433 research outputs found
Microsoft Powerapps -ohjelman soveltuvuus matka- ja kululaskutuksen mobiilisovelluksen luomiseen : toiminnallinen toteutus Digia Oyj:lle
No full textTässä opinnäytetyössä tarkastellaan mobiilisovelluksen luomista Microsoft PowerApps -virtuaalialustalla, joka ei vaadi aiempaa ohjelmointiosaamista. Tutkimus on toteutettu luomalla matka- ja kululaskujen syöttöön tarkoitettu mobiilisovellus. Matka- ja kululaskut syötetään mobiilisovelluksella web service -rajapinnan yli Microsoft D365 Business Central -toiminnanohjausjärjestelmän tietokantaan jatkokäsittelyä varten.
Työssä tutkimus on tehty toiminnallisena työnä hyödyntäen kirjallisuus- ja verkkomateriaalia, asiantuntijahaastatteluita ja vertailuanalyysia. Opinnäytetyön laatija on työskennellyt asiantuntijatehtävissä 2018 alkaen työn toimeksiantajayrityksessä, Digia Oyj:ssä.
Haastattelut on tehty opinnäytetyön kohdeyrityksen työntekijöille. Niissä tarkennetaan PowerApps-sovelluksen tarpeita ja sen tuomia mahdollisuuksia, ja verrataan niitä työssä tehtyihin havaintoihin. Vertailuanalyysi toteutuu luomalla vastaava mobiilisovellus suoraan toiminnanohjausjärjestelmän käyttöliittymään.
Tutkimuksen tuloksina syntyi matka- ja kululaskujen sovellus Microsoft PowerAppsilla ja Microsoft Business Centralilla toteutettuna. Näiden sovellusten kehitysten pohjalta on kirjattu päätelmät teknillisestä ja kaupallisesta näkökulmasta, vertailu asiakkaan ja sovellustoimittajan hyödyistä sekä sovelluksen jatkokehitysideat.In this thesis is inspected creating a mobile software with Microsoft PowerApps virtual platform which requires no prior programming experience. Study is done by creating a mobile software for feeding travel expense and bill of service entries. The entries are inserted over web service API to Microsoft D365 Business Central ERP’s database for further handling.
Research has been done through a practical implementation by utilizing book and web material, specialist interviews and comparison analysis. The author of the thesis has worked as a specialist from 2018 onwards in the case company, Digia Plc.
Interviews are done for the case company’s employees. Questions are to pinpoint needs and opportunities of PowerApps and to compare them to observations done by the author. Comparison analysis is done by creating a similar software UI in the ERP.
As a result of the research, a software for travel expense and bill of service was made with Microsoft PowerApps and Microsoft D365 Business Central. Conclusions have been written on the basis of the software development from technical and commercial aspects, comparison of customer’s and vendor’s benefits and further development ideas for the software
PARP Inhibitor Resistance - What Is Beyond BRCA1 or BRCA2 Restoration?
No full textNearly 10 years ago the usefulness of poly(ADP-ribose) polymerase (PARP) inhibitors to kill BRCA1 or BRCA2-deficient cells was reported, and this finding has served as a prime example of the concept of synthetic lethality in the context of anticancer therapy. The clinical translation of this finding has undergone several ups and downs, however. Despite spectacular responses seen in some patients with BRCA-deficient breast or ovarian cancers, other patients did not show the expected benefit from PARP inhibitor therapy. Thus, like for all novel tailored anti-cancer drugs, upfront and secondary resistance remain major hurdles in the implementation of the initial preclinical finding. We know at least one clinically relevant mechanism of PARP inhibitor resistance: the reversion of BRCA function by secondary mutations. Nevertheless, it is also clear that this mechanism does not explain all cases of resistance. At the moment, we only have a poor understanding of BRCA reversion-independent resistance mechanisms. Preclinical data have pointed in several directions, e.g. increased drug efflux, reduced drug target levels, or alternative DNA repair. Here, we discuss these mechanisms with a focus on potential DNA repair adaptations
Governance communication: A primer (In the context of disaster risk reduction and management)
No full textTABLE OF CONTENTS
Introduction
Communication and Governance
Government Communication
Governance Communication
Components of Governance Communication System
- Government policies supporting the provision of communication services
- Government institutions providing communication services
- Communication human resources or personnel
- Communication infrastructures/media to support communication services
- Coordination mechanism for governance communication
- Public sphere/platform for public dialogues
Annex(EXCERPT)
Governing is comparable to a situation where a family head talks and listens regularly to each of his/her family members’ concerns and interests. As with the head of the family, the government’s focus on its people’s welfare encompasses a multitude of concerns – health, food security, education, employment, peace and order, and disaster risk reduction and management (DRRM), to name a few. DRRM has been a vital concern in recent years due to worldwide climate change conditions that have been wreaking havoc in the country and unduly affecting all aspects of people’s lives.
In implementing the policies, programs, and projects, communication is seen as one of the fundamental and crucial factors in the process of governing and in achieving the government’s development-oriented objectives.
Basically, this primer on governance communication is essential in understanding governance communication (govcomm) and its components (policy, institutions, personnel, media, communication mechanisms, and public sphere). This is important among government officials and stakeholders because it will serve as guide in studying their govcomm that will lead policy makers, and all the participants in the process, in formulating policies and ordinances related to governance and communication.Disclaimer
"The views expressed in this paper are entirely and solely those of the author and do not necessarily reflect official thinking and policy of the Republic of the Philippines or any Local Government Unit in the Country.
DNA damage repair proteins as determinants of sensitivity to platinum chemotherapy
No full textDNA damage repair proteins are determinants of sensitivity to platinum chemotherapy in preclinical models and in patients with cancer. The XPF- ERCC1 heterodimer incises DNA strands adjacent to platinum-DNA adducts and is essential for repair of platinum-DNA interstrand cross-links (ICLs). High expression of ERCC1 has been correlated with lack of response to platinum chemotherapy, but less is known about the value of XPF in predicting response to platinum-based chemotherapy. MUS81- EME1 is also involved in replication-coupled ICL repair. The role of MUS81 as a biomarker for response to platinum-based chemotherapy has not been examined.
This project tested the hypothesis that high tumour levels of the DNA repair proteins XPF and MUS81 are associated with lack of response to platinum chemotherapy.
In the first part of this thesis, microarray analysis of gene expression in samples from patients with oesophageal adenocarcinomas treated with neoadjuvant oxaliplatin-fluorouracil demonstrated an association between high levels of genes encoding ICL repair proteins (including ERCC1, MUS81 and EME1) and poorer clinical outcomes. In addition, functional pathway analysis suggested a link between down regulation of cell cycle and anti- apoptotic pathways and response to treatment.
In the second part, high levels of XPF and MUS81 proteins in pre-treatment biopsies were correlated with worse outcomes following neoadjuvant oxaliplatin-fluorouracil chemotherapy for oesophageal adenocarcinoma. It was found that, in keeping with the microarray results presented in the first part, high pre-treatment levels of the G2/M-phase marker Cyclin B1 were associated with worse clinical outcomes. The relationship between XPF and MUS81 levels and response to DNA cross-linking agents in colorectal and anal cancers was also studied.
In the third part, it was demonstrated in vitro that reducing levels of XPF and MUS81 proteins increased sensitivity of colorectal and oesophageal cancer cells to oxaliplatin treatment.
These data suggest that XPF and MUS81 have the potential to be developed as biomarkers for clinical response to oxaliplatin-based chemotherapy
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A study of the musical settings of Langston Hughes' poetry in Ricky Ian Gordon's song cycle "Genius Child"
No full textThis study examines and describes Ricky Ian Gordon's musical interpretation of Langston Hughes' poetry in the song cycle, Genius Child. Chapters 2 and 3 contain biographies of the composer, Ricky Ian Gordon and the poet, Langston Hughes. Chapter 4 is a singer's analysis of each of the ten songs in Genius Child. Appendix A contains a discography. Appendix B contains a personal interview with the composer discussing his compositional process for Genius Child and his life in general. The author performed Genius Child in a doctoral recital on May 1, 2000. The song cycle was written for American soprano, Harolyn Blackwell, who sang the premiere at the Bermuda Festival in 1993. She also recorded Genius Child on her 1994 debut release from RCA Victor entitled Strange Hurt. Genius Child was published by Williamson Music in 1995.</p
Perfusion imaging and tissue biomarkers for colorectal cancer
No full textBackground: Systemic chemotherapy and radiotherapy play an important role in the treatment of colorectal cancer. Tumour perfusion and oxygenation is known to influence radiosensitivity and chemosensitivity. In this thesis, I propose that the evaluation of changes in tumour perfusion using perfusion CT (pCT) and dynamic contrast-enhanced (Dce) MRI can guide the rational sequencing of drugs and radiation. Methods: Dce-MRI and pCT scans were incorporated into a clinical trial of hypofractionated pelvic radiotherapy and nelfinavir in 10 patients with rectal cancer. Toxicity and tissue biomarkers (tumour cell density, microvessel density, CAIX, HIF1-alpha, phospho-Akt and phospho-PRAS40) were evaluated. pCT liver scans were incorporated into an imaging study in patients with colorectal liver metastases randomised to receive either oxaliplatin/ 5FU chemotherapy or oxaliplatin/ 5FU chemotherapy plus selective internal radiotherapy. Results: After 7 days of nelfinavir concurrent with hypo-fractionated pelvic radiotherapy, there was a mean 42% increase in median Ktrans (P=0.03, paired t test) on Dce-MRI and a median 30% increase in mean blood flow on pCT (P=0.028, Wilcoxon Rank Sum), although no statistically significant changes in perfusion parameters were demonstrated after 7 days of nelfinavir prior to radiotherapy. The feasibility of evaluating tumour cell density in rectal biopsies before and after radiotherapy and a radiosensitising drug as an early endpoint of response was demonstrated. In patients with colorectal liver metastases who received oxaliplatin and modified de Gramont chemotherapy alone, after 4 cycles of chemotherapy, a 28% decrease in the mean hepatic arterial fraction was observed (P=0.018, paired t test). Between pCT scans 2 days before SIRT and 39-47 days following SIRT and continued 2-weekly chemotherapy, there was a mean 62% (P=0.009) reduction in Blood Flow and 61% (P=0.006) reduction in Blood Volume (paired t test). Conclusions This research does not support the hypothesis that nelfinavir before radiotherapy improves blood flow to human rectal cancer. Increases in rectal tumour perfusion during radiotherapy and concurrent nelfinavir are likely to be primarily explained by the acute biological effects of radiation. Four or more cycles of oxaliplatin and modified de Gramont chemotherapy may result in changes in tumour perfusion of colorectal liver metastases which would be detrimental to subsequent radiotherapy. Selective internal radiotherapy resulted in substantial reductions in tumour perfusion 39-47 days after the treatment. Perfusion imaging can be used to detect changes in tumour perfusion in response to radiotherapy and systemic therapy which have implications for the sequencing of therapies
Maybe it\u27s us? An organizational and systems level approach to reducing barriers to student success.
No full textThe author will be presenting a deep dive on the project and subsequent publication Systemic Solutions Driving Retention and Graduation Efforts at a Large, Selective Private Institution: A Scalable Project for Student Success by Ricky Urgo and Sonja Ardoin. Through the lens of an organizational analysis, the author will provide tangible takeaways for practitioners and faculty to bring back to their campuses and replicate. This is an important and necessary venture, as institutions increase their attention and resources on the recruitment and retention of first generation and working class students. Institutions were not constructed with these populations in mind, but we can make organizational, structural, and systemic changes to better serve these students, especially as our shortcomings as universities disproportionately impact this community (Flaherty, 2023; Urgo & Ardoin, 2024). Simultaneously, the author hopes to encourage exploration of the following:1) identifying new institutional barriers to student success, 2) improving understanding of how stakeholders navigate institutional infrastructure, 3) creating a culture where auditing internal practices and knowledge bases are commonplace, 4) uplifting student voice and experience, and 5) creating greater outcomes for all students
The role of DNA polymerase eta in determining cellular responses to chemo-radiation treatment
No full textDNA polymerase η (pol η), a crucial component of the cellular translesion synthesis pathway, allows cells to bypass and thereby temporarily tolerate DNA damage. Inherited deficiency of pol η, as reported in the variant form of xeroderma pigmentosum, predisposes to UV light-induced skin cancers. To date, pol η is the only DNA polymerase shown to exhibit a causal link to the formation of cancers in humans. However, the role of pol η in the cellular response to forms of DNA damage other than UV-induced lesions is largely unknown. In the first part of this thesis, it is shown that cells deficient in pol η are resistant to ionising radiation. Deficiency in the polymerase was associated with accumulation of cells in S phase of the cell cycle. Cells deficient in pol η demonstrated increased homologous recombination-directed repair of DNA double-strand breaks created by ionising radiation, and depletion of the homologous recombination protein X-ray repair cross-complementing protein 3 (XRCC3), abrogated the radioresistance observed in pol η-deficient cells compared to pol η-complemented cells. These findings suggest that homologous recombination mediates S phase-dependent radioresistance associated with pol η-deficiency. In the second part of this thesis, it is shown that pol η-deficient cells have increased sensitivity to the chemotherapeutic compound, oxaliplatin, compared to pol η-deficient expressing cells, but not to the drug 5-fluorouracil that is usually administered in combination with oxaliplatin in the clinical setting. Despite the importance of pol η for cellular survival following exposure to oxaliplatin, the drug did not upregulate the enzyme after either short-term or long-term exposure. Inhibition of pol η activity by siRNA-mediated knockdown of the protein sensitised cells to oxaliplatin treatment, and partially reversed acquired resistance in oxaliplatin-resistant tumour cell lines. These data suggest that pol η is an interesting target whose function can potentially be interfered with to optimise oxaliplatin-based chemotherapy. In the third part of this thesis, clinical samples obtained from oesophageal cancer patients before and after treatment with oxaliplatin-containing chemotherapy were analysed for POLH mRNA levels encoding pol η protein. Malignant tissue specimens obtained before treatment demonstrated a significantly higher level of POLH mRNA than matched normal oesophageal tissue samples. Contrary to the preclinical data, high POLH mRNA expression before therapy was shown to correlate with increased overall and disease-free survival of the patient cohort in the clinical trial. Additionally, patients with high POLH mRNA-expressing cancers had better therapeutic responses (measured by PET-CT) to oxaliplatin-based treatment than those with low levels. These data suggest that POLH mRNA expression should be tested as a biomarker to predict survival and therapeutic responses in oesophageal cancer patients treated with oxaliplatin-containing chemotherapy
Hepatic resection following selective internal radiation therapy for colorectal cancer metastases in the FOXFIRE clinical trial: Clinical outcomes and distribution of microspheres
No full textThe FOXFIRE (5-Fluorouracil, OXaliplatin and Folinic acid ± Interventional Radio-Embolisation) clinical trial combined systemic chemotherapy (OxMdG: Oxaliplatin, 5-fluorouracil and folic acid) with Selective Internal Radiation Therapy (SIRT or radio-embolisation) using yttrium-90 resin microspheres in the first-line management for liver-dominant metastatic colorectal cancer (CRC). We report clinical outcomes for patients having hepatic resection after this novel combination therapy and an exploratory analysis of histopathology. Multi-Disciplinary Teams deemed all patients inoperable before trial registration and reassessed them during protocol therapy. Proportions were compared using Chi-squared tests and survival using Cox models. FOXFIRE randomised 182 participants to chemotherapy alone and 182 to chemotherapy with SIRT. There was no statistically significant difference in the resection rate between groups: Chemotherapy alone was 18%, (n = 33); SIRT combination was 21% (n = 38) (p = 0.508). There was no statistically significant difference between groups in the rate of liver surgery, nor in survival from time of resection (hazard ratio (HR) = 1.55; 95% confidence interval (CI) = 0.83–2.89). In the subgroup studied for histopathology, microsphere density was highest at the tumour periphery. Patients treated with SIRT plus chemotherapy displayed lower values of viable tumour in comparison to those treated with chemotherapy alone (p < 0.05). This study promotes the feasibility of hepatic resection following SIRT. Resin microspheres appear to preferentially distribute at the tumour periphery and may enhance tumour regression
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