cssi/SciSciGPT-SciSciNet huggingface dataset:
Original contributionN-acetyltransferase 1 and 2 genotypes do not predict response or toxicity to treatment with mesalamine and sulfasalazine in patients with ulcerative colitis

OBJECTIVES: 5-Aminosalicylate is metabolized in colonic mucosa by N-acetyltransferase 1 (NAT1), and sulfapyridine is metabolized in the liver by N-acetyltransferase 2 (NAT2). Common genetic polymorphisms in these enzymes result in rapid and slow acetylation. We determined the association between NAT1 genotype and response to mesalamine and sulfasalazine, as well as between NAT2 genotype and toxicity to sulfasalazine, in a population-based cohort of patients with ulcerative colitis. METHODS: DNA was obtained from 77 white patients with ulcerative colitis from Olmsted County, MN. NAT1 and NAT2 genotyping was performed using microelectronic array devices. Phenotypes were deduced from previously published genotype/phenotype correlations. Clinical response to mesalamine and sulfasalazine, and toxicity to sulfasalazine, were determined by medical record review and associated with NAT1 and NAT2 genotypes. RESULTS: The clinical response rates among 52 patients treated with mesalamine were 67% (31 of 46) for rapid acetylators and 83% (five of six) for slow acetylators (odds ratio = 0.4, 95% CI = < 0.1–3.9, p = 0.65). Similarly, the clinical response rates among 64 patients treated with sulfasalazine were 74% (43 of 58) for rapid acetylators and 67% (four of six) for slow acetylators (odds ratio = 1.4, 95% CI = 0.2–8.6, p = 0.65). The toxicity rates among the 64 patients treated with sulfasalazine were 34% (12 of 35) for slow acetylators and 45% (13 of 29) for rapid acetylators (odds ratio = 0.6, 95% CI = 0.2–1.8, p = 0.65). CONCLUSIONS: NAT1 and NAT2 genotypes did not predict response to mesalamine or sulfasalazine, or toxicity to sulfasalazine.
Impact Force Prediction for a Hopkinson Bar Using Axisymmetric Solid Elements

One of the most widely used experimental configurations for high strain-rate material measurements is the split Hopkinson pressure bar. The concept of the Hopkinson bar involves the determination of dynamic stresses, strains, or displacements occurring at the end of a bar. It uses the longitudinal impact of a cylindrical projectile to generate an incident pulse. That pulse allows the specimen, sandwiched between two Hopkinson bars, to be loaded dynamically. In order to study the influence of the strain rate on the mechanical properties of the specimen, it is useful to be able to change the profile of the incident wave. To that end, different cylindrical and conical projectiles can be used.
SCA policy association framework

SCA (Service Component Architecture) is a collaborative effort by the leading vendors in the enterprise software space to define an architecture for building applications and systems using a Service-Oriented Architecture. SCA allows developers to define components that implement business logic, which offer their capabilities through services and consume functions offered by other components through references in a relatively abstract manner. This paper discusses how infrastructure and Quality of Service constraints and capabilities can be associated with SCA artifacts either as abstract desires or as concrete policies.
Associated production of the Higgs boson and a single top quark at hadron colliders

We study the production of the Higgs boson in association with a single top quark at hadron colliders. The cross sections for the three production processes $(t$ channel, s channel, and W associated) at both the Fermilab Tevatron and the CERN Large Hadron Collider (LHC) are presented. We investigate the possibility of detecting a signal for the largest of these processes, the t-channel process at the LHC, via the Higgs boson decay into $b\overline{b}.$ The QCD backgrounds are large and difficult to curb, hindering the extraction of the signal. Extensions of our analysis to the production of supersymmetric Higgs bosons are also addressed. The cross section is enhanced for large values of $\mathrm{tan}\ensuremath{\beta},$ increasing the prospects for extracting a signal.
Improvement in usual gait speed predicts better survival in older adults.

OBJECTIVES: To estimate the relationship between 1-year improvement in measures of health and physical function and 8-year survival. DESIGN: Prospective cohort study. SETTING: Medicare health maintenance organization and Veterans Affairs primary care programs. PARTICIPANTS: Persons aged 65 and older (N=439). MEASUREMENTS: Six measures of health and function assessed at baseline and quarterly over 1 year. Participants were classified as improved at 1 year, transiently improved, or never improved for each measure using a priori definitions of meaningful change: gait speed (usual walking pace over 4 m), 0.1 m/s; Short Physical Performance Battery, 1 point; Medical Outcomes Study 36-item Short Form Health Survey physical function, 10 points; EuroQol, 0.1 point; National Health Interview activity of daily living scale, 2 points; and global health change, two levels or reaching the ceiling. Mortality was ascertained from the National Death Index. Covariates included demographics, comorbidity, cognitive function, and hospitalization. RESULTS: Of the six measures, only improved gait speed was associated with survival. Mortality after 8 years was 31.6%, 41.2%, and 49.3% for those with improved, transiently improved, and never improved gait speed, respectively. The survival benefit for improvement at 1 year persisted after adjustment for covariates (hazard ratio=0.42, 95% confidence interval=0.29–0.61, P<.001) and was consistent across subgroups based on age, sex, ethnicity, initial gait speed, healthcare system, and hospitalization. CONCLUSION: Improvement in usual gait speed predicts a substantial reduction in mortality. Because gait speed is easily measured, clinically interpretable, and potentially modifiable, it may be a useful “vital sign” for older adults. Further research is needed to determine whether interventions to improve gait speed affect survival.
Characterization of spin relaxation anisotropy in Co using spin pumping

Ferromagnets are believed to exhibit strongly anisotropic spin relaxation, with relaxation lengths for spin longitudinal to the magnetization significantly longer than those for spin transverse to the magnetization. Here, we characterize the anisotropy of spin relaxation in Co using the spin pumping contribution to Gilbert damping in noncollinearly magnetized ${\mathrm{Py}}_{1\ensuremath{-}x}{\mathrm{Cu}}_{x}$/Cu/Co trilayer structures. The static magnetization angle between ${\mathrm{Py}}_{1\ensuremath{-}x}{\mathrm{Cu}}_{x}$ and Co, adjusted under field bias perpendicular to film planes, controls the projections of longitudinal and transverse spin current pumped from ${\mathrm{Py}}_{1\ensuremath{-}x}{\mathrm{Cu}}_{x}$ into Co. We find nearly isotropic absorption of pure spin current in Co using this technique; fits to a diffusive transport model yield the longitudinal spin relaxation length $l2$ nm in Co. The longitudinal spin relaxation lengths found are an order of magnitude smaller than those determined by current-perpendicular-to-planes giant magnetoresistance measurements, but comparable with transverse spin relaxation lengths in Co determined by spin pumping.
Chapter 5 Magnetism and quasicrystals

Publisher Summary This chapter discusses the magnetism and quasicrystals (QCs). QCs are a new phase of condensed matter whose structures differ from those of either crystals or glasses. QCs exhibit long-range orientation order that is incompatible with three-dimensional periodic crystallographic packing. This non classical orientation order can only be accommodated in three dimensions by allowing for two sets of reciprocal lattice vectors of incommensurate length. Three-dimensional QCs are discovered thatexhibit five-fold symmetry (icosahedral QCs) and two-dimensional QCs with eight-fold (octahedral QCs) and ten-fold (decagonal QCs) orientational order are observed. However, other orientational orders are also possible. The important implications for crystal-field effects and moment formation on a local scale and for domain-wall symmetries on a long-range scale are reviewed in the chapter. New QC structures are metastable phases that are generally produced by rapid solidification or by some other nonequilibrium processing methods such as energetic particle-beam bombardment, solid-state reaction, and, in some cases, thermal transformation from an amorphous precursor, and mechanical alloying. The free energy of a given alloy composition decreases through a series of stable or metastable phases as the order increases from a short-range orientational order in amorphous metallic phases.
Capital Mobility and Exchange Market Intervention in Developing Countries

Official controls on interest rates and capital flows rule out the use of traditional interest rate parity conditions to measure changes in the degree of capital mobility confronting developing countries. This paper develops an alternative technique for measuring the cost of undertaking disguised capital flows when such official controls are present. This measure is derived from an intertemporal, optimizing model of an open economy incorporating the influence of the authorities` foreign exchange market activities. The paper suggests that the real cost of undertaking disguised capital flows declined on average by nearly 70 percent between the early 1970s and the late 1980s.
Age-related decrease in resting energy expenditure in sedentary white women: effects of regional differences in lean and fat mass

BACKGROUND Lean mass and resting energy expenditure (REE) decrease with age. However, it is unknown whether age-related changes in regional lean and fat mass are responsible for the age-related decrease in REE. OBJECTIVE Our objective was to determine how regional lean and fat mass vary with age and whether age is independently related to REE after adjustment for regional fat and lean mass. DESIGN The study was a cross-sectional evaluation of 58 white women aged 23-77 y. Regional and whole-body lean and fat mass were measured by dual-energy X-ray absorptiometry, subcutaneous abdominal tissue (SAT) and intraabdominal adipose tissue (IAF) by computed tomography, and REE by ventilated-canopy indirect calorimetry. RESULTS Independent of other significant correlates, age was significantly and independently associated with greater IAF (beta = 0.49) and less leg lean mass (beta = -0.35). IAF (r = -0.28) and IAF:SAT (r = -0.31) correlated negatively with REE. REE was negatively associated with greater age (beta = -0.42), independent of changes in lean and fat mass in different parts of the body. By contrast, trunk lean (beta = 0.27) and leg fat (beta = 0.27) mass were associated with greater REE independent of age and other body-composition variables. CONCLUSIONS These results suggest that trunk lean mass (presumably primarily organ tissue) is relatively resistant to age-related changes in body composition, whereas muscle mass, especially leg muscle, tends to be lost. These data also suggest that the age-related decreases in REE are not fully explained by changes in body composition.
Tweaking liver progenitor cells.

Liver regeneration can occur by proliferation of two different cell types, but generally only one at a time is fully turned on. A factor that may specifically activate one of these cell types now comes to light.
The pathology of head and neck tumors: Carcinoma of the nasopharynx, part 11

The past decade has witnessed extraordinary advances in the epidemiology, virology, and immunology of carcinomas of the nasopharynx. There has not been a parallel growth in the study of morphologic expressions of the neoplasms. In great part, this has been due to a lack of a universally accepted histologic classification. As a consequence, correlation between histology and other factors relating to the pathogenesis of these neoplasms has been impeded. The World Health Organization (WHO) has proposed a histologic classification of nasopharyngeal carcinomas as squamous-cell, nonkeratinizing, and undifferentiated. This report presents and argument in favor of using the WHO classification and a hypothesis relating to the histogenesis of the 3 types of nasopharyngeal carcinoma.
Map algebra: one perspective

Map algebra is a general set of conventions, capabilities, and techniques that have been widely adopted for use with geographic information systems (GISs). This paper presents several broad and introductory views of map algebra that attempt to place this approach in conceptual and historical context. These views focus respectively on the map algebraic data model, its data-processing construct, notational syntax, predecessors, and likely near-term future.
Effects of Resistive and Balance Exercises on Isokinetic Strength in Older Persons

OBJECTIVE: To determine the safety and efficacy of 3 months of resistive training of multiple lower extremity muscle groups compared with balance training in persons over 75 years. DESIGN: Randomized 3-month clinical trial. Subjects (n = 110, mean age 80) were randomized to 4 groups in a 2 × 2 design (control, resistive, balance, combined resistive/balance). INTERVENTIONS: Resistive training involved knee extension and flexion, hip abduction and extension, and plantar and dorsiflexion using simple resistive machines and sandbags. Balance training consisted of exercises to improve postural control. The control group attended 5 health-related discussion sessions. MEASUREMENTS: Summed isokinetic moments (N m) of 8 leg movements: hip, knee and ankle flexion/extension, and hip abduction/adduction. Secondary outcomes were gait velocity and chair rise time. MAIN RESULTS: Summed peak moment increased in both resistive exercise-trained groups (13% increase in the resistive group and 21% in the combined training group, P < 0.001). The effect of resistance training was significant (MANOVA F = 21.1, P < 0.001), but balance training did not improve strength, and there was no interaction (positive or negative) between balance and resistive training. Maximal gait velocity and chair rise time did not improve. Eleven subjects (20%) had musculoskeletal complaints related to resistive training, but all were able to complete the program with modifications. CONCLUSION: Resistive training using simple equipment is an effective and acceptable method to increase overall leg strength in older persons. Resistive or balance training did not improve maximal gait velocity or chair rise time in this sample of relatively healthy older persons.
Brugada syndrome: Insights of ST elevation, arrhythmogenicity, and risk stratification from experimental observations

Brugada syndrome (BrS), caused by ion channel abnormalities, is characterized by ST segment elevation and negative T waves in the right precordial electrocardiographic (ECG) leads recorded over the right ventricular outflow tract (RVOT). BrS is sensitive to body temperature and can lead to T-wave alternans (TWA), ventricular tachycardia, and sudden death. Recent studies in an isolated canine RVOT model of BrS demonstrated that reversal of the transmural gradient of repolarization caused the ECG characteristics and that major intraepicardial and transmural dispersion of action potentials (APs) initiated phase 2 reentry, premature ventricular activations, and tachyarrhythmias. Hypothermia enhanced the heterogeneity of the AP and promoted the origination of phase 2 reentry in the epicardium of the RVOT, but the prolonged AP duration frequently blocked reentry. Hyperthermia abbreviated the AP and facilitated the maintenance of reentry and tachyarrhythmias. Bradycardia promoted alternans in the phase 2 dome of the AP within the epicardium of the RVOT, resulting in TWA. The above phenomena were localized in the epicardium of the RVOT. Blockade of the transient outward current, I to , reduced AP heterogeneity and prevented arrhythmias in the BrS model. In addition, epicardial activation delay led to fragmented QRS, a risk marker of prognosis in BrS. Body surface mapping in patients with BrS supported these experimental findings. In conclusion, the AP heterogeneity within the epicardium of the RVOT contributes to the ECG characteristics, temperature sensitivity, TWA, and arrhythmias in BrS, and body surface mapping and fragmented QRS can be effective predictors of risk in patients with BrS.
Plastic coupling and stress relaxation during nonproportional axial-shear strain-controlled loading

A nonproportional strain-controlled load path consisting of two segments was applied to the cobalt-based alloy Haynes 188 at 650°C. The first segment was purely axial; the axial strain was then held constant while the shear strain was increased during the second segment. The alloy exhibited about a 95-percent reduction in axial stress (298 to 15 MPa) during shear straining. This reduction was due primarily to plastic coupling, but time-dependent stress relaxation also occurred. A rate-independent plasticity model approximated the stress reduction due to plastic coupling reasonably well, but as expected was unable to account for time-dependent stress relaxation. A viscoplasticity model capable of predicting the interaction between stress relaxation and plastic coupling also predicted the plastic coupling reasonably well. The accuracy of the viscoplastic model is shown to depend greatly upon the set of nonunique material parameters, which must be characterized from a sufficiently large range of load histories.
Maximization of process window for low-k 1 spacing using KrF lithography

The spaces between floating-gate poly-silicon are critical for the electrical properties of advanced non-volatile memory (NVM). However, the patterning of low-k1 semi-dense spaces in NVM cells is more challenging than the patterning of dense lines in DRAM cells as the former is of lower normalized image log slope (NILS) and optical contrast. Many experiments, including various NA/σ trials, binary intensity or attenuated phase-shift masks (AttPSM), application of various sizes of sub-resolution assist feature (SRAF), or even negative-type photoresist (N-PR) by clear-field patterning, are tested and compared for the 140nm spaces with L:S ratio of 3:1 using KrF lithography. Combined with aerial image simulations and a process window analyzer, the optimal process condition was found. The SRAF functions to mimic the environment of dense pattern and thereby extends the process latitude of the semi-dense spaces. But it damages the image pattern if the side-lobe intensity approaches the intensity threshold. The maximum allowable SRAF depends on mask type and field used. Generally speaking, the SRAF should be smaller in bright-field exposure using the negative-type photoresist (N-PR) than in dark-field exposure using the positive-type photoresist (P-PR) application. The N-PR, despite its intrinsic poorer pattern profile and larger line-edge-roughness as contributed from photoresist effect, was found to surpass the P-PR in process window. A trade-off among process window, mask error enhancement factor (MEEF), pattern profile and mask cost is unavoidable to the selection of mask type or mask bias, and is considered in this paper in the last.
Martian cratering 9: Toward resolution of the controversy about small craters

Abstract The Malin et al. [Malin, M.C., Edgett, K., Posiolova, L., McColley, S., Noe Dobrea, E., 2006. Science 314, 1573–1577] report of ongoing production of decameter scale primary craters matches within an order of magnitude the crater production curves of Hartmann [Hartmann, W.K., 2005. Icarus 174, 294–320], and appears to contradict models that say our curves grossly overpredict primary production. Nonetheless, such models may still predict correct order-of-magnitude secondary production. The new observations, if correct, require geologically recent martian surface modification in some areas, on timescales comparable to the cycles of obliquity changes, suggesting episodic martian climatic/environmental change driven by the obliquity cycles.
Molecular Dynamics Characterization of Rutile-Anatase Interfaces

We report molecular dynamics (MD) simulations of interfaces between rutile and anatase surfaces of TiO2. These interfaces are important for understanding mixed-phase catalysts, such as the Degussa P25 catalyst, and in particular as a first step toward characterizing electron/hole transport in these photoactive materials. Construction of these interfaces was possible with near-coincidence-site lattice (NCSL) theory. The results suggest adhesion energies for the most stable structures typically near −2 J/m2, and the interfaces appear energetically favorable due to an increase of six-coordinate Ti atoms (Ti6c). Two other notable observations emerge from this work. First, the interfaces are characterized as slightly disordered, with the disorder limited to a narrow region at the interface, in agreement with experiment. Second, formation of rutile octahedral structures was observed at the anatase side of the interface due to surface rearrangement. This appears as the beginning of an anatase-to-rutile phase tra...
Extracellular Matrix Remodeling in Heart Failure A Role for De Novo Angiotensin II Generation

Heart failure is a major health problem worldwide. In the United States, it represents the number one hospital discharge diagnosis among elderly persons each year. It appears most commonly in patients with previous MI.1,2 The chronically failing heart of ischemic origin is characterized by iterations in tissue structure, particularly fibrous tissue formation, that appear in infarcted and noninfarcted myocardium of both right and left ventricles.3,4 In other words, fibrosis appears at the site of MI as well as remote from it. Fibrosis remote from the infarct site is considered “the major cause of ventricular remodeling” in ischemic cardiomyopathy.4 Such an adverse accumulation of extracellular matrix initially raises myocardial stiffness; its continued accumulation further increases stiffness and impairs contractile behavior.5–10 Elucidating cellular and molecular mechanisms responsible for accumulation of extracellular matrix is essential to designing cardioprotective and reparative strategies that could prevent or regress fibrosis, respectively, after infarction.11,12 ACE inhibition has proved effective in reducing mortal and morbid events, improving symptomatic status, and attenuating the progressive nature of cardiac failure in symptomatic patients with ventricular diastolic and/or systolic dysfunction in whom activation of the circulating RAAS is present.1,13,14 ACE inhibitor–mediated reductions in circulating Ang II and aldosterone no doubt contribute to this salutary response. This would include an attenuation of well-recognized endocrine properties of these hormones, such as altered sodium homeostasis and vascular tonicity, and their adverse influence on matrix structure of atria and ventricles.15–20 Collectively, these adverse responses to RAAS effector hormones contribute to the progressive nature of chronic cardiac failure, which includes recurring bouts of symptomatic failure1,2,21 and reentrant arrhythmias originating in either atria or ventricles.22,23 ACEIs have also proved effective in asymptomatic patients with equivalent levels of ventricular systolic dysfunction but in whom chronic RAAS activation is not present. …
Src-mediated Tyrosine Phosphorylation of p47phox in Hyperoxia-induced Activation of NADPH Oxidase and Generation of Reactive Oxygen Species in Lung Endothelial Cells

Superoxide (O(2)(-)) production by nonphagocytes, similar to phagocytes, is by activation of the NADPH oxidase multicomponent system. Although activation of neutrophil NADPH oxidase involves extensive serine phosphorylation of p47(phox), the role of tyrosine phosphorylation of p47(phox) in NADPH oxidase-dependent O(2)(-) production is unclear. We have shown recently that hyperoxia-induced NADPH oxidase activation in human pulmonary artery endothelial cells (HPAECs) is regulated by mitogen-activated protein kinase signal transduction. Here we provided evidence on the role of nonreceptor tyrosine kinase, Src, in hyperoxia-induced tyrosine phosphorylation of p47(phox) and NADPH oxidase activation in HPAECs. Exposure of HPAECs to hyperoxia for 1 h resulted in increased O(2)(-) and reactive oxygen species (ROS) production and enhanced tyrosine phosphorylation of Src as determined by Western blotting with phospho-Src antibodies. Pretreatment of HPAECs with the Src kinase inhibitor PP2 (1 mum) or transient expression of a dominant-negative mutant of Src attenuated hyperoxia-induced tyrosine phosphorylation of Src and ROS production. Furthermore, exposure of cells to hyperoxia enhanced tyrosine phosphorylation of p47(phox) and its translocation to cell peripheries that were attenuated by PP2. In vitro, Src phosphorylated recombinant p47(phox) in a time-dependent manner. Src immunoprecipitates of cell lysates from control cells revealed the presence of immunodetectable p47(phox) and p67(phox), suggesting the association of oxidase components with Src under basal conditions. Moreover, exposure of HPAECs to hyperoxia for 1 h enhanced the association of p47(phox), but not p67(phox), with Src. These results indicated that Src-dependent tyrosine phosphorylation of p47(phox) regulates hyperoxia-induced NADPH oxidase activation and ROS production in HPAECs.
Helium Molecular Energy States as Detected by Collisions of the Second Kind in Helium

From a survey of the literature on spectra enhanced by collisions of the second kind, which take place in helium, evidence is presented for the existence in measurable concentrations of both the helium molecule-ion and the helium metastable molecule. From the intensity distribution of the enhanced spectra, the repulsive energy between two helium atoms at separations of 1.052A and 1.090A is derived to be 6.8 volts and 5.8 volts, respectively. The rates of formation of the molecular states are discussed in the special case of a steady-state discharge and the molecular states are shown to be very probable at high pressures. From this it is shown that the ion whose mobility is found to be 21.4 ${\mathrm{cm}}^{2}$/sec. volt is probably that of ${\mathrm{He}}_{2}^{+}$ in helium and, hence, the discrepancy between the theoretical and experimental values of the mobilities can be removed by such an interpretation. The existence of neon molecules is also suggested.
Food preference of young rhesus monkeys fed marginally zinc deficient diets

Zinc deprivation has been shown to produce hypogeusia in rhesus monkeys but the possible consequences of altered taste sensitivity for food preference and selection is not known. We studied 13 rhesus monkeys (2.5 to 3 years of age) for food preference in a structured choice situation. These animals were fed two levels of dietary zinc: marginally zinc deprived (fed 4 µg zinc/g diet from conception and throughout development;N=6), or control (fed a 100 µg zinc/g diet throughout the study;N=7). Preference for familiar vs unfamiliar food items, order of food preferences, persistence in retrieval of preferred and nonpreferred foods, and preference under four deprivation periods were examined. Animals were offered a choice of two food items, both containing minimal zinc levels, and food choice and latency of choice were measured. Results indicate that animals fed the marginal zinc diets had reduced preference for unfamiliar foods relative to controls and different patterns of food preference. These results may be relevant to maintenance of appropriate food selection in marginally zinc deprived populations.
Effects of salinity acclimation on the expression and activity of Phase I enzymes (CYP450 and FMOs) in coho salmon (Oncorhynchus kisutch)

Phase I biotransformation enzymes are critically important in the disposition of xenobiotics within biota and are regulated by multiple environmental cues, particularly in anadromous fish species. Given the importance of these enzyme systems in xenobiotic/endogenous chemical bioactivation and detoxification, the current study was designed to better characterize the expression of Phase I biotransformation enzymes in coho salmon (Oncorhynchus kisutch) and the effects of salinity acclimation on those enzymes. Livers, gills, and olfactory tissues were collected from coho salmon (O. kisutch) after they had undergone acclimation from freshwater to various salinity regimes of seawater (8, 16 and 32 g/L). Using immunoblot techniques coupled with testosterone hydroxylase catalytic activities, 4 orthologs of cytochrome P450 (CYP1A, CYP2K1, CYP2M1, and CYP3A27) were measured in each tissue. Also, the expression of 2 transcripts of flavin-containing monooxygenases (FMO A and B) and associated activities were measured. With the exception of CYP1A, which was down-regulated in liver, protein expression of the other 3 enzymes was induced at higher salinity, with the greatest increase observed in CYP2M1 from olfactory tissues. In liver and gills, 6β- and 16β-hydroxylation of testosterone was also significantly increased after hypersaline acclimation. Similarly, FMO A was up-regulated in all 3 tissues in a salinity-dependent pattern, whereas FMO B mRNA was down-regulated. FMO-catalyzed benzydamine N-oxygenase and methyl p-tolyl sulfoxidation were significantly induced in liver and gills by hypersalinity, but was either unchanged or not detected in olfactory tissues. These data demonstrate that environmental conditions may significantly alter the toxicity of environmental chemicals in salmon during freshwater/saltwater acclimation.
A comparison of four buprenorphine dosing regimens using open-dosing procedures: is twice-weekly dosing possible?

Aims To compare opioid withdrawal symptoms during 24-, 48-, 72- and 96-hour buprenorphine dosing regimens and to evaluate subjects' preferences for these different dosing schedules. Subjects Fourteen opioid-dependent subjects participated in this study. They received daily sublingual maintenance doses of 4 mg/70 kg (n = 4) or 8 mg/70 kg (n = 10) of buprenorphine. Intervention In the first study subjects received, in a random order, four dosing regimens for five repetitions of each: daily maintenance doses every 24 hours (4 or 8 mg/70 kg), double the daily maintenance dose every 48 hours (8 or 16 mg/70 kg), triple the daily maintenance dose every 72 hours (12 or 24 mg/70 kg), and quadruple the daily maintenance dose every 96 hours (16 or 32 mg/70 kg). Measures of subjective and observer opioid withdrawal symptoms were assessed prior to receipt of each dose. In a second study, subjects chose between the different dosing regimens. Findings Some withdrawal ratings increased during the less frequent dosing schedules in the first study. In the second study, 46% of subjects preferred the quadruple-every-fourth-day dosing regimen over every other option, and only 14% preferred to be dosed daily. Conclusions These results suggest that some opioid-dependent outpatients are willing and able to endure the withdrawal symptoms associated with less than daily dosing, and a twice-weekly dosing regimen may be possible.
Transcriptional activation of the Hepatocyte Growth Factor receptor (c- met ) gene by its ligand (Hepatocyte Growth Factor) is mediated through AP-1

Hepatocyte Growth Factor (HGF) exerts its biological effects via binding and activating a transmembrane protein tyrosine kinase receptor known as c-Met. Previous studies from our laboratory demonstrated that c-met gene expression is inducible by its own ligand (HGF). However, the molecular mechanism(s) involved in this process are unknown. The present study was carried out to address this question. Transfection of various c-met-CAT promoter constructs into the mouse hepatocellular carcinoma cell line Hepa 1-6 in combination with electrophoretic mobility shift assays (EMSA) identified the responsive element as an activated protein-1 (AP-1) binding site (TGAGTCA) within the c-met core promoter region at position -158 to -152. The c-met AP-1 element binds specifically to AP-1 protein as verified by supershift assays. EMSA studies and mutational analyses of the promoter region also revealed that the members of the Sp family of transcription factors (Sp-1 and Sp-3) bind to the c-met Sp-1 element (located at position -124) which is adjacent to the AP-1 site. We show that Sp binding dampens binding of AP-1 to its cognate site in the c-met promoter region. Stimulation of Hepa 1-6 cells with HGF resulted in a rapid and dramatic enhancement of the AP-1 binding activity as well as an overall increase in the level of AP-1 protein. Cotransfection of AP-1 expression vectors (c-Fos plus c-Jun) with c-met promoter constructs resulted in stimulation of c-met promoter activity. We found that transactivation of the c-met promoter by AP-1 can be blocked by Curcumin, an inhibitor of AP-1. Moreover, we found that the induction of the endogenous c-met gene by HGF is inhibited by the addition of Curcumin. The results demonstrate that the HGF-induced transcription of the c-met gene by HGF is, at least in part, due to activation of the AP-1 pathway.
Molecular Epidemiology and Recombination of Human Enteroviruses from AFP surveillance in Yunnan, China from 2006 to 2010

The study represents the genetic overview of non-polio enteroviruses (NPEV) isolated from acute flaccid paralysis (AFP) cases in Yunnan Province from 2006 to 2010. Molecular typing based on VP1 nucleotide sequence was carried out on 98 NPEV isolates, and 33 serotypes were identified. EV-B was detected most frequently with an overall prevalence of 71.4%, followed by EV-A (18.4%) and EV-C (10.2%). No EV-D was identified. NPEV positive rate was higher in children <3 years of age and in summer and autumn months. Clinically, 68.4% patients presented with fever, and 16 cases (16.3%) were classified as Guillain-Barre syndrome, followed by myositis (13.3%). The phylogenetic analysis on the VP1 and 3D regions of prevalent serotypes provided evidence for recombination events among them. EV-A71, an important pathogen previously demonstrated to be associated with paralysis, had also been detected (n = 8) in this study and they all belonged to genotype C4. Great genetic divergence between Yunnan isolates and strains from other regions of the world was revealed. The findings of the study are of great importance for further research on molecular evolution of EV under the circumstance of no specialized EV surveillance system in China.
The Role of Basement Membrane in Angiogenesis and Tumor Growth

Expansion of the tumor-cell mass is dependent on both the degree of tumor vascularization and the rate of angiogenesis. Blood vessel growth is controlled, in part, by the matrix surrounding it, in particular, the basement membrane underlying the endothelium. Here we illustrate that laminin, a major component of basement membrane, has several biologically active sites that can bind to endothelial and tumor cells, and have the ability to regulate angiogenesis and tumor growth. We show that synthetic peptides at two sites in the laminin B1 chain (the RGD and YIGSR sequences) inhibit angiogenesis, whereas a third site in the A chain, designated SIK-VAV, stimulates vessel and tumor cell growth. By developing strategies that promote or inhibit the activities of these sites in laminin, we may obtain methods to inhibit angiogenesis and subsequent tumor growth.
Oral corticosteroid use among children in TennCare.

Background.—Lack of information about medication effects and use in children is a long-standing and troublesome policy issue. Documenting patterns of use for medications with potential for suboptimal use and adverse effects, such as oral corticosteroids, would be useful. Objective.—To describe the use of oral corticosteroids among children enrolled in TennCare, Tennessee's managed care program for Medicaid enrollees and uninsured individuals. Design.—A retrospective cohort study. Drug Exposure.—Children enrolled in TennCare who had prescriptions filled in their name for oral corticosteroids during 1998 were identified. Descriptive information included age, race, sex, and county of residence. We identified possible indications for corticosteroid use for new users by searching encounter files for encounters temporally related to the index prescription. Subsequent use of corticosteroids was measured in the 365 days after the index prescription. Results.—Of 400 724 children continuously enrolled in TennCare during the study period, 29 362 (7327 per 100 000) children had a prescription filled for an oral corticosteroid. Steroid prescription filling was more common among young children and male children and less common among black children. Children in rural counties had oral corticosteroid prescriptions filled at a higher rate than children residing in urban counties. Nearly 75% of corticosteroid users filled only 1 prescription during the study period; 1319 children filled 4 or more prescriptions. Asthma was the most common indication for oral corticosteroid use (16%), whereas 1 in 5 users (22%) had an unknown indication for oral corticosteroid use. Conclusions.—A large number of children enrolled in TennCare had a prescription for oral corticosteroids filled in 1998. Further population-based studies describing the development of adverse effects in users of corticosteroids would be important.
Some interface growth features of Czochralski sapphire crystals

Abstract Czochralski crystals of sapphire and ruby have been grown with a planar-like interface. In the case of ruby, this morphology was related to an essentially constant radial chromium distribution. Three forms of gaseous segregates are described and their origin related to the interface morphologies which existed during growth. The crystals were obtained free from low angle boundaries by conventional techniques.
Develop Pleasurable Automotive Switch-Feel Through Perceptual Design

Automotive interior has become the next battleground for quality, customer satisfaction and emotional appeal. As an integral part of vehicle interior, operating quality of switches has a direct impact on the customer’s overall perception of quality. As of today, work in switch design and engineering has focused primarily on visual appeal, ergonomics and functionality while limited work has been done to understand and design switches that “feel” pleasurable to operate. As a result, specifications concerning the switch-feel are incomplete or ineffective and our automotive switches typically lack good and consistent operating feel. Switch-feel “quality” is affected by how sensory input is processed by the user, and as such, it falls into the category of perceptual quality. To effectively meet the challenge of engineering high quality switch-feel we present a novel approach based on perceptual design. With perceptual design the sensory pleasure of a product is considered as a forefront design objective rather than a bi-product of the traditional functionality and usability centered product design and development practice [1]. Our methodology employs several well-established science and engineering disciplines to gain knowledge of perceptual data, its relationship with physical stimuli, and the human sensitivity to such physical stimuli. Haptics simulators were developed to generate a wide range of switch-feel for use in our psychophysical studies. Multi-Dimensional Scaling (MDS) was used to identify the main components of human perception of switch-feel. Threshold analysis was carried out to determine how sensitive humans are in detecting changes of these parameters. A Design of Experiment (DOE) preference study was used to develop “Quality Functions” that map switch-feel physical parameters to subjective, perceived quality. New switch-feel specifications were created based on our perceptual design work. A switch-feel measurement system was also developed to verify whether the feel of a physical switch actually meets our specifications. We applied perceptual design to a production vehicle program to improve the operating feel of its climate control switches. The results demonstrated that it was effective in delivering good, pleasurable switch-feel, and at the same time, improved our engineering efficiency.Copyright © 2006 by ASME
Effect of pH and light on aggregation and conformation of an IgG1 mAb

During the purification process, monoclonal antibodies may be exposed to parts of UV-C (200 to 290 nm), UV-B (290 to 320 nm) and visible light (400 to 760 nm) under a variety of buffer and pH conditions. Together, these conditions can promote both chemical and physical degradation which may result in conformational changes. To examine this possibility, an IgG1 mAb at pH 3.5, 5, and 8 was exposed to UV light at multiple protein concentrations. Exposure to 302 nm light resulted in a pH-dependent formation of high molecular weight species where the degree of oligomerization increased with increasing pH. Characterization by SDS-PAGE under reducing and nonreducing conditions and size exclusion MALS revealed that the predominant species were nonreducible dimeric, trimeric and higher order oligomeric species which occurred through processes other than intermolecular disulfide bond formation. Biophysical characterization by differential scanning calorimetry demonstrated an overall loss of heat capacity suggesting a loss of conformational integrity with light exposure. A decrease in tryptophan fluorescence was paralleled by a significant decrease in the transition temperature measured during heat-induced unfolding following light exposure, also suggesting a significant change in conformational integrity. The observations by fluorescence spectroscopy coincided with pH-dependent changes in the alterations of secondary structure characterized by Fourier transform infrared spectroscopy and far-UV circular dichroism with the most acidic pH showing the greatest degree of change in the β-sheet structure. Exposure to UV light resulted in aggregation with pH-dependent yields decreasing in the order 8.0 > 5.0 > 3.5, while the opposite trend was observed for conformational changes, with pH-dependent extents decreasing in the following order 3.5 > 5.0 > 8.0. These pH-dependent trends suggest that different strategies will be required to stabilize the protein against these modifications during processing.
The Synthesis Theorem for finite regular semigroups, and its generalization

Abstract The Synthesis Theorem describes the global structure of a semigroup and gives its multiplication in ‘coordinate form’. Rees' theorem and the Krohn-Rhodes theorem are special cases. The theorem holds for all finite semigroups and also for a rather general class of infinite semigroups.
A statistical bias in the derivation of hardness-dependent metals criteria

Log-transformed values of lethal effect and hardness are often employed to predict metal effects. For example, they are used to develop water quality criteria. A statistical bias encountered with backtransformed, least-squares regression models can compromise the accuracy of associated predictions. A description and method of estimating this bias are discussed herein. In a selected data set, the bias was as high as 57%.
Neurodegenerative diseases and transglutaminase

The idea that transglutaminase (TG), a posttranslational protein crosslinking enzyme (for reviews, see refs. 1–6), might be involved in the pathology of neurodegenerative diseases, notably of Alzheimer disease (AD), was first suggested by the experiments of Selkoe et al. (7, 8). These authors drew particular attention to the reactions of TG with brain neurofilaments. Miller and Anderton (9) extended the observations by showing that, in addition to the neurofilament triplet proteins, the microtubule-associated proteins were also good substrates for TG. The dynamic quality of the neural intermediate filament network (10) is essential for maintaining the plasticity of the cytoskeleton and cell architecture, in general. Linking together noncovalently assembled segments of the network with intermolecular Nɛ(γ-glutamyl)lysine side chain bridges could impact adversely on the functions and viability of the neuron. Efforts are underway for documenting the TG-mediated covalent polymerization of the microtubule-associated τ proteins (11, 12) which are the main (if not the only) constituents of the intracellular neurofibrillary tangles (or paired helical filaments; PHF) often seen in AD (13) and other diseases (14). With recombinant human τ40 protein as substrate for human TG, a number of potential crosslinking sites were identified by employing dansylcadaverine for the enzyme-directed substitutions of Gln (or acceptor) residues (15) and dansyl-ɛ-aminocaproyl Gln-Gln-Ile-Val for those of the Lys (or donor) residues (16). Listed roughly in the order of reactivities, the following side chains in τ40 were derivatized: Gln-424, -88, -6, -244, -351, -124, -276, and -288; Lys-383, -385, -174, -180, -225, -263, and -24 (S. N. P. Murthy, J. A. Kuret, J. Wilson, T. J. Lukas, and L.L., unpublished). It remains to be determined which of these residues is involved in the homologous polymerization of τ to τ and which is involved in the crosslinking of τ to other neuronal …
Separation of laminar boundary layer induced by aerodynamic interference

Introduction A interference phenomena have been studied for many years. Principally these studies have been directed at situations in which real flow could be approximated by the use of potential theory. Indeed this approximation has served well to estimate both wind tunnel wall effects and the influence of adjacent surfaces on each other, including the interaction that induces a changing aerodynamic load on external stores or pilot escape capsules during their trajectory through the flowfield surrounding the parent aircraft. It is not our purpose to review aerodynamic interference as interpreted using potential theory. The reader interested in that aspect may wish to look up Ref. 1, which is a fairly recent summary of research in aerodynamic interference. Rather, our purpose here is to discuss a class viscous-outer flow aerodynamic interference. With the exception of shock-boundary layer interaction' and streamline displacement in boundary layers due to probes' this sort of flow seems not to have received a great deal of attention except for illustrating complex phenomena.' The present Note deals with separation on a surface covered by a laminar boundary layer. A nearby body causes a pressure gradient on the first surface that, under some circumstances, will in turn lead to boundary-layer separation on the first surface. For the case of flow in a wind tunnel containing a large model, when one uses self-streamlined wind tunnel walls to reduce wall interference, the induced separation is most likely at highinduced pressure gradients near the angle of attack where the airfoil stalls. The study presented here is based upon the use of simple shapes with laminar boundary layers on the extended surface. An objection based upon the fact that such walls are not likely to have laminar boundary layers in any practical case has considerable merit. Nevertheless, the use of laminar boundary layers allows the phenomenon to be illustrated simply. The quantitative aspects of the situation would clearly be different if the boundary layers are turbulent. The level of the pressure gradient, the distribution of the momentum thickness on the wall, and the size of the parameter defining separation will be different in a turbulent boundary layer. But the qualitative aspects of the situation will be similar, and therein lies the merit of studying the simple case. The analysis is based on two-dimensional incompressible flow. It will provide the approximation for the separation conditions. Several results will be presented showing circumstances under which external flow-induced separation is possible.
Analysis of the lattice-chiral-fermion proposal of Aoki, Funakubo, and Kashiwa.

We examine the lattice-chiral-fermion scheme proposed by Aoki, Funakubo, and Kashiwa (AFK) in the context of chiral QED in two and four dimensions. In four dimensions, we find that, although the AFK scheme ensures gauge invariance by rendering amplitudes transverse, it does not improve their ultraviolet behavior; as in the Wilson theory, the effective vacuum polarization is quadratically divergent. In both two and four dimensions, we find that there are contributions to the effective gauge-field action beyond those analyzed by AFK. These contributions are not accessible through finite-order perturbation theory.