Random Approach to Optimization of Overlay Public-Resource Computing Systems

The growing need for computationally demanding systems triggers the development of various network-oriented computing systems organized in a distributed manner. In this work we concentrate on one kind of such systems, i.e. public-resource computing systems. The considered system works on the top of an overlay network and uses personal computers and other relatively simple electronic equipment instead of supercomputers. We assume that two kinds of network flows are used to distribute the data in the public-resource computing systems: unicast and peer-to-peer. We formulate an optimization model of the system. After that we propose random algorithms that optimize jointly the allocation of computational tasks and the distribution of the output data. To evaluate the algorithms we run numerical experiments and present results showing the comparison of the random approach against optimal solutions provided by the CPLEX solver

A P2P Computing System for Overlay Networks

A distributed computing system is able to perform data computation and distribution of results at the same time. The input task is divided into blocks, which are then sent to system participants that offer their resources in order to perform calculations. Next, a partial result is sent back by the participants to the task manager (usually one central node). In the case when system participants want to get the final result, the central node may become overloaded, especially if many nodes request the result at the same time. In this paper we propose a novel distributed computation system, which does not use the central node as the source of the final result, but assumes that partial results are sent between system participants. This way we avoid overloading the central node, as well as network congestion. There are two major types of distributed computing systems: grids and Peer-to-Peer (P2P) computing systems. In this work we focus on the latter case. Consequently, we assume that the computing system works on the top of an overlay network. We present a complete description of the P2P computing system, considering both computation and result distribution. To verify the proposed architecture we develop our own simulator. The obtained results show the system performance expressed by the operation cost for various types of network flows: unicast, anycast and Peer-to-Peer. Moreover, the simulations prove that our computing system provides about 66% lower cost compared to a centralized computing system

Decision Strategies for a P2P Computing System

Peer-to-Peer (P2P) computing (also called ‘public-resource computing’) is an effective approach to perform computation of large tasks. Currently used P2P computing systems (e.g., BOINC) are most often centrally managed, i.e., the final result of computations is created at a central node using partial results – what may be not efficient in the case when numerous participants are willing to download the final result. In this paper, we propose a novel approach to P2P computing systems. We assume that results can be delivered to all peers in a distributed way using three types of network flows: unicast, Peer-to-Peer and anycast. We describe our concept of the system architecture with a special focus on the decision strategies developed for system participants. Using our discrete realtime simulator we evaluate the proposed strategies in various scenarios and present a comprehensive analysis of obtained results. According to obtained results, the Peer-to-Peer flow provides lower operational cost of the computing system compared to unicast and anycast flows. Moreover, an appropriate selection of decision strategy can significantly reduce the operational cost

Heuristic Algorithms for Optimization of Task Allocation and Result Distribution in Peer-to-Peer Computing Systems

Recently, distributed computing system have been gaining much attention due to a growing demand for various kinds of effective computations in both industry and academia. In this paper, we focus on Peer-to-Peer (P2P) computing systems, also called public-resource computing systems or global computing systems. P2P computing systems, contrary to grids, use personal computers and other relatively simple electronic equipment (e.g., the PlayStation console) to process sophisticated computational projects. A significant example of the P2P computing idea is the BOINC (Berkeley Open Infrastructure for Network Computing) project. To improve the performance of the computing system, we propose to use the P2P approach to distribute results of computational projects, i.e., results are transmitted in the system like in P2P file sharing systems (e.g., BitTorrent). In this work, we concentrate on offline optimization of the P2P computing system including two elements: scheduling of computations and data distribution. The objective is to minimize the system OPEX cost related to data processing and data transmission. We formulate an Integer Linear Problem (ILP) to model the system and apply this formulation to obtain optimal results using the CPLEX solver. Next, we propose two heuristic algorithms that provide results very close to an optimum and can be used for larger problem instances than those solvable by CPLEX or other ILP solvers

Effect of Short-Term Desiccation, Recovery Time, and CAPA–PVK Neuropeptide on the Immune System of the Burying Beetle Nicrophorus vespilloides

Environmental conditions, especially related to winter, are crucial for shaping activity of insect immune system. However, our previous research clearly indicates differences in the immune system functioning when the cold stress was induced in the laboratory conditions and when the beetles were collected from natural environment during winter. This is probably related to the multiplication of observed effects by simultaneous presence of different stress factors characteristic of winter, including desiccation. For these reasons, our next step was analysis of the effects of short-term desiccation and recovery time on the functioning of immune system of burying beetle Nicrophorus vespilloides. Also, the effect of Tenmo–PVK-2 (tenebrionid periviscerokinin), member of the CAPA–PVK neuropeptide family, was investigated to better understand observed changes. Short-term desiccation decreases the phagocytic activity of burying beetle haemocytes, which is correlated with a reduction in their adhesive ability. On the other hand, there was a significant increase in phenoloxidase (PO) activity and the level of proPO expression, which may suggest sealing the cuticula by melanin deposition and prevention of water loss. Additionally, the elevated level of defensin expression may be associated with the cross-talk between mechanisms, which participate in insect response to environmental stress, including pathogen infection. After 1 h of recovery time, the activity of tested cellular and humoral mechanisms was mostly back to the control level. However, inhibition of the activity of PO and down-regulation of proPO were noted. These results also indicate importance of melanin deposition during water loss. Moreover, it suggests that some changes in immune system functioning during stress conditions do not have an immune function. Interestingly, part of the effects characteristic of recovery time were also observed after the application of Tenmo–PVK-2, mainly related to haemocyte morphology. These results indicate that CAPA–PVK neuropeptides may also influence on activity of burying beetle immune system. It should be also highlighted that, because of the study of the effects of CAPA–PVK neuropeptides, homologs of vertebrate neuromedin U, the results may be interesting for search evolutionary similarities in the functioning of the neuroendocrine system of insects and vertebrates

Wysoka ekspresja WFDC2 w raku jajnika oraz prawidłowym jajowodzie nie koreluje z poziomem HE4 w surowicy krwi

Objectives: Recent evidence suggests that epithelial ovarian cancer (EOC) does not derive from ovarian surface epithelium but from the tissues of Mullerian origin, particularly from the fallopian tube. HE4, a protein of Mullerian origin, seems to be promising marker for EOC detection and treatment monitoring. This study was designed to compare the expression of WFDC2 gene, encoding HE4 protein, in normal tissue of the ovary, fallopian tube and EOC. The correlation between WFDC2 expression in cancer tissue and serum level of HE4 was additionally measured. Material and methods: Tumor specimens were obtained from EOC patients during primary surgery before chemotherapy. Samples of normal ovaries and fallopian tubes were collected from healthy patients operated for other reasons. Total RNA was isolated from the tissues and relative WFDC2 expression was evaluated by Real Time RTqPCR. HE4 serum level in cancer patients was measured using COBAS System. Results: EOC samples were distinguished by much higher WFDC2 expression in comparison to normal ovaries (p=0.000016). Transcriptional activity of WFDC2 in EOC specimens and in normal fallopian tubes was comparable (p=1.00). Additionally, lack of correlation between WFDC2 expression in cancer tissue and serum level of HE4 protein in ovarian cancer patients was observed (p=0.3). Conclusions: High expression of WFDC2 was demonstrated for both, EOC and fallopian tube, as opposed to its low expression observed in normal ovaries suggesting that EOC is derived from fallopian tube rather than ovary. Elevated HE4 serum concentration in EOC patients is not correlated with higher gene expression in cancer tissue.Cel pracy: Ostatnie badania sugerują, że rak jajnika (EOC) nie pochodzi z nabłonka jajnika lecz z tkanek pochodzenia Mullerowskiego, a najprawdopodobniej z jajowodu. HE4, białko pochodzenia Mullerowskiego, wydaje się być obiecującym markerem raka jajnika. To badanie zostało przeprowadzone, aby porównać ekspresję genu WFDC2 kodującego białko HE4 w tkance prawidłowego jajnika, jajowodu oraz raka jajnika. W raku jajnika dodatkowo została oceniona korelacja między ekspresją WFDC2 a stężeniem jego produktu białkowego w surowicy krwi. Materiał i metody: Materiał tkankowy został pobrany od pacjentek podczas pierwotnej operacji cytoredukcyjnej raka jajnika. Fragmenty prawidłowych jajników i jajowodów zostały pobrane od pacjentek operowanych z powodu mięśniaków macicy. Z tkanek zostało wyizolowane całkowite RNA. Za pomocą Real-Time RT-qPCR została określona ekspresja WFDC2. Stężenie białka HE4 w surowicy krwi pacjentek zostało zmierzone za pomocą systemu COBAS. Wyniki: Stwierdziliśmy istotnie wyższą ekspresję genu WFDC2 w tkankach EOC niż w tkankach prawidłowego jajnika (p=0.000016). Nie stwierdziliśmy natomiast różnic miedzy ekspresją WFDC2 w jajowodzie oraz w raku jajnika (p=1.00). Dodatkowo, wykazaliśmy brak korelacji między ekspresją tkankową WFDC2 oraz stężeniem HE4 w surowicy krwi u pacjentek z rakiem jajnika. (p=0.3). Wnioski: Wysoka ekspresja WFDC2 stwierdzona zarówno w raku jajnika jak i prawidłowym jajowodzie w przeciwieństwie do niskiej ekspresji stwierdzonej w jajniku sugeruje, że rak jajnika może wywodzić się raczej z jajowodu niż z jajnika. Wysokie stężenie HE4 w raku jajnika nie koreluje z nadekspresją WFDC2 w tkance nowotworowej

Human chorionic gonadotropin – a well-known hormone with unknown functions

Human chorionic gonadotropin (CG) belongs to the glycoprotein family consisting of LH, FSH and TSH. All of these hormones are composed of two subunits: common to the whole family alpha subunit and hormone-specific beta subunit. CG has paracrine effects on several processes such as placentation, implantation, angiogenesis and delaying the apoptosis of corpus luteum. Serum level of CG is used to monitor pregnancy and pregnancy disorders. Recent studies have shown that the synthesis of CG is a characteristic feature of a wide variety of malignant and non-malignant tumors. The role of CG in cancerogensis remains unclear, but the main hypothesis concerns its antiapoptotic impact of the hormone on the neoplastic cells. The synthesis of functional CG requires the activity of separate genes encoding both hormone’s subunits, but it is the beta subunit accessibility which controls the process. The protein synthesis must be followed by proper folding and posttranslational modifications of the molecule. Particularly, glycosylation of human chorionic gonadotropin was shown to have an impact on the hormone’s function. The amount and the structure of carbohydrate residuals attached to CG may be different and lead to the formation of hormone variants, which vary in molecular mass. Normal CG with a molecular mass of about 37.5 kDa is produced by the syncytiotrophoblast, while the variant with higher molecular mass – 38.5-40 kDa, described as hyperglicosylated CG, is secreted by undifferentiated trophoblast cells and some cancers. It is suggested that those forms have different but complementary biological functions. However, the mechanism of the action of particular variants and signaling pathways activated by those forms are still obscure

Structural studies suggest aggregation as one of the modes of action for teixobactin

Teixobactin is a new promising antibiotic that targets cell wall biosynthesis by binding to lipid II and has no detectable resistance thanks to its unique but yet not fully understood mechanism of operation. To aid in the structure-based design of teixobactin analogues with improved pharmacological properties, we present a 3D structure of native teixobactin in membrane mimetics and characterise its binding to lipid II through a combination of solution NMR and fast (90 kHz) magic angle spinning solid state NMR. In NMR titrations, we observe a pattern strongly suggesting interactions between the backbone of the C-terminal “cage” and the pyrophosphate moiety in lipid II. We find that the N-terminal part of teixobactin does not only act as a membrane anchor, as previously thought, but is actively involved in binding. Moreover, teixobactin forms a well-structured and specific complex with lipid II, where the N-terminal part of teixobactin assumes a b conformation that is highly prone to aggregation, which likely contributes to the antibiotic's high bactericidal efficiency. Overall, our study provides several new clues to teixobactin's modes of action

Regulation of human chorionic gonadotropin beta subunit expression in ovarian cancer

Expression of human chorionic gonadotropin beta subunit by cancers is extensively documented, yet regulation of the multiple genes that can code for this protein is poorly understood. The aim of the study was to examine the mechanisms regulating CGB gene expression in ovarian cancer. Expression of CGB genes and SP1, SP3, TFAP2A transcription factor genes was evaluated by RT-qPCR. The methylation status of CGB genes promoter regions was examined by methylation-specific PCR. mRNA arising from multiple CGB genes was detected in both ovarian control and malignant tissues. However, expression of CGB3-9 genes was shown to be significantly higher in malignant than healthy ovarian tissues. CGB1 and CGB2 transcripts were shown to be present in 20% of ovarian cancers, but were not detected in any of the control samples. Malignant tissues were characterized by DNA demethylation of CGB promoter regions. In ovarian cancer CGB expression positively correlated with TFAP2A transcripts level and expression of TFAP2A transcription factor was significantly higher in cancer than in control tissues. In contrast SP3 expression level was significantly lower in ovarian tumours than in control ovarian tissue. In ovarian cancers increased expression of human chorionic gonadotropin beta subunit is associated with demethylation of CGB promoter regions. CGB3-9 expression level strongly correlates with expression of the TFAP2A transcription factor. Presence of mRNA arising from CGB1 and CGB2 genes appears to be a unique feature of a subset of ovarian cancers