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Non-linear Effects in Asymmetric Catalysis: Whys and Wherefores
Full text linkIt is argued that the titled non-linear effects (NLE) may arise whenever the order of the reaction in the chiral catalyst in greater than 1. In a fundamental departure from previous approaches, this is mathematically elaborated for the second order case. (NLE may also be observed if the chiral catalyst forms non-reacting dimers in a competing equilibrium; practically, however, this implies the in situ resolution of the catalyst.) The amplification of enantiomeric excess by NLE implies a relative (although modest) reduction in the entropy of mixing. The consequent increase in free energy apparently indicates a non-equilibrium process. It is suggested, based on arguments involving the chemical potential, that kinetically-controlled reactions lead to a state of “quasi-equilibrium”: in this, although overall equilibrium is attained, the product-spread is far from equilibrium. Thus, both the linear and NLE cases of chiral catalysis represent departures from equilibrium (which requires that the product e.e. = 0). Interesting similarities exist with models of non-equilibrium systems, the NLE cases apparently being analogs of open systems just after the bifurcation point has been crossed
Quantitative Models for Efficient Cloning of Different Vectors with Various Clone sites
Full text linkWe developed an efficient "Combinatorial Strategy” for cloning different vectors with various clone sites. 1) Using originally existed clone sites from circular vectors to prepare the inserts, and if no appropriate sites are available, performing SDM to create compatible sites, to achieve maximal correct digestion of the inserts. 2) Different vectors were digested with various restriction endonucleases, and then dephosphorylated with CIP. 3) Top10 competent cells were used for transformation to increase the transformant colonies. Our results showed that, when blunt sites, or a Xba I site was adopted for ligation, the percentages of positive clones were about 50%. Whereas, when different sites, including one blunt and another Pst I sites, Not I and Xho I sites, the percentages of positive clones were nearly 100%. Using this strategy, most vectors could be successfully cloned through “one ligation, one transformation, three to five minipreps."
Improving metabolite evaluation in integrated pathway analysis
No full textBiological molecules such as proteins and metabolites interact to accomplish a biological function and to respond to environmental stimuli. Pathways capture this information derived through scientific experimentation and data analysis. They contain information about genes that appear in complexes, the interacting genes, the directionality of the interactions (e.g. inhibitors versus activators), the cellular locations where the reactions occur, and the metabolites that are affected by the processes. Using our open-source pathway analysis platform, PathVisio, we will connect pathway analysis to different quantitative approaches already in development for metabolic network modeling, such as flux balance analysis and dynamic simulation. In order to use system-wide measurements to gain insights into this mechanism, we have to integrate large scale data analysis with modeled or measured fluxomics data
results. For this we will develop a BridgeDb database for reaction identifiers, develop a PathVisio plugin for visualization of modeling results and architect a flexible, standards-based visualization approach (e.g. using MIM and SBGN) that will enable visualization of any conforming model, including visualization of the model output (e.g. flux changes). The focus here is on visualization of the modeling results, which will be critical for understanding how simulated models correlate with experimental measurements On the same lines, we will also find a solution to the problem of annotating metabolites in all pathways. The approach here is to use known Gene Ontology annotations for associated genes. Firstly we will incorporate automatically inferred GO categories into all WikiPathways. Develop GO visualization plugin to show gene categories on pathways and further assign automatically inferred GO categories to all addressable metabolites in WikiPathways. The last step would be to develop basic metabolite ontology analysis tools both with python GUIs and as Bioconductor modules
Development of Java based graphical user interface for Diagnosis of Hepatitis UsingI Mixture of Expert
Full text linkHepatitis is deadly, and the fifth leading cause of death after heart disease, stroke, chest disease and cancer. Worldwide, 1.5 million deaths per year have been estimated. Detection of hepatitis is a big problem for general practitioners. An expert doctor commonly makes decisions by evaluating the current test results of a patient or by comparing the patient with others with the same condition with reference to the previous decisions. Many machine learning and data mining techniques have been designed for the automatic diagnosis of hepatitis. However, no one tool is available to the general population for the diagnosis of Hepatitis. Hence, a graphical user interface-enabled tool needs to be developed, through which medical practitioners can feed patient data easily and find hepatitis diagnoses instantly and accurately. 
Methods: In this study a hepatitis dataset was taken from the UCI machine repository database with a total of 20 attributes of two classes, Affected and Not Affected. 
Results and Conclusion: The models have been generated with a mixture of experts as a classification method for the diagnosis of hepatitis. Very good accuracy has been observed in the generated models. Finally, the model having the least minimum square error was selected. This model was then linked with GUI for the design of tools for hepatitis prediction
Fundamental Principles of Neural Organization of Cognition
Full text linkThe manuscript advances a hypothesis that there are few fundamental principles of neural organization of cognition, which explain several wide areas of the cognitive functioning. We summarize the fundamental principles, experimental, theoretical, and modeling evidence for these principles, relate them to hypothetical neural mechanisms, and made a number of predictions. We consider cognitive functioning including concepts, emotions, drives-instincts, learning, “higher” cognitive functions of language, interaction of language and cognition, role of emotions in this interaction, the beautiful, sublime, and music. Among mechanisms of behavior we concentrate on internal actions in the brain, learning and decision making. A number of predictions are made, some of which have been previously formulated and experimentally confirmed, and a number of new predictions are made that can be experimentally tested. Is it possible to explain a significant part of workings of the mind from a few basic principles, similar to how Newton explained motions of planets? This manuscript summarizes a part of contemporary knowledge toward this goal
P300- like event related potential amplitude in rats is a correlate of conditioned reinforcement
Full text linkWe have developed a methodology for recording a robust P300 event related potential (ERP) in rats. In these experiments a contingency shaped model of the human “oddball’ paradigm was employed in which rats were shaped to press a lever for food reinforcement signaled by the click of the pellet dispenser. A target tone cued the insertion of the lever that retracted after 1­sec or immediately following a single reinforced response, while a non­target tone was randomly presented. Brain activity was recorded through stainless steel electrodes implanted 1mm below the skull. Here, we compared the amplitude of the P300 response to the click of the pellet dispenser to the amplitude of the P300 response to the target and non­target tones. We found that the amplitude to food click was significantly greater that the amplitude to the target tone that cued lever insertion. Since the food click is more proximal to the primary reinforcer than the lever tone, it is a stronger conditioned reinforcer than the lever tone that sets the occasion for the food click. Accordingly we suggest that the P300 in rats is a correlate of conditioned reinforcement
Generalized Theory of Life
Full text linkThe paper is mathematically, physically and biologically inspired - it is a deductive attempt of the biologist to find the most appropriate language for modelling of life. Applications of mathematical structures - groupoids, groups, categories, functors and monads, which are the most effective for the description of the complex objects, are discussed. Some new conceptions and interpretations were introduced: unified classification of complex systems; the generalized conception about stationary states of any autonomous agent ("Statology"); the total quantitative criterions of evolutionary direction; the generalized group of symmetry. The definitions of information, entropy, organization, behavior, evolution, creation, life, culture, cognition were formulated. An actually closed and potentially opened ecosystem was introduced as the elementary object of organization and evolution of life. Evolution considered as process of generating of a concrete group G of permutations of elements of ecosystems, which is based on activities of the intrinsic autonomous agents. Life was considered as the way of realization of extreme principles of physics through co-organizing of behavior of the ecosystem elements and through dilating borders of the ecosystem by an interiorization of an extrinsic environment
Deletion of the rat trpc4 gene and its influence on motivated responding for natural reward
Full text linkTRPC4 ion channels are expressed extensively in corticolimbic brain regions and a subpopulation of midbrain dopamine neurons. TRPC4 knockout (KO) rats show reduced sociability and social exploration, but show no differences in simple and complex strategic learning compared to normal wild type (WT) rats. Using water reward, we found no differences between TRPC4-KO and WT rats in the break point on a progressive ratio schedule of reinforcement. Although deletion of the trpc4 gene alters social interaction/anxiety it does not appear to affect motivation for natural rewards. Current experiments are underway testing the role of trpc4 gene deletion on cocaine reward (see www.neuro-cloud.net/nature-precedings/klipec3 for updates and collaborations)
From Machine Learning to Learning Machines - A Perspective toward Personalized Medicine
Full text linkWe describe how to learn a network using a bottom-up approach by building networks from expression profiles. Then we can analyze these networks with different graph mining approaches and by studying topological behaviors. Finally, how we can achieve personalized medicine from the network biology
Mining Co-expression Graphs: Applications to MicroRNA Regulation and Disease Analysis
Full text linkMicroRNAs (miRNAs) are known to translationally repress or post-transcriptionally regulate mRNAs and are responsible for many diseases. We are preparing a comprehensive framework of co-expression analysis to figure out co-expression, differential co-expression and co-expression dynamics within multiple phenotypes in expression profiles. The purpose is to elucidate the disease association of miRNAs via co-regulatory pattern analysis