OMA and OPA—Software-Supported Mass Spectra Analysis of Native and Modified Nucleic Acids

The platform-independent software package consisting of the oligonucleotide mass assembler (OMA) and the oligonucleotide peak analyzer (OPA) was created to support the analysis of oligonucleotide mass spectra. It calculates all theoretically possible fragments of a given input sequence and annotates it to an experimental spectrum, thus, saving a large amount of manual processing time. The software performs analysis of precursor and product ion spectra of oligonucleotides and their analogues comprising user-defined modifications of the backbone, the nucleobases, or the sugar moiety, as well as adducts with metal ions or drugs. The ability to expand the library of building blocks and to implement individual structural variations makes it extremely useful for supporting the analysis of therapeutically active compounds. The functionality of the software tool is demonstrated on the examples of a platinated doublestranded oligonucleotide and a modified RNA sequence. Experiments also reveal the unique dissociation behavior of platinated higher-order DNA structures.

Self-motion perception influences number processing: evidence from a parity task

We investigated the role of horizontal body motion on the processing of numbers. We hypothesized that leftward self-motion leads to shifts in spatial attention and therefore facilitates the processing of small numbers, and vice versa, we expected that rightward self-motion facilitates the processing of large numbers. Participants were displaced by means of a motion platform during a parity judgment task. We found a systematic influence of self-motion direction on number processing, suggesting that the processing of numbers is intertwined with the processing of self-motion perception. The results differed from known spatial numerical compatibility effects in that self-motion exerted a differential influence on inner and outer numbers of the given interval. The results highlight the involvement of sensory body motion information in higher-order spatial cognition.

Moving along the mental time line influences the processing of future related words

Abstract concepts like numbers or time are thought to be represented in the more concrete domain of space and the sensorimotor system. For example, thinking of past or future events has a physical manifestation in backward or forward body sway, respectively. In the present study, we investigated the reverse effect: can passive whole-body motion influence the processing of temporal information? Participants were asked to categorize verbal stimuli to the concepts future or past while they were displaced forward and backward (Experiment 1), or upward and downward (Experiment 2). The results showed that future related verbal stimuli were categorized faster during forward as compared to backward motion. This finding supports the view that temporal events are represented along a mental time line and that the sensorimotor system is linked to that representation. We showed that body motion is not just an epiphenomenon of temporal thoughts. Passive whole-body motion can influence higher-order temporal cognition.

Stress and hemostasis: an update

Numerous naturalistic, experimental, and mechanistic studies strongly support the notion that-as part of fight-or-flight response-hemostatic responses to acute psychosocial stress result in net hypercoagulability, which would protect a healthy organism from bleeding in case of injury. Sociodemographic factors, mental states, and comorbidities are important modulators of the acute prothrombotic stress response. In patients with atherosclerosis, exaggerated and prolonged stress-hypercoagulability might accelerate coronary thrombus growth following plaque rupture. Against a background risk from acquired prothrombotic conditions and inherited thrombophilia, acute stress also might trigger venous thromboembolic events. Chronic stressors such as job strain, dementia caregiving, and posttraumatic stress disorder as well as psychological distress from depressive and anxiety symptoms elicit a chronic low-grade hypercoagulable state that is no longer viewed as physiological but might impair vascular health. Through activation of the sympathetic nervous system, higher order cognitive processes and corticolimbic brain areas shape the acute prothrombotic stress response. Hypothalamic-pituitary-adrenal axis and autonomic dysfunction, including vagal withdrawal, are important regulators of hemostatic activity with longer lasting stress. Randomized placebo-controlled trials suggest that several cardiovascular drugs attenuate the acute prothrombotic stress response. Behavioral interventions and psychotropic medications might mitigate chronic low-grade hypercoagulability in stressed individuals, but further studies are clearly needed. Restoring normal hemostatic function with biobehavioral interventions bears the potential to ultimately decrease the risk of thrombotic diseases.

Jazz drummers recruit language-specific areas for the processing of rhythmic structure

Rhythm is a central characteristic of music and speech, the most important domains of human communication using acoustic signals. Here, we investigated how rhythmical patterns in music are processed in the human brain, and, in addition, evaluated the impact of musical training on rhythm processing. Using fMRI, we found that deviations from a rule-based regular rhythmic structure activated the left planum temporale together with Broca's area and its right-hemispheric homolog across subjects, that is, a network also crucially involved in the processing of harmonic structure in music and the syntactic analysis of language. Comparing the BOLD responses to rhythmic variations between professional jazz drummers and musical laypersons, we found that only highly trained rhythmic experts show additional activity in left-hemispheric supramarginal gyrus, a higher-order region involved in processing of linguistic syntax. This suggests an additional functional recruitment of brain areas usually dedicated to complex linguistic syntax processing for the analysis of rhythmical patterns only in professional jazz drummers, who are especially trained to use rhythmical cues for communication.

Personality dimensions in persons symptomatically at risk of psychosis: pronounced but lacking a characteristic profile

AIM Personality dimensions are frequently abnormal in psychosis. We examined if these abnormalities form a personality profile that is characteristic for patients symptomatically at risk of psychosis. METHODS Four higher order personality dimensions were assessed in 104 at-risk patients, 67 clinical and 97 healthy controls with the 'Dimensional Assessment of Personality Pathology', and analysed by two-step cluster procedure to detect personality profiles. Logistic regression was used to test for predictors of profile assignment. RESULTS Low and high scorers were distinguished by two profiles. Patients were more likely high scorers. The presence of clinically relevant depression, though equally frequent in clinical groups, best predicted high scorers among patients. CONCLUSIONS Though at-risk patients were significantly more often high scorers, this seemed to be a general reflection of the level of psychopathology rather than a group characteristic. Thus, personality dimensions might be of little value for facilitating early detection but might be important to consider in early intervention approaches.

Bounds for the probability generating functional of a Gibbs point process

We derive explicit lower and upper bounds for the probability generating functional of a stationary locally stable Gibbs point process, which can be applied to summary statistics such as the F function. For pairwise interaction processes we obtain further estimates for the G and K functions, the intensity, and higher-order correlation functions. The proof of the main result is based on Stein's method for Poisson point process approximation.

Balancing the mind: vestibular induced facilitation of egocentric mental transformations

The body schema is a key component in accomplishing egocentric mental transformations, which rely on bodily reference frames. These reference frames are based on a plurality of different cognitive and sensory cues among which the vestibular system plays a prominent role. We investigated whether a bottom-up influence of vestibular stimulation modulates the ability to perform egocentric mental transformations. Participants were significantly faster to make correct spatial judgments during vestibular stimulation as compared to sham stimulation. Interestingly, no such effects were found for mental transformation of hand stimuli or during mental transformations of letters, thus showing a selective influence of vestibular stimulation on the rotation of whole-body reference frames. Furthermore, we found an interaction with the angle of rotation and vestibular stimulation demonstrating an increase in facilitation during mental body rotations in a direction congruent with rightward vestibular afferents. We propose that facilitation reflects a convergence in shared brain areas that process bottom-up vestibular signals and top-down imagined whole-body rotations, including the precuneus and tempero-parietal junction. Ultimately, our results show that vestibular information can influence higher-order cognitive processes, such as the body schema and mental imagery.

Coherence and phase locking in the scalp EEG and between LORETA model sources, and microstates as putative mechanisms of brain temporo-spatial functional organization

Brain electric mechanisms of temporary, functional binding between brain regions are studied using computation of scalp EEG coherence and phase locking, sensitive to time differences of few milliseconds. However, such results if computed from scalp data are ambiguous since electric sources are spatially oriented. Non-ambiguous results can be obtained using calculated time series of strength of intracerebral model sources. This is illustrated applying LORETA modeling to EEG during resting and meditation. During meditation, time series of LORETA model sources revealed a tendency to decreased left-right intracerebral coherence in the delta band, and to increased anterior-posterior intracerebral coherence in the theta band. An alternate conceptualization of functional binding is based on the observation that brain electric activity is discontinuous, i.e., that it occurs in chunks of up to about 100 ms duration that are detectable as quasi-stable scalp field configurations of brain electric activity, called microstates. Their functional significance is illustrated in spontaneous and event-related paradigms, where microstates associated with imagery- versus abstract-type mentation, or while reading positive versus negative emotion words showed clearly different regions of cortical activation in LORETA tomography. These data support the concept that complete brain functions of higher order such as a momentary thought might be incorporated in temporal chunks of processing in the range of tens to about 100 ms as quasi-stable brain states; during these time windows, subprocesses would be accepted as members of the ongoing chunk of processing.

Elucidation of Nucleic Acid–Drug Interactions by Tandem Mass Spectrometry

In continuation of the long tradition of mass spectrometric research at the University of Bern, our group focuses on the characterization of nucleic acids as therapeutic agents and as drug targets. This article provides a short overview of our recent work on platinated single-stranded and higher-order nucleic acids. Nearly three decades ago the development of soft ionization techniques opened a whole new chapter in the mass spectrometric analysis of not only nucleic acids themselves, but also their interactions with potential drug candidates. In contrast to modern next generation sequencing approaches, though, the goal of the tandem mass spectrometric investigation of nucleic acids is by no means the complete sequencing of genetic DNA, but rather the characterization of short therapeutic and regulatory oligonucleotides and the elucidation of nucleic acid–drug interactions. The influence of cisplatin binding on the gas-phase dissociation of nucleic acids was studied by the means of electrospray ionization tandem mass spectrometry. Experiments on native and modified DNA and RNA oligomers confirmed guanine base pairs as the preferred platination site and laid the basis for the formulation of a gas-phase fragmentation mechanism of platinated oligonucleotides. The study was extended to double stranded DNA and DNA quadruplexes. While duplexes are believed to be the main target of cisplatin in vivo, the recently discovered DNA quadruplexes constitute another promising target for anti-tumor drugs owing to their regulatory functions in the cell cycle.

GOCE: assessment of GPS-only gravity field determination

The GOCE satellite was orbiting the Earth in a Sun-synchronous orbit at a very low altitude for more than 4 years. This low orbit and the availability of high-quality data make it worthwhile to assess the contribution of GOCE GPS data to the recovery of both the static and time-variable gravity fields. We use the kinematic positions of the official GOCE precise science orbit (PSO) product to perform gravity field determination using the Celestial Mechanics Approach. The generated gravity field solutions reveal severe systematic errors centered along the geomagnetic equator. Their size is significantly coupled with the ionospheric density and thus generally increasing over the mission period. The systematic errors may be traced back to the kinematic positions of the PSO product and eventually to the ionosphere-free GPS carrier phase observations used for orbit determination. As they cannot be explained by the current higher order ionospheric correction model recommended by the IERS Conventions 2010, an empirical approach is presented by discarding GPS data affected by large ionospheric changes. Such a measure yields a strong reduction of the systematic errors along the geomagnetic equator in the gravity field recovery, and only marginally reduces the set of useable kinematic positions by at maximum 6 % for severe ionosphere conditions. Eventually it is shown that GOCE gravity field solutions based on kinematic positions have a limited sensitivity to the largest annual signal related to land hydrology.

Hierarchical self-assembly of the DNA-grafted supramolecular polymers

Conjugation of functional entities with a specific set of optical, mechanical or biological properties to DNA strands allows engineering of sophisticated DNA-containing architectures. Among various hybrid systems, DNA-grafted polymers occupy an important place in modern materials science. In this contribution we present the non-covalent synthesis and properties of DNA-grafted linear supramolecular polymers (SPs), which are assembled in a controllable manner from short chimeric DNA-pyrene oligomers. The synthetic oligomers consist of two parts: a 10 nucleotides long DNA chain and a covalently attached segment of variable number of phosphodiester-linked pyrenes. The temperature-dependent formation of DNA-grafted SPs is described by a nucleation-elongation mechanism. The high tendency of pyrenes to aggregate in water, leads to the rapid formation of SPs. The core of the assemblies consists of stacked pyrenes. They form a 1D platform, to which the DNA chains are attached. Combined spectroscopic and microscopic studies reveal that the major driving forces of the polymerization are π-stacking of pyrenes and hydrophobic interactions, and DNA pairing contributes to a lesser extent. AFM and TEM experiments demonstrate that the 1D SPs appear as elongated ribbons with a length of several hundred nanometers. They exhibit an apparent helical structure with a pitch-to-pitch distance of 50±15 nm. Since DNA pairing is a highly selective process, the ongoing studies are aimed to utilize DNA-grafted SPs for the programmable arrangement of functional entities. For example, the addition of non-modified complementary DNA strands to the DNA-grafted SPs leads to the cooperative formation of higher-order assemblies. Also, our experiments suggest that the fluorescent pyrene core of 1D ribbons serves as an efficient donor platform for energy transfer applications.

Automated NNLL + NLO resummation for jet-veto cross sections

In electroweak-boson production processes with a jet veto, higher-order corrections are enhanced by logarithms of the veto scale over the invariant mass of the boson system. In this paper, we resum these Sudakov logarithms at next-to-next-to-leading logarithmic accuracy and match our predictions to next-to-leading-order (NLO) fixed-order results. We perform the calculation in an automated way, for arbitrary electroweak final states and in the presence of kinematic cuts on the leptons produced in the decays of the electroweak bosons. The resummation is based on a factorization theorem for the cross sections into hard functions, which encode the virtual corrections to the boson production process, and beam functions, which describe the low-pT emissions collinear to the beams. The one-loop hard functions for arbitrary processes are calculated using the MadGraph5_aMC@NLO framework, while the beam functions are process independent. We perform the resummation for a variety of processes, in particular for W+W− pair production followed by leptonic decays of the W bosons.

Hierarchical self-assembly of the DNA-grafted supramolecular polymers

Conjugation of functional entities with a specific set of optical, mechanical or biological properties to DNA strands allows engineering of sophisticated DNA-containing architectures. Among various hybrid systems, DNA-grafted polymers occupy an important place in modern materials science. In this contribution we present the non-covalent synthesis and properties of DNA-grafted linear supramolecular polymers (SPs), which are assembled in a controllable manner from short chimeric DNA-pyrene oligomers. The synthetic oligomers consist of two parts: a 10 nucleotides long DNA chain and a covalently attached segment of variable number of phosphodiester-linked pyrenes. The temperature-dependent formation of DNA-grafted SPs is described by a nucleation-elongation mechanism. The high tendency of pyrenes to aggregate in water, leads to the rapid formation of SPs. The core of the assemblies consists of stacked pyrenes. They form a 1D platform, to which the DNA chains are attached. Combined spectroscopic and microscopic studies reveal that the major driving forces of the polymerization are π-stacking of pyrenes and hydrophobic interactions, and DNA pairing contributes to a lesser extent. AFM and TEM experiments demonstrate that the 1D SPs appear as elongated ribbons with a length of several hundred nanometers. They exhibit an apparent helical structure with a pitch-to-pitch distance of 50±15 nm. Since DNA pairing is a highly selective process, the ongoing studies are aimed to utilize DNA-grafted SPs for the programmable arrangement of functional entities. For example, the addition of non-modified complementary DNA strands to the DNA-grafted SPs leads to the cooperative formation of higher-order assemblies. Also, our experiments suggest that the fluorescent pyrene core of 1D ribbons serves as an efficient donor platform for energy transfer applications.

Enabling the Next Generation of Spaceborne Quadrupole Mass Spectrometers

The quadrupole mass spectrometer (QMS) has over 30 years of spaceflight heritage in making important neutral gas and low energy ion observations. Given their geometrical constraints, these instruments are currently operated at the extreme limit of their capabilities. However, a technique called higher order auxiliary excitation provides a set of novel, robust, electronics-based solutions for improving the performance of these sensors. By driving the quadrupole rods with an additional frequency nearly twice that of the normal RF operating frequency, substantially increased abundance sensitivity, maximum attainable mass resolution, and peak stability can be achieved through operation of voltage scan lines through the center of formed upper stability islands. Such improvements are modeled using numerical simulations of ion trajectories in a quadrupole field with and without applied higher order auxiliary excitation. When compared to a traditional QMS with a mass range up to 500Da, sensors can be designed with the same precision electronics to have expected mass ranges beyond 1500Da with a power increase of less than twice that of its heritage implementations.