| 2771. |
- Henricsson, Cecilia, 1975, et al.
(författare)
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Engineering of a novel Saccharomyces cerevisiae wine strain with a respiratory phenotype at high external glucose concentrations
- 2005
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Ingår i: Applied and Environmental Microbiology. - 0099-2240 .- 1098-5336. ; 71:10, s. 6185-6192
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Tidskriftsartikel (refereegranskat)abstract
- The recently described respiratory strain Saccharomyces cerevisiae KOY.TM6*P is, to our knowledge, the only reported strain of S. cerevisiae which completely redirects the flux of glucose from ethanol fermentation to respiration, even at high external glucose concentrations (27). In the KOY.TM6*P strain, portions of the genes encoding the predominant hexose transporter proteins, Hxt1 and Hxt7, were fused within the regions encoding transmembrane (TM) domain 6. The resulting chimeric gene, TM6*, encoded a chimera composed of the amino-terminal half of Hxt1 and the carboxy-terminal half of Hxt7. It was subsequently integrated into the genome of an hxt null strain. In this study, we have demonstrated the transferability of this respiratory phenotype to the V5 hxt1-7 strain, a derivative of a strain used in enology. We also show by using this mutant that it is not necessary to transform a complete hxt null strain with the TM6* construct to obtain a nonethanol- producing phenotype. The resulting V5.TM6*P strain, obtained by transformation of the V5 hxt1-7 strain with the TM6* chimeric gene, produced only minor amounts of ethanol when cultured on external glucose concentrations as high as 5%. Despite the fact that glucose flux was reduced to 30% in the V5.TM6*P strain compared with that of its parental strain, the V5.TM6*P strain produced biomass at a specific rate as high as 85% that of the V5 wild-type strain. Even more relevant for the potential use of such a strain for the production of heterologous proteins and also of low-alcohol beverages is the observation that the biomass yield increased 50% with the mutant compared to its parental strain.
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| 2772. |
- Henriksson, J., et al.
(författare)
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A Model of Sympatric Speciation Through Reinforcement
- 2010
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Ingår i: Kinetic and Related Models. - : American Institute of Mathematical Sciences (AIMS). - 1937-5093 .- 1937-5077. ; 3:1, s. 143-163
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Tidskriftsartikel (refereegranskat)abstract
- Sympatric speciation, i.e. the evolutionary split of one species into two in the same environment, has been a highly troublesome concept. It has been a questioned if it is actually possible. Even though there have been a number of reported results both in the wild and from controlled experiments in laboratories, those findings are both hard to get and hard to analyze, or even repeat. In the current study we propose a mathematical model which addresses the question of sympatric speciation and the evolution of reinforcement. Our aim has been to capture some of the essential features such as: phenotype, resources, competition, heritage, mutation, and reinforcement, in as simple a way as possible. Still, the resulting model is not too easy to grasp with purely analytical tools, so we have also complemented those studies with stochastic simulations. We present a few results that both illustrates the usefulness of such a model, but also rises new biological questions about sympatric speciation and reinforcement in particular.
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| 2773. |
- Henriksson, Jens, 1991, et al.
(författare)
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Performance analysis of out-of-distribution detection on trained neural networks
- 2020
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Ingår i: Information and Software Technology. - : Elsevier B.V.. - 0950-5849 .- 1873-6025.
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Tidskriftsartikel (refereegranskat)abstract
- Context: Deep Neural Networks (DNN) have shown great promise in various domains, for example to support pattern recognition in medical imagery. However, DNNs need to be tested for robustness before being deployed in safety critical applications. One common challenge occurs when the model is exposed to data samples outside of the training data domain, which can yield to outputs with high confidence despite no prior knowledge of the given input. Objective: The aim of this paper is to investigate how the performance of detecting out-of-distribution (OOD) samples changes for outlier detection methods (e.g., supervisors) when DNNs become better on training samples. Method: Supervisors are components aiming at detecting out-of-distribution samples for a DNN. The experimental setup in this work compares the performance of supervisors using metrics and datasets that reflect the most common setups in related works. Four different DNNs with three different supervisors are compared during different stages of training, to detect at what point during training the performance of the supervisors begins to deteriorate. Results: Found that the outlier detection performance of the supervisors increased as the accuracy of the underlying DNN improved. However, all supervisors showed a large variation in performance, even for variations of network parameters that marginally changed the model accuracy. The results showed that understanding the relationship between training results and supervisor performance is crucial to improve a model's robustness. Conclusion: Analyzing DNNs for robustness is a challenging task. Results showed that variations in model parameters that have small variations on model predictions can have a large impact on the out-of-distribution detection performance. This kind of behavior needs to be addressed when DNNs are part of a safety critical application and hence, the necessary safety argumentation for such systems need be structured accordingly.
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| 2774. |
- Heras, Jónathan, et al.
(författare)
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Computing persistent homology within Coq/SSReflect
- 2013
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Ingår i: ACM Transactions on Computational Logic. - : Association for Computing Machinery (ACM). - 1529-3785 .- 1557-945X. ; 14:4
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Tidskriftsartikel (refereegranskat)abstract
- Persistent homology is one of the most active branches of Computational Algebraic Topology with applications in several contexts such as optical character recognition or analysis of point cloud data. In this paper, we report on the formal development of certified programs to compute persistent Betti numbers, an instrumental tool of persistent homology, using the Coq proof assistant together with the SSReflect extension. To this aim it has been necessary to formalize the underlying mathematical theory of these algorithms. This is another example showing that interactive theorem provers have reached a point where they are mature enough to tackle the formalization of nontrivial mathematical theories.
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| 2775. |
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| 2776. |
- Hermansson, Linn, et al.
(författare)
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Plasma concentration of neurofilament light chain protein decreases after switching from tenofovir disoproxil fumarate to tenofovir alafenamide fumarate
- 2019
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 14:12
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Tidskriftsartikel (refereegranskat)abstract
- Background Because tenofovir alafenamide (TAF) leads to significantly lower plasma tenofovir concentrations than tenofovir disoproxil fumarate (TDF) and is a stronger substrate for P-glycoprotein (P-gp) than TDF, TAF could lead to decreased central nervous system (CNS) tenofovir exposure than TDF. We aimed to determine if switching from TDF to TAF increases the risk of neuronal injury, by quantifying plasma levels of neurofilament light protein (NfL), a sensitive marker of neuronal injury in HIV CNS infection. Methods Plasma NfL concentration was measured at baseline, week 24, and week 84 in stored plasma samples from 416 participants (272 switching to elvitegravir (E)/cobicistat (C)/emtricitabine (F)/TAF and 144 continuing E/C/F/TDF) enrolled in the randomized, active-controlled, multicenter, open-label, noninferiority Gilead GS-US-292-0109 trial. Results While plasma NfL levels in both groups were within the normal range, we found a small but significant decrease in the E/C/F/TAF arm after 84 weeks from a geometric mean of 9.3 to 8.8 pg/mL (5.4% decline, 95% CI 2.0-8.4, p = 0.002). This change was significantly different (p = 0.001) from that of the E/C/F/TDF arm, in which plasma NfL concentration changed from 9.7 pg/mL at baseline to 10.2 pg/mL at week 84 (5.8% increase, 95% CI -0.8-12.9, p = 0.085). This increase is in line with what could be expected in normal ageing. Plasma NfL concentrations significantly correlated with age. No correlation was found between plasma NfL and serum creatinine. Conclusions We found no biomarker evidence of CNS injury when switching from TDF to TAF. It is unclear whether the small decrease in plasma NfL found after switch to TAF is of any clinical relevance, particularly with plasma NfL levels in both arms remaining within the limits found in HIV-negative controls. These results indicate that switching from TDF to TAF appears safe with regard to neuronal injury.
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| 2777. |
- Hernebring, Malin, 1978, et al.
(författare)
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Removal of damaged proteins during ES cell fate specification requires the proteasome activator PA28
- 2013
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 3:3, s. artikel nr 1381-
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Tidskriftsartikel (refereegranskat)abstract
- In embryonic stem cells, removal of oxidatively damaged proteins is triggered upon the first signs of cell fate specification but the underlying mechanism is not known. Here, we report that this phase of differentiation encompasses an unexpected induction of genes encoding the proteasome activator PA28 alpha beta (11S), subunits of the immunoproteasome (20Si), and the 20Si regulator TNF alpha. This induction is accompanied by assembly of mature PA28-20S(i) proteasomes and elevated proteasome activity. Inhibiting accumulation of PA28 alpha using miRNA counteracted the removal of damaged proteins demonstrating that PA28 alpha beta has a hitherto unidentified role required for resetting the levels of protein damage at the transition from self-renewal to cell differentiation.
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| 2778. |
- Hernqvist, Lisa, 1968, et al.
(författare)
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A statistical grouting decision method based on water pressure tests for the tunnel construction stage - A case study
- 2013
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Ingår i: Tunnelling and Underground Space Technology. - : Elsevier BV. - 0886-7798. ; 33, s. 54-62
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Tidskriftsartikel (refereegranskat)abstract
- In tunnel construction, a common method to reduce water inflow is pre-grouting. There is a need for a practical method, based on information about the rock mass, to assess whether inflow will remain below the set inflow requirements q(A), to form the basis for deciding at each tunnel front whether to grout or to proceed with excavation. The aim of this paper is to present a method for use at the tunnel construction stage to decide whether to grout or not. On the one hand, the aim is for it to be practical to use whilst on the other hand it must be scientifically founded and independent of the experience of the person responsible for making the decision. The input for the decision method consists of evaluated results from water pressure tests in a small number of tunnel front boreholes in combination with the specified inflow requirement for the tunnel. The method is statistically supported and is based on an equation for inflow prediction. To illustrate the decision method, it was applied to a 1 km section of the Onkalo Tunnel (built for Finland's spent nuclear fuel repository). The decision method results were compared with the results of decisions taken during the construction of the tunnel section and agreement between the two was investigated. The main findings of the paper are: For the case study tunnel section the same decisions would for the most part have been reached using the suggested decision method compared to the method that was actually used. The tunnel achieves the inflow requirement, indicating that the decision method would have led to satisfactory results. Further, a key advantage of the method is that it is transparent and scientifically based. Finally, one constraint on the method is that it is not recommended if a large part of the flow takes place in flow channels or if the probe holes are unlikely to intersect the water-bearing fractures. To increase the understanding of grouting in the Onkalo Tunnel, the grouting pressures were compared to the rock stress and a study was made of grout take in relation to the estimated hydraulic apertures of each grouting fan and to the expected grout penetrability.
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| 2779. |
- Hernroth, Bodil, 1951, et al.
(författare)
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Simulated climate change causes immune suppression and protein damage in the crustacean Nephrops norvegicus
- 2012
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Ingår i: Fish & Shellfish Immunology. - : Elsevier BV. - 1050-4648 .- 1095-9947. ; 33:5, s. 1095-1101
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Tidskriftsartikel (refereegranskat)abstract
- Rising atmospheric carbon dioxide concentration is causing global warming, which affects oceans by elevating water temperature and reducing pH. Crustaceans have been considered tolerant to ocean acidification because of their retained capacity to calcify during subnormal pH. However, we report here that significant immune suppression of the Norway lobster, Nephrops norvegicus, occurs after a 4-month exposure to ocean acidification (OA) at a level predicted for the year 2100 (hypercapnic seawater with a pH lowered by 0.4 units). Experiments carried out at different temperatures (5, 10, 12, 14, 16, and 18 °C) demonstrated that the temperature within this range alone did not affect lobster immune responses. In the OA-treatment, hemocyte numbers were reduced by almost 50% and the phagocytic capacity of the remaining hemocytes was inhibited by 60%. The reduction in hemocyte numbers was not due to increased apoptosis in hematopoetic tissue. Cellular responses to stress were investigated through evaluating advanced glycation end products (AGE) and lipid oxidation in lobster hepatopancreata, and OA-treatment was shown to significantly increase AGEs', indicating stress-induced protein alterations. Furthermore, the extracellular pH of lobster hemolymph was reduced by approximately 0.2 units in the OA-treatment group, indicating either limited pH compensation or buffering capacity. The negative effects of OA-treatment on the nephropidae immune response and tissue homeostasis were more pronounced at higher temperatures (12–18 °C versus 5 °C), which may potentially affect disease severity and spread. Our results signify that ocean acidification may have adverse effects on the physiology of lobsters, which previously had been overlooked in studies of basic parameters such as lobster growth or calcification.
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| 2780. |
- Herrero, Sebastian, 1988, et al.
(författare)
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A JENSEN-ROHRLICH TYPE FORMULA FOR THE HYPERBOLIC 3-SPACE
- 2019
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Ingår i: Transactions of the American Mathematical Society. - : American Mathematical Society (AMS). - 0002-9947 .- 1088-6850. ; 371:9, s. 6421-6446
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Tidskriftsartikel (refereegranskat)abstract
- We give a Jensen-Rohrlich type formula for a certain class of automorphic functions on the hyperbolic 3-space for the group
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