Regioselective reactions of 3,4-pyridynes enabled by the aryne distortion model.

The pyridine heterocycle continues to play a vital role in the development of human medicines. More than 100 currently marketed drugs contain this privileged unit, which remains highly sought after synthetically. We report an efficient means to access di- and trisubstituted pyridines in an efficient and highly controlled manner using transient 3,4-pyridyne intermediates. Previous efforts to employ 3,4-pyridynes for the construction of substituted pyridines were hampered by a lack of regiocontrol or the inability to later manipulate an adjacent directing group. The strategy relies on the use of proximal halide or sulfamate substituents to perturb pyridyne distortion, which in turn governs regioselectivities in nucleophilic addition and cycloaddition reactions. After trapping of the pyridynes generated in situ, the neighbouring directing groups may be removed or exploited using versatile metal-catalysed cross-coupling reactions. This methodology now renders 3,4-pyridynes as useful synthetic building blocks for the creation of highly decorated derivatives of the medicinally privileged pyridine heterocycle

Selective C(sp2)−H Halogenation of "click" 4-Aryl-1,2,3-triazoles

Selective bromination reactions of “click compounds” are described. Electron-neutral and electron-deficient arenes selectively undergo unprecedented Pd-catalyzed C–H ortho-halogenations assisted by simple triazoles as modular directing groups, whereas electron-rich arenes are regioselectively halogenated following an electrophilic aromatic substitution reaction pathway. These C–H halogenation procedures exhibit a wide group tolerance, complement existing bromination procedures, and represent versatile synthetic tools of utmost importance for the late-stage diversification of “click compounds”. The characterization of a triazole-containing palladacycle and density functional theory studies supported the mechanism proposal.We are grateful to Gobierno Vasco (ELKARTEK_KK-2015/0000101; IT_1033-16) and UPV/EHU (GIU15/31) for financial support. A. C. thanks MINECO for a Ramón y Cajal research contract (RYC-2012-09873). Cost-CHAOS action is also acknowledged

Proliferation tracing with single-cell mass cytometry optimizes generation of stem cell memory-like T cells.

Selective differentiation of naive T cells into multipotent T cells is of great interest clinically for the generation of cell-based cancer immunotherapies. Cellular differentiation depends crucially on division state and time. Here we adapt a dye dilution assay for tracking cell proliferative history through mass cytometry and uncouple division, time and regulatory protein expression in single naive human T cells during their activation and expansion in a complex ex vivo milieu. Using 23 markers, we defined groups of proteins controlled predominantly by division state or time and found that undivided cells account for the majority of phenotypic diversity. We next built a map of cell state changes during naive T-cell expansion. By examining cell signaling on this map, we rationally selected ibrutinib, a BTK and ITK inhibitor, and administered it before T cell activation to direct differentiation toward a T stem cell memory (TSCM)-like phenotype. This method for tracing cell fate across division states and time can be broadly applied for directing cellular differentiation

Directing Romeo and Juliet: teacher notes (Active Shakespeare: Capturing evidence of learning)

"Providing active and engaging ways to integrate Shakespeare in the ongoing periodic assessment of pupils’ reading. What is it for? To support the teaching and assessment of Shakespeare at Key Stage 3." - Back cover

Maximal subgroups of multi-edge spinal groups

A multi-edge spinal group is a subgroup of the automorphism group of a regular p-adic rooted tree, generated by one rooted automorphism and a finite number of directed automorphisms sharing a common directing path. We prove that torsion multi-edge spinal groups do not have maximal subgroups of infinite index. This generalizes a result of Pervova for GGS-groups

Application of a periodic table for the genetic code to influenza A/H3N2 virus

If biologists can utilize a table to have access to biological phenomena in the manner analogous to the periodic table for chemical elements, they may get hold of a directing post in life science. Currently the mutational rule of influenza viruses have remained perplexed and to reveal it should be now desired when avian influenza virus has just then threatened human beings. Here I examine the applicability of a novel periodic table for the genetic code to influenza A/H3N2 virus, while presenting two rules regarding single point mutations of its virus hemagglutinin gene. One rule is that non-synonymous single point mutations are intimately associated with the first or second base replacements between four groups (5, 6, 9, and 10) in the periodic table. Another rule is that there is a new index (inversion number) conserving in mutation. This paper will take the first step to such contribution of mutational reactions

Pola Interaksi Sosial Antar Siswa Berbeda Agama ( Kasuspada Kelas X A di SMA Negeri 2 Pontianak )

: This study aims to determine the patterns of interaction among students of different religions (case XA classes at SMAN 2 Pontianak). The method used is descriptive method with qualitative approach with the aim of researchers can learn more about the interaction between students of different faiths. The method used in data collection techniques were interviews, observation and documentation. These results indicate that the pattern of interaction among students of different religions are focused on associative interaction is cooperation and accommodation as well as interactions with dissociative ie competition and conflict. Cooperation directing how students work together to complete the task group.Accommodation directing how students solve problems that occur in schools among students.Competition directing how students compete for high scores and to get the champion class. And conflicts lead to any problems that often occur in class X A. The conclusion from this study is that there are students who are grouped according to their own religion well underway during recess they are always together, the task group, the students still choose friends believers to be invited to work groups

Interest groups and patent reform in India

India's patent reforms represent a shift in India's policy from one of enormous opposition to revising patent laws according to the WTO, to one of compliance with many aspects of TRIPs (Trade Related Intellectual Property Rights) Agreement. Industry and civil society had a strong interest in blocking reforms on IPRs (Intellectual Property Rights), and initially played an important role in preventing reforms of India's patent law. India has recently changed its patent regime, led by important industry groups who revised their positions, and new NGOs that promoted reform. The preferences of actors and their changing interests are important factors in the reform process. Perceived benefits from the new regime partly explain the rise of a pro-reform constituency among industry and NGOs. Yet preference formation is complex and depends on interpretation of strategies by various actors. The Indian pharmaceutical case reflects the imperatives both to forge ahead on patent reform, while protecting the generic market and restricting IPRs. NGOs that emerged to support patent reform also played a role in directing policy towards protecting traditional knowledge. The interests of actors do not always follow predictable paths, and are not fixed. Evaluating the preferences of actors rather than assuming them provides insights into the way policy processes are shaped.Intellectual Property Rights, industry groups, NGOs, reform, preferences

WormBase - Nematode Biology and Genomes

WormBase is the major public online database resource for the _Caenorhabditis_ research community. The database was developed primarily for the nematode _C. elegans_ but expanded to host genomes and biological data from other closely related nematode species including _C. briggsae_, _C. remanei_, _C. brenneri_, _C. japonica_ and _Pristionchus pacificus_. WormBase has developed tools to mine the data held within the database and compare the hosted species. Over the years we have developed a variety of curation pipelines which often begin in a "first-pass" literature curation step. This involves a brief overview of the literature before directing it to specialised data curators who extract all relevant information. Curators focus on particular data types or experimental techniques such as gene structure changes (see the Sequence curation poster), variations, phenotypes or RNAi and their expertise in these fields make curation efficient. WormBase works with many other groups and consortiums to validate, process and integrate both large and small scale data resources. WormBase also provides data that will be of interest to the wider biomedical and bioinformatics communities allowing researchers to utilise the information and techniques offered by nematodes to study wider aspects including medicine and disease.
&#xa

Synthesis of porous silicates

The issues of importance and future concern in the synthesis of porous silicates and porous materials that contain a large fraction of silica, e.g. zeolites and other crystalline molecular sieves, are reviewed. The thermodynamics of zeolite synthesis are discussed, including a detailed thermodynamic analysis of the synthesis of pure-silica ZSM-5. The kinetics of porous silicate synthesis are reviewed, with particular emphasis on the control of porous structure formation through the use of organic structure-directing agents. Ordered mesoporous materials are discussed in the context of distinguishing their features from zeolites in order to describe further the unique properties of each class of material. Finally, several unresolved issues in the understanding of the synthesis process are outlined, the resolutions of which would aid in the synthesis of porous silicates by design