Brief communication: A roadmap towards credible projections of ice sheet contribution to sea level

Accurately projecting mass loss from ice sheets is of critical societal importance. However, despite recent improvements in ice sheet models, our analysis of a recent effort to project ice sheet contribution to future sea level suggests that few models reproduce historical mass loss accurately and that they appear much too confident in the spread of predicted outcomes. The inability of models to reproduce historical observations raises concerns about the models' skill at projecting mass loss. Here we suggest that uncertainties in the future sea level contribution from Greenland and Antarctica may well be significantly higher than reported in that study. We propose a roadmap to enable a more realistic accounting of uncertainties associated with such forecasts and a formal process by which observations of mass change should be used to refine projections of mass change. Finally, we note that tremendous government investment and planning affecting tens to hundreds of millions of people is founded on the work of just a few tens of scientists. To achieve the goal of credible projections of ice sheet contribution to sea level, we strongly believe that investment in research must be commensurate with the scale of the challenge.

Downhole Steam Generation for Green Heavy Oil Recovery

The ultimate target of heavy oil recovery is to enhance oil mobility by transferring steam's thermal energy to the oil phase, incrementing its temperature, and reducing heavy oil's viscosity. While the various types of steam floods such as Cyclic Steam Injection (CSI) and Steam-Assisted Gravity Drainage (SAGD) are widely used worldwide, they have certain limitations that need further improvements. Notably, in surface steam generation systems, downhole steam quality is around 70% which means that 30% of latent heat is lost while steam travels from the surface to the pre-determined downhole location. Downhole steam generation (DHSG) can be a viable alternative for the surface steam injection in which steam will be generated downhole instead of on the surface. The asserted method presents significant benefits such as preventing steam quality loss, decreasing the environmental effects, and enhancing the heavy oil recovery by co-injecting the flue gas products such as CO2, and consequently, the economic outcomes will be increased. In this research, a comprehensive techno-economic case study has been conducted on a heavy oil reservoir to evaluate the economic and technical advantages of DHSG compared to surface steam generation. Various technical expenses and revenues such as investment costs, operating costs, royalties, and taxes have been considered in a simulation model in MATLAB. This DHSG feasibility assessment has been performed using data of a heavy oil reserve currently under steam flood. Results showed that DHSG could increase up to 50% economic and technical interest than conventional steam injection projects. One of the outstanding benefits of DHSG is the reduction of heat loss. Since steam is produced in-situ, either downhole or in the reservoir, no waste of heat occurs. Typically, most heat losses happen on surface lines and wellbore during steam injection from the surface, which accounts for approximately 32%. Thus, this issue is excluded using the DHSG method. The results of the recent effort fit well into the current industry's requirements. DHSG can (1) increase the rate of heavy oil production, (2) decrease the extra expenses, and (3) dwindle the environmental side effects of CO2 emission of surface steam generation. Compared with conventional thermal methods, in DHSG, the steam to oil ratio remains constant with depth change while the desired steam quality can be achieved at any location. The asserted benefits can ultimately optimize the steam injection with a significant reduction in UTC, hence, improved profitability.

Trehalose glycolipids as immunomodulators and their incorporation into liposomes for drug delivery

<p>The development of novel therapies for cancer and other diseases is an area of enormous research effort due to the growing need for better patient outcomes. As such, not only is the chemical synthesis of new drugs and adjuvants required, but ways to improve drug delivery also need to be explored. Accordingly, there has been much recent effort towards the synthesis and the biological evaluation of bacterial cell wall components as immunomodulatory compounds. To this end, trehalose glycolipids (TGs), which have been isolated from bacteria of the Mycobacteria family, are of significant interest, due to their anti-tumour and adjuvant activities. In this thesis, the efficient synthesis of trehalose monoesters (TMEs) was investigated and the ability of these monoesters to activate macrophages via Mincle was studied and compared to the activities of their trehalose diester (TDE) counterparts. In this way, a better understanding of how TG structure influences biological activity was explored. Liposomes containing a representative TG (the C26 TDE) were also synthesised, with the objective being to explore whether TGliposomes could be used as improved drug delivery vehicles. To meet these overall objectives, TGs in solution, as well as TG incorporated into liposomes, were tested for their ability to activate macrophages derived from both C57BL/6 and Mincle-/- mice, whereby the Mincle receptor is a known receptor for TDEs. In the TME studies, an optimised synthesis of the monoesters was developed. The ability of the TMEs to active macrophages was explored and, for the first time, it was observed that TMEs have similar biological activities to TDEs. In the TGliposome studies, a variety of liposomes containing different concentrations of phosphatidylcholine (PC) as well as the C26 TDE was prepared, so as to explore how differences in these two constituent parts influence the activation of macrophages. From this work, it was observed that increasing concentrations of TG in the liposome and increasing concentrations of liposomes gave increased macrophage activation. A concentration of PC above 200 !M also led to macrophage activation, and non-specific cell death was observed at time points > 48 h (for the wild type macrophages) and at time points ≥ 48 h for the Mincle-/- macrophages. Thus, in the case of the TG liposomes, macrophage activation is independent of Mincle, which was unusual as macrophage activation in the case of the individual TGs was dependent on this receptor. Taken as a whole, these results pave the way for further investigations into utilising TGs in the treatment of diseases. In particular, this work provided insight into the requirement of TG/Mincle binding for improved TGs as potential adjuvants. Moreover, these studies demonstrated that the incorporation of TGs into liposomes leads to enhanced macrophage activation and therefore, potentially enhanced phagocytosis by these immune cells. Accordingly, TG-liposomes may find future application as drug delivery vehicles, in diseases where macrophages play a prominent role.</p>

Trehalose glycolipids as immunomodulators and their incorporation into liposomes for drug delivery

<p>The development of novel therapies for cancer and other diseases is an area of enormous research effort due to the growing need for better patient outcomes. As such, not only is the chemical synthesis of new drugs and adjuvants required, but ways to improve drug delivery also need to be explored. Accordingly, there has been much recent effort towards the synthesis and the biological evaluation of bacterial cell wall components as immunomodulatory compounds. To this end, trehalose glycolipids (TGs), which have been isolated from bacteria of the Mycobacteria family, are of significant interest, due to their anti-tumour and adjuvant activities. In this thesis, the efficient synthesis of trehalose monoesters (TMEs) was investigated and the ability of these monoesters to activate macrophages via Mincle was studied and compared to the activities of their trehalose diester (TDE) counterparts. In this way, a better understanding of how TG structure influences biological activity was explored. Liposomes containing a representative TG (the C26 TDE) were also synthesised, with the objective being to explore whether TGliposomes could be used as improved drug delivery vehicles. To meet these overall objectives, TGs in solution, as well as TG incorporated into liposomes, were tested for their ability to activate macrophages derived from both C57BL/6 and Mincle-/- mice, whereby the Mincle receptor is a known receptor for TDEs. In the TME studies, an optimised synthesis of the monoesters was developed. The ability of the TMEs to active macrophages was explored and, for the first time, it was observed that TMEs have similar biological activities to TDEs. In the TGliposome studies, a variety of liposomes containing different concentrations of phosphatidylcholine (PC) as well as the C26 TDE was prepared, so as to explore how differences in these two constituent parts influence the activation of macrophages. From this work, it was observed that increasing concentrations of TG in the liposome and increasing concentrations of liposomes gave increased macrophage activation. A concentration of PC above 200 !M also led to macrophage activation, and non-specific cell death was observed at time points > 48 h (for the wild type macrophages) and at time points ≥ 48 h for the Mincle-/- macrophages. Thus, in the case of the TG liposomes, macrophage activation is independent of Mincle, which was unusual as macrophage activation in the case of the individual TGs was dependent on this receptor. Taken as a whole, these results pave the way for further investigations into utilising TGs in the treatment of diseases. In particular, this work provided insight into the requirement of TG/Mincle binding for improved TGs as potential adjuvants. Moreover, these studies demonstrated that the incorporation of TGs into liposomes leads to enhanced macrophage activation and therefore, potentially enhanced phagocytosis by these immune cells. Accordingly, TG-liposomes may find future application as drug delivery vehicles, in diseases where macrophages play a prominent role.</p>

A Systematic Review of Spatial-Temporal Scale Issues in Sociohydrology

Sociohydrology is a recent effort to integrate coupled human-water systems to understand the dynamics and co-evolution of the system in a holistic sense. However, due to the complexity and uncertainty involved in coupled human-water systems, the feedbacks and interactions are inherently difficult to model. Part of this complexity is due to the multi-scale nature across space and time at which different hydrologic and social processes occur and the varying scale at which data is available. This systematic review seeks to comprehensively collect those documents that conduct analysis within the sociohydrology framework to quantify the spatial-temporal scale(s) and the types of variables and datasets that were used. Overall, a majority of sociohydrology studies reviewed were primarily published in hydrological journals and contain more established hydrological, rather than social, models. The spatial extents varied by political and natural boundaries with the most common being cities and watersheds. Temporal extents also varied from event-based to millennial timescales where decadal and yearly were the most common. In addition to this, current limitations of sociohydrology research, notably the absence of an interdisciplinary unity, future directions, and implications for scholars doing sociohydrology are discussed.

EFFECTS OF AS-RECEIVED DEFECTS ON CERAMIC MATRIX COMPOSITES PROPERTIES USING HIGH- FIDELITY MICROSTRUCTURES WITH PERIODIC BOUNDARY CONDITIONS

The presence of microstructural defects in as-received specimens of ceramic matrix composites (CMCs) significantly influences their constitutive response and damage, highlighting the importance of characterization and quantification of these defects for accurate assessment of damage and failure in the service environment. In a recent effort, the authors developed an algorithm to generate stochastic representative volume elements (SRVEs) of Carbon fiber Silicon-Carbide-Nitride matrix (C/SiNC) CMCs based on extensive multiscale material and defect characterization data. This paper implements this algorithm within a commercial finite element solver with periodic boundary conditions (PBCs) for high-fidelity micromechanics analysis and investigation of macroscopic material behavior of C/SiNC composites. Different loading directions are used to predict the global mechanical properties, and the results are in excellent agreement with theoretical (rule of mixture) predictions. Subsequently, the effects of as-received defects on the global and local responses are investigated. The results show that intratow porosity has pronounced degradation effects on the global elastic properties and results in complex stress localization patterns, which can be attributed to potential damage initiation sites.

Experimental and numerical investigations of ventilated acoustic metamaterial based in-parallel arrangement of Helmholtz resonator for façade screen

Understanding urban noise as a serious environmental problem in urban centers, the development and application of noise control strategies have demanded a recent effort by several researches. In this case, the development of acoustic metamaterial artificially designed to manipulate the wave phenomena has become a recent topic, aiming at optimized responses, and enables the development of subwavelength devices with potential application in passive ventilation and noise mitigation, providing better environmental conditions in buildings. The present paper intends to contribute to the knowledge in this field by investigating the concept of an acoustic metamaterial with negative bulk modulus based in a parallel arrangement of Helmholtz Resonators. Experimental and numerical investigations are carried out to determine the acoustic potential of the proposed meta structure in terms of sound absorption and sound transmission loss. The developed concept exhibits significant benefits in the properties of sound transmission loss, and seems a potential application for noise control at specific frequency bands (mainly at low to middle frequency) in building façades.

Germ cells: ENCODE’s forgotten cell type

More than a decade ago, the ENCODE and NIH Epigenomics Roadmap consortia organized large multi-laboratory efforts to profile the epigenomes of &gt;110 different mammalian somatic cell types. This generated valuable publicly accessible datasets that are being mined to reveal genome-wide patterns of a variety of different epigenetic parameters. This consortia approach facilitated the powerful and comprehensive multiparametric integrative analysis of the epigenomes in each cell type. However, no germ cell types were included among the cell types characterized by either of these consortia. Thus, comprehensive epigenetic profiling data is not generally available for the most evolutionarily important cells, male and female germ cells. We discuss the need for reproductive biologists to generate similar multiparametric epigenomic profiling datasets for both male and female germ cells at different developmental stages, and summarize our recent effort to derive such data for mammalian spermatogonial stem cells and progenitor spermatogonia.

Brief communication: A roadmap towards credible projections of ice sheet contribution to sea-level

Accurately projecting mass loss from ice sheets is of critical societal importance. However, despite recent improvements in ice sheet models, our analysis of a recent effort to project Greenland's contribution to future sea-level suggests that few models reproduce historical mass loss accurately, and that they appear much too confident in the spread of predicted outcomes. The inability of models to reproduce historical observations raises concerns about the models' skill at projecting mass loss. Here we suggest that the future sea level contribution from Greenland may well be significantly higher than reported in that study. We propose a roadmap to enable a more realistic accounting of uncertainties associated with such forecasts, and a formal process by which observations of mass change be used to refine projections of mass change. Finally, we note that tremendous government investment and planning affecting 10s to 100s of millions of people is founded on the work of several tens of scientists involved in a significantly volunteer effort. To achieve the goal of credible projections of ice sheet contribution to sea-level, we strongly believe that investment in research must be commensurate with the scale of the challenge.

Random-effect based test for multinomial logistic regression: choice of the reference level and its impact on the testing

ABSTRACTRandom-effect score test has become an important tool for studying the association between a set of genetic variants and a disease outcome. While a number of random-effect score test approaches have been proposed in the literature, similar approaches for multinomial logistic regression have received less attention. In a recent effort to develop random-effect score test for multinomial logistic regression, we made the observation that such a test is not invariant to the choice of the reference level. This is intriguing because binary logistic regression is well-known to possess the invariance property with respect to the reference level. Here, we investigate why the multinomial logistic regression is not invariant to the reference level, and derive analytic forms to study how the choice of the reference level influences the power. Then we consider several potential procedures that are invariant to the reference level, and compare their performance through numerical studies. Our work provides valuable insights into the properties of multinomial logistic regression with respect to random-effect score test, and adds a useful tool for studying the genetic heterogeneity of complex diseases.