Genetic Analyses of the NF1 Gene in Turkish Neurofibromatosis Type I Patients and Definition of three Novel Variants.

Neurofibromatosis Type I (NF1) is a multi systemic autosomal dominant neurocutaneous disorder predisposing patients to have benign and/or malignant lesions predominantly of the skin, nervous system and bone. Loss of function mutations or deletions of the NF1 gene is responsible for NF1 disease. Involvement of various pathogenic variants, the size of the gene and presence of pseudogenes makes it difficult to analyze. We aimed to report the results of 2 years of multiplex ligation-dependent probe amplification (MLPA) and next generation sequencing (NGS) for genetic diagnosis of NF1 applied at our genetic diagnosis center. The MLPA, semiconductor sequencing and Sanger sequencing were performed in genomic DNA samples from 24 unrelated patients and their affected family members referred to our center suspected of having NF1. In total, three novel and 12 known pathogenic variants and a whole gene deletion were determined. We suggest that next generation sequencing is a practical tool for genetic analysis of NF1. Deletion/duplication analysis with MLPA may also be helpful for patients clinically diagnosed to carry NF1 but do not have a detectable mutation in NGS.

Von Hippel-Lindau disease: the clinical manifestations and genetic analysis results of two cases from a single family.

von Hippel-Lindau (VHL) disease is an autosomal dominant inherited multi systemic cancer syndrome that is classically associated with neoplasms in multiple organs, and caused by mutations in the VHL gene on chromosome 3p25-p26. Retinal hemangioblastoma (RH) is the most frequent and the earliest clinical sign of the disease, which is seen in 40.0-60.0% of patients. In recent years, studies of patients with VHL tried to put forward the relationship between genotype and phenotype. In this study, two VHL cases in the same family with clinical findings and genetic analysis results are presented. As a consequence of the genetic studies, a heterozygous missense mutation c.202 T>C, p.S68P (Ser68Pro) in exon 1 of the VHL gene that is mapped to chromosome 3p25.3, was found in the patients' DNA sample. The germline mutation of [c.202T>C, p.S68P (Ser68Pro)] that was detected in both cases, has been reported in only two cases in the literature. However, in these reported cases, any systemic involvement except RH, were not reported. Although our cases had the same mutation, we detected renal involve-ment in both cases, and also central nervous system (CNS) involvement in one case, in addition to RH.

Extreme fluctuations in noisy task-completion landscapes on scale-free networks.

We study the statistics and scaling of extreme fluctuations in noisy task-completion landscapes, such as those emerging in synchronized distributed-computing networks, or generic causally constrained queuing networks, with scale-free topology. In these networks the average size of the fluctuations becomes finite (synchronized state) and the extreme fluctuations typically diverge only logarithmically in the large system-size limit ensuring synchronization in a practical sense. Provided that local fluctuations in the network are short tailed, the statistics of the extremes are governed by the Gumbel distribution. We present large-scale simulation results using the exact algorithmic rules, supported by mean-field arguments based on a coarse-grained description.

[Detection of Babesia caballi (Nuttall, 1910) and Theileria equi (Syn. Babesia equi , Laveran, 1901) by the polymerase chain reaction (PCR) in show and sport horses in the region of Ankara]. / Ankara yöresinde sportif ve gösteri amaçli yetistirilen atlarda Babesia caballi (Nuttall, 1910) ve Theileria equi (Syn. Babesia equi, Laveran, 1901)'nin yayilisinin polimeraz zincir reaksiyonu ile arastirilmasi.

The aim of this study was to compare the diagnosis of Babesia caballi and Theileria equi by the polymerase chain reaction (PCR) and microscopic examination of blood specimens collected from show and sport horses in the region of Ankara in 2004. The blood specimens were collected from randomly selected 200 show and sport horses in the region of Ankara during the tick season as well as before and after the tick season for PCR testing. At the same time, Giemsa stained peripheral blood smears were examined for the presence of Babesia spp. and also the horses were examined for the presence of ticks. Of the 200 horse blood samples analyzed, 3% were found to be positive by microscopic examination and and 10 % (B.caballi %3; T.equi %7) by the polymerase chain reaction. The difference between these two methods was confirmed to be statistically important (p < 0,001). This is the first study in which Babesia species were investigated in horses in Turkey using the PCR method. Theileria equi was found to be more prevalent than Babesia caballi.

Synchronization landscapes in small-world-connected computer networks.

Motivated by a synchronization problem in distributed computing we studied a simple growth model on regular and small-world networks, embedded in one and two dimensions. We find that the synchronization landscape (corresponding to the progress of the individual processors) exhibits Kardar-Parisi-Zhang-like kinetic roughening on regular networks with short-range communication links. Although the processors, on average, progress at a nonzero rate, their spread (the width of the synchronization landscape) diverges with the number of nodes (desynchronized state) hindering efficient data management. When random communication links are added on top of the one and two-dimensional regular networks (resulting in a small-world network), large fluctuations in the synchronization landscape are suppressed and the width approaches a finite value in the large system-size limit (synchronized state). In the resulting synchronization scheme, the processors make close-to-uniform progress with a nonzero rate without global intervention. We obtain our results by "simulating the simulations," based on the exact algorithmic rules, supported by coarse-grained arguments.

Extreme fluctuations in small-world networks with relaxational dynamics.

We study the distribution and scaling of the extreme height fluctuations for Edwards-Wilkinson-type relaxation on small-world substrates. When random links are added to a one-dimensional lattice, the average size of the fluctuations becomes finite (synchronized state) and the extreme height diverges only logarithmically in the large system-size limit. This latter property ensures synchronization in a practical sense in small-world coupled multi-component autonomous systems. The statistics of the extreme heights is governed by the Fisher-Tippett-Gumbel distribution.

Suppressing roughness of virtual times in parallel discrete-event simulations.

In a parallel discrete-event simulation (PDES) scheme, tasks are distributed among processing elements (PEs) whose progress is controlled by a synchronization scheme. For lattice systems with short-range interactions, the progress of the conservative PDES scheme is governed by the Kardar-Parisi-Zhang equation from the theory of nonequilibrium surface growth. Although the simulated (virtual) times of the PEs progress at a nonzero rate, their standard deviation (spread) diverges with the number of PEs, hindering efficient data collection. We show that weak random interactions among the PEs can make this spread nondivergent. The PEs then progress at a nonzero, near-uniform rate without requiring global synchronizations.