Adeno-associated viruses (AAVs, genus dependoparvovirus) are promising gene therapy vectors. In strains AAV1-12, the capsid gene VP1 encodes a recently discovered protein, MAAP, in an overlapping frame. MAAP binds the cell membrane by an unknown mechanism. We discovered that MAAP is also encoded in bovine AAV and in porcine AAVs (which have shown promise for gene transfer into muscle tissues), in which it is probably translated from a non-canonical start codon. MAAP is predicted to be mostly disordered except for a predicted C-terminal, membrane-binding amphipathic α-helix. MAAP has a highly unusual composition. In particular, it lacks internal methionines, and is devoid of tyrosines in most strains. Unexpectedly, we discovered that the N-terminus of VP1 also lacks several amino acids. In all AAVs that encode MAAP, the first 200 aas of VP1 are devoid of internal methionines, probably owing to a selection against ATG codons that could prevent translation of MAAP and of capsid isoforms (VP2, VP3). The N-terminus of VP1 also lacks cysteines, likely to avoid the formation of disulfide bridges when it becomes exposed outside of the capsid during post-endocytic trafficking. Finally, the region common to VP1 and VP2 lacks tyrosine in the vast majority of AAVs that encode MAAP. Avoiding these "forbidden" aas in MAAP and VP1 when creating recombinant AAV capsids might increase the efficiency of capsid design. Conversely, the presence of "forbidden" aas in some rare strains probably indicates that they have unusual properties that could help us understand the viral cycle.

The altered nature of archaeological metals means they deteriorate at conditions where metals would be stable. The study of deterioration for such materials is hampered by their complexity, variability and difficulties in measuring deterioration. Placing an object in a sealed container, controlling the RH and pollutant gases and measuring any decrease in oxygen concentration is an accessible method to measure deterioration rate. It has been used for research into suitable environmental conditions to manage deterioration rates of such artefacts including differences in response for artefacts from different excavation sites. Some objects need careful control of RH to low values, this is expensive to maintain and poses risks to other artefacts displayed together. Many objects are actually stable up to quite high RH values and oxygen depletion testing has been used to identify those that can be safely displayed with minimal environmental control. The accelerated corrosion, ‘Oddy’ test is frequently used to sift out unsuitable display materials. The visual assessment is widely recognized to be subjective. The test container has been modified and oxygen depletion appears to give good quantitative measurements of corrosion that correspond with both visual comparison and corrosion quantification for copper, lead and steel, but not for silver.

The main focus of this paper is to analyze the effect of local public finance on spatial land use through economic models and empirical evidence from Israel. The theoretic models extends the Alonso-Mill-Muth model by incorporating local public finance. The first finding is that steady population growth provides a channel for land capitalization through the mechanism of long term land property right. This implies a possible conflict of interest if ownership of land leasing revenue and the ad valorem property tax are not consistent. The empirical section examines one of the implications derived from the models highlighting a possible inconsistency between central and local governments due to land ownership centralization. This causes local tax revenue inequality among Israeli municipalities. Statistical evidence shows that cities with a larger share business land use can generate more tax without assistance from the central government, and are therefore more fiscal independent. Fiscal status has a significant effect on the planning time of residential construction. Municipalities with higher local tax revenues have shorter planning time(higher probability of acceptance) conditional on the plan’s size and other features.

The emerging of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak is associated with high morbidity and mortality rates globally. One of the most prominent characteristics of coronavirus disease-19 (COVID-19) is lymphopenia which is in contrast to other viral infections. This controversy might be explained by the evaluation of impaired innate and adaptive immune responses during the SARS-CoV-2 infection. During the innate immune response, poly-ADP-ribose polymerase (PARP) hyperactivated due to virus entry and extensive DNA damage sequentially leading to NAD+ depletion, ATP depletion and finally cell death. In contrast to the immune response against viral infections, cytotoxic T lymphocytes decline sharply in SARS-CoV-2 infection which might be due to infiltration and trapping in the lower respiratory tract. In addition, there are more factors proposed to involve in lymphopenia in COVID-19 infection like the role of CD38 which functions as NADase and intensifies NAD depletion which in turn affects NAD+ dependent Sirtuin proteins, as the regulators of cell death and viability. Lung tissue sequestration following cytokine storm supposed to be another reason for lymphopenia in COVID-19 patients. Protein 7a as one of the virus-encoded proteins induces apoptosis in various organ-derived cell lines. These mechanisms proposed to induce lymphopenia, although there are still more studies needed to clarify the underlying mechanisms for lymphopenia in COVID-19 patients.

Solids in the interstellar medium consist of an intimate mixture of silicate and carbonaceous grains. Because 99% of silicates in meteorites were reprocessed at high temperatures in the inner regions of the Solar Nebula, we propose that similar levels of heating of carbonaceous materials in the oxygen-rich Solar Nebula would have converted nearly all carbon in dust and grain coatings to CO. We discuss catalytic experiments on a variety of grain surfaces that not only produce gas-phase species such as CH4, C2H6, C6H6, C6H5OH or CH3CN, but also produce carbonaceous solids and fibers that would be much more readily incorporated into growing planetesimals. CO and other more volatile products of these surface mediated reactions were likely transported outwards along with chondrule fragments and small Calcium Aluminum Inclusions (CAIs) to enhance the organic content in the outer regions of the nebula where comets formed. Carbonaceous fibers formed on the surfaces of refractory oxides may have significantly improved the aggregation efficiency of chondrules and CAIs. Carbonaceous fibers incorporated into chondritic parent bodies might have served as the carbon source for the generation of more complex organic species during thermal or hydrous metamorphic processes on the evolving asteroid.

Cameroon territory is experiencing significant land use and land cover (LULC) changes since its independence in 1960. But the main relevant impacts are recorded since 1990 due to intensification of agricultural activities and urbanization. LULC effects and dynamics vary from one region to another according to the type of vegetation cover and activities. Using remote sensing, GIS and subsidiary data, this paper attempted to model the land use and land cover (LULC) change in the Centre Region of Cameroon that host Yaoundé metropolis. The rapid expansion of the city of Yaoundé drives to the land conversion with farmland intensification and forest depletion accelerating the rate at which land use and land cover (LULC) transformations take place. This study aims at assessing the impacts of both agriculture and urbanization on the LULC change in the Centre Region of Cameroon. A detailed LULC map from MAPBOX high resolution images and three LULC maps were produced from Landsat TM-OLI images (1984-2015). A maximum likelihood classification techniques using ERDAS Imagine, showed forest decline with a total loss of 54% in thirty years. Also, Landsat and MAPBOX images to which we added 1951 aerial photograph and SPOT 6 (2006) were used to analyse urban growth in the city of Yaoundé. The results show a remarkable urban spatial spread of the metropolis between 1951 and 2015, with a peak in 2000. Images processing enabled us to analyse the long term dynamics of LULC change since the 1950s in this Region using ArcGIS & QGIS software’s. Based on this dynamic, a LULC projection map was produced using Markov model on IDRISI Selva, demonstrating the decrease of the dense forest (45% in 2015 to 0.25% in 2050). It was estimated that by 2050, the entire dense forest can be depleted if nothing is done, while only 12.67% of the secondary forest would remain in the Region. Such a projected map is very useful to decision makers for council development and urban planning. This effective forest depletion ties with the hypothesis that urbanization of Yaoundé and its secondary surrounding satellite cities (within a radius of 30-100km) is a veritable driving force of deforestation.

The reference method for cefiderocol antimicrobial susceptibility testing is broth microdilution (BMD) with iron-depleted-Mueller-Hinton (ID-MH) medium, whereas breakpoints recommended for disk diffusion (DD) are based on MH-agar plates. We aimed to compare the performance of the commercial BMD tests ComASP (Liofilchem) and UMIC (Bruker), DD and E-test using MH- and ID-MH-agar plates with the reference BMD method using 100 carbapenem-resistant-A. baumannii isolates. Standard BMD was performed according to the EUCAST guidelines, DD and E-test were carried out using two commercial MH-agar plates (bioMérieux and Liofilchem) and an in-house ID-MH-agar plate, while ComASP and UMIC were performed according to the manufacturer’s guidelines. DD performed with the ID-MH-agar plates led to a higher categorical agreement (CA, 95.1%) with standard BMD and fewer categorization errors compared to the commercial MH-agar plates (CA bioMérieux 91.1%, Liofilchem 89.2%). E-test on ID-MH-agar plates exhibited a significantly higher essential agreement (EA, 75%) with standard BMD compared to the two MH-agar plates (EA bioMérieux 57%, Liofilchem 44%), and showed a higher performance in detecting high-level resistance than ComASP and UMIC (mean log2 difference with standard BMD for resistant isolates of 0.5, 2.83 and 2.08, respectively). In conclusion, DD and E-test on ID-MH-agar plates exhibit a higher diagnostic performance than on MH-agar plates and the commercial BMD methods. Therefore, we recommend using ID-MH-agar plates for cefiderocol susceptibility testing of A. baumannii.

Water scarcity is a key challenge to global development. In Brazil, the Sao Francisco River Basin (SFB) has experienced water scarcity problems because of decreasing streamflow and increasing demands from multiple sectors. However, the drivers of decreased streamflow, particularly the potential role of surface-groundwater interaction, have not been yet investigated. Here, we assess long-term trends in baseflow, quickflow, and streamflow of the SFB during 1980–2015 and constrain the most likely drivers of observed decreases through trend analysis of precipitation (P), evapotranspiration (ET), and terrestrial water storage change (TWS). We found that over 82% of the observed decrease in streamflow can be attributed to a significant decreasing baseflow trend (< -20 m3 s-1 y-1) along the SFR with spatial agreement between decreased baseflow, increased ET, and irrigated agricultural land. We also noted a decrease in TWS across the SFB with trends exceeding -20 mm y-1. Overall, our findings indicate that decreasing groundwater contributions (i.e., baseflow) is providing the observed reduction in total SFR flow. A lack of significant P trends indicates that only P variability likely has not caused the observed baseflow reduction, mainly in the Middle and Sub-middle SFB. Therefore, groundwater and surface withdrawals may be likely a driver of water scarcity over the SFB.

Piezoelectric nanotransducers may offer key advantages in comparison with conventional piezoelectrics, including more choices for types of mechanical input, positions of the contacts, dimensionalities and shapes. However, since piezo-semiconductive nanostructures are generally much easier to fabricate and integrate into functional systems than insulating materials, modeling becomes significantly more intricate and the effects of free charges have been considered only in a few studies. The available reports are complicated by the absence of proper nomenclature and figures of merit. Besides, some analyses are incomplete. For instance, the local piezopotential and free charges within axially strained conical piezo-semiconductive nanowires have only been systematically investigated for very low doping (1016 cm-3) and under compression. Here we give the definitions for the enhancement, depletion, base and tip piezopotentials, their characteristic lengths and both the tip-to-base and the depletion-to-enhancement piezopotential-ratios. As an example, we use these definitions for analyzing the local piezopotential and free charges in n-type ZnO truncated conical nanostructures with different doping levels (intrinsic, 1016 cm-3, 1017 cm-3) for both axial compression and traction. The definitions and concepts presented here may offer insight for designing high performance piezosemiconductive nanotransducers.

Although 4Ce4YSZ has high corrosion resistance, it faces challenges concerning sinterability and ionic conductivity. Therefore, we studied destabilization behavior caused by corrosion and oxygen vacancy ordering according to ZnO doping. The powders of (4Ce4YSZ)1-x(ZnO)x (x=0.5, 1, 2, 4 mol%) were synthesized through the sol-gel method. With the addition of ZnO, the cubic phase increased, and secondary phases were not observed. The (111) peak showed a higher angle shift in ZnO-doped 4Ce4YSZ compared to 4Ce4YSZ, and TEM-SAED revealed a reduction in the spacing of the (011)t plane, suggesting lattice contraction due to the substitution of the smaller Zn2+ (60 Å) for Zr4+ (84 Å) in the lattice. The local atomic structure analysis was conducted using EXAFS to investigate the oxygen vacancy ordering behavior. Zr K-edge Fourier-transform data revealed a decrease in the Zr-O1 peak intensity with an increasing amount o ZnO doping, indicating an increase in oxygen vacancies. The Zr-O1 peak position shifted to the right, leading to an increase in the Zr-O1 interatomic distance. In the Y K-edge Fourier-transform data, the Y-O1 peak intensity did not decrease, and there was little variation in the Y-O1 interatomic distance. These results suggest that the oxygen vacancies formed due to ZnO doping are located in the neighboring oxygen shell of Zn, rather than in the neighboring oxygen shells of Y and Zr. Impedance measurements were conducted to measure the conductivity, and as the amount of ZnO doping increased, the total conductivity increased, while the activation energy decreased. The increase in oxygen vacancies by ZnO doping contributed to the enhancement of conductivity and it is considered that these created oxygen vacancies did not interact with Zn2+ and did not form defect associations. Fluoride-based molten salts were introduced to the specimens to assess corrosion behavior in a molten salt environment. Yttrium depletion layers (YDLs) were formed on the surfaces of all specimens due to the leaching of yttrium. However, Ce remained relatively stable at the interface according to EDS line scans, suggesting a reduction in the phase transformation (cubic, tetragonal to monoclinic) typically associated with yttrium leaching in YSZ.

Glioblastoma multiforme (GBM) and malignant gliomas are the most common primary malignant brain tumors. Temozolomide (TMZ) chemotherapy plus radiation therapy (RT), admi-nistered after debulking surgery, increased median survival time (MST) from 12.1 months with RT alone merely to 14.6 months. In this study, the action of deuterium-depleted water (DDW) on the survival of GBM patients who also received conventional therapies was investigated. Without changing the conventional treatment, the daily fluid intake of the patients was wholly replaced with DDW in 1.5-2 liters per day volume to reduce D concentration in their bodies. The primary endpoint was MST. The 55 patients involved, receiving conventional treatment and consuming DDW, showed longer MST (30 months) compared to the historical control (12.1-14.6 months). There was a massive difference between the two genders in the calculated MST values; it was 25 months in the male subgroup (n=33) and 42 months in the female subgroup (n=22). MST was 27 months without TMZ treatment (38 patients) and 42 months in the TMZ-treated group (17 patients). For the selected 31 patients, who consumed DDW in the correct way in addition to conventional treatments, MST was 30 months. Within this group, the 20 subjects who had relapsed before DDW treatment had 30 months of MST, but in those 10 subjects who were in remission when DDW treatment started, MST was 47 months. In the subgroup of patients who started DDW treatment parallel with radiotherapy, MST was 47 months again, and it was 25 months when DDW treatment started 8 weeks or later after the completion of radiotherapy. Altogether, survival times were substantially prolonged, compared to prospective clinical data of patients with primary GBM. Consequently, if conventional therapies are supplemented with D depletion, better survival is achieved in advanced stage of GBM than with the known targeted or combination therapies. Application of DDW is recommended in all stages of the disease, before surgery, parallel with radiotherapy, and repeated DDW courses are advised when remission has been achieved.

The licensing of new reactors implies the use of verified and validated neutronics codes. Numerical validation can rely on sensitivity and uncertainty studies but they require repeated execution of time-consuming neutron flux and depletion calculations. The computational costs can be shortened by using perturbation theories. However, Depletion Perturbation Theory is restricted to single integral values such as a nuclide density. Relying on reduced basis approaches, which reconstruct the whole nuclide densities at once, is one way to get around this restriction. Furthermore, the adjoint-based reduced-order model uses the direct and adjoint equations for the projection. For diffusion or transport calculations, Exact-to-Precision Generalized Perturbation Theory has been developed. Still, no models for depletion calculations are readily available. Therefore, this paper describes a novel adjoint-based reduced order model for the Bateman equation. It uses a range-finding algorithm to create the basis and the Depletion Perturbation Theory for the reconstruction of the nuclide densities at first order. Our paper shows that for several perturbed cases, the depletion reduced-order model successfully reconstructs the nuclide densities. As a result, this serves as a proof of concept for our adjoint-based reduced order model which can perform sensitivity and uncertainty burn-up analysis in a shorter time.

We replace the current industry-standard empirical forecasts of oil production from hydrofractured horizontal wells in shales with a statistically and physically robust, accurate and precise approach, using the Bakken shale as an illustration. The proposed oil production forecasting method extends our previous work on predicting fieldwide gas production in the Barnett shale and merges it with our new scaling of oil production in shales. We first divide the existing 14,678 horizontal oil wells in the Bakken into 12 static samples in which depositional settings and completion technologies are similar. For each sample, we construct a purely data-driven P50 well prototype by merging the GEV distribution fits of oil production from appropriate well cohorts. We fit the parameters of our physics-based scaling curve to the statistical well prototypes, and obtain their smooth extrapolations to 30 years on production. By calculating the number of potential wells of each Bakken region, and scheduling future drilling programs, we stack up the extended well prototypes to achieve the most plausible forecast. We predict that Bakken will ultimately produce 5 billion barrels of oil from the existing wells, with the possible increments of 2 and 6 billion barrels from core and noncore areas.

Nutrient depletion in Tanzanian sisal production has led to yield decreases over time. We use nutrient mass balances embedded within a life cycle assessment to quantify the extent of nutrient depletion for different production systems, then used circular economy principles to identify potential cosubstrates from within the Tanzanian economy to anaerobically digest with sisal wastes. The biogas produced is then used to generate bioelectricity and the digestate residual can be used as a fertilizer to address the nutrient depletion. If no current beneficial use of the cosubstrate was assumed, then beef manure and marine fish processing waste were the best cosubstrates. If agricultural wastes were assumed to have a current beneficial use as fertilizer, then marine fish processing waste and human urine were the best cosubstrates. The largest reduction in environmental impacts resulted from bioelectricity replacing electricity from fossil fuels in the national electricity grid and improved onsite waste management practices. There is significant potential to revitalize Tanzanian sisal production by applying circular economy principles to sisal waste management and bioenergy production.

Background: Increase of collagen I (COL I)/COL III ratio enhances vessel wall stiffness and renders vessels less resistant to blood flow and pressure changes. We hypothesized that COL I/COL III ratio is increased in the brain arteriovenous malformations (bAVMs), which is associated with bAVM hemorrhage. Method: Surgically resected human bAVM samples and mouse bAVMs induced in three transgenic mouse lines with activin receptor-like kinase 1 or endoglin deletion in the endothelial cells or in the brain focally. Colony-stimulating factor receptor inhibitor was used to transiently deplete microglia. COL I and COL III levels, hemorrhage, and gene expression in bAVMs were analyzed. Results: The COL I and COL III levels and the COL I/COL III ratio were higher on human and mouse bAVMs than controls, which was associated with bAVM hemorrhage. Col I and Col III mRNAs were also increased in mouse bAVMs. The degree of microhemorrhage in mouse bAVMs was positively correlated with Col I/Col III ratios. Transient depletion of microglia reduced Col I/Col III ratio and microhemorrhage in mouse bAVMs. Conclusion: COL I/COL III ratio are increased in bAVM vessels, which is associated with bAVM hemorrhage. Depletion of microglia reduces Col I/Col III ratio and hemorrhage in mice bAVMs.

Even though groundwater-based irrigation has increased agricultural productivity and economic activity in the United States (US), the current rate of groundwater withdrawals from major aquifers could significantly affect the sustainability of agricultural production systems in the near future. In the major agricultural regions, producers are now facing challenges to irrigate to meet full crop water needs. There is an increasing need to strategize irrigation management under various climatic and environmental conditions to optimize water use in agriculture while optimizing crop yields. This study reviews some of the major challenges facing irrigated agriculture in the US and the potential measures to ensure the sustainability of groundwater-based irrigation. Identified challenges included diminishing quantity and quality of groundwater resources, frequent droughts, low adoption rates of precision irrigation technologies, and rising energy requirements for irrigation abstractions. Irrigation efficiency improvements, shifting to high water use efficiency crops, wastewater reuse, groundwater monitoring, availing incentives, and policy changes, were identified as promising water management strategies to ensure irrigation sustainability. The success of these strategies will depend on the uptake and adoption by the producers in the affected agricultural regions.

The radiosensitivity of biological systems is strongly affected by the system oxygenation. On the nanoscopic scale and molecular level, this effect is considered to be strongly related to the indirect damage of radiation. Even though particle track radiolysis has been the object of several studies, still little is known about the nanoscopic impact of target oxygenation on the radical yields. We present here an extension of the chemical module of the Monte Carlo particle track structure code TRAX, taking into account the presence of dissolved molecular oxygen in the target material. The impact of the target oxygenation level on the chemical track evolution and the yields of all the relevant chemical species is studied in water under different irradiation conditions: different linear energy transfer (LET) values, different oxygenation levels, and different particle types. Especially for low LET radiation, a large production of two highly toxic species (HO₂^• and O₂^•− ), which are not produced in anoxic conditions, is predicted and quantified in oxygenated solutions. The remarkable correlation between the HO₂^• and O₂^•− production yield and the oxygen enhancement ratio observed in biological systems suggests a direct or indirect involvement of HO₂^• and O₂^•− in the oxygen sensitization effect. The results are in agreement with available experimental data and previous computational approaches. An analysis of the oxygen depletion rate in different radiation conditions is also reported.

The central nervous system (CNS) is an essential hub for neuronal communication. As a major component of the CNS, glial cells are vital in the maintenance and regulation of neuronal network dynamics. Research on microglia, the resident innate immune cells of the CNS, has advanced considerably in recent years, and our understanding of their diverse functions continues to grow. Microglia play critical roles in the formation and regulation of neuronal synapses, myelination, responses to injury, neurogenesis, inflammation and many other physiological processes. In parallel with advances in microglial biology, cutting-edge techniques for the characterization of microglial properties have emerged with increasing depth and precision. Labeling tools and reporter models are important for the study of microglial morphology, ultrastructure and dynamics, but also for microglial isolation, which is required to glean key phenotypic information through single-cell transcriptomics and other emerging approaches. Strategies for selective microglial depletion and modulation can provide novel insights into microglia-targeted treatment strategies in models of neuropsychiatric and neurodegenerative conditions, cancer and autoimmunity. Finally, fate mapping has emerged as an important tool to answer fundamental questions about microglial biology, including their origin, migration and proliferation throughout the lifetime of an organism. This review aims to provide a comprehensive discussion of these emerging techniques, with applications to the study of microglia in development, homeostasis and CNS pathologies.

Some cancer cells rely heavily on non-essential biomolecules for survival, growth, and proliferation. Enzyme based therapeutics can eliminate these biomolecules, thus specifically targeting neoplastic cells; however, enzyme therapeutics are susceptible to immune clearance, exhibit short half-lives, and require frequent administration. Encapsulation of therapeutic cargo within biocompatible and biodegradable poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) is a strategy for controlled release. Unfortunately, PLGA NPs exhibit burst release of cargo shortly after delivery or upon introduction to aqueous environments where they decompose via hydrolysis. Here we show the generation of hybrid silica-coated PLGA (SiLGA) NPs as viable drug delivery vehicles exhibiting sub-200 nm diameters, a metastable Zeta potential, and high loading efficiency and content. Compared to uncoated PLGA NPs, SiLGA NPs offer greater retention of enzymatic activity and slow the burst release of cargo. Thus, SiLGA encapsulation of therapeutic enzymes, such as asparaginase, could reduce frequency of administration, increase half-life, and improve efficacy for patients with a range of diseases.

Numerical models widely used for hydrocarbon phase behavior and compositional flow simulations are based on assumption of thermodynamic equilibrium. However, it is not uncommon for oil and gas-condensate reservoirs to exhibit essentially non-equilibrium phase behavior, e.g., in the processes of secondary recovery after pressure depletion below saturation pressure, or during gas injection, or for condensate evaporation at low pressures. In many cases the ability to match field data with equilibrium model depends on simulation scale. The only method to account for non-equilibrium phase behavior adopted by the majority of flow simulators is the option of limited rate of gas dissolution (condensate evaporation) in black oil models. For compositional simulations no practical yet thermodynamically consistent method has been presented so far except for some upscaling techniques in gas injection problems. Previously reported academic non-equilibrium formulations have a common drawback of doubling the number of flow equations and unknowns compared to the equilibrium formulation. In the paper a unified thermodynamically-consistent formulation for compositional flow simulations with non-equilibrium phase behavior model is presented. Same formulation and a special scale-up technique can be used for upscaling of an equilibrium or non-equilibrium model to a coarse-scale non-equilibrium model. A number of test cases for real oil and gas-condensate mixtures are given. Model implementation specifics in a flow simulator are discussed and illustrated with test simulations. A non-equilibrium constant volume depletion algorithm is presented to simulate condensate recovery at low pressures in gas-condensate reservoirs. Results of satisfactory model matching to field data are reported and discussed.

The article justifies the need to involve the technogenic deposits (off-balance ore and wastes) into the economic circulation of mining enterprises when there is natural resources depletion. It could be considered as one of the tools of the circular economy. The authors analyze global trends in the copper deposits development, global demand for copper, and design recommendations for possible alternative options for the copper production. The authors use a case of Erdenet Mining Corporation SOE based in Mongolia to develop the approach for economic, social and environmental problem-solving. The millions of mining dumps are proposed to develop as technogenic resources for recycled materials, prolonging profitable activities of the mine. The Hierarchy analysis method is used to obtain optimum order of the mining dumps development to get economic, social and environmental effect.

The authors of the article performed computer simulation of buffer amplifiers (BA), which have medium and extremely small values of the offset voltage's systematic component (V_off), for different technological processes (Si, GaAs and GaN). The proposed control units are distinguished by a small number of elements and allow operation in the range of low and high temperatures. The variants of circuitry implementation of control units based on GaAs, GaN depletion-mode CMOS and JFET technological processes are considered. The results of the comparative modeling showed that the basic circuit of the BA on two field-effect transistors, when implemented on various modifications of GaN MOS and depletion-mode MOS transistors, provides sufficiently low values of the offset voltage's systematic component (less than 2 μV). The proposed BAs are designed for use in the structure of the Sallen-Key low-pass filter (LPF) when they are implemented both on mid-frequency Si CJFET and on GaAs microwave transistors. Low values of the LPF V_off have a positive effect on the effective capacity of the ADC. An example of switching on a BA in the JFET OpAmp structure based on the depletion-mode MOS input stage and a “folded” cascode, which, with 100% negative feedback, can be used in the Sallen-Key LPF, is considered. Computer simulation of the JFET/MOS OpAmp showed that the OpAmp has an open-loop voltage gain of 76-85dB, and its V_off is within 7µV in the temperature range from -60°C to +120°C. The presented circuitry of buffer amplifiers is intended, first of all, for the tasks of designing precision Sallen-Key low-pass filter (low-pass filter, high-pass filter, PF, RF).

Classical models of gene expression were built using genetics and biochemistry. Although these approaches are powerful, they have very limited consideration of the spatial and temporal organization of gene expression. Although the spatial organization and dynamics of RNA polymerase II (RNAPII) transcription machinery has fundamental functional consequences for gene expression, its detailed studies have been for long time abrogated by the limits of classical light microscopy. The advent of super-resolution microscopy (SRM) techniques allowed for the visualization of the RNAPII transcription machinery with nanometer resolution and millisecond precision. In this review, we summarize the recent methodological advances in SRM, focus on its application for studies of the nanoscale organization in space and time of RNAPII transcription, and discuss its consequences for the mechanistic understanding of gene expression.

Diffuse intrinsic pontine glioma (DIPG) is an aggressive pediatric brainstem tumor with a 5-year survival of <1%. Up to 80% of DIPG tumors contain a specific K27M mutation in one of two genes encoding histone H3 (H3K27M). Furthermore, p53 mutations found in >70-80% of H3K27M DIPG, and mutant p53 status is associated with a decreased response to radiation treatment and worse overall prognosis. Recent evidence indicates that H3K27M mutation disrupts tri-methylation at H3K27 leading to aberrant gene expression. Jumonji family histone demethylases collaborates with H3K27 mutation in DIPG by erasing H3K27 trimethylation and thus contributing to derepression of genes involved in tumorigenesis. Since the first line treatment for pediatric DIPG is fractionated radiation, we investigated the effects of Jumonji demethylase inhibition with GSK-J4, and mutant p53 targeting/oxidative stress induction with APR-246, on radio-sensitization of human H3K27M DIPG cells. Both APR-246 and GSK-J4 displayed growth inhibitory effects as single agents in H3K27M DIPG cells. Furthermore, both of these agents elicited mild radiosensitizing effects in human DIPG cells (sensitizer enhancement ratios (SERs) of 1.12 and 1.35, respectively; p<0.05). Strikingly, a combination of APR-246 and GSK-J4 displayed a significant enhancement of radiosensitization, with SER of 1.50 (p<0.05) at sub-micro-molar concentrations of the drugs (0.5 μM). The molecular mechanism of the observed radiosensitization appears to involve DNA damage repair deficiency triggered by APR-246/GSK-J4, leading to the induction of apoptotic cell death. Thus, a therapeutic approach of combined targeting of mutant p53, oxidative stress induction, and Jumonji demethylase inhibition with radiation in DIPG warrants further investigation.

Theoretical and experimental approaches have been applied to study the polymer physics under-lying compaction of DNA in the bacterial nucleoid. Knowledge of the compaction mechanism is necessary to obtain a mechanistic understanding of the process of segregation of replicating chromosome arms (replichores) during the cell cycle. In the first part of this review light microscope observations are discussed that have demonstrated that the nucleoid has a lower refractive index and thus a lower density than the cytoplasm. A polymer-physical explanation for this phenomenon was given by the theory of Theo Odijk pro-posed in 1998. By assuming a phase separation between nucleoid and cytoplasm and by imposing equality of osmotic pressure and chemical potential between the two phases, a minimal energy situation is obtained in which soluble proteins are depleted from the nucleoid, thus explaining its lower density. The theory is compared with recent views for DNA compaction that are based on mere exclusion of polyribosomes from the nucleoid or on the transcriptional activity of the cell. These new views raise the question of whether they can still explain the lower refractive index or density of the nucleoid. In the second part of this review the question is discussed how DNA segregation occurs in Esche-richia coli, in the absence of the so-called active ParABS system, present in the majority of bacteria. How is entanglement prevented of nascent chromosome arms, generated at the origin in the pa-rental network of the E. coli nucleoid? The observations of the groups of Sherratt and Hansen in 2006, that the four nascent chromosome arms synthesized in the initial replication bubble, segre-gate to opposite halves of the sister nucleoids implies that extensive intermingling of daughter strands does not occur. Based on the hypothesis that leading and lagging replichores synthesized in the replication bubble, fold into micro-domains that do not intermingle, a passive "four-excluding-arms model" for segregation is proposed. This model implies that the key for seg-regation already lies in the structure of the replication bubble at the very start of DNA replication; it explains the different patterns of chromosome arms as well as the segregation distances between replicated loci as experimentally observed.

A method for calibrating models of agricultural production and resource use presented by Howitt [1] for policy analysis is proposed to leverage multidisciplinary agricultural research at the National Center for Alluvial Aquifer Research (NCAAR). An illustrative example for Sunflower County, MS is presented to show how plot-level research can be extended to draw systemic region or basin wide implications. A hypothetical improvement in yields for dryland soybean varieties is incorporated to the model and shown to have a positive impact on aquifer outcomes and producer profits. The example illustrates that a change in one practice-crop combination can have system-wide impacts as evidenced by the change in acreages for all crops and practices.