Solving large 0–1 multidimensional knapsack problems by a new simplified binary artificial fish swarm algorithm

The artificial fish swarm algorithm has recently been emerged in continuous global optimization. It uses points of a population in space to identify the position of fish in the school. Many real-world optimization problems are described by 0-1 multidimensional knapsack problems that are NP-hard. In the last decades several exact as well as heuristic methods have been proposed for solving these problems. In this paper, a new simpli ed binary version of the artificial fish swarm algorithm is presented, where a point/ fish is represented by a binary string of 0/1 bits. Trial points are created by using crossover and mutation in the different fi sh behavior that are randomly selected by using two user de ned probability values. In order to make the points feasible the presented algorithm uses a random heuristic drop item procedure followed by an add item procedure aiming to increase the profit throughout the adding of more items in the knapsack. A cyclic reinitialization of 50% of the population, and a simple local search that allows the progress of a small percentage of points towards optimality and after that refines the best point in the population greatly improve the quality of the solutions. The presented method is tested on a set of benchmark instances and a comparison with other methods available in literature is shown. The comparison shows that the proposed method can be an alternative method for solving these problems.

Effects of chlorthalidone and diltiazem on myocardial ischemia in elderly patients with hypertension and coronary artery disease

OBJETIVE: Antihypertensive therapy with thiazides decreases coronary events in elderly patients. However, the influence of diuretics on myocardial ischemia has not been fully investigated. The aim of this study was to compare the effect of chlorthalidone and diltiazem on myocardial ischemia. METHODS: Following a randomized, double-blind, crossover protocol, we studied 15 elderly hypertensive patients aged 73.6±4.6 years with myocardial ischemia. All patients had angiographically documented coronary artery disease. We measured patients using 48- hour ambulatory electrocardiogram monitoring and exercise testing. After a 2-week period using placebo, patients received chlorthalidone or diltiazem for 4 weeks. RESULTS: Both treatments lowered systolic and diastolic blood pressures. The number of ischemic episodes on ambulatory electrocardiogram recordings was reduced with the use of chlorthalidone (2.5±3.8) and diltiazem (3.2±4.2) when compared with placebo (7.9±8.8; p<0.05). The total duration of ischemic episodes was reduced in both treatments when compared with placebo (chlorthalidone: 19.2±31.9min; diltiazem: 19.3±29.6min; placebo: 46.1±55.3min; p<0.05). CONCLUSION: In elderly hypertensive patients with coronary artery disease, chlorthalidone reduced myocardial ischemia similarly to diltiazem. This result is consistent with epidemiological studies and suggests that reduction of arterial blood pressure with thiazide therapy plays an important role in decreasing myocardial ischemia.

Ablação do flutter atrial típico: estudo prospectivo e randomizado do cateter irrigado fechado versus cateter com eletrodo distal de 8 mm

OBJETIVOS: Trabalho prospectivo, randomizado para comparar a eficácia e a segurança do cateter irrigado em relação ao cateter com eletrodo distal de 8 mm para ablação com radiofreqüência (RF) do flutter atrial. MÉTODOS: Em 52 pacientes consecutivos referidos para tratamento do flutter atrial típico, a ablação do istmo cavotricuspídeo (Ist-CT) foi realizada com cateter de irrigação fechada (n=26) ou com cateter de eletrodo distal de 8 mm (n=26). Os pulsos de RF foram aplicados ponto a ponto por 60 segundos com potência limitada a 50 w com o cateter irrigado e por controle de temperatura (60ºC, 70 w) com cateter de 8 mm. O critério de fim do procedimento foi a obtenção de bloqueio bidirecional do Ist-CT. RESULTADOS: O bloqueio Ist-CT foi obtido em 98,1% dos pacientes. O "crossover" ocorreu em quatro pacientes do grupo com cateter irrigado. Não se encontrou diferença estatística significante em relação aos parâmetros da ablação, tais como tempo total de aplicação de RF (591,1±309,0s vs 486,2±250,8s), duração do procedimento (86,4 ± 23,6 vs 78,1±22,5min) e tempo de fluoroscopia (17,0±6,7 vs 15,4±4,6min) entre os dois grupos. Durante seguimento médio de 10,6 meses, um paciente do grupo irrigado apresentou recorrência do flutter atrial típico. CONCLUSÃO: A ablação do Ist-CT resultou ser efetiva e segura para o controle do flutter atrial com ambas as técnicas empregadas (cateter com eletrodo distal de 8 mm e cateter irrigado). A complexidade técnica do cateter irrigado proporciona menor competitividade.

Synthetic and mechanistic studies of the Thia-Fries Rearrangement

A study has been undertaken of the published literature on the Fries rearrangement, thermal, photo and microwave, since its discovery in 1908. A resume of these publications and especially of those pertaining to the thia-Fries rearrangement of sulfamate esters, has been compiled. Phenyl sulfamate, phenyl N,N-dimethylsulfamate, phenyl N,N-diethylsulfamate and phenyl N,N-di-n-propylsulfamate and many of their substituted compounds have been synthesised and purified, a total of thirty nine esters. The sulfamates have been characterised by mp / bp, infrared, C, H and N microanalysis and mass spectrum. Many of these sulfamates, twenty six in total, have been rearranged to sulfonamides in the thia-Fries rearrangement, and subsequently purified. The products were characterised by mp / bp, infrared, C, H and N microanalysis and mass spectrum. Mechanistic studies of the sulfamates have been investigated, particularly phenyl N,N-dimethylsulfamate. The rearrangement with various catalysts and catalytic ratios, the effect of solvents on the rearrangement and many crossover experiments have been carried out to determine the molecularity i.e. whether it is an inter-, intra- or bimolecular reaction. The microwave induced thia-Fries rearrangement has been examined to determine what effect this irradiation has on the rearrangement. Photo thia-Fries rearrangement has also been investigated.

Experimental and model-based analysis of the steady-state and dynamic operating behaviour of the direct methanol fuel cell (DMFC)

Direct methanol fuel cell, DMFC, model, mass transport, Maxwell-Stefan, Flory-Huggins, crossover, polymer electrolyte membrane, Nafion

Estudos genéticos sôbre o milho tunicata

The study of pod corn seems still of much importance from different points of view. The phylogenetical importance of the tunicate factor as a wild type relic gene has been recently discussed in much detail by MANGELSDORF and REEVES (1939), and by BRIEGER (1943, 1944a e b). Selection experiments have shown that the pleiotropic effect of the Tu factor can be modified very extensively (BRIEGER 1944a) and some of the forms thus obtained permitt comparison of male and female inflorescences in corn and related grasses. A detailed discussion of the botanical aspect shall be given shortly. The genetic apect, finally, is the subject of the present publication. Pod corn has been obtained twice: São Paulo Pod Corn and Bolivia Pod Corn. The former came from one half ear left in our laboratory by a student and belongs to the type of corn cultivated in the State of São Paulo, while the other belongs to the Andean group, and has been received both through Dr. CARDENAS, President of the University at Cochabamba, Bolivia, and through Dr. H. C. CUTLER, Harvard University, who collected material in the Andes. The results of the studies may be summarized as follows: 1) In both cases, pod corn is characterized by the presence of a dominant Tu factor, localized in the fourth chromosome and linked with sul. The crossover value differs somewhat from the mean value of 29% given by EMERSON, BEADLE and FRAZER (1935) and was 25% in 1217 plants for São Paulo Pod Corn and 36,5% in 345 plants for Bolivia Pod Corn. However not much importance should be attributed to the quantitative differences. 2) Segregation was completely normal in Bolivia Pod Corn while São Paulo Pod Corn proved to be heterozygous for a new com uma eliminação forte, funcionam apenas 8% em vez de 50%. Existem cerca de 30% de "jcrossing-over entre o gen doce (Su/su) e o fator gametofítico; è cerca de 5% entre o gen Tu e o fator gametofítico. A ordem dos gens no cromosômio IV é: Ga4 - Tu - Sul. 3) Using BRIEGER'S formulas (1930, 1937a, 1937b) the following determinations were made. a) the elimination of ga4 pollen tubes may be strong or weak. In the former case only about 8% and in the latter 37% of ga4 pollen tubes function, instead of the 50% expected in normal heterozygotes. b) There is about 30,4% crossing-over between sul and ga4 and 5,3% between Tu and ga3, the order of the factors beeing Su 1 - Tu - Ga4. 4) The new gametophyte factor differs from the two others factors in the same chromosome, causing competition between pollen tubes. The factor Gal, ocupies another locus, considerably to the left of Sul (EMERSON, BEADLE AND FRAZSER, 1935). The gen spl ocupies another locus and causes a difference of the size of the pollen grains, besides an elimination of pollen tubes, while no such differences were observed in the case of the new factor Ga4. 5) It may be mentioned, without entering into a detailed discussion, that it seems remarquable that three of the few gametophyte factors, so far studied in detail are localized in chromosome four. Actuality there are a few more known (BRIEGER, TIDBURY AND TSENG 1938), but only one other has been localized so far, Ga2, in chromosome five between btl and prl. (BRIEGER, 1935). 6) The fourth chromosome of corn seems to contain other pecularities still. MANGELSDORF AND REEVES (1939) concluded that it carries two translocations from Tripsacum chromosomes, and BRIEGER (1944b) suggested that the tu allel may have been introduced from a tripsacoid ancestor in substitution of the wild type gene Tu at the beginning of domestication. Serious disturbances in the segregation of fourth chromosome factors have been observed (BRIEGER, unpublished) in the hybrids of Brazilian corn and Mexican teosinte, caused by gametophytic and possibly zygotic elimination. Future studies must show wether there is any relation between the frequency of factors, causing gametophyte elimination and the presence of regions of chromosomes, tranfered either from Tripsacum or a related species, by translocation or crossing-over.

Pharmacokinetics and pharmacogenomics of once-daily raltegravir and atazanavir in healthy volunteers.

Atazanavir inhibits UDP-glucuronyl-transferase-1A1 (UGT1A1), which metabolizes raltegravir, but the magnitude of steady-state inhibition and role of the UGT1A1 genotype are unknown. Sufficient inhibition could lead to reduced-dose and -cost raltegravir regimens. Nineteen healthy volunteers, age 24 to 51 years, took raltegravir 400 mg twice daily (arm A) and 400 mg plus atazanavir 400 mg once daily (arm B), separated by ?3 days, in a crossover design. After 1 week on each regimen, raltegravir and raltegravir-glucuronide plasma and urine concentrations were measured by liquid chromatography-tandem mass spectrometry in multiple samples obtained over 12 h (arm A) or 24 h (arm B) and analyzed by noncompartmental methods. UGT1A1 promoter variants were detected with a commercially available kit and published primers. The primary outcome was the ratio of plasma raltegravir C(tau), or concentration at the end of the dosing interval, for arm B (24 h) versus arm A (12 h). The arm B-to-arm A geometric mean ratios (95% confidence interval, P value) for plasma raltegravir C(tau), area under the concentration-time curve from 0 to 12 h (AUC(0-12)), and raltegravir-glucuronide/raltegravir AUC(0-12) were 0.38 (0.22 to 0.65, 0.001), 1.32 (0.62 to 2.81, 0.45), and 0.47 (0.38 to 0.59, <0.001), respectively. Nine volunteers were heterozygous and one was homozygous for a UGT1A1 reduction-of-function allele, but these were not associated with metabolite formation. Although atazanavir significantly reduced the formation of the glucuronide metabolite, its steady-state boosting of plasma raltegravir did not render the C(tau) with a once-daily raltegravir dose of 400 mg similar to the C(tau) with the standard twice-daily dose. UGT1A1 promoter variants did not significantly influence this interaction.

Renal response to the angiotensin II receptor subtype 1 antagonist irbesartan versus enalapril in hypertensive patients.

OBJECTIVE: To compare the acute and sustained renal hemodynamic effects on hypertensive patients of 100 mg irbesartan and 20 mg enalapril each once daily. PATIENTS: Twenty patients (aged 35-70 years) with uncomplicated, mild-to-moderate essential hypertension and normal serum creatinine levels completed this study. STUDY DESIGN: After random allocation to treatment (n=10 per group), administration schedule (morning or evening) was determined by further random allocation, with crossover of schedules after 6 weeks' therapy. Treatment and administration assignments were double-blind. Twenty-four-hour ambulatory blood pressure was monitored before and after 6 and 12 weeks of therapy. Renal hemodynamics were determined on the first day of drug administration and 12 and 24 h after the last dose during chronic treatment. RESULTS: Administration of each antihypertensive agent induced a renal vasodilatation with no significant change in glomerular filtration rate. However, the time course appeared to differ: irbesartan had no significant acute effect 4 h after the first dose, but during chronic administration a renal vasodilatory response was found 12 and 24 h after the dose; enalapril was effective acutely and 12 h after administration, but no residual effect was found 24 h after the dose. Both antihypertensive agents lowered mean ambulatory blood pressure effectively, with no significant difference between treatments or between administration schedules (morning versus evening). CONCLUSIONS: Irbesartan and enalapril have comparable effects on blood pressure and renal hemodynamics in hypertensive patients with normal renal functioning. However, the time profiles of the renal effects appear to differ, which might be important for long-term renoprotective effects.

Acute endotoxemia inhibits microvascular nitric oxide-dependent vasodilation in humans.

Nitric oxide (NO) is crucial for the microvascular homeostasis, but its role played in the microvascular alterations during sepsis remains controversial. We investigated NO-dependent vasodilation in the skin microcirculation and plasma levels of asymmetric dimethylarginine (ADMA), a potent endogenous inhibitor of the NO synthases, in a human model of sepsis. In this double-blind, randomized, crossover study, microvascular NO-dependent (local thermal hyperemia) and NO-independent vasodilation (post-occlusive reactive hyperemia) assessed by laser Doppler imaging, plasma levels of ADMA, and l-arginine were measured in seven healthy obese volunteers, immediately before and 4 h after either a i.v. bolus injection of Escherichia coli endotoxin (LPS; 2 ng/kg) or normal saline (placebo) on two different visits at least 2 weeks apart. LPS caused the expected systemic effects, including increases in heart rate (+43%, P < 0.001), cardiac output (+16%, P < 0.01), and rectal temperature (+1.4°C, P < 0.001), without change in arterial blood pressure. LPS affected neither baseline skin blood flow nor post-occlusive reactive hyperemia but decreased the NO-dependent local thermal hyperemia response, l-arginine, and, to a lesser extent, ADMA plasma levels. The changes in NO-dependent vasodilation were not correlated with the corresponding changes in the plasma levels of ADMA, l-arginine, or the l-arginine/ADMA ratio. Our results show for the first time that experimental endotoxemia in humans causes a specific decrease in endothelial NO-dependent vasodilation in the microcirculation, which cannot be explained by a change in ADMA levels. Microvascular NO deficiency might be responsible for the heterogeneity of tissue perfusion observed in sepsis and could be a therapeutic target.

What to drink with cheese fondue

Comment on: Heinrich H, Goetze O, Menne D, Iten PX, Fruehauf H, Vavricka SR, Schwizer W, Fried M, Fox M. Effect on gastric function and symptoms of drinking wine, black tea, or schnapps with a Swiss cheese fondue: randomised controlled crossover trial. BMJ. 2010 Dec 14;341:c6731. doi: 10.1136/bmj.c6731. PMID 21156747

Structure of a multisubunit complex that promotes DNA branch migration.

The RuvA and RuvB proteins of Escherichia coli, which are induced in response to DNA damage, are important in the formation of heteroduplex DNA during genetic recombination and related recombinational repair processes. In vitro studies show that RuvA binds Holiday junctions and acts as a specificity factor that targets the RuvB ATPase, a hexameric ring protein, to the junction. Together, RuvA and RuvB promote branch migration, an ATP-dependent reaction that increases the length of the heteroduplex DNA. Electron microscopic visualization of RuvAB now provides a new insight into the mechanism of this process. We observe the formation of a tripartite protein complex in which RuvA binds the crossover and is sandwiched between two hexameric rings of RuvB. The Holliday junction within this complex adopts a square-planar structure. We propose a molecular model for branch migration, a unique feature of which is the role played by the two oppositely oriented RuvB ring motors.

Administering brief motivational interventions to young men: Results from a pilot census transmissible study among 19 year-old francophone Swiss men.

AIMS - To pilot the implementation of brief motivational intervention (BMI) among conscripts, and to test the effectiveness of BMI in young men voluntarily showing up for a single face-to-face alcohol BMI session. Participants were conscripts attending the army recruitment process in Lausanne. This process is mandatory for all Swiss males at age 19 and Lausanne serves all francophone Swiss men. METHODS - Of 3'227 young men that were seen during the army recruitment procedures, 445 voluntarily showed up for a BMI and 367 were included in the study (exclusions were random and unsystematic and related to organizational aspects in the recruitment center). After an initial assessment, subjects were randomized into two groups: an immediate BMI and a 6-month delayed BMI (waiting list design). A 6-month follow-up assessment was conducted in both groups. BMI was a face-to-face 20 minutes counseling session with a psychologist trained in motivational interviewing at baseline and a telephone session for the control group at follow-up. Strategies of BMI included the exploration and evocation of a possible behavior change, importance of future change, readiness to change, and commitment to change. A filmed example of such an intervention is available in French at www.alcoologie.ch. RESULTS - All procedures are now fully implemented and working and the provision of preventive efforts found general approval by the army. 3'227 were eligible for BMI and 445 of them (13.8%) showed up for receiving a BMI. 367 were included in the study, 181 in the BMI group and 186 in the control group. More than 86% of those included were reached at follow-up. With one exception all findings on alcohol use went in the expected direction, i.e. a stronger decrease in alcohol use (or a smaller increase as for usual weekly drinking amount) in the BMI group. The risk for risky single occasion drinking (RSOD) decreased from 57% at-risk users at baseline to 50.6%, i.e. a 6.4% point decrease in the BMI group, while there was only a 0.6% point decrease (from 57.5% to 56.9%) in the control group. Moreover, the study showed that there was a likelihood of crossover effects for other substances like tobacco smoking and cannabis use. Despite these encouraging and consistent positive findings, none reached significance at conventional levels (p < 0.05). DISCUSSION - Data suggest a beneficial impact of BMI on alcohol use outcomes and potential effect on other substance use in 19-year old men attending the army recruitment and showing up voluntarily for BMI. As the main aim was to implement and test feasibility of conducting BMI in this setting none of our findings reached statistical significance. The consistency of findings across measures and substances, however, raises hope that non-significance in the present study does not mean no effect, but mainly insufficient power of this pilot study. [Authors]

Angiotensin II receptor blockade prevents acute renal sodium retention induced by low levels of orthostatic stress.

BACKGROUND: Depending on its magnitude, lower body negative pressure (LBNP) has been shown to induce a progressive activation of neurohormonal, renal tubular, and renal hemodynamic responses, thereby mimicking the renal responses observed in clinical conditions characterized by a low effective arterial volume such as congestive heart failure. Our objective was to evaluate the impact of angiotensin II receptor blockade with candesartan on the renal hemodynamic and urinary excretory responses to a progressive orthostatic stress in normal subjects. METHODS: Twenty healthy men were submitted to three levels of LBNP (0, -10, and -20 mbar or 0, -7.5, and -15 mm Hg) for 1 hour according to a crossover design with a minimum of 2 days between each level of LBNP. Ten subjects were randomly allocated to receive a placebo and ten others were treated with candesartan 16 mg orally for 10 days before and during the three levels of LBNP. Systemic and renal hemodynamics, renal sodium excretions, and the hormonal response were measured hourly before, during, and for 2 hours after LBNP. RESULTS: During placebo, LBNP induced no change in systemic and renal hemodynamics, but sodium excretion decreased dose dependently with higher levels of LBNP. At -20 mbar, cumulative 3-hour sodium balance was negative at -2.3 +/- 2.3 mmol (mean +/- SEM). With candesartan, mean blood pressure decreased (76 +/- 1 mm Hg vs. 83 +/- 3 mm Hg, candesartan vs. placebo, P < 0.05) and renal plasma flow increased (858 +/- 52 mL/min vs. 639 +/- 36 mL/min, candesartan vs. placebo, P < 0.05). Glomerular filtration rate (GFR) was not significantly higher with candesartan (127 +/- 7 mL/min in placebo vs. 144 +/- 12 mL/min in candesartan). No significant decrease in sodium and water excretion was found during LBNP in candesartan-treated subjects. At -20 mbar, the 3-hour cumulative sodium excretion was + 4.6 +/- 1.4 mmol in the candesartan group (P= 0.02 vs. placebo). CONCLUSION: Selective blockade of angiotensin II type 1 (AT1) receptors with candesartan increases renal blood flow and prevents the antinatriuresis during sustained lower body negative pressure despite a modest decrease in blood pressure. These results thus provide interesting insights into potential benefits of AT1 receptor blockade in sodium-retaining states such as congestive heart failure.

The efficacy of melatonin for sleep problems in children with autism, fragile X syndrome, or autism and fragile X syndrome.

STUDY OBJECTIVE: To determine the efficacy of melatonin on sleep problems in children with autistic spectrum disorder (ASD) and fragile X syndrome (FXS). METHODS: A 4-week, randomized, double blind, placebo-controlled, crossover design was conducted following a 1-week baseline period. Either melatonin, 3 mg, or placebo was given to participants for 2 weeks and then alternated for another 2 weeks. Sleep variables, including sleep duration, sleep-onset time, sleep-onset latency time, and the number of night awakenings, were recorded using an Actiwatch and from sleep diaries completed by parents. All participants had been thoroughly assessed for ASD and also had DNA testing for the diagnosis of FXS. RESULTS: Data were successfully obtained from the 12 of 18 subjects who completed the study (11 males, age range 2 to 15.25 years, mean 5.47, SD 3.6). Five participants met diagnostic criteria for ASD, 3 for FXS alone, 3 for FXS and ASD, and 1 for fragile X premutation. Eight out of 12 had melatonin first. The conclusions from a nonparametric repeated-measures technique indicate that mean night sleep duration was longer on melatonin than placebo by 21 minutes (p = .02), mean sleep-onset latency was shorter by 28 minutes (p = .0001), and mean sleep-onset time was earlier by 42 minutes (p = .02). CONCLUSION: The results of this study support the efficacy and tolerability of melatonin treatment for sleep problems in children with ASD and FXS.

Evaluation of oral versus intravenous dose of vinorelbine to achieve equivalent blood exposures in patients with solid tumours.

Patient's preference is for oral chemotherapy when both oral and i.v. are available, provided that efficacy is equivalent. Reliable switch from oral to i.v. is possible if correspondence between respective doses has been established. Vinorelbine oral was developed as a line extension of VRL i.v. on the basis that similar AUCs result in similar activities. From a first crossover study on 24 patients receiving VRL 25 mg/m2 i.v. and 80 mg/m2 oral data extrapolation concluded on AUCs bioequivalence between Vinorelbine 30 mg/m2 i.v. and 80 mg/m2 oral. A new trial was performed to support this calculation. In a crossover design study on patients (PS 0-1) with advanced solid tumours (44% breast carcinoma), VRL was administered (30 mg/m2 i.v., 80 mg/m2 oral) with a standard meal and 5-HT3 antagonists, at 2 weeks interval. Pharmacokinetics was performed over 168 h and VRL was measured by LC-MS/MS. Statistics included bioequivalence tests. Forty-eight patients were evaluable for PK: median age 58 years (25-71), PS0/PS1: 20/28, M/F: 11/37. Mean AUCs were 1,230 +/- 290 and 1,216 +/- 521 ng/ml for i.v. and oral, respectively. The confidence interval of the AUC ratio (0.83-1.03) was within the required regulatory range (0.8-1.25) and proved the bioequivalence between the two doses. The absolute bioavailability was 37.8 +/- 16.0%, and close to the value from the first study (40%). Patient tolerability was globally comparable between both forms with no significant difference on either haematological or non-haematological toxicities (grade 3-4). This new study, conducted on a larger population, confirmed the reliable dose correspondence previously established between vinorelbine 80 mg/m2 oral and 30 mg/m2 i.v.