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The ArtGallery problem is a fundamental visibility problem in Computational Geometry. The input consists of a simple polygon P, (possibly infinite) sets G and C of points within P, and an integer k; the task is to decide if at most k guards can be placed on points in G so that every point in C is visible to at least one guard. In the classic formulation of ArtGallery, G and C consist of all the points within P. Other well-known variants restrict G and C to consist either of all the points on the boundary of P or of all the vertices of P. Recently, three new important discoveries were made: the above mentioned variants of ArtGallery are all W[1]-hard with respect to k [Bonnet and Miltzow in 24th Annual European Symposium on Algorithms (Aarhus 2016)], the classic variant has an O (log k) -approximation algorithm [Bonnet and Miltzow in 33rd International Symposium on Computational Geometry (Brisbane 2017)], and it may require irrational guards [Abrahamsen et al. in 33rd International Symposium on Computational Geometry (Brisbane 2017)]. Building upon the third result, the classic variant and the case where G consists only of all the points on the boundary of P were both shown to be ∃ R -complete [Abrahamsen et al. in 50th Annual ACM SIGACT Symposium on Theory of Computing (Los Angeles 2018)]. Even when both G and C consist only of all the points on the boundary of P, the problem is not known to be in NP. Given the first discovery, the following question was posed by Giannopoulos [Lorentz Workshop on Fixed-Parameter Computational Geometry (Leiden 2016)]: Is ArtGallery FPT with respect to r, the number of reflex vertices? In light of the developments above, we focus on the variant where G and C consist of all the vertices of P, called Vertex-Vertex Art Gallery. Apart from being a variant of ArtGallery, this case can also be viewed as the classic DominatingSet problem in the visibility graph of a polygon. In this article, we show that the answer to the question by Giannopoulos is positive: Vertex-VertexArtGallery is solvable in time r O (r 2) · n O (1) . Furthermore, our approach extends to assert that Vertex-BoundaryArtGallery and Boundary-VertexArtGallery are both FPT as well. To this end, we utilize structural properties of "almost convex polygons" to present a two-stage reduction from Vertex-VertexArtGallery to a new constraint satisfaction problem (whose solution is also provided in this paper) where constraints have arity 2 and involve monotone functions. [ABSTRACT FROM AUTHOR]

Given a graph G = (V , E) and an integer k, the Minimum Membership Dominating Set (MMDS) problem seeks to find a dominating set S ⊆ V of G such that for each v ∈ V , | N [ v ] ∩ S | is at most k. We investigate the parameterized complexity of the problem and obtain the following results for the MMDS problem. First, we show that the MMDS problem is NP-hard even on planar bipartite graphs. Next, we show that the MMDS problem is W[1]-hard for the parameter pathwidth (and thus, for treewidth) of the input graph. Then, for split graphs, we show that the MMDS problem is W[2]-hard for the parameter k. Further, we complement the pathwidth lower bound by an FPT algorithm when parameterized by the vertex cover number of input graph. In particular, we design a 2 O (v c) | V | O (1) time algorithm for the MMDS problem where vc is the vertex cover number of the input graph. Finally, we show that the running time lower bound based on ETH is tight for the vertex cover parameter. [ABSTRACT FROM AUTHOR]

A class of graphs ℱ ${\rm{ {\mathcal F} }}$ admits the Erdős–Pósa property if for any graph G $G$, either G $G$ has k $k$ vertex‐disjoint "copies" of the graphs in ℱ ${\rm{ {\mathcal F} }}$, or there is a set S⊆V(G) $S\subseteq V(G)$ of f(k) $f(k)$ vertices that intersects all copies of the graphs in ℱ ${\rm{ {\mathcal F} }}$. For any graph class G ${\mathscr{G}}$, it is natural to ask whether the family of obstructions to G ${\mathscr{G}}$ has the Erdős–Pósa property. In this paper, we prove that the family of obstructions to interval graphs—namely, the family of chordless cycles and asteroidal witnesses (AWs)—admits the Erdős–Pósa property. In turn, this yields an algorithm to decide whether a given graph G $G$ has k $k$ vertex‐disjoint AWs and chordless cycles, or there exists a set of O(k2logk) ${\mathscr{O}}({k}^{2}\mathrm{log}k)$ vertices in G $G$ that hits all AWs and chordless cycles. [ABSTRACT FROM AUTHOR]

A graph H is p-edge colorable if there is a coloring ψ : E (H) → { 1 , 2 , ⋯ , p } , such that for distinct u v , v w ∈ E (H) , we have ψ (u v) ≠ ψ (v w) . The Maximum Edge-Colorable Subgraph problem takes as input a graph G and integers l and p, and the objective is to find a subgraph H of G and a p-edge-coloring of H, such that | E (H) | ≥ l . We study the above problem from the viewpoint of Parameterized Complexity. We obtain FPT algorithms when parameterized by: (1) the vertex cover number of G, by using Integer Linear Programming, and (2) l, a randomized algorithm via a reduction to Rainbow Matching, and a deterministic algorithm by using color coding, and divide and color. With respect to the parameters p + k , where k is one of the following: (1) the solution size, l, (2) the vertex cover number of G, and (3) l - mm (G) , where mm (G) is the size of a maximum matching in G; we show that the (decision version of the) problem admits a kernel with O (k · p) vertices. Furthermore, we show that there is no kernel of size O (k 1 - ϵ · f (p)) , for any ϵ > 0 and computable function f, unless NP ⊆ coNP / poly . [ABSTRACT FROM AUTHOR]

We design exact algorithms for the following two problems in survivable network design: (i) designing a minimum cost network with a desired value of edge connectivity, which is called Minimum Weight λ -connected Spanning Subgraph and (ii) augmenting a given network to a desired value of edge connectivity at a minimum cost which is called Minimum Weight λ -connectivity Augmentation. It is easy to see that a minimum solution to these problems contains at most 2 λ (n - 1) edges. Using this fact one can design a brute-force algorithm which runs in time 2 O (λ n log n) , however no better algorithms were known previously. In this paper, we give the first single exponential time algorithm for these problems, i.e. running in time 2 O (λ n) , for both undirected and directed networks. Our results are obtained via well known characterizations of λ -connected graphs, their connections to linear matroids and the recently developed technique of dynamic programming with representative sets. [ABSTRACT FROM AUTHOR]

The Terrain Guarding problem is a well-known variant of the famous Art Gallery problem. Only second to Art Gallery, it is the most well-studied visibility problem in Discrete and Computational Geometry, which has also attracted attention from the viewpoint of Parameterized complexity. In this paper, we focus on the parameterized complexity of Terrain Guarding (both discrete and continuous) with respect to two natural parameters. First we show that, when parameterized by the number r of reflex vertices in the input terrain, the problem has a polynomial kernel. We also show that, when parameterized by the number c of minima in the terrain, Discrete Orthogonal Terrain Guarding has an XP algorithm. [ABSTRACT FROM AUTHOR]

For a graph G and c R : E (G) → [ k ] , a path P between u , v ∈ V (G) is a rainbow path if for distinct e , e ′ ∈ E (P) , we have c R (e) ≠ c R (e ′). Rainbow k -Coloring takes a graph G and the objective is to check if there is c R : E (G) → [ k ] such that for all u , v ∈ V (G) there is a rainbow path between u and v. Two variants of the above problem are Subset Rainbow k -Coloring and Steiner Rainbow k -Coloring , where we are additionally given a subset S ⊆ V (G) × V (G) and S ′ ⊆ V (G) , respectively. Moreover, the objective is to check if there is c R : E (G) → [ k ] , such that there is a rainbow path for each (u , v) ∈ S and u , v ∈ S ′ , respectively. Under ETH, we obtain that for each k ≥ 3 : 1. Rainbow k -Coloring has no 2 o (| E (G) |) n O (1) -time algorithm. 2. Steiner Rainbow k -Coloring has no 2 o (| S | 2) n O (1) -time algorithm. We also obtain that Subset Rainbow k -Coloring and Steiner Rainbow k -Coloring admit 2 O (| S |) n O (1) - and 2 O (| S | 2) n O (1) -time algorithms, respectively. [ABSTRACT FROM AUTHOR]

High altitude is an environmental stress that is accompanied with numerous adverse biological responses, including skeletal muscle weakness and muscle protein loss. Skeletal muscle wasting is an important clinical problem, progressing to critical illness, associated with increased morbidity and mortality. The present study explores the protective efficacy of endogenous dipeptide, carnosine (CAR), supplementation in ameliorating skeletal muscle protein loss under hypobaric hypoxia (HH). Male Sprague–Dawley rats (n = 5) were randomly divided into control group, HH‐exposed group (3 days HH exposure equivalent to 7,620 m), and HH‐exposed rats supplemented with carnosine (3 days; 150 mg/kg b.w, orally) (HH + CAR). HH‐exposed rats supplemented with CAR ameliorated HH‐induced oxidative protein damage, lipid peroxidation, and maintained pro‐inflammatory cytokines levels. HH‐associated muscle protein degradative pathways, including calpain, ubiquitination, endoplasmic reticulum stress, autophagy, and apoptosis were also regulated in carnosine‐supplemented rats. Further, the muscle damage marker, the levels of serum creatine phosphokinase were also reduced in HH + CAR co‐supplemented rats which proved the protective efficacy of CAR against hypobaric hypoxia‐induced muscle protein loss. Altogether, CAR supplementation ameliorated HH‐induced skeletal muscle protein loss via performing multifaceted ways, mainly by maintaining redox homeostasis and proteostasis in skeletal muscle. [ABSTRACT FROM AUTHOR]

Skeletal muscle protein concentrations are regulated by protein synthesis and protein degradation mechanisms. In the present study, we compared two muscle loss phenomenon i.e., hypobaric hypoxia and sarcopenia. Male SD rats were distributed into three groups: control, aged and hypobaric hypoxia (HH) exposed rats. Results showed elevated levels of oxidative stress marker, ROS and GSSG: GSH in both stresses which corroborated with decreased in thiol content. Ergo, protein and lipid oxidation also increased in aged rats as contrast to HH exposed and control rats. Moreover, protein degradative machinery and apoptosis related markers, 20S proteasome, caspase-3 and caspase-9 was also upregulated in the aged and HH-exposed rats. Interestingly, the activity of two important proteins i.e., p-Akt and heat shock protein-60 (HSP60) were found different in these two stresses. p-Akt and HSP60 protein were elevated in HH-exposed rats whilst decreased activity was noted in case of aged rats. These results suggest that age is natural phenomenon that resulted into muscle protein loss, whereas HH-exposure has entirely different degradation mechanism. In the event of HH-exposure, cell has mechanisms to cope up with the unfavorable stress condition but degradation mechanisms are highly activated which led to muscle protein loss. [ABSTRACT FROM AUTHOR]

We know that Tree Contraction does not admit a polynomial kernel unless NP ⊆ coNP/poly , while Path Contraction admits a kernel with O (k) vertices. The starting point of this article is the following natural questions: What is the structure of the family of paths that allows Path Contraction to admit a polynomial kernel? Apart from the size of the solution, what other additional parameters should we consider so we can design polynomial kernels for these basic contraction problems? To design polynomial kernels, we consider the family of trees with the bounded number of leaves (note that the family of paths are trees with at most two leaves). In particular, we study Bounded Tree Contraction. Here, an input is a graph G , integers k and ℓ , and the goal is to decide whether, there is a subset F ⊆ E (G) of size at most k such that G / F is a tree with at most ℓ leaves. We design a kernel with O (k ℓ) vertices and O (k 2 + k ℓ) edges for this problem. We complement this result by giving kernelization lower bound. We also prove similar results for Bounded Out-Tree Contraction and Bounded Cactus Contraction. [ABSTRACT FROM AUTHOR]

Agrawal et al. (ACM Trans Comput Theory 10(4):18:1–18:25, 2018. https://doi.org/10.1145/3265027) studied a simultaneous variant of the classic Feedback Vertex Set problem, called Simultaneous Feedback Vertex Set (Sim-FVS). Here, we consider the edge variant of the problem, namely, Simultaneous Feedback Edge Set (Sim-FES). In this problem, the input is an n-vertex graph G, a positive integer k, and a coloring function col: E (G) → 2 [ α ] , and the objective is to check whether there is an edge subset S of cardinality k in G such that for each i ∈ [ α ] , G i - S is acyclic. Unlike the vertex variant of the problem, when α = 1 , the problem is equivalent to finding a maximal spanning forest and hence it is polynomial time solvable. We show that for α = 3 , Sim-FES is NP-hard, and does not admit an algorithm of running time 2 o (k) n O (1) unless ETH fails. This hardness result is complimented by an FPT algorithm for Sim-FES running in time 2 ω k α + α log k n O (1) where ω is the exponent in the running time of matrix multiplication. The same algorithm gives a polynomial time algorithm for the case when α = 2 . We also give a kernel for Sim-FES with (k α) O (α) vertices. Finally, we consider a "dual" version of the problem called Maximum Simultaneous Acyclic Subgraph and give an FPT algorithm with running time 2 ω q α n O (1) , where q is the number of edges in the output subgraph. [ABSTRACT FROM AUTHOR]

Hypobaric hypoxic stress leads to oxidative stress, inflammation, and disturbance in protein turnover rate. Aggregately, this imbalance in redox homeostasis is responsible for skeletal muscle protein loss and a decline in physical performance. Hence, an urgent medical need is required to ameliorate skeletal muscle protein loss. The present study investigated the efficacy of ursolic acid (UA), a pentacyclic triterpene acid to ameliorate hypobaric hypoxia (HH)‐induced muscle protein loss. UA is a naturally occurring pentacyclic triterpene acid present in several edible herbs and fruits such as apples. It contains skeletal muscle hypertrophy activity; still its potential against HH‐induced muscle protein loss is unexplored. To address this issue, an in vivo study was planned to examine the beneficial effect of UA supplementation on HH‐induced skeletal muscle loss. Male Sprague Dawley rats were exposed to HH with and without UA supplementation (20 mg/kg; oral) for 3 continuous days. The results described the beneficial role of UA as supplementation of UA with HH exposure attenuated reactive oxygen species production and oxidative protein damage, which indicate the potent antioxidant activity. Furthermore, UA supplementation enhanced Akt, pAkt, and p70S6kinase activity (Akt pathway) and lowered the pro‐inflammatory cytokines in HH exposed rats. UA has potent antioxidant and anti‐inflammatory activity, and it enhanced the protein content via upregulation of Akt pathway‐related proteins against HH exposure. These three biological activities of UA make it a novel candidate for amelioration of HH‐induced skeletal muscle damage and protein loss. [ABSTRACT FROM AUTHOR]

At extreme altitude, prolonged and severe hypoxia menaces human function and survival, and also associated with profound loss of muscle mass which results into a debilitating critical illness of skeletal muscle atrophy. Hypobaric hypoxia altered redox homeostasis and impaired calcium ion handling in skeletal muscles. Dysregulated Ca2+ homeostasis and activated calpain is the prime stressor in high altitude hypoxia while the reason for subsequent abnormal release of pathological Ca2+ into cytoplasm is largely unexplored. The present study identified the redox remodeling in the Ca2+ release channel, Ryanodine Receptor (RyR1) owing to its hypernitrosylation state in skeletal muscles in chronic hypobaric hypoxia exposed rats. RyR1-hypernitrosylation decreases the binding of FKBP12/calstabin-1 and other complexes from the channel, causing "leakiness" in RyR1 ion-channel. A strong RyR1 stabilizer, S107 enhanced binding affinity of FKBP12 with hypernitrosylated RyR1, reduced Sarco(endo)plasmic reticulum (SR) Ca2+ leak and improved muscle strength and function under chronic hypoxia. Administration of S107 inhibited the skeletal muscle damage, maintained ultrastructure of sarcomere and sarcolemmal integrity. Histological analysis proved the increase in cross-sectional area of myofibers. Further, the number of apoptotic cells was also reduced by S107 treatment. Conclusively, we proposed that the redox remodeling of RyR1 (hypernitrosylated-RyR1) might be responsible for dysregulated Ca2+ homeostasis which consequently impaired muscle strength and function in response to chronic hypoxic stress. Reduced SR Ca2+ leak and enhanced binding affinity of FKBP12 may provide a novel therapeutic avenue in ameliorating skeletal muscle atrophy at high altitude. Image 1 • Hypobaric hypoxic is considered a major stress at high altitude. • Hypobaric hypoxia condition leads to hypernitrosylation of ryanodine receptor1 (RyR1) in skeletal muscle. • Maladaptation of RyR1 channel result into Ca2+ leak and skeletal muscle atrophy. • S107, the RyR1-stabilizing drug fixes Ca2+ leak and improves muscle strength during hypobaric hypoxia. [ABSTRACT FROM AUTHOR]

In a vertex-colored graph, an edge is happy if its endpoints have the same color. Similarly, a vertex is happy if all its incident edges are happy. Motivated by the computation of homophily in social networks, we consider the algorithmic aspects of the following Maximum Happy Edges (k -MHE) problem: given a partially k -colored graph G and an integer ℓ , find an extended full k -coloring of G making at least ℓ edges happy. When we want to make ℓ vertices happy on the same input, the problem is known as Maximum Happy Vertices (k -MHV). We perform an extensive study into the complexity of the problems, particularly from a parameterized viewpoint. For every k ≥ 3 , we prove both problems can be solved in time 2 n n O (1). Moreover, by combining this result with a linear vertex kernel of size (k + ℓ) for k -MHE , we show that the edge-variant can be solved in time 2 ℓ n O (1). In contrast, we prove that the vertex-variant remains W[1] -hard for the natural parameter ℓ. However, the problem does admit a kernel with O (k 2 ℓ 2) vertices for the combined parameter k + ℓ. From a structural perspective, we show both problems are fixed-parameter tractable for treewidth and neighborhood diversity, which can both be seen as sparsity and density measures of a graph. Finally, we extend the known Image 1 -completeness results of the problems by showing they remain hard on bipartite graphs and split graphs. On the positive side, we show the vertex-variant can be solved optimally in polynomial-time for cographs. [ABSTRACT FROM AUTHOR]

A graph is called a split graph if its vertex set can be partitioned into a clique and an independent set. Split graphs have rich mathematical structure and interesting algorithmic properties making it one of the most well-studied special graph classes. In the Split Vertex Deletion problem, given a graph and a positive integer k , the objective is to test whether there exists a subset of at most k vertices whose deletion results in a split graph. In this paper, we design a kernel for this problem with O (k 2) vertices, improving upon the previous cubic bound known. Also, by giving a simple reduction from the Vertex Cover problem, we establish that Split Vertex Deletion does not admit a kernel with O (k 2 − ϵ) edges, for any ϵ > 0 , unless NP ⊆ coNP/poly. [ABSTRACT FROM AUTHOR]

Evaporation of drops almost always deposits their suspended particles at the drop edge. The dynamics of this process and the resulting patterns depend upon various parameters related to the liquid, substrate, and particles. An interesting scenario is interactions among the particles leading to inhomogeneous depositions characterized by distinct edge-growth dynamics. Here, we study a more complex system with bacteria inside the evaporating drop. Bacteria interact like sticky particles forming inhomogeneous clusters, however, with edge-growth dynamics as that of non-interacting particles. We hypothesis that this contradicting behavior is due to the increased randomness introduced by bacteria–substrate interactions. Our findings have importance in understanding the patterns and their formation in growth systems of soft matter. [ABSTRACT FROM AUTHOR]

An input to a conflict-free variant of a classical problem Γ , called Conflict-Free Γ , consists of an instance I of Γ coupled with a graph H, called the conflict graph. A solution to Conflict-Free Γ in (I, H) is a solution to I in Γ , which is also an independent set in H. In this paper, we study conflict-free variants of Maximum Matching and Shortest Path, which we call Conflict-Free Maximum Matching (CF-MM) and Conflict-Free Shortest Path (CF-SP), respectively. We show that both CF-MM and CF-SP are W[1]-hard, when parameterized by the solution size. Moreover, W[1]-hardness for CF-MM holds even when the input graph where we want to find a matching is itself a matching, and W[1]-hardness for CF-SP holds for conflict graph being a unit-interval graph. Next, we study these problems with restriction on the conflict graphs. We give FPT algorithms for CF-MM when the conflict graph is chordal. Also, we give FPT algorithms for both CF-MM and CF-SP, when the conflict graph is d-degenerate. Finally, we design FPT algorithms for variants of CF-MM and CF-SP, where the conflicting conditions are given by a (representable) matroid. [ABSTRACT FROM AUTHOR]

Aims Human pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) provide a platform to identify and characterize factors that regulate the maturation of CMs. The transition from an immature foetal to an adult CM state entails coordinated regulation of the expression of genes involved in myofibril formation and oxidative phosphorylation (OXPHOS) among others. Lysine demethylase 5 (KDM5) specifically demethylates H3K4me1/2/3 and has emerged as potential regulators of expression of genes involved in cardiac development and mitochondrial function. The purpose of this study is to determine the role of KDM5 in iPSC-CM maturation. Methods and results KDM5A, B, and C proteins were mainly expressed in the early post-natal stages, and their expressions were progressively downregulated in the post-natal CMs and were absent in adult hearts and CMs. In contrast, KDM5 proteins were persistently expressed in the iPSC-CMs up to 60 days after the induction of myogenic differentiation, consistent with the immaturity of these cells. Inhibition of KDM5 by KDM5-C70 -a pan-KDM5 inhibitor, induced differential expression of 2372 genes, including upregulation of genes involved in fatty acid oxidation (FAO), OXPHOS, and myogenesis in the iPSC-CMs. Likewise, genome-wide profiling of H3K4me3 binding sites by the cleavage under targets and release using nuclease assay showed enriched of the H3K4me3 peaks at the promoter regions of genes encoding FAO, OXPHOS, and sarcomere proteins. Consistent with the chromatin and gene expression data, KDM5 inhibition increased the expression of multiple sarcomere proteins and enhanced myofibrillar organization. Furthermore, inhibition of KDM5 increased H3K4me3 deposits at the promoter region of the ESRRA gene and increased its RNA and protein levels. Knockdown of ESRRA in KDM5-C70-treated iPSC-CM suppressed expression of a subset of the KDM5 targets. In conjunction with changes in gene expression, KDM5 inhibition increased oxygen consumption rate and contractility in iPSC-CMs. Conclusion KDM5 inhibition enhances maturation of iPSC-CMs by epigenetically upregulating the expressions of OXPHOS, FAO, and sarcomere genes and enhancing myofibril organization and mitochondrial function. [ABSTRACT FROM AUTHOR]

In the DIRECTED FEEDBACK VERTEX SET (DFVS) problem, we are given a digraph D on n vertices and a positive integer k, and the objective is to check whether there exists a set of vertices S such that F = D − S is an acyclic digraph. In a recent paper, Mnich and van Leeuwen [STACS 2016 ] studied the kernelization complexity of DFVS with an additional restriction on F—namely that F must be an out-forest, an out-tree, or a (directed) pumpkin—with an objective of shedding some light on the kernelization complexity of the DFVS problem, a well known open problem in the area. The vertex deletion problems corresponding to obtaining an out-forest, an out-tree, or a (directed) pumpkin are OUT-FOREST/OUT-TREE/PUMPKIN VERTEX DELETION SET, respectively. They showed that OUT-FOREST/OUT-TREE/PUMPKIN VERTEX DELETION SET admit polynomial kernels. Another open problem regarding DFVS is that, does DFVS admit an algorithm with running time 2O(k)nO(1)? We complement the kernelization programme of Mnich and van Leeuwen by designing fast FPT algorithms for the above mentioned problems. In particular, we design an algorithm for OUT-FOREST VERTEX DELETION SET that runs in time O(2.732knO(1)) and algorithms for PUMPKIN/OUT-TREE VERTEX DELETION SET that runs in time O(2.562knO(1)). As a corollary of our FPT algorithms and the recent result of Fomin et al. [STOC 2016] which gives a relation between FPT algorithms and exact algorithms, we get exact algorithms for OUT-FOREST/OUT-TREE/PUMPKIN VERTEX DELETION SET that run in time O(1.633nnO(1)), O(1.609nnO(1)) and O(1.609nnO(1)), respectively. [ABSTRACT FROM AUTHOR]

Background: High altitude associated hypobaric hypoxia is one of the cellular and environmental perturbation that alters proteostasis network and push the healthy cell towards loss of muscle mass. The present study has elucidated the robust proteostasis network and signaling mechanism for skeletal muscle atrophy under chronic hypobaric hypoxia (CHH). Methods: Male Sprague Dawley rats were exposed to simulated hypoxia equivalent to a pressure of 282 torr for different durations (1, 3, 7 and 14 days). After CHH exposure, skeletal muscle tissue was excised from the hind limb of rats for biochemical analysis. Results: Chronic hypobaric hypoxia caused a substantial increase in protein oxidation and exhibited a greater activation of ER chaperones, glucose-regulated protein-78 (GRP-78) and protein disulphide isomerase (PDI) till 14d of CHH. Presence of oxidized proteins triggered the proteolytic systems, 20S proteasome and calpain pathway which were accompanied by a marked increase in [Ca2+]. Upregulated Akt pathway was observed upto 07d of CHH which was also linked with enhanced glycogen synthase kinase-3β (GSk-3β) expression, a negative regulator of Akt. Muscle-derived cytokines, tumor necrosis factor-α (TNF-α), interferon-ϒ (IFN-©) and interleukin-1β (IL-1β) levels significantly increased from 07d onwards. CHH exposure also upregulated the expression of nuclear factor kappa-B (NF-κB) and E3 ligase, muscle atrophy F-box-1 (Mafbx-1/Atrogin-1) and MuRF-1 (muscle ring finger-1) on 07d and 14d. Further, severe hypoxia also lead to increase expression of ER-associated degradation (ERAD) CHOP/ GADD153, Ub-proteasome and apoptosis pathway. Conclusions: The disrupted proteostasis network was tightly coupled to degradative pathways, altered anabolic signaling, inflammation, and apoptosis under chronic hypoxia. Severe and prolonged hypoxia exposure affected the protein homeostasis which overwhelms the muscular system and tends towards skeletal muscle atrophy. [ABSTRACT FROM AUTHOR]

A key result in the field of kernelization, a subfield of parameterized complexity, states that the classic Disjoint Cycle Packing problem, i.e., finding k vertex disjoint cycles in a given graph G, admits no polynomial kernel unless NP ⊆ coNP/poly. However, very little is known about this problem beyond the aforementioned kernelization lower bound (within the parameterized complexity framework). In the hope of clarifying the picture and better understanding the types of constraints that separate kernelizable from nonkernelizable variants of Disjoint Cycle Packing, we investigate two relaxations of the problem. The first variant, which we call Almost Disjoint Cycle Packing, introduces a global relaxation parameter t. That is, given a graph G and integers k and t, the goal is to find at least k distinct cycles such that every vertex of G appears in at most t of the cycles. The second variant, Pairwise Disjoint Cycle Packing, introduces a local relaxation parameter, and we seek at least k distinct cycles such that every two cycles intersect in at most t vertices. While the Pairwise Disjoint Cycle Packing problem admits a polynomial kernel for all t ≥ 1, the kernelization complexity of Almost Disjoint Cycle Packing reveals an interesting spectrum of upper and lower bounds. In particular, for t = k/c, where c could be a function of k, we obtain a kernel of size O(2c² k7+c log³ k) whenever c ∈ o(√k). Thus the kernel size varies from being subexponential when c ∈ o(√k), to quasi-polynomial when c ∈ o(logℓ k), ℓ ∈ R+, and polynomial when c ∈ O(1). We complement these results for Almost Disjoint Cycle Packing by showing that the problem does not admit a polynomial kernel whenever t ∈ O(k∈) for any 0≤∈< 1, unless NP 埦 coNP/poly. [ABSTRACT FROM AUTHOR]

For an undirected graph G , a pair of vertex disjoint subsets (A , B) is a pair of perfectly matched sets if each vertex in A (resp. B) has exactly one neighbor in B (resp. A). In the above, the size of the pair is | A | (= | B |). Given a graph G and a positive integer k , the Perfectly Matched Sets problem asks whether there exists a pair of perfectly matched sets of size at least k in G. This problem is known to be NP -hard on planar graphs and W[1] -hard on general graphs, when parameterized by k. However, little is known about the parameterized complexity of the problem in restricted graph classes. In this work, we study the problem parameterized by k , and design FPT algorithms for: i) apex-minor-free graphs running in time 2 O (k) ⋅ n O (1) , and ii) K b , b -free graphs. We obtain a linear kernel for planar graphs and k O (d) -sized kernel for d -degenerate graphs. It is known that the problem is W[1] -hard on chordal graphs, in fact on split graphs, parameterized by k. We complement this hardness result by designing a polynomial-time algorithm for interval graphs. [ABSTRACT FROM AUTHOR]

Cholesterol embolization syndrome (CES) is a multi-systemic disease caused by embolization of atherosclerotic plaque contents from proximal large-caliber artery to distal small to medium arteries, occurring spontaneously or more commonly after vascular intervention. This report is a comprehensive review of the reported cases of CES found in our literature search. We discuss the risk factors, clinical manifestations, management, and prognosis of CES. The major predisposing factors for CES include older age, male sex, atherosclerotic cardiovascular risk factors, anticoagulation, and femoral access route. The composite incidence of atheroembolic renal disease was 92% and mortality 63%. Our review highlights the importance to recognize this disease entity for the cardiologist and nephrologist. [ABSTRACT FROM AUTHOR]

Given a digraph D and an integer k , Directed Feedback Vertex Set (DFVS) asks whether there exists a set of vertices S of size at most k such that F = D ∖ S is DAG. Mnich and van Leeuwen [ STACS 2016  ] considered the kernelization complexity of DFVS with an additional restriction on F , namely that F must be an out-forest ( Out-Forest Vertex Deletion Set ), an out-tree ( Out-Tree Vertex Deletion Set ), or a (directed) pumpkin ( Pumpkin Vertex Deletion Set ). Their objective was to shed light on the kernelization complexity of DFVS , a well-known open problem in Parameterized Complexity. We improve the kernel sizes of Out-Forest Vertex Deletion Set from O ( k 3 ) to O ( k 2 ) and of Pumpkin Vertex Deletion Set from O ( k 18 ) to O ( k 3 ) . We also prove that the former kernel size is tight under certain complexity theoretic assumptions. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) is a ubiquitous organism which can infect multiple organs of the body. In an immunocompromised patient, it can have a myriad of gastrointestinal manifestations. We report a case of recurrent hematochezia and concomitant pseudotumor in an AIDS (acquired immunodeficiency syndrome) patient attributable to CMV infection. A 62-year-old man with a history of AIDS, noncompliant with highly active antiretroviral therapy (HAART), presented with bright red blood per rectum. Index colonoscopy showed presence of multiple ulcers, colonic stenosis, and mass-like appearing lesion. Biopsy confirmed CMV infection and ruled out malignancy. Cessation of dual antiplatelet therapy and compliance with HAART lead to clinical cessation of bleeding and endoscopic healing of ulcers with complete resolution of colon mass on follow-up colonoscopy. [ABSTRACT FROM AUTHOR]

Suspensions of solvent-less, polymer-grafted nanoparticles have previously been reported to exhibit enhanced elasticity, glassy dynamics, and jamming as temperature is increased. This so-called thermal jamming behavior is not predicted by current models for soft glassy materials and is opposite to what is normally observed for polymer melts. Here we report results from a detailed study of structural, dynamic, and rheological transitions in solvent-less silica-poly(ethylene glycol) methyl ether (SiO2-PEGME) hybrid particles aimed at understanding the molecular origins of the phenomenon. We find that interdigitated PEGME corona chains enforce coupling between SiO2 cores analogous to cross-links in associating polymer networks leading to elastic behavior at low strains and small deformation rates. Pullout and slippage of interdigitated corona chains is thought to produce yielding of the materials in nonlinear shear flow and stretched exponential relaxation following small amplitude step shear. We show with the help of small-angle X-ray scattering, density functional theoretical calculations, and a constitutive model previously reported for deformation and flow of physically associating polymer networks, that thermal jamming of solvent-less polymer-grafted nanoparticles originates from enhanced cross-linking of the cores produced by increased stretching and interpenetration of particle-tethered polymer molecules to satisfy the space-filling constraint on tethered polymer chains. [ABSTRACT FROM AUTHOR]

We report on the structure, jamming, and dynamics of blends of self-suspended hairy silica nanoparticles grafted with poly(ethylene glycol) (PEG) and poly(methyl methacrylate) (PMMA). We find that favorable enthalpic attraction between tethered PEG and PMMA chains augment previously reported entropic attractions between tethered polymer chains in self-suspended suspensions to enhance particle-particle correlations, increase jamming, and slow down chain dynamics. As with their single-component counterparts, the hairy SiO2-PEG/SiO2-PMMA nanoparticle blends exhibit soft glassy rheological behavior and both the energy dissipated at yielding and the plateau elastic modulus display strong maxima in the symmetric case. A comparison of the small angle X-ray scattering (SAXS) measurements with theoretical analysis from density functional theory (DFT) reveals that the addition of SiO2-PMMA to a self-suspended SiO2-PEG suspension initially leads to a higher degree of stretching of the corona chains, which produces stronger interdigitation of the tethered chains, enhanced jamming, and slower polymer relaxation than observed in the single-component materials. By means of an analysis of the heat of mixing released upon blending tethered and untethered PEG and PMMA chains, we find that the strong enthalpic attraction between the grafted polymer chains enhances entropic attractive forces produced by the space-filling constraint on tethered ligands in self-suspended suspensions to produce entangled-polymer-like physical properties in polymers with molecular weights below the thresholds normally associated with the transition to an entangled state. [ABSTRACT FROM AUTHOR]

The role of plasma therapy in the management of the COVID-19, pandemic has been speculated. However, in view of the varied response regarding its effectiveness from various multicenter studies, there is a need to conduct more single center population-specific studies. We, thus, aimed to assess the role of convalescent plasma therapy in COVID-19 patient management in a single -center. This retrospective study was conducted using records of all COVID-19 patients who received plasma therapy over a period of 6 months in a dedicated COVID-19 hospital in Delhi. Information pertaining to transfusion, disease severity, associated comorbidities, the treatment given and patient outcome were recorded. Data was analyzed using SPSSv23. Of the141 patients who received plasma therapy, 62% were discharged after treatment. Mortality was found to be significantly higher in patients > 60 years of age (p < 0.001), those with severe COVID-19 infection (p < 0.05) and pre-existing renal disease (p < 0.05). The admission-transfusion interval was significantly correlated to mortality and was a sensitive parameter for predicting outcome at cut off value of < 5 days (p < 0.001). There was no significant association of mortality with patient blood group, plasma antibody levels or donor hemoglobin levels. We report improvement and recovery in a large number of patients who received convalescent plasma within the first 5 days of hospitalization with moderate to severe disease. Further research to compare dosage and administration protocols to delineate role of CCP in survival of COVID-19 patients is needed before it is prematurely shelved. [ABSTRACT FROM AUTHOR]

Introduction. Electrocardiographic changes imitating myocardial ischemia have been occasionally reported in patients with intra-abdominal pathology including acute pancreatitis. Case Report. A 60-year-old man with no past medical history presented to the emergency department (ED) after a syncopal episode. In ED, his vitals were stable. His ECG showed sinus bradycardia at 53 beats per minute, peaked T waves, 1 mm ST-segment elevation in leads II, III, and aVF, and 2 mm ST elevation in V3 as shown in the figures. With the concern for STEMI, he was taken for left heart catheterization (LHC) emergently, showing nonobstructive coronary artery disease (CAD). His laboratory workup was remarkable for lipase of 25,304 IU/l (normal level 8–78 IU/l). His liver function test and triglyceride level were normal. Troponin was <0.01 ng/ml. A computed tomographic exam of the abdomen revealed acute interstitial pancreatitis with a small discrete fluid collection in the uncinate process. He was treated with aggressive intravenous fluid resuscitation and was discharged on day 3. Discussion. Intra-abdominal pathologies like acute pancreatitis can lead to transient ECG changes mimicking STEMI. It is important to use ECG clues, echocardiographic findings, and clinical judgement to avoid cardiac catheterization, contrast exposure, and associated health care costs. [ABSTRACT FROM AUTHOR]

Pseudomelanosis is a rare endoscopic finding of the upper gastrointestinal tract characterized by hemosiderin deposits in histiocytes of lamina propria. We report a case of 72-year-old lady on chronic oral iron supplementation diagnosed with gastric hyperplastic polyps with background pseudomelanosis of stomach and duodenum. Concomitant occurrence of gastric pseudomelanosis, duodenal pseudomelanosis, and gastric hyperplastic polyps has never been reported. Its presence in the absence of gastritis raises question if pseudomelanosis could be associated with hyperplastic polyp. With limited literature on its etiology and prognosis, these patients should be prospectively followed and reported to study the natural history of the disease. [ABSTRACT FROM AUTHOR]

Introduction: Landsteiner ABO system of blood groups is most important for transfusion medicine and has subtypes of A Antigen, A1 and A2, upon which further groups of A and AB have been classified. Of individuals with A antigen, approximately 20% belong to A2 while rest 80% belong to A1. Anti-A1 Lectin, a cold agglutinin which destroys A1 cells is clinically significant when they react at 37°C, causing transfusion reactions. Aim: To assess the prevalence of A1 and A2 subgroups in the population. Materials and Methods: This was two year retrospective analysis of blood groups of donors coming to the blood bank of Karnataka Institute of Medical Science, Hubli, Karnataka, India. The data of the subgroups A and AB was analysed. Results: 20,864 donors were analysed. Of 5466 (26.20%) of A group, 5406 (98.90%) belonged to A1 subgroup and only 60 (1.10%) belonged to A2 subgroup. Of 1708 donors with blood group AB, 1532 (89.70%) belonged to A1B subgroup and 176 (10.30%) belonged to A2B. It was noted that A2 in AB bloodgroup, as A2B, was more frequent in occurrence than presence of A2 as an A blood group. Rhesus negative frequency in these subgroups was also reported. Conclusion: Having known the prevalence of A1 and A2 subgroups and incorporating them into the ABO grouping system can limit these minor, yet dangerous, transfusion incompatibilities. [ABSTRACT FROM AUTHOR]

Abstract: This paper reports on the destabilization of oil-in-water macro-emulsions prepared with diesel oil dispersed in a continuous water phase and stabilized by an anionic surfactant—sodium dodecyl benzene sulphonate (SDBS). Phase inversion temperature (PIT) of anionic surfactant–oil–water emulsion system was determined by measuring the conductivity as a function of temperature at different surfactant to oil ratios. The influence of different kinds of inorganic salts on the PIT, electrophoretic properties and long-term stability of the o/w emulsion were studied by making measurements of conductivity, zeta potential and turbidity of the emulsion. PIT was found to be a linear function of logarithmic molar concentration of the electrolytes. Droplet size distribution of stable emulsion is found to have broader range for mono-valent electrolytes than that of higher valence cations. Larger the valence of cations, lower is the stability of the emulsion. By analyzing the evolution of emulsion droplet size, and turbidity of the resulting emulsion with time, the main destabilizing mechanisms of the o/w macro-emulsion were explained. It is found that coalescence, and Ostwald ripening could be the main destabilizing mechanisms of o/w macro-emulsion. [Copyright &y& Elsevier]

Rhino-orbital cerebral mucor mycosis is a rare disease entity, where retinal involvement is described in the literature mostly as CRAO. However, pathological studies have shown mucor invading the choroid and retina with a neutrophilic reaction. So, it is pertinent that retinal inflammation secondary to invading mucor has some role in microstructural changes seen in the vitreous and retina of these patients. This novel study aims to describe the vitreal and retinal features of patients with vision-threatening rhino-orbital cerebral mucor mycosis and how they evolve on spectral domain optical coherence tomography (SD-OCT). This study shall also provide insight into the pathophysiology of these vitreoretinal manifestations by in vitro analysis of the exenterated orbital content. Fifteen eyes of fifteen patients with vision-threatening ROCM treated with standard care were enrolled in this study and underwent complete ophthalmic examination, serial colour fundus photography, and SD-OCT for both qualitative and quantitative analysis, at baseline and follow-up visits. SD-OCT on serial follow-up revealed thickening and increased inner-retinal reflectivity at presentation followed by thinning of both, other features such as the loss of the inner-retinal organized layer structure, external limiting membrane (ELM) disruption, necrotic spaces in the outer retina, and hyperreflective foci. Vitreous cells with vitreous haze were also seen. There was a significant reduction in CMT, inner and outer retinal thickness, total retinal thickness (all p < 0.05) with time, the quantum of reduction concentrated primarily to the inner retina. In summary, in vivo and in vitro analysis revealed that early microstructural changes were primarily a result of retinal infarctions secondary to thrombotic angioinvasion. With the late microstructural changes, there was possible sequelae of retinal infarction with some contribution from the inflammation, resulting from mucor invading the choroid and retina. [ABSTRACT FROM AUTHOR]

Introduction: Infective endocarditis (IE) poses a great challenge to the field of cardiology due to high mortality, approaching 30% at 1-year, despite optimal care. Hypothesis: We studied causative organisms, in-hospital mortality and predictors of 30-day hospital readmission after a diagnosis of IE. Methods: Nationwide Readmissions Database was utilized to identify patients with a primary discharge diagnosis of IE using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9, CM), procedural code 421.0. Primary outcome was 30-day readmission. Hierarchical multivariable logistic regression was used to adjust for confounders. Results: Over 6 years (2010-2015), 187,438 patients were admitted with a primary diagnosis of IE. Twenty four percent were readmitted within 30 days. Staphylococcus aureus (27%), streptococcus viridians (22%), gram negative species (6%) and fungal species (0.24%) were identified as causative organisms. Predictors of increased readmissions were female sex (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.02 to 1.1, p<0.001), staphylococcus aureus infection (OR 1.06, 95% CI 1.02 to 1.1, p <0.001), diabetes (OR 1.11, 95%CI 1.07 to 1.63, p<0.001), chronic lung disease (OR 1.16, 95%ci 1.11 TO 1.2, P<0.001), chronic liver disease (or 1.06, 95%CI 1.1 to 1.23, p<0.001), acute kidney injury (OR 1.32, 95%CI 1.26 to 1.37, p<0.001), acute heart failure (OR 1.17, 95%CI 1.12 to 1.22, p<0.001) and anemia (OR 1.09, 95%CI 1.06 to 1.13, p<0.01). In-hospital mortality was 13% and average length of stay (LOS) was 12 days. Thirty-six percent patients were discharged to a facility. Conclusions: We identified high in-hospital mortality and 30-day readmission rates for IE patients between 2010 and 2015. Females, staphylococcus aureus infection, anemia, acute heart failure, chronic lung disease, chronic liver disease, acute kidney injury and diabetes were independently associated with increased 30-day readmissions in IE patients. [ABSTRACT FROM AUTHOR]

Introduction: Infective endocarditis (IE) is a frequent cause of morbidity and mortality in patients with intracardiac devices, prosthetic valves and unrepaired congenital anomalies. Hypothesis: We aim to look for comorbidities, etiologies and trends of 30-day hospital readmission after the diagnosis of IE. Methods: Nationwide Readmissions Database (2010-2015) was utilized to identify patients with primary discharge diagnosis of IE using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9, CM), procedural code 421.0. Primary outcome was 30-day readmission. Etiologies were identified using ICD-9 codes in primary diagnosis field. Results: Among 187,438 patients admitted with the primary diagnosis of IE, 44,151 patients (24%) were readmitted within 30 days (60% Male, average age 60 years). Most prevalent comorbidities included hypertension (56%), anemia (41%), chronic kidney disease (31%), diabetes (30%), valvular heart disease (22%), heart failure (21%) and intravenous drug abuse (15%). Most common etiologies included sepsis (14%), acute heart failure (HF) (8%), acute kidney injury (6%), intracardiac device infection (5.6%) and recurrence of IE (2.7%). Neurological complications and mechanical valvular dysfunction accounted for 2.7% and 1.6% of total 30-day readmissions. Half of the readmissions (51%) happened in first 11 days of discharge. Among the readmitted patients, 86% had 1 readmission, 13% had 2 readmissions and 1.5% of patients had 3 readmissions in 30 days after discharge. Conclusions: We identified sepsis, acute HF, acute kidney injury and intracardiac device infection as the most common etiologies of readmission. Identifying high risk patients during index admission can help reduce the high readmission rate. Prospective trials are warranted to identify these high-risk patients. [ABSTRACT FROM AUTHOR]

Background: Acute pericardial pathologies, such as pericardial effusion, pericarditis, and cardiac tamponade, have been reported rarely in patients presenting as ST-elevation myocardial infarction (STEMI). We present a series of 3 patients with STEMI, where an undiagnosed pericardial effusion led to pericardial tamponade and subsequent cardiocirculatory collapse.Case Reports: This is a case series of 3 patients, all women, aged 72, 64, and 54 years who presented to the emergency department with chest pain or syncope and were found to have STEMI with hemodynamic instability. They were taken to the catheterization laboratory for urgent coronary revascularization requiring mechanical circulatory support (intra-aortic balloon pump or impella). During catheterization, all 3 patients were diagnosed with large pericardial effusion using hemodynamic parameters and bedside transesophageal echocardiogram. Commonly ignored, pericardial tamponade and acute large pericardial effusion can be the cause of cardiocirculatory collapse. Two of the 3 patients survived with aggressive interventions requiring pericardial drains, long-term mechanical circulatory support, and effective postoperative rehabilitation. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: It is important for treating clinicians, including emergency physicians, intensivist, and cardiologist, to consider the differential of a cardiac tamponade due to a pericardial effusion as a potential cause for hypotension in patients with an acute STEMI. [ABSTRACT FROM AUTHOR]

Background: Takotsubo syndrome (TTS) is a peculiar clinical condition often resembling an acute coronary syndrome and mostly affecting postmenopausal women. We sought to describe the prevalence of acute kidney injury and acute renal failure in TTS patients during index event and assess the usefulness of speckle tracking echocardiography in predicting subjects at risk of developing acute kidney insult. Methods: We conducted a retrospective descriptive study reviewing study with the discharge diagnosis of TTS between 2003‐2016 at our Institution. One hundred and two patients met the Modified Mayo Clinic. Acute kidney injury (AKI) was defined as an increment of serum creatinine 2 times greater than baseline and/or at least 50% reduction in baseline eGFR. Acute renal failure (ARF) was defined as an increment of serum creatinine 3 times greater than baseline and/or at least 75% reduction in baseline eGFR as per RIFLE Classification. Results: AKI/ARF patients had longer length of stay (24 vs 10 days, P = 0.02), had higher mean peak troponin (16.7 ng/mL vs 3.2, P < 0.05) and later peak creatinine day (10 vs 3, P < 0.05). LV Longitudinal strain in the basal segment and apex upon admission was significantly worse in the AKI/ARF group (−4.7 and −6.5, respectively, vs −8.6 and −9.1 in the non‐AKI/ARF group, P < 0.05). Conclusions: One in every 10 TTS patients may develop AKI/ARF during the acute episode. Segmental longitudinal strain by speckle tracking may have important prognostic value in identifying TTS patients at risk of developing AKI/ARF. [ABSTRACT FROM AUTHOR]

Neurologic stunned myocardium (NSM) is a phenomenon where neurologic events give rise to cardiac abnormalities. Neurologic events like stroke and seizures cause sympathetic storm and autonomic dysregulation that result in myocardial injury. The clinical presentation can involve troponin elevation, left ventricular dysfunction, and ECG changes. These findings are similar to Takotsubo cardiomyopathy and acute coronary syndrome. It is difficult to distinguish NSM from acute coronary syndrome based on clinical presentation alone. Because of this difficulty, a patient with NSM who is at high risk for coronary heart disease may undergo cardiac catheterization to rule out coronary artery disease. The objective of this review of literature is to enhance physician's awareness of NSM and its features to help tailor management according to the patient's clinical profile. [ABSTRACT FROM AUTHOR]

Syncope is a common and pervasive medical problem. The etiology of 30-40% of syncope remains unknown. Laughter-induced syncope is a rare subtype of vasovagal syncope that is not well understood. With this literature review we hope to elucidate the epidemiology, symptomatology, pathophysiology, diagnosis and therapeutic options of laughter-induced syncope. Greater awareness of laughter-induced syncope may better direct clinical investigations and improve patient care. [ABSTRACT FROM AUTHOR]