cssi/SciSciGPT-SciSciNet huggingface dataset:
Evidence for alterations in α2-adrenergic receptor sensitivity in rats exposed to repeated cocaine administration

Abstract It is well established that cocaine stimulates monoamine transmission by blocking reuptake of norepinephrine (NE), dopamine and serotonin into nerve cells, yet few investigations have addressed the effects of chronic cocaine on NE function. In the present study, we examined the effects of repeated cocaine injections on neuroendocrine responses evoked by the α2-adrenergic receptor agonist, clonidine. Previous findings show that clonidine increases pituitary growth hormone (GH) secretion by a central mechanism involving postsynaptic α2-adrenergic receptors. Male rats previously fitted with indwelling jugular catheters received two daily injections of cocaine (15 mg/kg, i.p.) or saline for 7 days. At 42 h and 8 days after treatment, rats were challenged with clonidine (25 μg/kg, i.v.) or saline, and serial blood samples were withdrawn. Plasma GH and corticosterone levels were measured by radioimmunoassay. Prior cocaine exposure did not affect basal levels of either hormone. However, cocaine-pretreated rats displayed a significant reduction in clonidine-evoked GH secretion at 42 h, and this blunted response was still apparent 8 days later. Corticosterone responses produced by clonidine were similar regardless of pretreatment. The present data suggest that withdrawal from repeated cocaine injections may be accompanied by desensitization of postsynaptic α2-adrenoreceptors coupled to GH secretion. Since human patients with depression often exhibit blunted GH responses to clonidine, our findings provide evidence that cocaine withdrawal might produce depressive-like symptoms via dysregulation of NE mechanisms.
CHARGE EXCHANGE CROSS SECTIONS OF HYDROGEN IONS IN GASES

Measurements are reported of the cross section for electron capture (${\ensuremath{\sigma}}_{10}$), electron loss (${\ensuremath{\sigma}}_{01}$), and electron detachment (${\ensuremath{\sigma}}_{\ensuremath{-}10}$) for hydrogen atoms and ions traversing several gases. (${\ensuremath{\sigma}}_{\mathrm{if}}$ represents the cross section for charge transfer from initial state $i$ to final state $f$.) The kinetic energy of the particle was from 3 kev to 200 kev. The target gases used were ${\mathrm{H}}_{2}$, He, ${\mathrm{N}}_{2}$, ${\mathrm{O}}_{2}$, Ne, and A. Cross sections were determined by measuring the attenuation of the hydrogen beam in a gas cell under the influence of an electrostatic or magnetic field. The fraction of the beam in each charge state after passing through a "thick target" was also determined. This latter measurement served as a test for internal consistency of the data, since the fraction is relatable to the cross section for entry to and exit from the charge state. The loss cross section, ${\ensuremath{\sigma}}_{01}$, increased monotonically at low energies, reaching a maximum at a velocity approximately equal to the orbital electron velocity. For the higher energies studied the capture cross section could be represented by an expression of the form, $\ensuremath{\sigma}=A{e}^{\ensuremath{-}bv}$, where $A$ and $b$ are constants for each gas studied. The electron attachment cross section, ${\ensuremath{\sigma}}_{0\ensuremath{-}1}$, was of the order ${10}^{\ensuremath{-}17}$ ${\mathrm{cm}}^{2}$/gas atom for the gases studied and attained a maximum between 5 and 20 kev. The inverse transition, ${\ensuremath{\sigma}}_{\ensuremath{-}10}$, was approximately ${10}^{\ensuremath{-}15}$ ${\mathrm{cm}}^{2}$/gas atom in the energy range studied.
Atmospheric chemistry of alkanes: Review and recent developments

Abstract Alkanes comprise a significant fraction of gasolines and of the non-methane volatile organic compounds present in ambient air in urban areas. In this work, we have extended our previous studies to investigate the formation of 1,4-hydroxycarbonyls (and other products) from the reactions of OH radicals with C5–C8 n-alkanes in the absence of NO, and have investigated the rates of conversion of the commercially available 4,5-dihydro-2-methylfuran (DHMF) into 5-hydroxy-2-pentanone under various conditions in a ∼6900 l Teflon chamber in order to assess whether this conversion is a homogenous gas-phase or a heterogeneous wall process. We observe that the same 1,4-hydroxycarbonyls are formed in the absence of NO as in the presence of NO, but with formation yields approximately a factor of 10 lower as expected from the reaction mechanisms involved. The results of the experiments to investigate the conversion of 4,5-dihydro-2-methylfuran to 5-hydroxy-2-pentanone indicate that this conversion is not a homogeneous gas-phase process, but is a heterogeneous reaction at the chamber wall which is probably acid-catalyzed. The current understanding of the mechanisms and products of the atmospheric degradation reactions of alkanes is also presented.
Plasma 25‐Hydroxyvitamin D Concentrations and Periodontal Disease in Postmenopausal Women

Background: Vitamin D has anti-inflammatory and antimicrobial properties that, together with its influence on bone health, may confer periodontal benefit.Methods: Cross-sectional associations (years 1997-2000) between plasma 25-hydroxyvitamin D concentration [25(OH)D] and periodontal measure were investigated among 920 postmenopausal women. Measures of chronic disease were defined based on: 1) alveolar crestal height (ACH) measures from intraoral radiographs and tooth loss and 2) Centers for Disease Control and Prevention (CDC)/American Academy of Periodontology (AAP) criteria using measures of clinical attachment level and probing depth (PD). Acute oral inflammation was assessed by the percentage of gingival sites that bled upon assessment with a probe. Logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for periodontal disease among participants with adequate [25(OH)D ≥50 nmol/L] compared with deficient/inadequate [25(OH)D <50 nmol/L] vitamin D status adjust...
Application of the Brewster angle illumination technique to eliminate resist-induced alignment errors

Resist coating on alignment marks can be asymmetrical due to the spinning motion. Alignment errors may result from this asymmetrical coating because the alignment signal can contain asymmetry when the optics detects the mark through the resist. The amount of signal asymmetry depends on the mark topography, resist thickness, spin speed, location on the wafer and the alignment technique. We have proposed a Brewster angle illumination technique (BAIT) as an effective means to greatly reduce the resist-induced alignment error by reducing alignment signal reflections from the surface of the resist. In this paper, we present the experimental results. We built an interferometric alignment system to implement BAIT. By scanning a resist-coated mark in close proximity to an exposed reference mark, drift and other system offsets are minimized, allowing an offset detectability of 6 nm. Resist-induced alignment errors with a radial dependence on mark position and magnitudes up to 25 nm have been measured when BAIT is not used. However, when BAIT is employed the resist-induced errors at all positions on the wafer are reduced to less than 10 nm and are close to the resolution limit of the alignment setup. The validity of the data was established by changing the polarization of the light from TM to TE, thereby destroying the BAIT condition while holding all other parameters constant. A study of the dependence of resist-induced alignment error on spin speed reveals that the amount of asymmetry in the resist profile increases monotonically as the spin speed increases. This effect is due to two factors: that the resist is thinner and that the spin speed is also faster. Further study using a thinner to dilute the resist isolated these factors and showed that the resist-induced alignment errors depend more sensitively on spin speed than the resist thickness. In most of the cases, the BAIT alignment system is immune to resist coating asymmetry and the error magnitude stays below 10 nm. However, the BAIT cannot work effectively when resist thickness becomes thinner than 0.6 micrometer. This limitation of BAIT technique was attributed to the ripples in the resist profile causing local impinging angles to deviate significantly from the Brewster angle.
Return of individual genetic results in a high-risk sample: enthusiasm and positive behavioral change.

The goal of this study was to examine participant responses to disclosure of genetic results in a minority population at high risk for depression and anxiety. Eighty-two subjects in a genetic study of nicotine dependence were offered personalized genetic results. All were nicotine-dependent and 64% self-identified as African American. Pathway Genomics was used to evaluate genetic risks for five complex diseases. Participants returned 4–8 weeks after enrollment for in-person genetic counseling interviews and evaluation of baseline measures. A telephone follow-up was performed 4–8 weeks later to assess responses to results. Fifty of the 82 subjects (61%) were interested in receiving genetic results. These participants had multiple risk factors, including high baseline measures of depression (66%) and anxiety (32%), as well as low rates of employment (46%), adequate health literacy (46%), and health insurance (45%). Pathway Genomics reported “increased risk” for at least one disease in 77% of subjects. Ninety-five percent of participants reported that they appreciated the genetic results, and receiving these results was not associated with changes in symptoms of depression or anxiety. Furthermore, after return of genetic results, smoking cessation attempts increased (P = 0.003). Even in an underserved population at high risk for adverse psychological reactions, subjects responded positively to personalized genetic results. Genet Med 17 5, 374–379.
Workplace social support and work-family conflict: A meta-analysis clarifying the influence of general and work-family-specific supervisor and organizational support

This article uses meta-analysis to develop a model integrating research on relationships between employee perceptions of general and work–family-specific supervisor and organizational support and work–family conflict. Drawing on 115 samples from 85 studies comprising 72,507 employees, we compared the relative influence of 4 types of workplace social support to work–family conflict: perceived organizational support (POS); supervisor support; perceived organizational work–family support, also known as family-supportive organizational perceptions (FSOP); and supervisor work–family support. Results show work–family-specific constructs of supervisor support and organization support are more strongly related to work–family conflict than general supervisor support and organization support, respectively. We then test a mediation model assessing the effects of all measures at once and show positive perceptions of general and work–family-specific supervisor indirectly relate to work–family conflict via organizational work–family support. These results demonstrate that work–family-specific support plays a central role in individuals’ work–family conflict experiences.
Bounded approximation by polynomials

Abstract : This paper presents a complete solution to the following problem: if G is an arbitrary bounded open set in the complex plane, characterize those functions in G that can be obtained as the bounded pointwise limits of polynomials in G. Roughly speaking, the answer is that a function is such a limit if and only if it has a bounded analytic continuation throughout a certain bounded open set G* that contains G. This set G* is the inside of the 'outer boundary' of G. More precisely, if G is a bounded open set and if H is the unbounded component of the complement of G- (the closure of G), then G* denotes the complement of H-.
Determination of water surface temperature based on the use of Thermal Infrared Multispectral Scanner data

A straightforward method for compensating Thermal Infrared Multispectral Scanner (TIMS) digital data for the influence of atmospheric path radiance and the attenuation of target energy by the atmosphere is presented. A band ratioing model useful for estimating water surface temperatures, which requires no ground truth measurements, is included. A study conducted to test the potential of the model and the magnitudes of the corrections for atmosphere encountered is presented. Results of the study, which was based on data collected during an engineering evaluation flight of TIMS, indicate errors in the estimate of the surface temperature of the water fall from +/- 1.0 C for uncorrected data to +/- 0.4 C when data have been corrected according to the model presented. This value approaches the noise-limited thermal resolution of the sensor at the time of the flight.
Directed Assembly of Bimetallic Nanoparticles by Pulsed-Laser-Induced Dewetting: A Unique Time and Length Scale Regime

Pulsed-laser-induced dewetting (PLiD) was used to assemble patterned, nanoscale metallic thin film features into bimetallic nanoparticles. The liquid-phase flow is related to a conventional droplet impact test and, in appropriate dimensions, have inertial and viscoinertial flow characteristics. The final size, morphology, composition, and interdiffusion of the nanoparticles is governed by the interplay of capillary, inertial, and viscous forces and an appropriate dimensional regime defined by competing Rayleigh-Plateau and spinodal instabilities.
Protein quantification in complex mixtures by solid phase single-molecule counting.

Here we present a procedure for quantifying single protein molecules affixed to a surface by counting bound antibodies. We systematically investigate many of the parameters that have prevented the robust single-molecule detection of surface-immobilized proteins. We find that a chemically adsorbed bovine serum albumin surface facilitates the efficient detection of single target molecules with fluorescent antibodies, and we show that these antibodies bind for lengths of time sufficient for imaging billions of individual protein molecules. This surface displays a low level of nonspecific protein adsorption so that bound antibodies can be directly counted without employing two-color coincidence detection. We accurately quantify protein abundance by counting bound antibody molecules and perform this robustly in real-world serum samples. The number of antibody molecules we quantify relates linearly to the number of immobilized protein molecules (R2 = 0.98), and our precision (1−5% CV) facilitates the reliable d...
Electrochemical state and internal variables estimation using a reduced-order physics-based model of a lithium-ion cell and an extended Kalman filter

Abstract This paper addresses the problem of estimating the present value of electrochemical internal variables in a lithium-ion cell in real time, using readily available measurements of cell voltage, current, and temperature. The variables that can be estimated include any desired set of reaction flux and solid and electrolyte potentials and concentrations at any set of one-dimensional spatial locations, in addition to more standard quantities such as state of charge. The method uses an extended Kalman filter along with a one-dimensional physics-based reduced-order model of cell dynamics. Simulations show excellent and robust predictions having dependable error bounds for most internal variables.
Co-activators and co-repressors in the integration of transcriptional responses

The nuclear hormone receptors are DNA binding transcription factors that are regulated by binding of ligands, switching them from an inactive or repressive state to gene-activating functions. Recent evidence supports the hypothesis that many nuclear receptors switch, in a ligand-dependent manner, between binding of a multicomponent co-repressor complex containing histone deacetyltransferase activity, and binding of a co-activator complex containing factors with histone acetyltransferase activity that are further regulated by diverse signal transduction pathways. The identification of these limiting co-repressor and co-activator complexes and their specific interaction motifs, in concert with solution of the structures of the receptor ligand-binding domain in apo (empty) and ligand bound forms, indicates a common molecular mechanism by which these factors activate and repress gene transcription.
Linear dichroism of acrylodan-labeled tropomyosin and myosin subfragment 1 bound to actin in myofibrils

Muscle contraction can be activated by the binding of myosin heads to the thin filament, which appears to result in thin filament structural changes. In vitro studies of reconstituted muscle thin filaments have shown changes in tropomyosin-actin geometry associated with the binding of myosin subfragment 1 to actin. Further information about these structural changes was obtained with fluorescence-detected linear dichroism of tropomyosin, which was labeled at Cys 190 with acrylodan and incorporated into oriented ghost myofibrils. The fluorescence from three sarcomeres of the fibril was collected with the high numerical aperture objective of a microscope and the dichroic ratio, R (0/90 degrees), for excitation parallel/perpendicular to the fibril, was obtained, which gave the average probe dipole polar angle, Theta. For both acrylodan-labeled tropomyosin bound to actin in fibrils and in Mg2+ paracrystals, Theta congruent to 52 degrees +/- 1.0 degrees, allowing for a small degree of orientational disorder. Binding of myosin subfragment 1 to actin in fibrils did not change Theta; i.e., the orientation of the rigidly bound probe on tropomyosin did not change relative to the actin axis. These data indicate that myosin subfragment 1 binding to actin does not appreciably perturb the structure of tropomyosin near the probe and suggest that the geometry changes are such as to maintain the parallel orientation of the tropomyosin and actin axes, a finding consistent with models of muscle regulation. Data are also presented for effects of MgADP on the orientation of labeled myosin subfragment 1 bound to actin in myofibrils.
mTOR kinase: a possible pharmacological target in the management of chronic pain

Chronic pain represents a major public health problem worldwide. Current pharmacological treatments for chronic pain syndromes, including neuropathic pain, are only partially effective, with significant pain relief achieved in 40–60% of patients. Recent studies suggest that the mammalian target of rapamycin (mTOR) kinase and downstream effectors may be implicated in the development of chronic inflammatory, neuropathic, and cancer pain. The expression and activity of mTOR have been detected in peripheral and central regions involved in pain transmission. mTOR immunoreactivity was found in primary sensory axons, in dorsal root ganglia (DRG), and in dorsal horn neurons. This kinase is a master regulator of protein synthesis, and it is critically involved in the regulation of several neuronal functions, including the synaptic plasticity that is a major mechanism leading to the development of chronic pain. Enhanced activation of this pathway is present in different experimental models of chronic pain. Consistently, pharmacological inhibition of the kinase activity turned out to have significant antinociceptive effects in several experimental models of inflammatory and neuropathic pain. We will review the main evidence from animal and human studies supporting the hypothesis that mTOR may be a novel pharmacological target for the management of chronic pain.
Correlation between decreased sensitivity of the Daudi lymphoma cells to VP-16-induced apoptosis and deficiency in DNAS1L3 expression

A functional relationship between the apoptotic endonuclease DNAS1L3 and the chemotherapeutic drug VP-16 was established. The lymphoma cell line, Daudi, exhibited a significant resistance to VP-16 treatment in comparison to the lymphoma/leukemia cell line, U-937. While U-937 cells degraded their DNA into internucleosomal fragments, Daudi cells failed to undergo such fragmentation in response to the drug. Activation of both caspase-3 and DNA fragmentation factor was not sufficient to trigger internucleosomal DNA fragmentation in Daudi cells. No correlation was found between expression levels of topoisomerase-II, Pgp, Bcl-2, Bax, or Bad and decreased sensitivity of Daudi cells to VP-16. Daudi cells failed to express DNAS1L3 and ectopic expression of this protein significantly sensitized the cells to VP-16. An enhancement of caspase-3 activity and collapse of mitochondrial membrane potential underlie DNAS1L3-mediated sensitization of Daudi cells to VP-16, which may be a direct result of DNAS1L3-mediated increase in PARP-1-activating DNA breaks after VP-16 treatment. Our results suggest that DNAS1L3 plays an active role in lymphoma cell sensitization to VP-16 and that its deficiency may constitute a novel mechanism of drug resistance in these cells.
Sudden death in patients with implantable cardioverter-defibrillators

Abstract Of the 733 patients with implantable cardioverter-defibrillators (ICDs) from 1982 to 1995 in our center, 20 died suddenly while the ICD was activated. This number included 16 men and four women with a mean age of 60 ± 8 years and ejection fractions of 24.2% ± 8.6%. ICDs were implanted for drug refractory ventricular tachycardia (VT) in 13 patients and for resucitated cardiac arrest in seven patients. The clinical VT was associated with syncope in 7 of 13 patients. VT was induced in 18 patients and was hemodynamically unstable in 12 patients. Shock therapies associated with syncope were delivered in 7 of 15 patients during the follow-up. This subgroup of patients survived a median of only 18 months after ICD implant. Ventricular fibrillation-defibrillation was found to surround death in nine patients. Conclusions: (1) Sudden death victims of the ICD population are characterized by poor left ventricular function and hemodynamically unstable ventricular tachyarrhythmias. (2) Ventricular tachyarrhythmias are the major cause of sudden death in ICD patients.
Optical glucose detection across the visible spectrum using anionic fluorescent dyes and a viologen quencher in a two-component saccharide sensing system

A very general system is described in which anionic fluorescent dyes possessing a wide range of absorbance and emission wavelengths are used in combination with a boronic acid-modified viologen quencher to sense glucose at pH 7.4 in buffered aqueous solution. The present study demonstrates this capability with the use of eleven anionic fluorescent dyes of various structural types. Signal modulation occurs as the monosaccharide binds to the viologen quencher and alters its efficiency in quenching the fluorescence of the anionic dyes. The degree of quenching and the magnitude of the glucose signal were found to correlate roughly with the number of anionic groups on the dye. Optimal quencher : dye ratios were determined for each dye to provide a fairly linear signal in response to changes in glucose concentration across the physiological range.
Dispersive Auroral Hiss

AT the frequencies of auroral hiss (up to 500 kHz), the propagation of radio energy through the magnetosphere is in the whistler mode, which is dispersive: the velocity of propagation is dependent on frequency. Here I report bursts of auroral hiss so brief as to have distinctly exhibited whistler-mode dispersion. The duration of each of these bursts was of the order of 0.1 s. I have chosen the name “fast hisslers” to distinguish them from the more slowly varying, periodic hissler emissions reported by Carpenter et al.1 and to indicate their kinship with auroral hiss. These hisslers were observed at a ground station and therefore differ from the 0.05 s duration “auroral beam modes” observed by Smith2 with the very low frequency receiver on the Alouette II satellite.
The Type B Leukemogenic Virus Truncated Superantigen Is Dispensable for T-Cell Lymphomagenesis

Mouse mammary tumor virus (MMTV) is a slow-acting oncogenic retrovirus that causes mammary tumors in mice after a long period (6 to 9 months) (1, 29). An MMTV variant, type B leukemogenic virus (TBLV), has been demonstrated to cause thymic lymphomas with a short latency period (1.5 to 2 months) when injected intrathymically into neonatal mice (2). Compared to MMTV, TBLV has a deletion of 443 nucleotides and a substitution of 124 nucleotides in the U3 region of the long terminal repeat (LTR) (3). This deletion removes a negative regulatory element (NRE) present in the MMTV LTR (17-19, 23, 36, 37), which has been implicated in tissue-specific MMTV expression (6, 30). The substitution creates a triplication of a 62-bp element comprised of sequences flanking the deletion (3) (Fig. ​(Fig.1A1A). FIG. 1. Construction and characterization of hybrid MMTV-TBLV proviral clones. (A) Diagram of parental and hybrid MMTV clones. The pHYB-MTV plasmid contains a hybrid between Mtv1 and C3H MMTV. A white box indicates the region upstream of the EcoRI site that is ... The LTR deletion and substitution also truncate the open reading frame (ORF) encompassing the U3 region of the LTR (Fig. ​(Fig.1A).1A). This ORF encodes a 37-kDa, type II transmembrane glycoprotein known as superantigen (Sag) that functions in the milk-borne transmission of MMTV (1, 7, 9, 10, 16) by the stimulation of T cells through the T-cell receptor (TCR) (33, 35). The truncated Sag protein encoded in the TBLV LTR lacks the entire C-terminal region that interacts with the TCR, yet it retains the transmembrane region, a part of the extracellular region that includes the five glycosylation sites, a single proteolytic processing site, and the major histocompatibility complex class II protein binding motif (12, 20). This study shows that the truncated TBLV Sag protein is dispensable for virally induced T-cell lymphomas.
Observations on intracellular protein catabolism studied in vitro.

Abstract Protein degradation in rat liver and rat kidney slices was studied by two methods: (a) measurement of the release of radioactive amino acids from tissues previously labeled in vivo ; and (b) measurement of net changes in the nonprotein nitrogen fraction. Protein breakdown, measured by either method, was found to be strongly inhibited by anaerobiosis, by dinitrophenol, and by certain amino acid analogs. The properties of the protein breakdown observed suggest that in mammalian tissues there is a catabolic phase of protein metabolism and that there is, at the cellular level, a true dynamic state of proteins. Some of the other implications of the inhibitor effects are discussed.
Electron transfer 122. Reductions of an N4-coordinated complex of silver(III)

Abstract The silver(III) complex of ethylenebis(biguanide), (ebbg)AgIII, which is stable in aqueous acid, reacts readily with 2 equiv. each of V2+, Cr2+, Eu2+, Fe2+ and Ru(NH3)62+ yielding Ag+. Slower reactions with Ti(III) and Fe(Me2phen)32+ consume only 1 equiv, of these reductants but again yield Ag+. The 2e− reductants H3AsO3 and HSO3− do not react. No Ag(II) species is detected in these reactions, either as a product or as a transient. At low reductant concentrations, reactions are first order in both redox partners, but at high [Fe2+], there is evidence for partial formation of a 1:1 (ebbg)AgIIIFeII complex (Qassn = 10 M−1). Rates appear to be determined by the initial 1e− reduction of (ebbg)AgIII to its AgII analog, after which the latter is rapidly converted to Ag(I), either by a second reductant molecule or, in the case of the slower reductants, internal electron transfer with oxidation of the ligand. The latter process provides substantial driving force for it allows complete conversion to Ag(I) by several reductants having much more positive E° values than that reported for (ebbg)AgIII/II (0.32 V). Kinetic selectivity patterns are consistent with the predominance of an outer-sphere path for all metal-center reductants examined. Specific rates for these reductions, in conjunction with the treatment of Marcus, led to a self-exchange rate 105.8+0.8 M−1 s−1 for this AgIII/II couple. The latter value is comparable to rates recorded for a number of 4d- and 5d-based systems, is considerably greater than many of those for 3d-based couples, and lies close to that for AgIII/II when both states are porphyrin-bound. The present results support the view that reductions of Ag(III) to Ag(I) in this system take place most easily by successive 1e− steps, rather than by single 2e− transactions. These 2e− reductants that react most readily (e.g. ascorbic acid and H2O2) are those which can be oxidized in single electron steps. Reductions by formic acid and by primary alcohols, which may instead involve hydride transfer to Ag(III) are found to proceed much more sluggishly.
A Mn2(+)-dependent ribozyme

An RNA hairpin identical in sequence with the one formed during autocyclization of the 414-nucleotide Tetrahymena intervening sequence undergoes strand scission at a specific site in the presence of Mn2+. In addition to representing one of the smallest and simplest ribozymes possible, strand scission occurs readily under physiological conditions, is unaffected by the presence of Mg2+, and displays salt, pH, and temperature optima of potential use in exploiting Mn2+ as a regulatory switch in intact cells. The chemistry of strand scission of the RNA hairpin is described, as is the Mn2(+)-dependent solvolysis of a 231-nucleotide RNA transcript containing this structural motif.
Combination regimen with statins and NSAIDs : A promising strategy for cancer chemoprevention

Statins and nonsteroidal antiinflammatory drugs (NSAIDs) are commonly prescribed for lowering cholesterol and anti-inflammation, respectively. Recently, their potential roles as cancer chemopreventive agents have been subject to intensive studies. Human trials have not provided conclusive results on the protective effects of statins against different cancers, while more convincing results have been observed for cancer preventive effects of NSAIDs, especially on colorectal cancer. A promising strategy to enhance the cancer preventive efficacy of statins and NSAIDs is to use them in combination, which may produce synergy and lower the dose required for each agent. This strategy is of particular interest for potential use of low doses of statins and NSAIDs on a long-term basis for cancer chemoprevention; increased risks for gastrointestinal and cardiovascular side effects associated with the use of NSAIDs have been observed in colorectal cancer chemopreventive trials. This article reviews the evidence for the cancer preventive actions of statins and NSAIDs, as well as their possible synergistic action and the mechanisms involved.
Characterization of a heavy metal ATPase from the apicomplexan Cryptosporidium parvum

Abstract P1-ATPases are transporters which pump heavy metals across membranes, either to provide enzymes with essential cofactors or to remove excess, toxic metal cations from the cytosol. The first protist P1-ATPase ( CpATPase2 ) has been isolated from the apicomplexan Cryptosporidium parvum , an opportunistic pathogen of AIDS patients. This single copy gene encodes 1260 amino acids (aa), predicting a protein of 144.7 kDa. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis confirmed CpATPase2 expression. Immunofluorescence microscopy of C. parvum sporozoites using rabbit antiserum raised against a glutathione-S-transferase (GST) fusion protein suggests that CpATPase2 is associated with the plasma- and cytoplasmic membranes. The protein shares greatest overall sequence similarity to previously characterized copper P1-ATPases. Expression and subsequent biochemical analyses of the N-terminal heavy metal binding domain (HMBD, GMxCxxC) of CpATPase2 as a maltose-binding protein (MBP) in Escherichia coli reveals that the protein specifically binds reduced copper, Cu(I), in vitro and in vivo , and that the cysteine residues of HMBD are responsible for heavy metal coordination. Overall, these data show that the apicomplexan C. parvum possesses a heavy metal P-ATPase transporter with a specificity for reduced copper. Since this discovery represents the first time a heavy metal P-ATPase has been identified and characterized from a protist, further molecular and biochemical studies are needed to understand the roles heavy metal P-ATPases play in heavy metal metabolism and potential virulence for this and other apicomplexa.
Does foreign direct investment drive technological upgrading

This paper evaluates whether inward foreign direct investment stimulates technological upgrading, and if its impact depends on an economy’s level of social capability. FDI inflows exert a positive influence on technological upgrading over a lengthy time period for a large and diverse sample of countries. This effect is conditioned by an economy’s level of social capability, as well as its income. Among poor countries the effect of FDI on upgrading is bolstered for those endowed with higher levels of social capability. The effect of FDI on upgrading in rich countries remains positive but is weaker, and social capability exerts little disparate influence among these similarly socially capable economies.
Selective imaging of nano-particle contrast agents by a single-shot x-ray diffraction technique

Iron oxide nano-particles have very different x-ray diffraction properties from tissue. They can be clearly visualized against suppressed tissue background in a single-shot x-ray diffraction imaging technique. This technique is able to acquire both diffraction and absorption images from a single grating-modulated projection image through analysis in the spatial frequency domain. We describe the use of two orthogonal transmission gratings to selectively retain diffraction signal from iron oxide particles that are larger than a threshold size, while eliminating the background signal from soft tissue and bone. This approach should help the tracking of functionalized particles in cell labeling and targeted therapy.
Detecting racial identification: The role of phenotypic prototypicality

Little is known about what cues are used to infer the racial identification of others and whether or not identification inferences are accurate. Three studies provide evidence that phenotypic prototypicality (PP), the degree to which an individual looks like a prototypical member of his or her racial group, shapes inferences about racial identification. Participants assumed that high PP Blacks were more racially identified than low PP Blacks. In addition to serving as an identification cue for observers, PP was related to self-perceptions, as Blacks and Latinos who were higher in PP were in fact more identified with their racial group than minorities who were lower in PP. Furthermore, unacquainted judges accurately detected Black and Latino targets' racial identification based on PP. The results are discussed in terms of their implications for intergroup relationships.
Prevention of Induced Atherosclerosis by Peroxidase

Hepatocatalase peroxidase, an active peroxidase-oxidase subunit isolated from beef-liver catalase, prevents cholesterol deposition and aortic atherosclerosis in cholesterol-fed rabbits and has no apparent toxicity or undesirable de effects. No allergic or immunological reactions have been observed. The participation of this enzymatic subunit in homeostatic control mechanisms and its potential pharmacological value in the control of human atherosclerosis are suggested.
Quantitative comparison of fuel soot formation rates in laminar diffusion flames

In order to separate fuel structure from temperature effects, sooting behavior of several gaseous and liquid fuels was studied in diffusion flames whose temperature was controlled by nitrogen dilution. Soot volume fraction was measured by laser scattering/extinction; velocity and residence time information were obtained by laser induced vaporization; temperature was measured in the soot-free region of the flame by thermocouples. The fuels tested were: butene, acetylene, butadienes and benzene. The results show that of all fuels tested, at a given adiabatic flame temperature, benzene has the highest soot formation rate per unit volume and mass flow rate of fuel; butadiene, butene and acetylene follow in decreasing order. This finding holds even if the comparison were made with respect to the (radiatively corrected measured average peak temperature in the control volume, instead of the calculated temperature. The measured soot formation rates are in agreement with early qualitative indications obtained exclusively by smoke height tests and with purely pyrolytic studies reported in the literature. These results are the first quantitative confirmation of the controlling role of pyrolysis in the soot formation process. Furthermore, for a given fuel, nitrogen dilution decreases the maximum conversion of fuel into soot and the soot formation rates. This effects is attributed to a prevailing temperature decrease which causes a decrease in the pyrolysis rate and, in turn, in the soot formation rate. In all flames the velocity field is confirmed to be buoyancy controlled; the velocity at a given height correlates with the square root of the height, regardless of level of dilution or burner outlet velocity.
Challenges to Antibiotic Activity in Tissue

The most important determinants of antibiotic efficacy in infectious sites are the pharmacokinetic profile of the drug, the biochemical characteristics of the local environment, and the susceptibility of the infecting microorganisms under local growth conditions. The role of these variables is fairly clear for extracellular infections but not for intracellular infections or tissues as a whole. Many agents, including the macrolides, azalides, lincosamides, and quinolones, are concentrated within cells--notably, phagocytic cells. The mechanisms and pharmacokinetics of accumulation as well as the subcellular localization of accumulated drug are poorly understood in most instances. High intracellular drug concentrations do not necessarily translate into potent anti-infective activity. Many drugs with high intracellular concentrations are weak bases that accumulate within acidic lysosomes, where their activity may be reduced; the site at which drug accumulation is greatest may differ from that at which the microbe is found; and slow rates of intracellular growth may lessen the susceptibility of microbes to a variety of agents. Nevertheless, some drugs display good antimicrobial activity within cells. Future studies must better identify the determinants of this activity and clarify the clinical utility of drugs that reach high intracellular levels.
Pathomorphologic effects of N-methyl-D-aspartate antagonists in the rat posterior ingulate/retrosplenial cerebral cortex: A review

This review discusses available information on the neurotoxicity of N-methyl-D-aspartate (NMDA) antagonists in the posterior cingulate/retrosplenial (PC/RS) cortex of rats. NMDA antagonists block the NMDA receptor, a central nervous system ionotropic glutamate receptor, and are neuroprotective since they reduce injury in animal models of ischemia. There is interest in the development and use of NMDA antagonists in treating human cerebrovascular diseases. However, with certain NMDA antagonists, dose-dependent vacuolization of neurons in the neuroanatomically localized PC/RS cortex occurs as a side effect in rats. NMDA antagonists that cause vacuolization also appear to induce heat shock protein expression and heightened glucose metabolism in the same cortical region. Electron microscopy has shown that after treatment with MK-801 (dizocilpine maleate), a prototypic noncompetitive NMDA antagonist, the onset of vacuolization is very rapid. Additional studies with MK-801 have indicated that susceptibility to vacuolization increases between 30 and 90 days of age. Histologic time course studies have demonstrated that as the dose of MK-801 is increased, some vacuolated neurons become necrotic. Necrotic neurons are readily evident by light microscopy in routine preparations. At a given dose of MK-801, neuronal necrosis is more extensive in female rats than male rats. Furthermore, necrosis increases along an anterior to posterior gradient within the susceptible PC/RS cortex. A number of compounds with varied central nervous system (CNS) pharmacologic activity (anticholinergics, GABAmimetics, antipsychotics, and general anesthetics) partially or completely prevent neuronal vacuolization. These data suggest a complex pathogenesis for NMDA antagonist-mediated neurotoxicity and indicate variables which require consideration when designing and interpreting studies with these compounds. Since recent reports have described failure of some NMDA antagonists to produce these side effects, the issues discussed in this review may or may not apply to all NMDA antagonists.
Patterns of gaze behavior during an eye-tracking measure of joint attention in typically developing children and children with autism spectrum disorder

Abstract This study evaluated whether diagnostic classifications or features of ASD were associated with individual differences in children's gaze pattern during an eye-tracking measure of joint attention. The sample included 21 children with ASD (mean age, 7.3 ± 1.5 years) and 24 typically developing children (mean age, 6.8 ± 1.6 years), matched on receptive language abilities. Results revealed no significant group differences on global measures of gaze allocation (total gaze time allocation). However, significant group differences emerged using a measure evaluating a microstructure of children's gaze (duration of first fixation). In addition, individual differences in children's gaze pattern were reliably predicted by parent report measures of children's social abilities. The majority of children in this sample (including all typically developing children and those children with ASD who scored lowest on the SRS Social Awareness subscale) showed significant modulation in eye-gaze between the two experimental conditions. In contrast, children with ASD who also scored the highest on the SRS Social Awareness subscale consistently failed to modulate their eye gaze in accordance with the experimental condition. This failure to flexibly modulate gaze in the context of a joint attention eye-tracking paradigm may reveal children's limited awareness of social cues that may further limit social learning.
Emotional inhibition and personality traits: a comparison of women with anorexia, bulimia, and normal controls.

Background. Clinical experience has suggested that women with eating disorders (ED) are prone to displace negative feelings about the self onto the body. This study sought to evaluate these clinical observations by examining emotional inhibition and personality traits in women with ED.Methods. Female inpatients and intensive outpatients diagnosed with anorexia nervosa (N = 14) or bulimia nervosa (N = 11) were compared to women without an ED (N = 31).Results. The results of the study indicate that participants with ED inhibit their expression of both positive and negative emotions, even after controlling for neuroticism. Women with ED also reported higher levels of hostility and neuroticism. In addition, participants with ED were less aware of their inner thoughts and feelings (private self-consciousness) and had a heightened awareness of the thoughts and expectations of others (public self-consciousness). Finally, women with bulimia nervosa reported higher levels of emotional inhibition, neuroticism, publ...
Starting vortex, separation bubbles and stall: a numerical study of laminar unsteady flow around an airfoil

The stalling characteristics of an airfoil in a laminar viscous incompressible fluid are investigated. The governing equations in terms of the vorticity and stream function are solved using an implicit finite-difference scheme and point successive relaxation procedure. The development of the impulsively started flow, the initial generation of circulation, and the behavior of the forces at large times are studied. Following the impulsive start, the lift is at first very large and then it rapidly drops. The subsequent growth of circulation and lift is associated with the starting vortex. After incipient separation, the lift increases owing to enlargement of the separation bubble and intensification of the flow rotation in it. The extension of this bubble beyond the trailing edge causes it to rupture and brings about the stalling characteristics of the airfoil. Subsequently, new bubbles are formed near the upper surface of the airfoil and are swept away. The behavior of the lift acting on the airfoil is explained in terms of the strength and sense of these bubbles.
The stereochemistry of the reaction of 2-norbornylmagnesium bromide with formaldehyde

Abstract Diastereomeric endo -2-norbornylmagnesium bromide and mixtures of endo - and exo -2-norbornylmagnesium bromide react stereospecifically with retention of configuration at the carbon-magnesium bond with formaldehyde to form the expected primary alcohol. This stereochemical result, which is comparable to that observed previously in electrophilic substitutions of stereoisomeric organomagnesium reagents, is observed even when 5 mole % ferric chloride is added. The stereospecificity observed both with and without added metal salts suggests that single electron transfer is not important in 1,2 addition of sec -alkylmagnesium reagents to simple aliphatic aldehydes.
In vitro spontaneous lymphoproliferation in patients with human T-cell lymphotropic virus type I–associated neurologic disease: predominant expansion of CD8+ T cells

Peripheral blood mononuclear cells (PBMCs) from patients with human T-cell lymphotropic virus type I (HTLV-I)–associated myelopathy/tropical spastic paraparesis (HAM/TSP) proliferate spontaneously in vitro. This spontaneous lymphoproliferation (SP) is one of the immunologic hallmarks of HAM/TSP and is considered to be an important factor related to the pathogenesis of HAM/TSP. However, the cell populations involved in this phenomenon have not yet been definitively identified. To address this issue, the study directly evaluated proliferating cell subsets in SP with a flow cytometric method using bromodeoxyuridine and Ki-67. Although both CD4+ and CD8+ T cells proliferated spontaneously, the percentage of proliferating CD8+ T cells was 2 to 5 times higher than that of CD4+ T cells. In addition, more than 40% of HTLV-I Tax11-19–specific CD8+T cells as detected by an HLA-A*0201/Tax11-19 tetramer proliferated in culture. In spite of this expansion of HTLV-I–specific CD8+ T cells, HTLV-I proviral load did not decrease. This finding will help elucidate the dynamics of in vivo virus-host immunologic interactions that permit the coexistence of high HTLV-I–specific CD8+ cytotoxic T-lymphocyte responses and high HTLV-I proviral load in HAM/TSP.
The nuclear pacemaker: Is renewed interest warranted

Abstract From 1973 through 1987, 155 radioisotope-powered “nuclear” pacemakers were implanted in 132 patients at the Newark Beth Israel Medical Center. The longevity of the first 15 devices, all of which were fixed-rate (VOO) pacemakers, was significantly better than that of 15 lithium-chemistry demand (VVI) pacemakers used as control devices (p = 0.0002). Of the entire cohort of 155 nuclear pacemakers, 136 were VVI devices and 19 were VOO units. The patients with VOO pacemakers needed reoperations more often than did those with VVI pacemakers, chiefly for mode change (p