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Alzheimer’s disease (AD) is an irreversible, progressive neurodegenerative disease and the most common cause of dementia among older adults. There are no effective treatments available for the disease, and it is associated with great societal concern because of the substantial costs of providing care to its sufferers, whose numbers will increase as populations age. While multiple causes have been proposed to be significant contributors to the onset of sporadic AD, increased age is a unifying risk factor. In addition to amyloid-β (Aβ) and tau protein playing a key role in the initiation and progression of AD, impaired mitochondrial bioenergetics and dynamics are likely major etiological factors in AD pathogenesis and have many potential origins, including Aβ and tau. Mitochondrial dysfunction is evident in the central nervous system (CNS) and systemically early in the disease process. Addressing these multiple mitochondrial deficiencies is a major challenge of mitochondrial systems biology. We review evidence for mitochondrial impairments ranging from mitochondrial DNA (mtDNA) mutations to epigenetic modification of mtDNA, altered gene expression, impaired mitobiogenesis, oxidative stress, altered protein turnover and changed organelle dynamics (fission and fusion). We also discuss therapeutic approaches, including repurposed drugs, epigenetic modifiers, and lifestyle changes that target each level of deficiency which could potentially alter the course of this progressive, heterogeneous Disease while being cognizant that successful future therapeutics may require a combinatorial approach.

In today's "digital" world, where consumers are able to complete most every task, from grocery shopping to banking, from the comfort of their bed, a strong emphasis is placed on convenience and simplicity. For dental patients who want healthy, functional, and esthetically pleasing teeth and smiles, clear aligners can be utilized in a relatively expedient manner to create more optimal conditions for their overall dental wellness. With existing digital workflows, clinicians are able to provide patients a healthy and esthetic dentition more easily than in the past. Cases presented in this report demonstrate the use of OraFit™ clear aligners to correct simple malocclusions and help provide the patients with the smiles they desired.

We used RNA sequencing (RNA-seq) to quantitate gene expression in total RNA extracts of vulnerable brain tissues from Alzheimer's disease (AD, frontal cortical ribbon) and Parkinson's disease (PD, ventral midbrain) subjects and phenotypically negative control subjects. Paired-end sequencing files were processed with HISAT2 aligner/Cufflinks quantitation against the hg38 human genome. We observed a significant decrease in gene expression of all mtDNA OXPHOS genes in AD and PD tissues. Gene expression of the master mitochondrial biogenesis regulator PGC-1α (PPARGC1A) was significantly reduced in AD; expression of genes for mitochondrial transcription factors A (TFAM) and B1/B2 (TFB1M/TFB2M) were not significantly changed in AD and PD tissues. 2-way ANOVAs showed significant reduction in AD brain Complex I subunits' expressions and nearly significant reductions in PD brain. We found a significant reduction in both AD and PD brain samples of expression of genes for leucine-rich pentatricopeptide repeat containing (LRPPRC, a.k.a. LRP130), a known mtRNA-stabilizing protein. Our findings suggest that AD and PD brain tissues have a reduction in mitochondrial ATP production derived from a reduction of mitobiogenesis and mtRNA stability. If true, increased brain expression of PGC-1α and/or LRPPRC may improve bioenergetics of AD and PD and alter the course of neurodegeneration in both conditions. (201 words).

Adult human brains consume a disproportionate amount of energy substrates (2–3% of body weight; 20–25% of total glucose and oxygen). Adenosine triphosphate (ATP) is a universal energy currency in brains and is produced by oxidative phosphorylation (OXPHOS) using ATP synthase, a nano-rotor powered by the proton gradient generated from proton-coupled electron transfer (PCET) in the multi-complex electron transport chain (ETC). ETC catalysis rates are reduced in brains from humans with neurodegenerative diseases (NDDs). Declines of ETC function in NDDs may result from combinations of nitrative stress (NS)–oxidative stress (OS) damage; mitochondrial and/or nuclear genomic mutations of ETC/OXPHOS genes; epigenetic modifications of ETC/OXPHOS genes; or defects in importation or assembly of ETC/OXPHOS proteins or complexes, respectively; or alterations in mitochondrial dynamics (fusion, fission, mitophagy). Substantial free energy is gained by direct O2-mediated oxidation of NADH. Traditional ETC mechanisms require separation between O2 and electrons flowing from NADH/FADH2 through the ETC. Quantum tunneling of electrons and much larger protons may facilitate this separation. Neuronal death may be viewed as a local increase in entropy requiring constant energy input to avoid. The ATP requirement of the brain may partially be used for avoidance of local entropy increase. Mitochondrial therapeutics seeks to correct deficiencies in ETC and OXPHOS.

High temperature corrosion of a Pt-30 wt.% Rh alloy in a phosphorizing gas was isothermally investigated at 1285 K using a gas switching technique. Diffusion of P into the alloy created an outer layer of Pt-rich liquid and blocky (Pt, Rh)2P precipitates along with an inner layer of fcc and (Pt, Rh)2P plates in a cellular microstructure. Concentration profiles measured by SEM-WDS and EPMA across the layers at room temperature showed that there were three fcc phases: first was a 12 at.% Rh phase in the outer layer; second was a 37 at.% Rh phase in the cellular microstructure; and third was the initial 43 at.% Rh alloy. Also, the EPMA data registered approximately 0.1 at.% P in fcc of these layers. Based on the surrounding binary phase diagrams and the experimental data obtained in this study, a partial Pt-Rh-P phase diagram was constructed. A diffusion path for the corrosion microstructure was drawn on the partial phase diagram to help develop a step by step model for how the microstructure evolved. Growth kinetics of the inner layer were used to calculate a P diffusivity of about 10−12 m2/s in the Pt-Rh alloy at 1285 K, suggesting rapid diffusion by either an interstitial or interstitialcy mechanism.

Vanadium in petroleum coke can have environmental and technological impacts in gasification and combustion processes. The multitude of vanadium oxidation and coordination states has made it difficult to characterize vanadium-rich materials, particularly for materials where the vanadium is associated with an amorphous state and cannot be characterized by X-ray diffraction. This study presents two methods whereby vanadium is characterized by synchrotron-based X-ray absorption spectroscopy, which applies to both crystalline and amorphous phases. The first method, comparison of main edge energies, is relatively straightforward but presents multiple limitations. The other method, linear combination fitting, overcomes many of these limitations but relies on the availability of suitable reference materials. These methods, applied to pilot plant gasification and combustion samples, indicate various trends in vanadium speciation, such as higher oxidation states for combustion samples relative to gasification samples. Analysis of synthetic pseudo-binary materials, which is important for the development of thermodynamic equilibrium models, indicated that V 5+ is stable with high oxygen partial pressures encountered during combustion. With a lower oxygen partial pressure, representative of gasification conditions, V 5+ is stable if there is enough calcium present; otherwise, V 3+ is stable.

Background: Neuropathological changes of Alzheimer’s disease (AD) and Parkinson’s disease (PD) can coexist in the same sample, suggesting possible common degenerative mechanisms. Objective: The objective of this study was to use RNA-sequencing to compare gene expression in AD and PD vulnerable brain regions and search for co-expressed genes. Methods: Total RNA was isolated from AD/CTL frontal cortex and PD/CTL ventral midbrain. Sequencing libraries were prepared, multiplex paired-end RNA sequencing was carried out, and bioinformatics analyses of gene expression used both publicly available (tophat2/bowtie2/Cufflinks) and commercial (Qlucore Omics Explorer) algorithms. Results: Both AD (frontal cortex, n = 10) and PD (ventral midbrain, n = 14) samples showed extensive heterogeneity of gene expression. Hierarchical clustering of heatmaps revealed two gene populations (AD, 376 genes; PD, 351 genes) that separated AD or PD from control samples at false-discovery rates (q) of 1.5-fold under-expression) in both AD and PD. Ingenuity Pathways Analyses (IPA, Qiagen) revealed loss of NAD biosynthesis and salvage as the major canonical pathway significantly altered in both AD and PD. Conclusions: AD and PD in vulnerable brain regions appear to arise from and result in independent molecular genetic abnormalities, but we identified several under-expressed genes with potential to treat both diseases. NAD supplementation shows particular promise.

Alumina-supported Cu/Fe spinel particles were exposed to oxidation/reduction atmospheres at 800°C. Structural changes of the particles subjected to gas cycles between air and 10 vol.% CO-90 vol.% Ar were studied from physical data and real-time images collected using a confocal scanning laser microscope equipped with a heating chamber. Overall particle volume slowly expanded with cycles while surface roughness decreased. Cross-sections of the exposed particles showed segregation of Cu and Fe to the edges of inner grains, which may have acted as oxygen carriers during the exposures. The particles remained whole during the cyclic exposures without any noticeable structural breakdown.

Amyotrophic lateral sclerosis (ALS) is a generally fatal neurodegenerative disease of adults that produces weakness and atrophy due to dysfunction and death of upper and lower motor neurons. We used RNA-sequencing (RNA-seq) to analyze expression of all mitochondrial DNA (mtDNA)-encoded respiratory genes in ALS and CTL human cervical spinal cords (hCSC) and isolated motor neurons. We analyzed with RNA-seq mtDNA gene expression in human neural stem cells (hNSC) exposed to recombinant human mitochondrial transcription factor A (rhTFAM), visualized in 3-dimensions clustered gene networks activated by rhTFAM, quantitated their interactions with other genes and determined their gene ontology (GO) families. RNA-seq and quantitative PCR (qPCR) analyses showed reduced mitochondrial gene expression in ALS hCSC and ALS motor neurons isolated by laser capture microdissection (LCM), and revealed that hNSC and CTL human cervical spinal cords were similar. Rats treated with i.v. rhTFAM showed a dose-response increase in brain respiration and an increase in spinal cord mitochondrial gene expression. Treatment of hNSC with rhTFAM increased expression of mtDNA-encoded respiratory genes and produced one major and several minor clusters of gene interactions. Gene ontology (GO) analysis of rhTFAM-stimulated gene clusters revealed enrichment in GO families involved in RNA and mRNA metabolism, suggesting mitochondrial-nuclear signaling. In postmortem ALS hCSC and LCM-isolated motor neurons we found reduced expression of mtDNA respiratory genes. In hNSC's rhTFAM increased mtDNA gene expression and stimulated mRNA metabolism by unclear mechanisms. rhTFAM may be useful in improving bioenergetic function in ALS.

In this research, experimental parameters of the confocal scanning laser microscope (CSLM) system were investigated to understand their impact on artifact changes in the melting and crystallization behaviors of synthetic slag in an oxidizing environment as it underwent rapid changes in gas flow, heating, and cooling rates. This study aims to provide CSLM users with fundamental information in utilizing CSLM equipment to investigate molten and solid slag behaviors.

Mitochondria likely arose from serial endosymbiosis by early eukaryotic cells and control electron flow to molecular oxygen to facilitate energy transformation. Mitochondria translate between the quantum and macroscopic worlds and utilize quantum tunneling of electrons to reduce activation energy barriers to electron flow. Electron tunneling has been extensively characterized in Complex I of the electron transport chain. Age-related increases in oxidative damage to these electron tunneling systems may account for decreased energy storage found in aged and neurodegenerative disease tissues, such as those from sufferers of amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD) and Parkinson's disease (PD). This hypothesis is testable. If correct, this hypothesis supports pre-symptomatic, mitochondrially-directed oxygen free radical scavenging therapies.

Alzheimer’s disease (AD) is a neurodegenerative disease associated with human aging. Ten percent of individuals over 65 years have AD and its prevalence continues to rise with increasing age. There are currently no effective disease modifying treatments for AD, resulting in increasingly large socioeconomic and personal costs. Increasing age is associated with an increase in low-grade chronic inflammation (inflammaging) that may contribute to the neurodegenerative process in AD. Although the exact mechanisms remain unclear, aberrant elevation of reactive oxygen and nitrogen species (RONS) levels from several endogenous and exogenous processes in the brain may not only affect cell signaling, but also trigger cellular senescence, inflammation, and pyroptosis. Moreover, a compromised immune privilege of the brain that allows the infiltration of peripheral immune cells and infectious agents may play a role. Additionally, meta-inflammation as well as gut microbiota dysbiosis may drive the neuroinflammatory process. Considering that inflammatory/immune pathways are dysregulated in parallel with cognitive dysfunction in AD, elucidating the relationship between the central nervous system and the immune system may facilitate the development of a safe and effective therapy for AD. We discuss some current ideas on processes in inflammaging that appear to drive the neurodegenerative process in AD and summarize details on a few immunomodulatory strategies being developed to selectively target the detrimental aspects of neuroinflammation without affecting defense mechanisms against pathogens and tissue damage.

Synthetic coal ash bearing 560 ppm europium oxide, blended with aluminum phosphate, was heat treated above its melting temperature and crystal evolutions with respect to europium concentration under controlled cooling were studied. The sample in a boat crucible was subjected to a temperature gradient of 100 °C across it to cause zone refining effects on crystallization behaviors in the melt (slag). Post analysis found six mineral phases formed from the melt while europium was only present in calcium phosphate, implying the majority of europium was segregated to the calcium phosphate. Europium concentrations in the calcium phosphate phase tended to be higher at zones with higher temperatures: as high as 7200 ppm, a 13-fold increase from the initial concentration.

Mitochondria are responsible for the majority of energy production in energy-intensive tissues like brain, modulate Ca+2 signaling and control initiation of cell death. Because of their extensive use of oxygen and lack of protective histone proteins, mitochondria are vulnerable to oxidative stress (ROS)-induced damage to their genome (mtDNA), respiratory chain proteins and ROS repair enzymes. Animal and cell models of PD use toxins that impair mitochondrial complex I activity. Maintenance of mitochondrial mass, mitochondrial biogenesis (mitobiogenesis), particularly in high-energy brain, occurs through complex signaling pathways involving the upstream "master regulator" PGC-1alpha that is transcriptionally and post-translationally regulated. Alzheimer disease (AD) and Parkinson disease (PD) brains have reduced respiratory capacity and impaired mitobiogenesis, which could result in beta-amyloid plaques and neurofibrillary tangles. Aggregated proteins in genetic and familial AD and PD brains impair mitochondrial function, and mitochondrial dysfunction is involved in activated neuroinflammation. Mitochondrial ROS can activate signaling pathways that mediate cell death in neurodegenerative diseases. The available data support restoration of mitochondrial function to reduce disease progression and restore lost neuronal function in AD and PD.

The determination of whether a phase is a liquid or a vapor is somewhat arbitrary, particularly when the fluid is in the single-phase region. However, the calculation of multiphase flow in oil industry simulators is dependent upon the labeling of the phases. Key properties in flow modeling, such as relative permeabilities and capillary pressures, are dependent upon which phases are present. Correct labeling of the fluid phases is therefore critical to the success of simulations. Many methods have been proposed for identifying phases. These are reviewed here. Five methods have been selected for detailed comparison, including a new method, based on the thermal expansion coefficient. The results of the comparison and the relative advantages of the methods are discussed.

Gasifier operation is an intricate process because of the complex relationship between slag chemistry and temperature, limitations of feedstock materials, and operational preference. High gasification temperatures increase refractory degradation, while low gasification temperatures can lead to slag buildup on the gasifier sidewall or exit, either of which are problematic during operation. Maximizing refractory service life and gasifier performance require finding an optimized operating temperature range which is a function of the coal slag chemistry and viscosity. Gasifier operators typically use a slag’s viscosity-temperature relationship and/or ash-fusion fluid temperature to determine the gasification temperature range. NETL has built a slag management toolset to determine the optimal temperature range for gasification of a carbon feedstock. This toolset is based on a viscosity database containing experimental data, and a number of models used to predict slag viscosity as a function of composition and temperature. Gasifier users typically have no scientific basis for selecting an operational temperature range for gasification, instead using experience to select operational conditions. The use of the toolset presented in this paper provides a basis for estimating or modifying carbon feedstock slags generated from ash impurities in carbon feedstock.

Interactions between Pt–Rh sensor alloys and P-containing gas in an environment simulating a carbon feedstock gasification process were investigated. A series of exposure tests revealed materials failure through two distinct P diffusion mechanisms, depending on Rh concentrations; intergranular diffusion in low Rh alloys and intragranular diffusion in high Rh alloys. Upon exposure, P rapidly migrated into the alloys, lowering the melting temperature of the alloys and/or forming intermediate phases with Rh at grain boundaries or within grains. The failure mechanisms of Pt–Rh alloys by P-bearing gas in the conditions studied are proposed.

Coal gasification yields synthesis gas, an important intermediate in chemical manufacturing. It is also vital to the production of liquid fuels through the Fischer-Tropsch process and electricity in Integrated Gasification Combined Cycle power generation. Minerals naturally present in coal become molten in entrained-flow slagging gasifiers. Molten coal ash slag penetrates and dissolves refractory bricks, leading to costly plant shutdowns. The extent of coal ash slag penetration and refractory brick dissolution depends on the slag viscosity, the gasification temperature, and the composition of slag and bricks. We measured the viscosity of several synthetic coal ash slags with a high-temperature rotary viscometer and their ash fusion temperatures through optical image analysis. All measurements were made in a carbon monoxide-carbon dioxide reducing atmosphere that approximates coal gasification conditions. Empirical correlation models based on ash fusion temperatures were used to calculate critical viscosity temperatures based on the coal ash compositions. These values were then compared with those obtained from thermodynamic phase-transition models. An understanding of slag viscosity as a function of ash composition is important to reducing refractory wear in slagging coal gasifiers, which would help to reduce the cost and environmental impact of coal for chemical and electricity production.

Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis are a heterogeneous group of debilitating disorders with multifactorial etiologies and pathogeneses that manifest distinct molecular mechanisms and clinical manifestations with abnormal protein dynamics and impaired bioenergetics. Mitochondrial dysfunction is emerging as an important feature in the etiopathogenesis of these age-related neurodegenerative diseases. The prevalence and incidence of these diseases is on the rise with the increasing global population and average lifespan. Although many therapeutic approaches have been tested, there are currently no effective treatment routes for the prevention or cure of these diseases. We present the current status of our knowledge and understanding of the involvement of mitochondrial dysfunction in these diseases and highlight recent advances in novel therapeutic strategies targeting neuronal bioenergetics as potential approach for treating these diseases.

In chemical looping reactors, oxygen carrier’s physical and chemical properties may be continuously modified in response to reduction-oxidation (redox) cycling, affecting the oxygen exchange ability and therefore overall energy efficiency. Reports currently available on hematite’s high temperature redox behaviors have been based primarily on ‘bulk’ material testing in thermogravimetric units or fixed-bed/fluidized bed reactors, followed by post analysis. While ‘bulk’ based analysis effectively provides valuable information on oxygen exchange efficiency as a whole, interpretation of oxygen carrying behaviors occurring in an ‘individual’ particle caused by local particle alterations would be complicated. The present work discusses oxygen exchange behaviors of an ‘individual’ hematite particle based on real-time surface morphology changes subjected to redox cycling. In-operando observations were made possible by utilizing a custom-made high temperature fixed-bed reactor equipped to the confocal scanning laser microscope. The present technique revealed a unique particle expansion behavior that followed a zig-zag (up-down) pattern corresponding to each reduction and oxidation. After 10 redox cycles with 20 consecutive gas exposures, the overall volume was more than doubled, the surface area increased by 25%, and roughness increased by 4 times, resulting in meaningful alterations in the oxygen exchange capability. Reduction-oxidation transformation kinetics was accerelated at each cycle with a directional growth of the product layer over the particle surface; 1 s was long enough for a surface oxidation boundary to travel ≈385 μm after the 1st cycle. The surface transformation kinetics was of 2 dimensional growth in early cycles, which quickly became 3 dimensional growth in later cycles.

Physical and chemical degradation of the oxygen-carrier materials during high-temperature redox exposures may affect the overall efficiency of the chemical looping process. Therefore, studying real-time physical and chemical changes in these materials when exposed to repeated redox cycles is essential for further development of chemical looping technology. In this work, the National Energy Technology Laboratory’s Al2O3-supported Cu/Fe spinel oxygen carrier, in the form of a CuO · Fe2O3 solid solution, was examined in situ during 3-h exposures to either oxidizing or reducing environments at 800 °C using a controlled atmosphere heating chamber in conjunction with a confocal scanning laser microscope. A compilation of the physical changes of individual particles using a controlled atmosphere confocal microscope and the microstructural/chemical changes documented using a scanning electron microscope will be discussed.

Gases bearing elements such as As, S, and Si are known to degrade Pt and Pt–Rh alloys, leading to thermocouple sensor failure during industrial operations. While the corrosive impact of As, S, and Si gases have been discussed in the literature, the impact of P has not been well studied. P may originate from the carbon feedstock, ores, additives, and refractory bricks used in metallurgical and gasification processes. In this work, gaseous P interactions with Pt–Rh (Rh = 6 and 30 wt%) alloys were isothermally investigated at 1012° C in situ using a customized environmental white light/confocal scanning laser microscope. Changes in microstructure and P-diffusion into the Pt–Rh alloys are discussed based on real-time images recorded during the exposure tests and electron probe microscopy analysis from the quenched samples.

The results of a floristic study of lichens in Portage County, Wisconsin are presented. A total of 180 species in 73 genera were identified from field collections made in 2010 through 2013. A catalogue of species is included with 208 lichens presented as a result of field work, a literature search for previously reported collections and a physical search of the Wisconsin State Herbarium (WIS). There are 115 new records for the county and the following three species are reported for the first time for the State of Wisconsin: Leptogium rivulare, Heterodermia obscurata, and Peltigera extenuata. In addition to state and county records, two lichens of significant ecological interest were collected during this study; Lobaria pulmonaria, and Normandina pulchella.

James P Bennett Jr* speaks to Daphne Boulicault, Commissioning Editor: James P Bennett, Jr is a native of St Petersburg, FL, USA. He received a BS in chemistry (with Honors) from the University of Florida (1970), then attended Johns Hopkins University School of Medicine for his MD (1974) and PhD (pharmacology, 1977) degrees. He worked in the laboratory of Dr Solomon Snyder, MD, for 6 years while in medical and graduate schools and trained in neuropharmocology. He then trained clinically for 2 years in internal medicine (1978–1980), followed by Neurology residency at the University of Virginia (UVA; 1980–1983) where he was Chief Resident (1982–1983). He became a faculty member in the UVA Departments of Neurology, Psychiatry and Pharmacology (1983–2009) and held the Ebbert Chair in Medical Science. In 2009, he moved to Virginia Commonwealth University, where he is the Bemiss Professor, was Chair of Neurology (2009–2013) and is founding Director of the Parkinson’s Disease and Movement Disorder Center (2009–2015). He has held multiple NIH grants and directed the NIH-funded Udall Parkinson’s Center at UVA. He investigates mitochondrial dysfunction in adult neurodegenerative diseases. He holds multiple patents related to experimental therapies of degenerative disorders.

Causes of initiation and progression of sporadic Alzheimer’s disease (sAD) are likely multiple and include impair-ment of mitochondrial bioenergetics. We analyzed RNA expression levels of multiple mitochondrial oxidative phosphorylation(OXPHOS) and biogenesis (mitobiogenesis) genes in unfixed hippocampal (WH) frozen sections (10 sAD; 9 CTL) and laser-capturedhippocampalpyramidalneurons(PyNs,∼1000neuronsfromeachcase)from8sADand7CTLcases.Nuclear-encodedOXPHOS genes in WH were significantly increased in sAD, whereas in isolated sAD PyNs, these same genes were significantlydecreased. Mitochondrial DNA-encoded genes were increased in sAD PyNs but showed a non-significant downward trend insAD WH. Relationships among WH and PyN gene expression levels in sAD distributed in a different population compared toCTL. Principal component analysis (PCA) revealed clustering of CTL but widespread heterogeneity of sAD samples. In sAD,mitochondrial bioenergetics at the gene expression level are depressed in vulnerable PyNs. PCA revealed that CTL samplesclusteredtogether,whereassADsamplesvariedwidely.FromtheperspectiveofOXPHOSbioenergetics,sADisaheterogeneoussyndrome and not likely due to a single abnormality. Increased stimulation of nuclear-encoded OXPHOS gene expression inPyNs is a rational therapeutic approach for most but not all cases of sAD.Keywords: Laser capture microdissection, mitochondria, mitochondrial biogenesis, relative gene expression, quantitative PCR

Origins of onset and progression of motor neurodegeneration in amyotrophic lateral sclerosis (ALS) are not clearly known, but may include impairment of mitochondrial bioenergetics. We used quantitative PCR approaches to analyze the mitochondrial oxidative phosphorylation (OXPHOS) transcriptomes of spinal cord tissue and peripheral blood mononuclear cells (PBMC) from persons with sporadic ALS compared with those without neurological disease. Expression measurements of 88 different nuclear (n) and mitochondrial (mt) DNA-encoded OXPHOS genes showed mtDNA-encoded respiratory gene expression was significantly decreased in ALS spinal cord by 78-84% (ANOVA p < 0.002). We observed the same phenomenon in freshly isolated PBMC from ALS patients (reduced 24-35%, ANOVA p < 0.001) and reproduced it in a human neural stem cell model treated with 2',3'-dideoxycytidine (ddC) (reduced 52-78%, ANOVA p < 0.001). nDNA-encoded OXPHOS genes showed heterogeneously and mostly decreased expression in ALS spinal cord tissue. In contrast, ALS PBMC and ddC-treated stem cells showed no significant change in expression of nDNA OXPHOS genes compared with controls. Genes related to mitochondrial biogenesis (PGC-1α, TFAM, ERRα, NRF1, NRF2 and POLG) were queried with inconclusive results. Here, we demonstrate there is a systemic decrease in mtDNA gene expression in ALS central and peripheral tissues that support pursuit of bioenergetic-enhancing therapies. We also identified a combined nDNA and mtDNA gene set (n = 26), downregulated in spinal cord tissue that may be useful as a biomarker in the development of cell-based ALS models.

This communication reports conversion phenomena in which CO2 and H2O gases are transformed into CO and H2, respectively, when exposed to a mixture of molten CaO-rich metallurgical slag and V2O3-rich gasifier slag. On reaction, CO2 and H2O are thermodynamically driven to become CO and H2, respectively, by giving up oxygen over the formation of calcium orthovanadate in the slag. The concept was experimentally investigated with a synthetic slag heated to 1500 °C (an assumed slag tap-out temperature in the metallurgical industry) in a CO2 saturated atmosphere. On heating, a rapid drop in oxygen partial pressure occurred between 1405 °C and 1460 °C, where 97% of CO2 transformed to CO. Potential industrial applications with the H2O-to-H2 conversion are then explored using detailed process computations. If the process is made economically viable, CO2 and H2O could be converted into products that are environmentally and industrially attractive and that have the potential for energy savings and greenhouse gas reduction in a process.

Three species of Leptogium are reported as new to Wisconsin: L. byssinum, L. dactylinum and L. rivulare. The first and third species are extremely rare and were only found in one locality each.

Efficiency of the chemical looping combustion technology is adversely influenced by surface properties of oxygen carrier materials during oxidation–reduction process changes at elevated temperatures. In this work, natural hematite (Fe2O3) and alumina (Al2O3) supported Cu-spinel (CuFe2O4) oxygen carrier particles were isothermally exposed to redox gas cycles (air and 10 vol% CO–90 vol% Ar) at approximately 800 °C and studied using a high temperature confocal scanning laser microscope for real time alterations in surface morphology, roughness, and particle volume. 3D topological scans from each cyclic gas exposure indicated hematite particles exhibited noticeable volume expansion in reduction and shrinkage in oxidation, corresponding to respective phase transformations. Materials surface changes during the redox gas cycles are discussed.

Previous empirical research demonstrated that by mixing gasification and metallurgical slags at a specific composition in a CO2 enriched environment, enough exothermic heat would be generated to transform CO2 to CO. The process capacity may be limited by the availability of the slags, however, it could be used to supplement existing energy or chemical production to reduce overall carbon emission. In this study, computational simulations were performed to explore optimal process conditions based on effects of individual slag constituents and thermal input for maximal gas conversion rate, heat production, and volume increase. In simulated conversions of CO2 to CO and H2O to H2 , comparisons were made by varying CaO, FeO, versus V2O3 slag constituents. The result indicated the optimal slag composition may be obtained by appropriate source selection and mixing of gasification and metallurgical slags in order to maximize carbon reduction and/or H2 production.

Carbon feedstocks used in power, chemical and metallurgical industries typically contain numerous minerals or impurities that liquefy during high temperature processing to form slag as a byproduct. Slags have many industrial applications, for example, as construction materials and for element recovery. In addition to other variables, the extent of slag utilization is dependent on its composition and post treatments. In this work, the influence of temperature and phosphorus additions on phase evolution in coal slag was investigated. Synthetic slag mixtures with varying AlPO4 contents (0–14 wt%) were heated from 1380–1470 °C in air, then water-quenched to preserve the phases formed. SEM/EDS, XRF and XRD analyses were performed before/after testing to gain insight about slag chemistry and phases present. It was found that coal slag exhibited a large solubility of phosphorous, affecting morphology of mullite formed under the conditions studied. Results obtained and their significance are discussed.

Microneurotrophins (MNT’s) are small molecule derivatives of dehydroepiandrosterone (DHEA) and do not have significant interactions with sex steroid receptors. MNT’s retain high-affinity binding to protein tyrosine kinase (Trk) receptors and can mimic many pleiotropic actions of neurotrophin (NT) proteins on neurons. MNT’s offer therapeutic potential for diseases such as amyotrophic lateral sclerosis (ALS) where motor neurons (MN) degenerate. MNT’s cross artificial membranes mimicking the blood–brain barrier, are not major substrates for ABC (ATP-binding cassette) transporters and are metabolized rapidly by mouse but more slowly by human hepatocytes. A lead MNT (BNN27) and its mono-oxidation metabolites enter mouse brain rapidly. RNA-sequencing measured gene expression profiles of human H9eSC-(embryonic stem cell)-derived or CTL (control) subject iPSC-(induced pluripotential stem cell)-derived MN’s exposed to NT proteins or MNT molecules. Expression ratios (relative to DMSO (dimethylsulfoxide) vehicle) were calculated, and the resulting top 500 gene lists were analyzed for Gene Ontology (GO) grouping using DAVID (Database for Annotation, Visualization and Integrated Discovery). The MNT’s BNN20, BNN23, and BNN27 showed overlap of GO terms with NGF (nerve growth factor) and BDNF (brain-derived neurotrophic factor) in the H9eSC-derived MN’s. In the iPSC-derived MN’s two (BNN20, BNN27) showed overlap of GO terms with NGF or BDNF. Each NT protein had GO terms that did not overlap with any MNT in the MN cell lines.

A model discrete fracture or cleat network was developed for the Pennsylvanian Upper Freeport coal seam at a carbon sequestration pilot site in southeastern Marshall Co., West Virginia, U. S. A. The model reservoir cleat network was developed using 3D seismic post-stack processing and interpretation workflows combined with observations of fracture systems in the surrounding region. The Upper Freeport coal is unminable in this area and served as a test for the feasibility of combined enhanced coalbed methane recovery (ECBMR) operations with CO2 storage in unminable coals. Well log-derived subsurface structure maps were used to calibrate 3D seismic time-to-depth conversion. Post-stack processing was used to enhance and identify subtle discontinuities in the seismic data that could be related to field-scale faults, fracture zones or stratigraphic heterogeneity. The cleat model was developed using power law fracture length and aperture distributions. Spatial variations of cleat intensity in the model were controlled using measures of localized structural discontinuity extracted from 3D seismic attribute workflows. The cleat model identifies a permeable fracture facies within the reservoir most likely to be impacted by CO2 injection and migration. Areas of concentrated seismic discontinuity bear some spatial association to areas of positive vertical deformation observed in a tiltmeter survey of the site and attributed to CO2 injection. The model could help focus time-lapse processing and interpretation in regions estimated to have higher permeability and porosity and higher probability for change of acoustic properties in response to CO2 injection and methane production. The approach developed here has general applicability to identification of fracture facies and development of unconventional naturally fractured reservoirs in other lithologies and basins.

In entrained slagging gasifiers, the fluidity of the molten ash is a critical factor for process control since it affects slag formation, the capture of inorganic constituents, refractory wear, and slag drainage along the gasification chamber walls. The use of western coal, or mixtures of eastern and western coals as gasifier feedstock, is likely to occur as western coals become available and technological issues that hinder their use are being resolved. In the present work, the viscosity of synthetic slags with ash chemistries simulating the western U.S. coals, was experimentally measured at a Po2 = 10−8 atm in the temperature range of 1773–1573 K (1500–1300 °C) using a rotating-bob viscometer. Alumina spindles and containment crucibles of both alumina and zirconia were used. Crystallization studies of this slag using a confocal scanning laser microscope found that a (Mg,Fe)Al2O4-based spinel precipitated at temperatures below 1723 K (1450 °C), and this agreed with FactSage equilibrium phase prediction. The same spinels were observed in the post-viscometry experiment slags when ZrO2 crucibles were used and assumed to be in equilibrium with the slag at the higher temperatures. Zirconia dissolution resulted in a slight increase in the solid fraction present in slags at lower temperatures, compared to spinel fraction. Crystal precipitation changed the apparent activation energy and required a longer stabilization times for viscosity measurements. The viscosity results were used in predictive equations based on Veytsman and Einstein's models, with critical nucleation temperatures and the solid fraction calculated with FactSage. In the simulated eastern/western coal feedstock blends based on ash compositions, the fractions of the solid precipitates were also calculated using the thermodynamic program FactSage for each blend composition, and the plastic viscosity of each eastern/western coal slag blend was predicted using Veytsman's model and compared to available experimental data.

Mitochondrial function declines with age in postmitotic tissues such as brain, heart and skeletal muscle. Despite weekly exercise, aged mice showed substantial losses of mtDNA gene copy numbers and reductions in mtDNA gene transcription and mitobiogenesis signaling in brain and heart. We treated these mice with weekly intravenous injections of recombinant human mitochondrial transcription factor A (rhTFAM). RhTFAM treatment for one month increased mitochondrial respiration in brain, heart and muscle, POLMRT expression and mtDNA gene transcription in brain, and PGC-1 alpha mitobiogenesis signaling in heart. RhTFAM treatment reduced oxidative stress damage to brain proteins, improved memory in Morris water maze performance and increased brain protein levels of BDNF and synapsin. Microarray analysis showed co-expression of multiple Gene Ontology families in rhTFAM-treated aged brains compared to young brains. RhTFAM treatment reverses age-related memory impairments associated with loss of mitochondrial energy production in brain, increases levels of memory-related brain proteins and improves mitochondrial respiration in brain and peripheral tissues.