gebhart/patrepeval huggingface dataset:
Effects of bone marrow mesenchymal stem cells on healing of wound combined with local radiation injury (2002)

Objective To explore the effects of bone marrow mesenchymal stem cells(MSC) on healing of wounds combined with local skin irradiation injury. Methods MSC were injected into the wound combined with local skin irradiation injury.Light and electron microscopy,fibroblast and capillary vessel counts,detection of hydroxyproline content in the wound and demonstration of MSC distribution by fluorescence examination were carried out. Results MSC could accelerate the speed of wound healing,The number of fibroblasts and capillary vessels increased obviously during 5 to 20 days after wounding.Granular tissues were abundant in the wound,and the content of hydroxyproline increased in the MSC treated groups.The fluorescence labeling showed that MSC could be found during 1 to 20 days after injection. Conclusion MSC can remain alive in the wound for a long time and surely promote wound healing.\;
G Proteins in Cancer: The Prostate Cancer Paradigm (2004)

Signal transduction research investigating mechanisms of androgen-independent prostate cancer cell proliferation has historically focused on the role of androgen and peptide growth factor receptors. More recent work has raised the idea that intracellular signaling mechanisms triggered by extracellular hormonal factors acting through heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) can also mediate and sustain this pathologic process. Prostate cancer patients with advanced disease express elevated levels of GPCRs and GPCR ligands, suggesting that the GPCR system is activated in the cancerous gland and may contribute to tumor growth. Importantly, inhibition of G protein signaling attenuates prostate cancer cell growth in animal models. The nature of intracellular signaling pathways mediating mitogenic effects of GPCRs in prostate cancer is poorly defined, although the G protein-dependent activation of the Ras-to-mitogen-activated protein kinase pathway has emerged as a critical regulatory event. Activated GPCRs may also exert their mitogenic effects in the prostate by activating the androgen receptor.
Fixation conditions for DNA and RNA in situ hybridization: a reassessment of molecular morphology dogma. (1998)

Neutral buffered formalin (NBF) (4% neutral buffered formaldehyde) has been advocated by most investigators as the primary fixative of choice for in situ hybridization (ISH), and specific anecdotal cautions interdicting the use of precipitating fixatives, which otherwise may offer certain advantages such as superior nuclear detail, are common. Few systematic studies addressing ISH fixation conditions have been published. We reasoned that heavy metals present in some precipitating fixatives may compromise duplex formation during ISH. Cell lines containing known viral gene content (CaSki, 200 to 600 human papilloma virus 16 copies/cell, and SiHa, 1 to 2 human papilloma virus 16 copies/cell) and two negative cell lines (K562 and MOLT 4) were expanded to >10(10) and pellets fixed in NBF, zinc formalin, B5, and Bouin's and Hollande's solutions, and subjected to DNA ISH using biotinylated genomic probes. Ten tissue biopsies fixed in both Hollande's and NBF solutions were also evaluated for human papilloma virus content using DNA ISH. Additionally, 17 cases of Hodgkin's disease fixed in B5 and formalin were compared for Epstein-Barr encoded RNA detection using RNA ISH with fluorescein isothiocyanate-labeled oligonucleotides. Catalyzed reporter deposition combined with Streptavidin-Nanogold staining and silver acetate autometallography (Catalyzed reporter deposition-Ng-autometallography ISH) and a conventional indirect alkaline phosphatase method were used for detection for both DNA and RNA. Contaminating heavy metals entrapped in fixed tissues were removed by two exposures to Lugol's iodine. Results for both DNA and RNA ISH comparing B5 and NBF fixatives were virtually identical. Hollande's, Bouin's, B5, and zinc formalin fixed tissue showed results indistinguishable from NBF fixed tissue in DNA ISH. Precipitating fixatives such as B5 and Hollande's solution may be used for DNA and RNA ISH under appropriate conditions.
Miscellaneous biomaterials (1991)

The objective of this chapter is to review briefly a range of miscellaneous materials from biological sources and to cover aspects of some materials that have not been discussed elsewhere.
Epitaxial-Growth-Induced Junction Welding of Silver Nanowire Network Electrodes (2018)

In this study, we developed a roll-to-roll Ag electroplating process for metallic nanowire electrodes using a galvanostatic mode. Electroplating is a low-cost and facile method for deposition of metal onto a target surface with precise control of both the composition and the thickness. Metallic nanowire networks [silver nanowires (AgNWs) and copper nanowires (CuNWs)] coated onto a polyethylene terephthalate (PET) film were immersed directly in an electroplating bath containing AgNO<sub>3</sub>. Solvated silver ions (Ag<sup>+</sup> ions) were deposited onto the nanowire surface through application of a constant current via an external circuit between the nanowire networks (cathode) and a Ag plate (anode). The amount of electroplated Ag was systematically controlled by changing both the applied current density and the electroplating time, which enabled precise control of the sheet resistance and optical transmittance of the metallic nanowire networks. The optimized Ag-electroplated AgNW (Ag-AgNW) films exhibited a sheet resistance of ∼19 Ω/sq at an optical transmittance of 90% (550 nm). A transmission electron microscopy study confirmed that Ag grew epitaxially on the AgNW surface, but a polycrystalline Ag structure was formed on the CuNW surface. The Ag-electroplated metallic nanowire electrodes were successfully applied to various electronic devices such as organic light-emitting diodes, triboelectric nanogenerators, and a resistive touch panel. The proposed roll-to-roll Ag electroplating process provides a simple, low-cost, and scalable method for the fabrication of enhanced transparent conductive electrode materials for next-generation electronic devices.
Statins: mechanism of action and effects (2001)

The beneficial effects of statins are the result of their capacity to reduce cholesterol biosyntesis, mainly in the liver, where they are selectively distributed, as well as to the modulation of lipid metabolism, derived from their effect of inhibition upon HMG-CoA reductase. Statins have antiatherosclerotic effects, that positively correlate with the percent decrease in LDL cholesterol. In addition, they can exert antiatherosclerotic effects independently of their hypolipidemic action. Because the mevalonate metabolism generates a series of isoprenoids vital for different cellular functions, from cholesterol synthesis to the control of cell growth and differentiation, HMG-CoA reductase inhibition has beneficial pleiotropic effects. Consequently, statins reduce significantly the incidence of coronary events, both in primary and secondary prevention, being the most efficient hypolipidemic compounds that have reduced the rate of mortality in coronary patients. Independent of their hypolipidemic properties, statins interfere with events involved in bone formation and impede tumor cell growth.
Activation of the Phosphoinositide 3-Kinase-Akt-Mammalian Target of Rapamycin Signaling Pathway Is Required for Metabotropic Glutamate Receptor-Dependent Long-Term Depression (2004)

Hippocampal long-term depression (LTD) is a long-lasting decrease in synaptic strength that is most commonly studied at glutamatergic inputs to pyramidal cells in hippocampal area CA1. Activation of G-protein-coupled group I (including types 1 and 5) metabotropic glutamate receptors (mGluRs) by the pharmacological agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) elicits LTD in area CA1 of the hippocampus. Recent reports have shown that de novo protein synthesis is necessary for DHPG-induced LTD. However, relatively little is known about the signaling pathways that couple mGluRs to translation initiation. In this study, we investigated whether the activation of the phosphoinositide 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) pathway, which has been shown to regulate translation initiation, is necessary for mGluR-LTD induced by DHPG. We found that brief incubations of mouse hippocampal slices with DHPG resulted in increased phosphorylation of Akt and mTOR in hippocampal area CA1. Two structurally unrelated PI3K inhibitors, LY294002 and wortmannin, blocked the DHPG-induced increases in phosphorylation of Akt and mTOR. Biochemical fractionation studies showed that the DHPG-induced increase in the phosphorylation of Akt and mTOR could be detected in synaptoneurosome preparations, and immunohistochemical analysis revealed that similar increases could be detected in both stratum pyramidale and stratum radiatum in area CA1. Finally, we observed that both PI3K inhibitors and rapamycin, an mTOR inhibitor, prevented mGluR-LTD induced by DHPG. Together, our findings indicate that activation of the PI3K-Akt-mTOR signaling cascade is required for mGluR-LTD and suggest that this pathway may couple group I mGluRs to translation initiation in hippocampal area CA1.
Costimulation of Transduced T Lymphocytes via T Cell Receptor-CD3 Complex and CD28 Leads to Increased Transcription of Integrated Retrovirus (1999)

Primary human T lymphocytes were transduced at high efficiency with the Moloney murine leukemia virus (Mo-MuLV) vector, LNC-mB7-1, in which an internal cytomegalovirus (CMV) promoter drives expression of the murine B7-1 cDNA. Compared with transduced T cells expanded in IL-2 or reactivated with soluble antibodies to CD3 or CD28, transgene expression was significantly increased after activation on immobilized anti-CD3 antibodies (CD3i) or by simultaneous activation on immobilized anti-CD3 and anti-CD28 antibodies (CD3i/CD28i). A similar pattern of transgene expression was observed in T cells transduced with Mo-MuLV LNC-EGFP. Proviral copy number was maintained in LNC-mB7-1-transduced T cells expanded in IL-2 or reactivated on CD3i/CD28i. Substantial increases in LNC-mB7-1 steady state mRNA in reactivated T lymphocytes, compared with those maintained in IL-2, correlated with increased transcription of the LNC-mB7-1 proviral DNA. Furthermore, T cells transduced with the Mo-MuLV ZIPPGK-mADA, in which the mADA cDNA is driven by an internal human phosphoglycerate kinase (PGK) promoter, showed increases in steady state ZIPPGK-mADA RNA on reactivation. High levels of transgene expression were evident irrespective of cell cycle position in both CD4+ and CD8+ lymphocytes. After reactivation, increases in LNC-mB7-1 mRNA were observed in the presence of the protein synthesis inhibitor cycloheximide, indicating that proteins involved in upregulating transgene expression preexisted in transduced lymphocytes. Induction of transgene expression on CD3i/CD28i showed a dose-dependent decrease in transgene expression when incubated with selective protein kinase inhibitors. These data provide new insights into the mechanisms governing transgene expression driven by Mo-MuLV constructs containing internal promoters in transduced primary T lymphocytes.
Assignment of the human p27Kip1 gene to 12p13 and its analysis in leukemias. (1995)

The p27Kip1 (p27) gene encodes an inducible inhibitor of cyclin-dependent kinase activity. Using a murine p27 cDNA as probe, we obtained a human cDNA clone and subsequently used it to isolate a genomic clone of this gene. The coding region of the human p27 gene was contained in two exons. Both the amino acid sequence and intron-exon organization of p27 were similar to those previously found for the related cyclin-dependent kinase inhibitor p21Waf1 (p21). The p27 gene was localized to chromosome band 12p13 by a combination of somatic cell hybrid and fluorescence in situ hybridization analyses. The p27 gene product is thought to control the leukocyte cell cycle and the 12p13 chromosomal band is known to be deleted in leukemias, suggesting that the p27 gene may act as a tumor suppressor gene in leukemias. Although p27 was found to reside in the minimal region of chromosomal loss in hematological malignancies, no mutations of p27 were observed in leukemia samples. Haploinsufficiency of p27 may confer a growth advantage to leukemia cells.
Three-month, randomized, parallel-group comparison of brimonidine–timolol versus dorzolamide–timolol fixed-combination therapy (2009)

Fixed-combination brimonidine-timolol provided the same or greater IOP lowering compared with fixed-combination dorzolamide-timolol. Both fixed-combination medications were safe and well-tolerated. Brimonidine-timolol received higher ratings of ocular comfort than dorzolamide-timolol. The duration of the studies was 3 months, and additional studies will be needed to compare the efficacy and tolerability of brimonidine-timolol and dorzolamide-timolol during long-term treatment.
Transcriptional reprogramming of dendritic cells by differentiation stimuli (2001)

Immature and mature dendritic cells (DC) have been well characterized functionally and phenotypically. Microorganisms or bacterial products such as lipopolysaccharide (LPS) and inflammatory molecules, including tumor necrosis factor (TNF-α), are both believed to activate the DC maturation program which allows DC to initiate and amplify innate and adaptive immune responses. However, there is increasing evidence that the functional state of DC, induced by different stimuli, may be relevant for the immune response outcome. Thus, we compared the transcriptional program of mature, transitional and immature DC, after either LPS or TNF-α stimulation. GeneChip® oligonucleotide microarrays, representing approximately 6,500 murine genes and ESTs, were used for this analysis. A very diverse modulation of gene expression was observed with the two stimuli. Only LPS-treated cells showed a pattern of expression of genes compatible with a definitive growth arrest and with a suitable activation and control of the immune response.
Ataxia-telangiectasia: structural diversity of untranslated sequences suggests complex post-transcriptional regulation of ATM gene expression (1997)

Mutations in the ATM gene are responsible for the multisystem disorder ataxia-telangiectasia, characterized by neurodegeneration, immune deficiency and cancer predisposition. While no alternative splicing was identified within the coding region, the first four exons of the ATM gene, which fall within the 5'untranslated region (UTR), undergo extensive alternative splicing. We identified 12 different 5'UTRs that show considerable diversity in length and sequence contents. These mRNA leaders, which range from 150 to 884 nucleotides (nt), are expected to form variable secondary structures and contain different numbers of AUG codons. The longest 5'UTR contains a total of 18 AUGs upstream of the translation start site. The 3'UTR of 3590 nt is contained within a single 3'exon. Alternative polyadenylation results in 3'UTRs of varying lengths. These structural features suggest that ATM expression might be subject to complex post-transcriptional regulation, enabling rapid modulation of ATM protein level in response to environmental stimuli or alterations in cellular physiological states.
Haplotyping by double PCR amplification of specific alleles. (1991)

Haplotypes are useful in population genetics and medicine. Determining haplotypes in the absence of DNA samples from appropriate family members can be difficult and laborious. We have developed a rapid and reproducible method for haplotyping an individual in the absence of relatives. The method utilizes pairs of allele-specific PCR primers to differentially amplify each haplotype. Four amplifications can distinguish the haplotypes produced by two biallelic polymorphisms.
Adoptive transfer of activated marrow-infiltrating lymphocytes induces measurable antitumor immunity in the bone marrow in multiple myeloma (2015)

Marrow-infiltrating lymphocytes (MILs) may be used as adoptive cell therapy for multiple myeloma.
Practical Byzantine Fault Tolerance (2000)

Our growing reliance on online services accessible on the Internet demands highly-available systemsthat provide correct service without interruptions. Byzantine faults such as software bugs, operatormistakes, and malicious attacks are the major cause of service interruptions. This thesis describesa new replication algorithm, BFT, that can be used to build highly-available systems that tolerateByzantine faults. It shows, for the first time, how to build Byzantine-fault-tolerant systems that canbe used in practice to implement real services because they do not rely on unrealistic assumptionsand they perform well. BFT works in asynchronous environments like the Internet, it incorporatesmechanisms to defend against Byzantine-faulty clients, and it recovers replicas proactively. Therecovery mechanism allows the algorithm to tolerate any number of faults over the lifetime of thesystem provided fewer than 1=3 of the replicas become faulty within a small windowof vulnerability.The window may increase under a denial-of-service attack but the algorithm can detect and respondto such attacks and it can also detect when the state of a replica is corrupted by an attacker.BFT has been implemented as a generic program library with a simple interface. The BFTlibrary provides a complete solution to the problem of building real services that tolerate Byzantinefaults. We used the library to implement the first Byzantine-fault-tolerant NFS file system, BFS. TheBFT library and BFS perform well because the library incorporates several important optimizations.The most important optimization is the use of symmetric cryptography to authenticate messages.Public-key cryptography, which was the major bottleneck in previous systems, is used only toexchange the symmetric keys. The performance results show that BFS performs 2% faster to 24%slower than production implementations of the NFS protocol that are not replicated. Therefore, webelieve that the BFT library can be used to build practical systems that tolerate Byzantine faults.
NLRX1 prevents mitochondrial induced apoptosis and enhances macrophage antiviral immunity by interacting with influenza virus PB1-F2 protein (2014)

To subvert host immunity, influenza A virus (IAV) induces early apoptosis in innate immune cells by disrupting mitochondria membrane potential via its polymerase basic protein 1-frame 2 (PB1-F2) accessory protein. Whether immune cells have mechanisms to counteract PB1-F2-mediated apoptosis is currently unknown. Herein, we define that the host mitochondrial protein nucleotide-binding oligomerization domain-like receptor (NLR)X1 binds to viral protein PB1-F2, preventing IAV-induced macrophage apoptosis and promoting both macrophage survival and type I IFN signaling. We initially observed that Nlrx1-deficient mice infected with IAV exhibited increased pulmonary viral replication, as well as enhanced inflammatory-associated pulmonary dysfunction and morbidity. Analysis of the lungs of IAV-infected mice revealed markedly enhanced leukocyte recruitment but impaired production of type I IFN in Nlrx1(-/-) mice. Impaired type I IFN production and enhanced viral replication was recapitulated in Nlrx1(-/-) macrophages and was associated with increased mitochondrial mediated apoptosis. Through gain- and loss-of-function strategies for protein interaction, we identified that NLRX1 directly bound PB1-F2 in the mitochondria of macrophages. Using a recombinant virus lacking PB1-F2, we confirmed that deletion of PB1-F2 abrogated NLRX1-dependent macrophage type I IFN production and apoptosis. Thus, our results demonstrate that NLRX1 acts as a mitochondrial sentinel protecting macrophages from PB1-F2-induced apoptosis and preserving their antiviral function. We further propose that NLRX1 is critical for macrophage immunity against IAV infection by sensing the extent of viral replication and maintaining a protective balance between antiviral immunity and excessive inflammation within the lungs.
Centering, scaling, and transformations: improving the biological information content of metabolomics data (2006)

Different pretreatment methods emphasize different aspects of the data and each pretreatment method has its own merits and drawbacks. The choice for a pretreatment method depends on the biological question to be answered, the properties of the data set and the data analysis method selected. For the explorative analysis of the validation data set used in this study, autoscaling and range scaling performed better than the other pretreatment methods. That is, range scaling and autoscaling were able to remove the dependence of the rank of the metabolites on the average concentration and the magnitude of the fold changes and showed biologically sensible results after PCA (principal component analysis).In conclusion, selecting a proper data pretreatment method is an essential step in the analysis of metabolomics data and greatly affects the metabolites that are identified to be the most important.
Lactobacillus buchneri Genotyping on the Basis of Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) Locus Diversity (2013)

Clustered regularly interspaced short palindromic repeats (CRISPR) in combination with associated sequences (cas) constitute the CRISPR-Cas immune system, which uptakes DNA from invasive genetic elements as novel "spacers" that provide a genetic record of immunization events. We investigated the potential of CRISPR-based genotyping of Lactobacillus buchneri, a species relevant for commercial silage, bioethanol, and vegetable fermentations. Upon investigating the occurrence and diversity of CRISPR-Cas systems in Lactobacillus buchneri genomes, we observed a ubiquitous occurrence of CRISPR arrays containing a 36-nucleotide (nt) type II-A CRISPR locus adjacent to four cas genes, including the universal cas1 and cas2 genes and the type II signature gene cas9. Comparative analysis of CRISPR spacer content in 26 L. buchneri pickle fermentation isolates associated with spoilage revealed 10 unique locus genotypes that contained between 9 and 29 variable spacers. We observed a set of conserved spacers at the ancestral end, reflecting a common origin, as well as leader-end polymorphisms, reflecting recent divergence. Some of these spacers showed perfect identity with phage sequences, and many spacers showed homology to Lactobacillus plasmid sequences. Following a comparative analysis of sequences immediately flanking protospacers that matched CRISPR spacers, we identified a novel putative protospacer-adjacent motif (PAM), 5'-AAAA-3'. Overall, these findings suggest that type II-A CRISPR-Cas systems are valuable for genotyping of L. buchneri.
Recombinant norovirus-specific scFv inhibit virus-like particle binding to cellular ligands (2008)

scFv54.6 retained the functional properties of the parent mAb with respect to inhibiting norovirus particle interactions with cells. With further engineering into a form deliverable to the gut mucosa, norovirus neutralizing antibodies represent a prophylactic strategy that would be valuable in outbreak settings.