Repositorio de la Asociación Española de Neuropsiquiatría
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Preparation, characterization of upconverting nanoparticles for uricase immobilization and controlled manipulation of uricase activity by near-infrared light
No full textIn recent years, studies on the external stimulation of biotechnological enzyme drugs and their use in the treatment of diseases have gradually increased. Herein, for the first time, the near-infrared (NIR) was used as an external stimulant to manipulate the catalytic activity of the uricase (UOx) enzyme, which is used in the treatment of hyperuricemia, in a controlled manner. For this purpose, NaYF4: Yb3+, Er3+ upconverting nanoparticles (UCNPs) were synthesized by hydrothermal synthesis method and functionalized with diethylaminoethyldextran (DEAE-D) to facilitate UOx immobilization. The obtained materials were characterized in detail by various methods to confirm the preparation of UCNPs and immobilization of UOx. In addition, the biochemical parameters such as optimum pH, optimum temperature, thermal stability, and reusability were preliminarily investigated for free UOx and NaYF4: Yb3+, Er3+/DEAE-D/UOx. Moreover, a sequential experimental method was monitored to assess the effects of NIR excitation intensity, induction distance, and exposure time on the UOx activity. While the optimum pH value was found to be 6.0 for both enzyme forms, the optimum temperature value was recorded as 45 and 50 degrees C for free UOx and NaYF4: Yb3+, Er3+/DEAE-D/UOx, respectively. The activation energy (Ea) values of free UOx and NaYF4: Yb3+, Er3+/DEAE-D/UOx were calculated to be 7.59 and 2.98 kJ/mol, respectively, implying that the NaYF4: Yb3+, Er3+/DEAE-D/UOx was less temperature sensitive. After thermal incubation for 3 h at 55 degrees C, the NaYF4: Yb3+, Er3+/DEAE-D/UOx retained 54.68 % of its initial activity, while the free UOx retained 32.94 % of its initial activity at 50 degrees C. In addition, the findings from the reusability experiments revealed that NaYF4:Yb3+, Er3+/DEAE-D/UOx retained 57.94 % of its initial activity even after 10 reuse cycles. The most striking point in this study was the positive manipulation of UOx activity by NIR. Accordingly, it was observed that when the NIR power was 1500 mW, the UOx activity increased about 2 times compared to the control. Additionally, the UOx activity increased in parallel with the increase in NIR application time and the ideal application distance was 3 cm. In conclusion, this pioneering study provides valuable insights into the controlled manipulation of enzyme activity, showcasing the effectiveness of NIR in enhancing enzyme activity. The outcomes suggest that NIR holds great promise as an efficient, sustainable, and versatile approach applicable to various enzymatic catalysis scenarios.Scientific Research Projects Unit of.Inonu University [FBG-2020-2173]The authors would like to thank the Scientific Research Projects Unit of.Inonu University (FBG-2020-2173)
Preparation of pyridoxine-based polyurethane modified sensors and their use in simultaneous determination of Cu(II) - Co(II) ions
No full textIn this study, pyridoxine-based polyurethane-modified electrodes were prepared to simultaneously and sensitively measure copper (Cu(II)) and cobalt (Co(II)) ions in complex matrix samples. For the production of the electrodes, firstly, the synthesis of pyridoxine-based polyurethane structures was carried out. In these syntheses, the polymer structure was diversified by using different isocyanates. Polyethyleneglycol-200 (PEG), pyridoxine (B6), and beta- cyclodextrin ( beta- CD) groups were used as the source of polyol. The synthesized polyurethane structures were characterized by different instrumental techniques and used in gold electrode surface modification. Modified sensor surfaces were examined by scanning electron microscopy and atomic force microscopy techniques. The prepared modified sensors were used for the simultaneous detection of Cu(II) and Co(II) ions using the differential pulse voltammetry technique. The limit of detection (LOD), limit of quantitation (LOQ), and R 2 values for Cu(II) ions were calculated as 8.81 mu M, 29.4 mu M, and 0.993, respectively. LOD, LOQ, and R 2 values for Co(II) ions were calculated as 9.84 mu M, 32.8 mu M, and 0.9935, respectively. For repeatability, the relative standard deviation (RSD %) of the prepared simultaneous sensors was determined as 1.54 and 1.71 for Cu(II) and Co(II), respectively. As a result, Cu(II) and Co(II) ions were measured independently and simultaneously with high sensitivity. According to these results, it is predicted that pyridoxine-based polyurethane-modified sensors may be suitable for the simultaneous detection of Cu(II) and Co(II) in medical, food, and agricultural samples.The PCT application for this study and the designed sensor material were entered into the TURKPATENT records on 14/12/2023 with the application number PCT/TR2023/051546, and were transferred to the international stage
The effects of Zn and Yb co-dopants on the electronic, radiation shielding, structural, thermal and spectroscopic properties of hydroxyapatite
No full textThis work presents a comprehensive investigation of the electronic properties of hydroxyapatite (HA) doped with zinc (Zn) and ytterbium (Yb). Four different compositions, namely 0.33Zn-0.33Yb-HA, 0.33Zn-0.66Yb-HA, 0.66Zn-0.33Yb-HA, and 0.66Zn-0.66Yb-HA, were studied using Density of States (DOS) and band structure calculations. The computed band gap values for each composition were determined to be 4.3097 eV, 4.1324 eV, 4.2527 eV, and 4.2088 eV, respectively. The observed decrease in the band gap energy from 0.33Zn-0.33Yb-HA to 0.66Zn-0.66Yb-HA signifies a significant impact of the dopant composition on the electronic properties of the material. Furthermore, the inclusion of ytterbium in the HA matrix resulted in the formation of a distinct band and peak in the density of states. This indicates the emergence of specific energy levels associated with Yb, suggesting a distinct influence on the electronic structure of the material. These findings provide valuable insights into the tunability of the electronic properties of HA through controlled doping with Zn and Yb. Such knowledge is crucial for tailoring materials with desired electronic characteristics, thus holding promise for various applications in electronic devices and biocompatible coatings. The as-modeled structures were synthesized via a wet chemical route. Fourier transform infrared (FTIR), Raman, and X-ray diffraction (XRD) analyses verified the formation of the HA structure for each sample. Differential thermal analysis (DTA) results showed that all the as-prepared samples were thermally stable. The negligible mass losses were detected for all the samples in the thermogravimetric analysis (TGA) measurements. The addition of both co-dopants affected crystal structure related parameters and decreased the crystallinity and cell viability.Malatya Turgut Coordination Unit [2022/19]; University Scientific Research Projects (BAP)Malatya Turgut Coordination Unit, (Project no.: 2022/19) . Ozal University Scientific Research Projects (BAP
A comparative study on PI-PD controller design using stability region centroid methods for unstable, integrating and resonant systems with time delay
No full textIn this paper, controller tuning methods based on stability region centroid methods reported in the literature are used to design PI-PD controllers for unstable, integrating and resonant systems with time delay. By analyzing the stability boundary locus (SBL) for the PD controller, which is utilized in the inner loop of this structure, the controller parameters are obtained using three methods which are the Weighted Geometric Center (WGC), Centroid of Convex Stability Region (CCSR), and Stability Triangle Approach (STA). These techniques were applied analytically, step by step. For the closed loop transfer function obtained in the inner loop of the controlled system, these three methods were utilized to design the PI controller in the outer loop, individually. Unit step responses of the controlled system, using PI-PD gains determined by each method, have been obtained. Furthermore, a disturbance of a certain time and amplitude was added to the systems to test the disturbance rejection behavior and the robustness performance of the methods. Perturbed responses were obtained through changing the model parameters at a certain rate. Time domain performance metrics were analyzed to compare the responses. The simulations were evaluated using settling time, rise time, and percentage overshoot as the assessment criteria. As a result of this study, the effectiveness of three methods, namely WGC, CCSR, and STA, in controller design for unstable, integrating, and resonant time-delay systems has been demonstrated. In addition, a comparison of time domain performance metrics is presented for the nominal and perturbed systems. Based on these comparisons, it is concluded that the methods outperform each other only in some time response performance measures. The presented results showed the advantages of these methods over each other in terms of some performance criteria. The contribution of this study to the literature is the comparative analysis of these three analytical methods.Turkish Academy of Sciences (TUBA)We thank Turkish Academy of Sciences (TUBA) for supporting this work
The Effect of Music on Pregnancy Complaints with Sleep and Quality of Life in Risky Pregnant Women
No full textObjective: This study aimed to examine the effect of music therapy on pregnancy complaints and quality of sleep and life in risky pregnant women. Methods: This is a prospective randomized controlled study. The sample of the study consisted of a total of 112 pregnant women who referred to a hospital in a city in Turkey for pregnancy follow-up (56 in the experimental group, 56 in the control group). Risky pregnant women in the experimental group were listened to music for four weeks before going to sleep, and those in the control group received no intervention. The data were collected between July and October 2022, using an introductory information form (IIF), a risk assessment form (RAF), the Assessment Scale for Pregnancy Complaints and Their Impact on Life Quality (ASPCILQ), and the Richard -Campbell Sleep Questionnaire (RCSQ). Results: Risky pregnant women in the experimental group had higher ASPCILQ and RCSQ post-test mean scores than those in the control group, and the difference between them was statistically significant (p<.001). Conclusions: A music therapy reduced pregnancy complaints in risky pregnant women and increased their sleep and life quality.Coordinator Ship of Scientific Research Projects at Inonu University [TSA-2022-3021]Funding: The Coordinator Ship of Scientific Research Projects at Inonu University was applied for financial support for the design of this study (Project No: TSA-2022-3021)
High-fat and carbohydrate diet caused chronic kidney damage by disrupting kidney function, caspase-3, oxidative stress and inflammation
No full textThe study aimed to compare the effects of a diet rich in fat, carbohydrates and protein on rat kidneys. The study was conducted on 40 Wistar albino rats bred at Ino center dot nu University Faculty of Medicine after the approval of the ethics committee. Rats were randomly divided into 4 groups: Control group, and the groups where the animals were fed with high carbohydrate, fat and protein rich feed. After the applications, the rat kidney tissues were removed by laparoscopy under anesthesia and blood samples were collected. 13 weeks long fat-rich and carbohydrate feed application had negative effects on oxidant-antioxidant balance, oxidative stress index, inflammation markers, kidney functions tests, histopathology and immunohistochemistry caspase-3 findings in rat kidney tissues, especially in the carbohydrate group when compared to the controls. Protein-rich feed, there were no significant difference in biochemical and histopathology compared to the control group. Fat and carbohydrate rich feed led to an increase in oxidative stress in rat kidney tissues. Oxidative stress led to nephrotoxicity, which in turn led to chronic kidney tissue damages. A more balanced and protein-rich diet instead of excessive sugar and fatty food intake could be suggested to prevent chronic kidney damage
Comparasion of the results supine – percutaneous nephrolithotomy and prone percutaneous nephrolithotomy
No full textTıp Fakültesi, Üroloji Ana Bilim DalıAmaç: Bu çalışma perkütan nefrolitotomi yapılmış hastaların demografik verilerini, geçmiş tıbbı öykülerini, preop ve postop kan değerlerini, taş özelliklerini, komplikasyonları, hospitalizasyon sürelerini ve cerrahi etkinliği operasyon pozisyonuna göre karşılaştırmayı amaçlamıştır. Materyal ve Method: Bu çalışmaya 2020-2023 yılları arasında İnönü üniversitesi Turgut Özal Tıp Merkezi Üroloji kliniğimizde perkutan nefrolitotomi (PNL) operasyonu yapılan 200 hasta dahil edilmiştir. Supin ve prone pozisyon olmak üzere hastalar operasyonun gerçekleştirildiği hasta pozisyonuna göre iki gruba ayrılmıştır. Her iki gruba 100'er hasta dahil edilmiştir. Gruplar arası yaş, cinsiyet, cerrahi öykü, ek komorbiditeler, renal anomaliler, taş yüzey alanları,taş lokasyonu,ASA skoru,preop DJ stent uygulaması,nefrostomi uygulanması, hemoglobin, lökosit, trombosit,kreatinin, komplikasyon gelişimi, vaka süresi,skopi süresi,nefroskop boyutu,eritrosit süspansiyon ihtiyacı,postop ateş varlığı,rezidü taş varlığı,ek cerrahi girişim ihtiyacı,böbrek taraf bilgisi,pozisyon bilgisi,sheat boyutu, Guy's Stone Skorlaması, Houns-Field Üniti, PNL çeşidi, puncture bölgesi, hospitalizsyon süresi parametrelerindeki farklılıklar retrospektif olarak değerlendirilmiştir. Çalışmamıza pre-operatif ve post-operatif takip ve tedavileri kliniğimizde düzenlenen hastalar dahil edilmiştir. Postoperatif dönemde kontrole gelmeyen hastalar ile tüm verilerine ulaşılamayan hastalar çalışmadan çıkarılmıştır. Bulgular: Gruplar arası demografik veriler karşılaştırıldığında yaş, cinsiyet, ek hastalıklar, ASA skorları ve renal anomali varlığı parametrelerinde istatiksel farklılık izlenmemiştir(p>0,05). Geçirilmiş cerrahi öyküsü anlamlı farklıdır(p0,05). Taş lokalizasyonu, taş yüzey alanı parametreleri ise anlamlı farklılık içermektedir (p0,05). Gruplar arası preop kreatinin, lökosit, trombosit değerlerinin postop değerleriyle karşılaştırıldığında benzer değişimler görülüp anlamlı fark izlenmemiştir (p>0,05). Operasyon sonrası hemoglobin düşüş oranını farkı ise anlamlı tespit edilmiştir (p0,05). Operasyon süresi ve hospitalizasyon süresi parametrelerinde ise supin PNL lehine anlamlı fark izlenmiştir (p0.05). However, a significant difference was found in the history of previous surgeries (p0.05). However, significant differences were found in stone localization and stone surface area parameters (p0.05). When comparing preoperative creatinine, leukocyte, and platelet values with their postoperative values between groups, similar changes were observed with no significant differences (p>0.05). However, a significant difference was found in the rate of postoperative hemoglobin decrease (p0.05). However, significant differences were noted in operation duration and hospitalization duration parameters, favoring supine PNL (p<0.05). Significant parameters identified in the logistic regression model included the history of previous PNL, the number of punctures from the lower pole, stone localization in the middle pole, and postoperative nephrostomy application. Conclusion: Percutaneous nephrolithotomy (PNL) surgery can be safely preferred in both prone and supine positions for stone management. The surgeon's experience plays a crucial role in determining the preferred position. Prone position stands out more in accessing stones and achieving stone clearance, especially in patients with upper pole and middle pole stones. However, supine PNL appears to be more advantageous in terms of hospitalization and operation durations. The ability of the supine position to allow simultaneous endoscopic procedures (ECIRS) seems highly effective in this regard. Complication rates and the frequency of residual stones are similar for both methods, with no superiority observed in terms of surgical success and reliability. Considering the increasing prevalence of cardiac and pulmonary diseases in the population, we believe that supine PNL will become a more prominent and preferred surgical procedure not only in our clinic but also worldwide in the coming years. Key words : supine percutaneus nefrolitotomi, prone percutaneus nefrolitotomi, stone free rat
Sythesis, characterisation, anticancer and antimicrobial activity of Ag-N-heterocyclic carbene complexes containing benzimidazole derivatives
No full textTo prepare a novel series of silver(I) complexes, the interaction of benzimidazolium salts having their two nitrogen atoms substituted by bulky groups with Ag2O in DCM has been carried out. Their structures were characterized by elemental analyses, 1H NMR, 13C NMR, elemental analysis, and IR spectroscopy techniques. Further, the antimicrobial and antifungal activities properties of both the salts and their silver(I)-NHC complexes were tested against positive and negative bacteria using the Clinical and Laboratory Standards Institute (CLSI) and the European Committee for Antimicrobial Susceptibility Testing (EUCAST) respectively. The results show that silver complexes are effective against E. coli, P. aeruginosa and S. aureus bacterial species with moderate to high activity, and their minimum inhibitory concentrations ranging from 25 to 400 mu g/Ml. It was also observed that 3b compound, which has the best antifungal properties among the synthesized compounds, showed high antimicrobial activity when all bacterial species were taken into account. In addition, the salts and complexes were then evaluated for their ability to inhibit the proliferation of four different cancer cell lines (A549, MCF-7, HCT116, SH-SY5Y and BEAS-2B cells lines). AlamarBlue assay demonstrated that the salts and complexes exhibited potent cytotoxicity towards all cancer lines. 2c compound showed the highest cytotoxic activity against BEAS-2B, A549 and MCF-7 cell lines. Except for 2c, compounds 3d, 3e and 3f showed cytotoxic activity at the lowest concentrations against MCF7 cell line.The study highlights the importance of N-heterocyclic carbene ligands in the development of silver-based drugs with anticancer properties.Technological and Scientific Research Council of Turkey TUBITAK [120R030]; Inonue University Research Fund [FBG-2021-2562]; King Saud University, Riyadh, Saudi Arabia [RSP2024R75]This work was financially supported by: - The Technological and Scientific Research Council of Turkey TUBITAK (Project No: 120R030) and the Inonue University Research Fund (FBG-2021-2562).; - The authors extended their appreciation to the Researchers Supporting Project number (RSP2024R75), King Saud University, Riyadh, Saudi Arabia
Examining the methods used for the transition from relational databases to nosql storage systems and developing the schematransformation application
No full textFen Bilimleri Enstitüsü, Bilgisayar Mühendisliği Ana Bilim DalıVeri depolama sistemlerinin önemi günümüz büyük veri çağında önemli hale gelmiştir. İlişkisel veri tabanlarının katı olan ve esnek olmayan şema yapısı, NoSQL (Not Only SQL) veri depolama sistemlerinin ortaya çıkmasına zemin hazırlamıştır. İlişkisel veri tabanı yönetim sistemlerinin (RDBMS) katı şema yapısından NoSQL veri depolama sistemlerine dönüşüm, veri bütünlüğünü ve tutarlılığını sağlamak, uygun NoSQL veri depolama sisteminin seçimini yapmak ve geçiş sürecini doğru bir şekilde yürütmek için dikkatli bir değerlendirme gerektiren karmaşık bir işlemdir. Bu tez çalışmasında, ilişkisel veri tabanlarından NoSQL'e geçiş önemli bir konu olduğundan, ilişkisel veri tabanlarından istenilen kategorideki NoSQL'e geçiş imkânı sağlayan ve veriyi de yeni oluşturulan şemaya transfer edebilen RL2NoSQL metodu geliştirilmiştir. RL2NoSQL metodu, veri bütünlüğünü ve tutarlılığını korurken, veri modelleri arasındaki yapısal farklılıkları detaylıca ele almakta ve otomatik dönüşüm mekanizmaları sunmaktadır. Ayrıca, bu çözüm, karmaşıklığı yönetme ve veri depolama esnekliğini artırma konusunda önemli avantajlar sağlamaktadır. Bu sayede, veri kaybı veya veri bozulması gibi sorunlar yaşanmadan veri tabanı dönüşüm işlemi gerçekleştirilebilmektedir. Ek olarak, RL2NoSQL yaklaşımı tarafından üretilen şema önerilerini değerlendirmek için birkaç sorgu oluşturulmuştur. Oluşturulan sorgular her bir NoSQL veri depolama sisteminde çalıştırılmıştır. Elde edilen sonuçlar ve bulgular, veri sorgulama operasyonları için potansiyel iyileştirmeleri göstermiştir. RL2NoSQL yöntemi, NoSQL in her bir kategorisinde bulunan veri depolama sistemlerine geçiş imkânı sağladığından sektörde bulunan ve NoSQL'e geçiş yapmak isteyen firma ve organizasyonlara kritik bir katkı sağlamayı amaçlamakta ve çeşitli sektörlerdeki uygulamalar için yeni kapılar açmayı hedeflemektedir. Anahtar Kelimeler: Veri Modelleme, İlişkisel Veri Tabanı Yönetim Sistemleri, NoSQL, Şema DönüşümüThe rigid and inflexible schema structure of relational databases has paved the way for the emergence of NoSQL (Not Only SQL) data storage systems. The transition from Relational Database Management Systems (RDBMS) to NoSQL data storage systems is a complex process that requires careful evaluation to maintain data integrity and consistency, select the appropriate NoSQL system, and correctly manage the transition. In this thesis, given the importance of transitioning from relational databases to NoSQL, the RL2NoSQL method has been developed, which enables the transition to the desired category of NoSQL and also transfers the data to the newly created schema. The RL2NoSQL method meticulously addresses the structural differences between data models while providing automatic transformation mechanisms, offering significant advantages in managing complexity and enhancing storage flexibility. This ensures that the database transformation process can be conducted without data loss or corruption. Additionally, several queries have been created to evaluate the schema suggestions generated by the RL2NoSQL approach. These queries have been executed across various NoSQL storage systems. The results and findings indicate potential improvements for data querying operations. The RL2NoSQL method aims to provide a critical contribution to companies and organizations in the industry looking to transition to NoSQL, and it opens new doors for applications across various sectors. Keywords: Data Modeling, RDBMS, NoSQL, Schema Transformatio
Turkish translations of Ferîdüddîn-i Attâr's Tamâmî-i Esâmî (Review-text-dictionary-index)
No full textSosyal Bilimler Enstitüsü, İslam Tarihi ve Sanatları Ana Bilim DalıTasavvufi duyuşu ifade eden rumuzlar divan şiirini ve şairini besleyen temel kaynaklardandır. Divan şairi sıklıkla başvurduğu ve bir motif olarak şiirinde yer verdiği tasavvufi mefhumları Farisi üstatların şiirlerini okuyarak öğrenmiş ve bu remizleri kullanırken o şairlere öykünmüştür. Divan şiirinin filizlenmeye başladığı XII-XIV. asırlarda hatırı sayılır bir edebi birikimi haiz olmayan Türkler güçlü bir edebiyat birikimine sahip olan Farisilerden ilham almış ve Farsça muteber eserleri Türkçeye kazandırmaya gayret etmişlerdir. Bunun tabii bir neticesi olarak Farsça eserlerin Türkçe tercümelerinden zaman içinde geniş bir literatür meydana gelmiş ve bu, divan şairinin asırlar boyunca beslendiği mühim bir kaynağı teşkil etmiştir. Giriş ve üç ana bölümden müteşekkil olan "Ferîdüddîn-i Attâr'ın Tamâmî-i Esâmî Adlı Eserinin Türkçe Tercümeleri (İnceleme-Metin-Sözlük-Dizin) adlı çalışmamızın giriş bölümünde tez hakkında bazı umumi bilgiler aktarıldıktan sonra klasik dönem Türk edebiyatında Attâr tercümeleriyle alakalı genel bilgiler verilmiş; birinci bölümde Tamâmî-i Esâmî adlı eser tanıtılmış ve içerik bakımından Türkçe tercümeleriyle mukayese edilmiş; ikinci bölümde Tamâmî-i Esâmî'nin "Reşâdü'l-Meâd, Miftâhu'l-Ebrâr u Misbâhu'l-Envâr, Istılâhât-ı Mesnevî, Miftâhu'l-Esrâr u Misbâhu'l-Envâr" gibi farklı adları olan Türkçe tercümeleri incelenmiş; üçüncü bölümde tercümelerin nüsha tavsifi yapılmış ve tenkitli metni verilmiş; son olarak da eserde şerh edilen tasavvufi kavramların Tamâmî-i Esâmî'de yer alan kelime şerhlerinden hareketle lügatı hazırlanmış ve bu kavramları kapsayan bir dizin eklenmiştir.The rhyming symbols that express the Sufi sensibility are among the main sources that nourish divan poetry and its poet. The Divan poet learned the Sufi notions that he frequently used and included in his poetry as a motif by reading the poetry of Persian masters and emulated those poets in his use of these motifs. In the XII-XIVth centuries, when Divan poetry began to flourish, the Turks, who did not have a considerable literary background, were inspired by the Persians, who had a strong literary background, and endeavored to translate Persian works into Turkish. As a natural consequence of this, a vast literature of Turkish translations of Persian works emerged over time, and this constituted an important source of nourishment for the divan poets for centuries. In the introduction part of our study titled "Turkish Translations of Ferîdüddîn-i Attâr's Tamâmî-i Esâmî (Review-Text-Dictionary-Index)", which consists of an introduction and three main chapters, after giving some general information about the thesis, general information about Attâr translations in classical period Turkish literature is given; In the first chapter, Tamâmî-i Esâmî is introduced and compared with its Turkish translations in terms of content; In the second part, the Turkish translations of Tam?m? al-As?m? with different titles such as "Rash?d al-Me?d, Mift?? al-Abr?r u Misb?? al-Anw?r, Istılâh?t al-Masnaw?, Mift?? al-Asr?r u Misb?? al-Anw?r" are analyzed; In the third part, the translations are described and their critical text is given; finally, a glossary of the Sufi concepts annotated in the work is prepared based on the word annotations in Tam?m?-i Es?m? and an index covering these concepts is added