gebhart/patrepeval huggingface dataset:
Suppression of the proliferation of Ras-transformed cells by fluoromevalonate, an inhibitor of mevalonate metabolism. (1995)

Mevalonate is the precursor of a number of different products potentially required for the growth of cells, including the prenylated oncoprotein Ras. To determine whether inhibition of mevalonate metabolism would selectively block proliferation of Ras-transformed cells, 6-fluoromevalonate (Fmev), an inhibitor of diphosphomevalonate decarboxylase, was used to block the synthesis of prenyl-derived lipids and prenylated proteins in interleukin-3 (IL-3)-dependent FDC-P1 cells (control FDC-P1 cells) and FDC-P1 cells transformed with oncogenic Ras (RasDC cells) that proliferated in the absence of IL-3. Fmev completely inhibited synthesis of prenyl-derived lipids and prenylated proteins and blocked proliferation of FDC-P1 and RasDC cells. Restoration of the proliferation of Fmev-blocked FDC-P1 cells required both an exogenous source of cholesterol and prevention of the accumulation of mevalonate and the mevalonate phosphates with lovastatin. In contrast, ongoing IL-3-independent proliferation of Fmev-blocked RasDC cells was not completely restored by providing exogenous cholesterol and preventing the accumulation of inhibitory mevalonate product(s). However, these cells proliferated when cultures were supplemented with IL-3 together with exogenous cholesterol and lovastatin, implying that Fmev had prevented Ras-dependent, IL-3-independent growth. Fmev markedly diminished total cellular Ras in RasDC cells. In contrast, lovastatin depleted membrane-associated Ras and increased cytosolic Ras but did not diminish total cellular Ras. These data indicate that Fmev depletes total cellular Ras and specifically inhibits the autonomous growth of Ras-transformed cells.
Regulation of c- myc mRNA Decay by Translational Pausing in a Coding Region Instability Determinant (2002)

A 249-nucleotide coding region instability determinant (CRD) destabilizes c-myc mRNA. Previous experiments identified a CRD-binding protein (CRD-BP) that appears to protect the CRD from endonuclease cleavage. However, it was unclear why a CRD-BP is required to protect a well-translated mRNA whose coding region is covered with ribosomes. We hypothesized that translational pausing in the CRD generates a ribosome-deficient region downstream of the pause site, and this region is exposed to endonuclease attack unless it is shielded by the CRD-BP. Transfection and cell-free translation experiments reported here support this hypothesis. Ribosome pausing occurs within the c-myc CRD in tRNA-depleted reticulocyte translation reactions. The pause sites map to a rare arginine (CGA) codon and to an adjacent threonine (ACA) codon. Changing these codons to more common codons increases translational efficiency in vitro and increases mRNA abundance in transfected cells. These data suggest that c-myc mRNA is rapidly degraded unless it is (i) translated without pausing or (ii) protected by the CRD-BP when pausing occurs. Additional mapping experiments suggest that the CRD is bipartite, with several upstream translation pause sites and a downstream endonuclease cleavage site.
Phase I trial of an implanted battery-powered, programmable drug delivery system for continuous doxorubicin administration. (1985)

A second generation, implantable drug administration device (DAD, Medtronic, Inc, Minneapolis) which contains a 20-mL drug reservoir, a lithium-thionyl-chloride battery, a peristaltic roller pump, a microprocessor circuit, and an acoustic transducer has entered clinical trials. After surgical placement, drug is entered into and removed from the DAD percutaneously through a Silastic "fill port" using a standard gauge needle and syringe. The pump is noninvasively programmed using a hand-held telemetry wand to administer the drug in a continuous infusion, bolus, or bolus-delay mode. Because of the apparent improved therapeutic index of continuous-infusion doxorubicin (CID), a phase I trial of the Medtronic DAD with CID was begun. Thirteen pumps in 13 patients have functioned for a median of 153 days (range, 11 to 395 days) with one pump still functioning. Four pumps ceased function at 170, 278, 331, and 370 days, respectively; there was a catheter-tip clot on one of the pumps that later malfunctioned. All other pumps functioned until the death of the respective patients. In 84 pump refills, without drug extravasation, the median drug delivery error (actual residual volume--calculated residual volume/calculated residual volume X 100%) was 14%. Doxorubicin was compatible with all components of the drug pathway and did not significantly decompose during two weeks in the drug reservoir. The starting dose of CID was 2.0 mg/m2/d and the maximum tolerated dose was 4.1 mg/m2/d (range, 3.5 to 5.5). A median cumulative doxorubicin dose of 244 mg/m2 per patient (range, 10 to 583 mg/m2) has been infused.(ABSTRACT TRUNCATED AT 250 WORDS)
Association between a 15q25 gene variant, smoking quantity and tobacco-related cancers among 17 000 individuals (2009)

This study confirms the strong association between 15q gene variants and LC and shows an independent association with smoking quantity, as well as an association with UADT cancers.
Calorimetric measurements of the destabilisation of a ribosomal RNA hairpin by dimethyiation of two adjacent adenosines (1983)

Fragments of 16S ribosomal RNA from E. coli and B. stearothermophilus, respectively comprising the 49 and 52 3' terminal nucleotides have been studied thermodynamically using high sensitivity differential scanning calorimetry. The fragments were isolated after cleavage of 16S rRNA in the ribosome by the bacteriocin cloacin DF13. Comparison of the thermal properties of the E. coli fragments with those derived from a kasugamycin resistant mutant, which specifically lacks dimethylation of two adjacent adenosines was employed to study the effect of the methylgroups on the thermal stability. Both E. coli species exhibit similar complex melting patterns with several transitions. Overall molar transition enthalpies are equal and do not depend significantly on buffer conditions (120 kcal/mol at 15 mM Na+ to 136 kcal/mol at 215 mM Na+). However, the transition with the highest Tm, corresponding to unfolding of a nine basepair central helix is lowered by the dimethylation of the adenines in the four-membered loop. This decrease amounts to 4 degrees C at 15 mM Na+ and 2 degrees C at 215 mM Na+. The corresponding nine basepair long hairpin in the Bacillus fragment melts at a temperature of 70 degrees C at 15 mM Na+. This Tmax is much higher than expected on the basis of the sequence in the hairpin.
Influenza update 2007-2008: vaccine advances, pandemic preparation. (2007)

Influenza vaccination remains our best measure to prevent epidemic and pandemic influenza. We must continue to improve vaccination rates for targeted populations. Antiviral options are currently limited to the neuraminidase inhibitors.
Mapping the calcitonin receptor in human brain stem (2016)

The calcitonin receptor (CTR) is relevant to three hormonal systems: amylin, calcitonin, and calcitonin gene-related peptide (CGRP). Receptors for amylin and calcitonin are targets for treating obesity, diabetes, and bone disorders. CGRP receptors represent a target for pain and migraine. Amylin receptors (AMY) are a heterodimer formed by the coexpression of CTR with receptor activity-modifying proteins (RAMPs). CTR with RAMP1 responds potently to both amylin and CGRP. The brain stem is a major site of action for circulating amylin and is a rich site of CGRP binding. This study aimed to enhance our understanding of these hormone systems by mapping CTR expression in the human brain stem, specifically the medulla oblongata. Widespread CTR-like immunoreactivity was observed throughout the medulla. Dense CTR staining was noted in several discrete nuclei, including the nucleus of the solitary tract, the hypoglossal nucleus, the cuneate nucleus, spinal trigeminal nucleus, the gracile nucleus, and the inferior olivary nucleus. CTR staining was also observed in the area postrema, the lateral reticular nucleus, and the pyramidal tract. The extensive expression of CTR in the medulla suggests that CTR may be involved in a wider range of functions than currently appreciated.
Bioconjugated PLGA-4-arm-PEG branched polymeric nanoparticles as novel tumor targeting carriers (2011)

In this study, we have developed a novel carrier, micelle-type bioconjugated PLGA-4-arm-PEG branched polymeric nanoparticles (NPs), for the detection and treatment of pancreatic cancer. These NPs contained 4-arm-PEG as corona, and PLGA as core, the particle surface was conjugated with cyclo(arginine-glycine-aspartate) (cRGD) as ligand for in vivo tumor targeting. The hydrodynamic size of the NPs was determined to be 150-180 nm and the critical micellar concentration (CMC) was estimated to be 10.5 mg l( - 1). Our in vitro study shows that these NPs by themselves had negligible cytotoxicity to human pancreatic cancer (Panc-1) and human glioblastoma (U87) cell lines. Near infrared (NIR) microscopy and flow cytometry demonstrated that the cRGD conjugated PLGA-4-arm-PEG polymeric NPs were taken up more efficiently by U87MG glioma cells, over-expressing the α(v)β(3) integrin, when compared with the non-targeted NPs. Whole body imaging showed that the cRGD conjugated PLGA-4-arm-PEG branched polymeric NPs had the highest accumulation in the pancreatic tumor site of mice at 48 h post-injection. Physical, hematological, and pathological assays indicated low in vivo toxicity of this NP formulation. These studies on the ability of these bioconjugated PLGA-4-arm-PEG polymeric NPs suggest that the prepared polymeric NPs may serve as a promising platform for detection and targeted drug delivery for pancreatic cancer.
Preparation of superconducting Tl-Ca-Ba-Cu thin films by chemical deposition (1989)

A chemical deposition process for the preparation of superconducting thin films of Tl2CaBa2Cu2O8 (2122) and Tl2Ca2Ba2Cu3O10 (2223) has been developed. Oriented, superconducting 2122 and 2223 thin films have been successfully fabricated on single-crystal yttria-stabilized zirconia and magnesium oxide substrates (〈100〉 orientation). Epitaxial films have been prepared on magnesium oxide. Chemical analysis of the film composition by energy dispersive x-ray analysis is in agreement (2122 vs 2223) with the phases indicated by powder x-ray diffraction. The thin films of these compounds exhibited superconducting transition temperatures above 105 K as determined by variable-temperature resistivity and ac magnetic susceptibility measurements. In addition, microwave surface resistance measurements at 150 GHz show that these films have very low losses at 77 K (1 mΩ).
The major human AP endonuclease (Ape1) is involved in the nucleotide incision repair pathway (2004)

In nucleotide incision repair (NIR), an endonuclease nicks oxidatively damaged DNA in a DNA glycosylase-independent manner, providing the correct ends for DNA synthesis coupled to the repair of the remaining 5'-dangling modified nucleotide. This mechanistic feature is distinct from DNA glycosylase-mediated base excision repair. Here we report that Ape1, the major apurinic/apyrimidinic endonuclease in human cells, is the damage- specific endonuclease involved in NIR. We show that Ape1 incises DNA containing 5,6-dihydro-2'-deoxyuridine, 5,6-dihydrothymidine, 5-hydroxy-2'-deoxyuridine, alpha-2'-deoxyadenosine and alpha-thymidine adducts, generating 3'-hydroxyl and 5'-phosphate termini. The kinetic constants indicate that Ape1-catalysed NIR activity is highly efficient. The substrate specificity and protein conformation of Ape1 is modulated by MgCl2 concentrations, thus providing conditions under which NIR becomes a major activity in cell-free extracts. While the N-terminal region of Ape1 is not required for AP endonuclease function, we show that it regulates the NIR activity. The physiological relevance of the mammalian NIR pathway is discussed.
Tip-Scanning Dynamic Force Microscope Using Piezoelectric Cantilever for Full Wafer Inspection (1999)

In this study we demonstrate the structure of a new dynamic force microscope (DFM) compatible with full wafer inspection. It is a tip-scanning-type DFM based on a piezoelectric micro-cantilever integrated with a conical tip as a force sensor. The piezoelectric micro-force sensor is mounted on top of a tube scanner. The sample is put on the sample stage facing the tip. The novel DFM has proven to be stable for probing the surface of full wafers with a vertical resolution of about 0.12 nm. The design and performance of the novel tip scanning DFM is explained in detail in this report.
Correlations between Percolation Threshold, Dispersion State, and Aspect Ratio of Carbon Nanotubes (2007)

Abstract Critical factors that determine the percolation threshold of carbon nanotube (CNT)‐reinforced polymer nanocomposites are studied. An improved analytical model is developed based on an interparticle distance concept. Two dispersion parameters are introduced in the model to correctly reflect the different dispersion states of CNTs in the matrix—entangled bundles and well‐dispersed individual CNTs. CNT–epoxy nanocomposites with different dispersion states are fabricated from the same constituent materials by employing different processing conditions. The corresponding percolation thresholds of the nanocomposites vary over a wide range, from 0.1 to greater than 1.0 wt %, and these variations are explained in terms of dispersion parameters and aspect ratios of CNTs. Important factors that control the percolation threshold of nanocomposites are identified based on the comparison between modeling data and experimental results.
Improving the outcome of adoptive cell transfer by targeting tumor escape (2012)

Adoptive T-cell transfer is among the most promising immunotherapies against cancer. To continue increasing the potential of this therapy, our studies focus on the inhibition of tumor recurrence. Recently, we have demonstrated several ways in which combination therapies involving multiple T-cell populations and immunostimulatory chemotherapy can enhance long-term survival.
Altered Gap and Tight Junctions in Human Thyroid Oncocytic Tumors: A Study of 8 Cases by Freeze-fracture (1998)

Human oncocytic tumors of the thyroid gland may be either adenomas or carcinomas. The morphology and the ultrastructure of these oncocytes are well-known. Numerous studies have demonstrated the role of gap and tight junctions in experimental and human carcinogenesis; however, the junctional complexes of the oncocytic tumors have never been studied. The aim of this study is to analyze gap and tight junctions in the oncocytic tumors of the thyroid. Because they are morphologically similar, whether benign or malignant, they offer an attractive model for studying the junctional complexes in both benign and malignant lesions. Eight oncocytic human thyroid tumors were collected and studied by freeze-fracture. Four of these cases were benign and four were malignant. Four cases of normal gland were also studied to represent the control group. Normal tight and gap junctions were described for the control group. No gap junctions could be found for the oncocytic tumors. Furthermore, alterations of the tight junctions were described; especially focal tights in the oncocytic adenomas and well organized and labyrinthic tight junctions in the oncocytic carcinomas. The lack of gap junction in the benign as well as in the malignant oncocytomas may suggest that the absence of gap junction is not sufficient for malignancy. The alterations of the tight junctions found in the oncocytic tumors of the thyroid are similar to those observed in poorly differentiated tissues or tumors, and may suggest a cellular regression rather than a tumorogenic factor.
A Nyquist rate pixel level ADC for CMOS image sensors (2002)

A Nyquist rate Multi-Channel bit serial (MCBS) ADC using successive comparisons is presented. The ADC is suited to pixel level implementation in a CMOS image sensor. It comprises a 1-bit comparator/latch pair per 4 pixels and a DAC/controller shared by all pixels. A CMOS 320/spl times/240 sensor using the MCBS ADC is described. It achieves 8.9/spl times/8.9 /spl mu/m pixel size at 25% fill factor in 0.35 /spl mu/m CMOS technology. Measured INL/DNL for the ADC are 2.3/1.2 LSB at 8-bit. Gain/offset FPN due to ADC are 0.24%/0.2%.
Cholera Toxin B Subunits Assemble into Pentamers - Proposition of a Fly-Casting Mechanism (2010)

The cholera toxin B pentamer (CtxB(5)), which belongs to the AB(5) toxin family, is used as a model study for protein assembly. The effect of the pH on the reassembly of the toxin was investigated using immunochemical, electrophoretic and spectroscopic methods. Three pH-dependent steps were identified during the toxin reassembly: (i) acquisition of a fully assembly-competent fold by the CtxB monomer, (ii) association of CtxB monomer into oligomers, (iii) acquisition of the native fold by the CtxB pentamer. The results show that CtxB(5) and the related heat labile enterotoxin LTB(5) have distinct mechanisms of assembly despite sharing high sequence identity (84%) and almost identical atomic structures. The difference can be pinpointed to four histidines which are spread along the protein sequence and may act together. Thus, most of the toxin B amino acids appear negligible for the assembly, raising the possibility that assembly is driven by a small network of amino acids instead of involving all of them.
An improved microwave interferometer technique for plasma density measurements: II (1988)

A 4 mm microwave interferometer is described, together with a working system for numerical evaluation of the recorded signals. The interferometer signals are processed in a computer to provide an immediate display of the plasma column density. The numerical evaluation makes it possible to eliminate the influence of rather large imperfections in the components, and also to take into account large and rapid variations in the strength of the transmitted microwave signal. The limits of performance of the system are tested in a pulsed plasma source. Column plasma densities are measured from 1015 m-2 to 3*1018 m-2, corresponding to phase swings from less than one degree up to several times 360 degrees .
A modular misexpression screen in Drosophila detecting tissue-specific phenotypes. (1996)

Genetic screens in Drosophila have lead to the discovery of many genes important for patterning and signal transduction in diverse organisms. Traditionally, the phenotypic effects of loss-of-function mutations are analyzed. As an alternative way to link genes and function, I have developed a versatile misexpression screen in Drosophila, the first such screen in higher eukaryotes. The screen identifies genes that, when over- or misexpressed in a pattern of interest, give a specific phenotype or modulate an existing mutant phenotype. It is based on Gal4 transactivation of a mobile enhancer and promoter that "targets" random endogenous genes for expression. The modular design of the screen allows directed expression in any temporal or spatial pattern. When activated in the developing eye, 4% of target inserts gave dominant phenotypes. One insertion was in the gene encoding Ras GTPase-activating protein; its overexpression phenotype was strongly enhanced by a mutation in Ras1. Thus, biologically relevant phenotypes and genetic interactions are identified using this method. The screen is a powerful new tool for developmental genetics; similar approaches can also be developed for other organisms.
An essential role for free radicals and derived species in signal transduction (1997)

It is well accepted that extracellular ligands trigger nuclear signals through a cascade of protein-protein interactions. Many of these pathways have been carefully defined and provide an important framework by which we can understand and intervene in the processes they initiate. Recent data in the literature indicate that many extracellular ligands generate and/or require reactive free radicals or derived species to successfully transmit their signals to the nucleus. Thus, a novel signaling mechanism akin to one solely dependent on protein-protein interactions may exist. Here, we review this information, identify both the sources and targets of free radicals generated by various growth factors and cytokines, discuss how specificity can be achieved, and explore the pathophysiological implications.
A simple method for the isolation of chromosomal DNA from Gram positive or acid-fast bacteria (1991)

Journal Article A simple method for the isolation of chromosomal DNA from Gram positive or acid-fast bacteria Get access C. Bollet, C. Bollet * Laboratoire de Microbiologie et d'Hygiène HospitaièresHôpital Salvator, Marseille F13009, France * To whom correspondence should be addressed Search for other works by this author on: Oxford Academic PubMed Google Scholar M.J. Gevaudan, M.J. Gevaudan Laboratoire de Microbiologie et d'Hygiène HospitaièresHôpital Salvator, Marseille F13009, France Search for other works by this author on: Oxford Academic PubMed Google Scholar X. de Lamballerie, X. de Lamballerie Laboratoire de Microbiologie et d'Hygiène HospitaièresHôpital Salvator, Marseille F13009, France Search for other works by this author on: Oxford Academic PubMed Google Scholar C. Zandotti, C. Zandotti Laboratoire de Microbiologie et d'Hygiène HospitaièresHôpital Salvator, Marseille F13009, France Search for other works by this author on: Oxford Academic PubMed Google Scholar P. de Micco P. de Micco Laboratoire de Microbiologie et d'Hygiène HospitaièresHôpital Salvator, Marseille F13009, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 19, Issue 8, 25 April 1991, Page 1955, https://doi.org/10.1093/nar/19.8.1955 Published: 25 April 1991 Article history Received: 02 January 1991 Published: 25 April 1991
THE STRUCTURE AND PROCESS OF INTELLECTUAL DEVELOPMENT* (1987)

In the present article, a theory of intellectual development is summarized which attempts to integrate the general structural approach pioneered by Piaget, with the more recent ‘process’ oriented approaches proposed by information processing theorists on the one hand, and by Pascual‐Leone (in his M ‐Operator theory) on the other. The resultant theory is one which proposes that children's control structures progress through four general stages in the course of their development, with three recursive substages being identifiable at each. Transition to a new stage of development occurs as a result of the hierarchical integration of two qualitatively distinct control structures, each one of which was assembled and consolidated towards the end of the previous stage. By contrast, progress within a stage occurs as a result of the step‐wise attention to, and non‐hierarchical integration of, an increasing number of similar elements, each one of which was assembled towards the beginning of the new stage. The variable that determines the maximum rate at which within‐stage progress can take place is the size of the child's working memory, which is seen as growing in response to both maturational and experiential variables. A similar process is seen as determining the timing of across‐stage transitions; however, this process is as yet less well articulated. Several different sorts of empirical evidence have been gathered so far, to support the overall structure of the theory. After this evidence is described and illustrated, the article concludes with a summary of the theory in postulate form.