Molekularbiologische und immunbiochemische Charakterisierung der Antigene des monoklonalen Antikörpers TIM-11B2

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PARP-1 and Ku compete for repair of DNA double strand breaks by distinct NHEJ pathways

Poly(ADP-ribose)polymerase 1 (PARP-1) recognizes DNA strand interruptions in vivo and triggers its own modification as well as that of other proteins by the sequential addition of ADP-ribose to form polymers. This modification causes a release of PARP-1 from DNA ends and initiates a variety of responses including DNA repair. While PARP-1 has been firmly implicated in base excision and single strand break repair, its role in the repair of DNA double strand breaks (DSBs) remains unclear. Here, we show that PARP-1, probably together with DNA ligase III, operates in an alternative pathway of non-homologous end joining (NHEJ) that functions as backup to the classical pathway of NHEJ that utilizes DNA-PKcs, Ku, DNA ligase IV, XRCC4, XLF/Cernunnos and Artemis. PARP-1 binds to DNA ends in direct competition with Ku. However, in irradiated cells the higher affinity of Ku for DSBs and an excessive number of other forms of competing DNA lesions limit its contribution to DSB repair. When essential components of the classical pathway of NHEJ are absent, PARP-1 is recruited for DSB repair, particularly in the absence of Ku and non-DSB lesions. This form of DSB repair is sensitive to PARP-1 inhibitors. The results define the function of PARP-1 in DSB repair and characterize a candidate pathway responsible for joining errors causing genomic instability and cancer

Development of breast cancer diagnosis tool using hybrid magnetoacoustic method and artificial neural network

Breast cancer is a metabolic disease that causes the breast cells to acquire genetic alteration and allows them to grow beyond the normal tissue limit. With the yearly increasing trend in new cases and mortality rate, new approach in diagnosis and treatment of breast cancer is crucial to improve the existing management of breast cancer cases. This paper presents a new approach in breast cancer diagnosis by using Hybrid Magnetoacoustic Method (HMM) and artificial neural network. HMM is a newly developed one dimensional imaging system that combines the theory of acoustic and magnetism for breast imaging. It is capable to produce 2 outputs, the attenuation scale of ultrasound and the magnetoacoustic voltage. In this study, an artificial neural network is developed to automate the output of HMM for breast cancer classification. The ANN employs the steepest gradient descent with momentum back propagation algorithm with logsig and purelin transfer function. The best ANN architecture of 3-2-1 (3 network inputs, 2 neurons in the hidden layer, one network output) with learning rate of 0.3, iteration rate of 20000 and momentum constant of 0.3 was successfully developed with accuracy of 90.94% to testing data and 90% to validation data. The result shows the advantages of HMM outputs in providing a combination of bioelectric and acoustic information of tissue for a better breast cancer diagnosis consideration. The system’s high percentage of accuracy shows that the output of HMM is very useful in assisting diagnosis. This additional capability is hoped to improve the existing breast oncology diagnosis

Conformational transitions of proteins engaged in dna double-strand break repair, analysed by tryptophan fluorescence emission and fret

We analysed protein-DNA and protein-protein interactions relevant to the repair of DNA DSBs (double-strand breaks) by NHEJ (non-homologous end-joining). Conformational transitions in mammalian DNA ligases III (LigIII) and IV (LigIV), as well as in PARP-1 [poly(ADP-ribose) polymerase-1], were analysed upon binding to double-stranded DNA by changes in tryptophan emission and FRET (Förster resonance energy transfer) from tryptophan to DNA-conjugated Alexa Fluor® 532. For LigIII, two non-equivalent high- and low-affinity DNA-binding sites are detected interacting sequentially with DNA. PARP-1 displays a single high-affinity DNA-binding site and can displace bound DNA fragments from the low-affinity site of LigIII, consistent with its mediator role in LigIII-DNA interactions. For the LX [LigIV-XRCC4 (X-ray cross-complementation group 4)] complex, a single DNA-binding site is detected. Binding of Ku to DNA was accompanied by conformational changes in the protein and intermolecular FRET from dansyl chromophores of the labelled Ku to the Alexa Fluor® chromophores of Alexa Fluor® 532-conjugated DNA. The average distance of 5.7 nm calculated from FRET data is consistent with a location of Ku at the very end of the DNA molecule. Binding of LX to Ku-DNA complexes is associated with conformational changes in Ku, translocating the protein further towards the DNA ends. The protein-protein and protein-DNA interactions detected and analysed generate a framework for the characterization of molecular interactions fundamental to the function of NHEJ pathways in higher eukaryotes

Hybrid magnetoacoustic method for breast tumor detection: an in-vivo and in-vitro modelling and analysis

A new breast cancer detection method that is based on tissue bioelectric and acoustic characteristics has been developed by using a hybrid magnetoacoustics method. This method manipulates the interaction between acoustic and magnetic energy upon moving ions inside the breast tissue. Analytical in-vivo and in-vitro modelling and analysis on the system performance have been done on normal and pathological mice breast tissue models. Analysis result shows that, hybrid magnetoacoustic method is capable to give unique characteristics between normal and pathological mice breast tissue models especially in in-vitro application. However, additional parameter such as analysis of current distribution in tissue should be taken into account for in-vivo application due to the redundancy of the existing result

Abnormal tissue detection of breast ultrasound image using combination of morphological technique

Breast cancer is the most common killer in women worldwide, which is originating from breast tissue. Early detection of breast cancer plays an important role in its therapy. Existing breast cancer detection method like ultrasound imaging can not be used at all ages, also quality of obtained images affected by speckle noise. Thus, it is essential to introduce new method to overcome these problems. This paper proposes an approach of detecting abnormal tissue in ultrasound breast image. The objective is to detect the abnormal tissue such as cyst or tumor inside breast tissues using image segmentation and combination of morphological technique. Image was processed using threshold segmentation method followed by dilation and erosion. The region of abnormalities tissue were found and has been differentiating from other tissue through several step of method applied. Besides, the same method was applied to the other different type of breast abnormalities tissue and the necessary result was obtained. The finding results show that this method can be used for early detection of breast cancer since it can detect several types of abnormalities in breast tissues

Automatic detection system of cervical cancer cells using color intensity classification

The conventional Pap smear has been undeniably responsible in reducing the number of incidence and mortality of cervical cancer. However, few concerns have arisen such as the shortage of skilled and experienced pathologists and the increasing workload as a result of more individuals having gained access to preventive health care which eventually will make the reviewing procedure becomes time consuming and highly prone to human errors. In order to solve this problem, an automated detection system of cervical cancer cells has been developed. The detection of cervical cancer cells is based on the morphology of the cells and level set operations. Test result shows, that by using color intensity classification the system is able to differentiate between normal and cancerous cells. This system will hopefully help the pathologist to reduce the work-load and minimize human error while maintaining and improving the accuracy of the system