A Theory of Cheap Control in Embodied Systems

We present a framework for designing cheap control architectures for embodied agents. Our derivation is guided by the classical problem of universal approximation, whereby we explore the possibility of exploiting the agent's embodiment for a new and more efficient universal approximation of behaviors generated by sensorimotor control. This embodied universal approximation is compared with the classical non-embodied universal approximation. To exemplify our approach, we present a detailed quantitative case study for policy models defined in terms of conditional restricted Boltzmann machines. In contrast to non-embodied universal approximation, which requires an exponential number of parameters, in the embodied setting we are able to generate all possible behaviors with a drastically smaller model, thus obtaining cheap universal approximation. We test and corroborate the theory experimentally with a six-legged walking machine. The experiments show that the sufficient controller complexity predicted by our theory is tight, which means that the theory has direct practical implications. Keywords: cheap design, embodiment, sensorimotor loop, universal approximation, conditional restricted Boltzmann machineComment: 27 pages, 10 figure

Investigating the Epigenetic Effects of a Prototype Smoke-Derived Carcinogen in Human Cells

Global loss of DNA methylation and locus/gene-specific gain of DNA methylation are two distinct hallmarks of carcinogenesis. Aberrant DNA methylation is implicated in smoking-related lung cancer. In this study, we have comprehensively investigated the modulation of DNA methylation consequent to chronic exposure to a prototype smoke-derived carcinogen, benzo[a]pyrene diol epoxide (B[a]PDE), in genomic regions of significance in lung cancer, in normal human cells. We have used a pulldown assay for enrichment of the CpG methylated fraction of cellular DNA combined with microarray platforms, followed by extensive validation through conventional bisulfite-based analysis. Here, we demonstrate strikingly similar patterns of DNA methylation in non-transformed B[a]PDE-treated cells vs control using high-throughput microarray-based DNA methylation profiling confirmed by conventional bisulfite-based DNA methylation analysis. The absence of aberrant DNA methylation in our model system within a timeframe that precedes cellular transformation suggests that following carcinogen exposure, other as yet unknown factors (secondary to carcinogen treatment) may help initiate global loss of DNA methylation and region-specific gain of DNA methylation, which can, in turn, contribute to lung cancer development. Unveiling the initiating events that cause aberrant DNA methylation in lung cancer has tremendous public health relevance, as it can help define future strategies for early detection and prevention of this highly lethal disease

A Bio-Catalytic Approach to Aliphatic Ketones

Depleting oil reserves and growing environmental concerns have necessitated the development of sustainable processes to fuels and chemicals. Here we have developed a general metabolic platform in E. coli to biosynthesize carboxylic acids. By engineering selectivity of 2-ketoacid decarboxylases and screening for promiscuous aldehyde dehydrogenases, synthetic pathways were constructed to produce both C5 and C6 acids. In particular, the production of isovaleric acid reached 32 g/L (0.22 g/g glucose yield), which is 58% of the theoretical yield. Furthermore, we have developed solid base catalysts to efficiently ketonize the bio-derived carboxylic acids such as isovaleric acid and isocaproic acid into high volume industrial ketones: methyl isobutyl ketone (MIBK, yield 84%), diisobutyl ketone (DIBK, yield 66%) and methyl isoamyl ketone (MIAK, yield 81%). This hybrid “Bio-Catalytic conversion” approach provides a general strategy to manufacture aliphatic ketones, and represents an alternate route to expanding the repertoire of renewable chemicals

On the definition and examples of cones and finsler spacetimes

The authors warmly acknowledge Professor Daniel Azagra (Universidad Complutense, Madrid) his advise on approximation of convex functions as well as Profs. Kostelecky (Indiana University), Fuster (University of Technology, Eindhoven), Stavrinos (University of Athens), Pfeifer (University of Tartu), Perlick (University of Bremen) and Makhmali (Institute of Mathematics, Warsaw) their comments on a preliminary version of the article. The careful revision by the referee is also acknowledged. This work is a result of the activity developed within the framework of the Programme in Support of Excellence Groups of the Region de Murcia, Spain, by Fundacion Seneca, Science and Technology Agency of the Region de Murcia. MAJ was partially supported by MINECO/FEDER project reference MTM2015-65430-P and Fundacion Seneca project reference 19901/GERM/15, Spain and MS by Spanish MINECO/ERDF project reference MTM2016-78807-C2-1-P.A systematic study of (smooth, strong) cone structures C and Lorentz–Finsler metrics L is carried out. As a link between both notions, cone triples (Ω,T,F), where Ω (resp. T) is a 1-form (resp. vector field) with Ω(T)≡1 and F, a Finsler metric on ker(Ω), are introduced. Explicit descriptions of all the Finsler spacetimes are given, paying special attention to stationary and static ones, as well as to issues related to differentiability. In particular, cone structures C are bijectively associated with classes of anisotropically conformal metrics L, and the notion of cone geodesic is introduced consistently with both structures. As a non-relativistic application, the time-dependent Zermelo navigation problem is posed rigorously, and its general solution is provided.MINECO/FEDER project, Spain MTM2015-65430-PFundacion Seneca 19901/GERM/15Spanish MINECO/ERDF project MTM2016-78807-C2-1-

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Phenotypic Detection of Clonotypic B Cells in Multiple Myeloma by Specific Immunoglobulin Ligands Reveals their Rarity in Multiple Myeloma

In multiple myeloma, circulating “clonotypic” B cells, that express the immunoglobulin rearrangement of the malignant plasma cell clone, can be indirectly detected by PCR. Their role as potential “feeder” cells for the malignant plasma cell pool remains controversial. Here we established for the first time an approach that allows direct tracking of such clonotypic cells by labeling with patient-specific immunoglobulin ligands in 15 patients with myeloma. Fifty percent of patients showed evidence of clonotypic B cells in blood or bone marrow by PCR. Epitope-mimicking peptides from random libraries were selected on each patient's individual immunoglobulin and used as ligands to trace cells expressing the idiotypic immunoglobulin on their surface. We established a flow cytometry and immunofluorescence protocol to track clonotypic B cells and validated it in two independent monoclonal B cell systems. Using this method, we found clonotypic B cells in only one out of 15 myeloma patients. In view of the assay's validated sensitivity level of 10−3, this surprising data suggests that the abundance of such cells has been vastly overestimated in the past and that they apparently represent a very rare population in myeloma. Our novel tracing approach may open perspectives to isolate and analyze clonotypic B cells and determine their role in myeloma pathobiology

Qualitatively and quantitatively similar effects of active and passive maternal tobacco smoke exposure on in utero mutagenesis at the HPRT locus

BACKGROUND: Induced mutagenesis in utero is likely to have life-long repercussions for the exposed fetus, affecting survival, birth weight and susceptibility to both childhood and adult-onset diseases, such as cancer. In the general population, such exposures are likely to be a consequence of the lifestyle choices of the parents, with exposure to tobacco smoke one of the most pervasive and easily documented. Previous studies attempting to establish a direct link between active smoking and levels of somatic mutation have largely discounted the effects of passive or secondary exposure, and have produced contradictory results. METHODS: Data from three studies of possible smoking effects on in utero mutagenesis at the HPRT locus were compiled and reanalyzed, alone and in combination. Where possible, passive exposure to environmental tobacco smoke was considered as a separate category of exposure, rather than being included in the non-smoking controls. Molecular spectra from these studies were reanalyzed after adjustment for reported mutation frequencies from the individual studies and the entire data set. RESULTS: A series of related studies on mutation at the X-linked HPRT locus in human newborn cord blood samples has led to the novel conclusion that only passive maternal exposure to tobacco mutagens has a significant effect on the developing baby. We performed a pooled analysis of the complete data from these studies, at the levels of both induced mutation frequency and the resulting mutational spectrum. CONCLUSION: Our analysis reveals a more commonsensical, yet no less cautionary result: both active maternal smoking and secondary maternal exposure produce quantitatively and qualitatively indistinguishable increases in fetal HPRT mutation. Further, it appears that this effect is not perceptibly ameliorated if the mother adjusts her behavior (i.e. stops smoking) when pregnancy is confirmed, although this conclusion may also be affected by continued passive exposure

The Interplay Between Post-Critical Beliefs and Anxiety: An Exploratory Study in a Polish Sample

The present research investigates the relationship between anxiety and the religiosity dimensions that Wulff (Psychology of religion: classic and contemporary views, Wiley, New York, 1991; Psychology of religion. Classic and contemporary views, Wiley, New York, 1997; Psychologia religii. Klasyczna i współczesna, Wydawnictwo Szkolne i Pedagogiczne, Warszawa, 1999) described as Exclusion vs. Inclusion of Transcendence and Literal vs. Symbolic. The researchers used the Post-Critical Belief scale (Hutsebaut in J Empir Theol 9(2):48–66, 1996; J Empir Theol 10(1):39–54, 1997) to measure Wulff’s religiosity dimensions and the IPAT scale (Krug et al. 1967) to measure anxiety. Results from an adult sample (N = 83) suggest that three dimensions show significant relations with anxiety. Orthodoxy correlated negatively with suspiciousness (L) and positively with guilt proneness (O) factor—in the whole sample. Among women, Historical Relativism negatively correlated with suspiciousness (L), lack of integration (Q3), general anxiety and covert anxiety. Among men, Historical Relativism positively correlated with tension (Q4) and emotional instability (C), general anxiety, covert anxiety and overt anxiety. External Critique was correlated with suspiciousness (L) by men

Sensitive Detection of p65 Homodimers Using Red-Shifted and Fluorescent Protein-Based FRET Couples

BACKGROUND: Fluorescence Resonance Energy Transfer (FRET) between the green fluorescent protein (GFP) variants CFP and YFP is widely used for the detection of protein-protein interactions. Nowadays, several monomeric red-shifted fluorescent proteins are available that potentially improve the efficiency of FRET. METHODOLOGY/PRINCIPAL FINDINGS: To allow side-by-side comparison of several fluorescent protein combinations for detection of FRET, yellow or orange fluorescent proteins were directly fused to red fluorescent proteins. FRET from yellow fluorescent proteins to red fluorescent proteins was detected by both FLIM and donor dequenching upon acceptor photobleaching, showing that mCherry and mStrawberry were more efficient acceptors than mRFP1. Circular permutated yellow fluorescent protein variants revealed that in the tandem constructs the orientation of the transition dipole moment influences the FRET efficiency. In addition, it was demonstrated that the orange fluorescent proteins mKO and mOrange are both suitable as donor for FRET studies. The most favorable orange-red FRET pair was mKO-mCherry, which was used to detect homodimerization of the NF-kappaB subunit p65 in single living cells, with a threefold higher lifetime contrast and a twofold higher FRET efficiency than for CFP-YFP. CONCLUSIONS/SIGNIFICANCE: The observed high FRET efficiency of red-shifted couples is in accordance with increased Förster radii of up to 64 A, being significantly higher than the Förster radius of the commonly used CFP-YFP pair. Thus, red-shifted FRET pairs are preferable for detecting protein-protein interactions by donor-based FRET methods in single living cells