11 research outputs found
δ Lactones from δ-ketoesters-II : Mechanism changes in alkylation reactions and substituent effects on stereoselection
No full textAbstract
Alkylation of methyl 4-methyl 5-oxo 5-phenyl (m and p-X substituted) pentanoates 1a-b give cis and trans tetrahydro 5,6-dimethyl 6-phenyl 2H pyran-2-ones. LFER of isomer ratios as function of the X substituent on the phenyl ring is seen in MeLi-Et2O. The lactone ratios of reactions in THF with MeMgCl are not affected by the X phenyl substituent, while a more complex situation is showed by reactions of MeMgl in Et2O and benzene. Changes in the cis: trans-ratios with variations in reactant and solvent are discussed in terms of equilibrium between folded and unfolded conformations in transition states
Bromonitriles reduction. The effect of the electrode material on the structure of the reaction intermediates and the electrolysis products
No full text
XVII Convegno Nazionale della Divisione di Chimica organica della Società Chimica Italiana
No full textRecommended from our members
Legal Aspects of National Implementation of the Chemical Weapons Convention
No full textThe author discusses some legal aspects of measures at the national level to implement the Chemical Weapons Convention (CWC). These implementing measures are universal, applying not only to the few States Parties that will declare and destroy chemical weapons, but also to the many States Parties that have never had a chemical weapons program. This new need for national measures to implement multilateral arms control agreements has generated unease due to a perception that implementation may be burdensome and at odds with national law. In 1993, concerns arose that the complexity of integrating the treaty with national law would cause each nation to effectuate the Convention without regard to what other nations were doing, thereby engendering significant disparities in implementation steps among States Parties. The author discusses progress among several States in actually developing national CWC implementing measures. Implementing measures from Australia, Norway, South Africa, and Sweden were available to him in English through the PTS. He compares them in order to illustrate different approaches to national implementation that are emerging. Of course, it is important to note that this brief survey necessarily omitted examination of the existing ``background`` of other, related domestic laws that these signatories might also have adopted that affect CWC implementation
Enacting Reasoning-and-Proving in Secondary Mathematics Classrooms through Tasks
No full textProof is the mathematical way of convincing oneself and others of the truth of a claim for all cases in the domain under consideration. As such, reasoning-and-proving is a crucial, formative practice for all students in kindergarten through twelfth grade, which is reflected in the Common Core State Standards in Mathematics. However, students and teachers exhibit many difficulties employing, writing, and understanding reasoning-and-proving. In particular, teachers are challenged by their knowledge base, insufficient resources, and unsupportive pedagogy.
The Cases of Reasoning and Proving (CORP) materials were designed to offer teachers opportunities to engage in reasoning-and-proving tasks, discuss samples of authentic practice, examine research-based frameworks, and develop criteria for evaluating reasoning-and-proving products based on the core elements of proof. A six-week graduate level course was taught with the CORP materials with the goal of developing teachers’ understanding of what constitutes reasoning-and-proving, how secondary students benefit from reasoning-and-proving, and how they can support the development of students’ capacities to reason-and-prove. Research was conducted on four participants of the course during either their first or second year of teaching. The purpose of the research was to study the extent to which the participants selected, implemented, and evaluated students’ work on reasoning-and-proving tasks. The participants’ abilities were examined through an analysis of answers to interview questions, tasks used in class, and samples of student work, and scoring criteria. The results suggest that: 1.) participants were able to overcome some of the limitations of their insufficient resource by modifying and creating some reasoning-and-proving exercises; 2.) participants were able to maintain the level of cognitive demand of proof tasks during implementation; and 3) participants included some if not all of the core elements of proof in their definition of proof and in their evaluation criteria for student products of reasoning-and-proving products
Comprehensive reanalysis for CNVs in ES data from unsolved rare disease cases results in new diagnoses
No full text\ua9 The Author(s) 2024.We report the results of a comprehensive copy number variant (CNV) reanalysis of 9171 exome sequencing datasets from 5757 families affected by a rare disease (RD). The data reanalysed was extremely heterogeneous, having been generated using 28 different enrichment kits by 42 different research groups across Europe partnering in the Solve-RD project. Each research group had previously undertaken their own analysis of the data but failed to identify disease-causing variants. We applied three CNV calling algorithms to maximise sensitivity, and rare CNVs overlapping genes of interest, provided by four partner European Reference Networks, were taken forward for interpretation by clinical experts. This reanalysis has resulted in a molecular diagnosis being provided to 51 families in this sample, with ClinCNV performing the best of the three algorithms. We also identified partially explanatory pathogenic CNVs in a further 34 individuals. This work illustrates the value of reanalysing ES cold cases for CNVs
TP63 is implicated in apoptotic dysregulation in melanoma
No full textPhDCutaneous melanoma is an aggressive malignancy accounting for 4% of skin cancers but 80% of all skin-cancer related deaths. Its incidence is rapidly rising and advanced disease is notoriously treatment-resistant. The role of apoptosis in melanoma pathogenesis and chemoresistance is poorly characterised. Mutations in TP53 occur infrequently and are not critical for tumour development, yet the TP53 apoptotic pathway is abrogated; this may alternatively result from TP53 pathway defects or from alterations in other members of the TP53 family, including the TP53 homologue, TP63. The hypothesis of this thesis was that TP63 has an anti-apoptotic role in melanoma and is responsible for mediating chemoresistance. The primary aims were to investigate the biological role of TP63 in melanoma, to explore regulation of p63 expression and to understand its role in apoptosis and dysregulation of the TP53 apoptotic pathway in melanoma.
Although p63 was not expressed in primary melanocytes, upregulation of both p63 mRNA and protein was observed in melanoma cell lines and tissue samples. This is the first report of significant p63 expression in this lineage. Furthermore, aberrant cytoplasmic p63 expression significantly correlated with poor overall outcome in melanoma patients. Multiple possible mechanisms were demonstrated to regulate TP63 expression in melanoma, including epigenetic modulation, microRNA regulation of gene transcription and proteosome-dependent stability of p63 protein. In response to genotoxic stress, endogenous p63 isoforms were stabilised in both nuclear and mitochondrial subcellular compartments. Translocation of p63 to the mitochondria occurred through a co-dependent process with p53 but accumulation of wt-p53 in the nucleus was inhibited by p63. Using RNAi technology, both isoforms of p63 (TA and ΔNp63) were demonstrated to confer chemoresistance in melanoma. In addition, the truncated variant, ΔNp63, was enriched in a subset of melanomas expressing CD133, pointing to an anti-apoptotic role for p63 in putative cancer stem cells in this aggressive tumour.
Taken together, these data suggest that in melanoma, p63 is an oncogene which contributes to dysregulation of wt-p53 function and has an important role in mediating chemoresistance. Ultimately, these observations may provide the rationale for novel approaches aimed at sensitising advanced melanoma to chemotherapeutic agents
