SPH simulations and experimental investigation of water flow through a Venturi meter of rectangular cross-section.

The flow of water through a horizontal small-scale Venturi tube of rectangular cross-section is simulated using a modified version of the open-source code DualSPHysics, which is based on Smoothed Particle Hydrodynamics (SPH) methods. Water is simulated using the Murnaghan-Tait equation of state so that weak compressibility is allowed. The hydrodynamics is coupled to a Large-Eddy Simulation (LES) turbulence model. The convergence properties of SPH are improved by adopting a C[Formula: see text] Wendland function as the interpolation kernel, increased number of neighboring particles and non-reflective open boundary conditions at the outlet of the Venturi tube. The flow structure and differential pressure as well as the mainstream velocity profiles at different stations are compared with calibrated experimental data. A resolution independence test shows that good convergence to the experimental measurements is achieved using four million particles. At this resolution the simulations predict the experimental centerline velocity profile along the Venturi meter for a volumetric flow rate of ten liters per minutes (lpm) with a root-mean-square error of 4.3%. This error grows to 7.1% when the volumetric flow rate increases to 25 lpm. The predicted differential pressure matches the experimental data with errors varying from 1.4% (for 10 lpm) to 6.8% (for 25 lpm). Cross-sectional velocity profiles within the throat and divergent sections differ from the experimental measurements in less than 5.5%. In general, it is shown that the SPH model can provide an efficient and accurate method for recalibrating flow meters at moderately high Reynolds numbers instead of using costly experimental tests.

Evolution of some physical properties related to soil quality in the degraded ecosystems of "raña" formations from SW Spain.

The dynamics of some physical properties of the soil: bulk density, porosity and percentage of water stable aggregates, which usually are taken as indicators for evaluation of soil quality, have been studied on the flat surfaces of the Cañamero's "raña" formation (Cáceres, SW Spain). The study shows a high relationship between all these physical soil parameters, the degradation level of the natural vegetation, and years of the soil under tillage. As the deterioration of the natural soil increases the bulk density of the fine earth is increased, diminishing porosity, field capacity moisture content, percentage of water stable aggregates in soil and water infiltration.

Modern management of locally advanced cervical carcinoma.

Radiation was until recently the key and only modality for the routine treatment of locally advanced cervical carcinoma. However after years of studying multi-modality treatments as an alternative to radiation alone in randomized phase III trials, the standard treatment has changed to chemo-radiation based on cisplatin. Three recent meta-analyses have confirmed that cisplatin-based chemo-radiation adds an absolute 12% benefit in five-year survival over radiation therapy alone. Neoadjuvant chemotherapy followed by radiation has not been of proven benefit, but when neoadjuvant chemotherapy is followed by surgery, an absolute increase of 15% in five-year survival over radiation alone is seen. This benefit in survival is comparable to that obtained with the current chemo-radiation schedules based on cisplatin. Despite these encouraging results there remains room for improvement as the five-year survival of patients treated with chemo-radiation ranges from nearly 80% in bulky IB tumours to only 25% in stage IVA disease. Other therapeutic approaches need to be fully evaluated including the use of chemo-radiation after neoadjuvant chemotherapy; the use of new drug combinations and the multi-modality combination of neoadjuvant chemotherapy followed by radical surgery plus adjuvant chemo-radiation. Likewise, the addition of radiosensitizers to cisplatin, preoperative chemo-radiation and/or adjuvant chemotherapy may eventually improve the currents results of cisplatin-based chemo-radiation. Nevertheless, it is hard to foresee a dramatic increase in cure rate, even with the most optimal combination of cytotoxic drugs, surgery and radiation, and thus the testing of molecular targeted therapies against cervical cancer is a logical step to follow.

Reactivation of tumor suppressor genes by the cardiovascular drugs hydralazine and procainamide and their potential use in cancer therapy.

PURPOSE: The purpose of this study is to evaluate the demethylating and tumor suppressor-reactivating activity of hydralazine and procainamide. EXPERIMENTAL DESIGN: MDA-231, MCF-7, and T24 cell lines were treated for 5 days with 10 micro M hydralazine or 10 micro M procainamide. 5-aza-deoxycytidine at 0.75 micro M was used as positive control. BALB/c nu/nu mice xenografted with MDA-231 cells were treated with these drugs for 7 days by i.p. route. Methylation was assessed by PCR after digestion with methylation-sensitive enzymes for the ER gene and with methylation-specific PCR for retinoic acid receptor (RAR)beta and p16 genes. Gene expression was evaluated by reverse transcription-PCR and Western blot. The duration of the gene re-expressing effect of hydralazine was analyzed on T24 cells. Functionality of the re-expressed proteins was evaluated by the induction of the estrogen-responsive gene PS2 on MDA-231 cells and by the induction of G(1) arrest on T24 cells. The gene demethylating and re-expressing ability of hydralazine was tested in two patients with cervical and head and neck carcinomas, respectively. RESULTS: Hydralazine and procainamide induced de-methylation and re-expression of the ER, RARbeta, and p16 genes in cultured cells. Both drugs also demethylated and re-expressed the ER gene in mice. Hydralazine re-expressed the p16 gene longer as compared with 5-aza-deoxycytidine. The re-expressed genes were functional. In addition, the treatment with oral hydralazine demethylated and re-expressed the RARbeta and p16 genes in the cervical and head and cancer patients. CONCLUSIONS: These cardiovascular drugs have a promising tumor suppressor-reactivating action and could potentially be used in clinic as an anticancer treatment, most likely to increase the efficacy of current biological or chemotherapeutic treatments.

Circulating nucleosomes and response to chemotherapy: an in vitro, in vivo and clinical study on cervical cancer patients.

It is known that cell-free DNA circulates in plasma/serum of patients with cancer and that part of this DNA circulates as nucleosomes that can be quantified by ELISA. We analyzed the effect of tumor and chemotherapy upon the levels of nucleosomes in vitro, in vivo and in cervical cancer patients. The levels of nucleosomes pre- and post-treatment were correlated with response in 11 patients receiving chemotherapy. Nucleosomes were determined in nude mice treated with or without cisplatin and carrying tumors generated with HeLa cells, and in the cell lysate and supernatant of HeLa cells exposed to cisplatin in culture. In addition, nucleosomes were determined at different time points in patients and in rats receiving chemotherapy. Nucleosomes were higher in patients that controls (1,760 vs. 601, p = 0.0001). After 24 hr of treatment with oxaliplatin and gemcitabine, the levels decreased in 6 patients of whom 5 had response. Nucleosome levels differed between mice xenografted and not xenografted (765 vs. 378, p = 0.001) and between xenografted treated with or without cisplatin (650 vs. 765, p = 0.010), but not in tumor-free animals treated and untreated with cisplatin (378 vs. 379, p = 0.99). In vitro, nucleosomes reached at peak 8 hr in cell lysates to decrease thereafter, whereas in supernatant, levels continued to increase up to 24 hr. Serial determination of nucleosomes in patients showed a rise within 6-12 hr and then a reduction to below the basal at 24 hr. In rats, nucleosomes had no major changes in those receiving oxaliplatin or the triple combination of cisplatin, gemcitabine and paclitaxel as compared to untreated controls. An overdose of this triple combination produced a transient elevation of almost 1,000 AU over the basal. Our results demonstrate that most of circulating nucleosomes originate from the tumor and that chemotherapy produces an early rise most likely due to tumor apoptosis and that nucleosomes are rapidly cleared from circulation. On the contrary, chemotherapy within the therapeutic range of doses has no effect on nucleosome levels in healthy mice and rats. This data suggests that the determination of circulating nucleosomes pre- and post-treatment could be a useful test to predict response to chemotherapy in cancer patients.