cssi/SciSciGPT-SciSciNet huggingface dataset:
Rb and p53-Deficient Myxofibrosarcoma and Undifferentiated Pleomorphic Sarcoma Require Skp2 for Survival

Myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS) are highly genetically complex soft tissue sarcomas. Up to 50% of patients develop distant metastases, but current systemic therapies have limited efficacy. MFS and UPS have recently been shown to commonly harbor copy number alterations or mutations in the tumor suppressor genes RB1 and TP53. As these alterations have been shown to engender dependence on the oncogenic protein Skp2 for survival of transformed cells in mouse models, we sought to examine its function and potential as a therapeutic target in MFS/UPS. Comparative genomic hybridization and next-generation sequencing confirmed that a significant fraction of MFS and UPS patient samples (n = 94) harbor chromosomal deletions and/or loss-of-function mutations in RB1 and TP53 (88% carry alterations in at least one gene; 60% carry alterations in both). Tissue microarray analysis identified a correlation between absent Rb and p53 expression and positive expression of Skp2. Downregulation of Skp2 or treatment with the Skp2-specific inhibitor C1 revealed that Skp2 drives proliferation of patient-derived MFS/UPS cell lines deficient in both Rb and p53 by degrading p21 and p27. Inhibition of Skp2 using the neddylation-activating enzyme inhibitor pevonedistat decreased growth of Rb/p53-negative patient-derived cell lines and mouse xenografts. These results demonstrate that loss of both Rb and p53 renders MFS and UPS dependent on Skp2, which can be therapeutically exploited and could provide the basis for promising novel systemic therapies for MFS and UPS. SIGNIFICANCE: Loss of both Rb and p53 renders myxofibrosarcoma and undifferentiated pleomorphic sarcoma dependent on Skp2, which could provide the basis for promising novel systemic therapies.See related commentary by Lambert and Jones, p. 2437.
“This peculiar constitution of our nature”: John Owen’s perception of death, ontology, and the isangeloi

In 1680, the Puritan Congregationalist John Owen preached a sermon series called “The Christian’s Work of Daily Dying,” in which he argued that dying well depended upon living well. Owen admonished...
A powerful graphical display of technical information: Robert Serber's plot of physical conditions inside a nuclear explosion

A 1943 graph depicting the time evolution of physical conditions within an exploding nuclear weapon is reconstructed and discussed. The graph is remarkable for its combination of generality, simplicity, and density of information. Analyzing how Robert Serber constructed this graph proves to be a valuable exercise for developing deeper understanding of the physics of a nuclear explosion.
Solvent-Induced Assembly of Microbial Protein Nanowires into Superstructured Bundles

Protein-based electronic biomaterials represent an attractive alternative to traditional metallic and semiconductor materials due to their environmentally benign production and purification. However, major challenges hindering further development of these materials include (1) limitations associated with processing proteins in organic solvents and (2) difficulties in forming higher-order structures or scaffolds with multilength scale control. This paper addresses both challenges, resulting in the formation of one-dimensional bundles composed of electrically conductive protein nanowires harvested from the microbes Geobacter sulfurreducens and Escherichia coli. Processing these bionanowires from common organic solvents, such as hexane, cyclohexane, and DMF, enabled the production of multilength scale structures composed of distinctly visible pili. Transmission electron microscopy revealed striking images of bundled protein nanowires up to 10 μm in length and with widths ranging from 50-500 nm (representing assembly of tens to hundreds of nanowires). Conductive atomic force microscopy confirmed the presence of an appreciable nanowire conductivity in their bundled state. These results greatly expand the possibilities for fabricating a diverse array of protein nanowire-based electronic device architectures.
Kidney tubule health scores and their associations with incident CKD in women living with HIV.

OBJECTIVES Individual kidney tubule biomarkers are associated with chronic kidney disease (CKD) risk in people living with HIV (PLWH). Whether a combination of kidney biomarkers can be integrated into informative summary scores for PLWH is unknown. METHODS We measured eight urine biomarkers of kidney tubule health at two visits over a 3-year period in 647 women living with HIV in the Women's Interagency Health Study. We integrated biomarkers into factor scores using exploratory factor analysis. We evaluated associations between CKD risk factors and factor scores, and used generalized estimating equations to determine associations between factor scores and risk of incident CKD. RESULTS Factor analysis identified two unique factor scores: a tubule reabsorption score comprising alpha-1-microglobulin, beta-2-microglobulin and trefoil factor-3; and a tubule injury score comprising interleukin-18 and kidney injury molecule-1. We modelled the two factor scores in combination with urine epidermal growth factor (EGF) and urine albumin. Predominantly HIV-related CKD risk factors were independently associated with worsening tubule reabsorption scores and tubule injury scores. During a median follow-up of 7 years, 9.7% (63/647) developed CKD. In multivariable time-updated models that adjusted for other factor scores and biomarkers simultaneously, higher tubule reabsorption scores [risk ratio (RR) = 1.27, 95% confidence interval (CI): 1.01-1.59 per 1 SD higher time-updated score], higher tubule injury scores (RR = 1.36, 95% CI: 1.05-1.76), lower urine EGF (RR = 0.75, 95% CI: 0.64-0.87), and higher urine albumin (RR = 1.20, 95% CI: 1.02-1.40) were jointly associated with risk of incident CKD. CONCLUSIONS We identified two novel and distinct dimensions of kidney tubule health that appear to quantify informative metrics of CKD risk in PLWH.
Mini-Review: Genetic Literacy and Engagement With Genetic Testing for Autism Spectrum Disorder.

As genomic and personalized medicine is integrated into healthcare, the need for patients to understand and make decisions about their own genetic makeup increases. Genetic literacy, or one’s knowledge of genetic principles and their applications, measures an individual’s ability to apply genetic information to their own treatment. Increased genetic literacy can improve comprehension of genetic tests and therefore increase participation in testing to detect and treat genetic disorders. It can also help providers understand and explain genetic information to their patients. However, current research indicates that the population’s genetic literacy is generally low. Because many medical students, providers, and patients cannot adequately apply genetic information to their health, new and beneficial genetic technologies can be underused. More specifically, though genetic testing is recommended at the time of diagnosis for those affected by autism spectrum disorder (ASD), as few as 22% of families undergo genetic testing after diagnosis. While ASD, a neurodevelopmental condition characterized by impaired social communication and restricted interests, has both genetic and environmental risk, genetic testing can give clinicians useful information and help families avoid potentially painful and costly tests, even when many families do not receive a “positive” genetic result through microarrays or gene panels. Improving genetic literacy in populations affected by ASD can also improve attitudes towards genetic testing, thereby ensuring access to genetic health risk information. In this mini review, we discuss the current literature describing genetic literacy and genetic testing rates for ASD.
Fundamental Properties and Constructions

Despite the simplicity of the notion of a polytope, our understanding of what properties a polytope may, or may not, have is severely hampered by the difficulty of producing polytopes having certain desired features. One example of such a difficulty will help to focus the problem. Let us consider 4-polytopes with 8 vertices; with some patience, combining the different types of polytopes considered in Chapter 4, the reader will probably find 4-polytopes with 8 vertices and 16 edges, or with any number of edges between 18 and 28. Now he may ask himself whether it is possible to complete the list by a polytope with 17 edges. But how is one to start looking for such a polytope?
A Machine Approach for Field Weakening of Permanent-Magnet Motors

The commonly known technology of field weakening for permanent-magnet (PM) motors is achieved by controlling the direct-axis current component through an inverter, without using mechanical variation of the air gap, a new machine approach for field weakening of PM machines by direct control of air-gap fluxes is introduced. The demagnetization situation due to field weakening is not an issue with this new method. In fact, the PMs are strengthened at field weakening. The field-weakening ratio can reach 1O:1 or higher. This technology is particularly useful for the PM generators and electric vehicle drives.
Optimal placement of phase shifters considering contingencies

This paper presents an approach, which allows the optimal placement of thyristor controlled phase shifters (TCPS) to maximize the system loadability, not only for the base case network topology but also under important contingencies using the dc power flow model. The problem formulation follows that of Lima, FGM, et al. (2003) but extends its results to the case of contingencies. IEEE 30 bus is used as an example to demonstrate the effectiveness of the described method.
Recent developments in the improvement campaign for the high voltage converter modulator at the Spallation Neutron Source

The High Voltage Converter Modulator (HVCM) systems at the Spallation Neutron Source (SNS) are the primary power sources for the klystrons that supply RF power to the H-beam. The availability of the HVCMs exceeds 99% due to numerous improvements that have been implemented since SNS operations began in 2006. However, the HVCMs continue to operate in open-loop mode that results in significant voltage droop within each pulse. Control margin in the low-level RF control system is becoming a limitation as beam intensity and pulse length are increased to raise the beam power on target to 1.4 MW. This paper will discuss recent progress towards improving the pulse characteristics delivered by the HVCM systems and additional steps being pursued to further improve the system reliability. Alternative modulation schemes for switching the IGBTs, alternative system topologies and various enabling technologies to accomplish these goals will be the primary focus. The motivation, design details, test results and implementation will be presented.
Beaded of Goldschmidt, an Antimorphic Allele of Serrate, Encodes a Protein Lacking Transmembrane and Intracellular Domains

Serrate (Ser) is an essential gene in Drosophila melanogaster best known for the Ser dominant (SerD) allele and its effects on wing development. Animals heterozygous or homozygous for SerD are viable and exhibit loss of wing margin tissue and associated bristles and hairs. The Beaded of Goldschmidt (BdG) allele of Ser, when heterozygous to wild type, will also produce animals exhibiting loss of wing margin material. However, animals homozygous for BdG exhibit a larval lethal phenotype comparable to animals homozygous for loss-of-function Ser alleles. BdG is a partial duplication of the Ser locus with a single 5' Ser-homologous region and two distinct 3' regions. Meiotic recombination between BdG and a wild-type Ser chromosome demonstrated that only one DNA lesion, caused by the insertion of a transposable roo element into the coding regions of the Ser transcript, appears capable of generating BdG phenotypes. Due to the roo insertion, the protein product is predicted to be prematurely truncated and lack an extracellular cysteine-rich region along with the transmembrane and intracellular domains found within the normal SERRATE (SER) protein. The loss of these protein domains apparently contributes to the antimorphic nature of this mutation.
The effects of fatigue, distractibility, and absenteeism on school achievement in children with rheumatic diseases

Children with chronic health impairments have a variety of psychosocial, physical, and medical complications affecting daily life. This study investigated the relationship between the effects of a rheumatic disease (RD) and school functioning. Factors investigated were fatigue, distractibility, and absenteeism. In addition, disease severity and mobility were assessed. Forty-six children with RD and their parents participated in the study. Results indicated that inattention and distractibility were highly related to school achievement. A minimal relationship between fatigue and absenteeism and school performance was noted. In addition, ratings of mobility used by physicians were unrelated to success on math and reading achievement testing.
Demise of the Talented Tenth: Affirmative Action and the Increasing Underrpresentation of Ascendant Blacks at Selective Educational Institutions

Over the past 30 years America has experienced both a substantial increase in the percentage of blacks multiracial blacks and an unprecedented influx of voluntary immigration of blacks primarily from Africa and the Caribbean. The percentage of foreign-born black immigrants reached 8% of the black population in 2005, and no doubt is higher today. There is evidence that suggests not only that multiracial blacks and foreign-born black immigrants and their sons and daughters constitute a disproportionate percentage of black students in selective higher education programs, but their percentages are larger than most people realize. This article addresses the resulting change in the racial and ethnic ancestry of blacks on U.S. college campuses, particularly those in selective higher education programs. We argue that this occurs not just because of demographic shifts but also as a result of the ways in which affirmative action programs function. Ultimately, the Article questions the admissions process that lumps all blacks into a single category, an approach that pervades admissions decisions of so many selective colleges, universities, and graduate programs.
Laura Ellingson, Communicating in the Clinic: Negotiating Frontstage and Backstage Teamwork

Many studies have examined how doctors and patients interact and communicate. Medical school students receive training in how to properly communicate with and evaluate patients. These types of studies view communication as the process through which information is transmitted to and from the patient. However, few studies have been initiated to examine how team members within medical clinics communicate with each other away from patients. Laura Ellingson’s Communicating in the Clinic is an ethnographic study that provides a richer understanding of how medical team members communicate. Her interpretive ethnographic approach challenges positivist thinking by advocating that qualitative research methods have a place in generating knowledge and understanding of communicative interaction. Thus her book promotes qualitative research as a viable approach for examining communication within medical clinics.
Publishing pays: Economists’ salaries reflect productivity

Abstract We study salaries of economics faculty at the University of California to determine how publications affect salary. We find that each publication in a top 10 journal has a positive and significant effect on annual base salary of 1.5%, or $2,053. Unlike previous research, our analysis specifies the impact of publications in specific journals. Publications in American Economic Review , Econometrica , and Review of Economics and Statistics have an independent positive effect on salary. Compensation is also affected by faculty rank, seniority, university of employment, and teaching awards. Base salary does not significantly differ by gender, however, gross salary is about 9% lower for women. After controlling for migration and faculty rank, seniority has a negative impact on salary.
Underwater Acoustic Communications Performance Modeling in Support of Ad Hoc Network Design

This paper discusses a methodology for predicting underwater acoustic communications performance using high fidelity acoustic time series simulation and acoustic modem processing emulation. Multiple source/receiver combinations can be simultaneously simulated, so that aspects of a complete underwater network can be studied. Here, the fundamental modeling and emulation capability will be described, with examples of the propagation modeling, time series simulation, and modem processing over multiple realizations of example communications channels. The results show the dependence of source and receiver location in the water column with respect to the sound speed profile on communications performance. The utility of such simulations for ad hoc network design in the presence of moving communications nodes will be discussed.
Dynorphin(1-10)amide: a potent and selective analog of dynorphin(1-13).

Abstract Dynorphin(1–10)amide was more potent than Dynorphin(1–13) in inhibiting the twitch of the mouse vas deferens (IC 50 ) of Dynorphin(1–10)amide = 0.3 nM and IC 50 of Dynorphin (1–13) = 4.0 nM. Binding assaays indicated that two opioid peptides had similar profiles in that they enhanced dihydromorphine (DHM) binding in picomolar concentrations but displaced DHM binding in nanomolar concentrations (IC 50 for Dynorphin(1–10)amide = 5 nM). In the mouse tail-flick assay, however, Dynorphin(1–10)-amide showed a more selective action on morphine-induced analgesia. Although Dynorphin(1–10)amide had no significant analgesic activity by itself, it differed from the (1–13) analog by neither potentiating nor antagonizing morphine in naive animals. In tolerant animals, on the other hand, 50 ug of this analog administered icv shifted the ED 50 of morphine from 43.0(33.0–55.9) to 17.0 (12.4–23.3). Thus, Dynorphin(1–10)amide appears to be a more potent and selective analog of Dynorphin(1–13).
Constraining the stress tensor in the Visund field, Norwegian North Sea : Application to wellbore stability and sand production

Abstract In this study we examine drilling-induced tensile wellbore failures in five exploration wells in the Visund oil field in the northern North Sea. We use observations of drilling-induced wellbore failures as well as density, pore pressure, and leak-off test measurements to estimate the magnitudes and orientations of all three principal stresses. Each well yields a very consistent azimuth of the maximum horizontal stress (100°±10°), both with depth and laterally across the field. Stress orientations are constrained at depths as shallow as 2500 m and as deep as 5300 m in these wells. We show that the magnitudes of the three principal stresses ( S v , S hmin , and S Hmax ) are also consistent with depth and reflect a strike-slip to reverse faulting stress regime. The magnitude of the maximum horizontal stress is shown to be significantly higher than the vertical and minimum horizontal stresses (e.g. S v =55 MPa, S hmin =53 MPa, and S Hmax =71.5 MPa at 2.8 km depth). Data from earthquake focal plane mechanisms (Lindholm et al., 1995, Proceedings of the Workshop on Rock Stresses in the North Sea, Trondheim, Norway [1] ) show similar stress orientations and relative magnitudes and thus indicate a stress field that is relatively consistent throughout the thickness of the brittle crust. We illustrate how knowledge of the full stress tensor allows one to place bounds on in situ rock strength and determine optimally stable trajectories for wellbore stability and sand production during drilling, after the completion of drilling, and as pore pressure is reduced during oil and gas production.
Hemodynamic effects of oral smokeless tobacco in dogs and young adults.

Oral smokeless tobacco (snuff) is increasingly used among the young male population. To determine cardiovascular effects of an oral smokeless tobacco product, 10 anesthetized dogs were instrumented to measure blood pressure, heart rate, left ventricular end diastolic pressure, and circumflex coronary, renal, and femoral flows. After a 5-min baseline, a 2.5g, ∼ 1.2% nicotine bolus dose was placed in the buccal space, and measurements were made for 20 min. Significant increases were seen in heart rate, blood pressure, left ventricular pressure, left ventricular end diastolic pressure, and left ventricular dP/dt. Significant decreases in flow were noted in the coronary circumflex, renal, and femoral arteries. The flow reduction was thought to have been mediated by an α-adrenergic mechanism. Additionally, 20 human males, X age 20 years, without nicotine exposure for 72 hr, were given a 2.5-g dose of the same oral smokeless product. From baseline to 20 min, heart rate increased from 69 to 88 beats/min (P < 0.05), blood pressure from 118/72 to 126/78 mm Hg (P < 0.05). Thus, oral smokeless tobacco use can produce significant hemodynamic changes in both dogs and normal humans.
Alternative Goodness-of-Fit Tests for Linear Models

Fan and Huang (2001) presented a goodness-of-fit test for linear models based on Fourier transformations of the residuals of the fitted model. We present two more theoretically appealing tests in which the Fourier transforms are incorporated into a fitted model. We show that when suitably normalized, the new test statistics have the same asymptotic distribution as Fan and Huang’s test. We propose modifications to the asymptotic normalization constants to improve the small sample sizes of our tests while retaining their asymptotic distributions. Small sample sizes and powers are examined via simulations. An illustration is given.
Recovery of image distorted by turbulent atmosphere using phase-conjugate image generated by difference frequency generation

We demonstrate dynamic recovery of blurred images caused by atmospheric turbulence. In particular, using a phase-conjugate wave generated by a second-order nonlinear crystal or composite, we restore the original quality of the image after the optical radiation forming the image propagates through the turbulent atmosphere. One of the key elements for our experiment is a rotating phase plate being placed in the beam path for simulating turbulent atmosphere. Using the nonlinear composite, we demonstrate that the image recovery is insensitive to the polarization of the optical radiation forming the image.
Two-Dimensional Effects on the Response of Packed Bed Regenerators

Packed beds have a wide range of applications as heat transfer and energy storage devices. Employed as a regenerator, a packed bed is subject to the flow of a heat transfer fluid, which alternately stores and recovers energy from a packing of discrete particles. The flow direction reverses during the addition and removal of energy. The nature of a packing of discrete particles in a container is such that variations in the resistance to flow and in the void fraction occur across the cross section of the packing. Particularly, the region of the bed near the boundary of the container has a markedly reduced resistance to flow. In addition, the wall effect on the packing geometry changes the void fraction in the near-wall region. The purpose of the present study is to quantify the two-dimensional effects of nonuniform void fraction, velocity, and temperature distributions in a packed bed regenerator on the dynamic and steady periodic behavior. A two-dimensional numerical model of the transient response of a packed bed subject to the flow of a heat transfer fluid has been developed and verified through comparison with measured responses. The model includes the effects of nonuniform velocity and porosity in the bed, and the effects of axial and radial thermal dispersion. The results of the present computations are compared with one-dimensional transient periodic results to demonstrate the two-dimensional effects on the transient response of a packed bed regenerator to a step change in fluid temperature. The classical dimensionless parameters, such as reduced length and reduced time, are not sufficient to characterize the two-dimensional transient nature of a packed bed regenerator. This study identifies the range of bed-to-particle-diameter ratios over which the transient response is significantly influenced by the wall effect on void fraction and flow.
Meiofauna on the seagrass Thalassia testudinum: population characteristics of harpacticoid copepods and associations with algal epiphytes

The composition and abundance of bladedwelling meiofauna was determined over a 15 mo period (1983–1984) from a Thalassia testudinum Banks ex Konig meadow near Egmont Key, Florida, USA. Harpacticoid copepods, copepod nauplii, and nematodes were the most abundant meiofaunal taxa on T. testudinum blades. Temporal patterns in species composition and population life-history stages were determined for harpacticoid copepods, the numerically predominant taxon. Sixteen species or species complexes of harpacticoid copepods were identified. Harpacticus sp., the most abundant harpacticoid, comprised 47.8% of the total copepods collected, and was present throughout the study. Copepodites dominated the population structures of the blade-dwelling harpacticoid species on most collection dates. Ovigerous females and/or copepodites were always present, indicating continuous reproductive activity. Results suggest that epiphytic algae influence meiofaunal abundance on seagrass blades, as densities of most meiofaunal taxa at Egmont Key were positively associated with percent cover of epiphytic algae throughout the study. The majority of significant correlations between meiofaunal density and cover of epiphytic algae involved filamentous algae, although encrusting algae dominated the epiphytic community. It appears that resources provided by epiphytic algae to seagrass meiofauna (additional food, habitat, and/or shelter from predation) may be associated with algal morphology.
Can intra‐specific genetic variation in arbuscular mycorrhizal fungi (Glomus etunicatum) affect a mesophyll‐feeding herbivore (Tupiocoris notatus Distant)?

1. Arbuscular mycorrhizal fungal (AMF) infection can have negative, positive or neutral effects on insect herbivore populations, but patterns are difficult to predict. 2. Intra-specific genetic variation in nutrient uptake ability between fungal isolates may also have indirect effects on insect herbivores due to changes in plant quality. In preliminary studies mirid (Tupiocoris notatus) populations were significantly reduced on tobacco (Nicotiana rustica) colonised by AMF but it was unknown if same-species fungal isolates differed in their effect. 3. An experiment was performed as a first test of the effect of intra-specific genetic variation in the mycorrhizal fungus Glomus etunicatum on mirid nymphal population structure, dynamics, and growth rate. 4. Mirid nymphal populations were lower on mycorrhizal fungal-infected plants. Population size, however, did not differ between the mycorrhizal isolates. While no statistical difference in population between isolates was found, one isolate consistently had 1.7–2.4 times lower mirid populations compared with the controls, indicating that the magnitude of effect is different between mycorrhizal isolates. 5. The significantly negative effect of AMF on mirid populations likely resulted from AMF-induced changes in plant quality (e.g. increased defence). This study lends further support to recent demonstrations that below-ground symbionts significantly influence above-ground processes. In addition, mycorrhizal fungi can affect insect population structure, which may have consequences for future herbivory.
Tissaphernes in Thucydides

Of all the leading personalities who left their imprint on the history of the Peloponnesian war Tissaphernes was to Thucydides the most enigmatic. Although judgements on the ability and character of individuals occur more frequently in the eighth book of the History than in other parts, Thucydides apparently did not feel himself to be in a position to include an explicit judgement on Tissaphernes. Nor does Tissaphernes, unlike many major and minor characters, receive even a brief descriptive introduction, though such introductions are also exceptionally plentiful in the eighth book. Thucydides has been successful in collecting an abundance of detailed information about the part played by Tissaphernes in the opening phase of the Ionian war and yet has failed to produce a satisfactory picture of him. In this paper attention will first be drawn to special problems arising in the case of Tissaphernes which do not arise in the presentation of other leading characters. My main purpose, however, is to attempt to establish that the account of him by Thucydides is basically inconsistent and that this inconsistency occurs because the material in the eighth book has not been fully integrated.One source of difficulty for Thucydides in writing about Tissaphernes was that he seems to have had little opportunity to acquire knowledge of Persia and the Persians. There is no indication that he spent any part of his exile in or near Asia, and the notorious sparsity of his references to Greek relations with the Persians before the outbreak of the Ionian war suggests that his contacts with them were scanty. In this respect he was not exceptional. Before the end of the fifth century even the best educated Athenians seem to have possessed only a dim or distorted impression of Persia, as is illustrated in different ways by the Persae and the Acharnians.
The effects of pentoxifylline on the generation of human lymphokine-activated killer cell cytotoxicity

Pentoxifylline (PTX) is a methylated xanthine that has been shown to reduce the toxicity of Interleukin-2 (IL-2) therapy in animal models, possibly by inhibiting secretion of tumor necrosis factor-alpha. However, the use of PTX to reduce IL-2 toxicity in cancer patients would be advantageous only if PTX did not abrogate antitumor effector mechanisms. We therefore tested the effects of PTX on the induction of lymphokine-activated killer (LAK) cell reactivity in human peripheral blood mononuclear cells (PBMCs). LAK precursor and effector activity were defined as lysis of Daudi cells by PBMCs after incubation with IL-2 at 1,000 U/ml (LAKp) or without incubation (LAKe). PBMCs from four healthy subjects were cocultured for 5 days with IL-2 and PTX (0-1.0 mM). LAKp was inhibited in a PTX dose-dependent manner, as the mean % lysis at an E:T ratio of 50:1 was 62, 43, and 8% in the presence of 0, 0.1, and 1.0 mM PTX, respectively. To determine the effect of in vivo PTX on LAKp activity, four healthy subjects were tested after treatment with PTX at 2 g/day for 3 days. LAKp activity was detected in all four and was not inhibited by autologous serum containing PTX and biologically active metabolites. Because lymphocytes "preactivated" by IL-2 in vivo may respond to PTX differently than resting cells, two patients were tested after a 5 day infusion of IL-2 at 6 x 10(6) U/m2/day. PBMCs from both displayed LAKp activity, with far less inhibition by PTX than in resting cells (4, 17, and 37% inhibition at 0.05, 0.1, and 1.0 mM, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Calculating physical properties of organic compounds for environmental modeling from molecular structure

Mathematical models for predicting the transport and fate of pollutants in the environment require reactivity parameter values - that is the value of the physical and chemical constants that govern reactivity. Although empirical structure-activity relationships have been developed that allow estimation of some constants, such relationships are generally valid only within limited families of chemicals. The computer program, SPARC, uses computational algorithms based on fundamental chemical structure theory to estimate a large number of chemical reactivity parameters and physical properties for a wide range of organic molecules strictly from molecular structure. Resonance models were developed and calibrated using measured light absorption spectra, whereas electrostatic interaction models were developed using measured ionization pK(a)s in water. Solvation models (i.e., dispersion, induction, H-bonding, etc.) have been developed using various measured physical properties data. At the present time, SPARC's physical property models can predict vapor pressure and heat of vaporization (as a function of temperature), boiling point (as a function of pressure), diffusion coefficient (as a function of pressure and temperature), activity coefficient, solubility, partition coefficient and chromatographic retention time as a function of solvent and temperature. This prediction capability crosses chemical family boundaries to cover a broad range of organic compounds.
Long-Term Biological Monitoring of an Impaired Stream: Synthesis and Environmental Management Implications

The long-term ecological recovery of an impaired stream in response to an industrial facility’s pollution abatement actions and the implications of the biological monitoring effort to environmental management is the subject of this special issue of Environmental Management. This final article focuses on the synthesis of the biological monitoring program’s components and methods, the efficacy of various biological monitoring techniques to environmental management, and the lessons learned from the program that might be applicable to the design and application of other programs. The focus of the 25-year program has been on East Fork Poplar Creek, an ecologically impaired stream in Oak Ridge, Tennessee with varied and complex stressors from a Department of Energy facility in its headwaters. Major components of the long-term program included testing and monitoring of invertebrate and fish toxicity, bioindicators of fish health, fish contaminant accumulation, and instream communities (including periphyton, benthic macroinvertebrate, and fish). Key parallel components of the program include water chemistry sampling and data management. Multiple lines of evidence suggested positive ecological responses during three major pollution abatement periods. Based on this case study and the related literature, effective environmental management of impaired streams starts with program design that is consistent across space and time, but also adaptable to changing conditions. The biological monitoring approaches used for the program provided a strong basis for assessments of recovery from remedial actions, and the likely causes of impairment. This case study provides a unique application of multidisciplinary and quantitative techniques to address multiple and complex regulatory and programmatic goals, environmental stressors, and remedial actions.
ARmonica: a collaborative sonic environment

ARmonica is a 3D audiovisual augmented reality environment in which players can position and edit virtual bars that play sounds when struck by virtual balls launched under the influence of physics. Players experience ARmonica through head-tracked head-worn displays and tracked hand-held ultramobile personal computers, and interact through tracked Wii remotes and touch-screen taps. The goal is for players to collaborate in the creation and editing of an evolving sonic environment. Research challenges include supporting walk-up usability without sacrificing deeper functionality.
There goes the neighborhood: performance degradation due to nearby jobs

Predictable performance is important for understanding and alleviating application performance issues; quantifying the effects of source code, compiler, or system software changes; estimating the time required for batch jobs; and determining the allocation requests for proposals. Our experiments show that on a Cray XE system, the execution time of a communication-heavy parallel application ranges from 28% faster to 41% slower than the average observed performance. Blue Gene systems, on the other hand, demonstrate no noticeable run-to-run variability. In this paper, we focus on Cray machines and investigate potential causes for performance variability such as OS jitter, shape of the allocated partition, and interference from other jobs sharing the same network links. Reducing such variability could improve overall throughput at a computer center and save energy costs.
Fibroblast growth factor-2 converts PACAP growth action on embryonic hindbrain precursors from stimulation to inhibition.

Pituitary adenylyl cyclase activating peptide (PACAP) has been shown either to stimulate or to inhibit neural cell proliferation depending on the origin of the cell population. We show here that, depending on the presence or absence of fibroblast growth factor-2 (FGF-2, also called basic FGF), PACAP may either stimulate or inhibit DNA synthesis in neural precursors isolated from embryonic day 10.5 mouse hindbrain. In the absence of FGF-2, PACAP stimulated 3H-thymidine incorporation in a dose-dependent manner. This stimulatory action was unaffected by antagonists of protein kinases A and C but was abolished in the presence of the MEK1/2 antagonist PD98059. In contrast, when FGF-2 was present, PACAP inhibited DNA synthesis. This inhibitory action was insensitive to PD98059 but was fully blocked by the protein kinase A (PKA) inhibitor H89. The differential blockades by MEK1/2 and PKA inhibitors indicate that the FGF-2-induced switch in PACAP action on DNA synthesis was accomplished by a change in PACAP signaling pathways. We hypothesize that the actions of PACAP in the specific parts of the developing nervous system are determined in part by the presence or absence of FGFs and other growth factors. © 2002 Wiley-Liss, Inc.
Anthropoid origins and the modern symphysis.

To highlight adaptive transformations in craniomandibular form during anthropoid origins, symphyseal character states and underlying masticatory loading regimes were investigated vis-a-vis shifts in diet and body size. A study of fossil anthropoids is possible because variation in symphyseal fusion is continuous and directly proportional to the amount of symphyseal stress and because such variation can be considered a series of discrete character states each with unique functional underpinnings. Using recent systematic renderings of Eocene and Oligocene taxa as a template with which to assess character evolution, this analysis indicates when, and in which clade(s), specific masticatory features became fixed and thus diagnostic. A general trend throughout early anthropoid evolution is for descendent taxa to be progressively larger than ancestral forms. Coupled with this pattern is the tendency for larger-bodied fossil anthropoids to have ingested tougher diets variably consisting of thick-coated, unripe fruits and/or leaves. Mastication of mechanically tougher foods entails greater repetitive loading of the mandible and requires relatively larger amounts of balancing-side muscle force, thus resulting in correspondingly greater symphyseal fusion due to elevated dorsoventral shear. With a single exception, these adaptive transformations characterize the evolutionary pathway leading both to parapithecines and a catarrhine:platyrrhine clade (crown anthropoids). While the ancestor of crown anthropoids would have possessed a body size, diet and masticatory adaptations similar to parapithecines, such a common suite of features evolved independently. Moreover, the evolution of an early-fusing symphysis and associated wishboning loading regime of catarrhines and platyrrhines is unique among all anthropoids. Lastly, the apparent lack of reversals in symphyseal fusion indicates the improbability of phylogenetic hypotheses in which a relationship is proposed between 'ancestral' taxa with a greater degree of symphyseal fusion and 'descendent' anthropoids with a lesser degree of ossification.
Hydrogen-deuterium exchange of aromatic amines and amides using deuterated trifluoroacetic acid.

Abstract The H–D exchange of aromatic amines and amides, including pharmaceutically relevant compounds such as acetaminophen and diclofenac, was investigated using CF3COOD as both the sole reaction solvent and source of deuterium label. The described method is amenable to efficient deuterium incorporation for a wide variety of substrates possessing both electron-donating and electron-withdrawing substituents. Best results were seen with less basic anilines and highly activated acetanilides, reflecting the likelihood of different mechanistic pathways.
Applying educational gaming to public health workforce emergency preparedness

From natural disasters to terrorism, the demands of public health emergency response require innovative public health workforce readiness training. This training should be competency-based yet flexible, and able to foster a culture of professional and personal readiness more traditionally seen in non-public health first-response agencies. Building on the successful applications of game-based models in other organizational development settings, the Johns Hopkins Center for Public Health Preparedness piloted the Road Map to Preparedness curriculum in 2003. Over 1500 employees at six health departments in Maryland have received training via this program through November 2004. Designed to assist public health departments in creating and implementing a readiness training plan for their workforce, the Road Map to Preparedness uses the core competencies of the Centers for Disease Control and Prevention for all public health workers as its basic framework.
Optical Mapping in a New Guinea Pig Model of Ventricular Tachycardia Reveals Mechanisms for Multiple Wavelengths in a Single Reentrant Circuit

Background Although the relationship between cardiac wavelength (λ) and path length importantly determines the stability of reentrant arrhythmias, the physiological determinants of λ are poorly understood. To investigate the cellular mechanisms that control λ during reentry, we developed an experimental system for continuously monitoring λ within a reentrant circuit with the use of voltage-sensitive dyes and a new guinea pig model of ventricular tachycardia (VT). Methods and Results Action potentials were recorded simultaneously from 128 ventricular sites in Langendorff-perfused hearts (n=15) in which propagation was confined to a two-dimensional rim of epicardium by an endocardial cryoablating procedure. The reentrant path was precisely controlled by creating an epicardial obstacle (2×10 mm) with an argon laser. To control for fiber orientation and rate-dependent membrane properties, λ during reentry was compared with λ during plane wave propagation transverse and longitudinal to cardiac fibers at a stim...
Determination of the Length, Diameter, Molecular Mass, Density and Surfactant Adsorption of SWCNTs in Dilute Dispersion by Intrinsic Viscosity, Sedimentation, and Diffusion Measurements

A combination of intrinsic viscosity, sedimentation, and diffusion measurements is performed to characterize the structures of single-walled carbon nanotubes (SWCNTs) in dilute dispersion. It allows quantifying the bulk averaged length (L), diameter (d), molecular mass (M), and density (ρ) as well as the surfactant adsorption for SWCNTs. With this approach applied to the SWCNTs processed by sonication, a novel Mark–Houwink–Sakurada equation, [η]c = 1.17M0.33 is recovered. The less than 0.5 exponent is a result of the power-law relationship d ∝ L0.62 caused by the concurrently occurred cutting and exfoliation of SWCNT bundles in the sonication process. An in-depth analysis of the experimentally acquired d and ρ enables a quantification of sodium dodecylbenzenesulfonate (SDBS) adsorption on SWCNTs to reveal the curvature effect on the surface coverage of surfactant adsorption.
Prostaglandin H2 directly lowers human platelet cAMP levels.

Abstract In the present study we investigated the ability of prostaglandin H 2 (PGH 2 ) to lower platelet cAMP levels independent of thromboxane A 2 (TXA 2 ) production. Human platelet-rich plasma was incubated (37°C) with 13 nM prostacyclin (PGI 2 ) to increase platelet cAMP levels. Addition of 500 μM arachidonic acid (AA) to PGI 2 -treated platelets resulted in a return of cAMP to control levels. Inhibition of both PGH 2 and TXA 2 production with indomethacin (20 μM) blocked the ability of AA to lower PGI 2 -stimulated increases in cAMP. On the other hand, selective inhibition of TXA 2 production with the thromboxane synthetase blocker 7-(1 imidazoyl) heptanoic acid (7-IHA; 10 μM), did not prevent the cAMP lowering effect of added AA. These results provide evidence that PGH 2 need not be converted to TXA 2 in order to reduce platelet cAMP levels.
Induction Machine Design and Analysis for General Motors e-Assist Electrification Technology

The integrated starter generator replaces the conventional starter and alternator with one electrical machine handling both functions. Start/Stop functionality, vehicle launch assistance, and higher speed transient power supplementing enhance the vehicle performance at the lower fuel consumption rate. This functionality requires the electrical machine to provide high starting and launch assistant torque in motoring mode and relatively high power capability over the wide speed range for battery charging. The overall cost of the system is the underlining concern and crucial part of the design optimization. This paper focuses on advantages of induction machines (IMs) in automotive industry and an approach to design a cost-effective electrical machine for belted starter–alternator applications. Design optimization of the IM is described to achieve desired performance, including rotor bar count, solid conductor (bar winding) versus stranded winding design, rotor bar shape optimization, and finally performance maps for the electrical machine, including both predicted and measured results. A thermal study of the machine is also presented, as well as the noise, vibration, and harshness (NVH) consideration in the design selection.
Hymenoptera venom protease allergens.

Background Recent studies have shown the presence of additional allergenic proteins in honeybee and paper wasp venoms. Both venoms contain serine protease enzymes. Objective We isolated and obtained complete sequences of honeybee and Mediterranean paper wasp venom proteases, both of which have significant IgE binding activity. The structures are compared with bumblebee venom protease. Methods Venom proteases were chromatographically isolated from venoms and partial amino acid sequences determined. RT-PCR and rapid amplification of cDNA ends methods were used to clone cDNA, and complete sequences were determined for honeybee and a paper wasp venom protease. Results The venom proteases are all serine proteases of the trypsin type. The honeybee protease contains a complement, embryonic sea urchin protein, bone morphogenetic protein interaction domain as well as a linker and propeptide sequence, and a unique methionine residue near the active site. It has IgE binding activity. The paper wasp protease is a single trypsin domain and is an important allergen. The framework residues are poorly conserved among honeybee, bumblebee, and paper wasp enzymes. Conclusions The 3 venom serine proteases have significant IgE binding activities. The structures are poorly conserved even among the Apidae , suggesting little cross-reactivity among the protein portions. The paper wasp venom proteases are important allergens.