Miracle-dz/UniFAR-FTUs huggingface dataset:
Reactivation with a simple exposure to the experimental environment is sufficient to induce reconsolidation requiring protein synthesis in the hippocampal CA3 region in mice

Our understanding of the memory reconsolidation process is at an earlier stage than that of consolidation. For example, it is unclear if, as for memory consolidation, reconsolidation of a memory trace necessitates protein synthesis. In fact, conflicting results appear in the literature and this discrepancy may be due to differences in the experimental reactivation procedure. Here, we addressed the question of whether protein synthesis in the CA3 hippocampal region is crucial in memory consolidation and reconsolidation of allocentric knowledge after reactivation in different experimental conditions in the Morris water maze. We showed (1) that an injection of the protein synthesis inhibitor anisomycin in the CA3 region during consolidation or after a single reactivation trial disrupted performance and (2) that protein synthesis is required even after a simple contextual reactivation without any learning trial and independently of the presence of the reinforcement. This work demonstrates that a simple exposure to the spatial environment is sufficient to reactivate the memory trace, to make it labile, and that reconsolidation of this trace requires de novo protein synthesis. © 2007 Wiley‐Liss, Inc.
Quantification of Reverse Transcriptase Activity by Real-Time PCR as a Fast and Accurate Method for Titration of HIV, Lenti- and Retroviral Vectors

Quantification of retroviruses in cell culture supernatants and other biological preparations is required in a diverse spectrum of laboratories and applications. Methods based on antigen detection, such as p24 for HIV, or on genome detection are virus specific and sometimes suffer from a limited dynamic range of detection. In contrast, measurement of reverse transcriptase (RT) activity is a generic method which can be adapted for higher sensitivity using real-time PCR quantification (qPCR-based product-enhanced RT (PERT) assay). We present an evaluation of a modified SYBR Green I-based PERT assay (SG-PERT), using commercially available reagents such as MS2 RNA and ready-to-use qPCR mixes. This assay has a dynamic range of 7 logs, a sensitivity of 10 nU HIV-1 RT and outperforms p24 ELISA for HIV titer determination by lower inter-run variation, lower cost and higher linear range. The SG-PERT values correlate with transducing and infectious units in HIV-based viral vector and replication-competent HIV-1 preparations respectively. This assay can furthermore quantify Moloney Murine Leukemia Virus-derived vectors and can be performed on different instruments, such as Roche Lightcycler® 480 and Applied Biosystems ABI 7300. We consider this test to be an accurate, fast and relatively cheap method for retroviral quantification that is easily implemented for use in routine and research laboratories.
Heteroplasmy of mutant mitochondrial DNA A10398G and analysis of its prognostic value in non-small cell lung cancer

Mitochondrial dysfunction is associated with pathogenic mitochondrial (mt)DNA mutations. The majority of mtDNA point mutations have a heteroplasmic status, which is defined as the coexistence of wild-type and mutated DNA within a cell or tissue. Previous findings demonstrated that certain mtDNA heteroplasmic mutations contribute to widely spread chronic diseases, including cancer, and alterations in the heteroplasmy level are associated with the clinical phenotype and severity of cancer. In the present study, the proportions of mutant mtDNA 10398G were assessed using amplification-refractory mutation system-quantitative polymerase chain reaction (PCR) assay in 129 non-small cell lung cancer (NSCLC) tissue samples. Wild-type and mutant sequences were separately amplified using allele-specific primers and, subsequently, the PCR products containing the mtDNA 10398 site were ligated into vectors to construct a standard plasmid DNA construct. The association between mtDNA A10398G and the prognosis of patients was analyzed by survival analysis and Cox proportional hazards model. For the patient cohort, the median follow-up time and overall survival time were 20.6 and 26.3 months, respectively. The ratios of mutant heteroplasmy ranged between 0.31 and 97.04%. Patients with a high degree of mutant mtDNA 10398G had a significantly longer overall survival time compared with those with a low degree of mutant mtDNA 10398G (28.7 vs. 22.5 months, respectively; P<0.05). In addition, multivariate analysis demonstrated that epidermal growth factor receptor mutation status, tumor stage and the possession of a low degree of mutant 10398G were the three most independent prognostic factors. In conclusion, the present study suggests that, among NSCLC patients, there are large shifts in mutant mtDNA 10398G heteroplasmy and a low degree of mutant mtDNA 10398G heteroplasmy may be a marker of poor prognosis in patients with NSCLC.
Investigation of oral bioavailability and brain distribution of the Ind(8)‐Val conjugate of indinavir in rodents

Protease inhibitors are successfully used for the treatment of acquired immune deficiency syndrome (AIDS) although their biopharmaceutical characteristics are not optimal. Prodrugs have therefore been synthesized to increase protease inhibitor bioavailability and brain distribution. Among several compounds tested, a valine derivative of indinavir (Ind(8)‐Val) showed promising characteristics using an in‐vitro Caco‐2 cell model. The objective of this study was to further investigate this compound using in‐situ and in‐vivo approaches. The pharmacokinetics of indinavir (Ind) and Ind(8)‐Val were investigated in rats after intravenous and oral administration. Free indinavir resulting from in‐vivo hydrolysis of Ind(8)‐Val could not be detected in the plasma of rats receiving Ind(8)‐Val. Furthermore Ind(8)‐Val bioavailability was only 32% on average compared with 76% for indinavir, and effective permeability coefficients determined with a single‐pass intestinal perfusion method were close to 25 times 106 cms−1 for the two compounds. Brain‐to‐plasma concentration ratios in the post equilibrium phase after intravenous administration to mice were 9.7 ± 8.1% for indinavir and 2.5 ± 2.7% for Ind(8)‐Val. In conclusion, the promising biopharmaceutical characteristics of Ind(8)‐Val suggested from previous in‐vitro experiments with the Caco‐2 cell model were not confirmed by in‐situ and in‐vivo experiments.
Light activated antimicrobial agents can inactivate oral malodour causing bacteria

Oral malodour is a common condition which affects a large proportion of the population, resulting in social, emotional and psychological stress. Certain oral bacteria form a coating called a biofilm on the tongue dorsum and degrade organic compounds releasing volatile sulfur compounds that are malodourous. Current chemical treatments for oral malodour such as mouthwashes containing chlorhexidine or essential oils, are not sufficiently effective at reducing the bacterial load on the tongue. One potential alternative to current chemical treatments for oral malodour is the use of light activated antimicrobial agents (LAAAs), which display no toxicity or antimicrobial activity in the dark, but when exposed to light of a specific wavelength produce reactive oxygen species which induce damage to target cells in a process known as photodynamic inactivation. This study aimed to determine whether oral malodour causing bacteria were susceptible to lethal photosensitization. Five bacterial species that are causative agents of oral malodour were highly sensitive to lethal photosensitization and were efficiently killed by methylene blue in conjunction with 665 nm laser light. Between 4.5–5 log10 reductions in the number of viable bacteria were achieved with 20 µM methylene blue and 14.53 J cm−2 laser light for Porphyromonas gingivalis, Prevotella intermedia, Peptostreptococcus anaerobius and Solobacterium moorei. The number of viable cells fell below the limit of detection in the case of Fusobacterium nucleatum. These findings demonstrate that methylene blue in combination with 665 nm laser light is effective at killing bacteria associated with oral malodour, suggesting photodynamic therapy could be a viable treatment option for oral malodour.
Generating Explanatory Captions for Information Graphics

Graphical presentations can he used to communicate information in relational data sets suffciently and effectively However novel graphical presentations about numerous attributes and their relationships are often difficult to understand completely until explained Automatically generated graphical presenlations must therefore either be limited to simple conventional ones or risk incornprehensibility One way of alleviating this problem is to design graphical presentation systems that can work in conjunction with a natural language generator to produce explanatory captions This paper presents three strategies for generating explanatory captions to accompany information graphics based on (1) a representation of the structure of the graphical presentation (2) a framework for identifying the perceptual complexity of graphical elements and (3) the structure of the data expressed in the graphic We describe an implemented system and illustrate how it is used to generate explanatory captions for a range of graphics from a data set about real estate transactions in Pittsburgh.
Progesterone Synthesis in the Nervous System: Implications for Myelination and Myelin Repair

Progesterone is well known as a female reproductive hormone and in particular for its role in uterine receptivity, implantation, and the maintenance of pregnancy. However, neuroendocrine research over the past decades has established that progesterone has multiple functions beyond reproduction. Within the nervous system, its neuromodulatory and neuroprotective effects are much studied. Although progesterone has been shown to also promote myelin repair, its influence and that of other steroids on myelination and remyelination is relatively neglected. Reasons for this are that hormonal influences are still not considered as a central problem by most myelin biologists, and that neuroendocrinologists are not sufficiently concerned with the importance of myelin in neuron functions and viability. The effects of progesterone in the nervous system involve a variety of signaling mechanisms. The identification of the classical intracellular progesterone receptors as therapeutic targets for myelin repair suggests new health benefits for synthetic progestins, specifically designed for contraceptive use and hormone replacement therapies. There are also major advantages to use natural progesterone in neuroprotective and myelin repair strategies, because progesterone is converted to biologically active metabolites in nervous tissues and interacts with multiple target proteins. The delivery of progesterone however represents a challenge because of its first-pass metabolism in digestive tract and liver. Recently, the intranasal route of progesterone administration has received attention for easy and efficient targeting of the brain. Progesterone in the brain is derived from the steroidogenic endocrine glands or from local synthesis by neural cells. Stimulating the formation of endogenous progesterone is currently explored as an alternative strategy for neuroprotection, axonal regeneration, and myelin repair.
Placebo‐controlled evaluation of the irritant potential of tacalcitol (1α, 24‐dihydroxyvitamin D3) in healthy volunteers

In the treatment of psoriasis with topical vitamin D3 analogues, lesional and perilesional irritation is the main side‐effect. The aim of this study was to investigate whether local side‐effects generated by tacalcitol, a vitamin D3 analogue, show concentration dependence. 3 different concentrations of tacalcitol (0.4; 4; 40 μg/g ointment) and the vehicle were applied on normal skin of the back of 25 healthy volunteers under occlusive conditions for 5 days. Assessment of erythema, infiltration and scaling as well as measurement of transepidermal water loss (TEWL) was performed on days 1 to 5. On day 5, additional skin barrier tests (DMSO test, alkali resistance test) were performed. Erythema and slight infiltration, but no scaling, were observed in a number of subjects without significant differences. TEWL also did not show significant differences for the test formulations, though there was a tendency towards lower values in the untreated areas. In the skin barrier tests, a tendency towards higher alkali resistance in the test areas treated with 40 μg tacalcitol/g ointment was detected. Thus, under occlusive conditions, the irritant potential of tacalcitol is very low. There is no convincing evidence of concentration dependence in irritation generated by tacalcitol when applied under occlusive conditions.
Maltose Metabolism in the Hyperthermophilic Archaeon Thermococcus litoralis: Purification and Characterization of Key Enzymes

ABSTRACT Maltose metabolism was investigated in the hyperthermophilic archaeon Thermococcus litoralis. Maltose was degraded by the concerted action of 4-α-glucanotransferase and maltodextrin phosphorylase (MalP). The first enzyme produced glucose and a series of maltodextrins that could be acted upon by MalP when the chain length of glucose residues was equal or higher than four, to produce glucose-1-phosphate. Phosphoglucomutase activity was also detected inT. litoralis cell extracts. Glucose derived from the action of 4-α-glucanotransferase was subsequently metabolized via an Embden-Meyerhof pathway. The closely related organism Pyrococcus furiosus used a different metabolic strategy in which maltose was cleaved primarily by the action of an α-glucosidase, ap-nitrophenyl-α-d-glucopyranoside (PNPG)-hydrolyzing enzyme, producing glucose from maltose. A PNPG-hydrolyzing activity was also detected in T. litoralis, but maltose was not a substrate for this enzyme. The two key enzymes in the pathway for maltose catabolism in T. litoralis were purified to homogeneity and characterized; they were constitutively synthesized, although phosphorylase expression was twofold induced by maltodextrins or maltose. The gene encoding MalP was obtained by complementation in Escherichia coli and sequenced (calculated molecular mass, 96,622 Da). The enzyme purified from the organism had a specific activity for maltoheptaose, at the temperature for maximal activity (98°C), of 66 U/mg. AKm of 0.46 mM was determined with heptaose as the substrate at 60°C. The deduced amino acid sequence had a high degree of identity with that of the putative enzyme from the hyperthermophilic archaeon Pyrococcus horikoshii OT3 (66%) and with sequences of the enzymes from the hyperthermophilic bacteriumThermotoga maritima (60%) and Mycobacterium tuberculosis (31%) but not with that of the enzyme from E. coli (13%). The consensus binding site for pyridoxal 5′-phosphate is conserved in the T. litoralis enzyme.
Learning and the Disappearing Association Between Governance and Returns

During the period 1991-1999, stock returns were correlated with the G-Index based on twenty-four governance provisions (Gompers, Ishii, and Metrick (2003)) and the E-Index based on the six provisions that matter most (Bebchuk, Cohen, and Ferrell (2009)). This correlation, however, did not persist during the subsequent period 2000-2008. We provide evidence that both the identified correlation and its subsequent disappearance were due to market participants’ gradually learning to appreciate the difference between firms scoring well and poorly on the governance indices. Consistent with the learning hypothesis, we find that:(i) The disappearance of the governance-return correlation was associated with an increase in the attention to governance by a wide range of market participants; (ii) Until the beginning of the 2000s, but not subsequently, stock market reactions to earning announcements reflected the market’s being more positively surprised by the earning announcements of good-governance firms than by those of poor-governance firms; (iii) Stock analysts were also more positively surprised by the earning announcements of good-governance firms than by those of poor-governance firms until the beginning of the 2000s but not afterwards; (iv) While the G-Index and E-Index could no longer generate abnormal returns in the 2000s, their negative association with Tobin’s Q and operating performance persisted; and(v) The existence and subsequent disappearance of the governance-return correlation cannot be fully explained by additional common risk factors suggested in the literature for augmenting the Fame-French-Carhart four-factor model. ___________________________________Gompers, Ishii, and Metrick (2003) is available on SSRN at:http://ssrn.com/abstract=278920Bebchuk, Cohen, and Ferrell (2009) is available on SSRN at:http://ssrn.com/abstract=593423
Neuro-fuzzy extraction of angular information from muscle afferents for ankle control during standing in paraplegic subjects: an animal model

This paper is part of a project whose aim is the implementation of closed-loop control of ankle angular position during functional electrical stimulation (FES) assisted standing in paraplegic subjects using natural sensory information. Here, a neural fuzzy (NF) model is implemented to extract angular position information from the electroneurographic signals recorded from muscle afferents using cuff electrodes in an animal model. The NF model, named dynamic nonsingleton fuzzy logic system is a Mamdani-like fuzzy system, implemented in the framework of recurrent neural networks. The fuzzification procedure implemented was the nonsingleton technique which has been shown in previous works to be able to take into account the uncertainty in the data. The proposed algorithm was tested in different situations and was able to predict reasonably well the ankle angular trajectories especially for small excursions (as during standing) and when the stimulation sites are far from the registration sites. This suggests it may be possible to use activity from muscle afferents recorded with cuff electrodes for FES closed-loop control of ankle position during quiet standing.
The combined epidermal growth factor‐like modules of Plasmodium yoelii Merozoite Surface Protein‐1 are required for a protective immune response to the parasite

We have reported previously that immunization with a bacterial recombinant protein containing the two epidermal growth factor (EGF)‐like modules of Plasmodium yoelii Merozoite Surface Protein‐1 (MSP‐1) protected miced against challenge with this malaria parasite. Bacterial plasmids containing sequences coding for the individual modules fused to glutathione S‐transferase (GST) have now been made. The fusion protein containing the combined EGF‐like modules was recognized by anti‐parasite antibodies and was immunogenic, producing high litre anti‐parasite and anti‐GST antibodies. In contrast, fusion proteins containing the two individual EGF‐like modules reacted poorly with the natural antibodies and their proteins, as well as a simple mixture of them, induced low levels of anti‐parasite antibodies despite producing high levels of anti‐GST antibody. Antibodies raised to the recombinant proteins recognized the 230 kDa MSP‐1. Groups of mice immunized with the different recombinant proteins were challenged with parasites: protection was observed in the group which had received the recombinant protein containing both modules but not in those groups immunized with the individual modules, either alone or as a mixture. These results suggest that there are important structural determinants formed by the two modules together, which are not present in either of the individual domains alone, and which are responsible for the immunogenicity of the protein or are the target of protective antibodies.
Effect of plasma treatment on mechanical properties of jute fiber/poly (lactic acid) biodegradable composites

Surface treatment of natural fibers is one of the important methods to improve the mechanical properties of the composite material. In this paper, plasma treatment (PT) for various exposure timings (30, 60, 90, and 120 s) was performed to study the mechanical properties of jute fiber and its composites using poly (lactic acid) (PLA) as the matrix. The results were compared with alkali (AT) and plasma treated (PT) fiber composites. Bundle fiber test was carried out for untreated, AT, and PT jute fiber composites. PT fiber composites showed superior properties compared to other treatments. Micro-droplet test results showed that the interfacial shear strength (IFSS) of PT fiber composite is higher than that of AT fiber composites. Mechanical properties and hardness were increased on subjecting the fiber to plasma treatment. Tensile strength, young’s modulus and flexural strength were increased in an order of 28, 17, and 20%, respectively, for plasma polymerized jute fiber composites. Moreover, plasma polymerization leads to increase (>20%) in the flexural strength than untreated fiber composites. It is inferred that plasma treatment improves the interfacial adhesion between the jute fiber and PLA. These results were also confirmed by scanning electron microscopy observations of the fractured surfaces of the composites. Overall, plasma polymerization is an effective and eco-friendly method for the surface modification of the lingo cellulosic fiber to increase the compatibility between the matrix (hydrophobic) and fiber (hydrophilic).
Aggregated LDL and lipid dispersions induce lysosomal cholesteryl ester accumulation in macrophage foam cells Published, JLR Papers in Press, July 16, 2005. DOI 10.1194/jlr.M500059-JLR200

Macrophage foam cells in atherosclerotic lesions accumulate substantial cholesterol stores within large, swollen lysosomes. Previous studies with mildly oxidized low density lipoprotein (OxLDL)-treated THP-1 macrophages suggest an initial buildup of free cholesterol (FC), followed by an inhibition of lysosomal cholesteryl ester (CE) hydrolysis and a subsequent lysosomal accumulation of unhydrolyzed lipoprotein CE. We examined whether other potential sources of cholesterol found within atherosclerotic lesions could also induce similar lysosomal accumulation. Biochemical analysis combined with microscopic analysis showed that treatment of THP-1 macrophages with aggregated low density lipoprotein (AggLDL) or CE-rich lipid dispersions (DISP) produced a similar lysosomal accumulation of both FC and CE. Cotreatment with an ACAT inhibitor, CP113,818, confirmed that the CE accumulation was primarily the result of the inhibition of lysosomal CE hydrolysis. The rate of unhydrolyzed CE buildup was more rapid with DISP than with AggLDL. However, with both treatments, FC appeared to accumulate in lysosomes before the inhibition in hydrolysis and CE accumulation, a sequence shared with mildly OxLDL. Thus, lysosomal accumulation of FC and CE can be attributable to more general mechanisms than just the inhibition of hydrolysis by oxidized lipids.