95 research outputs found

    Ordered phase and scaling in ZnZ_n models and the three-state antiferromagnetic Potts model in three dimensions

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    Based on a Renormalization-Group picture of ZnZ_n symmetric models in three dimensions, we derive a scaling law for the ZnZ_n order parameter in the ordered phase. An existing Monte Carlo calculation on the three-state antiferromagnetic Potts model, which has the effective Z6Z_6 symmetry, is shown to be consistent with the proposed scaling law. It strongly supports the Renormalization-Group picture that there is a single massive ordered phase, although an apparently rotationally symmetric region in the intermediate temperature was observed numerically.Comment: 5 pages in REVTEX, 2 PostScript figure

    On the low-temperature phase of the three-state antiferromagnetic Potts model on the simple cubic lattice

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    The three-state antiferromagnetic Potts model on the simple cubic lattice is investigated using the cluster variation method in the cube and the star-cube approximations. The broken-sublattice-symmetry phase is found to be stable in the whole low-temperature region, contrary to previous results obtained using a modified cluster variation method. The tiny free energy difference between the broken-sublattice-symmetry and the permutationally-symmetric-sublattices phases is calculated in the two approximations and turns out to be smaller in the (more accurate) star-cube approximation than in the cube one.Comment: 4 pages REVTeX + 2 PostScript figures, to be published in Phys. Rev. E as a Rapid Communicatio

    Cardiovascular Magnetic Resonance Imaging Feature Tracking: Impact of Training on Observer Performance and Reproducibility

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    BACKGROUND: Cardiovascular magnetic resonance feature tracking (CMR-FT) is increasingly used for myocardial deformation assessment including ventricular strain, showing prognostic value beyond established risk markers if used in experienced centres. Little is known about the impact of appropriate training on CMR-FT performance. Consequently, this study aimed to evaluate the impact of training on observer variance using different commercially available CMR-FT software. METHODS: Intra- and inter-observer reproducibility was assessed prior to and after dedicated one-hour observer training. Employed FT software included 3 different commercially available platforms (TomTec, Medis, Circle). Left (LV) and right (RV) ventricular global longitudinal as well as LV circumferential and radial strains (GLS, GCS and GRS) were studied in 12 heart failure patients and 12 healthy volunteers. RESULTS: Training improved intra- and inter-observer reproducibility. GCS and LV GLS showed the highest reproducibility before (ICC \u3e0.86 and \u3e0.81) and after training (ICC \u3e0.91 and \u3e0.92). RV GLS and GRS were more susceptible to tracking inaccuracies and reproducibility was lower. Inter-observer reproducibility was lower than intra-observer reproducibility prior to training with more pronounced improvements after training. Before training, LV strain reproducibility was lower in healthy volunteers as compared to patients with no differences after training. Whilst LV strain reproducibility was sufficient within individual software solutions inter-software comparisons revealed considerable software related variance. CONCLUSION: Observer experience is an important source of variance in CMR-FT derived strain assessment. Dedicated observer training significantly improves reproducibility with most profound benefits in states of high myocardial contractility and potential to facilitate widespread clinical implementation due to optimized robustness and diagnostic performance

    A multi-vendor, multi-center study on reproducibility and comparability of fast strain-encoded cardiovascular magnetic resonance imaging

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    Myocardial strain is a convenient parameter to quantify left ventricular (LV) function. Fast strain-encoding (fSENC) enables the acquisition of cardiovascular magnetic resonance images for strain-measurement within a few heartbeats during free-breathing. It is necessary to analyze inter-vendor agreement of techniques to determine strain, such as fSENC, in order to compare existing studies and plan multi-center studies. Therefore, the aim of this study was to investigate inter-vendor agreement and test-retest reproducibility of fSENC for three major MRI-vendors. fSENC-images were acquired three times in the same group of 15 healthy volunteers using 3 Tesla scanners from three different vendors: at the German Heart Institute Berlin, the CharitĂ© University Medicine Berlin-Campus Buch and the Theresien-Hospital Mannheim. Volunteers were scanned using the same imaging protocol composed of two fSENC-acquisitions, a 15-min break and another two fSENC-acquisitions. LV global longitudinal and circumferential strain (GLS, GCS) were analyzed by a trained observer (Myostrain 5.0, Myocardial Solutions) and for nine volunteers repeatedly by another observer. Inter-vendor agreement was determined using Bland-Altman analysis. Test-retest reproducibility and intra- and inter-observer reproducibility were analyzed using intraclass correlation coefficient (ICC) and coefficients of variation (CoV). Inter-vendor agreement between all three sites was good for GLS and GCS, with biases of 0.01-1.88%. Test-retest reproducibility of scans before and after the break was high, shown by ICC- and CoV values of 0.63-0.97 and 3-9% for GLS and 0.69-0.82 and 4-7% for GCS, respectively. Intra- and inter-observer reproducibility were excellent for both parameters (ICC of 0.77-0.99, CoV of 2-5%). This trial demonstrates good inter-vendor agreement and test-retest reproducibility of GLS and GCS measurements, acquired at three different scanners from three different vendors using fSENC. The results indicate that it is necessary to account for a possible bias (< 2%) when comparing strain measurements of different scanners. Technical differences between scanners, which impact inter-vendor agreement, should be further analyzed and minimized.DRKS Registration Number: 00013253. Universal Trial Number (UTN): U1111-1207-5874

    Integration of imaging and circulating biomarkers in heart failure: a consensus document by the Biomarkers and Imaging Study Groups of the Heart Failure Association of the European Society of Cardiology

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    Circulating biomarkers and imaging techniques provide independent and complementary information to guide management of heart failure (HF). This consensus document by the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) presents current evidence-based indications relevant to integration of imaging techniques and biomarkers in HF. The document first focuses on application of circulating biomarkers together with imaging findings, in the broad domains of screening, diagnosis, risk stratification, guidance of treatment and monitoring, and then discusses specific challenging settings. In each section we crystallize clinically relevant recommendations and identify directions for future research. The target readership of this document includes cardiologists, internal medicine specialists and other clinicians dealing with HF patients

    Expression of a borage desaturase cDNA containing an N-terminal cytochrome b(5) domain results in the accumulation of high levels of Delta(6)-desaturated fatty acids in transgenic tobacco

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    Îł-Linolenic acid (GLA; C18:3 Δ6,9,12) is a component of the seed oils of evening primrose (Oenothera spp.), borage (Borago officinalis L.), and some other plants. It is widely used as a dietary supplement and for treatment of various medical conditions. GLA is synthesized by a Δ6-fatty acid desaturase using linoleic acid (C18:2 Δ9,12) as a substrate. To enable the production of GLA in conventional oilseeds, we have isolated a cDNA encoding the Δ6-fatty acid desaturase from developing seeds of borage and confirmed its function by expression in transgenic tobacco plants. Analysis of leaf lipids from a transformed plant demonstrated the accumulation of GLA and octadecatetraenoic acid (C18:4 Δ6,9,12,15) to levels of 13.2% and 9.6% of the total fatty acids, respectively. The borage Δ6-fatty acid desaturase differs from other desaturase enzymes, characterized from higher plants previously, by the presence of an N-terminal domain related to cytochrome b5. Δ6-Desaturated fatty acids are of major importance in animal cells as they have roles in the maintenance of membrane structure and function, in the regulation of cholesterol synthesis and transport, in the prevention of water loss from the skin, and as precursors of eicosanoids, including prostaglandins and leucotrienes (1). In animals, members of this class of fatty acids are synthesized from the essential fatty acid linoleic acid (C18:2 Δ9,12), the first step being the desaturation to Îł-linolenic acid (GLA; C18:3 Δ6,9,12) catalyzed by a Δ6-desaturase (1). Decreased activity of this key enzyme, observed for example in aging, stress, diabetes, eczema, and some infections, or increased catabolism of GLA resulting from oxidation or more rapid cell division (e.g., in cancer or inflammation) may lead to a deficiency of GLA (reviewed in ref. 2). Clinical trials have shown that dietary supplementation with GLA may be effective in treating a number of such conditions (e.g., atopic eczema, mastalgia, diabetic neuropathy, viral infections, and some types of cancer; ref. 2). Oils containing GLA are therefore widely used as a general health supplement and have been registered for pharmaceutical use. In the plant kingdom, GLA is an uncommon fatty acid (3). Only a small number of higher plant species synthesize GLA, and in many of these, the fatty acid is found exclusively in the seed. GLA is also present in some fungi (e.g., Mucor javanicus) and cyanobacteria (3). Major commercial sources of GLA (4) are evening primrose (Oenothera spp.), in which GLA accounts for about 8–10% of the seed oil and borage (starflower) (Borago officinalis L.) seeds that contain some 20–25% GLA. These plants, however, suffer from poor agronomic performance and low yield; borage, for example, produces 300–600 kg/ha in the United Kingdom (4) compared with about 3 t/ha for oilseed rape. There is therefore considerable interest in both increasing the GLA content of existing crops and the production of GLA in a conventional oil crop (such as high linoleate rape). In the higher plant cell, the synthesis of saturated fatty acids with chain lengths up to C18 and monounsaturated fatty acids (generally with a double bond at the Δ9 position) occurs in the plastid. Further desaturation can then occur either in the plastid or on the endoplasmic reticulum (ER; ref. 5). The desaturase enzymes of the plastid require reduced ferredoxin as an electron donor and are either soluble enzymes acting on saturated acyl-ACP substrates or membrane-bound enzymes using unsaturated fatty acids esterified to complex lipids such as monogalactosyldialglycerol. In contrast, the ER-located Δ12- and Δ15-desaturases use fatty acids located at the sn-2 position of phosphatidylcholine as substrates, and cytochrome b5 as a cofactor (5, 6). The Δ6-fatty acid desaturase in the developing cotyledons of borage is similar to the Δ12- and Δ15-desaturases in its location and substrate specificity (oleate/linoleate at the sn-2 position of phosphatidylcholine), and is assumed to use cytochrome b5 as its electron donor (7, 8). In addition, α-linolenic acid esterified to phosphatidylcholine may act as a substrate, resulting in the accumulation of octadecatetraenoic acid (OTA; C18:4 Δ6,9,12,15) in borage leaves (9). We describe the isolation of a cDNA clone encoding the Δ6-fatty acid desaturase from developing seeds of borage, using a PCR-based strategy. The identity of the cDNA has been confirmed by functional expression and analysis in transgenic tobacco plants. The encoded protein differs from other membrane-bound fatty acid desaturases of plants, such as those encoded by the FAD genes of Arabidopsis (10, 11), in that the desaturase domain is preceded at the N terminus by a sequence that is related to cytochrome b5 (12), the haemprotein involved in electron transport to other ER-located fatty acid desaturases (Δ12,15) from higher plants (8, 13)

    The Role of the Parkinson's Disease Gene PARK9 in Essential Cellular Pathways and the Manganese Homeostasis Network in Yeast

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    YPK9 (Yeast PARK9; also known as YOR291W) is a non-essential yeast gene predicted by sequence to encode a transmembrane P-type transport ATPase. However, its substrate specificity is unknown. Mutations in the human homolog of YPK9, ATP13A2/PARK9, have been linked to genetic forms of early onset parkinsonism. We previously described a strong genetic interaction between Ypk9 and another Parkinson's disease (PD) protein α-synuclein in multiple model systems, and a role for Ypk9 in manganese detoxification in yeast. In humans, environmental exposure to toxic levels of manganese causes a syndrome similar to PD and is thus an environmental risk factor for the disease. How manganese contributes to neurodegeneration is poorly understood. Here we describe multiple genome-wide screens in yeast aimed at defining the cellular function of Ypk9 and the mechanisms by which it protects cells from manganese toxicity. In physiological conditions, we found that Ypk9 genetically interacts with essential genes involved in cellular trafficking and the cell cycle. Deletion of Ypk9 sensitizes yeast cells to exposure to excess manganese. Using a library of non-essential gene deletions, we screened for additional genes involved in tolerance to excess manganese exposure, discovering several novel pathways involved in manganese homeostasis. We defined the dependence of the deletion strain phenotypes in the presence of manganese on Ypk9, and found that Ypk9 deletion modifies the manganese tolerance of only a subset of strains. These results confirm a role for Ypk9 in manganese homeostasis and illuminates cellular pathways and biological processes in which Ypk9 likely functions

    Role of cardiovascular imaging in cancer patients receiving cardiotoxic therapies: a position statement on behalf of the Heart Failure Association (HFA), the European Association of Cardiovascular Imaging (EACVI) and the Cardio‐Oncology Council of the European Society of Cardiology (ESC)

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    Cardiovascular (CV) imaging is an important tool in baseline risk assessment and detection of CV disease in oncology patients receiving cardiotoxic cancer therapies. This position statement examines the role of echocardiography, cardiac magnetic resonance, nuclear cardiac imaging and computed tomography in the management of cancer patients. The Imaging and Cardio‐Oncology Study Groups of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) in collaboration with the European Association of Cardiovascular Imaging (EACVI) and the Cardio‐Oncology Council of the ESC have evaluated the current evidence for the value of modern CV imaging in the cardio‐oncology field. The most relevant echocardiographic parameters, including global longitudinal strain and three‐dimensional ejection fraction, are proposed. The protocol for baseline pre‐treatment evaluation and specific surveillance algorithms or pathways for anthracycline chemotherapy, HER2‐targeted therapies such as trastuzumab, vascular endothelial growth factor tyrosine kinase inhibitors, BCr‐Abl tyrosine kinase inhibitors, proteasome inhibitors and immune checkpoint inhibitors are presented. The indications for CV imaging after completion of oncology treatment are considered. The typical consequences of radiation therapy and the possibility of their identification in the long term are also summarized. Special populations are discussed including female survivors planning pregnancy, patients with carcinoid disease, patients with cardiac tumours and patients with right heart failure. Future directions and ongoing CV imaging research in cardio‐oncology are discussed

    Instability of backoff protocols with arbitrary arrival rates

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    In contention resolution, multiple processors are trying to coordinate to send discrete messages through a shared channel with sharply limited communication. If two processors inadvertently send at the same time, the messages collide and are not transmitted successfully. An important case is acknowledgement-based contention resolution, in which processors cannot listen to the channel at all; all they know is whether or not their own messages have got through. This situation arises frequently in both networking and cloud computing. The most common acknowledgement-based protocols in practice are backoff protocols — variants of binary exponential backoff are used in both Ethernet and TCP/IP, and both Google Drive and AWS instruct their users to implement it to handle busy periods. In queueing models, where each processor has a queue of messages, stable backoff protocols are already known (H˚astad et al., SICOMP 1996). In queue-free models, where each processor has a single message but processors arrive randomly, it is a long-standing conjecture of Aldous (IEEE Trans. Inf. Theory 1987) that no stable backoff protocols exist for any positive arrival rate of processors. Despite exciting recent results for full-sensing protocols which assume far greater listening capabilities of the processors (see e.g. Bender et al. STOC 2020 or Chen et al. PODC 2021), this foundational question remains open; here instability is only known in general when the arrival rate of processors is at least 0.42 (Goldberg et al. SICOMP 2004). We prove Aldous’s conjecture for all backoff protocols outside of a tightly-constrained special case using a new domination technique to get around the main difficulty, which is the strong dependencies between messages

    Fine-grained reductions from approximate counting to decision

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    In this paper, we introduce a general framework for fine-grained reductions of approximate counting problems to their decision versions. (Thus we use an oracle that decides whether any witness exists to multiplicatively approximate the number of witnesses with minimal overhead.) This mirrors a foundational result of Sipser (STOC 1983) and Stockmeyer (SICOMP 1985) in the polynomialtime setting, and a similar result of MĂŒller (IWPEC 2006) in the FPT setting. Using our framework, we obtain such reductions for some of the most important problems in fine-grained complexity: the Orthogonal Vectors problem, 3SUM, and the NegativeWeight Triangle problem (which is closely related to All-Pairs Shortest Path). While all these problems have simple algorithms over which it is conjectured that no polynomial improvement is possible, our reductions would remain interesting even if these conjectures were proved; they have only polylogarithmic overhead, and can therefore be applied to subpolynomial improvements such as the n 3 /exp(Θ( p logn))-time algorithm for the Negative-Weight Triangle problem due to Williams (STOC 2014). Our framework is also general enough to apply to versions of the problems for which more efficient algorithms are known. For example, the Orthogonal Vectors problem over GF(m) d for constant m can be solved in time n · poly(d) by a result of Williams and Yu (SODA 2014); our result implies that we can approximately count the number of orthogonal pairs with essentially the same running time. We also provide a fine-grained reduction from approximate #SAT to SAT. Suppose the Strong Exponential Time Hypothesis (SETH) is false, so that for some 1 &lt; c &lt; 2 and all k there is an O(c n )- time algorithm for k-SAT. Then we prove that for all k, there is an O((c +o(1))n )-time algorithm for approximate #k-SAT. In particular, our result implies that the Exponential Time Hypothesis (ETH) is equivalent to the seemingly-weaker statement that there is no algorithm to approximate #3-SAT to within a factor of 1 + Δ in time 2 o(n) /Δ 2 (taking Δ &gt; 0 as part of the input). A full version of this paper containing detailed proofs is available at https://arxiv.org/ abs/1707.04609
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