Limiting Properties of a Continuous Local Mean-Field Interacting Spin System : Hydrodynamic Limit, Propagation of Chaos, Energy Landscape and Large Deviations

A key interest in the study of interacting spin systems is the rigorous analysis of the macroscopic dynamical behaviour of systems that are described by their microscopic evolution. In this dissertation, we investigate unbounded spin systems where the microscopic evolution is modelled by stochastic differential equations (SDE). To each site of the discrete d-dimensional torus a spin is associated. The spins are distributed on the whole real line and evolve randomly according to the SDEs. The interaction between the spins is of local mean-field type, a long-range spatially variable interaction. The strength of the interaction between two spins depends on the difference of their positions on the torus. We aim to understand rigorously the time evolution of random variables as the size of the system increases. We prove in Chapter I the convergence of (space and spin dependent) empirical processes under proper rescaling to the classical solution of a nonlinear partial differential equation (PDE). This PDE is called hydrodynamic equation. We use the relative entropy method, to show this hydrodynamic limit result. To apply this method, we need to prove the existence of a classical solution of the hydrodynamic equation, which is non-linear and non-elliptic. In Chapter II we prove the propagation of chaos property of the system. We show that finitely many tagged spins are in the limit mutually independent. They evolve in the limit according to stochastic differential equations, without an interaction term. Instead (compared to the original SDEs), there is a term involving the solution of the hydrodynamic equation. In Chapter III we derive large deviation principles for the corresponding equilibrium system. We look at random variables that are distributed according to the invariant measure of the stochastic differential equation. For the empirical measure, defined by these random variables, we derive large deviation principles. We use a generalisation of Varadhan’s lemma that is stated and proven in Appendix C. In Chapter IV we analyse the landscape of the rate function of one of the equilibrium large deviation principles. We interpret this rate function as energy of the system in the limit. This is motivated by the fact that the hydrodynamic equation is the Wasserstein gradient flow of this rate function. We determine minima, critical values, bifurcation properties and lowest paths between minima. Finally in Chapter V we prove a dynamical large deviation principle for the empirical processes and the empirical measures. We derive different representations of the rate functions. By one of these representations it becomes obvious that it is exponentially unlikely that empirical processes deviate from the deterministic flow. In this chapter we allow the system to be more general, e.g. it can contain a random environment and a more general diffusion coefficient. The main distinctive features of the spin system considered in this dissertation are the relevance of the spatially fixed positions of the spins and the possibility of unbounded spins. The spatial positions of the spins affect the interaction and the initial distributions. Therefore new approaches in the proofs are necessary, in particular compared to mean field models. All these results can be used in the future to study long time phenomena like tunnelling and metastability

Alteration of the Route to Menaquinone towards Isochorismate-Derived Metabolites

Chorismate and isochorismate constitute branch-point intermediates in the biosynthesis of many aromatic metabolites in microorganisms and plants. To obtain unnatural compounds, we modified the route to menaquinone in Escherichia coli. We propose a model for the binding of isochorismate to the active site of MenD ((1R,2S, 5S,6S)-2-succinyl-5-enolpyruvyl-6-hydroxycyclohex-3-ene-1-carboxylate (SEPHCHC) synthase) that explains the outcome of the native reaction with α-ketoglutarate. We have rationally designed variants of MenD for the conversion of several isochorismate analogues. The double-variant Asn117Arg–Leu478Thr preferentially converts (5S,6S)-5,6-dihydroxycyclohexa-1,3-diene-1-carboxylate (2,3-trans-CHD), the hydrolysis product of isochorismate, with a >70-fold higher ratio than that for the wild type. The single-variant Arg107Ile uses (5S,6S)-6-amino-5-hydroxycyclohexa-1,3-diene-1-carboxylate (2,3-trans-CHA) as substrate with >6-fold conversion compared to wild-type MenD. The novel compounds have been made accessible in vivo (up to 5.3 g L−1). Unexpectedly, as the identified residues such as Arg107 are highly conserved (>94 %), some of the designed variations can be found in wild-type SEPHCHC synthases from other bacteria (Arg107Lys, 0.3 %). This raises the question for the possible natural occurrence of as yet unexplored branches of the shikimate pathway.Fil: Fries, Alexander Erich. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias de la Tierra y Ambientales de La Pampa. Universidad Nacional de La Pampa. Facultad de Ciencias Exactas y Naturales. Instituto de Ciencias de la Tierra y Ambientales de La Pampa; Argentina. Albert Ludwigs University of Freiburg; AlemaniaFil: Mazzaferro, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias de la Tierra y Ambientales de La Pampa. Universidad Nacional de La Pampa. Facultad de Ciencias Exactas y Naturales. Instituto de Ciencias de la Tierra y Ambientales de La Pampa; Argentina. Albert Ludwigs University of Freiburg; AlemaniaFil: Grüning, Björn. Albert Ludwigs University of Freiburg; AlemaniaFil: Bisel, Philippe. Albert Ludwigs University of Freiburg; AlemaniaFil: Stibal, Karin. Albert Ludwigs University of Freiburg; AlemaniaFil: Buchholz, Patrick C. F.. University of Stuttgart; AlemaniaFil: Pleiss, Jürgen. Universität Stuttgart;Fil: Sprenger, Georg A.. Universität Stuttgart;Fil: Müller, Michael. Albert Ludwigs University of Freiburg; Alemani

Increase of the mean inner Coulomb potential in Au clusters induced by surface tension and its implication for electron scattering

Electron holography in a transmission electron microscope was applied to measure the phase shift induced by Au clusters as a function of the cluster size. Large phase shifts Df observed for small Au clusters cannot be described by the well-known equation Df=C_E V_0 t (C_E: interaction constant, V_0: mean inner Coulomb potential (MIP) of bulk gold, t: cluster thickness). The rapid increase of the Au MIP with decreasing cluster size derived from Df, can be explained by the compressive strain of surface atoms in the cluster

Diurnal variations in multi-sensor wearable-derived sleep characteristics in morning- and evening-type shift workers under naturalistic conditions

Consumer-grade, multi-sensor, rest-activity trackers may be powerful tools, to help optimize rest-activity management in shiftwork populations undergoing circadian misalignment. Nevertheless, performance testing of such devices under field conditions is scarce. We previously validated Fitbit Charge 2TM against home polysomnography and now evaluated the potential of this device to document differences in rest-activity behavior, including sleep macrostructure, in first-responder shift workers in an operational setting. We continuously monitored 89 individuals (54% females; mean age: 33.9 ± 7.7 years) for 32.5 ± 9.3 days and collected 2,974 individual sleep episodes scattered around the clock. We stratified the study participants according to their self-reported circadian preference on the reduced Horne-Östberg Morningness-Evening Questionnaire (rMEQ; the scores from 4 participants were missing). Fitbit estimates of sleep duration, wakefulness after sleep onset (WASO), REM sleep percentage in the first NREM-REM sleep cycle, and REM sleep latency formed approximately sinusoidal oscillations across 24 hours. Generalized additive mixed model analyses revealed that the phase position of sleep duration minimum was delayed by 2.8 h in evening types (ET; rMEQ ≤ 11; n = 20) and by 2.6 h in intermediate types (IT; 11 < rMEQ < 18; n = 45) when compared to morning types (MT; rMEQ ≥ 18; n = 20). Similarly, the phase position of WASO was delayed by 2.7 h in ET compared to MT. While nocturnal sleep duration did not differ among the three groups, sleep episodes during the biological day decreased in duration from ET to IT to MT. Together, the findings support the notion that a consumer-grade, rest-activity tracker allows estimation of behavioral sleep/wake cycles and sleep macrostructure in shift workers under naturalistic conditions that are consistent with their self-reported chronotype

AGO Recommendations for the surgical therapy of breast cancer: update 2022

The recommendations of the AGO Breast Committee on the surgical therapy of breast cancer were last updated in March 2022 (www.ago-online.de). Since surgical therapy is one of several partial steps in the treatment of breast cancer, extensive diagnostic and oncological expertise of a breast surgeon and good interdisciplinary cooperation with diagnostic radiologists is of great importance. The most important changes concern localization techniques, resection margins, axillary management in the neoadjuvant setting and the evaluation of the meshes in reconstructive surgery. Based on meta-analyses of randomized studies, the level of recommendation of an intraoperative breast ultrasound for the localization of non-palpable lesions was elevated to “++”. Thus, the technique is considered to be equivalent to wire localization, provided that it is a lesion which can be well represented by sonography, the surgeon has extensive experience in breast ultrasound and has access to a suitable ultrasound device during the operation. In invasive breast cancer, the aim is to reach negative resection margins (“no tumor on ink”), regardless of whether an extensive intraductal component is present or not. Oncoplastic operations can also replace a mastectomy in selected cases due to the large number of existing techniques, and are equivalent to segmental resection in terms of oncological safety at comparable rates of complications. Sentinel node excision is recommended for patients with cN0 status receiving neoadjuvant chemotherapy after completion of chemotherapy. Minimally invasive biopsy is recommended for initially suspect lymph nodes. After neoadjuvant chemotherapy, patients with initially 1 – 3 suspicious lymph nodes and a good response (ycN0) can receive the targeted axillary dissection and the axillary dissection as equivalent options

AGO recommendations for the surgical therapy of the axilla after neoadjuvant chemotherapy: 2021 Update

For many decades, the standard procedure to treat breast cancer included complete dissection of the axillary lymph nodes. The aim was to determine histological node status, which was then used as the basis for adjuvant therapy, and to ensure locoregional tumour control. In addition to the debate on how to optimise the therapeutic strategies of systemic treatment and radiotherapy, the current discussion focuses on improving surgical procedures to treat breast cancer. As neoadjuvant chemotherapy is becoming increasingly important, the surgical procedures used to treat breast cancer, whether they are breast surgery or axillary dissection, are changing. Based on the currently available data, carrying out SLNE prior to neoadjuvant chemotherapy is not recommended. In contrast, surgical axillary management after neoadjuvant chemotherapy is considered the procedure of choice for axillary staging and can range from SLNE to TAD and ALND. To reduce the rate of false negatives during surgical staging of the axilla in pN+(CNB) stage before NACT and ycN0 after NACT, targeted axillary dissection (TAD), the removal of > 2 SLNs (SLNE, no untargeted axillary sampling), immunohistochemistry to detect isolated tumour cells and micro-metastases, and marking positive lymph nodes before NACT should be the standard approach. This most recent update on surgical axillary management describes the significance of isolated tumour cells and micro-metastasis after neoadjuvant chemotherapy and the clinical consequences of low volume residual disease diagnosed using SLNE and TAD and provides an overview of this year's AGO recommendations for surgical management of the axilla during primary surgery and in relation to neoadjuvant chemotherapy

Khresmoi Professional: Multilingual Semantic Search for Medical Professionals

There is increasing interest in and need for innovative solutions to medical search. In this paper we present the EU funded Khresmoi medical search and access system, currently in year 3 of 4 of development across 12 partners . The Khresmoi system uses a component based architecture housed in the cloud to allow for the development of several innovative applications to support target users medical information needs. The Khresmoi search systems based on this architecture have been designed to support the multilingual and multimod al information needs of three target groups the general public, general practitioners and consultant radiologists. In this paper we focus on the presentation of the systems to support the latter two groups using semantic, multilingual text and image based (including 2D and 3D radiology images) search

Metabolism of halophilic archaea

In spite of their common hypersaline environment, halophilic archaea are surprisingly different in their nutritional demands and metabolic pathways. The metabolic diversity of halophilic archaea was investigated at the genomic level through systematic metabolic reconstruction and comparative analysis of four completely sequenced species: Halobacterium salinarum, Haloarcula marismortui, Haloquadratum walsbyi, and the haloalkaliphile Natronomonas pharaonis. The comparative study reveals different sets of enzyme genes amongst halophilic archaea, e.g. in glycerol degradation, pentose metabolism, and folate synthesis. The carefully assessed metabolic data represent a reliable resource for future system biology approaches as it also links to current experimental data on (halo)archaea from the literature

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe