Synchronization Problems in Automata without Non-trivial Cycles

We study the computational complexity of various problems related to synchronization of weakly acyclic automata, a subclass of widely studied aperiodic automata. We provide upper and lower bounds on the length of a shortest word synchronizing a weakly acyclic automaton or, more generally, a subset of its states, and show that the problem of approximating this length is hard. We investigate the complexity of finding a synchronizing set of states of maximum size. We also show inapproximability of the problem of computing the rank of a subset of states in a binary weakly acyclic automaton and prove that several problems related to recognizing a synchronizing subset of states in such automata are NP-complete.Comment: Extended and corrected version, including arXiv:1608.00889. Conference version was published at CIAA 2017, LNCS vol. 10329, pages 188-200, 201

Presence and Seeding Activity of Pathological Prion Protein (PrPTSE) in Skeletal Muscles of White-Tailed Deer Infected with Chronic Wasting Disease

Chronic wasting disease (CWD) is a contagious, rapidly spreading transmissible spongiform encephalopathy (TSE), or prion disease, occurring in cervids such as white tailed-deer (WTD), mule deer or elk in North America. Despite efficient horizontal transmission of CWD among cervids natural transmission of the disease to other species has not yet been observed. Here, we report for the first time a direct biochemical demonstration of pathological prion protein PrPTSE and of PrPTSE-associated seeding activity, the static and dynamic biochemical markers for biological prion infectivity, respectively, in skeletal muscles of CWD-infected cervids, i. e. WTD for which no clinical signs of CWD had been recognized. The presence of PrPTSE was detected by Western- and postfixed frozen tissue blotting, while the seeding activity of PrPTSE was revealed by protein misfolding cyclic amplification (PMCA). Semi-quantitative Western blotting indicated that the concentration of PrPTSE in skeletal muscles of CWD-infected WTD was approximately 2000-10000 -fold lower than in brain tissue. Tissue-blot-analyses revealed that PrPTSE was located in muscle-associated nerve fascicles but not, in detectable amounts, in myocytes. The presence and seeding activity of PrPTSE in skeletal muscle from CWD-infected cervids suggests prevention of such tissue in the human diet as a precautionary measure for food safety, pending on further clarification of whether CWD may be transmissible to humans

Annual review article: Is it time to rethink the gender agenda in entrepreneurship research?

This article develops a critique of contemporary approaches to analysing the impact of gender upon entrepreneurial propensity and activity. Since the 1990s, increasing attention has been afforded to the influence of gender upon women’s entrepreneurial behaviour; such analyses have highlighted an embedded masculinity within the entrepreneurial discourse which privileges men as normative entrepreneurial actors. Whilst invaluable in revealing a prevailing masculine bias within entrepreneurship, this critique is bounded by positioning women as a proxy for the gendered subject. This is a potentially limiting analysis that does not fully recognise gender as a human property with myriad articulations enacted throughout entrepreneurial activity. To progress debate, we engage more deeply with the notion of gender as a multiplicity exploring the implications of such for future studies of entrepreneurial activity

Experimental Oral Transmission of Chronic Wasting Disease to Reindeer (Rangifer tarandus tarandus)

Chronic wasting disease (CWD), a transmissible spongiform encephalopathy of cervids, remains prevalent in North American elk, white-tailed deer and mule deer. A natural case of CWD in reindeer (Rangifer tarandus tarandus) has not been reported despite potential habitat overlap with CWD-infected deer or elk herds. This study investigates the experimental transmission of CWD from elk or white-tailed deer to reindeer by the oral route of inoculation. Ante-mortem testing of the three reindeer exposed to CWD from white-tailed deer identified the accumulation of pathological PrP (PrPCWD) in the recto-anal mucosa associated lymphoid tissue (RAMALT) of two reindeer at 13.4 months post-inoculation. Terminal CWD occurred in the two RAMALT-positive reindeer at 18.5 and 20 months post-inoculation while one other reindeer in the white-tailed deer CWD inoculum group and none of the 3 reindeer exposed to elk CWD developed disease. Tissue distribution analysis of PrPCWD in CWD-affected reindeer revealed widespread deposition in central and peripheral nervous systems, lymphoreticular tissues, the gastrointestinal tract, neuroendocrine tissues and cardiac muscle. Analysis of prion protein gene (PRNP) sequences in the 6 reindeer identified polymorphisms at residues 2 (V/M), 129 (G/S), 138 (S/N) and 169 (V/M). These findings demonstrate that (i) a sub-population of reindeer are susceptible to CWD by oral inoculation implicating the potential for transmission to other Rangifer species, and (ii) certain reindeer PRNP polymorphisms may be protective against CWD infection

Expression of Bmi-1 is a prognostic marker in bladder cancer

<p>Abstract</p> <p>Background</p> <p>The molecular mechanisms of the development and progression of bladder cancer are poorly understood. The objective of this study was to analyze the expression of Bmi-1 protein and its clinical significance in human bladder cancer.</p> <p>Methods</p> <p>We examined the expression of Bmi-1 mRNA and Bmi-1 protein by RT-PCR and Western blot, respectively in 14 paired bladder cancers and the adjacent normal tissues. The expression of Bmi-1 protein in 137 specimens of bladder cancer and 30 specimens of adjacent normal bladder tissue was determined by immunohistochemistry. Statistical analyses were applied to test the relationship between expression of Bmi-1, and clinicopathologic features and prognosis.</p> <p>Results</p> <p>Expression of Bmi-1 mRNA and protein was higher in bladder cancers than in the adjacent normal tissues in 14 paired samples (<it>P </it>< 0.01). By immunohistochemical examination, five of 30 adjacent normal bladder specimens (16.7%) versus 75 of 137 bladder cancers (54.3%) showed Bmi-1 protein expression (<it>P </it>< 0.05). Bmi-1 protein expression was intense in 20.6%, 54.3%, and 78.8% of tumors of histopathological stages G1, G2, and G3, respectively (<it>P </it>< 0.05). Expression of Bmi-1 protein was greater in invasive bladder cancers than in superficial bladder cancers (81.5% versus 32.5%, <it>P </it>< 0.05). In invasive bladder cancers, the expression of Bmi-1 protein in progression-free cancers was similar to that of cancers that have progressed (80.0% versus 82.4%, <it>P </it>> 0.5). In superficial bladder cancers, the expression of Bmi-1 protein in recurrent cases was higher than in recurrence-free cases (62.5% versus 13.7%, <it>P </it>< 0.05). Bmi-1 expression was positively correlated with tumor classification and TNM stage (<it>P </it>< 0.05), but not with tumor number (<it>P </it>> 0.05). Five-year survival in the group with higher Bmi-1 expression was 50.8%, while it was 78.5% in the group with lower Bmi-1 expression (<it>P </it>< 0.05). Patients with higher Bmi-1 expression had shorter survival time, whereas patients with lower Bmi-1 expression had longer survival time (<it>P </it>< 0.05).</p> <p>Conclusion</p> <p>Expression of Bmi-1 was greater in bladder cancers than in the adjacent normal tissues. The examination of Bmi-1 protein expression is potentially valuable in prognostic evaluation of bladder cancer.</p

A Review of Chemosensation and Related Behavior in Aquatic Insects

Insects that are secondarily adapted to aquatic environments are able to sense odors from a diverse array of sources. The antenna of these insects, as in all insects, is the main chemosensory structure and its input to the brain allows for integration of sensory information that ultimately ends in behavioral responses. Only a fraction of the aquatic insect orders have been studied with respect to their sensory biology and most of the work has centered either on the description of the different types of sensilla, or on the behavior of the insect as a whole. In this paper, the literature is exhaustively reviewed and ways in which antennal morphology, brain structure, and associated behavior can advance better understanding of the neurobiology involved in processing of chemosensory information are discussed. Moreover, the importance of studying such group of insects is stated, and at the same time it is shown that many interesting questions regarding olfactory processing can be addressed by looking into the changes that aquatic insects undergo when leaving their aquatic environment

Systemic Immune Activation in HIV Infection Is Associated with Decreased MDC Responsiveness to TLR Ligand and Inability to Activate Naive CD4 T-Cells

HIV infection is characterized by ineffective anti-viral T-cell responses and impaired dendritic cell (DC) functions, including response to Toll-Like Receptor (TLR) ligands. Because TLR responsiveness may affect a host's response to virus, we examined TLR ligand induced Myeloid and Plasmacytoid DC (MDC and PDC) activation of naïve T-cells in HIV+ subjects.Freshly purified MDC and PDC obtained from HIV+ subjects and healthy controls were cultured in the presence and absence of TLR ligands (poly I∶C or R-848). We evaluated indices of maturation/activation (CD83, CD86, and HLA-DR expression), cytokine secretion (IFN-alpha and IL-6), and ability to activate allogeneic naïve CD4 T-cells to secrete IFN-gamma and IL-2.MDC from HIV+ subjects had increased spontaneous IL-6 production and increased CD83 and CD86 expression when compared to MDC of controls. MDC IL-6 expression was associated with plasma HIV level. At the same time, poly I∶C induced HLA-DR up-regulation on MDC was reduced in HIV+ persons when compared to controls. The latter finding was associated with impaired ability of MDC from HIV+ subjects to activate allogeneic naïve CD4 T-cells. PDC from HIV+ persons had increased spontaneous and TLR ligand induced IL-6 expression, and increased HLA-DR expression at baseline. The latter was associated with an intact ability of HIV PDC to activate allogeneic naïve CD4 T-cells.These results have implications for the ability of the HIV+ host to form innate and adaptive responses to HIV and other pathogens

Mathematical modeling of microRNA-mediated mechanisms of translation repression

MicroRNAs can affect the protein translation using nine mechanistically different mechanisms, including repression of initiation and degradation of the transcript. There is a hot debate in the current literature about which mechanism and in which situations has a dominant role in living cells. The worst, same experimental systems dealing with the same pairs of mRNA and miRNA can provide ambiguous evidences about which is the actual mechanism of translation repression observed in the experiment. We start with reviewing the current knowledge of various mechanisms of miRNA action and suggest that mathematical modeling can help resolving some of the controversial interpretations. We describe three simple mathematical models of miRNA translation that can be used as tools in interpreting the experimental data on the dynamics of protein synthesis. The most complex model developed by us includes all known mechanisms of miRNA action. It allowed us to study possible dynamical patterns corresponding to different miRNA-mediated mechanisms of translation repression and to suggest concrete recipes on determining the dominant mechanism of miRNA action in the form of kinetic signatures. Using computational experiments and systematizing existing evidences from the literature, we justify a hypothesis about co-existence of distinct miRNA-mediated mechanisms of translation repression. The actually observed mechanism will be that acting on or changing the limiting "place" of the translation process. The limiting place can vary from one experimental setting to another. This model explains the majority of existing controversies reported.Comment: 40 pages, 9 figures, 4 tables, 91 cited reference. The analysis of kinetic signatures is updated according to the new model of coupled transcription, translation and degradation, and of miRNA-based regulation of this process published recently (arXiv:1204.5941). arXiv admin note: text overlap with arXiv:0911.179