A model of cellular dosimetry for macroscopic tumors in radiopharmaceutical therapy.

PURPOSE: In the radiopharmaceutical therapy approach to the fight against cancer, in particular when it comes to translating laboratory results to the clinical setting, modeling has served as an invaluable tool for guidance and for understanding the processes operating at the cellular level and how these relate to macroscopic observables. Tumor control probability (TCP) is the dosimetric end point quantity of choice which relates to experimental and clinical data: it requires knowledge of individual cellular absorbed doses since it depends on the assessment of the treatment's ability to kill each and every cell. Macroscopic tumors, seen in both clinical and experimental studies, contain too many cells to be modeled individually in Monte Carlo simulation; yet, in particular for low ratios of decays to cells, a cell-based model that does not smooth away statistical considerations associated with low activity is a necessity. The authors present here an adaptation of the simple sphere-based model from which cellular level dosimetry for macroscopic tumors and their end point quantities, such as TCP, may be extrapolated more reliably. METHODS: Ten homogenous spheres representing tumors of different sizes were constructed in GEANT4. The radionuclide 131I was randomly allowed to decay for each model size and for seven different ratios of number of decays to number of cells, N(r): 1000, 500, 200, 100, 50, 20, and 10 decays per cell. The deposited energy was collected in radial bins and divided by the bin mass to obtain the average bin absorbed dose. To simulate a cellular model, the number of cells present in each bin was calculated and an absorbed dose attributed to each cell equal to the bin average absorbed dose with a randomly determined adjustment based on a Gaussian probability distribution with a width equal to the statistical uncertainty consistent with the ratio of decays to cells, i.e., equal to Nr-1/2. From dose volume histograms the surviving fraction of cells, equivalent uniform dose (EUD), and TCP for the different scenarios were calculated. Comparably sized spherical models containing individual spherical cells (15 microm diameter) in hexagonal lattices were constructed, and Monte Carlo simulations were executed for all the same previous scenarios. The dosimetric quantities were calculated and compared to the adjusted simple sphere model results. The model was then applied to the Bortezomib-induced enzyme-targeted radiotherapy (BETR) strategy of targeting Epstein-Barr virus (EBV)-expressing cancers. RESULTS: The TCP values were comparable to within 2% between the adjusted simple sphere and full cellular models. Additionally, models were generated for a nonuniform distribution of activity, and results were compared between the adjusted spherical and cellular models with similar comparability. The TCP values from the experimental macroscopic tumor results were consistent with the experimental observations for BETR-treated 1 g EBV-expressing lymphoma tumors in mice. CONCLUSIONS: The adjusted spherical model presented here provides more accurate TCP values than simple spheres, on par with full cellular Monte Carlo simulations while maintaining the simplicity of the simple sphere model. This model provides a basis for complementing and understanding laboratory and clinical results pertaining to radiopharmaceutical therapy.

Examination of Heterogeneous Crossing Sequences Between Toner and Rollerball Pen Strokes by Digital Microscopy and 3-D Laser Profilometry

The determination of line crossing sequences between rollerball pens and laser printers presents difficulties that may not be overcome using traditional techniques. This research aimed to study the potential of digital microscopy and 3-D laser profilometry to determine line crossing sequences between a toner and an aqueous ink line. Different paper types, rollerball pens, and writing pressure were tested. Correct opinions of the sequence were given for all case scenarios, using both techniques. When the toner was printed before the ink, a light reflection was observed in all crossing specimens, while this was never observed in the other sequence types. The 3-D laser profilometry, more time-consuming, presented the main advantage of providing quantitative results. The findings confirm the potential of the 3-D laser profilometry and demonstrate the efficiency of digital microscopy as a new technique for determining the sequence of line crossings involving rollerball pen ink and toner. With the mass marketing of laser printers and the popularity of rollerball pens, the determination of line crossing sequences between such instruments is encountered by forensic document examiners. This type of crossing presents difficulties with optical microscopic line crossing techniques involving ballpoint pens or gel pens and toner (1-4). Indeed, the rollerball's aqueous ink penetrates through the toner and is absorbed by the fibers of the paper, leaving the examiner with the impression that the toner is above the ink even when it is not (5). Novotny and Westwood (3) investigated the possibility of determining aqueous ink and toner crossing sequences by microscopic observation of the intersection before and after toner removal. A major disadvantage of their study resides in destruction of the sample by scraping off the toner line to see what was underneath. The aim of this research was to investigate the ways to overcome these difficulties through digital microscopy and three-dimensional (3-D) laser profilometry. The former was used as a technique for the determination of sequences between gel pen and toner printing strokes, but provided less conclusive results than that of an optical stereomicroscope (4). 3-D laser profilometry, which allows one to observe and measure the topography of a surface, has been the subject of a number of recent studies in this area. Berx and De Kinder (6) and Schirripa Spagnolo (7,8) have tested the application of laser profilometry to determine the sequence of intersections of several lines. The results obtained in these studies overcome disadvantages of other methods applied in this area, such as scanning electron microscope or the atomic force microscope. The main advantages of 3-D laser profilometry include the ease of implementation of the technique and its nondestructive nature, which does not require sample preparation (8-10). Moreover, the technique is reproducible and presents a high degree of freedom in the vertical axes (up to 1000 μm). However, when the paper surface presents a given roughness, if the pen impressions alter the paper with a depth similar to the roughness of medium, the results are not always conclusive (8). It becomes difficult in this case to distinguish which characteristics can be imputed to the pen impressions or the quality of the paper surface. This important limitation is assessed by testing different types of paper of variable quality (of different grammage and finishing) and the writing pressure. The authors will therefore assess the limits of 3-D laser profilometry technique and determine whether the method can overcome such constraints. Second, the authors will investigate the use of digital microscopy because it presents a number of advantages: it is efficient, user-friendly, and provides an objective evaluation and interpretation.

Inter and intra-guild interactions in egg parasitoid species of the soybean stink bug complex

The objective of this research was to evaluate the parasitism behavior of Telenomus podisi Ashmead, Trissolcus basalis (Wollaston) e Trissolcus urichi Crawford (Hymenoptera: Scelionidae) on eggs of Nezara viridula L., Euschistus heros F., Piezodorus guildinii Westwood and Acrosternum aseadum Rolston (Heteroptera: Pentatomidae), in no choice and multiple choice experiments. For all parasitoid species, the results demonstrated the existence of a main host species that maximizes the reproductive success. The competitive interactions among the parasitoid species were investigated in experiments of sequential and simultaneous release of different combinations of parasitoid pairs on the hosts N. viridula, E. heros and A. aseadum. Exploitative competition was observed for egg batches at the genus level (Telenomus vs. Trissolcus) and interference competition at the species level (T. basalis vs. T. urichi). Trissolcus urichi was the most aggressive species, interfering with the parasitism of T. basalis. Generally, T. basalis showed an opportunistic behavior trying to parasitise eggs after T. urichi had abandoned the egg batch. The selection of parasitoid species for use in augmentative biological control programs should take into account the diversity of pentatomids present in soybean in addition to the interactions among the different species of parasitoids.

Los constructos personales en la práctica sistémica

La teoría de los constructos personales (TCP) de Kelly (1955) y el enfoque sistémicoson, al menos a primera vista, dos tradiciones diferentes en el abordaje terapéutico.Originalmente, la TCP enfatizaba los procesos de construcción de un solo individuo (porejemplo, Bannister y Fransella, 1986), y sólo se amplió su objetivo gradualmente para incluir parejas (por ejemplo, G. Neimeyer, 1985; Ryle, 1975). Por lo tanto, su enfoque terapéutico era principalmente intrapsíquico o diádico. Por el contrario, la conceptualización de unproblema desde la perspectiva sistémica incluía siempre el contexto familiar. En dichocontexto, la conducta individual se entendía principalmente como una función dentro delsistema familiar más amplio. Como consecuencia, el tratamiento sistémico se centraba en grupos familiares y, por lo tanto, eliminaba el énfasis en la terapia individual...

Población de mosca blanca en tomate cultivado a campo con pantallas de sombreamiento

El objetivo de este trabajo fue analizar la población de mosca blanca Trialeurodes vaporariorum, Westwood (Hemiptera: Aleyrodidae) en tomate de verano en cultivos con sombreado, en Santa Fe, Argentina. Se transplantó tomate en hileras cubriendo un sector con malla negra de polipropileno, realizándose cada tres días, en 30 plantas un recuento de adultos en una hoja superior y de ninfas en diez folíolos al azar. El diseño experimental fue de bloques al azar analizándose la correlación entre la temperatura y la evolución de adultos y ninfas. El sombreado disminuyó la temperatura, pero incrementó diez veces la densidad de adultos y cinco veces la de ninfas respecto al cultivo al aire libre.

Networking of differentially expressed genes in human cancer cells resistant to methotrexate

BACKGROUND: The need for an integrated view of data obtained from high-throughput technologies gave rise to network analyses. These are especially useful to rationalize how external perturbations propagate through the expression of genes. To address this issue in the case of drug resistance, we constructed biological association networks of genes differentially expressed in cell lines resistant to methotrexate (MTX). METHODS: Seven cell lines representative of different types of cancer, including colon cancer (HT29 and Caco2), breast cancer (MCF-7 and MDA-MB-468), pancreatic cancer (MIA PaCa-2), erythroblastic leukemia (K562) and osteosarcoma (Saos-2), were used. The differential expression pattern between sensitive and MTX-resistant cells was determined by whole human genome microarrays and analyzed with the GeneSpring GX software package. Genes deregulated in common between the different cancer cell lines served to generate biological association networks using the Pathway Architect software. RESULTS: Dikkopf homolog-1 (DKK1) is a highly interconnected node in the network generated with genes in common between the two colon cancer cell lines, and functional validations of this target using small interfering RNAs (siRNAs) showed a chemosensitization toward MTX. Members of the UDP-glucuronosyltransferase 1A (UGT1A) family formed a network of genes differentially expressed in the two breast cancer cell lines. siRNA treatment against UGT1A also showed an increase in MTX sensitivity. Eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) was overexpressed among the pancreatic cancer, leukemia and osteosarcoma cell lines, and siRNA treatment against EEF1A1 produced a chemosensitization toward MTX. CONCLUSIONS: Biological association networks identified DKK1, UGT1As and EEF1A1 as important gene nodes in MTX-resistance. Treatments using siRNA technology against these three genes showed chemosensitization toward MTX.

Localitzador gràfic d'adreces IP

Internet s'ha convertit en una font extraordinària de recursos per una audiència en constant creixement arreu el món. A l'igual que en altres activitats de la nostra societat, el coneixement de la localització geogràfica d'aquests recursos i de la gent que hi accedeix és útil tant pels usuaris com pels proveïdors d'informació. La geolocalització IP, però, pot donar informació errònia o amb un nivell de precisió que no vagi més enllà de la referència a un país.Aquest treball recull els diferents actors que formen part de la geolocalització IP i s'ha analitzat el paper que juguen en aquest procés així com la seva influència en el nivell de fiabilitat i exactitud final. Amb aquests sòlids fonaments s'ha desenvolupat una aplicació per representar gràficament en un mapa la geolocalització IP d'un dispositiu i la dels nodes que formen el camí realitzat fins arribar-hi, així com tota la informació addicional que de cada IP s'ha pogut obtenir.El resultat ha estat una memòria tècnica de tot el treball de recerca juntament amb una aplicació que s'executa en l'entorn de Microsoft Windows i plataforma .NET, caracteritzada per la seva facilitat d'ús gràcies a un disseny simple molt intuïtiu i efectiu, la rapidesa d'execució per què aprofita la programació de fils, i un positiu impacte visual ja que fa servir l'API de Google Maps per a la representació visual de la traça.

Surface modification of biomaterials for conjugation with human fetal osteoblasts.

Surface functionalization of hydroxyapatite (HA) and beta-tricalcium phosphate (TCP) bioceramics with chemical ligands containing a pyrrogallol moiety was developed to improve the adhesion of bone cell precursors to the biomaterials. Fast and biocompatible copper-free click reaction with azido-modified human fetal osteoblasts resulted in improved cell binding to both HA and TCP bioceramics, opening the way for using this methodology in the preparation of cell-engineered bone implants.

Reactions and enzymes in the metabolism of drugs and other xenobiotics.

In this article, we offer an overview of the compared quantitative importance of biotransformation reactions in the metabolism of drugs and other xenobiotics, based on a meta-analysis of current research interests. Also, we assess the relative significance the enzyme (super)families or categories catalysing these reactions. We put the facts unveiled by the analysis into a drug discovery context and draw some implications. The results confirm the primary role of cytochrome P450-catalysed oxidations and UDP-glucuronosyl-catalysed glucuronidations, but they also document the marked significance of several other reactions. Thus, there is a need for several drug discovery scientists to better grasp the variety of drug metabolism reactions and enzymes and their consequences.

Caracterização molecular e variabilidade genética entre porta-enxertos de pessegueiro com base em marcadores codominantes

O objetivo deste trabalho foi estabelecer um padrão para a caracterização molecular e a diferenciação de porta-enxertos de pessegueiro, bem como estimar parâmetros de variabilidade genética com base em marcadores codominantes. Catorze genótipos foram avaliados com uso de iniciadores para locos microssatélites das séries BPPCT e UDP, e para locos STS e SCAR. O perfil eletroforético foi registrado quanto à presença ou à ausência de bandas, as quais foram usadas para calcular a similaridade genética entre cultivares, por meio do coeficiente "simple matching", e para a análise de agrupamento de cultivares, pelo método das médias aritméticas não ponderadas (UPGMA). Foram calculados: número de alelos por loco, frequências alélicas, heterozigosidade esperada e observada, endogamia e conteúdo de informação polimórfica (PIC). Os 18 locos avaliados produziram 82 polimorfismos e permitiram elaborar um dendrograma que discriminou os genótipos em três grupos principais. A heterozigosidade esperada e observada nos 18 locos SSR foi de 0, 66 e 0, 22, respectivamente. Valores máximos para endogamia (1, 0) foram identificados nos locos UDP 98407, UDP 98412, BPPCT 034, BPPCT 016, SCAR-SCAL 19 e STS OPAP4. O PIC variou de 0, 81, para SCAR-SCAL 19, a 0, 46, para UDP 98407. O polimorfismo dos 18 marcadores possibilita obter acurada relação genética entre os genótipos de pessegueiro avaliados e identificar os mais contrastantes para uso em programas de melhoramento.

Networking of differentially expressed genes in human cancer cells resistant to methotrexate

BACKGROUND: The need for an integrated view of data obtained from high-throughput technologies gave rise to network analyses. These are especially useful to rationalize how external perturbations propagate through the expression of genes. To address this issue in the case of drug resistance, we constructed biological association networks of genes differentially expressed in cell lines resistant to methotrexate (MTX). METHODS: Seven cell lines representative of different types of cancer, including colon cancer (HT29 and Caco2), breast cancer (MCF-7 and MDA-MB-468), pancreatic cancer (MIA PaCa-2), erythroblastic leukemia (K562) and osteosarcoma (Saos-2), were used. The differential expression pattern between sensitive and MTX-resistant cells was determined by whole human genome microarrays and analyzed with the GeneSpring GX software package. Genes deregulated in common between the different cancer cell lines served to generate biological association networks using the Pathway Architect software. RESULTS: Dikkopf homolog-1 (DKK1) is a highly interconnected node in the network generated with genes in common between the two colon cancer cell lines, and functional validations of this target using small interfering RNAs (siRNAs) showed a chemosensitization toward MTX. Members of the UDP-glucuronosyltransferase 1A (UGT1A) family formed a network of genes differentially expressed in the two breast cancer cell lines. siRNA treatment against UGT1A also showed an increase in MTX sensitivity. Eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) was overexpressed among the pancreatic cancer, leukemia and osteosarcoma cell lines, and siRNA treatment against EEF1A1 produced a chemosensitization toward MTX. CONCLUSIONS: Biological association networks identified DKK1, UGT1As and EEF1A1 as important gene nodes in MTX-resistance. Treatments using siRNA technology against these three genes showed chemosensitization toward MTX.

Virtuaalikoneiden hallinta ohjelmointirajapintaa käyttäen

Työssä tutustutaan VMwaren Vix- ja VmCOM-rajapintoihin sekä luodaan ohjelmia, joilla käyttäjä voi hallita VMware Server -ohjelmaa rajapintojen avulla. Vix-rajapinnan avulla luodaan C++-kielellä komentoliittymä-ohjelma, joka on suorassa yhteydessä VMware Server -ohjelmaan. Työssä luodaan palvelin joka käyttää yhteydenhallintaan käyttäjän ja palvelimen välillä TCP-teknologiaa. Palvelin keskustelee VMware Serverin kanssa käyttäen VmCOM-rajapintaa. Windows käyttöjärjestelmälle luodaan Client-ohjelma. Ohjelmasta luodaan suoraan VMware Serveriin yhteydessä oleva versio sekä palvelinpohjainen versio. ASP.NET:lla luodaan dynaamiset web-sivut, joka käyttää myös yhteydenhallintaa palvelinta. Dynaamisten web-sivujen avulla voidaan myös muokata SQL Serverillä olevia käyttäjien tietotauluja. Windows-ohjelmat, dynaamiset web-sivut sekä TCP-palvelin on kirjoitettu C#-ohjelmointikielellä.

Llave electrónica basada en patrones de movimiento

Sistema embebido capaz de almacenar y posteriormente reconocer patrones de movimiento realizados con él y avisar de la detección de un patrón reconocido a otro sistema mediante una conexión TCP/IP vía Wi-Fi.

SNMP:n hallintatietokantojen sisältämä palvelunlaatutieto IP- ja ATM-verkoissa

Tässä diplomityössä selvitetään SNMP:n (Simple Network Management Protocol) hallintatietokantojen sisältämiä palvelunlaatutietoja. Tarkastelun kohteena ovat IP:n (Internet Protocol) ja ATM:n (Asynchronous Transfer Mode) hallintatietokannat. Työn teoriaosassa tarkastellaan verkonhallinnan eri osa-alueita, TCP/IP-verkkojen (Transmission Control Protocol) hallintaan tarkoitettua SNMP-protokollaa ja sen eri versioita. Lisäksi käsitellään palvelunlaadun kannalta IP ja ATM-verkkojen erilaisia toteutuksia. Työn kokeellissa osassa arvioidaan eri hallintatietokantojen sisältöä palvelunlaadun kannalta. Työssä todetaan palvelunlaatutietojen puutteellisuus hallintatietokannoissa ja sekä IP:lle että ATM:lle toteutetaan soveltuvat hallintatietokannat.

Sulautetun järjestelmän Web-käyttö

Diplomityössä on tutkittu sulautetun järjestelmän liittämistä Ethernet-verkkoon sekä TCP/IP-protokollapinoon kuuluvien tavallisimpien protokollien toimintaa. Työn tuloksien perusteella on suunniteltu harjoitustyö, jota voidaan käyttää sähkötekniikan osaston opetuksessa. Työssä hankittiin Atmelin sulautettu Web-serverikortti (EWS) ja STK500-kortti serverin ohjelmointiin. Serverin mukana tuli Internet-yhteyden mahdollistava TCP/IP-pinon lähdekoodi. Työssä selvitettiin TCP/IP:hen kuuluvien protokollien toimintaa teoriassa ja käytännön toteutusta EWS:n avulla. Lähdekoodiin lisättiin ominaisuudet, joiden avulla laite hakee kellonaikatiedot aikapalvelimelta time-protokollaa käyttäen ja lähettää sähköpostia määriteltyyn osoitteeseen sähköpostipalvelimen kautta. Laitetta käytettiin sekä palvelimena että asiakkaana. Työssä perehdyttiin sulautettujen järjestelmien yleisiin ominaisuuksiin ja erilaisiin verkonhallinnan apuohjelmiin. Työssä tutkittiin palvelin- ja asiakaskoneen välillä Ethernetissä kulkevaa verkkoliikennettä. Työssä minimoitiin protokollatiedostojen viemä tila prosessorin muistista ja tutkittiin Internet-yhteyden kuluttamien kellojaksojen määrää. Työssä selvitettiin tietoturva-kysymysten merkitystä ja toteutusta sulautetuissa järjestelmissä.