gebhart/patrepeval huggingface dataset:
Latent antibiotics and the potential of the arylomycins for broad-spectrum antibacterial activity (2012)

The increasing trend of antibiotic resistance in bacterial pathogens has driven the need for new classes of antibiotics acting by novel mechanisms. The arylomycins are natural product antibiotics that inhibit bacterial type I signal peptidase (SPase), an endoprotease that is required for the translocation of most proteins across the cytoplasmic membrane. SPase is a promising antibiotic target due to its essentiality and its conserved and accessible active site. However, the initial reported spectrum of arylomycin activity was surprisingly narrow. The total synthesis of several members of this fascinating family of natural products has allowed for a more thorough study of its activity. It has been shown that their spectrum of activity is much broader than previously believed, and that their activity is generally limited not by factors intrinsic to their scaffold or to SPase as a target, but rather, by specific mutations in SPase. An interesting possibility is that past competition between producer and susceptible strains of bacteria may have led to the development of much of the intrinsic resistance observed today. The arylomycins may thus represent “latent” antibiotics, natural product antibiotics whose scaffolds once possessed potent and broad-spectrum activity, and are more likely to be optimized to again have potent and broad spectrum activity, than candidate scaffolds that have never been antibiotics.
Nanofibrillated Cellulose Surface Modification: A Review (2013)

Interest in nanofibrillated cellulose (NFC) has increased notably over recent decades. This bio-based nanomaterial has been used essentially in bionanocomposites or in paper thanks to its high mechanical reinforcement ability or barrier property respectively. Its nano-scale dimensions and its capacity to form a strong entangled nanoporous network have encouraged the emergence of new high-value applications. It is worth noting that chemical surface modification of this material can be a key factor to achieve a better compatibility with matrices. In order to increase the compatibility in different matrices or to add new functions, surface chemical modification of NFC appears to be the prior choice to conserve its intrinsic nanofibre properties. In this review, the authors have proposed for the first time an overview of all chemical grafting strategies used to date on nanofibrillated cellulose with focus on surface modification such as physical adsorption, molecular grafting or polymer grafting.
Transcriptional inaccuracy threshold attenuates differences in RNA-dependent DNA synthesis fidelity between retroviral reverse transcriptases (2018)

In M13mp2 lacZα forward mutation assays measuring intrinsic fidelity of DNA-dependent DNA synthesis, wild-type human immunodeficiency virus type 1 (HIV-1) RTs of group M/subtype B previously showed >10-fold higher error rates than murine leukaemia virus (MLV) and avian myeloblastosis virus (AMV) RTs. An adapted version of the assay was used to obtain error rates of RNA-dependent DNA synthesis for several RTs, including wild-type HIV-1<sub>BH10</sub>, HIV-1<sub>ESP49</sub>, AMV and MLV RTs, and the high-fidelity mutants of HIV-1<sub>ESP49</sub> RT K65R and K65R/V75I. Our results showed that there were less than two-fold differences in fidelity between the studied RTs with error rates ranging within 2.5 × 10<sup>-5</sup> and 3.5 × 10<sup>-5</sup>. These results were consistent with the existence of a transcriptional inaccuracy threshold, generated by the RNA polymerase while synthesizing the RNA template used in the assay. A modest but consistent reduction of the inaccuracy threshold was achieved by lowering the pH and Mg<sup>2+</sup> concentration of the transcription reaction. Despite assay limitations, we conclude that HIV-1<sub>BH10</sub> and HIV-1<sub>ESP49</sub> RTs are less accurate when copying DNA templates than RNA templates. Analysis of the RNA-dependent mutational spectra revealed a higher tendency to introduce large deletions at the initiation of reverse transcription by all HIV-1 RTs except the double-mutant K65R/V75I.
Simvastatin impairs humoral and cell‐mediated immunity in mice by inhibiting lymphocyte homing, T‐cell activation and antigen cross‐presentation (2008)

Statins block the activity of HMG-CoA reductase, which catalyses the production of mevalonate, an intermediate in cholesterol biosynthesis, which is also a precursor of isoprenoids. In addition to lowering circulating cholesterol, these drugs display anti-inflammatory and immunomodulatory activities in vitro; however, their effects on the development of adaptive immune responses in vivo, as well as the underlying mechanisms, are as yet largely unknown. Here we investigated the outcome of simvastatin treatment on a number of processes, which together orchestrate adaptive immunity to specific antigen. Simvastatin treatment resulted in a marked reduction of T and B cells in spleen, lymph nodes and peripheral blood in mice. This effect could be ascribed principally to an impairment of lymphocyte homing to secondary lymphoid organs. In addition, simvastatin was found to strongly inhibit T-cell responses to the MHCI restricted hen ovalbumin peptide antigen SIINFEKL and to impair ovalbumin uptake and cross-presentation by MHCI. Simvastatin also suppressed antibody responses to immunization with ovalbumin and delayed-type hypersensitivity to allergens. These activities could be largely accounted for by the simvastatin-dependent inhibition of HMG-CoA reductase. The data provide novel mechanistic insight into the activities of simvastatin in the highly complex context of the immune response.
Investigation of the Molecular Recognition of Amino Acids by Cyclopeptides with Reflectometric Interference Spectroscopy (1998)

IR spectroscopic mapping of resin beads allows destruction-free characterization of polymer-bound combinatorial compound libraries. By choice of different absorptions for IR reconstruction, resin beads with common structural elements can be "fished out" of a library and statistically investigated.
Differential clearance of glycoforms of IgG in normal and autoimmune-prone mice (1996)

In order to understand better the origins of the elevated levels of the glycoform of IgG that lacks galactose on both arms of the oligosaccharide chain (G0%) located in the Fc, which occurs in man and mouse with age, and in particular in autoimmune disease, we investigated the clearance of two glycosylated forms of IgG2a and IgG1 in normal (BALB/c) and autoimmune-prone (MRL/1pr, MRL/+, and non-obese diabetic (NOD)) mice. To investigate the possibility of different rates of catabolism, enzymatically generated glycoforms of monomeric IgG1 and IgG2a (fully glycosylated or G0%), were iodinated and injected into the tail vein of the mice. We found that the G0% IgG2a remained in circulation significantly longer than the fully glycosylated variants, in all of the mouse strains tested. In contrast, the two forms of IgG1 had similar kinetics in all the autoimmune-prone mice, whereas in BALB/c, there was a longer half-life (t1/2) for G0% IgG1. These data suggest that there may be differences in the ability of the IgG glycoforms to bind to the Fc gamma receptors, in particular Fc gamma RI. The clearance rates were found to vary among the strains studied, with MRL/1pr having the fastest catabolic rates for all glycoforms and IgG subclasses tested. This appeared to be due to the presence of circulating IgG and IgM rheumatoid factors (RF). There were significantly increased frequencies and titres for both IgM and IgG RF in MRL/1pr mice compared with the other strains. In contrast, interferon-gamma, known to induce the Fc gamma RI, was found to be similar in the sera, in all of the strains of mice examined. These results suggest that RF probably play an important biological function in the MRL/1pr mice and aid in the clearance of circulating IgG. Our study shows that the state of glycosylation of IgG affects the t1/2 in vivo, and that by removing the terminal sugars (sialic acid and galactose), the antibody (IgG2a) will remain in circulation significantly longer. These observations may thus provide a partial explanation for the increase in relative percentage of this glycoform that occurs with age.
Evaluation of the effect of the degree of acetylation on the inflammatory response to 3D porous chitosan scaffolds (2009)

The effect of the degree of acetylation (DA) of 3D chitosan (Ch) scaffolds on the inflammatory reaction was investigated. Chitosan porous scaffolds with DAs of 4 and 15% were implanted using a subcutaneous air-pouch model of inflammation. The initial acute inflammatory response was evaluated 24 and 48 h after implantation. To characterize the initial response, the recruitment and adhesion of inflammatory cells to the implant site was studied. The fibrous capsule formation and the infiltration of inflammatory cells within the scaffolds were evaluated for longer implantation times (2 and 4 weeks). Chitosan with DA 15% attracted the highest number of leukocytes to the implant site. High numbers of adherent inflammatory cells were also observed in this material. For longer implantation periods Ch scaffolds with a DA of 15% induced the formation of a thick fibrous capsule and a high infiltration of inflammatory cells within the scaffold. Our results indicate that the biological response to implanted Ch scaffolds was influenced by the DA. Chitosan with a DA of 15% induce a more intense inflammatory response when compared with DA 4% Ch. Because inflammation and healing are interrelated, this result may provide clues for the relative importance of acetyl and amine functional groups in tissue repair and regeneration.
Hyperphosphorylation and aggregation of tau in mice expressing normal human tau isoforms (2003)

Neurofibrillary tangles are composed of insoluble aggregates of the microtubule-associated protein tau. In Alzheimer's disease the accumulation of neurofibrillary tangles occurs in the absence of tau mutations. Here we present mice that develop pathology from non-mutant human tau, in the absence of other exogenous factors, including beta-amyloid. The pathology in these mice is Alzheimer-like, with hyperphosphorylated tau accumulating as aggregated paired helical filaments. This pathologic tau accumulates in the cell bodies and dendrites of neurons in a spatiotemporally relevant distribution.
Ethnographic decision tree for male decision criteria related to online games (2013)

Online games have emerged as an important and interesting research area in a variety of academic and official settings. This study adopts ethnographic decision tree modelling (EDTM) which here integrates qualitative and quantitative paradigms to model the decision-making process of whether or not to play online games by male undergraduate students. The model is built based on qualitative data gathered through in-depth interviews of 29 respondents, where 18 criteria for playing online games are elicited. The model is tested using qualitative and quantitative data from interviews, and a structured questionnaire involving 241 respondents. The predictability of the model is 90.04%. Armed with the results, this study provides online game industries an understanding of the decision-making process of male undergraduate players in Taiwan, and reveals methodology and theory standpoints for the researchers with similar interests.
Targeting multiple kinase pathways in leukemic progenitors and stem cells is essential for improved treatment of Ph + leukemia in mice (2006)

It is generally believed that shutting down the kinase activity of BCR-ABL by imatinib will completely inhibit its functions, leading to inactivation of its downstream signaling pathways and cure of the disease. Imatinib is highly effective at treating human Philadelphia chromosome-positive (Ph(+)) chronic myeloid leukemia (CML) in chronic phase but not Ph(+) B cell acute lymphoblastic leukemia (B-ALL) and CML blast crisis. We find that SRC kinases activated by BCR-ABL remain fully active in imatinib-treated mouse leukemic cells, suggesting that imatinib does not inactivate all BCR-ABL-activated signaling pathways. This SRC pathway is essential for leukemic cells to survive imatinib treatment and for CML transition to lymphoid blast crisis. Inhibition of both SRC and BCR-ABL kinase activities by dasatinib affords complete B-ALL remission. However, curing B-ALL and CML mice requires killing leukemic stem cells insensitive to both imatinib and dasatinib. Besides BCR-ABL and SRC kinases, stem cell pathways must be targeted for curative therapy of Ph(+) leukemia.
Advanced applications using [mu]MAD, the adhesion based dynamic micro-manipulator (2004)

A micro-manipulation method based on adhesion forces and dynamic effects has been proposed in our previous papers (2002). A prototype manipulator, called [mu]MAD, has been constructed and successfully experimented. This paper describes the advanced capabilities of [mu]MAD, especially two new interesting applications: sorting of micro-objects and mechanical characterizations.
Increased Hepatic Forkhead Box M1B (FoxM1B) Levels in Old-aged Mice Stimulated Liver Regeneration through Diminished p27Kip1 Protein Levels and Increased Cdc25B Expression (2002)

Recent liver regeneration studies indicate that maintaining hepatic Forkhead Box M1B (FoxM1B) expression in 12-month-old (old-aged) Transthyretin-FoxM1B transgenic mice increases hepatocyte proliferation and expression of cell cycle regulatory genes. Because these transgenic CD-1 mice maintain FoxM1B levels during the aging process, we conducted the current study to determine whether adenovirus delivery of the FoxM1B gene (AdFoxM1B) is sufficient to stimulate liver regeneration in old-aged Balb/c mice. Here we show that AdFoxM1B infection of old-aged mice caused a significant increase in FoxM1B expression, hepatocyte DNA replication, and mitosis following partial hepatectomy. This stimulation in hepatocyte S-phase progression was associated with diminished protein expression and perinuclear localization of cyclin-dependent kinase (Cdk) inhibitor p27(Kip1) (p27) protein following partial hepatectomy. In contrast, old-aged mice infected with control virus displayed high hepatocyte levels of p27 protein, which had been localized to the nucleus prior to S-phase. Furthermore, we found that restoring FoxM1B expression did not influence p27 mRNA levels, and this new finding implicates FoxM1B in regulation of p27 protein levels. Likewise, AdFoxM1B-infected regenerating livers displayed elevated S-phase levels of Cdk2 kinase activity compared with old-aged mice infected with control virus. Furthermore, restoring FoxM1B expression in old-aged mice caused elevated levels of Cyclin B1, Cyclin B2, Cdc25B, Cdk1, and p55CDC mRNA as well as stimulating Cdc25B nuclear localization during liver regeneration, all of which are required for mitosis. These studies indicated that an acute delivery of the FoxM1B gene in old-aged mice is sufficient to re-establish proliferation of regenerating hepatocytes, suggesting that FoxM1B can be used for therapeutic intervention to alleviate the reduction in cellular proliferation observed in the elderly.
Transcriptional regulation of acetyl coenzyme A carboxylase gene expression by tumor necrosis factor in 30A-5 preadipocytes. (1989)

Acetyl coenzyme A (acetyl-CoA) carboxylase activity, amount, and mRNA levels increase during the differentiation of 30A-5 preadipocytes to adipocytes. Tumor necrosis factor (TNF) completely prevents this differentiation, with concomitant inhibition of acetyl-CoA carboxylase mRNA accumulation. To investigate the mechanisms by which TNF prevents acetyl-CoA carboxylase mRNA accumulation, we determined the effect of TNF on the transcription rate of the carboxylase gene and the half-life of carboxylase mRNA. Nuclear runoff transcription assays revealed no differences in the number of RNA polymerase molecules actively engaged in transcription of the acetyl-CoA carboxylase gene in preadipocytes, adipocytes, TNF-treated preadipocytes, or at any time during the course of differentiation. However, changes in adipsin, glycerophosphate dehydrogenase, and actin mRNAs, whose levels are also differentiation dependent, can be accounted for in part by changes in the number of polymerase complexes on their respective genes. To determine whether TNF caused a decrease in the stability of carboxylase RNA transcripts, we measured the rate of decay of prelabeled acetyl-CoA carboxylase mRNA. Control and TNF-treated cells showed no difference between the apparent half-lives of acetyl-CoA carboxylase mRNAs (9 h). However, the rate of acetyl-CoA carboxylase mRNA synthesis in vivo was decreased three- to fourfold in the presence of TNF. These data demonstrate that TNF prevents accumulation of acetyl-CoA carboxylase mRNA during preadipocyte differentiation by decreasing the rate of acetyl-CoA carboxylase gene transcription. However, transcriptional control is not due to a change in the number of RNA polymerase complexes actively engaged in carboxylase transcript elongation which could be measured by a number runoff assay. Instead, transcriptional control may be related to the rate at which RNA polymerase traverses the acetyl-CoA carboxylase gene.
Human Cell Culture, Vol. I, Cancer Cell Lines, Part 1 (1999)

Edited by JRW Masters and B Palsson Publication details, Kluwer Academic Publishers, Amsterdam, 1999
Sphingosine‐1‐phosphate induces proliferation and morphological changes of neural progenitor cells (2004)

Sphingosine-1-phosphate (S1P) is a lipid mediator that exerts multiple cellular functions through activation of G-protein-coupled receptors. Although the role of S1P on angiogenesis is well established, its role in neurogenesis is unknown. We examined the effects of S1P on G-protein activation in brain sections of rat embryo and on neural progenitor cells in culture. Intense S1P-stimulated [35S]GTPgammaS labeling was observed as early as E15 in the neuroepithelium and differentiating fields throughout the brain, suggesting that functional S1P receptors are expressed in brain areas with active neurogenesis. mRNA transcripts for several S1P receptor subtypes (S1P1, S1P2, S1P3 and S1P5) were expressed in neural progenitor cells prepared from embryonic rat hippocampus. S1P induced phosphorylation of extracellular signal-regulated kinase (ERK) and proliferation of neural progenitor cells as determined by BrdU incorporation in a pertussis toxin-sensitive manner. These effects were prevented by the ERK signaling inhibitor U0126. S1P augmented telomerase activity in neural progenitor cells with similar potency as that of FGF-2. Furthermore, S1P induced cell-cell aggregation. This morphological change was transient and prevented by Y-27632, an inhibitor of Rho-associated kinase. These results suggest that S1P plays a pleiotropic role in neurogenesis via pathways involving S1P receptors, MAP kinases and Rho kinase.
The National Market for Medicare Clinical Laboratory Testing: Implications for Payment Reform (2012)

Current Medicare payment policy for outpatient laboratory services is outdated. Future reforms, such as competitive bidding, should consider the characteristics of the laboratory market. To inform payment policy, we analyzed the structure of the national market for Medicare Part B clinical laboratory testing, using a 5-percent sample of 2006 Medicare claims data. The independent laboratory market is dominated by two firms--Quest Diagnostics and Laboratory Corporation of America. The hospital outreach market is not as concentrated as the independent laboratory market. Two subgroups of Medicare beneficiaries, those with end-stage renal disease and those residing in nursing homes, are each served in separate laboratory markets. Despite the concentrated independent laboratory market structure, national competitive bidding for non-patient laboratory tests could result in cost savings for Medicare.
Type Synthesis of 3-DOF Translational Parallel Manipulators Based on Screw Theory (2004)

A method is proposed for the type synthesis of 3-DOF (degree-of-freedom) translational parallel manipulators (TPMs) based on screw theory. The wrench systems of a translational parallel kinematic chain (TPKC) and its legs are first analyzed. A general procedure is then proposed for the type synthesis of TPMs. The type synthesis of legs for TPKCs, the type synthesis of TPKCs as well as the selection of actuated joints of TPMs are dealt with in sequence. An approach to derive the full-cycle mobility conditions for legs for TPKCs is proposed based on screw theory and the displacement analysis of serial kinematic chains undergoing small joint motions. In addition to the TPKCs proposed in the literature, TPKCs with inactive joints are synthesized. The phenomenon of dependent joint groups in a TPKC is revealed systematically. The validity condition of actuated joints of TPMs is also proposed. Finally, linear TPMs, which are TPMs whose forward displacement analysis can be performed by solving a set of linear equations, are also revealed.
Adaptive frequency-domain equalization and diversity combining for broadband wireless communications (1998)

We introduce a new kind of adaptive equalizer that operates in the spatial-frequency domain and uses either least mean square (LMS) or recursive least squares (RLS) adaptive processing. We simulate the equalizer's performance in an 8-Mb/s quaternary phase-shift keying (QPSK) link over a frequency-selective Rayleigh fading multipath channel with /spl sim/3 /spl mu/s RMS delay spread, corresponding to 60 symbols of dispersion. With the RLS algorithm and two diversity branches, our results show rapid convergence and channel tracking for a range of mobile speeds (up to /spl sim/100 mi/h). With a mobile speed of 40 mi/h, for example, the equalizer achieves an average bit error rate (BER) of 10/sup -4/ at a signal-to-noise ratio (SNR) of 15 dB, falling short of optimum linear receiver performance by about 4 dB. Moreover, it requires only /spl sim/50 complex operations per detected bit, i.e., /spl sim/400 M operations per second, which is close to achievable with state-of-the-art digital signal processing technology. An equivalent time-domain equalizer, if it converged at all, would require orders-of-magnitude more processing.