88 research outputs found
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Technoeconomic and life-cycle analysis of single-step catalytic conversion of wet ethanol into fungible fuel blendstocks
Technoeconomic and life-cycle analyses are presented for catalytic conversion of ethanol to fungible hydrocarbon fuel blendstocks, informed by advances in catalyst and process development. Whereas prior work toward this end focused on 3-step processes featuring dehydration, oligomerization, and hydrogenation, the consolidated alcohol dehydration and oligomerization (CADO) approach described here results in 1-step conversion of wet ethanol vapor (40 wt% in water) to hydrocarbons and water over a metal-modified zeolite catalyst. A development project increased liquid hydrocarbon yields from 36% of theoretical to >80%, reduced catalyst cost by an order of magnitude, scaled up the process by 300-fold, and reduced projected costs of ethanol conversion 12-fold. Current CADO products conform most closely to gasoline blendstocks, but can be blended with jet fuel at low levels today, and could potentially be blended at higher levels in the future. Operating plus annualized capital costs for conversion of wet ethanol to fungible blendstocks are estimated at 1.44/GJ in the future, similar to the unit energy cost of producing anhydrous ethanol from wet ethanol (100 per barrel but not at 60 per barrel. Life-cycle greenhouse gas emission reductions for CADO-derived hydrocarbon blendstocks closely follow those for the ethanol feedstock
Intracranial meningiomas: an update of the 2021 World Health Organization classifications and review of management with a focus on radiation therapy
Meningiomas account for approximately one third of all primary intracranial tumors. Arising from the cells of the arachnoid mater, these neoplasms are found along meningeal surfaces within the calvarium and spinal canal. Many are discovered incidentally, and most are idiopathic, although risk factors associated with meningioma development include age, sex, prior radiation exposure, and familial genetic diseases. The World Health Organization grading system is based on histologic criteria, and are as follows: grade 1 meningiomas, a benign subtype; grade 2 meningiomas, which are of intermediately aggressive behavior and usually manifest histologic atypia; and grade 3, which demonstrate aggressive malignant behavior. Management is heavily dependent on tumor location, grade, and symptomatology. While many imaging-defined low grade appearing meningiomas are suitable for observation with serial imaging, others require aggressive management with surgery and adjuvant radiotherapy. For patients needing intervention, surgery is the optimal definitive approach with adjuvant radiation therapy guided by extent of resection, tumor grade, and location in addition to patient specific factors such as life expectancy. For grade 1 lesions, radiation can also be used as a monotherapy in the form of stereotactic radiosurgery or standard fractionated radiation therapy depending on tumor size, anatomic location, and proximity to dose-limiting organs at risk. Optimal management is paramount because of the generally long life-expectancy of patients with meningioma and the morbidity that can arise from tumor growth and recurrence as well as therapy itself
Outcomes of surgery and postoperative radiation therapy in managing medullary thyroid carcinoma
Background and Objectives We evaluated the outcomes of surgery with or without postoperative radiation therapy (PORT) in the management of medullary thyroid carcinoma (MTC). Methods From two tertiary cancer centers, 297 consecutive patients with MTC treated with PORT (n = 46) between 1990 and 2016 or surgery alone (n = 251) between 2000 and 2016 were reviewed. Results Ten-year cumulative incidences of locoregional and distant failure were 30.2% and 24.9% in the surgery cohort, and 16.9% and 55.2% in the PORT cohort. In the surgery alone cohort, T4 disease, extrathyroidal extension, N1 disease, extranodal extension (ENE), and residual disease after surgery were associated with local failure. The PORT cohort had significantly higher proportions of patients with T4 disease, N1 disease, ENE, and residual disease. Conclusions High-risk clinical features can help identify patients with MTC at high-risk for local failure after surgery alone. Patients with high-risk clinical features had effective locoregional control after PORT
PEERS - an open science “Platform for the Exchange of Experimental Research Standards” in biomedicine
Funding The PEERS Consortium is currently funded by Cohen Veterans Bioscience Ltd and grants COH-0011 from Steven A. Cohen. Acknowledgements We would like to thank IJsbrand Jan Aalbersberg, Natasja de Bruin, Philippe Chamiot-Clerc, Anja Gilis, Lieve Heylen, Martine Hofmann, Patricia Kabitzke, Isabel Lefevre, Janko Samardzic, Susanne Schiffmann and Guido Steiner for their valuable input and discussions during the conceptualization of PEERS and the initial phase of the project.Peer reviewedPublisher PD
Cerebral Blood Volume Changes During Radiotherapy May Predict Pseudoprogression versus Disease Progression for Patients with High Grade Glioma
https://openworks.mdanderson.org/sumexp21/1040/thumbnail.jp
The genome landscape of indigenous African cattle
Background: The history of African indigenous cattle and their adaptation to environmental and human selection pressure is at the root of their remarkable diversity. Characterization of this diversity is an essential step towards understanding the genomic basis of productivity and adaptation to survival under African farming systems.
Results: We analyze patterns of African cattle genetic variation by sequencing 48 genomes from five indigenous populations and comparing them to the genomes of 53 commercial taurine breeds. We find the highest genetic diversity among African zebu and sanga cattle. Our search for genomic regions under selection reveals signatures of selection for environmental adaptive traits. In particular, we identify signatures of selection including genes and/ or pathways controlling anemia and feeding behavior in the trypanotolerant N’Dama, coat color and horn development in Ankole, and heat tolerance and tick resistance across African cattle especially in zebu breeds.
Conclusions: Our findings unravel at the genome-wide level, the unique adaptive diversity of African cattle while emphasizing the opportunities for sustainable improvement of livestock productivity on the continent
Transcriptomic analysis of the temporal host response to skin infestation with the ectoparasitic mite Psoroptes ovis
<p>Abstract</p> <p>Background</p> <p>Infestation of ovine skin with the ectoparasitic mite <it>Psoroptes ovis </it>results in a rapid cutaneous immune response, leading to the crusted skin lesions characteristic of sheep scab. Little is known regarding the mechanisms by which such a profound inflammatory response is instigated and to identify novel vaccine and drug targets a better understanding of the host-parasite relationship is essential. The main objective of this study was to perform a combined network and pathway analysis of the <it>in vivo </it>skin response to infestation with <it>P. ovis </it>to gain a clearer understanding of the mechanisms and signalling pathways involved.</p> <p>Results</p> <p>Infestation with <it>P. </it>ovis resulted in differential expression of 1,552 genes over a 24 hour time course. Clustering by peak gene expression enabled classification of genes into temporally related groupings. Network and pathway analysis of clusters identified key signalling pathways involved in the host response to infestation. The analysis implicated a number of genes with roles in allergy and inflammation, including pro-inflammatory cytokines (<it>IL1A, IL1B, IL6, IL8 </it>and <it>TNF</it>) and factors involved in immune cell activation and recruitment (<it>SELE, SELL, SELP, ICAM1, CSF2, CSF3, CCL2 </it>and <it>CXCL2</it>). The analysis also highlighted the influence of the transcription factors NF-kB and AP-1 in the early pro-inflammatory response, and demonstrated a bias towards a Th2 type immune response.</p> <p>Conclusions</p> <p>This study has provided novel insights into the signalling mechanisms leading to the development of a pro-inflammatory response in sheep scab, whilst providing crucial information regarding the nature of mite factors that may trigger this response. It has enabled the elucidation of the temporal patterns by which the immune system is regulated following exposure to <it>P. ovis</it>, providing novel insights into the mechanisms underlying lesion development. This study has improved our existing knowledge of the host response to <it>P. ovis</it>, including the identification of key parallels between sheep scab and other inflammatory skin disorders and the identification of potential targets for disease control.</p
Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field
The genetic architecture of the human cerebral cortex
The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder
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