Hvem bør ha ansvar for kjemilab?

Mange ulike studieprogram har et innføringsemne i kjemi, ofte i første studieåret. Et slikt kjemiemne inkluderer vanligvis laboratorieundervisning, som er ressurskrevende å gjennomføre for et stort antall (flere hundre) studenter. Det er vanlig at instituttet som har ansvar for emnet også har ansvar for laboratorieundervisningen. Dermed får studentene på ulike studieprogram samme labøvelser av samme undervisere i samme laboratoriet med samme avsluttende rapportering. Etter innføringsemnet får studentene derimot laboratorieundervisning i andre emner, ofte i regi av faglærere fra eget studieprogram, på et mer spesialisert laboratorium og med rapportering i henhold til den aktuelle fagtradisjonen. I dette bidraget stiller vi oss spørsmålet hvem som bør ha ansvar for laboratorieundervisning i ett innføringsemne i kjemi: et kjemisk institutt som har ansvar for kjemiundervisning ellers, eller fagmiljøet som følger studentene opp etter innføringsemnet? Vi redegjør for utfordringer knyttet til den tradisjonelle måten hvor flere studieprogram følger samme laboratoriekurs, og presenterer en alternativ modell som vi har implementert og evaluert. Vi har evaluert tiltaket med fokus på studentenes opplevde relevans av laboratoriekurset, administrative aspekter og ikke minst ressursbruken. Våre erfaringer, som dokumentert her, vil kunne gi studieprogrammene et grunnlag for å balansere effektiv ressursbruk på den ene siden og relevans av laboratorieundervisning og (fag)tilhørighet på den andre siden. Slik kan fagpersoner på studieprogramnivå ta stilling til hvem de mener bør ha ansvar for kjemilab

Open-ended response theory with polarizable embedding:Multiphoton absorption in biomolecular systems

We present the theory and implementation of an open-ended framework for electric response properties at the level of Hartree–Fock and Kohn–Sham density functional theory that includes effects from the molecular environment modeled by the polarizable embedding (PE) model. With this new state-of-the-art multiscale functionality, electric response properties to any order can be calculated for molecules embedded in polarizable atomistic molecular environments ranging from solvents to complex heterogeneous macromolecules such as proteins. In addition, environmental effects on multiphoton absorption (MPA) properties can be studied by evaluating single residues of the response functions. The PE approach includes mutual polarization effects between the quantum and classical parts of the system through induced dipoles that are determined self-consistently with respect to the electronic density. The applicability of our approach is demonstrated by calculating MPA strengths up to four-photon absorption for the green fluorescent protein. We show how the size of the quantum region, as well as the treatment of the border between the quantum and classical regions, is crucial in order to obtain reliable MPA predictions

Averaged Solvent Embedding Potential Parameters for Multiscale Modeling of Molecular Properties

Published version available in J. Chem. Theory Comput., 2016, 12 (4), pp 1684–1695. We derive and validate averaged solvent parameters for embedding potentials to be used in polarizable embedding quantum mechanics/molecular mechanics (QM/MM) molecular property calculations of solutes in organic solvents. The parameters are solvent-specific atom-centered partial charges and isotropic polarizabilities averaged over a large number of geometries of solvent molecules. The use of averaged parameters reduces the computational cost to obtain the embedding potential, which can otherwise be a rate-limiting step in calculations involving large environments. The parameters are evaluated by analyzing the quality of the resulting molecular electrostatic potentials with respect to full QM potentials. We show that a combination of geometry-specific parameters for solvent molecules close to the QM region and averaged parameters for solvent molecules further away allows for efficient polarizable embedding multiscale modeling without compromising the accuracy. The results are promising for the de- velopment of general embedding parameters for biomolecules, where the reduction in computational cost can be considerable

Molecular quantum mechanical gradients within the polarizable embedding approach—Application to the internal vibrational Stark shift of acetophenone

We present an implementation of analytical quantum mechanical molecular gradients within the polarizable embedding (PE) model to allow for efficient geometry optimizations and vibrational analysis of molecules embedded in large, geometrically frozen environments. We consider a variational ansatz for the quantum region, covering (multiconfigurational) self-consistent-field and Kohn–Sham density functional theory. As the first application of the implementation, we consider the internal vibrational Stark effect of the C==O group of acetophenone in different solvents and derive its vibrational linear Stark tuning rate using harmonic frequencies calculated from analytical gradients and computed local electric fields. Comparisons to PE calculations employing an enlarged quantum region as well as to a non-polarizable embedding scheme show that the inclusion of mutual polarization between acetophenone and water is essential in order to capture the structural modifications and the associated frequency shifts observed in water. For more apolar solvents, a proper description of dispersion and exchange–repulsion becomes increasingly important, and the quality of the optimized structures relies to a larger extent on the quality of the Lennard-Jones parameters

Spillbasert læring: motivasjon for å ta i bruk ny teknologi

Vitenskapelig foredrag på MNT-konferansen 16.03. - 17.03.23, Stavanger: https://www.uis.no/nb/det-teknisk-naturvitenskapelige-fakultet/mnt-konferansen-2023.Spillbasert læring bruker prinsipper fra spill for å engasjere og motivere studenter i sin læring. I kombinasjon med innsikter om effektive læringsstrategier kan spillbaserte læringsressurser sikre både motivasjon til å lære og en effektiv læringsprosess. En forutsetning for å lykkes med introduksjon av ny teknologi generelt og spillbaserte læringsressurser spesifikt er at teknologien aksepteres av studentene og at teknologien er vel egnet til hva den brukes for. CranialGame er en nyutviklet digital spillbasert læringsressurs som tester om studentene mestrer navn, utspring og funksjoner til de tolv hjernenervene hos mennesker. I dette bidraget undersøker vi studentenes motivasjon til å ta i bruk CranialGame spesifikt og spillbaserte læringsressurser mer generelt. Et kull medisinstudenter har blitt introdusert til læringsressursen både individuelt og gruppevis i en modul om nevroanatomi. Studentene har deretter blitt oppfordret til å bruke CranialGame i sin læring. Gjennom en spørreundersøkelse har vi undersøkt bruken av CranialGame spesifikt og holdninger om spillbasert læring generelt. Vi bruker en kombinasjon av de to modellene Technology Acceptance Model og Task-Technology Fit for å måle studentenes opplevelse av velegnethet, brukervennlighet og nytte av spillbaserte læringsressurser. Selv om de aller fleste studentene fikk lyst til å bruke CranialGame etter dets introduksjon og var motivert til å bruke spillbaserte læringsressurser generelt, rapporterte bare omtrent en tredjedel at de faktisk har brukt denne læringsressursen. Vi diskuterer her hvorfor ikke flere studenter har tatt i bruk CranialGame, og mer generelt hvordan vi kan lykkes med å motivere studenter til å ta i bruk ny teknologi eller nye læringsressurser. Innsikt i studentenes motivasjon i møte med ny teknologi er viktig for planlegging og utvikling av nye ressurser

Harmonic Infrared and Raman Spectra in Molecular Environments Using the Polarizable Embedding Model

We present a fully analytic approach to calculate infrared (IR) and Raman spectra of molecules embedded in complex molecular environments modeled using the fragment-based polarizable embedding (PE) model. We provide the theory for the calculation of analytic second-order geometric derivatives of molecular energies and first-order geometric derivatives of electric dipole moments and dipole–dipole polarizabilities within the PE model. The derivatives are implemented using a general open-ended response theory framework, thus allowing for an extension to higher-order derivatives. The embedding-potential parameters used to describe the environment in the PE model are derived through first-principles calculations, thus allowing a wide variety of systems to be modeled, including solvents, proteins, and other large and complex molecular environments. Here, we present proof-of-principle calculations of IR and Raman spectra of acetone in different solvents. This work is an important step toward calculating accurate vibrational spectra of molecules embedded in realistic environments

Incidence, Stage, Treatment, and Survival of Noncardia Gastric Cancer

Importance: Gastric cancer is the fifth most common cancer worldwide, and investigating its incidence, characteristics, treatment, and outcomes over the past decades can help in selecting clinical strategies and future research directions. Objective: To analyze the trends in incidence, staging, and treatment of gastric cancer. Design, Setting, and Participants: This nationwide, population-based cohort study included patients diagnosed with noncardia gastric cancer (NCGC) between 1989 and 2021 in the Netherlands. Main Outcomes and Measures: Differences in tumor characteristics, treatment, and survival were analyzed per fixed time periods (1989-1993, 1994-1998, 1999-2003, 2004-2008, 2009-2013, 2014-2018, and 2019-2021). Results: In total, 47 014 patients (median [IQR] age, 73 [64-80] years; 28 032 [60%] male patients) were identified with mostly adenocarcinomas of the antrum region (when location was known). Age-standardized incidence decreased from 20.3 to 6.1 per 100 000 person-years between 1989 and 2021. During the study period, unknown T and N stages were recorded less frequently, and metastatic disease was diagnosed more frequently (1989-1993: 2633 of 9493 patients [28%]; 2019-2021: 1503 of 3200 patients [47%] in 2019-2021). Over time, fewer patients with metastatic disease underwent surgery with or without other treatment modalities (68% in 1989-1993 vs 64% in 2019-2021), and palliative chemotherapy in metastatic NCGC increased from 9% to 40%. For patients with nonmetastatic disease, 5-year relative survival improved from 28% (95% CI, 26.5%-29.2%) to 36% (95% CI, 33.5%-37.6%) between 1989 and 2021. For patients with nonmetastatic disease undergoing a resection, 5-year survival increased from 40% (95% CI, 38.3%-41.8%) to 51% (95% CI, 47.9%-53.3%). For patients with metastatic disease, 1-year relative survival increased from 10% (95% CI, 8.7%-11.1%) to 19% (95% CI, 17.2%-21.6%), but 3-year relative survival remained poor at 5% (95% CI, 3.6%-7.5%). Conclusions and Relevance: In this nationwide cohort study involving 47 014 patients diagnosed with NCGC (1989-2021), the results showed a decrease in incidence, more accurate staging, a shift in treatment modalities, and improved patient survival.</p

Enhanced tumour antiangiogenic effects when combining gefitinib with the antivascular agent ZD6126

Current experimental and clinical knowledge supports the optimisation of endothelial cell targeting using a strategy combining anti-EGFR drugs with antivascular agents. The purpose of the present study was to examine the effects of the association of ZD6126, an antivascular microtubule-destabilising agent, with gefitinib and irradiation on the growth of six head and neck human cancer cell lines xenografted in nude mice and to study predictive and molecular factors responsible for antitumour effects. CAL33- and Hep-2-grafted cell lines were the most sensitive to ZD6126 treatment, with VEGF levels significantly higher (P=0.0336) in these tumour xenografts compared to Detroit 562- and CAL27-grafted cell lines with relatively low VEGF levels that were not sensitive to ZD6126. In contrast, neither IL8 levels nor EGFR expression was linked to the antitumour effects of ZD6126. ZD6126 in combination with gefitinib resulted in a synergistic cytotoxic interaction with greater antitumour effects than gefitinib alone. The synergistic interaction between ZD6126 and gefitinib was corroborated by a significant decrease in CD31 labelling. The present study may serve for future innovative clinical applications, as it suggests that VEGF tumour levels are possible predictors for ZD6126 antitumour efficacy. It also supports the notion of antitumour supra-additivity when combining gefitinib and ZD6126, and identifies neoangiogenesis as the main determinant of this synergistic combination

Circulating endothelial cells are an early predictor in renal cell carcinoma for tumor response to sunitinib

<p>Abstract</p> <p>Background</p> <p>Tyrosine kinase inhibitors (TKI) have enriched the therapeutic options in patients with renal cell carcinoma (RCC), which frequently induce morphological changes in tumors. However, only little is known about the biological activity of TKI. Circulating endothelial cells (CEC) have been associated with endothelial damage and, hence, may serve as a putative marker for the biological activity of TKI. The main objective of our study was to evaluate the predictive value of CEC, monocytes, and soluble vascular endothelial growth factor receptor (sVEGFR)-2 in RCC patients receiving sunitinib treatment.</p> <p>Methods</p> <p>Analyses of CEC, monocytes, and sVEGFR-2 were accomplished for twenty-six consecutive patients with metastatic RCC who received treatment with sunitinib (50 mg, 4 wks on 2 wks off schedule) at our institution in 2005 and 2006.</p> <p>Results</p> <p>In RCC patients CEC are elevated to 49 ± 44/ml (control 8 ± 8/ml; P = 0.0001). Treatment with sunitinib is associated with an increase in CEC within 28 days of treatment in patients with a Progression free survival (PFS) above the median to 111 ± 61 (P = 0.0109), whereas changes in patients with a PFS below the median remain insignificant 69 ± 61/ml (P = 0.1848). Monocytes and sVEGFR2 are frequently altered upon sunitinib treatment, but fail to correlate with clinical response, defined by PFS above or below the median.</p> <p>Conclusions</p> <p>Sunitinib treatment is associated with an early increase of CEC in responding patients, suggesting superior endothelial cell damage in these patients as a putative predictive biomarker.</p