39 research outputs found
Faltung des alpha-Amylaseinhibitors Tendamistat
Die vorliegende Arbeit beschäftigt sich mit unterschiedlichen Aspekten der Faltung von Tendamistat, einem aus 74 Aminosäuren bestehenden a-Amylase lnhibitor aus Streptomyces tendae. Bei der oxidativen Rückfaltung des Tendamistats konnten bisher drei kinetische Phasen (t1, t2 und t3) identifiziert werden. Die mittlere (t2) bzw. langsame (ti) kinetische Phase, resultiert als Folge einer cis/trans lsomerisierung um eine der drei Xaa-Pro Bindungen im Tendamistat. Wie im ersten Teil dieser Arbeit gezeigt werden konnte, entsteht die prolinabhängige lsomerisierungsreaktion während der Rückfaltung (t3) als Folge einer trans -> cis Umlagerung um die A1a49-Pro50 Amidbindung nach Entfaltung des Proteins. Der Nachweis einer solchen lsomerisierung gelang auf rekombinantem Weg, durch gezielten Austausch der einzelnen Proline. Im Gegensatz dazu resultiert die mittlere kinetischen Phase (t2) als Folge einer Prolin-unabhängigen cis/trans-lsomerisierungsreaktion um mindestens eine vorhandenen nicht-Prolinbindungen im Protein. Diese Schlußfolgerung konnte durch Vergleich mit zahlreichen Literaturdaten und Experimenten weiter gestützt werden. Tendamistat ist damit das erste Protein in der Literatur, bei dem es gelang, eine solche Prolin-unabhängige lsomerisierungsreaktion experimentell nachzuweisen. Wie mit Hilfe von weiteren Substitutionsexperimenten im zweiten Teil der Arbeit gezeigt werden konnte, tragen hydrophobe Oberflächencluster entscheidend zur Stabilisierung des lnhibitors bei. Die dabei gemessenen Stabilisierungsbeiträge stehen in einem linearen Verhältnis zum Seitenkettenvolumen der eingeführten Aminosäurereste (Alanin << Valin << Isoleucin). Hierdurch ließ sich zeigen, daß der stabilisierende Einfluß solcher Cluster im Wesentlichen auf das Vorhandensein von hydrophoben Wechselwirkungen zurückzuführen ist. Für die Faltung von Proteinen, die wie das Tendamistat ausschließlich aus ß-Faltblättern bestehen, spielt die Bildung von ß-Hairpinstrukturen eine entscheidende Rolle Die in dieser Arbeit untersuchten ß-Hairpinmutanten L14A bzw. N25A zeigen im Vergleich zum Wildtyp eine extreme Destabilisierung der ß-Faltblattstruktur. Durch Vergleich der Aktivierungsenergien (DeltadeltaGD-TS) mit den freien Enthalpien (DeltadeltaG0N-D) konnte die strukturelle Entwicklung des ß-Hairpins im Übergangszustand an den beiden Positionen 14 bzw. 25 mitverfolgt werden (~-Wert Analyse). Entgegen den Erwartungen zeigen diese Untersuchungen, daß beide Positionen im Übergangszustand noch weitestgehend solvatisiert vorliegen. Damit scheint die nativ-ähnliche Zusammenlagerung des ersten ß-Hairpins erst nach Erreichen des Übergangszustands stattzufinden. Alle in dieser Arbeit vorgelegten Daten über die Faltung des alpha-Amylase lnhibitors sind konsistent mit dem Nukleations-Kondensations Modell. Analog der Tröpfchenbildung bei unterkühlten Gasen kommt es nach dem kollabieren der Proteinkette als Reaktion auf die veränderten Lösungsmittelbedingungen zur intramolekularen Suche nach Nukleationsstellen. Der Übergangszustand wird erreicht, wenn sich eine kritische Zahl stabilisierender Kontakte (unspezifische Nukleation) ausbilden konnte. Ob an einem solchen Nukleationskern stets bestimmte Seitenketten beteiligt sind (spezifische Nukleation), bleibt an dieser Stelle noch offen
Combining classification algorithms using Dempster?s rule of combination
<!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; text-align:justify; mso-pagination:widow-orphan; font-size:12.0pt; mso-bidi-font-size:10.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman"; mso-fareast-language:EN-US;} p.zetmetni, li.zetmetni, div.zetmetni {mso-style-name:"Özet metni"; margin-top:6.0pt; margin-right:0cm; margin-bottom:0cm; margin-left:0cm; margin-bottom:.0001pt; text-align:justify; mso-pagination:widow-orphan; font-size:11.0pt; mso-bidi-font-size:10.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman"; mso-fareast-language:EN-US; font-style:italic; mso-bidi-font-style:normal;} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 70.85pt 70.85pt 70.85pt; mso-header-margin:35.4pt; mso-footer-margin:35.4pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> Sürekli olarak büyümekte olan veri, mevcut istatistiksel yöntemlerin kullanılmasıyla, büyük miktardaki veri içindeki değerli bilginin bulunmasını ve analiz edilmesini imkansız hale getirmektedir. Mevcut analiz araçlarının yetersizliği nedeniyle çok büyük miktardaki veri içindeki değerli fakat saklanmış bilginin bulunup çıkarılması için yeni çözümler bulunmuştur. Bu çözümler veri madenciliği ve veri füzyonudur. Veri madenciliği önceden bilinmeyen, fakat yararlı bilginin büyük miktardaki veri arasından bulunup çıkarılmasıdır. Veri madenciliği, veri içindeki örüntünün keşfedilmesini ve geleceğe ilişkin tahminler yapılmasında kullanılabilecek ilişkilerin çıkarılmasını sağlayan analiz araçlarını kullanır. Veri füzyonu ise farklı sensörlerden gelen bilgilerin birleştirilmesi işlemidir. Veri füzyonu algoritmaları, savunma sektöründe hedef takibi, hedef kimlik tespiti amacıyla istihbarat, keşif ve gözetleme operasyonlarında kullanılmaktadır. Veri madenciliği ve veri füzyonu birbirini tamamlayan prosesler olmasına rağmen, araştırmacılar bu iki alanda birbirinden bağımsız olarak, herhangi bir ilişkiye girmeden çalışmaktadırlar. Sınıflandırmanın etkinliğini artırmak için bu alanlarda kullanılan teknikleri birleştiren çok az sayıda çalışma mevcuttur. Bu çalışmada sınıflandırma sonuçlarını iyileştirmek için yeni bir yöntem önerilmektedir. Söz konusu yöntem Dempster’in Birleştirme Algoritmasını kullanarak, sınıflandırıcıların doğruluğunun da göz önünde bulundurulmasıyla, farklı sınıflandırma algoritmalarından elde edilen sonuçların birleştirilmesinden oluşmaktadır. UCI kütüphanesinden alınan farklı veri takımlarıyla yapılan deneyler sonucunda Dempster’in Birleştirme Algoritmasının kullanımıyla yapılan birleştirme işleminin, birleşimde kullanılan her bir sınıflandırma algoritmasından ve mevcut birleşik algoritmalardan daha doğru sonuçlar verdiği görülmüştür. Anahtar Kelimeler: Sınıflandırma, Dempster’in birleştirme algoritması, güven derecesi.The constantly growing volume of data makes it impossible to analyze and capture the valuable knowledge among large amounts of data using the current statistical methods. Because of the insufficiency of the current analysis tools, new solutions have been found for extracting the valuable but hidden knowledge among huge data. These solutions are data mining and data fusion. Data mining tries to extract implicit, previously unknown, and potentially useful information from large amounts of data. It is a process that uses a variety of data analysis tools to discover patterns and relationships in data that may be used to make valid predictions. Data fusion, on the other hand, is the process of combining information coming from different sensors. Data fusion algorithms are mostly used for target tracking and target identification purposes in intelligence, surveillance and reconnaissance operations in the defense sector. Although data mining and data fusion are two reciprocal processes completing each other, people are generally working on these two areas independently without having any interaction. There are few studies which combine the techniques used in these areas in order to improve the performance of classification. What is missing in most of the studies performed on this issue is uncertainty management. Every classifier has uncertainty to some extent. The second issue regarding the current classification algorithms is the lack of degree of confidence. Degree of confidence is the success that a certain classifier has displayed on similar data sets in the past. A classification algorithm must be able to use degree of confidence in order to give more precise classification results. Dempster-Shafer?s Method, in other words evidence combination rule, has the capability to handle uncertainty. Dempster-Shafer?s Method is widely used for combining evidences obtained from different sensory information in the area of data fusion. Dempster-Shafer?s Method does not require exact probability values in order to combine evidences. Pieces of information, some being incomplete, obtained from different information sources can be combined using Dempster?s Rule of Combination. However, Dempster?s Rule of Combination does not include degree of confidence presently. In our proposed method of combining classification algorithms using Demspter?s Rule of Combination, we use degree of confidence during the combination in order to improve the accuracy of the classification. Our proposed combination method using Demspter?s Rule of Combination does the following contributions: Employment of degree of confidence during the combination, uncertainty management in combining classifiers and achievement of better classification results. In our proposed method, we first perform classification with different classification algorithms. Assuming the results of the classifiers as beliefs, we calculate mass functions for each classifier. We then combine the mass values in a pairwise fashion using Dempster?s Rule of Combination. When there are more than two classifiers to combine, we first combine the first two classifiers and then combine the result of this combination with the third classifier and this process continues until there are no classifiers to combine. We perform different experiments using data sets taken from the UCI machine learning repository. Firstly, we test the success rate of the current classifiers in WEKA using 10 different data sets taken from the UCI machine learning repository. In the experiments we use the default values of the classifiers. We then check the success rate of current hybrid classifiers using the same data sets with the default values. Afterwards we do tests with the proposed method of combining classifiers using Dempster?s Rule of Combination employing the same data sets. In the experiments we combine four different classification algorithms selected as represantatives for each class of classifiers, in several combinations. In order to be able to make a one-to-one comparison of the proposed method with the current hybrid classification algorithms, we perform experiments with the current hybrid algorithms which has the capability of combining multiple classifiers, using the same data sets. The results of the experiments show that combining classifiers using Demspter?s Rule of Combination with the employment of degree of confidence not only performs better than each of the classifiers taking place in the combination but also performs better than the current hybrid classifiers. The results of the experiments also show that the employment of degree of confidence during the combination gives more precise classification results which also decrease uncertainty in the combination. Keywords: Classification, Dempster?s rule of combination, degree of confidence
Predictive value of modified early warning scoring system for identifying critical patients with malignancy in emergency department
Background: Identification of critically ill patient is particularly important in the emergency department (ED). The prolonged duration from hospital admission to delivering intensive care service is related to increased mortality. The aim of this study is to evaluate the effectiveness of Modified Early Warning Score (MEWS) for identifying critical patients with malignancy in ED settings.
Methods: We evaluated patients with malignancy who were admitted to our ED of a tertiary university hospital in Turkey over a three-month period. We evaluated MEWS on admission as MEWS 1. After the initial treatment depending on the patients' health status in ED, at 2 hours after admission, we evaluated MEWS again and recorded as MEWS 2. All patients were followed up for 30 days after the initial admission.
Results: Mean age (SD) was 59.2 (13.5) and male/female ratio was 295/206. MEWS1 was higher than MEWS2, (MEWS1: 3.05 3.31, MEWS2: 2.35 +/- 3.17, P < 0.001). A total of 362 patients (72.3%) survived and 139 (27.7%) died within 30 days of initial admission. MEWS1/MEWS2 values for alive and dead patients were 1.66/0.87, and 6.67/6.21, respectively, and the difference was significant (P < 0.001). ROC analysis was performed for MEWS 1; the area under curve (AUC) for hospitalization was 0.768 (95% CI 0.729 to 0.804) and for mortality was 0.900 (95% CI 0.870 to 0.924). ROC analysis revealed a cut-off value of 2 for predicting both hospitalization and mortality in these patients. The sensitivity of the presented cut-off was 77.32% (72.1%-82.0%) for hospitalization and 76.24% (95% CI 71.5-80.5) for mortality; the specificity was 69.52 (95% CI 62.8-75.7) for hospitalization and 90.65 (95% CI 84.65-94.9) for mortality.
Conclusion: We found in our study that MEWS evaluation for patients with malignancy on admission to ED is predictive of mortality in the subsequent 30 days, and it is a valuable tool for identifying the critical group. Also, AVPU scores alone can predict mortality in patients admitted to ED
Oligonucleotides suppress PKB/Akt and act as superinductors of apoptosis in human keratinocytes
DNA oligonucleotides (ODN) applied to an organism are known to modulate the innate and adaptive immune system. Previous studies showed that a CpG-containing ODN (CpG-1-PTO) and interestingly, also a non-CpG-containing ODN (nCpG-5-PTO) suppress inflammatory markers in skin. In the present study it was investigated whether these molecules also influence cell apoptosis. Here we show that CpG-1-PTO, nCpG-5-PTO, and also natural DNA suppress the phosphorylation of PKB/Akt in a cell-type-specific manner. Interestingly, only epithelial cells of the skin (normal human keratinocytes, HaCaT and A-431) show a suppression of PKB/Akt. This suppressive effect depends from ODN lengths, sequence and backbone. Moreover, it was found that TGFα-induced levels of PKB/Akt and EGFR were suppressed by the ODN tested. We hypothesize that this suppression might facilitate programmed cell death. By testing this hypothesis we found an increase of apoptosis markers (caspase 3/7, 8, 9, cytosolic cytochrome c, histone associated DNA fragments, apoptotic bodies) when cells were treated with ODN in combination with low doses of staurosporin, a well-known pro-apoptotic stimulus. In summary the present data demonstrate DNA as a modulator of apoptosis which specifically targets skin epithelial cells
The Effect of Obturator Nerve Blockade on Oncological Outcomes of Patients with Lateral Wall Localized Non-Muscle Invasive Bladder Cancer
Objective:To investigate the effect of obturator nerve blockade on oncological outcomes of patients with a diagnosis of lateral wall localized non-muscle invasive bladder cancer.Materials and Methods:One hundred six patients diagnosed with lateral wall localized non-invasive bladder cancer were evaluated between January 2015 and March 2020 in this retrospective, cross-sectional observational study. The patients were divided into two groups: patients receiving only spinal anesthesia and those receiving spinal anesthesia combined with ultrasound-guided obturator nerve blockade. Oncological outcomes of the groups were compared statistically.Results:We observed recurrent tumors in 25 patients (45.5%) in Group 1 and 11 patients (21.6%) in Group 2. Additionally, we observed tumor progression in eight patients (14.5%) in Group 1 and two patients (3.9%) in Group 2. We observed statistical significance in differences between groups regarding tumor size, recurrence rate, adequate muscle tissue sampling, ability for complete resection, and persistent obturator reflex. The efficacy rate of obturator blockade was 92.1% in Group 2. One-year recurrence-free survival (RFS) was 98.0% and 5-year RFS was 23.5% for Group 1, while for Group 2, they were 97.4% and 57.2%, respectively.Conclusion:The obturator reflex is a common and challenging reflex that may cause major complications and result in unintended consequences, such as incomplete resection or tumor recurrence with transurethral resection of bladder tumors. In this study, we demonstrated that combining spinal anesthesia with obturator nerve blockade for lateral wall localized non-muscle invasive bladder cancer may prevent tumor recurrence and reduce peroperative complications
Determination of the mortality and the morbidity with "modified early warning score" (MEWS) for the Emergency Department patients with hematologic or oncologic malignities
Kritik hastaların büyük kısmı ilk olarak acil servislere başvururlar ve ilk tedavileri acil servislerde başlanır. Kritik hastalar hızlı şekilde belirlenmez ve tedavisine başlanmazsa kısa sürede kötüleşebilmektedirler. Acil servislere başvuruları giderek artan ve potansiyel kritik hasta sınıfında olan kanser hastalarının ayrımının hızlı ve etkin bir şekilde yapılması gerekmektedir. Bu çalışmada genel hasta popülasyonunda etkin olduğu gösterilmiş olan hastaların acil başvurularında MEWS'in kanser hastalarında 30 gün içindeki mortalite ve morbiditenin belirlemesinde kullanışlı olup olmadığı ve skor değerlerinin genel hasta değerleriyle karşılaştırılması amaçlandı.Çalışmamız 01.02.2012-01.05.2012 tarihleri arasında Uludağ Üniversitesi Acil Servisine başvuran onkolojik ve ya hematolojik malignitesi olan 501 hasta kayıt altına alınarak yapıldı.Hastaların yaş ortalaması 59.2±13.5 olup, %58.9'u erkektir. Tüm hastalarda MEWS ortalaması 3.05 olup, bu değer 30 gün içinde sağ kalanlarda 1.66, ölen hastalarda ise 6.67 olarak saptanmıştır, MEWS ile yaşama durumu arasındaki ilişki istatiksel olarak anlamlı bulundu. (p<0.001). Ayrıca genel hasta popülasyonunda MEWS için ortalama 4 ve üstü değerler yüksek riskli hasta olarak bildirilmekte iken, bizim çalışmamızda kanser hastaları için bu değerin 2 olduğunu saptadık.Kanser hastalarının acil servislere hayatı tehdit edici ve geri döndürülebilir pek çok nedenle başvururlar. Çalışmamızda bu hasta grubunun acil servis başvurusu esnasındaki MEWS değeri ile 30 günlük mortalite arasında ilişki olduğunu saptadık. Bu hastaların acil servis başvurularında MEWS'in rutin olarak kullanılması ve bu değeri 2 ve üzerinde olan hastaların kritik hasta grubunda değerlendirilmesi gerekmektedir.Most of the critical patients come to emergency departments firstly. And first treatments start at the emergency departments. If critical patients don’t be detected and started to be treated, they deteriorate fastly. Cancer patients ,who are potentially critical patients and increasingly come to emergency departments, must be discriminated fastly and efficiently. In this study the aim is to understand if the MEWS-which has been showen to be useful in general patient population- is usefull or not in determinating the morbidity and the mortality in 30 days, for cancer patients coming emergency departments and to compare the score rates with the general patients’s rates. Our study was made by recording the 501 patients with oncologic or hematologic malignities who have come to the Emergency Department of Medical Faculty of Uludağ University between the dates of 1.2.2012 and 1. 5. 2012. The patients’s average of age was 59.2+/- 13.5. 58.9% Of the patients was males. In all patients average MEWS was 3,05 ; in the patients who survived in 30 days, that value was 1.66 ; and in the patients who died in 30 days, it was 6.67. Relationship between MEWS and the survival was found statistically significant( p<0.001). Also, while 4 and higher average values of MEWS are declared as high-risk for general patient population, in our study, for the cancer patients, we determined that value as 2. Cancer patients, come to emergency departments with many reversible and life threatening reasons. In our study, we determined a relationship between 30 days mortality and MEWS value of that patient group while entering the emergency department. It is necessary to use MEWS routinely in these patients and to evaluate the values that are 2 and over in critical patient group
Kamu çalışanlarının uzaktan hizmet içi eğitim sistemlerine yönelik motivasyon düzeyleri üzerine bir araştırma: Adalet Bakanlığı örneği
YÖK Tez No: 712137Kamu yönetiminin ana hedeflerinden birisi, kamu çalışanlarının eğitimlerini sağlayarak niteliklerini arttırmak, yeni gelişmelere uyumlu hale getirmektir. Böylelikle kamu kurumlarından hizmet talep edenlere hizmetin ulaştırılmasında verimliliğin ve hizmet kalitesinin arttırılması hedeflenmektedir. Bu çalışmada uzaktan eğitim üzerinde durulacaktır. Uzaktan eğitim geleneksel eğitim ile karşılaştırılarak, avantaj ve dezavantajlarından bahsedilecektir. Uzaktan eğitimin kullanım alanları üzerinde durulacak, uzaktan eğitim üzerinde yapılan çalışmalardan bahsedilecektir. Araştırmada tanımlayıcı ve açıklayıcı model kullanılmıştır. Veri toplama işlemi anket formu ile gerçekleştirilmiştir. Anket formu demografik özelliklere yönelik sorulardan ve Uzaktan Hizmet İçi Eğitim Ölçeği'nden oluşmaktadır. Veri analizi SPSS paket programı ile yapılmıştır. Katılımcıların hizmet içi uzaktan eğitime yönelik algıları incelenmiştir.One of the main goals of public administration is to increase the qualifications of public employees by providing training and to adapt them to new developments. Thus, it is aimed to increase efficiency and service quality in delivering services to those who demand service from public institutions. This study will focus on distance education. The advantages and disadvantages of distance education will be discussed by comparing it with traditional education. The usage areas of distance education will be emphasized and the studies on distance education will be mentioned. A descriptive and explanatory model was used in the research. Questionnaire form was used as data collection tool. The questionnaire form consists of questions about demographic characteristics and the Distance In-Service Training Scale. Data analysis was done with SPSS package program. The perceptions of the participants towards in-service distance education were examined