Backward Reachability of Array-based Systems by SMT solving: Termination and Invariant Synthesis

The safety of infinite state systems can be checked by a backward reachability procedure. For certain classes of systems, it is possible to prove the termination of the procedure and hence conclude the decidability of the safety problem. Although backward reachability is property-directed, it can unnecessarily explore (large) portions of the state space of a system which are not required to verify the safety property under consideration. To avoid this, invariants can be used to dramatically prune the search space. Indeed, the problem is to guess such appropriate invariants. In this paper, we present a fully declarative and symbolic approach to the mechanization of backward reachability of infinite state systems manipulating arrays by Satisfiability Modulo Theories solving. Theories are used to specify the topology and the data manipulated by the system. We identify sufficient conditions on the theories to ensure the termination of backward reachability and we show the completeness of a method for invariant synthesis (obtained as the dual of backward reachability), again, under suitable hypotheses on the theories. We also present a pragmatic approach to interleave invariant synthesis and backward reachability so that a fix-point for the set of backward reachable states is more easily obtained. Finally, we discuss heuristics that allow us to derive an implementation of the techniques in the model checker MCMT, showing remarkable speed-ups on a significant set of safety problems extracted from a variety of sources.Comment: Accepted for publication in Logical Methods in Computer Scienc

Ein Me(e/h)r von Zeilen? Wie endlos sollten open-ended questions sein?

Die Fragebogenforschung belegt anhand zahlreicher Befunde, dass Respondenten formale Eigenschaften des Fragebogens heranziehen um ihre Antworten zu bilden. Der Forschungsfokus wurde hierbei überwiegend auf geschlossene Frageformate (z.B. Ratingskalen) gelegt; offene Frageformate, die insbesondere bei explorativen Fragestellungen und freien Meinungsäußerungen verwendet werden, wurden bislang kaum unter dieser Perspektive analysiert. Zwei experimentelle Fragebogenstudien untersuchen daher, wie bei freien Antworten auf eine Frage das Antwortverhalten durch unterschiedliche Zeilenvorgaben verändert wird. Es zeigt sich bei beiden Studien, dass mit steigender Zeilenvorgabe die Anzahl der zur Beantwortung gegebenen Wörter und Sätze steigt. Eine weitere Analyse vielzeiliger Antwortversionen und ein Vergleich mit einer Fragebogenversion ohne Zeilenvorgaben weisen auf eine Sättigungsgrenze und damit auf ein Optimum der angegebenen Zeilen hin. Implikationen für die Fragebogengestaltung werden diskutiert

A low‐temperature atomic force/scanning tunneling microscope for ultrahigh vacuum

We have built an ultrahigh vacuum atomic force/scanning tunneling microscope that works at 4.2 K. The microscope is incorporated into a very small chamber (100 ml) which can be evacuated and baked to UHV within a few hours by a specially designed valve. The instrument is about 20×20×70 mm3 in size and sturdy enough to operate without vibration isolation. The deflection of a microfabricated cantilever is detected by electron tunneling. Preliminary results show atomic resolution of HOPG in the STM mode and steps in KBr that range from one to four lattice constants in height at UHV conditions and 4.2 K

Mit welchem Wort soll ich´s benennen? Eine lexikalische und korpusbasierte Analyse deutscher Verben

Verbs either describe factual activities relating to objects (e.g. to plant) or interpersonal activities (e.g. to praise). These interpersonal verbs can be subdivided in action verbs (e.g. to hit) and state verbs (e.g. to admire). For action verbs as well as for state verbs it can be differentiated, if they induce either causal attributions to the subject (e.g. to hit, to frighten) or to the object (e.g. to punish, to admire) of the interaction. Previous linguistic and psychological research has predominantly used identical vocabularies from a small section of the whole language repertoire. Furthermore a comprehensive systematisation of Germen verbs based on the classification described above is still missing. To assess frequency estimates of these verbtypes for the whole language, an integrating analysis of different corpora of German language is conducted for the first time. Data record included more than 10 000 verbs. Frequency analyses confirm a dominance of factual activities compared to interpersonal verbs and within interpersonal verbs a dominance of action verbs. The resulting corpus can be used for representative analyses of interpersonal verbs and attributional analyses of linguistic data.Verben beschreiben entweder sachbezogene Vorgänge (z.B. anpflanzen) oder interpersonale Ereignisse (z.B. loben). Diese interpersonalen Verben können in Handlungs- (z. B. schlagen) und Zustandsverben (z.B. bewundern) unterteilt werden. Sowohl für Handlungs- als auch für Zustandsverben kann unterschieden werden, ob sie Kausalattributionen auf das Subjekt (z.B. schlagen, ängstigen) oder auf das Objekt(bestrafen, bewundern) der Interaktion auslösen. Bisherige sprachpsychologische Untersuchungen haben überwiegend identische Vokabeln aus einem kleinen Ausschnitt des Gesamtvokabulars verwendet. Auch fehlt eine umfassende Systematisierung deutscher Verben hinsichtlich der dargestellten Klassifikation. Um erstmals Häufigkeitsangaben der Verbverteilungen der gesamten Sprache zu erhalten, wird eine Analyse unterschiedlicher deutscher Verb- und Textkorpora durchgeführt, aus der ein Datensatz mit insgesamt über 10 000 Verben resultiert. Häufigkeitsanalysen belegen eine Dominanz sachbezogener im Vergleich zu interpersonalen Verben und innerhalb interpersonaler Verben eine deutliche Überzahl von Handlungsverben. Der erstellte Korpus erlaubt sprachlich repräsentative Analysen interpersonaler Verben, Aussagen zur sprachlichen Repräsentation interpersonaler Ereignisse und attributionstheoretische Analysen sprachlicher Daten

Crosslinking-MS analysis reveals RNA polymerase I domain architecture and basis of rRNA cleavage

RNA polymerase (Pol) I contains a 10-subunit catalytic core that is related to the core of Pol II and includes subunit A12.2. In addition, Pol I contains the heterodimeric subcomplexes A14/43 and A49/34.5, which are related to the Pol II subcomplex Rpb4/7 and the Pol II initiation factor TFIIF, respectively. Here we used lysine-lysine crosslinking, mass spectrometry (MS) and modeling based on five crystal structures, to extend the previous homology model of the Pol I core, to confirm the location of A14/43 and to position A12.2 and A49/34.5 on the core. In the resulting model of Pol I, the C-terminal ribbon (C-ribbon) domain of A12.2 reaches the active site via the polymerase pore, like the C-ribbon of the Pol II cleavage factor TFIIS, explaining why the intrinsic RNA cleavage activity of Pol I is strong, in contrast to the weak cleavage activity of Pol II. The A49/34.5 dimerization module resides on the polymerase lobe, like TFIIF, whereas the A49 tWH domain resides above the cleft, resembling parts of TFIIE. This indicates that Pol I and also Pol III are distantly related to a Pol II–TFIIS–TFIIF–TFIIE complex

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

Active Suppression of Early Immune Response in Tobacco by the Human Pathogen Salmonella Typhimurium

The persistence of enteric pathogens on plants has been studied extensively, mainly due to the potential hazard of human pathogens such as Salmonella enterica being able to invade and survive in/on plants. Factors involved in the interactions between enteric bacteria and plants have been identified and consequently it was hypothesized that plants may be vectors or alternative hosts for enteric pathogens. To survive, endophytic bacteria have to escape the plant immune systems, which function at different levels through the plant-bacteria interactions. To understand how S. enterica survives endophyticaly we conducted a detailed analysis on its ability to elicit or evade the plant immune response. The models of this study were Nicotiana tabacum plants and cells suspension exposed to S. enterica serovar Typhimurium. The plant immune response was analyzed by looking at tissue damage and by testing oxidative burst and pH changes. It was found that S. Typhimurium did not promote disease symptoms in the contaminated plants. Live S. Typhimurium did not trigger the production of an oxidative burst and pH changes by the plant cells, while heat killed or chloramphenicol treated S. Typhimurium and purified LPS of Salmonella were significant elicitors, indicating that S. Typhimurium actively suppress the plant response. By looking at the plant response to mutants defective in virulence factors we showed that the suppression depends on secreted factors. Deletion of invA reduced the ability of S. Typhimurium to suppress oxidative burst and pH changes, indicating that a functional SPI1 TTSS is required for the suppression. This study demonstrates that plant colonization by S. Typhimurium is indeed an active process. S. Typhimurium utilizes adaptive strategies of altering innate plant perception systems to improve its fitness in the plant habitat. All together these results suggest a complex mechanism for perception of S. Typhimurium by plants