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One of the main factors hampering the implementation in industry of transaminase-based processes for the synthesis of enantiopure amines is their often low storage and operational stability. Our still limited understanding of the inactivation processes undermining the stability of wild-type transaminases represents an obstacle to improving their stability through enzyme engineering. In this paper
Cathepsin C (CatC)is a dipeptidyl-exopeptidase which activates neutrophil serine protease precursors (elastase, proteinase 3, cathepsin G and NSP4)by removing their N-terminal propeptide in bone marrow cells at the promyelocytic stage of neutrophil differentiation. The resulting active proteases are implicated in chronic inflammatory and autoimmune diseases. Hence, inhibition of CatC represents a
Activation of the Met receptor tyrosine kinase, either by its ligand, hepatocyte growth factor (HGF), or via ligand-independent mechanisms, such as MET amplification or receptor overexpression, has been implicated in driving tumor proliferation, metastasis, and resistance to therapy. Clinical development of Met-targeted antibodies has been challenging, however, as bivalent antibodies exhibit agoni
With more than 50,000 members, terpenoids are one of the most important classes of natural products and show an enormous diversity. Due to their unique odors and specific bioactivities they already find wide application in the flavor, fragrance and pharma industries. Since most terpenoids can only be obtained by natural product extraction, the discovery of biosynthetic genes for the generation of
Dynamic kinetic resolution (DKR) reactions in which a stereoselective enzyme and a racemization step are coupled in one pot would represent powerful tools for the production of enantiopure amines through enantioconvergence of racemates. The exploitation of DKR strategies is currently hampered by the lack of effective, enzyme-compatible and scalable racemization strategies for amines. In the presen
We report the synthesis of linear and branched (1→4)-d-galactans. Four tetrasaccharides and one pentasaccharide were accessed by adopting a procedure of regioselective ring opening of a 4,6-O-naphthylidene protecting group followed by glycosylation using phenyl thioglycoside donors. The binding of the linear pentasaccharide with galectin-3 is also investigated by the determination of a co-crystal
CHANGES resulting in altered antigenic properties of viruses nearly always occur on their surface and have been attributed to the substitution of residues directly involved in binding antibody. To investigate the mechanism of antigenic variation in foot-and-mouth disease virus (FMDV), variants that escape neutralization by a monoclonal antibody have been compared crystallographically and serologic
ATTACHMENT of foot-and-mouth disease virus (FMDV) to its cellular receptor involves a long and highly antigenic loop containing the conserved sequence, Arg-Gly-Asp, a motif known to be a recognition element in many integrin-dependent cell adhesion processes1-7. In our original crystal structure of FMDV the Arg-Gly-Asp-containing loop ('the loop'), located between β-strands G and H of capsid protei
In pre-industrial Europe, many thousands of ‘middle-class’ individuals retired by purchasing a corrody: a contract allowing them life-long food and lodging, usually by spending their remaining years in a hospital. Given that people usually struggle to prepare for the later stages of life, this article asks whether corrodies were priced in line with the market. We study institutions that specialize
This study, based on a systematic literature review, aims to identify and analyze selected control mechanisms when project success criteria operationalize. The main theoretical contribution of this study involves identifying the dimension of control mechanisms in success criteria operationalization. The most easily identified control mechanisms in the data material were output control mechanisms,
Automated decision-making (ADM) has been introduced into the public sector in many countries, including for decisions made regarding the provision of economic support to people in need. This article analyses the value positions (the ‘desired intentions’) for using ADM to determine such decisions in four Swedish municipalities. The value positions related to efficiency of the application process, i
I en tid då tekniska lösningar blir allt vanligare behövs en problematisering av vad digitalisering i socialtjänsten betyder och hur olika verksamheter påverkas. Digitaliseringen väcker reaktioner, både i form av rädslor för att det personliga mötet ska försvinna och förhoppningar om effektiva lösningar för ett mer ekonomiskt, rättvist och mer likriktat beslutsfattande och utförande. Kan digital t
Automated decision-making is prevalent in numerous areas of the public sector. Based on the results of a qualitative, event-based study of how robotic process automation (RPA) is discussed and implemented in social work in Sweden, two questions are answered in this paper: What actors, intentions and network formations appear in the dissemination of RPA in the management of applications for social
This thesis consists of five chapters which focus on panel data theory. Four of them analyze explicit panel data models and one chapter deals with time series forecasting model, where external panel data help us estimate unobserved explanatory variables. The broad topics discussed in the thesis include i) simplification of distribution of a statistical test under double asymptotics, ii) eliminatio
The coronavirus disease-2019 (COVID-19) pandemic continues to be a cause of unprecedented global morbidity and mortality. Whilst COVID-19 vaccination has emerged as the only tangible solution to reducing poor clinical outcomes, vaccine hesitancy continues to be an obstacle to achieving high levels of vaccine uptake. This represents particular risk to patients with autoimmune diseases, a group alre
Background: The outcome in patients after surgery for acute type A aortic dissection without replacement of the part of the aorta containing the primary tear is undefined. Methods: Data of 1122 patients who underwent surgery for acute type A aortic dissection in 8 Nordic centers from January 2005 to December 2014 were retrospectively analyzed. The patients with primary tear location unfound, unkno
Exposure to elemental aluminum and its salts is unavoidable. Aluminum as a metal is present in transport, construction, packaging, and electronic equipment. Aluminum salts are present in consumer products, food items and drinking water, vaccines, drugs, and antiperspirants. Aluminum in vaccines and preparations for allergen-specific immunotherapy are the major sensitization sources. The predominen
Parkinson’s disease (PD) is a chronic, progressive, neurodegenerative disease involving both motor and non-motor symptoms (NMS). In the late stage of the disease, Hoehn and Yahr (HY) stages IV-V, the symptomatology is often severe and patients become increasingly dependent on help in their daily life, resulting in an increased burden for the informal caregivers. To assess the implications of the c
Allogeneic hematopoietic cell transplantation (allo-HCT) is the only curative treatment for patients with myeloid/lymphoid neoplasm (MLN) with FGFR1 rearrangement, but data on overall results are limited. We report on the largest series of patients (n = 22) with FGFR1-rearranged MLN undergoing allo-HCT. Distribution according to cytogenetic subtype was: t(8;13) in 11 cases, t(8;22) in 7 cases, t(6
