cssi/SciSciGPT-SciSciNet huggingface dataset:
IFN-β Mediates Suppression of IL-12p40 in Human Dendritic Cells following Infection with Virulent Francisella tularensis

Active suppression of inflammation is a strategy used by many viral and bacterial pathogens, including virulent strains of the bacterium Francisella tularensis, to enable colonization and infection in susceptible hosts. In this study, we demonstrated that virulent F. tularensis strain SchuS4 selectively inhibits production of IL-12p40 in primary human cells via induction of IFN-β. In contrast to the attenuated live vaccine strain, infection of human dendritic cells with virulent SchuS4 failed to induce production of many cytokines associated with inflammation (e.g., TNF-α and IL-12p40). Furthermore, SchuS4 actively suppressed secretion of these cytokines. Assessment of changes in the expression of host genes associated with suppression of inflammatory responses revealed that SchuS4, but not live vaccine strain, induced IFN-β following infection of human dendritic cells. Phagocytosis of SchuS4 and endosomal acidification were required for induction of IFN-β. Further, using a defined mutant of SchuS4, we demonstrated that the presence of bacteria in the cytosol was required, but not sufficient, for induction of IFN-β. Surprisingly, unlike previous reports, induction of IFN-β by F. tularensis was not required for activation of the inflammasome, was not associated with exacerbation of inflammatory responses, and did not control SchuS4 replication when added exogenously. Rather, IFN-β selectively suppressed the ability of SchuS4-infected dendritic cells to produce IL-12p40. Together, these data demonstrated a novel mechanism by which virulent bacteria, in contrast to attenuated strains, modulate human cells to cause disease.
The Link between Selenium and Chemoprevention: A Case for Selenoproteins

Selenium is effective in reducing cancer incidence in animal models, and epidemiologic data, as well as supplementation trials, have indicated that selenium is likely to be effective in humans. The mechanism by which selenium prevents cancer remains unknown. The mammalian genome encodes 25 selenoprotein genes, each containing one or more molecules of selenium in the form of the amino acid selenocysteine, translationally inserted into the growing peptide in response to the UGA codon. There is evidence that several of these proteins may be involved with the mechanism by which selenium provides its anticancer effects. Data are reviewed indicating that genetic variants of the cytosolic glutathione peroxidase are associated with increased cancer risk, and that loss of one of the copies of this same gene may be involved with malignant progression. Similarly, allelic differences in the gene for a second selenoprotein, Sep15, may be relevant to the protection provided by selenium, and allelic loss at this locus have been reported as well. These data, along with the differential expression patterns reported for other selenoproteins in tumor vs. normal tissues, support the role of selenoproteins in the chemoprotection by selenium.
Depression, physical health impairment and service use among older adults.

The purposes of this study were: (1) to compare service use and need among 80 community-dwelling older adults (55 women and 25 men); and (2) to examine the influence of depression on service use and need. Participants were divided into three groups based on their depression scores (no depression, mild depression, severe depression) and compared on a wide range of services. (e.g., medical services, social/recreational, transportation) typically used by older adults. There were no significant differences among the three groups for demographic characteristics and chronic illness types, but there were significant differences for physical health impairment (PHI). When controlling for PHI, significant differences were found among the groups for mental health services, psychotropic medications, number of sick days, hospitalizations, home help, frequency of transportation, social/recreational services, and sports-related activities. Mildly and severely depressed older adults used and needed more medical services than did their non-depressed cohorts, but used less of other types of services (e.g., social/recreational services). Depression was a significant predictor of social/recreational service use, and for need of mental health services, psychotropic medications, financial assistance, and assessment and referral services. A consistent pattern was found of depression influencing service use and need.
Liquid-Tunable Frequency Selective Surfaces

In this letter, a new technique for designing tunable frequency selective surfaces (FSSs) with the second-order band-pass response is presented and experimentally verified. The technique is applied to an FSS utilizing nonresonant, subwavelength, constituting unit cells. Frequency tuning is achieved by adjusting the location of a liquid metal slug within capillary tubes embedded between the FSS's metallic layers. A wideband flexible frequency tuning covering nearly the entire X band is tested in a waveguide environment and excellent agreement between the measured and simulated results is demonstrated.
Abstract T P416: Bilateral Common Carotid Artery Stenosis in Normotensive Rats Impairs Short-Term Memory and Dilation in Penetrating Arterioles

Chronic cerebral hypoperfusion (CCH) is a risk factor for cognitive impairment. Reduced blood flow through the common carotid arteries induced by bilateral common carotid artery stenosis (BCAS) is a physiologically relevant model of CCH. We hypothesized that BCAS in Wistar Kyoto (WKY) rats would impair cognitive function, we further proposed that in an effort to compensate for the reduced blood flow BCAS would lead to increased dilation and outward remodeling in the penetrating arterioles (PAs). Data are shown as mean±SEM, SHAM vs BCAS. BCAS reduced pial artery perfusion in 20-week-old male WKY rats (469±8 vs 299±21 perfusion units p<0.05). Short-term memory, evaluated by novel object recognition testing, was impaired (novel exploration quotient: 0.62±0.09 vs 0.46±0.14, p<0.05). PA reactivity and structure were assessed by pressure myography. There was no difference in myogenic tone between the groups [SHAM (n=4) and BCAS (n=7), % average tone: 34.5±9.8]. Contrary to our hypothesis, BCAS impaired endothelial function of PAs from 28-29 weeks old WKY rats, as evidenced by reduced dilation to endothelium dependent dilator carbachol (% change in diameter from baseline at 10-5M: 7.0±4.1 vs -1.8±5.6, Student’s t-test p<0.05). Inhibition of nitric oxide and prostacyclin production did not change the response to carbachol or the myogenic tone in either group. This suggests that endothelium derived hyperpolarizing factor (EDHF) plays a role in PA dilation in the SHAM rats; the role of EDHF in the PAs from the BCAS rats remains to be investigated but the lack of dilation to carbachol under any conditions suggests a general impairment in endothelial function. There was no difference in the PA passive structure between the groups. Work from our lab suggests that CCH leads to outward remodeling of the posterior communicating artery (PCA). Lumen diameter of the PCAs is important in regulating the severity of CCH. BCAS increased lumen diameter, wall-to-lumen ratio and distensibility of the PCAs (two-way ANOVA, p<0.05). These data suggest that BCAS impairs short-term memory, and may contribute to impaired endothelium dependent dilation of the PAs. BCAS in normotensive WKY rats also leads to outward remodeling in the PCAs but it did not alter PA passive structure.
FOXO3a & haematopoietic stem cells: Goodbye PI3K, hello SIRT1?

The transcription factor family FOXO and FOXO3a in particular is of central importance in the long-term maintenance of haematopoietic stem cell (HSC) quiescence, cell number, reactive oxygen specie...
SAT0339 Comparative Effectiveness of First-Line Biologics Used for Rheumatoid Arthritis in a Managed Care Population

Background Evidence on the comparative effectiveness of biologics used for rheumatoid arthritis (RA) is lacking. A validated claims-based algorithm had been developed to estimate the effectiveness of biologics for RA in administrative claims databases. Objectives The objective was to implement a claims-based algorithm in a US managed care database to estimate the effectiveness of first-line biologics approved to treat moderate-to-severe RA (abatacept [ABA], adalimumab [ADA], certolizumab pegol [CER], etanercept [ETN], golimumab [GOL], infliximab [INF]). Methods This is a retrospective cohort study using administrative data in the HealthCore Integrated Research Database (HIRD SM ). The cohort included patients with ≥1 claim for the first-line biologics used for RA between Jul 1, 2009 and Jan 31, 2013. Patients also had to be aged 18-63, have ≥1 claim for RA, have no prior exposure to biologics for RA (ABA, ADA, anakinra, CER, ETN, GOL, INF, rituximab, or tocilizumab) or other conditions for which the aforementioned biologics were approved to treat during the 6 months pre-index, and be continuously enrolled between 6 months prior to and 12 months post-index. The first biologic use following 6 months of enrollment defined the index event and date. The algorithm defines effectiveness as meeting all of the following criteria: Medication possession ratio ≥80% (or meeting number of infusions/injections as specified on US label), no increase in biologic dose or frequency, no biologic-switching, no addition of new non-biologic Disease Modifying Anti-Rheumatic Drugs (DMARD), no initiation or increase of oral glucocorticoid use, and ≤1 parenteral or intra-articular glucocorticoid injection during the follow-up period. Chi-square or Fisher9s exact tests were used to estimate the relative effectiveness of biologics in comparison to ETN. Pearson correlation coefficients were computed to estimate the correlation between each criterion. Results A total of 4,844 patients were eligible for analysis (mean age 48.6, 76.4% female). Overall, 30.2% patients were classified as effectively treated [ETN (33.3%), ADA (30.7%), ABA (28.7%), GOL (26.2%), CER (21.6%), and INF (19.3%)]. Statistically significant differences (p Conclusions Based on a validated claims-based algorithm, ETN users had the greatest likelihood of being effectively treated among first-line biologics users with RA in this managed care population. Despite this, real-world effectiveness appears to be low across biologics. Acknowledgements Research funded by Immunex Corporation, a wholly owned subsidiary of Amgen Inc. Disclosure of Interest T. Gu Grant/research support from: Amgen, N. Shah Shareholder of: Amgen, Employee of: Amgen, G. Deshpande Grant/research support from: Amgen, D. Tang Shareholder of: Amgen, Employee of: Amgen, D. Eisenberg Grant/research support from: Amgen, B. Stolshek Shareholder of: Amgen, Employee of: Amgen, D. Harrison Shareholder of: Amgen, Employee of: Amgen
Response of soil microbial community composition to vegetation types

There is no unifying conclusion among the considerable studies of soil microbial community composition under different vegetation types. We selected a distinct vertical vegetation distribution belt consisting of broad-leaved forests,coniferous forests,and subalpine meadows to study the effect of vegetation types on soil microbial community composition.Soil samples were collected at three different depths( 0—5cm,5—10cm,10—20cm) from sites of five vegetation types.These sites were distinguished by their dominating vegetation: poplar( Populus davidiana)( 1250—1300m),poplar( P.davidiana) mixed with birth( Betula platyphylla)( 1370—1550m),birth( B. platyphylla)( 1550—1720m),larch( Larix principis-rupprechtii)( 1840—1890m) and subalpine meadow( 1890—1951m). Soil microbial communitycompositions under the various vegetation types were determined by phospholipid fatty acid( PLFA) analysis. Ordination of individual PLFA signatures and correlations among soil properties and soil microbial PLFA indicators were analyzed by principal components analysis( PCA) and redundancy analysis( RDA),respectively. The results indicated that total PLFA contents of soil microbial community,biomasses of four main microbial taxa( fungi( f),bacteria( b),gram-positive bacteria( G+),gram-negative bacteria( G-)),and microbial community structure were significantly affected( P 0.05)by soil organic carbon( SOC) under all vegetations; PLFA contents of total microbial community and main taxa generally decreased as soil depth increased,while G+ / G-and f / b increased with soil depth. Among different vegetations,total PLFA contents and main taxa biomass under mixed broad-leaved forests were the highest; f / b and G+ / G-under coniferous forests were higher than those under broad-leaved forests; the availability of SOC under subalpine meadows was constrained on some level by the low p H value,which led to a relatively high f / b and G + / G-. In conclusion,the effect of SOC on soil microbial community composition was the most significant of all soil parameters under all vegetation types,though the availability of SOC could be constrained by relatively low p H values on some level; fungi was more sensitive to the changes of vegetation types while bacteria was more sensitive to the variability of nutrient availability and p H. This conclusion could have a significant impact on forecasting soil microbial community composition under different vegetations.
Control of Imported Fire Ants with Nonachlor

Field tests were conducted to evaluate Nonachlor (1,2,3,4,5,6,7,8,8-nonachloro-3a,4,7,7a-tetrahydro-4,7 – methanoindan) as a residual insecticide in the soil and as a toxicant in the corncob grits-soybean oil bait for control of the imported fire and solenopsis saevissima richteri Forel. Two field tests with 0.15% and 0.3% Nonachlor bait at 10 pounds per acre gave less control than 10 pounds per acre of 0.075% mirex bait. However, these tests indicate some potential for Nonachlor as a bait toxicant. In residual studies, ¼ pound per acre of Nonachlor consistently gave control equal or slight]y superior to a comparable dosage of heptachlor. Dosages of 1 and 2 pounds of Nonachlor per acre provided 99 to 100% control of the imported fire ant through 1 year.
Some Aspects of Duality in Combinatorial Optimization

The literature of combinatorial optimization, and of related fields such as graph theory. is replete with numerous examples of duality theorems and their applications: the Max-Flow Min-Cut Theorem, Konig-Egervary Theorem, Edmond’s Odd Set Covering Theorem, Hoffman’s Circulation Theorem, Minty’s Painting Theorem, Menger’s Theorem, Dilworth’s Theorem, etc. Our objective in this Chapter is to review a few of these duality results and to give some examples which may be convincing of the usefulness of duality concepts in problem formulation and solution.
Rapid Monitoring of Estradiol in Rat Serum with HPLC-MS

Objective To establish a rapid monitoring method of HPLC-MS of estradiol in rat serum.Methods The para-hydroxybiphenyl was used as internal standard,and dansyl chloride was used as derivatization reagents.Chromatographic column was Agilent Zorbax SB C18(4.6 mm×250.0 mm,5 μm),mobile phase was methanol-10 mmol/L ammonium acetate solution-acetic acid(97∶3∶1),flow rate was 1 ml/min;ionization ion source was atmospheric pressure chemical ionization ion source,monitoring mode was selective cation ion monitoring mode,drying gas flow was 7 L/min,drying gas temperature was 350℃,neb pressure was 345.5 kPa,and the validation of the method was analyzed.Results The trace estradiol in rat serum was determined,the contents was 14.44~1.68 pg/ml,and the recovery rate was 92.43%.Conclusion With the derivatization of dansyl chloride,the estradiol in rat serum can be rapidly determined with HPLC-MS,which is of certain application value.
Chemotherapy of metastatic bladder cancer.

Recent disease-oriented phase II clinical trials in advanced transitional cell carcinoma of the urothelial tract have defined the therapeutic efficacy of cis-diamminedichloride platinum II, Adriamycin and methotrexate. Other agents which may have some activity include cyclophosphamide, the podophyllotoxins, hexamethylmelamine, and possibly 5-flourouracil. While combination drug regimens have been reported to induce higher remission rates when compared to single agents, prospective randomized trials will be needed to document enhanced therapeutic benefit. The problems in selecting appropriate patients and in defining response criteria in clinical trials in urothelial tumors are discussed. Chemotherapy data in the treatment of bladder cancer is summarized, using strict response criteria.
Enhanced thermogenesis during recovery from diet-induced weight gain in the rat

The present study examined the contribution of energy expenditure to the recovery of body weight after a period of overfeeding. Three groups of 2-mo-old female rats (n = 24) were fed, respectively, a 10% (wt/wt)-fat diet (control), a 35% (wt/wt)-fat diet (high fat) or were force fed 130% of the control diet (tube fed). After 30 days, all groups received the control diet for 18 days of recovery. Both overfeeding protocols significantly increased weight above control levels. This difference disappeared after 7 days of recovery. Increases in resting oxygen consumption, serum 3,5,3'-triiodothyronine (T3) levels, and the thermogenic response to norepinephrine were observed at the end of overfeeding. Serum T3 and resting oxygen consumption returned to control levels by day 3 of recovery from overfeeding, whereas the thermogenic response to norepinephrine required 9 days to recover. Whereas total energy expenditure was not significantly elevated during overfeeding, significant increases of 9.6 and 13.9% were observed in the formerly high-fat and tube-fed animals, respectively, during recovery. These data indicate that changes in energy expenditure play an important role in maintaining the stability of body weight.
Theoretical consideration of contact angle hysteresis using surface-energy-minimization methods

Abstract In recent years, advances in coating manufacturing processes have allowed wetting characteristics of a surface to be tuned with micro/nano morphologies. Today, complex surface geometries can be created with various surface treatment methods. These advances can be implemented in phase-change heat-transfer applications, such as condensation, which relies on droplet behavior on a surface. Therefore, it is important to gain a fundamental understanding of wetting characteristics of textured surfaces having different geometrical configurations. This can be accomplished by studying the behavior of a single droplet on a given surface. Drop shapes and behaviors are affected by surface energies of different interfacial surfaces and surface morphologies. Contact angle hysteresis (CAH) – which is the difference between advancing and receding angles – can be estimated by utilizing concepts of surface-energy minimization. This is essential in heat transfer applications, as parameters such as drop size and distribution in condensation heat transfer are determined by CAH. In this study, a mathematical model has been developed to estimate CAH on different surface geometries and degrees of wetting. Modeling results suggest that CAH increases with increasing degree of wetting. Further, CAH remains low at both high and low droplet contact angles, whether the surface is hydrophilic or hydrophobic.
Enhancing Student Engagement in a Blended Resident and Online Course Using Clickers and Embedded Questions

This paper describes the use of Clickers (small, mobile phone like electronic devices) and embedded questions in streaming videos for the purpose of student engagement in a course that was taught with a blended delivery model in a live resident classroom and also delivered to distance education students online. In order to provide the ability for instructors to engage students in a rich interactive environment, a creative use of Clickers and embedded questions was developed for a course in Mechanical Engineering-ME 201: Introduction to Thermal Sciences at Penn State.Details of how Clicker devices and specially designed Clicker questions are used to receive feedback of students in a resident classroom are first presented, followed by details of using similar questions embedded in streaming videos for online delivery. The student feedback collection and its analysis for both resident and online courses is discussed. The study shows that such an approach makes creative use of the modern instructional technologies to enhance the teaching-learning process and improve the understanding of students.
Javamide-I-O-methyl ester increases p53 acetylation and induces cell death via activating caspase 3/7 in monocytic THP-1 cells.

Abstract Background Javamide-I and-II are phenolic amide compounds found in Coffea sp. Previous study suggested that javamide-II may be a potent compound with Sirt1/2 inhibition activity. Purpose However, the effects of javamide-I and the its O-methyl ester on Sirt inhibition, p53 acetylation and cell death have not been investigated. Methods The isolation and synthesis of javamide-I and its O-methyl ester analogue were confirmed by NMR. Their potential effects on Sirt1/2/3, p53 acetylation and cell death were examined using sirt assay, silico analysis, Western blot, caspase 3/7 and apoptotic assay methods. Results Javamide-I and its O-methyl ester demonstrated a similar inhibition pattern; Sirt1 (IC 50 of 19 µM) better than Sirt2 (IC 50 of 104 µM) and Sirt3 (IC 50 of 160 µM). However, javamide-I and its O-methyl ester were found to inhibit Sirt1 better than Sirt2, which is different from javamide-II able to inhibit Sirt2 stronger than Sirt1. In silico analysis, javamide-I and its O-methyl ester showed a competitive binding pattern against NAD +, which was also supported by the kinetic analysis with K i = 20.1 µM for javamide-I and 19.5 µM for the O-methyl ester. However, the O-methyl ester increased p53 acetylation better than javamide-I in monocytic THP-1 cells. Since caspase 3/7 activation is often followed by the p53 activation, we investigated their effects on caspase 3/7, and found that O-methyl ester again activated caspase 3/7 greater than javamide-I in the cells, eventually leading to apoptotic cell death. Conclusion These data suggest that the O-methyl modification in javamide-I may play a critical role in increasing p53 acetylation, activating caspase, and eventually inducing the THP-1 cell death.
National Standards, Subnational Enforcement: Regulating US Natural Gas Pipelines

This research focuses on the role of subnational units in the enforcement of interstate regulations of natural gas pipeline safety in the USA. It does so by developing a theoretical model of interstate regulatory enforcement of natural gas pipelines at both the national and subnational units, utilising the Advocacy Coalition Framework developed by Sabatier and Jenkins-Smith (1993). Particular emphasis is placed on the role of public and private actors at the local and state levels in monitoring, enforcing, and correcting issues with pipeline construction and maintenance. This work addresses this problem through an empirical approach that estimates a mixed-effects model of incidence (number of fines issued) and compliance rates (measured as the percent of the number of incidents corrected by the number of incidents reported) at the state and local levels, accounting for intertemporal variation by a geographic, existing infrastructure of natural gas pipelines and socioeconomic, regulatory type, and political factors (Energy Policy 35(1): 650–671, 2007). Moreover, this research addresses whether differences in approaches to enforcement styles (cooperative vs. coercive) of natural gas pipelines at the subnational unit result in increases in compliance and incidence rates among natural gas pipeline operators. Overall findings suggest that enforcement style and the frequency of contacts between regulators and regulated entities significantly increase compliance rates. The results indicate that increased input from subnational actors would further increase pipeline safety rates overall.
Crowdlearning: A framework for collaborative and personalized learning

This work presents a new technological learning paradigm that we call crowdlearning, where students are upgraded from mere passive content consumers to primary content creators and curators. Crowdlearning is all about allowing learners to share their particular vision of the world, understanding how different users learn, and putting in place mechanisms to safely, scalable, and accurately share and consume learning materials online. By providing an interactive learning framework, we expect that attention of underrepresented groups in STEM, particularly women, will be drawn towards computer science and other technology-related fields. In this paper we introduce all the necessary components of a crowdlearning framework, we provide a middleware implementation along with a proof of concept application. Finally, we discuss possible implications, limitations, and prospects of this approach, and how it could be shaped into a mainstream collaborative way of enhancing cyber learning. If successful in the long run, this paradigm has the potential of advancing technology aided education tools while promoting teaching, training, and collaborative learning.
Survey of New Pharmacy Schools:Insights on Structure and Planning

The purpose of this study is to provide insights into the structure and planning involved in opening a new school of pharmacy. The authors surveyed Pharmacy CEO-Deans at new schools of pharmacy in the US. A "48- item questionnaire" was developed and administered online through www.SurveyMonkey.com to 23 deans/provosts/presidents of institutions with a "new" school/college of pharmacy. A "new" school/ college of pharmacy was defined as academic entities that have received or are in the process of obtaining pre-candidate or candidate status from Accreditation Council for Pharmacy Education (ACPE). In addition, fully accredited schools that within the past year had started a new branch campus were also included. At the time of the survey in January of 2008, the authors identified a total of 26 schools or colleges that were at various stages of Pre-accreditation. Additionally, fully accredited schools that had started a branch campus within the past year were also included. Three schools indicated that they were too early in the process to answer the survey adequately. Twentythree schools comprised the sample size. Out of the 23 schools, 19 schools responded (83% response rate). The survey had five sections: organizational structure of the school/college, administrative structure, curriculum structure, faculty structure, and admissions process. This study provides an insight into the planning of a new pharmacy program including organization, administrative, faculty, curricular characteristics, and admission process. The results may be helpful to entities that are planning to open a new college or school of pharmacy.
Crystal structure of the Entamoeba histolytica RNA lariat debranching enzyme EhDbr1 reveals a catalytic Zn2+/Mn2+heterobinucleation.

The RNA lariat debranching enzyme, Dbr1, is a metallophosphoesterase that cleaves 2'-5' phosphodiester bonds within intronic lariats. Previous reports have indicated that Dbr1 enzymatic activity is supported by diverse metal ions including Ni2+ , Mn2+ , Mg2+ , Fe2+ , and Zn2+ . While in initial structures of the Entamoeba histolytica Dbr1 only one of the two catalytic metal-binding sites were observed to be occupied (with a Mn2+ ion), recent structures determined a Zn2+ /Fe2+ heterobinucleation. We solved a high-resolution X-ray crystal structure (1.8 A) of the E. histolytica Dbr1 and determined a Zn2+ /Mn2+ occupancy. ICP-AES corroborate this finding, and in vitro debranching assays with fluorescently labeled branched substrates confirm activity.
Molecular Basis of N,N-Diethyl-3-Methylbenzamide (DEET) in Repelling the Common Bed Bug, Cimex lectularius.

As the most extensively used chemical repellent, N,N-diethyl-3-methylbenzamide (DEET) displayed repellency to a wide range of insects, including the common bed bug, Cimex lectularius. While the neuronal or molecular basis involved in DEET’s repellency have been majorly focused on mosquitos and fruit flies, DEET’s repellency to the common bed bug is largely unreached. To gain new insights into the cellular and molecular mechanisms in DEET’s repellency to the common bed bug, we characterized the neuronal response of bed bugs to DEET, identified the olfactory receptors targeted by DEET and demonstrated the interfering effect of DEET on bed bug’s responses to human odorants. High doses of DEET were required for activating the olfactory receptor neurons in the sensilla of bed bugs and at least three DEET-sensitive receptors were functionally deciphered. These DEET-sensitive receptors presented even more sensitive to certain botanical terpenes/terpenoids which also displayed repellency at varying levels for bed bugs. In addition, DEET produced a blocking effect on the neuronal responses of bed bugs to specific human odors and showed inhibitory effect on the function of odorant receptors in responding to certain human odors. Taken together, our results indicate that DEET functions as a stimulus that triggered avoidance behaviors and a molecular ‘confusant’ for interrupting the host odor recognition in the odorant receptors of bed bugs. The receptors that coincidently responded to both synthetic DEET and botanical terpenes/terpenoids suggested that DEET may target on receptors that originally responded to terpenes/terpenoids. This study gave novel insights into the mechanisms of DEET’s repellency to bed bugs and also provided valuable information for developing new reagents for bed bug control.
Kinetic processivity of the two-step oxidations of progesterone and pregnenolone to androgens by human cytochrome P450 17A1

Cytochrome P450 (P450, CYP) 17A1 plays a critical role in steroid metabolism, catalyzing both the 17α-hydroxylation of pregnenolone and progesterone and the subsequent 17α,20-lyase reactions to form dehydroepiandrosterone (DHEA) and androstenedione (Andro), respectively, critical for generating glucocorticoids and androgens. Human P450 17A1 reaction rates examined are enhanced by the accessory protein cytochrome b5 (b5), but the exact role of b5 in P450 17A1-catalyzed reactions is unclear as are several details of these reactions. Here, we examined in detail the processivity of the 17α-hydroxylation and lyase steps. b5 did not enhance reaction rates by decreasing the koff rates of any of the steroids. Steroid binding to P450 17A1 was more complex than a simple two-state system. Pre-steady-state experiments indicated lag phases for Andro production from progesterone and for DHEA from pregnenolone, indicating a distributive character of the enzyme. However, we observed processivity in pregnenolone/DHEA pulse-chase experiments. (S)-Orteronel was three times more inhibitory toward the conversion of 17α-hydroxypregnenolone to DHEA than toward the 17α-hydroxylation of pregnenolone. IC50 values for (S)-orteronel were identical for blocking DHEA formation from pregnenolone and for 17α-hydroxylation, suggestive of processivity. Global kinetic modeling helped assign sets of rate constants for individual or groups of reactions, indicating that human P450 17A1 is an inherently distributive enzyme but that some processivity is present, i.e. some of the 17α-OH pregnenolone formed from pregnenolone did not dissociate from P450 17A1 before conversion to DHEA. Our results also suggest multiple conformations of P450 17A1, as previously proposed on the basis of NMR spectroscopy and X-ray crystallography.
Oxycodone Ingestion Patterns in Acute Fracture Pain With Digital Pills.

BACKGROUND:Opioid analgesics are commonly prescribed on an as-needed (PRN) basis for acute painful conditions. Uncertainty of how patients actually take PRN opioids, coupled with a desire to completely cover pain, leads to variable and overly generous opioid prescribing practices, resulting in a sur
Use of molecular techniques in the diagnosis of pulmonary and extrapulmonary tuberculosis

Abstract Tuberculosis, is a life-threatening infectious disease and one of the leading causes of mortality worldwide. It is a multisystemic disease, and involvement of lungs and pleura is seen in majority of patients. The global control of tuberculosis is impeded by the relatively low sensitive conventional diagnostic assays, especially for drug resistant strains. The current gold standard for tuberculosis diagnosis is the combination of culture and clinical diagnosis. Since conventional diagnostic assays require long time, are labor intensive and insufficient for species-level identification, new solutions for problems in routine diagnostic applications for tuberculosis are required. Implementation of reliable, highly specific and sensitive assays which were standardized for rapid diagnosis of Mycobacterium tuberculosis, is recommended by Centers for Disease Control and Prevention (CDC). Implementation of nucleic-acid amplification based tests (NATs) to support rapid diagnosis especially in reference laboratories or health-care clinical laboratories, which use the diagnostic algorithms denoted in CDC guidelines, meet American Thoracic Society class 2 and 3 standards and have smear positive sample counts ≥ 500 per year, is accepted as a logical and cost-effective approach. Analysis of cost-effectiveness for NATs are also required for global TB management plans. All current meta-analysis on NAT for tuberculosis indicate that in-house assays display considerable variations in sensitivity and specificity and exhibit discrepancies with commercial NATs. Evaluations also notified that the specificity for NAT is usually higher than expected in laboratory diagnosis of both forms of tuberculosis, whereas sensitivity is very low with considerable inter-assay variations. In conclusion, it is thought that current NATs are not reliable as single assays for rapid tuberculosis diagnosis for routine testing and should not be used in screening, but they are valuable methods in supporting conventional assays for clinical follow-up of patients. This review article discusses the diagnostic value of molecular methods in the evaluation of pulmonary and extrapulmonary tuberculosis in the light of the current literature.
Variational inequalities for the control of stochastic partial differential equations

The paper is concerned with variational inequalities arising from an optimal-stopping problem for some stochastic partial differential equations. For linear equations, the associated elliptic variational equation and inequality are formulated and studied in an L2-setting. By introducing appropriate Gaussian Sobolev type of Hilbert spaces, existence and uniqueness theorems are proved. Variational formulation for nonlinear equations is also discussed briefly.
Towards a non-invasive cardiac arrest monitor: An in vivo pilot study.

Abstract Introduction Hemodynamic-guided cardiopulmonary resuscitation (HGCPR) achieves better outcomes than standard resuscitation. Currently, HGCPR requires an invasive procedure, infeasible during resuscitation. Non-invasive measures of blood flow could provide useful hemodynamic guidance to rescuers. Objective We describe initial efforts to develop a device that detects, analyzes, and measures the velocity of carotid artery blood flow (CABF) towards the brain at pre-arrest baseline (‘baseline’) and during cardiopulmonary resuscitation, here tested in a swine model of cardiac arrest (CA). A key element of that device consists of non-imaging diagnostic ultrasound, due to its simplicity and small form factor, hence potential for deployment during HGCPR in a bandage placed on the neck. Methods Sixteen mixed-breed domestic swine were sedated, anesthetized and paralyzed, followed by endotracheal intubation and mechanical ventilation. Cardiac arrest was induced with a 3-s 100 mA transthoracic shock or bolus of fentanyl, after which all animals received mechanical CPR. A non-imaging ultrasound probe was manually applied to the neck over the carotid artery to capture CABF during baseline, as verified with diagnostic ultrasound imaging, and during mechanical resuscitation. Results We successfully collected CABF measurements at baseline in 14/16 swine and during attempted resuscitation with mechanical chest compression in 5/16 swine. Signal characteristics include peak blood flow both towards (90.4 +/−20.4 cm/s) and away from the brain (−44.2 +/−31.8 cm/s) during resuscitation, each larger than flow towards (41.7+/−14.8 cm/s) and away from brain (−3.0 +/−7.8 cm/s) during baseline. Conclusion Measurement of CABF before and during CPR in swine with a non-imaging ultrasound probe is feasible before CA and informative when achieved during CPR. For example, observations of reverse flow within the carotid artery during CPR merits further study for its prevalence and effect on resuscitation outcomes. Also, tissue motion represents a significant obstacle for CABF measurement during CPR. Additional work will determine the feasibility and utility of non-imaging ultrasound measurements of CABF during resuscitation.
Einleitung. Die Problematik der Definition des Kitsches, ihre Konsequenzen und die Ansätze der neueren und neuesten Forschung

Bereits 1925 formulierte Fritz Karpfen in seiner Schrift Der Kitsch, dass „[j]edermann weis, was Kitsch ist“, aber niemand „eine prazise Deutung daruber geben“ kann. Rund einundfunfzig Jahre spater fasst Henryk M. Broder weitere Kernproblematiken des Kitschbegriffs zusammen, wenn er schreibt, dass „Kitsch die Griffigkeit einer Qualle, die Spannweite eines Regenbogens und die Eindeutigkeit eines Horoskop-Spruches“ hat. Dass diese Befunde, die dem Kitsch eine grundlegende Uneindeutigkeit zuschreiben und ihm seine finale Definierbarkeit absprechen, nach wie vor Gultigkeit beanspruchen konnen, legt der Umstand nahe, dass sie auch von zeitgenossischen Kitsch-Experten in nahezu unveranderter Weise wiedergegeben werden.
Abstract 619: Dietary advanced glycation end-products and postmenopausal breast cancer risk in the NIH AARP diet and health study

Purpose: Advanced glycation end-products (AGE) are hypothesized to be involved in carcinogenesis. We analyzed dietary AGE intake in relation to invasive breast cancer (BC) to advance our knowledge of the impact of diet on BC risk. Methods: Dietary AGE intake was estimated from the food-frequency questionnaire in postmenopausal women in the NIH AARP Diet and Health study, prospective cohort (n=183,548). Incident BC cases were identified through linkage with state cancer registries. Cox proportional hazards regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for developing BC according to quintiles of AGE levels. Multivariate regression models were adjusted for established BC risk factors. Results: During a mean follow-up of 12.8 years, 9,851 BCs (1,978 advanced stage) were identified. Median daily AGE intake was 5,932 KU/1,000 kcal (10th- 90th percentile, 3,555 - 8,644). Women with higher AGE intake tended to have lower education level, higher BMI, younger age at menarche, menopause, first birth, more children, less physical activity, current smoking and higher total fat and meat intake. AGE intake was associated with increased risk of BC in the multivariate model 1, but the association was attenuated and no longer significant after adjusting for total meat and fat intakes (Table). The association between AGE intake and BC did not differ by BMI, hormone therapy use, or alcohol consumption. AGE intake was not related to BC hormone receptor status, histologic type, or grade. However, AGE intake was associated with increased risks of advanced stage tumors (highest vs. lowest quintile of AGE intake, RR 1.37 95% CI 1.09-1.74) even after controlling for total meat and fat intakes. The risk of advanced stage BC increased by 14% (RR 1.14 95% CI 1.04-1.25 in multivariate model 2) per 2,500 KU/1,000 kcal increase in AGE intake. Conclusions: Dietary AGEs may play a role in the development of postmenopausal BC, particularly in advanced stage BC. Citation Format: Lindsay L. Peterson, Seho Park, Yikyung Park, Narges Anbardar, David Turner. Dietary advanced glycation end-products and postmenopausal breast cancer risk in the NIH AARP diet and health study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 619.
The mechanomyographic and electromyographic responses to passive leg extension movements

The purpose of this investigation was to examine the mechanomyographic (MMG) responses to maximal concentric (CON) and passive leg extension movements. Eight adult females performed maximal CON muscle actions and passive leg extension movements of the dominant leg on a calibrated CYBEX 6000 dynamometer at velocities of 30, 90, and 150°.s -1 . MMG and Electromyographic (EMG) signals were simultaneously recorded from the vastus lateralis (VL). The results indicated velocity-related dissociations among MMG amplitude, EMG amplitude, and peak torque during the maximal CON muscle actions. For the passive leg extension movements, however, the EMG amplitude values at each velocity were not significantly (p > 0.05) different from the values at rest, but the MMG amplitude increased significantly (p < 0.05) with velocity. It was hypothesized that the velocity-related increase in MMG amplitude for the passive leg extension movements was independent of VL activation and may have been associated with turbulences of the intracellular and extracellular fluid mediums and/or cross-talk from the hamstring muscles.
Understanding Transformations in Battery Materials Using in Situ and Operando Experiments: Progress and Outlook

Over the past decade, significant progress has been made toward understanding the intricate dynamics that underlie the operation of batteries. The development of in situ and operando experimental t...
Recent research trends in controlling various types of disinfection by-products in drinking water: detection and treatment

Abstract Disinfection is a vital part of drinking water treatment process and chlorine is the most widely used disinfectant in the world. Though known for its effectiveness, usage of chlorine does lead to the formation of carcinogens called disinfection by-products (DBPs). Numerous treatment technologies and strategies are in use to address formation of DBPs depending on the type of DBP formation, source water quality, size of the treatment plants, regulations, and infrastructures in place. This chapter outlines major trends in handling most abundantly found DBPs in water systems including removal of organic precursors using advanced treatment technologies such as ultrafiltration, membrane filters, enhanced coagulation, sedimentation, and fractionation, using alternate disinfectants such as chloramine, hydrogen peroxide, peracetic acid, ultraviolet, and ozone, making operational adjustments such as using boosters and, finally, using advanced prediction tools such as EPANET, Bench, and pilot-scale models to help manage DBP formation in water distribution systems.
N-Hydroxy peptides: solid-phase synthesis and β-sheet propensity

Peptide backbone amide substitution can dramatically alter the conformational and physiochemical properties of native sequences. Although uncommon relative to N-alkyl substituents, peptides harboring main-chain N-hydroxy groups exhibit unique conformational preferences and biological activities. Here, we describe a versatile method to prepare N-hydroxy peptide on solid support and evaluate the impact of backbone N-hydroxylation on secondary structure stability. Based on previous work demonstrating the β-sheet-stabilizing effect of α-hydrazino acids, we carried out an analogous study with N-hydroxy-α-amino acids using a model β-hairpin fold. In contrast to N-methyl substituents, backbone N-hydroxy groups are accommodated in the β-strand region of the hairpin without energetic penalty. An enhancement in β-hairpin stability was observed for a di-N-hydroxylated variant. Our results facilitate access to this class of peptide derivatives and inform the use of backbone N-hydroxylation as a tool in the design of constrained peptidomimetics.
Thermoregulation and Heat Balance: General Anesthesia

The thermoregulatory system usually maintains core body temperature within 0.2°C of “normal,” which is near 37°C in humans. Yet, perioperative hypothermia is common due to anesthetic-induced inhibition of thermoregulation combined with exposure to a cold operating room environment. Hypothermia causes a number of complications including shivering, prolonged duration of drug action, coagulopathies, cardiac ischemia, and decreased resistance to surgical wound infections. It can be prevented and treated in a variety of ways. All data are presented as means ±SD.
Correction: Photothermal conversion of gold nanoparticles for uniform pulsed laser warming of vitrified biomaterials.

Correction for ‘Photothermal conversion of gold nanoparticles for uniform pulsed laser warming of vitrified biomaterials’ by Yilin Liu et al., Nanoscale, 2020, 12, 12346–12356, DOI: 10.1039/D0NR01614D.
Hair toxicology identifies greater substance use than self-report in high-risk 9-13 year-olds in the ABCD Study

Abstract Aim A key aim of the Adolescent Brain Cognitive DevelopmentSM (ABCD) Study is to document substance use onset, patterns, and sequelae across adolescent development. However, substance use misreporting obscures accurate drug use characterization. Hair toxicology tests provide objective historical substance use data, but are rarely investigated in youth. Here, we compare objective hair toxicology results with self-reported substance use in youth. Methods A literature-based substance use risk algorithm identified 696 ABCD Study® participants for hair sample collections between baseline and 2-year follow-up (spanning ages 9-13) for laboratory analysis. Chi-square and t-tests assessed differences between participants’ demographics, positive and negative hair tests, risk algorithm scores, and self-reported substance use. Results Hair testing confirmed that 17% of at-risk 9-13 year-olds had evidence of past 3-month use of one (n=99), two (n=17), three (n=3), or four (n=2) drug classes. After considering prescribed medication use, 11% had a positive test incongruent with self- or parent-report. No participant with a positive result self-reported substance use consistent with their toxicology results. Participants with positive tests under-reported use (p Conclusions An alarming 11% of tested samples in at-risk 9-13 year-olds were positive for at least one unreported substance, suggesting underreporting in this population when participating in a national healthy development study. The degree of underreporting cannot yet be calculated, as at-risk samples were prioritized for assays. Expanded toxicology testing is key to characterize substance use in youth.
Personalized Federated Learning for Heterogeneous Clients with Clustered Knowledge Transfer.

Personalized federated learning (FL) aims to train model(s) that can perform well for individual clients that are highly data and system heterogeneous. Most work in personalized FL, however, assumes using the same model architecture at all clients and increases the communication cost by sending/receiving models. This may not be feasible for realistic scenarios of FL. In practice, clients have highly heterogeneous system-capabilities and limited communication resources. In our work, we propose a personalized FL framework, PerFed-CKT, where clients can use heterogeneous model architectures and do not directly communicate their model parameters. PerFed-CKT uses clustered co-distillation, where clients use logits to transfer their knowledge to other clients that have similar data-distributions. We theoretically show the convergence and generalization properties of PerFed-CKT and empirically show that PerFed-CKT achieves high test accuracy with several orders of magnitude lower communication cost compared to the state-of-the-art personalized FL schemes.