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  • What are the main targets to address potential molecules to control Alzheimer´s Disease?
    Tau oligomers and aggregates have been shown to be the major target, on the basis of our neuroimmunomodulation theory of Alzheimer´s pathogenesis.
    Constantine Kaniklidis · No Surrender Breast Cancer Foundation (NSBCF)
    Outside of the usual and well-studied suspects, the following represent some of the molecular pathways for which we have some plausible preclinical data rising to the in vivo level, several (as I note) also with positive human clinical data. Therefore the list is not meant to be exhaustive, but suggestive based on recent review and critical appraisal of the field to date. 1. β-secretase (also named β-site APP cleaving enzyme, BACE1) inhibition. 2. γ-secretase Inhibition/Modulation. 3. α-secretase Activation/Modulation. 4. M1 Muscarinic Agonists Targeting (given their important role in linkage of three major hallmarks of AD: Aβ peptide; tau hyperphosphorylation and loss of cholinergic function conductive to cognitive impairments, with good RCT data on talsaclidine) 5. Aβ-aggregationInhibition (although trial data to date has been relatively disappointing). Aβ-degrading enzymes (the most promising based on preclinical data being the HDAC inhibitor valproic acid (VPA)) 6. Apolipoprotein E (ApoE)-directed therapeutics (which can decrease brain Aβ level and have disease-modifying potentials in AD prevention; example would be bexarotene, an ApoE activator.) 7. Inhibition of RAGE (receptor for advanced glycation end products) and/or activation of LRP-1 (lipoprotein receptor-related protein-1), via influencing blood–brain barrier transport. 8. Metal Chelation (example: a phase II clinical trial of clioquinol, a metal-protein-attenuating compound inhibiting zinc and copper ions from binding to Aβ found improved cognitive function and decreased plasma Aβ42 level; plausible positive RCT on clioquinol). 9. HMG-CoA Reductase Inhibition (via statins, with inconsistent results to date although still promising). 10. MAO Inhibition (deprenyl and ladostigil are the most studied preclinically). 11. Nicotinic Cholinergic Stimulation (most promising results but challenging adverse event profiles). 12. Melatonin Modulation (promising preclinical results). 13. Omega-3 / DHA / docosa-hexaenoic acid Modulation (showing anti-amyloid, antioxidant, and neuroprotective mechanisms BUT so far only in a small group of patients with very mild AD). 14. Sirtuin Activation (via polyphenolic resveratrol in preclinical studies). 15. MicroRNA (miRNA) Inhibition (especially of miR-26b and mi-RNA034a) 16. Insulin Pathway Targeting (for example, intriguing human clinical data suggests that intranasal insulin enhances brain insulin signaling to improve memory and learning processes in both cognitively healthy and impaired humans). 17. Vitamin D Receptor Targeting (given that AD cases consistently have lower serum vitamin D concentrations than matched controls).
  • Hassan Tallal asked a question in CNS Pharmacology
    What is the role of dopamine in releasing arachidonic acid?
    Dopamine and arachidonic
  • Satya Sharma added an answer in Epigenetics
    Why is mtDNA particularly susceptible to mutation?
    Can anybody please explain to me why mitochondrial DNA is particularly susceptible to mutation? I know that in the most organisms mtDNA lacks intron and repetitive DNA. Can anybody explain further? Thanks in advance.
    Satya Sharma · Pondicherry University
    Very True Michael. There is a combination of contributing factor. I think Reyhaneh is looking for something specific. It will be nice if you present your possible reason. May be me and Michael can be of more help then....
  • R package for using circuit theory to model ecological patch connectivity?
    I am currently looking into circuit theory resistance modelling (http://goo.gl/fPOSVw) as an alternative to least-cost path approaches for modelling ecological connectivity throughout a major surface water network in Australia. The Circuitscape (http://www.circuitscape.org/) software package seems to do everything I would like to do, but ideally I would prefer to conduct my analyses completely within the R environment. The "commuteDistance" function within the "gdistance" R package (http://cran.r-project.org/web/packages/gdistance/) comes close, but seems to only support resistance modelling between points/nodes, rather than two-dimensional patches/polygons as is possible in Circuitscape. Is anyone aware of an R package which allows for circuit theory resistance distance modelling between patches, or an alternative approach I could use to achieve similar results?
    William Peterman · University of Illinois, Urbana-Champaign
    I'm away from my work computer until Tuesday, but if you want to dig into a roughly built R package, here is a link to my GitHub project: https://github.com/wpeterman/ResistanceOptimization And the paper that describes its use: https://www.researchgate.net/publication/261477066_Ecological_resistance_surfaces_predict_fine_scale_genetic_differentiation_in_a_terrestrial_woodland_salamander?ev=prf_pub In the package there are functions to write .ini files, call Circuitscape, and import results back into R. I can pass along the relevant components next week if I get a better idea of what you're looking for.
  • Why cosmids can carry larger DNA segments than plasmids?
    People often says that plasmids become unstable if you use them to clone long DNA fragments (over 20 kb), and that for this purpose is better to use cosmids (can carry DNA fragments up to 50 kb). However, as far as I know the only difference between both vectors is the presence of cos sites in the latter, and that those cos sites are important for DNA packaging into viral particles (not involved in vector replication). Considering that, how can we explain that cosmids remain stable with larger DNA segments?. To bring up an example, pHC79 is a cosmid derived from pBR322 plasmid (they are exactly the same except for the presence of lambda cos sites). pHC79 has been successfully used to clone DNA segments up to 50 kb. The question is... can we expect that pBR322 works as well as pHC79?
    Zoia Stoytcheva · University of Hawai'i System
    BAC clones are up to 50-300kb versus regular plasmids ~20kb. Usually BACs are single copy per cell which allows for better propagation. Imagine the cell that have "multy copy BAC" it is a burden to propagate .......that is only one side of why BACs are more stable... and in some applications preferable than YAC....
  • Nelson Elias added an answer in Music Psychology
    Why does music evoke emotions or feelings?
    Music has many bodily effects. This is not trivial.
    Nelson Elias · Rio de Janeiro State University
    Dear Wilfried Emotion is a set of chemical and neural responses forming a different pattern than usual. These answers are produced when the normal brain receives a stimulus that "break" this "balance", triggering the emotion. Feelings are unique to humans, we can consider them an evolution of emotions. The feeling necessarily presupposes a judgment on a set of self perceptions and feeling this sense resembles a type of metacognition, but in essence, feelings are ideas. Feelings are more aware that emotion. It is important to note that emotions and feelings interact, emotions give rise to feelings, however, a negative feeling generates more negative emotions Music is the universal language . It touches those who listen and runs away from everything we can rationalize . It penetrates our senses and alters our perception magically! .The ability to perceive the ' soul' of the composer in every note or verse takes us to the world of sensations . A music is an act of love into words and sounds !
  • Susan MIchelle Close added an answer in Graffiti
    What is a good city to research contemporary street art & how can street art be integrated to allow for culture to be expressed?
    Many cities in the world have regulations of some sort that ban a number of cultural activities that 'vandalise' the city. However, in places like Melbourne, there are many alleyways filled with graffiti that celebrates the culture of the people. This intrigues me, and pushes my interest to find a way to allow for activities such as street art whilst preserving the streets and properties. So, how can street art be integrated with regulations to allow for this culture to be expressed in an acceptable manner, rather than being marked as 'vandalism'?
    Susan Close · University of Manitoba
    Consider Berlin, Melbourne or Sao Paulo.
  • What is a non-pure culture cell?
    Can it happen with continuous passage of pure cell culture ? Can the cell change its features?
    Francesco Roselli · Friedrich Miescher Institute for Biomedical Research
    I agree with blake. it is far too common to have one cell line contaminating another one, especially when they share the same medium. some time ago, a study on several cell lines showed that they were, actually, all hela cells!
  • Are patterns in human designs a mirror of patterns found in nature or are patterns in human designs somehow different from patterns found in nature?
    The word "pattern" in everyday parlance often means something typical that can be repeated, something characteristically capable of repetition into similar copies (Ulf Grenander, Elements of Pattern Theory, Johns Hopkins University Press, Baltimore, 1996, p. 94). For example, in nature one can observe myriads of patterns in plant leaves or in beehives or in branches of trees or in the honeycomb-like shapes in dragonfly wings. Again, for example, in nature definite patterns can be observed in the daily life of animals: waking at sunrise time, finding water, hunting for food, socializing, and going to sleep at sunset time. In each case, there are observable patterns. So then the question arises as to whether the patterns in human geometric designs simply reflect patterns found in nature. Or whether patterns in human designs are somehow different in noticeable ways. For an example of a human geometric pattern, consider a pattern in a Penrose tiling. A penrose tiling (inspired by Roger Penrose) is a non-periodic tiling generated by an aperiodic set of prototiles. For a sample Penrose tiling, see the attached image. A Penrose pattern is self-similar, so the same patterns are repeated in larger and larger scales. Such patterns, introduced by the British physicist and cosmologist, are examples of periodic tilings. M.C. Escher, the Dutch artist, is famous for pictures of periodic tilings with shapes that resemble living things.
    Mohammad Ayaz Ahmad · University of Tabuk
    Dear all editors and followers of RG, Congratulations for the holy festival of Jesus Christ.
  • Can the spacetime metric evolve into an elliptic region?
    Einstein's equations are quasi-linear in nature, i.e. second order derivatives of the metric appear only linearly. If we assume that the metric has a Lorentzian signature, then the equations are said to be hyperbolic, i.e. they have a well-posed initial value problem. Nevertheless, it is well known that many quasi-linear systems admit signature transitions in their causal structures. This happens, for instance, in k-essence models, nonlinear electrodynamics, relativistic hydrodynamics and wave maps equations. According to GR, Is it possible that initial data which lead to local-in-time hyperbolic evolution evolve into some elliptic signature regime (++++) afterwards? Is there any theorem proving the opposite?
    Bernd Schmeikal · Vienna Institute for Social Science Documentation and Methodology
    Many thanks, dear Mohammad Ayaz!
  • What is equity in education?
    In one of my earlier questions, there seemed to be an issue with what constituted equity in education. What does it really mean? How do we make it happen? Is it desirable really? I am particularly interested in hidden forms of inequity, eg related to possibly: class in the UK, race in some countries, gender and certainly socioeconomic status in Australia.
    Mohammad Ayaz Ahmad · University of Tabuk
    Dear All Editors and followers of RG, Congratulations for the holy festival of Jesus Christ.
  • Louis Brassard added an answer in Exoplanets
    How significant is the discovery of Kepler-186f, an earth-sized habitable zone planet?
    Kepler-186f is the first earth-sized planet located in the habitable zone of another star that has been discovered. With this discovery, the search for life on other planets has entered into a new zone of discovery.
    Barry, In the future we may discover new physics allowing to tune in a cosmic internet. But just detecting a few hundred or a few thousand year old radio broadcast not even intended for us to detect would be an incredible rosetta stone on our future. Imagine the challenge of decoding this broadcast. I think that all old civilisations have to mature into stellar being and that here on earth are rapidly converging towards it. Most of cosmic communications are probably in between stellar beings converging towards meta stellar beings. Someone should write a good science fiction book on how meta stellar beings trying to converge at the universe level to become God.
  • Is there an alternative and/or complement to the (Alcoholics Anonymous) support system for the treatment of alcoholism?
    Alcoholism is a disease with a biochemical and/or molecular (genetic) basis.
  • Is the smear caused by concentrated DNA indicative of any real problems?
    I am digesting and concentrating DNA for transformation, but with my more concentrated samples, the agarose gel smears with what appear almost like bubbles at heavier weights. I want to know if this is an indication of other problems. I have attached a gel image of a series of digests using different plasmid loads in the same reaction volume, but loaded on the gel so that the same mass is in each lane. The first lane is undigested and the rest are 50 ul digests of 1, 3, 5, 10, and 20 ug of plasmid - 1 ug was loaded from each.
    Albino Bacolla · University of Texas at Austin
    As a general rule, 50 - 200 ng DNA per lane would give you a rather sharp band.
  • Can someone explain me should I consider spliced version of the gene to build the qPCR primers or unspliced version which has intron?
    I had ran a RNAseq with Brugia malayi worms treated with a drug and untreated. I found a certain number of genes differentially expressed in the treated worms as compared to the untreated. I selected one upregulated gene to conduct confirmatory qPCR. I have selected Actin to be my control for the study as its expression is unaltered. Can someone explain me should I consider spliced version of the gene to build the primers or unspliced version which has intron? The aim is to not amplify the background genomic DNA. Many literature articles say use exon-exon span to design primers. What does this exactly mean?
    Zoia Stoytcheva · University of Hawai'i System
    As mentioned above (Rodrigo Aguilar, Ajay Saini) your best choise would be intron-spanning primers to distinguish from gDNA
  • How would one go about testing the frequency of parallel development of ideas without having threats to validity?
    I've been considering doing this as my dissertation, but I'm stuck on the research part. Clearly, parallel development of ideas happens in a demonstrable way. The question would be if completely isolated from each other and given the same set of parameters, how frequently is it going to happen that people come up with the same solutions to the problems? And, subsequently, what factors may predict that? Every idea that I've come up with so far seems like it might have threats to validity.
    Johnathan Clayborn · Walden University
    Thank you, Catherine. You might have provided some of the insight that I was looking for. I was originally just considering this topic in a broad over-reaching philosophical/psychological context, i.e.: why does that happen? Your suggestion to narrow the focus to a specific group of people is well-receieved. Patent applications may just well provide the quantifiable measures that I would need to perform basic calculations on this. The patents alone probably woudn't contain enough information to perform a regression analysis for predictive variables, but it's certainly a place to start. Thank you.
  • Do I need a paired or an unpaired test for my cell culture experiments?
    With paired and unpaired I do not mean dependent (experiments done on the same day) vs. independent (experiments done on different days). For example: I cultivated one cell line with substance A, B alone and with the combination of A and B. I repeated this experiment several times on independent days and weeks. I measured the viability of the substance groups in % of the control. Now I want to compare A, B and the combination and want to test for difference. To keep it simple I want to use a nonparametric test. My statistical adviser is not completely sure if my samples are paired or unpaired. She tends to that cell culture experiments are in general paired. As her colleagues do not show a consistent opinion if cell culture experiments are paired or unpaired she advises me to use the test which the majority uses. Please help me! What do you use for similar cell culture experiments? If you need more details please ask me. Thank you in advance!
    Noel Artiles-Leon · University of Puerto Rico at Mayagüez
    Sandra, 1.) I did not pool (average) any data; the measurements were entered into the statistical package as shown in the table in the example (120 rows corresponding to 4 treatment combinations x 6 replicates x 5 days; in you case you have 6 days, so you will have 144 data points). 2.) We also may have some communication problems because we are in different fields and use the same terms to signify different things; in "my book": a) You have done ONE experiment b) That has TWO Factors (or independent variables): substance A and B. c) Each of these two factors is set at two levels (present or not present) d) When both factors are set to "not present", you call that experimental condition your "control" e) We think of independent measurements (I believe you have 144 of them), not of independent experiments. f) For your description of the experiment, I have no reason to believe that one measurement might somehow affect the other. Even measurements done within the same day. Consequently, I may assume that the measurements are independent. This assumption can be (and should be) corroborated with an analysis of residuals of your final model. g) Because - I believe - measurements within the same day are going to have less variability than measurements between days, my advise is to introduce the variable "day" as a blocking variable. This is a precaution; if in the analysis "day" is not significant, then you can drop it from the model. 3) If you include the interaction term in the ANOVA, you can, not only answer the questions "Are the single effects of the substances antagonized in the combined treatment?" and "If not is there an addition or synergism of the single effects?" but you can also quantify these effects. I did that in the example that I sent you. We were able to state: "With a confidence level of 95%, when Substances A and B are combined (in whatever fixed proportion you decided) the response decreases by between 1.99 and 3.43 units (with respect to the control – no substances A or B used)" ... so, with the dummy data, combining the substances had an antagonistic effect (assuming that you want your response to be as large as possible). Finally, a disclaimer: I am not a biologist and I have no idea of (a) what you are measuring or (b) how your measuring it or (c) what are "fluorescence units" :-)
  • Roberta Brooks added an answer in Aphasia
    I would like to adapt child-language-therapy for adults with aphasia. Does anyone have literature or references?
    I am thinking about adapting language therapy for children to adults with aphasia and I know there is a debate among linguists and patholinguists, but I cannot find any literature. Could anyone help me?
    Roberta Brooks · Albert Einstein Healthcare Network
    Hi Cornilia, Cynthia K. Thompson and Lew Shapiro's work in looking at the results of training basic vs. complex linguistic structures in individual's who present with agrammatic aphasia compares the results of training basic vs. complex structures. Their work speaks to both the importance of understanding the structure of language and the differences between language acquistion and language rehabilitation. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1847567/ This link is for an abstract to in research published in Aphasiology. Good luck with your investigation.
  • How can we create a "no-blame culture" in the workplace?
    Management should focus on improving the atmosphere in the workplace. In case of errors, shall we blame the system or individuals? Is the no blame culture practical?
    Vahid Mohammadi · Shahrekord University
    I think "blame" just has disadvantages. So, It's rejected. But, about "no-blame culture", I think it's practical and instead of that it's better to use another term such as "award and fine system."
  • What are the optimization problems that exists in radio mobile network (GSM …) and have been solved using metaheuristics ?
    What are optimization problems that exist in radio mobile network resolved using metheuristics.one of these problems is the frequency assignement problem
  • What are the optimization problems that exists in radio mobile network (GSM …) and have been solved using metaheuristics ?
    What are optimization problems that exist in radio mobile network resolved using metheuristics.one of these problems is the frequency assignement problem
  • Do I need a normal distribution to run Cronbach's alpha?
    What is minimum number of responses to run Cronbach's alpha ?
    Vinayak Nahar · University of Mississippi
    Thank you very much Dr. Gerrard for you response.
  • What are the optimization problems that exists in radio mobile network (GSM …) and have been solved using metaheuristics ?
    What are optimization problems that exist in radio mobile network resolved using metheuristics.one of these problems is the frequency assignement problem
  • Gloria Latham added an answer:
    Which skills must 21st century teachers have to promote high quality learning?
    The industrial revolution is long gone, as well as teaching to follow a certain routine, procedure or task. Today's world is changing by the minute and we "all" have access to such changes almost immediately. So teachers, today, have to prepare students for a world that is totally unknown, for jobs that don't exist yet, and, hopefully, those future men/women will be able to create those innovative jobs. Are teachers, in your countries, being prepared for these responsibilities and challenges? How?
    Gloria Latham · University of Sydney
    Many wonderful threads have emerged from this discussion. I would be happy to assemble the themes next semester as I'm not teaching but threads with comments do not make a book. These themes would need to be fleshed out and analysed with literature as support. Who is the audience for this text? Is it an ebook? All contributors would need to give permission. Perhaps each section could have an author who takes charge. Is there a publisher in mind? What if we conjured a proposal together?
  • What are the optimization problems that exists in radio mobile network (GSM …) and have been solved using metaheuristics ?
    What are optimization problems that exist in radio mobile network resolved using metheuristics.one of these problems is the frequency assignement problem
  • What are the optimization problems that exists in radio mobile network (GSM …) and have been solved using metaheuristics ?
    What are optimization problems that exist in radio mobile network resolved using metheuristics.one of these problems is the frequency assignement problem
  • John Ryding added an answer in Banking
    What are the theories behind financial intermediation?
    Banks are playing a dominant role in job creation, economic growth, and managing financial and economic stability of a country. Very often researchers use basic theories on economics (i.e., supply and demand for loanable funds) to explain financial intermediation (FI). Can anyone suggest any theories that specifically address FI?
    John Ryding · RDQ Economics
    Thomas Philippon of NYU examined this question at the excellent Financial Markets Conference that the FRB Atlanta holds each year. The conference was this week and I gave just gotten back from it. Here is the link to the conference agenda and his paper http://www.frbatlanta.org/news/conferences/14fmc_agenda.cfm
  • What are the optimization problems that exists in radio mobile network (GSM …) and have been solved using metaheuristics ?
    What are optimization problems that exist in radio mobile network resolved using metheuristics.one of these problems is the frequency assignement problem
  • What programming language is best for a bioinformatics beginner?
    I will be doing NGS in the course of my research work and I will like to learn a programming language which is compatible with most bioinformatics tools or software. I basically want to do de-novo assembly, map reads, align reads, and expression analysis. Recommendations welcomed.
    Silvia Vasquez · Instituto Peruano de Energía Nuclear
    Ubuntu + Perl