gebhart/patrepeval huggingface dataset:
Use of a general purpose mammalian expression vector for studying intracellular protein targeting: identification of critical residues in the nuclear lamin A/C nuclear localization signal (1993)

We have constructed a general purpose mammalian expression vector for the study of intracellular protein targeting. The vector, p3PK, facilitates construction of N- and/or C-terminal fusions of an amino acid sequence of interest to the normally cytosolic protein chicken muscle pyruvate kinase (CMPK). The vector has been engineered such that any fusion construct can be subcloned into the versatile pJx omega family of mammalian expression vectors and into pGEX bacterial expression vectors, for the generation of affinity reagents. In this paper, we demonstrate the general utility of p3PK by redirecting CMPK to mitochondria (using the twelve amino acid pre-sequence of yeast cytochrome c oxidase subunit IV) and to the nucleus (using a putative eight amino acid nuclear localization signal from human nuclear lamins A and C). We also report that, contrary to the predictions of previously published work, substitution of a critical residue in the nuclear lamin A/C nuclear localization signal (the equivalent of lysine 128 in the SV40 large T nuclear localization signal) retains nuclear localization, and discuss how amino acid context might affect targeting to the nucleus.
Guidance on the use of miglustat for treating patients with type 1 Gaucher disease (2005)

Type 1 Gaucher disease (GD) is a progressive lysosomal storage disorder due to an autosomal recessive deficiency of glucocerebrosidase. Clinical manifestations include anemia, thrombocytopenia, hepatosplenomegaly, and bone and pulmonary disease. Intravenous enzyme replacement (ERT) with imiglucerase is the accepted standard for treatment of symptomatic patients. More than 3,500 patients worldwide have received ERT with well-documented beneficial effects on the hematological, visceral, skeletal, and pulmonary manifestations, and with resultant improvement in health-related quality of life. Miglustat, an imino sugar that reversibly inhibits glucosylceramide synthase and reduces intracellular substrate burden, is an oral treatment for patients with type 1 GD that was recently approved in the United States for symptomatic patients with mild to moderate clinical manifestations for whom ERT is not an option. Because responses to miglustat are slower and less robust than those observed with ERT, and because miglustat is associated with significant side effects, clinicians who care for patients with GD should become familiar with the limited indications for miglustat use and the circumstances when it may be prescribed appropriately. This review article and position statement represents the current opinion of American physicians with extensive expertise in GD regarding patient management in the context of the availability of standard imiglucerase treatment and the recent introduction of miglustat.
Post-Transcriptional Genetic Silencing of BCL11A to Treat Sickle Cell Disease (2020)

This study validates BCL11A inhibition as an effective target for HbF induction and provides preliminary evidence that shmiR-based gene knockdown offers a favorable risk-benefit profile in sickle cell disease. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT03282656).
Cytokines and Metabolic Dysfunction After Severe Head Injury (1994)

Patients with head injury must overcome central as well as peripheral metabolic insults. In addition to specific tissue damage to the brain, a cellular biochemical cascade occurs that can negatively affect organ function, cause a systemic response to injury, and may cause secondary tissue injury. The metabolites involved in this cascade are numerous and complex. Cytokines are important cell-to-cell communication mediators during injury. It is speculated that cytokines, such as interleukin 1 (IL-1), interleukin 6 (IL-6), tumor necrosis factor (TNF), and interleukin 8 (IL-8), which are found in elevated amounts in both human and basic trials after head injury, play a role in the cellular cascade of injury. Some of the metabolic events produced by small doses of cytokine infusion in animals, as well as humans, include fever, neutrophilia, muscle breakdown, altered amino acid metabolism, depression of serum zinc levels, production of hepatic acute phase reactants, increased endothelial permeability, and expression of endothelial adhesion molecules. These are all known sequelae of severe head injury. Cytokines have also been implicated in organ failure. Infusion of cytokines in basic science trials revealed that organ functions of the gut, liver, and lung are negatively altered by high-dose cytokine infusion. Infusion of certain cytokines has been shown to cause death of brain cells, increase blood-brain barrier permeability, and cause cerebral edema. This suggests that cytokines may also play a role in the sequelae of organ demise. These effects of cytokines have been attenuated in basic trials by blocking the initial signaling system of cytokines or by decreasing serum cytokine activity. We hypothesize that cytokines that are elevated after head injury play a role in the pathology of injury, including altered metabolism and organ demise.
Levodopa‐dyskinesia incidence by age of Parkinson's disease onset (2004)

We assessed the 5-year risk of levodopa-induced dyskinesias by age of Parkinson's disease (PD) onset in a population-based cohort. The medical records linkage system of the Rochester Epidemiology project was used to identify residents of Olmsted County, Minnesota, with incident PD for the period 1976 through 1990. In this population-based study, the 5-year dyskinesia incidence declined with age. With PD onset after 70 years of age, the incidence was 16%. With onset from 40 to 59 years of age, the incidence was higher at 50%. These incidence data may overestimate the functional importance, because patients with minimal or reversible dyskinesias were counted.
The gene ratios c-MYC:cyclin-dependent kinase (CDK)N2A and CCND1:CDKN2A correlate with poor prognosis in squamous cell carcinoma of the head and neck. (2003)

We conclude that CCND1 and/or c-MYC amplification, when combined with CDKN2A deletion, yield additional prognostic information as compared with analysis of single genetic aberrations. These gene ratios, as analyzed by a sensitive method like real-time PCR on diagnostic biopsies, might help clinicians to individualize the treatment of squamous cell carcinoma of the head and neck as they reflect the biological properties of the tumors. This could be used as an adjunct to the Tumor-Node-Metastasis classification system.
Avidity maturation, repertoire shift, and strain differences in antibodies to bacterial levan, a type 2 thymus-independent polysaccharide antigen (1996)

Our previous studies of 102 mAb from mice injected with bacterial levan (BL), a beta(2-->6) linked polyfructosan with beta(2-->1) branch points (inulin determinant, In) showed that BALB/c and CBA/Ca mAb differed in VH and VL gene family usage and fine specificity. We now show that BALB/c and CBA/Ca mAb used different VHJ606 germ-line genes in response to BL: V14A in BALB/c and a previously unidentified gene in CBA/Ca. CBA/Ca mice were found to lack the BALB/c V14A gene. Also, we have compared the responses to one (primary, 1 degree) or two (secondary, 2 degrees) injections of polysaccharide. The secondary BALB/c anti-BL panel has been expanded to a total of 22 mAb, and we report here the isotype, fine specificity, and VH/VL usage of the new mAb. Eight of nine primary BALB/c In-binding mAb were germ-line, whereas both secondary BALB/c In-binding mAb that were sequenced differed from the BALB/c germ-line gene V14A. Germ-line primary mAb were low avidity whereas all five secondary mAb and the one non-germ-line primary were high avidity. There was also a repertoire shift from approximately 90% VHJ606/V kappa 11 in primary mAb to only 50% in secondary mAb (p = 0.002). The data presented provide evidence that avidity maturation and repertoire shifts, features usually associated with a memory response to thymus-dependent Ags, also can occur in response to a second immunization with a thymus-independent type 2 polysaccharide Ag.
Segmental Bronchial Provocation Induces Nasal Inflammation in Allergic Rhinitis Patients (2000)

Allergic rhinitis and asthma often coexist and share a genetic background. Pathophysiologic connections between the nose and lungs are still not entirely understood. This study was undertaken to compare allergic inflammation and clinical findings in the upper and lower airways after segmental bronchial provocation (SBP) in nonasthmatic allergic rhinitis patients. Eight nonasthmatic, grass pollen-sensitive patients with allergic rhinitis and eight healthy controls were included. Bronchial biopsies and blood samples were taken before (T(0)) and 24 h (T(24)) after SBP. Nasal biopsies were obtained at T(0), 1 h after SBP (T(1)), and T(24). Immunohistochemical staining was performed for eosinophils (BMK13), interleukin (IL)-5, and eotaxin. The number of eosinophils increased in the challenged and unchallenged bronchial mucosa (p < 0.05) and in the blood (p = 0.03) of atopic subjects at T(24). We detected an increase of BMK13-positive and eotaxin-positive cells in the nasal lamina propria and enhanced expression of IL-5 in the nasal epithelium of atopic subjects only at T(24) (p < 0.05). SBP induced nasal and bronchial symptoms as well as reductions in pulmonary and nasal function in the allergic group. No significant changes could be observed in healthy controls. The study shows that SBP in nonasthmatic allergic rhinitis patients results in peripheral blood eosinophilia, and that SBP can induce allergic inflammation in the nose.
A cooperatively-controlled image guided robot system for skull base surgery. (2008)

We created an image-guided robot system to assist with skull base drilling by integrating a robot, a commercial navigation system, and an open source visualization platform. The objective of this procedure is to create a cavity in the skull base to allow access for neurosurgical interventions. The motivation for introducing an image-guided robot is to improve safety by preventing the surgeon from accidentally damaging critical structures during the drilling procedure. Our approach is to attach the cutting tool to the robot end-effector and operate the robot in a cooperative control mode, where robot motion is determined from the forces and torques applied by the surgeon. We employ "virtual fixtures" to constrain the motion of the cutting tool so that it remains in the safe zone that was defined on a preoperative CT scan. This paper presents the system design and the results of phantom and cadaveric experiments. Both experiments have demonstrated the feasibility of the system, with average overcut error at about 1 mm and maximum errors at 2.5 mm.
Visually Navigating the RMS Titanic with SLAM Information Filters (2005)

This paper describes a vision-based, large-area, simultaneous localization and mapping (SLAM) algorithm that respects the low-overlap imagery constraints typical of underwater vehicles while exploiting the inertial sensor information that is routinely available on such platforms. We present a novel strategy for efficiently accessing and maintaining consistent covariance bounds within a SLAM information filter, thereby greatly increasing the reliability of data association. The technique is based upon solving a sparse system of linear equations coupled with the application of constant-time Kalman updates. The method is shown to produce consistent covariance estimates suitable for robot planning and data association. Real-world results are presented for a vision-based 6-DOF SLAM implementation using data from a recent ROV survey of the wreck of the RMS Titanic.
Genetic analysis of the enterobactin gene cluster in Shigella flexneri (1991)

The genes for transport and synthesis of the phenolate siderophore enterobactin are present on the chromosomes of both Ent+ and Ent- clinical isolates of Shigella flexneri. To determine why Ent- S. flexneri isolates fail to express a functional enterobactin system, the structure and expression of enterobactin genes were examined. Several alterations may be responsible for the inability of S. flexneri to express enterobactin. (i) The mRNA levels produced from the entC and fepB genes were not derepressed in low-iron media. (ii) DNA sequence analysis of the entC-fepB intergenic region revealed an 83-bp noncontiguous deletion in the putative fepB leader sequence. The deleted sequences are in a region which would be capable of forming extensive stem-and-loop structures. (iii) An amber codon in the 5' portion of the entC gene was also detected. (iv) An IS1 element, previously mapped to the Ent- S. flexneri enterobactin gene cluster, was found to lie within a potential transcriptional termination sequence in the entF-fepE intergenic region. (v) A mutation responsible for the inactivation of the entF gene was mapped to the entF coding region by using entF hybrid gene fusions. (vi) A comparison of outer membrane profiles from an E. coli strain harboring the cloned fepA gene from either an Ent+ or Ent- Shigella isolate revealed that the Ent- FepA protein is present in the outer membrane but at greatly reduced levels than that of the Ent+ FepA protein. This observation, along with additional studies, suggests that the Ent- FepA may be defective in translation and/or translocation.
Mutations in genetic variants of human serum albumin found in Italy. (1990)

A long-term electrophoretic survey of genetic variants of serum albumin has identified an alloalbumin in 589 unrelated individuals in Italy. The alloalbumins were classified electrophoretically into 17 types. The number of unrelated carriers for each type varied from 1 for several variants reported here to 103 for albumin B. The structural change in 8 of these types has previously been determined, and the amino acid substitutions in 3 additional types are reported here. Albumin Varese has a substitution, -2 arginine to histidine (-2 Arg----His), the same as that reported for proalbumin Lille; albumin Torino has the substitution 60 Glu----Lys; and albumin Vibo Valentia has the substitution 82 Glu----Lys. The ability to distinguish so many alloalbumin types by electrophoresis at several pH values indicates that similar substitutions at different sites produce variants with different electrophoretic mobilities. Except for chain terminations in two Italian variants, all the mutations thus far determined for alloalbumins are attributable to a single-base change in the structural gene, and there is a preponderance of transitions and purine mutations. Seven alloalbumins for which the structural change has been established have been ascertained only in Italy. Several of these are clustered in specific geographic regions of Italy, which suggests an origin through a founder individual. Other variants that occur worldwide are nonetheless clustered in geographic regions within Italy. In these cases an independent mutation probably occurred at a hypermutable site such as a CpG dinucleotide.
Increased expression of the 72-kd type IV collagenase in prostatic adenocarcinoma. Demonstration by immunohistochemistry and in situ hybridization. (1994)

The expression of the 72-kd type IV collagenase has been implicated as an important factor in determining the invasive potential of malignant tumors. Using immunohistochemistry and nonisotopic in situ hybridization, type IV collagenase expression was assessed in benign and malignant prostatic tissue obtained from 117 surgical and autopsy specimens. Diffuse strong staining for type IV collagenase mRNA and protein was identified in the malignant cells of more than 85% of prostatic adenocarcinomas and the dysplastic cells of high grade prostatic intraepithelial neoplasia. Benign hyperplastic epithelium showed moderate expression in basal cells and mild expression in secretory cells. The qualitative patterns of type IV collagenase expression in prostatic epithelium at the protein and mRNA levels in individual cases were identical. There was no correlation between the level of type IV collagenase expression and either tumor grade or stage. In 10% of adenocarcinomas, focal mild to moderate stromal cell immunoreactivity was present but mRNA was not detectable in the stromal compartment in any case. The enhanced expression of type IV collagenase in dysplastic epithelium and prostatic adenocarcinoma suggests it contributes to the development of the invasive phenotype. The vast majority of the enzyme present in these tumors is synthesized by malignant cells and its production by stromal cells is negligible.
Comercio electrónico, mercados minoristas y competencia: su impacto como nueva tecnología de distribución (2001)

Using atomic emission spectrometry and EPR analysis metal-ligand homeostasis (MLH) has been studied in epidermal cells of 954 liquidators of the Chernobyl accident and 947 healthy individuals. A possible association of the redox status with the quantitative changes in the MLH, which could be used as discriminators of oxidative/nitrosative stress, attracts special interest. Characteristic features of oxidative stress mainly related to electrogenic metals (Ca, K, Na), were found not only among the liquidators examined, but also in some healthy individuals (18.1%); this suggests the presence of oxidative/nitrosative stress of non-radiation origin. Correlation between intracellular production of nitric oxide (NO) with quantitative changes in the electrogenic metals may indicate the possible involvement of NO in the generation of an electric potential of the cell.
Removal of platinum group metals from the used auto catalytic converter (2009)

Recycling of platinum group metals from the used auto catalytic converters is profitable from ecological and also economical point of view. This work presents the analysis of the chances of removing the platinum group metals (PGM) from the used auto catalytic converters applying pyrometallurgical and hydrometallurgical methods. The characteristics of auto catalytic converter is shown as well the available technologies used for processing the auto catalytic converters are also presented.
Drift in silicon integrated sensors and circuits due to thermo-mechanical stresses (2000)

These Ecole polytechnique federale de Lausanne EPFL, n° 2213 (2000)Faculte des sciences et techniques de l'ingenieurJury: Ioannis Botsis, Gerard Meijer, Philippe Renaud, Ninoslav Stojadinovic Public defense: 2000-7-28 Reference doi:10.5075/epfl-thesis-2213Print copy in library catalog Record created on 2005-03-16, modified on 2016-08-08
Dishevelled Proteins Lead to Two Signaling Pathways (1999)

Dishevelled (Dsh/Dvl) proteins are known to mediate Wnt signaling by up-regulating beta-catenin levels and stimulating T cell factor (TCF)/LEF-1-dependent transcription. We have identified a new Dvl-mediated signaling pathway in that mouse Dvl proteins, when expressed in COS-7 cells, stimulate c-Jun-dependent transcription activity and the kinase activity of the c-Jun N-terminal kinase (JNK). The DEP domain of Dvl1 is essential for JNK activation. By contrast, all three conserved domains of Dvl, including DIX, PDZ, and DEP, are required for up-regulation of beta-catenin and for stimulation of LEF-1-mediated transcription in mammalian cells. Thus, Dvl can lead to two different signaling pathways. Furthermore, the small G proteins of Cdc42 or Rac1, which are involved in JNK activation by many stimuli, do not appear to play a major role in Dvl-mediated JNK activation, because the dominant negative mutants of Cdc42 and Rac1 could not inhibit Dvl-induced JNK activation. This suggests that Dvl may activate JNK via novel pathways.
CDKL5 variants (2017)

These findings have implications for genetic diagnosis, providing evidence for the reclassification of specific variants previously thought to result in CDKL5 deficiency. Together, these analyses support the view that the predominant brain isoform in humans (hCDKL5_1) is crucial for normal neurodevelopment and that the catalytic domain is the primary functional domain.
Application of Fourier Transform Spectroscopy to Magnetic Resonance (1966)

The application of a new Fourier transform technique to magnetic resonance spectroscopy is explored. The method consists of applying a sequence of short rf pulses to the sample to be investigated and Fourier-transforming the response of the system. The main advantages of this technique compared with the usual spectral sweep method are the much shorter time required to record a spectrum and the higher inherent sensitivity. It is shown theoretically and experimentally that it is possible to enhance the sensitivity of high resolution proton magnetic resonance spectroscopy in a restricted time up to a factor of ten or more. The time necessary to achieve the same sensitivity is a factor of 100 shorter than with conventional methods. The enhancement of the sensitivity is essentially given by the square root of the ratio of line width to total width of the spectrum. The method is of particular advantage for complicated high resolution spectra with much fine structure.
Oxidation at Carbon-1' of DNA Deoxyriboses by the Mn-TMPyP/KHSO5 System Results from a Cytochrome P-450-type Hydroxylation Reaction (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOxidation at Carbon-1' of DNA Deoxyriboses by the Mn-TMPyP/KHSO5 System Results from a Cytochrome P-450-type Hydroxylation ReactionMarguerite Pitie, Jean Bernadou, and Bernard MeunierCite this: J. Am. Chem. Soc. 1995, 117, 10, 2935–2936Publication Date (Print):March 1, 1995Publication History Published online1 May 2002Published inissue 1 March 1995https://pubs.acs.org/doi/10.1021/ja00115a032https://doi.org/10.1021/ja00115a032research-articleACS PublicationsRequest reuse permissionsArticle Views235Altmetric-Citations106LEARN 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
Heterogeneous Epoxide Carbonylation by Cooperative Ion-Pair Catalysis in Co(CO)4–-Incorporated Cr-MIL-101 (2017)

Despite the commercial desirability of epoxide carbonylation to β-lactones, the reliance of this process on homogeneous catalysts makes its industrial application challenging. Here we report the preparation and use of a Co(CO)<sub>4</sub><sup>-</sup>-incorporated Cr-MIL-101 (Co(CO)<sub>4</sub>⊂Cr-MIL-101, Cr-MIL-101 = Cr<sub>3</sub>O(BDC)<sub>3</sub>F, H<sub>2</sub>BDC = 1,4-benzenedicarboxylic acid) heterogeneous catalyst for the ring-expansion carbonylation of epoxides, whose activity, selectivity, and substrate scope are on par with those of the reported homogeneous catalysts. We ascribe the observed performance to the unique cooperativity between the postsynthetically introduced Co(CO)<sub>4</sub><sup>-</sup> and the site-isolated Lewis acidic Cr(III) centers in the metal-organic framework (MOF). The heterogeneous nature of Co(CO)<sub>4</sub>⊂Cr-MIL-101 allows the first demonstration of gas-phase continuous-flow production of β-lactones from epoxides, attesting to the potential applicability of the heterogeneous epoxide carbonylation strategy.