A 2.75-Approximation Algorithm for the Unconstrained Traveling Tournament Problem

A 2.75-approximation algorithm is proposed for the unconstrained traveling tournament problem, which is a variant of the traveling tournament problem. For the unconstrained traveling tournament problem, this is the first proposal of an approximation algorithm with a constant approximation ratio. In addition, the proposed algorithm yields a solution that meets both the no-repeater and mirrored constraints. Computational experiments show that the algorithm generates solutions of good quality.Comment: 12 pages, 1 figur

Adenylyl Cyclase Isoform Specific Effects in Lipid Raft and Non-Lipid Raft Membrane Domains Regulate cAMP Compartmentation in Human Airway Smooth Muscle Cells

The formation of distinct macromolecular signaling complexes allows different G-protein coupled receptors to produce diverse functional responses, even while sharing a common second messenger such as cAMP. In human airway smooth muscle (HASM) cells, segregation of specific receptors into different membrane microdomains is thought to critically aid in generating compartmentalized cAMP responses. Whereas, E type prostaglandin receptors (EPRs) have been shown to be expressed in non-lipid raft domains of the plasma membrane, β-Adrenergic receptors (βARs) are predominantly expressed in caveolar lipid rafts. In the present study, we tested the hypothesis that adenylyl cyclase type 2 (AC2) preferentially couples to EPRs in a non-lipid raft domain, while adenylyl cyclase type 6 (AC6) selectively couples to βARs in lipid rafts. To do this, we examined the effect of overexpressing AC2 and AC6 on cAMP responses detected using genetically-encoded FRET-based biosensors targeted to lipid raft and non-lipid raft domains of the plasma membrane, as well as the bulk cytosolic compartment in HASM cells. This approach has the advantage of measuring the kinetics of cAMP production in living cells without the use of PDE inhibitors. Overexpression of AC2 enhanced the cAMP response to EPR activation associated with non-lipid raft domains, without significantly affecting responses detected elsewhere. AC2 overexpression also had no effect on cAMP responses to βAR activation detected in any subcellular location. These data confirm the hypothesis that AC2 couples exclusively with EPRs in a non-lipid raft membrane compartment. Overexpression of AC6, on the other hand, actually decreased the response to βAR stimulation associated with lipid rafts, without significantly affecting responses elsewhere. AC6 overexpression also had no effect on the responses to EPR activation detected anywhere in the cell. The ability of AC6 overexpression to inhibit βAR production of cAMP in lipid raft domains was reversed by inhibition of PDE4 activity with rolipram. It was also reversed by overexpression of Ht31 peptide, which disrupts the interaction of protein kinase A with A-kinase anchoring proteins (AKAPs). These results suggests that AC6 overexpression upregulates and/or recruits PKA and PDE4 activity, which then reduces βAR production of cAMP associated specifically with lipid raft domains

Tratamiento de aguas residuales mediante lodos activados a escala de laboratorio

The experiment was carried out at the laboratory scale. For this purpose a system with 6 mini reactors was designed, adapted from the literature. The used equations were deduced from the Eckenfelder (1970) and Metcalf & Eddy (1998) proceedings. The kinetics constants of biological growth at laboratory level were obtained using the activated sludge method. The obtained kinetic constants with synthetic wastewater were: a: 0,8763 (Parameter of oxygen utilization to substrate oxidation). b: 0,0744 (Parameter of oxygen utilization to substrate oxidation in the endogenous respiration). Y: 0,0494 (Ratio of the mass of cells formed to the mass of substrate consumed). kd: 0,00048 d-1 (Endogenous decay coefficient). k: 0,0025 h-1.L/mg (Velocity constant of substrate utilization). The wastewater were supplied to each mini reactor trough a dosificator and a peristaltic pump. It was found difficulty in the water flow distribution. It is recommended to carry out the experiment, pumping wastewater with a peristaltic pump to each mini reactor, because the used dosificator got obstructed frequently.Se realizó la prueba de tratamiento de aguas residuales a escala de laboratorio. Para lo cual se ha diseñado un módulo compuesto por 6 minirreactores, los cuales son una adaptación de los mostrados en la bibliografía. Las ecuaciones empleadas fueron deducidas según los procedimientos de Eckenfelder (1970) y Metcalf & Eddy (1998). Con los resultados analíticos obtenidos se determinó las constantes cinéticas de crecimiento biológico, a escala de laboratorio, utilizando el método de lodos activados. Las constantes cinéticas obtenidas empleando un agua residual sintética fueron: a: 0,8763 (Parámetro de utilización de oxígeno para la oxidación de sustrato), b: 0,0744 (Parámetro de utilización de oxígeno utilizado en la respiración endógena), Y: 0,0494 (Coeficiente de producción de biomasa por consumo de sustrato), kd: 0,00048 d-1 (Coeficiente de consumo de biomasa por respiración endógena), k: 0,0025 h-1.L/mg (Constante de velocidad de consumo de sustrato). Las aguas residuales fueron suministradas a cada minirreactor mediante un dosificador, el mismo que fue abastecido por medio de una bomba peristáltica. Encontrándose dificultades en la distribución apropiada de los caudales. Por lo cual se recomienda realizar el experimento con una bomba peristáltica para cada unidad de los minirreactores, pues los dosificadores utilizados tuvieron dificultad en operar óptimamente al obstruirse continuamente

Cytoplasmic BK\u3csub\u3eCa\u3c/sub\u3e channel intron-containing mRNAs contribute to the intrinsic excitability of hippocampal neurons

High single-channel conductance K+ channels, which respond jointly to membrane depolarization and micromolar concentrations of intracellular Ca2+ ions, arise from extensive cell-specific alternative splicing of pore-forming α-subunit mRNAs. Here, we report the discovery of an endogenous BKCa channel α-subunit intron-containing mRNA in the cytoplasm of hippocampal neurons. This partially processed mRNA, which comprises ≈10% of the total BKCa channel α-subunit mRNAs, is distributed in a gradient throughout the somatodendritic space. We selectively reduced endogenous cytoplasmic levels of this intron-containing transcript by RNA interference without altering levels of the mature splice forms of the BKCa channel mRNAs. In doing so, we could demonstrate that changes in a unique BKCa channel α-subunit introncontaining splice variant mRNA can greatly impact the distribution of the BKCa channel protein to dendritic spines and intrinsic firing properties of hippocampal neurons. These data suggest a new regulatory mechanism for modulating the membrane properties and ion channel gradients of hippocampal neurons

Analysis of a panel of antibodies to APC reveals consistent activity towards an unidentified protein

Acquisition of truncating mutations in the adenomatous polyposis coli (APC) protein underlies the progression of the majority of sporadic and familial colorectal cancers. As such, the localisation patterns and interacting partners of APC have been extensively studied in a range of systems, relying on the use of a broad panel of antibodies. Until recently, antibodies to APC have been used largely unchecked. However, several recent reports have been invaluable in clarifying the use of a number of antibodies commonly used to detect APC. Here, we analyse the specificity of a further subset of antibodies to APC. We used a panel of six commercially available antibodies (directed to the amino and carboxy termini of APC) and confirm the detection of full-length APC by immunoblotting. We demonstrate that a 150 kDa protein, also reproducibly detected by this panel of antibodies, is unlikely to be APC. We present data for the immunological staining patterns of the APC antibodies and validate the results through RNAi. Using this approach, we confirm that the apical staining pattern, observed by immunofluorescence and previously reported in cell systems, is unlikely to be APC. Finally, we present our data as a summary of APC-antibody specificities for APC

Autism as a disorder of neural information processing: directions for research and targets for therapy

The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself

Feedback Inhibition in the PhoQ/PhoP Signaling System by a Membrane Peptide

The PhoQ/PhoP signaling system responds to low magnesium and the presence of certain cationic antimicrobial peptides. It regulates genes important for growth under these conditions, as well as additional genes important for virulence in many gram-negative pathogens. PhoQ is a sensor kinase that phosphorylates and activates the transcription factor PhoP. Since feedback inhibition is a common theme in stress-response circuits, we hypothesized that some members of the PhoP regulon may play such a role in the PhoQ/PhoP pathway. We therefore screened for PhoP-regulated genes that mediate feedback in this system. We found that deletion of mgrB (yobG), which encodes a 47 amino acid peptide, results in a potent increase in PhoP-regulated transcription. In addition, over-expression of mgrB decreased transcription at both high and low concentrations of magnesium. Localization and bacterial two-hybrid studies suggest that MgrB resides in the inner-membrane and interacts directly with PhoQ. We further show that MgrB homologs from Salmonella typhimurium and Yersinia pestis also repress PhoP-regulated transcription in these organisms. In cell regulatory circuits, feedback has been associated with modulating the induction kinetics and/or the cell-to-cell variability in response to stimulus. Interestingly, we found that elimination of MgrB-mediated feedback did not have a significant effect on the kinetics of reporter protein production and did not decrease the variability in expression among cells. Our results indicate MgrB is a broadly conserved membrane peptide that is a critical mediator of negative feedback in the PhoQ/PhoP circuit. This new regulator may function as a point of control that integrates additional input signals to modulate the activity of this important signaling system

Late Cretaceous tectonic history of the Sierra‐Salinia‐Mojave arc as recorded in conglomerates of the Upper Cretaceous and Paleocene Gualala Formation, northern California

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95005/1/jgrb14012.pd