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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 1,801 records · Page 100
All sourcesNASA NTRSDOE OSTI
DOE OSTI2019

Safety and Short-Term Efficacy of Irreversible Electroporation and Allogenic Natural Killer Cell Immunotherapy Combination in the Treatment of Patients with Unresectable Primary Liver Cancer

Purpose: This study aimed to investigate the safety and short-term efficacy of irreversible electroporation (IRE) combined with allogenic natural killer (NK) cell immunotherapy in the treatment of patients with unresectable primary liver cancer. Materials and Methods: Between October 2015 and December 2016, 40 patients were enrolled and randomly allocated to either the IRE group (n = 22) or the IRE–NK group (n = 18). All adverse events experienced by the patients were recorded; the changes in tumor biomarkers [AFP, CA 19-9, circulating tumor cells (CTCs)], lymphocyte number and function, quality of life, clinical response, progression-free survival (PFS) and overall survival (OS) were assessed. Results: Patients who received combination therapy exhibited significantly longer median PFS and OS than who just received IRE (PFS 15.1 vs. 10.6 months, P < 0.05, OS 17.9 vs. 23.2 months, P < 0.05). The combination therapy of IRE and NK cell immunotherapy significantly reduced CTCs and increased immune function and Karnofsky performance status. Conclusion: Our data suggest a novel, promising combination therapy using IRE and allogenic NK cell immunotherapy. Larger clinical trials are required to confirm these conclusions.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Insights from 20 years of bacterial genome sequencing

Since the first two complete bacterial genome sequences were published in 1995, the science of bacteria has dramatically changed. Using third-generation DNA sequencing, it is possible to completely sequence a bacterial genome in a few hours and identify some types of methylation sites along the genome as well. Sequencing of bacterial genome sequences is now a standard procedure, and the information from tens of thousands of bacterial genomes has had a major impact on our views of the bacterial world. In this review, we explore a series of questions to highlight some insights that comparative genomics has produced. To date, there are genome sequences available from 50 different bacterial phyla and 11 different archaeal phyla. However, the distribution is quite skewed towards a few phyla that contain model organisms. But the breadth is continuing to improve, with projects dedicated to filling in less characterized taxonomic groups. The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system provides bacteria with immunity against viruses, which outnumber bacteria by tenfold. How fast can we go? Second-generation sequencing has produced a large number of draft genomes (close to 90 % of bacterial genomes in GenBank are currently not complete); third-generation sequencing can potentially produce a finished genome in a few hours, and at the same time provide methlylation sites along the entire chromosome. The diversity of bacterial communities is extensive as is evident from the genome sequences available from 50 different bacterial phyla and 11 different archaeal phyla. Genome sequencing can help in classifying an organism, and in the case where multiple genomes of the same species are available, it is possible to calculate the pan- and core genomes; comparison of more than 2000 Escherichia coli genomes finds an E. coli core genome of about 3100 gene families and a total of about 89,000 different gene families. Why do we care about bacterial genome sequencing? There are many practical applications, such as genome-scale metabolic modeling, biosurveillance, bioforensics, and infectious disease epidemiology. In the near future, high-throughput sequencing of patient metagenomic samples could revolutionize medicine in terms of speed and accuracy of finding pathogens and knowing how to treat them.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2012

The Implications of selenium deficiency for wild herbivore conservation: a review

Selenium (Se) has been identified as an essential micronutrient in all animals. It is required at the most fundamental physiological level as a component of the selenoproteins containing the 21st amino acid, selenocysteine. Adequate levels of Se are vital to proper reproductive performance, bone metabolism, immune function and iodine metabolism. Yet, Se is a relatively rare element, and is often present at low concentrations in soil and vegetation. Selenium deficiencies are widespread in domestic stock and are unavoidable in some wildlife populations. This may be especially true for populations confined to high elevation ranges, or on areas with granitic bedrock with low Se content, or that have lost access to Se-containing parts of their ranges such as mineral licks or low-elevation winter range. The condition may be exacerbated by increased levels of oxidative stress. Because our understanding of Se as a micronutrient is relatively new, many wildlife managers are unaware of the element’s importance in physiology and population dynamics. Severe deficiency results in obvious symptoms such as white muscle disease. However, more frequently, deficiency may be chronic and subclinical. Individuals then display no obvious signs of malady, yet performance suffers until their populations decline without apparent cause. While mysterious population declines are not always due to Se deficiency, the wildlife manager should be aware of the possibility. Therefore, this review presents not only a summary of the wildlife literature regarding Se nutrition, but also a comprehensive look at the role of Se in mammalian physiology, and the behavior of this important element in the environment. Finally, the role of the biogeochemical Se cycle is discussed, and evidence is provided that the levels of available Se in the environment are decreasing while physiological demands often are increasing.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Structural and Functional Parameters of the Thymus in Mice Exposed to γ-Irradiation after Restraint Stress

In mice exposed to γ-irradiation in a dose of 2 Gy after 15-days restraint stress, the body weight decreased by 21% and thymus weight decreased by 33.3% in comparison with the control, and significant changes in the histological structure of the thymus were observed. The medullary substance prevailed over the cortical substance. The absolute number of cells per 1 mm{sup 2} of histological section was reduced in the subcapsular area and medullary substance. The analysis of cell composition in functional areas of the thymus showed the most pronounced changes in the cortical substance. The decrease in the number of proliferating cells and low-differentiated lymphocytes and the increase in the number of destructed cells reflected impairment of the lymphocytopoietic function of the thymus. A minor decrease in the number of small lymphocytes indicated impaired migration processes in the thymus of mice exposed to γ-irradiation after restraint stress. The observed complex of histological and physiological changes in the thymus can lead to dysfunction of the lymphatic (immune) system.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Stellarator Research Opportunities: A Report of the National Stellarator Coordinating Committee

This paper is the product of a stellarator community workshop, organized by the National Stellarator Coordinating Committee and referred to as Stellcon, that was held in Cambridge, Massachusetts in February 2016, hosted by MIT. The workshop was widely advertised, and was attended by 40 scientists from 12 different institutions including national labs, universities and private industry, as well as a representative from the Department of Energy. The final section of this document describes areas of community wide consensus that were developed as a result of the discussions held at that workshop. Areas where further study would be helpful to generate a consensus path forward for the US stellarator program are also discussed. The program outlined in this document is directly responsive to many of the strategic priorities of FES as articulated in “Fusion Energy Sciences: A Ten-Year Perspective (2015–2025)” [1]. The natural disruption immunity of the stellarator directly addresses “Elimination of transient events that can be deleterious to toroidal fusion plasma confinement devices” an area of critical importance for the US fusion energy sciences enterprise over the next decade. Another critical area of research “Strengthening our partnerships with international research facilities,” is being significantly advanced on the W7-X stellarator in Germany and serves as a test-bed for development of successful international collaboration on ITER. Finally, this report also outlines how materials science as it relates to plasma and fusion sciences, another critical research area, can be carried out effectively in a stellarator. Additionally, significant advances along two of the Research Directions outlined in the report; “Burning Plasma Science: Foundations—Next-generation research capabilities”, and “Burning Plasma Science: Long pulse—Sustainment of Long-Pulse Plasma Equilibria” are proposed.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗
DOE OSTI2018

Recent Advances in Copper Intercalators as Anticancer Agents

Copper is a part of various enzymes and helps them to function properly. It can be effectively used to produce promising anticancer drugs and presently, many studies are being pursued worldwide on the development of copper-based complexes as potential anticancer drugs. Herein, we briefly discuss the importance of reactive oxygen species in biological applications and copper(II) complexes as anticancer drugs. The anti-angiogenic properties of mono-nuclear copper(II) complexes have been demonstrated by in vivo chick embryo angiogenesis analysis. The plausible mechanism behind anticancer activity of these complexes is by the formation of excessive intracellular Reactive Oxygen Species (ROS). ROS is a composite term used for oxygen derivative non-radicals and free radicals of highly reactive components, that enhances the killing response of immune cells to microbial invasion. Previous reports have shown that ROS plays an important role as a messenger in cell cycling and normal cell signal transduction. .

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Viral kinetic modeling: state of the art

Viral kinetic modeling has led to increased understanding of the within host dynamics of viral infections and the effects of therapy. Here we review recent developments in the modeling of viral infection kinetics with emphasis on two infectious diseases: hepatitis C and influenza. We review how viral kinetic modeling has evolved from simple models of viral infections treated with a drug or drug cocktail with an assumed constant effectiveness to models that incorporate drug pharmacokinetics and pharmacodynamics, as well as phenomenological models that simply assume drugs have time varying-effectiveness. We also discuss multiscale models that include intracellular events in viral replication, models of drug-resistance, models that include innate and adaptive immune responses and models that incorporate cell-to-cell spread of infection. Overall, viral kinetic modeling has provided new insights into the understanding of the disease progression and the modes of action of several drugs. In conclusion, we expect that viral kinetic modeling will be increasingly used in the coming years to optimize drug regimens in order to improve therapeutic outcomes and treatment tolerability for infectious diseases.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Discrete Control of a Dynamical System with Delay Under Conditions of Uncertainty

In this paper, we present a numerical solution of the discrete control problem for the immune response in an infectious disease under conditions of uncertainty. This problem is described by a nonlinear system of ordinary differential equation with delay. Conditions of uncertainty mean that values of the parameters of the model are unknown and their estimates are corrected by new experimental data. We propose an algorithm that allows one, within the framework of the mathematical model of an infectious disease, to construct the control and to identify parameters. By using the algorithm proposed, we develop treatment programs based on immunotherapy. We show that immunotherapy is an effective treatment for all main forms of disease: acute, chronic, and lethal.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Crystal structure of a macrophage migration inhibitory factor from Giardia lamblia

Macrophage migration inhibitory factor (MIF) is a eukaryotic cytokine that affects a broad spectrum of immune responses and its activation/inactivation is associated with numerous diseases. During protozoan infections MIF is not only expressed by the host, but, has also been observed to be expressed by some parasites and released into the host. To better understand the biological role of parasitic MIF proteins, the crystal structure of the MIF protein from Giardia lamblia (Gl-MIF), the etiological agent responsible for giardiasis, has been determined at 2.30 Å resolution. The 114-residue protein adopts an α/β fold consisting of a four-stranded β-sheet with two anti-parallel α-helices packed against a face of the β-sheet. An additional short β-strand aligns anti-parallel to β4 of the β-sheet in the adjacent protein unit to help stabilize a trimer, the biologically relevant unit observed in all solved MIF crystal structures to date, and form a discontinuous β-barrel. The structure of Gl-MIF is compared to the MIF structures from humans (Hs-MIF) and three Plasmodium species (falciparum, berghei, and yoelii). The structure of all five MIF proteins are generally similar with the exception of a channel that runs through the center of each trimer complex. Relative to Hs-MIF, there are differences in solvent accessibility and electrostatic potential distribution in the channel of Gl-MIF and the Plasmodium-MIFs due primarily to two “gate-keeper” residues in the parasitic MIFs. For the Plasmodium MIFs the gate-keeper residues are at positions 44 (Y==>R) and 100 (V==>D) and for Gl-MIF it is at position 100 (V==>R). If these gate-keeper residues have a biological function and contribute to the progression of parasitemia they may also form the basis for structure-based drug design targeting parasitic MIF proteins.

Environmental Molecular Sciences Laboratory↗
DOE OSTI2016

PET Imaging Study of S1PR1 Expression in a Rat Model of Multiple Sclerosis

Upregulation of sphingosine-1-phosphate receptor 1 (S1PR1) expression in multiple sclerosis (MS) lesions is associated with neuroinflammatory response. This study investigated the correlation between neuroinflammation and S1PR1 expression in the spinal cord of an experimental autoimmune encephalomyelitis (EAE) rat model of MS, using the S1PR1 positron emission tomography (PET) radiotracer [11C]TZ3321. MicroPET imaging studies of [11C]TZ3321 were performed to measure uptake of [11C]TZ3321 in the spinal cord of EAE rats. Immunohistochemical staining was performed to confirm the overexpression of S1PR1 and other inflammatory biomarkers. MicroPET imaging demonstrated a 20–30 % increase in [11C]TZ3321 uptake in the lumbar spinal cord of EAE rats versus sham controls at 35–60 min post injection. The increased uptake of [11C]TZ3321 was correlated with the overexpression of S1PR1 in the lumbar spinal cord of EAE rats that was confirmed by immunohistochemical staining. Upregulated S1PR1 expression was associated with glial cell activation and immune cell infiltration. MicroPET imaging modality with a specific radioligand [11C]TZ3321 is able to assess the expression of S1PR1 in EAE rat lumbar spinal cord. This may provide a new approach to the assessment of neuroinflammatory response in MS and other inflammatory diseases.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2016

Nodeless pairing in superconducting copper-oxide monolayer films on Bi 2 Sr 2 CaCu 2 O 8+δ

We report that the pairing mechanism of high-temperature superconductivity in cuprates remains the biggest unresolved mystery in condensed matter physics. To solve the problem, one of the most effective approaches is to investigate directly the superconducting CuO 2 layers. Here, by growing CuO 2 monolayer films on Bi 2 Sr 2 CaCu 2 O 8+δ substrates, we identify two distinct and spatially separated energy gaps centered at the Fermi energy, a smaller U-like gap and a larger V-like gap on the films, and study their interactions with alien atoms by low-temperature scanning tunneling microscopy. The newly discovered U-like gap exhibits strong phase coherence and is immune to scattering by K, Cs and Ag atoms, suggesting its nature as a nodeless superconducting gap in the CuO 2 layers, whereas the V-like gap agrees with the well-known pseudogap state in the underdoped regime. In conclusion, our results support an s-wave superconductivity in Bi 2 Sr 2 CaCu 2 O 8+δ , which, we propose, originates from the modulation-doping resultant two-dimensional hole liquid confined in the CuO 2 layers.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗
DOE OSTI2019

Anti-Neuroinflammatory Effects of Vanillin Through the Regulation of Inflammatory Factors and NF-κB Signaling in LPS-Stimulated Microglia

Microglia, resident macrophages of the central nervous system (CNS), is responsible for immune responses and homeostasis of the CNS. Microglia plays a complex role in neuroinflammation, which has been implicated in neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. Therefore, therapeutic agents that suppress the microglia-mediated inflammatory response could potentially be used in the prevention or treatment of neurodegenerative diseases. Vanillin, a primary component of vanilla bean extract, has anti-inflammatory, anticancer, and antitumor properties. However, the effects of vanillin on the anti-neuroinflammatory responses of microglial cells are still poorly understood. In this study, we investigated the mechanism by which vanillin induces anti-neuroinflammatory responses in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. We found that vanillin significantly decreased the production of nitric oxide and pro-inflammatory cytokines, including interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Vanillin also reduced the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), as well as the mRNA expression levels of IL-1β, TNF-α, and IL-6. Moreover, vanillin inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB. Collectively, these results suggest that vanillin has anti-neuroinflammatory properties and may act as a natural therapeutic agent for neuroinflammatory diseases.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Characteristics and impact of programmed death-ligand 1 expression, CD8+ tumor-infiltrating lymphocytes, and p16 status in head and neck squamous cell carcinoma

Background: No predictive biomarker of immune checkpoint inhibitors in head and neck squamous cell carcinoma (HNSCC) has been well established. The impact of programmed death-ligand 1 (PD-L1) expression, CD8+ tumor-infiltrating lymphocytes (TILs), and p16 status in HNSCC is unclear and may vary according to ethnicity. Methods: HNSCC patients treated between 2007 and 2013 were reviewed. Archival tissues were retrieved for PD-L1, CD8+ TILs, and p16 analyses. PD-L1 expression was evaluated by using the validated SP142 assay on the VENTANA platform. CD8+ TILs were defined by using semiquantitative scoring. Results: A total of 203 patients were analyzed. PD-L1 expression was observed in 80% of patients and was significantly associated with older age (P < 0.001). A high CD8+ TIL score (≥ 6) was significantly associated with never-smoking (P = 0.020), oral cavity cancer (P < 0.001), and stage M0 at presentation (P = 0.025). The p16 status was positive in 12% of patients. Patients with a high TIL score had a significantly longer OS (P = 0.032). Patients with PD-L1 expression of 1–49% and ≥ 50% were associated with a significantly shorter OS compared with those with PD-L1 < 1% (P = 0.027 and P = 0.011, respectively). Multivariate analysis showed that PD-L1 ≥ 50% was significantly associated with a poor OS. (HR 2.98 [95% CI 1.2–7.39]; P = 0.019.) Conclusions: A high prevalence of PD-L1 expression was observed in HNSCC using the validated SP142 assay. PD-L1 expression was associated with older age, while highly PD-L1 expression (≥ 50%) was an independent prognostic factor for poor OS in anti-PD1/PD-L1 untreated HNSCC patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Impact of early inflammatory cytokine elevation after commencement of PD-1 inhibitors to predict efficacy in patients with non-small cell lung cancer

Early elevation of inflammatory cytokines, such as IL-6 or TNF-α, or CRP, which is a surrogate marker for IL-6, following commencement of PD-1/L1 inhibitors (PD1-I) may represent early activation of immune-cells. Serum IL-6 and TNF-α were measured in 10 non-small cell lung cancer patients who were evaluable within the 7 days before and after commencement of PD1-I. For CRP, medical records were reviewed and 34 patients with measured CRP within the 7 days before and after the treatment were evaluated. In the 10 patients analyzed for IL-6/TNF-α, the serum levels of IL-6/TNF-α were not significantly different between pre- and post-initial PD1-I [IL-6 20.3 (2.6–49.9) and 22.9 (3.6–96.1) pg/mL, p = 0.453; TNF-α 1.6 (0.7–6.3) and 3.3 (0.7–9.6) pg/mL, p = 0.329]; however, all four responses were observed among the 7 IL-6-elevated cases, resulting in a response rate of 57%. In the 34 patients analyzed for CRP, CRP was significantly increased after initial PD1-I [1.8 (0.1–17.8) mg/dL, 2.4 (0.0–27.8), p = 0.001]. Notably, in the 31 evaluable cases, all responses were again observed in either the IL-6 or CRP elevated groups and the response rate was 46% (11 of 24). The median overall survival time was not reached in the elevated group and was 112 days in the non-elevated group (p = 0.069). The early increase in inflammatory cytokines with PD1-I was indicated to be predictive for the efficacy in patients with non-small cell lung cancer.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Correlation between the magnitude of best tumor response and patient survival in nivolumab therapy for metastatic renal cell carcinoma

The correlation between the magnitudes of best tumor response (bTR) and patient survival in immune checkpoint inhibitor therapy for metastatic renal cell carcinoma (mRCC) remains unclear. In this article, we retrospectively investigated the prognostic association of the magnitude of bTR in nivolumab therapy for mRCC. Fifty-five patients treated with nivolumab after failure of at least one molecular-targeted therapy were evaluated. Assessment of the magnitude of bTR was based on the Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1. Endpoints were progression-free survival (PFS) and overall survival (OS) after the initiation of nivolumab therapy. In regard to the magnitude of bTR, complete response, partial response, stable disease, and progressive disease were observed in three (5.46%), 15 (27.3%), 19 (34.5%), and 18 (32.7%) patients, respectively. PFS and OS were significantly correlated with the magnitude of bTR (median PFS: not reached (N.R.) [95% confidence interval (CI) 16.8–N.R.] vs. 13.0 [8.38–56.0] vs. 5.95 [4.27–7.30] vs. 1.92 [0.53–3.91] months, p < 0.0001; OS: N.R. [N.R.–N.R.] vs. N.R. [21.4–N.R.] vs. 23.3 [23.3–N.R.] vs. 7.36 [1.41–N.R.] months, p < 0.0001). In addition, multivariate analyses show that the magnitude of bTR was an independent factor for PFS (p < 0.0001) and OS (p = 0.0010). In conclusion, this retrospective study shows the significant correlation between the magnitude of bTR and patient survival in nivolumab therapy for mRCC. The magnitude of bTR can be an effective surrogate marker for survival.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Transient disease dynamics across ecological scales

Analyses of transient dynamics are critical to understanding infectious disease transmission and persistence. Identifying and predicting transients across scales, from within-host to community-level patterns, plays an important role in combating ongoing epidemics and mitigating the risk of future outbreaks. Moreover, greater emphases on non-asymptotic processes will enable timely evaluations of wildlife and human diseases and lead to improved surveillance efforts, preventive responses, and intervention strategies. Here, we explore the contributions of transient analyses in recent models spanning the fields of epidemiology, movement ecology, and parasitology. In addition to their roles in predicting epidemic patterns and endemic outbreaks, we explore transients in the contexts of pathogen transmission, resistance, and avoidance at various scales of the ecological hierarchy. Examples illustrate how (i) transient movement dynamics at the individual host level can modify opportunities for transmission events over time; (ii) within-host energetic processes often lead to transient dynamics in immunity, pathogen load, and transmission potential; (iii) transient connectivity between discrete populations in response to environmental factors and outbreak dynamics can affect disease spread across spatial networks; and (iv) increasing species richness in a community can provide transient protection to individuals against infection. Ultimately, we suggest that transient analyses offer deeper insights and raise new, interdisciplinary questions for disease research, consequently broadening the applications of dynamical models for outbreak preparedness and management.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Cardio-oncology: Understanding cardiotoxicity to guide patient focused imaging

Current cancer therapy has led to tremendous improvements in outcomes. These therapies rely both on established therapies, such as anthracyclines and radiation, and molecularly-targeted therapies, such as tyrosine kinase inhibitors and immune modulators. Integrative care for patients with cancer must consider the potential effects of these therapies on a variety of organ systems, including the cardiovascular system. As a result, specialties such as cardio-oncology have developed to identify these effects, determine how to best monitor for these effects, and how to treat and ultimately prevent these effects while allowing the patient to receive the therapy they require for their cancer. This review provides a basis for understanding the cardiovascular effects of cancer therapies so that the most appropriate imaging modality may be selected to prevent and treat these effects.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2018

Preconditioning in the Rhesus Macaque Induces a Proteomic Signature Following Cerebral Ischemia that Is Associated with Neuroprotection

Each year thousands of patients are at risk of cerebral ischemic injury, due to iatrogenic responses to surgical procedures. Prophylactic treatment of these patients as standard care could minimize potential neurological complications. We have shown that protection of brain tissue, in a non-human primate model of cerebral ischemic injury, is possible through pharmacological preconditioning using the immune activator D192935. We postulate that preconditioning with D192935 results in neuroprotective reprogramming that is evident in the brain following experimentally induced cerebral ischemia. We performed quantitative proteomic analysis of cerebral spinal fluid (CSF) collected post-stroke from our previously published efficacy study to determine whether CSF protein profiles correlated with induced protection. Four groups of animals were examined: naïve animals (no treatment or stroke); animals treated with vehicle prior to stroke; D192935 treated and stroked animals, further delineated into two groups, ones that were protected (small infarcts) and those that were not protected (large infarcts). We found that distinct protein clusters defined the protected and non-protected animal groups, with a 16-member cluster of proteins induced exclusively in D192935 protected animals. Seventy percent of the proteins induced in the protected animals have functions that would enhance neuroprotection and tissue repair, including several members associated with M2 macrophages, a macrophage phenotype shown to contribute to neuroprotection and repair during ischemic injury. Overall, these studies highlight the translational importance of CSF biomarkers in defining mechanism and monitoring responses to treatment in development of stroke therapeutics.

60 APPLIED LIFE SCIENCES↗

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