The Quadratic Cycle Cover Problem: special cases and efficient bounds

The quadratic cycle cover problem is the problem of finding a set of node-disjoint cycles visiting all the nodes such that the total sum of interaction costs between consecutive arcs is minimized. In this paper we study the linearization problem for the quadratic cycle cover problem and related lower bounds. In particular, we derive various sufficient conditions for the quadratic cost matrix to be linearizable, and use these conditions to compute bounds. We also show how to use a sufficient condition for linearizability within an iterative bounding procedure. In each step, our algorithm computes the best equivalent representation of the quadratic cost matrix and its optimal linearizable matrix with respect to the given sufficient condition for linearizability. Further, we show that the classical Gilmore-Lawler type bound belongs to the family of linearization based bounds, and therefore apply the above mentioned iterative reformulation technique. We also prove that the linearization vectors resulting from this iterative approach satisfy the constant value property. The best among here introduced bounds outperform existing lower bounds when taking both quality and efficiency into account

Integrality and cutting planes in semidefinite programming approaches for combinatorial optimization

Many real-life decision problems are discrete in nature. To solve such problems as mathematical optimization problems, integrality constraints are commonly incorporated in the model to reflect the choice of finitely many alternatives. At the same time, it is known that semidefinite programming is very suitable for obtaining strong relaxations of combinatorial optimization problems. In this dissertation, we study the interplay between semidefinite programming and integrality, where a special focus is put on the use of cutting-plane methods. Although the notions of integrality and cutting planes are well-studied in linear programming, integer semidefinite programs (ISDPs) are considered only recently. We show that manycombinatorial optimization problems can be modeled as ISDPs. Several theoretical concepts, such as the Chvátal-Gomory closure, total dual integrality and integer Lagrangian duality, are studied for the case of integer semidefinite programming. On the practical side, we introduce an improved branch-and-cut approach for ISDPs and a cutting-plane augmented Lagrangian method for solving semidefinite programs with a large number of cutting planes. Throughout the thesis, we apply our results to a wide range of combinatorial optimization problems, among which the quadratic cycle cover problem, the quadratic traveling salesman problem and the graph partition problem. Our approaches lead to novel, strong and efficient solution strategies for these problems, with the potential to be extended to other problem classes

SDP-based bounds for the Quadratic Cycle Cover Problem via cutting plane augmented Lagrangian methods and reinforcement learning

We study the Quadratic Cycle Cover Problem (QCCP), which aims to find a node-disjoint cycle cover in a directed graph with minimum interaction cost between successive arcs. We derive several semidefinite programming (SDP) relaxations and use facial reduction to make these strictly feasible. We investigate a nontrivial relationship between the transformation matrix used in the reduction and the structure of the graph, which is exploited in an efficient algorithm that constructs this matrix for any instance of the problem. To solve our relaxations, we propose an algorithm that incorporates an augmented Lagrangian method into a cutting plane framework by utilizing Dykstra's projection algorithm. Our algorithm is suitable for solving SDP relaxations with a large number of cutting planes. Computational results show that our SDP bounds and our efficient cutting plane algorithm outperform other QCCP bounding approaches from the literature. Finally, we provide several SDP-based upper bounding techniques, among which a sequential Q-learning method that exploits a solution of our SDP relaxation within a reinforcement learning environment

Extracorporeal treatment of metforminassociated lactic acidosis in clinical practice:A retrospective cohort study

Purpose To assess whether extracorporeal treatment (ECTR) improves outcome of patients with metformin-associated lactic acidosis (MALA) and to evaluate the clinical applicability of the Extracorporeal Treatments in Poisoning Workgroup (EXTRIP) criteria for starting ECTR in metformin poisoning. Methods Patients with metformin serum concentrations above 2 mg/l who were admitted in the Deventer Teaching Hospital between January 2000 and July 2019 and complied with the definition of MALA (pH 5 mmol/l) were included. Mortality and clinical parameters of patients treated with ECTR or not were compared. In addition, treatment of MALA in clinical practice was verified against the criteria of EXTRIP. Results Forty-two patients were included. Lactate (13.8 versus 10.5 mmol/l, p = 0.01), creatinine (575 versus 254 umol/l, p <0.01)), metformin (29.4 versus 8.6 mg/l, p <0.01) concentrations, and vasopressor requirement (72% versus 23%, p <0.01) were significantly higher in the ECTR-group. Blood pH (7.05 versus 7.19, p = 0.03) and bicarbonate (6 versus 11 mmol/l, p <0.01) were significantly lower. Mortality, length of hospital stay, and mechanical ventilation requirement were not statistically different. In 83% of patients, treatment of MALA was in accordance with the EXTRIP criteria. Conclusions Although there was no statistical benefit in mortality shown from ECTR, ECTR might be lifesaving in MALA, considering the ECTR-group was significantly sicker than the non-ECTR-group. The majority of patients were treated in line with the EXTRIP criteria. Severity of lactic acidosis and renal impairment were the main indications for initiating ECTR

Reducing avoidable visual impairment in elderly home healthcare patients by basic ophthalmologic screening

Contains fulltext : 203604.pdf (publisher's version ) (Open Access

Report Topsector Potato India and Ethiopia 2015/16

The Agricultural Counsellor of the Netherlands Embassy in Delhi initiated a BOCI project ‘Overview of the potato chain in India’ in early 2011. In September 2012 this initiative has been adopted by the Dutch and Indian stakeholders and the Pubic Private Partnership (PPS) was established to facilitate the intensification of collaboration between Dutch and Indian stakeholders of the potato chain. A team of Wageningen UR researchers was commissioned to carry out this project. In 2011, the team collected information from reports, personal files, internet and some Dutch companies and reported the information in “An overview of the potato sector in India and prospects of Indo & Dutch cooperation”. The team also participated in the Netherlands Trade mission to India (5 & 11 June 2011) and visited the Central Potato Research Institute at Shimla. Furthermore jointly with the Agricultural Counsellor we organized a potato seminar to present our findings on 5 October 2011 in Delhi. Major potato stakeholders both from India and from the Netherlands attended the seminar; total number of participants was about 60 persons. In 2012, 2013, 2014, 2015 and 2016 the team carried out different tasks such as presenting information on various subjects of the Dutch and Indian potato chain to exchange knowledge. In addition, several identified subjects were investigated. All actions and activities aimed to facilitate collaboration between Dutch and Indian stakeholders. Visits to different locations of India accompanied by Dutch stakeholders, meetings with experts of the Indian potato production chain both stakeholders and researchers, and topics such as skin curing and chemical haulm killing, reduce storage losses and the establishment of the Centres of Excellence (CoE) in Punjab (Jalandhar) and Uttar Pradesh, and the Centre of Potato Expertise (COPE) at Ludhiana (Punjab) were successfully accomplished

PIK3CA-mediated PI3-kinase signalling is essential for HPV-induced transformation in vitro

<p>Abstract</p> <p>Background</p> <p>High-risk human papillomavirus (hrHPV) infections are causally related to cervical cancer development. The additional (epi)genetic alterations driving malignant transformation of hrHPV-infected cells however, are not yet fully elucidated. In this study we experimentally assessed the role of the PI3-kinase pathway and its regulator PIK3CA, which is frequently altered in cervical cancer, in HPV-induced transformation.</p> <p>Methods</p> <p>Cervical carcinomas and ectocervical controls were assessed for PIK3CA mRNA and protein expression by quantitative RT-PCR and immunohistochemical staining, respectively. A longitudinal <it>in vitro </it>model system of hrHPV-transfected keratinocytes, representing the immortal and anchorage independent phenotype, was assayed for PI3-kinase activation and function using chemical pathway inhibition i.e. LY294002 treatment, and PIK3CA RNA interference. Phenotypes examined included cellular viability, migration, anchorage independent growth and differentiation. mRNA expression of hTERT and HPV16 E6E7 were studied using quantitative RT-PCR and Northern blotting.</p> <p>Results</p> <p>Cervical carcinomas showed significant overexpression of PIK3CA compared to controls. During HPV-induced transformation <it>in vitro</it>, expression of the catalytic subunit PIK3CA as well as activation of downstream effector PKB/AKT progressively increased in parallel. Inhibition of PI3-kinase signalling in HPV16-transfected keratinocytes by chemical interference or siRNA-mediated silencing of PIK3CA resulted in a decreased phosphorylation of PKB/AKT. Moreover, blockage of PI3-kinase resulted in reduced cellular viability, migration, and anchorage independent growth. These properties were accompanied with a downregulation of HPV16E7 and hTERT mRNA expression. In organotypic raft cultures of HPV16- and HPV18-immortalized cells, phosphorylated PKB/AKT was primarily seen in differentiated cells staining positive for cytokeratin 10 (CK10). Upon PI3-kinase signalling inhibition, there was a severe impairment in epithelial tissue development as well as a dramatic reduction in p-PKB/AKT and CK10.</p> <p>Conclusion</p> <p>The present data indicate that activation of the PI3-kinase/PKB/AKT pathway through PIK3CA regulates various transformed phenotypes as well as growth and differentiation of HPV-immortalized cells and may therefore play a pivotal role in HPV-induced carcinogenesis.</p

Manipulating the motion of large neutral molecules

Large molecules have complex potential-energy surfaces with many local minima. They exhibit multiple stereo-isomers, even at very low temperatures. In this paper we discuss the different approaches for the manipulation of the motion of large and complex molecules, like amino acids or peptides, and the prospects of state- and conformer-selected, focused, and slow beams of such molecules for studying their molecular properties and for fundamental physics studies. Accepted for publication in Faraday Disc. 142 (2009), DOI: 10.1039/b820045aComment: 12 page

Monitoring storage induced changes in the platelet proteome employing label free quantitative mass spectrometry

Shelf life of platelet concentrates is limited to 5-7 days due to loss of platelet function during storage, commonly referred to as the platelet storage lesion (PSL). To get more insight into the development of the PSL, we used label free quantitative mass spectrometry to identify changes in the platelet proteome during storage. In total 2501 proteins were accurately quantified in 3 biological replicates on at least 1 of the 7 different time-points analyzed. Significant changes in levels of 21 proteins were observed over time. Gene ontology enrichment analysis of these proteins revealed that the majority of this set was involved in platelet degranulation, secretion and regulated exocytosis. Twelve of these proteins have been shown to reside in α-granules. Upon prolonged storage (13-16 days) elevated levels of α-2-macroglobulin, glycogenin and Ig μ chain C region were identified. Taken together this study identifies novel markers for monitoring of the PSL that may potentially also be used for the detection of "young" and "old" platelets in the circulation