Thermophysical and structural investigations of a CuTi- and a Zr-based bulk metallic glass, the influence of minor additions, and the relation to thermoplastic forming

Bulk metallic glasses (BMGs) surpass the strength of steels and at the same time possess the elasticity and formability of thermoplastic polymers. These favorable properties make them interesting candidates for industrial applications. In this work, the thermophysical properties and the structure of the CuTi-based BMG Vit101 (Cu47Ti34Zr11Ni8) and the Zr-based BMG Vit105 (Zr52.5Cu17.9Ni14.6Al10Ti5) are investigated. Special focus lies on the influence of minor additions of sulfur and phosphorus, as they increase the thermal stability of the alloys in the supercooled liquid region. The thermodynamic functions of the alloys are determined, and viscosity and kinetic fragility are measured around the glass transition and in the stable liquid. In-situ synchrotron X-ray scattering experiments are performed, elucidating the crystallization sequence upon heating and cooling. Minor additions retard the formation of the primary crystalline phase upon heating. Based on the diffraction data, the temperature evolution of structural differences between the alloys is discussed. Thermoplastic forming experiments on a variety of BMGs are performed and the deformation is discussed with respect to their thermophysical properties, leading to a description of the thermoplastic formability and the ideal processing region. These findings are transferred to thermoplastic consolidation experiments on amorphous powder, evaluating this technique for additive manufacturing. Finally, thermoplastic deformation experiments are conducted on the CuTi- and Zr-based alloys with minor additions. Minor additions can be used to significantly improve the thermoplastic formability and hence ease the industrial processability.Metallische Massivgläser (MMG) übertreffen Stähle in ihrer Festigkeit und besitzen gleichzeitig die Elastizität und Formbarkeit von thermoplastischen Polymeren. Diese vorteilhaften Eigenschaften machen sie für industrielle Anwendungen interessant. In dieser Arbeit werden die thermophysikalischen Eigenschaften und die Struktur des CuTi-basierten MMG Vit101 (Cu47Ti34Zr11Ni8) und des Zr-basierten MMG Vit105 (Zr52.5Cu17.9Ni14.6 Al10Ti5) untersucht. Der Fokus liegt dabei auf dem Einfluss von geringen Schwefel- und Phosphorzusätzen, da diese die thermische Stabilität der Legierungen in der unterkühlten Schmelze erhöhen. Die thermodynamischen Funktionen der Legierungen werden bestimmt und Viskosität und kinetische Fragilität werden um den Glasübergang und in der stabilen Flüssigkeit gemessen. In-situ Synchrotron Röntgenstreuexperimente werden durchgeführt, um die Kristallisationssequenz beim Erhitzen und Abkühlen aufzuklären. Schwefel- und Phosphorzusätze verzögern die Bildung der primären kristallinen Phase beim Erhitzen. Basierend auf den Beugungsdaten wird auch die Temperaturentwicklung von Strukturunterschieden zwischen den Legierungen diskutiert. Thermoplastische Umformversuche an verschiedenen MMG werden durchgeführt und die Verformung in Bezug auf die thermophysikalischen Kennwerte der Legierungen diskutiert, was zu einer Beschreibung der thermoplastischen Umformbarkeit und des idealen Verarbeitungsbereichs führt. Diese Erkenntnisse fließen in Konsolidierungsexperimente an amorphem Pulver ein und erlauben eine Bewertung dieser additiven Fertigungstechnik. Schließlich werden an den Legierungen auf CuTi- und Zr-Basis mit Schwefel- und Phosphorzusätzen thermoplastische Verformungsexperimente durchgeführt. Diese Zusätze können verwendet werden, um die thermoplastische Formbarkeit signifikant zu verbessern und damit die industrielle Verarbeitbarkeit zu erleichtern

Indirect DNA Sequence Readout by LAGLIDADG Homing Endonucleases.

In this issue of Structure, Lambert et al. (2016) describe extensive structural and functional work on meganucleases, the group of homing endonucleases most commonly adapted to genome engineering applications. The data are of interest to structural biologists, evolutionary biologists, protein designers, and genome engineers

Authoritarian Member States of the UN: Determinants of Autocratic Co-Sponsorship of Draft Resolututions as a Signal of Foreign Policy Coordination at the United Nations

Do autocracies cooperate internationally? This working paper investigates whether regime-type explains co-sponsorship patterns at the United Nations General Assembly. Co-sponsorship is a relatively costly signal of international cooperation at the UN, which is analyzed based on a novel dataset, including newly validated issue categories and co-sponsorship behavior on 14.995 draft resolutions. Theoretically, the paper unifies three strands of literature: the recent literature on autocratic regional organizations, the growing literature on foreign policy of autocratic regimes and the traditional analysis of the United Nations. The results suggest that regime-type plays a strong role in co-sponsorship behavior: democracies co-sponsor with their peers, whereas autocracies, in line with existing findings, cooperate overall less at the UN. They do, however, prefer to co-sponsor with one another over partners of other regime-types. This seems to be particularly true in issue areas where autocratic regimes could attempt to counter democratic norm-setting, such as human rights. There is mixed results concerning the effect of autocratic regional organizations on autocratic co-sponsorship. Preliminary results suggest at least some positive effect on autocracies and highlight the need for further research

Radicals in mutually permutable products of finite groups

AbstractLet the finite group G=AB be the mutually permutable product of the subgroups A and B and let F be a Fitting class. Then the F-radicals AF and BF of the factors A and B are mutually permutable. Using this, we also prove the inclusion G′∩AFBF⩽GF, which generalizes the fact that A∈F and B∈F implies G′∈F

Haloferax volcanii UbaA, catalytic engine for sampylation and sulfur transfer

The Small Archaeal Modifier Proteins (SAMPs) from Haloferax volcanii belong to the group of ubiquitin like proteins (Ubls) that act both as protein modifiers and sulfur carriers. The E1-like enzyme UbaA is essential for SAMP activation and therefore required for both sampylation and sulfur transfer. Here, we provide a commentary on the thorough characterization of UbaA by J. Maupin-Furlow and colleagues

Does Cancer of Unknown Primary (CUP) Truly Exist as a Distinct Cancer Entity?

Cancer of unknown primary (CUP) designates an enigmatic cancer entity with histologic confirmation of malignancy from a metastasis but no identifiable primary tumor in spite of a thorough diagnostic work-up. In this review, we discuss the validity of CUP as a distinct cancer entity as well as diagnostic pitfalls. As arguments against a distinct entity, the diagnosis of CUP is erroneous in some cases. Diagnostic pitfalls include incomplete diagnostics, uncertainty in classifying a lesion as either primary or metastasis and mistaking a relapse of an antecedent malignancy as CUP due to histologic and immunohistologic disparities. Given the high frequency of prior malignancies in CUP patients, relapse of an antecedent cancer should always be carefully excluded. Gene expression profiling-based classifier assays aim at aligning the molecular profile of CUP patients with established primary cancer patterns for highest congruency in order to identify the putative primary and treat accordingly. However, the spectrum of predicted putative primaries by molecular techniques is somewhat at odds with the primaries identified in autopsy series. Also, a first randomized clinical trial did not show superiority of primary-tailored therapy over unspecific platinum-based chemotherapy. CUP cases share an aggressive clinical course, atypical metastasis pattern, rapid progression of metastases, a generally poor response to chemotherapy and dismal outcome as distinct clinical features. Metastatic spread appears to take place in the early stages of tumor evolution, with CUP metastases subsequently undergoing genetic evolution toward a chromosomally highly complex and instable karyotype independent from the primary tumor. In clinical practice, the diagnosis of CUP is valid when no primary tumor is detectable. Treatment should ideally offer broad spectrum coverage across numerous malignancies and be well-established in CUP as is the case for carboplatin/paclitaxel and cisplatin / gemcitabine in particular, but it should also cover the most likely putative primary. The diligent diagnosis of CUP is warranted for clinical trials, making the eligibility process particularly laborious. In conclusion, we deem CUP a distinct cancer entity and the diagnosis accurate in most patient cases

Nei-like 1 (NEIL1) excises 5-carboxylcytosine directly and stimulates TDG-mediated 5-formyl and 5-carboxylcytosine excision

Thymine DNA glycosylase (TDG) and Nei-like 1 (NEIL1) have both been implicated in the base excision repair step of active DNA demethylation. The robust glycosylase activity of TDG on DNA substrates containing 5-formylcytosine (5fC) or 5-carboxylcytosine (5caC) is universally accepted, but the mode of action of NEIL1 is still debated. Based on genetic experiments, it has been suggested that NEIL1 acts redundantly with TDG and excises 5fC and 5caC directly. However, this result has been disputed, and it was suggested instead that NEIL1 is recruited by the monofunctional TDG for the 2′-deoxyribose excision step. Using purified human NEIL1 and its catalytically impaired P2T and E3Q variants as controls, we detect NEIL1 activity on 5caC, but not a 5fC containing dsDNA substrate. We confirm direct NEIL1 TDG binding and NEIL1 mediated 2′ deoxyribose excision downstream of TDG glycosylase activity. NEIL1 acts not only downstream of TDG, but also enhances TDG activity on 5fC or 5caC containing DNA. NEIL1 mediated enhancement of the TDG glycosylase activity is substrate specifc and does not occur for dsDNA with a T/G mismatch

CFSP: the capability-expectation gap revisited; a data-based analysis

The global political situation in Europe's neighbourhood has deteriorated dramatically in recent years, and this has had significant consequences for the European Union (EU). Conflicts are multiplying in Eastern Europe and in the Mediterranean Sea; Russia and China are showing increasingly expansive tendencies in South Eastern Europe; and the USA is becoming less and less reliable as a security provider for Europe. Against this background, it is striking that the Common Foreign and Security Policy (CFSP) still falls far short of what would be expected from the EU given the size of its inter­nal market. The unanimity principle in the Council of the EU is often blamed for this. However, an analysis of CFSP data shows that the Member States are clearly satisfied with symbolic policy measures, despite their political rhetoric. This situation will not be resolved either by introducing simple majority voting or with mere declarations of political will from governments. The dialogue on the future of Europe should be seen as an opportunity to remedy the inability to act in the field of foreign policy by har­monising the CFSP. (author's abstract

Type II and type V CRISPR effector nucleases from a structural biologist’s perspective

The type II and type V CRISPR effector nucleases Cas9 and Cpf1 are “universal” DNA endonucleases, which can be programmed by an appropriate crRNA or sgRNA strand to cleave almost any DNA duplex at a preselected position (constrained only by short, so-called PAMs). In this review, we briefly introduce CRISPR bacterial adaptive immunity as the biological context in which Cas9 and Cpf1 proteins operate, and then present the structural insights that have been obtained in the last two or three years that illustrate the mode of operation of these proteins. We describe the R-loop structures at the core of the Cas9 and Cpf1 complexes, and the structure of the 5’- or 3’-handles that help anchor the nucleic acid complexes to the proteins in a manner that is independent of the target sequence. Next, we describe the molecular architecture of the Cas9 and Cpf1 proteins. We illustrate how Cas9 and Cpf1 proteins scan double stranded DNA for so-called protospacer associated motifs (PAMs), we explain how the phosphate loop (PLL) and basic helix (BH) promote the separation of target and non-target DNA strands and the formation of hybrids between crRNA or sgRNA and the target strand of DNA. We also describe the current understanding of the catalytic mechanisms of RuvC and HNH domains, and a possible, but still very uncertain catalytic role of the Nuc domain. At the end of the review, we briefly summarize key developments that have initiated the field of genomic engineering using Cas9 or Cpf1 nucleases

RIBER/DIBER: a software suite for crystal content analysis in the studies of protein–nucleic acid complexes

Summary: Co-crystallization experiments of proteins with nucleic acids do not guarantee that both components are present in the crystal. We have previously developed DIBER to predict crystal content when protein and DNA are present in the crystallization mix. Here, we present RIBER, which should be used when protein and RNA are in the crystallization drop. The combined RIBER/DIBER suite builds on machine learning techniques to make reliable, quantitative predictions of crystal content for non-expert users and high-throughput crystallography