The role of stoichiometric vacancy periodicity in pressure-induced amorphization of the Ga2SeTe2 semiconductor alloy

We observe that pressure-induced amorphization of Ga2SeTe2 (a III-VI semiconductor) is directly influenced by the periodicity of its intrinsic defect structures. Specimens with periodic and semi-periodic two-dimensional vacancy structures become amorphous around 10-11 GPa in contrast to those with aperiodic structures, which amorphize around 7-8 GPa. The result is a notable instance of altering material phase-change properties via rearrangement of stoichiometric vacancies as opposed to adjusting their concentrations. Based on our experimental findings, we posit that periodic two-dimensional vacancy structures in Ga2SeTe2 provide an energetically preferred crystal lattice that is less prone to collapse under applied pressure. This is corroborated through first-principles electronic structure calculations, which demonstrate that the energy stability of III-VI structures under hydrostatic pressure is highly dependent on the configuration of intrinsic vacancies

A dislocation dynamics study of the strength of stacking fault tetrahedra. Part II: interactions with mixed and edge dislocations

In this paper we present the sequel to Part I and present a comprehensive dislocation dynamics study of the strength of stacking fault tetrahedra to mixed and edge dislocation glides in fcc Cu

The association of hydration status with physical signs, symptoms and survival in advanced cancer-The use of Bioelectrical Impedance Vector Analysis (BIVA) technology to evaluate fluid volume in palliative care: An observational study

Background Hydration in advanced cancer is a controversial area; however, current hydration assessments methods are poorly developed. Bioelectrical impedance vector analysis (BIVA) is an accurate hydration tool; however its application in advanced cancer has not been explored. This study used BIVA to evaluate hydration status in advanced cancer to examine the association of fluid status with symptoms, physical signs, renal biochemical measures and survival. Materials and methods An observational study of 90 adults with advanced cancer receiving care in a UK specialist palliative care inpatient unit was conducted. Hydration status was assessed using BIVA in addition to assessments of symptoms, physical signs, performance status, renal biochemical measures, oral fluid intake and medications. The association of clinical variables with hydration was evaluated using regression analysis. A survival analysis was conducted to examine the influence of hydration status and renal failure. Results The hydration status of participants was normal in 43 (47.8%), 'more hydrated' in 37 (41.1%) and 'less hydrated' in 10 (11.1%). Lower hydration was associated with increased symptom intensity (Beta = -0.29, p = 0.04) and higher scores for physical signs associated with dehydration (Beta = 10.94, p = 0.02). Higher hydration was associated with oedema (Beta = 2.55, p<0.001). Median survival was statistically significantly shorter in 'less hydrated' patients (44 vs. 68 days; p = 0.049) and in pre-renal failure (44 vs. 100 days; p = 0.003). Conclusions In advanced cancer, hydration status was associated with clinical signs and symptoms. Hydration status and pre-renal failure were independent predictors of survival. Further studies can establish the utility of BIVA as a standardised hydration assessment tool and explore its potential research application, in order to inform the clinical management of fluid balance in patients with advanced cancer

Gene therapy for monogenic liver diseases: clinical successes, current challenges and future prospects

Over the last decade, pioneering liver-directed gene therapy trials for haemophilia B have achieved sustained clinical improvement after a single systemic injection of adeno-associated virus (AAV) derived vectors encoding the human factor IX cDNA. These trials demonstrate the potential of AAV technology to provide long-lasting clinical benefit in the treatment of monogenic liver disorders. Indeed, with more than ten ongoing or planned clinical trials for haemophilia A and B and dozens of trials planned for other inherited genetic/metabolic liver diseases, clinical translation is expanding rapidly. Gene therapy is likely to become an option for routine care of a subset of severe inherited genetic/metabolic liver diseases in the relatively near term. In this review, we aim to summarise the milestones in the development of gene therapy, present the different vector tools and their clinical applications for liver-directed gene therapy. AAV-derived vectors are emerging as the leading candidates for clinical translation of gene delivery to the liver. Therefore, we focus on clinical applications of AAV vectors in providing the most recent update on clinical outcomes of completed and ongoing gene therapy trials and comment on the current challenges that the field is facing for large-scale clinical translation. There is clearly an urgent need for more efficient therapies in many severe monogenic liver disorders, which will require careful risk-benefit analysis for each indication, especially in paediatrics

From Demonstrations to Task-Space Specifications:Using Causal Analysis to Extract Rule Parameterization from Demonstrations

Learning models of user behaviour is an important problem that is broadly applicable across many application domains requiring human-robot interaction. In this work, we show that it is possible to learn generative models for distinct user behavioural types, extracted from human demonstrations, by enforcing clustering of preferred task solutions within the latent space. We use these models to differentiate between user types and to find cases with overlapping solutions. Moreover, we can alter an initially guessed solution to satisfy the preferences that constitute a particular user type by backpropagating through the learned differentiable models. An advantage of structuring generative models in this way is that we can extract causal relationships between symbols that might form part of the user's specification of the task, as manifested in the demonstrations. We further parameterize these specifications through constraint optimization in order to find a safety envelope under which motion planning can be performed. We show that the proposed method is capable of correctly distinguishing between three user types, who differ in degrees of cautiousness in their motion, while performing the task of moving objects with a kinesthetically driven robot in a tabletop environment. Our method successfully identifies the correct type, within the specified time, in 99% [97.8 - 99.8] of the cases, which outperforms an IRL baseline. We also show that our proposed method correctly changes a default trajectory to one satisfying a particular user specification even with unseen objects. The resulting trajectory is shown to be directly implementable on a PR2 humanoid robot completing the same task.Comment: arXiv admin note: substantial text overlap with arXiv:1903.0126

Non-Integrative Lentivirus Drives High-Frequency cre-Mediated Cassette Exchange in Human Cells

Recombinase mediated cassette exchange (RMCE) is a two-step process leading to genetic modification in a specific genomic target sequence. The process involves insertion of a docking genetic cassette in the genome followed by DNA transfer of a second cassette flanked by compatible recombination signals and expression of the recombinase. Major technical drawbacks are cell viability upon transfection, toxicity of the enzyme, and the ability to target efficiently cell types of different origins. To overcome such drawbacks, we developed an RMCE assay that uses an integrase-deficient lentivirus (IDLV) vector in the second step combined with promoterless trapping of double selectable markers. Additionally, recombinase expression is self-limiting as a result of the exchangeable reaction, thus avoiding toxicity. Our approach provides proof-of-principle of a simple and novel strategy with expected wide applicability modelled on a human cell line with randomly integrated copies of a genetic landing pad. This strategy does not present foreseeable limitations for application to other cell systems modified by homologous recombination. Safety, efficiency, and simplicity are the major advantages of our system, which can be applied in low-to-medium throughput strategies for screening of cDNAs, non-coding RNAs during functional genomic studies, and drug screening

The Influence of Recent Climate Change on Tree Height Growth Differs with Species and Spatial Environment

Tree growth has been reported to increase in response to recent global climate change in controlled and semi-controlled experiments, but few studies have reported response of tree growth to increased temperature and atmospheric carbon dioxide (CO2) concentration in natural environments. This study addresses how recent global climate change has affected height growth of trembling aspen (Populus tremuloides Michx) and black spruce (Picea mariana Mill B.S.) in their natural environments. We sampled 145 stands dominated by aspen and 82 dominated by spruce over the entire range of their distributions in British Columbia, Canada. These stands were established naturally after fire between the 19th and 20th centuries. Height growth was quantified as total heights of sampled dominant and co-dominant trees at breast-height age of 50 years. We assessed the relationships between 50-year height growth and environmental factors at both spatial and temporal scales. We also tested whether the tree growth associated with global climate change differed with spatial environment (latitude, longitude and elevation). As expected, height growth of both species was positively related to temperature variables at the regional scale and with soil moisture and nutrient availability at the local scale. While height growth of trembling aspen was not significantly related to any of the temporal variables we examined, that of black spruce increased significantly with stand establishment date, the anomaly of the average maximum summer temperature between May-August, and atmospheric CO2 concentration, but not with the Palmer Drought Severity Index. Furthermore, the increase of spruce height growth associated with recent climate change was higher in the western than in eastern part of British Columbia. This study demonstrates that the response of height growth to recent climate change, i.e., increasing temperature and atmospheric CO2 concentration, did not only differ with tree species, but also their growing spatial environment

Diversity and Functional Traits of Lichens in Ultramafic Areas: A Literature Based Worldwide Analysis Integrated by Field Data at the Regional Scale

While higher plant communities found on ultramafics are known to display peculiar characteristics, the distinguishability of any peculiarity in lichen communities is still a matter of contention. Other biotic or abiotic factors, rather than substrate chemistry, may contribute to differences in species composition reported for lichens on adjacent ultramafic and non-ultramafic areas. This work examines the lichen biota of ultramafics, at global and regional scales, with reference to species-specific functional traits. An updated world list of lichens on ultramafic substrates was analyzed to verify potential relationships between diversity and functional traits of lichens in different Köppen–Geiger climate zones. Moreover, a survey of diversity and functional traits in saxicolous communities on ultramafic and non-ultramafic substrates was conducted in Valle d’Aosta (North-West Italy) to verify whether a relationship can be detected between substrate and functional traits that cannot be explained by other environmental factors related to altitude. Analyses (unweighted pair group mean average clustering, canonical correspondence analysis, similarity-difference-replacement simplex approach) of global lichen diversity on ultramafic substrates (2314 reports of 881 taxa from 43 areas) displayed a zonal species distribution in different climate zones rather than an azonal distribution driven by the shared substrate. Accordingly, variations in the frequency of functional attributes reflected reported adaptations to the climate conditions of the different geographic areas. At the regional scale, higher similarity and lower species replacement were detected at each altitude, independent from the substrate, suggesting that altitude-related climate factors prevail over putative substrate–factors in driving community assemblages. In conclusion, data do not reveal peculiarities in lichen diversity or the frequency of functional traits in ultramafic areas

Type II Heat-Labile Enterotoxins from 50 Diverse Escherichia coli Isolates Belong Almost Exclusively to the LT-IIc Family and May Be Prophage Encoded

Some enterotoxigenic Escherichia coli (ETEC) produce a type II heat-labile enterotoxin (LT-II) that activates adenylate cyclase in susceptible cells but is not neutralized by antisera against cholera toxin or type I heat-labile enterotoxin (LT-I). LT-I variants encoded by plasmids in ETEC from humans and pigs have amino acid sequences that are ≥95% identical. In contrast, LT-II toxins are chromosomally encoded and are much more diverse. Early studies characterized LT-IIa and LT-IIb variants, but a novel LT-IIc was reported recently. Here we characterized the LT-II encoding loci from 48 additional ETEC isolates. Two encoded LT-IIa, none encoded LT-IIb, and 46 encoded highly related variants of LT-IIc. Phylogenetic analysis indicated that the predicted LT-IIc toxins encoded by these loci could be assigned to 6 subgroups. The loci corresponding to individual toxins within each subgroup had DNA sequences that were more than 99% identical. The LT-IIc subgroups appear to have arisen by multiple recombinational events between progenitor loci encoding LT-IIc1- and LT-IIc3-like variants. All loci from representative isolates encoding the LT-IIa, LT-IIb, and each subgroup of LT-IIc enterotoxins are preceded by highly-related genes that are between 80 and 93% identical to predicted phage lysozyme genes. DNA sequences immediately following the B genes differ considerably between toxin subgroups, but all are most closely related to genomic sequences found in predicted prophages. Together these data suggest that the LT-II loci are inserted into lambdoid type prophages that may or may not be infectious. These findings raise the possibility that production of LT-II enterotoxins by ETEC may be determined by phage conversion and may be activated by induction of prophage, in a manner similar to control of production of Shiga-like toxins by converting phages in isolates of enterohemmorhagic E. coli