gebhart/patrepeval huggingface dataset:
Metabolic responses of CHO cells to limitation of key amino acids (2014)

Chinese hamster ovary (CHO) cells are the predominant host for production of therapeutic glycoproteins. In particular, the glutamine-synthetase (GS) expression system has been widely used in the biopharmaceutical industry for efficient selection of high-yielding clones. However, much remains unclear on how metabolic wiring affects culture performance. For instance, asparagine and serine have been observed to be the largest nitrogen sources taken up by GS-CHO cells, but their roles in biosynthesis and energy generation are poorly understood. In this work, a comprehensive profiling of extracellular metabolites coupled with an analysis of intracellular label distributions after 1-(13) C-pyruvate supplementation were used to trace metabolic rearrangements in different scenarios of asparagine and serine availability. The absence of asparagine in the medium caused growth arrest, and was associated with a dramatic increase in pyruvate uptake, a higher ratio of pyruvate carboxylation to dehydrogenation and an inability for de novo asparagine synthesis. The release of ammonia and amino acids such as aspartate, glutamate, and alanine were deeply impacted. This confirms asparagine to be essential for these GS-CHO cells as the main source of intracellular nitrogen as well as having an important anaplerotic role in TCA cycle activity. In turn, serine unavailability also negatively affected culture growth while triggering its de novo synthesis, confirmed by label incorporation coming from pyruvate, and reduced glycine and formate secretion congruent with its role as a precursor in the metabolism of one-carbon units. Overall, these results unfold important insights into GS-CHO cells metabolism that lay a clearer basis for fine-tuning bioprocess optimization.
Value of antibodies to citrulline-containing peptides for diagnosing early rheumatoid arthritis. (2003)

Rheumatologists can routinely use 2 or 3 tests for diagnosing RA (latex and/or IgM RF ELISA, and either AKA or anti-CCP ELISA) and can add a third or fourth test when the diagnosis remains in doubt.
Real-Time In Vivo Bioluminescent Imaging for Evaluating the Efficacy of Antibiotics in a Rat Staphylococcus aureus Endocarditis Model (2004)

Therapeutic options for invasive Staphylococcus aureus infections have become limited due to rising antimicrobial resistance, making relevant animal model testing of new candidate agents more crucial than ever. In the present studies, a rat model of aortic infective endocarditis (IE) caused by a bioluminescently engineered, biofilm-positive S. aureus strain was used to evaluate real-time antibiotic efficacy directly. This strain was vancomycin and cefazolin susceptible but gentamicin resistant. Bioluminescence was detected and quantified daily in antibiotic-treated and control animals with IE, using a highly sensitive in vivo imaging system (IVIS). Persistent and increasing cardiac bioluminescent signals (BLS) were observed in untreated animals. Three days of vancomycin therapy caused significant reductions in both cardiac BLS (>10-fold versus control) and S. aureus densities in cardiac vegetations (P < 0.005 versus control). However, 3 days after discontinuation of vancomycin therapy, a greater than threefold increase in cardiac BLS was observed, indicating relapsing IE (which was confirmed by quantitative culture). Cefazolin resulted in modest decreases in cardiac BLS and bacterial densities. These microbiologic and cardiac BLS differences during therapy correlated with a longer time-above-MIC for vancomycin (>12 h) than for cefazolin ( approximately 4 h). Gentamicin caused neither a reduction in cardiac S. aureus densities nor a reduction in BLS. There were significant correlations between cardiac BLS and S. aureus densities in vegetations in all treatment groups. These data suggest that bioluminescent imaging provides a substantial advance in the real-time monitoring of the efficacy of therapy of invasive S. aureus infections in live animals.
Smart Home Delay Tolerant Network for an Earthquake Disaster (2012)

In a previous paper, we proposed a rescue support system for victims buried in an earthquake disaster by constructing an ad-hoc network using home-server smart homes. However, this system has the following two problems: i) it cannot ensure sufficient density of home servers for a WLAN communication range, ii) the system does not consider areas in which home servers cannot be used such as in parks and factories, for example. In this research, we propose a new method using a delay tolerant network (DTN) technique. In this method, rescuers with mobile devices relay information between disconnected networks by walking around during rescue activities. For a performance evaluation, we performed simulation experiments using a map of Abeno-ku, Osaka. From our results, we show that the proposed method increases the information acquisition rate, and the network can be maintained. In addition, we quantitatively show the penetration of the smart home needed for our system.
Non-replicating recombinant vaccinia virus encoding murine B-7 molecules elicits effective costimulation of naive CD4+ splenocytes in vitro (1996)

Using a series of new insertion/expression vectors, we constructed a set of recombinant vaccinia viruses (recVV) encoding the murine T cell costimulatory molecules mB7-1 or mB7-2, or both together in the same construct. On infection with replication incompetent and non-cytopathic recVV, several tumour cell lines expressed the respective molecules and bound to CTLA-4. The highest binding capacity was found when both mB7 molecules were co-expressed. Mouse B16.F10 melanoma cells expressing mB7-1 or mB7-2 provided effective costimulation for proliferation of resting CD4+ T cells in the presence of concanavalin A and plate-bound anti-T cell receptor antibodies, respectively. If mB7-1 and mB7-2 were delivered together on the same cell, the proliferative response of CD4+ T cells increased further. The costimulatory effect could be blocked with CTLA-4, the soluble ligand for B7 molecules. The possibility of engineering tumour cells using recVV holds implications for the future design of vaccination strategies.
Poly(A) Tail Length Control in Saccharomyces cerevisiae Occurs by Message-Specific Deadenylation (1998)

We report that newly synthesized mRNA poly(A) tails are matured to precise lengths by the Pab1p-dependent poly(A) nuclease (PAN) of Saccharomyces cerevisiae. These results provide evidence for an initial phase of mRNA deadenylation that is required for poly(A) tail length control. In RNA 3'-end processing extracts lacking PAN, transcripts are polyadenylated to lengths exceeding 200 nucleotides. By contrast, in extracts containing PAN, transcripts were produced with the expected wild-type poly(A) tail lengths of 60 to 80 nucleotides. The role for PAN in poly(A) tail length control in vivo was confirmed by the finding that mRNAs are produced with longer poly(A) tails in PAN-deficient yeast strains. Interestingly, wild-type yeast strains were found to produce transcripts which varied in their maximal poly(A) tail length, and this message-specific length control was lost in PAN-deficient strains. Our data support a model whereby mRNAs are polyadenylated by the 3'-end processing machinery with a long tail, possibly of default length, and then in a PAN-dependent manner, the poly(A) tails are rapidly matured to a message-specific length. The ability to control the length of the poly(A) tail for newly expressed mRNAs has the potential to be an important posttranscriptional regulatory step in gene expression.
Concept lattice classifier : a first step towards an iterative process of recognition of noised graphic objects (2006)

International audience
Purification and characterization of a neurite outgrowth factor from chicken gizzard smooth muscle. (1985)

Chicken gizzard extract contains a macromolecular glycoprotein that promotes neurite outgrowth of dissociated neurons from the ciliary ganglia of chick embryos. Using conventional purification procedures, the factor responsible for the neurite outgrowth (neurite outgrowth factor (NOF)) was purified about 2000-fold to an apparent single protein band (as judged by agarose-polyacrylamide gel electrophoresis). Twenty fmol/cm2 of the purified NOF bound to the culture well was sufficient to exert maximal neuritic response of cultured ciliary ganglia neurons from 8-day-old chick embryos. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis revealed that NOF migrated as a single polypeptide of 700 and 210 kDa under nonreducing and reducing conditions, respectively. NOF stained with periodic acid-Schiff reagent and had a sedimentation coefficient of 12 s, a Stokes radius of 114 A, and an isoelectric point of about 5.1. Gizzard NOF was trypsin-sensitive, but resistant to treatment with heparinase, beta-galactosidase, and neuraminidase. Antibody prepared against the purified NOF blocked NOF activity in a dose-dependent manner. The antibody did not inhibit the biological activity of mouse laminin, although it cross-reacted weakly with laminin. Immunohistochemical analysis showed that the antibody against NOF strongly stained the extracellular matrix of cells in thin sections of gizzard, skeletal muscle, heart, liver, and ciliary ganglion, and also the membrane and the cytoplasm of cultured gizzard muscle cells. The present data suggest that gizzard NOF is a novel extracellular matrix glycoprotein which has a role in neurite outgrowth promotion from peripheral neurons in vivo. Although unlikely, the possibility that the NOF is a chick laminin could not be excluded.
Mechanism of Tracking and Cleavage of Adduct-damaged DNA Substrates by the Mammalian 5′- to 3′-Exonuclease/Endonuclease RAD2 Homologue 1 or Flap Endonuclease 1 (1996)

The mammalian 5'- to 3'-exonuclease/endonuclease, called RAD2 homologue 1 or flap endonuclease 1, has a unique cleavage activity, dependent on specific substrate structure. On a primer-template, in which the primer has an unannealed 5'-tail, endonucleolytic cleavage near the annealing point releases the tail intact. Entering at the 5'-end, the nuclease tracks along the entire tail to the point of cleavage. Genetic analyses suggest that this nuclease removes DNA adducts in vivo (Sommers, C. H., Miller, E. J., Dujon, B., Prakash, S., and Prakash, L. (1995) J. Biol. Chem. 270, 4193-4196). Micrococcal nuclease footprinting shows that after tracking the nuclease protects a region of the tail 25 nucleotides long, adjacent to the cleavage site. Substrates with adducts at specific locations were used to assess the mechanism of RAD2 homologue 1 nuclease tracking and its ability to cleave modified DNA. Either a conventional cis-diamminedichloroplatinum (II) (CDDP) or a bulky CDDP derivative was placed within or beyond the region protected by the nuclease. The nuclease cleaved the tail of both substrates. In contrast, a CDDP adduct just adjacent to the expected cleavage point was inhibitory. A CDDP adduct at the very 5'-end of the tail was also cleaved. The nuclease could remove tails containing adducts on the sugar-phosphate backbone. Apparently, the nuclease is designed to slide over various types of damage on single stranded DNA and then cut past the damaged site.
Two systems of resting state connectivity between the insula and cingulate cortex (2008)

The insula and cingulate cortices are implicated in emotional, homeostatic/allostatic, sensorimotor, and cognitive functions. Non-human primates have specific anatomical connections between sub-divisions of the insula and cingulate. Specifically, the anterior insula projects to the pregenual anterior cingulate cortex (pACC) and the anterior and posterior mid-cingulate cortex (aMCC and pMCC); the mid-posterior insula only projects to the posterior MCC (pMCC). In humans, functional neuroimaging studies implicate the anterior insula and pre/subgenual ACC in emotional processes, the mid-posterior insula with awareness and interoception, and the MCC with environmental monitoring, response selection, and skeletomotor body orientation. Here, we tested the hypothesis that distinct resting state functional connectivity could be identified between (1) the anterior insula and pACC/aMCC; and (2) the entire insula (anterior, middle, and posterior insula) and the pMCC. Functional connectivity was assessed from resting state fMRI scans in 19 healthy volunteers using seed regions of interest in the anterior, middle, and posterior insula. Highly correlated, low-frequency oscillations (< 0.05 Hz) were identified between specific insula and cingulate subdivisions. The anterior insula was shown to be functionally connected with the pACC/aMCC and the pMCC, while the mid/posterior insula was only connected with the pMCC. These data provide evidence for a resting state anterior insula-pACC/aMCC cingulate system that may integrate interoceptive information with emotional salience to form a subjective representation of the body; and another system that includes the entire insula and MCC, likely involved in environmental monitoring, response selection, and skeletomotor body orientation.
Limulus hemocyte transglutaminase. cDNA cloning, amino acid sequence, and tissue localization. (1993)

We have evidence that the limulus (Tachypleus tri-dentatus) hemocyte transglutaminase (TGase) has a molecular mass of 86 kDa and properties of the mammalian type II TGase-like enzyme (Tokunaga, F., Yamada, M., Miyata, T., Ding, Y.-L., Hiranaga-Kawabata, M., Muta, T., Iwanaga, S., Ichinose, A., and Davie, E.W. (1993) J. Biol. Chem. 268, 252-261). We present here the cDNA and amino acid sequences, and localization of the TGase in various tissues of limulus. The cloned cDNA for TGase consists of 2,884 base pairs. An open reading frame of 2,292 base pairs encodes a sequence comprising 764 residues of the mature protein with molecular masses of 87,021 and 87,110 Da, due to two different clones. The discrepancies of nucleotides in these two clones result in 3 amino acid exchanges at positions Gly452(GGT)-Arg(CGT), Ser477(AGT)-Cys(TGT), and Ile486(ATC)-Ser(AGC), respectively. Northern blot analysis on a total RNA extracted from various tissues of limulus revealed that TGase is expressed with 3.0 kilobases of a single type of mRNA, mainly in hemocytes, hepatopancreas, and gastric tissues. Limulus TGase shows significant sequence similarity with the mammalian TGase family, as follows: guinea pig liver TGase (32.7%), human factor XIIIa subunit (34.7%), human keratinocyte TGase (37.6%), and human erythrocyte band 4.2 (23.0%). Limulus TGase has a unique NH2-terminal cationic extension of 60 residues with no homology to the NH2 termini of mammalian TGases. Based on the alignment of the amino acid sequence of limulus TGase with those of the known TGase family, a phylogenetic tree representing an evolutionary relationship among the family members was inferred by the neighbor joining method.
The bone morphogenetic protein family and osteogenesis (1992)

The BMPs (bone morphogenetic proteins) are a group of related proteins originally identified by their presence in bone-inductive extracts of demineralized bone. By molecular cloning, at least six related members of this family have been identified and are called BMP-2 through BMP-7. These molecules are part of the TGF-beta superfamily, based on primary amino acid sequence homology, including the absolute conservation of seven cysteine residues between the TGF-betas and the BMPs. The BMPs can be divided into subgroups with BMP-2 and BMP-4 being 92% identical, and BMP-5, BMP-6, and BMP-7 being an average of about 90% identical. To examine the individual activities of these molecules, we are producing each BMP in a mammalian expression system. In this system, each BMP is synthesized as a precursor peptide, which is glycosylated, processed to the mature peptide, and secreted as a homodimer. These reagents have been used to demonstrate that single molecules, such as BMP-2, are capable of inducing the formation of new cartilage and bone when implanted ectopically in a rodent assay system. Whether each of the BMPs possesses the same inductive activities in an animal is the subject of ongoing research. Based on the chondrogenic and osteogenic abilities of the BMPs in the adult animal, the expression of the mRNAs for the BMPs has been examined in the development of the embryonic skeleton by in situ hybridization. These studies demonstrate that the BMP mRNAs are spatially and temporally expressed appropriately for the proteins involved in the induction and development of cartilage and bone in the embryonic limb bud.(ABSTRACT TRUNCATED AT 250 WORDS)
Differential effect of CD28 versus B7 blockade on direct pathway of allorecognition and self-restricted responses (2002)

Immunosuppression with B7 antagonists might have 2 opposite effects: reducing T-cell costimulation through CD28 but also preventing CTLA-4 from transmitting its negative regulatory signal. We therefore hypothesized that a selective blockade of CD28 might be qualitatively different from blocking B7. It was previously reported that CD28 modulation prolongs allograft survival in the rat and reverses induction of experimental autoimmune encephalomyelitis in mice. However, whether CD28 or B7 blockade results in similar immunosuppression on alloimmune and self-restricted responses to soluble antigens has not yet been investigated. Here, we addressed this issue in vitro with antagonist anti-CD28 Fab fragments and in vivo using the modulating anti-rat JJ319 monoclonal antibody. As in the inhibition of B7 with CTLA4 immunoglobulin, anti-CD28 Fab fragments inhibited allogenic T-cell proliferation in mixed cultures. In vivo modulation of CD28 blocked the expansion of alloreactive T cells and promoted their apoptosis. In contrast, selective blockade of CD28 did not modify T-cell proliferative responses and antibody production to soluble antigens, whereas blocking B7 with CTLA4 immunoglobulin did. Our data show that blocking CD28, while leaving CTLA4-B7 interactions undisturbed, inhibits alloreactive CD4+ T-cell expansion but does not modify the response to nominal antigens presented in the context of a self-major histocompatibility complex. That B7 engagement is needed for self-restricted responses whereas engagement of CD28 is not essential adds to the suggestion that another unidentified ligand of B7 might deliver a costimulatory signal in the absence of CD28.
The Chromosomal Basis of Human Neoplasia (1983)

High-resolution banding techniques for the study of human chromosomes have revealed that the malignant cells of most tumors analyzed have characteristic chromosomal defects. Translocations of the same chromosome segments with precise breakpoints occur in many leukemias and lymphomas, and a specific chromosome band is deleted in several carcinomas. Trisomy, or the occurrence of a particular chromosome in triplicate, is the only abnormality observed in a few neoplasias. It is proposed that chromosomal rearrangements play a central role in human neoplasia and may exert their effects through related genomic mechanisms. Thus, a translocation could serve to place an oncogene next to an activating DNA sequence, a deletion to eliminate an oncogene repressor, and trisomy to carry extra gene dosage.
Functions of the retinoblastoma protein (1999)

The retinoblastoma protein (pRB) can both positively and negatively regulate transcription. The former correlates with its ability to promote differentiation and the latter with its ability to regulate entry into S-phase. pRB negatively regulates transcription by forming complexes with members of the E2F transcription factor family. These complexes, when bound to E2F sites within certain target genes, actively repress transcription through a variety of mechanisms including physical interaction with adjacent transcriptional activation domains and recruitment of proteins that directly, or indirectly, lead to histone deacetylation. pRB function is, in turn, modulated by phosphorylation mediated by cyclin-dependent kinases. Emerging data suggest that combinatorial control of pRB function may be achieved through the use of different phosphoacceptor sites, different cyclin/cdk docking sites, and different cyclin/cdk complexes. The untimely activation of E2F responsive genes can induce apoptosis. This comes about at least partly through the induction of ARF, which leads to the stabilization and activation of p53. BioEssays 1999;21:950-958.
Synthesis, Structure and Properties of Novel Quaternized Carboxymethyl Chitosan with Drug Loading Capacity (2008)

Abstract A modified approach to prepare novel amphipathic octadecyl-quaternized carboxymethyl chitosan (QACMC) was reported, in which carboxymethyl chitosan (CMC), prepared from chitosan, was made to react with glycidyl octadecyl dimethylammonium chloride; thus, the octadecyl quaternary ammonium group was introduced into CMC. The structure and thermal properties of these derivatives were characterized by Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance spectroscopy ( 1 H-NMR), X-ray diffraction (XRD), and differential scanning calorimetry (DSC). The crystalline properties of QACMC were perfect, and it had a high degree of crystallinity. All the chitosan derivatives had good thermal stability when the temperature was lower than 200 °C. The moisture-absorption and retention abilities of QACMC were lower than that of hyaluronic acid (HA) and CMC. The carboxymethyl and quaternary ammonium groups did not show a synergistic effect, and the effects of both the molar mass and the hydrophobic side chains of long alkyl moieties were important. Minocycline hydrochloride was successfully incorporated into QACMC polymeric micelles with a remarkably high efficiency (10.9%, mass fraction). QACMC promises to be a high-potential delivery vector for lipophilic drugs.
Immunoliposomes as targeted delivery vehicles for cancer therapeutics (Review) (1997)

Advances in liposome technology over the last decade has seen the development of stealth liposomes for drug delivery and cationic liposomes for gene delivery. Many of these liposome formulations are now in clinical trials for the treatment of a variety of malignancies. Whilst some clinical efficacy has been demonstrated, the goal of specific tumor targeting is yet to be attained. For this reason, antibodies have been attached to the surface of liposomes to produce immunoliposomes. These liposomes have shown preferential binding to specific tumor cells in animal models. The construction of the immunoliposome, and in particular the optimal method of antibody coupling to its surface is, however, yet to be determined. Despite these difficulties, immunoliposomes have demonstrated anti-tumor properties, both in vitro and in vivo, and show great promise as targeted delivery vehicles for the treatment of cancer.
Uptake of glutamine antimetabolites 6‐diazo‐5‐oxo‐L‐norleucine (DON) and acivicin in sensitive and resistant tumor cell lines (1988)

The uptake system for 6-diazo-5-oxo-L-norleucine (DON) was studied in mouse P388 leukemia cells. The DON transport system was found to resemble that of another glutamine antimetabolite, Acivicin, in its strong temperature dependence, utilization of the "L" transport system, inhibition by glutamine but not by glutamate, potent inhibition by p-chloromercuribenzene sulfonate, Na+, and only minimal inhibition by various energy poisons. A Km of approximately 70 microM and a Vmax of 3.4 nmoles/10(6) cells/min was calculated for this cell line. The accumulated DON was not metabolized by P388 cells and moderate efflux occurred at 37 degrees C. The DON transport characteristics of a DON-resistant P388 cell line (100 times ID50 of parent line) were similar to those of the DON-sensitive parent line, indicating that altered drug transport may not be involved in development of resistance to this antimetabolite. The finding that an Acivicin-resistant subline of P388 cells which exhibited good transport of DON showed negligible transport of Acivicin suggests different modes of resistance towards the two glutamine antimetabolites.