Nichtdermatomgebundene somatosensorische Defizite bei chronischen Schmerzpatienten

Zusammenfassung: Nichtdermatomgebundene somatosensorische Defizite (NDSD) sind bei chronischen Schmerzpatienten häufig und weisen auf Schmerzsensibilisierung und Schmerzzentralisierung hin. Klinisch findet sich in der Regel eine Berührungs- und Thermhypästhesie mit oftmals quadrantenartiger oder halbseitiger Ausbreitung. Bei der Mehrzahl der Patienten liegt anamnestisch ein somatisch-nozizeptives Auslöseereignis vor, das aber wie das komplexe regionale Schmerzsyndrom (CRPS) in keiner eindeutigen Relation zur nachfolgenden Schmerzstörung steht. Wie bei vielen chronischen Schmerzstörungen weisen auch Patienten mit NDSD oft eine überdurchschnittliche psychobiografische Stressbelastung auf. Die Ergebnisse der funktionellen Bildgebung weisen auf ein komplexes Muster zentralnervöser Dysregulationen hi

A measure of majorisation emerging from single-shot statistical mechanics

The use of the von Neumann entropy in formulating the laws of thermodynamics has recently been challenged. It is associated with the average work whereas the work guaranteed to be extracted in any single run of an experiment is the more interesting quantity in general. We show that an expression that quantifies majorisation determines the optimal guaranteed work. We argue it should therefore be the central quantity of statistical mechanics, rather than the von Neumann entropy. In the limit of many identical and independent subsystems (asymptotic i.i.d) the von Neumann entropy expressions are recovered but in the non-equilbrium regime the optimal guaranteed work can be radically different to the optimal average. Moreover our measure of majorisation governs which evolutions can be realized via thermal interactions, whereas the nondecrease of the von Neumann entropy is not sufficiently restrictive. Our results are inspired by single-shot information theory.Comment: 54 pages (15+39), 9 figures. Changed title / changed presentation, same main results / added minor result on pure bipartite state entanglement (appendix G) / near to published versio

Nichtdermatomgebundene somatosensorische Defizite bei chronischen Schmerzpatienten

Nondermatomal somatosensory deficits (NDSDs) are frequently found in chronic pain patients and allude to pain sensitization and pain centralization. In the clinical examination NDSDs are as a rule accompanied by hyposensitivity to touch and heat perception often with a quadrantal or hemibody distribution. The majority of NDSD patients show a trigger episode with a somatic nociceptive trauma in the case history. These somatic findings, however, never fully explain the pain disorder, analogue to the complex regional pain syndrome (CRPS). Most patients with chronic pain disorders as well as those with NDSD often report an antecedent period of high psychobiological stress. The data from functional imaging reveal a complex pattern of a central nervous dysregulation

A mechanism for the Double-Spin Asymmetry in Electromagnetic ρ\rho Production at HERMES

We calculate the contribution of meson and pomeron exchanges to the double-spin asymmetry in $\rho$-meson electromagnetic production at HERMES energies. We show that the observed double-spin asymmetries, which are large, can be explained by the interference between the natural parity $f_2$-secondary Reggeon and the unnatural parity anomalous $f_1$ exchanges.Comment: 7 pages, 3 figures, Late

Collective firm bankruptcies and phase transition in rating dynamics

We present a simple model of firm rating evolution. We consider two sources of defaults: individual dynamics of economic development and Potts-like interactions between firms. We show that such a defined model leads to phase transition, which results in collective defaults. The existence of the collective phase depends on the mean interaction strength. For small interaction strength parameters, there are many independent bankruptcies of individual companies. For large parameters, there are giant collective defaults of firm clusters. In the case when the individual firm dynamics favors dumping of rating changes, there is an optimal strength of the firm's interactions from the systemic risk point of view

Loneliness, social support and cardiovascular reactivity to laboratory stress

Self-reported or explicit loneliness and social support have been inconsistently associated with cardiovascular reactivity (CVR) to stress. The present study aimed to adapt an implicit measure of loneliness, and use it alongside the measures of explicit loneliness and social support, to investigate their correlations with CVR to laboratory stress. Twenty-five female volunteers aged between 18 and 39 years completed self-reported measures of loneliness and social support, and an Implicit Association Test (IAT) of loneliness. The systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) reactivity indices were measured in response to psychosocial stress induced in the laboratory. Functional support indices of social support were significantly correlated with CVR reactivity to stress. Interestingly, implicit, but not explicit, loneliness was significantly correlated with DBP reactivity after one of the stressors. No associations were found between structural support and CVR indices. Results are discussed in terms of validity of implicit versus explicit measures and possible factors that affect physiological outcomes

RNA polymerase II stalling promotes nucleosome occlusion and pTEFb recruitment to drive immortalization by Epstein-Barr virus

Epstein-Barr virus (EBV) immortalizes resting B-cells and is a key etiologic agent in the development of numerous cancers. The essential EBV-encoded protein EBNA 2 activates the viral C promoter (Cp) producing a message of ~120 kb that is differentially spliced to encode all EBNAs required for immortalization. We have previously shown that EBNA 2-activated transcription is dependent on the activity of the RNA polymerase II (pol II) C-terminal domain (CTD) kinase pTEFb (CDK9/cyclin T1). We now demonstrate that Cp, in contrast to two shorter EBNA 2-activated viral genes (LMP 1 and 2A), displays high levels of promoter-proximally stalled pol II despite being constitutively active. Consistent with pol II stalling, we detect considerable pausing complex (NELF/DSIF) association with Cp. Significantly, we observe substantial Cp-specific pTEFb recruitment that stimulates high-level pol II CTD serine 2 phosphorylation at distal regions (up to +75 kb), promoting elongation. We reveal that Cp-specific pol II accumulation is directed by DNA sequences unfavourable for nucleosome assembly that increase TBP access and pol II recruitment. Stalled pol II then maintains Cp nucleosome depletion. Our data indicate that pTEFb is recruited to Cp by the bromodomain protein Brd4, with polymerase stalling facilitating stable association of pTEFb. The Brd4 inhibitor JQ1 and the pTEFb inhibitors DRB and Flavopiridol significantly reduce Cp, but not LMP1 transcript production indicating that Brd4 and pTEFb are required for Cp transcription. Taken together our data indicate that pol II stalling at Cp promotes transcription of essential immortalizing genes during EBV infection by (i) preventing promoter-proximal nucleosome assembly and ii) necessitating the recruitment of pTEFb thereby maintaining serine 2 CTD phosphorylation at distal regions

Exclusive diffractive processes and the quark substructure of mesons

Exclusive diffractive processes on the nucleon are investigated within a model in which the quark-nucleon interaction is mediated by Pomeron exchange and the quark substructure of mesons is described within a framework based on the Dyson-Schwinger equations of QCD. The model quark-nucleon interaction has four parameters which are completely determined by high-energy $\pi N$ and $K N$ elastic scattering data. The model is then used to predict vector-meson electroproduction observables. The obtained $\rho$- and $\phi$-meson electroproduction cross sections are in excellent agreement with experimental data. The predicted $q^2$ dependence of $J/\psi$-meson electroproduction also agrees with experimental data. It is shown that confined-quark dynamics play a central role in determining the behavior of the diffractive, vector-meson electroproduction cross section. In particular, the onset of the asymptotic $1/q^4$ behavior of the cross section is determined by a momentum scale that is set by the current-quark masses of the quark and antiquark inside the vector meson. This is the origin of the striking differences between the $q^2$ dependence of $\rho$-, $\phi$- and $J/\psi$-meson electroproduction cross sections observed in recent experiments.Comment: 53 pages, 23 figures, revtex and epsfig. Minor additions to tex

Nonperturbative and perturbative aspects of photo- and electroproduction of vector mesons

We discuss various aspects of vector meson production, first analysing the interplay between perturbative and nonperturbative aspects of the QCD calculation. Using a general method adapted to incorporate both perturbative and nonpertubative aspects, we show that nonperturbative effects are important for all experimentally available values of the photon virtuality Q2. We compare the huge amount of experimental information now available with our theoretical results obtained using a specific nonperturbative model without free parameters, showing that quite simple features are able to explain the data.Comment: 19 page

Highly potent bispecific sybodies neutralize SARS-CoV-2

The ongoing COVID-19 pandemic represents an unprecedented global health crisis. Here, we report the identification of a synthetic nanobody (sybody) pair (Sb#15 and Sb#68) that can bind simultaneously to the SARS-CoV-2 spike-RBD and efficiently neutralize pseudotyped and live-viruses by interfering with ACE2 interaction. Two spatially-discrete epitopes identified by cryo-EM translated into the rational design of bispecific and tri-bispecific fusions constructs, exhibiting up to 100- and 1000-fold increase in neutralization potency. Cryo-EM of the sybody-spike complex further revealed a novel up-out RBD conformation. While resistant viruses emerged rapidly in the presence of single binders, no escape variants were observed in presence of the bispecific sybody. The multivalent bispecific constructs further increased the neutralization potency against globally-circulating SARS-CoV-2 variants of concern. Our study illustrates the power of multivalency and biparatopic nanobody fusions for the development of clinically relevant therapeutic strategies that mitigate the emergence of new SARS-CoV-2 escape mutants