Нековалентная агрегация антибиотика митоксантрона: исследование методом диффузионно-упорядоченной 1H ЯМР-спектроскопии

Работа выполнена в рамках гранта Президента РФ для государственной поддержки ведущих научных школ № НШ-5889.2018.3

Differences and similarities in enzymes from the neopullulanase subfamily isolated from thermophilic species

Six glycoside hydrolase (GH) family 13 members, classified under the polyspecific neopullulanase subfamily GH13_20 (also termed cyclomaltodextrinase) were analysed. They originate from thermophilic bacterial strains (Anoxybacillus flavithermus, Laceyella sacchari, and Geobacillus thermoleovorans) or from environmental DNA, collected after in situ enrichments in Icelandic hot springs. The genes were isolated following the CODEHOP consensus primer strategy, utilizing the first two of the four conserved sequence regions in GH13. The typical domain structure of GH13_20, including an N-terminal domain (classified as CBM34), the catalytic module composed of the A-and B-domains, and a C-terminal domain, was found in five of the encoded enzymes (abbreviated Amy1, 89, 92, 98 and 132). These five enzymes degraded cyclomaltodextrins (CDs) and starch, while only three, Amy92 (L. sacchari), Amy98 (A. flavithermus) and Amy132 (environmental DNA), also harboured neopullulanase activity. The L. sacchari enzyme was monomeric, but with CD as the preferred substrate, which is an unusual combination. The sixth enzyme (Amy29 from environmental DNA), was composed of the ABC-domains only. Preferred substrate for Amy29 was pullulan, which was degraded to panose, and the enzyme had no detectable activity on CDs. In addition to its different activity profile and domain composition, Amy29 also displayed a different conservation (LPKF) in the fifth conserved region (MPKL) proposed to identify the subfamily. All enzymes had apparent temperature optima in the range 50–65°C, while thermostability varied, and was highest for Amy29 with a half-life of 480 min at 80°C. Calcium dependent activity or stability was monitored in four enzymes, but could not be detected for Amy29 or 98. Tightly bound calcium can, however, not be ruled out, and putative calcium ligands were conserved in Amy98

The BARD1 Cys557Ser Variant and Breast Cancer Risk in Iceland

BACKGROUND: Most, if not all, of the cellular functions of the BRCA1 protein are mediated through heterodimeric complexes composed of BRCA1 and a related protein, BARD1. Some breast-cancer-associated BRCA1 missense mutations disrupt the function of the BRCA1/BARD1 complex. It is therefore pertinent to determine whether variants of BARD1 confer susceptibility to breast cancer. Recently, a missense BARD1 variant, Cys557Ser, was reported to be at increased frequencies in breast cancer families. We investigated the role of the BARD1 Cys557Ser variant in a population-based cohort of 1,090 Icelandic patients with invasive breast cancer and 703 controls. We then used a computerized genealogy of the Icelandic population to study the relationships between the Cys557Ser variant and familial clustering of breast cancer. METHODS AND FINDINGS: The Cys557Ser allele was present at a frequency of 0.028 in patients with invasive breast cancer and 0.016 in controls (odds ratio [OR] = 1.82, 95% confidence interval [CI] 1.11–3.01, p = 0.014). The alleleic frequency was 0.037 in a high-predisposition group of cases defined by having a family history of breast cancer, early onset of breast cancer, or multiple primary breast cancers (OR = 2.41, 95% CI 1.22–4.75, p = 0.015). Carriers of the common Icelandic BRCA2 999del5 mutation were found to have their risk of breast cancer further increased if they also carried the BARD1 variant: the frequency of the BARD1 variant allele was 0.047 (OR = 3.11, 95% CI 1.16–8.40, p = 0.046) in 999del5 carriers with breast cancer. This suggests that the lifetime probability of a BARD1 Cys557Ser/BRCA2 999del5 double carrier developing breast cancer could approach certainty. Cys557Ser carriers, with or without the BRCA2 mutation, had an increased risk of subsequent primary breast tumors after the first breast cancer diagnosis compared to non-carriers. Lobular and medullary breast carcinomas were overrepresented amongst Cys557Ser carriers. We found that an excess of ancestors of contemporary carriers lived in a single county in the southeast of Iceland and that all carriers shared a SNP haplotype, which is suggestive of a founder event. Cys557Ser was found on the same SNP haplotype background in the HapMap Project CEPH sample of Utah residents. CONCLUSIONS: Our findings suggest that BARD1 Cys557Ser is an ancient variant that confers risk of single and multiple primary breast cancers, and this risk extends to carriers of the BRCA2 999del5 mutation

Utvikling av et hybrid varmerør for høytemperatur anvendelser

Det første målet med denne masteroppgaven er å utvikle en prosedyre for å vakuumere, fylle og forsegle et varmerør (heat pipe). Varmerør benyttes for å transportere varme med lave temperaturdifferanser. Ved høye temperaturer er det fordelaktig å ta i bruk kalium som arbeidsmedium i varmerør. I denne rapporten er det utarbeidet en metode for sikker vakuumering, fylling og forsegling av et varmerør med kalium som arbeidsmedium. Det er i tillegg utviklet en prosedyre for hvordan hele prosessen skal gjennomføres. En turbomolekylærpumpe skal brukes for å generere vakuum, og sammen med varmeelement utgasse varmerøret. Et påfyllingskammer benyttes for å smelte og overføre kalium, mens induksjonssveising skal benyttes for å forsegle varmerøret. Med prosedyren som er utviklet er det ventet at man vil få et lekkasjefritt varmerør med veldig ren kalium som arbeidsmedium.Det andre målet med denne oppgaven er å utarbeide en numerisk beregningsmodell for strømning i porøse medium. Beregningsmodellen skal kunne vise effekten av ujevnt varmepådrag på strømningen i veken. Et høyt varmepådrag i et lite område av veken vil gi mye avdamping i dette området. Dette vil føre til at man får 3D strømning. På grunn av at tykkelsen til veken er veldig liten, er det ventet at man får lite variasjon i tykkelsesretningen, og modellen kan forenkles til 2D strømning. Beregningsmodellen som er utarbeidet benytter Darcys lov, i kombinasjon med kontinuitetsligningen for masse, for å beregne det stasjonære trykk- og hastighetsfeltet som oppstår på grunn av et varmepådrag. Varmepådraget kan være uniformt eller ujevnt.Fordelingen av varmefluksen har mye å si for total varmetransportkapasitet for veken. En varmedistribusjon som fører til en høy fluks øverst i veken vil gi en lavere total varmestrøm enn en tilsvarende varmedistribusjon der den høye fluksen er plassert nede i veken. Det er sett på mange ulike varmepådrag, og effekten disse varmepådragene har på vekekapasiteten

Analysis of a vertical flat heat pipe using potassium working fluid and a wick of compressed nickel foam

Heat at high temperatures, in this work 400–650 °C, can be recovered by use of cooling panels/heat pipes in the walls of aluminum electrolysis cells. For this application a flat vertical heat pipe for heat transfer from a unilateral heat source was analyzed theoretically and in the laboratory, with special emphasis on the performance of the wick. In this heat pipe a wick of compressed nickel foam covered only the evaporator surface, and potassium was used as the working fluid. The magnitudes of key thermal resistances were estimated analytically and compared. Operating temperatures and wick performance limits obtained experimentally were compared to predictions. Thermal deformation due to unilateral heat flux was analyzed by the use of COMSOL Multiphysics®. The consequences of hot spots at different locations on the wick were analyzed by use of a numerical 2D model. A vertical rectangular wick was shown to be most vulnerable to hot spots at the upper corners

Dampening of wood batch combustion heat release using a phase change material heat storage: Material selection and heat storage property optimization

The use of wood stoves for space heating in energy effective residential buildings can be problematic due to the batch combustion giving a highly transient heat production and the limited regulation of the combustion process. Increasing the heat storage capacity and lowering the maximum heat release from the stove has been proposed to improve the utility of wood stoves. Latent Heat Storage (LHS) solutions will lower and even out the heat release from stoves. However, finding a suitable Phase Change Material (PCM) for a LHS solution can be problematic. In this work an analytical method for ranking PCM candidates for LHS solutions is proposed. The method takes into account PCM properties, in addition to LHS properties that have to be tailored to the selected PCM. The method is validated with numerical models using realistic heat production profiles from wood stoves. The numerical results show significant benefits of using PCMs in LHS solutions over traditional solutions. There exists significant work on PCMs and their properties, but little work on how to select a PCM for a given application. This work contributes to a more efficient selection process, decreasing the work required to select the optimum PCM for a LHS