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We present a new method to extract the beam shape incorporated in the pixelized map of CMB experiments. This method is based on the interplay of the amplitudes and phases of the signal and instrumental noise. By adding controlled white noise onto the map, the phases are perturbed in such a way that the beam shape manifests itself through the mean-squared value of the difference between original and perturbed phases. This method is useful in extracting preliminary antenna beam shape without time-consuming spherical harmonic computations.

We have demonstrated a record low 85 mV dec-1subthreshold slope (SS) at 300 K among the planar inversion-channel InGaAs metal-oxide-semiconductor field-effect transistors (MOSFETs). Our MOSFETs using in situ deposited Al2O3/Y2O3as a gate dielectric were fabricated with a self-aligned inversion-channel gate-first process. The temperature-dependent transfer characteristics showed a linear reduction of SS versus temperature, with the attainment of an SS of 22 mV dec-1at 77 K; the value is comparable to that of the state-of-the-art InGaAs FinFET. The slope factor of SS with temperature (m) is 1.33, which is lower than those reported in the planar InGaAs MOSFETs.

Abstract: The calibration of the in-flight antenna beam shape and possible beamdegradation is one of the most crucial tasks for the upcoming Planck mission. We examine several effects which could significantly influence the in-flight main beam calibration using planet transit: the problems of the variability of the Jupiter’s flux, the antenna temperature and passing of the planets through the main beam. We estimate these effects on the antenna beam shape calibration and calculate the limits on the main beam and far sidelobe measurements, using observations of Jupiter and Saturn. We also discuss possible effects of degradation of the mirror surfaces and specify corresponding parameters which can help us to determine these effects.

Heavy metal removal is mainly conducted by adjusting the wastewater pH to form metal hydroxide precipitates. However, in recent years, the xanthate process with a high metal removal efficiency, attracted attention due to its use of sorption/desorption of heavy metals from aqueous solutions. In this study, two kinds of agricultural xanthates, insoluble peanut‐shell xanthate (IPX) and insoluble starch xanthate (ISX), were used as sorbents to treat the copper‐containing wastewater (Cu concentration from 50 to 1,000 mg/L). The experimental results showed that the maximum Cu removal efficiency by IPX was 93.5 % in the case of high Cu concentrations, whereby 81.1 % of copper could rapidly be removed within one minute. Moreover, copper‐containing wastewater could also be treated by ISX over a wide range (50 to 1,000 mg/L) to a level that meets the Taiwan EPA's effluent regulations (3 mg/L) within 20 minutes. Whereas IPX had a maximum binding capacity for copper of 185 mg/g IPX, the capacity for ISX was 120 mg/g ISX. IPX is cheaper than ISX, and has the benefits of a rapid reaction and a high copper binding capacity, however, it exhibits a lower copper removal efficiency. A sequential IPX and ISX treatment (i.e., two‐stage xanthate processes) could therefore be an excellent alternative. The results obtained using the two‐stage xanthate process revealed an effective copper treatment. The effluent (Ce) was below 0.6 mg/L, compared to the influent (C0) of 1,001 mg/L at pH = 4 and a dilution rate of 0.6 h–1. Furthermore, the Cu‐ISX complex formed could meet the Taiwan TCLP regulations, and be classified as non‐hazardous waste. The xanthatilization of agricultural wastes offers a comprehensive strategy for solving both agricultural waste disposal and metal‐containing wastewater treatment problems.

Water-soluble oligo(ethylene glycolated) derivatives of two-photon absorptive diphenylaminofluorenocarbonyl-methano[60]fullerene, denoted as C60(>DPAF-EG6), were synthesized with their molecular self-assembly characteristics in H2O studied. The formation of nano- to submicron-sized spherical hollow vesicles with a shell width of 15−20 nm was observed by transmission electron microscopy (TEM) micrographs. This shell width fits approximately with the length of a disordered bilayer-like molecular packing of C60(>DPAF-EG6), arising from strong intermolecular hydrophobic interactions of fullerene cages. Photoinduced intramolecular charge separation followed by charge recombination on the nanosecond time scale, from the DPAF moiety to the C60 cage in the vesicle structure, was detected via transient spectroscopic measurements.

We have investigated the role of protein kinase C (PKC) and nuclear factor-κB (NF-κB) in cyclooxygenase-2 (COX-2) expression caused by Staphylococcus aureuslipoteichoic acid in RAW 264.7 macrophages. A phosphatidylcholine-phospholipase C (PC-PLQ inhibitor (D-609) and a phosphatidyl-inositol-phospholipase C (Pl-PLC) inhibitor (U-73122) attenuated lipoteichoic acid-induced COX-2 expression, while a phosphatidate phosphohydrolase inhibitor (propranolol) had no effect. Two PKC inhibitors (Go 6976 and Ro 31–8220) and the NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), also attenuated lipoteichoic acid-induced COX-2 expression. Lipoteichoic acid resulted in a decrease in PKC activity in the cytosol and an increase in PKC activity in membranes. The lipoteichoic acid-induced translocation of p65 NF-κB from the cytosol to the nucleus was inhibited by D-609, U-73122, Go 6976, Ro 31–8220, and PDTC., but not by propranolol. The results suggested that lipoteichoic acid might have activated PC-PLC and Pl-PLC to induce PKC activation, which in turn initiated NF-κB activation, and finally induced COX-2 expression in RAW 264.7 macrophages.

We have investigated the role of protein kinase C (PKC) and nuclear factor‐κB (NF‐κB) in cyclooxygenase‐2 (COX‐2) expression caused by Staphylococcus aureuslipoteichoic acid in RAW 264.7 macrophages. A phosphatidylcholine‐phospholipase C (PC‐PLQ inhibitor (D‐609) and a phosphatidyl‐inositol‐phospholipase C (Pl‐PLC) inhibitor (U‐73122) attenuated lipoteichoic acid‐induced COX‐2 expression, while a phosphatidate phosphohydrolase inhibitor (propranolol) had no effect. Two PKC inhibitors (Go 6976 and Ro 31–8220) and the NF‐κB inhibitor, pyrrolidine dithiocarbamate (PDTC), also attenuated lipoteichoic acid‐induced COX‐2 expression. Lipoteichoic acid resulted in a decrease in PKC activity in the cytosol and an increase in PKC activity in membranes. The lipoteichoic acid‐induced translocation of p65 NF‐κB from the cytosol to the nucleus was inhibited by D‐609, U‐73122, Go 6976, Ro 31–8220, and PDTC., but not by propranolol. The results suggested that lipoteichoic acid might have activated PC‐PLC and Pl‐PLC to induce PKC activation, which in turn initiated NF‐κB activation, and finally induced COX‐2 expression in RAW 264.7 macrophages.

Using small angle neutron scattering (SANS) and small angle X-ray scattering (SAXS), we have studied aqueous mixtures of fullerene-based ionomers, C60[(CH2)4SO3Na]6 (FC4S), and sodium dodecyl sulfate (SDS). With the contrast variation provided by SAXS and a selected deuteration of SDS for SANS, we have identified the formation of complex aggregates of FC4S and SDS. The aggregation structure of the complex obtained is similar to that for pure FC4S aggregates and is stable to the SDS concentration in the mixtures studied. Combining the contrast data sets of small angle scattering, we have obtained detailed aggregation information, including aggregation number, shape, size, and fractional ionization for the FC4S/SDS complex aggregates. It is found that the globular-like complex aggregate, with a radius of gyration of 20 Å, consists of five FC4S and two SDS, in an average.

The promutagenic etheno DNA adducts have been detected in tissue DNA of rodents and humans from various exogenous and endogenous sources. While other etheno DNA adducts have been detected and quantified by isotope dilution gas chromatography/negative ion chemical ionization/mass spectrometry (GC/NICI/MS), similar analysis for 3,N⁴-ethenocytosine (εCyt) has not been available. In this report, a GC/NICI/MS assay was developed for detection and quantification of εCyt in DNA and in human urine samples. The stable isotope of εCyt with 7 mass units higher than the normal εCyt was synthesized and used as internal standard of the assay. The adduct-enriched fraction of DNA hydrolysate was derivatized with pentafluorobenzyl bromide before GC/NICI/MS analysis with selective ion monitoring at [M − 181]^- fragments of pentafluorobenzylated εCyt and its isotope analogue. One femtogram (S/N > 40) of pentafluorobenzylated εCyt was detected when injected on column with selective ion monitoring mode. The limit of quantification for the entire assay was 7.4 fmol of εCyt, which was approximately one thousand times lower than that of the HPLC/fluorescence assay for the nucleoside 3,N⁴-etheno-2‘-deoxycytidine in DNA. Analysis of chloroacetaldehyde-treated calf thymus DNA by both GC/NICI/MS and HPLC/fluorescence methods provided similar adduct levels and thus verified the assay. This GC/NICI/MS method was used for analysis of εCyt in two smokers' urine samples and the average level of εCyt was 101 ± 17 pg/mL/g of creatinine. Thus, quantification of εCyt in DNA and in urine by this highly specific and ultrasensitive isotope dilution GC/NICI/MS assay may facilitate research on the role of εCyt in carcinogenesis and in cancer development.

Synaptic inhibition in the thalamus plays critical roles in sensory processing and thalamocortical rhythm generation. To determine kinetic, pharmacological, and structural properties of thalamic γ-aminobutyric acid type A (GABAA) receptors, we used patch-clamp techniques and single-cell reverse transcriptase polymerase chain reaction (RT-PCR) in neurons from two principal rat thalamic nuclei—the reticular nucleus (nRt) and the ventrobasal (VB) complex. Single-channel recordings identified GABAAchannels with densities threefold higher in VB than nRt neurons, and with mean open time fourfold longer for nRt than VB [14.6 ± 2.5 vs. 3.8 ± 0.7 (SE) ms, respectively]. GABAAreceptors in nRt and VB cells were pharmacologically distinct. Zn2+(100 μM) reduced GABAAchannel activity in VB and nRt by 84 and 24%, respectively. Clonazepam (100 nM) increased inhibitory postsynaptic current (IPSC) decay time constants in nRt (from 44.3 to 77.9 ms, P< 0.01) but not in VB. Single-cell RT-PCR revealed subunit heterogeneity between nRt and VB cells. VB neurons expressed α1–α3, α5, β1–3, γ2–3, and δ, while nRt cells expressed α3, α5, γ2–3, and δ. Both cell types expressed more subunits than needed for a single receptor type, suggesting the possibility of GABAAreceptor heterogeneity within individual thalamic neurons. β subunits were not detected in nRt cells, which is consistent with very low levels reported in previous in situ hybridization studies but inconsistent with the expected dependence of functional GABAAreceptors on β subunits. Different single-channel open times likely underlie distinct IPSC decay time constants in VB and nRt cells. While we can make no conclusion regarding β subunits, our findings do support α subunits, possibly α1 versus α3, as structural determinants of channel deactivation kinetics and clonazepam sensitivity. As the γ2 and δ subunits previously implicated in Zn2+sensitivity are both expressed in each cell type, the observed differential Zn2+actions at VB versus nRt GABAAreceptors may involve other subunit differences.

We have synthesized fullerene derivatives, C60[CO(CH2)5O(CH2)4SO3Na]6 (FC10S), which consists of a C60 cage covalently bonded with six sulfonated arms for a high water solubility. We study the aggregation structures of the novel C60-derivatives in 0.1 M NaCl aqueous solutions by small angle X-ray scattering (SAXS). In the concentration range studied, 0.5 wt% to 2 wt %, the rod-like structure of FC10S aggregates has a radius of 20 Å and a rod-length about 150 Å at 25°C, and the aggregation structure is insensitive to the concentration change. The aggregates, however, grow in length as the temperature increases, while the radius increases slightly with increasing temperature.

Optical absorption studies on aqueous solutions of C60(C4H8SO3Na)n (n = 4-6) revealed deviation from the Beer-Lambert law in the 250-350 nm region, which is assigned to the formation of solute aggregates at concentrations higher than 1 × 10-3 mol dm-3. Dynamic light scattering experiments showed aggregates with an average size of ∼100 nm. The solute has a broad weak fluorescence emission (ϕf = 1.8 × 10-3) in the 450-650 nm region, which remained independent of solute concentration. The broad transient absorption band in the 450-900 nm region (ε660 = 2170 dm3 mol-1 cm-1), which formed immediately on laser flash photolysis (λex = 355 nm, 35 ps), is assigned to singlet-singlet transition. It decays to a triplet excited state whose absorption is observed to depend strongly on solute concentration. In dilute solutions, an absorption band with λmax = 590 nm is seen, and at high solute concentration a broad absorption in the 500-900 nm region is observed. The eaq- reacts with the solute with a bimolecular rate constant of 1.7 × 108 dm3 mol-1 s-1 and forms weak broad absorption bands at 440, 540, 620, 870, 940, and 1020 nm. Isopropanol radicals also react with the solute with a bimolecular rate constant of 2.3 × 108 dm3 mol-1 s-1 with the formation of a transient optical absorption spectrum similar to that observed on reaction with eaq- and assigned to a solute radical anion. The •H and -OH radicals react with bimolecular rate constants of 3.2 × 109 and 4.4 × 109 dm3 mol-1 s-1, respectively, and form transient absorption bands at 440, 510, and 660 nm. Based on electron transfer studies with suitable electron donor/acceptor substrates, the ranges of the reduction and oxidation potentials of the solute an estimated.

Exocyclic DNA adducts have been reported to derive from various exogenous as well as endogenous sources, such as lipid peroxidation. Among them, 1,N⁶-ethenoadenine (εAde) has previously been detected in tissue DNA of untreated rodents and humans by an immunoaffinity/³²P-postlabeling method. This study reports detection and quantification of the endogenous εAde adduct in the same human placental DNA by three independent assays, namely, GC/MS, LC/MS, and HPLC/fluorescence. Using a recently reported gas chromatography/negative ion chemical ionization/mass spectrometry (GC/NICI/MS) method [Chen, H.-J. C., et al. (1998) Chem. Res. Toxicol. 11, 1474], the level of εAde in human placental DNA from a commercial source was found to be 2.3 adducts per 10⁶ Ade bases. To confirm these findings, a liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI/MS/MS) method was developed for εdAdo. With this LC/MS assay, εdAdo was detected at the level of 2.5 adducts per 10⁶ dAdo nucleosides in the same human placental DNA. The stable isotopes of εAde and εdAdo were added as internal standards in both GC/MS and LC/ESI/MS/MS assays, respectively, and thus provided high specificity, reproducibility, and accurate quantification. The relatively high levels of εAde in this human placental DNA detected by mass spectrometry were further verified by HPLC/fluorescence analysis. The GC/MS method was validated by the HPLC/fluorescence assay using calf thymus DNA treated with chloroacetaldehyde or by the LC/MS method with 2,3-epoxy-4-hydroxynonanal-modified calf thymus DNA. The εAde level in human placental DNA freshly isolated in the presence of an antioxidant was similar to that in DNA from the commercial source. Since εAde is a potential mutagenic lesion, analysis of εAde by the specific and sensitive GC/NICI/MS method may provide a useful biomarker in cancer risk assessment.

Water solutions of starlike hexaanionic fullerene derivatives, C60[(CH2)4SO3Na]6 (star-ionomer) consisting of a C60 cage covalently bonded with six ionic sulfonate arms, were studied using small-angle neutron scattering (SANS) and small-angle X-ray scattering (SAXS). Nearly monodisperse aggregates of the novel star-ionomers were observed in the solutions of concentrations from 4% down to 0.5%. The structure of the spherical-like aggregates bears high similarity in different concentrations studied. Information regarding the aggregation number, hydration number, size, and shape of the aggregates was obtained from a combined analysis of the SANS and SAXS data.

Antioxidants attenuate noncholinergic airway constriction. To further investigate the relationship between tachykinin‐mediated airway constriction and oxygen radicals, we explored citric acid‐induced bronchial constriction in 48 young Hartley strain guinea‐pigs, divided into six groups: control; citric acid; hexa(sulphobutyl)fullerenes+citric acid; hexa(sulphobutyl)fullerenes+phosphoramidon+citric acid; dimethylthiourea (DMTU)+citric acid; and DMTU+phosphoramidon+citric acid. Hexa(sulphobutyl)fullerenes and DMTU are scavengers of oxygen radicals while phosphoramidon is an inhibitor of the major degradation enzyme for tachykinins.Animals were anaesthetized, paralyzed, and artificially ventilated. Each animal was given 50 breaths of 4 ml saline or citric acid aerosol. We measured dynamic respiratory compliance (Crs), forced expiratory volume in 0.1 (FEV0.1), and maximal expiratory flow at 30% total lung capacity (V[dot above]max30) to evaluate the degree of airway constriction.Citric acid, but not saline, aerosol inhalation caused marked decreases in Crs, FEV0.1and V[dot above]max30, indicating marked airway constriction. This constriction was significantly attenuated by either hexa(sulphobutyl)fullerenes or by DMTU. In addition, phosphoramidon significantly reversed the attenuating action of hexa(sulphobutyl)fullerenes, but not that of DMTU.Citric acid aerosol inhalation caused increases in both lucigenin‐ and t‐butyl hydroperoxide‐initiated chemiluminescence counts, indicating citric acid‐induced increase in oxygen radicals and decrease in antioxidants in bronchoalveolar lavage fluid. These alterations were significantly suppressed by either hexa(sulphobutyl)fullerenes or DMTU.An elastase inhibitor eglin‐c also significantly attenuated citric acid‐induced airway constriction, indicating the contributing role of elastase in this type of constriction.We conclude that both oxygen radicals and elastase play an important role in tachykinin‐mediated, citric acid‐induced airway constriction.

The assembly of 6-12 subunits of Ca(2+)/calmodulin-dependent kinase II (CaM kinase II) into holoenzymes is an important structural feature of the enzyme and its postulated role as a molecular detector of Ca(2+) oscillations. Using single cell reverse transcriptase-polymerase chain reaction, we show that alpha- and beta-CaM kinase II mRNAs are simultaneously present in the majority of hippocampal neurons examined and that co-assembly of their protein products into heteromers is therefore possible. The subunit composition of CaM kinase II holoenzymes was analyzed by immunoprecipitation with subunit-specific monoclonal antibodies. Rat forebrain CaM kinase II consists of heteromers composed of alpha and beta subunits at a ratio of 2:1 and homomers composed of only alpha subunits. We examined the functional effect of the heteromeric assembly by analyzing the calmodulin dependence of autophosphorylation. Recombinant homomers of alpha- or beta-CaM kinase II, as well as of alternatively spliced beta isoforms, have distinct calmodulin dependences for autophosphorylation based on differences in their calmodulin affinities. Half-maximal autophosphorylation of alpha is achieved at 130 nM calmodulin, while that for beta occurs at 15 nM calmodulin. In CaM kinase II isolated from rat forebrain, however, the calmodulin dependence for autophosphorylation of the beta subunits is shifted toward that of alpha homomers. This suggests that Thr(287) in beta subunits is phosphorylated by alpha subunits present in the same holoenzyme. Once autophosphorylated, beta-CaM kinase II traps calmodulin by reducing the rate of calmodulin dissociation.

We have examined the ability of a water-soluble derivative of fullerene C60, C60(OH)18, to induce alterations in rat liver microsomes during photosensitization. When it was exposed to UV (330-370 nm), it induced significant membrane damage in terms of (i) lipid peroxidation as assayed by various products and (ii) damage to proteins as assessed by protein carbonyls and loss of the membrane-bound enzymes. The damage induced was both time and concentration-dependent and seems to be predominantly due to radicals and to a lesser extent singlet oxygen.

Following an examination of the design constraints for the formulation of good organic conductors and a brief review of the synthesis of heterocyclic selenium π-donors such as TMTSF and the zero pressure organic superconductor (TMTSF)2ClO4, the preparation and characterization of five new π-donors is outlined. These new π-donors are dithiophenotetrathiafulvalene, (DTTTF), dithiophenotetraselenafulvalene (DTTSF), dibenzotetraselenafulvalene (DBTSF), dibenzotetratellurafulvalene (DBTTeF), and benzotrisselenophene (BTS).

The role of polyhydroxylated C60(fullerenol), a novel free-radical trapper, in prevention of hydrogen peroxide- and cumene hydroperoxide-elicited damage was studied in hippocampal slices from the rat in-vitro. The interactions of polyhydroxylated C60, adenosine and 6,7-dinitroquinoxaline-2,3-dione (DNQX) were also compared.Hydrogen peroxide (0.006–0.02%) and cumene hydroperoxide (0.5–1.0 mm) both reversibly reduced the amplitudes of CA1-evoked population spikes in the hippocampal slices. Deferoxamine (1 mm) had little effect on the population spikes. Deferoxamine (1 mm) significantly prevented the hydrogen peroxide (0006%)-elicited inhibition of the population spikes. Polyhydroxylated C60(01 mm) significantly prevented hydrogen peroxide- or cumene hydroperoxide-elicited reduction of the population spikes and also prevented the effects of hydrogen peroxide and cumene hydroperoxide on paired-pulse facilitation in the hippocampal slice. Adenosine reduced the amplitude of population spikes and promoted paired-pulse facilitation in the CA1 region of the hippocampus. Polyhydroxylated C60did not alter either of the effects of adenosine on the population spikes. DNQX reduced the amplitude of the population spikes in the CA1 region but did not affect the ratio of paired-pulse facilitation. Fullerenol did not alter either effect of DNQX on the population spikes.These results suggested that polyhydroxylated C60prevented hydrogen peroxide- and cumene hydroperoxide-elicited damage in the hippocampus slices. These effects might be associated with the free-radical scavenging activity of polyhydroxylated C60.

Several N-acylglucosamine derivatives of sialyl Lewis X (1−3) were prepared using a combined chemical enzymatic approach and evaluated as an inhibitor of E-selectin-mediated cellular adhesion. Compounds with aromatic functionality, 1 and 2, were found to be 3−10 times more potent than the N-acetyl derivative (14) in an ELISA E-selectin cell adhesion assay. Conformational analysis with NMR indicated that the sialyl Lewis x domain of 1 retained the conformation of the N-acetyl derivative (14) despite the presence of the N-naphthamido group. The dramatic order of magnitude increase in potency of these monovalent structures can be utilized to design more potent selectin-based cell adhesion inhibitors.

Both hexakis(dimethylamino)benzene (HDMAB) and 1,3,5-tris(diisopropylamino)benzene (TDIAB) were synthesized by improved procedures. In contrast to the irreversibility of electron oxidations of many triaminobenzene derivatives, we demonstrate that, by substituting three hindered diisopropylamino groups on benzene, stable monocationic radicals can be obtained. In the case of HDMAB its cationic radical can be stabilized in a strong acid medium. The observed bulk spin densities of 0.18-0.23 spins ½ per donor molecule in TDIAB-PF6 and HDMAB-PF6 solids are significant comparing to the diamagnetic properties normally obtained in solids of simple cationic salts of planar organic donor molecules. The results imply that a small degree of molecular spin separation due to the steric effect can readily increase sharply the paramagnetic spin density of solids.

We report the feasibility of x-ray scattering studies of freely suspended strands of discotic liquid crystals of triphenylene hexa-n-dodecanoate (HATH) and of hexa-alcoxy derivatives of triphenylene (HET11). With use of a pin and cup configuration, we are able to grow strands, which are stable for days, of diameter > 50 μm with a few single crystal domains. In HATH, as a function of increasing temperature, the system exhibits two liquid crystal columnar phases labeled Dl and D2. In the columnar phases, the molecules segregate into infinite liquid columns arranged in two-dimensional lattices. We find that the quasi-two-dimensional columnar D2-D1 structural phase transition from hexagonal to centered rectangular (herringbone) is associated with a small lattice distortion consistent with a close-packed model with only the core of the molecule tilted in the Dl phase. By carrying out longitudinal (parallel to column axis) diffuse scattering scans in HATH and a series of both small core discotics: benzene-hexa-n-alkanote (BH8), and large core discotics: hexa-alcoxy derivatives of triphenylene (HET11), we are able to unambiguously distinguish that part of the scattering which is associated with intermolecular correlations of only the cores of discotic molecules. Rather surprisingly, we find that the tilt of the molecular core remains finite in the D2 phase. We propose that the tilted Dl to tilted D2 transition corresponds to an orientational order-disorder transition with the molecular tilt orientation ordered about the column axis in the Dl phase. In a simple model with no orientational short range order, the D2 phase may be thought of as rotationally uncorrelated columns of tilted molecules.

1 This study investigated the effects of increased antioxidants (administration of water-soluble fullerenol-1 and pre-exposure to chronic hypoxia) as well as an iron-chelating agent (deferoxamine) on exsanguination-induced noncholinergic airway constriction in guinea-pigs. 2 Fullerenol-1 usually did not cause significant alteration in respiratory function (lung volumes, dynamic respiratory compliance, maximal expiratory flow at 50% total lung capacity (V¨max50), and forced expiratory flow at 0.1 s (FEV0.1)) at low (200 μg kg⁻¹) or at high doses (2 mg kg⁻¹), except that it produced a slight bronchial constricting action (decreases in both V¨max50 and FEV0.1) at high doses (2 mg kg⁻¹) via intratracheal instillation. 3 Beginning 15 min after exsanguination, there was a marked temporal decrease in FEV0.1, indicating a gradual increase in airway constriction with time. 4 Administration of either fullerenol-1 or deferoxamine, or pre-exposure to chronic hypoxia significantly ameliorated the exsanguination-induced bronchoconstriction. The results provide evidence that oxygen radicals play an important role in exsanguination-induced airway constriction. 5 The significant effects of the increased antioxidants and deferoxamine, however, cannot be explained by the alteration in either tracheal neutral endopeptidase activity or lung tissue substance P level.

The role of polyhydroxylated C60(fullerenol), a novel free‐radical trapper, in prevention of hydrogen peroxide‐ and cumene hydroperoxide‐elicited damage was studied in hippocampal slices from the rat in‐vitro. The interactions of polyhydroxylated C60, adenosine and 6,7‐dinitroquinoxaline‐2,3‐dione (DNQX) were also compared.

The ultraviolet-visible absorption spectrum of C60(OH)18in water showed an absorption band with λmax= 215 nm and other characteristic absorption bands of C60are not observed. The singlet-singlet and triplet-triplet absorption bands are not observed in the 400–900 nm region. It has low reactivity with eaq−and formed an absorption band with λmax= 580 nm. The hydroxyl radicals react with a bimolecular rate constant of 2.4×109dm3mol−1s−1and showed an absorption band at 540 nm.

X-ray investigations were performed on 4-hexylphenyl 4-cyanobenzoyloxybenzoate (DB6CN) and on 4-heptyloxyphenyl 4-cyanobenzoyloxybenzoate (DB7OCN). For both compounds, the smectic A2 structure is observed. From the small angle meridional reflections, the angular distribution of the smectic units around the normal to the smectic layers and the longitudinal correlation length were studied. The orientational order parameter is calculated from the wide angle equatorial reflections. Based on the assumption of a layer structure with undulation in the liquid crystalline smectic A phase, the relationship between the dimensionless parameters χch/dL (correlation length/thickness of the smectic layer) and FWHM/2θ0 (full width at the half maximum/maximum point of the scattering peak) is simulated.

Gene therapy may be of benefit in human immunodeficiency virus type 1 (HIV-1)-infected individuals by virtue of its ability to inhibit virus replication and prevent viral gene expression. It is not known whether anti-HIV-1 gene therapy strategies based on antisense or transdominant HIV-1 mutant proteins can inhibit the replication and expression of clinical HIV-1 isolates in primary CD4+ T lymphocytes. We therefore transduced CD4+ T lymphocytes from uninfected individuals with retroviral vectors expressing either HIV-1-specific antisense-TAR or antisense-Tat/Rev RNA, transdominant HIV-1 Rev protein, and a combination of antisense-TAR and transdominant Rev. The engineered CD4+ T lymphocytes were then infected with four different clinical HIV-1 isolates. We found that replication of all HIV-1 isolates was inhibited by all the anti-HIV vectors tested. Greater inhibition of HIV-1 was observed with transdominant Rev than with antisense RNA. We hereby demonstrated effective protection by antisense RNA or transdominant mutant proteins against HIV-1 infection in primary CD4+ T lymphocytes using clinical HIV-1 isolates, and this represents an essential step toward clinical anti-HIV-1 gene therapy.

There is increasing evidence that cell cycle transit is potentially lethal, with survival depending on the activation of metabolic pathways which block apoptosis. However, the identities of those pathways coupling cell cycle transit to survival remain undefined. Here we show that the eukaryotic translation initiation factor 4E (eIF4E) can mediate both proliferative and survival signaling. Overexpression of eIF4E completely substituted for serum or individual growth factors in preserving the viability of established NIH 3T3 fibroblasts. An eIF4E mutant (Ser-53 changed to Ala) defective in mediating its growth-factor-regulated functions was also defective in its survival signaling. Survival signaling by enforced expression of eIF4E did not result from autocrine release of survival factors, nor did it lead to increased expression of the apoptosis antagonists Bcl-2 and Bcl-XL. In addition, the execution apparatus of the apoptotic response in eIF4E-overexpressing cells was found to be intact. Increased expression of eIF4E was sufficient to inhibit apoptosis in serum-restricted primary fibroblasts with enforced expression of Myc. In contrast, activation of Ha-Ras, which is required for eIF4E proliferative signaling, did not suppress Myc-induced apoptosis. These data suggest that the eIF4E-activated pathways leading to survival and cell cycle progression are distinct. This dual signaling of proliferation and survival might be the basis for the potency of eIF4E as an inducer of neoplastic transformation.

Tetramethyltetraselenafulvalene (TMTSF) and hexamethylenetetraselenafulvalene (HMTSF) can be conveniently synthesized using dimethyl phosgene iminium chloride as a starting material. The method and detailed experimental conditions are described.

The appearance of drug-resistant strains of viral pathogens is a major difficulty confounding current efforts to block viral infections. The identification and analysis of mutations responsible for drug resistance can provide important clues helpful in understanding the mechanisms of resistance and in the eventual development of better therapies. We have used a direct screening method to scan libraries of mutagenized genes encoding the reverse transcriptase of human immunodeficiency virus type 1, and have recovered a variant enzyme that is resistant to the chain-terminator inhibitor 2',3'-dideoxyguanosine triphosphate. The single substitution mutation in this variant conferred broad crossresistance to a variety of other antiviral compounds currently in clinical trials. Virus carrying the mutation was fully infectious in cultured human lymphocytes. The replication of the mutant virus was highly resistant to phosphonoformic acid but did not show increased resistance to the prodrug dideoxyguanosine.