cssi/SciSciGPT-SciSciNet huggingface dataset:
Fish oil cools the inflammasome

Snake oil elixirs were falsely sold as cure-all medicines in the American Old West, but fish oil may be closer to the real deal. Omega-3 fatty acids derived from dietary fish and seafood have been associated with a wide array of potentially beneficial health effects. A striking example is the ability of omega-3 fatty acids to suppress inflammation and improve insulin sensitivity. The inflammasome is a cytosolic protein complex that controls the production of the proinflammatory cytokines, interleukin-1β (IL-1β) and IL-18, in response to endogenous and exogenous danger signals. Abnormal activation of the NLRP3 inflammasome and IL-1β and IL-18 play a central role in the pathogenesis of obesity-induced tissue inflammation, insulin resistance, and type 2 diabetes. Yan and colleagues wanted to know whether the decreased IL-1β levels reported with omega-3 fatty acid treatment were due to a direct effect on the NLRP3 inflammasome that could be used therapeutically. The authors started by showing that stimulated mouse and human macrophages secrete less IL-1β and IL-18 after omega-3 fatty acid treatment and confirmed that this effect was not observed with non–omega-3 fatty acids or biologically active intermediates. Next, they showed that the anti–IL-1β effect of omega-3 fatty acids was dependent on the cell-surface G-protein–coupled receptors, GPR120 and GPR40, which are known to bind omega-3 fatty acids, and noted that a small-molecule GPR120/GPR40 agonist also decreased IL-1β production. As further confirmation of this pathway, the authors showed that β-arrestin-2 (ARRB2), a downstream scaffold protein of GPR120, interacted with NLRP3 inflammasome proteins and that ARRB2 deficiency abrogates the effect of omega-3 fatty acids on IL-1β secretion. Last, the authors connected omega-3 fatty acid–mediated inflammasome inhibition with insulin and glucose metabolism in vivo using a high-fat diet (HFD) mouse model of hyperglycemia and insulin resistance. In these experiments, omega-3 fatty acid dietary supplementation reduced fasting blood glucose and insulin levels and improved glucose tolerance and insulin sensitivity in HFD mice, suggesting that omega-3 fatty acids might help patients with type 2 diabetes. This study reveals an important new mechanism by which omega-3 fatty acids directly inhibit the NLRP3 inflammasome that could lead to new therapies for diseases in which abnormal inflammasome activation drives pathogenesis such as diabetes, arthritis, and atherosclerosis. Two crucial next steps are to determine whether omega-3 fatty acids inhibit the inflammasome in healthy and diseased people and whether omega-3 fatty acid–mediated inflammasome inhibition translates into meaningful differences in disease biomarkers and clinical outcomes. Y. Yan et al ., Omega-3 fatty acids prevent inflammation and metabolic disorder through inhibition of NLRP3 inflammasome activation. Immunity 38 , 1154–1163 (2013). [[Abstract]][1] [1]: http://www.cell.com/immunity/abstract/S1074-7613(13)00242-2
Issues Surrounding Tight Glycemic Control in People with Type 2 Diabetes Mellitus

OBJECTIVE:To review the prospective evidence surrounding the issue of tight glycemic control in people with type 2 diabetes mellitus and resultant long-term complications.DATA SOURCE:Conference proceedings and a MEDLINE search (1966–February 1998) identified pertinent English-language publications on type 2 diabetes in humans. Key search terms included insulin resistance, diabetes mellitus, non-insulin-dependent, macrovascular complications, microvascular complications, and intensive glycemic control.STUDY SELECTION:Selection of prospective epidemiologic and clinical studies were limited to those focusing on the management of type 2 diabetes. All articles with pertinent information relevant to the scope of this article were reviewed.DATA SYNTHESIS:The pathophysiology of type 1 and type 2 diabetes differ; however, both share chronic complications that significantly affect morbidity and mortality. People with type 1 diabetes have an absolute deficiency of insulin, whereas people with type 2 diabetes have va...
Human capital investment in resources‐dominated economies

The paper relaxes the perfectly competitive market assumptions of human capital theory to derive hypotheses about the impacts of imperfect markets on incentives to invest in human capital, particularly education. The paper then draws on existing studies to test whether the hypotheses are supported or not for resources‐dominated economies. Because of imperfect markets, individuals may make human capital decisions that lead to poverty.
Comment on "A novel data distribution technique for host-client type parallel applications

A paper by Nick Comino and V. Lakshmi Narasimhan is related to existing literature on divisible load scheduling theory. This includes the use of a Gantt-chart to illustrate timing relationships, basic model assumptions common to the divisible load scheduling literature, allowing time for the reporting back to the originator node of solutions the inclusion of fixed costs (charges) in the model, a proof that such load distribution can be optimized the product form solution for optimal load allocation of the first equation of page and the matrix multiplication application.
Speech events and natural speech: some implications for sociolinguistic methodology,

Samples of speech suitable for sociolinguistic analysis may be sought in several ways. Interviews (either formal or informal), and tape-recorded group sessions, are the methods most used currently. In research on a specific variable, the historical present tense (HP), none of these methods proved neutral or adequate. Although the historical present tense is very widely used in conversational narratives, its occurrence within interviews is so infrequent as to be striking. An explanation was found in the way in which the interview has a specific known place as a speech event in the culture of those whose speech was being studied. The so-called spontaneous interview does not have such a place, and for that very reason is even less satisfactory a source of data. The notion of natural speech is taken as properly equivalent to that of appropriate speech; as not equivalent to unselfconscious speech; and as observable easily, and often best, by simple techniques of participation. (Sociolinguistic methodology; speech events, interviews, observation, natural speech; United States English).
Sleep disruptions and nocturnal nursing interactions in the intensive care unit.

Abstract Background Sleep deprivation, common in intensive care unit (ICU) patients, may be associated with increased morbidity and/or mortality. We previously demonstrated that significant numbers of nocturnal nursing interactions (NNIs) occur during the routine care of surgical ICU patients. For this study, we assessed the quantity and type of NNIs in different ICU types: medical, surgical, cardiothoracic, pediatric, and neonatal. We hypothesized that the number and type of NNIs vary among different ICU types. Material and methods We performed a prospective observational cohort study at our academic medical center examining potential sleep disruption in ICU patients secondary to NNIs from the hours 2200–0600 nightly. From May through November 2011, bedside nursing staff in five different ICUs collected data on NNIs, including the frequency and nature of each event (patient care activity, nursing intervention, nursing assessment, or patient-initiated contact) as well as the length of time of each event and whether the bedside care provider thought that the event could have been safely omitted without negatively affecting patient care. Additional data collected included patient demographics, the need for mechanical ventilation, and sedative/narcotic use. Results Two hundred ICU patients were enrolled over 51 separate nocturnal time periods (3.9 patients/nocturnal time period). Of those 200 patients, 53 (26.5%) were mechanically ventilated; 12.5% underwent sedative infusion; and 23.0% underwent narcotic infusion. There were a total of 1831 NNIs; most (67%) were due to nursing assessment or patient care activity. The surgical ICU had the most frequent NNIs (11.8 ± 9.0), although they were the shortest (6.66 ± 6.06 min), as well as the highest proportion of NNIs that could have been safely omitted (20.9%). Nursing staff estimated that, of all NNIs in all ICU types, 13.9% could have been safely omitted. Conclusions NNIs occur frequently and vary across different ICU types. Many NNIs are due to nursing assessment and patient care activities, much of which could be safely omitted or clustered. A protocol for nocturnal sleep promotion is warranted in order to standardize ICU NNIs and minimize nighttime sleep disruptions.
Impact of neighborhood disadvantage on overt behavior problems during early childhood

Researchers have yet to examine the impact of neighborhood disadvantage on early child behavior problems (BPs) longitudinally. We examined the impact of neighborhood disadvantage on overt BPs in a low-income, urban sample of 281 African American and European American boys followed longitudinally from toddlerhood to school entry. Measures included census data and maternal report of BPs, sociocultural factors, parental criminality, and maternal depressive symptomatology. After controlling for age 2 overt BPs, family selection variables, and residential instability, neighborhood effects on boys' behavior emerged, but only at age 6 and only at the extreme of neighborhood disadvantage (i.e., underclass). Findings suggest boys in underclass neighborhoods are at risk for overt BPs as they make the transition to elementary school. Aggr. Behav. 33:1–13, 2007.© 2007 Wiley-Liss, Inc.
Risk estimation and value-of-information analysis for three proposed genetic screening programs for chronic beryllium disease prevention.

Genetic differences (polymorphisms) among members of a population are thought to influence susceptibility to various environmental exposures. In practice, however, this information is rarely incorporated into quantitative risk assessment and risk management. We describe an analytic framework for predicting the risk reduction and value-of-information (VOI) resulting from specific risk management applications of genetic biomarkers, and we apply the framework to the example of occupational chronic beryllium disease (CBD), an immune-mediated pulmonary granulomatous disease. One described Human Leukocyte Antigen gene variant, HLA-DP b 1*0201, contains a substitution of glutamate for lysine at position 69 that appears to have high sensitivity ( z 94%) but low specificity ( z 70%) with respect to CBD among individuals occupationally exposed to respirable beryllium. The expected postintervention CBD prevalence rates for using the genetic variant (1) as a required job placement screen, (2) as a medical screen for semiannual in place of annual lymphocyte proliferation testing, or (3) as a voluntary job placement screen are 0.08%, 0.8%, and 0.6%, respectively, in a hypothetical cohort with 1% baseline CBD prevalence. VOI analysis is used to examine the reduction in total social cost, calculated as the net value of disease reduction and financial expenditures, expected for proposed CBD intervention programs based on the genetic susceptibility test. For the example cohort, the expected net VOI per beryllium worker for genetically based testing and intervention is $13,000, $1,800, and $5,100, respectively, based on a health valuation of $1.45 million per CBD case avoided. VOI results for alternative CBD valuations are also presented. Despite large parameter uncertainty, probabilistic analysis predicts generally positive utility for each of the three evaluated programs when avoidance of a CBD case is valued at $1 million or higher. Although the utility of a proposed risk management program may be evaluated solely in terms of risk reduction and financial costs, decisions about genetic testing and program implementation must also consider serious social, legal, and ethical factors.
Changes in reporting of race/ethnicity, socioeconomic status, gender, and age over 10 years

Background. The recognition of health disparities as an important aspect of US health care has led to renewed interest in the reporting of race/ethnicity and socioeconomic status (SES) in original research reports. Purpose. To describe reporting of race/ethnicity and SES, in comparison with age and gender, and to report changes with time. Methods. All original research articles that focused on children and asthma that were published in The Journal of the American Medical Association, The New England Journal of Medicine, Pediatrics, The Journal of Pediatrics, and Archives of Pediatrics and Adolescent Medicine were reviewed for 2 time periods, 1991–1993 and 2000–2002. Each report was assessed for coding of age, gender, race/ethnicity (number of groups and which groups), and SES. Results. In 1991–1993, 27 reports met the inclusion criteria; in 2000–2002, 74 were reviewed. Overall, significantly more reports described age (90.1%) and gender (78.2%) than SES (41.6%) and race/ethnicity (54.5%). During the 2 study periods, there were significant increases in studies reporting race/ethnicity (from 29.6% to 63.5%) but not in studies reporting SES or gender. Coding of race/ethnicity, even in the later time period, was largely confined to white (78.7%) and black (89.4%). Fewer reports coded Latino (55.3%) or Asian (14.9%). Only 2 of the 31 articles that coded Latino subjects contained information on ethnic subgroups, whereas none of the 8 articles included Asian subgroups. Conclusions. Original research reports in a specific area (asthma) for which health disparities have been well documented still contain few data on race/ethnicity and SES, particularly in comparison with age and gender. There has been some improvement in the past decade in the reporting of race/ethnicity, but the reporting of Latino and Asian subgroups remains poor. If we are to understand health disparities, then more appropriate reporting of SES and race/ethnicity is necessary.
Pediatric assessment and management of concussions.

Concussions and mild traumatic brain injuries have become more widely recognized and understood during the past 5 to 10 years. Earlier and more active evaluation and management of this brain injury is necessary to reduce risk to the developing child and adolescent. Pediatricians play a central role in the evaluation and management of concussions and should develop a working understanding of the injury and its clinical manifestations. An individualized approach to evaluation and management by the pediatrician requires the development of a skillset to define the characteristics of the injury, conduct a full assessment of post-concussion symptoms, and define any risk history that may modify recovery. This evaluation forms the basis of concussion treatment, which involves the active management of the child’s daily routines at home, school learning and performance, and sports/recreational activities. The Acute Concussion Evaluation (ACE) and ACE Care Plan, published in the CDC’s “Heads Up: Concussion in Your Practice,” are presented as a set of tools that can assist the pediatrician in this endeavor.
TPM-SIM: a framework for performance evaluation of trusted platform modules

This paper presents a simulation toolset for estimating the impact of Trusted Platform Modules (TPMs) on the performance of applications that use TPM services, especially in multi-core environments. The proposed toolset, consisting of an integrated CPU/TPM simulator and a set of micro-benchmarks that exercise the major TPM services, can be used to analyze and optimize the performance of TPM-based systems and the TPM itself. In this paper, we consider two such optimizations: (1) exploiting multiple TPMs; and (2) reordering requests within the software stack to minimize queueing delays. Our studies indicate that both techniques result in significant performance improvement, especially as the number of concurrent applications using the TPM increases.
FIR filter design using quadratic programming

The optimum design of FIR (finite impulse response) filters is formulated as a quadratic program. An algorithm is described for the efficient use of computer memory and for guaranteed convergence to the solution of the original problem. Examples illustrating the design of decimation filters for sigma-delta A/D converters using the new technique are also presented. The quadratic programming approach is more flexible and often yields better results than the previously reported least-squares design approaches. >
Solar model uncertainties, MSW analysis, and future solar neutrino experiments.

Various theoretical uncertainties in the standard solar model and in the Mikheyev-Smirnov-Wolfenstein (MSW) analysis are discussed. It is shown that two methods give consistent estimations of the solar neutrino flux uncertainties: (a) a simple parametrization of the uncertainties using the core temperature and the ncuelar production cross sections; (b) the Monte Carlo method of Bahcall and Ulrich. In the MSW analysis, we emphasize proper treatments of correlations of theoretical uncertainties between flux components and between different detectors, the Earth effect, and multiple solutions in a combined [chi][sup 2] procedure. In particular the large-angle solution of the combined observation is allowed at 95% C.L. only when the theoretical uncertainties are included. If their correlations were ignored, the region would be overestimated. The MSW solutions for various standard and nonstandard solar models are also shown. The MSW predictions of the global solutions for the future solar neutrino experiments are given, emphasizing the measurement of the energy spectrum and the day-night effect in Sudbury Neutrino Observatory and Super-Kamiokande to distinguish the two solutions.
Effects of label-dose permethrin administration in yearling beef cattle: I. Reproductive function and embryo quality of superovulated heifers.

The objective was to study the effects of a commercial pyrethroid-based pour-on product, permethrin, on reproductive performance in superovulated beef heifers by assessing steroid biosynthesis and embryo quality. Nonpregnant, yearling beef heifers (n = 10; 418 ± 33 kg; 5.5 ± 0.2 body conditioning scores) were assigned by body weight and breed to either (1) saline control or (2) permethrin pour-on administered at label dose (PYR). Superovulation was achieved on all heifers using a timed, 17-day, CIDR-based protocol with GnRH and PGF2α and decreasing total dosage of 240-mg FSH administered twice daily for 4 days. Heifers were artificially inseminated twice (at onset of estrus and 12 hours later) by same technician with frozen semen from single bull collection. To determine short- and long-term effects of permethrin on embryo quality and steroid biosynthesis, superovulation was initiated twice with collection of embryos occurring at 17 and 51 days after treatment. Embryos were recovered 6.5 days after first artificial insemination via nonsurgical flush and were evaluated by International Embryo Transfer Society standards. Blood was collected at standing estrus and day of embryo recovery. Estradiol (E2) and progesterone (P4) concentrations were analyzed via RIA. MIXED and GLIMMIX procedures of SAS were used to analyze continuous and categorical data, respectively. Heifer per flush was the experimental unit. Total embryos recovered did not differ because of treatment (P = 0.30), but did decrease in flush 2 compared with flush 1 (P = 0.02). Quality grade, total transferable quality embryos, and overall flush success did not differ because of treatment (P ≥ 0.16). However, transferable quality embryos were decreased in flush 2 compared with flush 1 (P = 0.05). Total unfertilized oocytes were greater in saline control (P = 0.04). The PYR heifers tended to have less total P4 (P = 0.15) and P4 per CL (P = 0.06) at recovery. E2 per ovulated follicle and E2 per total ovarian structure was greater in flush 2 (P ≤ 0.03) but did not differ because of treatment (P ≥ 0.23). In summary, these data indicate that permethrin administration at label dose in superovulated beef heifers has a tendency to reduce P4, but embryo quality is not affected.
Response: American Indian Religious Traditions and the Academic Study of Religion

Cette 'reponse' de Lee Irwin au debat entre C. Jocks et Sam Gill sur la conclusion de l'etude et de l'enseignement des religions americaines autochtones s'ajoute a d'autres critiques deja formulees. Irwin dit qu'a l'interieur de la communaute academique, il y a une representation croissante des autres comme partenaires legitimes et riches de sens, dans une complexite grandissante des voix, des interets, et des interactions creatives. Ainsi dans le contexte americain autochtone, ce pluralisme exige une volonte nouvelle d'ecouter avec humilite les differentes facons que les indigenes utilisent pour construire leurs mondes spirituels. Mais cela signifie aussi qu'il faut acquerir un usage habile et une connaissance des perspectives theoriques des non-indigenes pour participer aux discours elargis de la theorisation reconstructive au sein de l'academie.
Magnetization transfer imaging of diffuse axonal injury following experimental brain injury in the pig: characterization by magnetization transfer ratio with histopathologic correlation.

Purpose : Out goal was to evaluate the use of the magnetization transfer ratio (MTR) in the detection of diffuse axonal injury (DAI) resulting from traumatic brain injury in a swine model. Method : DAI was created by applying a nonimpact, coronal plane, rotational acceleration to the heads of miniature swine (n = 4). GE imaging was performed with and without off-resonance MT saturation. Histologic correlation of axonal injury with MRI was performed 7 days postinjury. Thirty-one subcortical white matter regions and 10 deep white matter regions were selected for the direct comparison of histologic data and MTR measurements. Results : Nineteen of 41 examined locations exhibited histologic evidence of axonal injury. The mean MTR in regions with axonal damage was significantly less than in regions without axonal damage. These changes were observed both in regions demonstrating high signal intensity on T2-weighted images (T2WI) (p < 0.0001, n = 6) and in regions with no signal intensity change on T2WI (p < 0.05, n = 13). Conclusion : These results suggest that the measurement of MTR may have the potential for evaluating axonal damage in DAI following traumatic brain injury even when conventional T2WI does not demonstrate the lesion.
On-call System Design of Pump Stations

After retrospecting the development of the On-call system in pump stations and in combination with practical applications,this paper introduces two typical On-call system schemes,which are combined with the supervisory system and separated from the supervisory system respectively,including structure design and function design,offering an important reference for the design of On-call system in pump stations.
Iron Limitation Triggers Early Egress by the Intracellular Bacterial Pathogen Legionella pneumophila.

ABSTRACT Legionella pneumophila is an intracellular bacterial pathogen that replicates in alveolar macrophages, causing a severe form of pneumonia. Intracellular growth of the bacterium depends on its ability to sequester iron from the host cell. In the L. pneumophila strain 130b, one mechanism used to acquire this essential nutrient is the siderophore legiobactin. Iron-bound legiobactin is imported by the transport protein LbtU. Here, we describe the role of LbtP, a paralog of LbtU, in iron acquisition in the L. pneumophila strain Philadelphia-1. Similar to LbtU, LbtP is a siderophore transport protein and is required for robust growth under iron-limiting conditions. Despite their similar functions, however, LbtU and LbtP do not contribute equally to iron acquisition. The Philadelphia-1 strain lacking LbtP is more sensitive to iron deprivation in vitro. Moreover, LbtP is important for L. pneumophila growth within macrophages while LbtU is dispensable. These results demonstrate that LbtP plays a dominant role over LbtU in iron acquisition. In contrast, loss of both LbtP and LbtU does not impair L. pneumophila growth in the amoebal host Acanthamoeba castellanii, demonstrating a host-specific requirement for the activities of these two transporters in iron acquisition. The growth defect of the ΔlbtP mutant in macrophages is not due to alterations in growth kinetics. Instead, the absence of LbtP limits L. pneumophila replication and causes bacteria to prematurely exit the host cell. These results demonstrate the existence of a preprogrammed exit strategy in response to iron limitation that allows L. pneumophila to abandon the host cell when nutrients are exhausted.
Conductive properties of papillary surface epithelium

The surface epithelium of rabbit renal papilla was dissected free from its supporting tissue and mounted in an Ussing chamber. The conductive properties of the epithelium and of the apical and baso...
From qualitative to quantitative environmental scenarios

Scenarios are increasingly used for envisioning future social-ecological changes and consequences for human well-being. One approach integrates qualitative storylines and biophysical models to explore potential futures quantitatively and maximize public engagement. However, this integration process is challenging and sometimes oversimplified. Using the Yahara Watershed (Wisconsin, USA) as a case study, we present a transparent and reproducible roadmap to develop spatiotemporally explicit biophysical inputs climate, land use/cover (LULC), and nutrients that are consistent with scenario narratives and can be linked to a process-based biophysical modeling suite to simulate long-term dynamics of a watershed and a range of ecosystem services. Our transferrable approach produces daily weather inputs by combining climate model projections and a stochastic weather generator, annual narrative-based watershed-scale LULC distributed spatially using transition rules, and annual manure and fertilizer (nitrogen and phosphorus) inputs based on current farm and livestock data that are consistent with each scenario narrative. Novel approach to determine spatiotemporally explicit biophysical model inputs.Inputs include climate, land use/land cover, and land nutrient applications.Communication between scenario narrative writers and modeling team is critical.
Nutritional effects on T-cell immunometabolism.

T cells are highly influenced by nutrient uptake from their environment, and changes in overall nutritional status, such as malnutrition or obesity, can result in altered T-cell metabolism and behavior. In states of severe malnutrition or starvation, T-cell survival, proliferation, and inflammatory cytokine production are all decreased, as is T-cell glucose uptake and metabolism. The altered T-cell function and metabolism seen in malnutrition is associated with altered adipokine levels, most particularly decreased leptin. Circulating leptin levels are low in malnutrition, and leptin has been shown to be a key link between nutrition and immunity. The current view is that leptin signaling is required to upregulate activated T-cell glucose metabolism and thereby fuel T-cell activation. In the setting of obesity, T cells have been found to have a key role in promoting the recruitment of inflammatory macrophages to adipose depots along with the production of inflammatory cytokines that promote the development of insulin resistance leading to diabetes. Deletion of T cells, key T-cell transcription factors, or pro-inflammatory T-cell cytokines prevents insulin resistance in obesity and underscores the importance of T cells in obesity-associated inflammation and metabolic disease. Altogether, T cells have a critical role in nutritional immunometabolism.
Tricuspid Regurgitation Associated With Ischemic Mitral Regurgitation: Characterization, Evolution After Mitral Surgery, and Value of Tricuspid Repair

Background Tricuspid regurgitation (TR) often accompanies ischemic mitral regurgitation and is generally assumed to be a secondary consequence of altered hemodynamics of the left-sided regurgitation. We hypothesized that it may also be a direct consequence of right-sided ischemic disease. Therefore, our objectives were to (1) characterize the nature of this TR and (2) describe its time course after mitral valve surgery for ischemic mitral regurgitation, with or without concomitant tricuspid valve repair. Methods From 2001 to 2011, 568 patients with ischemic mitral regurgitation underwent mitral valve surgery. They had varying degrees of TR and altered right-side heart morphology and function; 131 had concomitant tricuspid valve repair. Postoperatively, 1,395 echocardiograms were available to assess residual and recurrent TR. Results Greater severity of preoperative TR was accompanied by larger tricuspid valve diameter, greater leaflet tethering, worse right ventricular function, and higher right ventricular pressure (all p [trend] ≤ 0.002). Without tricuspid valve repair, 31% of patients with no preoperative TR had moderate or greater TR by 5 years, as did 62% with moderate TR. With tricuspid valve repair, 25% with moderate preoperative TR remained in that grade at 5 years, but 11% had severe TR. Conclusions Tricuspid regurgitation accompanying ischemic mitral regurgitation is associated with right-side heart remodeling and dysfunction often mirroring that occurring in the left side of the heart—ischemic TR. Tricuspid valve repair is effective initially, but as with mitral valve repair, TR progressively returns. Therefore, when the severity of TR and right-sided remodeling reaches the point of irreversibility, it may be an indication to eliminate the TR by replacing the tricuspid valve.
Grain damage, phase mixing and plate-boundary formation

Abstract The generation of plate tectonics on Earth relies on complex mechanisms for shear localization, as well as for the retention and reactivation of weak zones in the cold ductile lithosphere. Pervasive mylonitization, wherein zones of high deformation coincide with extensive mineral grain size reduction, is an important clue to this process. In that regard, the grain-damage model of lithospheric weakening provides a physical framework for both mylonitization and plate generation, and accounts for the competition between grain size reduction by deformation and damage, and healing by grain growth. Zener pinning at the evolving interface between mineral components, such as olivine and pyroxene, plays a key role in helping drive grains to small mylonitic sizes during deformation, and then retards their growth once deformation ceases. The combined effects of damage and pinning, however, rely on the efficiency of inter-grain mixing between phases (e.g., olivine and pyroxene) and grain dispersal, which likely depends on grain size itself. Here we present a new model for inter-grain mixing and damage and the onset of rapid mixing. The model considers the competition between the formation of new grains behind a receding interphase triple junction (e.g., olivine growing into a boundary between two pyroxene grains) and their severance or spalling during progressive deformation and damage. The newly formed grains of one phase are then transported along the opposing phase's grain-boundaries and the two phases become dispersed at the grain-scale in a growing mixed layer. The small intermixed grains also affect the grain evolution of the surrounding host grains by Zener pinning, and hence influence the rheology and growth of the mixed layer. As the grains in the mixed layer shrink, subsequently spalled new grains are also smaller, causing a feedback that leads to more rapid mixing and shear localization in the mixed layer. The early stages of mixing can be compared to laboratory experiments, but the transition to a steady-state localized mixed layer, as a proxy for a mylonitic zone, can take a few million years at mid lithospheric conditions. Moreover, a transition in mixing efficiency occurs as grain size reduces, which can induce hysteretic behavior, wherein strong, slowly deforming regions can co-exist with weak rapidly deforming zones, analogous to plate tectonic states with large strong plates and narrow weak boundaries.
Microengineered cultures containing human hepatic stellate cells and hepatocytes for drug development.

In non-alcoholic steatohepatitis (NASH), hepatic stellate cells (HSC) differentiate into myofibroblast-like cells that cause fibrosis, which predisposes patients to cirrhosis and hepatocellular carcinoma. Thus, modeling interactions between activated HSCs and hepatocytes in vitro can aid in the development of anti-NASH/fibrosis therapeutics and lead to a better understanding of disease progression. Species-specific differences in drug metabolism and disease pathways now necessitate the supplementation of animal studies with data acquired using human liver models; however, current models do not adequately model the negative effects of primary human activated HSCs on the phenotype of otherwise well-differentiated primary human hepatocytes (PHHs) as in vivo. Therefore, here we first determined the long-term effects of primary human activated HSCs on PHH phenotype in a micropatterned co-culture (MPCC) platform while using 3T3-J2 murine embryonic fibroblasts as the control cell type since it has been shown previously to stabilize PHH functions for 4–6 weeks. We found that HSCs were not able to stabilize the PHH phenotype to the same magnitude and longevity as the fibroblasts, which subsequently inspired the development of a micropatterned tri-culture (MPTC) platform in which (a) micropatterned PHHs were functionally stabilized using fibroblasts, and (b) the PHH phenotype was modulated by culturing HSCs within the fibroblast monolayer at physiologically-relevant ratios with PHHs. Transwell inserts containing HSCs were placed atop MPCCs containing fibroblasts to confirm the effects of paracrine signaling between PHHs and HSCs. We found that while albumin and urea secretions were relatively similar in MPTCs and MPCCs (suggesting well-differentiated PHHs), increasing HSC numbers within MPTCs downregulated hepatic cytochrome-P450 (2A6, 3A4) and transporter activities, and caused steatosis over 2 weeks. Furthermore, MPTCs secreted higher levels of pro-inflammatory interleukin-6 (IL-6) cytokine and C-reactive protein (CRP) than MPCCs. Treatment of MPCCs with HSC-conditioned culture medium confirmed that HSC secretions mediate the altered phenotype of PHHs observed in MPTCs, partly via IL-6 signaling. Lastly, we found that NADPH oxidase (NOX) inhibition and farnesoid X receptor (FXR) activation using clinically relevant drugs alleviated hepatic dysfunctions in MPTCs. In conclusion, MPTCs recapitulate symptoms of NASH- and early fibrosis-like dysfunctions in PHHs and have utility for drug discovery in this space.
Toward carbon monoxide based therapeutics: carbon monoxide in a pill

As one of the three known gasotransmitters, carbon monoxide (CO) has demonstrated therapeutic potential against a wide range of human diseases. However, development of CO as a therapeutic agent is severely impeded, primarily due to the lack of pharmaceutically acceptable delivery forms of CO. Gaseous CO may only have limited utility under carefully controlled clinical environment. As a result, there have been efforts in developing metal-based CO-releasing molecules and organic CO-releasing molecules that require light activation. We are interested in developing CO prodrugs, which are metal free and release CO spontaneously under physiological conditions without light irradiation. In this review, we summarize progress in this area with a focus on a recent patent and related publications.
Characteristics of cladoceran and copepod communities in floodplain habitats of the Atchafalaya River Basin

In the summer of 1994, floodplain habitats of the Atchafalaya River Basin were surveyed for cladocera and copepoda. Collection sites were grouped into three distinct habitat types (black-water, brown-water and green-water) based on a principal components analysis of five hydrographic variables (current velocity, Secchi disk depth, surface percent saturation of dissolved oxygen, dissolved oxygen differential and surface water temperature). An ANOVA of four community indices (total abundance, Shannon–Weiner diversity (H'), richness, and evenness) was performed on both cladoceran and copepod communities among the three floodplain habitats. Common species were compared among habitats (χ2 goodness-of-fit) to determine where they were most abundant. Green-water habitats had the greatest overall abundance of cladocerans and copepods (dominated by Diaphanosoma birgei, Moina micrura and Mesocyclops edax), but ranked lower in diversity and evenness than black-water and brown-water habitats where Ilyocryptus spinifer, Simocephalus serrulatus, Macrocyclops albidus (black-water) and Bosmina longirostris and Acanthocyclops vernalis (brown-water) were most abundant, respectively. These results indicate that the mosaic of floodplain habitats within large temperate river systems support unique zooplankton communities, and that these habitats are largely a function of seasonal hydrographic features.
“If Only I Did Not Have That Label Attached to Me”: Foregrounding Self-Positioning and Intersectionality in the Experiences of Immigrant and Refugee Youth

In order to bring forth the specific intricacies of the migration experience among comparatively understudied immigrant and refugee youth, this article bridges an intersectionality framework with multicultural education scholars’ calls to flexibility and fluidity in conceptualizing culture and identity. Drawing on in-depth interviews, the analysis is anchored by two pervasive themes: (a) the dynamic nature of identity positions whose intersections make the adaption of youth irreducibly nuanced and (b) the need for self-definition in the process of adaptation. Racial and ethnic positioning, national origin, class, legal status, and religion intersected in the participants’ lives in important ways, but they did not fulfill the same role across the cases. Attention to how these social locations intersect offers insight into the importance of context-based examinations of immigrant youth positioning, in addition to the centrality of structural analyses. Taking on an intersectionality lens, educators can engag...
Central Nervous System (CNS) Depressants

The central nervous system (CNS) depressant drugs include a variety of medications, such as hypnotics, most antianxiety drugs (also called minor tranquilizers),and alcohol.1 As discussed in greater depth in Section 2.1.1.4.4, a new group of nonbenzodiazepine antianxiety drugs have appeared in recent years, but these are not CNS depressants. The general anesthetics are not presented here, as time and space constraints forced me to limit the discussion to the substances most clinically important in drug abuse. One anesthetic agent, phencyclidine (PCP), is abused as a hallucinogen and is discussed in Chapter 9.
Analysis of Sequential Patient Samples from the Mmrf Commpass Study Identifies a High Risk Progression Phenotype

Abstract Multiple myeloma (MM) is a hematological malignancy of plasma cells accounting for ~2% of new cancer cases each year in the United States. The Multiple Myeloma Research Foundation CoMMpass Study (NCT01454297) is a fully accrued, longitudinal, observational clinical trial with 1143 newly diagnosed MM patients from sites in the United States, Canada, Spain, and Italy. Tumor samples are collected and characterized using whole genome (WGS), exome (WES), and RNA (RNAseq) sequencing at diagnosis and each progression event. Clinical parameters are collected at baseline and every three months through the eight-year observation period. Although ongoing, longitudinal collection of molecular and clinical data from CoMMpass patients has aided in our understanding of the molecular mechanisms underpinning relapse in MM. The CoMMpass IA13 dataset includes 136 patients with longitudinal time points, including 25 patients with multiple progression events. We analyzed 100 patients with WES data at baseline and at least one progression event and identified 7 genes (KRAS, NRAS, SPEN, SRCAP, MACF1, ANK3, and RPRD2) with acquired non-synonymous mutations in at least 3% of patients at progression. We identified five patients with KRAS mutations at baseline in whom a clonal shift to NRAS Q61 mutations occurred at progression and four additional patients with novel NRAS Q61 mutations becoming detectable at progression. Patients with NRAS Q61 mutations at baseline exhibit poor OS outcomes as compared to patients with other NRAS mutations (p An integrated analysis leveraging WGS, WES, and RNAseq data identified gain- (GOF) and loss-of-function (LOF) genes for each sample. Longitudinal changes in gene functional status was determined for 47 patients with 57 paired time points. TRAF3 and CDKN2C/FAF1 were found to be the most common complete LOF events acquired at progression, found in 5 (10.6%) and 4 (8.5%) patients, respectively. Acquired complete LOF events are enriched for genes involved in cell cycle regulation (15% of patients, p 4% of longitudinal patients. In addition, 5 (10.6%) patients acquired GOF events in genes either up- or downstream of RAS, including HIST2H3C, OSMR, PAK2, PIK3R6, and STAT3, highlighting the complexity of targeting RAS in MM. Unsupervised consensus clustering of RNAseq data for 714 patients at baseline identified 12 expression subtypes of MM, which generally correspond with known subgroups. The proliferation (PR) group consists of patients whose tumors have an array of genetic backgrounds but a similar RNA expression profile, and exhibit poor OS (HR = 3.996, 95% CI = 2.632 - 6.067, p These observations suggest that progression in MM is often driven by marked shifts in gene expression and molecular events that further deregulate RAS and cell cycle pathways, highlighting the need for novel inhibitors in MM; protocols, such as MyDRUG, which aim to treat patients based on their tumor genetic profile; and molecular profiling of patients throughout their disease course. Disclosures Lonial: Amgen: Research Funding.
Towards Automatic Generation of Peer-Targeted Science Talk in Curiosity-Evoking Virtual Agent

Curiosity is a critical skill that spurs learning, but is often found to decline with age and schooling. Recent research has shown that peer interaction may serve a special role in inducing curiosity through increased uncertainty and conceptual conflicts, since peers have similar authority in knowledge. For a virtual agent to stimulate curiosity, it should be able to generate curiosity-eliciting verbal behaviors such as hypothesis verbalization and argumentation, in the manner that simulates peer-like cognitive and behavioral abilities. In this paper, we design and implement a virtual peer that can carry out key curiosity-eliciting science talk during a dialog-based multi-party board game. We propose a child-centered and data-driven approach to simulate the latent reasoning process of young children and age-appropriate language during open-ended game play. In particular, we use a combination of child knowledge-graph construction and child-child interaction driven modeling to generate game appropriate behaviors that are compatible with 9-14 year old children. Encouraging human evaluation of the generated behaviors and generalizability of the generation framework to other tasks opens up new directions in incorporating open-endedness and science talk in virtual agents that will make them truly play a peer role in learning.
Developing a Policy Brief on Child Mental Health Disparities to Promote Strategies for Advancing Equity among Racial/Ethnic Minority Youth

Research has identified a broad range of risk factors during early childhood that have neurobiological consequences and negatively affect children's mental health. Such risk factors disproportionately affect racial/ethnic minority youth. Disparities in children's mental health service use have also been documented for minority youth. Yet, compared with the focus on strategies to address health disparities (including mental health disparities) during adulthood, very little work has concentrated on addressing the roots of health disparities that occur in childhood. The purpose of this commentary is to describe the development and dissemination of a policy brief for policy advocates. The goal of this work is to help achieve the implementation of evidence-based programs, practices, and policies that target and modify risk factors to reduce disparities in child mental health burden.
High-fidelity experimental measurements for modeling and simulation of nuclear engineering applications

Abstract Modeling and simulation performed with advanced tools are important for thorough understanding of existing power plant response to accidents; for life extension decisions of existing plants; and to support licensing activities for new power plants. The use of computational fluid dynamics (CFD) tool in nuclear R&D has gained significantly due to its capabilities to predict complex flow phenomena at very fine resolutions. High-fidelity numerical simulations including direct numerical simulation (DNS) and large-eddy simulation (LES) have been considered as reliable CFD tools for the development and validation of turbulence models along with experiments. Compared to other CFD techniques, DNS is the most computationally expensive approach, and limited to flow studies at low to moderate Reynolds numbers. LES subgrid-scale (SGS) models require the specification of model coefficients that cannot be generally used to simulate a wide spectrum of flows. Performances of LES with modified SGS model coefficients need to be verified and validated versus high-resolution experimental database or DNS results. In this paper, we present the current state-of-the-art experimental measurements in complex geometries of advanced nuclear reactors, such as turbulent flows in wirewrapped fuel bundle for liquid metal reactors and randomly packed beds for gas-cooled and molten-salt reactors. It is important to achieve an in-depth understanding of flow phenomena and complex flow characteristics within these reactor cores because they are related to the safety and design scenarios. High-fidelity experimental measurements of velocity fields are acquired featuring a combination of time-resolved particle image velocimetry (TR-PIV) and matching-index-of-refraction approaches. Experimental results are obtained at high spatial and temporal resolutions of velocity fields and the first- and second-order flow statistics are suitable for the verification and validation of CFD codes currently used in nuclear engineering applications.