On FO2 quantifier alternation over words

We show that each level of the quantifier alternation hierarchy within FO^2[<] -- the 2-variable fragment of the first order logic of order on words -- is a variety of languages. We then use the notion of condensed rankers, a refinement of the rankers defined by Weis and Immerman, to produce a decidable hierarchy of varieties which is interwoven with the quantifier alternation hierarchy -- and conjecturally equal to it. It follows that the latter hierarchy is decidable within one unit: given a formula alpha in FO^2[<], one can effectively compute an integer m such that alpha is equivalent to a formula with at most m+1 alternating blocks of quantifiers, but not to a formula with only m-1 blocks. This is a much more precise result than what is known about the quantifier alternation hierarchy within FO[<], where no decidability result is known beyond the very first levels

The Word Problem for Omega-Terms over the Trotter-Weil Hierarchy

For two given $\omega$-terms $\alpha$ and $\beta$, the word problem for $\omega$-terms over a variety $\boldsymbol{\mathrm{V}}$ asks whether $\alpha=\beta$ in all monoids in $\boldsymbol{\mathrm{V}}$. We show that the word problem for $\omega$-terms over each level of the Trotter-Weil Hierarchy is decidable. More precisely, for every fixed variety in the Trotter-Weil Hierarchy, our approach yields an algorithm in nondeterministic logarithmic space (NL). In addition, we provide deterministic polynomial time algorithms which are more efficient than straightforward translations of the NL-algorithms. As an application of our results, we show that separability by the so-called corners of the Trotter-Weil Hierarchy is witnessed by $\omega$-terms (this property is also known as $\omega$-reducibility). In particular, the separation problem for the corners of the Trotter-Weil Hierarchy is decidable

Anatomy and origin of authochthonous late Pleistocene forced regression deposits, east Coromandel inner shelf, New Zealand: implications for the development and definition of the regressive systems tract

High-resolution seismic reflection data from the east Coromandel coast, New Zealand, provide details of the sequence stratigraphy beneath an autochthonous, wave dominated inner shelf margin during the late Quaternary (0-140 ka). Since c. 1 Ma, the shelf has experienced limited subsidence and fluvial sediment input, producing a depositional regime characterised by extensive reworking of coastal and shelf sediments during glacio-eustatic sea-level fluctuations. It appears that only one complete fifth-order (c. 100 000 yr) depositional sequence is preserved beneath the inner shelf, the late Pleistocene Waihi Sequence, suggesting any earlier Quaternary sequences were mainly cannibalised into successively younger sequences. The predominantly Holocene-age Whangamata Sequence is also evident in seismic data and modern coastal deposits, and represents an incomplete depositional sequence in its early stages of formation. A prominent aspect of the sequence stratigraphy off parts of the east Coromandel coast is the presence of forced regressive deposits (FRDs) within the regressive systems tract (RST) of the late Pleistocene Waihi Sequence. The FRDs are interpreted to represent regressive barrier-shoreface sands that were sourced from erosion and onshore reworking of underlying Pleistocene sediments during the period of slow falling sea level from isotope stages 5 to 2 (c. 112-18 ka). The RST is volumetrically the most significant depositional component of the Waihi Sequence; the regressive deposits form a 15-20 m thick, sharp-based, tabular seismic unit that downsteps and progrades continuously across the inner shelf. The sequence boundary for the Waihi Sequence is placed at the most prominent, regionally correlative, and chronostratigraphically significant surface, namely an erosional unconformity characterised in many areas by large incised valleys that was generated above the RST. This unconformity is interpreted as a surface of maximum subaerial erosion generated during the last glacial lowstand (c. 18 ka). Although the base of the RST is associated with a prominent regressive surface of erosion, this is not used as the sequence boundary as it is highly diachronous and difficult to identify and correlate where FRDs are not developed. The previous highstand deposits are limited to subaerial barrier deposits preserved behind several modern Holocene barriers along the coast, while the transgressive systems tract is preserved locally as incised-valley fill deposits beneath the regressive surface of erosion at the base of the RST. Many documented late Pleistocene RSTs have been actively sourced from fluvial systems feeding the shelf and building basinward-thickening, often stacked wedges of FRDs, for which the name allochthonous FRDs is suggested. The Waihi Sequence RST is unusual in that it appears to have been sourced predominantly from reworking of underlying shelf sediments, and thus represents an autochthonous FRD. Autochthonous FRDs are also present on the Forster-Tuncurry shelf in southeast Australia, and may be a common feature in other shelf settings with low subsidence and low sediment supply rates, provided shelf gradients are not too steep, and an underlying source of unconsolidated shelf sediments is available to source FRDs. The preservation potential of such autochthonous FRDs in ancient deposits is probably low given that they are likely to be cannibalised during subsequent sea-level falls

Genetical genomics: spotlight on QTL hotspots

No abstract available

Parent-child bonding and attachment during pregnancy and early childhood following congenital heart disease diagnosis

Diagnosis and treatment of congenital heart disease (CHD) can present challenges to the developing parent-child relationship due to periods of infant hospitalisation and intensive medical care, parent-infant separations, child neurodevelopmental delay and feeding problems, and significant parent and child distress and trauma. Yet, the ways in which CHD may affect the parent-child relationship are not well-understood. We systematically reviewed the evidence on parental bonding, parent-child interaction, and child attachment following CHD diagnosis, according to a pre-registered protocol (CRD42019135687). Six electronic databases were searched for English-language studies comparing a cardiac sample (i.e., expectant parents or parents and their child aged 0-5 years with CHD) with a healthy comparison group on relational outcomes. Of 22 identified studies, most used parent-report measures (73%) and yielded mixed results for parental bonding and parent-child interaction quality. Observational results also varied, although most studies (4 of 6) found difficulties in parent-child interaction on one or more affective or behavioural domains (e.g., lower maternal sensitivity, lower infant responsiveness). Research on parental-fetal bonding, father-child relationships, and child attachment behaviour was lacking. Stronger evidence is needed to determine the nature, prevalence, and predictors of relational disruptions following CHD diagnosis, and to inform targeted screening, prevention, and early intervention programs for at-risk dyads

High-throughput profiling of off-target DNA cleavage reveals RNA-programmed Cas9 nuclease specificity

The RNA-programmable Cas9 endonuclease cleaves double-stranded DNA at sites complementary to a 20-base-pair guide RNA. The Cas9 system has been used to modify genomes in multiple cells and organisms, demonstrating its potential as a facile genome-engineering tool. We used in vitro selection and high-throughput sequencing to determine the propensity of eight Cas9:guide RNA complexes to cleave each of 10^12 potential off-target DNA sequences. The selection results predicted five off-target sites in the human genome that were confirmed to undergo genome cleavage in HEK293T cells upon expression of one of two Cas9:guide RNA complexes. In contrast to previous models, our results show that Cas9:guide RNA specificity extends past a 7- to 12-base pair seed sequence. Our results also suggest a tradeoff between activity and specificity both in vitro and in cells as a shorter, less-active guide RNA is more specific then a longer, more-active guide RNA. High concentrations of Cas9:guide RNA complexes can cleave off-target sites containing mutations near or within the PAM that are not cleaved when enzyme concentrations are limiting

Characterization of a putative NsrR homologue in Streptomyces venezuelae reveals a new member of the Rrf2 superfamily

Members of the Rrf2 superfamily of transcription factors are widespread in bacteria but their functions are largely unexplored. The few that have been characterized in detail sense nitric oxide (NsrR), iron limitation (RirA), cysteine availability (CymR) and the iron sulfur (Fe-S) cluster status of the cell (IscR). In this study we combined ChIP-seq with in vitro biochemistry to characterize a putative NsrR homologue in the model organism Streptomyces venezuelae. ChIP seq analysis revealed that rather than regulating the nitrosative stress response like NsrR, Sven6563 binds to a different, much larger regulon of genes with a diverse range of functions, including a range of regulators, genes required for glutamine synthesis, NADH/NAD(P)H metabolism, as well as general DNA/RNA and amino acid/protein turn over. Our biochemical experiments further show that Sven6563 has a [2Fe-2S] cluster and that the switch between oxidized and reduced cluster controls its DNA binding activity in vitro. To our knowledge, both the sensing domain and the target gene regulon are novel for an Rrf2 protein, suggesting Sven6563 represents a new member of the Rrf2 superfamily. Given the redox sensitivity of its Fe-S cluster we have tentatively named the protein RsrR for Redox sensitive response Regulator

Evidence for thermal fatigue on Mars from rockfall patterns on impact crater slopes

Individual block falls are one of the currently active surface processes on Mars. Similarly to Earth, clasts detach from upslope outcrops roll or bounce downslope, leaving a track on the substratum (Fig. 1). The trails show that the rockfalls are recent, as aeolian processes would infill topographic lows over time. Using rover-track erasure rates, these tracks are likely <100 ka. On Earth, slope instability is usually caused by phase changes of H2O [1]. However, solar-induced thermal stress could also play a key-role in rock breakdown leading to rockfalls [2]. Although liquid water is not stable at the surface of Mars today, sub-surface water ice is known to be present from mid- to high-latitudes [3]. Water ice and CO2 seasonal frost on shadowed pole-facing slopes may exist at latitudes down to 30° [4] or less [5]. On the other hand, insolation-related thermal stress has been used to explain fracture orientation patterns in martian boulders observed by the Mars Exploration Rovers [6] and other studies suggest that it could cause rock breakdown on airless bodies [7]. Therefore, both phase transitions and solar-induced thermal stress are plausible mechanisms for rock breakdown and preconditioning slopes for rockfalls on modern Mars. In this study we analyze distribution of rockfalls on impact crater walls to assess whether one of these mechanisms could be involved in local rock breakdown

Evidence for thermal-stress-induced rockfalls on Mars impact crater slopes

Here we study rocks falling from exposed outcrops of bedrock, which have left tracks on the slope over which they have bounced and/or rolled, in fresh impact craters (1–10 km in diameter) on Mars. The presence of these tracks shows that these rocks have fallen relatively recently because aeolian processes are known to infill topographic lows over time. Mapping of rockfall tracks indicate trends in frequency with orientation, which in turn depend on the latitudinal position of the crater. Craters in the equatorial belt (between 15°N and 15°S) exhibit higher frequencies of rockfall on their N-S oriented slopes compared to their E-W ones. Craters >15° N/S have notably higher frequencies on their equator-facing slopes as opposed to the other orientations. We computed solar radiation on the surface of crater slopes to compare insolation patterns and rockfall spatial distribution, and find statistically significant correlations between maximum diurnal insolation and rockfall frequency. Our results indicate that solar-induced thermal stress plays a more important role under relatively recent climate conditions in rock breakdown and preconditioning slopes for rockfalls than phase transitions of H2O or CO2, at mid and equatorial latitudes. Thermal stress should thus be considered as an important factor in promoting mass-wasting process on impact crater walls and other steep slopes on Mars

Rapid assembly of customized TALENs into multiple

Transcriptional activator-like effector nucleases (TALENs) have become a powerful tool for genome editing. Here we present an efficient TALEN assembly approach in which TALENs are assembled by direct Golden Gate ligation into Gateway® Entry vectors from a repeat variable di-residue (RVD) plasmid array. We constructed TALEN pairs targeted to mouse Ddx3 subfamily genes, and demonstrated that our modified TALEN assembly approach efficiently generates accurate TALEN moieties that effectively introduce mutations into target genes. We generated "user friendly" TALEN Entry vectors containing TALEN expression cassettes with fluorescent reporter genes that can be efficiently transferred via Gateway (LR) recombination into different delivery systems. We demonstrated that the TALEN Entry vectors can be easily transferred to an adenoviral delivery system to expand application to cells that are difficult to transfect. Since TALENs work in pairs, we also generated a TALEN Entry vector set that combines a TALEN pair into one PiggyBac transposon-based destination vector. The approach described here can also be modified for construction of TALE transcriptional activators, repressors or other functional domains. © 2013 Zhang et al