cssi/SciSciGPT-SciSciNet huggingface dataset:
Multiple changes induced by cholera toxin contribute to the stimulation of aerobic lactate production in rat-1 fibroblasts.

Abstract Exposure of rat-1 fibroblasts to cholera toxin increased aerobic lactate production 3- to 8-fold with maximal stimulation observed between 1 and 2 h at a concentration of 1–2 μg/ml. Concomitant with this change was a 10- to 40-fold elevation in the intracellular concentration of cAMP. The cell permeable cAMP analogue, N 6 ,2′- O -dibutyryl cAMP and the cyclic nucleotide phosphodiesterase inhibitor RO-20-1724 also increased lactate production and intracellular cAMP levels, although less effectively. Cholera toxin and dibutyryl cAMP induced a 2- to 3-fold elevation of intracellular fructose 2,6-bisphosphate and 2- to 3-fold increases in both 3- O -methylglucose and inorganic phosphate transport. A survey of five additional cell lines revealed striking variabilities in their individual responses to cholera toxin and dibutyryl cAMP. All were observed to be considerably less sensitive to either agent than rat-1 cells. These data suggest that a cooperative effect involving multiple parameters may be responsible for the observed increases in aerobic lactate production in response to cAMP and that these parameters may vary significantly among cell lines.
Interpretation of the roles of adenylosuccinate lyase and of AMP deaminase in the anti-HIV activity of 2',3'-dideoxyadenosine and 2',3'-dideoxyinosine.

Some 2′,3′-dideoxynucleotides, of importance in the enzymology of the anti-HIV compounds, ddA and ddI, have been synthesized and purified by ion-exchange chromatography. 2′,3′-Dideoxyadenylosuccinate, an intermediate in the pathway of ddI to ddATP, is converted to ddAMP by AMPS lyase at 1.85% of the efficiency of the natural substrate, adenylosuccinate. Interestingly, ddAMP and other 2′,3′-dideoxygenated nucleotides are not substrates for AMP deaminase, another relevant enzyme in the conversion of ddA to ddATP via ddl.
The stereospecific cytotoxic potency of (6R) and (6S)-5,10-dideazatetrahydrofolate correlates with cellular folylpolyglutamate synthetase levels

Abstract The de novo purine synthesis inhibitor 5,10-dideazatetrahydrofolate (DDATHF) has previously been shown to inhibit the growth of mouse L1210 and human CCRF-CEM leukemia cells. The present study demonstrates that both the 6 R and 6 S diastereomers of DDATHF are also cytotoxic to mammalian cells in a stereospecific manner. The cytotoxic potency of (6 R )-DDATHF (also known as Lometrexol) towards different cell lines varied by approximately 14-fold and that of (6 S )-DDATHF by as much as 156-fold. Compared to (6 R )-DDATHF, (6 S )-DDATHF was 6.0- and 7.2-fold more cytotoxic to human WiDr colon adenocarcinoma and Chinese hamster ovary (CHO) cells, respectively, and only 1.5- and 2.0-fold more cytotoxic to human T24 bladder carcinoma and mouse L1210 leukemia cells, respectively. However, compared to (6 S )-DDATHF, (6 R )-DDATHF was 8.7- and 6.9-fold more cytotoxic to C3H/10T1/2 clone 8 and clone 16 mouse fibroblasts, respectively. Weak inhibition of aminoimidazolecarboximide ribonucleotide formylransferase (AICARFT, EC 2.1.2.3) appeared to have little role in the cytotoxicity of DDATFH diastereomers to WiDr cells during a 24-h exposure. Although glycinamide ribonucleotide formyltransferase (GARFT, EC 2.1.21) is the main biochemical target of DDATHF, DDATHF stereoisomers' cytotoxic potency showed no clear negative correlation with cellular GARFT levels. However, cellular folylpolyglutamate synthetase (FPGS, EC 6.3.2.17) levels correlated with cytotoxic potency in a positive manner. Suprisingly, two enzyme-dose/DDATHF LD 90 -response curves were observed for FPGS corresponding to differences in (6 R ) and (6 S )-DDATHF cytotoxic potency among the six cell lines studied.
Comparison of Recent Laboratory Models to Natural Deformation in Rocky Mountain Forelands: ABSTRACT

Several years ago for the first time the technique for experimental folding of layered real rocks under conditions expected within sedimentary basins was developed in our laboratory. In the initial experiments the samples had to be loaded parallel with the layering simulating horizontal compression. Though these experiments produced many insights into the overall folding process, they are not representative of most folds in the Rocky Mountain forelands where the folds result from differential vertical movements of the basement. However, within the last year the technique has been modified to produce loads at high angles to the layering and now we can produce a form of drape folding that does, indeed, have much in common with folds in the Rocky Mountain foreland. Making on -to-one correlations of simplified laboratory experiments to complicated natural features can be fraught with danger and completely misleading. However, these experiments verify so many long suspected natural phenomena that selected comparisons may be significant. Scale alone precludes complete observation of natural folds with thousands of feet of displacement, but if correlations to experimentally created folds can be validated, the overall fold process becomes subject to direct observation. Such observations lead to increased confidence in delineation of structural geometries on the natural scale. This is especially true for the more complicated fold forms that usually have to be predicted in the subsurface from limited exploration data. It is gratifying to see that the overall movements in the experiment correlate well with natural folds, because it allows us to develop conceptual models upon which we can draw when dealing with widespread subsurface control or masked seismic data. End_of_Article - Last_Page 911------------
Analysis of neutron-capture data in the resonance region

Abstract Methods for the hand calculation of resonance parameters from neutron capture data are presented. Shape analysis for the case of negligible multiple scattering and area analysis for the more general case Γn⪅Γγ have been worked out for non-fissile target nuclei. Special attention is given to the problems of multiple scattering, wing corrections, flux calibration and instrumental resolution. A convenient method for error estimation in area analysis is also described. As a numerical example, the 7.9 eV resonance of Er167 was treated by shape and area analysis. The result is Γγ = 95±25 meV, 2gΓn = 0.27±0.02 meV.
DMO Websites and the Role of Complementary Media in Tourism Advertising

ABSTRACT While destination marketing organizations' (DMO) websites are increasingly popular in tourism advertising, this study examined the extent to which DMO website advertising is effective when complemented by several offline advertising media. As the combination of website and local/state travel guide advertising results in high tourist visitation/impact, it was concluded that DMOs should not yet abandon their print advertising in favor of the Internet. A comparison of DMO website users and non-users revealed that the website users generate a stronger impact on the destination than the nonusers.
Anelastic piezoresistance associated with oxygen impurities in Ta

Abstract Measurements of piezoresistance associated with oxygen impurities in Ta are reported. By using an electrical bridge and a phase sensitive detector. a substantial increase in sensitivity is achieved over the pioneering work by Berry and Orehotsky (1964). It is estimated that an oxygen concentration in Ta of 30 atomic parts per million could be detected.
Area of residence and the risk of institutionalization

Many of the sociodemographic, health status, and social support characteristics that predict the use of health services by elders vary by area of residence. Yet, little is known about how these factors affect the risk of institutionalization in rural, small city, and urban areas. The purpose of this research was to: (a) determine the rate of institutionalization over a two-year period for impaired community-dwelling elders in rural, small city, and urban areas; (b) test for residence differences in sociodemographic, health status, and social support characteristics likely to influence the risk of institutionalization; and (c) examine their effect on the probability of being institutionalized in each area of residence. Although rural elders are less likely to be placed in a nursing home than their small city or urban counterparts, race and level of impairment affect the risk of institutionalization more in rural than in urban areas.
Prototype System For Digital Image Management In Combat Casualty Care

By the early 1990s, the U.S. Army intends to implement all-digital, filmless medical imaging throughout its deployable combat health care facilities. In addition to employing imaging devices whose outputs are comprised of digital, electronic images rather than film-based images, such a system must, at a minimum, include means for storing, displaying, and transporting the resultant images in accordance with existing military doctrine. Furthermore, compatibility with fixed medical facilities, both in the continental United States (CONUS) and elsewhere, and between military services must be assured to promote continuity of care. The aim of this undertaking is to develop an understanding of the imaging needs of the U.S. Army's deployable/combat Health Services Support (HSS) system, and address these needs in a prototype Digital Imaging Network System (DINS) (also known as Picture Archiving and Communication System (PACS) or an Image Management and Communication (IMAC) System), to be integrated and evaluated by The MITRE Corporation. The prototype will undergo iterative development by subjecting it to multiple evaluations in both the laboratory and Echelon 3 environments, by military and civilian medical, scientific, and engineering personnel. This project is part of a U.S. Army Medical Research and Development Command contract to The MITRE Corporation to assess the feasibility of filmless imaging in military health care.
A Direct Carbon-13 and Nitrogen-15 NMR Study of Cerium(III)–Isothiocyanate Complexation in Aqueous Solvent Mixtures

A study of lanthanide complexation with isothiocyanate is underway using a multinuclear magnetic resonance technique. For isothiocyanate solutions in water–acetone–Freon mixtures at low temperature, −85–−125°C, ligand exchange is slow enough to permit the observation of 13C and 15N NMR signals for coordinated and free anions. For the Ce3+–NCS− system, four coordinated anion signals, displaced from the free anion signal by about +450 to +550 ppm for 15N and +50 to +80 ppm for 13C, are observed. The 13C and 15N spectral data are complementary, showing a signal area concentration dependence and measured coordination numbers consistent with the formation of Ce(NCS)2+ through Ce(NCS)1-4. In water–methanol, the extent of complexing is decreased, presumably because of the higher dielectric constant of this medium. In addition, the results of a competitive study of NCS− and Cl− ion binding, carried out using 35Cl NMR, is presented.
Sustained treatment with a 5-HT2A receptor agonist causes functional desensitization and reductions in agonist-labeled 5-HT2A receptors despite increases in receptor protein levels in rats

Abstract Adaptive changes in serotonin2A (5-HT2A) receptor signaling are associated with the clinical response to a number of psychiatric drugs including atypical antipsychotics and selective serotonin reuptake inhibitors. The present study examined possible mechanisms of agonist-induced desensitization of 5-HT2A receptors in rat hypothalamic paraventricular nucleus (PVN) after 4 and 7 days of treatment with 1 mg/kg (−)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI). The magnitude of 5-HT2A receptor-mediated oxytocin release decreased 78% after 4 days and 61% after 7 days of DOI treatment. Similarly, the magnitude of ACTH release following 1 mg/kg DOI decreased by 31% after 4 days and 38% after 7 days of DOI treatment. Treatment with DOI for either 4 or 7 days caused a significant decrease (by approximately 50%) in the high-affinity 5-HT2A receptor binding as measured by 125I-DOI binding compared to saline-treated control rats. In contrast, western blot analysis demonstrated a significant increase in 5-HT2A receptor protein levels with 4 or 7 days of DOI treatment to 167% and 191% of control levels, respectively. Real time quantitative RT-PCR analysis revealed a small but nonsignificant increase in the levels of 5-HT2A mRNA following treatment with DOI for 4 or 7 days. Taken together, the 5-HT2A receptor-stimulated hormone responses, agonist binding data and western blot data suggest that although agonist treatment increases the levels of 5-HT2A receptor protein in the cell membrane, there is a reduction in the population of 5-HT2A receptors capable of high-affinity binding and mediating a functional response.
Gold nanoparticle assemblies by metal ion-pyridine complexation and their rectified quantized charging in aqueous solutions

Gold nanoparticle assemblies were constructed by exploiting the complexation interactions between divalent metal ions and pyridine moieties. The thickness (layers) of the particle thin films was readily controlled by the repetition of the alternate dipping cycles, as monitored by quartz crystal microbalance (QCM). Electrochemical studies of these surface-immobilized nanoparticle layers revealed rectified quantized charging characters in aqueous solutions in the presence of hydrophobic anions. The effects of the nature of the electrolyte ions were investigated in the context of their hydrophobicity and interactions with the surface-bound particle molecules. It was found that the onset voltammetric potentials, as well as the effective molecular capacitance of the nanoparticles, were sensitive to the solution compositions. The behaviors were quite similar to those with the nanoparticle assemblies fabricated by dithiol linkages. The present study provided additional experimental parameters that could be used ...
A novel high-performance asymmetric hetero-doped S/D high-voltage MOSFET

A novel high-voltage MOSFET structure, using a simple yet effective concept of an asymmetric hetero-doped source/drain (S/D) is proposed. The asymmetric hetero-doped S/D reduces the on-state resistance of the transistor due to the high doping used for device drain drift, provides excellent ruggedness for parasitic NPN turned-on due to a minimized n/sup +/ source spacer, and also raises the device breakdown voltage due to charge compensation in the composite drain drift region. Therefore, the asymmetric hetero-doped S/D structure allows the high voltage MOSFET to have a high current handling capability with a small device size. This in turn causes the R (sp, on) to be low, leading to high performance for the power device when used in a power integrated circuit. Measured results show that a 24-V breakdown voltage new device with a low-cost two-layer metal (Al) back-end achieves very low R (sp, on) of 0.166 m/spl Omega//spl middot/cm/sup 2/. Furthermore, the new device with a 65-V high-side capability achieves good isolation performance even when switching S/D to -20 V and also gets a cutoff frequency of 13 GHz at a gate voltage of 5.5 V.
Residents' perspectives on the final year of medical school.

Objectives: To characterize junior residents’ perspectives on the purpose, value, and potential improvement of the final year of medical school. Methods: Eighteen interviews were conducted with junior residents who graduated from nine different medical schools and who were in internal medicine, surgery, and psychiatry programs at one institution in the United States. Interview transcripts were coded and analyzed inductively for themes. Results: Participants’ descriptions of the purpose of their recently completed final year of medical school contained three primary themes: residency-related purposes, interestor need-based purposes, and transitional purposes. Participants commented on the most valued aspects of the final year. Themes included opportunities to: prepare for residency; assume a higher level of responsibility in patient care; pursue experiences of interest that added breadth of knowledge, skills and perspective; develop and/or clarify career plans; and enjoy a period of respite. Suggestions for improvement included enhancing the learning value of clinical electives, augmenting specific curricular content, and making the final year more purposeful and better aligned with career goals. Conclusions: The final year of medical school is a critical part of medical education for most learners, but careful attention is needed to ensure that the year is developmentally robust. Medical educators can facilitate this by creating structures to help students define personal and professional goals, identify opportunities to work toward these goals, and monitor progress so that the value of the final year is optimized and not exclusively focused on residency
The relationship between acculturation and job satisfaction among Chinese immigrants in the New York city restaurant business.

Abstract This exploratory study investigated the process of acculturation and its influence on job satisfaction. Our convenience sample consisted of 65 Chinese immigrant restaurant workers from New York City, (“NYC”) employed either in “Chinatown” (centralized Chinese area) or “City” (outside the Chinatown area) sites. The data were collected using acculturation and job satisfaction questionnaires augmented by open-ended questions. Results indicate that City workers are more acculturated than Chinatown workers, and seem to have higher levels of job satisfaction. Acculturation was related to job satisfaction. English proficiency and education were related to acculturation, but not to job satisfaction. Male workers are both more acculturated and more satisfied than their female counterparts.
Circadian Serotonin Rhythm Control: Sympathetic and Nonsympathetic Pathways in Rat Pineals of Different Ages

Immature rats (15–20 days) maintained in a 14 :10 hr light: dark cycle, and sacrificed at 1:00 and 11:00 PM, showed a circadian rhythm in pineal serotonin levels. When pineals of similar animals were sympathectomized by bilateral superior cervical ganglionectomy the serotonin rhythm persisted. Thus, in contrast to the adult, the serotonin rhythm in the immature pineal is independent of sympathetic innervation. At 60 days of age there was no rhythm in sympathectomized pineals; thus, the nerve dependent serotonin rhythm of the adultwas already established. When ganglionectomized immature rats were kept in constant light or in constant dark, the rhythm was abolished. Diurnal lighting, therefore, is important maintain the nerve independent serotonin rhythm of the immature rat. In contrast, the rhythm in the adult rat persists in constant dark. The mechanism controlling circadian serotonin rhythm in immature rats may be very different from that in adult animals. Ontogeny of the rhythm is proposed and discussed...
Mechanical and Chemical Effects of Pore Fluids on Rock Properties: ABSTRACT

The disposal of wastes underground involves injection of fluids into a rock mass that through natural processes has probably attained a state of at least metastable equilibrium. Injected fluids tend to disrupt this equilibrium mechanically and chemically. The primary question concerns what effect this disruption will have on the rock body. Fracturing, faulting, or the reactivation of old faults could lead to earthquakes and to the creation of fractures that may provide permeability channels through which injected fluids could escape from the intended disposal beds. Accelerated compaction, brought about by chemically weakening the load-bearing framework of the rock or by reducing fluid pressures upon withdrawal, can cause surface subsidence. At depths of 3-4 km most rocks are brittle, and fracture and rigid-body rotation are the dominant mechanisms of deformation. The most important physical parameter in this regime is the effective confining pressure Pe, defined as the difference between the confining pressure Pc and the pore-fluid pressure Pp. Both the breaking strength and the compaction of rocks are dependent upon the magnitude of Pe regardless of the absolute values of Pc and Pp. Increases in Pp produced by injection of fluids decrease the normal stresses but do not change shear stresses across potential failure surfaces. This could lead to fracturing, faulting, or the reactivation of pre-existing faults. Decreases in Pp produced y withdrawal of fluids from a reservoir can lead to compaction and surface subsidence as the Pe is increased. The second important aspect of the problem is the role of the pore-fluid chemistry. Significant reductions in rock strength have been shown to result from the lowering of the surface energy of solids that occurs from adsorption of pore fluids and associated modification of bonding. Triaxial compression tests on sandstone show that the coefficient of internal friction is not altered by pore solutions of 0.002 to 2 ppm of FeCl3. The lowering of the breaking strength is due rather to the reduction of the intragranular cohesive strength as a function of the concentration of the electrolyte solution. The frictional characteristics of already broken rocks may be significantly altered by the introduction of surface-active fluids. In light of man-made earthquakes, such as those near Denver, Colorado, the influence of pore-fluid pressure and chemistry suggests that more sophisticated tests of rock properties should be made if problems caused by unexpected rock failure are to be eliminated. End_of_Article - Last_Page 2090------------
Recent Experimental Results from HELIOS

The renewed emphasis on nuclear structure far from stability, studied with nucleon-transfer reactions that utilize radioactive beams, has led to many new and exciting results. Accompanying these developments are, however many technical challenges that confront studies of transfer reactions in inverse kinematics. Amongst these are the identification of reaction products and the resolution of states in the residual nuclei. A new device, HELIOS (the HELIcal Orbit Spectrometer) has been constructed to solve many of the problems encountered with such reactions. The device uses a uniform magnetic field produced by a large, superconducting solenoid to transport light reaction products from the target to a linear array of position-sensitive silicon detectors. In operation since August of 2008, HELIOS has been used to study a variety of (d,p) reactions with beams of stable and unstable ions with masses ranging from A=11 to 136.
Effect of elastic recovery on the electrical contact resistance in anisotropic conductive adhesive assemblies

The successful design of anisotropic conductive adhesive (ACA) assemblies depends mainly on the accurate prediction of their electrical contact resistance. Among the parameters that influence this resistance, the bonding force used to compress the conductive particles against the conductive tracks during the assembly process is very important. This paper investigates how the contact resistance changes as the bonding force is removed at the end of the assembly process when the epoxy resin used to bond the surfaces has cured. The final contact resistance is determined by examining, through theoretical, experimental and numerical analyzes, the evolution of the residual stress as the elastic recovery of the compressed conductive particles and tracks takes place when the bonding force is removed. An iterative algorithm derived from methods found in fracture mechanics analysis is used to determine the relationship between the contact resistance, the adhesive strength and the stiffness of the cured resin. It is shown that smaller values of adhesive strength yield higher contact resistance values; and similarly, smaller values of modulus of elasticity of the resin lead to higher contact resistance values.
Focal mechanism determination of induced microearthquakes in an oil field using full waveforms from shallow and deep seismic networks

A new, relatively high frequency, full waveform matching method was used to study the focal mechanisms of small, local earthquakes induced in an oil field, which are monitored by a sparse near-surface network and a deep borehole network. The determined source properties are helpful for understanding the local stress regime in this field. During the waveform inversion, we maximize both the phase and amplitude matching between the observed and modeled waveforms. We also use the polarities of the first P-wave arrivals and the average S/P amplitude ratios to better constrain the matching. An objective function is constructed to include all four criteria. For different hypocenters and source types, comprehensive synthetic tests showed that our method is robust enough to determine the focal mechanisms under the current array geometries, even when there is considerable velocity inaccuracy. The application to several tens of induced microseismic events showed satisfactory waveform matching between modeled and obs...
Rejoinder: Be All Our Insomnia Remembered…

The evolutionary history from DA to GIS and more generally to CIS may well be cited by a future Stephen Stigler to advance a new Stigler’s Law: “No scientific idea is originated from a single team.” Putting aside the well-known connection between EM and DA (see Tanner and Wong, 2010 and van Dyk and Meng, 2010), we have witnessed how the idea of introducing a non-identifiable parameter into DA schemes—for the purpose of better algorithmic efficiency—was independently and simultaneously developed by two research teams (Liu and Wu, 1999 and Meng and van Dyk, 1999). Subsequently, the idea of utilizing or combining multiple DA schemes has been pursued by (at least) three teams, from seemingly different angles. Roberts and Papaspiliopoulos’s team has been investigating the partially non-centered parametrization (see, e.g., Papaspiliopoulos, Roberts and Skold, 2007), whose power and versatility are nicely illustrated by the discussion by Papaspiliopoulos, Roberts, and Sermaidis (PRS). The idea of partially non-centering is to introduce a tuning parameter w into the non-centering scheme (i.e., a DA scheme) and then seek its optimal value for the fastest convergence. It is therefore equivalent to the conditional augmentation approach (Meng and van Dyk, 1999 and van Dyk and Meng, 2001), where w is known as a working parameter and is determined by the same optimality criterion; often the optimality calculations are approximate because exact optimality is hard to achieve in practice.
B. J. Verts: 1927–2011

Mammalogy and wildlife science lost a respected scientist, teacher, and mentor on 29 December 2011, when B. J. Verts died in Corvallis, Oregon, following an infection with Cryptococcus gattii, which followed an 11-year battle with chronic lymphocytic leukemia. He was born to William Trigg and Jeanette Poindexter Verts on 9 April 1927 in Nelson, Missouri. He lived in Nelson until the age of 9 when his father died, at which time he moved to Arrow Rock, Missouri, to live with his maternal grandmother and aunt. In 1939, he moved to Shelbina, Missouri, when his mother remarried. He and his stepfather did not get along; however, B. J. was befriended by a man who was the local game warden and truant officer. This man took B. J. under his wing because he understood that B. J. needed a positive adult male influence in his life. He taught B. J. to fish, hunt, and to simply enjoy being out-of-doors. During these years of living in rural areas, B. J. became an avid fisherman and hunter and keen observer of wildlife. His favorite tale to tell of this time period was being scolded by a teacher for missing school for 2 days. She stated that she was going to report him to the truant officer, who would determine a proper punishment. When he explained that during those 2 days he was with the truant officer off on a hunting trip, she simply stood there with her mouth agape and never said another word regarding any more days of school he missed. B. J. always gave credit for his becoming a university-trained wildlife biologist to the game warden. He joined the Navy in June 1945 (Fig. 1) and served as a Pharmacist's Mate Second Class in the South Pacific Northern Marianas on the islands …
Arrestins regulate cell spreading and motility via focal adhesion dynamics

Focal adhesions (FAs) play a key role in cell attachment, and their timely disassembly is required for cell motility. Both microtubule-dependent targeting and recruitment of clathrin are critical for FA disassembly. Here we identify nonvisual arrestins as molecular links between microtubules and clathrin. Cells lacking both nonvisual arrestins showed excessive spreading on fibronectin and poly-d-lysine, increased adhesion, and reduced motility. The absence of arrestins greatly increases the size and lifespan of FAs, indicating that arrestins are necessary for rapid FA turnover. In nocodazole washout assays, FAs in arrestin-deficient cells were unresponsive to disassociation or regrowth of microtubules, suggesting that arrestins are necessary for microtubule targeting-dependent FA disassembly. Clathrin exhibited decreased dynamics near FA in arrestin-deficient cells. In contrast to wild-type arrestins, mutants deficient in clathrin binding did not rescue the phenotype. Collectively the data indicate that arrestins are key regulators of FA disassembly linking microtubules and clathrin.
What determines biological fitness? The problem of the reference environment

Organisms’ environments are thought to play a fundamental role in determining their fitness and hence in natural selection. Existing intuitive conceptions of environment are sufficient for biological practice. I argue, however, that attempts to produce a general characterization of fitness and natural selection are incomplete without the help of general conceptions of what conditions are included in the environment. Thus there is a “problem of the reference environment”—more particularly, problems of specifying principles which pick out those environmental conditions which determine fitness. I distinguish various reference environment problems and propose solutions to some of them. While there has been a limited amount of work on problems concerning what I call “subenvironments”, there appears to be no earlier work on problems of what I call the “whole environment”. The first solution I propose for a whole environment problem specifies the overall environment for natural selection on a set of biological types present in a population over a specified period of time. The second specifies an environment relevant to extinction of types in a population; this kind of environment is especially relevant to certain kinds of long-term evolution.
Measuring thin-film elastic constants by line-focus acoustic microscopy

The determination of elastic constants of bulk specimens and anisotropic films deposited on anisotropic substrates from V(z) measurements obtained by using a line-focus acoustic microscope is discussed. The procedure has three essential components: (1) V(z) curve measurement as a function of direction of wave mode propagation in the sample at fixed frequency and/or as a function of the frequency or film thickness for a fixed direction, (2) use of a measurement model for parametric studies of V(z) curves, and (3) determination of elastic constants by systematically comparing wave-mode velocities obtained from the measurement model and the V(z) measurement. Some examples are presented for transition metal nitride films used as hard protective coatings of softer surfaces. Attention is also directed to certain advantages of using multiple modes. It is shown that multiple-mode results reduce the region in a plane of material constants for which a deviation function between theoretical and experimental results has prescribed small values. Finally a brief discussion is presented of some recent results obtained at much lower frequencies by time resolved acoustic microscopy.
Anticancer activity of the iron facilitator LS081

Cancer cells have increased levels of transferrin receptor and lower levels of ferritin, an iron deficient phenotype that has led to the use of iron chelators to further deplete cells of iron and limit cancer cell growth. As cancer cells also have increased reactive oxygen species (ROS) we hypothesized that a contrarian approach of enhancing iron entry would allow for further increased generation of ROS causing oxidative damage and cell death. A small molecule library consisting of ~11,000 compounds was screened to identify compounds that stimulated iron-induced quenching of intracellular calcein fluorescence. We verified the iron facilitating properties of the lead compound, LS081, through 55Fe uptake and the expression of the iron storage protein, ferritin. LS081-induced iron facilitation was correlated with rates of cancer cell growth inhibition, ROS production, clonogenicity, and hypoxia induced factor (HIF) levels. Compound LS081 increased 55Fe uptake in various cancer cell lines and Caco2 cells, a model system for studying intestinal iron uptake. LS081 also increased the uptake of Fe from transferrin (Tf). LS081 decreased proliferation of the PC-3 prostate cancer cell line in the presence of iron with a lesser effect on normal prostate 267B1 cells. In addition, LS081 markedly decreased HIF-1α and -2α levels in DU-145 prostate cancer cell line and the MDA-MB-231 breast cancer cell lines, stimulated ROS production, and decreased clonogenicity. We have developed a high through-put screening technique and identified small molecules that stimulate iron uptake both from ferriTf and non-Tf bound iron. These iron facilitator compounds displayed properties suggesting that they may serve as anti-cancer agents.
Human sodium channel gating defects caused by missense mutations in S6 segments associated with myotonia: S804F and V1293I

1 Missense mutations in the α-subunit of the human skeletal muscle sodium channel (hSkM1) have been detected in some heritable forms of myotonia. By recording Na+ currents from cells transfected with cDNA encoding either wild-type or mutant hSkM1, we characterized the functional consequences of two myotonia-associated mutations that lie at the cytoplasmic end of the sixth transmembrane segment in domain II (S804F) or domain III (V1293I). 2 Both mutations caused modest, but unequivocal, alterations in the voltage-dependent gating behaviour of hSkM1. For S804F, the abnormalities were limited to fast inactivation: the persistent Na+ current at the end of a 50 ms depolarization was increased 3-fold, the rate of inactivation from the open state was slowed 2-fold, and the voltage dependence of fast inactivation (h∞) was shifted by +3 mV. V1293I also disrupted fast inactivation, as evidenced by a 3-fold faster rate of recovery at hyperpolarized potentials (<= -70 mV). Activation was altered as well for V1293I: the voltage dependence was shifted by -6 mV (hyperpolarized). 3 Slow inactivation was not altered by S804F or V1293I. 4 We conclude that S804F and V1293I are not benign polymorphisms. Either mutation causes detectable alterations in channel gating and, in model simulations, the magnitude of the defects is sufficient to produce runs of myotonic discharges.
Enterprise strategy concept, measurement, and validation: Integrating stakeholder engagement into the firm's strategic architecture

Abstract A firm's enterprise strategy is its overarching strategic orientation, addressing questions regarding its general purpose and the specific nature of its relationships with stakeholders along two dimensions: (a) scope, which represents the range of stakeholders the organization attempts to serve, and (b) type, which represents the general motivation behind stakeholder initiatives. The corporate social responsibility literature has played an important role in bringing a concern with stakeholder issues; however, this literature does not provide a systematic means of integrating these concerns into the firm's strategic architecture. Enterprise strategy offers a unifying construct, grounded in strategic considerations of both the social and economic demands placed on an organization. However, despite its conceptual importance to strategy and social issues, this construct is empirically underdeveloped. This study develops a reliable and valid measure of the enterprise strategy construct to advance the field's understanding of this increasingly important stream of research. Based on computer-aided text analyses of company letters to stakeholders, we systematically identify terminology that reflects the scope and type of a firm's espoused enterprise strategy. Overall, these data support four fundamental orientations of enterprise strategy: (1) narrow defensive, (2) narrow offensive, (3) broad defensive, and (4) broad offensive.
Complete metastasectomy after high-dose interleukin-2 (HD IL-2) therapy for melanoma

Meeting abstracts Our aim was to describe our experience with surgery after High-dose Interleukin-2 (HD IL-2) therapy in patients who were eligible for complete metastasectomy after treatment. A retrospective chart review was performed on patients with metastatic melanoma seen at Saint Louis
Regional blood flows and cardiac function changes induced by angiotensin II in conscious dogs

Hemodynamic properties of angiotensin (ANG) II 1, 5, 10 and 100 ng/kg i.v. and 10, 100 and 1000 ng/kg i.v.t. were assessed in conscious dogs. ANG II i.v. produced a dose-dependent pressor response (59 +/- 5-124 +/- 16 mmHg) and renal vasoconstriction (1.3 +/- 0.4-96 +/- 32 mmHg/ml/min). Ganglionic blockade (chlorisondamine 2 mg/kg i.v.) diminished mean arterial responses without altering peptide effects on renal circulation. At the highest dose, ANG II i.v. induced cardiac stimulation: increased heart rate (75 +/- 4-115 +/- 6 beats/min), cardiac output (2.0 +/- 0.1-2.4 +/- 0.2 l/min), dP/dt (2308 +/- 181-2773 +/- 173 mmHg/sec) and coronary blood flow (49 +/- 10-96 +/- 23 ml/min). Although with chlorisondamine cardiac response was more pronounced, subsequent beta blockade abolished it. Concomitantly, an isolated increase in plasma epinephrine was recorded (63 +/- 8-1505 +/- 354 pg/ml). A pressor response (59 +/- 8-89 +/- 13 mmHg) and renal vasoconstriction (1.1 +/- 0.1-2.2 +/- 0.5 mmHg/ml/min) were also produced by ANG II i.v.t. at the highest dose. These centrally mediated changes were prevented by chlorisondamine. Our study demonstrates 1) i.v. ANG II-mediated pressor responses are dependent on direct and indirect components, the relative contribution of each being dependent on the regional circulation; ANG II i.v. also produced a biphasic cardiac response--an initial centrally mediated depression and a secondary stimulation dependent on epinephrine via cardiac beta receptors and 2) i.v.t. ANG II-mediated pressor effects are essentially indirect. Finally, no evidence was found to support the role of vasopressin in ANG II effects.
Interplay of the physical microenvironment, contact guidance, and intracellular signaling in cell decision making.

The peritumoral physical microenvironment consists of complex topographies that influence cell migration. Cell decision making, upon encountering anisotropic, physiologically relevant physical cues...
Germicidal Ultraviolet Light to Lower Numbers of Listeria monocytogenes on Broiler Breast Fillets

Raw broiler breast fillets were subjected to germicidal ultraviolet (UV) light (dose of 1,000 microW/cm(2) for 5 min at a wavelength of 254 nm) to evaluate its potential to reduce Listeria monocytogenes numbers on raw product before shipment to a poultry further-processing plant. Boneless, skinless breast fillets were inoculated with 4 different strains of L. monocytogenes 5 min before treatment. After the UV treatment, breast fillets were stored at 4 degrees C for 24 h. Enumeration of remaining L. monocytogenes was performed using the spread plate method on modified Oxford agar. An approximate 2-log reduction in viable L. monocytogenes was observed with all 4 strains on UV-treated breast fillets as compared with the nontreated breast fillets. The UV treatment caused only slight changes in meat color (lightness, redness, and yellowness) on day of treatment or after 7 d of storage. This study suggests that UV treatment of raw breast fillets at a slaughter plant can significantly reduce L. monocytogenes without negatively affecting meat color. This process could be used to reduce the negative effect of raw poultry as a transmission vector of L. monocytogenes into a poultry further-processing plant.
Ascospore Discharge by Erysiphe Trina

Ascospores appear to be the major if not the only means of dispersal of Erysiphe trina Harkn. on Quercus agrifolia Nee. When living leaves bearing perithecia were wetted, spore discharge began in less than 10 min. Maximum discharge was in the first hour and continued for about 40 hr. Ascospores were discharged vertically to a maximum of 31 mm above the perithecia. Many ascospores disintegrated explosively in a moist chamber and the splash drops stained heavily with Sudan IV. At 21 C and 50% relative humidity the turgid ascospores decreased in volume more slowly than did conidia of Erysiphe polypgoni DC. or Erysiphe graminis DC.
DESIGNING EXPERIMENTS TO MAXIMIZE THE POWER OF DETECTING CORRELATIONS.

Studies investigating correlations among traits are increasingly common in evolutionary biology. By providing power calculations, minimum sample sizes, and standard errors of correlation coefficients in a variety of contexts, this note provides guidelines to insure that nonzero correlations will not be erroneously dismissed as nonsignificant in properly designed experiements. Forty individuals is often sufficient for reasonable estimation of correlation coefficients, although 100 or more individuals may be nexessary if a large number of traits are involved or comparisons are to be made among the coefficients.
Premenstrual Distress among Caucasian, African-American and Chinese Women

While clinical research on Premenstrual Syndrome (PMS) has focused mainly on women’s prevalence and symptomology in the west, PMS is a disorder that affects women of many cultures. A limited number of cross-cultural studies have compared the western experience of PMS with that of other cultures and have found that the prevalence of specific symptoms varies amongst cultures. Given the lack of research on PMS across cultures, this study explores the symptoms of PMS in Caucasian and African-American women in the US and Chinese women in Hong Kong and the differences and/or similarities among these groups. This research study utilized a quantitative survey research design with a convenience sample of 700 women (193 African-American, 180 Caucasian and 327 Chinese) aged between 20 to 55 years in both the US and Hong Kong. It was found that race/ethnicity significantly contributes to the prediction of each symptom subscale with the exception of the autonomic symptoms. The amount of variance in symptoms that can be explained by race/ethnicity ranges from about 5% (for pain symptoms) to almost 19% (for arousal symptoms). In general, the Chinese participants reported significantly fewer premenstrual distress symptoms than African-American and Caucasian participants. The results suggest this is true in the case of pain-related symptoms and concentrationrelated symptoms. In addition, compared to the Caucasian and African-American participants, the Chinese participants reported significantly lower levels of affective symptoms.
Patient participation in cancer clinical trials: A pilot test of lay navigation.

Abstract Background Clinical trials (CT) represent an important treatment option for cancer patients. Unfortunately, patients face challenges to enrolling in CTs, such as logistical barriers, poor CT understanding and complex clinical regimens. Patient navigation is a strategy that may help to improve the delivery of CT education and support services. We examined the feasibility and initial effect of one navigation strategy, use of lay navigators. Methods A lay CT navigation intervention was evaluated in a prospective cohort study among 40 lung and esophageal cancer patients. The intervention was delivered by a trained lay navigator who viewed a 17-min CT educational video with each patient, assessed and answered their questions about CT participation and addressed reported barriers to care and trial participation. Results During this 12-month pilot project, 85% (95% CI: 72%–93%) of patients eligible for a therapeutic CT consented to participate in the CT navigation intervention. Among navigated patients, CT understanding improved between pre- and post-test (means 3.54 and 4.40, respectively; p-value 0.004), and 95% (95% CI: 82%–98%) of navigated patients consented to participate in a CT. Navigated patients reported being satisfied with patient navigation services and CT participation. Conclusions In this formative single-arm pilot project, initial evidence was found for the potential effect of a lay navigation intervention on CT understanding and enrollment. A randomized controlled trial is needed to examine the efficacy of the intervention for improving CT education and enrollment.
Study on the efficacy of quarantine during outbreaks of acute hemorrhagic conjunctivitis outbreaks at schools through the susceptive-infective-quarantine-removal model

To assess the efficacy of quarantine for acute hemorrhagic conjunctivitis (AHC) outbreaks control in schools, by using the Compartment Model. Through combining the characters of both AHC and compartment model, we built a susceptive-infective-removal (SIR) model suited for AHC outbreaks control in schools, and then quarantine was added into the model to develop a susceptive-infective-quarantine-removal (SIQR) model. An outbreak of AHC in Changsha in 2011 was employed as a sample to assess the effect of quarantine for the prevention and control of AHC. Basic reproduction number (λ0) of the AHC outbreak without intervention was 6.80, thus the transmission speed of the disease became quite fast. If no intervention had been adopted, almost all the students, faculties and staff members would have been infected within 23 days, and the accumulative cases would become 738, with the total attack rate (TAR) as 99.73%. The peak of the outbreak was at Sep. 11th and the number of new cases was 126 on that day. The efficacy would have been different if quarantine forces had been taken at different time and differently. The bigger and earlier the quarantine force had been adopted, the lower morbidity peak and the smaller TAR would have been appeared, with better efficacy of outbreak control. If the quarantine rate had been taken at the level of 90% on the sixth day, the accumulative case would have been reduced to 132 and the TAR had become 17.84% consequently. Quarantine program could be used as a main intervention approach to be employed for ACH outbreak at schools.
Physiologically Based Absorption Modeling to Design Extended-Release Clinical Products for an Ester Prodrug

Absorption modeling has demonstrated its great value in modern drug product development due to its utility in understanding and predicting in vivo performance. In this case, we integrated physiologically based modeling in the development processes to effectively design extended-release (ER) clinical products for an ester prodrug LY545694. By simulating the trial results of immediate-release products, we delineated complex pharmacokinetics due to prodrug conversion and established an absorption model to describe the clinical observations. This model suggested the prodrug has optimal biopharmaceutical properties to warrant developing an ER product. Subsequently, we incorporated release profiles of prototype ER tablets into the absorption model to simulate the in vivo performance of these products observed in an exploratory trial. The models suggested that the absorption of these ER tablets was lower than the IR products because the extended release from the formulations prevented the drug from taking advantage of the optimal absorption window. Using these models, we formed a strategy to optimize the ER product to minimize the impact of the absorption window limitation. Accurate prediction of the performance of these optimized products by modeling was confirmed in a third clinical trial.