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Conventional cancer treatment is mainly based on the surgical removal of the tumor followed by radiotherapy and/or chemotherapy. When surgical removal is not possible, radiotherapy and, less often, chemotherapy is the only way to treat patients. However, despite significant progress in understanding the molecular mechanisms of carcinogenesis and developments in modern radiotherapy techniques, radiotherapy (alone or in combination) does not always guarantee treatment success. One of the main causes is the radioresistance of cancer cells. Increasing the radiosensitivity of cancer cells improves the processes leading to their elimination during radiotherapy and prolonging the survival of cancer patients. In order to enhance the effect of radiotherapy in the treatment of radioresistant neoplasms, radiosensitizers are used. In clinical practice, synthetic radiosensitizers are commonly applied, but scientists have recently focused on using natural products (phytocompounds) as adjuvants in radiotherapy. In this review article, we only discuss naturally occurring radiosensitizers currently in clinical trials (paclitaxel, curcumin, genistein, and papaverine) and those whose radiation sensitizing effects, such as resveratrol, have been repeatedly confirmed by many independent studies. [ABSTRACT FROM AUTHOR]

Background. Plasma membrane Ca2+-ATPase (PMCA) is the most sensitive cellular calcium detector. It exists in four main isoforms (PMCA1-4), among which PMCA2 and PMCA3 are considered as fast-acting neuron-specific forms. In the brain, PMCA function declines progressively during aging; thereby impaired calcium homeostasis may contribute to some neurodegenerative diseases. These destructive processes can be propagated by proinflammatory chemokines, including chemokine CCL5, which causes phospholipase C-mediated liberation of Ca2+ from endoplasmic reticulum by IP3-gated channels. Methods. To mimic the changes in aged neurons we used stable transfected differentiated PC12 cells with downregulated PMCA2 or PMCA3 and analyzed the effect of CCL5 on calcium transients with Fluo-4 reagent. Chemokine receptors were evaluated using Western blot, and IP3 receptors expression level was assessed using qRT-PCR and Western blot. Results. In PMCA-reduced cell lines, CCL5 released more Ca2+ by IP3-sensitive receptors, and the time required for Ca2+ clearance was significantly longer. Also, in these lines we detected altered expression level of CCR5 and IP3 receptors. Conclusion. Although modification of PMCAs composition could provide some protection against calcium overload, reduction of PMCA2 appeared to be more detrimental to the cells than deficiency of PMCA3. Under pathological conditions, including inflammatory CCL5 action and long-lasting Ca2+ dyshomeostasis, insufficient cell protection may result in progressive degeneration and death of neurons. [ABSTRACT FROM AUTHOR]

We consider the single-machine time-dependent scheduling problem with linearly deteriorating jobs arriving over time. Each job i is associated with a release time r i and a processing time p i (s i) = α i + β i s i , where α i , β i > 0 are parameters and s i is the job's start time. In this setting, the approximability of both single-machine minimum makespan and total completion time problems remains open. We develop new bounds and approximation results for the special case of the problems with uniform deterioration, i.e. β i = β , for each i. The main contribution is a O (1 + 1 / β) -approximation algorithm for the makespan problem and a O (1 + 1 / β 2) approximation algorithm for the total completion time problem. Further, we propose greedy constant-factor approximation algorithms for instances with β = O (1 / n) and β = Ω (n) , where n is the number of jobs. Our analysis is based on an approach for comparing computed and optimal schedules via bounding pseudomatchings. [ABSTRACT FROM AUTHOR]

Background: Neurodegenerative and mood disorders represent growing medical and social problems, many of which are provoked by oxidative stress, disruption in the metabolism of various neurotransmitters, and disturbances in calcium homeostasis. Biologically active plant compounds have been shown to exert a positive impact on the function of calcium in the central nervous system. Methods: The present paper reviews studies of naturally occurring terpenes and derivatives and the calcium-based aspects of their mechanisms of action, as these are known to act upon a number of targets linked to neurological prophylaxis and therapy. Results: Most of the studied phytochemicals possess anticancer, antioxidative, anti-inflammatory, and neuroprotective properties, and these have been used to reduce the risk of or treat neurological diseases. Conclusion: The neuroprotective actions of some phytochemicals may employ mechanisms based on regulation of calcium homeostasis and should be considered as therapeutic agents. [ABSTRACT FROM AUTHOR]

The aging process is a physiological phenomenon associated with progressive changes in metabolism, genes expression, and cellular resistance to stress. In neurons, one of the hallmarks of senescence is a disturbance of calcium homeostasis that may have far-reaching detrimental consequences on neuronal physiology and function. Among several proteins involved in calcium handling, plasma membrane Ca2+-ATPase (PMCA) is the most sensitive calcium detector controlling calcium homeostasis. PMCA exists in four main isoforms and PMCA2 and PMCA3 are highly expressed in the brain. The overall effects of impaired calcium extrusion due to age-dependent decline of PMCA function seem to accumulate with age, increasing the susceptibility to neurotoxic insults. To analyze the PMCA role in neuronal cells, we have developed stable transfected differentiated PC12 lines with down-regulated PMCA2 or PMCA3 isoforms to mimic age-related changes. The resting Ca2+ increased in both PMCA-deficient lines affecting the expression of several Ca2+-associated proteins, i.e., sarco/endoplasmic Ca2+-ATPase (SERCA), calmodulin, calcineurin, GAP43, CCR5, IP3Rs, and certain types of voltage-gated Ca2+ channels (VGCCs). Functional studies also demonstrated profound changes in intracellular pH regulation and mitochondrial metabolism. Moreover, modification of PMCAs membrane composition triggered some adaptive processes to counterbalance calcium overload, but the reduction of PMCA2 appeared to be more detrimental to the cells than PMCA3. [ABSTRACT FROM AUTHOR]

The key objective of a Distributed Denial of Service (DDoS) attack is to compile multiple systems across the Internet with infected zombies/agents and form botnets of networks. Such zombies are designed to attack a particular target or network with different types of packets. The infected systems are remotely controlled either by an attacker or by self-installed Trojans (e.g. roj/Flood-IM) that are programmed to launch packet floods. Within this context, the purpose of this paper is to detect and mitigate known and unknown DDoS attacks in real time environments. We have chosen an Artificial Neural Network (ANN) algorithm to detect DDoS attacks based on specific characteristic features (patterns) that separate DDoS attack traffic from genuine traffic. [ABSTRACT FROM AUTHOR]

A garden is populated by n bamboos, each with its own daily growth rate. The Bamboo Garden Trimming Problem (BGT) is to design for a robotic gardener a perpetual schedule of cutting bamboos to keep the elevation of the garden as low as possible. The frequency of cutting is constrained by the time needed to move from one bamboo to the next, which is one day in Discrete BGT and is defined by the distance between the two bamboos in Continuous BGT. The bamboo garden is a metaphor for a collection of machines which have to be serviced, with different frequencies, by a robot which can service only one machine at a time. For Discrete BGT, we show tighter approximation algorithms, with one of them settling a long-standing conjecture about the related Pinwheel problem. For Continuous BGT, we propose approximation algorithms which achieve logarithmic approximation ratios. [ABSTRACT FROM AUTHOR]

Population protocols are a model for distributed computing that is focused on simplicity and robustness. A system of n identical agents (finite state machines) performs a global task like electing a unique leader or determining the majority opinion when each agent has one of two opinions. Agents communicate in pairwise interactions with randomly assigned communication partners. Quality is measured in two ways: the number of interactions to complete the task and the number of states per agent. We present protocols for the majority problem that allow for a trade-off between these two measures. Compared to the only other trade-off result (Alistarh et al. in Proceedings of the 2015 ACM symposium on principles of distributed computing, Donostia-San Sebastián, 2015), we improve the number of interactions by almost a linear factor. Furthermore, our protocols can be made uniform (working correctly without any information on the population size n), yielding the first uniform majority protocols that stabilize in a subquadratic number of interactions. [ABSTRACT FROM AUTHOR]

The rotor-router model, also called the Propp machine, was first considered as a deterministic alternative to the random walk. The edges adjacent to each node v (or equivalently, the exit ports at v) are arranged in a fixed cyclic order, which does not change during the exploration. Each node v maintains a port pointer $$\pi _v$$ which indicates the exit port to be adopted by an agent on the conclusion of the next visit to this node (the 'next exit port'). The rotor-router mechanism guarantees that after each consecutive visit at the same node, the pointer at this node is moved to the next port in the cyclic order. It is known that, in an undirected graph G with m edges, the route adopted by an agent controlled by the rotor-router mechanism eventually forms an Euler tour based on arcs obtained via replacing each edge in G by two arcs with opposite direction. The process of ushering the agent to an Euler tour is referred to as the lock-in problem. In Yanovski et al. (Algorithmica 37(3):165-186, 2003), it was proved that, independently of the initial configuration of the rotor-router mechanism in G, the agent locks-in in time bounded by $$2mD$$ , where $$D$$ is the diameter of G. In this paper we examine the dependence of the lock-in time on the initial configuration of the rotor-router mechanism. Our analysis is performed in the form of a game between a player $${\mathcal {P}}$$ intending to lock-in the agent in an Euler tour as quickly as possible and its adversary $${\mathcal {A}}$$ with the counter objective. We consider all cases of who decides the initial cyclic orders and the initial values $$\pi _v$$ . We show, for example, that if $${\mathcal {A}}$$ provides its own port numbering after the initial setup of pointers by $${\mathcal {P}}$$ , the worst-case complexity of the lock-in problem is $${\varTheta }(m\cdot \min \{\log m,D\})$$ . We also investigate the robustness of the rotor-router graph exploration in presence of faults in the pointers $$\pi _v$$ or dynamic changes in the graph. We show, for example, that after the exploration establishes an Eulerian cycle, if k edges are added to the graph, then a new Eulerian cycle is established within $$\mathcal {O}(km)$$ steps. [ABSTRACT FROM AUTHOR]