Evolution in heterogeneous populations: from migration models to fixation probabilities.

Although dispersal is recognized as a key issue in several fields of population biology (such as behavioral ecology, population genetics, metapopulation dynamics or evolutionary modeling), these disciplines focus on different aspects of the concept and often make different implicit assumptions regarding migration models. Using simulations, we investigate how such assumptions translate into effective gene flow and fixation probability of selected alleles. Assumptions regarding migration type (e.g. source-sink, resident pre-emption, or balanced dispersal) and patterns (e.g. stepping-stone versus island dispersal) have large impacts when demes differ in sizes or selective pressures. The effects of fragmentation, as well as the spatial localization of newly arising mutations, also strongly depend on migration type and patterns. Migration rate also matters: depending on the migration type, fixation probabilities at an intermediate migration rate may lie outside the range defined by the low- and high-migration limits when demes differ in sizes. Given the extreme sensitivity of fixation probability to characteristics of dispersal, we underline the importance of making explicit (and documenting empirically) the crucial ecological/ behavioral assumptions underlying migration models.

Total shoulder arthroplasty: downward inclination of the glenoid component to balance supraspinatus deficiency.

HYPOTHESIS: Supraspinatus deficiency associated with total shoulder arthroplasty (TSA) provokes eccentric loading and may induce loosening of the glenoid component. A downward inclination of the glenoid component has been proposed to balance supraspinatus deficiency. METHODS: This hypothesis was assessed by a numeric musculoskeletal model of the glenohumeral joint during active abduction. Three cases were compared: TSA with normal muscular function, TSA with supraspinatus deficiency, and TSA with supraspinatus deficiency and downward inclination of the glenoid. RESULTS: Supraspinatus deficiency increased humeral migration and eccentric loading. A downward inclination of the glenoid partly balanced the loss of stability, but this potential advantage was counterbalanced by an important stress increase within the glenoid cement. The additional subchondral bone reaming required to incline the glenoid component indeed reduced the bone support, increasing cement deformation and stress. CONCLUSION: Glenoid inclination should not be obtained at the expense of subchondral bone support.

Plano Detalhado de Chã de Caldeiras na Ilha do Fogo – Cabo Verde

A presente dissertação procurou identificar os principais problemas e desafios que o Processo de Planeamento Urbano Sustentável (Amado,2005) coloca ao nível local no contexto insular e, através do desenhar de soluções, promover o desenvolvimento equilibrado, coeso e sustentável do respetivo território. Através de uma análise teórica procurou-se conhecer e compreender o Quadro Legal do Ordenamento do Território em Cabo Verde. A fase inicial do Ordenamento do Território no País, com a aprovação da Lei de Bases do Ordenamento do Território e Planeamento Urbanístico na década de 90, bem como a insularidade do território, a mão-de-obra pouco qualificada e os poucos recursos financeiros são os grandes desafios que o país enfrenta a nível do Ordenamento do Território. O núcleo urbano de Chã de Caldeiras, que pertence ao município de Santa Catarina do Fogo, Freguesia de Santa Catarina do Fogo, é caraterizado por uma paisagem única, comportando zonas de reserva como o Parque Natural do Fogo e pela proximidade ao vulcão, sendo uma das localidades com maiores atrativos naturais no arquipélago de Cabo Verde. Ora, devido à inexistência de qualquer instrumento de gestão territorial até à atualidade, a área de intervenção do Plano Detalhado, apresenta uma fraca hierarquização da rede urbana e malha viária, construções inacabadas e de fraca qualidade, inexistência de praças e locais de convívio e carencias em termos de infraestruturas básicas (agua, luz e saneamento). Este trabalho pretende ser um contributo para um Desenvolvimento Sustentável para Chã de Caldeiras, (re)qualificando o espaço urbano, zelando pelos interesses da população local e garantindo desta forma a melhoria da qualidade de vida num espaço temporal alargado.

Iowa Budget Report Fiscal Year 2010.

Governor Chet Culver and Lt. Governor Patty Judge submitted their $6.2 billion budget for fiscal year 2010. The proposal recommends further budget cuts – rather than tax increases – to help meet the challenges of declining state revenues. “In recent months, we have reduced state government spending by nearly $180 million in order to maintain a balanced budget,” said Governor Culver. "My budget proposal for fiscal year 2010 will reflect a 6.5 percent cut to almost every state department and program,” the Governor continued. “In fact, 207 of the 253 line items in my budget proposal will be cut by 6.5 percent. That represents a savings of $400 million to Iowa taxpayers.”

Postprandial thermogenesis in obese children before and after weight reduction.

The thermic effect of a meal (TEM) was measured in a group of 10 prepubertal obese children before (OB) and after (OA) weight reduction, and in a group of 10 age-matched control children (C) of normal body weight. Following a hypocaloric balanced diet for 6 +/- 1 months, the obese children lost 5.2 +/- 1.3 kg i.e. 11% of their initial body weight. The thermic response to the mixed liquid meal - fed at an energy level corresponding to 30% of the 24 h premeal resting metabolic rate - was found to be significantly lower in OB than in C children (61 +/- 25 kJ.3h-1 vs 79 +/- 21 kJ.3h-1, P less than 0.05), despite their higher test meal energy. After slimming, the TEM of obese children increased towards the controls' values (73 +/- 30 kJ.3h-1). These results support the hypothesis of the existence of a moderate thermogenic defect in some obese children which represents a consequence rather than an aetiological factor of obesity.

2010- 2014 Iowa Transportation Improvement Program

The Iowa Transportation Improvement Program (Program) is published to inform Iowans of planned investments in our state’s transportation system. The Iowa Transportation Commission (Commission) and Iowa Department of Transportation (Iowa DOT) are committed to programming those investments in a fiscally responsible manner. A major component of the 2010-2014 Program is the full integration of funding allocated to the Iowa DOT from the American Recovery and Reinvestment Act of 2009 (Recovery Act). To date, the Recovery Act has provided over $400 million of additional federal funding for transportation in Iowa, including funding that is allocated to local governments and entities. Recovery Act funding will result in a record year for transportation construction in Iowa and the creation and retention of jobs. Opportunities for additionalRecovery Act transportation funding remain and will be pursued as they becomeavailable. While Recovery Act funding will make a one-time significant impact in addressing Iowa’s backlog of needs, it is important to note that there remains a large shortfall in sustained annual transportation investment to meet Iowa’s current and future critical transportation needs. In recognition of this shortfall, Governor Culver introduced and the legislature passed an I-JOBS proposal. I-JOBS will result in an additional $50 million of state funding to reduce structurally deficient and functionally obsolete bridges on the primary road system and approximately $10 million in funding for other modes of transportation including $3 million of new funding to support the expansion of passenger rail service in Iowa. I-JOBS, and the continuing gradual increase in funding due to TIME-21, will complement and extend the benefits of Recovery Act funding and set the stage for addressing the shortfall in annual funding in the next few years. Iowa’s transportation system is multi-modal; therefore, the Program encompasses investments in aviation, transit, railroads, trails, and highways. A major component of the Program is the highway section. The FY2010-2014 highway section is financially balanced and was developed to achieve several objectives. The Commission’s primary highway investment objective is stewardship (i.e. safety, maintenance and preservation) of Iowa’s existing highway system. The highway section includes an annual average of $104 million for preserving the interstate system; an annual average of $78 million for non-interstate pavement preservation; an annual average of $36 million for non-interstate bridges; and an annual average of $14 million for safety projects. Another objective is to maintain the scheduled completion of interstate and non-interstate capacity and economic development projects that were identified in the previous Program and this Program does so. The final Commission objective is to further address capacity and economic development needs and the Commission has done so by adding several such projects to the Program. Construction improvements are partially funded through the current federal transportation act, Safe, Accountable, Flexible, Efficient Transportation Equity Act: A Legacy for Users (SAFETEA-LU). The act will expire September 30, 2009. With the expiration of SAFETEA-LU, there is significant uncertainty in the forecast of federal revenues in the out-years of this Program. The Commission and Iowa DOT will monitor federal actions closely and make adjustments to the Program as necessary. The Iowa DOT and Commission appreciate the public’s involvement in the state’s transportation planning process. Comments received personally, by letter, or through participation in the Commission’s regular meetings or public input meetings held around the state each year are invaluable in providing guidance for the future of Iowa’s transportation system. It should be noted that this document is a planning guide. It does not represent a binding commitment or obligation of the Commission or Iowa DOT, and is subject to change. You are invited to visit the Iowa DOT’s Web site at iowadot.gov for additional and regular updates about the department’s programs and activities.

Iowa DOT Quick Tour, May 12, 2009

The DOT, created by the Iowa Legislature, began operating July 1,1975. The newly formed Department of Transportation had a staff of 4,568 full-time equivalents (FTEs). These employees and their responsibilities came from the Highway Commission, Reciprocity Board, Aeronautics Commission, and parts of the Commerce Commission, Department of Revenue and Finance, Department of Public Safety and the Energy Policy Council. The DOT continually looks at ways to become more efficient in serving our customers. As a result the current workforce equals approximately 3,049 full-time employees. The seven transportation commissioners set policy for the department and are appointed by the governor, with no more than four from one political party. Membership on the commission is gender-balanced. Commissioners are confirmed by the Iowa Senate and serve on a staggered basis for four-year terms. Commission meetings are usually held monthly in Ames. The meetings are open to the public and follow a printed agenda.

Censura gubernativa, Iglesia e inquisición en el siglo XVIII

Government censorship in Eighteenth Century Spain was another means of the Spanish Enlightenment policy. Until mid-century both powers of Church and State were balanced, from Charles III’s reign on the censorship of the Consejo de Castilla tried to control and restrict not only the traditional power of the Inquisition, but also the intellectual output of the country, either ideological -criticism on the Crown’s policy- or cultural-publishing religious Works. It is important to notice that many members of the elergy collaborated with the State in that task; and also that, after the French Revolution, the Inquisition regained its previous role. In the last decade of the Seventeenth century the irreconcilable clash between the advocates and the critics of the Inquisition became evident

Role of NINJA in root jasmonate signaling.

Wound responses in plants have to be coordinated between organs so that locally reduced growth in a wounded tissue is balanced by appropriate growth elsewhere in the body. We used a JASMONATE ZIM DOMAIN 10 (JAZ10) reporter to screen for mutants affected in the organ-specific activation of jasmonate (JA) signaling in Arabidopsis thaliana seedlings. Wounding one cotyledon activated the reporter in both aerial and root tissues, and this was either disrupted or restricted to certain organs in mutant alleles of core components of the JA pathway including COI1, OPR3, and JAR1. In contrast, three other mutants showed constitutive activation of the reporter in the roots and hypocotyls of unwounded seedlings. All three lines harbored mutations in Novel Interactor of JAZ (NINJA), which encodes part of a repressor complex that negatively regulates JA signaling. These ninja mutants displayed shorter roots mimicking JA-mediated growth inhibition, and this was due to reduced cell elongation. Remarkably, this phenotype and the constitutive JAZ10 expression were still observed in backgrounds lacking the ability to synthesize JA or the key transcriptional activator MYC2. Therefore, JA-like responses can be recapitulated in specific tissues without changing a plant's ability to make or perceive JA, and MYC2 either has no role or is not the only derepressed transcription factor in ninja mutants. Our results show that the role of NINJA in the root is to repress JA signaling and allow normal cell elongation. Furthermore, the regulation of the JA pathway differs between roots and aerial tissues at all levels, from JA biosynthesis to transcriptional activation.

Preretinal partial pressure of oxygen gradients before and after experimental pars plana vitrectomy.

PURPOSE: To evaluate preretinal partial pressure of oxygen (PO2) gradients before and after experimental pars plana vitrectomy. METHODS: Arteriolar, venous, and intervascular preretinal PO2 gradients were recorded in 7 minipigs during slow withdrawal of oxygen-sensitive microelectrodes (10-μm tip diameter) from the vitreoretinal interface to 2 mm into the vitreous cavity. Recordings were repeated after pars plana vitrectomy and balanced salt solution (BSS) intraocular perfusion. RESULTS: Arteriolar, venous, and intervascular preretinal PO2 at the vitreoretinal interface were 62.3 ± 13.8, 22.5 ± 3.3, and 17.0 ± 7.5 mmHg, respectively, before vitrectomy; 97.7 ± 19.9, 40.0 ± 21.9, and 56.3 ± 28.4 mmHg, respectively, immediately after vitrectomy; and 59.0 ± 27.4, 25.2 ± 3.0, and 21.5 ± 4.5 mmHg, respectively, 2½ hours after interruption of BSS perfusion. PO2 2 mm from the vitreoretinal interface was 28.4 ± 3.6 mmHg before vitrectomy; 151.8 ± 4.5 mmHg immediately after vitrectomy; and 34.8 ± 4.1 mmHg 2½ hours after interruption of BSS perfusion. PO2 gradients were still present after vitrectomy, with the same patterns as before vitrectomy. CONCLUSION: Preretinal PO2 gradients are not eliminated after pars plana vitrectomy. During BSS perfusion, vitreous cavity PO2 is very high. Interruption of BSS perfusion evokes progressive equilibration of vitreous cavity PO2 with concomitant progressive return of preretinal PO2 gradients to their previtrectomy patterns. This indicates that preretinal diffusion of oxygen is not altered after vitrectomy. The beneficial effect of vitrectomy in ischemic retinal diseases or macular edema may be related to other mechanisms, such as increased oxygen convection currents or removal of growth factors and cytokines secreted in the vitreous.

Disseny pràctic d'un transmissor d'àudio complert utilitzant una modulació AM

RESUM Un transmissor d’AM (modulació per amplitud), utilitza una de les moltes tècniques de modulació existents avui en dia. És molta la importància que té la modulació de senyals i aquests en són alguns exemples: -Facilita la propagació del senyal per cable o per aire. -Ordena l’espectre, distribuint Canals a les diferents informacions. -Disminueix la dimensió de les antenes. -Optimitza l’ample de banda de cada canal. -Evita interferències entre Canals. -Protegeix la informació de les degradacions per soroll. -Defineix la qualitat de la informació transmesa. L’objectiu principal d’aquest treball, serà realitzar un transmissor d’AM utilitzant components electrònics disponibles al mercat. Això es realitzarà mitjançant diversos procediments de disseny. Es realitzarà un procediment de disseny teòric, tot utilitzant els “datasheets” dels diferents components. Es realitzarà un procediment de disseny mitjançant la simulació, gràcies al qual es podrà provar el disseny del dispositiu i realitzar-ne algunes parts impossibles a reproduir teòricament. I finalment es realitzarà el dispositiu a la pràctica. Entre les conclusions més rellevants obtingudes en aquest treball, voldríem destacar la importància de la simulació per poder dissenyar circuits de radiofreqüència. En aquest treball s’ha demostrat que gràcies a una bona simulació, el primer prototip de dispositiu creat ens ha funcionat a la perfecció. D’altre banda, també comentar la importància d’un disseny adequat d’antena per poder aprofitar al màxim el rendiment del nostre dispositiu. Per concloure, la realització d’un aparell transmissor aporta unes nocions equilibrades d’electrònica i telecomunicacions importants per al disseny de dispositius de comunicació.

Iowa Efficiency Review Report to Governor Chet Culver and Lieutenant Governor Patty Judge, December 18,2009

Public Works is pleased to present the following Iowa Efficiency Review Report to Governor Chet Culver and Lieutenant Governor Patty Judge. This report is the product of a collaboration between our consulting team and very dedicated Iowa state employees who worked with us to share ideas and cost‐saving proposals under very difficult circumstances caused by the national financial crisis that is affecting state budgets throughout the country. For example, during the course of this review, Iowa departments were also asked to develop across‐the‐board cuts to achieve immediate reductions in state spending. It is a credit to Iowa state government that departmental staff continued to work on this Efficiency Review Report despite these challenges of also having to develop across‐the‐board budget cuts to achieve a balanced budget. We hope that these ideas will set the stage for further future budget improvements from achieving efficiencies, eliminating outdated practices, increasing the use of information technology solutions and finding new sources of non‐tax funding. The Efficiency Review Team faced a second challenge. Statewide Efficiency Reviews usually take from nine to 12 months to complete. In Iowa, we worked with dedicated department staff to complete our work in less than 4 months. The Governor challenged all of us to work intensely and to give him our best thinking on efficiency proposals so that he could act as quickly as possible to position state government for success over the next several years.

Autoinduction of 2,4-diacetylphloroglucinol biosynthesis in the biocontrol agent Pseudomonas fluorescens CHA0 and repression by the bacterial metabolites salicylate and pyoluteorin.

The antimicrobial metabolite 2,4-diacetylphloroglucinol (2,4-DAPG) contributes to the capacity of Pseudomonas fluorescens strain CHA0 to control plant diseases caused by soilborne pathogens. A 2, 4-DAPG-negative Tn5 insertion mutant of strain CHA0 was isolated, and the nucleotide sequence of the 4-kb genomic DNA region adjacent to the Tn5 insertion site was determined. Four open reading frames were identified, two of which were homologous to phlA, the first gene of the 2,4-DAPG biosynthetic operon, and to the phlF gene encoding a pathway-specific transcriptional repressor. The Tn5 insertion was located in an open reading frame, tentatively named phlH, which is not related to known phl genes. In wild-type CHA0, 2, 4-DAPG production paralleled expression of a phlA'-'lacZ translational fusion, reaching a maximum in the late exponential growth phase. Thereafter, the compound appeared to be degraded to monoacetylphloroglucinol by the bacterium. 2,4-DAPG was identified as the active compound in extracts from culture supernatants of strain CHA0 specifically inducing phlA'-'lacZ expression about sixfold during exponential growth. Induction by exogenous 2,4-DAPG was most conspicuous in a phlA mutant, which was unable to produce 2, 4-DAPG. In a phlF mutant, 2,4-DAPG production was enhanced severalfold and phlA'-'lacZ was expressed at a level corresponding to that in the wild type with 2,4-DAPG added. The phlF mutant was insensitive to 2,4-DAPG addition. A transcriptional phlA-lacZ fusion was used to demonstrate that the repressor PhlF acts at the level of transcription. Expression of phlA'-'lacZ and 2,4-DAPG synthesis in strain CHA0 was strongly repressed by the bacterial extracellular metabolites salicylate and pyoluteorin as well as by fusaric acid, a toxin produced by the pythopathogenic fungus Fusarium. In the phlF mutant, these compounds did not affect phlA'-'lacZ expression and 2, 4-DAPG production. PhlF-mediated induction by 2,4-DAPG and repression by salicylate of phlA'-'lacZ expression was confirmed by using Escherichia coli as a heterologous host. In conclusion, our results show that autoinduction of 2,4-DAPG biosynthesis can be countered by certain bacterial (and fungal) metabolites. This mechanism, which depends on phlF function, may help P. fluorescens to produce homeostatically balanced amounts of extracellular metabolites.

Iowa Budget Recommendations, FY 2011, January 27, 2010

Our FY 2011 General Fund budget is balanced, fiscally conservative, and does not raise sales or income taxes. We have already proposed and signed three balanced state budgets and have demonstrated the leadership to ensure that the current year (FY 2010) budget is balanced in the face of dramatic and quick declines in state revenues last year that occurred as a result of the national recession.

Is Less Chemotherapy Detrimental in Adults with Philadelphia Chromosome (Ph)-Positive Acute Lymphoblastic Leukemia (ALL) Treated with High-Dose Imatinib? Results of the Prospective Randomized Graaph-2005 Study

Aim: To compare a less intensive regimen based on high-dose imatinib (IM) to an intensive IM/HyperCVAD regimen in adults with Ph+ ALL, in terms of early response and outcome after stem cell transplantation (SCT). Methods: Patients aged 18-60 years with previously untreated Ph+ ALL not evolving from chronic myeloid leukemia were eligible if no contra-indication to chemotherapy and SCT (ClinicalTrials.gov ID, NCT00327678). After a steroid prephase allowing Ph and/or BCR-ABL diagnosis, cycle 1 differed between randomization arms. In arm A (IM-based), IM was given at 800 mg on day 1-28, combined with vincristine (2 mg, day 1, 8, 15, 22) and dexamethasone (40 mg, day 1-2, 8-9, 15-16, and 22-23) only. In arm B (IM/HyperCVAD), IM was given at 800 mg on day 1-14, combined with adriamycin (50 mg/m2, day 4), cyclophosphamide (300 mg/m2/12h, day 1, 2, 3), vincristine (2 mg, day 4 and 11), and dexamethasone (40 mg, day 1-4 and 11-14). All patients received a cycle 2 combining high-dose methotrexate (1 g/m2, day 1) and AraC (3 g/m2/12h, day 2 and 3) with IM at 800 mg on day 1-14, whatever their response. Four intrathecal infusions were given during this induction/consolidation period. Minimal residual disease (MRD) was centrally evaluated by quantitative RQ-PCR after cycle 1 (MRD1) and cycle 2 (MRD2). Major MRD response was defined as BCR-ABL/ABL ratio <0.1%. Then, all patients were to receive allogeneic SCT using related or unrelated matched donor stem cells or autologous SCT if no donor and a major MRD2 response. IM/chemotherapy maintenance was planned after autologous SCT. In the absence of SCT, patients received alternating cycles 1 (as in arm B) and cycles 2 followed by maintenance, like in the published IM/HyperCVAD regimen. The primary objective was non-inferiority of arm A in term of major MRD2 response. Secondary objectives were CR rate, SCT rate, treatment- and transplant-related mortality, relapse-free (RFS), event-free (EFS) and overall (OS) survival. Results: Among the 270 patients randomized between May 2006 and August 2011, 265 patients were evaluable for this analysis (133 arm A, 132 arm B; median age, 47 years; median follow-up, 40 months). Main patient characteristics were well-balanced between both arms. Due to higher induction mortality in arm B (9 versus 1 deaths; P=0.01), CR rate was higher in the less intensive arm A (98% versus 89% after cycle 1 and 98% versus 91% after cycle 2; P= 0.003 and 0.006, respectively). A total of 213 and 205 patients were evaluated for bone marrow MRD1 and MRD2. The rates of patients reaching major MRD response and undetectable MRD were 45% (44% arm A, 46% arm B; P=0.79) and 10% (in both arms) at MRD1 and 66% (68% arm A, 63.5% arm B; P=0.56) and 25% (28% arm A, 22% arm B; P=0.33) at MRD2, respectively. The non-inferiority primary endpoint was thus demonstrated (P= 0.002). Overall, EFS was estimated at 42% (95% CI, 35-49) and OS at 51% (95% CI, 44-57) at 3 years, with no difference between arm A and B (46% versus 38% and 53% versus 49%; P=0.25 and 0.61, respectively). Of the 251 CR patients, 157 (80 arm A, 77 arm B) and 34 (17 in both arms) received allogeneic and autologous SCT in first CR, respectively. Allogeneic transplant-related mortality was similar in both arms (31.5% versus 22% at 3 years; P=0.51). Of the 157 allografted patients, 133 had MRD2 evaluation and 89 had MRD2 <0.1%. In these patients, MRD2 did not significantly influence post-transplant RFS and OS, either when tested with the 0.1% cutoff or as a continuous log covariate. Of the 34 autografted patients, 31 had MRD2 evaluation and, according to the protocol, 28 had MRD2 <0.1%. When restricting the comparison to patients achieving major MRD2 response and with the current follow-up, a trend for better results was observed after autologous as compared to allogeneic SCT (RFS, 63% versus 49.5% and OS, 69% versus 58% at 3 years; P=0.35 and P=0.08, respectively). Conclusions: In adults, the use of TK inhibitors (TKI) has markedly improved the results of Ph+ ALL therapy, now close to those observed in Ph-negative ALL. We demonstrated here that chemotherapy intensity may be safely reduced when associated with high-dose IM. We will further explore this TKI-based strategy using nilotinib prior to SCT in our next GRAAPH-2013 trial. The trend towards a better outcome after autologous compared to allogeneic SCT observed in MRD responders validates MRD as an important early surrogate endpoint for treatment stratification and new drug investigation in this disease.