Edge Elimination in TSP Instances

The Traveling Salesman Problem is one of the best studied NP-hard problems in combinatorial optimization. Powerful methods have been developed over the last 60 years to find optimum solutions to large TSP instances. The largest TSP instance so far that has been solved optimally has 85,900 vertices. Its solution required more than 136 years of total CPU time using the branch-and-cut based Concorde TSP code [1]. In this paper we present graph theoretic results that allow to prove that some edges of a TSP instance cannot occur in any optimum TSP tour. Based on these results we propose a combinatorial algorithm to identify such edges. The runtime of the main part of our algorithm is $O(n^2 \log n)$ for an n-vertex TSP instance. By combining our approach with the Concorde TSP solver we are able to solve a large TSPLIB instance more than 11 times faster than Concorde alone

Regulated Inositol‐Requiring Protein 1‐Dependent Decay as a Mechanism of Corin RNA and Protein Deficiency in Advanced Human Systolic Heart Failure

BACKGROUND: The compensatory actions of the endogenous natriuretic peptide system require adequate processing of natriuretic peptide pro‐hormones into biologically active, carboxyl‐terminal fragments. Natriuretic peptide pro‐peptide processing is accomplished by corin, a transmembrane serine protease expressed by cardiomyocytes. Brain natriuretic peptide (BNP) processing is inadequate in advanced heart failure and is independently associated with adverse outcomes; however, the molecular mechanisms causing impaired BNP processing are not understood. We hypothesized that the development of endoplasmic reticulum stress in cardiomyocytes in advanced heart failure triggers inositol‐requiring protein 1 (IRE1)‐dependent corin mRNA decay, which would favor a molecular substrate favoring impaired natriuretic peptide pro‐peptide processing. METHODS AND RESULTS: Two independent samples of hearts obtained from patients with advanced heart failure at transplant demonstrated that corin RNA was reduced as Atrial natriuretic peptide (ANP)/BNP RNA increased. Increases in spliced X‐box protein 1, a marker for IRE1‐endoribonuclease activity, were associated with decreased corin RNA. Moreover, ≈50% of the hearts demonstrated significant reductions in corin RNA and protein as compared to the nonfailing control sample. In vitro experiments demonstrated that induction of endoplasmic reticulum stress in cultured cardiomyocytes with thapsigargin activated IRE1s endoribonuclease activity and time‐dependent reductions in corin mRNA. In HL‐1 cells, overexpression of IRE1 activated IRE1 endoribonuclease activity and caused corin mRNA decay, whereas IRE1‐RNA interference with shRNA attenuated corin mRNA decay after induction of endoplasmic reticulum stress with thapsigargin. Pre‐treatment of cells with Actinomycin D to inhibit transcription did not alter the magnitude or time course of thapsigargin‐induced corin mRNA decline, supporting the hypothesis that this was the result of IRE1‐mediated corin mRNA degradation. CONCLUSIONS: These data support the hypothesis that endoplasmic reticulum stress‐mediated, IRE1‐dependent targeted corin mRNA decay is a mechanism leading to corin mRNA resulting in corresponding corin protein deficiency may contribute to the pathophysiology of impaired natriuretic peptide pro‐hormone processing in humans processing in humans with advanced systolic heart failure

Impaired clearance of ceftizoxime and cefotaxime after orthotopic liver transplantation.

The pharmacokinetics of ceftizoxime (CZX) and of cefotaxime (CTX) were studied in five children and five adults after orthotopic liver transplantation (OLT). Delayed clearance of CZX (clearance of 0.21 to 1.26 ml/min per kg [body weight]) and CTX (clearance of 0.40 to 1.49 ml/min per kg) occurred in 7 of the 10 OLT patients. We conclude that abnormal CZX and CTX clearance is common after OLT and may be associated with minimal change in serum creatinine

Integrated electronic prescribing and robotic dispensing: a case study

INTRODUCTION: To quantify the benefits of electronic prescribing directly linked to a robotic dispensing machine. CASE DESCRIPTION: Quantitative case study analysis is used on a single case. Hospital A (1,000 beds) has used an integrated electronic prescribing system for 10 years, and in 2009 linked two robotic dispensing machines to the system. The impact on dispensing error rates (quality) and efficiency (costs) were assessed. EVALUATION AND DISCUSSION: The implementation delivered staff efficiencies above expectation. For the out-patient department, this was 16% more than the business case had suggested. For the in-patients dispensary, four staff were released for re-deployment. Additionally, £500,000 in stockholding efficiency above that suggested by the business case was identified. Overall dispensing error rates were not adversely affected and products dispensed by the electronic prescribing - robot system produced zero dispensing errors. The speed of dispensing increased also, as the electronic prescribing - robot combination permitted almost instantaneous dispensing from the point of a doctor entering a prescription. CONCLUSION: It was significant that the combination of electronic prescribing and a robot eliminated dispensing errors. Any errors that did occur were not as a result of the electronic prescribing - robotic system (i.e. the product was not stocked within the robot). The direct linking of electronic prescribing and robots as a dispensing system together produces efficiencies and improves the quality of the dispensing process

Genetic analysis of the human tumor necrosis factor alpha/cachectin promoter region in a macrophage cell line.

The 615-bp 5' flanking region of the human TNF-alpha/cachectin gene was isolated and ligated to the luciferase reporter gene. In addition, a series of truncated promoter constructs was generated by exonuclease III digestion. The promoter activity of these constructs was studied in a transient transfection system using the TNF-alpha-producing U937 cell line. Full-length and truncated TNF promoter constructions extending from -615 to -95 bp relative to the transcription start site (TSS) could be induced by phorbol esters. A construct truncated to within 36 bp of the TSS (and within 11 bp of the TATAA box) was inactive. Therefore, the phorbol ester responsive is localized in the TNF/cachectin promoter to a relatively short region proximal to the TATAA box

Low myo-inositol and high glutamine levels in brain are associated with neuropsychological deterioration after induced hyperammonemia

The neuropsychological effect of hyperammonemia is variable. This study tests the hypothesis that the effect of ammonia on the neuropsychological function in patients with cirrhosis is determined by the ability of the brain to buffer ammonia-induced increase in glutamine within the astrocyte by losing osmolytes like myo-inositol (mI) and not by the magnitude of the induced hyperammonemia. Fourteen cirrhotic patients with no evidence of overt hepatic encephalopathy were given a 75-g amino acid (aa) solution mimicking the hemoglobin molecule to induce hyperammonemia. Measurement of a battery of neuropsychological function tests including immediate memory, ammonia, aa, and short-echo time proton magnetic resonance spectroscopy were performed before and 4 h after administration of the as solution. Eight patients showed deterioration in the Immediate Memory Test at 4 h. Demographic factors, severity of liver disease, change in plasma ammonia, and as profiles after the as solution were similar in those that showed a deterioration compared with those who did not. In patients who showed deterioration in the memory test, the mI-to-creatine ratio (mI/Cr) was significantly lower at baseline than those that did not deteriorate. In contrast, the glutamate/glutamine-to-Cr ratio was significantly greater in the patients that deteriorated. The observation that deterioration in the memory test scores was greater in those with lower mI/Cr supports the hypothesis that the neuropsychological effects of induced hyperammonemia is determined by the capacity of the brain to handle ammonia-induced increase in glutamine

SIRT1 Activity Is Linked to Its Brain Region-Specific Phosphorylation and Is Impaired in Huntington’s Disease Mice

Huntingtons disease (HD) is a neurodegenerative disorder for which there are no disease-modifying treatments. SIRT1 is a NAD+-dependent protein deacetylase that is implicated in maintaining neuronal health during development, differentiation and ageing. Previous studies suggested that the modulation of SIRT1 activity is neuroprotective in HD mouse models, however, the mechanisms controlling SIRT1 activity are unknown. We have identified a striatum-specific phosphorylation-dependent regulatory mechanism of SIRT1 induction under normal physiological conditions, which is impaired in HD. We demonstrate that SIRT1 activity is down-regulated in the brains of two complementary HD mouse models, which correlated with altered SIRT1 phosphorylation levels. This SIRT1 impairment could not be rescued by the ablation of DBC1, a negative regulator of SIRT1, but was linked to changes in the sub-cellular distribution of AMPK-α1, a positive regulator of SIRT1 function. This work provides insights into the regulation of SIRT1 activity with the potential for the development of novel therapeutic strategies

Dust penetrated morphology in the high redshift Universe

Images from the Hubble Deep Field (HDF) North and South show a large percentage of dusty, high redshift galaxies whose appearance falls outside traditional classification systems. The nature of these objects is not yet fully understood. Since the HDF preferentially samples restframe UV light, HDF morphologies are not dust or `mask' penetrated. The appearance of high redshift galaxies at near-infrared restframes remains a challenge for the New Millennium. The Next Generation Space Telescope (NGST) could routinely provide us with such images. In this contribution, we quantitatively determine the dust-penetrated structures of high redshift galaxies such as NGC 922 in their near-infrared restframes. We show that such optically peculiar objects may readily be classified using the dust penetrated z ~ 0 templates of Block and Puerari (1999) and Buta and Block (2001).Comment: 4 pages, 2 figures. Presented at the conference "The Link between Stars and Cosmology", 26-30 March, 2001, Puerto Vallarta, Mexico. To be published by Kluwer, eds. M. Chavez, A. Bressan, A. Buzzoni, and D. Mayya. High-resolution version of Figure 2 can be found at http://www.inaoep.mx/~puerari/conf_puertovallart