals to Ethers by Means of Lithium Aluminum Hydride-Aluminum Chloride (1958)

ADVERTISEMENT RETURN TO ISSUEPREVArticleCommunications Reduction of Acetals to Ethers by Means of Lithium Aluminum Hydride-Aluminum ChlorideErnest Eliel and Mark RerickCite this: J. Org. Chem. 1958, 23, 7, 1088Publication Date (Print):July 1, 1958Publication History Published online1 May 2002Published inissue 1 July 1958https://pubs.acs.org/doi/10.1021/jo01101a029https://doi.org/10.1021/jo01101a029research-articleACS PublicationsRequest reuse permissionsArticle Views222Altmetric-Citations24LEARN 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
Vaccine Trials for the Clinician: Prospects for Viral and Non-Viral Vectors (1997)

Recent progress in tumor genetics, tumor biology, and tumor immunology has renewed interest in the development of tumor vaccines. Unlike the previous generation of vaccines that consisted of the patient's own tumor cells in some form, the new vaccines contain defined peptides or genes with a known function. In order to induce a potent and long-lasting cell-mediated antitumor response, viral as well as nonviral vectors have been explored as vehicles for gene delivery. Both types of vectors have shown encouraging results in animal models. However, because of the many possible vectors that have been designed, it may be too early to say which type of vector is most efficient in the human. Clearly viral vectors have a higher transduction efficiency than most nonviral delivery systems. A drawback is that viral vectors may be toxic or immunogenic. Current research focuses on enhancing the targeting and specificity of both viral and nonviral vectors and control of transgene expression levels. Clinical studies using a variety of both viral and nonviral vectors have begun, and the results are forthcoming.
Laser Speckle and Its Elimination (1970)

“Objective” speckle arises from the uneven illumination of an object with a multiplicity of waves that interfere at its surface. “Subjective” speckle arises at rough objects even if they are illuminated evenly by a single wave. The noise in the image is caused by the interference of the point-figures, which have random phases. Subjective speckle cannot be reduced except by extending the aperture. On the other hand the “objective” speckle in a plane, for instance in the plane of a transparency, can be reduced, and in the limit made invisible, by a special type of wide-angle illumination. This consists of a one-parameter family of plane waves, which can be produced by diffraction at a special grating, or two crossed gratings, close to the object plane. This makes it possible to produce multiple holograms, with the same insensitivity to dust or scratches as diffused holograms, but without any visible speckle in the reconstruction.
Proteolytic processing of pro-alpha and pro-beta precursors from human beta-hexosaminidase. Generation of the mature alpha and beta a beta b subunits. (1988)

There are two major isozymes of human lysosomal beta-hexosaminidase (beta-N-acetylhexosaminidase, EC 3.2.1.52), hexosaminidase A, alpha(beta a beta b), and hexosaminidase B, 2(beta a beta b). The alpha subunit contains a single polypeptide chain, while the beta subunit is composed of two nonidentical chains (beta a and beta b) derived from a common pro-beta precursor. The mature subunits, like those of most lysosomal enzymes, are produced through the proteolytic processing of propolypeptides once they enter the lysosome. In order to define the structure of the alpha and beta subunits generated in the lysosome, the alpha, beta a, and beta b polypeptides of hexosaminidase A and B were separated by a combination of molecular sieve and ion exchange high performance liquid chromatography, and amino-terminal sequences were determined. These were localized to the deduced amino acid sequences of previously isolated cDNAs coding for the prepro-alpha and beta polypeptides. From this analysis, the sites of hydrolysis generating the mature alpha, beta a, and beta b chains from hexosaminidase A and B could be determined. First, the signal peptide, required for processing of the pre-propolypeptides through the rough endoplasmic reticulum was predicted from the first in-frame Met residue on the cDNA. Second, amino acid sequencing defined the amino termini of the mature polypeptide chains and identified the pro-sequences removed from both the pro-alpha and pro-beta polypeptides. Third, an internal cleavage resulted in the removal of a tetrapeptide, Arg-Gln-Asn-Lys, and tripeptide, Arg-Gln-Asn, from the pro-beta chain of hexosaminidase A and B, respectively , to generate the beta b and beta a chains. This result localized the beta b and beta a chains to the amino-terminal and carboxyl-terminal halves of the pro-beta sequence, respectively. Finally, we previously reported minimal or no carboxyl-terminal processing of the pro-beta chain in the lysosome. On the other hand, we suggest that there is trimming at the carboxyl terminus of the pro-alpha chain based on comparison of molecular weights of deglycosylated alpha with the isolated beta b and beta a chains comprising the mature beta subunit with those predicted from the cDNA. Thus, in the lysosome the pro forms of hexosaminidase A and B undergo extensive proteolytic processing which, while specific in nature, has the appearance of removing easily accessible, nonessential domains, rather than contributing to biosynthetic maturation of function.
Positioning biologic agents in the treatment of Crohnʼs disease (2009)

One decade after the emergence of biologic therapy for Crohn's disease (CD), our treatment algorithms are beginning to change. Once reserved for patients with refractory disease, disease unresponsive to conventional therapies, or those requiring multiple courses of corticosteroids, there is increasing evidence that early, aggressive interventions with immunosuppressants or biologic therapies targeting tumor necrosis factor-alpha or alpha-4 integrins can alter the natural history of CD by reducing the transmural complications of structuring and fistulization and the nearly inevitable requisite for surgical resections. More recent trials are beginning to suggest that intervention with combination therapy for selected patients with a poor prognosis may modify the long-term course of CD. Selection of patients with features predicting a complex or progressive course and early, combined intervention is now possible. Future studies are still needed to best identify predictors of response to individual agents with differing mechanisms of action, as well as to optimize the risk-benefit of long-term maintenance therapy.
[Preparation, characterization of paclitaxel-loaded Pluronic P105 polymeric micelles and in vitro reversal of multidrug resistant tumor]. (2008)

Drug delivery system (DDS) is a novel approach to overcome multidrug resistance (MDR) in tumors nowadays. This work was designed to investigate a new micellar delivery system for in vitro reversal of resistant ovarian tumor cells, based on a nonionic triblock copolymer Pluronic P105 and paclitaxel (PTX). The PTX-loaded polymeric micelles (P105/PTX) were prepared by thin film-hydration methods. Based on the results of single factor experiments, the P105/PTX micelle formulation was optimized by employing the central composite design-response surface methodology. The physico-chemical properties of the P105/PTX micelles were characterized, including micelle size, drug loading coefficient, in vitro release behavior, etc. The cytotoxicity of the P105/PTX micelles was assessed against human ovarian tumor cell line, SKOV-3/PTX, by a standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl (MTT) assay. In order to understand the possible mechanism of Pluronic effects in resistant tumor cells, cellular uptake study of micellar PTX or Rhodamine-123 (R-123) was also carried out. The results showed that the micelle size was about 24 nm with drug loading coefficient of 1.1% and PTX concentration of 700 microg x mL(-1). The cumulative release amount of PTX from the P105/PTX micelles was only 45.4% in 6 h (P < 0.05) and 79.6% in 24 h, whereas Taxol injection in 6 h released 95.2% PTX. The IC50 values of the P105/PTX micelles and Taxol injection against SKOV-3/PTX were 1.14 and 5.11 microg x mL(-1), and resistance reversion index (RRI) was 9.65 and 2.15, respectively. The micellar PTX or R-123 exhibited a significant increase in cellular uptake in resistant SKOV-3/PTX cells compared with free PTX or R-123. These results indicated that PTX could effectively be solubilized by Pluronic P105 block copolymers via thin film-hydration process and formulation optimization, producing nano-scale polymeric micelles with sustained release property in vitro. The P105/PTX micelles were effectively able to reverse resistance to PTX in SKOV-3/PTX tumor cells compared with Taxol injection or free PTX solution, and the enhanced cytotoxicity in the resistant SKOV-3/PTX cell was related to the improved cellular uptake of PTX by Pluronic P105 copolymers.
Experimental visualization of lithium conduction pathways in garnet-type Li7La3Zr2O12 (2012)

The evolution of the Li-ion displacements in the 3D interstitial pathways of the cubic garnet-type Li(7)La(3)Zr(2)O(12), cubic Li(7)La(3)Zr(2)O(12), was investigated with high-temperature neutron diffraction (HTND) from RT to 600 °C; the maximum-entropy method (MEM) was applied to estimate the Li nuclear-density distribution. Temperature-driven Li displacements were observed; the displacements indicate that the conduction pathways in the garnet framework are restricted to diffusion through the tetrahedral sites of the interstitial space.
Synthesis of 7- and 9-.beta.-D-ribofuranosides of 3-deaza-6-thioguanine and 3-deaza-2,6-diaminopurine by a novel ring closure of 4(5)-cyano-5(4)-cyanomethylimidazole .beta.-D-ribofuranosides (1978)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of 7- and 9-.beta.-D-ribofuranosides of 3-deaza-6-thioguanine and 3-deaza-2,6-diaminopurine by a novel ring closure of 4(5)-cyano-5(4)-cyanomethylimidazole .beta.-D-ribofuranosidesP. Dan Cook and Roland K. RobinsCite this: J. Org. Chem. 1978, 43, 2, 289–293Publication Date (Print):January 1, 1978Publication History Published online1 May 2002Published inissue 1 January 1978https://doi.org/10.1021/jo00396a025Request reuse permissionsArticle Views130Altmetric-Citations12LEARN 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 InReddit PDF (743 KB) Get e-Alertsclose Get e-Alerts
Serotypes of Neisseria meningitidis isolated from patients in Norway during the first six months of 1978 (1979)

During the first 6 months of 1978, 114 strains of Neisseria meningitidis isolated from patients in Norway were serotyped. Among 27 group C strains, type 2 was most common, whereas 82% of the 82 group B isolates did not react with antisera to the standard serotypes 1 to 12. These strains were shown to belong to a new serotype, type 15. Also some group A and C strains had the type 15 antigen. Investigations on a possible immunoprophylaxis against group B meningococcal disease in Norway should accordingly proceed with type 15 rather than with type 2 meningococci.
An NIH Career: from Bedside to Basic Research and Back (2005)

I was trained as a physician at Tufts Medical School where I had the opportunity to work in the laboratory of Ted Astwood, a premier endocrine researcher. This was my first taste of research, and I found it so exciting that in the summer of 1956, I actually braved a hurricane in order to go to the laboratory to finish an experiment. After medical school, I spent 2 years at Yale as an intern and assistant resident in internal medicine and then came to NIH in 1959 as a clinical associate in the Clinical Endocrinology Branch (CEB). My plan was to have a career in clinical medicine or clinical research.
Headache‐type adverse effects of NO donors: vasodilation and beyond (2010)

Although nitrate therapy, used in the treatment of cardiovascular disorders, is frequently associated with side-effects, mainly headaches, the summaries of product characteristics of nitrate-containing medicines do not report detailed description of headaches and even do not highlight the possibility of nitrate-induced migraine. Two different types of nitrate-induced headaches have been described: (i) immediate headaches that develop within the first hour of the application, are mild or medium severity without characteristic symptoms for migraine, and ease spontaneously; and (ii) delayed, moderate or severe migraine-type headaches (occurring mainly in subjects with personal or family history of migraine), that develop 3-6 h after the intake of nitrates, with debilitating, long-lasting symptoms including nausea, vomiting, photo- and/or phono-phobia. These two types of headaches are remarkably different, not only in their timing and symptoms, but also in the persons who are at risk. Recent studies provide evidence that the two headache types are caused by different mechanisms: immediate headaches are connected to vasodilation caused by nitric oxide (NO) release, while migraines are triggered by other actions such as the release of calcitonin gene-related peptide or glutamate, or changes in ion channel function mediated by cyclic guanosine monophosphate or S-nitrosylation. Migraines usually need anti-attack medication, such as triptans, but these drugs are contraindicated in most medical conditions that are treated using nitrates. In conclusion, these data recommend the correction of summaries of nitrate product characteristics, and also suggest a need to develop new types of anti-migraine drugs, effective in migraine attacks, that could be used in patients with risk for angina pectoris.
Low frequency of p53 mutations observed in a diverse collection of primary hepatocellular carcinomas. (1992)

Recent studies of the p53 tumor suppressor locus (designated TP53) in primary hepatocellular carcinoma (PHC) have identified a high frequency of codon 249 mutations. Due to the geographic location from which the samples were obtained and the substitution observed, the mutation was suggested to be attributable to aflatoxin B1 (AFB1) exposure. To determine the generality of this phenomenon, we have examined PHC tissues from 107 geographically and ethnically diverse sources. The frequency of p53 gene mutations was evaluated by using PCR/restriction-digest methods, GC-clamp (G+C-rich sequence) denaturing gradient gel electrophoresis, and DNA sequencing. The mutation rate observed in tumors from high-AFB1-exposure regions (25%) was more than double the rate observed in low-exposure regions (12%) but lower than the 50% frequency previously reported. Codon 249 mutations occurred at a much lower frequency than previously reported (2 of 107 samples examined). These results suggest that changes in DNA encoding p53 may not represent primary oncogenic effects but instead represent genetic changes related to tumor progression. High AFB1 levels may facilitate the generation of these progressional changes, but not by inducing a specific p53 gene mutation at codon 249 as previously reported.
Molecular anatomy of the thalamic complex and the underlying transcription factors (2015)

Thalamocortical loops have been implicated in the control of higher-order cognitive functions, but advances in our understanding of the molecular underpinnings of neocortical organization have not been accompanied by similar analyses in the thalamus. Using expression-based correlation maps and the manual mapping of mouse and human datasets available in the Allen Brain Atlas, we identified a few individual regions and several sets of molecularly related nuclei that partially overlap with the classic grouping that is based on topographical localization and thalamocortical connections. These new molecular divisions of the adult thalamic complex are defined by the combinatorial expression of Tcf7l2, Lef1, Gbx2, Prox1, Pou4f1, Esrrg, and Six3 transcription factor genes. Further in silico and experimental analyses provided the evidence that TCF7L2 might be a pan-thalamic specifier. These results provide substantial insights into the "molecular logic" that underlies organization of the thalamic complex.
Croquis congolais : de Buis à Vaucleroy, quelques regards d’artistes belges sur le Congo (1898-1930) (1993)

Au sein d’un colloque consacré aux images de l’Afrique et du Congo-Zaïre dans les lettres belges de langue française, il est tentant de s’interroger sur les images rapportées par des artistes plasticiens, non dans leur œuvre picturale, mais dans les écrits qu’ils ont laissés par ailleurs. Une telle approche complètera l’étude que nous avons publiée dans Papier blanc, encre noire. Cent ans de culture francophone en Afrique centrale (Zaïre, Rwanda et Burundi). Cette dernière contribution concer...
CD34+ progenitor cell isolation from blood and marrow: a comparison of techniques for small-scale selection. (1994)

The isolation and characterization of primitive hematopoietic cells and their purification in sufficient numbers is important in clinical and research marrow transplantation settings. As systems for large-scale isolation and amplification of such cells are developed, they may assume importance in transplantation, treatment of marrow failure and for gene therapy applications. Such cells have been isolated by numerous techniques and in this work, small-scale isolation of CD34+ cells by two immunoadsorption purification methods is compared with isolation by flow cytometry. While the immunoadsorption techniques allow for the processing of large numbers of density gradient-separated or unseparated cells for progenitor isolation, such techniques do not achieve the purity afforded by fluorescence activated cell sorter separation.
Twist Modulates Breast Cancer Stem Cells by Transcriptional Regulation of CD24 Expression (2009)

The cancer stem cell paradigm postulates that dysregulated tissue-specific stem cells or progenitor cells are precursors for cancer biogenesis. Consequently, identifying cancer stem cells is crucial to our understanding of cancer progression and for the development of novel therapeutic agents. In this study, we demonstrate that the overexpression of Twist in breast cells can promote the generation of a breast cancer stem cell phenotype characterized by the high expression of CD44, little or no expression of CD24, and increased aldehyde dehydrogenase 1 activity, independent of the epithelial-mesenchymal transition. In addition, Twist-overexpressing cells exhibit high efflux of Hoechst 33342 and Rhodamine 123 as a result of increased expression of ABCC1 (MRP1) transporters, a property of cancer stem cells. Moreover, we show that transient expression of Twist can induce the stem cell phenotype in multiple breast cell lines and that decreasing Twist expression by short hairpin RNA in Twist-overexpressing transgenic cell lines MCF-10A/Twist and MCF-7/Twist as well as in MDA-MB-231 partially reverses the stem cell molecular signature. Importantly, we show that inoculums of only 20 cells of the Twist-overexpressing CD44(+)/CD24(-/low) subpopulation are capable of forming tumors in the mammary fat pad of severe combined immunodeficient mice. Finally, with respect to mechanism, we provide data to indicate that Twist transcriptionally regulates CD24 expression in breast cancer cells. Taken together, our data demonstrate the direct involvement of Twist in generating a breast cancer stem cell phenotype through down-regulation of CD24 expression and independent of an epithelial-mesenchymal transition.