A Computer-Aided Decision Support System for Making Locational Decisions, 1990

This report is the product of a first-year research project in the University Transportation Centers Program. This project was carried out by an interdisciplinary research team at The University of Iowa's Public Policy Center. The project developed a computerized system to support decisions on locating facilities that serve rural areas while minimizing transportation costs. The system integrates transportation databases with algorithms that specify efficient locations and allocate demand efficiently to service regions; the results of these algorithms are used interactively by decision makers. The authors developed documentation for the system so that others could apply it to estimate the transportation and route requirements of alternative locations and identify locations that meet certain criteria with the least cost. The system was developed and tested on two transportation-related problems in Iowa, and this report uses these applications to illustrate how the system can be used.

The design and Evaluation of 'CAP Tools' - A computer aided parallelisation tool-kit

Abstract not available

Computer simulations of soft particles in flow

Understanding the dynamics of blood cells is a crucial element to discover biological mechanisms, to develop new efficient drugs, design sophisticated microfluidic devices, for diagnostics. In this work, we focus on the dynamics of red blood cells in microvascular flow. Microvascular blood flow resistance has a strong impact on cardiovascular function and tissue perfusion. The flow resistance in microcirculation is governed by flow behavior of blood through a complex network of vessels, where the distribution of red blood cells across vessel cross-sections may be significantly distorted at vessel bifurcations and junctions. We investigate the development of blood flow and its resistance starting from a dispersed configuration of red blood cells in simulations for different hematocrits, flow rates, vessel diameters, and aggregation interactions between red blood cells. Initially dispersed red blood cells migrate toward the vessel center leading to the formation of a cell-free layer near the wall and to a decrease of the flow resistance. The development of cell-free layer appears to be nearly universal when scaled with a characteristic shear rate of the flow, which allows an estimation of the length of a vessel required for full flow development, $l_c \approx 25D$, with vessel diameter $D$. Thus, the potential effect of red blood cell dispersion at vessel bifurcations and junctions on the flow resistance may be significant in vessels which are shorter or comparable to the length $l_c$. The presence of aggregation interactions between red blood cells lead in general to a reduction of blood flow resistance. The development of the cell-free layer thickness looks similar for both cases with and without aggregation interactions. Although, attractive interactions result in a larger cell-free layer plateau values. However, because the aggregation forces are short-ranged at high enough shear rates ($\bar{\dot{\gamma}} \gtrsim 50~\text{s}^{-1}$) aggregation of red blood cells does not bring a significant change to the blood flow properties. Also, we develop a simple theoretical model which is able to describe the converged cell-free-layer thickness with respect to flow rate assuming steady-state flow. The model is based on the balance between a lift force on red blood cells due to cell-wall hydrodynamic interactions and shear-induced effective pressure due to cell-cell interactions in flow. We expect that these results can also be used to better understand the flow behavior of other suspensions of deformable particles such as vesicles, capsules, and cells. Finally, we investigate segregation phenomena in blood as a two-component suspension under Poiseuille flow, consisting of red blood cells and target cells. The spatial distribution of particles in blood flow is very important. For example, in case of nanoparticle drug delivery, the particles need to come closer to microvessel walls, in order to adhere and bring the drug to a target position within the microvasculature. Here we consider that segregation can be described as a competition between shear-induced diffusion and the lift force that pushes every soft particle in a flow away from the wall. In order to investigate the segregation, on one hand, we have 2D DPD simulations of red blood cells and target cell of different sizes, on the other hand the Fokker-Planck equation for steady state. For the equation we measure force profile, particle distribution and diffusion constant across the channel. We compare simulation results with those from the Fokker-Planck equation and find a very good correspondence between the two approaches. Moreover, we investigate the diffusion behavior of target particles for different hematocrit values and shear rates. Our simulation results indicate that diffusion constant increases with increasing hematocrit and depends linearly on shear rate. The third part of the study describes development of a simulation model of complex vascular geometries. The development of the model is important to reproduce vascular systems of small pieces of tissues which might be gotten from MRI or microscope images. The simulation model of the complex vascular systems might be divided into three parts: modeling the geometry, developing in- and outflow boundary conditions, and simulation domain decomposition for an efficient computation. We have found that for the in- and outflow boundary conditions it is better to use the SDPD fluid than DPD one because of the density fluctuations along the channel of the latter. During the flow in a straight channel, it is difficult to control the density of the DPD fluid. However, the SDPD fluid has not that shortcoming even in more complex channels with many branches and in- and outflows because the force acting on particles is calculated also depending on the local density of the fluid.

Computer aided parallelisation of unstructured mesh codes

Abstract not available

Masson’s tumor: a soft tissue tumor simulating a tendon cyst. Case report

Introduction. Intravascular papillary endothelial hyperplasia (Masson's hemangioma or Masson’s tumor) is a benign vascular disease with an exuberant endothelial proliferation in normal blood vessels. Although relatively uncommon, its correct diagnosis is important because it can clinically be like both benign lesions and malignant neoplasms. We present a case of intravascular proliferative endothelial hyperplasia simulating a tendon cyst both clinically and on ultrasound. Case report. A 74-year old Caucasian female presented with a 4-month history of soreness and swelling in the fourth finger of the right hand. Ultrasound showed an oval mass with fluid content, referred to a tendon cyst. A wide surgical excision was subsequently performed. The final histological diagnosis was Masson’s tumor. Discussion. The pathogenesis of intravascular papillary endothelial hyperplasia is still unclear but the exuberant endothelial cell proliferation might be stimulated by an autocrine loop of endothelial basic fibroblast growth factor (bFGF) secretion. There are three types of papillary endothelial hyperplasia: primary, or intravascular; secondary, or mixed; and extravascular. The main differential diagnosis is against pyogenic granuloma, Kaposi sarcoma, hemangioma, and angiosarcoma. Conclusions. Masson's tumor can be like both benign lesions and malignant neoplasms clinically and on ultrasound. For this reason, the right diagnosis can be made only by histology, which reveals a papillary growth composed of hyperplastic endothelial cells supported by delicate fibrous stalks entirely confined within the vascular lumen.

"Soft Law" in der Europäischen Union und Österreich

Arbeit an der Bibliothek noch nicht eingelangt - Daten nicht geprüft

Effet de réduction en sodium sur la texture et la bioaccessibilité des protéines d’un fromage à pâte molle à croûte fleurie

Le sel (NaCl) joue plusieurs rôles importants dans les fromages aux niveaux technologique, microbiologique et organoleptique. Cependant, le sodium, un facteur de risque des maladies cardiovasculaires, est consommé en trop grande quantité par les Canadiens. Comme la réduction du sodium pourrait affecter la texture des fromages à pâte molle à croûte fleurie et la libération des nutriments pendant la digestion, l’impact de la réduction du sodium sur la bioaccessibilité des protéines dans le fromage Brie a été étudié. Ainsi, la composition et les caractéristiques texturales de fromages Brie ayant différentes teneurs en sodium (standard, réduite, substituée au KCl) ont été analysées. Une réduction du sodium de 23 % a été obtenue pour les fromages réduits en sodium. Le temps d’affinage affecte la protéolyse et la texture des fromages. La cinétique de dégradation de la matrice fromagère et la libération des protéines ont été déterminées par une approche de digestion in vitro. La désintégration de la matrice fromagère et la libération des protéines pendant la digestion in vitro ne sont pas différentes entre les fromages expérimentaux. Ces travaux démontrent qu’il est possible de réduire le sodium sans affecter le profil de protéolyse et la texture pendant l’affinage du fromage Brie ainsi que son comportement à la digestion.

Intelligent Systems and Soft Computing for Nuclear Science and Industry, Proc. 2nd Int. FLINS Workshop, ed. D. Ruan & al., World Scientific, 1996 [Book review]

Abstract not available

Computer-aided tool for the teaching of relational algebra in data base courses

This article describes the design and implementation of computer-aided tool called Relational Algebra Translator (RAT) in data base courses, for the teaching of relational algebra. There was a problem when introducing the relational algebra topic in the course EIF 211 Design and Implementation of Databases, which belongs to the career of Engineering in Information Systems of the National University of Costa Rica, because students attending this course were lacking profound mathematical knowledge, which led to a learning problem, being this an important subject to understand what the data bases search and request do RAT comes along to enhance the teaching-learning process.It introduces the architectural and design principles required for its implementation, such as: the language symbol table, the gramatical rules and the basic algorithms that RAT uses to translate from relational algebra to SQL language. This tool has been used for one periods and has demonstrated to be effective in the learning-teaching process.  This urged investigators to publish it in the web site: www.slinfo.una.ac.cr in order for this tool to be used in other university courses.

Determinação de curva glicolítica em carcaças de aves PSE (Pale, soft, exsudative) e normal em linha de abate industrial

Some quality defects can cause changes in attributes of the meat, among these we can detach the PSE meat (Pale, Soft and Exudative). The PSE meat is pale, flaccid and exudative and result from sudden pH decrease while the carcass is still under high temperature. The identification of PSE meat has been done by measuring pH and L* (Lightness). However, studies suggest that a more precise evaluation of the kinetics of pH and temperature decrease has to be conducted to better understand the etiology of PSE meat in poultry. The aim of this study was to obtain the glycolytic curve for normal and PSE meat of chicken, through the pH, L* and CRA (water holding capacity) analysis. This experiment was conducted with carcasses obtained from a commercial slaughterhouse (n = 35) of Cobb lineage, 50 days old, from the same batch of creation and with the same pre-slaughter fasting time (10h). Samples of breast fillets were obtained from carcasses randomly collected immediately at the output of pre-cooling chiller, and the analysis of pH, temperature and L * were conducted in the same in times 1h35, 2h35, 3h35, 5h35, 8h35, 11h35, 14h35, 17h35, 20h35, 23h35 and 25h35 post mortem. The CRA analyzes were performed at the time of 25h35 post mortem. The pH measurements indicated that only from the 04 time (8h35 post mortem) was possible to verify an indicative of stabilization, being that PSE meat pH was 5,69±0,07, and normal meat was 5,93±0,09. The final pH (25h35 post mortem) was 5,98±0,06 and L* 57,30± 2,39 for normal meat, while for PSE meat the result was 5,72±0,06 and L* 59,44±1,51. To CRA, the average of the samples (67,19±3.13 and 64,45± 2.66) showed a difference between the normal chicken fillets and PSE respectively. The data found in this study are consistent with those reported by own research group in another slaughterhouse and contradicts similar works, but made at room temperature, indicating that for chickens under commercial conditions the resolution of rigor mortis occurs after 8h35 post mortem.

Soft tissue sarcoma: biology and therapeutic correlates

Soft tissue sarcomas (STS) comprise a heterogenenous group of greater than 50 malignancies of putative mesenchymal cell origin and as such they may arise in diverse tissue types in various anatomical locations throughout the whole body. Collectively they account for approximately 1% of all human malignancies yet have a spectrum of aggressive behaviours amongst their subtypes. They thus pose a particular challenge to manage and remain an under investigated group of cancers with no generally applicable new therapies in the past 40 years and an overall 5-year survival rate that remains stagnant at around 50%. From September 2000 to July 2006 I undertook a full time post-doctoral level research fellowship at the MD Anderson Cancer Center, Houston, Texas, USA in the department of Surgical Oncology to investigate the biology of soft tissue sarcoma and test novel anti- sarcoma adenovirus-based therapy in the preclinical nude rat model of isolated limb perfusion against human sarcoma xenografts. This work, in collaboration with colleagues as indicated herein, led to a number of publications in the scientific literature furthering our understanding of the malignant phenotype of sarcoma and reported preclinical studies with wild-type p53, in a replication deficient adenovirus vector, and oncolytic adenoviruses administered by isolated limb perfusion. Additional collaborative and pioneering preclinical studies reported the molecular imaging of sarcoma response to systemically delivered therapeutic phage RGD-4c AAVP. Doxorubicin chemotherapy is the single most active broadly applicable anti-sarcoma chemotherapeutic yet only has an approximate 30% overall response rate with additional breakthrough tumour progression and recurrence after initial chemo-responsiveness further problematic features in STS management. Doxorubicin is a substrate for the multi- drug resistance (mdr) gene product p-glycoprotein drug efflux pump and exerts its main mode of action by induction of DNA double-strand breaks during the S-phase of the cell cycle. Two papers in my thesis characterise different aspects of chemoresistance in sarcoma. The first shows that wild-type p53 suppresses Protein Kinase Calpha (PKCα) phosphorylation (and activation) of p-glycoprotein by transcriptional repression of PKCα through a Sp-1 transcription factor binding site in its -244/-234 promoter region. The second paper demonstrates that Rad51 (a central mediator of homologous recombination repair of double strand breaks) has elevated levels in sarcoma and particularly in the S- G2 phase of the cell cycle. Suppression of Rad51 with small interfering RNA in sarcoma cell culture led to doxorubicin chemosensitisation. Reintroduction of wild-type p53 into STS cell lines resulted in decreased Rad51 protein and mRNA expression via transcriptional repression of the Rad51 promoter through increased AP-2 binding. In light of poor response rates to chemotherapy, escape from local control portends a poor prognosis for patients with sarcoma. Two papers in my thesis characterise aspects of sarcoma angiogenesis, invasion and metastasis. Human sarcoma samples were found to have high levels of matrix metalloproteinase-9 (MMP-9) with expression levels that correlated with p53 mutational status. MMP-9 is known to degrade extracellular collagen, contribute to the control of the angiogenic switch necessary in primary tumour progression and facilitate invasion and metastasis. Reconstitution of wild-type p53 function led to decreased levels of MMP-9 protein and mRNA as well as zymography-assessed MMP-9 proteolytic activity and decreased tumour cell invasiveness. Reintroduction of wild-type p53 into human sarcoma xenografts in-vivo decreased tumour growth and MMP-9 protein expression. Wild-type p53 was found to suppress mmp-9 transcription via decreased binding of NF-κB to its -607/-595 mmp-9 promoter element. Studies on the role of the VEGF165 in sarcoma found that sarcoma cells stably transfected with VEGF165 formed more aggressive xenografted tumours with increased vascularity, growth rate, metastasis, and resistance to chemotherapy. Use of the anti-VEGFR2 antibody DC101 enhanced doxorubicin sensitivity at sub-conventional dosing, inhibited tumour growth, decreased development of metastases, and reduced tumour micro-vessel density while increasing the vessel maturation index. These effects were explained primarily through effects on endothelial cells (e.c.s), rather than the tumour cells per se, where DC101 induced e.c. sensitivity to doxorubicin and suppressed e.c. production of MMPs. The p53 tumour suppressor pathway is the most frequently mutated pathway in sarcoma. Recapitulation of wild-type p53 function in sarcoma exerts a number of anti-cancer outcomes such as growth arrest, resensitisation to chemotherapy, suppression of invasion, and attenuation of angiogenesis. Using a modified nude rat-human sarcoma xenograft model for isolated limb perfusion (ILP) delivery of wild-type p53 in a replication deficient adenovirus vector I showed that functionally competent wild-type p53 could be delivered to and detected in human leiomyosarcoma xenografts confirming preclinical feasibility - although not efficacious due to low transgene expression. Viral fibre modification to express the RGD tripeptide motif led to greater viral uptake by sarcoma cells in vitro (transductional targeting) and changing the transgene promoter to a response element active in cells with active telomerase expression restricted the transgene expression to the tumour intracellular environment (transcriptional targeting). Delivery of the fibre-modified, selectively replication proficient oncolytic adenovirus Ad.hTC.GFP/ E1a.RGD by ILP demonstrated a more robust, and tumour-restricted, transgene expression with evidence of anti-sarcoma effect confirmed microscopically. Collaborative studies using the fibre modified phage RGD-4C AAVP confirmed that systemic delivery specifically, efficiently, and repeatedly targets human sarcoma xenografts, binds to αv integrins in tumours, and demonstrates a durable, though heterogeneous, transgene expression of 1-4 weeks. Incorporation of the Herpes Simplex Virus thymidine kinase (HSVtk) transgene into RGD-4C AAVP permitted CT-PET spatial and temporal molecular imaging in vivo of transgene expression and allowed quantification of tumour metabolic activity both before and after interval administration of a systemic cytotoxic with predictable and measurable response to treatment before becoming apparent clinically. These papers further the medical and scientific community’s understanding of the biology of soft tissue sarcoma and report preclinical studies with novel and promising anti- sarcoma therapeutics.