cssi/SciSciGPT-SciSciNet huggingface dataset:
Complement factor D, a novel serine protease

Factor D is unique among serine proteases in that it requires neither enzymatic cleavage for expression of proteolytic activity nor inactivation by a serpin for its control. Regulation of factor D activity is instead attained by a novel mechanism that depends on reversible conformational changes for expression and control of catalytic activity. These conformational changes are believed to be induced by the single natural substrate, C3bB, and to result in realignment of the catalytic triad, the specificity pocket, and the nonspecific substrate binding site, all of which have atypical conformations. Mutational studies have defined structural determinants responsible for these unique structural features of factor D and for the resultant low reactivity with synthetic esters.
The magma system of Mount St. Helens: non-linear high-resolution P-wave tomography

Abstract High-resolution, three-dimensional images of P-wave velocity anomalies below Mt. St. Helens, Washington, were derived using tomographic inversion. The model is a 27.5 × 21 × 20 km target volume parameterized by blocks 0.5 km per side. The area included 39 stations and 5454 local events leading to 35,475 rays used in the inversion. To diminish the effects of noisy data, the Laplacian was constrained to be small within horizontal layers, providing smoothing of the model. Non-linear effects were compensated for by iterating three-dimensional ray tracing (using pseudo-bending) between inversions and relocating earthquakes relative to the updated three-dimensional model. The structural differences between the linear and non-linear inversions appear to be insignificant, although the amplitudes of the anomalies are larger in the non-linear models. Results indicate a low-velocity anomaly (> 7%), approximately 1 km in lateral extent, from 1.5 to 3 km depths. Between 3 and 6 km depth the anomaly appears to spread out. Below 6 km depth the low-velocity feature changes to a higher-velocity perturbation with lower-velocity perturbations flanking around the perimeter of the volcano. The higher-velocity material, which correlates with the higher seismicity at that depth, is interpreted as being a plug capping the low-velocity magma chamber which begins below 9 km depth.
X-ray line spectropolarimetry as a new diagnostic of anisotropic plasma sources

The results of theoretical and experimental studies of anisotropic plasma sources are reported. They are based on x-ray line spectropolarimetry, a powerful new tool for investigating anisotropy of high-temperature plasmas. It is based on theoretical modeling of polarization-sensitive x-ray line spectra recorded simultaneously by two spectrometers with different sensitivities to polarization. The difference in these polarization-sensitive spectra is used to diagnose the parameters of anisotropic electron beams in plasmas. Theoretical predictions of polarization which cover a broad spectral range from K- to M-shell line radiation are presented. The results of Ti and Mo x-pinch polarization-sensitive experiments at UNR are overviewed. This diagnostic can be applied not only to x-pinches as demonstrated here but to laser-generated and other laboratory x-ray sources.
Consequences of Telomere Shortening at an Active VSG Expression Site in Telomerase-Deficient Trypanosoma brucei

Trypanosoma brucei evades the host immune response by sequential expression of a large family of variant surface glycoproteins (VSG) from one of approximately 20 subtelomeric expression sites (ES). VSG transcription is monoallelic, and little is known about the regulation of antigenic switching. To explore whether telomere length could affect antigenic switching, we created a telomerase-deficient cell line, in which telomeres shortened at a rate of 3 to 6 bp at each cell division. Upon reaching a critical length, short silent ES telomeres were stabilized by a telomerase-independent mechanism. The active ES telomere progressively shortened and frequently broke. Upon reaching a critical length, the short active ES telomere stabilized, but the transcribed VSG was gradually lost from the population and replaced by a new VSG through duplicative gene conversion. We propose a model in which subtelomeric-break-induced replication-mediated repair at a short ES telomere leads to duplicative gene conversion and expression of a new VSG.
Do principals with stronger academic backgrounds hire better teachers? Policy implications for improving high-poverty schools

Principals play an important role in determining the quality of their schools by the selection of teachers. A preponderance of evidence from the economic and education policy literature indicates that teachers with stronger academic backgrounds produce better student outcomes. This article hypothesizes that school principals with certain attributes are likely to favor teachers with similar attributes to their own. This study uses the Schools and Staffing Surveys from 1993 to 1994 to test whether school administrators who attended more selective universities are more or less likely to hire teachers who attended more selective undergraduate institutions. Findings suggest that principals’undergraduate background matters when it comes to their recruitment, selection, and perhaps retention of teachers with strong academic undergraduate backgrounds, especially in high-poverty schools. Principals in high-poverty schools who attended highly or the most selective undergraduate institutions were 3.3 times more like...
Adenosine 3',5'-monophosphate effects on cartilage ribonucleic acid synthesis.

We have previously shown that N6-monobutyryicAMP stimulates the incorporation of radiolabeled precursors into the macromolecules of embryonic chicken cartilage incubated in organ culture. The present study assessed the specific effects of N6-monobutyryl-cAMP on RNA synthesis in the cartilage organ culture system. The data show that treatment of cartilage with N6-monobutyryl-cAMP results in a coordinated stimulation of mRNA, rRNA, and tRNA synthesis. Incubation of cartilage with N6-monobutyryl-cAMP causes an increase of [5-3H]uridine incorporation into poly A-containing cartilage RNA and 28S, 18S, and 4S RNA as well. Increased incorporation of the radiolabeled nucleotide occurs without a measurable change in uridine triphosphate specific activity or in the rate of RNA degradation. Further, the isolated poly A-containing RNA directs protein synthesis in an in vitro cell-free system, and stimulation of cartilage mRNA by N6-monobutyryl-cAMP does not alter the size distribution of the mRNA species synthesized ...
A Study of the Acid Catalyzed Dehydration of Fructose in Near-Critical Water

Products of the acid catalyzed dehydration of fructose in near-critical water at 34.5 MPa and 250 oC are described as a function of residence time (2–32s), reactant concentration (0.01 – 0.1 M), and catalyst H2SO4 concentration (0 – 5 mM). The combined yields of 5-hydroxymethyl furfural and 2-furaldehyde reach 60% of the fructose feedstock.
Repaglinide induced Acute Hepatotoxicity

Repaglinide is considered a safe drug; adverse events are mild to moderate which includes hypoglycemia, headache, nausea, vomiting, diarrhea and dyspepsia as similar to sulphonylureas. This case report describes a rare side effect of repaglinide. In rare cases, elevated liver enzymes have been noted. We report a case of acute hepatotoxicity in a 78-year-old woman who developed acute hepatotoxicity while taking repaglinide.
The Upper Limit of the Cutoff Frequency in Ultrashort Gate-Length InGaAs/InAlAs HEMTs: A New Definition of Effective Gate Length

Ultrashort gate-length pseudomorphic high-electron mobility transistors have been modeled using a full-band cellular Monte Carlo simulator. The RF response and the cutoff frequency fT have been obtained for physical gate lengths ranging from 10 to 50 nm. These results, in turn, have been used in a transit-time analysis to determine the effective gate length in each case. By interpolation, one can make an estimate of the absolute upper limit for fT, which we find to be 2.9 THz in the device studied. Importantly, the effective gate lengths are considerably shorter than the depletion lengths. Thus, in general, any estimate of fT based on the latter quantity is likely too small by a quite significant amount.
Immune reconstitution inflammatory syndrome: More answers, more questions

The institution of highly active antiretroviral therapy (HAART) in HIV-infected patients restores protective immune responses against a wide variety of pathogens and dramatically decreases mortality. In a subset of patients receiving HAART, immune reconstitution is associated with a pathological inflammatory response leading to substantial short-term morbidity and even mortality. The past several years have seen marked advances in our clinical understanding of the immune reconstitution inflammatory syndrome (IRIS), but many questions remain. This article summarizes recent data on clinical risk factors for the development of IRIS. A consistent finding from multiple groups is that IRIS develops in a substantial percentage of HIV-infected patients who have an underlying opportunistic infection and receive HAART. As the use of HAART stands to markedly increase over the next several years, optimal care of patients receiving HAART will need to incorporate monitoring for and treating complications of IRIS.
X-ray tests of microfocusing mono-capillary optic for protein crystallography

A single, borosilicate-glass capillary was drawn into a 30.5 cm long elliptical shape. The inside diameter was 0.40 mm at the large base end and 0.13 mm at the tip. With 12 keV X-rays from the CHESS D1 bending magnet, the singlebounce capillary produced a focus of better than 18mm in diameter (FHWM) at a 3 cm distance from the capillary tip. A flux gain of 110 in the focus position was observed along with a total flux in the spot of 4 10 10 X-rays/s (conditions: 5.3 GeV, 182 mA, 1.5% bandwidth multilayer, 12 keV X-rays). A measurement of the far field focus ring diameter yielded a divergence of 3.8 mrad, in good agreement with the 4 mrad design of the optic for protein crystallography. Using a small 25mm square beam, we measured the local reflectivity to be greater than 95% and the inner slope errors of the capillary to average about 150mrad, both from raw and elliptically shaped tubing. Our conclusion is that more perfect starting tubing (i.e. one with lower slope errors) is needed to make even more perfect elliptically figured optics in the future. # 2001 Elsevier Science B.V. All rights reserved. PACS: 07.85.Qe; 42.15.Gs
Stress generation in a developmental context: the role of youth depressive symptoms, maternal depression, the parent-child relationship, and family stress.

The present study examined stress generation in a developmental and family context among 171 mothers and their preadolescent children, ages 8–12 years, at baseline (Time 1) and 1-year follow-up (Time 2). In the current study, we examined the bidirectional relationship between children’s depressive symptoms and dependent family stress. Results suggest that children’s baseline level of depressive symptoms predicted the generation of dependent family stress 1 year later. However, baseline dependent family stress did not predict an increase in children’s depressive symptoms 1 year later. In addition, we examined whether a larger context of both child chronic strain (indicated by academic, behavioral, and peer stress) and family factors, including socioeconomic status and parent–child relationship quality, would influence the stress generation process. Although both chronic strain and socioeconomic status were not associated with dependent family stress at Time 2, poorer parent–child relationship quality significantly predicted greater dependent family stress at Time 2. Child chronic strain, but neither socioeconomic status nor parent–child relationship quality, predicted children’s depression symptoms at Time 2. Finally, gender, maternal depression history, and current maternal depressive symptoms did not moderate the relationship between level of dependent family stress and depressive symptoms. Overall, findings provide partial support for a developmental stress generation model operating in the preadolescent period.
Shuttle mutagenesis: a method of transposon mutagenesis for Saccharomyces cerevisiae

We have extended the method of transposon mutagenesis to the eukaryote, Saccharomyces cerevisiae. A bacterial transposon containing a selectable yeast gene can be transposed into a cloned fragment of yeast DNA in Escherichia coli, and the transposon insertion can be returned to the yeast genome by homologous recombination. Initially, the cloned yeast DNA fragment to be mutagenized was transformed into an E. coli strain containing an F factor derivative carrying the transposable element. The culture was grown to allow transposition and cointegrate formation and, upon conjugation, recipients were selected that contained yeast sequences with transposon insertions. The yeast DNA was removed from the vector by restriction endonuclease digestion, and the transposon insertion was transformed into yeast. The procedure required a minimum number of manipulations, and each transconjugant colony contained an independent insertion. We describe 12 transposon Tn3 derivatives for this procedure as well as several cloning vectors to facilitate the method.
BMS-284756 in Experimental Cephalosporin-Resistant Pneumococcal Meningitis

BMS-284756 is a novel des-fluoro(6) quinolone with a broad antimicrobial activity, including Streptococcus pneumoniae. The purpose of this study was to evaluate the pharmacodynamic profile and effectiveness of BMS-284756 for therapy of experimental meningitis caused by penicillin- and cephalosporin-resistant S. pneumoniae (CRSP). Meningitis was induced in rabbits by intracisternal inoculation of CRSP. BMS-284756 was given intravenously 16 h after intracisternal inoculation in single doses of 2.5 (n = 5 animals), 5 (n = 6), 10 (n = 6), 20 (n = 8), and 30 mg/kg (n = 6), in two doses of 10 mg/kg each separated by 5 h (n = 4), and as a 20-mg/kg dose followed 5 h later by 10 mg/kg (n = 5). The MICs and MBCs of BMS-284756, ceftriaxone, and vancomycin were 0.06 and 0.06, 4 and 4, and 0.25 and 0.25 microg/ml, respectively. After single doses of 10, 20, and 30 mg/kg, the maximum concentrations in cerebrospinal fluid (CSF) (mean +/- standard deviation) were 0.32 +/- 0.12, 0.81 +/- 0.38, and 1.08 +/- 0.43 microg/ml, respectively; the elimination half-life in CSF was 4.5 to 6.3 h. The CSF bacterial killing rates (BKR) at 5 h of the single-dose regimens of 10, 20 and 30 mg/kg were -0.84 +/- 0.48, -1.09 +/- 0.32, and -1.35 +/- 0.05 Deltalog(10) CFU/ml/h. The BKR(0-5) of the divided regimens (10 mg/kg twice and 20 mg/kg followed by 10 mg/kg) was -0.82 +/- 0.52 and -1.24 +/- 0.34 Deltalog(10) CFU/ml/h, respectively. The BKR(0-5) of the combined therapy with vancomycin and ceftriaxone was -1.09 +/- 0.39 Deltalog(10) CFU/ml/h. The penetration of BMS-284756 into purulent CSF relative to plasma was 14 to 25%. The bactericidal effect of BMS-284756 in CSF was concentration dependent. BMS-284756 at 30 mg/kg as a single or divided dose was as effective as standard therapy with vancomycin and ceftriaxone.
Hybrid Analysis Method for Reliability-Based Design Optimization

Reliability-Based Design Optimization (RBDO) involves evaluation of probabilistic constraints, which can be done in two different ways, the Reliability Index Approach (RIA) and the Performance Measure Approach (PMA). It has been reported in the literature that RIA yields instability for some problems but PMA is robust and efficient in identifying a probabilistic failure mode in the RBDO process. However, several examples of numerical tests of PMA have also shown instability and inefficiency in the RBDO process if the Advanced Mean Value (AMV) method, which is a numerical tool for probabilistic constraint evaluation in PMA, is used, since it behaves poorly for a concave performance function, even though it is effective for a convex performance function. To overcome difficulties of the AMV method, the Conjugate Mean Value (CMV) method is proposed in this paper for the concave performance function in PMA. However, since the CMV method exhibits the slow rate of convergence for the convex function, it is selectively used for concave-type constraints. That is, once the type of the performance function is identified, either the AMV method or the CMV method can be adaptively used for PMA during the RBDO iteration to evaluate probabilistic constraints effectively. This is referred to as the Hybrid Mean Value (HMV) method. The enhanced PMA with the HMV method is compared to RIA for effective evaluation of probabilistic constraints in the RBDO process. It is shown that PMA with a spherical equality constraint is easier to solve than RIA with a complicated equality constraint in estimating the probabilistic constraint in the RBDO process. NOMENCLATURE X
Statistical methods for modeling repeated measures of maternal environmental exposure biomarkers during pregnancy in association with preterm birth

Background: It is of critical importance to evaluate the role of environmental chemical exposures in premature birth. While a number of studies investigate this relationship, most utilize single exposure measurements during pregnancy in association with the outcome. The studies with repeated measures of exposure during pregnancy employ primarily cross-sectional analyses that may not be fully leveraging the power and additional information that the data provide. Methods: We examine 9 statistical methods that may be utilized to estimate the relationship between a longitudinal exposure and a binary, non-time-varying outcome. To exemplify these methods we utilized data from a nested case–control study examining repeated measures of urinary phthalate metabolites during pregnancy in association with preterm birth. Results: The methods summarized may be useful for: 1) Examining sensitive windows of exposure in association with an outcome; 2) Summarizing repeated measures to estimate the relationship between average exposure and an outcome; 3) Identifying acute exposures that may be relevant to the outcome; and 4) Understanding the contribution of temporal patterns in exposure levels to the outcome of interest. In the study of phthalates, changes in urinary metabolites over pregnancy did not appear to contribute significantly to preterm birth, making summary of average exposure across gestation optimal given the current design. Conclusions: The methods exemplified may be of great use in future epidemiologic research projects intended to: 1) Elucidate the complex relationships between environmental chemical exposures and preterm birth; 2) Investigate biological mechanisms in prematurity using repeated measures of maternal factors throughout pregnancy; and 3) More generally, address the relationship between a longitudinal predictor and a binary, non-time-varying outcome.
Cross-Polar Nomalies

Generally, explanations for the anomaly of these examples are based on the intuition that degrees of ‘tallness’ and degrees of ‘shortness’ are of a different nature and hence cannot be compared. Note that this is not obvious, since pre-theoretically one may think that tallness and shortness are different words for the same measurement, roughly: vertical spacial extension (or simply: height). Kennedy (2001) (following Rullmann 1995, Seuren 1978, 1984, von Stechow 1984: a.o.) provides a very elegant implementation of this idea: An A+ like tall relates an individual to a positive length, an Alike short to a negative one, where a positive length is an interval (a set of degrees) that starts just above 0 and extends up to an object’s height (length/width/richness. . . ), whereas a negative length is an interval that starts just above an object’s height (length/width/richness . . . ) and goes up to ∞. Whatever the semantics of (mo)re, it cannot compare a positive with a negative length (in this technical sense), hence the anomaly of (1). On the other hand, since, say, tallness and shortness ‘live’ on the same scale and are logically related to an object’s height, the usual entailment patterns (A is taller than B iff B is shorter than A etc.) follow under any reasonable semantics for relational measure constructions.
Persistent Peripheral Inflammation Attenuates Morphine-induced Periaqueductal Gray Glial Cell Activation and Analgesic Tolerance in the Male Rat

Abstract Morphine is among the most prevalent analgesics prescribed for chronic pain. However, prolonged morphine treatment results in the development of analgesic tolerance. An abundance of evidence has accumulated indicating that central nervous system glial cell activity facilitates pain transmission and opposes morphine analgesia. While the midbrain ventrolateral periaqueductal gray (vlPAG) is an important neural substrate mediating pain modulation and the development of morphine tolerance, no studies have directly assessed the role of PAG glia. Here we test the hypothesis that morphine-induced increases in vlPAG glial cell activity contribute to the development of morphine tolerance. As morphine is primarily consumed for the alleviation of severe pain, the influence of persistent inflammatory pain was also assessed. Administration of morphine, in the absence of persistent inflammatory pain, resulted in the rapid development of morphine tolerance and was accompanied by a significant increase in vlPAG glial activation. In contrast, persistent inflammatory hyperalgesia, induced by intraplantar administration of complete Freund’s adjuvant (CFA), significantly attenuated the development of morphine tolerance. No significant differences were noted in vlPAG glial cell activation for CFA-treated animals versus controls. These results indicate that vlPAG glia are modulated by a persistent pain state, and implicate vlPAG glial cells as possible regulators of morphine tolerance. Perspective The development of morphine tolerance represents a significant impediment to its use in the management of chronic pain. We report that morphine tolerance is accompanied by increased glial cell activation within the vlPAG, and that the presence of a persistent pain state prevented vlPAG glial activation and attenuated morphine tolerance.
Additive Levy Processes: Capacity and Hausdorff Dimension

This is a survey on recently-developed potential theory of additive Levy processes and its applications to fractal geometry of Levy processes.
Predicting nonmarital romantic relationship dissolution: A meta-analytic synthesis

A meta-analysis of predictors of nonmarital romantic relationship dissolution was conducted, including data collected from 37,761 participants and 137 studies over 33 years. Individual, relationship, and external variables were investigated, and results suggest that commitment, love, inclusion of other in the self, and dependence were among the strongest predictors of dissolution. Other relational variables such as satisfaction, perceptions of alternatives, and investments were modest predictors of breakup, and the external factor of social network support was also a robust predictor. Personality measures were found to have limited predictive utility, with small effects found for dimensions relational in nature (e.g., adult attachment orientations). Theoretical and methodological implications are discussed within the context of future research on nonmarital relationship dissolution.
A multienzyme complex channels substrates and electrons through acetyl-CoA and methane biosynthesis pathways in Methanosarcina.

Multienzyme complexes catalyze important metabolic reactions in many organisms, but little is known about the complexes involved in biological methane production (methanogenesis). A crosslinking-mass spectrometry (XL-MS) strategy was employed to identify proteins associated with coenzyme M-coenzyme B heterodisulfide reductase (Hdr), an essential enzyme in all methane-producing archaea (methanogens). In Methanosarcina acetivorans, Hdr forms a multienzyme complex with acetyl-CoA decarbonylase synthase (ACDS), and F420-dependent methylene-H4MPT reductase (Mer). ACDS is essential for production of acetyl-CoA during growth on methanol, or for methanogenesis from acetate, whereas Mer is essential for methanogenesis from all substrates. Existence of a Hdr:ACDS:Mer complex is consistent with growth phenotypes of ACDS and Mer mutant strains in which the complex samples the redox status of electron carriers and directs carbon flux to acetyl-CoA or methanogenesis. We propose the Hdr:ACDS:Mer complex comprises a special class of multienzyme redox complex which functions as a “biological router” that physically links methanogenesis and acetyl-CoA biosynthesis pathways.
Laser altimetry using pseudo-noise code modulated fiber lasers and photon counting detectors

Laser altimeters using pulse code modulated fiber lasers and photon counting detectors appear to have attractive features for future airborne and space-based altimeter missions. We report some initial performance calculations and laboratory measurements using this technique.
A hike through post-EJB J2EE Web application architecture. Part II

This is the second article in an occasional series on Web application development. The first installment, published in the September/October 2005 issue ("A Hike through Post-EJB J2EE Web Application Architecture," vol. 7, no. 5, pp. 80-88), focused on the upper tiers that comprise the user interface; here, the author focuses on the lower tiers. He started with a blueprint of a typical post-Enterprise JavaBeans (EJB) Java 2 Enterprise Edition (J2EE) Web application architecture. Several functional and nonfunctional requirements drive such architectures, and they've become relatively standard. Within this architecture, we looked at the core functionality of our running example - linear regression over a persistent set of points - and then hiked our way upward through successive user interface layers, including dynamic behavior, presentation, internationalization, navigation, layout, and visual styles. During the hike, we looked at typical technologies for each layer. In this article, we descend into our application's invisible innards. Specifically, the author examines business service objects, object-relational mappings, lightweight containers (for painlessly connecting the various pieces), security, and concurrency. Our ultimate goal is to facilitate the development of reliable, flexible, and efficient server-based Web applications
Pseudomembranous Colitis: Not Always Caused by Clostridium difficile

Although classically pseudomembranous colitis is caused by Clostridium difficile, it can result from several etiologies. Certain medications, chemical injury, collagenous colitis, inflammatory bowel disease, ischemia, and other infectious pathogens can reportedly cause mucosal injury and subsequent pseudomembrane formation. We present the case of a middle-aged woman with vascular disease who was incorrectly diagnosed with refractory C. difficile infection due to the presence of pseudomembranes. Further imaging, endoscopy, and careful histopathology review revealed chronic ischemia as the cause of her pseudomembranous colitis and diarrhea. This case highlights the need for gastroenterologists to consider non-C. difficile etiologies when diagnosing pseudomembranous colitis.
INSTITUTIONS FOR MARINE ECOSYSTEMS: ECONOMIC INCENTIVES AND FISHERY MANAGEMENT

The expansion of the scope of fishery management from single species to ecosystems requires more than a set of rules for multiple species. It requires sets of institutions and property rights regimes that reflect the attributes of the ecosystem and its human users, value ecosystem services as well as ecosystem commodities, and coordinate interest groups and managers on a broad ecosystem scale. Institutions that properly coordinate the human use of ecosystems have several functions. They must create management structures that promote the definition of multiple objectives and coordinate organizational tasks in a cost-effective way. They must also create management processes that are legitimate, flexible, and promote socially appropriate time horizons that recognize intergenerational rights to resource use. Each of these functions has economic dimensions that are critical to their successful implementation. This paper identifies some of the important economic dimensions of resource management institutions th...
Guidelines for enhancing homework compliance.

The ability to enhance compliance with therapeutic tasks such as homework may be a crucial therapeutic skill that determines the success of psychotherapy in real-world clinical settings. This article presents guidelines for enhancing homework compliance through careful attention to: features of homework assignments, such as whether they are meaningful and doable and include a clear rationale and backup plan; and the therapist's manner when developing and reviewing homework assignments, such as whether that therapist is curious, collaborative, and reinforces all behavior that supports the homework's purposes. Clinical examples are used to illustrate the application of the guidelines.
Angle of arrival detection using compressive sensing

The conventional method for determining target angle of arrival with an array of sensors is to digitize the output of each sensor at the Nyquist sampling rate for the system bandwidth and use digital signal processing algorithms such as maximum likelihood estimation or multiple signals classification (MUSIC). Here we show that if the targets sparsely populate the angle/frequency domain, the angles and frequencies can be obtained from a much smaller number of measurements by randomly summing sensor outputs and by randomly sampling in time through the use of a novel application of recently developed compressive sensing algorithms.
Constituents of Mammea Americana L. VIII: Novel Structural Variations on the Mammein Theme and Antitumor Activity of Mammein and Related Coumarin and Phloroglucinol Derivatives

Mammein (4-n-propyl-5,7-dihydroxy-6-isopentenyl-8-isovalerylcoumarin) was shown to be accompanied by two difficultly separable congeners: the 8-α-methylbutyryl isomer (neomammein) and the 8-n-butyryl homolog (normammein). In addition, new analogs of these compounds in which the 6-isopentenyl groups have undergone oxidative cyclization with the 5-hydroxyl groups were isolated and identified by spectroscopic means. Each of these substances was also obtained by peracid oxidation of its noncyclized relatives. Significant antitumor activity against Sarcoma 180 grown in stationary cell culture was exhibited by mammein and certain of its companions, as well as by various degradation and synthetic intermediates.
Insight into DEG/ENaC Channel Gating from Genetics and Structure

A review and reinterpretation of mutagenesis in a structural framework of the DEG/ENaC channels required for touch and pain sensation.
Values influencing nursing practice: responses from neonatal nurses.

purpose. An analysis of narrative comments from neonatal nurses to illustrate the values that motivate behavior in the practice setting. design. A descriptive study using content analysis of written, narrative text data. participants. A self-selected subsample (N = 97) of a larger random sample of the membership of the National Association of Neonatal Nurses (NANN). main outcome measures. The application of philosophical concepts of human relationships, patient need, keeping promises, human dignity, and unrestricting circumstances in the neonatal care setting. results. Individual participants made cognitive choices related to the application of conceptual ideals of the profession to the practice setting. However, there was a lack of congruence between what the individual nurse believes is important or good and the behavior enacted in the practice setting. conclusion. As a discipline, nursing needs to identify and implement strategies that support proactive accountable nursing practice consistent with the philosophical foundation of the profession.
Emergency-management situational-awareness prototype (EMSAP)

This paper describes the architecture and requirements of an integrated system that is needed to support command and control for the interoperability-capability focus area. The architecture is designed to enhance situational awareness during emergencies such as earthquakes, volcanic eruptions, wild fires, floods, tsunamis, mud slides, storms, tornadoes, hurricanes, extreme heat, extreme cold, massive disease outbreaks, wars, terror-ist attacks, power outages, cyber-attacks on utility grids and civil unrest. A net-centric approach that emphasizes cognitive aspects, such as cognitive-information operations, in decision support ensures information superiority by networking sensors and human-factors monitoring. This enables decision makers to achieve shared awareness. Linking knowledgeable entities effectively leads to in-creased speed of command and a higher tempo of operations with a degree of self-synchronization. The resulting system will decrease cognitive over-load and improve cognitive monitoring by providing a more systematic and less labor-intensive method to manage information from and for first res-ponders at the local, tribal, state, and federal levels.
Mono- and tri-ester hydrogenolysis using tandem catalysis. Scope and mechanism

The scope and mechanism of thermodynamically leveraged ester RC(O)O–R′ bond hydrogenolysis by tandem metal triflate + supported Pd catalysts are investigated both experimentally and theoretically by DFT and energy span analysis. This catalytic system has a broad scope, with relative cleavage rates scaling as, tertiary > secondary > primary ester at 1 bar H2, yielding alkanes and carboxylic acids with high conversion and selectivity. Benzylic and allylic esters display the highest activity. The rate law is ν = k[M(OTf)n]1[ester]0[H2]0 with an H/D kinetic isotope effect = 6.5 ± 0.5, implying turnover-limiting C–H scission following C–O cleavage, in agreement with theory. Intermediate alkene products are then rapidly hydrogenated. Applying this approach with the very active Hf(OTf)4 catalyst to bio-derived triglycerides affords near-quantitative yields of C3 hydrocarbons rather than glycerol. From model substrates, it is found that RC(O)O–R′ cleavage rates are very sensitive to steric congestion and metal triflate identity. For triglycerides, primary/external glyceryl CH2–O cleavage predominates over secondary/internal CH–O cleavage, with the latter favored by less acidic or smaller ionic radius metal triflates, raising the diester selectivity to as high as 48% with Ce(OTf)3.
The Impact of Expectations Manipulation on the Usefulness of Analyst Forecasts in Firm Valuation

This paper examines the impact of expectations manipulation on the usefulness of analyst forecasts in the residual income valuation model. Recognizing that firms may guide down analyst forecast to either truthfully communicate information (legitimate guidance) or mislead analysts to produce beatable forecasts (expectations manipulation), this study first develops a measure to isolate expectations manipulation from the overall forecast guidance. It then assesses forecast usefulness by the performance of forecast-based intrinsic value metrics (V) to predict firm value. The results show that V estimated using manipulated forecasts have less ability to explain stock price and predict future returns. These results remain after controlling for firm size, earnings performance, forecast accuracy, etc. Based on these findings, I conclude that expectations manipulation reduces the usefulness of analyst forecasts in firm valuation, as it impairs the performance of forecast-based valuation models to predict firm value.
RNA and protein synthesis in control and follicularly-aged rat oocytes.

SummaryAutoradiographic analysis revealed that follicularly-aged oocytes show a significant reduction in RNA synthesis, but the capacity to synthesize protein was unaltered. Abnormally low amounts of RNA were synthesized by 54% of the oocytes obtained from delayed-ovulatory rats and 7% of the control oocytes. The reduced RNA synthesis characteristic of the aged oocyte could be associated with metabolic changes which are responsible for the developmental anomalies.Evaluation of RNA and protein synthesis in the cumulus cell mass, which surrounds the tubal oocyte, demonstrated that neither the percentage of cells labeled, nor the amount of RNA or protein synthesized by the cumulus cells, is altered during the follicular aging process. However, the cumulus cells which enclose the oocyte are more loosely associated with the aged oocyte.
Uptake of dietary milk miRNAs by adult humans: a validation study

Breast milk is replete with nutritional content as well as nucleic acids including microRNAs (miRNAs). In a recent report, adult humans who drank bovine milk appeared to have increased circulating levels of miRNAs miR-29b-3p and miR-200c-3p. Since these miRNAs are homologous between human and cow, these results could be explained by xeno-miRNA influx, endogenous miRNA regulation, or both. More data were needed to validate the results and explore for additional milk-related alterations in circulating miRNAs. Samples from the published study were obtained, and 223 small RNA features were profiled with a custom OpenArray, followed by individual quantitative PCR assays for selected miRNAs. Additionally, small RNA sequencing (RNA-seq) data obtained from plasma samples of the same project were analyzed to find human and uniquely bovine miRNAs. OpenArray revealed no significantly altered miRNA signals after milk ingestion, and this was confirmed by qPCR. Plasma sequencing data contained no miR-29b or miR-200c reads and no intake-consistent mapping of uniquely bovine miRNAs. In conclusion, the results do not support transfer of dietary xenomiRs into the circulation of adult humans.
Trends in demographics, incidence, and survival in children, adolescents and young adults (AYA) with melanoma: A Surveillance, Epidemiology and End Results (SEER) population-based analysis.

9058 Background: Whilemelanoma incidence continues to rise in the United States, trends in children and AYA groups are poorly defined.Understanding the burden in these groups is critical in develop...
Effect of NBCe1 deletion on renal citrate and 2-oxoglutarate handling.

Abstract The bicarbonate transporter, NBCe1 (SLC4A4), is necessary for at least two components of the proximal tubule contribution to acid‐base homeostasis, filtered bicarbonate reabsorption, and ammonia metabolism. This study9s purpose was to determine NBCe19s role in a third component of acid‐base homeostasis, organic anion metabolism, by studying mice with NBCe1 deletion. Because NBCe1 deletion causes metabolic acidosis, we also examined acid‐loaded wild‐type adult mice to determine if the effects of NBCe1 deletion were specific to NBCe1 deletion or were a non‐specific effect of the associated metabolic acidosis. Both NBCe1 KO and acid‐loading decreased citrate excretion, but in contrast to metabolic acidosis alone, NBCe1 KO decreased expression of the apical citrate transporter, NaDC‐1. Thus, NBCe1 expression is necessary for normal NaDC‐1 expression, and NBCe1 deletion induces a novel citrate reabsorptive pathway. Second, NBCe1 KO increased 2‐oxoglutarate excretion. This could not be attributed to the metabolic acidosis as experimental acidosis decreased excretion. Increased 2‐oxoglutarate excretion could not be explained by changes in plasma 2‐oxoglutarate levels, the glutaminase I or the glutaminase II generation pathways, 2‐oxoglutarate metabolism, its putative apical 2‐oxoglutarate transporter, OAT10, or its basolateral transporter, NaDC‐3. In summary: (1) NBCe1 is necessary for normal proximal tubule NaDC‐1 expression; (2) NBCe1 deletion results in stimulation of a novel citrate reabsorptive pathway; and (3) NBCe1 is necessary for normal 2‐oxoglutarate metabolism through mechanisms independent of expression of known transport and metabolic pathways.
Does Social Endorsement Influence Physiological Arousal

Endorsement cues on social media (e.g., "Trending", "Like"s or "Retweet"s) lead to greater interest in the content [6]. This preliminary study explores how the perceived social endorsement of both stimulating and non-stimulating content influences physiological arousal (skin conductance level). Stimulating pictures triggered more physiological arousal than non-stimulating pictures, but only when the picture was framed as a "trending" picture. When the picture was labeled as a "non-trending" picture, non-stimulating pictures induced higher levels of physiological arousal than stimulating pictures. The present study lends insight into how people respond to endorsement cues on social media from an affective level. More importantly, it shows that endorsement on social media is not the panacea for receiving attention; the inherent nature of the content plays a critical role in how social cues are perceived.
The Research on Radiation Environmental Impact of the Container Radiographic Inspection System

Based on field investigation and monitoring,with a Large container inspection system as the study object,comparing the regulations of Radiological protection standard for container inspection system(GBZ143-2002) and Basic standards for protection against ionizing radiation and for the safety of radiation sources(GB18871-2002),environmental impaction of ionizing radiation to project circumjacent area was quantitatively assessed.Then some conclusions and corresponding suggestions for ionizing radiation were proposed.
Rebuilding the ED.

A nurse manager of a busy urban emergency department (ED) recounts a $10.7 million complete renovation and expansion that added close to 20,000 square feet to the unit. Advice includes how to plan for security and equipment needs, create a design that exceeds expectations, get the ED through the ambitious construction phase--and anticipate the personal needs that accompany added responsibility.
A Molecule-Scale View of the Structure and Specificity of the RNA-Guided Endonuclease Cas9

CRISPR-associated endonuclease Cas9 binds to and cleaves DNA at sites dictated by a variable sequence in an RNA molecule that is bound to it. This ability of Cas9 to be directed by a modular ‘single-guide’ RNA molecule (sgRNA) to target nearly any DNA sequence has recently been exploited for a number of emerging biological and biomedical applications: in particular, Cas9-based technologies have been re-appropriated in heterologous systems for remarkably facile genomic engineering. Therefore, understanding the molecular-scale factors that drive Cas9 to target these sites and the nature of its reported off-target activity are of paramount importance for its practical usage and will be vital in developing new ways to improve its specificity. Using atomic force microscopy (AFM), we are able to directly resolve individual Cas9 and nuclease-inactivate dCas9 proteins as they bind along engineered DNA substrates. High-resolution imaging allows us to determine their relative propensities to bind to targeted or off-target sequences, which we are able to modulate performance and specificity by re-engineering sgRNAs with variant structures, and map the structural properties of Cas9 and dCas9 to their respective binding sites. In combination with kinetic Monte Carlo (KMC) simulations, these results reveal a progressive conformational transformation at DNA sites with increasing sequence similarity to its target is identified and provide evidence of a conformational gating’ governing Cas9 and dCas9 specificity. Additionally, we are able to correlate the results of our KMC simulations and model for Cas9-DNA interactions with reported off-target cleavage rates of Cas9 in vivo. Our results reveal new methodologies to engineer guide RNA sequences and structures that improve Cas9 and dCas9 specificity.
Land acquisition, rural protests, and the local state in China and India

As China and India urbanize, land acquisition by state and private actors has become highly contentious in both countries. This article compares two large-scale anti-land acquisition protests—the Wukan protest in China’s Guangdong province and the Singur protest in the Indian state of West Bengal—to examine how the subnational state partakes in land acquisition and how rural protesters engage with different levels of the state in their resistance. The comparative analysis finds that the different involvement of the subnational state in land speculation has produced different spatiality and dynamics of protests. In China, rural protesters target the bottom-level authority such as village councils, often taking on a cellular form of mobilization geographically confined to their particular villages. By comparison, in India rural protesters target the regional state governments and they engage in associational forms of mobilization by building ad hoc alliances with political parties and NGOs beyond the affect...
Nonmedical use of prescription drugs in emerging adulthood: differentiating sex from gender.

AbstractMale–female variations in health-behavior continue to be of national and international significance with men generally being more likely to be engaged in behaviors that enhance risk across an array of preventable diseases and injuries as well as premature deaths. The literature has identified nonmedical use of prescription drugs (NMUPD) as a developing and particularly dangerous substance use behavior among college students. The literature has reported sex differences (male; female) in NMUPD but has yet to explain how gender orientation (e.g. masculine, feminine) might impact NMUPD. The purpose of this study is to address this gap by examining the influence of gender-orientation on NMUPD. Using survey data collected during the 2013–2014 academic year from a convenience sample of college students at a mid-sized Midwestern university, we examine the association of gender-orientation and NMUPD (N = 796). To do this, we separated masculine and feminine scales from the BEM Sex Role Inventory and used l...
Unconventional Oil and Gas Spills: Risks, Mitigation Priorities, and State Reporting Requirements

Rapid growth in unconventional oil and gas (UOG) has produced jobs, revenue, and energy, but also concerns over spills and environmental risks. We assessed spill data from 2005 to 2014 at 31 481 UOG wells in Colorado, New Mexico, North Dakota, and Pennsylvania. We found 2–16% of wells reported a spill each year. Median spill volumes ranged from 0.5 m3 in Pennsylvania to 4.9 m3 in New Mexico; the largest spills exceeded 100 m3. Seventy-five to 94% of spills occurred within the first three years of well life when wells were drilled, completed, and had their largest production volumes. Across all four states, 50% of spills were related to storage and moving fluids via flowlines. Reporting rates varied by state, affecting spill rates and requiring extensive time and effort getting data into a usable format. Enhanced and standardized regulatory requirements for reporting spills could improve the accuracy and speed of analyses to identify and prevent spill risks and mitigate potential environmental damage. Tran...
Maternal occupational physical activity and risk for orofacial clefts

Objectives To perform a case-control study of maternal occupational physical activity and risk for orofacial clefts in Texas during 1999-2009. Methods We used logistic regression to assess 14 measures of physical activity estimated from a job exposure matrix, using the maternal occupation reported on the birth certificate, among 887 children with cleft lip with or without cleft palate (CLP), 436 children with cleft palate only (CP), and 1932 controls. Results After adjusting for several potential confounders, seven measures of physical activity (as a categorical and/or continuous variable) were significantly associated with CLP, CP, or both. Positive associations were seen for keeping balance, kneeling, standing, and walking/running (odds ratio 95% confidence interval range 1.0-1.9 for fourth versus first quartile). A significant positive trend was also seen for bending/twisting. Negative associations were seen for repetitive motion and sitting. Conclusions Maternal occupational physical activity may be related to the etiology of orofacial clefts.