On the intersection of tolerance and cocomparability graphs.

It has been conjectured by Golumbic and Monma in 1984 that the intersection of tolerance and cocomparability graphs coincides with bounded tolerance graphs. Since cocomparability graphs can be efficiently recognized, a positive answer to this conjecture in the general case would enable us to efficiently distinguish between tolerance and bounded tolerance graphs, although it is NP-complete to recognize each of these classes of graphs separately. The conjecture has been proved under some – rather strong – structural assumptions on the input graph; in particular, it has been proved for complements of trees, and later extended to complements of bipartite graphs, and these are the only known results so far. Furthermore, it is known that the intersection of tolerance and cocomparability graphs is contained in the class of trapezoid graphs. In this article we prove that the above conjecture is true for every graph G, whose tolerance representation satisfies a slight assumption; note here that this assumption concerns only the given tolerance representation R of G, rather than any structural property of G. This assumption on the representation is guaranteed by a wide variety of graph classes; for example, our results immediately imply the correctness of the conjecture for complements of triangle-free graphs (which also implies the above-mentioned correctness for complements of bipartite graphs). Our proofs are algorithmic, in the sense that, given a tolerance representation R of a graph G, we describe an algorithm to transform R into a bounded tolerance representation R  ∗  of G. Furthermore, we conjecture that any minimal tolerance graph G that is not a bounded tolerance graph, has a tolerance representation with exactly one unbounded vertex. Our results imply the non-trivial result that, in order to prove the conjecture of Golumbic and Monma, it suffices to prove our conjecture. In addition, there already exists evidence in the literature that our conjecture is true

Recursive circulants and their embeddings among hypercubes

AbstractWe propose an interconnection structure for multicomputer networks, called recursive circulant. Recursive circulant G(N,d) is defined to be a circulant graph with N nodes and jumps of powers of d. G(N,d) is node symmetric, and has some strong hamiltonian properties. G(N,d) has a recursive structure when N=cdm, 1⩽c<d. We develop a shortest-path routing algorithm in G(cdm,d), and analyze various network metrics of G(cdm,d) such as connectivity, diameter, mean internode distance, and visit ratio. G(2m,4), whose degree is m, compares favorably to the hypercube Qm. G(2m,4) has the maximum possible connectivity, and its diameter is ⌈(3m−1)/4⌉. Recursive circulants have interesting relationship with hypercubes in terms of embedding. We present expansion one embeddings among recursive circulants and hypercubes, and analyze the costs associated with each embedding. The earlier version of this paper appeared in Park and Chwa (Proc. Internat. Symp. Parallel Architectures, Algorithms and Networks ISPAN’94, Kanazawa, Japan, December 1994, pp. 73–80)

Humanin G (HNG) protects age-related macular degeneration (AMD) transmitochondrial ARPE-19 cybrids from mitochondrial and cellular damage.

Age-related macular degeneration (AMD) ranks third among the leading causes of visual impairment with a blindness prevalence rate of 8.7%. Despite several treatment regimens, such as anti-angiogenic drugs, laser therapy, and vitamin supplementation, being available for wet AMD, to date there are no FDA-approved therapies for dry AMD. Substantial evidence implicates mitochondrial damage and retinal pigment epithelium (RPE) cell death in the pathogenesis of AMD. However, the effects of AMD mitochondria and Humanin G (HNG), a more potent variant of the mitochondrial-derived peptide (MDP) Humanin, on retinal cell survival have not been elucidated. In this study, we characterized mitochondrial and cellular damage in transmitochondrial cybrid cell lines that contain identical nuclei but possess mitochondria from either AMD or age-matched normal (Older-normal (NL)) subjects. AMD cybrids showed (1) reduced levels of cell viability, lower mtDNA copy numbers, and downregulation of mitochondrial replication/transcription genes and antioxidant enzyme genes; and (2) elevated levels of genes related to apoptosis, autophagy and ER-stress along with increased mtDNA fragmentation and higher susceptibility to amyloid-β-induced toxicity compared to NL cybrids. In AMD cybrids, HNG protected the AMD mitochondria, reduced pro-apoptosis gene and protein levels, upregulated gp130 (a component of the HN receptor complex), and increased the protection against amyloid-β-induced damage. In summary, in cybrids, damaged AMD mitochondria mediate cell death that can be reversed by HNG treatment. Our results also provide evidence of Humanin playing a pivotal role in protecting cells with AMD mitochondria. In the future, it may be possible that AMD patient's blood samples containing damaged mitochondria may be useful as biomarkers for this condition. In conclusion, HNG may be a potential therapeutic target for treatment of dry AMD, a debilitating eye disease that currently has no available treatment. Further studies are needed to establish HNG as a viable mitochondria-targeting therapy for dry AMD

Etude de l'activité cérébrale motrice lors de mouvements isolés successifs de l'index

International audienceDe nombreuses études ont été réalisées sur profil de la réponse cérébrale motrice dans différentes conditions et en fonction de différents types de mouvement. Cependant certaines zones d'ombre restent à éclaircir. Très peu d'études mettent en avant les différences entres la réponse cérébrale obtenue lors de la réalisation de tâches motrices simples et isolées dans le temps, c'est-à-dire séparés d'une fenêtre temporelle relativement longue et en comparant les conditions yeux ouverts/yeux fermés. Cette étude consiste à comparer ces réponses cérébrales et pourrait apporter des informations complémentaires à la connaissance scientifique dans le domaine des interfaces cerveau-ordinateur. Le but principal de notre étude a été d'observer l'activité cérébrale lors de la réalisation de mouvements successifs de plus en plus rapprochés, plus particulièrement au niveau du rythme bêta qui est le plus représentatif du mouvement volontaire. Cette étude nous a permis d'émettre certaines hypothèses vis-à-vis de la modulation de la réponse cérébrale lors de la réduction des intervalles de temps qui séparent deux mouvements successifs. En effet, lors de deux mouvements rapprochés, l'Event-Related Synchronization (ERS) semble ne plus s'exrimer

Towards Compositional Mixed-Criticality Real-Time Scheduling in Open Systems

Although many cyber-physical systems are both mixed-criticality system and compositional system, there are little work on intersection of mixed-criticality system and compositional system. We propose novel concepts for task-level criticality mode and reconsider temporal isolation in terms of compositional mixed-criticality scheduling

MC-ADAPT: Adaptive Task Dropping in Mixed-Criticality Scheduling

Recent embedded systems are becoming integrated systems with components of different criticality. To tackle this, mixed-criticality systems aim to provide different levels of timing assurance to components of different criticality levels while achieving efficient resource utilization. Many approaches have been proposed to execute more lower-criticality tasks without affecting the timeliness of higher-criticality tasks. Those previous approaches however have at least one of the two limitations; i) they penalize all lower-criticality tasks at once upon a certain situation, or ii) they make the decision how to penalize lowercriticality tasks at design time. As a consequence, they underutilize resources by imposing an excessive penalty on lowcriticality tasks. Unlike those existing studies, we present a novel framework, called MC-ADAPT, that aims to minimally penalize lower-criticality tasks by fully reflecting the dynamically changing system behavior into adaptive decision making. Towards this, we propose a new scheduling algorithm and develop its runtime schedulability analysis capable of capturing the dynamic system state. Our proposed algorithm adaptively determines which task to drop based on the runtime analysis. To determine the quality of task dropping solution, we propose the speedup factor for task dropping while the conventional use of the speedup factor only evaluates MC scheduling algorithms in terms of the worst-case schedulability. We apply the speedup factor for a newly-defined task dropping problem that evaluates task dropping solution under different runtime scheduling scenarios. We derive that MC-ADAPT has a speedup factor of 1.619 for task drop. This implies that MC-ADAPT can behave the same as the optimal scheduling algorithm with optimal task dropping strategy does under any runtime scenario if the system is sped up by a factor of 1.619

European mtDNA Variants Are Associated With Differential Responses to Cisplatin, an Anticancer Drug: Implications for Drug Resistance and Side Effects.

Background: Cisplatin, a powerful antitumor agent, causes formation of DNA adducts, and activation of apoptotic pathways. Presently, cisplatin resistance develops in up to 70% of patients but the underlying molecular mechanism(s) are unclear and there are no markers to determine which patients will become resistant. Mitochondria play a significant role not only in energy metabolism but also retrograde signaling (mitochondria to nucleus) that modulates inflammation, complement, and apoptosis pathways. Maternally inherited mitochondrial (mt) DNA can be classified into haplogroups representing different ethnic populations that have diverse susceptibilities to diseases and medications. Methods: Transmitochondrial cybrids, where all cell lines possess identical nuclear genomes but either the H (Southern European) or J (Northern European) mtDNA haplogroups, were treated with cisplatin and analyzed for differential responses related to viability, oxidative stress, and expression levels of genes associated with cancer, cisplatin-induced nephrotoxicity and resistance, apoptosis and signaling pathways. Results: The cisplatin-treated-J cybrids showed greater loss of cell viability along with lower levels of reactive oxygen species and mitochondrial membrane potential compared to cisplatin-treated-H cybrids. After cisplatin treatment, J cybrids showed increased gene expression of BAX, CASP3, and CYP51A, but lower levels of SFRP1 compared to untreated-J cybrids. The cisplatin-treated-H cybrids had elevated expression of CDKN1A/P21, which has a role in cisplatin toxicity, compared to untreated-H cybrids. The cisplatin-treated H had higher transcription levels of ABCC1, DHRS2/HEP27, and EFEMP1 compared to cisplatin-treated-J cybrids. Conclusions: Cybrid cell lines that contain identical nuclei but either H mtDNA mitochondria or J mtDNA mitochondria respond differently to cisplatin treatments suggesting involvement of the retrograde signaling (from mitochondria to nucleus) in the drug-induced cell death. Varying toxicities and transcription levels of the H vs. J cybrids after cisplatin treatment support the hypothesis that mtDNA variants play a role in the expression of genes affecting resistance and side effects of cisplatin

Effects of fluoroquinolones and tetracyclines on mitochondria of human retinal MIO-M1 cells

Our goal was to explore the detrimental impacts of ciprofloxacin (CPFX) and tetracycline (TETRA) on human retinal Müller (MIO-M1) cells in vitro. Cells were exposed to 30, 60 and 120 μg/ml of CPFX and TETRA. The cellular metabolism was measured with the MTT assay. The JC-1 and CM-H2DCFDA assays were used to evaluate the levels of mitochondrial membrane potential (MMP) and ROS (reactive oxygen species), respectively. Mitochondrial DNA (mtDNA) copy number, along with gene expression levels associated with apoptotic (BAX, BCL2-L13, BCL2, CASP-3 and CASP-9), inflammatory (IL-6, IL-1β, TGF-α, TGF-β1 and TGF-β2) and antioxidant pathways (SOD2, SOD3, GPX3 and NOX4) were analyzed via Quantitative Real-Time PCR (qRT-PCR). Bioenergetic profiles were measured using the Seahorse® XF Flux Analyzer. Cells exposed 24 h to 120 μg/ml TETRA demonstrated higher cellular metabolism compared to vehicle-treated cells. At each time points, (i) all TETRA concentrations reduced MMP levels and (ii) ROS levels were reduced by TETRA 120 μg/ml treatment. TETRA caused (i) higher expression of CASP-3, CASP-9, TGF-α, IL-1B, GPX3 and SOD3 but (ii) decreased levels of TGF-B2 and SOD2. ATP production and spare respiratory capacity declined with TETRA treatment. Cellular metabolism was reduced with CPFX 120 μg/ml in all cultures and 60 μg/ml after 72 h. The CPFX 120 μg/ml reduced MMP in all cultures and ROS levels (72 h). CPFX treatment (i) increased expression of CASP-3, CASP-9, and BCL2-L13, (ii) elevated the basal oxygen consumption rate, and (iii) lowered the mtDNA copy numbers and expression levels of TGF-B2, IL-6 and IL-1B compared to vehicle-control cells. We conclude that clinically relevant dosages of bactericidal and bacteriostatic antibiotics can have negative effects on the cellular metabolism and mitochondrial membrane potential of the retinal MIO-M1 cells in vitro. It is noteworthy to mention that apoptotic and inflammatory pathways in exposed cells were affected significantly This is the first study showing the negative impact of fluoroquinolones and tetracyclines on mitochondrial behavior of human retinal MIO-M1 cells