Identification of a non-competitive inhibitor of Plasmodium falciparum aspartate transcarbamoylase

Aspartate transcarbamoylase catalyzes the second step of de-novo pyrimidine biosynthesis. As malarial parasites lack pyrimidine salvage machinery and rely on de-novo production for growth and proliferation, this pathway is a target for drug discovery. Previously, an apo crystal structure of aspartate transcarbamoylase from Plasmodium falciparum (PfATC) in its T-state has been reported. Here we present crystal structures of PfATC in the liganded R-state as well as in complex with the novel inhibitor, 2,3-napthalenediol, identified by high-throughput screening. Our data shows that 2,3-napthalediol binds in close proximity to the active site, implying an allosteric mechanism of inhibition. Furthermore, we report biophysical characterization of 2,3-napthalenediol. These data provide a promising starting point for structure based drug design targeting PfATC and malarial de-novo pyrimidine biosynthesis

The Association between Patient Characteristics and the Efficacy and Safety of Selinexor in Diffuse Large B-Cell Lymphoma in the SADAL Study.

Selinexor, an oral selective inhibitor of nuclear export, was evaluated in the Phase 2b SADAL study in patients with diffuse large B-cell lymphoma (DLBCL) who previously received two to five prior systemic regimens. In post hoc analyses, we analyzed several categories of patient characteristics (age, renal function, DLBCL subtype, absolute lymphocyte count, transplant status, number of prior lines of therapy, refractory status, Ann Arbor disease stage, and lactate dehydrogenase) at baseline, i.e., during screening procedures, to determine their potential contributions to the efficacy (overall response rate [ORR], duration of response [DOR], overall survival [OS]) and tolerability of selinexor. Across most categories of characteristics, no significant difference was observed in ORR or DOR. OS was significantly longer for patients ULN. The most common adverse events (AEs) across the characteristics were thrombocytopenia and nausea, and similar rates of grade 3 AEs and serious AEs were observed. With its oral administration, novel mechanism of action, and consistency in responses in heavily pretreated patients, selinexor may help to address an important unmet clinical need in the treatment of DLBCL

The Association between Patient Characteristics and the Efficacy and Safety of Selinexor in Diffuse Large B-Cell Lymphoma in the SADAL Study.

Selinexor, an oral selective inhibitor of nuclear export, was evaluated in the Phase 2b SADAL study in patients with diffuse large B-cell lymphoma (DLBCL) who previously received two to five prior systemic regimens. In post hoc analyses, we analyzed several categories of patient characteristics (age, renal function, DLBCL subtype, absolute lymphocyte count, transplant status, number of prior lines of therapy, refractory status, Ann Arbor disease stage, and lactate dehydrogenase) at baseline, i.e., during screening procedures, to determine their potential contributions to the efficacy (overall response rate [ORR], duration of response [DOR], overall survival [OS]) and tolerability of selinexor. Across most categories of characteristics, no significant difference was observed in ORR or DOR. OS was significantly longer for patients ULN. The most common adverse events (AEs) across the characteristics were thrombocytopenia and nausea, and similar rates of grade 3 AEs and serious AEs were observed. With its oral administration, novel mechanism of action, and consistency in responses in heavily pretreated patients, selinexor may help to address an important unmet clinical need in the treatment of DLBCL

The Association between Patient Characteristics and the Efficacy and Safety of Selinexor in Diffuse Large B-Cell Lymphoma in the SADAL Study.

Selinexor, an oral selective inhibitor of nuclear export, was evaluated in the Phase 2b SADAL study in patients with diffuse large B-cell lymphoma (DLBCL) who previously received two to five prior systemic regimens. In post hoc analyses, we analyzed several categories of patient characteristics (age, renal function, DLBCL subtype, absolute lymphocyte count, transplant status, number of prior lines of therapy, refractory status, Ann Arbor disease stage, and lactate dehydrogenase) at baseline, i.e., during screening procedures, to determine their potential contributions to the efficacy (overall response rate [ORR], duration of response [DOR], overall survival [OS]) and tolerability of selinexor. Across most categories of characteristics, no significant difference was observed in ORR or DOR. OS was significantly longer for patients ULN. The most common adverse events (AEs) across the characteristics were thrombocytopenia and nausea, and similar rates of grade 3 AEs and serious AEs were observed. With its oral administration, novel mechanism of action, and consistency in responses in heavily pretreated patients, selinexor may help to address an important unmet clinical need in the treatment of DLBCL

Digitaliseringens inflytande på revision : En kvalitativ studie om hur digitaliseringen har påverkat revisorn och dess roll

Sammanfattning Datum:   2022-06-01 Nivå:    Kandidatuppsats Företagsekonomi, 15 hp Akademi:   Akademi för Ekonomi, Mälardalens Universitet Författare:   Agrali, Ersin            Chabo, Gabriel        George Chamoun                      (00-05-25)                (00-03-29)         (99-01-08) Titel:    Digitaliseringens inflytande på revision  Handledare:  Leanne Johnstone Nyckelord:   Revision, Digitalisering, Automatisering, Kvalifikationer  Forskningsfrågor: - Vilket inflytande har digitaliseringen på revisorns arbete? - Vad för kvalifikationer kommer att erfordras hos revisorer i förhållande till digitaliseringen? Syfte: Syftet med denna studie är att få en bättre inblick på digitaliseringens inflytande på revision samt vilka kvalifikationer som kommer efterfrågas hos revisorer. Detta syfte ska åstadkommas  genom att studien svarar på forskningsfrågorna.               Metod:  Studien tillämpar en kvalitativ metod som inkluderar ett urval respondenter från fyra olika bolag.  Slutsats: Digitaliseringen är ett aktuellt ämne idag inom revisionsbranschen och i takt med digitaliseringens utveckling påverkar det revisorns roll positivt. Digitaliseringen är ett alternativ för revisorn att effektivisera arbetet men dock behövs det kvalifikationer för att behärska digitaliseringen. För att revisorerna ständigt ska vara konkurrenskraftiga krävs vissa kvalifikationer som efterfrågas i branschen i takt med digitaliseringens utveckling. Arbetsrollen som en revisor kräver kvalificerad kompetens i takt med de arbetsuppgifter som automatiseras. Abstract Date:   2022-06-01 Level:   Bachelor thesis in Business Administration, 15cr Institution:   School of Business, Society and Engineering, Mälardalen University Authors:  Ersin Agrali  Gabriel Chabo  George Chamoun                  (00-05-25)  (00-03-29)  (99-01-08) Title:    The influence of digitalisation on auditing  Supervisor:  Leanne Johnstone Keywords:   Auditing, Digitization, Automation, Qualifications Research Question:  - What influence does digitalisation have on the auditor's work? - What qualifications will be required of auditors in relation to digitalisation? Purpose:  The purpose of this study is to gain a better insight into the influence of       digitization of auditing and its growth thus what qualification will be requested from auditors. This purpose is to be achieved by the study answering two research questions.      Method:  The study applies a qualitative method that includes a selection of respondents from four different companies. Conclusion: Digitization is a current topic today in the auditing industry and in step    with the development of digitization, this has a positive effect on the    auditor’s role. Digitization is an alternative for the auditor to improve    the work, but qualifications are still needed to master digitization. In    order for the auditors to be constantly competitive, certain      qualifications are required that are in demand in the industry, in step   with the development of digitization. The work role as an auditor requires qualified competence in step with the tasks that are automated.

Digitaliseringens inflytande på revision : En kvalitativ studie om hur digitaliseringen har påverkat revisorn och dess roll

Sammanfattning Datum:   2022-06-01 Nivå:    Kandidatuppsats Företagsekonomi, 15 hp Akademi:   Akademi för Ekonomi, Mälardalens Universitet Författare:   Agrali, Ersin            Chabo, Gabriel        George Chamoun                      (00-05-25)                (00-03-29)         (99-01-08) Titel:    Digitaliseringens inflytande på revision  Handledare:  Leanne Johnstone Nyckelord:   Revision, Digitalisering, Automatisering, Kvalifikationer  Forskningsfrågor: - Vilket inflytande har digitaliseringen på revisorns arbete? - Vad för kvalifikationer kommer att erfordras hos revisorer i förhållande till digitaliseringen? Syfte: Syftet med denna studie är att få en bättre inblick på digitaliseringens inflytande på revision samt vilka kvalifikationer som kommer efterfrågas hos revisorer. Detta syfte ska åstadkommas  genom att studien svarar på forskningsfrågorna.               Metod:  Studien tillämpar en kvalitativ metod som inkluderar ett urval respondenter från fyra olika bolag.  Slutsats: Digitaliseringen är ett aktuellt ämne idag inom revisionsbranschen och i takt med digitaliseringens utveckling påverkar det revisorns roll positivt. Digitaliseringen är ett alternativ för revisorn att effektivisera arbetet men dock behövs det kvalifikationer för att behärska digitaliseringen. För att revisorerna ständigt ska vara konkurrenskraftiga krävs vissa kvalifikationer som efterfrågas i branschen i takt med digitaliseringens utveckling. Arbetsrollen som en revisor kräver kvalificerad kompetens i takt med de arbetsuppgifter som automatiseras. Abstract Date:   2022-06-01 Level:   Bachelor thesis in Business Administration, 15cr Institution:   School of Business, Society and Engineering, Mälardalen University Authors:  Ersin Agrali  Gabriel Chabo  George Chamoun                  (00-05-25)  (00-03-29)  (99-01-08) Title:    The influence of digitalisation on auditing  Supervisor:  Leanne Johnstone Keywords:   Auditing, Digitization, Automation, Qualifications Research Question:  - What influence does digitalisation have on the auditor's work? - What qualifications will be required of auditors in relation to digitalisation? Purpose:  The purpose of this study is to gain a better insight into the influence of       digitization of auditing and its growth thus what qualification will be requested from auditors. This purpose is to be achieved by the study answering two research questions.      Method:  The study applies a qualitative method that includes a selection of respondents from four different companies. Conclusion: Digitization is a current topic today in the auditing industry and in step    with the development of digitization, this has a positive effect on the    auditor’s role. Digitization is an alternative for the auditor to improve    the work, but qualifications are still needed to master digitization. In    order for the auditors to be constantly competitive, certain      qualifications are required that are in demand in the industry, in step   with the development of digitization. The work role as an auditor requires qualified competence in step with the tasks that are automated.