| 1. |
- Allard, Christina, et al.
(författare)
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Rasbiologiskt språkbruk i statens rättsprocess mot sameby
- 2015
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Ingår i: Dagens Nyheter. - 1101-2447.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Statens hantering av forskningsresultat i rättsprocessen med Girjas sameby utgör ett hot mot Sverige som rättsstat och kunskapsnation. Åratal av svensk och internationell forskning underkänns och man använder ett språkbruk som skulle kunna vara hämtat från rasbiologins tid. Nu måste staten ta sitt ansvar och börja agera som en demokratisk rättsstat, skriver 59 forskare.
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| 2. |
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| 3. |
- Gad, Helge, et al.
(författare)
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MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
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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.
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| 4. |
- Johansson, Björn, 1978-
(författare)
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Distributed resource allocation in networked systems using decomposition techniques
- 2006
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The Internet and power distribution grids are examples of ubiquitous systems that are composed of subsystems that cooperate using a communication network. We loosely define such systems as networked systems. These systems are usually designed by using trial and error. With this thesis, we aim to fill some of the many gaps in the diverse theory of networked systems. Therefore, we cast resource allocation in networked systems as optimization problems, and we investigate a versatile class of optimization problems. We then use decomposition methods to devise decentralized algorithms that solve these optimization problems. The thesis consists of four main contributions: First, we review decomposition methods that can be used to devise decentralized algorithms for solving the posed optimization problems. Second, we consider cross-layer optimization of communication networks. Network performance can be increased if the traditionally separated network layers are jointly optimized. We investigate the interplay between the data sending rates and the allocation of resources for the communication links. The communication networks we consider have links where the data transferring capacity can be controlled. Decomposition methods are applied to the design of fully distributed protocols for two wireless network technologies: networks with orthogonal channels and network-wide resource constraints, as well as wireless networks using spatial-reuse time division multiple access. Third, we consider the problem of designing a distributed control strategy such that a linear combination of the states of a number of vehicles coincide at a given time. The vehicles are described by linear difference equations and are subject to convex input constraints. It is demonstrated how primal decomposition techniques and incremental subgradient methods allow us to find a solution in which each vehicle performs individual planning of its trajectory and exchanges critical information with neighbors only. We explore various communication, computation, and control structures. Fourth, we investigate the resource allocation problem for large-scale server clusters with quality-of-service objectives, in which key functions are decentralized. Specifically, the problem of selecting which services the servers should provide is posed as a discrete utility maximization problem. We develop an efficient centralized algorithm that solves this problem, and we propose three suboptimal schemes that operate with local information.
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| 5. |
- Johansson, Björn, 1978-
(författare)
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On Distributed Optimization in Networked Systems
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Numerous control and decision problems in networked systems can be posed as optimization problems. Examples include the framework of network utility maximization for resource allocation in communication networks, multi-agent coordination in robotics, and collaborative estimation in wireless sensor networks (WSNs). In contrast to classical distributed optimization, which focuses on improving computational efficiency and scalability, these new applications require simple mechanisms that can operate under limited communication. In this thesis, we develop several novel mechanisms for distributed optimization under communication constraints, and apply these to several challenging engineering problems. In particular, we devise three tailored optimization algorithms relying only on nearest neighbor, also known as peer-to-peer, communication. Two of the algorithms are designed to minimize a non-smooth convex additive objective function, in which each term corresponds to a node in a network. The first method is an extension of the randomized incremental subgradient method where the update order is given by a random walk on the underlying communication graph, resulting in a randomized peer-to-peer algorithm with guaranteed convergence properties. The second method combines local subgradient iterations with consensus steps to average local update directions. The resulting optimization method can be executed in a peer-to-peer fashion and analyzed using epsilon-subgradient methods. The third algorithm is a center-free algorithm, which solves a non-smooth resource allocation problem with a separable additive convex objective function subject to a constant sum constraint. Then we consider cross-layer optimization of communication networks, and demonstrate how optimization techniques allow us to engineer protocols that mimic the operation of distributed optimization algorithms to obtain an optimal resource allocation. We describe a novel use of decomposition methods for cross-layer optimization, and present a flowchart that can be used to categorize and visualize a large part of the current literature on this topic. In addition, we devise protocols that optimize the resource allocation in frequency-division multiple access (FDMA) networks and spatial reuse time-division multiple access (TDMA) networks, respectively. Next we investigate some variants of the consensus problem for multi-robot coordination, for which it is usually standard to assume that agents should meet at the barycenter of the initial states. We propose a negotiation strategy to find an optimal meeting point in the sense that the agents' trajectories to the meeting point minimize a quadratic cost criterion. Furthermore, we also demonstrate how an augmented state vector can be used to boost the convergence rate of the standard linear distributed averaging iterations, and we present necessary and sufficient convergence conditions for a general version of these iterations. Finally, we devise a generic optimization software component for WSNs. To this end, we implement some of the most promising optimization algorithms developed by ourselves and others in our WSN testbed, and present experimental results, which show that the proposed algorithms work surprisingly well.
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| 6. |
- Ludvigsson, Johnny, 1943-, et al.
(författare)
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GAD treatment and insulin secretion in recent-onset type 1 diabetes
- 2008
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Ingår i: New England Journal of Medicine. - Boston, Mass : Massachusetts medical society. - 0028-4793 .- 1533-4406. ; 359:18, s. 1909-1920
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Tidskriftsartikel (refereegranskat)abstract
- Background The 65-kD isoform of glutamic acid decarboxylase (GAD) is a major autoantigen in patients with type 1 diabetes mellitus. This trial assessed the ability of alum-formulated GAD (GAD-alum) to reverse recent-onset type 1 diabetes in patients 10 to 18 years of age. Methods We randomly assigned 70 patients with type 1 diabetes who had fasting C-peptide levels above 0.1 nmol per liter (0.3 ng per milliliter) and GAD autoantibodies, recruited within 18 months after receiving the diagnosis of diabetes, to receive subcutaneous injections of 20 μg of GAD-alum (35 patients) or placebo (alum alone, 35 patients) on study days 1 and 30. At day 1 and months 3, 9, 15, 21, and 30, patients underwent a mixed-meal tolerance test to stimulate residual insulin secretion (measured as the C-peptide level). The effect of GAD-alum on the immune system was also studied. Results Insulin secretion gradually decreased in both study groups. The study treatment had no significant effect on change in fasting C-peptide level after 15 months (the primary end point). Fasting C-peptide levels declined from baseline levels significantly less over 30 months in the GAD-alum group than in the placebo group (−0.21 vs. −0.27 nmol per liter [−0.62 vs. −0.81 ng per milliliter], P = 0.045), as did stimulated secretion measured as the area under the curve (−0.72 vs. −1.02 nmol per liter per 2 hours [−2.20 vs. −3.08 ng per milliliter per 2 hours], P = 0.04). No protective effect was seen in patients treated 6 months or more after receiving the diagnosis. Adverse events appeared to be mild and similar in frequency between the two groups. The GAD-alum treatment induced a GAD-specific immune response. Conclusions GAD-alum may contribute to the preservation of residual insulin secretion in patients with recent-onset type 1 diabetes, although it did not change the insulin requirement. (ClinicalTrials.gov number, NCT00435981.)
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| 7. |
- Soldati, Pablo, et al.
(författare)
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Distributed optimization of end-to-end rates and radio resources in WiMax single-carrier networks
- 2006
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Ingår i: GLOBECOM - IEEE Global Telecommunications Conference. - 9781424403561
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Konferensbidrag (refereegranskat)abstract
- We consider the problem of joint end-to-end band-width allocation and radio resource management in WiMax single-carrier wireless networks. The design problem is posed as a utility maximization problem subject to link rate constraints which involve transmission scheduling and power allocation. Inspired by a centralized algorithm for solving the associated optimization problem, we proceed systematically in our development of distributed resource allocation mechanisms. Contrary to the centralized algorithm, the proposed solution is distributed and of low computational complexity, generates schedules of finite length and with fixed time-slot durations, and acts on local neighborhood information only. Although the final scheme is suboptimal, we isolate and quantify the performance losses incurred and demonstrate strong performance in examples.
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| 8. |
- Soldati, Pablo, et al.
(författare)
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Proportionally fair allocation of end-to-end bandwidth in STDMA wireless networks
- 2006
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Ingår i: Proceedings of the International Symposium on Mobile Ad Hoc Networking and Computing. - New York, NY, USA : ACM. - 9781595933683 ; , s. 286-297
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Konferensbidrag (refereegranskat)abstract
- We consider the problem of designing distributed mechanisms for joint congestion control and resource allocation in spatial-reuse TDMA wireless networks. The design problem is posed as a utility maximization subject to link rate constraints that involve both power allocation and transmission scheduling over multiple time-slots. Starting from the performance limits of a centralized optimization based on global network information, we proceed systematically in the development of distributed and transparent protocols. In the process, we introduce a novel decomposition method for convex optimization, establish its convergence for the utility maximization problem and demonstrate how it suggests a distributed solution based on flow control optimization and incremental updates of the transmission schedule. We develop a two-step procedure for finding the schedule updates and suggest two schemes for distributed channel reservation and power control under realistic interference models. Although the final protocols are suboptimal, we isolate and quantify the performance losses incurred by each simplification and demonstrate strong performance in examples.
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| 9. |
- Aissaoui, Nesrine, 1983, et al.
(författare)
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FRET enhancement close to gold nanoparticles positioned in DNA origami constructs
- 2017
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Ingår i: Nanoscale. - Cambridge, United Kingdom : Royal Society of Chemistry (RSC). - 2040-3372 .- 2040-3364. ; 9:2, s. 673-683
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Tidskriftsartikel (refereegranskat)abstract
- Here we investigate the energy transfer rates of a Förster resonance energy transfer (FRET) pair positioned in close proximity to a 5 nm gold nanoparticle (AuNP) on a DNA origami construct. We study the distance dependence of the FRET rate by varying the location of the donor molecule, D, relative to the AuNP while maintaining a fixed location of the acceptor molecule, A. The presence of the AuNP induces an alteration in the spontaneous emission of the donor (including radiative and non-radiative rates) which is strongly dependent on the distance between the donor and AuNP surface. Simultaneously, the energy transfer rates are enhanced at shorter D-A (and D-AuNP) distances. Overall, in addition to the direct influence of the acceptor and AuNP on the donor decay there is also a significant increase in decay rate not explained by the sum of the two interactions. This leads to enhanced energy transfer between donor and acceptor in the presence of a 5 nm AuNP. We also demonstrate that the transfer rate in the three "particle" geometry (D + A + AuNP) depends approximately linearly on the transfer rate in the donor-AuNP system, suggesting the possibility to control FRET process with electric field induced by 5 nm AuNPs close to the donor fluorophore. It is concluded that DNA origami is a very versatile platform for studying interactions between molecules and plasmonic nanoparticles in general and FRET enhancement in particular.
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| 10. |
- Arnström, Daniel, 1994-
(författare)
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On Complexity Certification of Active-Set QP Methods with Applications to Linear MPC
- 2021
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In model predictive control (MPC) an optimization problem has to be solved at each time step, which in real-time applications makes it important to solve these efficiently and to have good upper bounds on worst-case solution time. Often for linear MPC problems, the optimization problem in question is a quadratic program (QP) that depends on parameters such as system states and reference signals. A popular class of methods for solving such QPs is active-set methods, where a sequence of linear systems of equations is solved. The primary contribution of this thesis is a method which determines which sequence of subproblems a popular class of such active-set algorithms need to solve, for every possible QP instance that might arise from a given linear MPC problem (i.e, for every possible state and reference signal). By knowing these sequences, worst-case bounds on how many iterations, floating-point operations and, ultimately, the maximum solution time, these active-set algorithms require to compute a solution can be determined, which is of importance when, e.g, linear MPC is used in safety-critical applications. After establishing this complexity certification method, its applicability is extended by showing how it can be used indirectly to certify the complexity of another, efficient, type of active-set QP algorithm which reformulates the QP as a nonnegative least-squares method. Finally, the proposed complexity certification method is extended further to situations when enhancements to the active-set algorithms are used, namely, when they are terminated early (to save computations) and when outer proximal-point iterations are performed (to improve numerical stability).
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