Control of aggregation-induced emission by DNA hybridization

Aggregation-induced emission (AIE) was studied by hybridization of dialkynyl-tetraphenylethylene (DATPE) modified DNA strands. Molecular aggregation and fluorescence of DATPEs are controlled by duplex formation.

Brain electric correlates of strong belief in paranormal phenomena: intracerebral EEG source and regional Omega complexity analyses

The neurocognitive processes underlying the formation and maintenance of paranormal beliefs are important for understanding schizotypal ideation. Behavioral studies indicated that both schizotypal and paranormal ideation are based on an overreliance on the right hemisphere, whose coarse rather than focussed semantic processing may favor the emergence of 'loose' and 'uncommon' associations. To elucidate the electrophysiological basis of these behavioral observations, 35-channel resting EEG was recorded in pre-screened female strong believers and disbelievers during resting baseline. EEG data were subjected to FFT-Dipole-Approximation analysis, a reference-free frequency-domain dipole source modeling, and Regional (hemispheric) Omega Complexity analysis, a linear approach estimating the complexity of the trajectories of momentary EEG map series in state space. Compared to disbelievers, believers showed: more right-located sources of the beta2 band (18.5-21 Hz, excitatory activity); reduced interhemispheric differences in Omega complexity values; higher scores on the Magical Ideation scale; more general negative affect; and more hypnagogic-like reveries after a 4-min eyes-closed resting period. Thus, subjects differing in their declared paranormal belief displayed different active, cerebral neural populations during resting, task-free conditions. As hypothesized, believers showed relatively higher right hemispheric activation and reduced hemispheric asymmetry of functional complexity. These markers may constitute the neurophysiological basis for paranormal and schizotypal ideation.

International palliative care experts' view on phenomena indicating the last hours and days of life

BACKGROUND Providing the highest quality care for dying patients should be a core clinical proficiency and an integral part of comprehensive management, as fundamental as diagnosis and treatment. The aim of this study was to provide expert consensus on phenomena for identification and prediction of the last hours or days of a patient's life. This study is part of the OPCARE9 project, funded by the European Commission's Seventh Framework Programme. METHOD The phenomena associated with approaching death were generated using Delphi technique. The Delphi process was set up in three cycles to collate a set of useful and relevant phenomena that identify and predict the last hours and days of life. Each cycle included: (1) development of the questionnaire, (2) distribution of the Delphi questionnaire and (3) review and synthesis of findings. RESULTS The first Delphi cycle of 252 participants (health care professionals, volunteers, public) generated 194 different phenomena, perceptions and observations. In the second cycle, these phenomena were checked for their specific ability to diagnose the last hours/days of life. Fifty-eight phenomena achieved more than 80% expert consensus and were grouped into nine categories. In the third cycle, these 58 phenomena were ranked by a group of palliative care experts (78 professionals, including physicians, nurses, psycho-social-spiritual support; response rate 72%, see Table 1) in terms of clinical relevance to the prediction that a person will die within the next few hours/days. Twenty-one phenomena were determined to have "high relevance" by more than 50% of the experts. Based on these findings, the changes in the following categories (each consisting of up to three phenomena) were considered highly relevant to clinicians in identifying and predicting a patient's last hours/days of life: "breathing", "general deterioration", "consciousness/cognition", "skin", "intake of fluid, food, others", "emotional state" and "non-observations/expressed opinions/other". CONCLUSION Experts from different professional backgrounds identified a set of categories describing a structure within which clinical phenomena can be clinically assessed, in order to more accurately predict whether someone will die within the next days or hours. However, these phenomena need further specification for clinical use.

Fuzzy Web Knowledge Aggregation, Representation, and Reasoning for Online Privacy and Reputation Management

A social Semantic Web empowers its users to have access to collective Web knowledge in a simple manner, and for that reason, controlling online privacy and reputation becomes increasingly important, and must be taken seriously. This chapter presents Fuzzy Cognitive Maps (FCM) as a vehicle for Web knowledge aggregation, representation, and reasoning. With this in mind, a conceptual framework for Web knowledge aggregation, representation, and reasoning is introduced along with a use case, in which the importance of investigative searching for online privacy and reputation is highlighted. Thereby it is demonstrated how a user can establish a positive online presence.

Computational selection of inhibitors of Abeta aggregation and neuronal toxicity.

Alzheimer's disease (AD) is characterized by the cerebral accumulation of misfolded and aggregated amyloid-beta protein (Abeta). Disease symptoms can be alleviated, in vitro and in vivo, by 'beta-sheet breaker' pentapeptides that reduce plaque load. However the peptide nature of these compounds, made them biologically unstable and unable to penetrate membranes with high efficiency. The main goal of this study was to use computational methods to identify small molecule mimetics with better drug-like properties. For this purpose, the docked conformations of the active peptides were used to identify compounds with similar activities. A series of related beta-sheet breaker peptides were docked to solid state NMR structures of a fibrillar form of Abeta. The lowest energy conformations of the active peptides were used to design three dimensional (3D)-pharmacophores, suitable for screening the NCI database with Unity. Small molecular weight compounds with physicochemical features and a conformation similar to the active peptides were selected, ranked by docking and biochemical parameters. Of 16 diverse compounds selected for experimental screening, 2 prevented and reversed Abeta aggregation at 2-3microM concentration, as measured by Thioflavin T (ThT) fluorescence and ELISA assays. They also prevented the toxic effects of aggregated Abeta on neuroblastoma cells. Their low molecular weight and aqueous solubility makes them promising lead compounds for treating AD.

Search for new phenomena in photon+jet events collected in proton–proton collisions at √s = 8 TeV with the ATLAS detector

This Letter describes a model-independent search for the production of new resonances in photon + jet events using 20 inverse fb of proton--proton LHC data recorded with the ATLAS detector at a centre-of-mass energy of s√ = 8 TeV. The photon + jet mass distribution is compared to a background model fit from data; no significant deviation from the background-only hypothesis is found. Limits are set at 95% credibility level on generic Gaussian-shaped signals and two benchmark phenomena beyond the Standard Model: non-thermal quantum black holes and excited quarks. Non-thermal quantum black holes are excluded below masses of 4.6 TeV and excited quarks are excluded below masses of 3.5 TeV.

Search for new phenomena in events with three charged leptons at a center-of-mass energy of 7 TeV with the ATLAS detector

A generic search for anomalous production of events with at least three charged leptons is presented. The search uses a pp-collision data sample at a center-of-mass energy of root s = 7 TeV corresponding to 4.6 fb(-1) of integrated luminosity collected in 2011 by the ATLAS detector at the CERN Large Hadron Collider. Events are required to contain at least two electrons or muons, while the third lepton may either be an additional electron or muon, or a hadronically decaying tau lepton. Events are categorized by the presence or absence of a reconstructed tau-lepton or Z-boson candidate decaying to leptons. No significant excess above backgrounds expected from Standard Model processes is observed. Results are presented as upper limits on event yields from non-Standard-Model processes producing at least three prompt, isolated leptons, given as functions of lower bounds on several kinematic variables. Fiducial efficiencies for model testing are also provided. The use of the results is illustrated by setting upper limits on the production of doubly charged Higgs bosons decaying to same-sign lepton pairs.

ATLAS search for new phenomena in dijet mass and angular distributions using pp collisions at sqrts=7 TeV

Mass and angular distributions of dijets produced in LHC proton-proton collisions at a centre-of-mass energy root s = 7TeV have been studied with the ATLAS detector using the full 2011 data set with an integrated luminosity of 4.8 fb(-1). Dijet masses up to similar to 4.0TeV have been probed. No resonance-like features have been observed in the dijet mass spectrum, and all angular distributions are consistent with the predictions of QCD. Exclusion limits on six hypotheses of new phenomena have been set at 95% CL in terms of mass or energy scale, as appropriate. These hypotheses include excited quarks below 2.83 TeV, colour octet scalars below 1.86TeV, heavy W bosons below 1.68 TeV, string resonances below 3.61 TeV, quantum black holes with six extra space-time dimensions for quantum gravity scales below 4.11 TeV, and quark contact interactions below a compositeness scale of 7.6 TeV in a destructive interference scenario.

Search for new phenomena in the W W to ell u ell' u' final state in pp collisions at sqrts=7 TeV with the ATLAS detector

This Letter reports a search for a heavy particle that decays to WW using events produced in pp collisions at root s = 7 TeV. The data were recorded in 2011 by the ATLAS detector and correspond to an integrated luminosity of 4.7 fb(-1). WW -> lvl'v' (l,l' = e or mu) final states are considered and the distribution of the transverse mass of the W W candidates is found to be consistent with Standard Model expectations. Upper limits on the production cross section times branching ratio into W boson pairs are set for Randall-Sundrum and bulk Randall-Sundrum gravitons, which result in observed 95% CL lower limits on the masses of the two particles of 1.23 TeV and 0.84 TeV, respectively.

Search for new phenomena in final states with large jet multiplicities and missing transverse momentum at sqrt(s)=8 TeV proton-proton collisions using the ATLAS experiment

A search is presented for new particles decaying to large numbers (7 to greater or equal to 10) of jets, missing transverse momentum and no isolated electrons or muons. This analysis uses 20.3/fb of pp collision data at sqrt(s)=8 TeV collected by the ATLAS experiment at the Large Hadron Collider. The sensitivity of the search is enhanced by considering the number of b-tagged jets and the scalar sum of masses of large-radius jets in an event. No evidence is found for physics beyond the Standard Model. The results are interpreted in the context of various simplified supersymmetry-inspired models where gluinos are pair produced, as well as a mSUGRA/CMSSM model.

Time-Series Panel Analysis (TSPA): Multivariate Modeling of Temporal Associations in Psychotherapy Process.

Objective: Processes occurring in the course of psychotherapy are characterized by the simple fact that they unfold in time and that the multiple factors engaged in change processes vary highly between individuals (idiographic phenomena). Previous research, however, has neglected the temporal perspective by its traditional focus on static phenomena, which were mainly assessed at the group level (nomothetic phenomena). To support a temporal approach, the authors introduce time-series panel analysis (TSPA), a statistical methodology explicitly focusing on the quantification of temporal, session-to-session aspects of change in psychotherapy. TSPA-models are initially built at the level of individuals and are subsequently aggregated at the group level, thus allowing the exploration of prototypical models. Method: TSPA is based on vector auto-regression (VAR), an extension of univariate auto-regression models to multivariate time-series data. The application of TSPA is demonstrated in a sample of 87 outpatient psychotherapy patients who were monitored by postsession questionnaires. Prototypical mechanisms of change were derived from the aggregation of individual multivariate models of psychotherapy process. In a 2nd step, the associations between mechanisms of change (TSPA) and pre- to postsymptom change were explored. Results: TSPA allowed a prototypical process pattern to be identified, where patient's alliance and self-efficacy were linked by a temporal feedback-loop. Furthermore, therapist's stability over time in both mastery and clarification interventions was positively associated with better outcomes. Conclusions: TSPA is a statistical tool that sheds new light on temporal mechanisms of change. Through this approach, clinicians may gain insight into prototypical patterns of change in psychotherapy.

Functional proteomics and biochemsitry: working together to unravel mitochondrial phenomena of African trypansomes

Eukaryotic cells are compartmentalized into membrane-bound organelles in order to provide sheltered reaction rooms for various specific processes. Organelles are not randomly distributed in a cell or operate isolated from each other. At the contrary — some organelles are closely linked and their functions are tightly orchestrated. The most well-known example of two such organelles acting in concert are the ER and the mitochondrion that work together in order to coordinate cellular lipid biosynthesis, maintain Ca2+-homeostasis, regulate mitochondrial division and control mitochondrial/ER shape as well as to synchronize the movement of these organelles within a cell. To study the mitochondrion and its interface to the ER requires a simplified mitochondrial system. African trypanosomes represent such a system. The unicellular parasite that causes devastating diseases in humans and animals has only one large mitochondrion that does not undergo fission/fusion events except for the context of cell division. Moreover, mitochondrial functions and morphology are highly regulated throughout the life cycle of the protozoan. Central to the understanding of how mitochondria control their morphology, communicate with their surroundings and manage exchange of metabolites and transport of biopolymers (proteins, RNAs) is the mitochondrial outer membrane (MOM), as the MOM defines the boundary of the organelle. Recently, we have purified the MOM of T. brucei and characterized its proteome using label-free quantitative mass spectrometry for protein abundance profiling in combination with statistical analysis. Our results show that the trypanosomal MOM proteome consists of 82 proteins, two thirds of which have never been associated with mitochondria before. Among these, we identified novel factors required to regulate mitochondrial morphology and the long-elusive protein import machinery of T. brucei. A comparison with the MOM proteome of yeast defines a set of 17 common proteins that are likely present in the mitochondrial outer membrane of all eukaryotes. One of these is the Miro-GTPase Gem1. In yeast, this Ca2+-EF-Hand containing polypeptide is thought to be involved in a protein complex that physically tethers the mitochondrion to the ER. Interestingly, a putative tethering complex in mammalian cells was linked to the mitochondrial fusion/fission machinery. Thus, the concept of a protein complex-mediated connection seems to be a general and conserved feature. We are currently investigating, if such a protein complex exists in T. brucei and if the trypanosomal Gem1 protein is involved. This ER-subdomain associated with mitochondria has been termed mitochondria-associated ER-membranes or MAM. The MAM has recently been implicated to play a key role in Alzheimer’s disease. It is therefore of broad and general interest to establish other eukaryotic model systems in order to investigate the MAM-MOM connection in more detail.

Functional proteomics and biochemsitry: working together to unravel mitochondrial phenomena of African trypansomes

Central to the understanding of how mitochondria control their morphology, communicate with their surroundings and manage exchange of metabolites and transport of biopolymers (proteins, RNAs) is the mitochondrial outer membrane (MOM), as the MOM defines the boundary of the organelle. Recently, we have purified the MOM of the mitochondrial model organism T. brucei and characterized its proteome. Our results show that the trypanosomal MOM proteome consists of 82 proteins. Among these, we identified novel factors required to regulate mitochondrial morphology and the long-elusive protein import machinery of T. brucei. A comparison with the MOM proteome of yeast defines a set of 17 common proteins that are likely present in the mitochondrial outer membrane of all eukaryotes. One of these is the Miro-GTPase Gem1. In yeast, this Ca2+-EF-Hand containing polypeptide is thought to be involved in a protein complex that physically tethers the mitochondrion to the ER. In mammalian cells, a putative tethering complex was linked to the mitochondrial fusion/fission machinery. Thus, the concept of a protein complex-mediated connection seems to be a general and conserved feature. We are currently investigating if such a protein complex exists in T. brucei and if the trypanosomal Gem1 protein is involved.