Inhibition of the Kit Ligand/c-Kit Axis Attenuates Metastasis in a Mouse Model Mimicking Local Breast Cancer Relapse after Radiotherapy.

PURPOSE: Local breast cancer relapse after breast-saving surgery and radiotherapy is associated with increased risk of distant metastasis formation. The mechanisms involved remain largely elusive. We used the well-characterized 4T1 syngeneic, orthotopic breast cancer model to identify novel mechanisms of postradiation metastasis. EXPERIMENTAL DESIGN: 4T1 cells were injected in 20 Gy preirradiated mammary tissue to mimic postradiation relapses, or in nonirradiated mammary tissue, as control, of immunocompetent BALB/c mice. Molecular, biochemical, cellular, histologic analyses, adoptive cell transfer, genetic, and pharmacologic interventions were carried out. RESULTS: Tumors growing in preirradiated mammary tissue had reduced angiogenesis and were more hypoxic, invasive, and metastatic to lung and lymph nodes compared with control tumors. Increased metastasis involved the mobilization of CD11b(+)c-Kit(+)Ly6G(high)Ly6C(low)(Gr1(+)) myeloid cells through the HIF1-dependent expression of Kit ligand (KitL) by hypoxic tumor cells. KitL-mobilized myeloid cells homed to primary tumors and premetastatic lungs, to give rise to CD11b(+)c-Kit(-) cells. Pharmacologic inhibition of HIF1, silencing of KitL expression in tumor cells, and inhibition of c-Kit with an anti-c-Kit-blocking antibody or with a tyrosine kinase inhibitor prevented the mobilization of CD11b(+)c-Kit(+) cells and attenuated metastasis. C-Kit inhibition was also effective in reducing mobilization of CD11b(+)c-Kit(+) cells and inhibiting lung metastasis after irradiation of established tumors. CONCLUSIONS: Our work defines KitL/c-Kit as a previously unidentified axis critically involved in promoting metastasis of 4T1 tumors growing in preirradiated mammary tissue. Pharmacologic inhibition of this axis represents a potential therapeutic strategy to prevent metastasis in breast cancer patients with local relapses after radiotherapy. Clin Cancer Res; 18(16); 4365-74. ©2012 AACR.

An Investigation of Signing Needs at Uncontrolled Local Road Intersections, HR-230, 1982

Iowa Counties have been experiencing significant tort claim liability due to the signing of local roads. One such problem is relative to the real or alleged need for signing at uncontrolled intersections of local roads. It has been assumed that the standard CROSS ROAD sign, which calls for a yellow diamond with a black cross, was sufficient to provide the necessary warning that a driver may be approaching an intersection which requires special precautionary driving attention. However, it is possible that this sign on a through highway might conflict with the legal status of the local county road. In light of this situation, it seemed worthwhile to know the extent to which uncontrolled local road intersections were perceived as a potential liability problem; the degree to which the standard CROSS ROAD sign communicated to the driver the message a county engineer wanted at these local road intersections; and whether there were any better signing alternatives available to communicate this hazard to the driver in this situation.

Efeito da freqüência de sangria e estimulação no desempenho produtivo e econômico de clones de seringueira

Este trabalho teve como objetivo avaliar o desempenho produtivo e os aspectos econômicos de dez clones de seringueira [Hevea brasiliensis (Willd. ex Adr. de Juss.) Muell. Arg.] em diferentes freqüências de sangria e com estimulação à base de ethefon. O experimento foi instalado na Fazenda Indiana, no município de Indiana, SP, sob o delineamento de blocos ao acaso com parcelas subdivididas. Os tratamentos principais foram os clones GT 1, RRIM 701, RRIM 600, PB 235, PR 261, PB 252, Fx 4098, Fx 2261, Fx 3864 e IAN 873, submetidos a três sistemas de sangria: 1/2S d/2 6d/7 (testemunha), 1/2S d/4 6d/7.10m/y. ET 5,0% Ba 10y e 1/2S d/6 6d/7.10m/y. ET 5,0% Ba 10/y. As variáveis estudadas foram: perímetro do caule, produção, secamento do painel e os aspectos econômicos. Os resultados mostraram superioridade no sistema 1/2S d/2 6d/7 na maioria dos clones, exceto o GT 1 e o PB 235, que no sistema 1/2S d/4 ET 5,0% apresentaram ganhos líquidos de 12,0% e 54,0%, respectivamente, acima do obtido no sistema testemunha. Somente os clones Fx 3864 e PB 235 apresentaram ganhos líquidos de 18,0% e 28,0% no sistema 1/2S d/6 ET 5% superiores em relação ao obtido no sistema testemunha. A maior porcentagem de secamento do painel foi observada no clone PB 235 no sistema 1/2S d/4 ET 5,0%.

Planning for disaster : local government's role in civil preparedness,1975

This handbook deals with the duties and responsibilities of a mayor of a city, a member of a county board of supervisor or a sheriff of a county from the standpoint of their relationship with a county/municipal civil defense and emergency planing administration.

The Local Rural Road System: Alternative Investment Strategies, HR-242, 1989

A benefit-cost analysis was used to examine the effects of alternative investment strategies on the local rural road system. The study first estimated the change in costs to the traveling public of various investment strategies, then compared the change for each investment strategy to the cost of implementing that strategy on the county rural road system. The basic purpose of this study was to develop guidelines for local supervisors and engineers in evaluating investment or disinvestment proposals, and to provide information to state legislatures in developing local rural road and bridge policies. Three case study areas of 100 sq mi each were selected in Iowa. A questionnaire was used to collect data from farm and non-farm residents in the study areas. Data were obtained on the number of 1982 trips by origin, destination, and type of vehicle.

Comportamento produtivo de caupi em regimes irrigado e de sequeiro em Petrolina e Juazeiro

O caupi (Vigna unguiculata (L.) Walp.) é a cultura de grãos mais importante da região Semi-Árida brasileira. O objetivo deste trabalho foi avaliar a adaptabilidade e a estabilidade produtiva de 18 genótipos de caupi em regimes irrigado e de sequeiro, em quatro anos (1995 a 1998), nos Municípios de Petrolina, PE, e Juazeiro, BA. Os genótipos compuseram dois experimentos repetidos cinco vezes em delineamento de blocos casualizados, com quatro repetições. A produção de grãos foi corrigida por covariância no estande ideal de plantas e submetida a análises estatísticas. A presença de variações na fertilidade do solo, no manejo e no quadro pluviométrico, alterou o comportamento produtivo dos genótipos (P<0,01). O genótipo Balinha, selecionado e mantido por pequenos produtores, produziu 1.779 kg/ha em áreas irrigadas, comportamento, este, superior ou similar ao de cultivares das instituições de pesquisa. Em regime de sequeiro, os resultados indicam genótipos superiores, como a cultivar EPACE 10, com 1.343 kg/ha e a linhagem TE 901781F, com 1.176 kg/ha. A cultivar EPACE 11 apresentou bom comportamento produtivo, tanto em regime de sequeiro como em regime irrigado, com 1.497 kg/ha. Esses resultados indicam a necessidade do desenvolvimento de genótipos de caupi específicos para diferentes ambientes, com ênfase especial para áreas irrigadas.

Resposta de genótipos de arroz irrigado ao arranjo de plantas

O aumento do rendimento de grãos do arroz irrigado pode ser buscado através da manipulação do arranjo de plantas. O objetivo desta pesquisa foi determinar a resposta de genótipos de arroz irrigado, com distintos tipos de planta e potenciais de rendimento, ao espaçamento entre linhas e à densidade de semeadura. Conduziram-se três experimentos no campo, no sistema de cultivo convencional, em Cachoeirinha, RS, nos anos agrícolas de 1994/95, 1997/98 e 1998/99. No primeiro ano, os tratamentos constituíram-se de três espaçamentos entre linhas (12,5, 20 e 30 cm), de três densidades de semeadura (75, 150 e 225 kg/ha) e de duas cultivares (BRIRGA 410 e IRGA 416). Nos outros dois experimentos, os tratamentos constaram de quatro espaçamentos entre linhas (12,5, 20, 30 e 40 cm), três densidades de semeadura (30, 90 e 150 kg/ha), e de quatro genótipos de arroz irrigado (linhagem 959, híbrido XL5 e as cultivares BRIRGA 410 e IRGA 416). Nos três anos, a redução do espaçamento entre linhas aumentou o rendimento de grãos, independentemente do genótipo de arroz irrigado. Sob condições de cultivo com controle de plantas daninhas e de adequado manejo da irrigação, pode-se reduzir a densidade de semeadura.

Local Public-Services Provision under Public-Private Partnerships : Contractual Design and Contracting Parties Incentives

When deciding to resort to a PPP contract for the provision of a local public service, local governments have to consider the demand risk allocation between the contracting parties. In this article, I investigate the effects of demand risk allocation on the accountability of procuring authorities regarding consumers changing demand, as well as on the cost-reducing effort incentives of the private public-service provider. I show that contracts in which the private provider bears demand risk motivate more the public authority from responding to customer needs. This is due to the fact that consumers are empowered when the private provider bears demand risk, that is, they have the possibility to oust the private provider in case of non-satisfaction with the service provision, which provides procuring authorities with more credibility in side-trading and then more incentives to be responsive. As a consequence, I show that there is a lower matching with consumers' preferences over time when demand risk is on the public authority rather than on the private provider, and this is corroborated in the light of two famous case studies. However, contracts in which the private provider does not bear demand risk motivate more the private provider from investing in cost-reducing efforts. I highlight then a tradeoff in the allocation of demand risk between productive and allocative efficiency. The striking policy implication of this article for local governments would be that the current trend towards a greater resort to contracts where private providers bear little or no demand risk may not be optimal. Local governments should impose demand risk on private providers within PPP contracts when they expect that consumers' preferences over the service provision will change over time.

Introduction to Homeland Security and Emergency Management for Local Officials, 2012

The purpose of the Introduction to Homeland Security and Emergency Management for Local Officials is to provide you with information regarding this system. Inside, you will learn about local and state emergency management and homeland security; the phases of homeland security and emergency management; hazards that affect the state; comprehensive planning requirements; emergency declarations; available state and federal assistance; and other important topics that will help you become more versed in homeland security and emergency management in Iowa.

Aplicação dos conceitos de modelagem e de redes de Petri na análise do processo produtivo da indústria sucroalcooleira

A modelagem, como meio de análise de processos do agronegócio, bem como de cadeias produtivas, atende à demanda por métodos apropriados. O presente trabalho objetivou avaliar a aderência dos conceitos de modelagem e de rede de Petri aplicados ao complexo agroindustrial da cana-de-açúcar. Utilizou-se uma empresa real para a aquisição das informações. Os modelos das cadeias de atividades foram validados com o uso da rede de Petri, por meio de um método de análise em que são simulados todos os caminhos possíveis e os estados que o sistema modelado pode atingir. O estudo resultou em 14 conjuntos de etapas de produção, englobando todas as operações unitárias das cadeias produtivas do açúcar e do álcool, desde o plantio da cana até o armazenamento do açúcar e do álcool.

Local Ca(2+) detection and modulation of synaptic release by astrocytes.

Astrocytes communicate with synapses by means of intracellular calcium ([Ca(2+)](i)) elevations, but local calcium dynamics in astrocytic processes have never been thoroughly investigated. By taking advantage of high-resolution two-photon microscopy, we identify the characteristics of local astrocyte calcium activity in the adult mouse hippocampus. Astrocytic processes showed intense activity, triggered by physiological transmission at neighboring synapses. They encoded synchronous synaptic events generated by sparse action potentials into robust regional (∼12 μm) [Ca(2+)](i) elevations. Unexpectedly, they also sensed spontaneous synaptic events, producing highly confined (∼4 μm), fast (millisecond-scale) miniature Ca(2+) responses. This Ca(2+) activity in astrocytic processes is generated through GTP- and inositol-1,4,5-trisphosphate-dependent signaling and is relevant for basal synaptic function. Thus, buffering astrocyte [Ca(2+)](i) or blocking a receptor mediating local astrocyte Ca(2+) signals decreased synaptic transmission reliability in minimal stimulation experiments. These data provide direct evidence that astrocytes are integrated in local synaptic functioning in adult brain.