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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.

Simulating large systems often leaves the programmer with only one option: parallel distributed simulations where parts of the system are allocated and simulated on different processing elements (PEs). A large [...], 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.

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. [ABSTRACT FROM AUTHOR]

Synchronization is a fundamental problem in natural and artificial coupled multi-component systems. We investigate to what extent small-world couplings (extending the original local relaxational dynamics through the random links) lead to the suppression of extreme fluctuations in the synchronization landscape of such systems. In the absence of the random links, the steady-state landscape is "rough" (strongly de-synchronized state) and the average and the extreme height fluctuations diverge in the same power-law fashion with the system size (number of nodes). With small-world links present, the average size of the fluctuations becomes finite (synchronized state). For exponential-like noise the extreme heights diverge only logarithmically with the number of nodes, while for power-law noise they diverge in a power-law fashion. The statistics of the extreme heights are governed by the Fisher–Tippett–Gumbel and the Fréchet distribution, respectively. We illustrate our findings through an actual synchronization problem in parallel discrete-event simulations. [ABSTRACT FROM AUTHOR]

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.