gebhart/patrepeval huggingface dataset:
Nuclear Import of Insulin-like Growth Factor-binding Protein-3 and -5 Is Mediated by the Importin β Subunit (2000)

Although insulin-like growth factor-binding protein (IGFBP)-3 and IGFBP-5 are known to modulate cell growth by reversibly sequestering extracellular insulin-like growth factors, several reports have suggested that IGFBP-3, and possibly also IGFBP-5, have important insulin-like growth factor-independent effects on cell growth. These effects may be related to the putative nuclear actions of IGFBP-3 and IGFBP-5, which we have recently shown are transported to the nuclei of T47D breast cancer cells. We now describe the mechanism for nuclear import of IGFBP-3 and IGFBP-5. In digitonin-permeabilized cells, where the nuclear envelope remained intact, nuclear translocation of wild-type IGFBP-3 appears to occur by a nuclear localization sequence (NLS)-dependent pathway mediated principally by the importin beta nuclear transport factor and requiring both ATP and GTP hydrolysis. Under identical conditions, an NLS mutant form of IGFBP-3, IGFBP-3[(228)KGRKR --> MDGEA], was unable to translocate to the nucleus. In cells where both the plasma membrane and nuclear envelope were permeabilized, wild-type IGFBP-3, but not the mutant form, accumulated in the nucleus, implying that the NLS was also involved in mediating binding to nuclear components. By fusing wild-type and mutant forms of NLS sequences (IGFBP-3 [215-232] and IGFBP-5 [201-218]) to the green fluorescent protein, we identified the critical residues of the NLS necessary and sufficient for nuclear accumulation. Using a Western ligand binding assay, wild-type IGFBP-3 and IGFBP-5, but not an NLS mutant form of IGFBP-3, were shown to be recognized by importin beta and the alpha/beta heterodimer but only poorly by importin alpha. Together these results suggest that the NLSs within the C-terminal domain of IGFBP-3 and IGFBP-5 are required for importin-beta-dependent nuclear uptake and probably also accumulation through mediating binding to nuclear components.
Trans Complementation of an E1A-Deleted Adenovirus with Codelivered E1A Sequences to Make Recombinant Adenoviral Producer Cells (1994)

Replication-incompetent adenovirus is conventionally produced by cells that supply replication-enabling proteins from viral sequences present in trans. As an alternative means of recombinant adenovirus production, replication-enabling E1A sequences were cotransduced into human prostate carcinoma cells infected with an E1A-deleted adenovirus containing a luciferase expression cassette. The replication-enabling plasmid was cotransduced by ionic linkage to the recombinant adenovirus exterior. Cells cotransduced with the replication-enabling plasmid made new adenovirus with titers up to 8 x 10(6) in the supernatants 72-120 hr after transduction. Like the parent virus, the virus present in the cotransduced supernatants and lysates was capable of transferring luciferase activity to new cells. The virus present in the cotransduced cell supernatants was amplified and shown to be identical to the parent virus by genomic analysis. It was concluded that simultaneous addition of a replication-defective adenovirus and a replication-enabling gene sequence in a trans configuration converts some of the cotransduced cells into recombinant adenovirus-producing cells.
Development and Properties of β-Glucuronide Linkers for Monoclonal Antibody−Drug Conjugates (2006)

A beta-glucuronide-based linker for attaching cytotoxic agents to monoclonal antibodies (mAbs) was designed and evaluated. We employed the cytotoxic auristatin derivatives MMAE (1a) and MMAF (1b) and doxorubicin propyloxazoline (DPO, 2) to give the beta-glucuronide drug-linkers 9a, 9b, and 17, respectively. Cysteine-quenched derivatives of 9b and 17 were determined to be substrates for E. coli beta-glucuronidase, resulting in facile drug release. The beta-glucuronide MMAF drug-linker 9b was highly stable in rat plasma with an extrapolated half-life of 81 days. Each drug-linker when conjugated to mAbs c1F6 (anti-CD70) and cAC10 (anti-CD30) gave monomeric antibody-drug conjugates (ADCs) with as many as eight drugs per mAb and had high levels of immunologically specific cytotoxic activity on cancer cell lines. cAC10-9a displayed pronounced antitumor activity in a subcutaneous Karpas 299 lymphoma tumor model. A single dose treatment led to cures in all animals at the 0.5 mg/kg dose level and above, and the conjugate was well tolerated at 100 mg/kg. In mice with subcutaneous renal cell carcinoma xenografts, the MMAF conjugate c1F6-9b was tolerated at 25 mg/kg and efficacious at 0.75 mg/kg. These results demonstrate that the beta-glucuronide linker system is an effective strategy for targeting cytotoxic agents providing ADCs with high degrees of efficacy at well-tolerated doses.
Toward an Artificial Oxidative DNA Photolyase (2003)

The design, synthesis, structure, and binding affinity of two dioptic receptors for the selective molecular recognition of the cis,syn cyclobutane pyrimidine dimer are reported. The design is based on two 2,6-di(acetamino)pyridine recognition units that are covalently linked via triple bonds to an anthraquinone functional spacer unit. The convergent synthesis uses a modified Sonogashira reaction involving a zinc transmetalation as the key step. The crystal structure of one of the receptors reveals a supramolecular 1D polymer with strong interactions mediated by shape self-complementarity, pi-stacking, and hydrogen bonding between adjacent molecules. Hydrogen bonding between adjacent strands enforces a parallel orientation, which leads to a noncentrosymmetric crystal structure of the highly polar compound. The receptor has an association constant of K(a) = 1.0 x 10(3) M(-1) with the cis,syn pyrimidine dimer, whereas binding of the trans,syn isomer is approximately 1 order of magnitude weaker.
20 W CW monolithic AlGaAs (810 nm) laser diode arrays (1992)

Good continuous-wave (CW) lifetimes have been demonstrated for 1 cm wide monolithic AIGaAs laser diode arrays (810 nm) with a 4800 μm total aperture width at a power level of 20 W. This represents the highest CW power level at which long lifetimes have been obtained.
The Synthesis of Morphine (1956)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Synthesis of MorphineMarshall Gates and Gilg TschudiCite this: J. Am. Chem. Soc. 1956, 78, 7, 1380–1393Publication Date (Print):April 1, 1956Publication History Published online1 May 2002Published inissue 1 April 1956https://pubs.acs.org/doi/10.1021/ja01588a033https://doi.org/10.1021/ja01588a033research-articleACS PublicationsRequest reuse permissionsArticle Views6797Altmetric-Citations222LEARN 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
A Comparison of the Autism Treatment Evaluation Checklist (ATEC) and the Childhood Autism Rating Scale (CARS) for the Quantitative Evaluation of Autism (2013)

The purpose of this study was to evaluate scores generated from the Autism Treatment Evaluation Checklist (ATEC), a parent-rated measure, and those derived from professionally completed Childhood Autism Rating Scale (CARS) evaluations. A cohort of 56 participants diagnosed with an autism spectrum disorder was used for the study, and each child was evaluated independently by the parent using the ATEC and a health care professional using the CARS. The Spearman's rank correlation statistic ρ was used to evaluate the correlation between ATEC and CARS scores. It was observed that there was a significant correlation between total ATEC and CARS scores (ρ = .71). Specific domains in the ATEC evaluation significantly correlated with CARS scores. Sensitivity, specificity, and receiver operating characteristic confirmed the association between CARS and ATEC domains. The results help to validate the utility of the parentally completed ATEC in comparison with an established, professional-related measure of autism.
Minimizing atmospheric dispersion effects in compensated imaging (1977)

A compensated imaging system that corrects optical path length distortions due to atmospheric turbulence by means of an achromatic corrector will have residual errors caused by the dispersion of the atmosphere. These errors become significant for astronomical objects at large zenith angles, but they may be minimized by special dispersion correctors.
The Pregnancy Hormone Relaxin Binds to and Activates the Human Glucocorticoid Receptor (2005)

The insulin-like peptide relaxin is a central hormone of pregnancy, but it also produces antifibrotic, myocardial, renal, central nervous, and vascular effects. Recently, two G-protein-coupled receptors, LGR7 and LGR8, were identified as relaxin receptors. Prompted by reports on the immunoregulatory effects of relaxin, we investigated possible interactions with the human glucocorticoid receptor (GR). Relaxin blunted the endotoxin-induced production of inflammatory cytokines (interleukin 1 [IL-1], IL-6, and tumor necrosis factor- alpha) by human macrophages, an effect that was suppressed by the GR antagonist RU-486. In three different cell lines, relaxin induced GR activation, nuclear translocation, and DNA binding as assessed in glucocorticoid response element (GRE)-luciferase assays. Coimmunoprecipitation experiments revealed physical interaction of endogenous and exogenous relaxin with cytoplasmic and nuclear GR. Relaxin competed with GR agonists for GR binding both in vivo, in whole-cell assays, and in vitro, in fluorescence polarization assays. In LGR7- and LGR8-free cells, the relaxin-mediated activation of GR was preserved. In conclusion, relaxin acts as a GR agonist, a pathway pivotal to relaxin's effects on cytokine secretion by human macrophages. These findings may deepen our understanding of relaxin's many physiologic actions as well as our insights into general principles of hormone signaling.
Axicon on a gradient index lens (AXIGRIN): integrated optical bench for Bessel beam generation from a point-like source (2014)

We propose and demonstrate a novel concept of a compact optical component aimed at transforming a point-like source into a Bessel beam. This component, called AXIGRIN, consists of an axicon fabricated at the end facet of a gradient index lens. It can be directly coupled to an optical fiber, a microscope objective, or vertical-external-cavity surface-emitting-laser to be used without preliminary adjustments, which is of practical interest for end users. This opens new avenues in domains, such as imaging, particle acceleration and manipulation, optical coherence tomography, data storage, laser cutting, etc. AXIGRIN also opens the perspective of using Bessel beams for endoscopy. The generation of linearly and radially polarized Bessel beams is demonstrated with a fiber AXIGRIN.
Endo-β-N-acetylglucosaminidases from Infant Gut-associated Bifidobacteria Release Complex N-glycans from Human Milk Glycoproteins (2012)

Breastfeeding is one of the main factors guiding the composition of the infant gut microbiota in the first months of life. This process is shaped in part by the high amounts of human milk oligosaccharides that serve as a carbon source for saccharolytic bacteria such as Bifidobacterium species. Infant-borne bifidobacteria have developed various molecular strategies for utilizing these oligosaccharides as a carbon source. We hypothesized that these species also interact with N-glycans found in host glycoproteins that are structurally similar to free oligosaccharides in human milk. Endo-β-N-acetylglucosaminidases were identified in certain isolates of Bifidobacterium longum subsp. longum, B. longum subsp. infantis, and Bifidobacterium breve, and their presence correlated with the ability of these strains to deglycosylate glycoproteins. An endoglycosidase from B. infantis ATCC 15697, EndoBI-1, was active toward all major types of N-linked glycans found in glycosylated proteins. Its activity was not affected by core fucosylation or extensive fucosylation, antenna number, or sialylation, releasing several N-glycans from human lactoferrin and immunoglobulins A and G. Extensive N-deglycosylation of whole breast milk was also observed after coincubation with this enzyme. Mutation of the active site of EndoBI-1 did not abolish binding to N-glycosylated proteins, and this mutant specifically recognized Man(3)GlcNAc(2)(α1-6Fuc), the core structure of human N-glycans. EndoBI-1 is constitutively expressed in B. infantis, and incubation of the bacterium with human or bovine lactoferrin led to the induction of genes associated to import and consumption of human milk oligosaccharides, suggesting linked regulatory mechanisms among these glycans. This work reveals an unprecedented interaction of bifidobacteria with host N-glycans and describes a novel endoglycosidase with broad specificity on diverse N-glycan types, potentially a useful tool for glycoproteomics studies.
Real time PCR profiling of 330 human micro‐RNAs (2006)

The small size of miRNAs makes profiling of all the 462 known human miRNAs difficult using single cell samples. Recently, we showed that judicious sequence partitioning between RT primers and second strand synthesis primers permitted multiplexed RT-PCR amplification of miRNA in very small samples to allow individual real time PCR quantification. Here, we show that zip coding the primers and TaqMan probes with sequences specific to each miRNA greatly improves reaction specificity, which permits the profiling of all miRNAs in a single multiplexed RT-PCR reaction.
Serum albumin as a modulator on growth of the human breast cancer cell line, MCF-7. (1990)

The growth of the estrogen responsive human breast cancer cell line, MCF-7, is inhibited by high serum concentrations, and this growth inhibition can be abolished by estradiol (E2). To investigate this inhibitory phenomenon further, we decided to purify the inhibitory factor from newborn calf serum (NCS). After the use of various fractionation methods, we found that inhibitory activity in NCS was exclusively expressed by albumin containing fractions. The inhibitory potential of several commercial bovine serum albumin (BSA) preparations and one human serum albumin preparation were analysed. They all exerted inhibitory activity comparable to that of NCS, and BSA inhibited MCF-7 cell proliferation in a concentration-dependent manner similar to that of NCS. Albumin itself or a contaminating factor in the albumin preparations seemed to be responsible for the growth inhibition. It could be excluded that the growth inhibitor TGF-beta, known to be present in serum, was the factor which inhibited MCF-7 cell proliferation. We separated contaminating proteins from albumin by gel filtration of a BSA preparation, revealing that neither low mol.wt nor high mol.wt proteins in the preparation exerted any significant growth inhibitory activity. NCS and BSA affected the secretion of specific proteins from MCF-7 cells similarly, when grown with or without E2. In conclusion, we assume that albumin is the factor in serum exerting a growth inhibition which can be reversed by E2. Our results indicate that albumin may affect cell proliferation by modulating the activities of autocrine growth regulatory factors.
Rapid clonal growth and serial passage of human diploid fibroblasts in a lipid-enriched synthetic medium supplemented with epidermal growth factor, insulin, and dexamethasone. (1981)

A serum-free, hormone-supplemented medium, enriched with a mixture of lipids, has been developed that supports rapid clonal growth of human diploid fetal lung fibroblasts (Flow 2000, WI-38, MRC-5, and IMR-90) and of low-passage human foreskin fibroblasts. The medium, which contains less than 1 microgram of total protein per ml, also supports serial passage of Flow 2000 cells under totally serum-free conditions. It provides lipid at a total of 10 micrograms/ml as a liposome prepared from a mixture of soybean lecithin, cholesterol, sphingomyelin, vitamin E, and vitamin E acetate. The soybean lecithin, which contains a variety of naturally occurring phospholipids, can be replaced with a mixture of highly purified phospholipids. Except for possible contaminants in the substances used in its preparation, the serum-free medium is fully defined chemically. It consists of an optimized basal nutrient medium, MCDB 110, supplemented with insulin, epidermal growth factor, dexamethasone, prostaglandins E1 and F2 alpha, phosphoenolpyruvate, dithiothreitol, glutathione, and the lipids listed above.
Human RNA Slows Down a Primate Retrovirus (2005)

On page
 557, researchers describe a so-called microRNA in human cells that appears to restrict the proliferation of a retrovirus, the viral family to which HIV belongs.
Transcriptionally Defective Retroviruses Containing lacZ for the In Situ Detection of Endogenous Genes and Developmentally Regulated Chromatin (1989)

Previously, we demonstrated that expression of transduced Escherichia coli lacZ can be detected in individual mammalian cells with a fluorescence-activated cell sorter (Nolan et al. 1988), a technique referred to as FACS-GAL. This fluorogenic assay permits the quantitative measurement of E. coli β-galactosidase (β-Gal) in individual viable cells. This technique also permits rare cells expressing β-Gal to be isolated utilizing the sorting capacity of the FACS. We have taken advantage of this feature to isolate β-Gal-expressing cells where the lacZ gene is under the control of endogenous transcription control elements. To permit the isolation of such cells, we have developed systems for delivering a reporter gene, E. coli lacZ, into the genome of mammalian cells in such a way that its expression is dependent on endogenous transcription control elements. We have stably introduced lacZ into the genome of mammalian cell lines by infection with lacZ gene search retroviruses, as well...
Prognostic significance of clinical and pathologic features in diffuse large B-cell lymphoma (1993)

The authors suggest that the evaluation of pathologic features in diffuse large B-cell lymphoma has little prognostic utility and recommend that the pathology evaluation be limited to features that are useful for diagnostic purposes.
Halogen bonds in biological molecules (2004)

Short oxygen-halogen interactions have been known in organic chemistry since the 1950s and recently have been exploited in the design of supramolecular assemblies. The present survey of protein and nucleic acid structures reveals similar halogen bonds as potentially stabilizing inter- and intramolecular interactions that can affect ligand binding and molecular folding. A halogen bond in biomolecules can be defined as a short C-X...O-Y interaction (C-X is a carbon-bonded chlorine, bromine, or iodine, and O-Y is a carbonyl, hydroxyl, charged carboxylate, or phosphate group), where the X...O distance is less than or equal to the sums of the respective van der Waals radii (3.27 A for Cl...O, 3.37 A for Br...O, and 3.50 A for I...O) and can conform to the geometry seen in small molecules, with the C-X...O angle approximately 165 degrees (consistent with a strong directional polarization of the halogen) and the X...O-Y angle approximately 120 degrees . Alternative geometries can be imposed by the more complex environment found in biomolecules, depending on which of the two types of donor systems are involved in the interaction: (i) the lone pair electrons of oxygen (and, to a lesser extent, nitrogen and sulfur) atoms or (ii) the delocalized pi -electrons of peptide bonds or carboxylate or amide groups. Thus, the specific geometry and diversity of the interacting partners of halogen bonds offer new and versatile tools for the design of ligands as drugs and materials in nanotechnology.
Active and latent forms of transforming growth factor beta activity in synovial effusions. (1989)

We have evaluated the possible involvement of TGF-beta in rheumatoid arthritis by assay of 16 cell-free synovial fluids for the presence of its active and "latent" forms. Evidence has been obtained for TGF-beta-like activity in synovial effusions by four criteria: (a) TGF-beta receptor competition, (b) soft-agar colony formation of AKR-2B and NRK-49F indicator cells, (c) immunological neutralization of the biological activity, and (d) biochemical activation of a latent form.
A Ten‐Year Safety Study of the Oral Androgen Testosterone Undecanoate (1994)

Testosterone undecanoate (Andriol) is an oral androgen that provides the hypogonadal patient with the unmodified testosterone molecule. It was introduced in the mid-1970s. This is a report on the safety of this oral androgen. Of 35 men originally included in the study, 33 could be followed up for a minimum of 10 years. In them no alteration in the biochemical parameters of liver function could be detected. Upon annual measurements (7-9 hours after ingestion of testosterone undecanoate), serum levels of testosterone ranged between 5.4 +/- 1.9 and 6.5 +/- 1.9 nmol/L (normal range 8-24) and of 5 alpha-dihydrotestosterone between 3.2 +/- 1.8 and 3.5 +/- 1.7 nmol/L (normal range 0.8-2.5). These levels remained constant during the study period, indicating that there is no increased hepatic enzymatic breakdown of the androgen over time. Eight men were older than 50 years at the start of the study. Over the 10-year period in two of them a mild reduction in urine flow was measured, whereas in the other six this could not be demonstrated. Digital examination of the prostate did not reveal signs of prostate tumors. Testosterone undecanoate appears to be a safe oral androgen. A yearly checkup of the patient on therapy with this androgen seems adequate.