Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of Protein Kinase A and Protein Kinase C Phosphorylation of the N-Methyl-D-aspartate Receptor NR1 Subunit Using Phosphorylation Site-specific Antibodies*

Modulation of N-methyl-D-aspartate receptors in the brain by protein phosphorylation may play a central role in the regulation of synaptic plasticity. To examine the phosphorylation of the NR1 subunit of N-methyl-D-aspartate receptors in situ, we have generated several polyclonal antibodies that recognize the NR1 subunit only when specific serine residues are phosphorylated. Using these antibodies, we demonstrate that protein kinase C (PKC) phosphorylates serine residues 890 and 896 and cAMP-dependent protein kinase (PKA) phosphorylates serine residue 897 of the NR1 subunit. Activation of PKC and PKA together lead to the simultaneous phosphorylation of neighboring serine residues 896 and 897. Phosphorylation of serine 890 by PKC results in the dispersion of surface-associated clusters of the NR1 subunit expressed in fibroblasts, while phosphorylation of serine 896 and 897 has no effect on the subcellular distribution of NR1. The PKC-induced redistribution of the NR1 subunit in cells occurs within minutes of serine 890 phosphorylation and reverses upon dephosphorylation. These results demonstrate that PKA and PKC phosphorylate distinct residues within a small region of the NR1 subunit and differentially affect the subcellular distribution of the NR1 subunit.
A novel plant toxin, persin, with in vivo activity in the mammary gland, induces Bim-dependent apoptosis in human breast cancer cells

Phytochemicals have provided an abundant and effective source of therapeutics for the treatment of cancer. Here we describe the characterization of a novel plant toxin, persin, with in vivo activity in the mammary gland and a p53-, estrogen receptor–, and Bcl-2-independent mode of action. Persin was previously identified from avocado leaves as the toxic principle responsible for mammary gland–specific necrosis and apoptosis in lactating livestock. Here we used a lactating mouse model to confirm that persin has a similar cytotoxicity for the lactating mammary epithelium. Further in vitro studies in a panel of human breast cancer cell lines show that persin selectively induces a G2-M cell cycle arrest and caspase-dependent apoptosis in sensitive cells. The latter is dependent on expression of the BH3-only protein Bim. Bim is a sensor of cytoskeletal integrity, and there is evidence that persin acts as a microtubule-stabilizing agent. Due to the unique structure of the compound, persin could represent a novel class of microtubule-targeting agent with potential specificity for breast cancers. [Mol Cancer Ther 2006;5(9):2300–9]
Non-invasive Brain Stimulation and Auditory Verbal Hallucinations: New Techniques and Future Directions

Auditory verbal hallucinations (AVHs) are the experience of hearing a voice in the absence of any speaker. Results from recent attempts to treat AVHs with neurostimulation (rTMS or tDCS) to the left temporoparietal junction have not been conclusive, but suggest that it may be a promising treatment option for some individuals. Some evidence suggests that the therapeutic effect of neurostimulation on AVHs may result from modulation of cortical areas involved in the ability to monitor the source of self-generated information. Here, we provide a brief overview of cognitive models and neurostimulation paradigms associated with treatment of AVHs, and discuss techniques that could be explored in the future to improve the efficacy of treatment, including alternating current and random noise stimulation. Technical issues surrounding the use of neurostimulation as a treatment option are discussed (including methods to localize the targeted cortical area, and the state-dependent effects of brain stimulation), as are issues surrounding the acceptability of neurostimulation for adolescent populations and individuals who experience qualitatively different types of AVH.
Frontline: Induction of apoptosis and modulation of c‐FLIPL and p53 in immature dendritic cells infected with herpes simplex virus

Herpes simplex virus (HSV) can perturb the function of dendritic cells (DC). The underlying mechanisms are not defined. In the present study we demonstrate that HSV induces a substantial number of immature DC to undergo apoptosis by a mechanism involving caspase‐8. We found strongly enhanced expression of TNF‐α and TRAIL but not CD95 ligand after HSV infection. Blocking experiments suggested that these classical death ligands contribute to HSV‐induced cell death of immature DC. Because uninfected DC are resistant to the apoptosis‐inducing effect of death ligands we searched fora viral "competence‐to‐die" signal. Further analysis revealed that HSV‐infected immature DC down‐regulate long cellular FLICE‐inhibitory protein (c‐FLIPL) and up‐regulate p53 whereas otherapoptosis‐regulating proteins (e.g. Bcl‐2, RIP, FADD) were not affected. Down‐regulation of c‐FLIPL was not due to diminished gene transcription or reduced mRNA stability because the level of c‐FLIPL mRNA was rather increased. Moreover, down‐regulation of c–FLIPL could not be blocked by the anti‐herpetic drug acyclovir. Finally, the underlying mechanism was also operative in human umbilical vein endothelial cells, which show a similar susceptibility to HSV infection and strength of c‐FLIPL expression. These results suggest that HSV targets c‐FLIPL protein in immature DC and other infectable cells to disrupt their function.
Probabilistic Generation of Random Networks Taking into Account Information on Motifs Occurrence

Because of the huge number of graphs possible even with a small number of nodes, inference on network structure is known to be a challenging problem. Generating large random directed graphs with prescribed probabilities of occurrences of some meaningful patterns (motifs) is also difficult. We show how to generate such random graphs according to a formal probabilistic representation, using fast Markov chain Monte Carlo methods to sample them. As an illustration, we generate realistic graphs with several hundred nodes mimicking a gene transcription interaction network in Escherichia coli.
Weighted Norms of Ambiguity Functions and Wigner Distributions

In this article new bounds on weighted p-norms of ambiguity functions and Wigner functions are derived. Such norms occur frequently in several areas of physics and engineering. In pulse optimization for Weyl-Heisenberg signaling in wide-sense stationary uncorrelated scattering channels for example it is a key step to find the optimal waveforms for a given scattering statistics which is a problem also well known in radar and sonar waveform optimizations. The same situation arises in quantum information processing and optical communication when optimizing pure quantum states for communicating in bosonic quantum channels, i.e. find optimal channel input states maximizing the pure state channel fidelity. Due to the non-convex nature of this problem the optimum and the maximizers itself are in general difficult find, numerically and analytically. Therefore upper bounds on the achievable performance are important which will be provided by this contribution. Based on a result due to E. Lieb, the main theorem status a new upper bound which is independent of the waveforms and becomes tight only for Gaussian weights and waveforms. A discussion of this particular important case, which tighten recent results on Gaussian quantum fidelity and coherent states, will be given. Another bound is presented for the case where scattering is determined only by some arbitrary region in phase space
Haemophilus influenzae and oxidative stress

Haemophilus influenzae is a commensal of the human upper respiratory tract. H. influenzae can, however, move out of its commensal niche and cause multiple respiratory tract diseases. Such diseases include otitis media in young children, as well as exacerbations of chronic obstructive pulmonary disease (COPD), sinusitis, conjunctivitis, and bronchitis. During the course of colonization and infection, H. influenzae must withstand oxidative stress generated by multiple reactive oxygen species produced endogenously, by other co-pathogens and by host cells. H. influenzae has, therefore, evolved multiple mechanisms that protect the cell against oxygen-generated stresses. In this review, we will describe these systems relative to the well-described systems in Escherichia coli. Moreover, we will compare how H. influenzae combats the effect of oxidative stress as a necessary phenotype for its roles as both a successful commensal and pathogen.
Utilizing doctors' attitudes toward staff training to inform a chiropractic technology curriculum.

OBJECTIVE The purpose of this study is to determine attitudes of doctors of chiropractic regarding the importance of staff training in specific skill areas to inform the curriculum management process of a chiropractic technology program. METHODS A survey was distributed to registrants of a chiropractic homecoming event. On a 5-point Likert scale, respondents were asked to rate the degree of importance that staff members be trained in specific skills. Descriptive statistics were derived, and a 1-way analysis of variance (ANOVA) was used to test differences between groups based on years in practice and level of staff training. RESULTS Doctors place a high level of importance on oral communication skills and low importance on nutrition and physical examinations. Comparing groups based on years in practice revealed differences in the areas of passive physiotherapies (F = 3.61, p = .015), legal issues/regulations (F = 3.01, p = .032), occupational safety and health regulation (F = 4.27, p = .006), and marketing (F = 2.67, p = .049). Comparing groups based on level of staff training revealed differences in the areas of occupational safety and health regulations (F = 4.56, p = .005) and cardiopulmonary resuscitation (F = 4.91, p = .003). CONCLUSION With regard to their assistants, doctors of chiropractic tend to place high importance on office skills requiring effective communication and place less importance on clinical skills such as physical examinations and physiotherapy.
Multi-modality: a new approach for the treatment of major depressive disorder

Effective treatment with antidepressants is currently limited by factors that affect treatment compliance, including delay in onset of therapeutic effects and intolerable side-effects. Recent data suggest that use of antidepressant combinations with different mechanisms of action may be a better first-line strategy prior to augmentation with other drug classes. The rationale for this approach is that combining multiple pharmacological actions affecting multiple monoamine targets produces greater efficacy. Several new multi-modal compounds are in development and early results for the most advanced agents indicate shorter onset of therapeutic effects and improved tolerability. By modulating multiple receptors and transmitter systems, it is hoped that these new agents may also treat some of the associated symptoms of major depressive disorder, such as anxiety and cognitive dysfunction.
Towards Reproducible Descriptions of Neuronal Network Models

Progress in science depends on the effective exchange of ideas among scientists. New ideas can be assessed and criticized in a meaningful manner only if they are formulated precisely. This applies to simulation studies as well as to experiments and theories. But after more than 50 years of neuronal network simulations, we still lack a clear and common understanding of the role of computational models in neuroscience as well as established practices for describing network models in publications. This hinders the critical evaluation of network models as well as their re-use. We analyze here 14 research papers proposing neuronal network models of different complexity and find widely varying approaches to model descriptions, with regard to both the means of description and the ordering and placement of material. We further observe great variation in the graphical representation of networks and the notation used in equations. Based on our observations, we propose a good model description practice, composed of guidelines for the organization of publications, a checklist for model descriptions, templates for tables presenting model structure, and guidelines for diagrams of networks. The main purpose of this good practice is to trigger a debate about the communication of neuronal network models in a manner comprehensible to humans, as opposed to machine-readable model description languages. We believe that the good model description practice proposed here, together with a number of other recent initiatives on data-, model-, and software-sharing, may lead to a deeper and more fruitful exchange of ideas among computational neuroscientists in years to come. We further hope that work on standardized ways of describing—and thinking about—complex neuronal networks will lead the scientific community to a clearer understanding of high-level concepts in network dynamics, and will thus lead to deeper insights into the function of the brain.
EFFECTS OF CALCIUM-CONTAINING FIXATION SOLUTIONS ON CHOLINERGIC SYNAPTIC VESICLES

Calcium (Ca)-containing fixation solutions applied to slices of electric organ of the electric ray, Narcine brasiliensis, have been shown to have three distinct ultrastructural effects on cholinergic synaptic vesicles of the nerve terminals. (a) An electron-dense particle (EDS) is observed within the vesicle; the particle is seen in unosmicated, unstained tissues and can be removed from thin sections by Ca-chelating agents. It is concluded that the EDS represents Ca bound by the vesicle. It is suggested that the bound ATP of the vesicle provides anionic Ca binding sites. (b) The vesicle membrane tends to ‘crinkle’ or collapse depending on the concentration of the other components of the fixative solution. The ‘crinkling’ or collapse are largely reversed by a wash step in the absence of Ca. (c) The presence of Ca results in the appearance of a population of vesicles which form characteristic fusions or ‘tight’ junctions with the terminal membrane. This appears to be morphological evidence for the proposal, which has been frequently put forward, that Ca facilitates such a fusion before discharge of vesicle-bound transmitter. With the discovery that the use of Ca-containing fixatives leads to the demonstration of a subpopulation of synaptic vesicles fused to the terminal membrane, we are led to propose that this is the ultrastructural location of the newly synthesized acetylcholine which has been shown by others to be preferentially released by stimulation.
Effects of Zofenopril on Cardiac Sarcoplasmic Reticulum Calcium Handling

Isolated rat hearts were perfused for 120 minutes in the presence or in the absence of 10 μM zofenoprilat, the active metabolite of zofenopril. At the end of perfusion, cardiac tissue was used to assay sarcoplasmic reticulum (SR) 45Ca uptake and SR calcium release, which was determined by automatized quick filtration technique after SR vesicle loading with 45Ca. The expression of genes involved in the control of calcium homeostasis was evaluated by polymerase chain reaction after reverse transcription. In chronic experiments, SR 45Ca uptake and gene expression were measured in hearts derived from rats treated with 15 mg·kg−1·day−1 zofenopril for 15 days. Acute or chronic zofenopril administration did not produce any change in contractile performance. In acute experiments, SR 45Ca uptake was significantly increased after exposure to zofenoprilat. The rate constant of calcium-induced calcium release was slightly although not significantly higher, and the calcium leak measured under conditions promoting SR channel closure was significantly increased. In the chronic model, significant increase in the rate of SR 45Ca uptake was confirmed. Gene expression was not modified, except for decreased phospholamban expression, which is observed in the acute but not in the chronic model. In conclusion, zofenopril increases SR calcium cycling and stimulates active calcium uptake into the SR.
Modular thinking: evolving modular neural networks for visual guidance of agents

This paper investigates whether replacing non-modular artificial neural network brains of visual agents with modular brains improves their ability to solve difficult tasks, specifically, survive in a changing environment. A set of experiments was conducted and confirmed that agents with modular brains are in fact better. Further analysis of the evolved modules characterised their function and determined their mechanism of operation. The results indicate that the greater survival ability is obtained due to functional specialisation of the evolved modules; good agents do well because their modules are more specialised at tasks such as reproduction and consumption. Overall, the more specialised the modules, the fitter the agents.
EXPERIMENTAL APPLICATION OF THE ITERATIVE LEARNING CONTROL TO THE TEMPERATURE CONTROL OF BATCH REACTOR

Abstract A learning control solution to the problem of finding a finite-time optimal control history that minimizes a quadratic cost is presented. Learning is achieved without requiring a detailed knowledge of the system, which may be affected by unknown but repetitive disturbances. The objective of this work is considered as a validation of the results obtained in (Mezghani, et al. , 2001). It focuses on the temperature control of a semi-batch chemical reactor used for fine chemicals production. Such reactor is equipped with a heating/cooling system composed of different thermal fluids. With less modelling investigation, a feedback-feedforward control structure is proposed for ensuring the tracking performance of the desired temperature profile. Such strategy is derived from the family of the Iterative Learning Control named Batch Model Predictive Control ( BMPC ). The synthesis of the considered strategy is studied and improvements of the algorithm features are proposed. A robust supervisory control procedure is employed to choose the right fluid and to reduce the superfluous fluid changeovers. Experimental results are presented to illustrate the practical appeal and effectiveness of the proposed scheme.
Further delineation of the immunoarchitecture of the human spleen.

Using a battery of monoclonal antibodies directed at B and T cell antigens, we delineate the immunotopography of the human spleen. The tissue section immunohistochemical methods employed demonstrate the complexity of white pulp reactivity with both light and heavy chain immunoglobulin expression appearing polyclonal. Zonal expression of heavy chains suggests an anatomic basis for the known sequence of heavy chain switching due to immunoglobulin gene rearrangement. Localization of universal B-cell antigen, B1, delineates the entire B-cell zone whereas antibodies directed at universal T antigens (e.g. Leu 1, 4, 9) delineate the T cell zone. Leu 14 demonstrates striking B-zone staining in normal spleen and in hairy cell leukemia, suggesting that leukemic cells in this disease arise from Leu 14+ B cells. Leu 2a staining occurs not only on lymphoid cells but probably also on sinusoidal endothelial lining cells.
Patients with giant cell arteritis have a lower prevalence of diabetes mellitus: A systematic review and meta-analysis

Abstract Objective: The aim of this study is to compare the prevalence of diabetes mellitus (DM) in patients who are recently diagnosed with giant cell arteritis (GCA) with age- and sex-matched controls. Methods: We conducted a systematic review and meta-analysis of observational studies that (1) consisted of GCA cohort and non-GCA cohort that was randomly selected from the same population and (2) provided prevalences of DM at the time of diagnosis for patients with GCA and at the index date for controls. Pooled odds ratios and 95% confidence intervals (CIs) were calculated using a random-effect, Mantel–Haenszel analysis. Results: Five studies with 903 patients with GCA and 1064 controls were identified and included in our data analysis. We demonstrated a statistically significant lower prevalence of DM among patients with GCA with the pooled OR of 0.74 (95% CI, 0.57–0.97). Conclusion: At diagnosis, patients with GCA had a lower prevalence of DM. Whether DM could be a protective factor against the development of GCA needs further investigations.
Doing-being-becoming: occupational experiences of persons with life-threatening illnesses.

OBJECTIVE Life-threatening illness profoundly affects people's occupational functioning, yet continuing occupational engagement seems vital to their well-being. This qualitative study used a doing-being-becoming framework to explore the place of occupation in human lives threatened by illness. METHOD The experiences of 13 male and 10 female day hospice participants were investigated through a combination of focus groups, individual interviews, and participant observation. These data were interpreted by a process of constant comparison, coding, and theme building. RESULTS Experiences of doing were evident in accounts of losing and maintaining valued occupations and striving to preserve physical and mental functioning. A sense of being through occupational engagement arose in social relationships and self-exploration that enhanced feelings of self-worth. Occupation promoted the experience of becoming by providing fresh learning opportunities and a sense of contributing to others' welfare. CONCLUSION The data offer new insights into the potential benefits of occupational engagement for persons dealing with life-threatening illnesses. Use of the doing-being-becoming framework enriched analysis of these data, which, in turn, have contributed to the understanding of the framework's theoretical concepts.
CHRONIC OBSTRUCTIVE PULMONARY DISEASE Sputum eosinophilia and the short term response to inhaled mometasone in chronic obstructive pulmonary disease

Background: An association between the sputum eosinophil count and the response to a 2 week course of prednisolone has previously been reported in patients with chronic obstructive pulmonary disease (COPD). Whether the response to inhaled corticosteroids is related to the presence of eosinophilic inflammation is unclear. Methods: A randomised, double blind, crossover trial of placebo and mometasone furoate (800 mg/day), each given for 6 weeks with a 4 week washout period, was performed in subjects with COPD treated with bronchodilator therapy only. Spirometric tests, symptom scores, chronic respiratory disease questionnaire (CRQ), and induced sputum were performed before and after each treatment phase. Results: Ninety five patients were recruited of which 60 were randomised. Overall there were no treatment associated changes in forced expiratory volume in 1 second (FEV1), total CRQ, or sputum characteristics. After stratification into tertiles by baseline eosinophil count, the net improvement in post-bronchodilator FEV1 increased with mometasone compared with placebo progressively from the least to the most eosinophilic tertile. The mean change in post-bronchodilator FEV1 with mometasone compared with placebo in the highest tertile was 0.11 l (95% CI 0.03 to 0.19). This improvement was not associated with a fall in the sputum eosinophil count. Conclusions: An increased sputum eosinophil count is related to an improvement in post-bronchodilator FEV1 following treatment with inhaled mometasone in COPD, but the improvement is not associated with a reduction in the sputum eosinophil count.