gebhart/patrepeval huggingface dataset:
Cytochrome c oxidase deficiency in neurons decreases both oxidative stress and amyloid formation in a mouse model of Alzheimer's disease (2007)

Defects in the mitochondrial cytochrome c oxidase (COX) have been associated with Alzheimer's Disease, in which the age-dependent accumulation of beta-amyloid plays an important role in synaptic dysfunction and neurodegeneration. To test the possibility that age-dependent decline in the mitochondrial respiratory function, especially COX activity, may participate in the formation and accumulation of beta-amyloid, we generated mice expressing mutant amyloid precursor protein and mutant presenilin 1 in a neuron-specific COX-deficient background. A neuron-specific COX-deficient mouse was generated by the Cre-loxP system, in which the COX10 gene was deleted by a CamKIIalpha promoter-driven Cre-recombinase. COX10 is a farnesyltransferase involved in the biosynthesis of heme a, required for COX assembly and function. These KO mice showed an age-dependent COX deficiency in the cerebral cortex and hippocampus. Surprisingly, COX10 KO mice exhibited significantly fewer amyloid plaques in their brains compared with the COX-competent transgenic mice. This reduction in amyloid plaques in the KO mouse was accompanied by a reduction in Abeta42 level, beta-secretase activity, and oxidative damage. Likewise, production of reactive oxygen species from cells with partial COX activity was not elevated. Collectively, our results suggest that, contrary to previous models, a defect in neuronal COX does not increase oxidative damage nor predispose for the formation of amyloidgenic amyloid precursor protein fragments.
Synthesis of a C22-34 Subunit of the Immunosuppressant FK-506 (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of a C22-34 Subunit of the Immunosuppressant FK-506James A. Marshall and Shiping XieCite this: J. Org. Chem. 1995, 60, 22, 7230–7237Publication Date (Print):November 1, 1995Publication History Published online1 May 2002Published inissue 1 November 1995https://pubs.acs.org/doi/10.1021/jo00127a031https://doi.org/10.1021/jo00127a031research-articleACS PublicationsRequest reuse permissionsArticle Views1585Altmetric-Citations73LEARN 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-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts
Total matrix addressing (2008)

Abstract— A new passive‐matrix OLED drive technology, Total matrix addressing (TMA™), has been developed, which substantially extends the application space for passive panels beyond the limited panel size and resolution of existing passive‐matrix drive schemes. A number of demonstration systems have been constructed to test the viability and performance of this drive scheme. The development of both the TMA drive methodology and image factorization algorithm will be described, and preliminary performance figures from the demonstration systems presented.
Platinum(IV) Prodrugs with Haloacetato Ligands in the Axial Positions can Undergo Hydrolysis under Biologically Relevant Conditions (2013)

Losing ligands rapidly: Pt(IV) complexes with haloacetato ligands can hydrolyze rapidly under biological conditions (pH 7 and 37 °C, see scheme) and the rate increases with increasing pH value. Possible mechanisms for this hydrolysis are examined using H2(18)O and ESI-MS analysis.
A phase II irinotecan–cisplatin combination in advanced pancreatic cancer (2003)

We report a cisplatin and irinotecan combination in patients with biopsy-proven advanced pancreatic adenocarcinoma. Patients were selected from a specialist centre and required good performance status (KPS>70%), measurable disease on CT scan, and biochemical and haematological parameters within normal limits. Based on a two-stage phase II design, we aimed to treat 22 patients initially. The study was stopped because of the death of the 19th patient during the first treatment cycle, with neutropenic sepsis and multiorgan failure. A total of 89 treatments were administered to 17 patients. Serious grade 3/4 toxicities were haematological (neutropenia) 6%, diarrhoea 6%, nausea 7% and vomiting 6%. Using the clinical benefit response (CBR) criteria, no patients had an overall CBR. For responses confirmed by CT examination, there was one partial response (5%), three stable diseases lasting greater than 6 weeks (16%), with an overall 22% with disease control (PR+SD). The median progression-free and overall survival was 3.1 months (95% CI: 1.3-3.7) and 5.0 (95% CI: 3.9-10.1) months, respectively. Although this synergistic combination has improved the response rates and survival of other solid tumours, we recommend caution when using this combination in the palliation of advanced pancreatic cancer, because of unexpected toxicity.
Scalable and Concise Synthesis of Dichlorofluorescein Derivatives Displaying Tissue Permeation in Live Zebrafish Embryos (2007)

Don't be so negative. We have synthesized new dichlorofluorescein derivatives that are less negatively charged than fluorescein. The synthesis is concise and scalable, and the compounds are conjugation-ready. In addition, these compounds permeate zebrafish embryos; this suggests that they might be useful fluorescent probes for bioimaging. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2268/2008/z700565_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Picosecond optoelectronic detection, sampling, and correlation measurements in amorphous semiconductors (1980)

The rapid relaxation of the photoresponse of high-defect-density amorphous semiconductors such as evaporated a-Si has been utilized to develop an electronic measurement capability which can generate and sample electronic transients with speeds ≲10 ps.
Cell–Cell Communication in Yeast Using Auxin Biosynthesis and Auxin Responsive CRISPR Transcription Factors (2015)

An engineering framework for synthetic multicellular systems requires a programmable means of cell-cell communication. Such a communication system would enable complex behaviors, such as pattern formation, division of labor in synthetic microbial communities, and improved modularity in synthetic circuits. However, it remains challenging to build synthetic cellular communication systems in eukaryotes due to a lack of molecular modules that are orthogonal to the host machinery, easy to reconfigure, and scalable. Here, we present a novel cell-to-cell communication system in Saccharomyces cerevisiae (yeast) based on CRISPR transcription factors and the plant hormone auxin that exhibits several of these features. Specifically, we engineered a sender strain of yeast that converts indole-3-acetamide (IAM) into auxin via the enzyme iaaH from Agrobacterium tumefaciens. To sense auxin and regulate transcription in a receiver strain, we engineered a reconfigurable library of auxin-degradable CRISPR transcription factors (ADCTFs). Auxin-induced degradation is achieved through fusion of an auxin-sensitive degron (from IAA corepressors) to the CRISPR TF and coexpression with an auxin F-box protein. Mirroring the tunability of auxin perception in plants, our family of ADCTFs exhibits a broad range of auxin sensitivities. We characterized the kinetics and steady-state behavior of the sender and receiver independently as well as in cocultures where both cell types were exposed to IAM. In the presence of IAM, auxin is produced by the sender cell and triggers deactivation of reporter expression in the receiver cell. The result is an orthogonal, rewireable, tunable, and, arguably, scalable cell-cell communication system for yeast and other eukaryotic cells.
Structural properties of tetrahedrally coordinated crystals from first-principles calculations of pressure and total energies (1985)

The total-energy and pressure-volume relations are calculated nonrelativistically for Si, Ge, and \ensuremath{\alpha}-Sn within the local-density-functional formalism, with use of first-principles nonlocal pseudopotentials. Ground-state static structural properties (total energy, lattice constant, and bulk modulus and its pressure derivative) are obtained and are in good agreement with experimental values. A prediction of these for \ensuremath{\alpha}-Sn from pressure determinations has not yet been reported. Its bulk modulus from both total-energy and pressure calculations is much smaller than that determined by experimental measurement. This confirms a recent theoretical prediction from other authors casting doubts on the experimental value. An assessment has been made on the advantages and disadvantages of pressure calculations over total-energy calculations and on the influence on the results of the size of all cutoff parameters and perturbative schemes used.
Citrate‐Phosphate‐Dextrose Solution for Preservation of Human Blood: A Further Report (1961)

A comparison of clinically significant in vitro characteristics of ACD and CPD blood is presented. In clinical trials conducted at three hospitals, 586 units of blood collected in CPD in plastic bags were utilized for 622 individual treatments as single units or subdivided aliquots of whole blood, and as packed red cells in 332 patients. The expiration period was 28 days, and five bloods were discarded as outdated. There was one reported pyrexial reaction and one proven bacterial contamination. Forty‐two per cent of the bloods or components were issued during the first week, 43 per cent during the second and third weeks, and 15 per cent during the fourth week of storage. Of the total bloods or components issued, 9 per cent of the whole bloods, 25 per cent of the subdivided blood aliquots, and 23 per cent of the packed red cells were transfused during the fourth week of storage. No difficulty with clotting was observed during collection, storage, or transfusion.
Up-regulation of IL-23p19 expression in rheumatoid arthritis synovial fibroblasts by IL-17 through PI3-kinase-, NF- B- and p38 MAPK-dependent signalling pathways (2006)

IL-23p19 is over-expressed in RA synovial fibroblasts and IL-17 appears to up-regulate the expression of IL-23p19 in RA synovial fibroblasts via PI3-kinase/Akt, NF-kappaB- and p38-MAPK-mediated pathways. These results suggest that a disruption of interaction between IL-17 and IL-23p19 may provide a new therapeutic approach in the treatment of RA.
Quadruple Immunofluorescence: A Direct Visualization Method (1997)

We describe fluorescence immunostaining of four different antigens in the same section. The fluorochrome conjugates used show highest emission in the blue, green, yellow, and red regions of the visible light spectrum, respectively. Specially designed single fluorochrome filter combinations allow selective visualization of each fluorochrome label in turn, without visible crosstalk with the others.
Effect of combinations of EGF-R antibodies on complement-dependent tumor cell lysis (2008)

14005 Background: Therapeutic EGF-R antibodies have advanced the treatment of colon and head & neck tumors and bear great promise for other cancers. While several methods of action have been identified for EGF-R antibodies, induction of complement depending cytotoxicity (CDC) has so far not been observed. We asked whether antibody combinations might provide benefit for this mechanism. Methods and Results: We investigated 8 EGF-R antibodies of human IgG1 (cetuximab, matuzumab, zalutumumab, 003, 005, 008, 011 and 018) and 1 of human IgG2 isotype (panitumumab). Select combinations led to increased C1q and C4c fixation - determined by immunofluorescence - and correspondingly induced strong CDC of A431 and A1207 cells in 51-Cr release assays. Experiments with Ca++/Mg++ depletion and heat inactivation of serum indicated the classical complement pathway to be responsible. Studies comparing a human IgG1 with its murine parental antibody, respective F(ab’)2 fragments, or its IgA1 variant demonstrated two human IgG1 antibodies to be mandatory for CDC. Immunofluorescence-based cross-competition studies identified two clusters of EGF-R binding epitopes (cluster 1: cetuximab, matuzumab, panitumumab, zalutumumab, 018; cluster 2: 003, 005, 008, 011). In cluster 1, three combinations were non-crossblocking, while the remaining combinations competed with each other. In cluster 2, all combinations were crossblocking. None of the combinations of cluster 1 and cluster 2 was crossblocking. All possible dual combinations of the 8 IgG1 antibodies were investigated for complement activation. Strong synergism was observed for all non-crossblocking combinations, whereas none of the crossblocking combinations triggered CDC. Conclusions: Here, we demonstrate a remarkable synergy for EGF-R antibodies. Antibody combinations were identified resulting in potent complement activation via the classical pathway and effective CDC of tumor cells. Studies on a large antibody panel indicated that the observed synergy is a general mechanism which can be activated by combining human IgG1 antibodies recognizing different, non-overlapping epitopes. Our findings demonstrate an unexpected quality of EGF-R antibodies which may be exploited to develop novel and more effective treatments for solid cancers. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genmab
Morphogenesis and release of fowlpox virus (2000)

Release of fowlpox virus (FWPV) as extracellular enveloped virus (EEV) appears to proceed both by the budding of intracellular mature virus (IMV) through the plasma membrane and by the fusion of intracellular enveloped virus (IEV) with the plasma membrane. Based on the frequency of budding events compared to wrapping events observed by electron microscopy, FWPV FP9 strain seems to exit chick embryo fibroblast cells predominantly by budding. In contrast to vaccinia virus (VV), the production of FWPV extracellular virus particles is not affected by N(1)-isonicotinoyl-N(2)-3-methyl-4-chlorobenzoylhydrazine (IMCBH). Comparison of the sequence of the VV F13L gene product with its FWPV orthologue showed a mutation, in the fowlpox protein, at the residue involved in IMCBH resistance in a mutant VV. Glucosamine, monensin or brefeldin A did not have any specific effect on FWPV extracellular virus production. Cytochalasin D, which inhibits the formation of actin filaments, reduces the production of extracellular virus particles by inhibiting the release of cell-associated enveloped virus (CEV) particles from the plasma membrane. Involvement of actin filaments in this mechanism is further supported by the co-localization of actin with viral particles close to the plasma membrane in the absence of cytochalasin D. Actin is also co-localized with virus factories.
Free and protein-conjugated polyamines in mouse epidermal cells. Effect of high calcium and retinoic acid. (1988)

We have investigated polyamine metabolism in primary cultures of mouse epidermal cells. These cells, which grow at low Ca2+ levels as a monolayer with characteristics of basal cells, terminally differentiate when the extracellular Ca2+ level is raised above 1 mM. The cellular levels of free polyamines were measured, and, after incubation of cell cultures with [3H]putrescine, the distribution of label in both acid-soluble and acid-insoluble cellular components was examined. Free polyamine levels were reduced in cells induced to differentiate. Treatment with retinoic acid, which prevents differentiation and causes increased proliferation, resulted in an increase in free putrescine. Upon adjustment of the calcium concentration to a level that induces differentiation, the enzyme transglutaminase was activated, and a concomitant increase in the level of both protein-bound mono- and bis-gamma-glutamyl derivatives of putrescine and spermidine was observed. Isolation of a material of apparent molecular weight about 6000 which contains only mono-gamma-glutamylpolyamines and the finding of both mono- and bis-gamma-glutamylpolyamines in the protein fraction containing cornified cell envelopes provided the basis for speculation on polyamines in envelope formation. Our data suggest that polyamines play a role during epidermal cell differentiation through transglutaminase-mediated post-translational modification.
Study of equilibrium in liquid-gas phases in the bromine-hydrobromic acid-water system. Final report. [For Mark-13 process] (1980)

Within the framework of studies relating to the MARK 13 cyclic process of producing hydrogen, the phase diagram of vapour-liquid equilibrium in the bromine-hydrobromic acid-water (Br/sub 2/-HBr-H/sub 2/O) system at atmospheric pressure was studied at temperatures greater than 300/sup 0/K. Because of its bearing on the production process, the area of concentration under study is restricted considerably by a zone of demixing at ambient temperature within the system and by the reactions among the phases. Complete investigation of the ternary diagram would necessitate the use of another kind of ebulliometer. Examination of the results gives rise to some remarks related to the separation by distillation of bromine, hydrobromic acid and water following the electrolysis stage 3 of the cycle. Since the gaseous phase in the equilibrium is very rich in bromine compared to the liquid phase, separation should be easy and consumption of energy moderate if it is acceptable that hydrobromic acid recycled to electrolysis is contaminated with bromine at a concentration of a few parts per thousand. On the other hand, it seems difficult to eliminate those trace amounts of bromine, particularly as the composition of the mixture is similar to the azeotrope HBr-H/sub 2/O. 19 references, 11 tables
Extractive electrospray ionization for direct analysis of undiluted urine, milk and other complex mixtures without sample preparation (2006)

On-line droplet-droplet extraction occurs when a sample spray intersects a reagent electrospray; this allows continuous analysis of trace amounts of compounds directly in complex matrices including undiluted urine, milk and polluted water over extended periods of time.
Chitotriosidase - a putative biomarker for sporadic amyotrophic lateral sclerosis (2013)

Elevated CHIT-1 levels in the ALS-CSF suggest a definitive role for the enzyme in the disease pathogenesis. Its synthesis and release from microglia into the CSF may be an aligned event of neurodegeneration. Thus, high levels of CHIT-1 signify enhanced microglial activity which may exacerbate the process of neurodegeneration. In view of the multifold increase observed in ALS-CSF, it can serve as a potential CSF biomarker for the diagnosis of SALS.
RNA processing : a practical approach (1994)

3'-end processing of mRNA Capping and methylation of mRNA RNA editing in mitochondria Analysis of messenger RNA turnover in cell-free extracts from mammalian cells Ribosomal RNA processing in vertebrates Processing of transfer RNA precursors Ribozymes Appendix
Gain and noise characteristics of a 1.5 μm near-travelling-wave semiconductor laser amplifier (1989)

The spectral dependence of the gain and noise characteristics of a gas source molecular beam epitaxy (GSMBE)-grown BH-GaInAsP near-travelling-wave semiconductor laser amplifier are presented, from which an indication of nonresonant internal losses is given. An intrinsic noise figure of 6 dB at an internal gain of 28 dB is obtained.
High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation (2007)

The relative importance of various human leukocyte antigen (HLA) loci and the resolution level at which they are matched has not been fully defined for unrelated donor transplantation. To address this question, National Marrow Donor Program data from 3857 transplantations performed from 1988 to 2003 in the United States were analyzed. Patient-donor pairs were fully typed for HLA-A, -B, -C, -DRB1, -DQB1, -DQA1, -DPB1, and -DPA1 alleles. High-resolution DNA matching for HLA-A, -B, -C, and -DRB1 (8/8 match) was the minimum level of matching associated with the highest survival. A single mismatch detected by low- or high-resolution DNA testing at HLA-A, -B, -C or -DRB1 (7/8 match) was associated with higher mortality (relative risk, 1.25; 95% CI, 1.13-1.38; P < .001) and 1-year survival of 43% compared with 52% for 8/8 matched pairs. Single mismatches at HLA-B or HLA-C appear better tolerated than mismatches at HLA-A or HLA-DRB1. Mismatching at 2 or more loci compounded the risk. Mismatching at HLA-DP or -DQ loci and donor factors other than HLA type were not associated with survival. In multivariate modeling, patient age, race, disease stage, and cytomegalovirus status were as predictive of survival as donor HLA matching. High-resolution DNA matching for HLA-A, -B, -C, and -DRB1 alleles is associated with higher rates of survival.
Matrix‐assisted laser‐desorption mass spectrometry using 355 nm radiation (1989)

Matrix-assisted laser desorption of proteins with the 355 nm frequency-tripled output of a neodymium:yttrium-aluminium-garnet laser has been demonstrated. In order to produce desorption at this wavelength, the cinnamic acid derivatives ferulic, caffeic and sinapinic acids have been employed as matrices. Excellent sensitivity (routinely one pmol of protein) and good mass resolution (m/delta m 400, Full width at half maximum) have been obtained by this new method. Ultraviolet photo-spectrometry of the cinnamic acid derivative matrices suggests strongly that they can be used as protein laser-desorption matrices at any wavelength between 260 nm and 360 nm, allowing the development of laser-desorption mass spectrometers based on nitrogen or excimer lasers.
Autochthonous murine models for the study of smoker and never-smoker associated lung cancers (2018)

Lung cancer accounts for the greatest number of cancer deaths in the world. Tobacco smoke-associated cancers constitute the majority of lung cancer cases but never-smoker cancers comprise a significant and increasing fraction of cases. Recent genomic and transcriptomic sequencing efforts of lung cancers have revealed distinct sets of genetic aberrations of smoker and never-smoker lung cancers that implicate disparate biology and therapeutic strategies. Autochthonous mouse models have contributed greatly to our understanding of lung cancer biology and identified novel therapeutic targets and strategies in the era of targeted therapy. With the emergence of immuno-oncology, mouse models may continue to serve as valuable platforms for novel biological insights and therapeutic strategies. Here, we will review the variety of available autochthonous mouse models of lung cancer, their relation to human smoker and never-smoker lung cancers, and their application to immuno-oncology and immune checkpoint blockade that is revolutionizing lung cancer therapy.