cssi/SciSciGPT-SciSciNet huggingface dataset:
Calcium-dependent cyclic nucleotide phosphodiesterase from brain identification of phospholipids as calcium-independent activators.

Abstract Phosphatidyl inositol and lysophosphatidyl choline have been identified as activators of a partially purified brain cyclic nucleotide phosphodiesterase previously shown to be regulated in vitro by Ca 2+ and a Ca 2+ -binding protein. Microgram quantities of either phospholipid produced a linear, immediate and reversible activation of the enzyme in the absence of Ca 2+ and the Ca 2+ -dependent regulator (CDR). Fatty acids were also found to activate the phosphodiesterase to varying degrees, with oleic acid being the most effective. Phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl serine and lysophosphatidyl ethanolamine were not effective as activators. Only sodium dodecyl sulfate, of a variety of nonionic, cationic, and anionic detergents tested, activated the phosphodiesterase. Sodium dodecyl sulfate produced a modest degree of activation over a narrow concentration range, followed by enzyme denaturation at higher concentrations. The interaction of the phosphodiesterase with the phospholipid activators has been compared to its interaction with the Ca 2+ ·CDR complex. Both Ca 2+ ·CDR and lysophosphatidyl choline decreased the thermal stability of the enzyme to a similar extent. The apparent K m of the lysophosphatidyl choline-dependent phosphodiesterase activity was approximately 30 μ m with guanosine-3′,5′-monophosphate (cGMP) as substrate and 1 m m with adenosine-3′,5′-monophosphate (cAMP) as substrate. With increasing lysophosphatidyl choline concentration, the apparent K m for each nucleotide remained unchanged while the V increased. The apparent K d for Mg 2+ of the lysophosphatidyl choline-dependent phosphodiesterase activity was approximately 3 μ m and was unaffected by lysophosphatidyl choline concentration. Activation of the phosphodiesterase by lysophosphatidyl choline was characterized by a high degree of positive cooperativity, exhibiting a Hill coefficient of 3.8. Fluphenazine was a competitive inhibitor of both Ca 2+ ·CDR and lysophosphatidyl choline activation of the enzyme.
Relationships between plasma cytokine concentrations and leukocyte functional antigen expression in patients with sepsis

OBJECTIVE To determine the relationships between cytokine concentrations and alterations in leukocyte functional antigen expression in sepsis. DESIGN Prospective, cross-sectional study. SETTING Respiratory, coronary, and medical intensive care units in a university hospital. PATIENTS Forty subjects consisting of: a) patients with severe sepsis, b) patients with sepsis, c) critically ill nonseptic patients, and d) normal controls. INTERVENTIONS None. MEASUREMENTS Plasma concentrations of interleukin (IL)-1 beta, IL-6, IL-8, IL-10, interleukin-1 receptor antagonist (IL-1Ra), and tumor necrosis factor (TNF)-alpha were determined by enzyme-linked immunosorbent assay (ELISA). Peripheral blood monocyte HLA-DR and CD14 expression and neutrophil CD11b expression were determined by flow cytometry. Measurements were taken within 24 hrs of admission to the intensive care unit and/or clinical presentation. MAIN RESULTS Significantly increased plasma IL-6, IL-8, IL-10, and TNF-alpha concentrations were observed in the severe sepsis group compared to normal controls. Increases in IL-1Ra were not significant. Monocyte HLA-DR expression, significantly decreased in patients with severe sepsis, was correlated both with IL-6 (p < .005) and IL-8 concentrations (p < .001). Both of these cytokines had close correlations to Acute Physiology and Chronic Health Evaluation (APACHE) II scores which were also correlated with monocyte HLA-DR. Neutrophil CD11b, which was increased in all infected patients, was significantly correlated with the ratio between IL-1 and IL-1Ra concentrations (p < .001). The percent of CD14+ monocytes was lowest in patients with severe sepsis and showed a significant covariate effect from IL-8 concentrations (p < .001). CONCLUSION These findings suggest that the expression of specific functional molecules on peripheral blood leukocytes is variably related to the net production of certain monokines in sepsis.
Smooth muscle cells: the source of foam cells in atherosclerotic white Carneau pigeons.

Abstract Although the endothelium and adventitia in pigeon aortas are typical, the normal architecture of the tunica media differs from that in aortas from other species. The media contains two cell types: smooth muscle cells and nonmuscular interlaminar cells, which are present in alternate layers. Clusters of bleb-like surface differentiations from smooth muscle cells pass through fenestrations in the elastic laminae and impinge upon adjacent interlaminar cells. Aortic structure in embryos, squabs, immature, and mature birds is described. The earliest detectable atherosclerotic involvement was observed at 4 months in distal portions of the thoracic aorta of White Carneau pigeons. These alterations consisted of foci of modified smooth muscle cells in areas where the normal alternating layers of smooth muscle cells and interlaminar cells were disrupted. Interlaminar cells were not found in the atherosclerotic foci. In advanced lesions, modified smooth muscle cells were observed in progressively rounded forms with clear vacuoles, myelin figures, and clefts. No types of blood-derived cells were present in contrast to other species in which both smooth muscle cells and blood-derived cells are reported to transform to foam cells. Smooth muscle cell changes in orientation and cytoplasmic degeneration are postulated to be the basic phenomena in pigeon atherosclerosis.
Participation of the fingers subdomain of Escherichia coli DNA polymerase I in the strand displacement synthesis of DNA.

The replication of the genome requires the removal of RNA primers from the Okazaki fragments and their replacement by DNA. In prokaryotes, this process is completed by DNA polymerase I by means of strand displacement DNA synthesis and 5 ′-nuclease activity. Here, we demonstrate that the strand displacement DNA synthesis is facilitated by the collective participation of Ser769, Phe771, and Arg841 present in the fingers subdomain of DNA polymerase I. The steady and presteady state kinetic analysis of the properties of appropriate mutant enzymes suggest that: (a) Ser769 and Phe771 together are involved in the strand separation via the formation of a flap structure, and (b) Arg841 interacts with the template strand to achieve the optimal strand separation and DNA synthesis. The amino acid residues Ser769 and Phe771 are constituents of the O1-helix, which together with O and O2 helices form a 3-helix bundle structure. We note that this 3-helix bundle motif also exists in prokaryotic RNA polymerase. Thus in both DNA and RNA polymerases, this motif may have been adopted to achieve the strand separation function.
Research Note: A Longitudinal Study of the Stability of Interpretative Schemes, Organizational Structure, and their Contextual Correlates

This article reports the results of a longitudinal investigation of how interpretative schemes of organizational members change through time, and whether any contextual factors are related to this change. In an exploratory study of two bureaux of an American state highway department, which are different in terms of work demands, interpersonal interactions, and subordinate-superior relations, multidimensional scaling methodology is utilized to detect any changes in the perception of interpersonal interaction, which is assumed to represent the interpretative schemes of organization members. Results show that during a period of five years neither the perception of interpersonal interaction nor the contextual variables changed to a considerable degree. The only change which occurred is related to the surface articulation of interpersonal interaction, which is directly influenced by the day-to-day activities of the members.
Chronic immune activation in the eosinophiliamyalgia syndrome

Eosinophilia–myalgia syndrome (EMS) is a multisystem illness of uncertain pathogenesis that occurred in an epidemic related to the ingestion of contaminated L-tryptophan. To investigate the role of immune dysfunction in EMS we prospectively measured a serologic index of T-cell activation, the soluble interleukin-2 receptor (slL-2R), in 7 patients followed into the late stages of the illness. As a group, EMS patients had significantly elevated slL-2R levels throughout the study. Five patients suffered chronic symptoms of myalgia, arthralgia, muscle cramps, fatigue, or subjective memory impairment and all had persistently elevated slL-2R levels. Two patients had near-resolution of EMS and normal slL-2R levels. We conclude that chronic symptoms are common in EMS and are associated with persistent T-cell activation as measured by serum slL-2R levels. These findings suggestthat immunosuppressive treatment may be beneficial in EMS. © 1993 John Wiley & Sons, Inc.
Changes in the self-efficacy of multiple sclerosis clients following massage therapy

Summary Objective This preliminary study was conducted to examine self-efficacy changes in multiple sclerosis (MS) clients following a series of massage therapy treatments. Method The study was based on a prospective single group pre-test post-test design with follow-up. Self-efficacy scores were obtained before the first treatment, after the last treatment in the series, and again 8–12 weeks after the final treatment had been received. Intervention The intervention involved a series of weekly 1 h therapeutic massage treatments conducted over a 16-week period. All treatments were delivered by supervised student therapists in the final term of their 2-year program. Outcome measures Self-efficacy (SE) was the outcome measure for the study. Descriptive statistics for SE scores were assessed, and inferential analysis involved the testing of differences between baseline, post-intervention, and follow-up scores. Results Statistically significant improvement in self-efficacy was noted when baseline and post-intervention scores were compared ( t = 3.212 ; P 0.002 ). At the point of follow-up 8–12 weeks after the last treatment had been received, self-efficacy scores had decreased and did not differ significantly from baseline ( t = 0.303 ; P 0.382 ). Conclusion The results suggest that massage therapy may increase the self-efficacy of clients with MS, potentially resulting in a better overall adjustment to the disease and an improvement in psycho-emotional state. The increase in self-efficacy noted at the end of the treatment series had dissipated at point of follow-up, suggesting that on-going treatment is required in order to maintain the positive changes observed.
Sequential tunneling transport in GaN/AlGaN quantum cascade structures

We demonstrate electronic sequential tunneling transport through the ground-state subbands of GaN/Al0.15Ga0.85N quantum cascade structures grown on free-standing GaN substrates. A pronounced transition from a high- to a low-resistance state is observed as the applied voltage is increased. The measured current-voltage characteristics are found to vary with temperature, structure design, and polarity of the applied bias, in a way that is fully consistent with theoretical expectations. The dominant transport mechanism is determined to be scattering-assisted tunneling. (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)
Application of {(DMF)10Ln2[Pd(CN)4]3}∞ (Ln = Yb, Sm) as lanthanide–palladium catalyst precursors dispersed on sol–gel–TiO2 in the reduction of NO by methane in the presence of oxygen

Abstract Cyanide bridged lanthanide–palladium transition metal complexes were employed as catalyst precursors in the catalytic reduction of NO with methane. Complexes {(DMF) 10 Ln 2 [Pd(CN) 4 ] 3 } ∞ (Ln=Yb, Sm; DMF=dimethyl formamide) were dispersed (10 wt.% loading based upon palladium) on sol–gel titania supports and reduced by ammonia or hydrogen to metallic nanoparticles containing palladium and lanthanide metals. They were tested for catalytic activity in NO reduction by CH 4 in the presence of oxygen. The bimetallic catalysts were found to be active for NO reduction up to the stoichiometric oxygen concentrations. They displayed improved performance over a palladium only catalyst. Catalysts were examined by TEM, and XPS techniques before, during, and after the reaction.
Using simulation to assess undergraduate nursing students' competency with medication administration to a limited- English language proficiency patient

Background/Objectives: Medication errors continue to be an area of concern in health care and are a significant cause of morbidity and mortality in both inpatient and outpatient settings. Little consideration has been given to the role of the patient in the medication process; patients with limited-English language proficiency (LEP) may be at risk for medical errors and drug complications. The purpose of this research study is to assess undergraduate nursing students’ competency with medication administration to a simulated patient with LEP. Methods: A non-experimental quantitative design using the Medication Administration Safety Assessment Tool (MASAT) (Copyright © 2013 Goodstone & Goodstone) for student competency in medication administration perfor- mance was conducted in a simulation environment. Qualitative data was also collected during debriefing for questions specific to safety, medication administration, and barriers related to care. Results: Student scores on the MASAT identified a less than expected probability of success. Students’ performance did not show proficiency in the six rights of medication administration; in addition, students’ were inattentive to the language needs of a LEP patient. Conclusion: Results from this study indicate further experiential learning activities may be necessary to reinforce safety in medication administration. Students were not attentive to the language needs of the simulated patient and may require additional learning opportunities through simulation to assist students in responsive behaviors that support LEP patients.
Using tobacco control policies to increase consumer demand for smoking cessation.

Population-based indicators of smoking cessation have stalled in recent years. This commentary focuses attention on tobacco control policies that can be used to stimulate renewed consumer demand for smoking cessation. Tobacco use as reflected in population trends is the product of the interaction of three broad categories of factors: agent, host, and environment. Government policies are an important, modifiable environmental influence that can directly or indirectly influence smoking behavior. For example, numerous studies have shown that a hike in tobacco taxes reduces cigarette consumption and encourages smokers to quit. Such policies typically cause the tobacco industry to respond by offering consumers incentives, such as price discounts on cigarettes, to lessen the impact of tax increases. The challenge faced by tobacco control practitioners is how to market smoking cessation to make it a more attractive consumer choice when compared with what cigarette marketers are doing to keep consumers puffing away. This commentary reviews factors that drive consumer demand for cessation products and services, and discusses how tobacco companies excel at driving consumer demand for their products. Finally, there is a discussion on how tobacco control practitioners and advocates can exploit various policy options that are likely to create demand for smoking-cessation products and services.
Differential regulation of amoA and amoB gene copies in Nitrosomonas europaea

Nitrosomonas europaea contains two nearly identical copies of the operon, amoCAB, which encodes the ammonia monooxygenase (AMO) enzyme. Cells of N. europaea containing single mutations in either amoA or amoB gene copies were incubated in ammonium both prior to and after exposure to acetylene or light. For each strain, the O2 consumption rates and amounts of AmoA polypeptide, the active site-containing subunit of AMO, produced in each strain were determined. Strains carrying a mutation in either the amoA2 or amoB2 genes responded similarly to wild-type cells, but the strains carrying mutations in the amoA1 or amoB1 genes responded differently from the wild-type, or from each other. These results suggest that the copies of amoA and amoB are differentially regulated upon exposure to different external stimuli.
Rethinking the Hellenistic Gulf: The New Greek Inscription from Bahrain

The recent discovery in Bahrain of a Greek inscription, dating to the 120s BC, transforms our understanding of the Arab-Persian Gulf in the Hellenistic period. The inscription, recording the dedication of a shrine to the Dioskouroi on behalf of the first independent king of Characene, indicates that Bahrain was a garrisoned node within the Seleucid Empire and the centre of the previously unknown archipelagic administrative district 'Tylos (Bahrain) and the Islands'. Seleucid and Characenian control of Bahrain is placed within the longue duree political history of relations between southern Mesopotamia and Dilmun. The cultic dedication to the Dioskouroi traces the consciously Hellenizing modalities of Characenian emancipation from the Seleucid Empire and the development of a coherent maritime religious network in the Gulf. The absence of substantial epigraphic or literary attestation for the Seleucid Empire in the Arab- Persian Gulf has led to conservative estimates of the geographical extent of Seleucid and early Characenian dominance, the scale of Seleucid colonizing activities, the existence of a Gulf trade policy and the depth of cultural interpenetration. Over 20 years ago Jean-Francois Salles categor- ically asserted, in political terms, 'nothing suggests that the region was under the direct control of the Seleucid kings, nor is there any clear evidence that it formed part of their area of influence' 1 and, in cultural terms, 'il n'y a pas d'inscription grecque, pas d'expression artistique "occidentalisee", pas de manifestation religieuse qui temoignent de contacts etroits avec le monde mediterraneen ou mesopotamien'. 2 Likewise, in his masterful analysis of the ancient Gulf, Daniel Potts argues that, with the exception of Failaka island (lying just off the Mesopotamian coastline), the region lay outside the boundaries of the Seleucid Empire and was never deeply impacted by Hellenism. 3 Dominance over the Arab-Persian Gulf, and Bahrain in particular, by the southern Mesopotamian Kingdom of Characene was understood as a later, Common Era development, attested by a bilingual caravan-inscription from Palmyra. 4
Three new species of Luttrellia from temperate and tropical freshwater habitats.

Three pyrenomycetes collected from woody debris submerged in freshwater habitats are described as new species of Luttrellia: L. guttulata sp. nov., L. halonata sp. nov. and L. parvulospora sp. nov. A collection of L. estuarina, the type species of the genus, having ascospores surrounded by a gelatinous sheath, a characteristic not observed in the type specimen, is reported. The genus description is emended to include fungi with 4- or 8-spored asci and ascospores with or without a gelatinous sheath. Luttrellia is distinguished from other genera in the Halosphaeriaceae by hyaline, phragmoseptate, and thick-walled ascospores with or without a gelatinous sheath.
A nonreentrant crossed-field amplifier with cycloiding injected beam

Nonreentrant injected-beam crossed-field amplifiers usually employ a thin laminar beam positioned well above the sole electrode. In operation, the beam is gradually bunched by a phase-focusing action. This paper describes the analysis and demonstration of such an amplifier, with an important difference: the electrons of the beam have random cycloidal trajectories extending to the sole instead of following the usual linear paths, Rapid and effective bunching is accomplished by collecting antiphase electrons on the sole. Experimental results are presented to show that the approach is useful for high current beams. For example, an output power of 600 watts was obtained at 10 dB gain from an 800 mA beam. The advantages and disadvantages of the cycloidal motion are discussed. The results of computations are given to show the desirable characteristics attainable; for example, a design for an amplifier with a cycloiding beam requires only 35 percent of the interaction length of a laminar-beam type for the same computed power output, gain and efficiency at the same cathode voltage.
Effectiveness of direct manipulation interaction in the supervisory control of FMS part movement

The use of direct manipulation interface technology as a valuable design technique for operator interaction and control with a real-time supervisory control system was examined. To evaluate the effectiveness of a direct manipulation interface, two user interfaces to a simulation of a flexible manufacturing system were evaluated. Five measures that reflected operator performance were analyzed. Subjects using the direct manipulation interface operated the system significantly better on three of the five measures. >
Recursive subtyping revealed

Algorithms for checking subtyping between recursive types lie at the core of many programming language implementations. But the fundamental theory of these algorithms and how they relate to simpler declarative specifications is not widely understood, due in part to the difficulty of the available introductions to the area. This tutorial paper offers an ‘end-to-end’ introduction to recursive types and subtyping algorithms, from basic theory to efficient implementation, set in the unifying mathematical framework of coinduction.
Materials Science Issues of Plasma Source Ion Implantation

Ion beam processing, including ion implantation and ion beam assisted deposition (IBAD), are established surface modification techniques which have been used successfully to synthesize materials for a wide variety of tribological applications. In spite of the flexibility and promise of the technique, ion beam processing has been considered too expensive for mass production applications. However, an emerging technology, Plasma Source Ion Implantation (PSII), has the potential of overcoming these limitations to become an economically viable tool for mass industrial applications. In PSII, targets are placed directly in a plasma and then pulsed-biased to produce a non-line-of-sight process for intricate target geometries without complicated fixturing. If the bias is a relatively high negative potential (20-100kV) ion implantation will result. At lower voltages (50-1200V), deposition occurs. Potential applications for PSII are in low-value-added products such as tools used in manufacturing, orthopedic devices, and the production of wear coatings for hard disk media. This paper will focus on the technology and materials science associated with PSII.
Predictive models for proactive network management: application to a production Web server

Proactive management holds the promise of taking corrective actions in advance of service disruptions. Achieving this goal requires predictive models so that potential problems can be anticipated. Our approach builds on previous research in which HTTP operations per second are studied in a Web server. As in this prior work, we model HTTP operations as two subprocesses, a (deterministic) trend subprocess and a (random but stationary) residual subprocess. Herein, the trend model is enhanced by using a low-pass filter. Further, we employ techniques that reduce the required data history, thereby reducing the impact of changes in the trend process. As in the prior work, an autoregressive model is used for the residual process. We study the limits of the autoregressive model in the prediction of network traffic. Then we demonstrate that long-range dependencies remain in the residual process even after autoregressive components are removed, which impacts our ability to predict future observations. Last, we analyze the validity of assumptions employed, especially the normality assumption.
EVALUATING A SUPERVISION PROGRAM FOR DEVELOPING AND MAINTAINING THERAPEUTIC STAFF-RESIDENT INTERACTIONS DURING INSTITUTIONAL CARE ROUTINES

This study evaluated a program to teach and maintain language training interactions between institutional staff and profoundly handicapped children during a routine care task. Following baseline observations of bath sessions, staff were sequentially taught in multiple baseline fashion to vocalize more during the bath, praise child vocalizations, imitate sounds, and provide sound prompts. Procedures included a brief in-service meeting followed by a series of supervisory prompts and feedback. Results indicated that staff acquired the interaction skills in the bath sessions and that the skills generalized to another direct care task, dressing. The number of days on which components of supervision were implemented decreased from 47% of all days during the experimental conditions to 19% of the days during a 19-week maintenance period with no decrease in staff behavior. The interactions were shown not to interfere with the quality of the direct care task nor to increase the amount of time necessary to complete it. Also, some increases were noted for child vocalization frequencies. The advantages of providing therapeutic interactions during care routines are discussed along with the need for staff management techniques with long-term maintenance value.
An Extension of the Commonality Index for Product Family Optimization

One critical aim of product family design is to offer distinct variants that attract a variety of market segments while maximizing the number of common parts to reduce manufacturing cost. Several indices have been developed for measuring the degree of commonality in existing product lines to compare product families or assess improvement of a redesign. In the product family optimization literature, commonality metrics are used to define the multi-objective tradeoff between commonality and individual variant performance. These metrics for optimization differ from indices in the first group: While the optimization metrics provide desirable computational properties, they generally lack the desirable properties of indices intended to act as appropriate proxies for the benefits of commonality, such as reduced tooling and supply chain costs. In this paper, we propose a method for computing the commonality index introduced by Martin and Ishii using the available input data for any product family without predefined configuration. The proposed method for computing the commonality index, which was originally defined for binary formulations (common / not common), is relaxed to the continuous space in order to solve the discrete problem with a series of continuous relaxations, and the effect of relaxation on the metric behavior is investigated. Several relaxation formulations are examined, and a new function with desirable properties is introduced and compared with prior formulations. The new properties of the proposed metric enable development of an efficient and robust single-stage gradient-based optimization of the joint product family platform selection and design problem, which is examined in a companion paper.Copyright © 2007 by ASME
An inverse theorem about the magnetic field line velocity.

It is shown that every field line velocity is associated with a set of Euler potentials (alpha prime, beta prime) such that particles moving with this velocity observe constant values of alpha prime and beta prime. The field line and flux preservation properties of the motion follow immediately, and a short independent proof of the Helmholtz-Zorawski criterion for field line preservation is also given. Arguments are given to show that in general it is not possible to single out one 'basic' field line velocity when only the time dependent magnetic field configuration is given.
Mechanisms of m-cresol-induced protein aggregation studied using a model protein cytochrome c

ABSTRACT Multidose protein formulations require an effective antimicrobial preservative (AP) to inhibit microbial growth during long-term storage of unused formulations. m- cresol (CR) is one such AP, but it has been shown to cause protein aggregation. However, the fundamental physical mechanisms underlying such AP-induced protein aggregation are not understood. In this study, we used a model protein cytochrome c to identify the protein unfolding that triggers protein aggregation. CR induced cytochrome c aggregation at preservative concentrations that are commonly used to inhibit microbial growth. Addition of CR decreased the temperature at which the protein aggregated and increased the aggregation rate. However, CR did not perturb the tertiary or secondary structure of cytochrome c . Instead, it populated an “invisible” partially unfolded intermediate where a local protein region around the methionine residue at position 80 was unfolded. Stabilizing the Met80 region drastically decreased the protein aggregation, which conclusively shows that this local protein region acts as an aggregation “hotspot.” On the basis of these results, we propose that APs induce protein aggregation by partial rather than global unfolding. Because of the availability of site-specific probes to monitor different levels of protein unfolding, cytochrome c provided a unique advantage in characterizing the partial protein unfolding that triggers protein aggregation.
Pediatricians and Gay and Lesbian Youth

The Epidemiology of Adolescent Homosexuality PREVALENCE Sexual orientation refers to an individual9s pattern of physical and emotional arousal toward other persons. It is not synonymous with gender identity (the knowledge of being male or female) or gender role (outward expression of maleness or femaleness). Gender identity and gender role generally are defined by anatomic and chromosomal gender in both heterosexual and homosexual individuals. Sexual orientation also is not synonymous with sexual activity; many homosexual individuals, especially during adolescence, participate in heterosexual behavior and relationships,1,2 and many adults who identify themselves as heterosexual report homosexual activity during adolescence.3-5 It is difficult to know with certainty the number of people who identify themselves as exclusively or predominantly homosexual. It is more difficult still to estimate the number who have questions about their sexual orientation during adolescence because of the well-known fluidity and complexity of sexual attractions and activities during this period. The original Kinsey study of sexuality reported that from puberty to age 20, 28% of boys and 17% of girls had one or more homosexual experiences. The same survey reported that 37% of adults have had homosexual experiences and that 10% consider themselves to be predominantly homosexual.3,4 In a somewhat more recent cross-sectional study of 13- to 19-year-olds, 11% of boys and 6% of girls reported at least one homosexual experience, with 17% of boys aged 16 to 19 reporting such activities.6
Steering a New Course for Stem Cell Research: NIH's Intramural Center for Regenerative Medicine

Summary The phenomenal progress made in stem cell biology in the past few years has infused the field of regenerative medicine with a great deal of scientific enthusiasm. However, along with the excitement of discovery comes a new sense of translational urgency. The prospect of using embryonic and induced pluripotent stem cell tools and technologies to produce cell-based therapies and other treatments is no longer a distant dream; it is a very real opportunity that demands our attention today. As with most new fields, regenerative medicine has experienced some significant growing pains, and we have identified a number of key obstacles to progress. Given our role as the lead U.S. biomedical research agency and the world's largest supporter of medical research, the National Institutes of Health (NIH) has a responsibility to find ways to reduce or remove many of these obstacles and, consequently, has—and continues—to respond to these challenges in a variety of ways. In this brief essay, we will review our progress and highlight a new development: the founding of a Center for Regenerative Medicine on the NIH campus.
Novel HSP90 Inhibitors Effectively Target Functions of Thyroid Cancer Stem Cell Preventing Migration and Invasion

Background Thyroid cancer stem cells (CSCs) with ALDH and CD44 markers contribute to tumor growth and aggressiveness. We hypothesized that novel HSP90 inhibitors (KU711, WGA-TA) and 17-AAG can effectively target the function of thyroid CSCs in vitro and prevent migration and invasion. Methods Validated papillary (TPC1), follicular (FTC238,WRO), and anaplastic (ACT1) human thyroid cancer cell lines were treated with 3 HSP90 inhibitors. CSCs were quantified for aldehyde dehydrogenase by flow cytometry, CD44 expression by Western blot, and thyrosphere formation assay. Cellular pathway proteins were analyzed by Western blot and migration/invasion by Boyden-chambers. Results WGA-TA and 17-AAG induced HSP70 compensation (not observed with KU711) on Western blot in all cell lines (>1,000 fold vs controls). Only WGA-TA degraded HSP90-Cdc37 complexing by 60–70% versus controls. Expression of HSP90 clients β-catenin, BRAF, Akt, and phospho-Akt were significantly inhibited by WGA-TA treatment (50–80%, 50–90%, >80%, and >90%) compared with controls, KU711, and 17-AAG treatment. KU711 and WGA-TA decreased CD44 expression in all cell lines (25–60% vs controls/17-AAG), decreased ALDEFLOR activity by 69–98% (P Conclusion KU711 and WGA-TA are novel HSP90 inhibitors targeting CSC function and inhibiting cell migration/invasion in differentiated and anaplastic thyroid cancers, warranting further translational evaluation in vivo.
The relationship between historical risk-adjusted 30-day mortality and subsequent hip fracture outcomes: Retrospective cohort study

Abstract Background While 30-day risk-adjusted mortality is a performance measure for hip fracture care, it has not been shown to predict long-term outcomes. We assessed whether hospital rankings based on historical 30-day mortality predicted subsequent hip fracture outcomes. Methods Using national Medicare data, we calculated annual hospital performance rankings based on standardized 30-day hip fracture mortality ratios. We used logistic regression to measure the association of patients’ survival at 180 days with their hospital's ranking for the year prior to admission. Subgroup analyses assessed whether associations between hospital performance and 180-day outcomes were similar for community-dwelling patients as well as those living in nursing homes prior to fracture. Results Out of 378,077 patients hospitalized with hip fractures between January 1, 2007 and June 30, 2009, 81,653 (21.6%) died by 180 days. Worse historical hospital performance was associated with a greater adjusted odds of 30 day mortality (odds ratio (OR), fourth vs. first quartile: 1.24, 95% confidence interval (CI): 1.18, 1.29, P P P P =0.229). Conclusions Better historical hospital hip fracture mortality predicts modest decreases in mortality at 180 days for subsequent patients, but is inconsistently associated with changes in functional outcomes. Level of evidence Level 3 (Non-randomized controlled cohort study).
Special Focus Issue: Transdermal, Topical and Folicular Drug Delivery Systems.

With a promise of ease of drug administration and the potential for a high degree of patient compliance and reduced side effects, there has been increasing interest in the areas of transdermal, top...
Northern Men with Southern Loyalties: The Democratic Party and the Sectional Crisis

Attempting to redress the “shockingly scant attention” historians have paid to 1850s northern Democrats, Michael Todd Landis highlights their role in the coming of the Civil War, contending that “t...
Nebulized Fentanyl in Acute Pain: A Systematic Review.

Objective: To provide a systematic review of the current role of nebulized fentanyl in acute pain and potentially other conditions. Data Sources: A MEDLINE literature search inclusive of the dates 1946 to May 2016 was performed using the following search terms: fentanyl and administration, inhaled. Excerpta Medica was searched from 1980 to May 2016 using the following search terms: exp fentanyl/inhalation drug administration. Additionally, Web of Science was searched using the terms fentanyl and pain inclusive of 1945 to May 2016. Study Selection and Data Extraction: We utilized the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines to select English language, human primary literature, review articles, and supporting data assessing the efficacy of nebulized fentanyl in acute pain. Data Synthesis: Seven clinical trials have demonstrated no difference in efficacy between nebulized fentanyl and intravenous (IV) opioids. Few adverse effects were reported; however, the trial...
Permeation of Moisture and Oxygen Through Polymeric O-Rings

The permeation coefficients of H2O and O2 through polymeric O-rings were obtained in this study. Increases of trace level impurities in an ultra-high purity nitrogen purge gas due to the permeation processes were measured using an atmospheric pressure ionization mass spectrometer (APIMS). In this paper, the experimental results of nine different O-ring samples (Kalrez, Chemraz, Teflon, Vespel, Viton) are reported. The Kalrez "wet" O-ring showed the lowest moisture permeation coefficient of 1.5×-1010 [cm3 gas(STP). cm polymer]/[cm2 polymer · sec · torr] and Vespel displayed the lowest oxygen permeation coefficient of 0.01×-1010 [cm3 gas(STP) · cm polymer]/[cm2 polymer · sec · torr] and room temperature. In addition, permeation coefficients at 50°C and 75°C are presented. The activation energies varied from about 18 to 51 kJ/mole/°K for both H2O and O2.
New Perspectives in Rheumatology: Avoiding Antimalarial Toxicity

This report inaugurates New Perspectives in Rheumatology, a series of authoritative articles that focus on recent scientific and clinical developments and their potential to reshape rheumatology practice. Anticipated topics include the implementation of new guidelines and emerging information from clinical and translational research. Richard J. Bucala, MD, PhDEditor-in-ChiefRobert Terkeltaub, MDCo-Editor and Review Article Editor.
Vaccination mitigates the impact of PRRSv infection on the pharmacokinetics of ceftiofur crystalline‐free acid in pigs

The pharmacokinetics of intramuscularly administered ceftiofur crystalline-free acid (CCFA) were determined in pigs that were clinically healthy (n = 8), vaccinated with a Porcine reproductive and respiratory syndrome modified live virus (PRRS MLV) (n = 10), challenged with wild-type porcine reproductive and respiratory syndrome virus (PRRSv) VR-2385 (n = 10), or vaccinated with PRRS MLV and later challenged with wild-type PRRSv VR-2385 (n = 10). Animals were given a single dose of CCFA intramuscularly at 5 mg/kg body weight. Blood was collected at 0 (pretreatment), 0.25, 0.5, 1, 6, 12, 24, 48, 96, 144, 192, and 240 h postinjection. Plasma was analyzed using liquid chromatography-mass spectrometry. Plasma concentration–time curves for each group were evaluated with noncompartmental modeling. When compared to control animals, those receiving the PRRSv wild-type challenge only had a lower AUC0-last, higher Cl/F, and higher Vz/F. The PRRSv wild-type challenge only group had the longest T1/2λ. The Cmax did not differ among all four treatments. Control animals had no statistically significant differences from animals vaccinated with PRRS MLV alone or animals vaccinated with PRRS MLV and later challenged with wild-type PRRSv. Our results suggest that PRRSv wild-type infection has the potential to alter CCFA pharmacokinetics and PRRS MLV vaccination may attenuate those changes.
Translanguaging in higher education: beyond monolingual ideologies

This collection of nine essays edited by Mazak and Carroll includes a wide range of perspectives on translanguaging in higher education. Chapters focus on some creative uses of translanguaging in b...
Design of fracture resistant energy absorbing structures using elastoplastic topology optimization

This paper introduces a novel elastoplastic topology optimization method for fracture resistant energy absorbing structural designs. The target is to find the optimal structural topologies with high plastic work absorption capacity while constraining the fracture indicators below the prescribed constraints. As the two main fracture mechanisms in ductile metals, the ductile fracture and shear fracture criteria are considered using uncoupled CrachFEM fracture model. A consistent adjoint method is presented for the path-dependent sensitivity analysis under the plane stress assumption. Several numerical examples are carried out to demonstrate the effectiveness of the proposed method. It is shown that by constraining the fracture indicators, the optimized designs have a more uniform plastic work distribution and high ductility with a significant delay of failure points. This eventually leads to much better material utilization with enhanced ultimate energy absorption capacities.
Explaining features of fine-grained phenomena using abstract analyses of phenomena and mechanisms: two examples from chronobiology

Explanations of biological phenomena such as cell division, protein synthesis or circadian rhythms commonly take the form of models of the responsible mechanisms. Recently philosophers of science have attempted to analyze this practice, presenting mechanisms as organized collections of parts performing operations that together produce the phenomenon. But in some cases what researchers seek to explain is not a general phenomenon, but a specific feature of a more fine-grained phenomenon. In some of these cases, it is not the model of the mechanism that performs the explanatory work. I consider a case in which the investigator offered an abstract representation of a fine-grained phenomenon to show why in had the feature in question. I consider a second case in which a researcher abstracted from the mechanism to identify a design principle that explains why the functioning mechanism exhibits a specific feature.
Head injury while on anticoagulation: Small numbers, big risks.

Treatment of mild traumatic brain injury (mTBI)/concussion is usually handled by emergency medicine and primary care physicians or the injured person might not seek medical care. When a patient is evaluated, imaging may not be not required if the neurologic examination is normal. However, if there are focal neurologic deficits, vomiting, headache, coagulopathy, age >60 years, outward evidence of head or neck trauma, intoxication, or a dangerous mechanism of trauma, then head CT or brain MRI is recommended. In situations where a patient has an initially negative head CT without any residual signs or symptoms, discharge from the emergency department (ED) is considered safe. However, this is not the case for patients on anticoagulation—immediate discharge from ED after a normal head CT may not be appropriate.1 Traumatic brain injury (TBI) affects more than 1.7 million Americans yearly, and the proportion of Americans on anticoagulation is increasing (prescriptions at outpatient visits are up 38% from 2009 to 2014), so that more physicians are being faced with this dilemma without much literature to guide them.2,3 Due to unknown rates of delayed intracranial hemorrhage (ICH), providers typically err on the side of caution and allow for a prolonged period of observation and obtain repeat head imaging.
Aorto-esophageal fistula associated with vascular ring: Double the arch trouble

Aorto-esophageal fistula (AEF) is a rare form of upper gastrointestinal bleeding that is associated with high mortality if not surgically addressed. It is most commonly associated with descending thoracic aneurysms and foreign body ingestion. We report a case of surgical treatment of AEF associated with double aortic arch vascular ring.
Recent Progress in Chaplaincy-Related Research:

In light of the continued growth of chaplaincy-related research this paper presents an overview of important findings. The review summarizes research in six broad areas: what chaplains do; the importance of religion and spiritual care to patients and families; the impact of chaplains' spiritual care on the patient experience; the impact of chaplain care on other patient outcomes; spiritual needs and chaplain care in palliative and end of life care; and chaplain care for staff colleagues. It concludes with a description of several innovative and important new studies of chaplain care and notes areas for future investigation.
Natural Language Based Multimodal Interface for UAV Mission Planning

As the number of viable applications for unmanned aerial vehicle (UAV) systems increases at an exponential rate, interfaces that reduce the reliance on highly skilled engineers and pilots must be developed. Recent work aims to make use of common human communication modalities such as speech and gesture. This paper explores a multimodal natural language interface that uses a combination of speech and gesture input modalities to build complex UAV flight paths by defining trajectory segment primitives. Gesture inputs are used to define the general shape of a segment while speech inputs provide additional geometric information needed to fully characterize a trajectory segment. A user study is conducted in order to evaluate the efficacy of the multimodal interface.
A signal for beta-cell failure.

A hallmark of human type 2 diabetes is hyperglycaemia — an excess of glucose in the bloodstream. Normally, the pancreatic β-cell compensate for this by secreting more insulin, but this fail-safe mechanism seems to malfunction in patients with the condition. Now, by generating mice that lack the insulin-receptor substrate-2 (IRS-2) gene, one group has shown that IRS-2 may be responsible for both increased insulin resistance and reduced insulin compenation. The knockout mice develop a syndrome that closely resembles human type 2 diabetes and, importantly, they have fewer β-cells than wild-type mice.
Sociobiology and Differential Psychology

Rushton has performed a most necessary service to the advancement of behavioral science. He has indicated, succinctly yet quite comprehensively, how differential psychology can fruitfully be brought under the purview of the newly developing science of sociobiology. We may rather safely predict that his effort will meet at least temporary resistance. In the long history of differential psychology (i.e., the study of individual and group differences in behavioral traits) and in the comparatively short history of sociobiology (i.e., the study of the biological basis of social behavior) we have seen tides of opposition beyond the usual technical criticism and analysis which are a normal accompaniment to all important scientific endeavor. The resistance has evinced more of the character of the resistance which has been seen historically in connection, not with normal science, but with true scientific revolutions in the Kuhnian sense. In such cases, science has invaded areas of deep human concern and seemingly threatened entrenched theories of man’s nature and place in the universe. The apposition of evolutionary biology and human individual and group differences and social behavior, as proposed in Rush-ton’s essay, will be perceived by some as a similar threat to humans’ welfare and self-esteem.
Hospital Data Sources

This paper addresses the hospital as a site for pharmacoepidemiology studies, particularly with respect to the development and use of automated data. A brief history of efforts to develop automated data in this site will be presented, followed by an example of one data base, and, finally, descriptions of the types of studies which have been or could be carried out. The advantages and limitations of these studies and the resources will be outlined to point out needs for future development in this part of the discipline.