gebhart/patrepeval huggingface dataset:
Gene regulation by phosphate in enteric bacteria (1993)

The Escherichia coli phosphate (PHO) regulon includes 31 (or more) genes arranged in eight separate operons. All are coregulated by environmental (extra-cellular) phosphate and are probably involved in phosphorus assimilation. Pi control of these genes requires the sensor PhoR, the response regulator PhoB, the binding protein-dependent Pi-specific transporter Pst, and the accessory protein PhoU. During Pi limitation, PhoR turns on genes of the PHO regulon by phosphorylating PhoB that in turn activates transcription by binding to promoters that share an 18-base consensus PHO Box. When Pi is in excess, PhoR, Pst, and PhoU together turn off the PHO regulon, presumably by dephosphorylating PhoB. In addition, two Pi-independent controls that may be forms of cross regulation turn on the PHO regulon in the absence of PhoR. The sensor CreC, formerly called PhoM, phosphorylates PhoB in response to some (unknown) catabolite, while acetyl phosphate may directly phosphorylate PhoB. Cross regulation of the PHO regulon by CreC and acetyl phosphate may be examples of underlying control mechanisms important for the general (global) control of cell growth and metabolism.
Genetic approaches to study Legionella pneumophila pathogenicity (1994)

Legionella pneumophila is an intracellular pathogen replicating in human macrophages during the course of infection of the lungs, infection by legionellae often leads to severe pneumonia, termed Legionnaires’ disease. Genetic approaches to identify the factors responsible for L. pneumophila pathogenicity started with the construction of genomic libraries in Escherichia coli. Various L. pneumophila-specific genes were cloned in E. coli K-12 by identifaction using functional assays, antibody screening and hybridization (’reverse genetics’). By disrupting the genes via allelic exchange, mutants have been created to assess the influence of the factors on pathogenicity. Among the cloned genes, only for the gene product of the mip gene, encoding a 24-kDa surface-associated protein (macrophage infectivity potentiator) unequivocal evidence for its contribution to pathogenicity could be provided. Two hemolytic factors that have been cloned do not seem to play a role in L. pneumophila pathogenicity. Genetic systems for transposon mutagenesis of the L. pneumophila genome (Tn5, Tn903dIIlacZ, Mud phoA), including TnphoA shuttle mutagenesis, have been established and specifically adapted to identify mutants which displayed an impaired capability to multiply inside macrophages and with a reduced in vivo virulence. Furthermore, by complementation of avirulent mutants, genetic loci could be identified which restored the virulence.
Cloning and Functional Expression of a Novel Endoprotease Involved in Prohormone Processing at Dibasic Sites1 (1991)

We cloned and sequenced a cDNA from a library of mouse pituitary AtT-20 cells which are known to cleave an endogenous and various foreign prohormones at dibasic sites. This cDNA encodes a novel 753-residue protein, named PC3, which is structurally related to the yeast Kex2 protease involved in precursor cleavage at dibasic sites and to recently identified mammalian Kex2-like proteins, furin and PC2. Among examined cell lines and tissues, PC3 mRNA was only detected in AtT-20 cells. The substrate specificity of PC3 expressed in mammalian cells was similar to that observed in AtT-20 cells. We conclude that PC3 is a resident prohormone processing endoprotease in AtT-20 cells.
A Large-Scale Rheumatoid Arthritis Genetic Study Identifies Association at Chromosome 9q33.2 (2008)

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease affecting both joints and extra-articular tissues. Although some genetic risk factors for RA are well-established, most notably HLA-DRB1 and PTPN22, these markers do not fully account for the observed heritability. To identify additional susceptibility loci, we carried out a multi-tiered, case-control association study, genotyping 25,966 putative functional SNPs in 475 white North American RA patients and 475 matched controls. Significant markers were genotyped in two additional, independent, white case-control sample sets (661 cases/1322 controls from North America and 596 cases/705 controls from The Netherlands) identifying a SNP, rs1953126, on chromosome 9q33.2 that was significantly associated with RA (OR(common) = 1.28, trend P(comb) = 1.45E-06). Through a comprehensive fine-scale-mapping SNP-selection procedure, 137 additional SNPs in a 668 kb region from MEGF9 to STOM on 9q33.2 were chosen for follow-up genotyping in a staged-approach. Significant single marker results (P(comb)<0.01) spanned a large 525 kb region from FBXW2 to GSN. However, a variety of analyses identified SNPs in a 70 kb region extending from the third intron of PHF19 across TRAF1 into the TRAF1-C5 intergenic region, but excluding the C5 coding region, as the most interesting (trend P(comb): 1.45E-06 --> 5.41E-09). The observed association patterns for these SNPs had heightened statistical significance and a higher degree of consistency across sample sets. In addition, the allele frequencies for these SNPs displayed reduced variability between control groups when compared to other SNPs. Lastly, in combination with the other two known genetic risk factors, HLA-DRB1 and PTPN22, the variants reported here generate more than a 45-fold RA-risk differential.
Steps in the development of a Vibrio cholerae El Tor biofilm (1999)

We report that, in a simple, static culture system, wild-type Vibrio cholerae El Tor forms a three-dimensional biofilm with characteristic water channels and pillars of bacteria. Furthermore, we have isolated and characterized transposon insertion mutants of V. cholerae that are defective in biofilm development. The transposons were localized to genes involved in (i) the biosynthesis and secretion of the mannose-sensitive haemagglutinin type IV pilus (MSHA); (ii) the synthesis of exopolysaccharide; and (iii) flagellar motility. The phenotypes of these three groups suggest that the type IV pilus and flagellum accelerate attachment to the abiotic surface, the flagellum mediates spread along the abiotic surface, and exopolysaccharide is involved in the formation of three-dimensional biofilm architecture.
Glycemic control in the diabetic pregnancy: Is tighter always better? (2000)

Glucose is the principal nutrient that the mother supplies to the fetus through the placenta by way of concentration-dependent mechanisms. In the presence of maternal hypoglycemia, with limited glucose supply, fetal hypoglycemia and hypoinsulinism ensue. This may be viewed as an adaptive mechanism to increase the chances of fetal survival in the face of limited maternal supply, albeit of a growth-restricted fetus. Fetal nutrient deprivation and the resulting hypoinsulinism may have both short- and long-term consequences. Intrauterine growth failure is associated with higher rates of gestational age-specific neonatal mortality and with long-term cognitive deficits. Furthermore, epidemiologic data suggest that diabetes, coronary artery disease, and hypertension are more common among adults who were small for gestational age at birth. Thus, pancreatic failure in adulthood may be either a response to excessive exposure to glucose as a result of maternal hyperglycemia, or as a result of hypoglycemia where nutrient deprivation leads to fetal growth restriction and reduced islet cell proliferation. Because low mean concentrations of maternal glucose in gestational diabetes are associated with an increased risk of fetal growth restriction, overzealous glycemic control during pregnancy may raise concerns regarding the possible effects on the infant. In the mother with Type 1 diabetes, strict glycemic control is often associated with an increased incidence of severe hypoglycemia. Up to 40% of women report at least one episode of severe hypoglycemia during pregnancy, requiring assistance by another person or professional intervention. It is quite possible that in some patients striving to optimize pregnancy outcome by maintaining the best possible glycemic control jeopardizes the well-being of the mother and the fetus. Thus, with respect to tight glycemic control of pregnant women with diabetes, the question arises: How tight is too tight? Is there a threshold below which the trade-off in terms of maternal morbidity as well as fetal growth restriction and its consequences outweighs the benefits of preventing the effects of maternal hyperglycemia?
Optimal open loop maneuver profiles for flexible spacecraft (1978)

Using the Calculus of Variations, optimal slewing profiles minimizing a structural e xcitation criterion are e stablished for a dynamically s imple spacecraft maneuvering between two quiescent states. Two problem types are considered. In the free end point problem, the structural deformation and its time derivative are unconstrained at maneuver's end. For the constrained end point problem, these variables a re r equired to vanish, which necessarily degrades the excitation criterion. Several figures are presented that illustrate both the n ature and the limitations inherent in maneuvering the spacecraft from one attitude state to another. For a given maneuver amplitude, en, the key parameter influencing structural e xcitation is the product of the maneuver time, Ta, and the lowest significant structural frequency, w. It is shown that when wTa 10, however, this penalty is fairly minor, and some reasonable control of terminal conditions is then practical. Thus it is generally d esirable that all maneuver times meet this criterion. When this is the case, it is possible to derive a normalized suboptimal slewing profile, F(x), applicable to a1 1 maneuvers. Given 0 and Ta, the commanded maneuver rate becomes e( t) = eO F(t/Ta)/Ta. Only a minor computational and memory burden is therefore necessary to perform almost optimal re-orientations.
Synthesis and Radiolabeling of Selective High-Affinity Ligands Designed to Target Non-Hodgkin's Lymphoma and Leukemia (2007)

Selective high-affinity ligands (SHALs) were synthesized as molecular targeting agents for HLA-DR10, a cell surface receptor upregulated on malignant B-cell lymphocytes in non-Hodgkin's lymphoma and leukemia. SHALs are designed to mimic the affinity and selectivity of Lym-1, an antibody that binds to the beta-subunit of HLA-DR10. To bind selectively to HLA-DR10, SHALs were constructed to bind to two adjacent pockets on the surface of the beta-subunit of HLA-DR10 located within an epitope recognized by the Lym-1 antibody. A series of multivalent SHALs with molecular masses of 1500-3000 Da were synthesized using solid/polymer-supported synthesis on chlorotrityl chloride resin in 50-80% yield. To enable their use as radionuclide carriers in mouse studies, SHALs were conjugated to DOTA in a solution-phase reaction with 70-100% yield. 57Co/CoCl2 titrations revealed that 50-60% of the DOTA in the DOTA-conjugated SHALs was available for radiometal chelation. These DOTA-SHALs were labeled with 111In and used to carry out pharmacokinetic studies in mice. Radiolabeling reactions of DOTA-SHALs, with exactly one DOTA entity per targeting SHAL molecule, yielded products with greater than 90% radiochemical purity and specific activities ranging from 97 to 150 muCi/mug.
Self-Assembling a Molecular Pegboard (2005)

This paper describes the design, construction, and application of a self-assembled, chemically addressable DNA nanogrid composed of DNA tiles of nanometer dimensions. This self-assembled structure permits precise placement of molecules at predetermined locations on a “molecular pegboard”. We used the indexed DNA nanogrids to identify single molecules of DNA that hybridize at particular locations.
Muscarinic receptors, leukotriene B4 production and neutrophilic inflammation in COPD patients (2005)

The results obtained show that muscarinic receptors may be involved in airway inflammation in COPD subjects through ACh-induced, ERK1/2-dependent LTB4 release. Muscarinic antagonism may contribute to reduce neutrophil infiltration and activation in COPD.
Internet standards and protocols (1998)

This exclusive, one-volume guide concentrates on the basic technology behind the Internet. And unlike technical dictionaries, it makes terms and protocols more useful by organizing them according to what they do--and accompanying them with in-depth descriptions.
Identification of the MAGE-1 gene product by monoclonal and polyclonal antibodies. (1994)

The human MAGE-1 gene encodes a melanoma peptide antigen recognized by autologous cytotoxic T lymphocytes. To produce antibodies against the MAGE-1 gene product, several approaches were taken. Three oligopeptides were synthesized based on predicted MAGE-1 amino acid sequences and were used to generate rabbit anti-peptide anti-sera. In addition, a truncated MAGE-1 cDNA was cloned into an Escherichia coli expression vector, and recombinant protein was produced and purified. All three rabbit anti-peptide antisera showed reactivity against the immunizing peptide, and one reacted with the recombinant MAGE-1 protein by immunoblotting, but none reacted with cell lysates from MAGE-1 mRNA-positive cells. The recombinant MAGE-1 protein was then used for the generation of mouse monoclonal and rabbit polyclonal antibodies. One IgG1 monoclonal antibody, MA454, as well as rabbit polyclonal antisera recognized a 46-kDa protein in extracts of MAGE-1 mRNA-positive melanoma cell lines. The antibodies showed no apparent cross-reactivity with products of the closely related MAGE-2 and MAGE-3 genes. Serological typing of normal and tumor cell lysates was in full agreement with mRNA analysis, showing expression of MAGE-1 protein in MAGE-1 mRNA-positive testis and a subset of melanomas but not in MAGE-1 mRNA-negative normal or tumor tissues. Transfection of the MAGE-1 gene into a MAGE-1 mRNA-negative melanoma cell line resulted in the expression of the 46-kDa protein, confirming the identity of this protein as the MAGE-1 gene product.
Collaboration awareness in support of collaboration transparency: requirements for the next generation of shared window systems (1990)

Shared window systems enable existing applications to be shared in the context of a real-time teleconference. The development and successful use of several such systems, albeit within limited user communities, testifies to the merits of the basic idea. However, experience to date has suggested a number of areas that have not been adequately addressed, namely: spontaneous interactions, shared workspace management, floor control, and annotation and telepointing. This paper focuses on the ramifications, for the software designer, of various user requirements in these areas. While the recommendations that result are motivated by the desire to enable continued use of collaboration-transparent applications, addressing them involves the development of systems software that is distinctly collaboration-aware.
The Extracellular Matrix Protein MAGP-2 Interacts with Jagged1 and Induces Its Shedding from the Cell Surface (2005)

Elastic fibers are composed of the protein elastin and a network of 10-12-nm microfibrils, which are composed of several glycoproteins, including fibrillin-1, fibrillin-2, and MAGP1/2 (microfibril-associated glycoproteins-1 and -2). Although fibrillins and MAGPs covalently associate, we find that the DSL (Delta/Serrate/LAG2) protein Jagged1, an activating ligand for Notch receptor signaling, also interacts with MAGP-2 in both yeast two-hybrid and coimmunoprecipitation studies. Interaction between Jagged1 and MAGP-2 requires the epidermal growth factor-like repeats of Jagged1. MAGP-2 was found complexed with the Jagged1 extracellular domain shed from 293T cells and COS-7 cells coexpressing full-length Jagged1 and MAGP-2. MAGP-2 shedding of the Jagged1 extracellular domain was decreased by the metalloproteinase hydroxamate inhibitor BB3103 implicating proteolysis in its release. Although MAGP-2 also interacted with the other DSL ligands, Jagged2 and Delta1, they were not found associated with MAGP-2 in the conditioned media, identifying differential effects of MAGP-2 on DSL ligand shedding. The related microfibrillar protein MAGP-1 was also found to interact with DSL ligands but, unlike MAGP-2, was unable to facilitate the shedding of Jagged1. Our findings suggest that in addition to its role in microfibrils, MAGP-2 may also affect cellular differentiation through modulating the Notch signaling pathway either by binding to cell surface DSL ligands or by facilitating release and/or stabilization of a soluble extracellular form of Jagged1.
Microglia in the Mouse Retina Alter the Structure and Function of Retinal Pigmented Epithelial Cells: A Potential Cellular Interaction Relevant to AMD (2009)

These findings share similarities with important pathological features found in AMD and suggest the relevance of microglia-RPE interactions in AMD pathogenesis. We speculate that the migration of retinal microglia into the subretinal space in early stages of the disease induces significant changes in RPE cells that perpetuate further microglial accumulation, increase inflammation in the outer retina, and fosters an environment conducive for the formation of neovascular changes responsible for much of vision loss in advanced AMD.
A Crystal Structure of the Bifunctional Antibiotic Simocyclinone D8, Bound to DNA Gyrase (2009)

Simocyclinones are bifunctional antibiotics that inhibit bacterial DNA gyrase by preventing DNA binding to the enzyme. We report the crystal structure of the complex formed between the N-terminal domain of the Escherichia coli gyrase A subunit and simocyclinone D8, revealing two binding pockets that separately accommodate the aminocoumarin and polyketide moieties of the antibiotic. These are close to, but distinct from, the quinolone-binding site, consistent with our observations that several mutations in this region confer resistance to both agents. Biochemical studies show that the individual moieties of simocyclinone D8 are comparatively weak inhibitors of gyrase relative to the parent compound, but their combination generates a more potent inhibitor. Our results should facilitate the design of drug molecules that target these unexploited binding pockets.
Studies on Antioxidative Substances in Sesame Seed (1985)

Journal Article Studies on Antioxidative Substances in Sesame Seed Get access Yasuko Fukuda, Yasuko Fukuda Ichimura Gakuen Junior College, Uchikubo 61–1, Inuyama-shi, Aichi 484, Japan Search for other works by this author on: Oxford Academic Google Scholar Toshihiko Osawa, Toshihiko Osawa Department of Food Science and Technology, Nagoya University, Chikusa-ku, Nagoya, Aichi 464, Japan Search for other works by this author on: Oxford Academic Google Scholar Mitsuo Namiki, Mitsuo Namiki Department of Food Science and Technology, Nagoya University, Chikusa-ku, Nagoya, Aichi 464, Japan Search for other works by this author on: Oxford Academic Google Scholar Tatsuhiko Ozaki Tatsuhiko Ozaki Takemoto Oil & Fat Co., Ltd., Minato-machi 2–5, Gamagori-shi, Aichi 443, Japan Search for other works by this author on: Oxford Academic Google Scholar Agricultural and Biological Chemistry, Volume 49, Issue 2, 1 February 1985, Pages 301–306, https://doi.org/10.1080/00021369.1985.10866739 Published: 01 February 1985 Article history Received: 27 February 1984 Published: 01 February 1985
Cultured Hepatocytes Adopt Progenitor Characteristics and Display Bipotent Capacity to Repopulate the Liver (2013)

Clinical studies have proved the therapeutic potential of hepatocyte transplantation as a promising alternative to whole organ liver transplantation in the treatment of hereditary or end-stage liver disease. However, donor shortage seriously restricts cell availability, and the lack of appropriate cell culture protocols for the storage and maintenance of donor cells constitutes a significant obstacle. The aim of this study was to stimulate mature hepatocytes in culture to multiply in vitro and track their fate on transplantation. Rat hepatocytes isolated nonenzymatically were cultured serum free for up to 10 days. They were stimulated into proliferation in the presence of growth factors and conditioned media from nonparenchymal and hepatocyte culture supernatants, as well as 10 mM lithium chloride (LiCl). Cell proliferation was assessed by determining DNA content. Additionally, the extent of cell differentiation was estimated using immunofluorescence staining of hepatic, biliary, progenitor, and mesenchymal markers and gene expression analyses. Transplantation studies were performed on the Fischer CD26-mutant rat following pretreatment with retrorsine and partial hepatectomy. Proliferating hepatocytes increasingly adopted precursor characteristics, expressing progenitor (OV6, CD133), hepatic lineage (CK18), biliary (CD49f, CK7, CK19), and mesenchymal (vimentin) markers. The supplement of LiCl further enhanced the proliferative capacity by 30%. Transplantation studies revealed extensive repopulation by large donor hepatocyte clusters. Furthermore, bile duct-like structures deriving from donor cells proved to be immunoreactive to ductular markers and formed in close proximity to endogenous bile ducts. Mature hepatocytes reveal their potential to "switch" between phenotypes, adopting progenitor characteristics during proliferation in vitro. Following transplantation, these "retrodifferentiated" cells further expanded in vivo, thereby generating bipotentially differentiated progenies (hepatocytes and bile duct-like structures). This apparent plasticity of mature hepatocytes may open new approaches for cell-based strategies to treat liver disease.
Cognitive Therapy for the Prevention of Suicide Attempts (2005)

Cognitive therapy was effective in preventing suicide attempts for adults who recently attempted suicide.
Treponemal Phospholipids Inhibit Innate Immune Responses Induced by Pathogen-associated Molecular Patterns (2003)

Host innate immune responses to microbial components, known as pathogen-associated molecular patterns (PAMPs), are regulated and modified by cellular receptors and serum proteins, including Toll-like receptors (TLRs), CD14, and LPS-binding protein (LBP). We demonstrated that a treponemal membrane lipid inhibited PAMPs-induced immune responses. The chemical structure of the lipid was elucidated as a phosphatidylglycerol (PG) derivative, which is scarce in most mammalian tissues, but relatively abundant in treponemal membrane lipids. Natural and synthetic PG counterparts as well as related natural anionic phospholipids, phosphatidylinositol, phosphatidylserine, and cardiolipin, also demonstrated an inhibitory effect. Further, we noted that PG inhibited PAMPs-induced immune responses by blocking the binding of PAMPs with LBP and CD14. In addition, PG decreased proinflammatory cytokine production in serum of LPS-injected mice and depressed abscess formation in mice infected with treponemes. These results suggest that treponemal phospholipid interfere the function of LBP/CD14 and act as a modulator of innate immune responses.