Evidence for Suzuki–Miyaura cross-couplings catalyzed by ligated Pd3-clusters: from cradle to grave

Pdn clusters offer unique selectivity and exploitable reactivity in catalysis. Understanding the behavior of Pdn clusters is thus critical for catalysis, applied synthetic organic chemistry and greener outcomes for precious Pd. The Pd3 cluster, [Pd3(μ-Cl)(μ-PPh2)2(PPh3)3][Cl] (denoted as Pd3Cl2), which exhibits distinctive reactivity, was synthesized and immobilized on a phosphine-functionalized polystyrene resin (denoted as immob-Pd3Cl2). The resultant material served as a tool to study closely the role of Pd3 clusters in a prototypical Suzuki–Miyaura cross-coupling of 4-fluoro-1-bromobenzene and 4-methoxyphenyl boronic acid at varying low Pd ppm concentrations (24, 45, and 68 ppm). Advanced heterogeneity tests such as Hg poisoning and the three-phase test showed that leached mononuclear or nanoparticulate Pd are unlikely to be the major active catalyst species under the reaction conditions tested. EXAFS/XANES analysis from (pre)catalyst and filtered catalysts during and after catalysis has shown the intactness of the triangular structure of the Pd3X2 cluster, with exchange of chloride (X) by bromide during catalytic turnover of bromoarene substrate. This finding is further corroborated by treatment of immob-Pd3Cl2 after catalyzing the Suzuki–Miyaura reaction with excess PPh3, which releases the cluster from the polymer support and so permits direct observation of [Pd3(μ-Br)(μ-PPh2)2(PPh3)3]+ ions by ESI-MS. No evidence is seen for a proposed intermediate in which the bridging halogen on the Pd3 motif is replaced by an aryl group from the organoboronic acid, i.e. formed by a transmetallation-first process. Our findings taken together indicate that the ‘Pd3X2’ motif is an active catalyst species, which is stabilized by being immobilized, providing a more robust Pd3 cluster catalyst system. Non-immobilized Pd3Cl2 is less stable, as is followed by stepwise XAFS of the non-immobilized Pd3Cl2, which gradually changes to a species consistent with ‘Pdx(PPh3)y’ type material. Our findings have far-reaching future implications for Pd3 cluster involvement in catalysis, showing that immobilization of Pd3 cluster species offers advantages for rigorous mechanistic examination and applied chemistries

The Reporting on ERAS Compliance, Outcomes, and Elements Research (RECOvER) Checklist: A Joint Statement by the ERAS^® and ERAS^® USA Societies.

Enhanced recovery after surgery (ERAS) programs are multimodal care pathways designed to minimize the physiological and psychological impact of surgery for patients. Increased compliance with ERAS guidelines is associated with improved patient outcomes across surgical types. As ERAS programs have proliferated, an unintentional effect has been significant variation in how ERAS-related studies are reported in the literature. To improve the quality of ERAS reporting, ERAS <sup>®</sup> USA and the ERAS <sup>®</sup> Society launched an effort to create an instrument to assist authors in manuscript preparation. Criteria to include were selected by a combination of literature review and expert opinion. The final checklist was refined by group consensus. The Societies present the Reporting on ERAS Compliance, Outcomes, and Elements Research (RECOvER) Checklist. The tool contains 20 items including best practices for reporting clinical pathways, compliance auditing, and formatting guidelines. The RECOvER Checklist is intended to provide a standardized framework for the reporting of ERAS-related studies. The checklist can also assist reviewers in evaluating the quality of ERAS-related manuscripts. Authors are encouraged to include the RECOvER Checklist when submitting ERAS-related studies to peer-reviewed journals

In depth analysis of kinase cross screening data to identify CaMKK2 inhibitory scaffolds

The calcium/calmodulin‐dependent protein kinase kinase 2 (CAMKK2) activates CAMK1, CAMK4, AMPK, and AKT, leading to numerous physiological responses. The deregulation of CAMKK2 is linked to several diseases, suggesting the utility of CAMKK2 inhibitors for oncological, metabolic and inflammatory indications. In this work, we demonstrate that STO‐609, frequently described as a selective inhibitor for CAMKK2, potently inhibits a significant number of other kinases. Through an analysis of literature and public databases, we have identified other potent CAMKK2 inhibitors and verified their activities in differential scanning fluorimetry and enzyme inhibition assays. These inhibitors are potential starting points for the development of selective CAMKK2 inhibitors and will lead to tools that delineate the roles of this kinase in disease biology.252CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP465651/2014-32013/50724-5; 2014/50897-0; 2019/14275-

Biobased economy: de potentie van eiwitten voor technische toepassingen

Eiwitten zijn, behalve essentiële bouwstoffen voor mens en dier, tevens bruikbaar voor toepassingen in bijvoorbeeld shampoos, bioplastics, coatings of lijmen. In deze studie is een inventarisatie gemaakt van zowel de huidige beschikbare eiwitbronnen als de bronnen waar in de toekomst veel van verwacht wordt. Mits er voldoende efficiënt met grondstoffen wordt omgesprongen, kunnen voor zowel food als non-food toepassingen wereldwijd voldoende eiwitten worden geproduceerd. Het is wel belangrijk dat de eiwitten die door bioraffinage uit grondstoffen worden gehaald, hun unieke eigenschappen behouden

Spelling errors and keywords in born-digital data: a case study using the Teenage Health Freak Corpus

The abundance of language data that is now available in digital form, and the rise of distinct language varieties that are used for digital communication, means that issues of non-standard spellings and spelling errors are, in future, likely to become more prominent for compilers of corpora. This paper examines the effect of spelling variation on keywords in a born-digital corpus in order to explore the extent and impact of this variation for future corpus studies. The corpus used in this study consists of e-mails about health concerns that were sent to a health website by adolescents. Keywords are generated using the original version of the corpus and a version with spelling errors corrected, and the British National Corpus (BNC) acts as the reference corpus. The ranks of the keywords are shown to be very similar and, therefore, suggest that, depending on the research goals, keywords could be generated reliably without any need for spelling correction

Towards a new philosophy of engineering: structuring the complex problems from the sustainability discourse

This dissertation considers three broad issues which emerge from the sustainability discourse. First is the nature of the discourse itself, particularly the underlying philosophical positions which are represented. Second, is the nature of the highly complex types of problem which the discourse exposes. And third is whether the engineering profession, as it is practised currently, is adequate to deal with such problems. The sustainability discourse exposes two distinct, fundamentally irreconcilable philosophical positions. The first, “sustainable development”, considers humanity to be privileged in relation to all other species and ecosystems. It is only incumbent upon us to look after the environment to the extent to which it is in our interests to do so. The second, “sustainability”, sees humanity as having no special moral privilege and recognises the moral status of other species, ecosystems, and even wilderness areas. Thus, sustainability imposes upon us a moral obligation to take their status into account and not to degrade or to destroy them. These two conflicting positions give rise to extremely complex problems. An innovative taxonomy of problem complexity has been developed which identifies three broad categories of problem. Of particular interest in this dissertation is the most complex of these, referred to here as the Type 3 problem. The Type 3 problem recognises the systemic complexity of the problem situation but also includes differences of the domain of interests as a fundamental, constituent part of the problem itself. Hence, established systems analysis techniques and reductionist approaches do not work. The domain of interests will typically have disparate ideas and positions, which may be entirely irreconcilable. The dissertation explores the development of philosophy of science, particularly in the last 70 years. It is noted that, unlike the philosophy of science, the philosophy of engineering has not been influenced by developments of critical theory, cultural theory, and postmodernism, which have had significant impact in late 20th-century Western society. This is seen as a constraint on the practice of engineering. Thus, a set of philosophical principles for sustainable engineering practice is developed. Such a change in the philosophy underlying the practice of engineering is seen as necessary if engineers are to engage with and contribute to the resolution of Type 3 problems. Two particular challenges must be overcome, if Type 3 problems are to be satisfactorily resolved. First, issues of belief, values, and morals are central to this problem type and must be included in problem consideration. And second, the problem situation is usually so complex that it challenges the capacity of human cognition to deal with it. Consequently, extensive consideration is given to cognitive and behavioural psychology, in particular to choice, judgement and decision-making in uncertainty. A novel problem-structuring approach is developed on three levels. A set philosophical foundation is established; a theoretical framework, based on general systems theory and established behavioural and cognitive psychological theory, is devised; and a set of tools is proposed to model Type 3 complex problems as a dynamic systems. The approach is different to other systems approaches, in that it enables qualitative exploration of the system to plausible, hypothetical disturbances. The problem-structuring approach is applied in a case study, which relates to the development of a water subsystem for a major metropolis (Sydney, Australia). The technique is also used to critique existing infrastructure planning processes and to propose an alternative approach

Unwrapping Closed Timelike Curves

Closed timelike curves (CTCs) appear in many solutions of the Einstein equation, even with reasonable matter sources. These solutions appear to violate causality and so are considered problematic. Since CTCs reflect the global properties of a spacetime, one can attempt to change its topology, without changing its geometry, in such a way that the former CTCs are no longer closed in the new spacetime. This procedure is informally known as unwrapping. However, changes in global identifications tend to lead to local effects, and unwrapping is no exception, as it introduces a special kind of singularity, called quasi-regular. This "unwrapping" singularity is similar to the string singularities. We give two examples of unwrapping of essentially 2+1 dimensional spacetimes with CTCs, the Gott spacetime and the Godel universe. We show that the unwrapped Gott spacetime, while singular, is at least devoid of CTCs. In contrast, the unwrapped Godel spacetime still contains CTCs through every point. A "multiple unwrapping" procedure is devised to remove the remaining circular CTCs. We conclude that, based on the two spacetimes we investigated, CTCs appearing in the solutions of the Einstein equation are not simply a mathematical artifact of coordinate identifications, but are indeed a necessary consequence of General Relativity, provided only that we demand these solutions do not possess naked quasi-regular singularities.Comment: 29 pages, 9 figure

Reactivity of a Dinuclear PdIComplex [Pd2(μ-PPh2)(μ2-OAc)(PPh3)2] with PPh3 : Implications for Cross-Coupling Catalysis Using the Ubiquitous Pd(OAc)2/nPPh3Catalyst System

[PdI2(μ-PPh2)(μ2-OAc)(PPh3)2] is the reduction product of PdII(OAc)2(PPh3)2, generated by reaction of ‘Pd(OAc)2’ with two equivalents of PPh3. Here, we report that the reaction of [PdI2(μ-PPh2)(μ2-OAc)(PPh3)2] with PPh3results in a nuanced disproportionation reaction, forming [Pd0(PPh3)3] and a phosphinito-bridged PdI-dinuclear complex, namely [PdI2(μ-PPh2){κ2-P,O-μ-P(O)Ph2}(κ-PPh3)2]. The latter complex is proposed to form by abstraction of an oxygen atom from an acetate ligand at Pd. A mechanism for the formal reduction of a putative PdIIdisproportionation species to the observed PdIcomplex is postulated. Upon reaction of the mixture of [Pd0(PPh)3] and [PdI2(μ-PPh2){κ2-P,O-μ-P(O)Ph2}(κ-PPh3)2] with 2-bromopyridine, the former Pd0complex undergoes a fast oxidative addition reaction, while the latter dinuclear PdIcomplex converts slowly to a tripalladium cluster, of the type [Pd3(μ-X)(μ-PPh2)2(PPh3)3]X, with an overall 4/3 oxidation stateperPd. Our findings reveal complexity associated with the precatalyst activation step for the ubiquitous ‘Pd(OAc)2’/nPPh3catalyst system, with implications for cross-coupling catalysis

A Mechanism-Based Explanation of the Institutionalization of Semantic Technologies in the Financial Industry

Part 3: Creating Value through ApplicationsInternational audienceThis paper explains how the financial industry is solving its data, risk management, and associated vocabulary problems using semantic technologies. The paper is the first to examine this phenomenon and to identify the social and institutional mechanisms being applied to socially construct a standard common vocabulary using ontology-based models. This standardized ontology-based common vocabulary will underpin the design of next generation of semantically-enabled information systems (IS) for the financial industry. The mechanisms that are helping institutionalize this common vocabulary are identified using a longitudinal case study, whose embedded units of analysis focus on central agents of change—the Enterprise Data Management Council and the Object Management Group. All this has important implications for society, as it is intended that semantically-enabled IS will, for example, provide stakeholders, such as regulators, with better transparency over systemic risks to national and international financial systems, thereby mitigating or avoiding future financial crises