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.

Fast Geodesic Active Fields for Image Registration Based on Splitting and Augmented Lagrangian Approaches.

In this paper, we present an efficient numerical scheme for the recently introduced geodesic active fields (GAF) framework for geometric image registration. This framework considers the registration task as a weighted minimal surface problem. Hence, the data-term and the regularization-term are combined through multiplication in a single, parametrization invariant and geometric cost functional. The multiplicative coupling provides an intrinsic, spatially varying and data-dependent tuning of the regularization strength, and the parametrization invariance allows working with images of nonflat geometry, generally defined on any smoothly parametrizable manifold. The resulting energy-minimizing flow, however, has poor numerical properties. Here, we provide an efficient numerical scheme that uses a splitting approach; data and regularity terms are optimized over two distinct deformation fields that are constrained to be equal via an augmented Lagrangian approach. Our approach is more flexible than standard Gaussian regularization, since one can interpolate freely between isotropic Gaussian and anisotropic TV-like smoothing. In this paper, we compare the geodesic active fields method with the popular Demons method and three more recent state-of-the-art algorithms: NL-optical flow, MRF image registration, and landmark-enhanced large displacement optical flow. Thus, we can show the advantages of the proposed FastGAF method. It compares favorably against Demons, both in terms of registration speed and quality. Over the range of example applications, it also consistently produces results not far from more dedicated state-of-the-art methods, illustrating the flexibility of the proposed framework.

Thin Bonded Concrete Overlay with Fast Track Concrete, HR-531, Condition and Performance Report, 1987

This report is a supplement to one issued in late summer 1986 which covered construction on U.S. 71, in Buena Vista County Iowa. The work involved rehabilitation of an older 20 feet wide pavement by placing a four inch thick bonded concrete overlay monolithically with two feet of widening on each side. The work was performed on one lane at a time while construction traffic and limited public traffic used the adjacent traffic lane. When work on the first lane was complete traffic was moved onto it and rehabilitation was completed on the second lane. This report covers the condition of the rehabilitated roadway in May 1987 after the first winter. The condition is described by visual observations, core conditions, and various test results including core compressive strength, direct shear tests on cores for bond strength, profilometer results and delamtect test results.

Fast Track Portland Cement Concrete Pavement, HR-538, 1997

In 1987, 1.5 km (0.935 mi.) of Spruce Hill Drive in Bettendorf, Iowa was reconstructed. It is an arteriel street with commercial usage on both termini with single family residential dwellings along most of the project. A portland cement concrete (PCC) pavement design was selected, but a 14 day curing period would have been an undue hardship on the residents and commercial businesses. An Iowa DOT Class F fast track concrete was used so the roadway could be used in 7 to 10 days. The Class F concrete with fly ash was relatively sticky and exhibited early stiffening problems and substantial difficulty in obtaining the target entrained air content of 6.5%. These problems were never completely resolved on the project. Annual visual field reviews were conducted through 1996. In November 1991, severe premature distress was identified on the westbound two lanes of the full width replacement. The most deteriorated section in a sag vertical, 152 m (500 ft.) of the westbound roadway, was replaced in 1996. Premature distress has been identified on a dozen other conventional PCC Iowa pavements constructed between 1983 and 1989, so the deterioration may not be related to the fact that it was fast track pavement.

Special Cements for Fast Track Concrete, MLR-87-4, 1988

Two specialty cements are currently being marketed as a way to achieve portland cement concrete pavement opening strengths at less than 12 hours after placement. The cements are Pyrament from Pyrament/Lone Star Industries of Houston, Texas and Ideal Regulated-Set (RS) Portland Cement from Ideal Cement Company of Saratoga, Arkansas. The objective of the study was to evaluate the strength gain and durability of concrete produced with Pyrament and Ideal RS cement as Fast Track concrete. Mixes with 610 lb/cu yd (362 kg/cu m) cement were made and tested. Both Pyrament and Ideal RS are capable of producing pavement opening times less than 12 hours. Recent changes to Ideal RS cement have produced concrete flexural strengths of 550 psi (3792 kPa) at 4 hours in Iowa tests. Freeze/thaw durability of the concrete was not adversely affected by using either cement.

Evaluation of Type I Cement Fast Track Concrete, MLR-87-6, 1988

There are projects where opening the pavement to traffic in less than the 5 to 7 days is needed, but an 8 to 12 hour opening time is not necessary. The study examined fast track concrete with Type I cement and admixtures. The variables studied were: (1) cure temperature, (2) cement brand, (3) accelerators, and (4) water reducers. A standard water reducer and curing blankets appear to be effective at producing a 24 hour to 36 hour opening strength. An accelerator and/or high range water reducer may produce opening strength in 12 to 24 hours. Calcium chloride was most effective at achieving high-early strength.

Quantitative X-Ray Diffraction Measurements by Fast Scanning, HR-111

Two goals were pursued in this research: first, to evaluate statistically some effects of sample preparation and instrument geometry on reproducibility of X-ray diffraction intensity data; and second, to develop a procedure for finding minimum peak and background counting times for a desired level of accuracy. The ratio of calcite to dolomite in limestones was determined in trials. Ultra-fine wet grinding of the limestone in porcelain impact type ball mill gave most consistent X-ray results, but caused considerable line broadening, and peaks were best measured on an area count basis. Sample spinning reduced variance about one third, and a coarse beam-medium detector slit arrangement was found to be best. An equation is developed relating coefficient of variation of a count ratio to peak and background counts. By use of the equation or graphs the minimum coefficient of variation is predicted from one fast scan, and the number and optimum arrangement of additional counting periods to reduce variation to a desired limit may be obtained. The calculated coefficient is the maximum which may be attributed to the counting statistic but does not include experimental deviations.

Thin Bonded Concrete Overlay with Fast Track Concrete, Final Report, HR-531, 1990

Pavements have been overlaid with thin bonded portland cement concrete (PCC) for several years. These projects have had traffic detoured for a period of 5-10 days. These detours are unacceptable to the traveling public and result in severe criticism. The use of thin bonded fast track overlay was promoted to allow a thin bonded PCC overlay with minimal disruption of local traffic. This project demonstrated the concept of using one lane of the roadway to maintain traffic while the overlay was placed on the other and then with the rapid strength gain of the fast track concrete, the construction and local traffic is maintained on the newly placed, thin bonded overlay. The goals of this project were: 1. Traffic usage immediately after placement and finishing. 2. Reduce traffic disruption on a single lane to less than 5 hours. 3. Reduce traffic disruption on a given section of two-lane roadway to less than 2 days. 4. The procedure must be economically viable and competitive with existing alternatives. 5. Design life for new construction equivalent to or in excess of conventional pavements. 6. A 20 year minimum design life for rehabilitated pavements.

Fast Track and Fast Track II Cedar Rapids, Iowa, HR-544, 1993

Two lanes of a major four-lane arterial street in Cedar Rapids, Iowa, needed reconstruction. Because of the traffic volume and the detour problem, closure of the intersections, even for 1 day was not feasible. Use of Fast Track concrete paving on the mainline portion of the project permitted achievement of the opening strength of 400 psi in less than 12 hr. Fast Track II, used for the intersections, achieved the opening strength of 350 psi in 6 to 7 hr. Flexural and compression specimens of two sections each in the Fast Track and Fast Track II sections were subjected to pulse velocity tests. Maturity curves were developed by monitoring the temperatures. Correlations were performed between the pulse velocity and flexural strength and between the maturity and flexural strength. The project established the feasibility of using Fast Track II to construct portland cement concrete pavement at night and opening the roadway to traffic the next day.

Anomalous crystallization of hydrogenated amorphous silicon during fast heating ramps

Thermal crystallization experiments carried out using calorimetry on several a-Si:H materials with different microstructures are reported. The samples were crystallized during heating ramps at constant heating rates up to 100 K/min. Under these conditions, crystallization takes place above 700 C and progressively deviates from the standard kinetics. In particular, two crystallization processes were detected in conventional a-Si:H, which reveal an enhancement of the crystallization rate. At100 K/min, such enhancement is consistent with a diminution of the crystallization time by a factor of 7. In contrast, no systematic variation of the resulting grain size was observed. Similar behavior was also detected in polymorphous silicon and silicon nanoparticles, thus showing that it is characteristic of a variety of hydrogenated amorphous silicon materials

Fast analysis of doping agents in urine by ultra-high-pressure liquid chromatography-quadrupole time-of-flight mass spectrometry I. Screening analysis.

The general strategy to perform anti-doping analyses of urine samples starts with the screening for a wide range of compounds. This step should be fast, generic and able to detect any sample that may contain a prohibited substance while avoiding false negatives and reducing false positive results. The experiments presented in this work were based on ultra-high-pressure liquid chromatography coupled to hybrid quadrupole time-of-flight mass spectrometry. Thanks to the high sensitivity of the method, urine samples could be diluted 2-fold prior to injection. One hundred and three forbidden substances from various classes (such as stimulants, diuretics, narcotics, anti-estrogens) were analysed on a C(18) reversed-phase column in two gradients of 9min (including two 3min equilibration periods) for positive and negative electrospray ionisation and detected in the MS full scan mode. The automatic identification of analytes was based on retention time and mass accuracy, with an automated tool for peak picking. The method was validated according to the International Standard for Laboratories described in the World Anti-Doping Code and was selective enough to comply with the World Anti-Doping Agency recommendations. In addition, the matrix effect on MS response was measured on all investigated analytes spiked in urine samples. The limits of detection ranged from 1 to 500ng/mL, allowing the identification of all tested compounds in urine. When a sample was reported positive during the screening, a fast additional pre-confirmatory step was performed to reduce the number of confirmatory analyses.

Fast Approximation of Nonlinearities for improving inversion algorithms of PNL mixtures and Wiener systems

This paper proposes a very fast method for blindly approximating a nonlinear mapping which transforms a sum of random variables. The estimation is surprisingly good even when the basic assumption is not satisfied.We use the method for providing a good initialization for inverting post-nonlinear mixtures and Wiener systems. Experiments show that the algorithm speed is strongly improved and the asymptotic performance is preserved with a very low extra computational cost.

Nuevas técnicas de estadística espacial para la detección de clusters residenciales de población inmigrante

La estadística aplicada a la geografía ha experimentado un avance espectacular en las últimas dos décadas introduciéndose el espacio como eje fundamental del análisis. Este avance se ha visto acompañado por un rápido desarrollo de aplicaciones estadísticas integradas en los sistemas de información geográfica, constituyéndose de esta forma en un conjunto de herramientas imprescindibles en la planificación territorial. Por otro lado, en España, el incremento de población inmigrada en un corto intervalo de tiempo ha hecho necesario analizar su distribución espacial en las áreas urbanas. Los índices de autocorrelación espacial, tanto global como local, y su representación cartográfica constituyen una técnica adecuada para la detección de clusters y patrones espaciales y abre la posibilidad de plantear diferentes modelos econométricos. A partir del caso de la ciudad de Barcelona se aplican las técnicas descritas y se observan los diferentes comportamientos según el grupo de población estudiado.