1,721,006 research outputs found
A Novel Strategy to Coat Dopamine-Functionalized Titanium Surfaces With Agarose-Based Hydrogels for the Controlled Release of Gentamicin
Full text linkIntroduction The use of spinal implants for the treatment of back disorders is largely affected by the insurgence of infections at the implantation site. Antibacterial coatings have been proposed as a viable solution to limit such infections. However, despite being effective at short-term, conventional coatings lack the ability to prevent infections at medium and long-term. Hydrogel-based drug delivery systems may represent a solution controlling the release of the loaded antibacterial agents while improving cell integration. Agarose, in particular, is a biocompatible natural polysaccharide known to improve cell growth and already used in drug delivery system formulations. In this study, an agarose hydrogel-based coating has been developed for the controlled release of gentamicin (GS). Methods Sand blasted Ti6Al4V discs were grafted with dopamine (DOPA) solution. After, GS loaded agarose hydrogels have been produced and additioned with tannic acid (TA) and calcium chloride (CaCl2) as crosslinkers. The different GS-loaded hydrogel formulations were deposited on Ti6Al4V-DOPA surfaces, and allowed to react under UV irradiation. Surface topography, wettability and composition have been analyzed with profilometry, static contact angle measurement, XPS and FTIR spectroscopy analyses. GS release was performed under pseudo-physiological conditions up to 28 days and the released GS was quantified using a specific ELISA test. The cytotoxicity of the produced coatings against human cells have been tested, along with their antibacterial activity against S. aureus bacteria. Results A homogeneous coating was obtained with all the hydrogel formulations. Moreover, the coatings presented a hydrophilic behavior and micro-scale surface roughness. The addition of TA in the hydrogel formulations showed an increase in the release time compared to the normal GS-agarose hydrogels. Moreover, the GS released from these gels was able to significantly inhibit S. aureus growth compared to the GS-agarose hydrogels. The addition of CaCl2 to the gel formulation was able to significantly decrease cytotoxicity of the TA-modified hydrogels. Conclusions Due to their surface properties, low cytotoxicity and high antibacterial effects, the hereby proposed gentamicin-loaded agarose-hydrogels provide new insight, and represent a promising approach for the surface modification of spinal implants, greatly impacting their application in the orthopedic surgical scenario
Tümör hedefli mangan-demir oksit manyetik nanoparçacık hibrit görüntüleme ajanının potansiyelinin değerlendirilmesi
Full text linkMeme kanseri, kadınlarda en sık görülen malignitelerden biri olup, özellikle HER2 pozitif alt tipi agresif biyolojik davranışıyla dikkat çekmektedir. Günümüzde moleküler görüntüleme ve hedefe yönelik tedavi alanında nanoteknolojik yaklaşımlar büyük önem kazanmıştır. Bu tez çalışmasında, HER2+ meme kanserinin tanı ve tedavisinde kullanılmak üzere, manyetik rezonans görüntüleme (MRG) ve pozitron emisyon tomografisi (PET) için uygun, hibrit ve hedeflenebilir bir görüntüleme ajanı geliştirilmiştir. Çekirdek-kabuk yapısında tasarlanan nanoparçacıklar, Fe₃O₄ manyetik çekirdek mezoporlu silika (mSi) kaplanarak hazırlanmış, ardından Mn yüklenmiş ve yüzeyine HER2+'e özgü Trastuzumab (Tra) antikoru konjuge edilmiştir. SEM analizine göre nanoparçacıkların boyutları sırasıyla Fe₃O₄ için 8±2 nm, Fe₃O₄-mSi-NH₂ için 10±1 nm, Fe₃O₄-mSi-NH₂-Mn için 13±1 nm ve Fe₃O₄-mSi-NH₂-Mn-Tra için 24±2 nm olarak ölçülmüştür. Trastuzumab'ın nanoparçacıklara bağlanma verimi %58.2±3.8, nanoparçacığın stabilitesi ise 48 saat boyunca fizyolojik koşullarda yapısında bozulma gözlenmiştir. SKBR-3 hücre hattında IC₅₀ değerleri Fe₃O₄ ve Fe₃O₄-mSi-NH₂ için 100 µg, Fe₃O₄-mSi-NH₂-Mn için 6.25 µg ve Fe₃O₄-mSi-NH₂-Mn-Tra için 3.12 µg olarak belirlenmiştir. Apoptoz analizleri sonucunda, Fe₃O₄-mSi-NH₂-Mn-Tra nanoparçacığı MDA-MB-231 hücre hattında %26.74 geç apoptoz, %11.93 erken apoptoz oranı; SKBR-3 hücre hattında ise %36.97 geç apoptoz, %8.60 erken apoptoz oranı ile yüksek apoptotik etki göstermiştir. Trastuzumab'ın tek başına uygulandığı SKBR-3 hücrelerinde bu oranlar sırasıyla %10.55, %9.42 olarak belirlenmiştir. PET görüntüleme kapasitesini test etmek amacıyla nanoparçacıklar, DFO şelatlayıcı aracılığıyla ⁸⁹Zr ile radyoişaretlenmiş ve ⁸⁹Zr-DFO-Fe₃O₄-mSi-NH₂-Mn-Tra için %78±2, ⁸⁹Zr-DFO-Tra için ise %98±2 radyoişaretleme verimi elde edilmiştir. LogD₇.₄ lipofiliklik katsayısı 1.7±0,3 olarak belirlenmiş ve nanoparçacıkların hücre membranı geçiş potansiyelinin yüksek olduğu saptanmıştır. MDA-MB-231 hücre hattında, ⁸⁹Zr-DFO-Fe₃O₄-mSi-NH₂-Mn-Tra nanoparçacıkları ile yapılan tutulum deneyinde en yüksek tutulum %20.22 ile 4. saatte elde edilmiştir. Aynı koşullarda test edilen serbest ⁸⁹Zr-DFO-Tra bileşiği ise 4. saatte %23.03'lük tutulum göstermiştir. (HER2⁺) hücre hattında ise nanoparçacık tutulum oranı 2. saatte %65.25 ile maksimum seviyeye ulaşmıştır. Reseptör doyurma deneylerinde, HER2 ekspresyonu yüksek SKBR-3 hücre hattında Trastuzumab ile ön doyurma sonrası tutulumun %11 azaldığı tespit edilmiştir. Buna karşın HER2-negatif MDA-MB-231 hücrelerinde tutulum oranlarında anlamlı bir değişiklik gözlenmemiştir. Bu veriler, ⁸⁹Zr-DFO-Fe₃O₄-mSi-NH₂-Mn-Tra nanoparçacıklarının hücrelere bağlanmasının HER2 reseptör ekspresyonuna bağlı, spesifik bir hedefleme mekanizması ile gerçekleştiğini göstermiştir. İn vivo biyodağılım çalışmalarında ⁸⁹Zr-DFO-Fe₃O₄-mSi-NH₂-Mn-Tra nanoparçacıkları intravenöz olarak sıçanlara uygulanmıştır. Karaciğer ve akciğer gibi retiküloendotelyal sistem (RES) organlarında yüksek alım gözlenmiştir. Karaciğerde 120. dakikada maksimum birikim (ID/g %15.53±7.6) elde edilmiş ve zamanla azalma gözlenmiştir. Ayrıca böbreklerde zamanla artan tutulumla renal atılım doğrulanmıştır. Beyin dokusunda anlamlı bir tutulum izlenmemiştir, bu da kan-beyin bariyerine nanoparçacık geçişinin sınırlı olduğunu göstermiştir. Çift modlu MR görüntüleme sonuçları, manganın dahil edilmesinin T1 ağırlıklı sinyal yoğunluklarının artmasına neden olduğunu, Fe₃O₄ çekirdeğinin ise belirgin bir T2 kontrastı sağladığını göstermiştir. Sentezlenen nanoparçacıkları, yüksek yapısal stabiliteye sahip olup, HER2+ meme kanseri hücrelerinde sitotoksik etki oluşturma, apoptozu indükleme, hem T1 hem de T2 modlarında MR kontrastı sağlama ve 89Zr ile işaretlendiğinde yüksek bağlanma verimi göstererek nükleer görüntüleme gerçekleştirilebilecek yenilikçi bir çözüm sunmaktadır. Fe₃O₄-mSi-NH₂-Mn-Tra nanoparçacığın kanser teşhisi ve hedefe yönelik tedavide umut vadeden bir PET/MR ajanı olabilme potansiyeli gösterilmiştir.Breast cancer has been identified as one of the most prevalent malignancies in women, with the HER2-positive subtype being particularly noteworthy for its aggressive biological behaviour. In recent years, nanotechnological approaches have gained significant importance in the fields of molecular imaging and targeted therapy. In this thesis study, a dual-modal and targetable magnetic nanoparticle system has been developed for both magnetic resonance imaging (MRI) and positron emission tomography (PET), intended for the diagnosis and treatment of HER2+ breast cancer. The core–shell designed nanoparticles were prepared by coating Fe₃O₄ magnetic cores with mesoporous silica (mSi), followed by manganese loading and surface conjugation with HER2-specific Trastuzumab (TRA) antibodies. SEM analysis yielded the following size measurements for the nanoparticles: 8±2 nm for Fe₃O₄, 10±1 nm for Fe₃O₄-mSi-NH₂, 13±1 nm for Fe₃O₄-mSi-NH₂-Mn, and 24±2 nm for Fe₃O₄-mSi-NH₂-Mn-Tra. The binding efficiency of trastuzumab to the nanoparticles was found to be 58.2±3.8 and the stability of the nanocomposite was maintained without structural degradation for 48 hours under physiological conditions. The IC₅₀ values in the SKBR-3 cell line were determined as 100 µg for Fe₃O₄ and Fe₃O₄-mSi-NH₂, 6.25 µg for Fe₃O₄-mSi-NH₂-Mn, and 3.12 µg for Fe₃O₄-mSi-NH₂-Mn-Tra. Apoptosis analysis revealed that Fe₃O₄-mSi-NH₂-Mn-Tra induced a high apoptotic response in MDA-MB-231 cells with 26.74% late apoptosis, 11.93% early apoptosis, in SKBR-3 cells, these values were 36.97% and 8.60% respectively. In comparison, free Trastuzumab applied to SKBR-3 cells resulted in 10.55% late apoptosis and 9.42% early apoptosis. To evaluate the PET imaging capability, nanoparticles were radiolabeled with ⁸⁹Zr via the DFO chelator, yielding radiolabeling efficiencies of 78±2% for ⁸⁹Zr-DFO-Fe₃O₄-mSi-NH₂-Mn-Tra and 98±2% for ⁸⁹Zr-DFO-Tra. The logD₇.₄ lipophilicity coefficient was measured as 1.7±0.3, indicating a high membrane permeation potential. In the HER2-negative MDA-MB-231 cell line, time-dependent uptake analysis of ⁸⁹Zr-DFO-Fe₃O₄-mSi-NH₂-Mn-Tra showed a maximum uptake of 20.22% at 4 hours, decreasing to 7.27% at 24 hours. Under the same conditions, free ⁸⁹Zr-DFO-Tra achieved 23.03% uptake at 4 hours. In the HER2-positive SKBR-3 cells, nanoparticle uptake peaked at 65.25% at 2 hours, reducing to 47.05% at 24 hours. In receptor saturation experiments, SKBR-3 cells with high HER2 expression showed an 11% decrease in uptake after pre-saturation with TRA. However, no significant difference in uptake was observed in MDA-MB-231 cells. These results demonstrate that ⁸⁹Zr-DFO-Fe₃O₄-mSi-NH₂-Mn-Tra nanoparticles bind to cells through a receptor-specific mechanism dependent on HER2 expression. In vivo biodistribution studies were conducted using ⁸⁹Zr-DFO-Fe₃O₄-mSi-NH₂-Mn-Tra nanoparticles administered intravenously to rats, and organ uptake was investigated. High uptake was observed in organs belonging to the reticuloendothelial system (RES), such as the liver and lungs. In the liver, maximum accumulation (ID/g %15.53 ± 7.6) was achieved at 120 minutes, followed by a decrease over time. Furthermore, increasing uptake over time in the kidneys confirmed renal excretion. No significant uptake was observed in brain tissue, indicating limited nanoparticle penetration through the blood-brain barrier. Dual-mode imaging results showed that the inclusion of manganese increased T1-weighted signal intensity, while the Fe₃O₄ core provided a distinct T2 contrast. The synthesized nanoparticles exhibit high structural stability, demonstrate cytotoxic effects on HER2+ breast cancer cells, induce apoptosis, provide MR contrast in both T1 and T2 modes, and show high binding efficiency when labeled with ⁸⁹Zr, offering an innovative solution for nuclear imaging. Fe₃O₄-mSi-NH₂-Mn-Tra nanoparticles have demonstrated potential as a promising PET/MR agent for cancer diagnosis and targeted therapy
68Ga-PSMA-11 PET pet görüntülemesinde böbreklerlekaraciğerdeki internal dozimetrinin deneysel ve Monte Carloyöntemi ile belirlenmesi
No full text68Ga-PSMA ile yapılan prostat PET görüntüleme protokülü esnasında ortalama olarak 148 MBq 68Ga-PSMA enjeksiyonu sonrasında hedef organ olan prostat bezi dışında diğer kritik organlarda özellikle karaciğer ve böbreklerde tutulum gerçekleşmektedir. Radyasyona duyarlı olan karaciğer ve böbrek gibi kritik organların maruz kaldığı dozlar toksik etki oluşturma sebebiyle iyi belirlenmelidir. Bu sebeple 68Ga-PSMA PET/BT görüntülenmesi işlemi ile hastaya verilen ve karaciğerde ve böbreklerde tutulum gösteren absorbe radyasyon doz miktarının termolüminisans dozimetresi, Monte Carlo metodu ve IDAC Dose yazılım programı kullanılarak belirlenmiştir. Çalışmanın ilk aşamasında; 148 MBq 68Ga-PSMA enjeksiyonu yapıldıktan 60 dk. sonra karaciğer ve böbreklerin soğurduğu dozların belirlenmesi için boyut ve yoğunluk gibi özellikler açısından birebir insan karaciğeri ve böbreği ile benzerlik gösteren fantom modelleri oluşturulmuştur. Oluşturulan fantomlarda farklı konumlara yerleştirilen TLD-100 dozimetre ile absorbe edilen dozlar belirlenmiştir. İkinci aşamada EGSnrc programında 68Ga aktivite miktarı için karaciğerde ve böbreklerde oluşan absorbe doz dağılımı simüle edilerek aynı konumlar için absorbe edilen doz değerleri hesaplanmıştır. Üçüncü aşamada IDAC Dose yazılım programı kullanılarak karaciğer ve böbreklerde ki absorbe dozlar belirlenmiştir. Son aşamada; karaciğer için 22,2 MBq, böbrek için 11,1 MBq aktivite miktarı ile karaciğer ve böbrek doz değerlerinin sırasıyla fantom TLD'de 0,01 mGy/MBq ve 0,3 mGy/MBq, IDAC Dose içsel radyasyon yazılım programında 0,007 mGy/MBq ve 0,045 mGy/MBq, EGSnrc simülasyon da 0,08 mGy/MBq ve 0,009 mGy/MBq sonuçları karşılaştırılarak yapılan hesaplamaların doğruluğu test edilmiştir
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Evaluation of BrachyDose Monte Carlo code for HDR brachytherapy: dose comparison against Acuros (R) BV and TG-43 algorithms
No full textAim: The aim of this study is to investigate the accuracy of dose distributions calculated by the BrachyDose Monte Carlo (MC) code in heterogeneous media for high-dose-rate (HDR) brachytherapy and to evaluate its usability in the clinical brachytherapy treatment planning systems. Materials and methods: For dose comparisons, three different dose calculation algorithms were used in this study. Namely, BrachyDose MC code, Eclipse TG-43 dose calculation tool and Acuros (R) BV model-based dose calculation algorithm (MBDCA). Dose distributions were obtained using any of the above codes in various scenarios including 'homogenous water medium scenario', an 'extreme case heterogeneous media scenario' and clinically important 'a patient with a cervical cancer scenario'. In the 'extreme case, heterogeneous media scenario', geometry is a rare combination of unusual high-density and low-density materials and it is chosen to provide a test environment for the propagation of photons in the interface of two materials with different absorption and scattering properties. GammaMed Ir-192 Model 12i Source is used as the HDR brachytherapy source in this study. Dose calculations were performed for the cases where there is either a single source or five sources planted into the phantom geometry in all homogenous water phantom and extreme case heterogeneous media scenarios. For the scenario a patient with a cervical cancer, dose calculations were performed in a voxelized rectilinear phantom, which is constructed from a series of computed tomography (CT) slices of a patient, which are obtained from a CT device. Results: In homogeneous water phantom scenario, we observed no statistically significant dose differences among the dose distributions calculated by any of the three algorithms at almost every point in the geometry. In the extreme case heterogeneous media scenario, the dose calculation engines Acuros (R) BV and BrachyDose are agreed well within statistics in every region of the geometry and even in the points close to the interfaces of low-density and high-density materials. On the other hand, the dose values calculated by these two codes are significantly different from those calculated by the TG-43 algorithm. In the 'a patient with a cervical cancer scenario', the calculated D-2cc dose difference between Acuros (R) BV and BrachyDose codes is within 2% in the rectum and 11% for the bladder and sigmoid. There was no meaningful difference in the mean dose values between MBDCAs in the bone structures. Conclusions: In this study, the accurate dose calculation capabilities of the BrachyDose program in HDR brachytherapy were investigated on various scenarios and, as a MC dose calculation tool, its effectiveness in HDR brachytherapy was demonstrated by comparative dose analysis
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