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Urban mobility is an important component of a well-functioning city. Moreover, it is an important sector that must be considered in the steady transition of cities. During this transition, new opportunities for mobility technologies are constantly emerging, as, for example, electric Vertical Take-Off and Landing (eVTOL) aircraft. However, due to various factors, not every new mobility technology is suitable for every city. Finding suitable cities for implementing such a technology is therefore a crucial task. In our research, we address the problem of evaluating and ranking potential cities in terms of their suitability for the deployment of a particular emerging mobility technology. For this, we introduce an index and a framework for evaluating and ranking these cities. In this framework, we apply the novel Urban Mobility Innovation Adaption (UMIA) index and the well-known Analytical Hierarchy Process (AHP) to evaluate and rank each city regarding a chosen mobility technology. In our case study, we evaluate and rank cities on deploying eVTOL aircraft. Our results indicate the effectiveness and validity of our framework and the index. Based on this, a comprehensive analyze can be conducted for the top-ranked cities instead of all potential cities. Thus, the framework can support in the decision-making process for implementing new mobility technologies, but also support city officials to assess the current state of their city.

An advanced process for the manufacturing of aerogel-lined capillaries is presented; these are applicable as liquid-core waveguides for gaining the Raman signal of aqueous samples. With respect to the spin-coating process we have used so far for the manufacturing of aerogel-lined capillaries, the here-presented manufacturing process is advanced as it enables (i) the lining of longer capillaries, (ii) the adjustment of the lining-thickness via the lining velocity, and (iii) the reproducible generation of crack-free linings. The key parameters of the advanced process and their effect on the fabrication of aerogel-lined capillaries with optimal Raman signal gain are reported and related to the thickness and topography of the aerogel linings by the support of scanning electron microscopy.

Standardizing and translating species names from different databases is key to the successful integration of data sources in biodiversity research. There are numerous taxonomic name-resolution applications that implement increasingly powerful name-cleaning and matching approaches, allowing the user to resolve species relative to multiple backbones simultaneously. Yet there remains no principled approach for combining information across these underlying taxonomic backbones, complicating efforts to combine and merge species lists with inconsistent and conflicting taxonomic information. Here, we present Treemendous, an open-source software package for the R programming environment that integrates taxonomic relationships across four publicly available backbones to improve the name resolution of tree species. By mapping relationships across the backbones, this package can be used to resolve datasets with conflicting and inconsistent taxonomic origins, while ensuring the resulting species are accepted and consistent with a single reference backbone. The user can chain together different functionalities ranging from simple matching to a single backbone, to graph-based iterative matching using synonym-accepted relations across all backbones in the database. In addition, the package allows users to ‘translate’ one tree species list into another, streamlining the assimilation of new data into preexisting datasets or models. The package provides a flexible workflow depending on the use case, and can either be used as a stand-alone name-resolution package or in conjunction with existing packages as a final step in the name-resolution pipeline. The Treemendous package is fast and easy to use, allowing users to quickly merge different data sources by standardizing their species names according to the regularly updated database. By combining taxonomic information across multiple backbones, the package increases matching rates and minimizes data loss, allowing for more efficient translation of tree species datasets to aid research into forest biodiversity and tree ecology.

Soil microbial growth, respiration, and carbon (C) use efficiency (CUE) are essential parameters to understand, describe and model the soil carbon cycle. While seasonal dynamics of microbial respiration are well studied, little is known about how microbial growth and CUE change over the course of a year, especially outside the plant growing season. In this study, we measured soil microbial respiration, gross growth via 18O incorporation into DNA, and biomass in an agricultural field and a deciduous forest 16 times over the course of two years. We sampled soils to a depth of 5 cm from plots at which harvest residues or leaf litter remained on the plot or was removed. We observed strong seasonal variations of microbial respiration, growth, and biomass. All these microbial parameters were significantly higher at the forest site, which contained 4.3 % organic C compared to the agricultural site with 0.9 % organic C. CUE also varied strongly (0.1 to 0.7) but was overall significantly higher at the agricultural site compared to the forest site. We found that microbial respiration and to a lesser extent microbial growth followed the seasonal dynamics of soil temperature. Microbial growth was further affected by the presence of plants in the agricultural system or foliage in the forest. At low temperatures in winter, both microbial respiration and gross growth showed the lowest rates, whereas CUE (calculated from both respiration and growth) showed amongst the highest values determined during the two years, due to the higher temperature sensitivity of microbial respiration. Microbial biomass C strongly increased in winter. Surprisingly, this winter peak was not connected to high microbial growth or an increase in DNA content. This suggests that microorganisms accumulated C and N, potentially in the form of osmo- or cryoprotectants or increased in cell size but did not divide. This microbial winter bloom and following decline, where C is released from microbial biomass and freely available, might constitute a highly dynamic time in the annual C cycle in temperate soil systems. Highly variable CUE, which was observed in our study, and the fact that CUE is calculated from independently controlled microbial respiration and microbial growth, ask for great caution when CUE is used to describe soil microbial physiology, soil C dynamics or C sequestration. Instead, microbial respiration, microbial growth, and microbial biomass C should be investigated individually in combination to better understand the soil C cycle.

Feeling safe is a major issue for cyclists, and some potential cyclists are still deterred from using the bicycle because they feel too unsafe. Assessing the subjective safety of existing cycling infrastructures and locations can be done by questionnaires that show pictures of infrastructures and ask participants for their safety ratings. However, future cycling infrastructures should also be evaluated as safe even before they are implemented. Therefore, it is desirable to have a method that is able to predict safety from infrastructural information. This study aims to propose two different ways for such a method and to test both ways in a use case. We first developed two scores, namely the Repertory Grid (RG) Score and the FixMyBerlin (FMB) Score, which predict subjective safety from objective environmental information but use different data bases and different methodologies. In a second step, we validated these scores by comparing them to questionnaire ratings that evaluated cyclists’ subjective safety at 20 locations in the city of Braunschweig, Germany. Finally, we compared the two scores as well as the questionnaire ratings with objective safety measures, namely crash statistics, at the respective locations. The results show that the RG Score has a moderate agreement and the FMB Score has a fair agreement with the questionnaire ratings. All methods agree on the overall safety evaluation of various cycling facilities. However, the RG Score showed less variance in the safety ratings, whereas the FMB Score rated most locations more unsafe than the participants in the questionnaire. Interestingly, neither the scores nor the questionnaire ratings could sufficiently deduce the occurrence of a crash at one of the locations. The findings strengthen the importance of subjective safety as a construct independent of objective safety. Furthermore, they provide insights into aspects of subjective safety that can easily be measured by objective scores, and into aspects that are important for cyclists but were not yet covered by the scores. This study, therefore, provides a basis for future considerations and future evaluation methods to assess the subjective safety of cyclists.

That light propagating in a gravitational field gets frequency-shifted is one of the basic consequences of any metric theory of gravity rooted in the equivalence principle. At the same time, also a time dependent material’s refractive index can frequency-shift light propagating in it. The mathematical analogy between the two effects is such that the latter has been used to study the optical analogue of a black-hole spacetime. Here, we combine these two effects by showing that light propagation in non-linear media in the presence of a moving refractive index perturbation can lead to a gravity-dependent blueshift. We find that the predicted blueshift surpasses the gravitational redshift even if the medium is considered to be perfectly stiff. In realistic scenarios, by far the strongest frequency shift arises due to the deformation of the dielectric medium and the corresponding photoelastic change of refractive index. This has the potential to facilitate optical sensing of small gravity gradients.

The topology of the surface states of a bismuth crystal remains an ongoing debate. Here, the authors observe surface electric conductivity with a magnetic field parallel to the two-dimensional boundary between the three-dimensional bismuth crystal and vacuum, but this effect is absent in antimony crystals indicating a link between band symmetry and boundary conductance.

Transport of energetic electrons in the heliosphere is governed by resonant interaction with plasma waves, for electrons with sub-GeV kinetic energies specifically with dispersive modes in the whistler regime. In this paper, particle-in-cell simulations of kinetic turbulence with test-particle electrons are performed. The pitch-angle diffusion coefficients of these test particles are analyzed and compared to an analytical model for left-handed and right-handed polarized wave modes.

The electromagnetic emission from neutron star mergers is comprised of multiple components. Synchrotron emission from the disk-powered jet and thermal emission from the merger ejecta (powered by a variety of sources) are among the most studied sources. The low masses and high velocities of the merger ejecta quickly develop conditions where emission from collisionless shocks becomes critical and synchrotron emission from the merger ejecta constitutes a third component to the observed signal. The aim of this project is to examine shock development, magnetic field generation, and particle acceleration in the case of mildly relativistic shocks, which are expected when the tidal ejecta of neutron star mergers drive a shock into the external medium. Using LANL’s vector particle-in-cell (VPIC) code, we have run simulations of such mildly relativistic, collisionless, weakly magnetized plasmas and computed the resultant magnetic fields and particle energy spectra. We show the effects of varying plasma conditions, as well as explore the validity of using different proton-to-electron mass ratios in VPIC. Our results have implications for observing late-time electromagnetic counterparts to gravitational wave detections of neutron star mergers.

Abstract The determination of the neutrino mass is one of the major challenges in astroparticle physics today. Direct neutrino mass experiments, based solely on the kinematics of $$\upbeta $$ β -decay, provide a largely model-independent probe to the neutrino mass scale. The Karlsruhe Tritium Neutrino (KATRIN) experiment is designed to directly measure the effective electron antineutrino mass with a sensitivity of $$0.2\hbox { eV}$$ 0.2eV ($$90\%$$ 90% CL). In this work we report on the first operation of KATRIN with tritium which took place in 2018. During this commissioning phase of the tritium circulation system, excellent agreement of the theoretical prediction with the recorded spectra was found and stable conditions over a time period of 13 days could be established. These results are an essential prerequisite for the subsequent neutrino mass measurements with KATRIN in 2019.

We report an experimental study on the gain of the Raman signal of aqueous mixtures and liquid water when confined in aerogel-lined capillaries of various lengths of up to 20 cm and various internal diameters between 530 and 1000 µm. The lining was made of hydrophobised silica aerogel, and the carrier capillary body consisted of fused silica or borosilicate glass. Compared to the Raman signal detected from bulk liquid water with the same Raman probe, a Raman signal 27 times as large was detected when the liquid water was confined in a 20 cm-long capillary with an internal diameter of 700 µm. In comparison with silver-lined capillaries of the same length and same internal diameter, the aerogel-lined capillaries featured a superior Raman signal gain and a longer gain stability when exposed to mixtures of water, sugar, ethanol and acetic acid.

We study possibilities of creation and detection of oscillating gravitational fields from lab-scale high energy, relativistic sources. The sources considered are high energy laser beams in an optical cavity and the ultra-relativistic proton bunches circulating in the beam of the large hadron collider (LHC) at CERN. These sources allow for signal frequencies much higher and far narrower in bandwidth than what most celestial sources produce. In addition, by modulating the beams, one can adjust the source frequency over a very broad range, from Hz to GHz. The gravitational field of these sources and responses of a variety of detectors are analyzed. We optimize a mechanical oscillator such as a pendulum or torsion balance as detector and find parameter regimes such that—combined with the planned high-luminosity upgrade of the LHC as a source—a signal-to-noise ratio substantially larger than 1 should be achievable at least in principle, neglecting all sources of technical noise. This opens new perspectives of studying general relativistic effects and possibly quantum-gravitational effects with ultra-relativistic, well-controlled terrestrial sources.

The Karlsruhe Tritium Neutrino (KATRIN) experiment aims at measuring the effective electron neutrino mass with a sensitivity of 0.2 eV/c2, i.e., improving on previous measurements by an order of magnitude. Neutrino mass data taking with KATRIN commenced in early 2019, and after only a few weeks of data recording, analysis of these data showed the success of KATRIN, improving on the known neutrino mass limit by a factor of about two. This success very much could be ascribed to the fact that most of the system components met, or even surpassed, the required specifications during long-term operation. Here, we report on the performance of the laser Raman (LARA) monitoring system which provides continuous high-precision information on the gas composition injected into the experiment’s windowless gaseous tritium source (WGTS), specifically on its isotopic purity of tritium—one of the key parameters required in the derivation of the electron neutrino mass. The concentrations cx for all six hydrogen isotopologues were monitored simultaneously, with a measurement precision for individual components of the order 10−3 or better throughout the complete KATRIN data taking campaigns to date. From these, the tritium purity, εT, is derived with precision of −3 and trueness of −3, being within and surpassing the actual requirements for KATRIN, respectively.

Within the scope of this work, a new surface engineering technology named laser implantation has been investigated, in order to improve the tribological performance of hot stamping tools. This technique is based on manufacturing highly wear-resistant, separated, and elevated microfeatures by embedding hard ceramic particles into the tool surface via pulsed laser radiation. Hence, the topography and material properties of the tool are modified, which influences the thermal and tribological interactions at the blank-die interface. To verify these assumptions and to clarify the cause–effect relations, different titanium-based particles (TiB2, TiC, TiN) were laser-implanted and subsequently analyzed regarding to their geometrical shape and mechanical properties. Afterwards, quenching tests as well as tribological experiments were carried out by using titanium-diboride as the most promising implantation material for reducing the tribological load due to high hardness value of the generated implants. Compared to conventional tooling systems, the modified tool surfaces revealed a significantly higher wear resistance as well as reduced friction forces while offering the possibility to adjust the thermal interactions at the blank-die interface. Based on these results, a tailored tool surface modification can be pursued in future research work, in order to enhance the effectiveness of the hot stamping technology.

The actomyosin ring generates force to ingress the cytokinetic cleavage furrow in animal cells, yet its filament organization and the mechanism of contractility is not well understood. We quantified actin filament order in human cells using fluorescence polarization microscopy and found that cleavage furrow ingression initiates by contraction of an equatorial actin network with randomly oriented filaments. The network subsequently gradually reoriented actin filaments along the cell equator. This strictly depended on myosin II activity, suggesting local network reorganization by mechanical forces. Cortical laser microsurgery revealed that during cytokinesis progression, mechanical tension increased substantially along the direction of the cell equator, while the network contracted laterally along the pole-to-pole axis without a detectable increase in tension. Our data suggest that an asymmetric increase in cortical tension promotes filament reorientation along the cytokinetic cleavage furrow, which might have implications for diverse other biological processes involving actomyosin rings.

Nanocrystalline ZnO, ZnO(Ga), and ZnO(Ga, In) samples with different indium contents were prepared by wet-chemical method and characterized in detail by ICP-MS and XRD methods. Gas sensing properties toward NO2 were studied at 150–450 °C by DC conductance measurements. The optimal temperature for gas sensing experiments was determined. The dependence of the ZnO(Ga, In) sensor signal to NO2 at 250 °C correlates with the change of conductivity of the samples. The introduction of indium into the system leads to an increase in the values of the sensor signal in the temperature range T < 250 °C. The investigation of the local sample conductivity by scanning spreading resistance microscopy demonstrates that, at high indium content, the sensor properties are determined by the In–Ga–Zn–O layer that forms on the ZnO surface.

For improved tumor staging and therapy control, imaging biomarkers are of great interest allowing a noninvasive characterization of invasiveness. In squamous epithelial skin and cervix lesions, transition to invasive stages is associated with enhanced matrix metalloproteinase (MMP) activity, increased angiogenesis, and worsened prognosis. Thus, we investigated MMP activity as imaging biomarker of invasiveness and the potential of optical tomography in characterizing the angiogenic and invasive behavior of skin squamous cell carcinoma (SCC) xenografts. MMP activity was measured in vivo in HaCaT-ras A-5RT3 tumors at different angiogenic and invasive stages (onset of angiogenesis, intermediate and highly angiogenic, invasive stage) and after 1 week of sunitinib treatment by fluorescence molecular tomography–microcomputed tomography imaging using an activatable probe. Treatment response was additionally assessed morphologically by optical coherence tomography (OCT). In vivo MMP activity significantly differed between the groups, revealing highest levels in the highly angiogenic, invasive tumors that were confirmed by immunohistochemistry. At the onset of angiogenesis with lowest MMP activity, fibroblasts were detected in the MMP-positive areas, whereas macrophages were absent. Accumulation of both cell types occurred in both invasive groups, again to a significantly higher degree at the most invasive and angiogenic stage. Sunitinib treatment significantly reduced the MMP activity and accumulation of fibroblasts and macrophages and blocked tumor invasion that was additionally visualized by OCT. Human cervical SCCs also showed high MMP activity and a similar stromal composition as the HaCaT xenografts, whereas normal tissue was negative. This study strongly suggests MMP activity as imaging biomarker and demonstrates the high sensitivity of optical tomography in determining tumor invasiveness that can morphologically be supported by OCT.

In this contribution, the first examples of the catalytic highly enantioselective reduction of cyclic meso-anhydrides to lactones and of thioanhydrides to thiolactones are described. The N-benzyl protected key building blocks in the industrial synthesis of (+)-biotin were so far only accessible by usage of expensive reagents in multi-step procedures. In contrast, homogeneous catalytic enantioselective hydrogenation of the corresponding meso-anhydride mediated by a metal phosphane complex proceeds with high optical induction (ee >95%) and excellent yield. The catalytic system provides a generally applicable new method for the preparation of lactones from cyclic anhydrides.

The development of enantioselective catalytic processes for the manufacture of chiral intermediates is a very complex endeavor and can be very time consuming and expensive. In this contribution the major issues which might lead to long development times will be discussed and strategies to deal with these problems are described. The general part is illustrated with the approach Solvias has chosen for assisting and supporting the development of enantioselective homogeneous hydrogenation processes, at the moment the most important industrial application of asymmetric catalysis. Special emphasis is given to the application of high-throughput screening (HTS) using a Symyx HiP system and the description of the Solvias portfolio of chiral ligands which makes a broad variety of diphosphine ligands available for all phases of process development from the first screening experiments to the large-scale manufacturing phase. Four case histories serve to illustrate the generic description of the development process.

The synthesis of P-stereogenic ligands bearing 2,6-disubstituted phenyl groups at the P atom is a challenging problem. The results reported herein help define the scope and limitations of the existing synthetic protocols, such as Jugé's oxazaphospholidine borane method and the enantioselective deprotonation of P(BH3)(CH3)2(R) developed by Evans and Imamoto. Jugé's new approach based on chlorophosphine boranes was exploited for the preparation of a C1-symmetric MiniPhos-like ligand. Preliminary results concerning the application of the new ligands in the rhodium and ruthenium hydrogenation of olefins are also reported.

The development of an enantioselective catalytic process for the technical preparation of chiral agrochemicals is illustrated by the case history of the herbicide (S)-metolachlor (trade name Dual Magnum®). Four synthetic routes were investigated in some detail. The key step for the technical process of the enantiomerically enriched compound is the asymmetric hydrogenation of an imine intermediate made possible by a new iridium ferrocenyl diphosphine catalyst system. Using optimized conditions, the isolated imine can be hydrogenated at a hydrogen pressure of 80 bar and 50°C with a substrate-to-catalyst ratio of >1'000'000. Complete conversion is reached within 4 h with an enantioselectivity of 79% with an initial turnover frequency (tof) exceeding 1'800'000 h?1. This sets a new standard for the technical application of enantioselective catalysts. Important aspects and results for the different phases of the process development of the catalyst system as well as minimal prerequisites for the use of enantioselective catalysts for the production of agrochemicals are discussed.

The use of enantioselective catalytic methods for the technical preparation of chiral agrochemicals is illustrated by the case history of the herbicide (S)-merolachlor (trade name DUAL MAGNUM®). The key step for the technical synthesis of the enantiomerically enriched compound is the asymmetric hydrogenation of an imine intermediate, made possible by a new iridium-ferrocenyldiphosphine catalyst system. Important aspects of the development of the catalyst system as well as minimal prerequisites for the use of enantioselective catalysts for the production of agrochemicals are discussed.

Objective:  Similar to Human Papillomavirus (HPV) genotypes, different lineages of a genotype also have different carcinogenic capabilities. Studies have shown that specific genotype lineages of oncogenic HPV are associated with variable risks for the development of cervical intraepithelial neoplasia (CIN2/CIN3) and cervical cancer. The present study aimed to analyze the genetic diversity of the HPV16 genotype in women with CIN2/CIN3 and cervical cancer, from the northeast region of Brazil., Methods:  A cross-sectional multicenter study was conducted in the northeast region of Brazil, from 2014 to 2016. This study included 196 cases of HPV16 variants (59 and 137 cases of CIN2/CIN3 and cervical cancer, respectively). The difference of proportion test was used to compare patients with CIN2/CIN3 and cervical cancer, based on the prevalent HPV16 lineage ( p  < 0.05)., Results:  According to the histopathological diagnosis, the percentage of lineage frequencies revealed a marginal difference in the prevalence of lineage A in CIN2/CIN3, compared with that in cervical cancer ( p  = 0.053). For lineage D, the proportion was higher in cancer cases (32.8%), than in CIN2/CIN3 cases (16.9%), with p  = 0.023., Conclusion:  HPV16 lineage A was the most frequent lineage in both CIN2/CIN3 and cervical cancer samples, while lineage D was predominant in cervical cancer, suggesting a possible association between HPV16 lineage D and cervical cancer., Competing Interests: The authors have no conflict of interest to declare., (Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Multiple infections by HPV genotypes are frequently detected in HPV+ cervical lesions but the interaction between each viral genotype during carcinogenesis is poorly understood. Here we carried out a comprehensive study to characterize the multiple HPV expression and integration by RNA-seq analyses of 19 invasive cervical carcinomas coinfected by several HPV genotypes. Analysis of tumor DNA by a hybridization assay indicated multiple infections ranging from 2 to 6 different HPV genotypes. RNA-seq analysis showed that a single HPV genotype was preferentially expressed. Finally, the search for HPV/human chimeric transcripts indicated integration from preferentially expressed genotypes. In conclusion, the present study indicated that, in invasive cervical carcinomas infected by multiple HPV genotypes, one HPV was preferentially expressed, supporting the hypothesis that a single HPV genotype was associated with cancer development., Competing Interests: Declaration of Competing Interest The authors declare that they do not have conflicting interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: The human papillomavirus (HPV) E5 gene encodes a small and highly hydrophobic oncoprotein that affects immune evasion, cell proliferation, loss of apoptotic capacity and angiogenesis in tumors. E5 shows an affinity for biological membranes and was associated with an increase of epidermal growth factor/epidermal growth factor receptor (EGF/EGFR) signaling through the accumulation of EGFR in cellular membranes. Due to the frequent integration of the HPV genome into the host cell genome, E5 is frequently not transcribed in cervical tumors., Aim: In this study we looked forward to verifying whether the potential expression of E5 protein in human papillomavirus 16 positive (HPV16 + ) and human papillomavirus 18 positive (HPV18 + ) cervical tumors was associated with levels of EGFR and vascular endothelial growth factor A (VEGFA) transcription and with patients overall survival., Results: Association between the presence of E5 transcripts and viral genome disruption was observed for HPV16 + and HPV18 + tumors. Association was not observed between tumors potentially capable of translating E5 and EGFR or VEGFA transcriptional levels. Similarly, the capability of translating E5 and overall survival in patients with HPV16 + squamous cell carcinoma tumors stage ≥ IB2 were not associated., Conclusion: The likely presence of E5 transcripts was neither associated to a higher activity of the EGFR-VEGFA pathway nor to the overall survival of patients with HPV16 + squamous cell carcinoma in stages ≥ IB2., (© 2019 Wiley Periodicals, Inc.)

Scarce data are available on the expression of papillomavirus genome and the frequency of alternatively spliced E6E7 mRNAs in invasive cervical cancer. We carried out a comprehensive characterization of HPV expression by RNA-Seq analysis in 22 invasive cervical cancer with HPV16 or HPV18, characterizing the presence of integrated/episomal viral DNA, the integration sites in human genome and the proportion of alternative splicing products of E6 and E7 genes. The expression patterns suggested the presence of episomal and/or integrated viral DNA, with integration detected in most tumors, frequently occurring within human genes in HPV18+ and in intergenic regions in HPV16+ tumors. Alternative splicing of E6E7 transcripts showed E6*I as the most frequent isoform for both viral types, followed by E6*II and E6/E7 (unspliced) transcripts in HPV16+, and by E6/E7 in HPV18+ tumors. Previously described E6*VI and E6*V transcript isoforms for HPV16, and E6*X for HPV18, were rare or not detected., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: To compare and describe type-specific characteristics of HPV16, HPV18 and HPV45 in cervical cancer with respect to 3'LCR methylation and disruption of E1/E2., Methods: The methylation level of 137 cervical cancer samples (70 with HPV16, 37 with HPV18, and 30 with HPV45) of Brazilian patients was analyzed by pyrosequencing. PCR amplifications were performed to characterize E1 and E2 disruption as an episomal surrogate., Results: The 3'LCR of HPV16 showed a higher methylation at all CpG sites (7%, 9%, 11%, 10% and 10%) than homologous HPV18 regions (4%, 5%. 6%, 9% and 5%) and HPV45 regions (7%, 7% and 5%). Presence of intact E1/E2 was associated with higher HPV16 and HPV18 methylation levels at all CpG sites (p < 0.05). Disruption of E1/E2 was more frequently found in HPV45 (97%) and HPV18 (84%) than in HPV16 DNA (30%). HPV16 disruption was more frequently found in E1 (48%) unlike HPV18, where it was found in E2 (61%). Concomitant disruption of E1/E2 was most frequent in HPV45 (72%)., Conclusions: The findings showed a higher methylation associated with intact E1/E2 for HPV16 and HPV18. The closely phylogenetic related HPV18 and HPV45 share a similar methylation level and the frequency of viral genome disruption., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

In Brazil, most studies of intra-type variants of human papillomavirus (HPV) have focused on HPV16 and HPV18, but other high-risk HPV types have not been studied. Here, we report the prevalence of lineages and variants of HPV35, HPV45 and HPV58 in cervical cancers from the Amazonian and Southeast Brazilian regions. The most frequent sublineages were A1 for HPV35, B2 for HPV45, and A2 for HPV58. The Southeast region had a higher frequency of the B2 sublineage of HPV45, and for HPV35, the genetic and nucleotide sequence diversity were higher in the Southeast region, suggesting that regional factors are influencing the diversity and lineage prevalence.

CpG methylation at early promoter of HPV16 DNA, in the 3' end of the Long Control Region (3'LCR), has been associated to the presence of episomal forms of viral genome and, consequently, intact E1 and E2 ORFs. The DNA methylation would block the access of E2 viral protein to the E2 binding sites at early-promoter. However, is still unclear if methylation at 3'LCR of HPV16 DNA can also vary depending of other tumor characteristics in addition to viral DNA physical state. In this study, we evaluate whether the methylation level at the five CpG located at 3'LCR of HPV16 is associated to patient age and E1 and/or E2 ORFs integrity. DNA pyrosequencing was used to measure the methylation level in 69 invasive cervical cancer samples obtained from biopsies of patients attended at Brazilian National Institute of Cancer (INCA). PCR amplifications were performed to assess disruption status of E1 and E2 genes of HPV16. The methylation average per sample ranged widely, from <1 to 88.00%. Presence of intact E1/E2 genes and patient age were positively associated with average methylation in both bivariate analyses (p=0.003 and p=0.006, respectively), and multivariate analysis (p=0.002 and p=0.021, respectively), adjusted for tumor type (squamous cell carcinomas or adenocarcinomas) and HPV16 lineage. These findings showed that presence of intact E1/E2 open reading frames was associated with high levels of DNA methylation, and older patients showed higher levels of methylation than younger ones independently of viral genome disruption., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Cervical cancer is the fourth most common cancer among women, and ∼70-80% of these cancers are associated with two human papillomavirus types: HPV16 and HPV18. Several studies have reported that intra-type diversity is associated with the progression of infection to invasive cancer. Herein, we report the genetic diversity of HPV16 and HPV18 in a cohort of 594 Brazilian women with invasive cervical cancer and describe the prevalence of lineages and intra-type diversity prior to the implementation of the public immunization program in Brazil. HPV detection and genotyping were performed using PCR, PGMY/GP primers, and DNA extracted from fresh tumors. The HPV16 (378 women) and HPV18 (80 women) lineages were identified by PCR and sequencing of the LCR and E6 fragments, followed by SNV comparison and phylogenetic analysis. In our cohort, was found a higher frequency of the lineage A (in 217 women), followed by lineage D (in 97 women) and lineages B and C (in 10 women each) for HPV16; and a higher frequency of lineage A (in 56 women) followed by lineage B (in 15 women) in HPV18. The genetic diversity of HPV16 indicated a recent expansion of specific variants or a selective advantage that is associated with invasive cancer; this pattern was not observed for HPV18., (© 2016 Wiley Periodicals, Inc.)

Background: The allergenicity of Ricinus communis L. (castor bean, Euphorbiaceae) is associated with components of its seeds and pollen. Castor bean allergy has been described not only in laboratory workers, but also in personnel working in oil processing mills, fertilizer retail, the upholstery industry and other industrial fields. In the present study, we describe the critical amino acids in the IgE-binding epitopes in Ric c 1 and Ric c 3, two major allergens of R. communis. In addition, we also investigate the cross-reactivity between castor bean and some air and food allergen extracts commonly used in allergy diagnosis., Methodology/principal Findings: The IgE reactivity of human sera from atopic patients was screened by immune-dot blot against castor bean allergens. Allergenic activity was evaluated in vitro using a rat mast cell activation assay and by ELISA. Cross-reactivity was observed between castor bean allergens and extracts from shrimp, fish, gluten, wheat, soybean, peanut, corn, house dust, tobacco and airborne fungal allergens. We observed that treatment of rat and human sera (from atopic patients) with glutamic acid reduced the IgE-epitope interaction., Conclusions/significance: The identification of glutamic acid residues with critical roles in IgE-binding to Ric c 3 and Ric c 1 support the potential use of free amino acids in allergy treatment.

Significant effort has been made world-wide to boost biofuels with the expectation of a positive contribution to renewable fuel and greenhouse gas reduction. Jatropha curcas L. has proved to be an opportunistic crop in tropical areas, particularly in unfavorable environments. For this reason, analyses of toxicity and allergy caused by its seeds and pollen are necessary. A 12kDa, allergenic 2S albumin, denoted Jat c 1, was isolated from Physic nut (J. curcas) seeds. Jat c 1 binds IgE attached to rat mast cells, inducing histamine release. It also showed strong cross-reactivity with the major allergens from castor bean, Ric c 1 and Ric c 3.

Ric c 1 and Ric c 3 are the major castor bean allergens. In order to identify continuous IgE-epitopes in Ric c 1 and Ric c 3, pools of sera from rats immunized with a pool of 2S albumin from these seeds, Ric c 1 and Ric c 3 overlapping synthetic peptides, were used to screen for IgE-binding epitopes. The allergenic properties were monitored by mast cell degranulation assays, histamine quantification and human-IgE binding. Large and small chains isolated from these proteins present allergenic properties. Four continuous epitopes were identified in Ric c 3 and two in Ric c 1. This knowledge may allow the induction of protective antibody responses to antagonize the IgE recognition.