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Highlights • Perineal inclusion cysts may harbor clinically occult malignant degeneration. • Histological analysis of large inclusion cysts required to rule out occult malignancy. • Perineal cysts with malignant degeneration are diagnostic, reconstructive challenge. • Risk of malignancy in perineal inclusion cysts helps treatment decisions. • Large perineal cyst requires multidisciplinary surgical team for excision and closure. • Colostomy as adjunct of perineal reconstruction after excision of inclusion cyst. • Perineal inclusion cysts may present as atypical, cavitating lesions., Introduction Cutaneous squamous cell cancer (cSCC) is a common condition, with straight forward and well-known heuristics regarding diagnosis, treatment, and surveillance. cSCC arising in an epidermal inclusion cyst is rare, but not unheard of. In contrast, the authors’ are unaware of any prior reports of cSCC arising in an epidermal inclusion cyst within an atypical cavernous and cavitating lesion in the perineum. Presentation of case A 48-year-old male presented with a cavitating and rapidly growing cutaneous perineal lesion. Preliminary diagnostic procedures (biopsy) showed benign pathology and imaging showed no involvement of perineal organs such as prostate or rectum. Discordance between initial diagnostics and clinical features prompted multi-specialty consultation, including dermatological pathology. Repeat biopsy yielded in situ, possibly invasive squamous cell cancer, arising in the background of an epidermal inclusion cyst. Wide excision with advancement flap reconstruction was employed, with temporary diverting colostomy to avoid perineal sepsis. Discussion Location and appearance of this lesion provided a diagnostic and treatment challenge requiring multi-specialty involvement for diagnosis and successful treatment. Specialists from urology, general surgery, dermatology, general and dermatological pathology, plastic and reconstructive surgery, colorectal surgery and medical and radiation oncology were involved in diagnosis, treatment plan and execution. None of the specialists involved had seen this singular presentation before, and this created an ownership and management challenge. Conclusion The cavitating, atypical appearance of lesion complicated diagnosis. Location required pre-treatment coordination and deliberation between dermatology, urology, general surgery, and plastic surgery. Malignant degeneration of inclusion cysts, although rare, has to be kept in mind, especially when presenting with rapid growth, and persistence in ruling out malignant diagnosis is fundamental.

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Autonomous vehicles are expected to play a key role in the future of urban transportation systems, as they offer potential for additional safety, increased productivity, greater accessibility, better road efficiency, and positive impact on the environment. Research in autonomous systems has seen dramatic advances in recent years, due to the increases in available computing power and reduced cost in sensing and computing technologies, resulting in maturing technological readiness level of fully autonomous vehicles. The objective of this paper is to provide a general overview of the recent developments in the realm of autonomous vehicle software systems. Fundamental components of autonomous vehicle software are reviewed, and recent developments in each area are discussed. Keywords: autonomous vehicles; localization; perception; planning; automotive control; multi-vehicle cooperation

Replicating plasmids are highly unstable in yeast, because they are retained in mother cells. The 2 mu circle plasmid overcomes this maternal inheritance bias by using a partitioning system that involves the plasmid encoded proteins Rep1p and Rep2p, and the cis-acting locus STB. It is thus widely exploited as a cloning vehicle in yeast. However, little is known about the cellular or molecular mechanisms by which effective partitioning is achieved, and models of both free diffusion and plasmid localisation have been proposed. Here we show that Rep1p and Rep2p proteins interact to form homo- and hetero-complexes in vitro. In vivo, Rep1p and Rep2p are shown to be nuclear proteins, exhibiting sub-nuclear concentration in distinct foci. The number of foci appears constant regardless of plasmid copy number and cell ploidy level. Before cell division, the number of foci increases, and we observe approximately equal allocation of foci to mother and daughter cell nuclei. We show that whereas Rep2p expressed alone is found exclusively in the nucleus, Rep1p requires the presence of Rep2p for effective nuclear localisation. High levels of 2 mu plasmid induce a multiple-budded elongated cell phenotype, which we show can be phenocopied by overexpression of both REP1 and REP2 together but not alone. Taken together, these results suggest that Rep1p and Rep2p interact in vivo, and occupy defined nuclear sites that are allocated to both mother and daughter nuclei during division. We propose a model for 2 mum plasmid partitioning based on these results, involving the association of plasmid DNA with specific, segregated subnuclear sites.

The stable maintenance of the 2 microm circle plasmid depends on its ability to overcome intrinsic maternal inheritance bias, which in yeast normally results in the failure to transmit DNA molecules efficiently to daughter cells. In addition to the plasmid proteins Rep1 and Rep2 acting on the plasmid DNA locus STB, it is likely that other chromosomally encoded yeast proteins are required. We have isolated mutants of yeast unable to maintain 2 microm and found that RSC2 is essential for 2 microm to overcome maternal inheritance bias. Rsc2 is part of a multisubunit RSC chromatin remodeling complex, and we show that in the absence of Rsc2 the chromatin structure of the STB region is significantly altered and the Rep1 protein loses its normal localization to subnuclear foci. Rsc1, a closely related homolog of Rsc2 present in an alternative form of the RSC complex, is not required for 2 microm maintenance and does not replace the requirement for Rsc2 when overexpressed. This represents the first specific role for Rsc2 that has been related to a change in chromatin structure, as well as the first direct evidence linking chromatin structure to 2 microm segregation.

In eukaryotic cells, surveillance mechanisms detect and respond to DNA damage by triggering cell-cycle arrest and inducing the expression of DNA-repair genes [1]. In budding yeast, a single DNA double-strand break (DSB) is sufficient to trigger cell-cycle arrest [2]. One highly conserved pathway for repairing DNA DSBs is DNA non-homologous end-joining (NHEJ), which depends on the DNA end-binding protein Ku [3]. NHEJ also requires the SIR2, SIR3 and SIR4 gene products [4,5], which are responsible for silencing at telomeres and the mating-type loci [6]. Because of the link between NHEJ and the Sir proteins, we investigated whether DNA damage influences telomeric silencing. We found that DNA damage triggers the reversible loss of telomeric silencing and relocation of Sir3p from telomeres. Complete Sir3p relocation was triggered by a single DNA DSB, suggesting that the singal is amplified. Consistent with this idea, Sir3p relocation depended on the DNA damage-signalling components Ddc1p and Mec1p. Thus, signalling of DNA damage may release Sir3p from telomeres and permit its subsequent association with other nuclear subdomains to regulate transcription, participate in DNA repair and/or enhance genomic stability by other mechanisms.

Developmental studies of oligodendrocyte precursor cell migration and their implications for transplantation as therapy for multiple sclerosis