gebhart/patrepeval huggingface dataset:
Correlation Between Number of Eosinophils and Reflux Index on Same Day Esophageal Biopsy and 24 Hour Esophageal pH Monitoring (2004)

The presence of denser infiltrates of eosinophils does not correlate with increased gastroesophageal reflux. The finding of more than 20 eosinophils/hpf is likely associated with a normal reflux index and a nonacid-related cause of esophagitis.
Expression of Biologically Active Human Factor IX in Human Hematopoietic Cells after Retroviral Vector-Mediated Gene Transduction (1995)

Gene therapy is a potential treatment for hemophilia, wherein cells transduced with a normal factor IX gene could provide a continuous in vivo source of circulating factor IX. In this study, we examined the potential use of hematopoietic cells as a target for factor IX gene therapy. Human myeloid leukemia cells (HL-60) were transduced by retroviral vectors carrying a normal human factor IX cDNA under control of either the Moloney murine leukemia virus long terminal repeat (MoMuLV LTR) (LIXSN), the SV40 promoter (LNSVIX), or a cytomegalovirus (CMV) promoter (LNCIX). Factor IX production was measured in the transduced cells both in the uninduced state and after induction of granulocytic differentiation [with dimethylsulfoxide (DMSO)] or monocytoid differentiation [with phorbol myristic acetate (PMA)]. Transcription of factor IX from the MoMuLV LTR was seen in all cells, with a two-fold increase upon differentiation. Induction with PMA led to an 8- to 15-fold increase in factor IX transcripts from an internal CMV promoter. No factor IX transcripts from the internal SV40 promoter were detected. Immunoreactive factor IX protein was identified by Western blot from induced HL-60 cells transduced by either LIXSN or LNCIX. Factor IX production by HL-60 cells transduced by LNCIX ranged from 38-93 ng/10(6) cells/24 hr following induction of monocytic differentiation. The factor IX antigen titer was directly related to factor IX coagulant titer (r = 0.98; p < 0.001). These data indicate that human myelomonocytic cells are capable of performing the necessary post-translational modifications to produce functional factor IX.(ABSTRACT TRUNCATED AT 250 WORDS)
PROTEOMICS Reviews 2015 (2015)

This double issue of PROTEOMICS contains the 2015 collection of review articles covering various aspects of proteomics technologies and their application in the biosciences. We firmly believe that such an annual collection of review articles is an excellent way for both relative newcomers and experts to keep abreast of developments in the field and we hope that you will find this year's collection of 23 review articles interesting, informative and stimulating. Please remember that the Proteomics Clinical Applications Reviews 2015 issue was also published recently (issue 1/2, Volume 9). You should certainly not miss this issue in order to keep up to date with exciting recent developments in the field of biomedical proteomics! Finally, we are already planning the next collection of review articles that will be published in February 2016 as the PROTEOMICS Reviews 2016 (issue 4, Volume 16). Michael J. Dunn Editor-in-Chief
Classification and evolution of type II CRISPR-Cas systems (2014)

The CRISPR-Cas systems of archaeal and bacterial adaptive immunity are classified into three types that differ by the repertoires of CRISPR-associated (cas) genes, the organization of cas operons and the structure of repeats in the CRISPR arrays. The simplest among the CRISPR-Cas systems is type II in which the endonuclease activities required for the interference with foreign deoxyribonucleic acid (DNA) are concentrated in a single multidomain protein, Cas9, and are guided by a co-processed dual-tracrRNA:crRNA molecule. This compact enzymatic machinery and readily programmable site-specific DNA targeting make type II systems top candidates for a new generation of powerful tools for genomic engineering. Here we report an updated census of CRISPR-Cas systems in bacterial and archaeal genomes. Type II systems are the rarest, missing in archaea, and represented in ∼ 5% of bacterial genomes, with an over-representation among pathogens and commensals. Phylogenomic analysis suggests that at least three cas genes, cas1, cas2 and cas4, and the CRISPR repeats of the type II-B system were acquired via recombination with a type I CRISPR-Cas locus. Distant homologs of Cas9 were identified among proteins encoded by diverse transposons, suggesting that type II CRISPR-Cas evolved via recombination of mobile nuclease genes with type I loci.
Conditional Cytomegalovirus Replication In Vitro and In Vivo (2004)

We have established a conditional gene expression system for cytomegalovirus which allows regulation of genes independently from the viral replication program. Due to the combination of all elements required for regulated expression in the same viral genome, conditional viruses can be studied in different cell lines in vitro and in the natural host in vivo. The combination of a self-sufficient tetracycline-regulated expression cassette and Flp recombinase-mediated insertion into the viral genome allowed fast construction of recombinant murine cytomegaloviruses carrying different conditional genes. The regulation of two reporter genes, the essential viral M50 gene and a dominant-negative mutant gene (m48.2) encoding the small capsid protein, was analyzed in more detail. In vitro, viral growth was regulated by the conditional expression of M50 by 3 orders of magnitude and up to a millionfold when the dominant-negative small capsid protein mutant was used. In vivo, viral growth of the dominant-negative mutant was reduced to detection limits in response to the presence of doxycycline in the organs of mice. We believe that this conditional expression system is applicable to genetic studies of large DNA viruses in general.
Surface Chemistries and Photoelectrochemistries of Thin Film Molecular Semiconductor Materials (1990)

Abstract Thin films of vacuum deposited trivalent and tetravalent metal phthalocyanines (Pc), and derivatives of perylenes (Pe), have been explored by a combination of ultrahigh vacuum deposition, surface spectroscopic characterization techniques, and measurement of photoconductivity and photocurrent spectral responses involving a) interdigitated array microcircuits (MC), and b) photoelectrochemical cells. Of particular interest has been the way adsorbed molecules such as O2 and NH3 affect the photoconductivity of these thin film materials, and the effect on photoactivity of the formation of a sharp interface between a phthalocyanine and a perylene. Multiple chemisorption sites are implicated for molecules such as O2 and NH3 on trivalent metal Pc thin film surfaces. These sites may either increase or decrease photoconductivity, depending on the partial pressure of the adsorbant, and the coverage of molecules competing for the same chemisorption sites. Photoelectrochemical modification of the Pc surface introduces submonolayer coverages of metals like Ag, providing a chemisorption site for molecules such as NH3, thereby improving the performance of these photoconductivity-based chemical sensors. Photoelectrochemical techniques can be used to characerize Pc/Pe bilayers, since the electrolyte provides a noncorrosive, optically transparent electrical contact. Photocurrent yield spectra, obtained from two different illumination directions, have been used to estimate the width of the interfacial region which is most active for exciton dissociation in the Pc/Pe bilayer. Transient photocurrent yields in Pc/Pe multilayers (up to 16 total layers), show that the photocurrent increases linearly with the number of Pc/Pe interfaces. These increases occur up to the point where the width of the individual layers becomes narrower than the interface resolution that our present vacuum deposition technologies can provide.
Effect vergelijkbaar met effect lagere bezetting : proef met overdekte uitloop bij kalkoenhanen (2006)

In een proef met kalkoenhanen heeft de Animal Sciences Group van Wageningen UR onderzocht wat het effect is van wel of geen overdekte uitloop en een hogere of lagere bezettingsdichtheid
Dissent in Organizations (1981)

Dissent in organizations is not always tolerated and is rarely encouraged. Lack of dissent can lead to managerial miscalculations and major strategic and tactical errors. In this article, I examine the use of countervailing views in religious, government, and business organizations, and across cultural lines, as a means of improving management decision making.
Structural Constraints in Protein Engineering (1997)

In a previous study we reported on the successful inversion of coenzyme specificity in isocitrate dehydrogenase (IDH) from NADP to NAD [Chen, R., Greer, A. & Dean, A. M. (1995) A highly active decarboxylating dehydrogenase with rationally inverted coenzyme specificity, Proc. Natl Acad. Sci. USA 92, 11666-11670]. Here, we explore alternative means to generate NAD dependence in the NADP-dependent scaffold of Escherichia coli IDH. The results reveal that engineering a preference for NAD is constrained by the architecture of the IDH coenzyme binding pocket and confirms that the substituted Asp344 in the engineered enzyme is the major determinant of coenzyme specificity. Mutations in the 316-325 loop, which forms part of the coenzyme binding site, reduce activity through transmission of long-range conformational changes into the active site some 14 A distant. Conformational changes seen upon substituting Cys332-->Tyr are not directly involved with improving activity. Replacements at Cys201 reveal that subtle changes in the packing of hydrophobic residues (Met and Ile versus Leu) can elicit markedly different responses. We caution against using sequence alignments as the sole guide for mutagenesis and show how a combination of rational design of active-site residues based on X-ray structures and random substitutions at surrounding residues provides an efficient means to improve enzyme preference and catalytic efficiency towards novel substrates.
Quantitative Analysis of α-Synuclein Solubility in Living Cells Using Split GFP Complementation (2012)

Presently incurable, Parkinson's disease (PD) is the most common neurodegenerative movement disorder and affects 1% of the population over 60 years of age. The hallmarks of PD pathogenesis are the loss of dopaminergic neurons in the substantia nigra pars compacta, and the occurrence of proteinaceous cytoplasmic inclusions (Lewy bodies) in surviving neurons. Lewy bodies are mainly composed of the pre-synaptic protein alpha-synuclein (αsyn), an intrinsically unstructured, misfolding-prone protein with high propensity to aggregate. Quantifying the pool of soluble αsyn and monitoring αsyn aggregation in living cells is fundamental to study the molecular mechanisms of αsyn-induced cytotoxicity and develop therapeutic strategies to prevent αsyn aggregation. In this study, we report the use of a split GFP complementation assay to quantify αsyn solubility. Particularly, we investigated a series of naturally occurring and rationally designed αsyn variants and showed that this method can be used to study how αsyn sequence specificity affects its solubility. Furthermore, we demonstrated the utility of this assay to explore the influence of the cellular folding network on αsyn solubility. The results presented underscore the utility of the split GFP assay to quantify αsyn solubility in living cells.
Landscape of Next-Generation Sequencing Technologies (2011)

ADVERTISEMENT RETURN TO ISSUEReviewNEXTLandscape of Next-Generation Sequencing TechnologiesThomas P. Niedringhaus†, Denitsa Milanova‡, Matthew B. Kerby§, Michael P. Snyder⊥, and Annelise E. Barron*§View Author Information† Department of Chemical Engineering, Stanford University, Palo Alto, California, United States‡ Department of Mechanical Engineering, Stanford University, Palo Alto, California, United States§ Department of Bioengineering, Stanford University, Palo Alto, California, United States⊥ Department of Genetics, Stanford University, Palo Alto, California, United StatesAddress: Stanford University, Department of Bioengineering, W300B James H. Clark Center, 318 Campus Drive, Stanford, CA 94305-5444. E-mail: [email protected]. Phone: (650) 796-4002. Fax: (650) 498-8004.Cite this: Anal. Chem. 2011, 83, 12, 4327–4341Publication Date (Web):May 25, 2011Publication History Published online25 May 2011Published inissue 15 June 2011https://pubs.acs.org/doi/10.1021/ac2010857https://doi.org/10.1021/ac2010857review-articleACS PublicationsCopyright © 2011 American Chemical SocietyRequest reuse permissionsArticle Views10073Altmetric-Citations261LEARN 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 SUBJECTS:Genetics,Genomics,Ions,Monomers,Nanopores Get e-Alerts
Expression and characterization of Rab38, a new member of the Rab small G protein family (2005)

Rab38 is a new member of the Rab small G protein family that regulates intracellular vesicle trafficking. Rab38 is expressed in melanocytes and it has been clarified that a point mutation in the postulated GTP-binding domain of Rab38 is the gene responsible for oculocutaneous albinism in chocolate mice. However, basic information regarding recombinant protein production, intracellular location, and tissue-specific expression pattern has not yet been reported. We produced recombinant Rab38 using a baculovirus/insect cell-protein expression system. A combination of Triton X-114 phase separation and nickel-affinity chromatography yielded exclusively prenylated Rab38 that bound [alpha-32P]-GTP. The mRNA and the native protein were expressed in a tissue-specific manner, e.g., in the lung, skin, stomach, liver, and kidney. Freshly isolated rat alveolar type II cells were highly positive for the mRNA signal, but the signal was rapidly lost over time. Immunofluorescence staining demonstrated that expressed GST-tagged Rab38 was mainly co-localized with endoplasmic reticulum-resident protein and also partly with intermittent vesicles between the endoplasmic reticulum and the Golgi complex. These results indicate that Rab38 is expressed non-ubiquitously in specific tissues and regulates early vesicle transport relating to the endoplasmic reticulum, and hence suggest that Rab38 abnormality may cause multiple organ diseases as well as oculocutaneous albinism.
Facilitation of optimal binary morphological filter design via structuring element libraries and design constraints (1992)

For both the binary and gray scales, mean square optimal digital morphological filters have been characterized previously in terms of the Matheron erosion representation for increasing, translation-invariant mappings. Included in the characterization is the minimal search strategy for the optimal filter basis; however, without prior statistical information or an adequate image-noise model, even in the binary setting, filter design is computationally intractable for moderately sized observation windows. The mitigation of the computational burden via design constraints is the focus here. Although the resulting filter will be suboptimal, if the constraints are imposed in a suitable manner, little loss of filter performance occurs in return for design tractability. Three approaches are considered: limiting the number of terms in the Matheron expansion, constraining the observation window, and employing structuring element libraries. In the latter methodology various sublibraries are formed and a suboptimal filter is derived from image-noise statistics in conjunction with a basis search restricted to relevant sublibraries. This study analyzes two techniques for library construction: the <i>expert</i> approach involves prior sublibrary formation based on knowledge of important filter bases and the <i>first-order</i> approach employs single-erosion statistical information to limit the basis search to likely useful candidates.
Memory T Cells in Flavivirus Vaccination (2018)

Flaviviruses include many medically important viruses, such as Dengue virus (DENV), Japanese encephalitis (JEV), tick-borne encephalitis (TBEV), West Nile (WNV), yellow fever (YFV), and Zika viruses (ZIKV). Currently, there are licensed human vaccines for DENV, JEV, TBEV and YFV, but not for WNV or ZIKV. Memory T cells play a central role in adaptive immunity and are important for host protection during flavivirus infection. In this review, we discuss recent findings from animal models and clinical trials and provide new insights into the role of memory T cells in host protective immunity upon vaccination with the licensed flavivirus vaccines.
Art-175 Is a Highly Efficient Antibacterial against Multidrug-Resistant Strains and Persisters of Pseudomonas aeruginosa (2014)

Artilysins constitute a novel class of efficient enzyme-based antibacterials. Specifically, they covalently combine a bacteriophage-encoded endolysin, which degrades the peptidoglycan, with a targeting peptide that transports the endolysin through the outer membrane of Gram-negative bacteria. Art-085, as well as Art-175, its optimized homolog with increased thermostability, are each composed of the sheep myeloid 29-amino acid (SMAP-29) peptide fused to the KZ144 endolysin. In contrast to KZ144, Art-085 and Art-175 pass the outer membrane and kill Pseudomonas aeruginosa, including multidrug-resistant strains, in a rapid and efficient (∼ 5 log units) manner. Time-lapse microscopy confirms that Art-175 punctures the peptidoglycan layer within 1 min, inducing a bulging membrane and complete lysis. Art-175 is highly refractory to resistance development by naturally occurring mutations. In addition, the resistance mechanisms against 21 therapeutically used antibiotics do not show cross-resistance to Art-175. Since Art-175 does not require an active metabolism for its activity, it has a superior bactericidal effect against P. aeruginosa persisters (up to >4 log units compared to that of the untreated controls). In summary, Art-175 is a novel antibacterial that is well suited for a broad range of applications in hygiene and veterinary and human medicine, with a unique potential to target persister-driven chronic infections.
DEVELOPMENTAL DEREGULATION AND TUMORIGENESIS INHIBITION IN 14-3-3ZETA KNOCKOUT MOUSE (2011)

Cancer is second leading cause of death in the United States. Improving cancer care through patient care, research, education and prevention not only saves lives, but reduces health care cost as well. Breast cancer is the most leading cause of cancer incidence and cancer related death in women of the United States. 14-3-3s are a family of conserved proteins ubiquitously expressed in all eukaryotic organisms. They form complexes with hundreds of proteins by binding to specific phospho-serine/threonine containing motifs. In this way they regulate a variety of cellular processes and are involved in many human diseases especially cancer to our interest. Our lab and others recently reported that the 14-3-3z (zeta) isoform is overexpressed in ~45% breast cancers, which predicted poor patient outcome. 14-3-3z overexpression confers chemotherapy resistance. Additionally, 14-3-3z prevents anoikis by suppressing p53 and promotes epithelial mesenchymal transition by activating the TGB-b signaling pathway, which plays important roles during tumor formation and progression. Based on these l hypothesized that 14-3-3z plays an important role in breast cancer. To systematically study the role of 14-3-3z in breast cancer in vivo, I generated a strong 14-3-3z hypomorphic mutant mouse model by Gene Trap. We found that the homozygous mutant mice are lethal neonatally due to respiratory failure. This lethality could be rescued when outbred to CD-1 or backcrossed to FVB/N mouse strain. Early mammary gland development was not significantly affected in 14-3-3z homozygous mutant mice. When crossed with MMTV driven Polyoma Middle-T or Neu oncogene transgenic tumor prone mouse, the 14-3-3z mutant mice had longer tumor latency and reduced lung metastasis compared to their wild type counterpart. The tumor samples from the 14-3-3z mutant mice displayed reduced proliferation, increased apoptosis and reduced angiogenesis. Multiple genes were differentially expressed in the 14-3-3z knockout tumors. MiR-126 was an important microRNA mediating both the lethality and tumorigenesis inhibition phenotype. In addition, 14-3-3z knockout mice are smaller than their litter mates. This growth retardation was accompanied with reduced growth hormone but increased IGF-1 level in the circulation. The knockout mice had a defect in glucose homeostasis. They have lower blood glucose and tolerate glucose better than their wild type counterparts due to reduced glucose uptake. The aberrant glucose homeostasis was accompanied by reduced Hif1-a and Igf1r expression. The 14-3-3z knockout mice had other phenotypes that need to be further characterized. This mouse strain provided new resource to study 14-3-3z function in vivo and potentially could benefit patients that have aberrant expression of 14-3-3z.
Purification, Characterization, and Biosynthesis of Human Acid Ceramidase (1995)

Acid ceramidase (N-acylsphingosine deacylase, EC 3.5.1.23) is the lysosomal enzyme catalyzing the hydrolysis of ceramide to sphingosine and free fatty acid. Its inherited deficiency causes ceramide accumulation in Farber's disease. The enzyme was purified to apparent homogeneity from human urine by sequential chromatography on octyl-Sepharose, concanavalin A-Sepharose, blue-Sepharose, and DEAE-cellulose. The final preparation, which was enriched approximately 4450-fold over the starting material, resulted in a polypeptide of approximately 50 kDa and could be reduced into two subunits of approximately 13 (alpha) and approximately 40 (beta) kDa. Treatment of the purified enzyme with endoglycosidase H or peptido-N-glycanase F reduced the molecular mass of the beta subunit to approximately 30-35 and approximately 27 kDa, respectively. In contrast, the molecular mass of the alpha subunit was unchanged. The purified enzyme had an apparent Km of 149 microM and a Vmax of 136 nmol/mg/h using N-lauroylsphingosine as substrate. Polyclonal antibodies were raised against the purified urinary enzyme and used to investigate the biosynthesis of acid ceramidase. Immunoprecipitation studies on metabolically labeled skin fibroblasts indicated that both subunits arose from a single precursor of approximately 55 kDa. A minor portion of newly synthesized acid ceramidase was secreted into the medium as a monomeric 47-kDa protein, indicating that generation of the mature heterodimeric enzyme occurred in endosomal and/or lysosomal compartments.