gebhart/patrepeval huggingface dataset:
Targeted inactivation of the insulin receptor gene in mouse 3T3-L1 fibroblasts via homologous recombination. (1991)

To study the role of the insulin receptor in determining adipocyte differentiation of the mouse cell line 3T3-L1, we have introduced a mutation that inactivates the insulin receptor gene by homologous recombination. In two independent clones, inactivation of one allele of the insulin receptor gene was associated with a 50-70% reduction in the number of insulin receptors. In addition, both clones were markedly impaired in their ability to differentiate into adipocytes. The defect in adipocyte-specific differentiation was corrected by expression of transfected human insulin receptor cDNA. These data suggest that the insulin receptor may play an important role in promoting differentiation of 3T3-L1 cells into adipocytes in vitro.
Precise Molecular Fission and Fusion: Quantitative Self‐Assembly and Chemistry of a Metallo‐Cuboctahedron (2015)

Inspiration for molecular design and construction can be derived from mathematically based structures. In the quest for new materials, the adaptation of new building blocks can lead to unexpected results. Towards these ends, the quantitative single-step self-assembly of a shape-persistent, Archimedean-based building block, which generates the largest molecular sphere (a cuboctahedron) that has been unequivocally characterized by synchrotron X-ray analysis, is described. The unique properties of this new construct give rise to a dilution-based transformation into two identical spheres (octahedra) each possessing one half of the molecular weight of the parent structure; concentration of this octahedron reconstitutes the original cuboctahedron. These chemical phenomena are reminiscent of biological fission and fusion processes. The large 6 nm cage structure was further analyzed by 1D and 2D NMR spectroscopy, mass spectrometry, and collision cross-section analysis. New routes to molecular encapsulation can be envisioned.
High Prevalence of RET, RAS, and ERK Expression in Hashimoto's Thyroiditis and in Papillary Thyroid Carcinoma in the Korean Population (2007)

The expression of RET, nuclearRAS, and ERK proteins is greatly enhanced in PTC cells and HT oxyphil cells. Thus, the RET/PTC-RAS-BRAF cascade may be involved in the development of PTC and oxyphil cell metaplasia in HT. Our results show the possibility of a molecular link between oxyphil cell metaplasia in HT and the progression of PTC.
Thrombospondin mediates adherence of CD36+ sickle reticulocytes to endothelial cells (1992)

Abstract Initiation of vasocclusion in sickle disease pathophysiology may involve abnormal red blood cell (RBC) adhesivity to endothelium, a phenomenon influenced by both RBC and plasma factors. Using human umbilical vein endothelial cells and a gravity sedimentation adherence assay, we have examined thrombospondin (TSP) as a plasma factor in this adhesive event. The already-abnormal adherence of sickle RBCs in buffer/albumin is significantly augmented (P &lt; .001) by the addition of TSP, with half-maximal effect at about 0.3 microgram/mL. This effect is abolished by antibodies to either TSP or glycoprotein (GP) IV (CD36), as well as peptides RGDS and CSVTCG. The even greater adherence (P &lt; .005) of sickle RBCs in autologous platelet-rich plasma (without added TSP) is dramatically inhibited by alpha CD36 antibodies (OKM5 and alpha GPIV) and significantly diminished by alpha TSP, by peptides RGDS and CSVTCG, and by two antibodies to the vitronectin receptor (7E3 and LM609). Studies of density-separated subpopulations and of RBC adhesion to immobilized proteins, as well as analysis of sickle RBCs using fluorescence-activated cell sorting and single cell microfluorometry, show that TSP responsiveness is a feature of the immature sickle “stress” reticulocytes, which carry CD36 (and not GPIIbIIIa-like receptors) as the TSP-receptive moiety. The endothelial cell's participation in this phenomenon appears to be more complex, and the data are consistent with the notion that it involves TSP interaction with other plasma proteins and/or multiple receptor structures. Other potential adhesogenic proteins (plasma von Willebrand factor, vitronectin, fibrinogen, and fibronectin) neither exhibited an affinity for reticulocytes nor supported increased sickle RBC adherence when added to buffer/albumin in these assay systems. In aggregate, our results indicate that TSP may be the major promoter of RBC adhesivity in plasma, and they suggest that therapeutic benefit might derive from interference with sickle reticulocyte CD36, as achieved by antibodies and CSVTCG in these studies.
Flow Caml in a Nutshell (2003)

Flow Caml is an extension of the Objective Caml language with a type system tracing information flow. It automatically checks information flow within Flow Caml programs, then translates them to regular Objective Caml code that can be compiled by the ordinary compiler to produce secure programs. In this paper, we give a short overview of this system, from a practical viewpoint. 1
The I-CreI meganuclease and its engineered derivatives: applications from cell modification to gene therapy (2010)

Meganucleases (MNs) are highly specific enzymes that can induce homologous recombination in different types of cells, including mammalian cells. Consequently, these enzymes are used as scaffolds for the development of custom gene-targeting tools for gene therapy or cell-line development. Over the past 15 years, the high resolution X-ray structures of several MNs from the LAGLIDADG family have improved our understanding of their protein-DNA interaction and mechanism of DNA cleavage. By developing and utilizing high-throughput screening methods to test a large number of variant-target combinations, we have been able to re-engineer scores of I-CreI derivatives into custom enzymes that target a specific DNA sequence of interest. Such customized MNs, along with wild-type ones, have allowed for exploring a large range of biotechnological applications, including protein-expression cell-line development, genetically modified plants and animals and therapeutic applications such as targeted gene therapy as well as a novel class of antivirals.
Human fibroblasts release reactive oxygen species in response to interleukin-1 or tumour necrosis factor-α (1989)

Human fibroblasts in primary culture released reactive oxygen species upon stimulation with cytokines such as interleukin-1 alpha (IL-1) or tumour necrosis factor-alpha (TNF). The primary radical produced was O2.- as determined by e.s.r. spin trapping and cytochrome c reduction. In contrast to the oxidative burst in granulocytes and monocytes, radical formation took place continuously for at least 4 h. Low-level chemiluminescence was increased by stimulation with IL-1 and TNF. Spectral characteristics and tests with azide led to the conclusion that the photoemissive species were excited carbonyls and not singlet oxygen. Further, there was a liberation of ethane from the cells. Radical production and light emission were not altered by either xanthine or allopurinol, nor by azide, cyanide or rotenone. O2.- production increased in the presence of NADH or NADPH, making an NAD(P)H oxidase a likely source.
Thiazole orange: A new dye for reticulocyte analysis (1986)

The purpose of this study was to find a 488-nm excitable fluorescent dye for reticulocyte analysis by the use of fluorescence activated cell cytometry. The chemical structure of thioflavin T, a dye used for reticulocyte analysis with 457-nm excitation, was used as a model. Several dyes were synthesized and evaluated by quantum yield determination, fluorescence microscopy, and flow cytometry. The best results were obtained with a dye we have named "thiazole orange"; analysis of several blood samples with thiazole orange gave a correlation coefficient of 0.97 as compared to a manual determination of reticulocyte percentage.
Structural Transitions and pH-Dependent Equilibria between Unusual Double and Triple Helical Conformations of Nucleic Acid Polymers, Studied by UV Resonance Raman Spectroscopy (1993)

In order to study pH-driven associations and equilibria between nucleic acid helices containing the homopolymers poly(A) and poly(U), the pH-value of solutions of poly(A) or poly(A)*poly(U) or the triple helix poly(U)*poly(A)*poly(U) was varied in steps of 0.5 pH units between pH = 7.0 and pH = 2.5. Resonance Raman spectra were taken with 260-nm and 220-nm excitation, both in H 2 O and in D 2 O solvent. For the solutions containing poly(A) only, marked spectral changes between pH = 6.0 and pH = 5.5 can be attributed to the formation of the parallel stranded double helix poly(A) + *poly(A) + . The cooperativity of this duplex formation is better represented in the 260-nm than in the 220-nm excitation spectra. The double helix poly(A)*poly(U) remains stable down to pH = 5.0. At pH = 4.5 and 4.0, the experimental spectra can be understood by means of a superposition of the spectra of the triple helix poly(U)*poly(A)*poly(U) and the protonated double helix poly(A) + *poly(A) + . The triple helix itself is stable at these pH values, as can be concluded from the spectra of solutions of this polymer. Below pH = 4.0, the spectra can be calculated by the sum of poly(A) + *poly(A) + and the single-stranded poly(U) polymer. All the helical transitions observed are better represented in the spectra excited with 260 nm, whereas the protonation state is better resolved in the 220-nm spectra. The data reported here provide a basis for further studies of unusual nucleic acid structures as triple and quadruple helices and they show that UV-resonance Raman spectroscopy is a sensitive tool for studying the kinetics and dynamics of the formation of these structures.
Lymphangiogenesis and lymph node metastasis in breast cancer (2008)

In summary, the findings from this study show that lymphangiogenesis, measured by specific lymphatic marker expression, is higher in breast cancers than in normal breast tissue. Secondly, breast cancers which have metastasised to the regional lymphatics show higher expression compared to those which have not, although the individual differences for all five markers were not statistically significant.
Measurements and extractions of parasitic capacitances in ulsi layouts (2003)

This paper deals with the extraction of parasitic capacitances of interconnects in submicron layouts. It is well known that, in integrated circuits, the signal delay due to interconnects is comparable to that of gates. This aspect becomes particularly important, for example, during the design of clock trees in high-speed applications. In general, capacitance extraction is carried out with software tools but they should be validated on a set of geometrical structures, which have been accurately characterized and that are representative of the circuit layouts. Experimental characterization of these structures and their set up in a golden set of measures is still a challenging task. In this paper, we first describe some experimental approaches to measure capacitances of structures from the golden set and in particular we identify a high accuracy transducer based on pass-gate transistors. We then propose a software implementation of the floating random walk algorithm that solves the drawbacks in the extraction of capacitances of interconnects in a nonhomogeneous medium as an industrial layout. Finally, experimental and simulation results are presented, validating the adopted approach.
Efficient transformation of Neurospora crassa by utilizing hybrid plasmid DNA (1979)

An efficient transformation system has been developed for Neurospora crassa that uses spheroplasts and pVK88 plasmid DNA. pVK88 is a recombinant Escherichia coli plasmid carrying the N. crassa qa-2(+) gene which encodes catabolic dehydroquinase (3-dehydroquinate hydro-lyase, EC 4.2.1.10) and is part of the qa gene cluster. The recipient strain carries a stable qa-2(-) mutation and an arom-9(-) mutation, thus lacking both catabolic and biosynthetic dehydroquinase activities. Transformants were selected as colonies able to grow in the absence of an aromatic amino acid supplement. These colonies were qa-2(+) and had normal levels of catabolic dehydroquinase. DNA.DNA hybridization evidence with appropriate labeled probes indicates clearly that in some instances transformation involves the integration of bacterial plasmid sequences together with the qa-2(+) gene into the N. crassa genome. On the basis of genetic, enzyme assay, and DNA hybridization data, at least three types of transformation events can be distinguished: (i) replacement of the qa-2(-) gene by the qa-2(+) gene without any effect on the expression of the other genes in the qa cluster, (ii) linked insertion of a normal qa-2(+) gene accompanied by inactivation of the adjacent qa-4(+) gene, and (iii) insertion of a normal qa-2(+) gene at an unlinked site in the N. crassa genome. This newly integrated qa-2(+) genetic material is inherited in a typical Mendelian fashion. A low level of transformation has also been obtained by using linear total N. crassa DNA. Two such qa-2(+) transformants are unlinked to the qa-2(-) gene of the recipient.
In Vitro Differentiation of Size‐Sieved Stem Cells into Electrically Active Neural Cells (2002)

Size-sieved stem (SS) cells isolated from human bone marrow and propagated in vitro are a population of cells with consistent marker typing, and can form bone, fat, and cartilage. In this experiment, we demonstrated that SS cells could be induced to differentiate into neural cells under experimental cell culture conditions. Five hours after exposure to antioxidant agents (beta-mercaptoethanol +/- retinoic acid) in serum-free conditions, SS cells expressed the protein for nestin, neuron-specific enolase (NSE), neuron-specific nuclear protein (NeuN), and neuron-specific tubulin-1 (TuJ-1), and the mRNA for NSE and Tau. Immunofluorescence showed that almost all the cells (>98%) expressed NeuN and TuJ-1. After 5 days of beta-mercaptoethanol treatment, the SS cells expressed neurofilament high protein but not mitogen-activated protein-2, glial filament acidic protein, and galactocerebroside. For such long-term-treated cells, voltage-sensitive ionic current could be detected by electrophysiological recording, and the intracellular calcium ion, Ca(2+), concentration can be elevated by high potassium (K(+)) buffer and glutamate. These findings suggest that SS cells may be an alternative source of undifferentiated cells for cell therapy and gene therapy in neural dysfunction.
Hypermethylation of TUSC5 genes in breast cancer tissue. (2012)

A total of 149 genes exhibited the highest difference in expression in cancer versus normal appearing tissue of breast. Most prominent down-regulated candidates, TUSC5 and TP53INK1, were reported for the first time in breast cancer and may be considered as potential markers of the disease. Aberrant DNA hypermethylation of TUSC5 suggests epigenetic mechanism of cancer associated down-regulation.
The co-dependence of BxpB/ExsFA and BclA for proper incorporation into the exosporium of Bacillus anthracis (2010)

The outermost layer of the Bacillus anthracis spore consists of an exosporium comprised of two distinct layers, an outer hair-like nap layer and an internal basal layer. The hair-like nap is primarily comprised of the glycosylated collagen-like protein BclA. BclA is found in a trimeric form in close association with many other exosporium proteins in high-molecular weight complexes. We previously had characterized an N-terminal sequence of BclA that is sufficient for incorporation into the exosporium. Here we utilized site-directed mutagenesis to identify BclA residues critical to two steps in this process, positioning of the protein at the site of the developing exosporium basal layer and stable incorporation which includes a proteolytic cleavage of BclA after residue 19. The BxpB (ExsFA) protein is known to be important for proper incorporation of BclA onto the exosporium. BxpB and BclA were found to be expressed at the same time in sporulating cells of B. anthracis and immediately colocalize to high-molecular weight complexes. The BxpB protein was found to be in close proximity to the BclA NTD. BxpB and BclA are co-dependent for exosporium incorporation, with the BclA NTD being sufficient to deliver BxpB to the exosporium.
Architecture of a Complex between the ς70 Subunit of Escherichia coli RNA Polymerase and the Nontemplate Strand Oligonucleotide (1999)

We used luminescence energy transfer measurements to determine the localization of 5'- and 3'-ends of a 12-nucleotide nontemplate strand oligonucleotide bound to sigma70 holoenzyme. Five single reactive cysteine mutants of sigma70 (cysteine residues at positions 1, 59, 366, 442, and 596) were labeled with a europium chelate fluorochrome (donor). The oligonucleotide was modified at the 5'- or at the 3'-end with Cy5 fluorochrome (acceptor). The energy transfer was observed upon complex formation between the donor-labeled sigma70 holoenzyme and the acceptor-labeled nontemplate strand oligonucleotide, whereas no interaction was observed with the template strand oligonucleotide. The oligonucleotide was bound in one preferred orientation. This observation together with the sequence specificity of single-stranded oligonucleotide interaction suggests that two mechanisms of discrimination between the template and nontemplate strand are used by sigma70: sequence specificity and strand polarity specificity. The bound oligonucleotide was found to be close to residue 442, confirming that the single-stranded DNA binding site of sigma70 is located in an alpha-helix containing residue 442. The 5'-end of the oligonucleotide was oriented toward the COOH terminus of the helix.
Plasma membrane rafts play a critical role in HIV-1 assembly and release (2001)

HIV-1 particle production occurs in a series of steps promoted by the viral Gag protein. Although it is well established that assembly and release take place at the plasma membrane, the nature of membrane assembly sites remains poorly understood. We show here that Gag specifically associates with cholesterol-enriched microdomains ("rafts") at the plasma membrane. Kinetic studies demonstrate that raft association follows membrane binding, and the analysis of Gag mutants reveals that, whereas the N terminus of Gag mediates raft binding, this association is greatly enhanced by Gag-Gag interaction domains. We observe that depletion of cellular cholesterol markedly and specifically reduces HIV-1 particle production. Furthermore, treatment of virus-producing cells or virus particles with raft-disrupting agents significantly impairs virus infectivity. These results identify the association of Gag with plasma membrane rafts as an important step in HIV-1 replication. These findings may lead to novel strategies for suppressing HIV-1 replication in vivo.
Medicinal Attributes of Imidazo[1,2-a]pyridine Derivatives: An Update (2016)

The imidazo[1,2-a]pyridine scaffold is recognized as a privileged structure as it represents a promising area for identification of lead structures towards the discovery of new synthetic drug molecules. Several commercial drugs such as Zolpidem, Olprinone, Soraprazan and many other compounds in biological testing and preclinical evaluation, illustrate the wide therapeutic spectrum in this class of drug scaffolds. The present manuscript represents the assimilation of literature pertaining to medicinal aspects of this pharmacophore including the structure-activity relationships.
Searching for Evidence of Altered Gene Expression: a Comment on Statistical Analysis of Microarray Data (1999)

Hilsenbeck et al. (1) have presented an intriguing experimentthat raises important methodologic problems for approaching theassessment of the expression of specific genes. They comparedtumors from animals killed at various times to obtain estrogen-stimulated tumors before tamoxifen treatment, tamoxifen-sensitive tumors during tamoxifen treatment but before acquiredresistance, and tamoxifen-resistant tumors after resumption oftumor growth. They measured expression values for 588 genesfor each of the three tumor types. They argue that a significantdeviation in expression between tumor types for a particulargene represents evidence that the specific gene is altered duringthe development of tamoxifen resistance. In their report, Hilsen-beck et al. define a procedure for identifying “significant” de-viations, and they use this method to identify outlier genes. Infuture studies, they intend to study these outliers to identify“which of the outlier genes are most contributory to the tamoxi-fen-stimulated phenotype....”Before embarking on such a search for outlier genes, oneneeds to know whether different genes need different scales ofmeasurement. Hilsenbeck et al. (1) imply that one can indeedassume the same scale of measurement, i.e., the same variability,for each gene. We believe that replication is essential to deter-mine whether the 588 genes have the same natural scales ofmeasurement. If an individual gene is expressed differentially intamoxifen-resistant or tamoxifen-sensitive tumors, how do weknow that the differential expression reflects the true effect ofthe tumor rather than underlying differential variability? Forexample, erk-2 appears as an outlier in the ES/TS and ES/TRplots, where the variables ES, TS, and TR are estrogen-stimulated, tamoxifen-sensitive, and tamoxifen-resistant, respec-tively; the authors interpret the fact that the expression of erk-2differs in the estrogen-stimulated tumor as evidence that tamoxi-fen modifies erk-2 expression. The observation is, however, alsoconsistent with the quite different hypothesis that erk-2 has morevariability in expression than most of the other 587 genes. In thecase of erk-2, Hilsenbeck et al. have independent verificationthat the gene is involved in the pathway of interest. What aboutthe genes close to erk-2? How do we know that they are fruitfulcandidates for further study? Similarly, a gene that does notappear as an outlier and, hence, is not selected as a candidategene for study may be missed simply because its variability ofexpression is very low compared with that of other genes. Theauthors have some data relevant to assessment of within-genevariability, for they measured five tumors of each type; however,they do not describe whether they used those observations toconfirm their assumption that the same scale is appropriate forall genes.If indeed the same scale of measurement is appropriate for allgenes, the question then arises whether the authors have em-ployed a useful method for detecting outliers. They have chosen
Transduction in Bacillus stearothermophilus (1988)

Temperate and virulent bacteriophages isolated from soil were shown to carry out generalized transduction of Bacillus stearothermophilus NUB36. A transducing frequency of 1 X 10(-5) to 7 X 10(-4) was obtained for temperate phages TP-42 and TP-56. The transducing frequency for virulent phage TP-68 was two to three orders of magnitude lower. Cotransfer analysis with the three phages showed that hom-1 is linked to thr-1 and that gly-1 is linked to his-1.