Parabolic Anderson model with a finite number of moving catalysts

We consider the parabolic Anderson model (PAM) which is given by the equation $\partial u/\partial t = \kappa\Delta u + \xi u$ with $u\colon\, \Z^d\times [0,\infty)\to \R$, where $\kappa \in [0,\infty)$ is the diffusion constant, $\Delta$ is the discrete Laplacian, and $\xi\colon\,\Z^d\times [0,\infty)\to\R$ is a space-time random environment that drives the equation. The solution of this equation describes the evolution of a "reactant" $u$ under the influence of a "catalyst" $\xi$. In the present paper we focus on the case where $\xi$ is a system of $n$ independent simple random walks each with step rate $2d\rho$ and starting from the origin. We study the \emph{annealed} Lyapunov exponents, i.e., the exponential growth rates of the successive moments of $u$ w.r.t.\ $\xi$ and show that these exponents, as a function of the diffusion constant $\kappa$ and the rate constant $\rho$, behave differently depending on the dimension $d$. In particular, we give a description of the intermittent behavior of the system in terms of the annealed Lyapunov exponents, depicting how the total mass of $u$ concentrates as $t\to\infty$. Our results are both a generalization and an extension of the work of G\"artner and Heydenreich 2006, where only the case $n=1$ was investigated.Comment: In honour of J\"urgen G\"artner on the occasion of his 60th birthday, 25 pages. Updated version following the referee's comment

Inductive queries for a drug designing robot scientist

It is increasingly clear that machine learning algorithms need to be integrated in an iterative scientific discovery loop, in which data is queried repeatedly by means of inductive queries and where the computer provides guidance to the experiments that are being performed. In this chapter, we summarise several key challenges in achieving this integration of machine learning and data mining algorithms in methods for the discovery of Quantitative Structure Activity Relationships (QSARs). We introduce the concept of a robot scientist, in which all steps of the discovery process are automated; we discuss the representation of molecular data such that knowledge discovery tools can analyse it, and we discuss the adaptation of machine learning and data mining algorithms to guide QSAR experiments

Identification of the upward movement of human CSF in vivo and its relation to the brain venous system.

CSF flux is involved in the pathophysiology of neurodegenerative diseases and cognitive impairment after traumatic brain injury, all hallmarked by the accumulation of cellular metabolic waste. Its effective disposal via various CSF routes has been demonstrated in animal models. In contrast, the CSF dynamics in humans are still poorly understood. Using novel real-time MRI, forced inspiration has been identified recently as a main driving force of CSF flow in the human brain. Exploiting technical advances toward real-time phase-contrast MRI, the current work analyzed directions, velocities, and volumes of human CSF flow within the brain aqueduct as part of the internal ventricular system and in the spinal canal during respiratory cycles. A consistent upward CSF movement toward the brain in response to forced inspiration was seen in all subjects at the aqueduct, in 11/12 subjects at thoracic level 2, and in 4/12 subjects at thoracic level 5. Concomitant analyses of CSF dynamics and cerebral venous blood flow, that is, in epidural veins at cervical level 3, uniquely demonstrated CSF and venous flow to be closely communicating cerebral fluid systems in which inspiration-induced downward flow of venous blood due to reduced intrathoracic pressure is counterbalanced by an upward movement of CSF. The results extend our understanding of human CSF flux and open important clinical implications, including concepts for drug delivery and new classifications and therapeutic options for various forms of hydrocephalus and idiopathic intracranial hypertension

Inspiration is the major regulator of human CSF flow.

The mechanisms behind CSF flow in humans are still not fully known. CSF circulates from its primary production sites at the choroid plexus through the brain ventricles to reach the outer surface of the brain in the subarachnoid spaces from where it drains into venous bloodstream and cervical lymphatics. According to a recent concept of brain fluid transport, established in rodents, CSF from the brain surface also enters the brain tissue along para-arterial routes and exits through paravenous spaces again into subarachnoid compartments. This unidirectional flow is mainly driven by arterial pulsation. To investigate how CSF flow is regulated in humans, we applied a novel real-time magnetic resonance imaging technique at high spatial (0.75 mm) and temporal (50 ms) resolution in healthy human subjects. We observed significant CSF flow exclusively with inspiration. In particular, during forced breathing, high CSF flow was elicited during every inspiration, whereas breath holding suppressed it. Only a minor flow component could be ascribed to cardiac pulsation. The present results unambiguously identify inspiration as the most important driving force for CSF flow in humans. Inspiratory thoracic pressure reduction is expected to directly modulate the hydrostatic pressure conditions for the low-resistance paravenous, venous, and lymphatic clearance routes of CSF. Furthermore, the experimental approach opens new clinical opportunities to study the pathophysiology of various forms of hydrocephalus and to design therapeutic strategies in relation to CSF flow alterations

Micrometer-sized Water Ice Particles for Planetary Science Experiments: Influence of Surface Structure on Collisional Properties

Models and observations suggest that ice-particle aggregation at and beyond the snowline dominates the earliest stages of planet formation, which therefore is subject to many laboratory studies. However, the pressure–temperature gradients in protoplanetary disks mean that the ices are constantly processed, undergoing phase changes between different solid phases and the gas phase. Open questions remain as to whether the properties of the icy particles themselves dictate collision outcomes and therefore how effectively collision experiments reproduce conditions in protoplanetary environments. Previous experiments often yielded apparently contradictory results on collision outcomes, only agreeing in a temperature dependence setting in above ≈210 K. By exploiting the unique capabilities of the NIMROD neutron scattering instrument, we characterized the bulk and surface structure of icy particles used in collision experiments, and studied how these structures alter as a function of temperature at a constant pressure of around 30 mbar. Our icy grains, formed under liquid nitrogen, undergo changes in the crystalline ice-phase, sublimation, sintering and surface pre-melting as they are heated from 103 to 247 K. An increase in the thickness of the diffuse surface layer from ≈10 to ≈30 Å (≈2.5 to 12 bilayers) proves increased molecular mobility at temperatures above ≈210 K. Because none of the other changes tie-in with the temperature trends in collisional outcomes, we conclude that the surface pre-melting phenomenon plays a key role in collision experiments at these temperatures. Consequently, the pressure–temperature environment, may have a larger influence on collision outcomes than previously thought

The long noncoding RNA neuroLNC regulates presynaptic activity by interacting with the neurodegeneration-associated protein TDP-43

The cellular and the molecular mechanisms by which long noncoding RNAs (lncRNAs) may regulate presynaptic function and neuronal activity are largely unexplored. Here, we established an integrated screening strategy to discover lncRNAs implicated in neurotransmitter and synaptic vesicle release. With this approach, we identified neuroLNC, a neuron-specific nuclear lncRNA conserved from rodents to humans. NeuroLNC is tuned by synaptic activity and influences several other essential aspects of neuronal development including calcium influx, neuritogenesis, and neuronal migration in vivo. We defined the molecular interactors of neuroLNC in detail using chromatin isolation by RNA purification, RNA interactome analysis, and protein mass spectrometry. We found that the effects of neuroLNC on synaptic vesicle release require interaction with the RNA-binding protein TDP-43 (TAR DNA binding protein-43) and the selective stabilization of mRNAs encoding for presynaptic proteins. These results provide the first proof of an lncRNA that orchestrates neuronal excitability by influencing presynaptic function

Therapie der blanden Struma: Erfahrungen mit einer Kombination von 100 µg L-Thyroxin und 10 µg L-Trijodthyronin

Dtsch med Wochenschr 1981; 106: 579-583 DOI: 10.1055/s-2008-1070359 © Georg Thieme Verlag KG Stuttgart · New York Therapie der blanden Struma: Erfahrungen mit einer Kombination von 100 µg L-Thyroxin und 10 µg L-Trijodthyronin Treatment of non-toxic goitre: results of combined treatment with 100 µg L-thyroxine and 10 µg L-triiodothyronine C. R. Pickardt, R. Gärtner, J. Habermann, K. Horn, P. C. Scriba, F. A. Horster, H. Wagner, K. Hengst Medizinische Klinik Innenstadt der Universität München, Klinik für Innere Medizin, Medizinische Hochschule Lübeck, Medizinische Klinik C und Poliklinik der Universität Düsseldorf sowie Medizinische Klinik und Poliklinik der Universität Münster Zusammenfassung Bei 96 Patienten mit blander Struma wurde eine offene Prüfung mit einem neuen Schilddrüsenhormonpräparat durchgeführt, das 100 µg L-Thyroxin (T4) und 10 µg L-Trijodthyronin (T3) pro Tablette enthält. Als Parameter für die therapeutisch wirksame Tagesdosis wurde die Suppression des TRH-stimulierten Thyreotropinspiegels im Serum gewählt. Hierbei war eine Tagesdosis von 50 µg T4 und 5 µg T3 bei 16 Patienten unwirksam; 75 µg T4 und 7,5 µg T3waren bei nur 4 von 12 Patienten suppressiv wirksam, während 100 µg T4 und 10 µg T3 bei allen Düsseldorfer und Münsteraner Patienten, aber nur bei 17 von 31 Patienten in München den TRH-stimulierten TSH-Anstieg supprimierte. Während der gesamten Therapiedauer blieben Thyroxin- und Trijodthyroninspiegel im Serum im Normbereich; bei einigen Patienten erhöhte sich der Quotient aus Thyroxin und thyroxinbindendem Globulin über die Norm. Zeichen einer Überdosierung oder Unverträglichkeit wurden nicht beobachtet. In pharmakokinetischen Untersuchungen an acht freiwilligen schilddrüsengesunden Probanden erreichte der mittlere Thyroxin- und Trijodthyroninspiegel etwa 2 Stunden nach Applikation sein Maximum und näherte sich nach sechs Stunden wieder der Norm. Es zeigten sich deutliche individuelle Schwankungen in den ersten Stunden nach Applikation. Wir empfehlen deshalb, Schilddrüsenhormonspiegel erst 12 oder 24 Stunden nach Applikation eines Schilddrüsenhormonpräparates zu bestimmen; zu dieser Zeit sollte auch der TRH-Test durchgeführt werden. Die Untersuchungen bestätigen die Notwendigkeit, bei der Strumatherapie mit einem Schilddrüsenhormonpräparat die suppressiv wirksame Dosis individuell zu ermitteln; diese Dosis beträgt vorzugsweise 100 µg Thyroxin und 10 µg Trijodthyronin oder 150 µg Thyroxin oder 100 µg Thyroxin und 20 µg Trijodthyronin pro Tag.A new thyroid hormone preparation (100 µg L-thyroxine [T4] and 10 µg L-triiodothyronine [T3] per tablet) was given to 96 patients with non-toxic goitre. Suppression of the TRH-stimulated thyrotropin level in serum was chosen as a measure of therapeutic effectiveness. Daily dose of 50 µg T4 and 5 µg T3 was ineffective in 16 patients; 75 µg T4 and 7.5 µg T3 was effective in only four of twelve patients, while 100 µg T4and 10 µg T3 was effective in all patients from clinics in Düsseldorf and Münster, but in only 17 of 31 patients from Munich, in suppressing the TRH-stimulated TSH rise. During the entire period of treatment serum thyroxine and triiodothyronine levels remained normal. In some patients the ratio of thyroxine to thyroxine-binding globulin was above normal. Signs of overdosage or intolerance were not observed. Pharmacokinetic studies on eight volunteers with normal thyroid function demonstrated that the mean thyroxine and triiodothyronine levels reached maximum about two hours after administration, returning towards normal after six hours. There were marked individual variations in the first hours after administration. It is therefore recommended that the thyroid hormone level be determined no earlier than 12 or 24 hours after the thyroid hormone preparation has been administered; TRH test should also be performed at this time. These results indicate the need for determining individually the effective suppressive dose of a thyroid hormone preparation in the treatment of goitre. Preferably the dose should be 100 µg thyroxine and 10 µg triiodothyronine, or 150 µg thyroxine or 100 µg thyroxine and 20 µg triiodothyronine per day