Libyan breast cancer: Health services and biology. Diagnosis delay and prognostic value of DNA pploidy, S-phase fraction, and Ki-67 and Bcl-2 immunohistochemistry

The aim of this study was to investigate the diagnosis delay and its impact on the stage of disease. The study also evaluated a nuclear DNA content, immunohistochemical expression of Ki-67 and bcl-2, and the correlation of these biological features with the clinicopathological features and patient outcome. 200 Libyan women, diagnosed during 2008–2009 were interviewed about the period from the first symptoms to the final histological diagnosis of breast cancer. Also retrospective preclinical and clinical data were collected from medical records on a form (questionnaire) in association with the interview. Tumor material of the patients was collected and nuclear DNA content analysed using DNA image cytometry. The expression of Ki-67 and bcl-2 were assessed using immunohistochemistry (IHC). The studies described in this thesis show that the median of diagnosis time for women with breast cancer was 7.5 months and 56% of patients were diagnosed within a period longer than 6 months. Inappropriate reassurance that the lump was benign was an important reason for prolongation of the diagnosis time. Diagnosis delay was also associated with initial breast symptom(s) that did not include a lump, old age, illiteracy, and history of benign fibrocystic disease. The patients who showed diagnosis delay had bigger tumour size (p<0.0001), positive lymph nodes (p<0.0001), and high incidence of late clinical stages (p<0.0001). Biologically, 82.7% of tumors were aneuploid and 17.3% were diploid. The median SPF of tumors was 11% while the median positivity of Ki-67 was 27.5%. High Ki-67 expression was found in 76% of patients, and high SPF values in 56% of patients. Positive bcl-2 expression was found in 62.4% of tumors. 72.2% of the bcl-2 positive samples were ER-positive. Patients who had tumor with DNA aneuploidy, high proliferative activity and negative bcl-2 expression were associated with a high grade of malignancy and short survival. The SPF value is useful cell proliferation marker in assessing prognosis, and the decision cut point of 11% for SPF in the Libyan material was clearly significant (p<0.0001). Bcl-2 is a powerful prognosticator and an independent predictor of breast cancer outcome in the Libyan material (p<0.0001). Libyan breast cancer was investigated in these studies from two different aspects: health services and biology. The results show that diagnosis delay is a very serious problem in Libya and is associated with complex interactions between many factors leading to advanced stages, and potentially to high mortality. Cytometric DNA variables, proliferative markers (Ki-67 and SPF), and oncoprotein bcl-2 negativity reflect the aggressive behavior of Libyan breast cancer and could be used with traditional factors to predict the outcome of individual patients, and to select appropriate therapy.

Relationship of breast fillet deboning time to shear force, pH, cooking loss and color in broilers stunned by high electrical current

Selostus: Korkealla virranvoimakkuudella tainnutettujen broilereiden rintafileen irroitushetken vaikutus lihaksen leikkausvoiman vastukseen, pH:hon, keittohävikkiin ja väriin

Effect of anionic salts in concentrate mixture on some blood and urine minerals, acid-base balance and feed intake of dry pregnant cows on grass silage based feeding with high calcium intake

Selostus: Kationi-anionitasapaino ummessaolevien lypsylehmien säilörehuruokinnassa kalsiumin saannin ollessa runsas

Rheology of high solids surface size starches

Tämän diplomityön tarkoituksena oli tutkia pintaliimatärkkelysten reologista käyttäytymistä korkeissa kuiva-ainepitoisuuksissa. Tarve työn suorittamiselle syntyi kun tutkittiin pintaliimausta filminsiirtopuristimella tavallista korkeammissa kuiva-ainepitoisuuksissa, sileän sauvan ollessa applikointilaitteena. Koska applikointi sileällä sauvalla tapahtuu hydrodynaamisten periaatteiden mukaisesti, sen käyttö edellyttää pintaliimojen reologisten ominaisuuksien tarkkaa tuntemusta ja hallintaa.Kiinnostuksen kohteena olevat ominaisuudet olivat tärkkelysten kuiva-ainepitoisuuden (8 – 30 %) vaikutus viskositeettiin eri lämpötiloissa (20, 30, 40 ja 50 ºC), leikkausnopeus alueella 1 s-1 - 700 000 s-1. Myös tärkkelysten myötörajat määritettiin tutkimuksessa. Viskositeetti eri leikkausnopeusalueilla mitattiin seuraavilla laitteilla: Bohlin VOR (matalat leikkausnopeudet ja myötöraja) ja Hercules HiShear (keskitason leikkausnopeudet) reometrit sekä Eklund kapillaariviskometri (korkeat leikkausno-peudet). Analysoidut tärkkelykset olivat kaksi anionista matalaviskoottista peruna (tärkkelys A) ja ohra (tärkkelys C) tärkkelystä, sekä yksi kationinen korkeaviskoottinen peruna tärkkelys (tärkkelys B). Tutkittujen tärkkelysten Brookfield viskositeetit (100 rpm) olivat (10 % liuos, 60 °C:ssa) tärkkelys A ja C: 25 ± 5 mPas ja tärkkelys B: 100 ± 20 mPas.Tärkkelysliuosten kuiva-ainepitoisuuden noustessa muuttui virtauskäyttäytyminen Newtoniaalisesta leikkausohenevaksi. Leikkausoheneva käyttäytyminen oli voimakkainta tärkkelys B:n kohdalla. Viskositeetti – lämpötila riippuvuus korkeissa leikkausnopeuksissa (esim. 500 000 s-1) oli vähäisempää, mitä oli oletettavissa Brookfield viskositeettiarvojen perusteella. Kaikki tarkkelykset osoittautuivat tiksotrooppisiksi, myös tiksotrooppisuus lisääntyi kuiva-ainepitoisuuden kasvaessa. Tärkkelysten myötörajat osoittautuivat odottamattoman alhaisiksi, kuitenkin varsinkin tärkkelys B:n myötörajat olivat selvästi riippuvaisia lämpötilasta ja kuiva-ainepitoisuudesta. Tutkittujen tärkkelysten virtauskäyttäytyminen oli kirjallisuudessa esitetyn kaltaista. Tärkkelysmolekyylien ketjun pituus oli tärkein tärkkelyksen reologisia ominaisuuksia määrittävä tekijä; mitä matalampi on tärkkelyksen molekyylimassa, sitä matalammat ovat viskositeetti ja myötöraja. Pintaliimauksessa tärkkelysmolekyylien ketjunpituudella on suuri vaikutus ajettavuuteen ja lopputuotteen ominaisuuksiin. Haasteellista pintaliimatärkkelyksen valinnassa on sellaisen yhdistelmän löytäminen, jossa sopivan reologisen käyttäytymisen omaava tärkkelys ja pintaliimatulle paperille tai kartongille asetetut vaatimukset kohtaavat.

Water circulations for effective bleaching of high-brightness mechanical pulps

The amount of water available is usually restricted, which leads to a situation where a complete understanding of the process, including water circulations and the influence of water components, is essential. The main aim of this thesis was to clarify the possibilities for the efficient use of residual peroxide by means of water circulation rearrangements. Rearranging water circulations and the reduction of water usage may cause new problems, such as metal induced peroxide decomposition that needs to be addressed. This thesis introduces theoretical methods of water circulations to combine two variables; effective utilization of residual peroxide and avoiding manganese in the alkaline peroxide bleaching stage. Results are mainly based on laboratory and mill site experiments concerning the utilization of residual peroxide. A simulation model (BALAS) was used to evaluate the manganese contents and residual peroxide doses. It was shown that with optimum recirculation of residual peroxide the brightness can be improved or chemical costs can be decreased. From the scientific perspective, it was also very important to discover that recycled peroxide was more effective pre-bleaching agent compared to fresh peroxide. This can be due to the organic acids i.e. per acetic acid in wash press filtrate that have been formed in alkaline bleaching stage. Even short retention time was adequate and the activation of residual peroxide using sodium hydroxide was not necessary. There are several possibilities for using residual peroxide in practice regarding bleaching. A typical modern mechanical pulping process line consist of defibering, screening, a disc filter, a bleach press, high consistency (HC) peroxide bleaching and a wash press. Furthermore there usually is not a particular medium consistency (MC) pre-bleaching stage that includes additional thickening equipment. The most advisable way to utilize residual peroxide in this kind of process is to recycle the wash press filtrate to the dilution of disc filter pulp (low MC pre-bleaching stage). An arrangement such as this would be beneficial in terms of the reduced convection of manganese to the alkaline bleaching stage. Manganese originates from wood material and will be removed to the water phase already in the early stages of the process. Recycling residual peroxide prior to the disc filter is not recommended because of low consistencies. Regarding water circulations, the novel point of view is that, it would be beneficial to divide water circulations into two sections and the critical location for the division is the disc filter. Both of these two sections have their own priority. Section one before the disc filter: manganese removal. Section two after the disc filter: brightening of pulp. This division can be carried out if the disc filter pulp is diluted only by wash press filtrate before the MC storage tower. The situation is even better if there is an additional press after the disc filter, which will improve the consistency of the pulp. This has a significant effect on the peroxide concentration in the MC pre-bleaching stage. In terms of manganese content, it is essential to avoid the use of disc filter filtrate in the bleach press and wash press showers. An additional cut-off press would also be beneficial for manganese removal. As a combination of higher initial brightness and lower manganese content, the typical brightness increase varies between approximately 0.5 and 1% ISO units after the alkaline peroxide bleaching stage. This improvement does not seem to be remarkable, but as it is generally known, the final brightness unit is the most expensive and difficult to achieve. The estimation of cost savings is not unambiguous. For example in GW/TMP mill case 0.6% ISO units higher final brightness gave 10% savings in the costs of bleaching chemicals. With an hypothetical 200 000 ton annual production, this means that the mill could save in the costs of bleaching chemicals more than 400 000 euros per year. In general, it can be said that there were no differences between the behavior of different types of processes (GW, PGW, TMP and BCTMP). The enhancement of recycling gave a similar response in all cases. However, we have to remember that the utilization of residual peroxide in older mills depends a great deal on the process equipment, the amount of water available and existing pipeline connections. In summary, it can be said that processes are individual and the same solutions cannot be applied to all cases.

Behavioral Responses in Mice Selectively Bred for High and Low Levels of Open-Field Thigmotaxis

In animal psychology, the open-field (OF) test is a traditional method for studying different aspects of rodent behavior, with thigmotaxis (i.e., wallseeking behavior) being one of the best validated OF parameters employed to measure emotionality. The main purpose of the present study was to investigate the selection response in mice selectively bred for high and low levels of OF thigmotaxis (the HOFT and LOFT lines, respectively). The mice (N = 2048) were selected for 23 generations, resulting in bidirectional phenotypic divergence between the two lines; that is, the HOFT mice were more thigmotactic (i.e., more emotional) than the LOFT mice across the different generations. The origin of the line difference in thigmotaxis was further investigated by using the crossfostering paradigm, with the results suggesting that the divergence between the two lines was primarily innate in origin and not influenced by differing maternal behavior. The stability of the selection trait was examined by testing the animals at different ages as well as in varying conditions. The results indicated that the line difference in thigmotaxis was not affected by age at the time of testing, and it also persisted in the different OF testing situations as well as during pregnancy and lactation. The examination of a possible coselection of other characteristics revealed that the more thigmotactic HOFT mice lived longer than the less thigmotactic LOFT mice. In addition, the HOFT mice tended to rear and explore less than the LOFT mice, supporting the general assumption that emotionality and exploration are inversely related. The two lines did not generally differ in ambulation and defecation, that is, in the traditional OF indexes of emotionality, conforming to the suggestion that emotionality is a multidimensional construct. The effects of sex on different OF parameters were also assessed, with the results suggesting that among the HOFT and LOFT lines, the female mice were more emotional than the male mice. The examination of the temporal changes in the HOFT and LOFT lines’ OF behavior revealed some contradictory findings that also partially conflicted with general assumptions. Although this study did not show prominent differences in maternal responsiveness between the HOFT and LOFT mothers, the results suggested that the line divergence in emotionality was more pronounced in the presence of a pup after parturition than during pregnancy. The present study clearly demonstrates that OF thigmotaxis is a strong characteristic for producing two diverging lines of mice. The difference in thigmotaxis between the selectively bred HOFT and LOFT mice seemed to be a stable and robust feature of these animals, and it appeared to stem from a genetic background.

Performance and scalability of isolated DC-DC converter topologies in low voltage, high current applications

Fuel cells are a promising alternative for clean and efficient energy production. A fuel cell is probably the most demanding of all distributed generation power sources. It resembles a solar cell in many ways, but sets strict limits to current ripple, common mode voltages and load variations. The typically low output voltage from the fuel cell stack needs to be boosted to a higher voltage level for grid interfacing. Due to the high electrical efficiency of the fuel cell, there is a need for high efficiency power converters, and in the case of low voltage, high current and galvanic isolation, the implementation of such converters is not a trivial task. This thesis presents galvanically isolated DC-DC converter topologies that have favorable characteristics for fuel cell usage and reviews the topologies from the viewpoint of electrical efficiency and cost efficiency. The focus is on evaluating the design issues when considering a single converter module having large current stresses. The dominating loss mechanism in low voltage, high current applications is conduction losses. In the case of MOSFETs, the conduction losses can be efficiently reduced by paralleling, but in the case of diodes, the effectiveness of paralleling depends strongly on the semiconductor material, diode parameters and output configuration. The transformer winding losses can be a major source of losses if the windings are not optimized according to the topology and the operating conditions. Transformer prototyping can be expensive and time consuming, and thus it is preferable to utilize various calculation methods during the design process in order to evaluate the performance of the transformer. This thesis reviews calculation methods for solid wire, litz wire and copper foil winding losses, and in order to evaluate the applicability of the methods, the calculations are compared against measurements and FEM simulations. By selecting a proper calculation method for each winding type, the winding losses can be predicted quite accurately before actually constructing the transformer. The transformer leakage inductance, the amount of which can also be calculated with reasonable accuracy, has a significant impact on the semiconductor switching losses. Therefore, the leakage inductance effects should also be taken into account when considering the overall efficiency of the converter. It is demonstrated in this thesis that although there are some distinctive differences in the loss distributions between the converter topologies, the differences in the overall efficiency can remain within a range of a few percentage points. However, the optimization effort required in order to achieve the high efficiencies is quite different in each topology. In the presence of practical constraints such as manufacturing complexity or cost, the question of topology selection can become crucial.

AMB system for high-speed motors using automatic commissioning

The general trend towards increasing e ciency and energy density drives the industry to high-speed technologies. Active Magnetic Bearings (AMBs) are one of the technologies that allow contactless support of a rotating body. Theoretically, there are no limitations on the rotational speed. The absence of friction, low maintenance cost, micrometer precision, and programmable sti ness have made AMBs a viable choice for highdemanding applications. Along with the advances in power electronics, such as signi cantly improved reliability and cost, AMB systems have gained a wide adoption in the industry. The AMB system is a complex, open-loop unstable system with multiple inputs and outputs. For normal operation, such a system requires a feedback control. To meet the high demands for performance and robustness, model-based control techniques should be applied. These techniques require an accurate plant model description and uncertainty estimations. The advanced control methods require more e ort at the commissioning stage. In this work, a methodology is developed for an automatic commissioning of a subcritical, rigid gas blower machine. The commissioning process includes open-loop tuning of separate parts such as sensors and actuators. The next step is to apply a system identi cation procedure to obtain a model for the controller synthesis. Finally, a robust model-based controller is synthesized and experimentally evaluated in the full operating range of the system. The commissioning procedure is developed by applying only the system components available and a priori knowledge without any additional hardware. Thus, the work provides an intelligent system with a self-diagnostics feature and an automatic commissioning.

Identification of Some Additional Loss Components in High-Power Low-Voltage Permanent Magnet Generators

Permanent magnet generators (PMG) represent the cutting edge technology in modern wind mills. The efficiency remains high (over 90%) at partial loads. To improve the machine efficiency even further, every aspect of machine losses has to be analyzed. Additional losses are often given as a certain percentage without providing any detailed information about the actual calculation process; meanwhile, there are many design-dependent losses that have an effect on the total amount of additional losses and that have to be taken into consideration. Additional losses are most often eddy current losses in different parts of the machine. These losses are usually difficult to calculate in the design process. In this doctoral thesis, some additional losses are identified and modeled. Further, suggestions on how to minimize the losses are given. Iron losses can differ significantly between the measured no-load values and the loss values under load. In addition, with embedded magnet rotors, the quadrature-axis armature reaction adds losses to the stator iron by manipulating the harmonic content of the flux. It was, therefore, re-evaluated that in salient pole machines, to minimize the losses and the loss difference between the no-load and load operation, the flux density has to be kept below 1.5 T in the stator yoke, which is the traditional guideline for machine designers. Eddy current losses may occur in the end-winding area and in the support structure of the machine, that is, in the finger plate and the clamping ring. With construction steel, these losses account for 0.08% of the input power of the machine. These losses can be reduced almost to zero by using nonmagnetic stainless steel. In addition, the machine housing may be subjected to eddy current losses if the flux density exceeds 1.5 T in the stator yoke. Winding losses can rise rapidly when high frequencies and 10–15 mm high conductors are used. In general, minimizing the winding losses is simple. For example, it can be done by dividing the conductor into transposed subconductors. However, this comes with the expense of an increase in the DC resistance. In the doctoral thesis, a new method is presented to minimize the winding losses by applying a litz wire with noninsulated strands. The construction is the same as in a normal litz wire but the insulation between the subconductors has been left out. The idea is that the connection is kept weak to prevent harmful eddy currents from flowing. Moreover, the analytical solution for calculating the AC resistance factor of the litz-wire is supplemented by including an end-winding resistance in the analytical solution. A simple measurement device is developed to measure the AC resistance in the windings. In the case of a litz-wire with originally noninsulated strands, vacuum pressure impregnation (VPI) is used to insulate the subconductors. In one of the two cases studied, the VPI affected the AC resistance factor, but in the other case, it did not have any effect. However, more research is needed to determine the effect of the VPI on litz-wire with noninsulated strands. An empirical model is developed to calculate the AC resistance factor of a single-layer formwound winding. The model includes the end-winding length and the number of strands and turns. The end winding includes the circulating current (eddy currents that are traveling through the whole winding between parallel strands) and the main current. The end-winding length also affects the total AC resistance factor.

Study of Control Methods of a High-Frequency Cycloconverter for Domestic Induction Heating Appliances

A high-frequency cyclonverter acts as a direct ac-to-ac power converter circuit that does not require a diode bidge rectifier. Bridgeless topology makes it possible to remove forward voltage drop losses that are present in a diode bridge. In addition, the on-state losses can be reduced to 1.5 times the on-state resistance of switches in half-bridge operation of the cycloconverter. A high-frequency cycloconverter is reviewed and the charging effect of the dc-capacitors in ``back-to-back'' or synchronous mode operation operation is analyzed. In addition, a control method is introduced for regulating dc-voltage of the ac-side capacitors in synchronous operation mode. The controller regulates the dc-capacitors and prevents switches from reaching overvoltage level. This can be accomplished by variating phase-shift between the upper and the lower gate signals. By adding phase-shift between the gate signal pairs, the charge stored in the energy storage capacitors can be discharged through the resonant load and substantially, the output resonant current amplitude can be improved. The above goals are analyzed and illustrated with simulation. Theory is supported with practical measurements where the proposed control method is implemented in an FPGA device and tested with a high-frequency cycloconverter using super-junction power MOSFETs as switching devices.

Tandem-MAG-welding of high strength steels for shipbuilding applications

Tämän työn tavoitteena oli hitsata tandem MAG –laitteistolla 25 mm paksua Ruukin E500 TMCP terästä. Työssä oli tarkoituksena vähentää railotilavuutta mahdollisimman paljon sekä suorittaa testihitsaukset 0.8 kJ/mm sekä 2.5 kJ/mm lämmöntuonneilla. Teoriaosuudessa käsiteltiin Tandem MAG-hitsaukseen, sen tuottavuuteen ja laatukysymyksiin liittyviä asioita sekä siinä perehdyttiin suurlujuusteräksien käyttöön hitsauksessa sekä laivanrakennuksessa. Kokeellisessa osuudessa perehdyttiin hitsauksessa huomattuihin etuihin, ongelmiin sekä ongelmien ratkaisumahdollisuuksiin. Hitsausliitoksen mekaaniset ominaisuudet tutkittiin rikkomattomin sekä rikkovin menetelmin. Alustavat hitsausohjeet luotiin kummallekin lämmöntuonnille. Testaukset aloitettiin 30 º railokulmalla pienentäen kulmaa mahdollisuuksien mukaan. Testauksissa ei saatu hitsattua onnistuneesti alle 30 º railokulmalla. Hitsaustestien aikana huomattiin magneettisen puhalluksen vaikutus hitsaustapahtumaan. Kaasunvirtausnopeuden tuli olla tietyn suuruinen jotta palkokerrokset onnistuivat ilman huokoisuusongelmaa. Pienemmällä lämmöntuonnilla hitsattaessa kaasunvirtausnopeudet olivat tärkeämpiä hitsatessa ylempiä palkokerroksia. Kääntämällä hitsauspoltinta sivuttaissuunnassa 7-10 astetta auttoi ehkäisemään reunahaavan syntymistä. Rikkovista menetelmistä testitulokset olivat hyväksyttyjä kaikkien muiden paitsi päittäishitsin sivutaivutuskokeen osalta.

Narrow Gap flux-cored arc welding of high strength shipbuilding steels

This thesis is part of the Arctic Materials Technologies Development –project. The research of the thesis was done in cooperation with Arctech Helsinki Shipyard, Lappeenranta University of Technology and Kemppi Oy. Focus of the thesis was to study narrow gap flux-cored arc welding of two high strength steels with three different groove angles of 20°, 10° and 5°. Welding of the 25 mm thick E500 TMCP and 10 mm thick EH36 steels was mechanized and Kemppi WisePenetration and WiseFusion processes were tested with E500 TMCP steel. EH36 steel test pieces were welded without Wise processes. Shielding gases chosen were carbon dioxide and a mixture of argon and carbon dioxide. Welds were tested with non-destructive and destructive testing methods. Radiographic, visual, magnetic particle and liquid penetrant testing proved that welds were free from imperfections. After non-destructive testing, welds were tested with various destructive testing methods. Impact strength, bending, tensile strength and hardess tests proved that mechanized welding and Wise processes produced quality welds with narrower gap. More inconsistent results were achieved with test pieces welded without Wise processes. Impact test results of E500 TMCP exceeded the 50 J limit on weld, set by Russian Maritime Register of Shipping. EH36 impact test results were much closer to the limiting values of 34 J on weld and 47 on HAZ. Hardness values of all test specimens were below the limiting values. Bend testing and tensile testing results fulfilled the the Register requirements. No cracking or failing occurred on bend test specimens and tensile test results exceeded the Register limits of 610 MPa for E500 TMCP and 490 MPa for EH36.

High-Tech Commercialization Research Projects: A Pragmatic View

In the Finnish university society the commercialization research projects has not been a focus of interest until now. The reasons for the growing interest towards commercialization research projects are their possibility to develop our economy simultaneously by providing new technologies and products. This study focuses on the examination of what kind of high-technology oriented research can be commercialized and how. The aim is to generate understanding of how commercialization research projects should proceed and to find concrete ways of improving the of commercialization research projects. As its research method, the study analyzes four different university high-technology research projects which have been commercially oriented and have to some degree been able to commercialize the product or technology developed during the research phase. The data has been gathered mainly by semi-structured interviews of people involved in these particular projects or cases. The findings from the interviews have been reflected to the final reports of the projects, provided by TEKES, and later on the data gained has been compared to each other. Also a literature review has been produced about the subject of commercializing university research with the purpose of providing known theories and framework connected with the subject. The study reveals five main factors related to commercializing high-tech research. These factors are: The Team, Market potential and competitiveness, Product and technology, Funding and Steering Group. Also the uncertainties related to these factors have been addressed. As a conclusion the study provides the main aspects that should be considered when starting a commercialization research project. Also a combining hierarchical framework has been provided related to the five factors presented. In Chapter 5 the study addresses the main tasks or steps to be taken in order to get public funding for a commercially oriented research project and later on the actual steps to be executed in order to successfully commercialize these high-tech research projects.

Metal-Ion-Binding Oligonucleotides: High-Affinity Probes for Nucleic Acid Sequences

Small non-coding RNAs have numerous biological functions in cell and are divided into different classes such as: microRNA, snoRNA, snRNA and siRNA. MicroRNA (miRNA) is the most studied non-coding RNA to date and is found in plants, animals and some viruses. miRNA with short sequences is involved in suppressing translation of target genes by binding to their mRNA post-transcriptionally and silencing it. Their function besides silencing of the viral gene, can be oncogenic and therefore the cause of cancer. Hence, their roles are highlighted in human diseases, which increases the interest in using them as biomarkers and drug targets. One of the major problems to overcome is recognition of miRNA. Owing to a stable hairpin structure, chain invasion by conventional Watson-Crick base-pairing is difficult. One way to enhance the hybridization is exploitation of metal-ion mediated base-pairing, i. e. oligonucleotide probes that tightly bind a metal ions and are able to form a coordinative bonds between modified and natural nucleobases. This kind of metallo basepairs containing short modified oligonucleotides can also be useful for recognition of other RNA sequences containing hairpin-like structural motives, such as the TAR sequence of HIV. In addition, metal-ion-binding oligonucleotides will undoubtedly find applications in DNA-based nanotechnology. In this study, the 3,5-dimethylpyrazol-1-yl substituted purine derivatives were successfully incorporated within oligonucleotides, into either a terminal or non-terminal position. Among all of the modified oligonucleotides studied, a 2-(3,5-dimethylpyrazol-1-yl)-6-oxopurine base containing oligonucleotide was observed to bind most efficiently to their unmodified complementary sequences in the presence of both Cu2+ or Zn2+. The oligonucleotide incorporating 2,6-bis(3,5-dimethylpyrazol-1-yl)purine base also markedly increased the stability of duplexes in the presence of Cu2+ without losing the selectivity.