| 1. |
- Zamora, Juan Carlos, et al.
(författare)
-
Considerations and consequences of allowing DNA sequence data as types of fungal taxa
- 2018
-
Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
-
Tidskriftsartikel (refereegranskat)abstract
- Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
|
|
| 2. |
- Berntsson Svensson, Richard, 1978, et al.
(författare)
-
Not all requirements prioritization criteria are equal at all times: A quantitative analysis
- 2024
-
Ingår i: Journal of Systems and Software. - 0164-1212. ; 209
-
Tidskriftsartikel (refereegranskat)abstract
- Requirement prioritization is recognized as an important decision-making activity in requirements engineering. Requirement prioritization is applied to determine which requirements should be implemented and released. In order to prioritize requirements, there are several approaches/techniques/tools that use different requirements prioritization criteria, which are often identified by gut feeling instead of an in-depth analysis of which criteria are most important to use. Therefore, in this study we investigate which requirements prioritization criteria are most important to use in industry when determining which requirements are implemented and released, and if the importance of the criteria change depending on how far a requirement has reached in the development process. We conducted a quantitative study where quantitative data was collected through a case study of one completed project from one software developing company by extracting 32,139 requirements prioritization decisions based on eight requirements prioritization criteria for 11,110 requirements. The results show that not all requirements prioritization criteria are equally important, and this change depending on how far a requirement has reached in the development process. For example, for requirements prioritization decisions before iteration/sprint planning, having high Business value had an impact on the decisions, but after iteration/sprint planning, having high Business value had no impact. Editor's note: Open Science material was validated by the Journal of Systems and Software Open Science Board.
|
|
| 3. |
- Berntsson Svensson, Richard, et al.
(författare)
-
Prioritization of quality requirements : State of practice in eleven companies
- 2011
-
Ingår i: 2011 IEEE 19th International Requirements Engineering Conference, RE 2011; Trento; 29 August 2011 through 2 September 2011. - Trento : IEEE. - 9781457709234 ; , s. 69-78, s. 69-78
-
Konferensbidrag (refereegranskat)abstract
- Requirements prioritization is recognized as an important but challenging activity in software product development. For a product to be successful, it is crucial to find the right balance among competing quality requirements. Although literature offers many methods for requirements prioritization, the research on prioritization of quality requirements is limited. This study identifies how quality requirements are prioritized in practice at 11 successful companies developing software intensive systems. We found that ad-hoc prioritization and priority grouping of requirements are the dominant methods for prioritizing quality requirements. The results also show that it is common to use customer input as criteria for prioritization but absence of any criteria was also common. The results suggests that quality requirements by default have a lower priority than functional requirements, and that they only get attention in the prioritizing process if decision-makers are dedicated to invest specific time and resources on QR prioritization. The results of this study may help future research on quality requirements to focus investigations on industry-relevant issues.
|
|
| 4. |
- Berntsson Svensson, Richard, et al.
(författare)
-
Quality Requirements in Industrial Practice – An Extended Interview Study at Eleven Companies
- 2012
-
Ingår i: IEEE Transactions on Software Engineering. - : IEEE. - 0098-5589 .- 1939-3520. ; 38:4, s. 923-935
-
Tidskriftsartikel (refereegranskat)abstract
- In order to create a successful software product and assure its quality, it is not enough to fulfill the functional requirements, it is also crucial to find the right balance among competing quality requirements (QR). An extended, previosluy piloted, interview study was performed to identify specific challenges associated with the selection, trade-off, and management of QR in industrial practice. Data was collected through semi-structured interviews with eleven product managers and eleven project leaders from eleven software companies. The contribution of this study is fourfold: First, it compares how QR are handled in two cases, companies working in business-to-business markets, and companies that are working in business-to-consumer markets. These two are also compared in terms of impact on the handling of QRs. Second, it compares the perceptions and priorities of QR by product and project management respectively. Third, it includes an examination of the interdependencies among quality requirements perceived as most important by the practitioners. Fourth, it characterizes the selection and management of QR in down-stream development activities.
|
|
| 5. |
- Berntsson Svensson, Richard, 1978, et al.
(författare)
-
Quality Requirements in Industrial Practice - An Extended Interview Study at Eleven Companies
- 2011
-
Ingår i: IEEE Transactions on Software Engineering. - 0098-5589 .- 1939-3520.
-
Tidskriftsartikel (refereegranskat)abstract
- In order to create a successful software product and assure its quality, it is not enough to fulfill the functional requirements, it is also crucial to find the right balance among competing quality requirements (QR). An extended, previously piloted, interview study was performed to identify specific challenges associated with the selection, trade-off, and management of QR in industrial practice. Data was collected through semi-structured interviews with eleven product managers and eleven project leaders from eleven software companies. The contribution of this study is fourfold: First, it compares how QR are handled in two cases, companies working in business-to-business markets, and companies that are working in business-to-consumer markets. These two are also compared in terms of impact on the handling of QRs. Second, it compares the perceptions and priorities of QR by product and project management respectively. Third, it includes an examination of the interdependencies among quality requirements perceived as most important by the practitioners. Fourth, it characterizes the selection and management of QR in down-stream development activities.
|
|
| 6. |
- Berntsson Svensson, Richard, 1978, et al.
(författare)
-
The unfulfilled potential of data-driven decision making in agile software development
- 2019
-
Ingår i: Lecture Notes in Business Information Processing. - Cham : Springer International Publishing. - 1865-1356 .- 1865-1348. - 9783030190330 ; 355, s. 69-85
-
Konferensbidrag (refereegranskat)abstract
- With the general trend towards data-driven decision making (DDDM), organizations are looking for ways to use DDDM to improve their decisions. However, few studies have looked into the practitioners view of DDDM, in particular for agile organizations. In this paper we investigated the experiences of using DDDM, and how data can improve decision making. An emailed questionnaire was sent out to 124 industry practitioners in agile software developing companies, of which 84 answered. The results show that few practitioners indicated a wide-spread use of DDDM in their current decision making practices. The practitioners were more positive to its future use for higher-level and more general decision making, fairly positive to its use for requirements elicitation and prioritization decisions, while being less positive to its future use at the team level. The practitioners do see a lot of potential for DDDM in an agile context; however, currently unfulfilled.
|
|
| 7. |
- Estrada, Karol, et al.
(författare)
-
Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
- 2012
-
Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
-
Tidskriftsartikel (refereegranskat)abstract
- Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
|
|
| 8. |
- Gad, Helge, et al.
(författare)
-
MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
- 2014
-
Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
-
Tidskriftsartikel (refereegranskat)abstract
- Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
|
|
| 9. |
- Glantz, Maria, et al.
(författare)
-
Impact of protease and lipase activities on quality of Swedish raw milk
- 2020
-
Ingår i: International Dairy Journal. - : Elsevier BV. - 0958-6946. ; 107
-
Tidskriftsartikel (refereegranskat)abstract
- An increasing demand for dairy products with long shelf-life is foreseen. A limiting factor for maintaining high quality of these products is the activity of spoilage enzymes during storage. Lipase and protease activities in Swedish raw milk at farm and dairy level were investigated, analysing milk samples from three geographical regions and two seasons. Lipase activity in milk at farm level was affected by regional and seasonal variations, whereas at dairy level only season had an effect. Lipase activity was positively correlated with ionic calcium. For protease activity, no effect of either region or season was seen. Degradation products, e.g., free fatty acids, peptides and plasmin proteolysis products, varied differently between season and geographical origin at both farm and dairy level. The results indicate that lipase and protease activities are important for raw milk quality, while ionic calcium might be a future indicator for milk fat stability.
|
|
| 10. |
- Kuang, Qie, et al.
(författare)
-
A refined atomic model for microsomal glutathione transferase 1 from electron crystallography
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Microsomal glutathione transferase 1 (MGST1) is a detoxification enzyme belonging to the Membrane Associated Proteins in Eicosanoid and Glutathione Metabolism (MAPEG) superfamily. Here we have used electron crystallography of two-dimensional (2D) crystals in order to determine an atomic model of rat MGST1 in a lipid environment. The 2D crystals were of the p6 two-sided plane group symmetry. For the refinement, information to 3.5 Å resolution from 225 electron diffraction patterns recorded from specimens at tilt angles up to 66° was used. The model comprises 123 of the 155 amino acid residues, two structured phospholipid molecules, two hydrocarbon chains, and one glutathione (GSH) molecule. Interactions between subunits form trimers centered on the crystallographic three-fold axes of the unit cell. The GSH substrate binds in an extended conformation at the interface between two subunits of the trimer. The location of GSH is supported by mutagenesis data in vitro.
|
|
| 11. |
- Larsson, Pär, et al.
(författare)
-
The complete genome sequence of Francisella tularensis, the causative agent of tularemia
- 2005
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 37:2, s. 153-159
-
Tidskriftsartikel (refereegranskat)abstract
- Francisella tularensis is one of the most infectious human pathogens known. In the past, both the former Soviet Union and the US had programs to develop weapons containing the bacterium. We report the complete genome sequence of a highly virulent isolate of F. tularensis (1,892,819 bp). The sequence uncovers previously uncharacterized genes encoding type IV pili, a surface polysaccharide and iron-acquisition systems. Several virulence-associated genes were located in a putative pathogenicity island, which was duplicated in the genome. More than 10% of the putative coding sequences contained insertion-deletion or substitution mutations and seemed to be deteriorating. The genome is rich in IS elements, including IS630 Tc-1 mariner family transposons, which are not expected in a prokaryote. We used a computational method for predicting metabolic pathways and found an unexpectedly high proportion of disrupted pathways, explaining the fastidious nutritional requirements of the bacterium. The loss of biosynthetic pathways indicates that F. tularensis is an obligate host-dependent bacterium in its natural life cycle. Our results have implications for our understanding of how highly virulent human pathogens evolve and will expedite strategies to combat them.
|
|
| 12. |
|
|
| 13. |
- Spahiu, Linda, et al.
(författare)
-
Global Kinetic Mechanism of Microsomal Glutathione Transferase 1 and Insights into Dynamic Enzyme Activation
- 2017
-
Ingår i: Biochemistry. - : AMER CHEMICAL SOC. - 0006-2960 .- 1520-4995. ; 56:24, s. 3089-3098
-
Tidskriftsartikel (refereegranskat)abstract
- Microsomal glutathione transferase 1 (MGST1) has a unique ability to be activated, <= 30-fold, by modification with sulfhydryl reagents. MGST1 exhibits one-third-of-the-sites reactivity toward glutathione and hence heterogeneous binding to different active sites in the homotrimer. Limited turnover stopped-flow kinetic measurements of the activated enzyme allowed us to more accurately determine the KD for the "third" low-affinity GSH binding site (1.4 +/- 0.3 mM). The rate of thiolate formation, k(2) (0.77 +/- 0.06 s(-1)), relevant to turnover, could also be determined. By deriving the steadystate rate equation for a random sequential mechanism for MGST1, we can predict K-M, k(cat), and k(cat)/K-M values from these and previously determined pre-steady-state rate constants (all determined at 5 C). To assess whether the pre-steady-state behavior can account for the steady-state kinetic behavior, we have determined experimental values for kinetic parameters at 5 degrees C. For reactive substrates and the activated enzyme, data for the microscopic steps account for the global mechanism of MGST1. For the unactivated enzyme and more reactive electrophilic substrates, pre steady -state and steady-state data can be reconciled only if a more active subpopulation of MGST1 is assumed. We suggest that unactivated MGST1 can be partially activated in its unmodified form. The existence of an activated subpopulation (approximately 10%) could be demonstrated in limited turnover experiments. We therefore suggest that MSGT1 displays a preexisting dynamic equilibrium between high- and low-activity forms.
|
|
| 14. |
- Sunduru, Naresh, et al.
(författare)
-
N-aryl 2-aryloxyacetamides as a new class of fatty acid amide hydrolase (FAAH) inhibitors
- 2017
-
Ingår i: Journal of enzyme inhibition and medicinal chemistry (Print). - : Informa UK Limited. - 1475-6366 .- 1475-6374. ; 32:1, s. 513-521
-
Tidskriftsartikel (refereegranskat)abstract
- Fatty acid amide hydrolase (FAAH) is a promising target for the development of drugs to treat neurological diseases. In search of new FAAH inhibitors, we identified 2-(4-cyclohexylphenoxy)-N-(3-(oxazolo[4,5-b] pyri-din-2-yl) phenyl) acetamide, 4g, with an IC50 of 2.6 mu M as a chemical starting point for the development of potent FAAH inhibitors. Preliminary hit-to-lead optimisation resulted in 2-(4-phenylphenoxy)-N-(3-(oxazolo[4,5-b] pyridin-2-yl)phenyl) acetamide, 4i, with an IC50 of 0.35 mu M.
|
|
| 15. |
- Zheng, Hou-Feng, et al.
(författare)
-
Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture
- 2015
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 526:7571, s. 112-
-
Tidskriftsartikel (refereegranskat)abstract
- The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF <= 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants(1-8), as well as rare, population specific, coding variants(9). Here we identify novel non-coding genetic variants with large effects on BMD (n(total) = 53,236) and fracture (n(total) = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD8 (rs11692564(T), MAF51.6%, replication effect size510.20 s.d., P-meta = 2 x 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 x 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size +10.41 s.d., P-meta = 1 x 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
- Abdelwahab, Mahmoud Tareq, et al.
(författare)
-
Effect of Clofazimine Concentration on QT Prolongation in Patients Treated for Tuberculosis
- 2021
-
Ingår i: Antimicrobial Agents and Chemotherapy. - : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 65:7
-
Tidskriftsartikel (refereegranskat)abstract
- Clofazimine is classified as a WHO group B drug for the treatment of rifampin-resistant tuberculosis. QT prolongation, which is associated with fatal cardiac arrhythmias, is caused by several antitubercular drugs, including clofazimine, but there are no data quantifying the effect of clofazimine concentration on QT prolongation. Our objective was to describe the effect of clofazimine exposure on QT prolongation. Fifteen adults drug-susceptible tuberculosis patients received clofazimine monotherapy as 300mg daily for 3 days, followed by 100mg daily in one arm of a 2-week, multiarm early bactericidal activity trial in South Africa. Pretreatment Fridericia-corrected QT (QTcF) (105 patients, 524 electrocardiograms [ECGs]) and QTcFs from the clofazimine monotherapy arm matched with clofazimine plasma concentrations (199 ECGs) were interpreted with a nonlinear mixed-effects model. Clofazimine was associated with significant QT prolongation described by a maximum effect (Emax) function. We predicted clofazimine exposures using 100-mg daily doses and 2 weeks of loading with 200 and 300mg daily, respectively. The expected proportions of patients with QTcF change from baseline above 30 ms (DQTcF. 30) were 2.52%, 11.6%, and 23.0% for 100-, 200-, and 300-mg daily doses, respectively. At steady state, the expected proportion with Delta QTcF of >30 ms was 23.7% and with absolute QTcF of >450 ms was 3.42% for all simulated regimens. The use of loading doses of 200 and 300mg is not predicted to expose patients to an increased risk of QT prolongation, compared with the current standard treatment, and is, therefore, an alternative option for more quickly achieving therapeutic concentrations.
|
|
| 19. |
- Agren, P., et al.
(författare)
-
Agile software development one year into the COVID-19 pandemic
- 2022
-
Ingår i: Empirical Software Engineering. - : Springer Science and Business Media LLC. - 1382-3256 .- 1573-7616. ; 27:6
-
Tidskriftsartikel (refereegranskat)abstract
- As a result of the COVID-19 pandemic, many agile practitioners had to transition into a remote work environment. Despite remote work not being a new concept for agile software practitioners, the forced or recommended nature of remote work is new. This study investigates how the involuntary shift to remote work and how social restrictions imposed by the COVID-19 pandemic have affected agile software development (ASD), and how agile practitioners have been affected in terms of ways of working. An explanatory sequential mixed methods study was performed. Data were collected one year into the COVID-19 pandemic through a questionnaire with 96 respondents and in-depth semi-structured interviews with seven practitioners from seven different companies. Data were analyzed through Bayesian analysis and thematic analysis. The results show, in general, that the aspects of ASD that have been the most affected is communication and social interactions, while technical work aspects have not experienced the same changes. Moreover, feeling forced to work remotely has a significant impact on different aspects of ASD, e.g., productivity and communication, and industry practitioners' employment of agile development and ways of working have primarily been affected by the lack of social interaction and the shift to digital communication. The results also suggest that there may be a group maturing debt when teams do go back into office, as digital communication and the lack of psychological safety stand in the way for practitioners' ability to have sensitive discussions and progress as a team in a remote setting.
|
|
| 20. |
|
|
| 21. |
- Ainsworth, Richard I, et al.
(författare)
-
Systems-biology analysis of rheumatoid arthritis fibroblast-like synoviocytes implicates cell line-specific transcription factor function.
- 2022
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- Rheumatoid arthritis (RA) is an immune-mediated disease affecting diarthrodial joints that remains an unmet medical need despite improved therapy. This limitation likely reflects the diversity of pathogenic pathways in RA, with individual patients demonstrating variable responses to targeted therapies. Better understanding of RA pathogenesis would be aided by a more complete characterization of the disease. To tackle this challenge, we develop and apply a systems biology approach to identify important transcription factors (TFs) in individual RA fibroblast-like synoviocyte (FLS) cell lines by integrating transcriptomic and epigenomic information. Based on the relative importance of the identified TFs, we stratify the RA FLS cell lines into two subtypes with distinct phenotypes and predicted activepathways. We biologically validate these predictions for the top subtype-specific TF RARα and demonstrate differential regulation of TGFβ signaling in the two subtypes. This study characterizes clusters of RA cell lines with distinctive TF biology by integrating transcriptomic and epigenomic data, which could pave the way towards a greater understanding of disease heterogeneity.
|
|
| 22. |
- Al-Amin, Rasel A., Researcher, 1983-, et al.
(författare)
-
Monitoring drug–target interactions through target engagement-mediated amplification on arrays and in situ
- 2022
-
Ingår i: Nucleic Acids Research. - : Oxford University Press. - 0305-1048 .- 1362-4962. ; 50:22, s. e129-e129
-
Tidskriftsartikel (refereegranskat)abstract
- Drugs are designed to bind their target proteins in physiologically relevant tissues and organs to modulate biological functions and elicit desirable clinical outcomes. Information about target engagement at cellular and subcellular resolution is therefore critical for guiding compound optimization in drug discovery, and for probing resistance mechanisms to targeted therapies in clinical samples. We describe a target engagement-mediated amplification (TEMA) technology, where oligonucleotide-conjugated drugs are used to visualize and measure target engagement in situ, amplified via rolling-circle replication of circularized oligonucleotide probes. We illustrate the TEMA technique using dasatinib and gefitinib, two kinase inhibitors with distinct selectivity profiles. In vitro binding by the dasatinib probe to arrays of displayed proteins accurately reproduced known selectivity profiles, while their differential binding to fixed adherent cells agreed with expectations from expression profiles of the cells. We also introduce a proximity ligation variant of TEMA to selectively investigate binding to specific target proteins of interest. This form of the assay serves to improve resolution of binding to on- and off-target proteins. In conclusion, TEMA has the potential to aid in drug development and clinical routine by conferring valuable insights in drug–target interactions at spatial resolution in protein arrays, cells and in tissues.
|
|
| 23. |
- Al-Amin, Rasel A., 1983-, et al.
(författare)
-
Target Engagement-Mediated Amplification for Monitoring Drug-Target Interactions in Situ
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- It is important to determine the localization of drugs or drug candidates at cellular and subcellular resolution in relevant clinical specimens. This is necessary to evaluate drug candidates from early stages of drug development to clinical evaluation of mutations potentially causing resistance to targeted therapy. We describe a technology where oligonucleotide-conjugated drug molecules are used to visualize and measure target engagement in situ via rolling-circle amplification (RCA) of circularized oligonucleotide probes (padlock probes). We established this target engagement-mediated amplification (TEMA) technique using kinase inhibitor precursor compounds, and we applied the assay to investigate target interactions by microscopy in pathology tissue sections and using flow cytometry for blood samples from patients, as well as in commercial arrays including almost half of all human proteins. In the variant proxTEMAtechnique, in situ proximity ligation assays were performed by combining drug-DNA conjugates with antibody-DNA conjugates to specifically reveal drug binding to particular on- or off-targets in pathological tissues sections. In conclusion, the TEMA methods successfully visualize drug-target interaction by experimental and clinically approved kinase inhibitors in situ and with kinases among a large collection of arrayed proteins.
|
|
| 24. |
- Alahyari, Hiva, 1979, et al.
(författare)
-
A study of value in agile software development organizations
- 2017
-
Ingår i: Journal of Systems and Software. - : Elsevier BV. - 0164-1212 .- 1873-1228. ; 125, s. 271-288
-
Tidskriftsartikel (refereegranskat)abstract
- The Agile manifesto focuses on the delivery of valuable software. In Lean, the principles emphasise value, where every activity that does not add value is seen as waste. Despite the strong focus on value, and that the primary critical success factor for software intensive product development lies in the value domain, no empirical study has investigated specifically what value is. This paper presents an empirical study that investigates how value is interpreted and prioritised, and how value is assured and measured. Data was collected through semi-structured interviews with 23 participants from 14 agile software development organisations. The contribution of this study is fourfold. First, it examines how value is perceived amongst agile software development organisations. Second, it compares the perceptions and priorities of the perceived values by domains and roles. Third, it includes an examination of what practices are used to achieve value in industry, and what hinders the achievement of value. Fourth, it characterises what measurements are used to assure, and evaluate value-creation activities. (C) 2016 Elsevier Inc. All rights reserved.
|
|
| 25. |
- Alahyari, Hiva, 1979, et al.
(författare)
-
An exploratory study of waste in software development organizations using agile or lean approaches : A multiple case study at 14 organizations
- 2019
-
Ingår i: Information and Software Technology. - : Elsevier B.V.. - 0950-5849 .- 1873-6025. ; 107, s. 78-94
-
Tidskriftsartikel (refereegranskat)abstract
- Context: The principal focus of lean is the identification and elimination of waste from the process with respect to maximizing customer value. Similarly, the purpose of agile is to maximize customer value and minimize unnecessary work and time delays. In both cases the concept of waste is important. Through an empirical study, we explore how waste is approached in agile software development organizations. Objective: This paper explores the concept of waste in agile/lean software development organizations and how it is defined, used, prioritized, reduced, or eliminated in practice Method: The data were collected using semi-structured open-interviews. 23 practitioners from 14 embedded software development organizations were interviewed representing two core roles in each organization. Results: Various wastes, categorized in 10 different categories, were identified by the respondents. From the mentioned wastes, not all were necessarily waste per se but could be symptoms caused by wastes. From the seven wastes of lean, Task-switching was ranked as the most important, and Extra-features, as the least important wastes according to the respondents’ opinion. However, most companies do not have their own or use an established definition of waste, more importantly, very few actively identify or try to eliminate waste in their organizations beyond local initiatives on project level. Conclusion: In order to identify, recognize and eliminate waste, a common understanding, and a joint and holistic view of the concept is needed. It is also important to optimize the whole organization and the whole product, as waste on one level can be important on another, thus sub-optimization should be avoided. Furthermore, to achieve a sustainable and effective waste handling, both the short-term and the long-term perspectives need to be considered. © 2018 Elsevier B.V.
|
|
