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The discovery of PIPE-359, a brain-penetrant and selective antagonist of the muscarinic acetylcholine receptor subtype 1 is described. Starting from a literature-reported M1 antagonist, linker replacement and structure-activity relationship investigations of the eastern 1-(pyridinyl)piperazine led to the identification of a novel, potent, and selective antagonist with good MDCKII-MDR1 permeability. Continued semi-iterative positional scanning facilitated improvements in the metabolic and hERG profiles, which ultimately delivered PIPE-359. This advanced drug candidate exhibited robust efficacy in mouse myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalitis (EAE), a preclinical model for multiple sclerosis.

Background Whether bisphenol A (BPA) exposure is a contributing factor to benign prostatic hyperplasia (BPH) remains unclear. This study evaluated the association between chronic BPA exposure and BPH risk, and explored whether this association was modified by alcohol drinking. Methods This study included a total of 650 BPH cases and 650 controls recruited from the same hospital in Hong Kong during 2011-2016. Chronic BPA exposure level was estimated by a validated cumulative BPA exposure index (CBPAI). We performed unconditional logistic regression model to examine the association of BPH risk with potential sources of BPA exposure via oral intake and CBPAI. We further tested the interactions between CBPAI and alcohol consumption habits on BPH risk. Results A positive exposure-response relationship was observed between CBPAI and BPH risk. Frequent BPA exposure via oral intake of foods heated in a plastic box/bag (odds ratio [OR] = 3.52, 95% confidence interval [CI]: 1.51-8.22), cooling water in a plastic bottle (OR = 2.65, 95% CI: 1.33-5.27), or using a plastic cup to contain hot water (OR = 4.14, 95% CI: 1.02-16.89), was significantly associated with increased BPH risk. Compared with nonalcohol drinkers, alcohol drinkers was insignificantly associated with BPH risk (OR = 1.10, 95% CI: 0.77-1.57), but it demonstrated a more remarkable positive gradient between CBPAI exposure and BPH risk among alcohol drinkers, indicating an additive interaction between CBPAI and alcohol on BPH risk (synergy index = 4.24, 95% CI: 1.21-14.94). Conclusions Chronic oral BPA exposure increased BPH risk with a positive exposure-response relationship among Hong Kong Chinese, and alcohol drinking amplified the effect of BPA on BPH. Hence, minimizations of containing food or water/beverage in plastic containers and drinking alcohol are recommended in the community to mitigate BPH risk. Future larger and designated studies are warranted.

Thermal desorption profiles were modelled based on SIMS measurements of implantation profiles and using the multi-trap diffusion code TMAP7 [G.R. Longhurst, TMAP7: Tritium Migration Analysis Program, User Manual, Idaho National Laboratory, INEEL/EXT-04-02352 (2004)]. The thermal desorption profiles were the result of 500 eV/D + irradiations on single crystal tungsten at 300 and 500 K to fluences of 10 22 –10 24 D + /m 2 . SIMS depth profiling was performed after irradiation to obtain the distribution of trapped D within the top 60 nm of the surface. Thermal desorption spectroscopy (TDS) was performed subsequently to obtain desorption profiles and to extract the total trapped D inventory. The SIMS profiles were calibrated to give D concentrations. To account for the total trapped D inventory measured by TDS, SIMS depth distributions were used in the near-surface (surface to 30 nm), NRA measurements [V.Kh. Alimov, J. Roth, M. Mayer, J. Nucl. Mater. 337–339 (2005) 619] were used in the range 1–7 μm, and a linear drop in the D distribution was assumed in the intermediate sub-surface region (∼30 nm to 1 μm). Traps were assumed to be saturated so that the D distribution also represented the trap distribution. Three trap energies, 1.07 ± 0.03, 1.34 ± 0.03 and 2.1 ± 0.05 eV were required to model the 520, 640 and 900 K desorption peaks, respectively. The 1.34 and 1.07 eV traps correspond to trapping of a first and second D atom at a vacancy, respectively, while the 2.1 eV trap corresponds to atomic D trapping at a void. A fourth trap energy of 0.65 eV was used to fit the 400 K desorption peak observed by Quastel et al. [A.D. Quastel, J.W. Davis, A.A. Haasz, R.G. Macaulay-Newcombe, J. Nucl. Mater. 359 (2006) 8].

Experiments have been performed to evaluate the changes in surface structure and the resulting effects on the optical properties of stainless steel due to hydrogen ion irradiation. Stainless steel (SS) is a standard material used for in-vessel components, including the first mirrors (FMs), in some current generation fusion devices. Optical microscopy, interferometry, scanning electron microscopy (SEM) and ellipsometry were used to characterize the surfaces. Results are presented for the bombardment of SS mirrors with H 3 + ions having various fixed energies (0.3, 0.65, and 1.5 keV/H+), with ion flux densities of (0.5–2) × 1020 H+/m2s and fluences of ∼2.2 × 1024 H+/m2. Variation of the ion energy at a constant fluence had a considerable effect on the damage structure that forms on the SS mirror surfaces. Possible mechanisms for the ion energy effect on the surface are discussed and a model of the damaged surface layer is proposed.

Background and objectives: This preliminary laboratory-based study looks at the paracrine release from human skin cells subject to sublethal Q-switched Nd:YAG 532 nm laser irradiation. Study design/Materials and methods: Human dermal fibroblast and keratinocyte cultures were exposed to sublethal energy using the Nd:YAG 532 nm laser. Altered gene expression was then screened using RT-PCR for a range of paracrine factors known to affect melanogenesis, basic fibroblast growth factor (b-FGF), hepatocyte growth factor (HGF), stem cell factor (SCF), melanocyte stimulating hormone (MSH), endothelin-1 (ET-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and protease-activated receptor-2 (PAR-2). Enzyme-linked immunosorbent assay (ELISA) was used to confirm protein production. Conditioned medium was used to assess altered melanogenesis in a melanoma cell line. Results: Fibroblasts exposed to sublethal radiation showed upregulation of b-FGF, HGF and SCF. This contrasts with keratinocytes which showed upregulation of IL-6. Elevated protein levels of b-FGF and SCF were confirmed by ELISA assay. Conditioned fibroblast medium was shown to stimulate melanogenesis in a melanoma cell line. Conclusions: This preliminary laboratory study reports, for the first time, specific gene upregulation using the Q-switched Nd:YAG 532 nm laser.

The level of impurities in the background gas during 500 eV D + irradiation was found to influence D trapping in single crystal tungsten. Reduced D retention levels were observed for lower partial pressures of impurity gases during irradiation. D + irradiations created near-surface peaks in the C and O depth distributions; the peak magnitudes depended on the background gas impurity levels. It is proposed that the recoil implantation of carbon and oxygen impurities arriving at the surface created vacancies in tungsten, thereby increasing D trapping.

Surface roughening of polycrystalline stainless steel mirrors due to hydrogen bombardment was studied as a function of ion fluence and energy (1–4.3 × 10 24 H/m 2 , 300–1500 eV/H). A strong micro-relief (100 nm scale) on single grains and a strong variation of the erosion depth between different grains were observed by scanning electron microscopy (SEM). A broad variation of the in-grain micro-relief was found to be independent of impact energy. The sputtering yield (Y) depends on the grain orientation, varying by a factor of about 2 for all impact energies. The correlation between surface morphology and orientation of the single grains was investigated using electron back-scattering diffraction (EBSD). Grains with nearly (1 1 1) surface orientation do not show any significant in-grain micro-relief, although they have nearly the highest Y. For other orientations close to low indexed surfaces, e.g., (3 1 1), no correlation was found between Y and roughness.

In this study, we look at the cytotoxic effects of silver on keratinocytes and fibroblasts. We have assessed the viability of monolayer cultures using the MTT and BrdU assays. The composition of the culture medium and also the culture technique were modified to assess the effects of culture 'environment' on the susceptibility of the cells to the toxic action of silver. Further in vitro, experiments were performed using tissue culture models to allow cellular behavior in three dimensional planes which more closely simulated in vivo behavior. The silver source was both silver released from silver nitrate solution but also nanocrystalline silver released from a commercially available dressing. The results show that silver is highly toxic to both keratinocytes and fibroblasts in monolayer culture. When using optimized and individualized culture the fibroblasts appear to be more sensitive to silver than keratinocytes. However, when both cell types were grown in the same medium their viability was the same. Using tissue culture models again indicated an 'environmental effect' with decreased sensitivity of the cells to the cytotoxic effects of the silver. Nevertheless in these studies the toxic dose of skin cells ranging from 7 x 10(-4) to 55 x 10(-4)% was similar to that of bacteria. These results suggest that consideration of the cytotoxic effects of silver and silver-based products should be taken when deciding on dressings for specific wound care strategies. This is important when using keratinocyte culture, in situ, which is playing an increasing role in contemporary wound and burn care.

Deuterium retention in single crystal tungsten was measured as a function of implantation temperature (300–700 K), fluence (10 21 –10 25 D + /m 2 s) and impurity levels for 500 eV/D + implantation. Prior to implantation, specimens were annealed under vacuum at temperatures up to 2200 K with the intention of reducing the impurity and defect contents. Secondary ion mass spectrometry measurements showed that near-surface carbon and oxygen levels decreased after annealing at 1775 K, but increased after annealing at 2200 K, and also increased after D + implantation. Thermal desorption spectra indicated that D retention increased with increasing D + fluence (with an apparent trend to saturation for implantation at 300 K), and decreased with increasing implant temperature. The desorption peaked at T =600–900 K, depending on the implant fluence and temperature. There was little or no D retention for implantation at T >700 K. C and O impurities are affected by the D + irradiation and appear to influence the D trapping mechanism and the amount of D retained.

The retention of deuterium in single crystal tungsten has been measured as a function of the incident ion flux in the range of 1×10 17 –5×10 19 D + /m 2 s at 300 K. Incident D 3 + ions were implanted to fluences of 10 21 , 10 22 , and 10 23 D + /m 2 with ion energies (500 eV/D + ) below the threshold energy for elastic collision damage. Above 3×10 18 D + /m 2 s, little or no flux dependence is seen. However, a rapid decrease in retention is seen for incident fluxes below 10 18 D + /m 2 s at the 10 21 D + /m 2 fluence, suggesting a threshold value below which retention is strongly reduced. Flux dependence at the higher fluences show a smaller decrease in retention with decreasing flux. The observed results are consistent with trapping and trap evolution by cluster and cavity formation. The effect of specimen surface preparation has proved to be very significant, especially for the lower fluence.

The retention of deuterium in single crystal tungsten (SCW) has been measured at 300 and 500 K, as a function of incident ion fluence over the range 10 21 –10 24 D + / m 2 . Irradiation of SCW with 1.5 keV D 3 + ions at 300 K leads to saturation at a much lower incident fluence than seen in polycrystalline tungsten (PCW), but with the same levels of D retention at saturation, ≈5×10 20 D / m 2 . Implantations at 500 K reached saturation at a very low incident fluence, below 10 21 D + / m 2 , with the amount of D retained at saturation ≈1.5×10 20 D / m 2 . This level is 3–4 times lower than the saturation value for 300 K implantation of the same single crystal of tungsten. Deuterium depth profile analysis by secondary ion mass spectrometry (SIMS) shows D trapping primarily within the 500 eV D + ion implantation range for both 300 and 500 K profiles. SIMS also revealed that the depth profiles for oxygen and deuterium were similar. When the tungsten was annealed at 500 K for 1 h after implantation at 500 K, SIMS indicated that the deuterium retention decreased by an order of magnitude.

The effect of pre-implanted carbon on deuterium retention in tungsten was investigated using polycrystalline tungsten foils. Pre-implantation was performed with 1 keV C + ions to fluences of 10 21 C + /m 2 and 10 22 C + /m 2 at 300 and 500 K. Using this newly created W/C structure, a deuterium retention study with 1.5 keV D + 3 (500 eV/D + ) ions was performed as a function of incident D + fluence and implantation temperature. For 1 keV C + implantations to 10 21 C + /m 2 at 300 K followed by 1.5 keV D + 3 implantations to

A systematic study investigating the effect of ion-induced damage, due to prior ion implantation, on deuterium retention in tungsten has been performed. Implantations with 1.5 keV D 3 + ions (500 eV/D + ) to 10 23 D/m 2 at 500 K show a factor of 3–4 increase in retention for specimens previously exposed to a fluence of 10 24 D/m 2 and a factor of 6–7 increase for specimens previously exposed to a fluence of 3 × 10 24 D/m 2 over specimens exposed only to an incident fluence of 10 23 D/m 2 . However, implantations with 1.5 keV D 3 + (500 eV/D + ) ions to 10 23 D/m 2 at 500 K on specimens previously exposed to a fluence of 10 25 D/m 2 show no increase in retention. Implantations with 3 keV D 3 + ions (1 keV/D + ) at the above conditions give retention results which do not depend on prior implantation treatments; only a slight increase in retention values with cumulative fluence is observed. Possible mechanisms are suggested to explain the observed effects.

The retention of deuterium in polycrystalline W foils has been measured as a function of ion fluence and implantation temperature. At temperatures in the range 350–550 K, retention levels were found to be above the 300 K value. This retention enhancement is attributed to an increase in the D diffusion coefficient, which allows a greater diffusion depth. Furthermore, while retention at room temperature saturates as a function of fluence, at 500 K no saturation is observed. D(3He,4He)p nuclear reaction analysis measurements show that at room temperature most of the D is trapped in the near-surface region of the specimen, but significantly beyond the implantation range. At higher temperatures, much lower levels are observed in the near-surface, and diffusion through to the back of thin specimens is observed; the front and back surface D concentrations are similar. While the D retention in a proposed W alloy for ITER applications (W–1%La2O3) is similar to that measured in the pure W foils over most of the range of the experiments, two important differences are noted: a trend to saturation of the amount retained is observed at fluences >1024 D/m2 and 500 K, and the D concentration at the back of the W–1%La2O3 alloy is about 1% of that at the implanted surface.

Treatment of dilithium dialkyl compounds derived from dilithiation of 3,3‘-dimethyl-2,2‘-bipyridine and its trimethylsilylated compound with R‘2MCl2 afford axially asymmetric metal dialkyls R‘2M(LL) (R‘ = Me, LL = (CH2C5H3N)2, M = Si (2), Sn (3)) and R‘2M(L‘L‘) (R‘ = Me, L‘L‘ = (CHSiMe3C5H3N)2, M = Si (4), Ge (5), Sn (6); R‘ = Ph, M = Sn (7)), respectively. Compounds 5−7 can react further with W(CO)6 to form bimetallic complexes R‘2M(L‘L‘)W(CO)4 (R‘ = Me, M = Ge (8), Sn (9); R‘ = Ph, M = Sn (10)) via the coordination of the two pyridyl nitrogens. The variable-temperature 1H NMR spectra of 2−4 have been recorded to investigate the fluxional behavior due to the torsional motion along the C−C axis that joins the two pyridine groups. X-ray structures of compounds 4, 6, and 9 have been determined.

The fracture toughness K&, and crack propagation of four types of ultrahighmodulus polyethylene (UHMPE) fiber-reinforced composites were investigated under conventional testing conditions and using a scanning electron microscope. The value of Kk is found to depend on the nature of the matrix and interface and the volume fraction of the fibers. The machining method has no significant effect on K,. The fracture mechanisms of UHMPE fiber composites are discussed.

Metalation of 3,3‘-dimethyl-2,2‘-bipyridine and its trimethylsilyl derivatives (2-RCH2C5H3N)2 (R = H, SiMe3) using appropriate stoichiometries of BunLi/tmeda yields the corresponding mono- and dilithiated compounds. Deprotonation was found to occur selectively at the α-methyl carbon, as established by quenching the lithiated compounds with Me3SiCl or D2O and analyzing the products by NMR spectroscopy. The C2 molecular structure of the dilithium compound [{2-CH(SiMe3)C5H3N}2{Li(tmeda)}2] (2a) has been determined by X-ray structure analysis, which shows that each lithium atom is C,N-chelated by the α-carbon atom and the nitrogen atom of the other pyridine ring within the molecule. The Li−Cα and the Li−Npyridyl distances are 2.274(10) and 2.046(9) A, respectively, and the torsion angle between the pyridine rings is 50.7°. In the lithiation of the gem-bis-silylated derivative 2-CH(SiMe3)2C5H3N-C5H3NCH3, the anionic species 2-CH(SiMe3)2C5H3N-C5H3NCH2 undergoes a 1,6-silyl migration to form the α,α‘-bis-silyla...

Local translation of dendritic mRNAs plays an important role in neuronal development and synaptic plasticity. Although several hundred putative dendritic transcripts have been identified in the hippocampus, relatively few have been verified by in situ hybridization and thus remain uncharacterized. One such transcript encodes the protein neuronatin. Neuronatin has been shown to regulate calcium levels in non-neuronal cells such as pancreatic or embryonic stem cells, but its function in mature neurons remains unclear. Here we report that neuronatin is translated in hippocampal dendrites in response to blockade of action potentials and NMDA-receptor dependent synaptic transmission by TTX and APV. Our study also reveals that neuronatin can adjust dendritic calcium levels by regulating intracellular calcium storage. We propose that neuronatin may impact synaptic plasticity by modulating dendritic calcium levels during homeostatic plasticity, thereby potentially regulating neuronal excitability, receptor trafficking, and calcium dependent signaling.

Hepatosplenic candidiasis (HSC) in patients with acute leukemia poses management challenges because the therapeutic limitations of the present antifungal armamentarium may adversely impact on treatment outcomes of the underlying leukemia. We report a patient with acute myeloid leukemia who developed HSC during post-remission consolidation chemotherapy and was treated with a prolonged course of caspofungin followed by fluconazole. The stabilization of infection permitted further chemotherapy and autologous hematopoietic cell transplant (HCT) without breakthrough fungemia and further dissemination of candidiasis. The favorable outcome provides further evidence that with optimal treatment, the presence of stable or non-progressive HSC is not an absolute contraindication for HCT. The use of caspofungin in the primary treatment of HSC appears to be a promising approach. The favorable outcome seen in this case is encouraging, although further study on its efficacy is warranted.

Retinoic acid (RA) plays important roles in development by modulating gene transcription through nuclear receptor activation. Increasing evidence supports a role for RA and RA receptors (RARs) in synaptic plasticity in the brain. We have recently reported that RA mediates a type of homeostatic synaptic plasticity through activation of dendritic protein synthesis, a process that requires dendritically localized RARalpha and is independent of transcriptional regulation. The molecular basis of this translational regulation by RA/RARalpha signaling, however, is unknown. Here we show that RARalpha is actively exported from the nucleus. Cytoplasmic RARalpha acts as an RNA-binding protein that associates with a subset of mRNAs, including dendritically localized glutamate receptor 1 (GluR1) mRNA. This binding is mediated by the RARalpha carboxyl terminal F-domain and specific sequence motifs in the 5'UTR of the GluR1 mRNA. Moreover, RARalpha association with the GluR1 mRNA directly underlies the translational control of GluR1 by RA: RARalpha represses GluR1 translation, while RA binding to RARalpha reduces its association with the GluR1 mRNA and relieves translational repression. Taken together, our results demonstrate a ligand-gated translational regulation mechanism mediated by a non-genomic function of RA/RARalpha signaling.

This report is a summary of our investigations of D retention in various forms of tungsten: high purity polycrystalline W (PCW), polycrystalline W containing 1% La2O3, and two grades of single crystal W (SCW). The experiments have been primarily implantations followed by thermal desorption measurements. Nuclear reaction analysis and SIMS were used to measure the depth distributions near the surface. By using low energy ions (500 eV/D+), it has been possible to eliminate most if not all elastic collision defect creation, yet this has not reduced the trapping significantly. Comparing the results for the various forms of W has enabled us to assess the effects of grain boundaries, dislocations and impurities. Recent work has included a study of the effects of ion flux on deuterium retention in SCW. The conclusion drawn is that D is trapped in clusters or nano-bubbles, and that these traps grow with increasing fluence, particularly at higher temperatures. The large variations in the retention of D in W show that the processes controlling D trapping are many and complex. In order to form a more comprehensive picture, and eventually attempt to predict retention under fusion relevant conditions, modeling has been performed using TMAP4[1].

Since their introduction as improved agents for in vitro and in vivo cell tracking,34,56,79 the lipophilic membrane intercalating fluorochromes known as PKH dyes have been used to study a wide variety of cell types and biological processes. Originally developed by Horan and colleagues at Zynaxis Cell Science as part of a larger class of multifunctional drug delivery molecules known as Zyn-Linkers, this family of patented fluorescent dyes and cell labeling reagents became available in kit form for research use in 1989 and was purchased by Phanos Technologies in 1995. PKH dyes are therefore found in the literature under a variety of names, including Cell Linker dyes, Zyn-linkers, Zyn-linker® dyes, cell tracking dyes, and PKH dyes. A number of suppliers are also found in the literature, including Zynaxis Cell Science (which no longer sells these reagents), Sigma and Dainippon Pharmaceuticals Laboratory Products Division (both of which continue to distribute PKH kits for Phanos).

Abstract 3879 Tumor-specific metabolic changes could serve as new therapeutic targets. While much attention has been given to the metabolism of glucose in cancer cells and intervening therapies, relatively little attention has been given to fatty acids and fatty acid β-oxidation (FAO) in promoting cancer cell survival. Here, we reveal new findings implicating fatty acid metabolism in Chronic lymphocytic leukemia (CLL) and have developed a small molecule inhibitor of this pathway as a novel therapeutic approach to treat CLL. We have found that B cells isolated from CLL patients show increased levels of b-oxidation as compared to B cells isolated from PBMCs of healthy donor controls. NXT629, a small molecule inhibitor of the FAO pathway, dose-dependently reduced b-oxidation in CLL cells but did not reduce b-oxidation in B cells isolated from healthy volunteers. A negative control compound (NXT962) that has a similar chemical structure to NXT629, but does not significantly bind to the relevant target, did not inhibit FAO. NXT629 exerted dose-dependent cytotoxicity in CLL cells (CC50=10 mM, n=5 different patient samples) whereas NXT962 was inactive. Since the cellular microenvironment can protect CLL cells from spontaneous and drug-induced apoptosis, it is pivotal to evaluate novel drugs in this context. As expected, we found that macrophages protected CLL cells from spontaneous and fludarabine-induced apoptosis in vitro. However, NXT629 significantly reduced CLL cells viablity in the co-cultures. NXT629 (at 10 mM, n=2 different patient samples) induced apoptosis in 80% of cells after 7 days of co-culture in a setting where fludarabine was inactive. Though most CLL cells in the periphery are in a resting state, CLL cells proliferate in lymphoid organs. To mimic these conditions, we examined the activity of FAO inhibition on CLL cells that were induced to proliferate in vitro. To induce proliferation, CLL cells were cultured in media containing human interleukin (IL)-4, IL-10, and allogeneic T blasts. Labeling CLL cells with carboxyfluorescein succinimidyl ester, allowed us to monitor several rounds of induced CLL-cell division via flow cytometry, and within 5 days the CLL cells had expanded 3-fold. We found that addition of NXT629 to such cultures resulted in a dose-dependent reduction in the number of leukemia cells induced to undergo cell-division (IC50=3.7 mM, n=6), whereas the negative control compound showed no activity. Furthermore, when used in combination with dexamethasone (0.3 mM), NXT629 (3 mM) showed a significant decrease in the number of viable cells (38% +/−3%) over either dexamethasone (65% +/−12%) or NXT629 (74%+/−15%) alone. The additivity of FAO inhibition and dexamethasone in vitro suggests that a combination warrants further testing and might yield improved clinical responses. Overall, these results suggest that fatty acids promote primary CLL cell survival and proliferation, and that targeting the FAO pathway could be a new therapeutic approach to treating CLL. Disclosures: Messmer: Inception Sciences: Employment, Equity Ownership. Lorrain:Inception Sciences: Employment, Equity Ownership. Bravo:Inception Sciences: Employment, Equity Ownership. Stock:Inception Sciences: Employment, Equity Ownership. Bundey:Inception Sciences: Employment, Equity Ownership. Correa:Inception Sciences: Employment, Equity Ownership. Poon:Inception Sciences: Employment, Equity Ownership. Stebbins:Inception Sciencees: Employment, Equity Ownership. Cabrera:Inception Sciences: Employment, Equity Ownership. Chen:Inception Sciences: Employment, Equity Ownership. Jacintho:Inception Sciences: Employment, Equity Ownership. Spaner:Inception Sciences: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding. Prasit:Inception Sciences: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Lorrain:Inception Sciences: Employment, Equity Ownership.

Poly(ethylene terephthalate) films were irradiated by ultraviolet laser with a subsequent electrification by corona discharging. Surface potential and surface morphology of samples were measured and analyzed. A significant increase of surface potential resulted from the samples irradiated of about 15 pulses. From SEM pictures, melted ripple tips were observed on the film surface and some of them were fused together. This surface layer may probably enhance the surface potential of the samples. This result suggests the possibility of enhancing the charge storage capability of polymeric electret by altering their surface morphology.

Stokke has described a lysosomal cholesterol ester hydrolase (CEH) in human liver. To clarify the significance of this enzyme, we first modified Stokke's assay to enable CEH determination in hepatic needle biopsies. Studies established optimal pH of 4.6-5.2 and linearity of hydrolysis for at least 12 hours, using homogenates containing about 2 mg liver and radiolabeled cholesterol oleate as substrate. The assay was then applied to patients undergoing percutaneous needle biopsy. Hepatic CEH activity in alcoholic liver disease, obstructive jaundice and a variety of other hepatic disorders was not significantly different from that in histologically normal livers. In patients with acute hepatitis, however, mean CEH activity was more than 3-fold increased (P < 0.01). Values paralleled SGOT levels, returned to normal as hepatitis resolved, and were unrelated to serum cholesterol levels or to lecithin: cholesterol acyltransferase activity. In contrast to CEH, activity of acid phosphatase, a standard lysosomal ma...

Several effects of Intense laser pulses, Including ablation, desorptlon, and structural changes are correlated wlth electron transfer activation of glassy carbon (GC) electrodes. By use of ferri-/ferrocyanide, ascorbic acid, and dopamine as test systems, It was found that ablatlon of bulk GC Is a sufflcient but not necessary process for activation. I n addltion, no correiatlon was found between increases In background current and activation, and several arguments are made agalnst the promotlon of electron transfer by oxygen-contalning functlonai groups. Furthermore, adsorption of ascorbic acld and dopamine occurred wlth several pretreatment procedures but was unnecessary to achieve electron transfer activation. Fast electron transfer for ferri-Iferrocyanlde, dopamlne, and ascorblc acld is uncorrelated wlth background current, adsorption, ablation, surface oxygen content, and microscoplc surface area. The most llkely laser effects that promote electron transfer are desorptlon of impurities and formation or exposure of active regions on the GC surface.

Estimates of the contributions of the electrostatically correlated crystal field (ECCF) to the S ground-state splitting of Mn2+ are made based on an overlap model. It is shown that the ECCF contributes oppositely to the dominant contributions due to the relativistic crystal field and is a significant cancellation mechanism.

According to the work of Hecht, Varga, Lewis, and Boring [J. Chem. Phys. 70, 101 (1979)], the spectroscopic parameters of Np5+ are very different to those for the tri‐ and quadrivalent actinide ions. We have re‐examined the experimental data, and find that an alternative fit can be obtained with parameters close to those obtained for other ions.

Summary Spontaneous intraperitoneal bladder rupture in a 38 year old man with a spastic paraparesis since infancy is described. Delayed diagnosis resulted in peritoneal autodialysis so providing an opportunity for documentation of biochemical abnormalities. Surgery resulted in a successful outcome. The literature on this rare condition is outlined and difficulties in diagnosis are discussed. The diagnostic value of urea and electrolyte levels in ascitic fluid is emphasized.

By means of a sensitive competition assay, serum, urine, and CSF from patients with Huntington's disease (HD) and controls were tested for the presence of molecules capable of displacing radioactive kainic acid (KA) from rat brain receptors. No difference was found between HD and control samples. It is unlikely that systemic production of an endogenous toxin structurally related to KA occurs in HD.

The effects of hydrogen ion (H3+) bombardment on the optical properties of polycrystal stainless steel (SS) mirrors were investigated. Ellipsometry, profilometry, scanning electron microscopy, angle distribution of scattered light, and spectral reflectance were used to characterize the surfaces. Results for the bombardment of SS mirrors with ions of fixed energy (0.3, 0.65 and 1.5 keV/H), with ion flux density (0.5–2) · 1020 H/m2s up to fluences of (1.1–4.3) · 1024 H/m2 are presented. The data show that the surface roughness rises with both increasing ion energy and ion fluence, and that surface roughening leads to an increase of the scattered light with a corresponding decrease of reflectance at normal incidence. The thickness of the apparent layer, obtained by ellipsometry, was found to rise with increasing ion energy at fixed ion fluence and with increasing ion fluence at fixed ion energy. Possible mechanisms for the ion energy effect on the degradation rate of stainless steel mirrors and the origin of the apparent layer are discussed.

The scaling of the crystal field parameter in the energy level analysis of Carnall et al. for Np3+:LaCl3 and Np3+:LaBr3 is questioned.(AIP)