gebhart/patrepeval huggingface dataset:
Sox9+ ductal cells are multipotent progenitors throughout development but do not produce new endocrine cells in the normal or injured adult pancreas (2011)

One major unresolved question in the field of pancreas biology is whether ductal cells have the ability to generate insulin-producing β-cells. Conclusive examination of this question has been limited by the lack of appropriate tools to efficiently and specifically label ductal cells in vivo. We generated Sox9CreER(T2) mice, which, during adulthood, allow for labeling of an average of 70% of pancreatic ductal cells, including terminal duct/centroacinar cells. Fate-mapping studies of the Sox9(+) domain revealed endocrine and acinar cell neogenesis from Sox9(+) cells throughout embryogenesis. Very small numbers of non-β endocrine cells continue to arise from Sox9(+) cells in early postnatal life, but no endocrine or acinar cell neogenesis from Sox9(+) cells occurs during adulthood. In the adult pancreas, pancreatic injury by partial duct ligation (PDL) has been suggested to induce β-cell regeneration from a transient Ngn3(+) endocrine progenitor cell population. Here, we identify ductal cells as a cell of origin for PDL-induced Ngn3(+) cells, but fail to observe β-cell neogenesis from duct-derived cells. Therefore, although PDL leads to activation of Ngn3 expression in ducts, PDL does not induce appropriate cues to allow for completion of the entire β-cell neogenesis program. In conclusion, although endocrine cells arise from the Sox9(+) ductal domain throughout embryogenesis and the early postnatal period, Sox9(+) ductal cells of the adult pancreas no longer give rise to endocrine cells under both normal conditions and in response to PDL.
Ambisonic Synthesis of Complex Sources (2007)

Exterior expansions of complex sound sources are presented as flexible objects for producing Ambisonic sound-field encodings. The sources can be synthesized or recorded directly, rotated, and positioned in space. Related techniques can also be used to efficiently add high-quality reverberation, depending on the orientation and location of the source and listener.
A Convenient Synthesis of New Pentaazacyclopentanaphthalene and Pentaazaphenanthrene Derivates (2003)

Reaction of N-{3-cyano-6-[4(5-oxo-2-phenylhydrazono-4,5-dihydroimidazol-1-yl)phenyl]-4-phenylpyridin- 2-yl}formimidic ethyl ester (3) and 3-[4-(3-amino-4-imino-5-phenyl-3,4-dihydropyrido[ 2,3-d]pyrimidin-7-yl)phenyl]-2-phenyl-5-phenylhydrazono-3,5-dihydroimidazol-4-one (4) with different reagents has been investigated and discussed. Some of the obtained compounds were tested for their antimicrobial activity.
Non-lipid-related effects of statins (2000)

The beneficial effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) on coronary events have generally been attributed to their hypocholesterolaemic properties. However, as mevalonate and other intermediates of cholesterol synthesis (isoprenoids) are necessary for cell proliferation and other important cell functions, effects other than cholesterol reduction may explain the pharmacological properties of statins. In the present review, we discuss the current knowledge on the nonlipid-related effects of statins, with a special emphasis on their potential benefits in different diseases, such as atherosclerosis and cancer. The mechanism(s) responsible for their favourable properties are also reviewed.
Cloning, overexpression, purification, and characterization of the Escherichia coli RuvC Holliday junction resolvase. (1994)

The ruvC gene has been cloned into the plasmid pT7-7 under the control of the T7 phi 10 promoter. Following induction with isopropyl-1-thio-beta-D-galactopyranoside, the 19-kDa RuvC protein was overexpressed to 20-30% of total cell protein. RuvC has been purified to homogeneity by a simple procedure involving precipitation from the crude lysate, followed by three chromatographic steps. The purified protein resolves synthetic Holliday junctions (60 nucleotides in length) by cleavage at the 3'-side of a phosphate group, to produce nicked duplex DNA. Under the same conditions no cleavage of linear duplex or single-stranded DNA was detected. However, low levels of cleavage were observed with supercoiled form I and single-stranded circular DNA substrates, consistent with the interaction of RuvC with secondary structures. Using synthetic Holliday junctions, we show that RuvC-mediated resolution requires Mg2+ (10 mM) and exhibits an alkaline pH optimum (pH 9.0). No energy cofactors are needed. When RuvC was analyzed by gel filtration and polyacrylamide gel electrophoresis, monomeric and dimeric forms of the protein were observed.
Impact of intravascular ultrasound in understanding transplant coronary artery disease (1999)

Intravascular ultrasound imaging has been recognized as a sensitive tool to study early transplant vasculopathy lesions. An early examination performed soon after transplantation allows one to study donor atherosclerosis. Further, serial follow-up imaging with meticulous site matching provides important information regarding the progression of donor atherosclerosis and the development of transplant vasculopathy lesions. This review highlights the contribution of intravascular imaging in understanding the transplant coronary artery disease. This review also outlines various methodologies employed by different investigators, and stresses the strengths and weaknesses of these methodologies for correct interpretation as well as comparison of data from different studies.
A homogeneous fluorescence assay for PCR amplicons: its application to real-time, single-tube genotyping (1998)

We have developed a method whereby a single TaqMan probe can be used for many PCR reactions. We demonstrate its application as an integrated system for the direct measurement of allele-specific amplicon generation coupled to the suppression of primer-dimer accumulation in PCR. The system uses a 5'-exonuclease assay of amplicon annealed fluorogenic probes that operates in conjunction with the Amplification Refractory Mutation System, whereby relative changes in reporter fluorescent emission are monitored in real-time using an analytical thermal cycler. We have called this system Three-STAR, and it is universal in that it can either use a single probe for the detection of any one target DNA sequence or a single pair of probes for genotyping any bi-allelic polymorphism. Three-STAR is, therefore, particularly useful for the single-tube genotype analysis of a variety of human DNA polymorphisms and mutations.
Reducing Concurrency Bottlenecks in Parallel I/O Workloads (2011)

To enable high performance parallel checkpointing we introduced the Parallel Log Structured File System (PLFS). PLFS is middleware interposed on the file system stack to transform concurrent writing of one application file into many non-concurrently written component files. The promising effectiveness of PLFS makes it important to examine its performance for workloads other than checkpoint capture, notably the different ways that state snapshots may be later read, to make the case for using PLFS in the Exascale I/O stack. Reading a PLFS file involved reading each of its component files. In this paper we identify performance limitations on broader workloads in an early version of PLFS, specifically the need to build and distribute an index for the overall file, and the pressure on the underlying parallel file system's metadata server, and show how PLFS's decomposed components architecture can be exploited to alleviate bottlenecks in the underlying parallel file system.
The biology of long-term bone marrow cultures and its application to bone marrow transplantation (1991)

Long-term bone marrow cultures have been applied to the study and to the treatment of hemopoietic disease. The incidence of murine primitive (stem) cells with the ability to repopulate irradiated bone morrow stroma is similar to that of cells able to repopulate the hemopoietic system of potentially lethally irradiated mice. In human bone marrow, cells with in vitro repopulating ability have been estimated as 0.5% to 1% of the CD34+ cells. The increase in primitive cells in the circulation seen after administration of growth factors has been exploited by harvesting those cells for use together with bone marrow in autologous transplants. The ability of primitive cells (harvested after granulocyte colony-stimulating factor plus chemotherapy) to reconstitute irradiated marrow stromas indicates that their repopulation capacity in vitro is at least as good as that of bone marrow. This is confirmed by experimental data in mice showing that small volumes of peripheral blood (after granulocyte colony-stimulating factor administration) are capable of long-term repopulation. The regulator capacity of marrow stroma has been exploited to purge bone marrow cultures from patients with acute myeloblastic leukemia in first remission and from treated patients with chronic myelogenous leukemia before using the cultured cells for autologous transplant. The results to date, although preliminary, indicate a role for this methodology in the treatment of leukemia.
Experimental models for predicting drug absorption and metabolism (2013)

The current models developed have greatly contributed to our knowledge of drug interactions with physiological factors, while also useful in the prediction of drug intestinal absorption and metabolism. However, much work remains in this area for the successful extrapolation of in vitro-in vivo data and in furthering the development of reliable and accurate models.
Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases (1999)

Not "from above", but "from the side": Configuration-retaining β-glycosidases protonate their substrate either anti or syn to the endocyclic C1-O bond as the first step in the enzymic cleavage of the glycosidic bond (see schematic drawing). Insights into the mechanism of action of glycosidases have been gained by a combination of the synthesis of inhibitors, the study of the kinetics of their inhibition, and the analysis of the crystal structures of glycosidases and glycosidase-ligand complexes.
Organic smart pixels and complementary inverter circuits formed on plastic substrates by casting and rubber stamping (2000)

This letter describes the characteristics of two organic electronic devices-monolithically integrated transistors and light emitting diodes (e.g. smart pixels), and complementary inverter circuits-that are fabricated on flexible plastic substrates with low cost, low-temperature casting and microcontact printing techniques. Both devices incorporate micron-sized features and have geometries and performance comparable to similar components produced with photolithographic techniques on rigid, inorganic supports.
Source coding with side information at several decoders (1977)

A source coding problem is considered which generalizes source coding with side information [1], [2]. Three correlated information sources <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">X,Y</tex> and <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Z</tex> , are block-encoded: <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Y</tex> is to be reconstructed by two different decoders, one having access to the encoded version of <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">X</tex> and the other having access to the encoded version of <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Z</tex> . The region of achievable rates is determined, assuming that thc sources are discrete, memoryless, and stationary. The resuit is generalized to an arbitrary finite number of decoders.
Enhanced Cancer Immunotherapy by Chimeric Antigen Receptor–Modified T Cells Engineered to Secrete Checkpoint Inhibitors (2017)

<b>Purpose:</b> Despite favorable responses of chimeric antigen receptor (CAR)-engineered T-cell therapy in patients with hematologic malignancies, the outcome has been far from satisfactory in the treatment of solid tumors, partially owing to the development of an immunosuppressive tumor microenvironment. To overcome this limitation, we engineered CAR T cells secreting checkpoint inhibitors (CPI) targeting PD-1 (CAR.αPD1-T) and evaluated their efficacy in a human lung carcinoma xenograft mouse model.<b>Experimental Design:</b> To evaluate the effector function and expansion capacity of CAR.αPD1-T cells <i>in vitro</i>, we measured the production of IFNγ and T-cell proliferation following antigen-specific stimulation. Furthermore, the antitumor efficacy of CAR.αPD1-T cells, CAR T cells, and CAR T cells combined with anti-PD-1 antibody was determined using a xenograft mouse model. Finally, the underlying mechanism was investigated by analyzing the expansion and functional capacity of TILs.<b>Results:</b> Human anti-PD-1 CPIs secreted by CAR.αPD1-T cells efficiently bound to PD-1 and reversed the inhibitory effect of PD-1/PD-L1 interaction on T-cell function. PD-1 blockade by continuously secreted anti-PD-1 attenuated the inhibitory T-cell signaling and enhanced T-cell expansion and effector function both <i>in vitro</i> and <i>in vivo</i> In the xenograft mouse model, we demonstrated that the secretion of anti-PD-1 enhanced the antitumor activity of CAR T cells and prolonged overall survival.<b>Conclusions:</b> With constitutive anti-PD-1 secretion, CAR.αPD1-T cells are more functional and expandable, and more efficient at tumor eradication than parental CAR T cells. Collectively, our study presents an important and novel strategy that enables CAR T cells to achieve better antitumor immunity, especially in the treatment of solid tumors. <i>Clin Cancer Res; 23(22); 6982-92. ©2017 AACR</i>.
A tomato gene expressed during fruit ripening encodes an enzyme of the carotenoid biosynthesis pathway. (1992)

In the initial stages of carotenoid biosynthesis in plants the enzyme phytoene synthase converts two molecules of geranylgeranyl diphosphate into phytoene, the first carotenoid of the pathway. We show here that a tomato (Lycopersicon esculentum) cDNA for a gene (Psy1) expressed during fruit ripening directs the in vitro synthesis of a 47-kDa protein which, upon import into isolated chloroplasts, is processed to a mature 42-kDa form. The imported protein is largely associated with membranes, but it can be easily solubilized by dilution or by treatment at high pH. A plasmid construct containing prokaryotic promoter and ribosome-binding sequences fused to the Psy1 cDNA complements the carotenoidless phenotype of a Rhodobacter capsulatus crtB mutant. We conclude that Psy1 encodes phytoene synthase and that this enzyme is a peripheral plastid membrane protein.
Epigenetics: poly(ADP‐ribosyl)ation of PARP‐1 regulates genomic methylation patterns (2008)

In the postgenome era, attention is being focused on those epigenetic modifications that modulate chromatin structure to guarantee that information present on DNA is read correctly and at the most appropriate time to meet cellular requirements. Data reviewed show that along the chain of events that induce DNA methylation-dependent chromatin condensation/decondensation, a postsynthetic modification other than histone acetylation, phosphorylation, and methylation--namely poly(ADP-ribosyl)ation (PARylation)--participates in the establishment and maintenance of a genome methylation pattern. We hypothesize that the right nuclear balance between unmodified and PARylated poly(ADP-ribose) polymerase 1 (PARP-1), which depends on the dynamics of PARPs/PARG activity, is key to maintaining genomic methylation pattern. According to our data, decreased or increased levels of PARylated PARP-1 are responsible for diffuse hypermethylation or hypomethylation of DNA, respectively. In our model, polymers present on PARP-1 interact noncovalently with DNA methyltransferase 1 (Dnmt1), preventing its enzymatic activity. In the absence of PARylated PARP-1, Dnmt1 is free to methylate DNA; if, in contrast, high levels of PARylated PARP-1 persist, Dnmt1 will be stably inhibited, preventing DNA methylation.
A Method for Single-Cell Sorting and Expansion of Genetically Modified Human Embryonic Stem Cells (2007)

Genetic modification of human embryonic stem (hES) cells is essential for studies of gene function and differentiation. The expression of transgenes may direct tissue-specific differentiation and aid in the identification of various differentiated cell types. Stable genomic integration of transgenes is optimal because hES cell differentiation can span several days to weeks and include numerous cell divisions, and establishing homogeneous modified cell lines will facilitate research studies. Herein we provide a method for producing and expanding hES cell lines from single cells that have been isolated by fluorescence-activated cell sorting (FACS) following genetic modification by lentivirus vectors. Using this method, we have established enhanced green fluorescent protein (eGFP)-expressing hES cell lines that are pluripotent, contain a diploid chromosomal content, and stably express eGFP following more than 2 months of routine culture and in vivo differentiation.
Evaluation of a-Olefin Sulfonates for Steam Diversion (1984)

Abstract Enhanced oil recovery studies have consistently demonstrated the need to mitigate gas channeling in processes involving use of gaseous substances (such as steam, carbon dioxide, nitrogen and air) to stimulate oil production. The use of foam to control the mobility of the gas was suggested thirty years ago, and earlier field tests2,3 indicated that significant benefit in oil production could be achieved using this concept. The use of foam to improve mobility control is based on the observation that most foams have great flow impeding characteristics and provide greater flow impedence in high permeability porous media than in low permeability media. Sibree4 was probably the first to report that froth has an apparent viscosity much higher than either of its constituents. He compared the rheological behavior of a froth to that of a coarse emulsion and attempted to relate apparent viscosity to the volume fraction of gas in the liquid.
Cyclic Nucleotide Regulation of Type-1 Plasminogen Activator-Inhibitor mRNA Stability in Rat Hepatoma Cells (1998)

Type-1 plasminogen activator-inhibitor (PAI-1) is a major physiologic inhibitor of plasminogen activation. Incubation of HTC rat hepatoma cells with the cyclic nucleotide analogue, 8-bromo-cAMP, causes a dramatic increase in tissue-type plasminogen activator activity secondary to a 90% decrease in PAI-1 mRNA. Although 8-bromo-cAMP causes a modest decrease in PAI-1 transcription, regulation is primarily the result of a 3-fold increase in the rate of PAI-1 mRNA degradation. To determine the cis-acting sequences required for cyclic nucleotide regulation, we have stably transfected HTC cells with chimeric genes containing sequences from the rat PAI-1 cDNA and the mouse beta-globin gene and examined the effect of cyclic nucleotides on the decay rate of these transcripts. The mRNA transcribed from the beta-globin gene is stable and not cyclic nucleotide-regulated, whereas the transcript from a construct containing the beta-globin coding region and the PAI-1 3'-untranslated region (UTR) is destabilized in the presence of 8-bromo-cAMP, suggesting that this response is mediated by sequences in the PAI-1 3'-UTR. Analyses by deletion of sequences from this chimeric construct indicate that, whereas more than one region of the PAI-1 3'-UTR can confer cyclic nucleotide responsiveness, the 3'-most 134-nucleotide sequence alone is sufficient to do so. Insertion of PAI-1 sequences within the beta-globin 3'-UTR confirms that the 3'-most 134 nucleotides of PAI-1 mRNA can confer cyclic nucleotide regulation of stability on a heterologous transcript, suggesting that this sequence may play a major role in hormonal regulation of PAI-1 mRNA stability.
Mouse Models of Liver Fibrosis (2007)

Liver fibrosis is the final common pathway in a variety of liver diseases. To model liver fibrosis in mice is important as mechanisms not only of fibrogenesis, but also of fibrolysis, need to be clearly defined. Also, small rodents present a possibility to test potential treatments in vivo. Today, there are several mouse models of liver fibrosis available--induced by administration of hepatotoxins, by bile duct ligation or by immunological mechanisms--and, more and more widespread, transgenic animal models elucidating pathogenesis and common pathways in liver fibrosis. These different mouse models are complementary as they represent different pathways to fibrosis--as also seen in human disease. Recently, several promising treatment methods interfering with cytokine signaling have been published, offering new potential therapeutic interventions. This review seeks to summarize the different methods of fibrosis induction as well as to briefly review some promising new treatment options for fibrosis in the mouse model.
Retinoid Receptors and Their Coregulators (2003)

Retinoids regulate gene transcription by binding to the nuclear receptors, the retinoic acid (RA) receptors (RARs), and the retinoid X receptors (RXRs). RARs and RXRs are ligand-activated transcription factors for the regulation of RA-responsive genes. The actions of RARs and RXRs on gene transcription require a highly coordinated interaction with a large number of coactivators and corepressors. This review focuses on our current understanding of these coregulators known to act in concert with RARs and RXRs. The mechanisms of action of these coregulators are beginning to be uncovered and include the modification of chromatin and the recruitment of basal transcription factors. Challenges remain to understand the specificity of action of RARs and RXRs and the formation of specific transcription complexes consisting of the receptors, coregulators, and other unknown factors.
The Abundance of Short Proteins in the Mammalian Proteome (2006)

Short proteins play key roles in cell signalling and other processes, but their abundance in the mammalian proteome is unknown. Current catalogues of mammalian proteins exhibit an artefactual discontinuity at a length of 100 aa, so that protein abundance peaks just above this length and falls off sharply below it. To clarify the abundance of short proteins, we identify proteins in the FANTOM collection of mouse cDNAs by analysing synonymous and non-synonymous substitutions with the computer program CRITICA. This analysis confirms that there is no real discontinuity at length 100. Roughly 10% of mouse proteins are shorter than 100 aa, although the majority of these are variants of proteins longer than 100 aa. We identify many novel short proteins, including a "dark matter" subset containing ones that lack detectable homology to other known proteins. Translation assays confirm that some of these novel proteins can be translated and localised to the secretory pathway.