| 1. |
- Lener, Thomas, et al.
(författare)
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Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper.
- 2015
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Ingår i: Journal of extracellular vesicles. - : Wiley. - 2001-3078. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Extracellular vesicles (EVs), such as exosomes and microvesicles, are released by different cell types and participate in physiological and pathophysiological processes. EVs mediate intercellular communication as cell-derived extracellular signalling organelles that transmit specific information from their cell of origin to their target cells. As a result of these properties, EVs of defined cell types may serve as novel tools for various therapeutic approaches, including (a) anti-tumour therapy, (b) pathogen vaccination, (c) immune-modulatory and regenerative therapies and (d) drug delivery. The translation of EVs into clinical therapies requires the categorization of EV-based therapeutics in compliance with existing regulatory frameworks. As the classification defines subsequent requirements for manufacturing, quality control and clinical investigation, it is of major importance to define whether EVs are considered the active drug components or primarily serve as drug delivery vehicles. For an effective and particularly safe translation of EV-based therapies into clinical practice, a high level of cooperation between researchers, clinicians and competent authorities is essential. In this position statement, basic and clinical scientists, as members of the International Society for Extracellular Vesicles (ISEV) and of the European Cooperation in Science and Technology (COST) program of the European Union, namely European Network on Microvesicles and Exosomes in Health and Disease (ME-HaD), summarize recent developments and the current knowledge of EV-based therapies. Aspects of safety and regulatory requirements that must be considered for pharmaceutical manufacturing and clinical application are highlighted. Production and quality control processes are discussed. Strategies to promote the therapeutic application of EVs in future clinical studies are addressed.
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| 2. |
- Björklund, Andreas, et al.
(författare)
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Approximate counting of K-paths : Deterministic and in polynomial space
- 2019
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Ingår i: 46th International Colloquium on Automata, Languages, and Programming, ICALP 2019. - 9783959771092 ; 132
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Konferensbidrag (refereegranskat)abstract
- A few years ago, Alon et al. [ISMB 2008] gave a simple randomized O((2e)km∊−2)-time exponential-space algorithm to approximately compute the number of paths on k vertices in a graph G up to a multiplicative error of 1 ± ∊. Shortly afterwards, Alon and Gutner [IWPEC 2009, TALG 2010] gave a deterministic exponential-space algorithm with running time (2e)k+O(log3 k)m log n whenever ∊−1 = kO(1). Recently, Brand et al. [STOC 2018] provided a speed-up at the cost of reintroducing randomization. Specifically, they gave a randomized O(4km∊−2)-time exponential-space algorithm. In this article, we revisit the algorithm by Alon and Gutner. We modify the foundation of their work, and with a novel twist, obtain the following results. We present a deterministic 4k+O(√k(log2 k+log2 ∊−1))m log n-time polynomial-space algorithm. This matches the running time of the best known deterministic polynomial-space algorithm for deciding whether a given graph G has a path on k vertices. Additionally, we present a randomized 4k+O(log k(log k+log ∊−1))m log n-time polynomial-space algorithm. While Brand et al. make non-trivial use of exterior algebra, our algorithm is very simple; we only make elementary use of the probabilistic method. Thus, the algorithm by Brand et al. runs in time 4k+o(k)m whenever ∊−1 = 2o(k), while our deterministic and randomized algorithms run in time 4k+o(k)m log n whenever ∊−1 = 2o(k 4 ) and 1 ∊−1 = 2o(log k k ), respectively. Prior to our work, no 2O(k)nO(1)-time polynomial-space algorithm was known. Additionally, our approach is embeddable in the classic framework of divide-and-color, hence it immediately extends to approximate counting of graphs of bounded treewidth; in comparison, Brand et al. note that their approach is limited to graphs of bounded pathwidth.
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| 3. |
- Björklund, Andreas, et al.
(författare)
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Computing permanents and counting Hamiltonian cycles by listing dissimilar vectors
- 2019
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Ingår i: 46th International Colloquium on Automata, Languages, and Programming : ICALP 2019 - ICALP 2019. - 1868-8969. - 9783959771092 ; 132, s. 1-25
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Konferensbidrag (refereegranskat)abstract
- We show that the permanent of an n × n matrix over any finite ring of r ≤ n elements can be computed with a deterministic 2n−Ω(nr ) time algorithm. This improves on a Las Vegas algorithm running in expected 2n−Ω(n/(r log r)) time, implicit in [Björklund, Husfeldt, and Lyckberg, IPL 2017]. For the permanent over the integers of a 0/1-matrix with exactly d ones per row and column, we provide a deterministic 2n−Ω(d3 n /4) time algorithm. This improves on a 2n−Ω(nd ) time algorithm in [Cygan and Pilipczuk ICALP 2013]. We also show that the number of Hamiltonian cycles in an n-vertex directed graph of average degree δ can be computed by a deterministic 2n−Ω(nδ ) time algorithm. This improves on a Las Vegas algorithm running in expected 2n−Ω(poly(n δ)) time in [Björklund, Kaski, and Koutis, ICALP 2017]. A key tool in our approach is a reduction from computing the permanent to listing pairs of dissimilar vectors from two sets of vectors, i.e., vectors over a finite set that differ in each coordinate, building on an observation of [Bax and Franklin, Algorithmica 2002]. We propose algorithms that can be used both to derandomise the construction of Bax and Franklin, and efficiently list dissimilar pairs using several algorithmic tools. We also give a simple randomised algorithm resulting in Monte Carlo algorithms within the same time bounds. Our new fast algorithms for listing dissimilar vector pairs from two sets of vectors are inspired by recent algorithms for detecting and counting orthogonal vectors by [Abboud, Williams, and Yu, SODA 2015] and [Chan and Williams, SODA 2016].
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| 4. |
- Björklund, Andreas, et al.
(författare)
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Solving systems of polynomial equations over GF(2) by a parity-counting self-reduction
- 2019
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Ingår i: 46th International Colloquium on Automata, Languages, and Programming : ICALP 2019 - ICALP 2019. - 1868-8969. - 9783959771092 ; 132, s. 1-26
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Konferensbidrag (refereegranskat)abstract
- We consider the problem of finding solutions to systems of polynomial equations over a finite field. Lokshtanov et al. [SODA'17] recently obtained the first worst-case algorithms that beat exhaustive search for this problem. In particular for degree-d equations modulo two in n variables, they gave an O∗2(1−1/(5d))n time algorithm, and for the special case d = 2 they gave an O∗20.876n time algorithm. We modify their approach in a way that improves these running times to O∗2(1−1/(27d))n and O∗20.804n, respectively. In particular, our latter bound - that holds for all systems of quadratic equations modulo 2 - comes close to the O∗20.792n expected time bound of an algorithm empirically found to hold for random equation systems in Bardet et al. [J. Complexity, 2013]. Our improvement involves three observations: 1. The Valiant-Vazirani lemma can be used to reduce the solution-finding problem to that of counting solutions modulo 2. 2. The monomials in the probabilistic polynomials used in this solution-counting modulo 2 have a special form that we exploit to obtain better bounds on their number than in Lokshtanov et al. [SODA'17]. 3. The problem of solution-counting modulo 2 can be “embedded” in a smaller instance of the original problem, which enables us to apply the algorithm as a subroutine to itself.
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| 5. |
- Björklund, Andreas, et al.
(författare)
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The shortest even cycle problem is tractable
- 2022
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Ingår i: STOC 2022 - Proceedings of the 54th Annual ACM SIGACT Symposium on Theory of Computing. - New York, NY, USA : ACM. - 0737-8017. - 9781450392648 ; , s. 117-130
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Konferensbidrag (refereegranskat)abstract
- Given a directed graph as input, we show how to efficiently find a shortest (directed, simple) cycle on an even number of vertices. As far as we know, no polynomial-time algorithm was previously known for this problem. In fact, finding any even cycle in a directed graph in polynomial time was open for more than two decades until Robertson, Seymour, and Thomas (Ann. of Math. (2) 1999) and, independently, McCuaig (Electron. J. Combin. 2004; announced jointly at STOC 1997) gave an efficiently testable structural characterisation of even-cycle-free directed graphs. Methodologically, our algorithm relies on the standard framework of algebraic fingerprinting and randomized polynomial identity testing over a finite field, and in fact relies on a generating polynomial implicit in a paper of Vazirani and Yannakakis (Discrete Appl. Math. 1989) that enumerates weighted cycle covers by the parity of their number of cycles as a difference of a permanent and a determinant polynomial. The need to work with the permanent-known to be #P-hard apart from a very restricted choice of coefficient rings (Valiant, Theoret. Comput. Sci. 1979)-is where our main technical contribution occurs. We design a family of finite commutative rings of characteristic 4 that simultaneously (i) give a nondegenerate representation for the generating polynomial identity via the permanent and the determinant, (ii) support efficient permanent computations by extension of Valiant's techniques, and (iii) enable emulation of finite-field arithmetic in characteristic 2. Here our work is foreshadowed by that of Björklund and Husfeldt (SIAM J. Comput. 2019), who used a considerably less efficient commutative ring design-in particular, one lacking finite-field emulation-to obtain a polynomial-time algorithm for the shortest two disjoint paths problem in undirected graphs. Building on work of Gilbert and Tarjan (Numer. Math. 1978) as well as Alon and Yuster (J. ACM 2013), we also show how ideas from the nested dissection technique for solving linear equation systems-introduced by George (SIAM J. Numer. Anal. 1973) for symmetric positive definite real matrices-leads to faster algorithm designs in our present finite-ring randomized context when we have control on the separator structure of the input graph; for example, this happens when the input has bounded genus.
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| 6. |
- Landi, Antonio, et al.
(författare)
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Transient vs In-Hospital Persistent AcuteKidney Injury in Patients With Acute Coronary Syndrome.
- 2023
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Ingår i: JACC. Cardiovascular interventions. - : Elsevier BV. - 1876-7605 .- 1936-8798. ; 16:2, s. 193-205
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Tidskriftsartikel (refereegranskat)abstract
- The occurrence of acute kidney injury (AKI) among patients with acute coronary syndrome (ACS) undergoing invasive management is associated with worse outcomes. However, the prognostic implications of transient or in-hospital persistent AKI may differ.The aim of this study was to evaluate the prognostic implications of transient or in-hospital persistent AKI in patients with ACS.In the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial, 203 subjects were excluded because of incomplete information or end-stage renal disease, with a study population of 8,201 patients. Transient and persistent AKI were defined as renal dysfunction no longer or still fulfilling the AKI criteria (>0.5mg/dL or a relative >25% increase in creatinine) at discharge, respectively. Thirty-day coprimary outcomes were the out-of-hospital composite of death, myocardial infarction, or stroke (major adverse cardiovascular events [MACE]) and net adverse cardiovascular events (NACE), defined as the composite of MACE or Bleeding Academic Research Consortium type 3 or 5 bleeding.Persistent and transient AKI occurred in 750 (9.1%) and 587 (7.2%) subjects, respectively. After multivariable adjustment, compared with patients without AKI, the risk for 30-day coprimary outcomes was higher in patients with persistent AKI (MACE: adjusted HR: 2.32; 95%CI: 1.48-3.64; P< 0.001; NACE: adjusted HR: 2.29; 95%CI: 1.48-3.52; P< 0.001), driven mainly by all-cause mortality (adjusted HR: 3.43; 95%CI: 2.03-5.82; P< 0.001), whereas transient AKI was not associated with higher rates of MACE or NACE. Results remained consistent when implementing the KDIGO (Kidney Disease Improving Global Outcomes) criteria.Among patients with ACS undergoing invasive management, in-hospital persistent but not transient AKI was associated with higher risk for 30-day MACE and NACE. (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox [MATRIX]; NCT01433627).
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| 7. |
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| 8. |
- Lyu, Yezhe, 1987-, et al.
(författare)
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Friction, wear and airborne particle emission from Cu-free brake materials
- 2020
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Ingår i: Tribology International. - : Elsevier. - 0301-679X .- 1879-2464. ; 141
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Tidskriftsartikel (refereegranskat)abstract
- Cu is required to be abated in brake pads due to its toxicity. There are on the market several Cu-free brake pads. These Cu-free brake pads are only evaluated regarding their friction and wear performance, whereas, their airborne particle emissions are not considered. A pin-on-disc tribometer is used to evaluate the friction, wear and airborne particle emission from two Cu-free commercial brake pads used in the Europe. Moreover, a commercial brake pad containing Cu is evaluated as a reference. The results indicate that Cu-free brake pads yield comparable coefficient of friction as the Cu-contained brake pad. All three brake materials result in similar wear to the mating brake rotor. Cu-free brake pads generate more airborne particles than Cu-contained brake pad.
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| 9. |
- Sundin, Johan, et al.
(författare)
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Heat transfer increase by convection in liquid-infused surfaces for laminar and turbulent flows
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Liquid-infused surfaces (LIS) can reduce friction drag in both laminar and turbulent flows. However, the heat transfer properties of such multi-phase surfaces have still not been investigated to a large extent. We use numerical simulations to study conjugate heat transfer of liquid-filled grooves. It is shown that heat transfer can increase for both laminar and turbulent liquid flows due to recirculation in the surface texture. For the increase to be substantial, the thermal conductivity of the solid must be similar to the thermal conductivity of the fluids, and the recirculation in the grooves must be sufficiently strong (Péclet number larger than 1). The ratio of the surface cavity to the system height is an upper limit of the direct contribution from the recirculation. While this ratio can be significant for laminar flows in microchannels, it is limited for turbulent flows, where the system scale (e.g. channel height) usually is much larger than the texture height. However, heat transfer enhancement on the order of 10% is observed (with a net drag reduction) in a turbulent channel flow at a friction Reynolds number Reτ ≈ 180. It is shown that the turbulent convection in the bulk can be enhanced indirectly from the recirculation in the grooves.
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| 10. |
- Sundin, Johan, et al.
(författare)
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Heat transfer increase by convection in liquid-infused surfaces for laminar and turbulent flows
- 2022
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Ingår i: Journal of Fluid Mechanics. - : Cambridge University Press (CUP). - 0022-1120 .- 1469-7645. ; 941
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Tidskriftsartikel (refereegranskat)abstract
- Liquid-infused surfaces can reduce friction drag in both laminar and turbulent flows. However, the heat transfer properties of such multi-phase surfaces have still not been investigated to a large extent. We use numerical simulations to study conjugate heat transfer of liquid-filled grooves. It is shown that heat transfer can increase for both laminar and turbulent liquid flows due to recirculation in the surface texture. Laminar flow simulations show that for the increase to be substantial, the thermal conductivity of the solid must be similar to the thermal conductivity of the fluids, and the recirculation in the grooves must be sufficiently strong (Peclet number larger than 1). The ratio of the surface cavity to the system height is an upper limit of the direct contribution from the recirculation. While this ratio can be significant for laminar flows in microchannels, it is limited for turbulent flows, where the system scale (e.g. channel height) usually is much larger than the texture height. However, heat transfer enhancement of the order of 10 % is observed (with a net drag reduction) in a turbulent channel flow at a friction Reynolds number Re-tau approximate to 180. It is shown that the turbulent convection in the bulk can be enhanced indirectly from the recirculation in the grooves.
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