New pathways for sustainable terpene materials from wood

Polymers play an essential role in everyday life as materials in automotive, packaging and electronics to compounds in medicine. Nevertheless, the finite supply of fossil fuels and lacking biodegradability of most synthetic polymers leads to an increased need for the development of more sustainable materials from renewable sources. The use of renewable natural products from forestry, especially hemicellulose and terpenes,1 offers a highly versatile platform for green building blocks. By using Nature’s own biofunctionalizations, enzymes can be used as green catalysts for the valorization of abundant terpenes from pine wood extractives. Enzymatic biotransformations enable mild processes for “activating” inert molecular building blocks to afford renewable monomers. By combining in vitro synthetic biology and polymer chemistry, we have generated a new bio based polymer starting from, a naturally abundantterpene found in wood. Specifically, acrylation of the terpene Sobrerol, which can be achieved§ both enzymatically and by using traditional chemistry, constituted a suitable synthon for Atom Transfer Radical Polymerization (ATRP); a common and widely used, controlled polymerization technique. Furthermore, we demonstrate that sobrerol can be generated from other abundant monoterpenes using P450-based biocatalysis. Please click Additional Files below to see the full abstract

High-resolution genomic and expression analyses of copy number alterations in HER2-amplified breast cancer

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldINTRODUCTION: HER2 gene amplification and protein overexpression (HER2+) define a clinically challenging subgroup of breast cancer with variable prognosis and response to therapy. Although gene expression profiling has identified an ERBB2 molecular subtype of breast cancer, it is clear that HER2+ tumors reside in all molecular subtypes and represent a genomically and biologically heterogeneous group, needed to be further characterized in large sample sets. METHODS: Genome-wide DNA copy number profiling, using bacterial artificial chromosome (BAC) array comparative genomic hybridization (aCGH), and global gene expression profiling were performed on 200 and 87 HER2+ tumors, respectively. Genomic Identification of Significant Targets in Cancer (GISTIC) was used to identify significant copy number alterations (CNAs) in HER2+ tumors, which were related to a set of 554 non-HER2 amplified (HER2-) breast tumors. High-resolution oligonucleotide aCGH was used to delineate the 17q12-q21 region in high detail. RESULTS: The HER2-amplicon was narrowed to an 85.92 kbp region including the TCAP, PNMT, PERLD1, HER2, C17orf37 and GRB7 genes, and higher HER2 copy numbers indicated worse prognosis. In 31% of HER2+ tumors the amplicon extended to TOP2A, defining a subgroup of HER2+ breast cancer associated with estrogen receptor-positive status and with a trend of better survival than HER2+ breast cancers with deleted (18%) or neutral TOP2A (51%). HER2+ tumors were clearly distinguished from HER2- tumors by the presence of recurrent high-level amplifications and firestorm patterns on chromosome 17q. While there was no significant difference between HER2+ and HER2- tumors regarding the incidence of other recurrent high-level amplifications, differences in the co-amplification pattern were observed, as shown by the almost mutually exclusive occurrence of 8p12, 11q13 and 20q13 amplification in HER2+ tumors. GISTIC analysis identified 117 significant CNAs across all autosomes. Supervised analyses revealed: (1) significant CNAs separating HER2+ tumors stratified by clinical variables, and (2) CNAs separating HER2+ from HER2- tumors. CONCLUSIONS: We have performed a comprehensive survey of CNAs in HER2+ breast tumors, pinpointing significant genomic alterations including both known and potentially novel therapeutic targets. Our analysis sheds further light on the genomically complex and heterogeneous nature of HER2+ tumors in relation to other subgroups of breast cancer

På vilka grunder bedöms elevernas insatser under APU:n? : En granskning av det nuvarande bedömningsunderlaget för elevernas APU på Sjömansskolan i Stockholm och ett förslag till bättre bedömningsunderlag med portfolio som hjälpmedel.

Vi har på förslag från Johan Östergren, rektor på Sjömansskolan i Stockholm, kartlagt vad som fungerar bra och vad som fungerar mindre bra med det nuvarande systemet för bedömning av elevernas insatser när de är ute på APU (Arbetsplatsförlagd utbildning). Genom att intervjua elever, handledare, lärare och rektor, har vi bland annat undersökt hur kommunikationen mellan grupperna ser ut och vad de olika grupperna anser om de nuvarande dokumenten som eleverna arbetar med under APU:n. När elevens APU är slut ska handledaren lämna en betygsrekommendation till läraren, men på vilka grunder görs denna bedömning? Vi gör en historisk återblick för att ge läsaren förståelse för den yrkeskultur och tradition som finns inom sjömansyrket. Den svenska sjömansutbildningen jämförs i ett internationellt perspektiv med den lärlingsanpassade sjömansutbildningen i Danmark. Sjöfartens Utbildnings Institut (SUI) har en central roll i den arbetsplatsförlagda utbildningen. SUI ordnar APU-platser åt alla sjömansskolorna i Sverige. De har ett antal dokument som reglerar hur APU:n ska fungera och vilka åtaganden de delaktiga parterna åtar sig. Med hjälp av olika teorier om att arbeta med portfolio, har vi utvecklat en portfoliomodell för maskinelever. Modellen är flexibel och går att anpassa för däckselever men också andra inriktningar. Syftet med portfoliomodellen är dels att skapa ett didaktiskt redskap som kan underlätta kunskapandet för eleven, dels att förbättra bedömningsunderlaget för lärarens betygsättning av eleven under APU:n

Incidence of and risk factors for medication-related osteonecrosis of the jaw in women with breast cancer with bone metastasis : a population-based study

Objective: The aim of this study was to prospectively determine the incidence of medication-related osteonecrosis of the jaw (MRONJ) and define risk factors in patients with metastatic breast cancer treated with zoledronic acid and/or denosumab. Study Design: In a prospective cohort study performed in Region Skåne, Sweden, from January 1, 2012, until December 31, 2015, all patients with breast cancer who had radiographic evidence of bone metastases and were treated with zoledronic acid or denosumab were included and followed up until May 31, 2018. Results: Of the 242 patients, MRONJ developed in 16 (6.6%) during the 77 months of study. The incidence of MRONJ in patients treated with zoledronic acid was 4.1%, and in patients treated with denosumab, it was 13.6%. The risk of MRONJ was higher in patients on denosumab than in those treated with zoledronic acid (P =.011). Corticosteroid use was associated with a decreased risk of MRONJ (P =.008), and diabetes was associated with an increased risk of MRONJ (P =.02). Conclusions: The incidence of MRONJ is 13.6% (>3 times higher) in denosumab-treated patients with breast cancer compared with that in patients treated with zoledronic acid (4.1%). Corticosteroid use decreased the risk of MRONJ

Lactone monomers obtained by enzyme catalysis and their use in reversible thermoresponsive networks

Enzyme-catalyzed transformations have a great potential in both the pharmaceutical and chemical industry to achieve complex and (stereo)selective synthesis under mild reaction conditions. Still, the implementation of biocatalysis in the prerequisite upgrading of inert synthons into activated monomers for polymer applications has not yet been fully realized. In this contribution, we show that scaled-up synthesis of bicyclic norcamphor lactone using an engineered Baeyer-Villiger monooxygenase (BVMO) is feasible to reach complete conversion of the corresponding ketone in 24 h in shake-flask. The lactone monomer obtained by enzyme catalysis was copolymerized with epsilon-caprolactone via ring-opening polymerization to study the impact of the additional ring on material properties. Moreover, four-arm star-like, homo and block copolymers were designed from epsilon-caprolactone, epsilon-decalactone, and norcamphor lactone and characterized for their structural and thermal properties. These newly explored macromolecules were functionalized with furan rings using the enzyme Candida antarctica lipase B which allowed the formation of thermolabile networks via the pericyclic reaction with bismaleimide by means of Diels-Alder chemistry. The bonding/debonding state of these star-like based materials can be tuned by a suitable selection of thermal treatment. The temperature-dependent reversibility was assessed by thermal analysis and solubility test. Our results presented here shed light on the high potential of the use of chemoenzymatic approaches in the synthesis of new functional materials with tuned physiochemical properties. (c) 2020 The Authors. Journal of Applied Polymer Science published by Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48949

Long-term effects on the incidence of second primary cancers in a randomized trial of two and five years of adjuvant tamoxifen

Background: Tamoxifen is a well established treatment for breast cancer, but its long-term effects on the incidence of secondary cancers are not fully evaluated. Material and methods: We have studied 4128 postmenopausal patients with early stage breast cancer who were alive and free of breast cancer recurrence after two years of tamoxifen, and who were randomized to receive totally two or five years of therapy. Results: Compared to patients randomized to two years of tamoxifen the incidence of contralateral breast cancer [hazard ratio (HR) 0.73; 95% CI 0.56–0.96] and of lung cancer (HR 0.45; 95% CI 0.27–0.77), especially squamous cell and small cell lung cancer, were reduced in the five-year group, and similar results were seen when restricting the analysis to the 10-year period after treatment stopped. An increased incidence of endometrial cancer was observed in the five-year group, but the excess risk decreased over time. Conclusion: Further studies of the effects of tamoxifen on the risk of different histological types of lung cancer are needed

TOP2A and HER2 gene amplification as predictors of response to anthracycline treatment in breast cancer

The purpose of this study was to evaluate amplification of topoisomerase IIalpha (TOP2A) and HER2 genes as predictors of response to chemotherapy in advanced breast cancer. Gene copy number of TOP2A and HER2 were analysed with chromogenic in situ hybridization (CISH) on paraffin-embedded tissue sections from the primary tumour of 85 patients treated with anthracycline containing chemotherapy. TOP2A gene amplification was present in 14 (16%) and HER2 gene amplification in 38 (45%) of the primary tumours. Two of the 14 cases with TOP2A amplification were amplified without concurrent HER2 amplification. Neither TOP2A nor HER2 gene amplification were significantly associated with response to chemotherapy (p = 0.35 and p = 0.49, respectively)