cssi/SciSciGPT-SciSciNet huggingface dataset:
Robust moral realism: an excellent religion

According to robust moral realism, there exist objective, non-natural moral facts. Moral facts of this sort do not fit easily into the world as illuminated by natural science. Further, if such facts exist at all, it is hard to see how we could know of their existence by any familiar means. Yet robust realists are not moral skeptics; they believe that we do know (some of) the moral facts. Thus robust moral realism comes with a number of hard-to-defend ontological and epistemological commitments. Recently, Sharon Street has claimed, in light of these commitments, that robust moral realism requires a kind of faith and “has become a strange form of religion.” I believe that Street is right. I argue at some length that robust moral realism does require faith, and is a religion. However, I further argue that it is an excellent religion. I argue that it has three principal advantages: it is avoids wishful thinking, is guaranteed not to contradict the results of natural science, and is profoundly simple in its ontological commitments. Further, robust moral realism may be rationally defensible on evidentialist grounds. Consequently, even if the standard arguments for traditional religions are not compelling, there might still be compelling arguments for robust moral realism.
Effect of liquids on the Drude dielectric function of Ag and Au films.

Spectroscopic ellipsometric measurements were made of the free-electron dielectric functions of Ag and Au films in air and immersed in dielectric liquids of different refractive indexes. The effects seen by Gugger et al. were reproduced for Ag and Au films prepared similarly to theirs, and in Ag films with larger grains. Different effects were seen with an (oxidized) single crystal of Ag and a single crystal of Au. The ''anomalous'' data could be fitted with an effective-medium model by assuming that the liquid penetrates all, or most, of the intergrain regions within the optical penetration depth. The dielectric functions of ''ideal'' Ag and Au samples were obtained from fits with an effective-medium model.
Chromatid autonomy in Banasa (Hemiptera: Pentatomidae)

1. Of the ten species ofBanasa investigated, one has the typical chromosome complement of the TribePentatomini (2n=12+2 sex chromosomes); three have an extra pair of autosomes (2n=14+2 sex chromosomes); and six have doubled the number of autosomes (2n=24+2 sex chromosomes). 2. The autosomes in the 26-chromosome species ofBanasa are distinctly smaller than in either the 14- or the 16-chromosome species, but the size of the sex chromosomes has undergone no such decrease. 3. In five of the species in which the number of autosomes has been doubled, the DNA value remains close to that found in the presumably more primitive species with 14 chromosomes. No DNA data are available for the sixth species. 4. It is concluded that the evidence argues against both polyploidy and an accumulation of random changes in chromosomal structure as primary factors in the evolution of the 26-chromosome species. It is proposed instead that the doubling of the autosome number is due to a separation and individuation of the two chromatids that compose each autosome. 5. The suggestion is made that both chromatid autonomy and polyteny have played important roles in the chromosomal evolution of many other species also. But it is emphasized that only rarely can these two factors be solely responsible for evolutionary changes; fortuitous alterations in chromosome structure as well as true polyploidy (especially in plants) have also been involved in arriving at the conditions as we see them today.
The Culture of Poverty: An Ideological Analysis:

For three decades Oscar Lewis's subculture of poverty concept has been misinterpreted as a theory bent on blaming the victims of poverty for their poverty. This essay corrects this misunderstanding. Using a sociology of knowledge approach, it explores the historical origins of this misreading and shows how current poverty scholarship replicates this erroneous interpretation of Lewis's work. An attempt is made to remedy this situation by arguing that Lewis's subculture of poverty idea, far from being a poor-bashing, ideological ploy, is firmly grounded in a Marxist critique of capital and its productive contradictions. As such, Lewis's work is a celebration of the resilience and resourcefulness of the poor, not a denigration of the lower class and the cultural defenses they erect against poverty's everyday uncertainty.
Pharmacological analysis of 4-carboxyphenylglycine derivatives: Comparison of effects on mGluR1α and mGluR5a subtypes

The antagonist effects of the 4-carboxyphenylglycines: (S)-4-carboxy-3hydroxyphenylglycine (4C3HPG), (S)-4-carboxyphenylglycine (4CPG) and (+)-alpha-methyl-4-carboxyphenylglycine (M4CPG) were compared on functional responses of human metabotropic glutamate receptor (mGluR) subtypes mGluR1 alpha and mGluR5a. These receptors both belong to group 1 type mGluRs which couple to the phosphoinositide (PI) hydrolysis/[Ca2+]i mobilization signal transduction pathway and are closely related in both structure and agonist pharmacology. In this study, the IC50 values obtained for quisqualate induced PI hydrolysis responses show that although all the phenylglycines are antagonists for both mGluR1 alpha and mGluR5a, the compounds exhibit differential potencies at these receptor subtypes. The 4C3HPG derivative was the most potent antagonist for both mGluR1 alpha (IC50 range: 19-50 microM) and mGluR5a (IC50 range: 53-280 microM). 4CPG produced an IC50 range of 4r-72 microM for mGluR1 alpha and 150-156 microM for mGluR5a cells. The potency of the M4CPG could not be distinguished from that of 4CPG with IC50 ranges of 29-100 microM and 115-210 microM for mGluR1 alpha and mGluR5a respectively. Further characterization of the dose-response effects of the compounds on quisqualate induced [Ca2+]i mobilization showed that although the magnitude of phenylglycine inhibition was reduced for both mGluR subtypes compared to those observed for stimulation of PI hydrolysis (except for 4C3HPG on mGluR1 alpha), similar differences in the relative potencies of the phenylglycines between mGluR1 alpha (IC50s: 40 +/- 10 microM for 4C3HPG: 300-1000 microM for 4CPG and M4CPG) and mGluR5a (IC50s: > 1000 microM) were evident.(ABSTRACT TRUNCATED AT 250 WORDS)
A neighborhood in which the Van Der Waerden permanent conjecture is valid

We show that if A is n ×n doubly stochasticn > 2, and if then per is the Euclidean norm; Jn is the n×n matrix whose entries are all n −
Identification and extent of fluid bilayer regions in membranous cytochrome oxidase

Abstract Membranous cytochrome oxidase isolated from mitochondria provides a useful model membrane for studies of hydrophobic lipid association with a fairly well characterized functional protein complex. In order to examine the lipid environments, isotropic and oriented samples of cytochrome oxidase of varying phospholipid content were spin labeled with 5-doxylstearic acid (the 4′,4′-dimethyloxazolidine-N-oxyl derivative of 5-ketostearic acid), and examined by ESR spectroscopy. The isotropic samples exhibit two spectral components. Based on the relative intensity of the two components, the mobility, and the response to hydration, the two components are interpreted as arising from two lipid environments: (1) a layer of lipid bound to the hydrophobic protein surface (boundary lipid) and (2) fluid phospholipid bilayer regions. The extent of the bilayer regions is estimated from integration of the two components of the ESR spectra for samples with different phospholipid/protein ratios. The anisotropy of macroscopically oriented membranous cytochrome oxidase samples containing 0.33 and 0.49 mg phospholipid/mg protein confirms the presence of phospholipd bilayer regions. A spectral analysis reveals a remarkable similarity between the phospholipid bilayer regions in the cytochrome oxidase model membranes and bilayers formed by the isolated lipids, whereas the boundary lipid component has no counterpart in lipid bilayers.
Consumer Reaction to Inequitable Exchange: The Role of Causal Inferences

Abstract The influence of causal attributions on consumers' reactions to inequitable exchange was examined in three contexts: the level of distress perceived as a function of the degree of inequity; the moderating effect of consumer attributions on the inequity-distress relationship; and consumers' likely response as a function of their perceived locus of causality. Results, based on a field experiment using 300 American women in a deceptive advertising setting, support the traditional distributive and procedural justice model but suggest that more complex (cognitive) paradigms are necessary to explain aggrieved consumers' interpretations of fairness by marketers.
Lovastatin, Nicotinic Acid, and Rhabdomyolysis

Excerpt To the Editor:We recently observed a case of severe rhabdomyolysis in a patient being treated with lovastatin and nicotinic acid. Our report of this case may be both instructive and benefic...
The proliferative response in vitro of vascular endothelial and smooth muscle cells exposed to wound fluids and macrophages.

The ability of wound-derived macrophages and of fluids obtained from wounds to stimulate the proliferation of vascular endothelial cells and vascular smooth muscle cells in vitro has been investigated. Sparse cultures of endothelial and smooth muscle cells maintained in the presence of optimal concentrations of serum and wound fluid showed a 25-fold increase and a 10-fold increase, respectively, in final cell density when compared to cultures maintained in the presence of serum alone. The response of both endothelial and smooth muscle cells to the wound fluid was dependent on the serum or plasma-serum concentrations in which they were maintained. The ability of the wound fluid to stimulate endothelial cell proliferation was compared to that of fibroblast growth factor (FGF), which has already been shown to be a potent mitogen for endothelial cells in vitro. The growth response of endothelial cell cultures, when exposed to either 2% wound fluid or 100 ng/ml of FGF, was found to be similar, and the normal cell morphology was maintained. To examine the possibility that the growth stimulating activity present in the wound fluid originated from macrophages, endothelial cells or smooth muscle cells were co-cultured with macrophages obtained from the wound fluid. A significant stimulation of both endothelial and smooth muscle cells was observed with 2 × 106 macrophages, which would suggest that macrophages may be the source of the mitogenic activity of the wound fluid in vivo.
Extension of integrated system optimization and parameter estimation to hierarchical control of steady state systems with output-dependent constraints

This paper proposes an alternative hierarchical integrated system optimization and parameter estimation technique obtained by combining a modified two-step method with the price method. The aim is to find a general hierarchical approach for the case where inequality constraints are output dependent. In this algorithm a new modifier is introduced to cope with the output-dependent constraints. This algorithm has the advantages that the existence of the model-based optimal solution is ensured during the course of iteration and the model optimization is simplified considerably. This technique uses an output feedback structure and a single loop iteration strategy. Optimality properties and convergence conditions are investigated. A simulation study is also presented.
Toward a Better Cross-Cultural Understanding of U.S. and Russian Lodging Employees: A Discriminant Analysis Approach

The lodging industry has appeared to be a successful exception to the difficulties that business in Russia has faced since perestroika. In spite of these successes, lodging operations have continued to face human resource challenges that arise out of the cross-cultural differences between Eastern and Western expectations, along with economic and political history. This study looks at differences in attitudes with regard to job satisfaction and organizational commitment between Russian and American lodging employees. Important attitudinal differences and similarities were found, and the Job Description Index (JDI) was confirmed as useful in understanding the differences. These findings imply that programs that work in U.S. organizations may have to be tested and adjusted to determine the extent to which they are transferable into the Russian lodging industry without significant modification.
Mexiletine and Persistent Ophthalmic Changes

Mexilitine is an anti-arrhythmic agent used to treat neuropathic pain. The drug has a low side-effect profile with gastritis as the predominant complaint. The following two cases suggest that mexilitine can potentially cause persistent ophthalmic changes and should be used with caution in chronic pain patients with preexisting ocular disease.
The BART case: Ethics and the employed engineer

There has been an upsurge of discussion recently about the status of engineering as a profession, the obligations of the engineer toward the public, and the relationship of the engineer to his employer. Some very important facets of these questions are illuminated by the fate of three engineers employed by BART. (Bay Area Rapid Transit).
A method for assessing environmental risk: A case study of Green Bay, Lake Michigan, USA

The Science Advisory Board of the US Environmental Protection Agency has recommended that risk reduction strategies become the centerpiece of environmental protection. The goal in developing such strategies is to identify opportunities for greatest reduction of ecological risks. This is a perspective that is significantly more comprehensive than the traditional focus on human health risks arising from environmental degradation. The identification of ecological risks upon which environmental protection efforts should be focused requires an ecological risk assessment methodology that is based on anthropogenic stressors affecting an ecosystem and a set of impaired use criteria. A methodology based on this concept is developed and discussed in this article. The methodology requires that risk values be assigned to each ecosystem stressor-impaired use pair that reflect the degree to which the given stressor contributes to ecosystem risk as measured by the given impaired use criterion. Once these data are available, mathematical analyses based on concepts from fuzzy set theory are performed to obtain a ranking of ecosystem stressors. The methodology has been tested by applying it to a case study involving Green Bay of Lake Michigan. A workshop was held in which 11 persons with extensive knowledge of the Green Bay ecosystem determined risk values through a group-consensus process. The analytical portion of the methodology was then used to rank the ecosystem risks (stressors) from several perspectives, including prevention management and remediation management. The overall conclusion of the workshop participants was that the fuzzy set decision model is a useful and effective methodology for differentiating environmental risk.
Reliability critical thermal model for double‐drift IMPATT diodes on diamond heat sinks

A thermal model of double-drift IMPATT diodes on diamond heat sinks has been developed. The thermal model approximates the temperature-dependent thermal conductivities of Si and diamond (Type II) by means of simple empirical formulae. The application of the thermal model to three IMPATT diode lots indicates that under life test, junction temperatures are greater than 700°C, and that the metal/Si interface temperatures exceed 500°C. An explanation of the failure mechanism is presented. Designs that result in a lower junction temperature are proposed.
Aerosol properties from EP-TOMS near UV observations

Abstract A method of aerosol detection and characterization using satellite measured radiances in the near ultraviolet has recently been developed. The retrieval approach is based on the interaction between the processes of aerosol absorption and scattering and the strong near-UV Rayleigh scattering. That interaction produces spectral variations of the backscattered radiances that can be used to separate aerosol absorption from scattering effects. In this paper, we briefly discuss the physical basis of the near UV approach for aerosol sensing from space, and illustrate its application to specific aerosol events using data from the currently operational Total Ozone Mapping Spectrometer on the Earth Probe satellite (EP-TOMS). EP-TOMS derived optical depths of mineral, carbonaceous and sulfate aerosols are in good agreement with ground-based AERONET sun-photometer measurements.
Precursor Balancing for Metabolic Engineering of Lycopene Production in Escherichia coli

One issue that must be addressed in the rational design of metabolic pathways is the elimination of potential bottlenecks in the upstream pathways. We have reconstructed the isoprenoid pathway to overproduce the carotenoid lycopene in Escherichia coli. Here we show that the distribution between pyruvate and glyceraldehyde 3-phosphate (G3P), the originating precursors of the isoprenoid pathway, is a major factor that can limit isoprenoid production yields in E. coli. In particular, alterations in the central metabolism that redirect flux from pyruvate back to G3P enhance lycopene production, while alterations that channel carbon flux away from the G3P pool have the opposite effect. These results suggest that G3P may be limiting in the biosynthesis of lycopene, and modifications that achieve a more equitable distribution between the two precursors are able to increase the lycopene yield in metabolically engineered E. coli.
Effects of crus cerebri lesions and repeated amphetamine treatment on the activity of nigral dopaminergic neurons.

Previous research suggests that the firing rate of dopamine (DA) neurons in the substantia nigra pars compacta (SNC) may be altered by repeated DA agonist treatment. Because changes in the frequency of DA activity could reflect the firing patterns (e.g., bursting) of the neurons sampled, this study examined both the firing rate and pattern of SNC DA neurons after long-term amphetamine (AMPH) treatment (5 mg/kg d-AMPH s.c. twice daily for 6 days). To assess the contribution of postsynaptic feedback from the forebrain, unilateral electrolytic lesions were made to the crus cerebri (CC), containing the striatonigral pathway, prior to AMPH treatment. Single-unit activity of presumed SNC DA neurons was recorded in adult male rats under urethane anesthesia. Spontaneous firing rate was reduced by AMPH treatment, relative to saline vehicle, but was unaffected by CC or sham lesions. Neurons categorized as bursting had faster rates of activity than nonbursting cells. AMPH treatment reduced the number of bursts seen in intact rats but increased bursting in lesioned rats. These results suggest that changes in DA firing rate previously found after chronic AMPH may reflect altered patterns of activity. In addition, the effects of long-term AMPH on the firing patterns of DA neurons appear to be mediated by fibers in the CC.
PyLOM: an interpreted language for planning applications

Controlling software systems autonomously has been a challenging research area. Modern autonomous systems are guided by a plan, which is a sequence of actions to take to achieve a goal. Many planning algorithms exist today to produce plans given a problem definition and goal. To ease programmability of autonomous systems, many languages have been developed for defining problems and goals. However, planning algorithms tend to need to be customized not only for the problem definition language, but also for the problem definition itself. This work presents a new problem definition language called PyLOM, an interpreted, object-oriented language. The PyLOM run-time system uses generic algorithms, which do not need to be customized for each problem definition. Thus, PyLOM separates problem definitions from planning algorithms to ease programmability and software reuse. The choice of an object-oriented language also is intended to aid programmability, since prior problem definition languages adopt a functional programming style.
Lattices with Few Distances

Abstract The n -dimensional lattices that contain fewest distances are characterized for all n ≠ 2.
Robust hybrid control of robot manipulators in an unstructured environment

A hybrid (position and force) control algorithm of a robot manipulator with internal uncertainty and working in an unstructured environment is proposed. The internal uncertainty can be due to imperfect modelling, friction, payload or external disturbances. The unstructured environment can be due to the lack of knowledge of the designer. The problem has been cast into the framework of control of dynamical systems whose mathematical model contain uncertainties. Based solely on the bound of the uncertainties, controllers can be constructed which guarantee certain desirable performance. >
The CWP/SU: Seismic Un ∗ x package

Abstract Seismic Un ∗ x provides programs for processing seismic data, including the following tasks: (1) tape reading/writing, (2) trace sorting, windowing, geometry setting, (3) data format conversion, (4) frequency, frequency-wavenumber, 2D wavenumber filtering, (5) Fourier, Hilbert, Gabor and Radon transforms, (6) tau-p filtering, (7) trace attributes, (8) wavespeed profile construction for modelling and migration, (9) seismic modelling, (10) NMO and velocity analysis, (11) several types of DMO, (12) a variety of pre-stack and post-stack migration algorithms, (13) wavelet transform-based data compression, (14) wiggle-trace, image and graph plotting and (15) trace picking.
Stimulation of 17β‐estradiol metabolism in MCF‐7 cells by bromochloro‐ and chloromethyl‐substituted dibenzo‐p‐dioxins and dibenzofurans: Correlations with antiestrogenic activity

Mixed halo‐ and haloalkyl‐substituted dibenzo‐p‐dioxins (DD) and dibenzofurans (DF) are known environmental contaminants, although there is limited information on the toxic effects of these compoun...
Cerebral Synaptic Transmission and Behavioral Effects of Dimethoxyphenylethylamine: A Potential Psychotogen

Dimethoxyphenylethylamine, like mescaline which it resembles, impairs cerebral synaptic transmission and behavior in cats. It has properties associated with hallucinogens and, on this score, qualifies as a potential inducer of psychosis. The idea of such an endogenous inducer is thus reaffirmed by the candidacy of dimethoxyphenylethylamine.
Influence diagnostics for the proportional hazards model

Influence diagnostics based on Cook's curvature diagnostic (1986) are developed for the proportional hazards model. Three perturbation schemes are considered: perturbation of the likelihood, perturbation of the censoring information and perturbation of covariate values.
Carbohydrate and enzyme distribution in protoplasts from valencia orange juice sacs

Abstract The subcellular distribution of neutral sugars, organic acids and their metabolic enzymes was investigated in protoplasts from ‘Valencia’ orange juice sacs. The vacuole was found to contain 70% of the malic acid, 75% of the fructose and glucose, 89% of the citric acid and 100% of the sucrose. Of the enzymes assayed, α-mannosidase, phosphohexoisomerase and phosphoglucomutase showed activity in the vacuole fraction at 100, 5 and 29%, respectively. The activities of acid and neutral invertases, UDPG pyrophosphorylase and both ATP and PPi phosphofructokinase were present only in the cytoplasmic fraction. The remaining enzymes (sucrose synthase, hexokinase, fructokinase and aconitase) showed no activity in any of the samples assayed (protoplast, vacuole and cytoplasm). From the data presented, it appears that vacuolar sugars are the major form of carbohydrate supplying energy to the mature juice sac cells. Possible mechanisms of sugar transport across the tonoplast prior to their oxidation are discussed.
The cyclone column culture vessel for batch and continuous, synchronous or asynchronous, culture of microorganisms

A simple inexpensive apparatus with a working volume of 10 liters of culture is described. Details of construction and procedures for operation of the cyclone column vessel are given. The vessel is self-contained, so that experimental parameters of temperature and aeration are individually controlled; homogeneous mixing and representative sampling of the culture, besides control of foam without need for antifoam, are obtained. The vessel may be used in single or multistage systems for aerobic or anaerobic cultivation of organisms in batch, chemostat, or phased cultures.
Developing a management plan for oral anticoagulant reversal

Purpose To describe a process for prompt evaluation and management— including reversal of the effects of warfarin and target-specific oral anticoagulants—of patients with or at high risk for bleeding during oral anticoagulant therapy or when such therapy is interrupted for an urgent invasive procedure or surgery. Summary The use of pharmacologic interventions for anticoagulant reversal may depend on the measured level of anticoagulation, time since the last anticoagulant dose, target level of coagulation, reliability of laboratory tests of coagulation, severity of or risk for bleeding, the agents’ mechanism of action and pharmacokinetics, and pharmacodynamics of the reversal agent. The patient’s age, weight, renal function, comorbid conditions, and other drug therapy, as well as the risk for thromboembolism and other adverse effects of the reversal therapies, also enter into therapeutic decisions. Hemodialysis may be used to remove the direct thrombin (factor IIa) inhibitor dabigatran and reverse its anticoagulant effects. Limited experience with clotting factor concentrates suggests that activated prothrombin complex concentrate may be useful for reversing the anticoagulant effects of dabigatran. The activity of oral factor Xa inhibitors (i.e., rivaroxaban and apixaban) is higher up the common pathway of the coagulation cascade and thus may be easier to reverse than that of direct thrombin inhibitors. Additional clinical experience is needed to identify the optimal reversal agents, dosage, and impact on thrombosis or bleeding outcomes for both classes of agents. Conclusion A comprehensive plan individualized to each agent should be developed to promptly reverse the effects of oral anticoagulants and optimize outcomes in patients with bleeding or an urgent need for surgery.
Writing to Persuade: A Systemic Functional View

This study explores how a genre-based approach to writing instruction influenced by both genre theory and systemic functional linguistics supported the academic writing development of English language learners (ELLs) transitioning to middle school. Drawing on Systemic Functional Linguistics (SFL) as a tool for pedagogy and linguistic analysis, the teacher-researcher analyzed three instantiations of texts composed by ELLs to determine changes in the register of their texts during the course of genre-based writing pedagogy. Methods were qualitative in nature, involving both analysis of the text and the surrounding context of composition. Data came from multiple sources. They included videotaped observations of classroom interactions, transcriptions of semi-structured interviews with the student, collection of lesson plans, and materials used in lesson implementation, and field notes made by the participant observer. Findings suggest that a genre-based approach to writing instruction supported ELLs in producing texts that more closely approximated the register of the target genre.
Pheochromocytoma penetrance varies by RET mutation in MEN 2A.

Background The occurrence of pheochromocytoma in multiple endocrine neoplasia type 2A (MEN 2A) carriers varies greatly. This study aims to determine PC expression for specific MEN 2A RET mutations. Methods Charts of MEN 2A patients enrolled in our multiple endocrine neoplasia program from 1990 to 2001 were reviewed retrospectively. Statistical analysis was performed using SAS software (SAS Institute, Inc, Cary, NC). Results RET mutation data and pheochromocytoma data were compiled for 323 patients. Overall, penetrance of pheochromocytoma occurred in 102 of 323 patients (32%). Bilateral pheochromocytomas were observed in 67 patients (66%). The following codon-specific expression of pheochromocytoma was observed: 1 of 24 patients expressed codon 609 (4%), 0 of 5 patients expressed codon 611 (0%), 23 of 105 patients expressed codon 618 (22%), 4 of 45 patients expressed codon 620 (9%), and 74 of 149 patients expressed codon 634 (50%) (P Conclusions The penetrance of PC varies between MEN 2A RET codon mutations. Furthermore, we observed variable expression with different amino acid substitutions at the same codon. These results may help guide screening and therapy for MEN 2A patients.
Inhibition of Protein Kinase CK2 Reduces Cyp24a1 Expression and Enhances 1,25-Dihydroxyvitamin D3 Antitumor Activity in Human Prostate Cancer Cells

Vitamin D has broad range of physiological functions and antitumor effects. 24-Hydroxylase, encoded by the CYP24A1 gene, is the key enzyme for degrading many forms of vitamin D including the most active form, 1,25D3. Inhibition of CYP24A1 enhances 1,25D3 antitumor activity. To isolate regulators of CYP24A1 expression in prostate cancer cells, we established a stable prostate cancer cell line PC3 with CYP24A1 promoter driving luciferase expression to screen a small molecular library for compounds that inhibit CYP24A1 promoter activity. From this screening, we identified, 4,5,6,7-tetrabromobenzimidazole (TBBz), a protein kinase CK2 selective inhibitor as a disruptor of CYP24A1 promoter activity. We show that TBBz inhibits CYP24A1 promoter activity induced by 1,25D3 in prostate cancer cells. In addition, TBBz downregulates endogenous CYP24A1 mRNA level in TBBz-treated PC3 cells. Furthermore, siRNA-mediated CK2 knockdown reduces 1,25D3-induced CYP24A1 mRNA expression in PC3 cells. These results suggest that CK2 contributes to 1,25D3-mediated target gene expression. Finally, inhibition of CK2 by TBBz or CK2 siRNA significantly enhances 1,25D3-mediated antiproliferative effect in vitro and in vivo in a xenograft model. In summary, our findings reveal that protein kinase CK2 is involved in the regulation of CYP24A1 expression by 1,25D3 and CK2 inhibitor enhances 1,25D3-mediated antitumor effect. Cancer Res; 73(7); 2289–97. ©2013 AACR.
HIF-2α-mediated activation of the epidermal growth factor receptor potentiates head and neck cancer cell migration in response to hypoxia

Despite their individual key roles in promoting head and neck squamous cell carcinoma (HNSCC) progression and treatment resistance, little is known about the impact of intratumoral hypoxia on the activity of the epidermal growth factor receptor (EGFR) signaling pathway in this cancer type. Here, we show that in highly EGFR-expressing HNSCC cells, hypoxic stress triggers the activation of the EGFR and downstream targets, including Akt and phospholipase C (PLC) gamma1. In support of these findings, we also demonstrate that EGFR activation takes place within hypoxic foci in a subset of human HNSCC tissues. Whereas hypoxia had no major effect on HNSCC cell proliferation, it markedly altered tumor cell shape by inducing morphological changes consistent with a more spindle-shaped, fibroblast-like morphology together with an enhanced migratory capacity. We found that hypoxia-induced EGFR activation and cell migration could be prevented by targeting EGFR signaling with the tyrosine kinase inhibitor tyrphostin, the phospholipase C inhibitor U73122, or by inhibiting the expression of the alpha subunit of hypoxia-inducible factor 2 via RNA interference or the topoisomerase II inhibitor etoposide. Our results position hypoxia-inducible factor-2alpha as a novel regulator of EGFR activation under low oxygen conditions, and suggest that hypoxia-induced EGFR signaling may promote a more aggressive phenotype in a fraction of HNSCC tumors. Because EGFR continues in the forefront as a highly attractive target in clinical oncology, further studies are warranted to define the mechanistic and therapeutic implications of the hypoxic response relative to the EGFR signaling pathway in head and neck cancer.
Exact average symbol error probability of optimum combining with arbitrary interference power

A new expression is derived for the exact average symbol error probability for optimum combining with M-ary phase-shift keying. The expression adds to the significant body of work in this field by handling interferers with arbitrary power levels. The expression involves a single integral with finite limits and finite integrand. A closed-form expression is also derived for the average symbol error probability for binary phase-shift keying.
Long-term results and outcome predictors in one-stage hip reconstruction in children with cerebral palsy.

Background: One-stage hip reconstruction is the gold standard for treatment of hip displacement in children with cerebral palsy. The aims of this study were (1) to report the subjective clinical, objective clinical, and radiographic outcomes; and (2) to investigate outcome predictors, including the influence of the following risk factors: femoral head shape, migration percentage, direction of migration, and age at surgery. Methods: We reviewed 168 hip reconstructions (eighty-two right, eighty-six left) in 121 patients (101 male, twenty female) at a mean follow-up of 7.3 ± 4.6 years (range, four to eighteen years). Surgical outcomes were assessed on the basis of the pain intensity and frequency (measured on 10-point visual analog scales) as well as GMFCS (Gross Motor Function Classification System) and MCPHCS (Melbourne Cerebral Palsy Hip Classification System) scores and postoperative migration percentage. The effects of femoral head shape, preoperative migration percentage, direction of migration, and age at surgery on surgical outcome were assessed by multivariate regression adjusting for potential confounders including sex, triradiate cartilage status, type of cerebral palsy, and surgical technique. Results: Pain intensity and frequency were reduced significantly. Preoperative femoral head shape had no significant effect on the changes in pain, MCPHCS grade, and GMFCS level. The preoperative migration percentage was the most influential risk factor with respect to postoperative outcome. Age at surgery had no effect on the changes in pain score and GMFCS level. The overall surgical complication rate was 10.5%. Conclusions: Our data on 168 hip reconstructions at a mean follow-up of seven years showed significant and clinically meaningful improvements in pain intensity and frequency as well as in clinical scores and hip coverage. Analysis of potential risk factors showed only the preoperative migration percentage to have a relevant influence on outcomes. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Protein-Lipid Interactions Shaping the Electrostatic Membrane Search of a Pleckstrin Homology Domain

The membrane-targeting domains of peripheral proteins play an important role in mediating cell signaling events originating at the plasma membrane. The pleckstrin homology (PH) domain is the most common membrane targeting domain, and many PH domains specifically recognize membrane-bound PIP lipids. Recently, the representative PH domain of the General Receptor for Phosphoinositides (GRP1 PH) has been found to use an electrostatic search mechanism requiring anionic background lipids of the plasma membrane to more rapidly and tightly bind the rare phosphatidylinositol-3,4,5-phosphate (PIP3) lipid second messenger. The contributions of the seven basic residues on the GRP1 PH membrane-proximal face to the protein-lipid interactions that occur during electrostatic searching were investigated. Point and double mutants of the isolated Grp1 PH domain were purified with alanine replacing each of the seven basic residues. For each mutant domain, the relative affinities for phosphatidylinositol-(3,4,5)-trisphosphate (PIP3) were determined in the presence and absence of anionic background lipids. While the wild-type PH domain displays a ∼10-fold enhanced affinity for PIP3 in the presence of anionic background lipids, this enhancement is significantly decreased in the point and double mutant PH domains possessing the R322A and K279A mutations. Thus far, the results suggest that while most basic residues interact with the membrane at a detectable level, the protein-lipid interactions between basic residues R322 and K279 and the membrane are most crucial to electrostatic searching. Additional experiments are in progress to determine the specificity of these protein-lipid interactions, and the effect of mutations on membrane binding kinetics.
Nasal application of neuropeptide S inhibits arthritis pain-related behaviors through an action in the amygdala

Recently discovered neuropeptide S (NPS) has anxiolytic and pain-inhibiting effects in rodents. We showed previously that NPS increases synaptic inhibition of amygdala output to inhibit pain behaviors. The amygdala plays a key role in emotional-affective aspects of pain. Of clinical significance is that NPS can be applied nasally to exert anxiolytic effects in rodents. This study tested the novel hypothesis that nasal application of NPS can inhibit pain-related behaviors in an arthritis model through NPS receptors (NPSR) in the amygdala. Behaviors and electrophysiological activity of amygdala neurons were measured in adult male Sprague Dawley rats. Nasal application of NPS, but not saline, inhibited audible and ultrasonic vocalizations and had anxiolytic-like effects in the elevated plus-maze test in arthritic rats (kaolin/carrageenan knee joint arthritis model) but had no effect in normal rats. Stereotaxic application of a selective non-peptide NPSR antagonist (SHA68) into the amygdala by microdialysis reversed the inhibitory effects of NPS. NPS had no effect on hindlimb withdrawal thresholds. We showed previously that intra-amygdala application of an NPSR antagonist alone had no effect. Nasal application of NPS or stereotaxic application of NPS into the amygdala by microdialysis inhibited background and evoked activity of amygdala neurons in arthritic, but not normal, anesthetized rats. The inhibitory effect was blocked by a selective NPSR antagonist ([D-Cys(tBu)5]NPS). In conclusion, nasal application of NPS can inhibit emotional-affective, but not sensory, pain-related behaviors through an action in the amygdala. The beneficial effects of non-invasive NPS application may suggest translational potential.
Bone Properties Surrounding Hydroxyapatite-Coated Custom Osseous Integrated Dental Implants

Dental implants are widely used for replacement of teeth and correction of defects in maxillary and mandibular bone. Their effectiveness is largely dependent upon biostability and osteointegration between the bone and implant. One of the major causes of dental implant failure is aseptic loosening or resorption of bone at the interface [2]. In order to diminish such failures, coatings and surface roughening are used to enhance osteointegration and biostability between the bone and the implant [3].Copyright © 2010 by ASME
Determinants of migraine-specific quality of life.

This paper reports an analysis of two randomized controlled trials of rizatriptan, in which the 24-h Migraine Quality of Life Questionnaire© was used to assess migraine-specific quality of life in patients receiving acute treatment. The objective of the analysis was to determine which clinical effects of a migraine medication, as measured by traditional clinical trial endpoints, contribute to a better short-term health-related quality of life. The results demonstrate that patients who experience complete pain relief and are able to function at their normal ability within 2 h and experience no headache recurrence have the highest migraine-specific quality of life scores. Patients who were satisfied with medication at 2 h had higher migraine-specific quality of life scores than those who were not satisfied. In conclusion, migraine therapy that provides rapid, complete, and sustained pain relief, with restoration of functional ability, has the most beneficial impact on short-term health-related quality of li...
Flow-induced reconfiguration of buoyant and flexible aquatic vegetation

Plant posture can play a key role in the health of aquatic vegetation, by setting drag, controlling light availability, and mediating the exchange of nutrients and oxygen. We study the flow-induced reconfiguration of buoyant, flexible aquatic vegetation through a combination of laboratory flume experiments and theoretical modeling. The laboratory experiments measure drag and posture for model blades that span the natural range for seagrass stiffness and buoyancy. The theoretical model calculates plant posture based on a force balance that includes posture-dependent drag and the restoring forces due to vegetation stiffness and buoyancy. When the hydrodynamic forcing is small compared to the restoring forces, the model blades remain upright and the quadratic law, Fx 3 U2, predicts the drag well (Fx is drag, U is velocity). When the hydrodynamic forcing exceeds the restoring forces, the blades are pushed over by the flow, and the quadratic drag law no longer applies. The model successfully predicts when this transition occurs. The model also predicts that when the dominant restoring mechanism is blade stiffness, reconfiguration leads to the scaling Fx 3 U4/3. When the dominant restoring mechanism is blade buoyancy, reconfiguration can lead to a sub-linear increase in drag with velocity, i.e., Fx 3 Ua with a , 1. Laboratory measurements confirm both these predictions. The model also predicts drag and posture successfully for natural systems ranging from seagrasses to marine macroalgae of more complex morphology. The most obvious hydrodynamic effect of aquatic vegetation is that it provides resistance to flow. In the past, this has led to aquatic vegetation being removed from river channels to increase conveyance capacity and reduce
SAGA-mediated H2B deubiquitination controls the development of neuronal connectivity in the Drosophila visual system

Nonstop, which has previously been shown to have homology to ubiquitin proteases, is required for proper termination of axons R1–R6 in the optic lobe of the developing Drosophila eye. Herein, we establish that Nonstop actually functions as an ubiquitin protease to control the levels of ubiquitinated histone H2B in flies. We further establish that Nonstop is the functional homolog of yeast Ubp8, and can substitute for Ubp8 function in yeast cells. In yeast, Ubp8 activity requires Sgf11. We show that in Drosophila , loss of Sgf11 function causes similar photoreceptor axon‐targeting defects as loss of Nonstop. Ubp8 and Sgf11 are components of the yeast SAGA complex, suggesting that Nonstop function might be mediated through the Drosophila SAGA complex. Indeed, we find that Nonstop does associate with SAGA components in flies, and mutants in other SAGA subunits display nonstop phenotypes, indicating that SAGA complex is required for accurate axon guidance in the optic lobe. Candidate genes regulated by SAGA that may be required for correct axon targeting were identified by microarray analysis of gene expression in SAGA mutants.
Individual and Combined Effects of Multiple High-Risk Triggers on Postcessation Smoking Urge and Lapse

Introduction Negative affect, alcohol consumption, and presence of others smoking have consistently been implicated as risk factors for smoking lapse and relapse. What is not known, however, is how these factors work together to affect smoking outcomes. This paper uses ecological momentary assessment (EMA) collected during the first 7 days of a smoking cessation attempt to test the individual and combined effects of high-risk triggers on smoking urge and lapse. Methods Participants were 300 female smokers who enrolled in a study that tested an individually tailored smoking cessation treatment. Participants completed EMA, which recorded negative affect, alcohol consumption, presence of others smoking, smoking urge, and smoking lapse, for 7 days starting on their quit date. Results Alcohol consumption, presence of others smoking, and negative affect were, independently and in combination, associated with increase in smoking urge and lapse. The results also found that the relationship between presence of others smoking and lapse and the relationship between negative affect and lapse were moderated by smoking urge. Conclusions The current study found significant individual effects of alcohol consumption, presence of other smoking, and negative affect on smoking urge and lapse. Combing the triggers increased smoking urge and the risk for lapse to varying degrees, and the presence of all 3 triggers resulted in the highest urge and lapse risk.
Spectral distribution methods in effective interaction theory

Abstract Spectral distribution methods are used to suggest alternative forms for effective interaction calculation. Using the configuration centroid operator as the unperturbed Hamiltonian is found to yield a residual interaction with minimal Euclidean norm. If the effective interaction is expanded in terms of orthogonal polynomials appropriate to the configuration density, the leading term is more meaningful than those in existing series. Using the same technique of orthogonal polynomial expansion, the calculation of diagonal matrix elements of higher order terms in the perturbation expansions reduces to an evaluation of traces which are more easily calculable. Convergence of both polynomial expansions is tied to the convergence of the spectral density to normal form which itself is governed by a strong principle, the central limit theorem.
A direct digital frequency synthesizer utilizing quasi-linear interpolation method

In this paper, a novel direct digital frequency synthesizer (DDFS) is introduced in which a combination of linear and even piecewise parabolic polynomial interpolation (EPIP) is used to interpolate the first quadrant of a cosine signal. An appropriate combination of these two methods is employed to maximize the spurious free dynamic range and reduce the complexity of the entire system. The even parabolic polynomial can be treated as a linear interpolation with respect to the squared of the accumulator's output, thus the proposed system is called quasi linear interpolation (QLIP) direct digital frequency synthesizer.
Human liver microsomal thiol methyltransferase : inhibition by arylalkylamines

1. Thiol methyltransferase (TMT) is a microsomal enzyme catalyzing the S-methylation of aliphatic sulphydryl drugs and xenobiotics. Studies of the functional significance of S-methylation catalysed by TMT have been hampered by lack of a potent, relatively specific, non-toxic inhibitor of the enzyme.2. Human hepatic microsomal TMT was inhibited by the arylalkylamine 2,3-dichloro-α;-methylbenzylamine (DCMB), and by a series of arylalkylamines, as well as the arylamme, aniline.3. Inhibition kinetic studies with DCMB, benzylamine, aniline, phenylethylamine and phenylethanolamine, five compounds with a wide range of IC50 values, showed ‘mixed’ inhibition of TMT with respect to the methyl acceptor substrate, 2-mercaptoethanol. Kis and Kii values were, respectively, 1.1 and 0.29 μM for DCMB, 160 μM each for benzylamine, 680 and 370 μM for aniline, 1640 and 1380 μM for phenylethylamine, and 2300 and 1400 μM for phenylethanolamine. Inhibition was at least partially reversible.4. H.p.l.c. analyses were carried out ...