CUPID pre-CDR

CUPID is a proposed future tonne-scale bolometric neutrinoless double beta decay ($0\nu\beta\beta$) experiment to probe the Majorana nature of neutrinos and discover Lepton Number Violation in the so-called inverted hierarchy region of the neutrino mass. CUPID will be built on experience, expertise and lessons learned in CUORE, and will exploit the current CUORE infrastructure as much as possible. In order to achieve its ambitious science goals, CUPID aims to dramatically reduce the backgrounds in the region of interest introducing a high efficiently $\alpha$/$\beta$ discrimination techniques, also demonstrated by the CUPID-0 and CUPID-Mo experiments, and using a high transition energy double beta decay nucleus, $^{100}$Mo. This document describe the main concepts related with the design of the CUPID experiment and indicates the projected sensitivities and the global scientific goal of the experiment

New France and the Illicit Fur Trade, 1663-1740

This thesis examines the illicit fur trade in New France between 1663 and 1740, and focuses on the relationship between illicit trade and colonial governance. It argues that French illicit fur traders (coureurs de bois) undermined New France governance by subverting licensed trade, which was crucial to France's economic, diplomatic, and military policies in North America

Story Retelling (SR) Technique in Improving Reading Comprehension of Sixth-Graders

The PHIL-IRI results of the sixth graders during their fifth grade were seriously alarming. All learners were identified as frustration readers. Thus, this study aimed to improve sixth graders' reading comprehension through Story Retelling (SR) technique. The study used a pretest-post-test quasi-experimental design consisting of two intact classes with 43 grade 6 learners. One class was exposed to SR Technique, while the other was exposed to the traditional method. The comparison of posttest results revealed no significant difference in the comprehension level of the respondents with (p>.01) between groups. The data proved that SR did not significantly enhance the reading comprehension of the learners. There was a slight increase in the posttest mean scores of the experimental group. However, the increase was not significant. It showed that the learners lacked solid general knowledge and vast vocabulary, which are essential in reading. The interviews discovered that the learners were not exposed to the English language and were not adequately monitored about their academic progress. These pre-existing background conditions significantly affected the intervention, preventing a significant difference in the learners' reading comprehension. Based on the results, it is recommended that the Story Retelling (SR) technique is only introduced to the learners after they learn the basic reading skills, including vocabulary, and establish solid general knowledge. Moreover, the amount of time spent on the intervention added to the undesirable results. Thus, the intervention should be conducted in more than six weeks to achieve better results

Chemical synthesis of oligodeoxyribonucleotides containing N3- and O4-carboxymethylthymidine and their formation in DNA

Humans are exposed to N-nitroso compounds from both endogenous and exogenous sources. Many N-nitroso compounds can be metabolically activated to give diazoacetate, which can result in the carboxymethylation of DNA. The remarkable similarity in p53 mutations found in human gastrointestinal tumors and in shuttle vector studies, where the human p53 gene-containing vector was treated with diazoacetate and propagated in yeast cells, suggests that diazoacetate might be an important etiological agent for human gastrointestinal tumors. The O6-carboxymethyl-2′-deoxyguanosine was previously detected in isolated DNA upon exposure to diazoacetate and in blood samples of healthy human subjects. The corresponding modifications of thymidine and 2′-deoxyadenosine have not been assessed, though significant mutations at A:T base pairs were found in the p53 tumor suppressor gene in human gastrointestinal tumors and in shuttle vector studies. To understand the implications of the carboxymethylation chemistry of thymidine in the observed mutations at A:T base pairs, here we synthesized authentic N3-carboxymethylthymidine (N3-CMdT) and O4-carboxymethylthymidine (O4-CMdT), incorporated them into DNA, and demonstrated, for the first time, that they were the major carboxymethylated derivatives of thymidine formed in calf thymus DNA upon exposure to diazoacetate. The demonstration of the formation of N3-CMdT and O4-CMdT in isolated DNA upon treatment with diazoacetate, together with the preparation of authentic oligodeoxyribonucleotide substrates housing these two lesions, laid the foundation for investigating the replication and repair of these lesions and for understanding their implications in the mutations observed in human gastrointestinal tumors

A refresh of the top 10 research priorities in cystic fibrosis

In 2018 we published the James Lind Alliance (JLA) top 10 priorities for clinical research in cystic fibrosis (CF), chosen jointly by the patient and clinical communities. These priorities have led to new research funding. To establish whether priorities have changed with novel modulator therapies, we undertook an online international update through a series of surveys and a workshop. Patients and clinicians (n=1417) chose the refreshed top 10 from 971 new research questions (suggested by patients and clinicians) and 15 questions from 2018. We are working with the international community to promote research based on these refreshed top 10 priorities