Poly[[μ-1,4-anhydro­erythritolato-di-μ-aqua-sodium(I)] monohydrate]

In the title compound, {[Na(C4H7O3)(H2O)2]·H2O}n, the sodium ion is octa­hedrally coordinated by two bridging 1,4-anhydro­erythritolate ligands, unexpectedly coordinated by the ring oxygen and four water ligands. This bonding pattern leads to one-dimensional anti­tactical polymeric chains along [010]. One of the exocyclic O atoms of the anhydro­erythritolate group is an acceptor in four hydrogen bonds, giving further evidence that it is deprotonated

H3K9me is dispensable for C. elegans development but essential for genome integrity

Epigenetic mechanisms as key regulators of chromatin biology have been the focus of intensive research over the past 20 years. It has become clear that epigenetic pathways play a major role in the pathology of numerous diseases ranging from neurodegenerative repeat expansion diseases to certain cases of cancer. One of the best-studied epigenetic marks is the methylation of histone 3 on lysine 9 (H3K9me). H3K9 methylation plays a major role in silencing parts of the genome. H3K9me domains encompass a broad variety of sequences, ranging from single genes to repetitive elements. In addition to its function in transcriptional repression, H3K9me is implicated in chromosome segregation and the maintenance of genome integrity. Lately the H3K9me mark received even more attention due to an identified role in mis-silencing of tumor suppressor genes during the development of cancer. Consequently, some of the first drugs to manipulate H3K9me are tested as cancer therapies. Studying H3K9me in complex multicellular organisms has so far proven to be difficult. Both mice and Drosophila have at least five histone methyl transferase (HMTs) enzymes that are essential and partially redundant, allowing only for the study of partial reductions in H3K9me. In the nematode C. elegans our lab identified the two methyl transferases, essential for all H3K9 methyltaion throughout development MET-2 and SET-25. Astonishingly C. elegans is viable and fertile in the complete absence of H3K9me. This allowed us to use the met-2 set-25 mutant to characterize the development of a multicellular organism in the absence of this central heterochromatic mark and ask: what is the main role of H3K9me in C. elegans and is there a functional difference between H3K9me3 and H3K9me1, me2 states. The major site of H3K9 methylation are repetitive elements (RE). Chapter 2 will therefore give an overview of the current state of knowledge on RE classes found in the genome, how they are controlled and what danger they pose. A special focus is put on the interplay of different epigenetic silencing mechanisms, with H3K9me at its center, that ensure repeat silencing at all stages of development. Chapter 3 contains the majority of the experimental work characterizing the role of H3K9me in C. elegans. Starting with the observation of a striking increase of DNA damage checkpoint dependent apoptosis in met-2 set-25 germlines, we identify increased mutagenesis specifically in the context of derepressed RE. We suggest that RNA:DNA hybrids that accumulate on derepressed RE drive these mutations by provoking conflicts with the DNA replication machinery. In the second experimental part (Chapter 4) we closely analyze the distinct contribution of H3K9me2 and me3 to the roles identified in Chapter 3. We identify a partially interdependent role of MET-2 and SET-25, making SET-25 dependent on, and at the same time, redundant with MET-2 at the majority of its target loci. Similarly, the majority of H3K9me associated phenotypes are not, or only mildly observed in worms lacking H3K9me3, arguing for very similar abilities in silencing of H3K9me2 and me3. Besides quantitative differences in the number of transposable elements and genes depending on MET-2 or SET-25 for their transcriptional silencing, tandem repeats depended exclusively on MET-2. Interestingly, the identified silencing pathways occur in different nuclear sub-compartments. In contrast to our previous model we found that SET-25 dependent silencing occurs all over the genome, while MET-2 repressed regions are enriched at the nuclear periphery. The tethering of endogenous heterochromatic sequences was also found to completely depend on the function of MET-2 and was independent of SET-25. We speculate that peripheral localization is involved in the MET-2 silencing function. In the same study we also take an additional unbiased approach to identify previously overlooked roles of H3K9me by performing a whole genome synthetic lethality screen with the met-2 set-25 double mutant. The hits were then further tested in each of the single mutants, met-2 and set-25, showing exclusive genetic interaction with met-2. Finding many factors shown or suggested to be involved in RNA:DNA hybrid prevention and DNA damage repair, we conclude that the role of H3K9me in genome integrity described in Chapter 3 as one of its most important roles in C. elegans. This thesis thereby provides evidence how repetitive elements derepression in the absence of H3K9me can lead to the occurrence of spontaneous DNA damage, putting a special emphasis on the danger of tandem repeat expression

Ensuring referential integrity under causal consistency

Referential integrity (RI) is an important correctness property of a shared, distributed object storage system. It is sometimes thought that enforcing RI requires a strong form of consistency. In this paper, we argue that causal consistency suffices to maintain RI. We support this argument with pseudocode for a reference CRDT data type that maintains RI under causal consistency. QuickCheck has not found any errors in the model

Changing the Magnetic Configurations of Nanoclusters Atom-by-Atom

The Korringa-Kohn-Rostoker Green (KKR) function method for non-collinear magnetic structures was applied on Mn and Cr ad-clusters deposited on the Ni(111) surface. By considering various dimers, trimers and tetramers, a large amount of collinear and non-collinear magnetic structures is obtained. Typically all compact clusters have very small total moments, while the more open structures exhibit sizeable total moments, which is a result of the complex frustration mechanism in these systems. Thus, as the motion of a single adatom changes the cluster structure from compact to open and vice versa, this can be considered as a magnetic switch, which via the local exchange field of the adatom allows to switch the cluster moment on and off, and which might be useful for future nanosize information storage.Comment: 7 page

When general practitioners don't feel appreciated by their patients: prospective effects on well-being and work-family conflict in a Swiss Longitudinal Study

Background: Impaired well-being and high work-family conflict are critical issues among GPs. This research examined an understudied psychosocial risk factor for these outcomes, namely GPs' perception that they invest more in the relationship with their patients than what they receive in return (i.e. lack of reward in their relationship with patients). Objective: To test the effect of lack of reward as a risk factor for poor well-being and work-family conflict among GPs. Methods: Longitudinal study (12 months time lag). 272 GPs in Switzerland [mean age 54.5 (SD = 8.3), 73% male] volunteered to participate in the study. 270 participants completed the baseline survey and 252 completed the follow-up survey. Of these, six retired between the baseline and the follow-up survey, resulting in a sample size of 246 participants at t2. Outcome measures were burnout, sleep problems, self-perceived health and work-family conflict. Results: Strength and direction of prospective effects were tested using cross-lagged models. Lack of reward was related to an increase in emotional exhaustion (β = 0.15), sleep problems (β = 0.16) and work-family conflict (β = 0.19) and a decrease in self-perceived health (β = −0.17). Effects on depersonalization and personal accomplishment were not significant. Regarding reversed effects of impaired well-being on lack of reward, emotional exhaustion (β = 0.14) and self-perceived health (β = −0.13) predicted future level of lack of reward. Conclusion: Lack of reward by patients is a risk factor in GPs' mental healt

Jakob Meisenheimer - Mehr als nur Komplexe

Mit diesem Beitrag wird ein Überblick über das breite wissenschaftliche Werk Jakob Meisenheimers gegeben. Sein erster großer Wurf gelang ihm mit der korrekten Interpretation der Additionsprodukte zwischen Nitroaromaten und Basen (Meisenheimer-Komplexe). Ein weiterer Meilenstein war die Revision der syn-anti-Zuordnungen stereoisomerer Oxime und die daraus abgeleitete Erkenntnis, dass die Beckmann-Umlagerung unter Wanderung des anti-ständigen Restes verläuft. Mit eleganten Experimenten untermauerte Meisenheimer die Hantzsch-Wernersche Ammoniumtheorie über die Vierbindigkeit des Stickstoffs in Ammoniumverbindungen. Meisenheimer gelangen die ersten Racematspaltungen chiraler Amin- und Phosphinoxide und er erkannte früh, dass Amine eine pyramidale Struktur besitzen müssen, obwohl es nie gelungen war, unsymmetrisch substituierte tert. Amine in optische Antipoden zu spalten. Den Widerspruch erklärte er mit einem schnellen Hin- und Herschwingen zwischen den beiden Antipoden mit der ebenen Anordnung als Mittellage. Zahlreiche Beispiele aus der Literatur, in denen Isomeriefälle mit einem „asymmetrischen Stickstoffatom“ erklärt wurden, widerlegte Meisenheimer. Als „Nebenprodukt“ seiner Arbeiten zur Racematspaltung von tert. Aminoxiden entdeckte Meisenheimer die Umlagerung von Allyl/Benzyl-substituierten Aminoxiden in O-Allyl/Benzylhydroxylamine (Meisenheimer-Umlagerung). Auf dem damals noch jungen Gebiet der Biochemie untersuchte Meisenheimer den Chemismus der alkoholischen, Milch- und Buttersäuregärung und bearbeitete zusammen mit Buchner das Thema zellfreie Gärungsprozesse. In einer Serie zur Konstitution und Reaktivität der Grignardverbindungen gelang Meisenheimer u.a. die Aufklärung der Grignard-Reduktion, die je nach Struktur und Bedingungen mit der eigentlichen Grignard-Addition konkurrieren kann. In mechanistischen Studien zur Substitution und Addition lieferte Meisenheimer erste Erklärungen zur Waldenschen Umkehr, der trans-Addition von Brom an Doppelbindungen und der „anormalen“ Substitution an Allylverbindungen.This contribution delivers an overview over the wide scientific work of Jakob Meisenheimer. His first notable achievement was the correct interpretation of the adduct formed between nitro-group containing arenes and bases (Meisenheimer complexes). A further milestone was the revision of the syn-anti assignment of stereoisomeric oximes and the consequential realization, that in the course of the Beckmann rearrangement a migration of the residue in the anti-position occurs. With elegant experiments, Meisenheimer supported the ammonium theory of Hantzsch and Werner about the tetravalency of nitrogen in ammonium compounds. Meisenheimer succeeded with the first racemate separation of chiral amine oxides and phosphine oxides and he recognized early, that amines must have a pyramidal structure, although a separation of unsymmetrically substituted tert. amines in optical antipodes never succeeded. He explained this discrepancy by a fast inversion between the two antipodes, with a planar arrangement as the middle position. Meisenheimer disproved many examples in the literature, in which isomerism was explained by an „asymmetrical nitrogen atom“. As a „by-product“ of his work to separate the racemates of tert. amine oxides, Meisenheimer discovered the rearrangement of allyl/benzyl substituted amino oxides in O-allyl/benzylhydroxylamines (Meiseheimer rearrangement). In the, at that time, young area of biochemistry Meisenheimer investigated the chemism of the alcoholic, lactic acid and butyric fermentation and together with Buchner worked on cell-free fermentation processes. In a series on the structure and reactivity of Grignard reagents, Meisenheimer succeeded amongst other things in explaining the Grignard reduction, which depending on structure and conditions can compete with the actual Grignard addition. In mechanistic studies on substitution and addition, Meisenheimer delivered the first explanation for the Walden inversion, the trans-addition of bromine to double bonds and the “abnormal” substitution of allyl compounds

4-Butyl-1-(2,3,4-tri-O-acetyl-β-l-fuco­pyranos­yl)-1H-1,2,3-triazole

The title compound, C18H27N3O7, was synthesized by CuI-catalysed coupling of an azide with an alkyne as part of a study into the synthesis of N-glycosyl-1,2,3-triazoles. The crystal structure confirms the selective formation of the β-conformer of the pyran­ose N-glycoside, thus confirming the retention of stereochemistry during heterocycle formation with the N-glycosyl triazole group occupying the equatorial position at the anomeric C atom. The structure exhibits two crystallographically independent mol­ecules (A and B) with essentially identical conformations with a weighted r.m.s. deviation of only 0.09 Å. The mol­ecules are arranged in layers with hydro­phobic and more polar sections built from the butyl triazole units on the one hand and the more polar moieties dominated by the carbohydrate units on the other. Within the polar layers, inter­molecular inter­actions are dominated by a three-dimensional network of weak C—H⋯O hydrogen bonds with the acetyl keto O atoms as the hydrogen-bond acceptors. The triazole units inter­act with each other via C—H⋯N hydrogen bonds which connect the mol­ecules into two infinite chains of mol­ecules made up of either A mol­ecules or B mol­ecules that stretch parallel to each other along [100]. Between the butyl groups no directional inter­actions are observed

Replication-Aware Linearizability

Geo-distributed systems often replicate data at multiple locations to achieve availability and performance despite network partitions. These systems must accept updates at any replica and propagate these updates asynchronously to every other replica. Conflict-Free Replicated Data Types (CRDTs) provide a principled approach to the problem of ensuring that replicas are eventually consistent despite the asynchronous delivery of updates. We address the problem of specifying and verifying CRDTs, introducing a new correctness criterion called Replication-Aware Linearizability. This criterion is inspired by linearizability, the de-facto correctness criterion for (shared-memory) concurrent data structures. We argue that this criterion is both simple to understand, and it fits most known implementations of CRDTs. We provide a proof methodology to show that a CRDT satisfies replication-aware linearizability which we apply on a wide range of implementations. Finally, we show that our criterion can be leveraged to reason modularly about the composition of CRDTs