Iowa Motorcycle Operator's Manual, 2002

The rules and regualtions for owning and operating a motorcycle in Iowa

Evidence for classification of c.1852_1853AA>GC in MLH1 as a neutral variant for Lynch syndrome

Background: Lynch syndrome (LS) is an autosomal dominant inherited cancer syndrome characterized by early onset cancers of the colorectum, endometrium and other tumours. A significant proportion of DNA variants in LS patients are unclassified. Reports on the pathogenicity of the c.1852_1853AA>GC (p.Lys618Ala) variant of the MLH1 gene are conflicting. In this study, we provide new evidence indicating that this variant has no significant implications for LS.Methods: The following approach was used to assess the clinical significance of the p.Lys618Ala variant: frequency in a control population, case-control comparison, co-occurrence of the p.Lys618Ala variant with a pathogenic mutation, co-segregation with the disease and microsatellite instability in tumours from carriers of the variant. We genotyped p.Lys618Ala in 1034 individuals (373 sporadic colorectal cancer [CRC] patients, 250 index subjects from families suspected of having LS [revised Bethesda guidelines] and 411 controls). Three well-characterized LS families that fulfilled the Amsterdam II Criteria and consisted of members with the p.Lys618Ala variant were included to assess co-occurrence and co-segregation. A subset of colorectal tumour DNA samples from 17 patients carrying the p.Lys618Ala variant was screened for microsatellite instability using five mononucleotide markers.Results: Twenty-seven individuals were heterozygous for the p.Lys618Ala variant; nine had sporadic CRC (2.41%), seven were suspected of having hereditary CRC (2.8%) and 11 were controls (2.68%). There were no significant associations in the case-control and case-case studies. The p.Lys618Ala variant was co-existent with pathogenic mutations in two unrelated LS families. In one family, the allele distribution of the pathogenic and unclassified variant was in trans, in the other family the pathogenic variant was detected in the MSH6 gene and only the deleterious variant co-segregated with the disease in both families. Only two positive cases of microsatellite instability (2/17, 11.8%) were detected in tumours from p.Lys618Ala carriers, indicating that this variant does not play a role in functional inactivation of MLH1 in CRC patients.Conclusions: The p.Lys618Ala variant should be considered a neutral variant for LS. These findings have implications for the clinical management of CRC probands and their relatives.

Expression of neutral endopeptidase, endothelin-1, and nuclear factor kappa B in prostate cancer: interrelations and associations with prostate-specific antigen recurrence after radical prostatectomy.

Objective. To study the impact of the neutral endopeptidase (NEP)/neuropeptides (NPs) axis and nuclear factor kappa B (NFκB) as predictors of prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP). Patients and Methods. 70 patients with early-stage PC were treated with RP and their tumor samples were evaluated for expression of NEP, endothelin-1 (ET-1) and NFκB (p65). Time to PSA recurrence was correlated with the examined parameters and combined with preoperative PSA level, Gleason score, pathological TNM (pT) stage, and surgical margin (SM) assessment. Results and Limitations. Membranous expression of NEP (P < 0.001), cytoplasmic ET-1 (P = 0.002), and cytoplasmic NFκB (P < 0.001) were correlated with time to PSA relapse. NEP was associated with ET-1 (P < 0.001) and NFκB (P < 0.001). ET-1 was also correlated with NFκB (P < 0.001). NEP expression (P = 0.017), pT stage (P = 0.013), and SMs (P = 0.036) were independent predictors of time to PSA recurrence. Conclusions. There seems to be a clinical model of NEP/NPs and NFκB pathways interconnection, with their constituents following inverse patterns of expression in accordance with their biological roles and molecular interrelations.

A total order in [0,1] defined through a 'next' operator

A `next' operator, s, is built on the set R1=(0,1]-{ 1-1/e} defining a partial order that, with the help of the axiom of choice, can be extended to a total order in R1. Besides, the orbits {sn(a)}nare all dense in R1 and are constituted by elements of the samearithmetical character: if a is an algebraic irrational of degreek all the elements in a's orbit are algebraic of degree k; if a istranscendental, all are transcendental. Moreover, the asymptoticdistribution function of the sequence formed by the elements in anyof the half-orbits is a continuous, strictly increasing, singularfunction very similar to the well-known Minkowski's ?(×) function.

Renal hemodynamic and natriuretic effects of concomitant Angiotensin-converting enzyme and neutral endopeptidase inhibition in men.

This double-blind placebo-controlled study was designed to investigate the acute and sustained hormonal, renal hemodynamic, and tubular effects of concomitant ACE and neutral endopeptidase (NEP) inhibition by omapatrilat, a vasopeptidase inhibitor, in men. Thirty-two normotensive subjects were randomized to receive a placebo, omapatrilat (40 or 80 mg), or the fosinopril/hydrochlorothiazide (FOS/HCTZ; 20 and 12.5 mg, respectively) fixed combination for 1 week. Blood pressure, renal hemodynamics, urinary electrolytes and atrial natriuretic peptide excretion, and several components of the renin-angiotensin system were measured for 6 hours on days 1 and 7 of drug administration. When compared with the placebo and the FOS/HCTZ combination, omapatrilat induced a significant decrease in plasma angiotensin II levels (P<0.001 versus placebo; P<0.05 versus FOS/HCTZ) and an increase in urinary atrial natriuretic peptide excretion (P<0.01). These hormonal effects were associated with a significant fall in blood pressure (P<0.01) and a marked renal vasodilatation, but with no significant changes in glomerular filtration rate. The FOS/HCTZ markedly increased urinary sodium excretion (P<0.001). The acute natriuretic response to FOS/HCTZ was significantly greater than that observed with omapatrilat (P<0.01). Over 1 week, however, the cumulative sodium excretion induced by both doses of omapatrilat (P<0.01 versus placebo) was at least as great as that induced by the dose of FOS/HCTZ (P=NS versus FOS/HCTZ). In conclusion, the results of the present study in normal subjects demonstrate that omapatrilat has favorable renal hemodynamic effects. Omapatrilat combines potent ACE inhibition with a sustained natriuresis, which explains its well-documented potent antihypertensive efficacy.

Iowa Motorcycle Operator's Manual, April 27, 2009

The rules and regulations for owning and operating a motorcycle in Iowa

Voluntary Explicit versus Involuntary Conceptual Memory Are Associated with Dissociable fMRI Responses in Hippocampus, Amygdala, and Parietal Cortex for Emotional and Neutral Word Pairs.

Although functional neuroimaging studies have supported the distinction between explicit and implicit forms of memory, few have matched explicit and implicit tests closely, and most of these tested perceptual rather than conceptual implicit memory. We compared event-related fMRI responses during an intentional test, in which a group of participants used a cue word to recall its associate from a prior study phase, with those in an incidental test, in which a different group of participants used the same cue to produce the first associate that came to mind. Both semantic relative to phonemic processing at study, and emotional relative to neutral word pairs, increased target completions in the intentional test, but not in the incidental test, suggesting that behavioral performance in the incidental test was not contaminated by voluntary explicit retrieval. We isolated the neural correlates of successful retrieval by contrasting fMRI responses to studied versus unstudied cues for which the equivalent "target" associate was produced. By comparing the difference in this repetition-related contrast across the intentional and incidental tests, we could identify the correlates of voluntary explicit retrieval. This contrast revealed increased bilateral hippocampal responses in the intentional test, but decreased hippocampal responses in the incidental test. A similar pattern in the bilateral amygdale was further modulated by the emotionality of the word pairs, although surprisingly only in the incidental test. Parietal regions, however, showed increased repetition-related responses in both tests. These results suggest that the neural correlates of successful voluntary explicit memory differ in directionality, even if not in location, from the neural correlates of successful involuntary implicit (or explicit) memory, even when the incidental test taps conceptual processes.

Neutral endopeptidase versus angiotensin converting enzyme inhibition in essential hypertension.

OBJECTIVE: To evaluate the antihypertensive efficacy of sinorphan, an orally active inhibitor of neutral endopeptidase EC 3.4.24.11. DESIGN: The ability of sinorphan (100 mg twice a day) to lower blood pressure was compared with that of the angiotensin converting enzyme (ACE) inhibitor captopril (25 mg twice a day) using a randomized-sequence, double-blind crossover design in 16 patients with essential hypertension. Each treatment was administered for 4 weeks and treatments were separated by a 3-week placebo period. At the end of the last phase of treatment sinorphan was combined with captopril for a further 4-week period. The changes in systolic (SBP) and diastolic blood pressure (DBP) were monitored using repeated ambulatory blood pressure monitoring. RESULTS: When given as monotherapy for 4 weeks, neither sinorphan nor captopril significantly reduced the 24-h or the 14-h daytime mean SBP or DBP. However, a significant decrease in DBP was observed during the first 6 h after the morning administration of captopril. With sinorphan only a significant decrease in night-time SBP was found. With the combined therapy of sinorphan and captopril, significant decreases both in SBP and in DBP were observed, which were sustained over 24 h. After 4 weeks of sinorphan alone or in combination with captopril, no change in plasma atrial natriuretic peptide level was found. However, urinary cyclic GMP excretion increased transiently after administration of the neutral endopeptidase inhibitor. CONCLUSIONS: Neutral endopeptidase inhibition with sinorphan has a limited effect on blood pressure in hypertensive patients when given alone. However, simultaneous neutral endopeptidase and ACE inhibition induces a synergistic effect, and might therefore represent an interesting new therapeutic approach to the treatment of essential hypertension.

The induced generalized OWA operator

[spa] Se presenta el operador OWA generalizado inducido (IGOWA). Es un nuevo operador de agregación que generaliza al operador OWA a través de utilizar las principales características de dos operadores muy conocidos como son el operador OWA generalizado y el operador OWA inducido. Entonces, este operador utiliza medias generalizadas y variables de ordenación inducidas en el proceso de reordenación. Con esta formulación, se obtiene una amplia gama de operadores de agregación que incluye a todos los casos particulares de los operadores IOWA y GOWA, y otros casos particulares. A continuación, se realiza una generalización mayor al operador IGOWA a través de utilizar medias cuasi-aritméticas. Finalmente, también se desarrolla un ejemplo numérico del nuevo modelo en un problema de toma de decisiones financieras.

The induced 2-tuple linguistic generalized OWA operator and its application in linguistic decision making

[spa] Se presenta el operador de media ponderada ordenada generalizada lingüística de 2 tuplas inducida (2-TILGOWA). Es un nuevo operador de agregación que extiende los anteriores modelos a través de utilizar medias generalizadas, variables de ordenación inducidas e información lingüística representada mediante el modelo de las 2 tuplas lingüísticas. Su principal ventaja se encuentra en la posibilidad de incluir a un gran número de operadores de agregación lingüísticos como casos particulares. Por eso, el análisis puede ser visto desde diferentes perspectivas de forma que se obtiene una visión más completa del problema considerado y seleccionar la alternativa que parece estar en mayor concordancia con nuestros intereses o creencias. A continuación se desarrolla una generalización mayor a través de utilizar medias cuasi-aritméticas, obteniéndose el operador Quasi-2-TILOWA. El trabajo finaliza analizando la aplicabilidad del nuevo modelo en un problema de toma de decisiones sobre gestión de la producción.

The induced generalized OWA operator

[spa] Se presenta el operador OWA generalizado inducido (IGOWA). Es un nuevo operador de agregación que generaliza al operador OWA a través de utilizar las principales características de dos operadores muy conocidos como son el operador OWA generalizado y el operador OWA inducido. Entonces, este operador utiliza medias generalizadas y variables de ordenación inducidas en el proceso de reordenación. Con esta formulación, se obtiene una amplia gama de operadores de agregación que incluye a todos los casos particulares de los operadores IOWA y GOWA, y otros casos particulares. A continuación, se realiza una generalización mayor al operador IGOWA a través de utilizar medias cuasi-aritméticas. Finalmente, también se desarrolla un ejemplo numérico del nuevo modelo en un problema de toma de decisiones financieras.

The induced 2-tuple linguistic generalized OWA operator and its application in linguistic decision making

[spa] Se presenta el operador de media ponderada ordenada generalizada lingüística de 2 tuplas inducida (2-TILGOWA). Es un nuevo operador de agregación que extiende los anteriores modelos a través de utilizar medias generalizadas, variables de ordenación inducidas e información lingüística representada mediante el modelo de las 2 tuplas lingüísticas. Su principal ventaja se encuentra en la posibilidad de incluir a un gran número de operadores de agregación lingüísticos como casos particulares. Por eso, el análisis puede ser visto desde diferentes perspectivas de forma que se obtiene una visión más completa del problema considerado y seleccionar la alternativa que parece estar en mayor concordancia con nuestros intereses o creencias. A continuación se desarrolla una generalización mayor a través de utilizar medias cuasi-aritméticas, obteniéndose el operador Quasi-2-TILOWA. El trabajo finaliza analizando la aplicabilidad del nuevo modelo en un problema de toma de decisiones sobre gestión de la producción.

Is the impact of public investment neutral across the regional income distribution?: evidence from Mexico

This paper investigates the contribution of public investment to the reduction of regional inqualities, with a specific application to Mexico. We use quantile regressions to examine the impact of public investment on regional disparities according to the position of each region in the conditional distribution of regional income. Results confirm the hypothesis that regional inequalities can indeed be atrributed to the regional distribution of public investment, where the observed pattern shows that public investment mainly helped to reduce regional inequalities between the richest regions