Erg-O: ergonomic optimization of immersive virtual environments

Interaction in VR involves large body movements, easily inducing fatigue and discomfort. We propose Erg-O, a manipulation technique that leverages visual dominance to maintain the visual location of the elements in VR, while making them accessible from more comfortable locations. Our solution works in an open-ended fashion (no prior knowledge of the object the user wants to touch), can be used with multiple objects, and still allows interaction with any other point within user's reach. We use optimization approaches to compute the best physical location to interact with each visual element, and space partitioning techniques to distort the visual and physical spaces based on those mappings and allow multi-object retargeting. In this paper we describe the Erg-O technique, propose two retargeting strategies and report the results from a user study on 3D selection under different conditions, elaborating on their potential and application to specific usage scenarios

Geometrical principles of homomeric β-barrels and β-helices: Application to modeling amyloid protofilaments

Examples of homomeric β-helices and β-barrels have recently emerged. Here we generalise the theory for the shear number in β-barrels to encompass β-helices and homomeric structures. We introduce the concept of the “β-strip”, the set of parallel or antiparallel neighbouring strands, from which the whole helix can be generated giving it n-fold rotational symmetry. In this context the shear number is interpreted as the sum around the helix of the fixed register shift between neighbouring identical β-strips. Using this approach we have derived relationships between helical width, pitch, angle between strand direction and helical axis, mass per length, register shift, and number of strands. The validity and unifying power of the method is demonstrated with known structures including α-haemolysin, T4 phage spike, cylindrin, and the HET-s(218-289) prion. From reported dimensions measured by X-ray fibre diffraction on amyloid fibrils the relationships can be used to predict the register shift and the number of strands within amyloid protofilaments. This was used to construct models of transthyretin and Alzheimer β(40) amyloid protofilaments that comprise a single strip of in-register β-strands folded into a “β-strip helix”. Results suggest both stabilisation of an individual β-strip helix as well as growth by addition of further β-strip helices involves the same pair of sequence segments associating with β-sheet hydrogen bonding at the same register shift. This association would be aided by a repeat sequence. Hence understanding of how the register shift (as the distance between repeat sequences) relates to helical dimensions, will be useful for nanotube design

Increased Mortality Exposure within the Family Rather than Individual Mortality Experiences Triggers Faster Life-History Strategies in Historic Human Populations

Life History Theory predicts that extrinsic mortality risk is one of the most important factors shaping (human) life histories. Evidence from contemporary populations suggests that individuals confronted with high mortality environments show characteristic traits of fast life-history strategies: they marry and reproduce earlier, have shorter birth intervals and invest less in their offspring. However, little is known of the impact of mortality experiences on the speed of life histories in historical human populations with generally higher mortality risk, and on male life histories in particular. Furthermore, it remains unknown whether individual-level mortality experiences within the family have a greater effect on life-history decisions or family membership explains life-history variation. In a comparative approach using event history analyses, we study the impact of family versus individual-level effects of mortality exposure on two central life-history parameters, ages at first marriage and first birth, in three historical human populations (Germany, Finland, Canada). Mortality experience is measured as the confrontation with sibling deaths within the natal family up to an individual's age of 15. Results show that the speed of life histories is not adjusted according to individual-level mortality experiences but is due to family-level effects. The general finding of lower ages at marriage/reproduction after exposure to higher mortality in the family holds for both females and males. This study provides evidence for the importance of the family environment for reproductive timing while individual-level mortality experiences seem to play only a minor role in reproductive life history decisions in humans

Interferon-ß regulates the production of IL-10 by toll-like receptor-activated microglia

Pattern recognition receptors, such as toll-like receptors (TLRs), perceive tissue alterations and initiate local innate immune responses. Microglia, the resident macrophages of the brain, encode TLRs which primary role is to protect the tissue integrity. However, deregulated activation of TLRs in microglia may lead to chronic neurodegeneration. This double role of microglial responses is often reported in immune-driven neurologic diseases, as in multiple sclerosis (MS). Consequently, strategies to manipulate microglia inflammatory responses may help to ameliorate disease progression. In this context, the anti-inflammatory cytokine interleukin (IL)-10 appears as an attractive target. In this study, we investigated how activation of microglia by TLRs with distinct roles in MS impacts on IL-10 production. We found that activation of TLR2, TLR4, and TLR9 induced the production of IL-10 to a greater extent than activation of TLR3. This was surprising as both TLR3 and IL-10 play protective roles in animal models of MS. Interestingly, combination of TLR3 triggering with the other TLRs, enhanced IL-10 through the modulation of its transcription, via interferon (IFN)-beta, but independently of IL-27. Thus, in addition to the modulation of inflammatory responses of the periphery described for the axis TLR3/IFN-beta, we now report a direct modulation of microglial responses. We further show that the presence of IFN-gamma in the microenvironment abrogated the modulation of IL-10 by TLR3, whereas that of IL-17 had no effect. Considering the therapeutic application of IFN-beta in MS, our study bears important implications for the understanding of the cytokine network regulating microglia responses in this setting.Portuguese Foundation for Science and Technology (FCT), Grant/Award Numbers: SFRH/BD/88081/2012 and SFRH/BPD/72710/2010; FEDER - Competitiveness Factors Operational Programme (COMPETE), Grant/Award Numbers: POCI-01-0145-FEDER-007038 and NORTE-01-0145-FEDER-000013; Norte Portugal Regional Operational Programme, PORTUGAL 2020, European Regional Development Fund (ERDF), Grant/Award Number: NORTE 2020; FCT-ANR, Grant/Award Number: FCT-ANR/BIM-MEC/0007/2013; FEDER - Fundo Europeu de Desenvolvimento Regional; COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020; Institute for Research and Innovation in Health Sciences, Grant/Award Number: POCI-01-0145-FEDER-007274info:eu-repo/semantics/publishedVersio

Identifying allosteric fluctuation transitions between different protein conformational states as applied to Cyclin Dependent Kinase 2

BACKGROUND: The mechanisms underlying protein function and associated conformational change are dominated by a series of local entropy fluctuations affecting the global structure yet are mediated by only a few key residues. Transitional Dynamic Analysis (TDA) is a new method to detect these changes in local protein flexibility between different conformations arising from, for example, ligand binding. Additionally, Positional Impact Vertex for Entropy Transfer (PIVET) uses TDA to identify important residue contact changes that have a large impact on global fluctuation. We demonstrate the utility of these methods for Cyclin-dependent kinase 2 (CDK2), a system with crystal structures of this protein in multiple functionally relevant conformations and experimental data revealing the importance of local fluctuation changes for protein function. RESULTS: TDA and PIVET successfully identified select residues that are responsible for conformation specific regional fluctuation in the activation cycle of Cyclin Dependent Kinase 2 (CDK2). The detected local changes in protein flexibility have been experimentally confirmed to be essential for the regulation and function of the kinase. The methodologies also highlighted possible errors in previous molecular dynamic simulations that need to be resolved in order to understand this key player in cell cycle regulation. Finally, the use of entropy compensation as a possible allosteric mechanism for protein function is reported for CDK2. CONCLUSION: The methodologies embodied in TDA and PIVET provide a quick approach to identify local fluctuation change important for protein function and residue contacts that contributes to these changes. Further, these approaches can be used to check for possible errors in protein dynamic simulations and have the potential to facilitate a better understanding of the contribution of entropy to protein allostery and function

Measurement of the Dipion Mass Spectrum in X(3872) -> J/Psi Pi+ Pi- Decays

We measure the dipion mass spectrum in X(3872)--> J/Psi Pi+ Pi- decays using 360 pb-1 of pbar-p collisions at 1.96 TeV collected with the CDF II detector. The spectrum is fit with predictions for odd C-parity (3S1, 1P1, and 3DJ) charmonia decaying to J/Psi Pi+ Pi-, as well as even C-parity states in which the pions are from Rho0 decay. The latter case also encompasses exotic interpretations, such as a D0-D*0Bar molecule. Only the 3S1 and J/Psi Rho hypotheses are compatible with our data. Since 3S1 is untenable on other grounds, decay via J/Psi Rho is favored, which implies C=+1 for the X(3872). Models for different J/Psi-Rho angular momenta L are considered. Flexibility in the models, especially the introduction of Rho-Omega interference, enable good descriptions of our data for both L=0 and 1.Comment: 7 pages, 4 figures -- Submitted to Phys. Rev. Let

Search for Higgs Boson Decaying to b-bbar and Produced in Association with W Bosons in p-pbar Collisions at sqrt{s}=1.96 TeV

We present a search for Higgs bosons decaying into b-bbar and produced in association with W bosons in p-pbar collisions at sqrt{s}=1.96 TeV. This search uses 320 pb-1 of the dataset accumulated by the upgraded Collider Detector at Fermilab. Events are selected that have a high-transverse momentum electron or muon, missing transverse energy, and two jets, one of which is consistent with a hadronization of a b quark. Both the number of events and the dijet mass distribution are consistent with standard model background expectations, and we set 95% confidence level upper limits on the production cross section times branching ratio for the Higgs boson or any new particle with similar decay kinematics. These upper limits range from 10 pb for mH=110 GeV/c2 to 3 pb for mH=150 GeV/c2.Comment: 7 pages, 3 figures; updated title to published versio

Measurement of B(t->Wb)/B(t->Wq) at the Collider Detector at Fermilab

We present a measurement of the ratio of top-quark branching fractions R= B(t -> Wb)/B(t -> Wq), where q can be a b, s or a d quark, using lepton-plus-jets and dilepton data sets with integrated luminosity of ~162 pb^{-1} collected with the Collider Detector at Fermilab during Run II of the Tevatron. The measurement is derived from the relative numbers of t-tbar events with different multiplicity of identified secondary vertices. We set a lower limit of R > 0.61 at 95% confidence level.Comment: 7 pages, 2 figures, published in Physical Review Letters; changes made to be consistent with published versio