gebhart/patrepeval huggingface dataset:
Subcellular Localization of Moesin in Dynamic Filopodia, Retraction Fibers, and Other Structures Involved in Substrate Exploration, Attachment, and Cell-Cell Contacts (1995)

Moesin, a member of the talin-4.1 superfamily, is a linking protein of the submembraneous cytoskeleton. It is expressed in variable amounts in cells of different phenotypes such as macrophages, lymphocytes, fibroblastic, endothelial, epithelial, and neuronal cell lines. In this report we show that moesin is not randomly distributed throughout the cortical cytoskeleton, but rather that it is concentrated in specialized microdomains. It is localized in the intracellular core of microextensions known as filopodia, microvilli, microspikes, and retraction fibers. This subcellular distribution follows closely the dynamic changes in cell shape that take place when cells attach, spread, and move spontaneously or in response to extracellular signals. This suggests a similar function for moesin in diverse cell types related to the dynamic restructuring of domains of the plasma membrane and underlying membrane skeleton. Support for this comes from studies on PC-12 cells, which respond to NGF by extending neurites and moesin is redistributed from a diffuse localization to growth cone filopodia. In fibroblastic (NIH3T3) or macrophage (RAW264.7) cell lines, moesin is found in filopodia appearing at random on the cell surface soon after the cells are placed in culture, begin to attach, and spread. In polarized epithelial cells (LLC-PK1), moesin is associated with peripheral filopodia and apical microvilli. The cellular microextensions containing moesin are devoid of microtubules, focal contact proteins such as vinculin, and cortical cytoskeletal elements such as protein 4.1, but they do contain varying amounts of actin microfilaments. This localization of moesin in microextensions is not influenced by cytochalasin B. Treatment of cells with phorbolester (PMA) causes rapid cell spreading, disappearance of filopodia and retraction fibers, and moesin does not accumulate in the actin-rich lamellae that form at the cellular edges. After removal of PMA, cells retract and moesin again becomes concentrated in filopodia and retraction fibers. These studies support the hypothesis that filopodia, retraction fibers, and other microextensions of the plasma membrane are unique cellular microdomains with characteristic submembraneous components. Moesin could be involved in the dynamic restructuring of such microdomains by regulating binding interactions between the plasma membrane and the actin cytoskeleton.
Artificial Vision for the Blind by Connecting a Television Camera to the Visual Cortex (2000)

Blindness is more feared by the public than any ailment with the exception of cancer and AIDS. We report the development of the first visual prosthesis providing useful "artificial vision" to a blind volunteer by connecting a digital video camera, computer, and associated electronics to the visual cortex of his brain. This device has been the objective of a development effort begun by our group in 1968 and represents realization of the prediction of an artificial vision system made by Benjamin Franklin in his report on the "kite and key" experiment, with which he discovered electricity in 1751.
.beta.-Substituted organolithium compounds. New reagents for synthesis (1979)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT.beta.-Substituted organolithium compounds. New reagents for synthesisJose Barluenga, Francisco J. Fananas, and Miguel YusCite this: J. Org. Chem. 1979, 44, 26, 4798–4801Publication Date (Print):December 1, 1979Publication History Published online1 May 2002Published inissue 1 December 1979https://pubs.acs.org/doi/10.1021/jo00394a011https://doi.org/10.1021/jo00394a011research-articleACS PublicationsRequest reuse permissionsArticle Views568Altmetric-Citations34LEARN 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
Structural and kinetic analysis of drug resistant mutants of HIV‐1 protease (1999)

Mutants of HIV-1 protease that are commonly selected on exposure to different drugs, V82S, G48V, N88D and L90M, showed reduced catalytic activity compared to the wild-type protease on cleavage site peptides, CA-p2, p6pol-PR and PR-RT, critical for viral maturation. Mutant V82S is the least active (2-20% of wild-type protease), mutants N88D, R8Q, and L90M exhibit activities ranging from 20 to 40% and G48V from 50 to 80% of the wild-type activity. In contrast, D30N is variable in its activity on different substrates (10-110% of wild-type), with the PR-RT site being the most affected. Mutants K45I and M46L, usually selected in combination with other mutations, showed activities that are similar to (60-110%) or greater than (110-530%) wild-type, respectively. No direct relationship was observed between catalytic activity, inhibition, and structural stability. The mutants D30N and V82S were similar to wild-type protease in their stability toward urea denaturation, while R8Q, G48V, and L90M showed 1.5 to 2.7-fold decreased stability, and N88D and K45I showed 1.6 to 1.7-fold increased stability. The crystal structures of R8Q, K45I and L90M mutants complexed with a CA-p2 analog inhibitor were determined at 2.0, 1.55 and 1.88 A resolution, respectively, and compared to the wild-type structure. The intersubunit hydrophobic contacts observed in the crystal structures are in good agreement with the relative structural stability of the mutant proteases. All these results suggest that viral resistance does not arise by a single mechanism.
Molecular cloning and chromosomal mapping of DNA rearranged with the parathyroid hormone gene in a parathyroid adenoma. (1989)

Parathyroid adenomas are common benign neoplasms for which no chromosomal defects have been described. We recently found two parathyroid adenomas bearing clonal restriction fragment abnormalities involving the PTH locus, and now show that in one of these tumors: (a) a DNA rearrangement occurred at the PTH locus; (b) the rearrangement separated the PTH gene's 5' flanking region from its coding exons, conceivably placing a newly adjacent gene under the influence of PTH regulatory elements; (c) the DNA that recombined with PTH normally maps to 11q13, the known chromosomal location of several oncogenes and the gene for multiple endocrine neoplasia type I; and (d) the rearrangement was a reciprocal, conservative recombination of the locus on 11q13 (Human Gene Mapping Library assignment D11S287) with PTH (on 11p15). These data provide molecular cytogenetic evidence for the clonal occurrence of a major chromosome 11 aberrancy in this benign parathyroid tumor. The D11S287 clone could prove useful in genetic linkage analyses, in determining precise 11q13 breakpoints in other neoplasms, and in identifying a gene on chromosome 11 that may participate in parathyroid tumor development.
Constitutive activation of MEK1 in chondrocytes causes Stat1-independent achondroplasia-like dwarfism and rescues the Fgfr3-deficient mouse phenotype (2004)

We generated transgenic mice that express a constitutively active mutant of MEK1 in chondrocytes. These mice showed a dwarf phenotype similar to achondroplasia, the most common human dwarfism, caused by activating mutations in FGFR3. These mice displayed incomplete hypertrophy of chondrocytes in the growth plates and a general delay in endochondral ossification, whereas chondrocyte proliferation was unaffected. Immunohistochemical analysis of the cranial base in transgenic embryos showed reduced staining for collagen type X and persistent expression of Sox9 in chondrocytes. These observations indicate that the MAPK pathway inhibits hypertrophic differentiation of chondrocytes and negatively regulates bone growth without inhibiting chondrocyte proliferation. Expression of a constitutively active mutant of MEK1 in chondrocytes of Fgfr3-deficient mice inhibited skeletal overgrowth, strongly suggesting that regulation of bone growth by FGFR3 is mediated at least in part by the MAPK pathway. Although loss of Stat1 restored the reduced chondrocyte proliferation in mice expressing an achondroplasia mutant of Fgfr3, it did not rescue the reduced hypertrophic zone, the delay in formation of secondary ossification centers, and the achondroplasia-like phenotype. These observations suggest a model in which Fgfr3 signaling inhibits bone growth by inhibiting chondrocyte differentiation through the MAPK pathway and by inhibiting chondrocyte proliferation through Stat1.
BIGL: Biochemically Intuitive Generalized Loewe null model for prediction of the expected combined effect compatible with partial agonism and antagonism (2017)

Clinical efficacy regularly requires the combination of drugs. For an early estimation of the clinical value of (potentially many) combinations of pharmacologic compounds during discovery, the observed combination effect is typically compared to that expected under a null model. Mechanistic accuracy of that null model is not aspired to; to the contrary, combinations that deviate favorably from the model (and thereby disprove its accuracy) are prioritized. Arguably the most popular null model is the Loewe Additivity model, which conceptually maps any assay under study to a (virtual) single-step enzymatic reaction. It is easy-to-interpret and requires no other information than the concentration-response curves of the individual compounds. However, the original Loewe model cannot accommodate concentration-response curves with different maximal responses and, by consequence, combinations of an agonist with a partial or inverse agonist. We propose an extension, named Biochemically Intuitive Generalized Loewe (BIGL), that can address different maximal responses, while preserving the biochemical underpinning and interpretability of the original Loewe model. In addition, we formulate statistical tests for detecting synergy and antagonism, which allow for detecting statistically significant greater/lesser observed combined effects than expected from the null model. Finally, we demonstrate the novel method through application to several publicly available datasets.
Microfluidic Devices for High Throughput Cell Sorting and Chemical Treatment (2011)

Separation by size is a fundamental analytical and preparative technique in biology, medicine, and chemistry. Deterministic lateral displacement (DLD) arrays are mi-crofluidic devices capable of high-precision particle sorting based on size. In this thesis, we will discuss improvements in the functionality of DLD arrays and several new applications. We’ll first discuss a methodology for performing sequential on-chip chemical treatment by using the DLD array to direct particles in the “bumping” trajectory across co-flowing reagent streams and demonstrates this technique with platelet labeling and washing and E. Coli lysis and chromosomal separation. We then discuss a deterministic microfluidic ratchet that could separate particles in an intermediate size range using a DLD array with triangular posts in an oscillating flow. We then extended this idea of using triangular posts in DLD arrays to continuous-flow operation and showed significant performance enhancements over arrays with circu-lar posts when the triangle vertex is used as the displacement edge. Taking this idea of increasing device throughput to the next step, we developed a highly parallelized
Safety and immunogenicity of a serogroups A/C Neisseria meningitidis oligosaccharide-protein conjugate vaccine in young children. A randomized controlled trial (1996)

Objective. - To assess the safety and immunogenicity of a bivalent serogroups A/C meningococcal oligosaccharide-protein conjugate vaccine compared with the licensed meningococcal polysaccharide vaccine. Design. - Randomized controlled trial. Study population. - Ninety healthy 18- to 24- month-old children who were seen at a southern California Kaiser Permanente clinic. Interventions. - Vaccination with either the meningococcal conjugate vaccine (at 1 of 2 dosages) or the polysaccharide vaccine, with 2 doses given 2 months apart. Main Outcome Measures. - Immune response to each vaccine dose as determined by measurement of serogroup-specific total antibodies by enzyme-linked immunosorbent assay (ELISA) and by assessment of serum bactericidal activity. Results. - Both vaccines appeared to be safe, and nearly all children responded with greater than 4-fold increases in antibody levels. The 2 dosages of the conjugate vaccine induced similar antibody responses; therefore, the data for the 2 conjugate vaccine groups were combined. Following 2 doses. ELISA antibody levels against group C meningococcus were significantly higher in conjugate vaccine recipients than in polysaccharide vaccine recipients (16.66 μg/mL vs 8.31 μg/mL; P&lt;.001), but antibody levels against group A were not significantly different (22.75 μg/mL vs 21.24 μg/mL; P=.70). The serum bactericidal assays showed striking differences between the conjugate and polysaccharide vaccine groups. Geometric mean serum bactericidal titers were significantly higher in conjugate vaccine recipients (755.6 vs 37.6 for group A, P&lt;.001; 3197.9 vs 11.4 for group C, P&lt;.001). Conclusions. - The immune response induced by this meningococcal oligosaccharide-protein conjugate vaccine was qualitatively different from that induced by the polysaccharide vaccine, and the antibodies it elicited provided greater functional activity.
Identification of a Zinc Finger Protein That Binds to the Sterol Regulatory Element (1989)

Cholesterol balance in mammalian cells is maintained in part by sterol-mediated repression of gene transcription for the low density lipoprotein receptor and enzymes in the cholesterol biosynthetic pathway. A promoter sequence termed the sterol regulatory element (SRE) is essential for this repression. With the use of an oligonucleotide containing the SRE to screen a human hepatoma complementary DNA expression library, a clone for a DNA binding protein was isolated that binds to the conserved SRE octanucleotide in both a sequence-specific and a single-strand--specific manner. This protein contains seven highly conserved zinc finger repeats that exhibit striking sequence similarity to retroviral nucleic acid binding proteins (NBPs). We have designated the protein "cellular NBP" (CNBP). CNBP is expressed in a wide variety of tissues, is up regulated by sterols, and exhibits binding specificity that correlates with in vivo function. These properties are consistent with a role in sterol-mediated control of transcription.
Efficacy and Toxicity Studies with Radiopaque Perfluorocarbon (1972)

Brominated perfiuorocarbon compounds were investigated for use as radiographic contrast media. Perfiuoroctylbromide and perfluorohexylbromide were found to have very low toxicity and satisfactory radiographic density. These compounds have properties not found in other radiopaque agents, such as low surface tension, chemical and biological nonreactivity, nondissociated molecules, and relatively rapid and complete vaporization.
Articular cartilage repair. Behavior of rabbit chondrocytes during tissue culture and subsequent allografting. (1977)

Chondrocytes from rabbit articular cartilage were freed from their matrix by enzymatic digestion. Under appropriate conditions of culture, these cells proliferated through many generations while maintaining their chondrocytic differentiation. They produced a cartilage-like matrix which was studied by histologic, electron microscopic, and chemical techniques. Chondroid tissue from subculture on decalcified bone, allografted into the rabbit knee, repaired a large articular defect in 10 days.
Reelin and apolipoprotein E receptor 2 in the embryonic and mature brain: effects of an evolutionary change in the apoER2 gene (2009)

In the mature cerebral cortex of higher vertebrates, neurons are arranged in layers, each layer containing neurons of the same functional class. The cortical layering pattern is laid down during development by migration of young post-mitotic neurons along glial fibres to their correct positions in the cortical plate. The mechanics of whole-cell movement are well understood, but there is still uncertainty as to how a migrating neuron is instructed to leave its glial support when it reaches its destination. An intraneuronal signalling pathway initiated by reelin and containing apolipoprotein E receptor 2 (apoER2) is essential for normal cortical layering, and there is strong evidence that detachment of a migrating neuron is brought about by reelin-dependent downregulation of alpha3 integrin. But there remains the problem of how the reelin signal is switched on at a position in the cortex appropriate for each class of neuron. ApoER2 of placental mammals contains an amino acid sequence that is encoded in a separate exon in the apoER2 gene and is required for normal memory and spatial learning. The separate exon is not present in marsupials, birds or reptiles. The addition of this exon to the evolving apoER2 gene may have contributed to the success of placental mammals.
Imidazole- and alkylamine-ligated iron(II,III) chlorin complexes as models for histidine and lysine coordination to iron in dihydroporphyrin-containing proteins: characterization with magnetic circular dichroism spectroscopy (1993)

An extensive series of five- and six-coordinate (1-methylimidazole)-, (1-butylamine)-, and (pyridine)iron(II, III) chlorin complexes are characterized for the first time with magnetic circular dichroism (MCD) spectroscopy. The chlorins (dihydroporphyrins) employed are octaethylchlorin, mesochlorin, and “methyl” chlorin (2,2,4-trimethyldeuterochlorin, featuring a gem-dimethyl-substituted peripheral carbon). The species studied include the bis(1-methylimidazole)ferric, bis(1-methylimidazole)ferrous, (1,2-dimethylimidazole)ferrous, and 1-methylimidazole/CO or NO complexes together with analogous bis(pyridine)- and bis(1-butylamine)ferrous adducts and their CO-ligated derivatives. The results presented establish MCD spectral signatures for use in determining whether an iron chlorin-containing protein bears either a histidine or a lysine axial ligand. Analysis of data obtained with different ring-reduced mesochlorin isomers shows that the method is insensitive to the site of pyrrole ring reduction. This latter observation will facilitate the use of mesochlorins in reconstitution experiments with structurally-defined heme proteins in order to investigate mixed-ligand complexes which are difficult to generate synthetically. In general, the MCD spectra of iron chlorin complexes are most sensitive to the identity, number, and type of axial ligand, along with the oxidation and spin state, and are relatively insensitive to changes in the equatorial plane such as the site of pyrrole ring reduction. Therefore, it appears that MCD spectroscopy will be of particular use in the identification of proximal and distal axial ligands in chlorin-containing proteins, as has repeatedly been shown to be the case with protoheme-based iron porphyrins. © 1993, American Chemical Society. All rights reserved.
Inhibition of Hepatitis B Virus Replication during Adenovirus and Cytomegalovirus Infections in Transgenic Mice (1998)

We have previously demonstrated that hepatitis B virus (HBV) replication and gene expression are abolished in the livers of HBV transgenic mice by cytotoxic T lymphocytes (CTLs) and during lymphocytic choriomeningitis virus (LCMV) infection, stimuli that trigger the production of alpha/beta interferon, gamma interferon, and tumor necrosis factor alpha in the liver. We now report that hepatic HBV replication and gene expression are inhibited by the local induction of these cytokines during adenovirus- and murine cytomegalovirus (MCMV)-induced hepatitis. Further, we show that MCMV also blocks HBV replication and gene expression in the proximal convoluted tubules of the kidney by causing interstitial nephritis and inducing the same cytokines in the renal parenchyma. These results suggest that inflammatory cytokines probably contribute to viral clearance during acute viral hepatitis in humans, and they imply that induction of these cytokines in the liver and other infected tissues of chronically infected patients might have therapeutic value.
Neurotolerability of Gadobenate Dimeglumine in a Rat Model of Focal Brain Ischemia: (1999)

In experimental conditions of focal brain ischemia associated with BBB lesions, gadobenate dimeglumine was well tolerated up to doses even 10 times higher than the maximum clinical dose (0.3 mmol/kg) intended for brain imaging procedures.
MIMO Broadcast Channels with Block Diagonalization and Finite Rate Feedback (2007)

Block diagonalization is a linear precoding technique for the multiple antenna broadcast (downlink) channel that involves transmission of multiple data streams to each receiver such that no multi-user interference is experienced at any of the receivers. This low-complexity scheme operates only a few dB away from capacity but does require very accurate channel knowledge at the transmitter, which can be very difficult to obtain in fading scenarios. We consider a limited feedback system where each receiver knows its channel perfectly, but the transmitter is only provided with a finite number of channel feedback bits from each receiver. Using a random vector quantization argument, we quantify the throughput loss due to imperfect channel knowledge as a function of the feedback level. The quality of channel knowledge must improve proportional to the SNR in order to prevent interference-limitations, and we show that scaling the number of feedback bits linearly with the system SNR is sufficient to maintain a bounded rate loss. Finally, we investigate a simple scalar quantization scheme that is seen to achieve the same scaling behavior as vector quantization.
Properties of Zn-doped VPE-grown GaN. I. Luminescence data in relation to doping conditions (1980)

Experimental results on optical and electrical properties of VPE-grown GaN doped with Zn under various conditions of growth are presented. The incorporation of Zn into GaN was found to be critically dependent on growth conditions. Four different Zn-related acceptorlike centers A–D were found to occur, with broad radiative emissions peaking at 2.87 (A), 2.6 (B), 2.2 (C), and 1.8 eV (D). Their broad shape was found to be due to a moderate lattice relaxation upon optical transitions. A linear model for phonon coupling was found adequate, with a principal mode resonant with the optical band [h/ω, varying between 74 (A level) and about 84 meV (C level)] and an additional lower-energy mode, yielding Franck-Condon shifts for these centers ΔFC,A =0.25±0.03, ΔFC,B=0.25±0.04, ΔFC,C =0.28±0.04 eV, and ΔFC,D=0.28±0.05 eV. Data for electrical compensation related to the occurrence of these different emissions indicate that the A level could be the ZnGa substitutional acceptor, while the more efficiently compensating B–D levels might be associated with Zn occupying N sites.