cssi/SciSciGPT-SciSciNet huggingface dataset:
Optimization of Folch, Bligh-Dyer, and Matyash sample-to-extraction solvent ratios for human plasma-based lipidomics studies

Abstract In order to profile the lipidome for untargeted lipidomics applications, analysis by ultra-high performance liquid chromatography – high resolution mass spectrometry (UHPLC-HRMS) typically requires the extraction of lipid content from sample matrices using matrix-specific conditions. The Folch, Bligh-Dyer, and Matyash extraction methods, while promising approaches, were originally tailored to specific matrices (brain tissue, fish muscle, and E. coli, respectively). Each of these methods have specific solvent ratios that must be adhered to achieve optimal extraction. Thus, the sample-to-solvent ratios for these methods should be optimized for the sample matrix of interest prior to employment. This study evaluated the appropriate sample-to-extraction solvent ratios for human plasma-based lipidomics studies. An advantage of employing biphasic lipid extractions is the ability to investigate both the aqueous and organic layers for increased analyte coverage in untargeted studies. Therefore, this work also evaluated the multi-omic capability of each lipid extraction method for plasma in an effort to provide a workflow capable of increasing analyte coverage in a single extraction, thus providing a more complete understanding of complex biological systems. In plasma, a decrease in sample-to-solvent ratios from 1:4, 1:10, 1:20, to 1:100 (v/v) resulted in a gradual increase in the peak area of a diverse range of metabolite (aqueous layer) and lipid (organic layer) species for each extraction method up to the 1:20(v/v) sample-to-solvent ratio. The Bligh-Dyer and Folch methods yielded the highest peak areas at every plasma sample-to-solvent ratios for both metabolite and lipid species. Depending on the lipid class of interest, the Folch or Bligh-Dyer method is best suited for analysis of human plasma at a 1:20 (v/v) sample to total solvent ratio.
Serendipitous scaffolding to improve a genetic algorithm's speed and quality

A central challenge to evolutionary computation is enabling techniques to evolve increasingly complex target end products. Frequently direct approaches that reward only the target end product itself are not successful because the path between the starting conditions and the target end product traverses through a complex fitness landscape, where the directly accessible intermediary states may be require deleterious or even simply neutral mutations. As such, a host of techniques have sprung up to support evolutionary computation techniques taking these paths. One technique is scaffolding where intermediary targets are used to provide a path from the starting state to the end state. While scaffolding can be successful within well-understood domains it also poses the challenge of identifying useful intermediaries. Within this paper we first identify some shortcomings of scaffolding approaches --- namely, that poorly selected intermediaries may in fact hurt the evolutionary computation's chance of producing the desired target end product. We then describe a light-weight approach to selecting intermediate scaffolding states that improve the efficacy of the evolutionary computation.
Adherence to Pediatric Cardiac Arrest Guidelines Across a Spectrum of Fifty Emergency Departments: A Prospective, In Situ, Simulation‐based Study

BACKGROUND AND OBJECTIVES Pediatric out-of-hospital cardiac arrest survival outcomes are dismal ( 10,000). Cardiac arrest adherence and domains were evaluated by pediatric patient volume and other team and hospital-level characteristics, and path analyses were performed to evaluate the contribution of patient volume, systems readiness, and teamwork on BLS, PEA, and VF adherence. RESULTS A total of 101 teams from a spectrum of 50 EDs participated including nine low pediatric volume (<1,800/year), 36 medium volume (1,800-4,999/year), 24 medium-high (5,000-9,999/year), and 32 high volume (≥10000/year). The median total adherence score was 57.1 (interquartile range = 50.0-78.6). This was not significantly different across the four volume groups. The highest level of adherence for BLS and PEA domains was noted in the medium-high-volume sites, while no difference was noted for the VF domain. The lowest level of BLS adherence was noted in the lowest-volume EDs. Improved adherence was not directly associated with higher pediatric readiness survey (PRS) score provider experience, simulation teamwork performance, or more providers with Pediatric Advanced Life Support (PALS) training. EDs in teaching hospitals with a trauma center designation that served only children demonstrated higher adherence compared to nonteaching hospitals (64.3 vs 57.1), nontrauma centers (64.3 vs. 57.1), and mixed pediatric and adult departments (67.9 vs. 57.1), respectively. The overall effect sizes for total cardiac adherence score are ED type γ = 0.47 and pediatric volume (low and medium vs. medium-high and high) γ = 0.41. A series of path analyses models was conducted that indicated that overall pediatric ED volume predicted significantly better guideline adherence, but the effect of volume on performance was only mediated by the PRS for the VF domain. CONCLUSIONS This study demonstrated variable adherence to pediatric cardiac arrest guidelines across a spectrum of EDs. Overall adherence was not associated with ED pediatric volume. Medium-high-volume EDs demonstrated the highest levels of adherence for BLS and PEA. Lower-volume EDs were noted to have lower adherence to BLS guidelines. Improved adherence was not directly associated with higher PRS score provider experience, simulation teamwork performance, or more providers with PALS training. This study demonstrates that current approaches optimizing the care of children in cardiac arrest in the ED (provider training, teamwork training, environmental preparation) are insufficient.
High glucose induces a priming effect in macrophages and exacerbates the production of pro-inflammatory cytokines after a challenge

Introduction Painful diabetic neuropathy is associated with chronic inflammation, in which macrophages are the key effectors. We utilized an in vitro approach to determine the effects of high glucose on macrophage phenotype. Materials and methods We exposed human THP-1 macrophages to normal glucose (5 mM) and a clinically relevant high glucose environment (15 mM) and measured the expression and concentration of molecules associated with a diabetic cellular phenotype. Results We found that THP-1 macrophages in high glucose conditions did not influence the basal expression of cyclooxygenase-2, Toll-like receptor-4, or class A scavenger receptor mRNA, or the concentrations of the cytokines interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, and IL-10, but induced a priming effect on tumor necrosis factor (TNF)-α. Then, we stimulated THP-1 macrophages with a strong pro-inflammatory stimulus lipopolysaccharide (LPS; 5 µg/mL). After stimulation with LPS, we observed an exacerbated increase in TNF-α, IL-6, and MCP-1 concentration in the high glucose condition compared to the normal glucose environment. THP-1 macrophages in high glucose conditions developed tolerance to IL-10 anti-inflammatory effects (TNF-α production) when challenged with LPS. Conclusion Our in vitro approach allows the study of macrophages as potential targets for therapeutic purposes since it compares them to primary human macrophages exposed to high glucose and macrophages from patients with diabetes or complications of painful diabetic neuropathy (i.e. ulcers, adipocytes, and pancreas).
A Nonlinear Analytical Redundancy Method for Sensor Fault Diagnosis in an Automotive Application

Sensors have been widely implemented in vehicle systems for control, driving, and vehicle condition monitoring purposes. In a typical automotive vehicle, there are 60-100 sensors on board and is projected to reach 200 sensors per car. Those sensors provide rich information to ensure safe vehicle operation. However, like any dynamic systems, sensors are vulnerable to degrade or fail over time, which leads to the need of real-time sensor fault diagnosis. Analytical redundancy has been the key model-based approach for sensor fault diagnosis. However, existing analytical redundancy approaches are limited to linear systems, or some special cases of nonlinear systems. In this paper, the analytical redundancy approach is extended to nonlinear systems in general to ensure the accuracy of sensor measurements. Parity relations based on nonlinear observation matrix are formulated to characterize system dynamics and sensor measurements. Robust optimization is designed to identify the coefficient of parity relations that can tolerate certain level of measurement noise and model uncertainties. At last, sensor fault diagnosis in an air intake system is employed to demonstrate the effectiveness of the proposed method.
The in vitro activity and beta-lactamase stability of cefpirome (HR 810), a pyridine cephalosporin agent active against staphylococci, Enterobacteriaceae and Pseudomonas aeruginosa.

Thein vitro activity of cefpirome, a new cyclopyridinium cephalosporin, was evaluated against 947 aerobic and anaerobic bacteria. Cefpirome inhibited 90% ofEscherichia coli, Klebsiella spp.,Citrobacter diversus, Morganella morganii, Proteus vulgaris, Proteus mirabilis, Aeromonas spp.,Salmonella spp.,Shigella spp. andHaemophilus andNeisseria species at ≤0.4 mg/l. It had activity comparable to that of cefotaxime, ceftizoxime, ceftazidime, aztreonam, and moxalactam against these species. Only a fewCitrobacter freundii, Enterobacter spp. andSerratia marcescens had MICs above 3.1 mg/l. The activity of cefpirome againstPseudomonas aeruginosa, 90% MIC of 12.5 mg/l, was superior to piperacillin, moxalactam, cefotaxime and cefoperazone. The 90% MIC againstStaphylococcus aureus was 0.8 mg/l, but methicillin-resistant staphylococci were not inhibited. Cefpirome was not significantly hydrolyzed by most plasmid beta-lactamases (TEM, SHV-1, PSE, OXA) nor by chromosomal enzymes (P99,Branhamella catarrhalis, Kl). Cefpirome did not inhibit chromosomal or plasmid betalactamases. Mice systemically infected withE. coli, Klebsiella pneumoniae, P. aeruginosa andS. aureus were protected by concentrations of cefpirome ranging from 0.85 mg/kg forK. pneumoniae to 4.467 mg/kg forP. aeruginosa.
Switching and HTRB characteristics of Highly reliable GaN MOS-HFET

The GaN MOS-HFET we have proposed could significantly reduce the maximum electric field of the MOS gate to 1/3 when the high reverse bias is applied. With this effect, High Temperature Reverse Bias (HTRB) characteristics were greatly improved compared with a conventional MOS-HFET. The device with saturation current exceeding 60 A are fabricated and good switching characteristics are also reported in the paper.
INI1 negative sarcoma diagnosed as malignant rhabdoid tumor presenting as hydrops fetalis metastatic to the placenta: a case report and review of the literature on congenital sarcomas.

Rhabdoid tumor is a highly aggressive sarcoma found in young children that occurs in the kidney, central nervous system and soft tissue sites. Rarely, it presents in the fetus or neonate and is ass...
Serotonin in cortical development: implications for autism spectrum disorder

Abstract Autism spectrum disorder (ASD) is a complex, multifaceted, developmental brain disorder that is based on behavioral criteria and is increasing in frequency. Despite decades of research, reliable biomarkers and effective therapeutic approaches remain elusive. Here we provide a focused review of research literature that suggests an involvement of the neurotransmitter serotonin (5-HT) in the etiology of the disorder. We describe the role that 5-HT plays in the maturation of brain structure and function as relevant to the neuropathologies of ASD. We discuss the role of 5-HT in autoimmune disorders, inflammation, and the gut–brain axis, all of which have been associated with ASD and are identified as risk factors for maternal transmission. Our review supports the hypothesis that the interplay of peripheral and central 5-HT levels in the mother and offspring, and placental 5-HT synthesis impacts early brain development in genetically vulnerable individuals and result in the neuropathologies associated with ASD.
Paucity of economic analyses of phase III clinical trials conducted by the cooperative oncology groups: A review of the evidence

17052 Background: Cancer care is expensive, accounting for $72 billion in direct medical costs. New oncology drugs are frequently costly, and can be > $100,000 per patient. Hence, assessments of th...
RATE, CAUSES AND PREDICTORS OF 30-DAY READMISSIONS FOLLOWING CORONARY ARTERY BYPASS GRAFTING IN THE UNITED STATES

Studies on hospital readmissions following coronary artery bypass grafting (CABG) are very limited. We investigated the rate, causes, and predictors of 30-day readmissions following CABG. We analyzed the National Readmission Database for the year 2016 using appropriate ICD-10-CM codes to identify
Reflection on Building Hybrid Access Control by Configuring RBAC and MAC Features

This paper reflects on the paper titled Building Hybrid Access Control by Configuring RBAC and MAC Features which was published in Information and System Technology, 2014. The publication presents an approach for building a hybrid access control model of Role-Based Access Control and Mandatory Access Control by defining and configuring them in terms of features. The publication has been cited three times, which shows limited impact. We review the citing papers as to how the publication is cited and discuss possible reasons for the limited impact. We also discuss its position in the current state of the arts since the publication. Then, we describe an ongoing effort for a new approach to address the weaknesses of the publication with expected impact.
Systematic review of corpus callosotomy utilizing MRI guided laser interstitial thermal therapy

Abstract Corpus callosotomy is a palliative surgical option for patients with refractory epilepsy and frequent drop attacks, decreasing seizure frequency and severity by disconnecting the cerebral hemispheres. Though often successful, open surgery is not without risk. Corpus callosotomy by MRI-guided laser interstitial thermal therapy (MRgLITT) is a minimally invasive alternative to the standard open procedure. This report aims to present an illustrative case and systematically review the current literature on the surgical technique. A systematic review of the English literature through January 2019 was performed. Articles were searched by title utilizing the following key word combinations: “laser” and “callosotomy”, “callosotomy” and “ablation”, “laser” and “corpus”, “callosotomy” and “thermal”, and “stereotactic” and callosotomy”. The articles recovered were then classified by level of evidence and summarized. Fifteen papers were reviewed, of which 6 met inclusion and exclusion criteria. All included studies were classified as level IV evidence. There was a total of 13 patients ranging from 13 months to 44 years old (mean 23.5 years old). The number of laser fibers utilized ranged from 1 to 3. Engel class I was achieved in 5 patients, II in 4, III in 2, IV in 1. Reported patient follow up was 4–39.7 months (mean 15.43). Corpus callosotomy utilizing MRI-guided laser interstitial thermal therapy results in improvement in seizure frequency and severity with minimal complications. Prospective trials are needed to compare its seizure control and long-term outcomes to that of standard open callosotomy.
Neurologic Diseases Associated with Use of Plant Components with Toxic Potential1

Epidemics of neurotoxic disease in developing regions of the world are often associated with dietary dependence on plant components with inherent toxic potential or which have spoiled and become contaminated with mycotoxins. Diseases triggered by plant toxins include lathyrism and cassavism, types of irreversible spastic parapareses associated with staple diets of grass pea and bitter cassava root, respectively. Mildewed sugarcane poisoning, an encephalopathy and tardive dystonia, illustrates the neurotoxic effects of a widely distributed plant and fungal toxin. Food and medicinal use of the neurotoxic cycad plant is thought to have a role in the etiology of western Pacific amyotrophic lateral sclerosis and parkinsonism-dementia. Plant-associated neurotoxicity is a significant and preventable cause of morbidity in certain regions of Africa, Asia, and Oceania. © 1993 Academic Press, Inc.
Changes in kidney function during the menopausal transition: the Study of Women's Health Across the Nation (SWAN) - Michigan site.

OBJECTIVE The aim of the study was to examine changes in kidney function during the menopausal transition (MT) and associations with levels of sex hormones (follicle stimulating hormone [FSH], sex hormone binding globulin [SHBG], estradiol, and testosterone). METHODS We used data from the Michigan site of Study of the Women's Health Across the Nation, a longitudinal study of the MT. For this analysis, we included women who had at least one creatinine measure before the final menstrual period (FMP) and at least one creatinine measure after the FMP (n = 101 women with 440 observations). To determine whether the declines in estimated glomerular filtration rate (eGFR) remained constant during the MT, we used local weighted regression curves to fit eGFR estimates. We examined the association between sex hormones and eGFR with longitudinal mixed models adjusting for baseline age, day of menstrual cycle, and time from FMP. RESULTS At baseline, women had a mean age of 45.4 ± 2.5 years; 54% were African-American and 46% were white. Although eGFR declined significantly over time, declines were linear, consistent with declines in eGFR due to age alone rather than the MT. Total testosterone, estradiol, ratio of testosterone:estradiol, and free androgen index were not significantly associated with eGFR, whereas lower FSH (-0.039, 95% confidence interval [CI] -0.067 to -0.012) and higher SHBG (0.050, 95% CI 0.004-0.096) were associated with higher eGFR. CONCLUSIONS Kidney function declines during the MT. Although associated with levels of FSH and SHBG, the rate of decline in eGFR is consistent with what would be expected of age alone.
Effects of Inhaled Corticosteroids on Growth in Children with Persistent Asthma.

Inhaled fluticasone (Flovent; 200 mcg per day) is associated with a greater linear growth velocity when compared with beclomethasone (400 mcg per day; an equivalent dose).
An autoregulatory negative feedback loop controls thermomorphogenesis in Arabidopsis

Plant growth and development are acutely sensitive to high ambient temperature ascribable in part to climate change. However, the mechanism of high ambient temperature signaling is not well defined. Here, we show that HECATEs (HEC1 and HEC2), two helix-loop-helix transcription factors, inhibit thermomorphogenesis. While the expression of HEC1 and HEC2 is increased and HEC2 protein is stabilized at high ambient temperature, hec1hec2 double mutant showed exaggerated thermomorphogenesis. Analyses of the four major PIF (PIF1, PIF3, PIF4 and PIF5) mutants and overexpression lines showed that they all contribute to promote thermomorphogenesis. Furthermore, genetic analysis showed that pifQ is epistatic to hec1hec2. HECs and PIFs oppositely control the expression of many genes in response to high ambient temperature. HEC2 interacts with PIF4 both in yeast and in vivo. In the absence of HECs, PIF4 binding to its own promoter as well as the target gene promoters was enhanced, indicating that HECs control PIF4 activity via heterodimerization. Overall, these data suggest that PIF4-HEC forms an autoregulatory composite negative feedback loop that controls growth genes to modulate thermomorphogenesis.
Patterns of Violence Exposure and Substance Use among Child Welfare Involved Youth

Emerging research suggests an association between exposure to violence, specifically indirect forms, and substance use among youth involved in the child welfare (CW) system. However, this has only been recently and tentatively explored. This study examined the associations among various forms of indirect violence exposure and substance use among subgroups of youth involved in the CW system. The analytic sample consisted of participants (aged 11 years or older) in the baseline year of the second National Survey of Child and Adolescent Well-Being (2008–2012), including youth and their caregivers. Latent class analysis was used to examine associations among distinct forms of indirect violence exposure and substance use and the potential identification of unique at-risk groups. Models for the overall sample suggested two classes of at-risk youth, with the higher-risk class having higher probabilities of alcohol, marijuana, and hard drug use, which coincided with higher probabilities of exposure to arrests, stealing, drug deals, and weapon use. However, stratified models suggested unique results for youth aged 13–14 and 15–17, suggesting that the confluence of these risks appears to differ developmentally. Prevention and intervention services for CW-involved youth should assess and address violence exposure types among youth as a potential opportunity to mitigate substance use and subsequent high-risk behavior.
The Ai Localism Canvas

This article examines the emerging field AI Localism – a global move toward innovative governance of AI at the subnational level. The piece introduces the current state of play in the field, and introduces an “AI Localism Canvas” to help decision-makers identify, categorize and assess instances of AI Localism specific to a city or region.
Consumed by the Catalogue

The 21st meeting of the American Astronomical Society convened at the Dudley Observatory in Albany on August 29, 1917. In a growing but still small profession, the occasion combined the atmosphere of a scientific session with the feel of a family reunion. Members of the audience at esoteric astronomical talks could be seen knitting warm clothing to be sent to American soldiers training for the war in Europe.
Closing Materials Research Structural Design Cycle

A capability is described for the simultaneous optimization of material and structural design. This capability is based upon the materials evaluation function concept. It draws upon existing methods of analysis, structural synthesis, numerical analysis and mathematical programming. The capability is applied to the optimization of thermostructural, anisotropic composite plates subjected to complex loading environment. Results are presented to demonstrate the feasibility and importance of the simultaneous material and structural design optimization, and the closing of the loop in the Materials-Research Structural-Design Cycle.
Incremental effects of 28 days of beta-alanine supplementation on high-intensity cycling performance and blood lactate in masters female cyclists

Within the aging population, there exists a subset of individuals termed masters athletes (MA). As masters-level competition increases in popularity, MA must find methods to enhance individual athletic performance. Longitudinal beta-alanine (BA) supplementation is suggested to enhance physical capability during exercise; however, these effects have not been evaluated in MA. To examine the longitudinal effects of BA on time to exhaustion (TTE), total work completed (TWC), and lactate clearance in female MA cyclists. Twenty-two female MA (age = 53.3 ± 1.0) participated in this double-blind design. Subjects were randomly assigned to BA (n = 11; 800 mg BA + 8 g dextrose) or placebo (PLA; n = 11; 8 g dextrose) groups and supplemented 4 doses/day over 28 days. Every 7 days, subjects completed a cycling TTE at 120% VO2max, and TWC was calculated. Blood lactate was measured at baseline, immediate post, and 20-min post each TTE. No significant differences existed between groups for any variable at baseline (p > 0.05). After 28 days supplementation, BA had greater TTE (23 vs 1% change) and TWC (21 vs 2% change) than PLA (p < 0.05). Following the 20-min TTE recovery, lactate was 24% lower in BA compared to PLA (4.35 vs. 5.76 mmol/L, respectively). No differences existed for variables during intermittent weeks. 28 days of BA supplementation increased cycling performance via an enhanced time to exhaustion and total work completed with associated lactate clearance during passive rest in female MA.
Chapter 24. In Vitro Mutagenesis:Relationships in Proteins Powerful New Techniques for Studying Structure-Function Relationships in Proteins

To be able to generate, at will, any sequence of amino acids allows rational study of the relation between protein structure and function. For structure–function studies of proteins, a second powerfully complementary approach that takes advantage of the ability of biological systems to produce a very large number of random structural variants is also discussed in the chapter; these can then be screened for those variants that have a particular function. In this case, a particular function is specified, and then it is determined that the structures, of many millions that can be easily tested, have that function. The procedures useful in this approach are those of random mutagenesis, perhaps directed toward a particular region of the protein. This chapter describes particularly those aspects of mutagenesis that have a direct bearing on the study of protein function. These techniques have also been used to address a large variety of genetic problems as well as to probe structure–function relationships; the more general subject has been discussed extensively. The chapter discusses many techniques that have recently been developed that allow a variety of quite novel approaches to the studies of the relationship between the linear sequence and the function of proteins. Much of the discussion has focused on the procedures for manipulating the DNA to achieve proteins with altered function.
Spatiotemporal index for analyzing controls on snow climatology: application in the Colorado Front Range

Mountain snowpacks are important water supplies that are susceptible to climate change, yet snow measurements are sparse relative to snowpack heterogeneity. We used remote sensing to derive a spatiotemporal index of snow climatology that reveals patterns in snow accumulation, persistence, and ablation. Then we examined how this index relates to climate, terrain, and vegetation. Analyses were based on Moderate Resolution Imaging Spectroradiometer eight-day snow cover from 2000 to 2010 for a mountain watershed in the Colorado Front Range, USA. The Snow Cover Index (SCI) was calculated as the fraction of years that were snow covered for each pixel. The proportion of SCI variability explained by independent variables was evaluated using regression analysis. Independent variables included elevation, northing, easting, slope, aspect, northness, solar radiation, precipitation, temperature, and vegetation cover. Elevation was the dominant control on SCI patterns, due to its influence on both temperature and preci...
FAILURE TESTS ON BEAMS WITH ECCENTRIC WEB HOLES

Laboratory tests on two W16x45 A36 steel beams and three W16x40 A36 steel beams with reinforced eccentric web openings are described and summarized. The principal test parameters were the opening size and the amount of opening reinforcement. Tests were carried to failure and the deflections, modes of failure, and ultimate loads recorded. The results of inelastic finite element analyses of the test beams are also summarized. It is concluded that both the experimental and finite element results are reasonably consistent with the four hinge failure mechanism assumed in a previously developed ultimate strength analysis, and that this ultimate strength analysis provides an adequate prediction of the strength of beams with reinforced eccentric web openings.
The Political Economy of Post-Katrina Recovery: Public Choice Style Critiques from the Ninth Ward, New Orleans

This paper provides an account of the political economy critique residents and other stakeholders in New Orleans' Ninth Ward communities hold of the post-Katrina policy environment. Of particular interest are policies that restricted access and delayed delivery of municipal services to some Ninth Ward neighborhoods, the city-wide redevelopment planning process, and Louisiana's Road Home rebuilding assistance program. We argue that the criticism emanating from Ninth Ward communities is similar in significant ways to the public choice critique of the state, particularly in its affinity with rent seeking explanations for why government response has been so disappointing. The qualitative analysis presented here challenges the view that poor predominantly African-American communities devastated by post-Katrina flooding limit their explanations of government performance to race-based explanations alone. We consider why, despite the nuanced critiques of government inaction manifest within the interview data, so many respondents still held out hope that government policies and programs might bring about recovery. We argue that this puzzle is addressed, at least in part, by an overestimation of government's capacity (if not inclination) to successfully re-engineer societies from the ground up.
Influx of neutral amino acids across the brush border of rabbit ileum. Stereospecificity and the roles of the -amino and -carboxylate groups.

Abstract The influxes of the l - and d -stereoisomers of alanine, valine, serine, leucine, histidine, phenylalanine and tryptophan across the brush border of rabbit ileum and the roles of the α-carboxylate and α-amino groups in the influx process have been examined. Our results indicate that: 1. 1. The interactions between neutral amino acids and the influx mechanism(s) invovle the α-amino and α-carboxylate groups as well as the side chain. 2. 2. The requirement for both the α-amino and α-carboxylate groups indicate that their interactions with the influx mechanism are cooperative rather than independent. 3. 3. With the exception of d -valine, the influxes of all of the d -amino acids examined display saturation kinetics, are Na+-dependent and are subject to classical competitive inhibition by their l -enantiomorphs. The influx of d -valine appears to be largely attributable to simple diffusion, although a small mediated component characterized by a high K 1 cannot be excluded. 4. 4. When d -amino acids interact with their influx mechanisms, the neutral side chain is displaced by 180 degrees from the “natural” position, and the ability of the d -amino acids to interact with their influx mechanisms appears to depend upon the ability of the displaced side chain to engage in interactions with neighboring groups.
28 GBshape: a genome browser database for DNA shape annotations

Many regulatory mechanisms require a high degree of specificity in protein-DNA binding. Nucleotide sequence does not provide an answer to the question of why a protein binds only to a small subset ...
Multifunctional CD26hi Th17 cells eradicate large human tumors (TUM2P.902)

Human CD4+ T cells differentiate into multiple effector subsets, but their distinct roles in anti-tumor immunity remain elusive. CD4+ T cell subsets enriched from bulk human CD4+ T cells [Th1 (CXCR3+), Th2 (CCR4+), and Th17 (CCR6+ or CD26hi)] were stimulated with anti-CD3 beads bearing agonists to either CD28 or ICOS and were then engineered with a chimeric antigen receptor that recognizes human mesothelioma. In vitro, ICOS costimulation proved superior to CD28 for augmenting the function of human Th1, Th2, CCR6+ Th17 and CD26hi Th17 cells, as indicated by elevated production of IFN-γ, IL-4 and IL-17A, respectively. Moreover, CD26hi Th17 cells possessed strikingly enhanced polyfunctionality compared to Th1, Th2 or CCR6+ Th17 cells, as demonstrated by their heightened capacity to co-secrete IL-17A, IFN-γ, IL-22, IL-2, and TNF-α simultaneously. Compared to other enriched T cell subsets, a greater percentage of CD26hi Th17 cells exhibit an effector memory phenotype. In vivo, CD26hi Th17 cells more efficiently reconstituted immunodeficient hosts and persisted long-term. Furthermore, CD26hi Th17 cells possessed a superior ability to kill large human tumors (>150mm2) when infused into mice compared to Th1, Th2 or CCR6+ Th17 cells. These results suggest that the generation of multifunctional, long-lived human Th17 populations could be instrumental to the design of novel, effective T cell-based cancer therapies.
Power supply noise coupling in a standard voltage reference circuit

Power supply noise (PSN) coupling represents a challenge in the design of current and future analog and mixed-signal circuits. This paper studies the impact of PSN coupling on a key analog circuit building block: a voltage reference. A model representing the amount of noise coupling in the frequency domain is developed and verified through simulations. A design solution for increasing high frequency PSN rejection is identified and evaluated. Finally, the effect of technology scaling on PSN is studied in two successive CMOS processes.
One-way topological transitions in magnetoplasmonic hyperbolic metamaterials

By utilizing an analytical effective medium and an exact numerical approaches we design a magnetoplasmonic hyperbolic metamaterial with broadband nonreciprocal response. It is shown that such metamaterial, with reduced spatial symmetry and the time-reversal symmetry broken by magnetization, exhibits multiple nonreciprocal hyperbolic regimes. Magnetization induced one-way topological phase transitions between elliptical and hyperbolic regimes are demonstrated.
Hematopoietic Stem and Immune Cells in Chronic HIV Infection

Hematopoietic stem cell (HSC) belongs to multipotent adult somatic stem cells. A single HSC can reconstitute the entire blood system via self-renewal, differentiation into all lineages of blood cells, and replenishment of cells lost due to attrition or disease in a person's lifetime. Although all blood and immune cells derive from HSC, immune cells, specifically immune memory cells, have the properties of HSC on self-renewal and differentiation into lineage effector cells responding to the invading pathogens. Moreover, the interplay between immune memory cell and viral pathogen determines the course of a viral infection. Here, we state our point of view on the role of blood stem and progenitor cell in chronic HIV infection, with a focus on memory CD4 T-cell in the context of HIV/AIDS eradication and cure.
What'd I Say?: Coase, Demsetz and the Unending Externality Debate

Economists study various problems referred to as "market failure" - situations that, at least potentially, justify government intervention to solve them. Externalities (or "social costs") are viewed as perhaps the greatest market failure problems. The externality issue has also occasioned much re-thinking of fundamental economic principles, particularly in the context of Ronald Coase's article on "The Problem of Social Cost." Coase explained that externalities manifested a more fundamental issue in economics, the costs of transacting over rights to affect other's welfare. Following Coase's work, economists almost reflexively consider social costs problematic only when transaction costs are relatively high. Yet, Coase's analysis has resulted in much confusion, even disagreement. For example, Harold Demsetz has recently objected to aspects of the Coase approach, as a matter of both economics and of government policy. As economics, Demsetz says, Coase's focus on transactions costs is not helpful in resolving questions concerning externalities. Even if transaction costs were zero, externalities would still exist. Moreover, Demsetz objects that focus on transaction costs to explain persistent externalities furnishes spurious reasons for undesirable government intervention in markets. This paper summarizes and evaluates Demsetz objections, maintaining that Demsetz sometimes ignores points that Coase has made. At the same time, Demsetz adds new insights to the Coase Theorem.
Interaction of Mimetic Analogs of Insect Kinin Neuropeptides with Arthropod Receptors

Insect kinin neuropeptides share a common C-terminal pentapeptide sequence Phe1-Xaa1(2)-Xaa2(3)-Trp4-Gly5-NH2 (Xaa1(2) = His, Asn, Phe, Ser or Tyr; Xaa2(3) = Pro, Ser or Ala) and have been isolated from a number of insects, including species of Dictyoptera, Orthoptera and Lepidoptera. They have been associated with the regulation of such diverse processes as hindgut contraction, diuresis and the release of digestive enzymes. In this chapter, the chemical, conformational and stereochemical aspects of the activity ofthe insect kinins with expressed receptors and/or biological assays are reviewed. With this information, biostable analogs are designed that protect peptidase-susceptible sites in the insect kinin sequence and demonstrate significant retention of activity on both receptor and biological assays. The identification of the most critical residue of the insect kinins for receptor interaction is used to select a scaffold for a recombinant library that leads to identification ofa nonpeptide mimetic analog. C-terminal aldehyde insect kinin analogs modify the activity of the insect kinins leading to inhibition of weight gain and mortality in corn earworm larvae and selective inhibition ofdiuresis in the housefly. Strategies for the modification of insect neuropeptide structures for the enhancement ofthe topical and oral bioavailability of insect neuropeptides and the promotion of time-release from the cuticle and/or foregut are reviewed. Promising mimetic analog leads for the development of selective agents capable of disrupting insect kinin regulated processes are identified that may provide interesting tools for arthropod endocrinologists and new pest insect management strategies in the future.
Incidence of hospital‐acquired pressure ulcers – a population‐based cohort study

Our study sought to estimate the association between race, gender, comorbidity and body mass index (BMI) on the incidence of hospital-acquired pressure ulcer (PU) from a population-based retrospective cohort comprising 242 745 unique patient hospital discharges in two fiscal years from July 2009 to June 2010 from 15 general and tertiary care hospitals. Cases were patients with a single inpatient encounter that led to an incident PU. Controls were patients without a PU at any encounter during the two fiscal years with the earliest admission retained for analysis. Logistic regression models quantified the association of potential risk factors for PU incidence. Spline functions captured the non-linear effects of age and comorbidity. Overall 2·68% of patients experienced an incident PU during their inpatient stay. Unadjusted analyses revealed statistically significant associations by age, gender, race, comorbidity, BMI, admitted for a surgical procedure, source of admission and fiscal year, but differences by gender and race did not persist in adjusted analyses. Interactions between age, comorbidity and BMI contributed significantly to the likelihood of PU incidence. Patients who were older, with multiple comorbidities and admitted for a surgical diagnosis-related groups (DRG) were at greater risk of experiencing a PU during their stay.
Studies on the degradation of human very low density lipoproteins by human milk lipoprotein lipase.

Abstract Human milk lipoprotein lipase (LPL) was purified by heparin-Sepharose 4B affinity chromatography. The time required for the purification was approximately 2 h. The acetone-diethyl ether powder of milk cream was extracted by a 0.1% Triton X-100 buffer solution and the extract was applied to the heparin-Sepharose 4B column. The partially purified LPL eluted by heparin had a specific activity of 5120 units/mg which represented a 2500-fold purification of the enzyme. The LPL was found to be stable in the heparin solution for at least 2 days at 4 °C. This enzyme preparation was found to be free of the bile salt-activated lipase activity, esterase activity, and cholesterol esterase activity. The LPL had no demonstrable basal activity with emulsified triolein in the absence of a serum cofactor. The enzyme was activated by serum and by apolipoprotein C-II. The application of milk LPL to studies on the in vitro degradation of human very low density lipoproteins can result in a 90–97% triglyceride hydrolysis. The LPL degraded very low density lipoprotein triglyceride and phospholipid without any effect on cholesterol esters. Of the partial glycerides potentially generated by lipolysis with milk LPL, only monoglycerides were present in measurable amounts after 60 min of lipolysis. These results show that the partially purified human milk LPL with its high specific activity and ease of purification represents a very suitable enzyme preparation for studying the kinetics and reaction mechanisms involved in the lipolytic degradation of human triglyceride-rich lipoproteins.
Subduction zones: observations and geodynamic models

Abstract This review of subduction and geodynamic models is organized around three central questions: (1) Why is subduction asymmetric? (2) Are subducted slabs strong or weak? (3) How do subducted slabs interact with phase transformations, changes in mantle rheology, and possibly chemical boundaries in the mantle? Based on laboratory measurements of the temperature dependence of olivine, one would conclude that the core of a subducting slab is at least 10,000 times more viscous than ambient mantle; however, there are a number of complementary but independent observations that suggest that slabs are much weaker than this. Slabs undergo significant deformation in the upper mantle and may thicken to twice their original width by the time they reach the base of the transition zone. The lack of a clear correlation between the observed dip angle of deep slabs and plate velocity, rate of trench migration, and slab age in modern subduction zones is consistent with hypothesis that subduction is a time-dependent phenomenon. Both tank and numerical convection experiments with plates conclude that subduction is not a steady phenomenon, but that slabs bend, thicken, stretch, and change dip through time. This is at odds with the assumptions used in steady-state slab thermal models, where slab deformation is not considered.
Tri-metallic transition metal–nitrogen–carbon catalysts derived by sacrificial support method synthesis

Abstract A series of tri-metallic oxygen reduction catalysts derived from pyrolyzed Fe-M 1 -M 2 (where M = Co, Ni, Cu and Mn) and 4-aminoantipyrine (Fe-M 1 -M 2 -AAPyr) were prepared using a sacrificial support method (SSM). The influence of the iron interacting with the two transition metals on the catalytic activity of the oxygen reduction reaction (ORR) was investigated. This series of materials was analyzed and characterized by scanning electron microscopy (SEM) and the BET method (BET) in order to establish structural morphology, and rotating ring disk electrode (RRDE) experiments were performed to evaluate catalytic activity. The results were then correlated to one another, thereby establishing a composition to function relationship. Data from the ring current was used to execute a mechanistic study of the materials for the ORR, and it was found that supplementation of the iron with transition metals significantly improved catalytic activity, in addition to decreasing the hydrogen peroxide yield. The most pronounced enhancement of ORR catalysts is when the base transition metal Fe is supplemented with Co as a secondary metal and Cu or Mn are the tertiary metal in the system.
In vivo covalent binding of trans-4-hydroxy-2-hexenal to rat liver macromolecules

Abstract Trans-4-hydroxy-2-hexenal (t-4HH), a metabolite isolated from the macrocyclic pyrrolizidine alkaloid senecionine, was tritiated to perform in vivo covalent binding studies. The in vivo binding of [ 3 H ]t-4 HH to rat liver DNA, RNA and protein was investigated. No significant binding to hepatic DNA or RNA could be detected, but levels of 429 ± 139 mol/mg were found covalently bound to hepatic proteins 16 h after exposure. Levels as high as 916 pmol/mg protein were detected 2 h after administration of [ 3 H ]t−4 HH via the hepatic portal.
Fundus Flavimaculatus without Maculopathy: A Clinicopathologic Study

Abstract We studied the eyes of a 51-year-old man with the clinical diagnosis of fundus Flavimaculatus without macular involvement by light and electron microscopy. Scanning and transmission electron microscopy revealed elevated aggregates of enlarged retinal pigment epithelial cells with apices distended by accumulated lipid membranes with a tubulo-vesicular appearance. Histochemical and ultrastructural studies failed to demonstrate abnormal accumulation of lipofuscin or acid mucopolysaccharide. The disorder, known clinically as fundus flavimaculatus, may represent two or more metabolic disorders of the retinal pigment epithelium characterized by distinct histochemical and ultrastructural features.
Subtotal coronoid ostectomy for treatment of medial coronoid disease in 263 dogs.

Objective— To document clinical outcomes after subtotal coronoid ostectomy (SCO) for treatment of medial coronoid disease (MCD). Study Design— Prospective clinical study. Animals— Dogs (n=263) with MCD. Methods— MCD was treated by a combination of SCO via mini-arthrotomy, cage confinement (6 weeks), leash restricted exercise (12 weeks) and pentosan polysulfate administration. Outcomes were assessed by clinical examination in the short-term (324 elbows), owner questionnaires (146 dogs), clinical examination (90 dogs), subjective assessment of gait (110 elbows) and radiographic examination (180 elbows), 4 months to 7 years 7 months after surgery. Results— One intraoperative complication occurred (1 elbow with fissuring of the ulna) and 8.2% elbows had immediate postoperative complications, the most common being wound infection (7%). Improvement in subjective lameness assessment to a score of 0 was noted at 5 weeks in 74.4% of elbows (veterinary) and 45.6% (owner) and at 12 weeks in 71.5% (veterinary), and 91.2% (owner). Subjective assessments of outcomes in the medium-term revealed 81.9% dogs remained sound, with significantly (P<.05) improved daily function scores compared with preoperative values, 83.5% of dogs received no NSAID. Clinical examination revealed good limb function and subjective assessment showed 51% of limbs were free from lameness. Radiographic progression of osteophytosis occurred on average by one grade. Conclusion— Management of MCD using the described management regime, including SCO via mini-arthrotomy, deserves consideration and comparison with existing treatment methods. Clinical Significance— Management of MCD by SCO can be considered when gross fissuring or fragmentation of the MCP is not evident. This technique does not require specialized instrumentation.
A kinetic study of the oxygen‐initiated polymerization of ethylene

The kinetics of the oxygen-initiated polymerization of ethylene show some features previously unrecorded in vinyl polymerizations. Preceding formation of polyethylene, there is an induction period which depends strongly on temperature and pressure but only slightly on oxygen concentration. During the induction period the rate of oxygen consumption increases exponentially with time and approximately one-half of the oxygen is consumed prior to polymerization which can take place only if certain critical conditions depending primarily on pressure and oxygen concentration are exceeded (critical boundary). A formal reaction mechanism with degenerate kinetic chain branching is postulated from which the most important experimentally observed relations can be deduced. The induction period for polymerization then becomes the reciprocal branching factor for the oxidation of ethylene and the critical boundary a kinetic limit familiar in hydrocarbon oxidations with degenerate branching. The shape of the critical boundary can be derived by postulating, in addition, a sequence of reaction steps similar to those frequently used to represent the low temperature oxidation of hydrocarbons. Under the conditions investigated, the initiation mechanism dominates the polymerization, and an interpretation of the propagation and termination steps cannot be made.