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High-pressure ice polymorphs are important for our understanding of hydrogen bonding and exist in the interior of the earth and icy moons. Nonetheless, spectroscopic information about them is scarce, where no information about their optical properties in the near-infrared (NIR) region is available at all. We here report NIR spectra of six ice polymorphs differing in terms of their density and O-atom topology, namely, ices II, IV, V, VI, IX, and XII, in comparison with the known spectra of ice Ih. By contrast to earlier work, we do not use mulling agents or transmission of thin films but use diffuse reflectance on powdered samples in liquid nitrogen. The first overtone of the OH-stretching mode is identified as the marker band most suitable to distinguish between these ices. There is a clear blue shift of this band that increases with increasing topological density in addition to a significant narrowing of the band.

In this Perspective, owing to an error in the HTML, the surname of author Alejandro López-Tobón of the LifeTime Community Working Groups consortium was indexed as ‘Tobon’ rather than ‘López-Tobón’ and the accents were missing. The HTML version of the original Perspective has been corrected; the PDF and print versions were always correct. © 2021, The Author(s).

The concept of Wireless Sensor Network (WSN) plays an essential role in the Internet of Things (IoT). It represents a reliable way of communication and information exchange between ubiquitous smart objects. Also, WSNs have been used tremendously in many applications in recent years. They are deployed to collect valuable information in different environments. Although the limited power and process resources of these networks, they remain a perfect solution in different fields. Energy efficiency is a crucial issue in WSN to minimize the power consumption of the network nodes leading to increasing the network lifetime. Clustering is regarded to be the key method used to prolong the lifespan of the network and to offer more effective functioning procedures. In this paper, a centralized energy-efficient clustering model using the Genetic Algorithm (GA) is proposed. The model aims to minimize the nodes’ energy dissipation. The simulation results show a substantial improvement in our proposed protocol compared to Low Energy Adaptive Clustering Hierarchy (LEACH) and many related works protocols in terms of stability duration and lifetime of the network

Mre11-Rad50-Xrs2 (MRX) is a highly conserved complex with key roles in various aspects of DNA repair. Here, we report a new function for MRX in limiting transcription in budding yeast. We show that MRX interacts physically and colocalizes on chromatin with the transcriptional co-regulator Mediator. MRX restricts transcription of coding and noncoding DNA by a mechanism that does not require the nuclease activity of Mre11. MRX is required to tether transcriptionally active loci to the nuclear pore complex (NPC), and it also promotes large-scale gene-NPC interactions. Moreover, MRX-mediated chromatin anchoring to the NPC contributes to chromosome folding and helps to control gene expression. Together, these findings indicate that MRX has a role in transcription and chromosome organization that is distinct from its known function in DNA repair.

SummaryInhibition of the TOR pathway (TORC2, or Ypk1/2), or the depolymerization of actin filaments results in catastrophic fragmentation of the yeast genome upon exposure to low doses of the radiomimetic drug Zeocin. We find that the accumulation of double-strand breaks (DSB) is not due to altered DSB repair, but by the uncoordinated activity of base excision repair (BER) at Zeocin-modified DNA bases. We inhibit DSB formation by eliminating glycosylases and/or the endonucleases Apn1/2 and Rad1, implicating these conserved BER enzymes, or events downstream of them, in the conversion of base damage into DSBs. Among DNA polymerases, the reduction of Pol δ, and to a lesser extent Pol ε and Trf4 (a Pol β-like polymerase), reduces DSB formation. Finally, the BER enzymes, Ogg1 and AP endonuclease, are shown to co-precipitate with actin from yeast extracts and as purified proteins, suggesting that actin may interfere directly with the repair of Zeocin-induced damage.

The advent of transfer hydrogenation and borrowing hydrogen reactions paved the way to manipulate simple alcohols in previously unthinkable manners and circumvent the need for hydrogen gas. Analogously, transfer hydrocarbylation could greatly increase the versatility of tertiary alcohols. However, this reaction remains unexplored because of the challenges associated with the catalytic cleavage of unactivated C–C bonds. Herein, we report a rhodium(I)-catalyzed shuttle arylation cleaving the C(sp2)–C(sp3) bond in unstrained triaryl alcohols via a redox-neutral β-carbon elimination mechanism. A selective transfer hydrocarbylation of substituted (hetero)aryl groups from tertiary alcohols to ketones was realized, employing benign alcohols as latent C-nucleophiles. All preliminary mechanistic experiments support a reversible β-carbon elimination/migratory insertion mechanism. In a broader context, this novel reactivity offers a new platform for the manipulation of tertiary alcohols in catalysis.

Eukaryotic cells package their genomes around histone octamers. In response to DNA damage, checkpoint activation in yeast induces core histone degradation resulting in 20%-40% reduction in nucleosome occupancy. To gain insight into this process, we developed a new approach to analyze the chromatin-associated proteome comprehensively before and after damage. This revealed extensive changes in protein composition after Zeocin-induced damage. First, core histones and the H1 homolog Hho1 were partially lost from chromatin along with replication, transcription, and chromatin remodeling machineries, while ubiquitin ligases and the proteasome were recruited. We found that the checkpoint- and INO80C-dependent recruitment of five ubiquitin-conjugating factors (Rad6, Bre1, Pep5, Ufd4, and Rsp5) contributes to core and linker histone depletion, reducing chromatin compaction and enhancing DNA locus mobility. Importantly, loss of Rad6/Bre1, Ufd4/TRIP12, and Pep5/VPS11 compromise DNA strand invasion kinetics during homology-driven repair. Thus we provide a comprehensive overview of a functionally relevant genome-wide chromatin response to DNA damage.

DNA2 is an essential nuclease–helicase implicated in DNA repair, lagging-strand DNA synthesis, and the recovery of stalled DNA replication forks (RFs). In Saccharomyces cerevisiae, dna2Δ inviability is reversed by deletion of the conserved helicase PIF1 and/or DNA damage checkpoint-mediator RAD9. It has been suggested that Pif1 drives the formation of long 5′-flaps during Okazaki fragment maturation, and that the essential function of Dna2 is to remove these intermediates. In the absence of Dna2, 5′-flaps are thought to accumulate on the lagging strand, resulting in DNA damage-checkpoint arrest and cell death. In line with Dna2’s role in RF recovery, we find that the loss of Dna2 results in severe chromosome under-replication downstream of endogenous and exogenous RF-stalling. Importantly, unfaithful chromosome replication in Dna2-mutant cells is exacerbated by Pif1, which triggers the DNA damage checkpoint along a pathway involving Pif1’s ability to promote homologous recombination-coupled replication. We propose that Dna2 fulfils its essential function by promoting RF recovery, facilitating replication completion while suppressing excessive RF restart by recombination-dependent replication (RDR) and checkpoint activation. The critical nature of Dna2’s role in controlling the fate of stalled RFs provides a framework to rationalize the involvement of DNA2 in Seckel syndrome and cancer.

In fission yeast and plants, RNA-processing pathways contribute to heterochromatin silencing, complementing well-characterized pathways of transcriptional repression. However, it was unclear whether this additional level of regulation occurs in metazoans. In a genetic screen, we uncovered a pathway of silencing in

Actin is the most abundant protein in eukaryotic cells and is key to many cellular functions. Natural products that specifically recognize the filamentous form of actin (F-actin) such as the bicyclic peptide phalloidin are important tools to study actin and are widely applied for imaging the cytoskeleton in cells. Herein, we aimed at developing peptide-based affinity reagents that selectively bind to the monomeric form of actin (G-actin), for which synthetic probes are not available. Panning a phage display library comprising more than a trillion different bicyclic peptides against G-actin yielded binders with low nanomolar affinity and greater than 1000-fold selectivity over F-actin. Sequence analysis revealed a strong similarity of the peptides' sequences to a region of thymosin-b4, a protein that weakly binds G-actin, and competition binding experiments confirmed a common binding region at the cleft between the subdomains 1 and 3 of actin. We tested the G-actin peptides as probes in pull-down and imaging experiments and applied a peptide variant with improved dissociation constant (Kd = 5 ± 2 nM) to measure the affinity of G-actin-binding natural product toxins.

Gas hydrates are usually synthesized by bringing together a pressurized gas and liquid or solid water. In both cases, the transport of gas or water to the hydrate growth site is hindered once an initial film of hydrate has grown at the water-gas interface. A seemingly forgotten gas-phase technique overcomes this problem by slowly depositing water vapor on a cold surface in the presence of the pressurized guest gas. Despite being used for the synthesis of low-formation-pressure hydrates, it has not yet been tested for hydrates of CO

To determine whether double-strand break (DSB) mobility enhances the physical search for an ectopic template during homology-directed repair (HDR), we tested the effects of factors that control chromatin dynamics, including cohesin loading and kinetochore anchoring. The former but not the latter is altered in response to DSBs. Loss of the nonhistone high-mobility group protein Nhp6 reduces histone occupancy and increases chromatin movement, decompaction, and ectopic HDR. The loss of nucleosome remodeler INO80-C did the opposite. To see whether enhanced HDR depends on DSB mobility or the global chromatin response, we tested the ubiquitin ligase mutant uls1Δ, which selectively impairs local but not global movement in response to a DSB. Strand invasion occurs in uls1Δ cells with wild-type kinetics, arguing that global histone depletion rather than DSB movement is rate limiting for HDR. Impaired break movement in uls1Δ correlates with elevated MRX and cohesin loading, despite normal resection and checkpoint activation.

Electrocardiogram (ECG) signal analysis is a critical task in diagnosing the presence of any cardiac disorder. There are limited studies on detecting P-waves in various atrial arrhythmias, such as atrial fibrillation (AFIB), atrial flutter, junctional rhythm, and other arrhythmias due to P-wave variability and absence in various cases. Thus, there is a growing need to develop an efficient automated algorithm that annotates a 2D printed version of P-waves in the well-known ECG signal databases for validation purposes. To our knowledge, no one has annotated P-waves in the MIT-BIH atrial fibrillation database. Therefore, it is a challenge to manually annotate P-waves in the MIT-BIH AF database and to develop an automated algorithm to detect the absence and presence of different shapes of P-waves. In this paper, we present the manual annotation of P-waves in the well-known MIT-BIH AF database with the aid of a cardiologist. In addition, we provide an automatic P-wave segmentation for the same database using a fully convolutional neural network model (U-Net). This algorithm works on 2D imagery of printed ECG signals, as this type of imagery is the most commonly used in developing countries. The proposed automatic P-wave detection method obtained an accuracy and sensitivity of 98.56% and 98.78%, respectively, over the first 5 min of the second lead of the MIT-BIH AF database (a total of 8280 beats). Moreover, the proposed method is validated using the well-known automatically and manually annotated QT database (a total of 11,201 and 3194 automatically and manually annotated beats, respectively). This results in accuracies of 98.98 and 98.9%, and sensitivities of 98.97 and 97.24% for the automatically and manually annotated QT databases, respectively. Thus, these results indicate that the proposed automatic method can be used for analyzing long-printed ECG signals on mobile battery-driven devices using only images of the ECG signals, without the need for a cardiologist.

Mutations in the nuclear structural protein lamin A produce rare, tissue-specific diseases called laminopathies. The introduction of a human Emery-Dreifuss muscular dystrophy (EDMD)-inducing mutation into the C. elegans lamin (LMN-Y59C), recapitulates many muscular dystrophy phenotypes, and correlates with hyper-sequestration of a heterochromatic array at the nuclear periphery in muscle cells. Using muscle-specific emerin Dam-ID in worms, we monitored the effects of the mutation on endogenous chromatin. An increased contact with the nuclear periphery along chromosome arms, and an enhanced release of chromosomal centers, coincided with the disease phenotypes of reduced locomotion and compromised sarcomere integrity. The coupling of the LMN-Y59C mutation with the ablation of CEC-4, a chromodomain protein that anchors H3K9-methylated chromatin at the nuclear envelope (NE), suppressed the muscle-associated disease phenotypes. Deletion of cec-4 also rescued LMN-Y59C-linked alterations in chromatin organization and some changes in transcription. Sequences that changed position in the LMN-Y59C mutant, are enriched for E2F (EFL-2)-binding sites, consistent with previous studies suggesting that altered Rb-E2F interaction with lamin A may contribute to muscle dysfunction. In summary, we were able to counteract the dominant muscle-specific defects provoked by LMNA mutation by the ablation of a lamin-associated H3K9me anchor, suggesting a novel therapeutic pathway for EDMD., J.C.H. was supported by an FP7 Marie Curie Action Intra-European Fellowship and by a grant from the Foundation Suisse de Recherche sur les Maladies Musculaires. A.M. was funded by the same and by a Marie Heim-Vögtlin grant from the Swiss National Science Foundation. C.M.-J., R.R.-B., and P.A. thank the Spanish State Research Agency and the European Regional Development Fund (BFU2016-79313-P and MDM-2016- 0687) for support. This project received funding from the European Research Council under the European Union’s Horizon 2020 Research and Innovation program (Epiherigans grant no. 743312 to S.M.G.).

Summary: Multiple pathways regulate the repair of double-strand breaks (DSBs) to suppress potentially dangerous ectopic recombination. Both sequence and chromatin context are thought to influence pathway choice between non-homologous end-joining (NHEJ) and homology-driven recombination. To test the effect of repetitive sequences on break processing, we have inserted TG-rich repeats on one side of an inducible DSB at the budding yeast MAT locus on chromosome III. Five clustered Rap1 sites within a break-proximal TG repeat are sufficient to block Mre11-Rad50-Xrs2 recruitment, impair resection, and favor elongation by telomerase. The two sides of the break lose end-to-end tethering and show enhanced, uncoordinated movement. Only the TG-free side is resected and shifts to the nuclear periphery. In contrast to persistent DSBs without TG repeats that are repaired by imprecise NHEJ, nearly all survivors of repeat-proximal DSBs repair the break by a homology-driven, non-reciprocal translocation from ChrIII-R to ChrVII-L. This suppression of imprecise NHEJ at TG-repeat-flanked DSBs requires the Uls1 translocase activity. : Marcomini et al. show that the presence of interstitial telomeric repeat sequences near a double-strand break alters the outcome of repair. A TG-flanked break loads MRX asymmetrically, supports resection only on one side, and allows uncoordinated movement of the break ends. The resected TG-free end invades homology on another chromosome driving a unidirectional translocation event. Keywords: double-strand break repair, interstitial repeat sequences, telomeres, end resection, homology-driven recombination, imprecise non-homologous end joining, MRX, Uls1

Chromatin is organized and compacted in the nucleus through the association of histones and other proteins, which together control genomic activity. Two broad types of chromatin can be distinguished: euchromatin, which is generally transcriptionally active, and heterochromatin, which is repressed. Here we examine the current state of our understanding of repressed chromatin in Caenorhabditis elegans, focusing on roles of histone modifications associated with repression, such as methylation of histone H3 lysine 9 (H3K9me2/3) or the Polycomb Repressive Complex 2 (MES-2/3/6)-deposited modification H3K27me3, and on proteins that recognize these modifications. Proteins involved in chromatin repression are important for development, and have demonstrated roles in nuclear organization, repetitive element silencing, genome integrity, and the regulation of euchromatin. Additionally, chromatin factors participate in repression with small RNA pathways. Recent findings shed light on heterochromatin function and regulation in C. elegans, and should inform our understanding of repressed chromatin in other animals.

We report on the discovery and characterization of ice β-XV, which represents the second hydrogen ordered polymorph related to ice VI., In the last twelve years five new ice phases were experimentally prepared. Two of them are empty clathrate hydrates and three of them represent hydrogen ordered counterparts of previously known disordered ice phases. Here, we report on hydrogen ordering in ice VI samples produced by cooling at pressures up to 2.00 GPa. Based on results from calorimetry, dielectric relaxation spectroscopy, Raman spectroscopy, and powder X-ray diffraction the existence of a second hydrogen ordered polymorph related to ice VI is suggested. Powder X-ray data show the oxygen network to be the one of ice VI. For the 1.80 GPa sample the activation energy from dielectric spectroscopy is 45 kJ mol–1, which is much larger than for the known hydrogen ordered proxy of ice VI, ice XV. Raman spectroscopy indicates the 1.80 GPa sample to be more ordered than ice XV. It is further distinct from ice XV in that it experiences hydrogen disordering above ≈103 K which is 26 K below the ice XV to ice VI disordering transition. Consequently, below 103 K it is thermodynamically more stable than ice XV, adding a stability region to the phase diagram of water. For the time being we suggest to call this new phase ice β-XV and to relabel it ice XVIII once its crystal structure is known.

One of the most promising 5G waveform candidates is the universal-filtered multicarrier system (UFMC). The UFMC system reduces the out-of-band (OoB) emission, bringing about higher spectral efficiency. This is assumed to reach robustness against frequency offset and low latency. Although, as aforementioned, the UFMC system offers many advantages, it lacks high peak-to-average power ratio (PAPR) as a multicarrier transmission technique. This research paper tackles two approaches; firstly, RCS, by developing a simulated conventional SLM system, with modifications to generate the same number of waveforms, while using fewer UFMC modulators. Secondly, by developing a simulated conventional SLM system, with modifications using the same number of modulators to generate more waveforms that would be generated in the conventional scheme. The two sets of results from the proposed M-SLM scheme are compared to each other, and to other PAPR reduction schemes using OFDM and UFMC. To reduce PAPR in UFMC systems, (M-SLM) scheme with low complexity is proposed. The essence of the proposed M-SLM scheme is represented in making use of the cyclically shifting process and FMC modulator’s linearity property. The proposed M-SLM scheme uses Um UFMC modulators to produce Uw alternative UFMC waveforms, where Uw = Um (2Um − 1). As a result, drawing a comparison with existing SLM based PAPR reduction schemes for UFMC systems; the proposed M-SLM scheme's computational complexity is reduced. Finally, there is a comparison between the proposed M-SLM scheme and the schemes there in the literature according to PAPR reduction ability.

Chromatin is organized into higher-order structures that form subcompartments in interphase nuclei. Different categories of specialized enzymes act on chromatin and regulate its compaction and biophysical characteristics in response to physiological conditions. We present an overview of the function of chromatin structure and its dynamic changes in response to genotoxic stress, focusing on both subnuclear organization and the physical mobility of DNA. We review the requirements and mechanisms that cause chromatin relocation, enhanced mobility, and chromatin unfolding as a consequence of genotoxic lesions. An intriguing link has been established recently between enhanced chromatin dynamics and histone loss.

On induction of DNA damage with 405-nm laser light, proteins involved in base excision repair (BER) are recruited to DNA lesions. We find that the dynamics of factors typical of either short-patch (XRCC1) or long-patch (PCNA) BER are altered by chemicals that perturb actin or tubulin polymerization in human cells. Whereas the destabilization of actin filaments by latrunculin B, cytochalasin B, or Jasplakinolide decreases BER factor accumulation at laser-induced damage, inhibition of tubulin polymerization by nocodazole increases it. We detect no recruitment of actin to sites of laser-induced DNA damage, yet the depolymerization of cytoplasmic actin filaments elevates both actin and tubulin signals in the nucleus. While published evidence suggested a positive role for F-actin in double-strand break repair in mammals, the enrichment of actin in budding yeast nuclei interferes with BER, augmenting sensitivity to Zeocin. Our quantitative imaging results suggest that the depolymerization of cytoplasmic actin may compromise BER efficiency in mammals not only due to elevated levels of nuclear actin but also of tubulin, linking cytoskeletal integrity to BER.

In recent years socially responsible investing has become a popular subject with both private and institutional investors. At the same time, a number of scientific papers have been published on socially responsible investments (SRIs), covering a broad range of topics, from what actually defines SRIs to the financial performance of SRI funds in contrast to non-SRI funds. In this paper, we revisit Markowitz’ Portfolio Selection Theory and propose a modification allowing to incorporate not only asset-specific return and risk but also a social responsibility measure into the investment decision making process. Applied in an a posteriori fashion, the model results in a three-dimensional capital allocation plane illustrating the complete set of feasible optimal portfolios. It enables investors to custom–tailor their asset allocations and incorporate all personal preferences regarding return, risk and social responsibility. In an empirical analysis with a data set of over 6000 international companies (including the complete universe of social responsibility-rated stocks), we find that investors opting to maximize the social impact of their investments do indeed face a statistically significant decrease in expected returns. However, the social responsibility/risk-optimal portfolio yields a statistically significant higher social responsibility rating than the return/risk-optimal portfolio.

Chromatin moves with subdiffusive and spatially constrained dynamics within the cell nucleus. Here, we use single-locus tracking by time-lapse fluorescence microscopy to uncover information regarding the forces that influence chromatin movement following the induction of a persistent DNA double-strand break (DSB). Using improved time-lapse imaging regimens, we monitor trajectories of tagged DNA loci at a high temporal resolution, which allows us to extract biophysical parameters through robust statistical analysis. Polymer modeling based on these parameters predicts chromatin domain expansion near a DSB and damage extrusion from the domain. Both phenomena are confirmed by live imaging in budding yeast. Calculation of the anomalous exponent of locus movement allows us to differentiate forces imposed on the nucleus through the actin cytoskeleton from those that arise from INO80 remodeler-dependent changes in nucleosome organization. Our analytical approach can be applied to high-density single-locus trajectories obtained in any cell type.

One of the most attractive candidate waveforms used in 5G systems is based the orthogonal frequency division multiplexing (OFDM) technology for its robustness against frequency selective fading and its high spectral efficiency. However, it suffers from high peak-to-average power ratio (PAPR) drawback. The partial transmit sequence (PTS) approach is used for reducing the PAPR of the wavelet-OFDM (WOFDM) system without signal distortion. In this paper, a modified PAPR reduction approach using a PTS-WOFDM based on genetic algorithm (GA) is proposed. The simulation results show that the proposed system provides PAPR reduction gain of 0.11 dB and 0.46 dB compared to optimum PTS-OFDM and PTS-OFDM based GA systems respectively. Also, the search complexity of the proposed GA based PTS-WOFDM system is significantly reduced by 97.25% compared to the optimum PTS-OFDM.

In Saccharomyces cerevisiae, the silent information regulator (SIR) proteins Sir2/3/4 form a complex that suppresses transcription in subtelomeric regions and at the homothallic mating-type (HM) loci. Here, we identify a non-canonical BRCA1 C-terminal domain (H-BRCT) in Sir4, which is responsible for tethering telomeres to the nuclear periphery. We show that Sir4 H-BRCT and the closely related Dbf4 H-BRCT serve as selective phospho-epitope recognition domains that bind to a variety of phosphorylated target peptides. We present detailed structural information about the binding mode of established Sir4 interactors (Esc1, Ty5, Ubp10) and identify several novel interactors of Sir4 H-BRCT, including the E3 ubiquitin ligase Tom1. Based on these findings, we propose a phospho-peptide consensus motif for interaction with Sir4 H-BRCT and Dbf4 H-BRCT. Ablation of the Sir4 H-BRCT phospho-peptide interaction disrupts SIR-mediated repression and perinuclear localization. In conclusion, the Sir4 H-BRCT domain serves as a hub for recruitment of phosphorylated target proteins to heterochromatin to properly regulate silencing and nuclear order.

SummaryIn fission yeast and plants, RNA-processing pathways contribute to constitutive and facultative heterochromatin silencing, complementing well-characterized pathways of transcriptional repression. However, it was unclear whether this additional level of regulation occurs in metazoans. Here we describe a pathway of silencing in C. elegans somatic cells, in which the highly conserved, RNA binding complex LSM2-8 selectively silences heterochromatic reporters and endogenous genes bearing the Polycomb mark H3K27me3. Importantly, the LSM2-8 complex works cooperatively with XRN-2, a 5’-3’ exoribonuclease, and disruption of the pathway leads to mRNA stabilization. This selective LSM2-8-mediated RNA degradation does not target nor depend on H3K9me2/me3, unlike previously described pathways of heterochromatic RNA degradation. Intriguingly, the loss of LSM2-8 coincides with a localized drop in H3K27me3 levels on lsm-8-sensitive loci only. Together this defines a mechanism of RNA degradation that selectively targets a subset of H3K27me3-marked genes, revealing an unrecognized layer of regulation for facultative heterochromatin in animals.

The freezing of ionic aqueous solutions is common in both nature and human-conducted cryopreservation. The cooling rate and the dimensions constraining the solution are known to fundamentally influence the physicochemical characteristics of the sample, including the extent of vitrification, morphology, and distribution of ions. The presence of some salts in an aqueous solution often suppresses the ice crystallization, allowing bulk vitrification during relatively slow cooling. Such a process, however, does not occur in NaCl solutions, previously observed to vitrify only under hyperquenching and/or in sub-micrometric confinements. This work demonstrates that, at freezing rates of ≥100 K min

This work reports on frequency dependent ambient-pressure dielectric measurements of hyperquenched glassy water, ice IV, ice VI, as well as a CO2-filled clathrate hydrate, the latter featuring a chiral water network. The dipolar time scales and the spectral shapes of the loss spectra of these specimens are mapped out and compared with literature data on low-density and high-density amorphous ices as well as on amorphous solid water. There is a trend that the responses of the more highly dense amorphous ices are slightly more dynamically heterogeneous than those of the lower-density amorphous ices. Furthermore, practically all of the amorphous ices, for which broadband dielectric spectra are available, display a curved high-frequency wing. Conversely, the high-frequency flanks of the nominally pure ice crystals including ice V and ice XII can be characterized by an approximate power-law behavior. While the spectral shapes of the nominally pure ices thus yield some hints regarding their amorphicity or crystallinity, a comparison of their time scale appears less distinctive in this respect. In the accessible temperature range, the relaxation times of the crystalline ices are between those of low-density and high-density amorphous ice. Hence, with reference also to previous work, the application of suitable doping currently seems to be the best dielectric spectroscopy approach to distinguish amorphous from crystalline ices.

A commonly used approach for assessing DNA repair factor recruitment in mammalian cells is to induce DNA damage with a laser in the UV or near UV range and follow the local increase of GFP-tagged proteins at the site of damage. Often these measurements are performed in the presence of the blue DNA dye Hoechst, which is used as a photosensitizer. However, a light-induced switch of Hoechst from a blue-light to a green-light emitter will give a false positive signal at the site of damage. Thus, photoconversion signals must be subtracted from the overall green-light emission to determine true recruitment. Here we demonstrate the photoconversion effect and suggest control experiments to exclude false-positive results.

Nuclear actin has been implicated in a variety of DNA-related processes including chromatin remodeling, transcription, replication, and DNA repair. However, the mechanistic understanding of actin in these processes has been limited, largely due to a lack of research tools that address the roles of nuclear actin specifically, that is, distinct from its cytoplasmic functions. Recent findings support a model for homology-directed DNA double-strand break (DSB) repair in which a complex of ARP2 and ARP3 (actin-binding proteins 2 and 3) binds at the break and works with actin to promote DSB clustering and homology-directed repair. Further, it has been reported that relocalization of heterochromatic DSBs to the nuclear periphery in Drosophila is ARP2/3 dependent and actin–myosin driven. Here we provide an overview of the role of nuclear actin and actin-binding proteins in DNA repair, critically evaluating the experimental tools used and potential indirect effects.

Proper repair of double-strand breaks (DSBs) is key to ensure proper chromosome segregation. In this study, we found that the deletion of the SRS2 gene, which encodes a DNA helicase necessary for the control of homologous recombination, induces aberrant chromosome segregation during budding yeast meiosis. This abnormal chromosome segregation in srs2 cells accompanies the formation of a novel DNA damage induced during late meiotic prophase-I. The damage may contain long stretches of single-stranded DNAs (ssDNAs), which lead to aggregate formation of a ssDNA binding protein, RPA, and a RecA homolog, Rad51, as well as other recombination proteins inside of the nuclei. The Rad51 aggregate formation in the srs2 mutant depends on the initiation of meiotic recombination and occurs in the absence of chromosome segregation. Importantly, as an early recombination intermediate, we detected a thin bridge of Rad51 between two Rad51 foci or among the foci in the srs2 mutant, which is rarely seen in wild type. These might be cytological manifestation of the connection of two DSB ends and multi-invasion. The DNA damage with Rad51 aggregates in the srs2 mutant is passed through anaphase-I and -II, suggesting the absence of DNA damage-induced cell-cycle arrest after the pachytene stage. We propose that Srs2 helicase resolves early protein-DNA recombination intermediates to suppress the formation of aberrant lethal DNA damage during late prophase-I.

A commonly used approach for assessing DNA repair factor recruitment in mammalian cells is to induce DNA damage with a laser in the UV or near UV range and follow the local increase of GFP-tagged proteins at the site of damage. Often these measurements are performed in the presence of the blue DNA dye Hoechst, which is used as a photosensitizer. However, a light-induced switch of Hoechst from a blue-light to a green-light emitter will give a false positive signal at the site of damage. Thus, photoconversion signals must be subtracted from the overall green-light emission to determine true recruitment. Here we demonstrate the photoconversion effect and suggest control experiments to exclude false-positive results.

Delaney et al. show that the unstructured domain cofactor LIN-65 is essential for the stable formation of heterochromatic foci. It stably interacts with the H3K9 methyltransferase MET-2/SETDB1 and modulates MET-2 nuclear localization, activity, and H3K9me-mediated silencing in C. elegans., The segregation of the genome into accessible euchromatin and histone H3K9-methylated heterochromatin helps silence repetitive elements and tissue-specific genes. In Caenorhabditis elegans, MET-2, the homologue of mammalian SETDB1, catalyzes H3K9me1 and me2, yet like SETDB1, its regulation is enigmatic. Contrary to the cytosolic enrichment of overexpressed MET-2, we show that endogenous MET-2 is nuclear throughout development, forming perinuclear foci in a cell cycle–dependent manner. Mass spectrometry identified two cofactors that bind MET-2: LIN-65, a highly unstructured protein, and ARLE-14, a conserved GTPase effector. All three factors colocalize in heterochromatic foci. Ablation of lin-65, but not arle-14, mislocalizes and destabilizes MET-2, resulting in decreased H3K9 dimethylation, dispersion of heterochromatic foci, and derepression of MET-2 targets. Mutation of met-2 or lin-65 also disrupts the perinuclear anchoring of genomic heterochromatin. Loss of LIN-65, like that of MET-2, compromises temperature stress resistance and germline integrity, which are both linked to promiscuous repeat transcription and gene expression.

2019 Klein et al., Understanding the plasticity of genomes has been greatly aided by assays for recombination, repair and mutagenesis. These assays have been developed in microbial systems that provide the advantages of genetic and molecular reporters that can readily be manipulated. Cellular assays comprise genetic, molecular, and cytological reporters. The assays are powerful tools but each comes with its particular advantages and limitations. Here the most commonly used assays are reviewed, discussed, and presented as the guidelines for future studies., HLK was supported by NIH grant R01-CA146940. AA was supported by the European research Council (ERC2014- ADG669898 TARLOOP), the Spanish Ministry of Economy and Competitiveness (BFU2016-75058-P), and the Junta de Andalucía (BIO1238). JLA was supported by NIH grant R35G-GM119788. CHF was supported by NIH grants P01- GM105473 and R01-GM122880. SMG was supported by the Swiss national Science Foundation and the Novartis Research Foundation. DAG was supported by National Institutes of Health (Intramural Research Program Project Z1AES103266. JEH was supported by NIH grants R35- GM127029 and P01-GM105473. GI was supported by NIH grants R01-GM125650 and R01-GM080600. SJ-R was supported by NIH grant R35-GM118077. MCK was supported by National Science Foundation Graduate Research Fellowship DGE-1122492, NIH training grant T32-GM007223 and NIH grant DP20D008429. RDK and CDP were supported by NIH grants R01-GM26017 and R01-GM50006. AK was supported by NIH grant R01-GM073115. SAEL was supported by grants from Agence Nationale de la Recherche ANR-14- CE10-0010-01 and the Foundation pour la Recherche Médicale Equipe FRM DEQ20160334889. SEL was supported by NIH grant R01-GM071011. SMM was supported by NIH grants R01-GM60987 and P01-GM105473. TDP was supported by NIH grant R35-GM118020. SMR was supported by a gift from WM Keck Foundation, NIH Director’s Pioneer Award DP1-CA174424 and NIH grant R35-GM122598. DMF was supported by the Cancer Prevention and Research Institute of Texas, Baylor College of Medicine Comprehensive Cancer Training Program Postdoctoral Fellowship RP160283. RR was supported by NIH grant R35-GM118180 and JM-H was supported by a Marie Curie International Outgoing Fellowship and the ANR-12-PDOC-0035-01. LSS was supported by NIH grant R35-GM126997. PZ was supported by National Science Centre Poland 2015/19/103859 and FNP First TEAM/2016-1/9. NK was supported by NIH grant R01-GM116007 and the Welch Foundation (AU1875). ML was supported by grants from the Danish Agency for Science, Technology and Innovation, the Villum Foundation and the Danish National Research Foundation (DNRF115). AM was supported by NIH grants R35-GM127006 and R03- ES029306.

This chapter explores the question whether Bitcoin as an unregulated cryptocurrency can have a positive effect on already well-diversified investment portfolios. Bitcoin was originally introduced in 2008 in a paper titled “Bitcoin: A Peer-to-Peer Electronic Cash System”. Since then, Bitcoin has seen increasing trading volumes (as well as major capital gains and losses) in a high-volatility environment while also experiencing growing attention by regulators, academics, the media and the general public. At the same time, more and more online and offline businesses worldwide started to adopt Bitcoin as an alternative means of payment, even though Bitcoin does not have legal tender status. Today, Bitcoin is still the most popular unregulated cryptocurrency. Bitcoin’s share of the total market capitalization of all cryptocurrencies currently amounts to just under 45% according to Coinmarketcap (2018), and Bitcoin is also the top-searched cryptocurrency of the top five cryptocurrencies in terms of market capitalization (Google Trends 2018). This is largely due to the fact that Bitcoin was the first cryptocurrency based on a decentralized peer-to-peer network (to confirm transactions and generate a limited amount of new Bitcoins in doing so) and functioning without the backing of a central bank or any other monitoring authority. For the general public and most media outlets, Bitcoin is still seen as the leading cryptocurrency.

The extensive utilization of Internet of Things (IoT) devices in a wide range of services prompts spectrum scarcity. Recently, Cognitive Radio Networks (CRNs) have shown promising results in addressing the spectrum scarcity problem. Therefore, CRNs are envisaged to play a crucial role in accommodating the massive number of emerging IoT devices. However, two dominant shortcomings hinder the coalescence of IoT and CRNs. First, the selfish behavior among Secondary Users (SUs) during the spectrum sensing process. Second, the inability to construct a convenient metric for fair spectrum assignment. The contribution of this paper is quadruple: (i) a Direct Strategy Selection (DSS) mechanism that satisfies Aspiration Equilibrium (AE) and enforces cooperation among SUs during the spectrum sensing process; (ii) a spectrum allocation scheme that takes cooperative behavior as a fairness parameter; (iii) studying the effects of three windowing techniques on the proposed allocation scheme and selecting the window that achieves maximum fairness; (iv) exploring the trade-off between the utility function and cooperation among SUs. The results show that DSS yields instant convergence and a threefold increase in the index of cooperation. Regarding spectrum allocation, the proposed scheme combined with the Reverse Attenuation Window (RAW) shows a 22% increase in the Average Satisfaction Ratio (ASR) for SUs. The simulations are conducted in the worst case scenario, where all SUs in the CRN are requesting to access the spectrum at the same time.

The combinatorial action of transcription factors drives cell-type-specific gene expression patterns. However, transcription factor binding and gene regulation occur in the context of chromatin, which modulates DNA accessibility. High-resolution chromatin interaction maps have defined units of chromatin that are in spatial proximity, called topologically associated domains (TADs). TADs can be further classified based on expression activity, replication timing, or the histone marks or non-histone proteins associated with them. Independently, other chromatin domains have been defined by their likelihood to interact with non-DNA structures, such as the nuclear lamina. Lamina-associated domains (LADs) correlate with low gene expression and late replication timing. TADs and LADs have recently been evaluated with respect to cell-type-specific gene expression. The results shed light on the relevance of these forms of chromatin organization for transcriptional regulation, and address specifically how chromatin sequestration influences cell fate decisions during organismal development.

With the continuous increase in environmental requirements and regulations for wastewater treatment a lot of wastewater treatment plants in Austria had to be extended. Extension of the plant requires in general an additional area, which is not always available. This study shows the extension of the WWTP Hard Hofsteig and doubling its capacity by using the Hybrid concept, which is a special two stage activated sludge process for extensive nutrient removal. The plant was extended from 170,000 PE to 270,000 PE without changing the footprint of the plant and the extension costs could be kept very low. Operational data shows that by operating the plant in the two stage Hybrid mode the energy balance of the plant can be improved.

It is striking that within a eukaryotic nucleus, the genome can assume specific spatiotemporal distributions that correlate with the cell's functional states. Cell identity itself is determined by distinct sets of genes that are expressed at a given time. On the level of the individual gene, there is a strong correlation between transcriptional activity and associated histone modifications. Histone modifications act by influencing the recruitment of non‐histone proteins and by determining the level of chromatin compaction, transcription factor binding, and transcription elongation. Accumulating evidence also shows that the subnuclear position of a gene or domain correlates with its expression status. Thus, the question arises whether this spatial organization results from or determines a gene's chromatin status. Although the association of a promoter with the inner nuclear membrane (INM) is neither necessary nor sufficient for repression, the perinuclear sequestration of heterochromatin is nonetheless conserved from yeast to man. How does subnuclear localization influence gene expression? Recent work argues that the common denominator between genome organization and gene expression is the modification of histones and in some cases of histone variants. This provides an important link between local chromatin structure and long‐range genome organization in interphase cells. In this review, we will evaluate how histones contribute to the latter, and discuss how this might help to regulate genes crucial for cell differentiation.

In eukaryotic organisms, gene regulation occurs in the context of chromatin. In the interphase nucleus, euchromatin and heterochromatin occupy distinct space during cell differentiation, with heterochromatin becoming enriched at the nuclear and nucleolar peripheries. This organization is thought to fine-tune gene expression. To elucidate the mechanisms that govern this level of genome organization, screens were carried out in C. elegans which monitored the loss of heterochromatin sequestration at the nuclear periphery. This led to the identification of a novel chromodomain protein, CEC-4 (Caenorhabditis elegans chromodomain protein 4) that mediates the anchoring of H3K9 methylation-bearing chromatin at the nuclear periphery in early to mid-stage embryos. Surprisingly, the loss of CEC-4 does not derepress genes found in heterochromatic domains, nor does it affect differentiation under standard laboratory conditions. On the other hand, CEC-4 contributes to the efficiency with which muscle differentiation is induced following ectopic expression of the master regulator, HLH-1. This is one of the first phenotypes specifically attributed to the ablation of heterochromatin anchoring.

Most of the human genome is compacted into heterochromatin, a form that encompasses multiple forms of inactive chromatin structure. Transcriptional silencing mechanisms in budding and fission yeasts have provided genetically tractable models for understanding heritably repressed chromatin. These silent domains are typically found in regions of repetitive DNA, that is, either adjacent to centromeres or telomeres or within the tandemly repeated ribosomal DNA array. Here we address the mechanisms of centromeric, telomeric and locus-specific gene silencing, comparing simple and complex animals with yeast. Some aspects are universally shared, such as histone-tail modifications, while others are unique to either centromeres or telomeres. These may reflect roles for heterochromatin in other chromosomal functions, like kinetochore attachment and DNA ends protection.

High resolution radar signals demands the use of high speed signal processor. Due to the sparse nature of radar signals, Compressive sensing (CS) enables the wide-band radar signals to be sampled at a low sampling rate, rather than a high sampling rate. This is attained through the use of a sparse sensing matrix. Complex approximate message passing (CAMP) algorithm is vastly used in reconstructing radar signals, because of its low complexity for real-time recovery and suitable for hardware integration. However, the CAMP algorithm achieves low detection performance at low Signal to Noise Ratios (SNRs). This paper proposes a new adaptive CAMP algorithm based on signal threshold, in order to solve the aforementioned shortcoming. Through simulation, the new adaptive CAMP is compared against the classical CAMP and the digital matched filter (DMF) algorithm using the Receiver Operating Characteristic (ROC) curves. The receivers operating characteristic curves (ROC) show that the new adaptive CAMP improves the probability of detection at lower SNRs.

Eine chronisch-kritische Ischämie bei Patienten mit zugrunde liegender arterieller Verschlusskrankheit erfordert rekonstruktive vaskuläre chirurgische Eingriffe, die bislang mit körpereigenen Venensegmenten oder synthetischem Gefäßmaterial durchgeführt werden. Die begrenzte Verfügbarkeit von geeigneten autologen Gefäßtransplantaten mit niedrigem Durchmesser bei vielen Patienten und die offensichtlichen Nachteile von synthetischem Bypassmaterial zeigen die Notwendigkeit zur Entwicklung von klinisch verwendbaren biologisch konstruierten Blutgefäßsubstituten auf. Trotz erheblicher Fortschritte in diesem Bereich in den letzten zwei Jahrzehnten war ihre Implementierung in die klinische Routine eine Herausforderung. Die begrenzte replikative Lebensdauer von menschlichen adulten Gefäßzellen und ihre langsame Rate bei der Produktion von Kollagenmatrix in vitro stellten gravierende Probleme bei der Entwicklung mechanisch robuster und biologisch funktioneller künstlicher Transplantate dar. Mit den jüngsten Fortschritten in der Stammzellenforschung sind neue Zelltypen für das vaskuläre Tissue-Engineering verfügbar geworden. Insbesondere die Entdeckung von humanen induzierten pluripotenten Stammzellen (iPS-Zellen), die aus adulten differenzierten Zellen stammen, sowie von humanen multipotenten adulten mesenchymalen Stammzellen (ohne Genmodifizierungen und den mit ihnen verbundenen Sicherheitsbedenken) können die Entwicklung von neuem autologem Zellgewebe vorantreiben. Wir stellen die aktuellen Entwicklungen auf dem Gebiet der vaskulären Progenitorzellen vor und diskutieren die Möglichkeiten und Herausforderungen für den klinischen Einsatz von biologisch konstruierten Gefäßsubstituten.

Sister chromatid cohesion on chromosome arms is essential for the segregation of homologous chromosomes during meiosis I while it is dispensable for sister chromatid separation during mitosis. It was assumed that, unlike the situation in mitosis, chromosome arms retain cohesion prior to onset of anaphase-I. Paradoxically, reduced immunostaining signals of meiosis-specific cohesin, including the kleisin Rec8, were observed on chromosomes during late prophase-I of budding yeast. This decrease is seen in the absence of Rec8 cleavage and depends on condensin-mediated recruitment of Polo-like kinase (PLK/Cdc5). In this study, we confirmed that this release indeed accompanies the dissociation of acetylated Smc3 as well as Rec8 from meiotic chromosomes during late prophase-I. This release requires, in addition to PLK, the cohesin regulator, Wapl (Rad61/Wpl1 in yeast), and Dbf4-dependent Cdc7 kinase (DDK). Meiosis-specific phosphorylation of Rad61/Wpl1 and Rec8 by PLK and DDK collaboratively promote this release. This process is similar to the vertebrate “prophase” pathway for cohesin release during G2 phase and pro-metaphase. In yeast, meiotic cohesin release coincides with PLK-dependent compaction of chromosomes in late meiotic prophase-I. We suggest that yeast uses this highly regulated cleavage-independent pathway to remove cohesin during late prophase-I to facilitate morphogenesis of condensed metaphase-I chromosomes., Author summary In meiosis the life and health of future generations is decided upon. Any failure in chromosome segregation has a detrimental impact. Therefore, it is currently believed that the physical connections between homologous chromosomes are maintained by meiotic cohesin with exceptional stability. Indeed, it was shown that cohesive cohesin does not show an appreciable turnover during long periods in oocyte development. In this context, it was long assumed but not properly investigated, that the prophase pathway for cohesin release would be specific to mitosis and would be safely suppressed during meiosis so as not to endanger essential connections between chromosomes. However, a previous study on budding yeast meiosis suggests the presence of cleavage-independent pathway of cohesin release during late prophase-I. In the work presented here we confirmed that the prophase pathway is not suppressed during meiosis, at least in budding yeast and showed that this cleavage-independent release is regulated by meiosis-specific phosphorylation of two cohesin subunits, Rec8 and Rad61(Wapl) by two cell-cycle regulators, PLK and DDK. Our results suggest that late meiotic prophase-I actively controls cohesin dynamics on meiotic chromosomes for chromosome segregation.