Exploring the Potential of Environmental Impact Investing for Sustainable Development: The Cases of Dominion Energy and Tesla Motors

The health of our planet and the existence of our species faces an uncertain future. Climate change is the single largest issue facing society today, as carbon-based fuel and combustion engines have driven development in nearly every industry. Public investment through securities markets have enabled corporations to extract coal and oil, build combustion engines, and distribute fuel commercially for over one hundred and fifty years. However, it is now widely accepted that if business-as-usual continues, carbon emissions will cause irreversible and devastating effects to the environment and humankind. International, national, local governments, companies, and general populations have taken steps to combat the existential threat of climate change. Divestment in fossil fuel can come both from market mechanics encouraging investment in alternatives, as well as strategic decisions by corporations to make a change. Offering investors financial vehicles to promote sustainable development will improve the capacity of our world to have a more sustainable future, as well as offer investors competitive returns that are not subject to liabilities expected to continue in the fossil fuel industries. This research describes a quantitative additive preference model based on environmental criteria to analyze both Dominion Energy and Tesla Motors through the lens of environmental impact investing utility. The purpose of the model is to quantify the potential environmental impact of individual companies to inform institutional and retail investment decisions geared at environmentally conscious investing. Future work should focus on refining the criteria and weights, integrating the model into a fund-management toolkit, and providing greater transparency for all investors to make positive environmentally impactful investment decisions

Defining the Cerebral Cavernous Malformation Protein Signaling Network in Endothelial Cells

Cerebral cavernous malformations (CCM) are cerebrovascular lesions occurring with homozygous loss of function mutations of CCM1, -2, and -3. CCMs can cause neurological deficits, seizures, and fatal hemorrhagic stroke. Loss of function in any one of the three CCM proteins leads to defects in in vitro angiogenesis assays, along with increased actin stress fibers in endothelial cells. Elevated RhoA and Rho kinase (ROCK)-LIM kinase hyperactivity results upon loss of the CCM proteins, likely from dysregulation of the E3 ubiquitin ligase SMURF1. Phosphorylation of the LIM kinase substrate and actin depolymerizing factor cofilin is increased in primary endothelial cells and surgically resected human CCM lesions, providing a novel biomarker for CCM disease. The CCM phenotype and RhoA-ROCK hyperactivity can be recapitulated in endothelial progenitor-derived endothelial cells, primary cells that can be isolated from the peripheral blood of human CCM patients. Significantly, treatment with structurally distinct small molecule ROCK inhibitors rescues the CCM phenotype in vitro and reverses the hyperactivation of ROCK effectors seen with loss of the CCM proteins. Interrogation of the kinome in endothelial cells with CCM2 knockdown using multiplexed kinase inhibitor beads coupled to mass spectroscopy reveals striking dysregulation, likely multifactorial from loss of the scaffold-like CCM2 protein, dysregulation of SMURF1, and concomitant hyperactivation of the small GTPase RhoA. Of particular interest are the loss of two critical angiogenesis kinases, TIE-2 and BMX. Together, these data provides insight to the molecular mechanism of CCM pathophysiology and provides clues for future successful pharmacological treatment of the disease.Doctor of Philosoph

Systems biology and proteomic analysis of cerebral cavernous malformation

Cerebral cavernous malformations (CCM) are vascular anomalies caused by mutations in genes encoding KRIT1, OSM and PDCD10 proteins causing hemorrhagic stroke. We examine proteomic change of loss of CCM gene expression. Using human umbilical vein endothelial cells, label-free differential protein expression analysis with multidimensional liquid chromatography/tandem mass spectrometry was applied to three CCM protein knockdown cell lines and two control cell lines: ProteomeXchange identifier PXD000362. Principle component and cluster analyses were used to examine the differentially expressed proteins associated with CCM. The results from the five cell lines revealed 290 and 192 differentially expressed proteins (p < 0.005 and p < 0.001, respectively). Most commonly affected proteins were cytoskeleton-associated proteins, in particular myosin-9. Canonical genetic pathway analysis suggests that CCM may be a result of defective cell–cell interaction through dysregulation of cytoskeletal associated proteins

Development of efficient, integrated cellulosic biorefineries : LDRD final report.

Cellulosic ethanol, generated from lignocellulosic biomass sources such as grasses and trees, is a promising alternative to conventional starch- and sugar-based ethanol production in terms of potential production quantities, CO{sub 2} impact, and economic competitiveness. In addition, cellulosic ethanol can be generated (at least in principle) without competing with food production. However, approximately 1/3 of the lignocellulosic biomass material (including all of the lignin) cannot be converted to ethanol through biochemical means and must be extracted at some point in the biochemical process. In this project we gathered basic information on the prospects for utilizing this lignin residue material in thermochemical conversion processes to improve the overall energy efficiency or liquid fuel production capacity of cellulosic biorefineries. Two existing pretreatment approaches, soaking in aqueous ammonia (SAA) and the Arkenol (strong sulfuric acid) process, were implemented at Sandia and used to generated suitable quantities of residue material from corn stover and eucalyptus feedstocks for subsequent thermochemical research. A third, novel technique, using ionic liquids (IL) was investigated by Sandia researchers at the Joint Bioenergy Institute (JBEI), but was not successful in isolating sufficient lignin residue. Additional residue material for thermochemical research was supplied from the dilute-acid simultaneous saccharification/fermentation (SSF) pilot-scale process at the National Renewable Energy Laboratory (NREL). The high-temperature volatiles yields of the different residues were measured, as were the char combustion reactivities. The residue chars showed slightly lower reactivity than raw biomass char, except for the SSF residue, which had substantially lower reactivity. Exergy analysis was applied to the NREL standard process design model for thermochemical ethanol production and from a prototypical dedicated biochemical process, with process data supplied by a recent report from the National Research Council (NRC). The thermochemical system analysis revealed that most of the system inefficiency is associated with the gasification process and subsequent tar reforming step. For the biochemical process, the steam generation from residue combustion, providing the requisite heating for the conventional pretreatment and alcohol distillation processes, was shown to dominate the exergy loss. An overall energy balance with different potential distillation energy requirements shows that as much as 30% of the biomass energy content may be available in the future as a feedstock for thermochemical production of liquid fuels

Derivation and validation of a clinical prediction rule for upper limb functional outcomes after traumatic cervical spinal cord injury

IMPORTANCE: Traumatic cervical spinal cord injury (SCI) can result in debilitating paralysis. Following cervical SCI, accurate early prediction of upper limb recovery can serve an important role in guiding the appropriateness and timing of reconstructive therapies. OBJECTIVE: To develop a clinical prediction rule to prognosticate upper limb functional recovery after cervical SCI. DESIGN, SETTING, AND PARTICIPANTS: This prognostic study was a retrospective review of a longitudinal cohort study including patients enrolled in the National SCI model systems (SCIMS) database in US. Eligible patients were 15 years or older with tetraplegia (neurological level of injury C1-C8, American Spinal Cord Injury Association [ASIA] impairment scale [AIS] A-D), with early (within 1 month of SCI) and late (1-year follow-up) clinical examinations from 2011 to 2016. The data analysis was conducted from September 2021 to June 2022. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of dependency in eating, bladder management, transfers, and locomotion domains of functional independence measure at 1-year follow-up. Each domain ranges from 1 to 7 with a lower score indicating greater functional dependence. Composite dependency was defined as a score of 4 or higher in at least 3 chosen domains. Multivariable logistic regression was used to predict the outcome based on early neurological variables. Discrimination was quantified using C statistics, and model performance was internally validated with bootstrapping and 10-fold cross-validation. The performance of the prediction score was compared with AIS grading. Data were split into derivation (2011-2014) and temporal-validation (2015-2016) cohorts. RESULTS: Among 2373 patients with traumatic cervical SCI, 940 had complete 1-year outcome data (237 patients [25%] aged 60 years or older; 753 men [80%]). The primary outcome was present in 118 patients (13%), which included 92 men (78%), 83 (70%) patients who were younger than 60 years, and 73 (62%) patients experiencing AIS grade A SCI. The variables significantly associated with the outcome were age (age 60 years or older: OR, 2.31; 95% CI, 1.26-4.19), sex (men: OR, 0.60; 95% CI, 0.31-1.17), light-touch sensation at C5 (OR, 0.44; 95% CI, 0.44-1.01) and C8 (OR, 036; 95% CI, 0.24-0.53) dermatomes, and motor scores of the elbow flexors (C5) (OR, 0.74; 95% CI, 0.60-0.89) and wrist extensors (C6) (OR, 0.61; 95% CI, 0.49-0.75). A multivariable model including these variables had excellent discrimination in distinguishing dependent from independent patients in the temporal-validation cohort (C statistic, 0.90; 95% CI, 0.88-0.93). A clinical prediction score (range, 0 to 45 points) was developed based on these measures, with higher scores increasing the probability of dependency. The discrimination of the prediction score was significantly higher than from AIS grading (change in AUC, 0.14; 95% CI, 0.10-0.18; P \u3c .001). CONCLUSIONS AND RELEVANCE: The findings of this study suggest that this prediction rule may help prognosticate upper limb function following cervical SCI. This tool can be used to set patient expectations, rehabilitation goals, and aid decision-making regarding the appropriateness and timing for upper limb reconstructive surgeries

Personalized practice dosages may improve motor learning in older adults compared to standard of care practice dosages: A randomized controlled trial

Standard dosages of motor practice in clinical physical rehabilitation are insufficient to optimize motor learning, particularly for older patients who often learn at a slower rate than younger patients. Personalized practice dosing (i.e., practicing a task to or beyond one\u27s plateau in performance) may provide a clinically feasible method for determining a dose of practice that is both standardized and individualized, and may improve motor learning. The purpose of this study was to investigate whether personalized practice dosages