Deoxyribonucleic acid content as an indicator of progression of squamous cell carcinogenesis in the esophagus: comparative analysis on imprint-cytospin and tissue section preparation.

BACKGROUND: The purpose of this study was to explore the potential use of image analysis on tissue sections preparation as a predictive marker of early malignant changes during squamous cell (SC) carcinogenesis in the esophagus. Results of DNA ploidy quantification on formalin-fixed, paraffin-embedded tissue using two different techniques were compared: imprint-cytospin and 6 microm thick tissue sections preparation. METHODS: This retrospective study included 26 surgical specimens of squamous cell carcinoma (SCC) from patients who underwent surgery alone at the Department of Surgery in CHUV Hospital in Lausanne between January 1993 and December 2000. We analyzed 53 samples of healthy tissue, 43 tumors and 7 lymph node metastases. RESULTS: Diploid DNA histogram patterns were observed in all histologically healthy tissues, either distant or proximal to the lesion. Aneuploidy was observed in 34 (79%) of 43 carcinomas, namely 24 (75%) of 32 early squamous cell carcinomas and 10 (91%) of 11 advanced carcinomas. DNA content was similar in the different tumor stages, whether patients presented with single or multiple synchronous tumors. All lymph node metastases had similar DNA content as their primary tumor. CONCLUSIONS: Early malignant changes in the esophagus are associated with alteration in DNA content, and aneuploidy tends to correlate with progression of invasive SCC. A very good correlation between imprint-cytospin and tissue section analysis was observed. Although each method used here showed advantages and disadvantages; tissue sections preparation provided useful information on aberrant cell-cycle regulation and helped select the optimal treatment for the individual patient along with consideration of other clinical parameters.

Water planning law and government.

Water planning efforts typically identify problems and needs. But simply calling attention to issues is usually not enough to spur action; the end result of many well-intentioned planning efforts is a report that ends up gathering dust on a shelf. Vague recommendations like “Water conservation measures should be implemented” usually accomplish little by themselves as they don’t assign responsibility to anyone. Success is more likely when an implementation strategy — who can and should do what — is developed as part of the planning process. The more detailed and specific the implementation strategy, the greater the chance that something will actually be done. The question then becomes who has the legal authority or responsibility to do what? Are new laws and programs needed or can existing ones be used to implement the recommendations? ... This document is divided into four main parts. The first, “Carrots and Sticks” looks at two basic approaches — regulatory and non-regulatory — that can be, and are, used to carry out water policy. Both have advantages and disadvantages that need to be considered. The second, “The powers of federal, state and local governments…,” looks at the constitutional powers the federal government and state and local governments have to carry out water policy. An initial look at the U. S. Constitution might suggest the federal government’s regulatory authority over water is limited but, in fact, its powers are very substantial. States have considerable authority to do a number of things but have to be mindful of any federal efforts that might conflict with those state efforts. And local governments can only do those things the state constitution or state legislature says they can do and must conform to any requirements or limitations on those powers that are contained in the enabling acts. Parts three and four examine in more detail the main programs and agencies at the federal level as well as Iowa’s state and local levels and the roles they play in national and state water policy.

Use of phycoerythrin and allophycocyanin for fluorescence resonance energy transfer analyzed by flow cytometry: advantages and limitations.

BACKGROUND: This study validates the use of phycoerythrin (PE) and allophycocyanin (APC) for fluorescence energy transfer (FRET) analyzed by flow cytometry. METHODS: FRET was detected when a pair of antibody conjugates directed against two noncompetitive epitopes on the same CD8alpha chain was used. FRET was also detected between antibody conjugate pairs specific for the two chains of the heterodimeric alpha (4)beta(1) integrin. Similarly, the association of T-cell receptor (TCR) with a soluble antigen ligand was detected by FRET when anti-TCR antibody and MHC class I/peptide complexes (<<tetramers>>) were used. RESULTS: FRET efficiency was always less than 10%, probably because of steric effects associated with the size and structure of PE and APC. Some suggestions are given to take into account this and other effects (e.g., donor and acceptor concentrations) for a better interpretation of FRET results obtained with this pair of fluorochromes. CONCLUSIONS: We conclude that FRET assays can be carried out easily with commercially available antibodies and flow cytometers to study arrays of multimolecular complexes.

Combined radioimmunotherapy and chemotherapy of human colon carcinoma grafted in nude mice, advantages and limitations.

In order to determine if 5-fluorouracil (5FU) could potentiate the effect of radioimmunotherapy (RIT), nude mice bearing subcutaneous human colon carcinoma xenografts were treated by 1 or 2 intravenous injection(s) of subtherapeutic doses of 131I labeled F(ab')2 from anti-carcinoembryonic antigen monoclonal antibodies combined with 5 daily intraperitoneal injections of 5FU. Control mice received either 131I F(ab')2 alone, 5FU alone or no treatment. RIT alone induced significant tumor regression, while 5FU alone gave only minimal tumor growth inhibition. The combined treatment group also resulted in long-term tumor regression with tumors remaining significantly smaller than in the RIT alone group. There was however, no significant difference in tumor recurrence time between the groups treated with RIT alone or with RIT + 5FU. Myelotoxicity, the major side effect of RIT, detected by the decrease of peripheral white blood cells (WBC), was shown to be almost identical between the groups receiving only RIT or only 5FU. Surprisingly, there was no cumulative bone marrow toxicity in animals which received 5FU before RIT. Furthermore, in the latter group, the WBC levels after RIT were significantly higher than in the control group receiving only RIT. Taken together, the results demonstrate the higher therapeutic efficiency of RIT as compared to 5FU in this model. They do not show, however, that the combination of the two forms of treatment can induce longer tumor remission. Interestingly, the WBC results suggest that 5FU given before RIT can have a radioprotective effect on bone marrow, possibly by selecting radioresistant bone marrow stem cells.

Grade and Cross Slope Estimation from LIDAR-based Surface Models, 2003

Many transportation agencies maintain grade as an attribute in roadway inventory databases; however, the information is often in an aggregated format. Cross slope is rarely included in large roadway inventories. Accurate methods available to collect grade and cross slope include global positioning systems, traditional surveying, and mobile mapping systems. However, most agencies do not have the resources to utilize these methods to collect grade and cross slope on a large scale. This report discusses the use of LIDAR to extract roadway grade and cross slope for large-scale inventories. Current data collection methods and their advantages and disadvantages are discussed. A pilot study to extract grade and cross slope from a LIDAR data set, including methodology, results, and conclusions, is presented. This report describes the regression methodology used to extract and evaluate the accuracy of grade and cross slope from three dimensional surfaces created from LIDAR data. The use of LIDAR data to extract grade and cross slope on tangent highway segments was evaluated and compared against grade and cross slope collected using an automatic level for 10 test segments along Iowa Highway 1. Grade and cross slope were measured from a surface model created from LIDAR data points collected for the study area. While grade could be estimated to within 1%, study results indicate that cross slope cannot practically be estimated using a LIDAR derived surface model.

Cryo-negative staining: advantages and applications for three-dimensional electron microscopy of biological macromolecules

Les échantillons biologiques ne s?arrangent pas toujours en objets ordonnés (cristaux 2D ou hélices) nécessaires pour la microscopie électronique ni en cristaux 3D parfaitement ordonnés pour la cristallographie rayons X alors que de nombreux spécimens sont tout simplement trop << gros D pour la spectroscopie NMR. C?est pour ces raisons que l?analyse de particules isolées par la cryo-microscopie électronique est devenue une technique de plus en plus importante pour déterminer la structure de macromolécules. Néanmoins, le faible rapport signal-sur-bruit ainsi que la forte sensibilité des échantillons biologiques natifs face au faisceau électronique restent deux parmi les facteurs limitant la résolution. La cryo-coloration négative est une technique récemment développée permettant l?observation des échantillons biologiques avec le microscope électronique. Ils sont observés à l?état vitrifié et à basse température, en présence d?un colorant (molybdate d?ammonium). Les avantages de la cryo-coloration négative sont étudiés dans ce travail. Les résultats obtenus révèlent que les problèmes majeurs peuvent êtres évités par l?utilisation de cette nouvelle technique. Les échantillons sont représentés fidèlement avec un SNR 10 fois plus important que dans le cas des échantillons dans l?eau. De plus, la comparaison de données obtenues après de multiples expositions montre que les dégâts liés au faisceau électronique sont réduits considérablement. D?autre part, les résultats exposés mettent en évidence que la technique est idéale pour l?analyse à haute résolution de macromolécules biologiques. La solution vitrifiée de molybdate d?ammonium entourant l?échantillon n?empêche pas l?accès à la structure interne de la protéine. Finalement, plusieurs exemples d?application démontrent les avantages de cette technique nouvellement développée.<br/><br/>Many biological specimens do not arrange themselves in ordered assemblies (tubular or flat 2D crystals) suitable for electron crystallography, nor in perfectly ordered 3D crystals for X-ray diffraction; many other are simply too large to be approached by NMR spectroscopy. Therefore, single-particles analysis has become a progressively more important technique for structural determination of large isolated macromolecules by cryo-electron microscopy. Nevertheless, the low signal-to-noise ratio and the high electron-beam sensitivity of biological samples remain two main resolution-limiting factors, when the specimens are observed in their native state. Cryo-negative staining is a recently developed technique that allows the study of biological samples with the electron microscope. The samples are observed at low temperature, in the vitrified state, but in presence of a stain (ammonium molybdate). In the present work, the advantages of this novel technique are investigated: it is shown that cryo-negative staining can generally overcome most of the problems encountered with cryo-electron microscopy of vitrified native suspension of biological particles. The specimens are faithfully represented with a 10-times higher SNR than in the case of unstained samples. Beam-damage is found to be considerably reduced by comparison of multiple-exposure series of both stained and unstained samples. The present report also demonstrates that cryo-negative staining is capable of high- resolution analysis of biological macromolecules. The vitrified stain solution surrounding the sample does not forbid the access to the interna1 features (ie. the secondary structure) of a protein. This finding is of direct interest for the structural biologist trying to combine electron microscopy and X-ray data. developed electron microscopy technique. Finally, several application examples demonstrate the advantages of this newly

Selected Aspects Related to Pre-development Stages of International Software projects. Case of Finland and Russia

The question of Pilot Project creation, due to support pre-development stage of software product elaboration, nowadays might be used as an approach, which allows improving the whole scheme of information technology project running. This subject is not new, but till now no model has been presented, which gives deep description of this important stage on the early phase of project. This Master's Thesis represents the research's results and findings concerning the pre-development study from the Software Engineering point of view. The aspects of feasibility study, pilot prototype developments are analyzed in this paper. As the result, the technique of Pilot Project is formulated and scheme has been presented. The experimental part is focused on particular area Pilot Project scheme's implementation- Internationally Distributed Software projects. The specific characteristic, aspects, obstacles, advantages and disadvantages are considered on the example of cross border region of Russia and Finland. The real case of Pilot Project technique implementation is given.

Measuring organizational capabilities in the engineering and consulting industry

Tämän työn tarkoituksena oli tutkia kuinka organisaation kyvykkyyksiä voidaan mitata engineering- ja konsultointialalla käyttämällä ns. kyvykkyysauditointimenetelmää. Päämotiivit aineettoman omaisuuden mittaamiseksi tunnistettiin kirjallisuuskatsauksen pohjalta. Erilaisten menetelmien etuja ja haittoja tutkittiin, jotta kyvykkyysauditoinnin suorittamiseen liittyvät haasteet ja vaatimukset tulisivat tunnistetuiksi. Kyvykkyysauditoinnin rakentaminen vaati teollisuudenalan erityispiirteiden tunnistamista. Niiksi havaittiin tietointensiivisyys ja projektikeskeisyys. Auditoinnin implementaatioprosessi koostui neljästä osasta, joista kolmen ensimmäisen suorittamiseen case-yritys antoi merkittävän panoksensa. Kriittisten menestystekijöiden selvittämisen jälkeen voitiin niihin vaikuttavat organisaation kyvykkyydet tunnistaa ja arviointi suorittaa. Arvioinnit kerättiin sisäisiltä ja ulkoisilta arvioijilta, ja ne muodostivat pohjan analyysille, joka selvitti yrityksen kehittämistarpeita. Kyvykkyysauditoinnin hyödyiksi laskettiin kasvanut tietämys yrityksen vahvuuksista ja heikkouksista sekä mahdollisuus tarkkailla säännöllisesti sen kokonaissuorituskykyä ja parantaa sitä.

Electronic Commerce - Advantages and Requirements through Supply Chain

Työ käsittelee Metso Paper Servicen varaosa- ja kulutusosatuotelinjojen mahdollisuuksia sähköiseen liiketoimintaan ulkoisten asiakkaiden kanssa sekä sähköisten transaktioiden vaikutuksia, etuja ja edellytyksiä. Työssä selvitetään Metson ja sen kymmenen kotimaisen asiakastehtaan myynti- ja ostoprosessin toiminta. Prosessimallin avulla arvioidaan valmiuksia sähköisiin transaktioihin nykyisessä myynti- ja ostotoiminnassa. Tarkastelu painottuu toimintoihin tarjontaketjun eri vaiheissa. Teknisiä näkökohtia käsitellään kokonaiskuvan luomiseksi. Lisäksi työssä arvioidaan muutoksia, joita sähköinen liiketoiminta aiheuttaisi. Haastatteluin tehdyssä tutkimuksessa kartoitetaan näkemyksiä sähköiseen liiketoimintaan erilaisilla organisaation tasoilla. Kokonaisnäkemys syntyy erilaisista näkökulmista sähköiseen kauppaan. Sähköiseen liiketoimintaan suhtaudutaan myönteisesti. Kokemuksia on kuitenkin vielä vähän. Vaikka hankkeita sähköisen liiketoiminnan lisäämiseksi on vireillä, yhtä tärkeää on parantaa valmiuksia tehostamalla paitsi informaatiovirtaa, myös materiaalivirtaa.

Novel Genome-Editing Tools to Model and Correct Primary Immunodeficiencies.

Severe combined immunodeficiency (SCID) and other severe non-SCID primary immunodeficiencies (non-SCID PID) can be treated by allogeneic hematopoietic stem cell (HSC) transplantation, but when histocompatibility leukocyte antigen-matched donors are lacking, this can be a high-risk procedure. Correcting the patient's own HSCs with gene therapy offers an attractive alternative. Gene therapies currently being used in clinical settings insert a functional copy of the entire gene by means of a viral vector. With this treatment, severe complications may result due to integration within oncogenes. A promising alternative is the use of endonucleases such as ZFNs, TALENs, and CRISPR/Cas9 to introduce a double-stranded break in the DNA and thus induce homology-directed repair. With these genome-editing tools a correct copy can be inserted in a precisely targeted "safe harbor." They can also be used to correct pathogenic mutations in situ and to develop cellular or animal models needed to study the pathogenic effects of specific genetic defects found in immunodeficient patients. This review discusses the advantages and disadvantages of these endonucleases in gene correction and modeling with an emphasis on CRISPR/Cas9, which offers the most promise due to its efficacy and versatility.

Co-opetition: Coexistence of cooperation and competition in public sector – A case study in one city’s public companies

Business actions do not take place in isolation. Complementary competencies and capabilities are the most important resources in the exponential knowledge growth. These resources are partially accessed via business partners. A company needs partners and the capability to cooperate, but also the awareness of the competitive tension, when operating in the market with multiple actors. The co-opetition research studies the occurrence and the forms of simultaneous cooperation and competition between companies or their units. Public sector’s governmental and municipal organs have been transformed into companies over the past years. Despite of their non-profit nature, public sector and public companies are adopting business doctrines from private sector towards efficient business operations. This case study aims to show, how co-opetition concept can be observed within public sector companies and in their operations with others, how public companies cooperate but also compete with others and why this happens. This thesis also explicates advantages and disadvantages of the co-opetition phenomenon.

Contract manufacturing networks structure and supply chain management

The usual objectives that companies have for subcontracting are studied in this thesis. The case company’s objectives for contract manufacturing now and in the future are identified. The main objective of the thesis is to create a focused model for the structure and supply chain management in the contract manufacturing network. This model is made for case company’s certain profit center. The different possibilities and their advantages and disadvantages for the structure and supply chain management are examined trough a theoretical review of literature. The possibilities found are then examined from the case company’s point of view. The case company point of view is established based on the opinions of the case company’s representatives. The outcome of the thesis is that the star shaped structure with supply chain management centralized to case company would be the best choice for the case company to manage the contract manufacture network.

Mechanistic population Models in Biology: Model Derivation and Application

In general, models of ecological systems can be broadly categorized as ’top-down’ or ’bottom-up’ models, based on the hierarchical level that the model processes are formulated on. The structure of a top-down, also known as phenomenological, population model can be interpreted in terms of population characteristics, but it typically lacks an interpretation on a more basic level. In contrast, bottom-up, also known as mechanistic, population models are derived from assumptions and processes on a more basic level, which allows interpretation of the model parameters in terms of individual behavior. Both approaches, phenomenological and mechanistic modelling, can have their advantages and disadvantages in different situations. However, mechanistically derived models might be better at capturing the properties of the system at hand, and thus give more accurate predictions. In particular, when models are used for evolutionary studies, mechanistic models are more appropriate, since natural selection takes place on the individual level, and in mechanistic models the direct connection between model parameters and individual properties has already been established. The purpose of this thesis is twofold. Firstly, a systematical way to derive mechanistic discrete-time population models is presented. The derivation is based on combining explicitly modelled, continuous processes on the individual level within a reproductive period with a discrete-time maturation process between reproductive periods. Secondly, as an example of how evolutionary studies can be carried out in mechanistic models, the evolution of the timing of reproduction is investigated. Thus, these two lines of research, derivation of mechanistic population models and evolutionary studies, are complementary to each other.

Energy Supply of Detached Houses in Russia and Finland

The problem of choosing the heating system is always relevant when building new houses. Type of energy source (solid fuel, liquid fuel, gas, electricity, alternative sources) is the main issue in choosing the heating system. The work gives a comprehensive overview of heating methods, determines their advantages and disadvantages taking into account economical and ecological situations in Finland and Russia. Quantitative contribution of single Finnish and Russian detached houses in the overall level of carbon dioxide emissions is estimated when using each method. Comparison of Russian and Finnish energy markets and their impact on electricity pricing is made in the work. The influence of air pollution on environmental offsets according to Russian and Finnish legislative and normative acts is determined.

EDTA- and DTPA-functionalized silica gel and chitosan adsorbents for the removal of heavy metals from aqueous solutions

Adsorbents functionalized with chelating agents are effective in removal of heavy metals from aqueous solutions. Important properties of such adsorbents are high binding affinity as well as regenerability. In this study, aminopolycarboxylic acid, EDTA and DTPA, were immobilized on the surface of silica gel, chitosan, and their hybrid materials to achieve chelating adsorbents for heavy metals such as Co(II), Ni(II), Cd(II), and Pb(II). New knowledge about the adsorption properties of EDTA- and DTPA-functionalizedadsorbents was obtained. Experimental work showed the effectiveness, regenerability, and stability of the studied adsorbents. Both advantages and disadvantages of the adsorbents were evaluated. For example, the EDTA-functionalized chitosan-silica hybrid materials combined the benefits of the silica gel and chitosan while at the same time diminishing their observed drawbacks. Modeling of adsorption kinetics and isotherms is an important step in design process. Therefore, several kinetic and isotherm models were introduced and applied in this work. Important aspects such as effect of error function, data range, initial guess values, and linearization were discussed and investigated. The selection of the most suitable model was conducted by comparing the experimental and simulated data as well as evaluating the correspondence between the theory behind the model and properties of the adsorbent. In addition, modeling of two-component data was conducted using various extended isotherms. Modeling results for both one- and twocomponent systems supported each other. Finally, application testing of EDTA- and DTPA-functionalized adsorbents was conducted. The most important result was the applicability of DTPA-functionalized silica gel and chitosan in the capturing of Co(II) from its aqueous EDTA-chelate. Moreover, these adsorbents were efficient in various solution matrices. In addition, separation of Ni(II) from Co(II) and Ni(II) and Pb(II) from Co(II) and Cd(II) was observed in two- and multimetal systems. Lastly, prior to their analysis, EDTA- and DTPA-functionalized silica gels were successfully used to preconcentrate metal ions from both pure and salty waters