Analysis of Simulation Methods for Far-end Crosstalk Cancellation

The information capacity of current digital subscriber lines is limited mainly by a crosstalk in metallic cables. The influence of near-end crosstalk (NEXT) can be well cancelled by frequency duplex method, but the elimination of far-end crosstalk (FEXT) is not so easy. Therefore FEXT is the dominant source of disturbance in current digital subscriber lines (xDSL). One of the most promising solutions for far-end crosstalk cancellation is Vectored Discrete Multi-tone modulation (VDMT). For the testing of VDMT modulation efficiency it will be necessary to implement advanced methods for modeling of far-end crosstalk to obtain required predictions of the crosstalk behavior in a cable. The actual simple FEXT model is not very accurate and does not provide realistic results. That is why the new method for modeling of far-end crosstalk was developed and is presented in this paper. This advanced model is based on the capacitive and inductive unbalances between pairs in a cable and it also respects the cable’s internal structure. The results of the model are subsequently used for the simulation of VDMT modulation and its impact on the FEXT cancellation. These simulations are based on the estimations of transmission speed of VDSL2 lines with VDMT modulation

Quality control in the initiation of eukaryotic DNA replication

Origins of DNA replication must be regulated to ensure that the entire genome is replicated precisely once in each cell cycle. In human cells, this requires that tens of thousands of replication origins are activated exactly once per cell cycle. Failure to do so can lead to cell death or genome rearrangements such as those associated with cancer. Systems ensuring efficient initiation of replication, while also providing a robust block to re-initiation, play a crucial role in genome stability. In this review, I will discuss some of the strategies used by cells to ensure once per cell cycle replication and provide a quantitative framework to evaluate the relative importance and efficiency of individual pathways involved in this regulation

The long road to protect infants against severe RSV lower respiratory tract illness [version 1; peer review: 2 approved]

Severe respiratory syncytial virus (RSV) lower respiratory tract illness (LRTI) in infants has proven challenging to prevent. In the last 50 years, conceptually different approaches failed to evolve into viable preventive alternatives for routine use. Inactivated RSV vaccine (that is, formalin-inactivated RSV) elicited severe LRTI in RSV-infected toddlers pre-immunized as infants; early purified F protein approaches in pregnant women failed to elicit sufficient immunity more than a decade ago; a second-generation monoclonal antibody (mAb) of high potency against the virus (that is, motavizumab) caused severe adverse reactions in the skin, and owing to lack of efficacy against RSV subgroup B, an extended half-life mAb targeting site V in the RSV fusion protein (that is, REG2222) did not meet its primary endpoint. In the meantime, two protein F vaccines failed to prevent medically attended LRTI in the elderly. However, palivizumab and the recent results of the Novavax maternal immunization trial with ResVax demonstrate that severe RSV LRTI can be prevented by mAb and by maternal immunization (at least to a certain extent). In fact, disease prevention may also decrease the rates of recurrent wheezing and all-cause pneumonia for at least 180 days. In this review, we discuss the history of RSV vaccine development, previous and current vaccine strategies undergoing evaluation, and recent information about disease burden and its implications for the effects of successful preventive strategies

Xenopus Mcm10 is a CDK-substrate required for replication fork stability

<p>During S phase, following activation of the S phase CDKs and the DBF4-dependent kinases (DDK), double hexamers of Mcm2-7 at licensed replication origins are activated to form the core replicative helicase. Mcm10 is one of several proteins that have been implicated from work in yeasts to play a role in forming a mature replisome during the initiation process. Mcm10 has also been proposed to play a role in promoting replisome stability after initiation has taken place. The role of Mcm10 is particularly unclear in metazoans, where conflicting data has been presented. Here, we investigate the role and regulation of Mcm10 in <i>Xenopus</i> egg extracts. We show that <i>Xenopus</i> Mcm10 is recruited to chromatin late in the process of replication initiation and this requires prior action of DDKs and CDKs. We also provide evidence that Mcm10 is a CDK substrate but does not need to be phosphorylated in order to associate with chromatin. We show that in extracts depleted of more than 99% of Mcm10, the bulk of DNA replication still occurs, suggesting that Mcm10 is not required for the process of replication initiation. However, in extracts depleted of Mcm10, the replication fork elongation rate is reduced. Furthermore, the absence of Mcm10 or its phosphorylation by CDK results in instability of replisome proteins on DNA, which is particularly important under conditions of replication stress.</p

Inferring hidden Markov models from noisy time sequences: a method to alleviate degeneracy in molecular dynamics

We present a new method for inferring hidden Markov models from noisy time sequences without the necessity of assuming a model architecture, thus allowing for the detection of degenerate states. This is based on the statistical prediction techniques developed by Crutchfield et al., and generates so called causal state models, equivalent to hidden Markov models. This method is applicable to any continuous data which clusters around discrete values and exhibits multiple transitions between these values such as tethered particle motion data or Fluorescence Resonance Energy Transfer (FRET) spectra. The algorithms developed have been shown to perform well on simulated data, demonstrating the ability to recover the model used to generate the data under high noise, sparse data conditions and the ability to infer the existence of degenerate states. They have also been applied to new experimental FRET data of Holliday Junction dynamics, extracting the expected two state model and providing values for the transition rates in good agreement with previous results and with results obtained using existing maximum likelihood based methods.Comment: 19 pages, 9 figure

What potential do mosses have as biomonitors of POPs? A comparative study of hexachlorocyclohexane sorption

Persistent organic pollutants (POPs) pose a significant global threat to human health and the environment, and require continuous monitoring due to their ability to migrate long distances. Active biomonitoring using cloned mosses is an inexpensive but underexplored method to assess POPs, mainly due to the poor understanding of the loading mechanisms of these pollutants in mosses. In this work, Fontinalis antipyretica (aquatic moss) and Sphagnum palustre (terrestrial moss) were evaluated as potential biomonitors of hexachlorocyclohexanes (HCHs: α-, β-, γ-, δ-HCH), crucial POPs. Moss clones, grown in photobioreactors and subsequently oven-dried, were used. Their lipid composition and distribution were characterized through molecular and histochemical studies. Adsorption experiments were carried out in the aqueous phase using the repeated additions method and in the gas phase using an active air sampling technique based on solid-phase extraction, a pioneering approach in moss research. F. antipyretica exhibited greater lipid content in the walls of most cells and higher adsorption capacity for all HCH isomers in both gaseous and liquid environments. These findings highlight the need for further investigation of POP loading mechanisms in mosses and open the door to explore other species based on their lipid contentThis work was supported by the Governments of Spain (PID2019- 107879RB-100; PID2022-140985NB-C22) and Galicia (ED431C 2022/ 40; ED431B 2023/04, ED431C 2020/19) and was co-funded by ERDF (EU

MicroRNAs expression, chromosomal alterations and immunoglobulin variable Heavy chain hypermutations in Mantle Cell Lymphomas

The contribution of microRNAs (miR) to the pathogenesis of mantle cell lymphoma (MCL) is not well known.We investigated the expression of 86 mature miRs mapped to frequently altered genomic regions in MCL in CD5+/CD5 normal B cells, reactive lymph nodes, and purified tumor cells of 17 leukemic MCL, 12 nodal MCL, and 8MCL cell lines. Genomic alterations of the tumors were studied by single nucleotide polymorphism arrays and comparative genomic hybridization. Leukemic and nodal tumors showed a high number of differentially expressed miRs compared with purified normal B cells, but only some of them were commonly deregulated in both tumor types. An unsupervised analysis of miR expression profile in purified leukemic MCL cells revealed two clusters of tumors characterized by different mutational status of the immunoglobulin genes, proliferation signature, and number of genomic alterations. The expression of most miRs was not related to copy number changes in their respective chromosomal loci. Only the levels of miRs included in the miR-17-92 cluster were significantly related to genetic alterations at 13q31. Moreover, overexpression of miR-17-5p/miR-20a from this cluster was associated with high MYC mRNA levels in tumors with a more aggressive behavior. In conclusion, the miR expression pattern of MCL is deregulated in comparison with normal lymphoid cells and distinguishes two subgroups of tumors with different biological features.Postprint (updated version

'Islamic' consumers, markets, and marketing : a critique of El-Bassiouny's (2014) "The one-billion-plus marginalization"

In her article entitled 'The one-billion-plus marginalization: Toward a scholarly understanding of Islamic consumers', El-Bassiouny (2014) attempts to provide 'a comprehensive conceptualization for Islamic marketing and its foundational principles within the context of the Islamic faith' (p. 48). The present essay critiques some of the key assumptions that underpin El-Bassiouny’s discussion and her subsequent propositions for “future testing”, which are meant to offer an 'enlightened understanding of Islamic consumers' and 'benefit academics, practitioners, and policy makers' (pp. 42-43). This critical account argues: (1) apolitical and ahistorical analyses of markets and marketing phenomena in relation to Moslem geographies will only replicate imaginary juxtapositions between the West and Islam; (2) exceptionalist depictions of Moslem consumers can exacerbate inter- and/or intra-cultural misunderstandings; (3) theological and ethnocentric definitions of Islam and the oversimplification of Islamicness are less likely to help advance marketing theory, practice, and education in a global era