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Age-related macular degeneration (AMD) is a leading cause of blindness among the elderly. Canonical disease models suggest that defective interactions between complement factor H (CFH) and cell surface heparan sulfate (HS) result in increased alternative complement pathway activity, cytolytic damage, and tissue inflammation in the retina. Although these factors are thought to contribute to increased disease risk, multiple studies indicate that noncanonical mechanisms that result from defective CFH and HS interaction may contribute to the progression of AMD as well. A total of 60 ciliated sensory neurons in the nematode Caenorhabditis elegans detect chemical, olfactory, mechanical, and thermal cues in the environment. Here, we find that a C. elegans CFH homolog localizes on CEP mechanosensory neuron cilia where it has noncanonical roles in maintaining inversin/NPHP-2 within its namesake proximal compartment and preventing inversin/NPHP-2 accumulation in distal cilia compartments in aging adults. CFH localization and maintenance of inversin/NPHP-2 compartment integrity depend on the HS 3-O sulfotransferase HST-3.1 and the transmembrane proteoglycan syndecan/SDN-1. Defective inversin/NPHP-2 localization in mouse and human photoreceptors with CFH mutations indicates that these functions and interactions may be conserved in vertebrate sensory neurons, suggesting that previously unappreciated defects in cilia structure may contribute to the progressive photoreceptor dysfunction associated with CFH loss-of-function mutations in some AMD patients.

Natural products (NPs) are an important inspirational source for developing drugs and chemical probes. In 1999, the group of Ōmura reported the constitutional elucidation of zelkovamycin. Although largely unrecognized so far, this NP displays structural similarities as well as differences to the argyrin NP family, a class of peptidic NPs with promising anticancer activities and diverse mode‐of‐action at the molecular level. By a combination of structure elucidation experiments, the first total synthesis of zelkovamycin and bioassays, the zelkovamycin configuration was determined and its previously proposed molecular structure was revised. The full structure assignment proves zelkovamycin as an additional member of the argyrins with however unique OXPHOS inhibitory properties. Zelkovamycin may therefore not only serve as a new starting point for chemical inhibitors of the OXPHOS system, but also guide customized argyrin NP isolation and biosynthesis studies., Zelkovamycin is an argyrin natural product. By a combination of structural elucidation methodologies, total synthesis and bioassays, the exact molecular structure of zelkovamycin was assigned and revised and its OXHPOS inhibitory properties revealed.

Mutations in ATP13A2 cause Kufor-Rakeb syndrome (KRS), a juvenile form of Parkinson's disease (PD) with dementia. However, the mechanisms by which mutations in ATP13A2 cause KRS is not understood. The mutations lead to misfolding of the translated Atp13a2 protein and its premature degradation in the endoplasmic reticulum, never reaching the lysosome where the protein is thought to function. Atp13a2 is a P-type ATPase, a class of proteins that function in ion transport. Indeed, studies of human, mouse, and yeast Atp13a2 proteins suggest a possible involvement in regulation of heavy metal toxicity. Here we report on the cytoprotective function of Atp13a2 on HeLa cells and dopamine neurons of Caenorhabditis elegans (C. elegans). HeLa cells stably overexpressing V5- tagged Atp13a2Isoform-1 protein were more resistant to elevated manganese exposure and to starvation-induced cell death compared to cells not overexpressing the protein. Because PD is characterized by loss of dopamine neurons, we generated transgenic C. elegans expressing GFP-tagged human Atp13a2 protein in dopamine neurons. The transgenic animals exhibited higher resistance to dopamine neuron degeneration after acute exposure to manganese compared to nematodes that expressed GFP alone. The results suggest Atp13a2 Isoform-1 protein confers cytoprotection against toxic insults, including those that cause PD syndromes.

Electrical conductivity is a fundamental characteristic determining the performance of lithium-ion batteries. However, methods to measure the conductivity nondestructively have proven difficult. This is due to the presence of a metallic conductive current collector as well as dominating effect of the contact resistance between the film and the probe. In previous research we developed a micro-four-line probe [1] that can measure thin-film electrodes without removing the current collector. We found that the conductivity of even high-quality electrodes is not homogenous, and has variation on length scales much larger than the size of the active material particles. Even though the micro-four-line probe worked well, we continue to improve the design. The previous design was fabricated in a clean room on a rigid glass substrate. This limited the geometry of the sample and made adaptation to industrial use difficult. To address this problem, we switched to a flexible polymer substrate, as shown in the figure, which allows for increased sample size and potential low-cost manufacturing. In addition, changes were made to the computer-controlled probe holder and stage, again with an aim toward lowering cost and increasing usability. The stage is used to move the probe over the surface of the sample in order to produce a conductivity map. We will report conductivity results using the new probe for both anodes and cathodes, including the effect of cycling. Results will also be compared to related work on ionic conductivity of the same electrodes. The hope is that this probe technology can be adapted to manufacturing use as well as to assist other researchers in understanding limiting mechanisms in battery performance. [1] Lanterman et al., J. Electrochem. Soc. 162, A2145 (2015). Figure 1

Background Numerous epidemiological studies support an inverse association between serum bilirubin levels and the incidence of cardiovascular disease; however, the mechanism(s) by which bilirubin may protect against atherosclerosis is undefined. The goals of the present investigations were to assess the ability of bilirubin to prevent atherosclerotic plaque formation in low‐density lipoprotein receptor‐deficient ( Ldlr −/− ) mice and elucidate the molecular processes underlying this effect. Methods and Results Bilirubin, at physiological concentrations (≤20 μmol/L), dose‐dependently inhibits THP ‐1 monocyte migration across tumor necrosis factor α–activated human umbilical vein endothelial cell monolayers without altering leukocyte binding or cytokine production. A potent antioxidant, bilirubin effectively blocks the generation of cellular reactive oxygen species induced by the cross‐linking of endothelial vascular cell adhesion molecule 1 ( VCAM ‐1) or intercellular adhesion molecule 1 ( ICAM ‐1). These findings were validated by treating cells with blocking antibodies or with specific inhibitors of VCAM ‐1 and ICAM ‐1 signaling. When administered to Ldlr −/− mice on a Western diet, bilirubin (30 mg/kg intraperitoneally) prevents atherosclerotic plaque formation, but does not alter circulating cholesterol or chemokine levels. Aortic roots from bilirubin‐treated animals exhibit reduced lipid and collagen deposition, decreased infiltration of monocytes and lymphocytes, fewer smooth muscle cells, and diminished levels of chlorotyrosine and nitrotyrosine, without changes in VCAM ‐1 or ICAM ‐1 expression. Conclusions Bilirubin suppresses atherosclerotic plaque formation in Ldlr −/− mice by disrupting endothelial VCAM ‐1‐ and ICAM ‐1‐mediated leukocyte migration through the scavenging of reactive oxygen species signaling intermediaries. These findings suggest a potential mechanism for the apparent cardioprotective effects of bilirubin.

The deposition of one-dimensional objects (such as polymers) on a one-dimensional lattice with the presence of impurities is studied in order to find saturation conditions in what is known as jamming. Over a critical concentration of k-mers (polymers of length k), no further depositions are possible. Five different nematic (directional) depositions are considered: baseline, irreversible, configurational, loose-packing, and close-packing. Correspondingly, five jamming functions are found, and their dependencies on the length of the lattice, L, the concentration of impurities, p=M/L (where M is the number of one-dimensional impurities), and the length of the k-mer (k) are established. In parallel, numeric simulations are performed to compare with the theoretical results. The emphasis is on trimers (k=3) and p in the range [0.01,0.15], however other related cases are also considered and reported. Fil: Vogel, E.E.. Universidad de La Frontera; Chile. Center for the Development of Nanoscience and Nanotechnology; Chile Fil: Valdes, J. F.. Universidad de La Frontera; Chile Fil: Lebrecht, W.. Universidad de La Frontera; Chile Fil: Ramirez Pastor, Antonio Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Física Aplicada "Dr. Jorge Andrés Zgrablich". Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto de Física Aplicada "Dr. Jorge Andrés Zgrablich"; Argentina Fil: Centres, Paulo Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Física Aplicada "Dr. Jorge Andrés Zgrablich". Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto de Física Aplicada "Dr. Jorge Andrés Zgrablich"; Argentina

N-(Pyridin-2-yl) arylsulfonamides 1 and 2 (PF-915275) were identified as potent inhibitors of 11β-hydroxysteroid dehydrogenase type 1. A screen for bioactivation revealed that these compounds formed glutathione conjugates. This communication presents the results of a risk benefit analysis carried out to progress 2 (PF-915275) to a clinical study and the strategies used to eliminate reactive metabolites in this series of inhibitors. Based on the proposed mechanism of bioactivation and structure-activity relationships, design efforts led to N-(pyridin-2-yl) arylsulfonamides such as 18 and 20 that maintained potent 11β-hydroxysteroid dehydrogenase type 1 activity, showed exquisite pharmacokinetic profiles, and were negative in the reactive metabolite assay.

Background: Epidemiologic studies support an inverse association between serum bilirubin levels and the risk of cardiovascular disease. Monocyte infiltration into the vascular endothelium, a critical early step in atherosclerotic plaque formation, is mediated primarily by the adhesion molecules VCAM-1 and ICAM-1. We postulate that bilirubin, a potent antioxidant, inhibits plaque formation by preventing monocyte transendothelial migration through the scavenging of VCAM-1 and ICAM-1 reactive oxygen species (ROS) signaling intermediaries. Methods: The effect of physiological concentrations (≤ 1.2 mg/dL) of bilirubin on the migration of THP-1 monocytes across HUVEC monolayers activated with TNFα to express VCAM-1 and ICAM-1 was assessed by Boyden chamber assay. The influence of bilirubin on monocyte adhesion, cytokine production, and VCAM-1- and ICAM-1-mediated ROS production was quantified by fluorescence assay, RT-PCR, and time-lapse confocal microscopy, respectively. To evaluate the effect on plaque formation in vivo , LDLR -/- mice were fed a Western diet and administered i.p. bilirubin (30 mg/kg), vehicle, or sham for 8 weeks. Aortic roots were stained with Oil Red O (lipids), Sirius Red (collagen), α-smooth muscle actin (SMCs), chlorotyrosine and nitrotyrosine (oxidation), CD68 (macrophages), and for VCAM-1 and ICAM-1. Results: THP-1 migration across activated HUVEC monolayers is dose-dependently inhibited by bilirubin. Bilirubin did not alter monocyte binding or cytokine production by activated HUVEC, but effectively abolished cellular ROS production induced by crosslinking anti-VCAM-1 and anti-ICAM-1 antibodies. Bilirubin treatment markedly inhibited plaque formation in the aortic root of LDLR -/- mice, and was associated with significant reductions in plaque lipid and collagen deposition, SMC infiltration, oxidation, and macrophage infiltration, without altering VCAM-1 or ICAM-1 protein expression. Conclusion: Bilirubin prevents atherosclerotic plaque formation in LDLR -/- mice by disrupting endothelial VCAM-1- and ICAM-1-mediated monocyte migration through the scavenging of ROS signaling intermediaries. These findings suggest a potential mechanism for the purported cardioprotective effects of bilirubin.

There is a growing body of evidence that bilirubin, which is generated during the physiological breakdown of heme, exerts potent anti-inflammatory effects. Previous work by our group suggests that bilirubin is able to suppress inflammatory responses by preventing the migration of leukocytes into target tissues through disruption of vascular cell adhesion molecule-1 (VCAM-1)-dependent cell signaling. As VCAM-1 is an important mediator of tissue injury in the dextran sodium sulfate (DSS) murine model of inflammatory colitis, we examined whether bilirubin prevents colonic injury in DSS-treated mice. As anticipated, bilirubin-treated animals manifested significantly less colonic injury and reduced infiltration of inflammatory cells into colon tissues. We further observed that bilirubin administration was associated with a reduced number of eosinophils and monocytes in the small intestine, with a corresponding increase in peripheral blood eosinophilia, regardless of whether mice received DSS. These findings suggest that bilirubin impairs the normal migration of eosinophils into intestinal tissues, as supported by in vitro experiments showing that bilirubin blocks the VCAM-1-dependent movement of Jurkat cells across human endothelial cell monolayers. Taken together, our findings support that bilirubin ameliorates DSS-induced colitis and disrupts the physiological trafficking of leukocytes to the intestine by preventing transmigration across the vascular endothelium, potentially through the inhibition VCAM-1-mediated signaling. Our findings raise the possibility that bilirubin functions as an endogenous regulator of inflammatory responses.

N-(Pyridin-2-yl) arylsulfonamides are identified as inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1), an enzyme that catalyzes the reduction of the glucocorticoid cortisone to cortisol. Dysregulation of glucocorticoids has been implicated in the pathogenesis of diabetes and the metabolic syndrome. In this Letter, we present the development of an initial lead to an efficient ligand with improved physiochemical properties using a deletion strategy. This strategy allowed for further optimization of potency leading to the discovery of the clinical candidate PF-915275.

Analytical expressions for the total magnetic energy of two characteristic internal configurations of nanometric tubes are calculated. A magnetic phase diagram with respect to the aspect ratio of the tubes is obtained which allows a discussion about the possibility of getting ensembles of nanotubes with low coercive fields. A comparison with recently reported coercive fields of three different cobalt nanotube arrays agrees well with the phase diagram derived here.

The neuraminidase inhibitors (NI) Oseltamivir and Zanamivir are a valuable supplementation to vaccines for the control and prevention of influenza. To support the appropriate clinical use of these new antiviral drugs, guidelines have been developed in Germany. A prerequisite for an accurate clinical diagnosis is that the physicians obtain actual information on the epidemic situation, particularly in their region. Reliable, real-time information can be provided by the newly developed surveillance system, RealFlu™. The results of an evaluation of 99 NI-treated influenza patients and their medical laboratory values are presented.

Using a previously established non-stationary thermal model it is possible to calculate the distribution of temperature and thermal stresses in emf sensors based on stabilised ZrO2 which are frequently applied for the measurement of oxygen activity in steel melts. The model may provide a basis for optimised construction of these sensors. The preheating behaviour is in the first step characterised for the sensor itself and in the second step for the complete one-reading measuring device.

background. Over the last decade surgical management of hair loss has become an increasingly popular and satisfying procedure for both men and women, as innovations in donor harvesting, graft size, and hairline design have resulted in consistently natural-appearing hair restoration. objective. In addition, a better understanding of the regulation of the hair-growth cycle has led to advances in the pharmacologic treatment of androgenetic alopecia. methods. Currently there are two U.S. Food and Drug Administration (FDA)-approved agents that promote hair regrowth: over-the-counter topical minoxidil solution for men and women and prescription oral finasteride tablets for men. In October 2001, a group of 11 international experts on hair loss and hair transplantation convened to review the physiology and effects of pharmacologic treatments of hair loss and to discuss the value of administering topical minoxidil therapy as an adjunct to hair transplantation. results. This article presents the key findings and consensus points among the participants, including their current use of pharmacologic treatments, strategies for optimal results both pre- and postsurgery, and the importance of realistic patient expectations and compliance. conclusions. Based on the surgeons' clinical experience, the use of approved hair regrowth agents in hair transplant patients with viable but suboptimally functioning follicles in the region to be transplanted can increase hair density, speed regrowth in transplanted follicles, and complement the surgical result by slowing down or stopping further hair loss.

Preprosomatostatin is a gene expressed ubiquitously among vertebrates, and at least two duplications of this gene have occurred during evolution. Somatostatin-28 (S-28) and somatostatin-14 (S-14), C-terminal products of prosomatostatin (ProS), are differentially expressed in mammalian neurons, D cells, and enterocytes. One pathway for the generation of S-14 entails the excision of Arg13-Lys14 in S-28, leading to equivalent amounts of S-28(1-12). Using an antiserum (F-4), directed to the N-terminal region of S-28 that does not react with S-28(1-12), we detected a peptide, in addition to S-28 and ProS, that was present in human plasma and in the intestinal tract of rats and monkeys. This F-4 reacting peptide was purified from monkey ileum; and its amino acid sequence, molecular mass, and chromatographic characteristics conformed to those of S-28(1-13), a peptide not described heretofore. When extracts of the small intestine were measured by RIA, there was a discordance in the ratio of peptides reacting with F-4 and those containing the C terminus of ProS, suggesting sites of synthesis for S-28(1-13) distinct from those for S-14 and S-28. This was supported by immunocytochemistry, wherein F-4 reactivity was localized in gastrointestinal (GI) endocrine cells and a widespread plexus of neurons within the wall of the distal gut while immunoreactivity to C-terminal domains of S-14 and S-28 in these neurons was absent. Further, F-4 immunoreactivity persisted in similar GI endocrine cells and myenteric neurons in mice with a targeted deletion of the preprosomatostatin gene. We believe that these data suggest a novel peptide produced in the mammalian gut, homologous with the 13 residues of the proximal region of S-28 but not derived from the Pros gene. Pending characterization of the gene from which this peptide is derived, its distribution, and function, we have designated this peptide as thrittene. Its localization in both GI endocrine cells and gut neurons suggests that thrittene may function as both a hormone and neurotransmitter. Fil: Ensinck, John W.. University of Washington; Estados Unidos Fil: Baskin, Denis G.. University of Washington; Estados Unidos. Department of Veterans Affairs Puget Sound Health Care System; Estados Unidos Fil: Vahl, Torsten P.. University of Cincinnati; Estados Unidos Fil: Vogel, Robin E.. University of Washington; Estados Unidos Fil: Laschansky, Ellen C.. University of Washington; Estados Unidos Fil: Francis, Bruce H.. University of Washington; Estados Unidos Fil: Hoffman, Ross C.. ZymoGenetics; Estados Unidos Fil: Krakover, Jonathan D.. ZymoGenetics; Estados Unidos Fil: Stamm, Michael R.. ZymoGenetics; Estados Unidos Fil: Low, Malcolm J.. Oregon Health Sciences University; Estados Unidos Fil: Rubinstein, Marcelo. Oregon Health Sciences University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Otero Corchon, Veronica. Oregon Health Sciences University; Estados Unidos Fil: D'Alessio, David A.. University of Cincinnati; Estados Unidos

Since 1983, it has been claimed that pressure applied on a lead-acid battery increases its cycle life. But until now, the use of pressure in production batteries was limited by the mechanical properties of the conventional separation systems (absorptive glass mat (AGM), and gel) which cannot withstand mechanical pressure. In 1997, Daramic developed the new acid jellying separator (AJS) with the aim of combining the advantages of both conventional separation systems and to allow the application of lasting plate group pressure. The new separation system was evaluated and much information was gained on the effect of pressure in a lead-acid battery, e.g. on the evolution of the mechanical pressure during one cycle and during cycle life.

Bile acids have increasingly been recognized to play a modulatory role in cancer formation. We previously have shown that administering oral sodium taurocholate to APCmin/+ mice decreases cellular ...

WOS:000335061100001 PubMed:24552611 Background: Methionine is an important nutrient in animal feed and several approaches have been developed to increase methionine concentration in maize (Zea mays L.) grain. One approach is through traditional breeding using recurrent selection. Using divergent selection, genetically related populations with extreme differences in grain methionine content were produced. In order to better understand the molecular mechanisms controlling grain methionine content, we examined seed proteins, transcript levels of candidate genes, and genotypes of these populations. Results: Two populations were selected for high or low methionine concentration for eight generations and 40 and 56% differences between the high and low populations in grain methionine concentration were observed. Mean values between the high and low methionine populations differed by greater than 1.5 standard deviations in some cycles of selection. Other amino acids and total protein concentration exhibited much smaller changes. In an effort to understand the molecular mechanisms that contribute to these differences, we compared transcript levels of candidate genes encoding high methionine seed storage proteins involved in sulfur assimilation or methionine biosynthesis. In combination, we also explored the genetic mechanisms at the SNP level through implementation of an association analysis. Significant differences in methionine-rich seed storage protein genes were observed in comparisons of high and low methionine populations, while transcripts of seed storage proteins lacking high levels of methionine were unchanged. Seed storage protein levels were consistent with transcript levels. Two genes involved in sulfur assimilation, Cys2 and CgS1 showed substantial differences in allele frequencies when two selected populations were compared to the starting populations. Major genes identified across cycles of selection by a high-stringency association analysis included dzs18, wx, dzs10, and zp27. Conclusions: We hypothesize that transcriptional changes alter sink strength by altering the levels of methionine-rich seed storage proteins. To meet the altered need for sulfur, a cysteine-rich seed storage protein is altered while sulfur assimilation and methionine biosynthesis throughput is changed by selection for certain alleles of Cys2 and CgS1. USDA-NIFA-OREI; Higher Education Ministry of Pakistan The authors wish to thank the Monsanto genotyping laboratory in Ankeny, Iowa for their assistance with genotyping and hourly workers and technicians who assisted with the breeding program. Names are necessary to report factually on the available data; however, the USDA neither guarantees nor warrants the standard of the product, and the use of the name by the USDA implies no approval of the product to the exclusion of others that may be suitable. This work was funded in part by grants from USDA-NIFA-OREI and the Higher Education Ministry of Pakistan.

Mechanical pressure applied to the plate group is known to increase the cycle life of lead-acid batteries. However, the mechanism of the active material stabilisation process is not completely understood yet. The evolution of mechanical pressure in a lead-acid battery during a cycle and through cycle life is also a topic with still many open questions. Additionally, the separation systems available today are not able to exert high compression on the electrode plates: glass mats crush when compressed too much and the gel design does not allow any significant pressure generation at all. Daramic have developed the new acid jellying separator (AJS) allowing the application of mechanical pressure on the plate group. This paper reports on 1. The capacity evolution during cycling for cells with different separation systems namely AGM, gel and AJS, under a variety of initial compression levels. 2. The evolution of mechanical pressure on the cell walls during a cycle and through cycle life for different separation systems, and initial compression levels. 3. The condition of the active materials at the end of life for cells cycled under compression. 4. The effect of the addition of phosphoric acid to the electrolyte. 5. The effect of the application of mechanical pressure on the corrosion of pure lead based on cyclic voltammetry measurements under compression. The results of these studies are presented together with some conclusions about the mechanism and effect of compression on a VRLA battery.

Infrared, Raman and SERS spectra of two cationic dyes—cresyl violet perchlorate and coumarin 152—were measured. Density function theory calculations were performed in order to support the vibrational spectra assignment. The data obtained indicate that cresyl violet is weakly physisorbed on the silver surface. The molecule is attached to the metal in a “vertical” configuration with its molecular plane perpendicular to the surface. Both amino groups of the molecule are in proximity to the metal surface. Coumarin 152 interacts with the silver surface through the carbonyl group. The CyO bond is weakened by the adsorption. The interaction with the metal also influences the adjacent double bonds in the lactone ring. Coumarin 152 is bonded to silver in a “vertical” configuration with its molecular plane perpendicular to the surface as well. q 2000 Elsevier Science B.V. All rights reserved.

Cd and Zn concentrations were determined by optical emission spectroscopy in various parts of the fruiting body and the mycelium of two wild mushrooms, Agaricus macrosporus and Agaricus silvicola, and in cultivated Stropharia rugosoannulata. Cd was distributed in a characteristic manner within the fruiting body of all three species. The Cd content of the cap was a function of its radius as well as its height. Concentrations of Cd and the chemically related Zn in the investigated mushroom segments were strongly correlated, whereas Al, Cu and Ag correlated poorly with Cd. To our knowledge, this is the first study of Cd contents in wild mycelia. We found similar concentrations of Cd and Zn in isolated mycelia and stems of the corresponding fruiting bodies. In addition, substrates were analysed to study soil-specific effects on Cd accumulation. The extent of Cd and Zn transfer from soil to mushroom was species-specific and influenced by the availability of these two heavy metals, as well as the age of the mushroom. Interestingly, the typical Cd and Zn distributions described here were not affected by the extent of accumulation, indicating that uptake and distribution of Cd and Zn are actually two separate mechanisms.

Materials for orthopaedic or dental implants may be further improved by chemical modification of biocompatible surfaces applying the sol–gel chemistry. The aim is to direct the adhesion of proteins, which stimulate the adhesion of load bearing cells, like osteoblasts. In this work, titanium substrates were coated with a titanium(IV)ethoxide–lysinate complex by means of sol–gel technique. Subsequently a thin layer of silver was deposited on top of the substrate by vapour deposition. A comparison of the SERS and the corresponding normal Raman spectra reveals a selective enhancement of some vibrational modes of the sol–gel layer of the modified substrate.

Surface enhanced Raman scattering (SERS) spectra of Vitamin PP (VPP) in aqueous silver and gold colloids as well as on thermal evaporated and laser ablated silver island films were recorded and compared to the corresponding FT-Raman spectrum of the free species. The enhancement on different surfaces was compared through the relative intensities I 1 / I 12 of the SERS bands assigned to the symmetric ν 1 and ν 12 modes of VPP. Interaction between the N ring and each metal substrate was confirmed based on the near coincidence both in wave numbers and relative intensities of the SERS fingerprint bands assigned to the ν 1 and ν 12 modes. The electromagnetic resonance of the surface plasmons in each VPP–metal system was a prerequisite for the chemical enhancement. The VPP–Au colloidal system was found to be the most efficient SERS complex.

Humic acid from Oak Forest extracted at pH 7, was investigated by means of surface enhanced Raman spectroscopy (SERS). The substance was deposited on two different SERS substrates: ex-situ roughened silver electrodes and silver island films. A comparison of the SERS spectra excited with the 514 nm and the 647 nm lines shows considerable differences in the relative intensities of the bands. These alterations may be a result of resonance enhancement and/or photochemically induced conformation changes of the molecule. Differences in the SERS spectra of the sample adsorbed on different SERS substrates indicate a strong dependence of the adsorption configuration of the humic acid on the metal surface, on the surface potential, and on the coadsorption of anions.

Theoretical ab initio (3-STO) and semiempiric (PM3) IR spectra of isolated B 6 vitamin (pyridoxine hydrochloride) molecule have been obtained and found in good agreement with the experimental IR spectrum. FT-Raman spectrum of the B 6 vitamin in solid polycrystalline state, polarised Raman as well as the Raman and SERS spectra on Ag colloidal surface at different pH have been recorded and discussed. The protonated or deprotonated form of the B 6 molecule was evidenced from the pH dependence Raman spectra. SERS bands associated to the chemical interaction between the deprotonated N ring atom and Ag colloidal particles were absent. Compared to related polysubstituted pyridine molecules, a different SERS behaviour of B 6 molecule was concluded.

Analytical expressions for the total magnetic energy of two characteristic internal configurations of nanometric tubes are calculated. A magnetic phase diagram with respect to the aspect ratio of the tubes is obtained considering anisotropy properties of four materials: iron, cobalt, permalloy and nickel. Conditions for low/high coercive field are discussed.

Silver island ‐lms prepared by pulsed laser deposition were tested as substrates for surface enhanced raman spectroscopy. They exhibit a position-dependent thickness and SERS activity distribution. Cresyl Violet and Crystal Violet were chosen as test molecules. The annealing of the ‐lms leads to coalescence of the initial island structures and the development of longer ellipsoidal particles, which generally improves the enhancement properties of the substrates. The dimensions of the surface structures depend on the local initial ‐lm thickness. The changes in the island shape and dimensions manifest themselves in changes in the absorption spectra. 1998 John Wiley & Sons, ( Ltd.

New measurements of the gas-phase viscosity of 1,1,1,2-tetrafluoroethane (R134a) were carried out within an international round-robin project of IUPAC, which was initiated because of the large discrepancies between the results reported by various authors for the transport properties of R134a. Six isochoric series of high-precision measurements were performed by means of a quartz oscillating-disk viscometer between 297 and 438 K and at densities from 12 to 90 mol m −3 . Isothermal values recalculated from the experimental data were evaluated with a first-order expansion for the viscosity, in terms of density, to deduce zero-density and initial-density viscosity coefficients. The accuracy of the zero-density values is estimated to be ±0.2%. A representation based on the new results and on reliable data sets from literature is proposed for the viscosity in the limit of zero density to replace a correlation recommended by Krauss et al. Reduced second viscosity virial coefficients deduced from the experiments are in close agreement with predictions of the Rainwater-Friend theory.

The intramolecular dipolar cycloaddition of an azide with an alkyne has provided a useful entry into triazole fused tricyclic heterocycles containing both the triazole ring and the oxazolidin-2-one ring system. The requisite azido-alkynes have been prepared via a two-step sequence from fused ring aziridines. A series of 6–12 membered rings containing both the oxazolidinone and triazole rings have been prepared. These ring systems have been designed as conformationally restrained analogs of RNA-binding oxazolidinones.

The intramolecular dipolar cycloaddition of an azide with an alkyne has provided a useful entry into triazole fused tricyclic heterocycles containing both the triazole ring and the oxazolidin-2-one ring system. The requisite azido-alkynes have been prepared via a two-step sequence from fused ring aziridines. A series of 6–12 membered rings containing both the oxazolidinone and triazole rings have been prepared. These ring systems have been designed as conformationally restrained analogs of RNA-binding oxazolidinones.

The neuraminidase inhibitors signifies a breakthrough in the treatment of influenza. We compared the outcomes of influenza in 56 patients treated with zanamivir or oseltamivir to a group of 52 influenza patients from the time before these drugs were available. The duration of illness was reduced by 45%, the severity of symptoms by 40% and the administration of antibiotics by 32%. The data from this small group of patients of our ambulatory practice correspond to the results of large randomized placebo-controlled double-blind studies on zanamivir and oseltamivir. Our clinical observations and painful experiences have taught us to take every case of suspected influenza seriously. Since considerable influenza-related complications are common even in otherwise healthy individuals, patients should immediately consult their doctor when an illness with sudden onset of fever and cough or another respiratory symptom occur.

The viscosity of the vapor mixtures benzene-toluene (four mole fractions at densities up to 0.012 mol · L−1) and benzene-p-xylene (four mole fractions at densities up to 0.023 mol · L−1) has been measured in an all-quartz oscillating-disk viscometer with small gaps for temperatures between 330 and 630 K (benzene-toluene) and between 355 and 625 K (benzene-p-xylene). The values of the interaction viscosity in the limit of zero density resulting from a first evaluation of the experimental data for different mole fractions by means of the Chapman-Enskog theory have shown differences larger than the experimental uncertainties. Consistent values are obtained by taking into account the initial density dependence of viscosity according to the modified Enskog theory for gaseous mixtures. Binary diffusion coefficients have been calculated using the results of the interaction viscosity in the limit of zero density.

A method based on generalized Glauber states is developed to deal with the Jahn-Teller effect on magnetic impurities in II-VI semiconductors, and is successfully applied to ZnTe:Fe 2+ . The method is also applied to ZnS:Fe 2+ which reaches stability for a lower number of vibrational quanta N, in order to have a basis for comparison with another method. It is found that the present method is more powerful than a previous one based on Born-Oppenheimer functions. The low-energy vibronic functions remain as stable solutions for all values of the coupling parameter. In the case of ZnTe:Fe 2+ , good agreement with both experimental results and previous theoretical calculations is obtained for a Jahn-Teller energy of 250 cm -1

Several studies have addressed the interaction of the HIV Tat protein with the cell surface. Our analysis of the cell attachment-promoting activity of Tat and peptides derived from it revealed that the basic domain of Tat, not the arg-gly-asp (RGD) sequence, is required for cell attachment to Tat. Affinity chromatography with Tat peptides and immunoprecipitation with various anti-integrin antibodies suggest that the vitronectin-binding integrin, alpha v beta 5, is the cell surface protein that binds to the basic domain of Tat. The Tat basic domain contains the sequence RKKRRQRRR. A related sequence, KKQRFRHRNRKG, present in the heparin-binding domain of an alpha v beta 5 ligand, vitronectin, also bound alpha v beta 5 in affinity chromatography and, in combination with an RGD peptide, was an inhibitor of cell attachment to vitronectin. The alpha v beta 5 interaction with these peptides was not solely due to high content of basic amino acids in the ligand sequences; alpha v beta 5 did not bind substantially to peptides consisting entirely of arginine or lysine, whereas a beta 1 integrin did bind to these peptides. The interaction of alpha v beta 5 with Tat is atypical for integrins in that the binding to Tat is divalent cation independent, whereas the binding of the same integrin to an RGD-containing peptide or to vitronectin requires divalent cations. These data define an auxiliary integrin binding specificity for basic amino acid sequences. These basic domain binding sites may function synergistically with the binding sites that recognize RGD or equivalent sequences.

New measurements of the vapor phase viscosity of toluene and p-xylene have been performed in an all-quartz oscillating-disk viscometer with small gaps. Thus, including own measurements reported earlier experimental data are available in the temperature range between 305 and 630 K (toluene) and between 340 and 635 K (p-xylene) and for densities from 0.002 up to 0.045 mol·L −1 (toluene) and from 0.003 up to 0.038 mol·L −1 (p-xylene). The data have been evaluated with a density series for the viscosity in which only a linear density contribution has been included. The values of the second viscosity virial coefficient obtained for toluene, p-xylene as well as for benzene have been compared with results of the Rainwater-Friend theory on the basis of the Lennard-Jones 12-6 potential. The agreement is excellent when using the potential parameter ratios determined by Bich and Vogel.

Native chemical ligation (NCL) is a chemoselective reaction that joins synthetic or recombinant peptide and protein fragments through a native peptide bond. Advances in generating the required peptide and protein components for NCL have enabled the homogeneous incorporation of unnatural amino acids, fluorescent probes, and other modifications into protein domains and full-length proteins. The resulting semisynthetic proteins, which can be made in multi-milligram quantities, may be used in biophysical and biochemical studies to address challenging biological problems not accessible with traditional methods. This chapter provides an overview of NCL, B. Imperiali Department of Chemistry and Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA, e-mail: imper@mit.edu

129 I is preconcentrated from environmental samples and its accessibility is addressed for inductively coupled plasma quadrupole mass spectrometer with collision/reaction interface (ICP-CRI-QMS). By applying oxygen as CRI gas through skimmer cone, the signal of the interfering 129 Xe from the impurity of plasma gas can be eliminated while the formation of 127 I 1 H 1 H + can be partially removed. The improved ICP-QMS can be employed for investigation of 129 I in environmental samples with a 129 I/ 127 I ratio down to 10 -7 . The detection capability was demonstrated by measuring 129 I in seaweed samples collected around the nuclear fuel reprocessing plant at La Hague. The abundant 127 I in the sample matrix causes a serious problem and degrades the detection capability of the instrument when the concentration of 127 I is larger than 10 5 ng/g. Even combined with a sufficient pre-concentration procedure, ICP-QMS is not considered as a suitable technique for the analysis of 129 I in uncontaminated environmental samples with 129 I/ 127 I ratio of less than 10 -7 . Results are presented for seaweed samples collected around La Hague. In addition, time dependant I concentrations and ratios are given for colloids and water sampled from Lake Thun.

The interaction energy and force between two parallel thin magnetic nanotubes is calculated using four different approaches. Although they agree for separation distances over 10 times the radius of any tube, some differences appear for shorter distances. Two exact methods giving identical results face handling difficulties in comparison with an approximate method based on a truncated expansion which produces fair enough results for distances to be found in the range of interest. Numerical calculations are done for cobalt particles of dimensions corresponding to nanotubes already manufactured and with properties reported in the literature. The force between two identical and parallel Co nanotubes ( L = 60 μ m , D = 180 nm ) , separated by a distance of 300 nm is of the order of few microdynes.

The Jahn-Teller coupling between local vibrations of the host III-V semiconductors and the electronic orbitals of ${\mathrm{Fe}}^{2+}$ substitutional impurities are studied from a theoretical point of view. Coupling to both multiplets resulting after crystal-field splitting is considered. Calculations are performed with just one adjustable parameter, namely, the Jahn-Teller energy (${\mathit{E}}_{\mathrm{JT}}$). The compounds GaP:${\mathrm{Fe}}^{2+}$, GaAs:${\mathrm{Fe}}^{2+}$, and InP:${\mathrm{Fe}}^{2+}$ are fully discussed, especially the latter. Other III-V semiconductors such as GaSb:${\mathrm{Fe}}^{2+}$, InAs:${\mathrm{Fe}}^{2+}$, and InSb:${\mathrm{Fe}}^{2+}$ are referred to for particular applications of the model. The results for the lower multiplet show good agreement for the predicted lines with luminescence spectra; the coupling phonon is identified as belonging to the points TA(L) of the Brillouin zone; values for ${\mathit{E}}_{\mathrm{JT}}$ are about 8 ${\mathrm{cm}}^{\mathrm{\ensuremath{-}}1}$ for this coupling. The coupling to the upper multiplet is described in terms of upper limits as the available infrared-absorption spectra do not show evidence for more than one zero-phonon line. A comparison with similar calculations for II-VI compounds with ${\mathrm{Fe}}^{2+}$ as substitutional impurity is also performed.

The paper reports experimental results for the viscosity of the vapor mixtures methanol-benzene (five mole fractions with densities up to 1.5kg·m−3 and 0.022 mol·L −1) and methanol-cyclohexane (four mole fractions with densities up to 1.9kg·m−3 and 0.026 mol·L −1). In analogy to the pure components, the measurements on the mixtures were carried out with an oscillating-disk viscometer with small gaps, completely made of quartz, beginning as near as possible to room temperature and continuing to a maximum temperature of 630 K. A first evaluation by means of the Chapman-Enskog theory of dilute gases has shown differences in the resulting values of the interaction viscosity η ij (0) in the limit of zero density exceeding the experimental errors. Consistent results were obtained by taking into account the initial density dependence of the viscosity within the framework of the modified Enskog theory for gaseous mixtures. The values of η ij (0) were also used to estimate binary diffusion coefficients of the mixtures.

Previous studies on photooxidation of 9,10-diethoxyanthracene (DEA) with diphenyliodonium cation revealed dealkylation of DEA radical cation. Fluorescence, dealkylation quantum yield, and laser-flash transient absorption spectroscopic studies on DEA and its dimethoxy (DMA) and diisopropoxy (DIPA) analogs, probed solvent and substituent effects on this reaction. We reconsider our original inferences as to relative rates of dealkylation and back electron transfer; the results pose new questions, e.g., as to the role of orbital symmetry in controlling rate of back electron transfer.

The effect of maternal alcohol exposure before mating was investigated in the offspring over a period of 6 months concerning some specific aspects of energy metabolism in the brain and the liver. The following biochemical parameters were analyzed: superoxide dismutase (involved in elimination of free radicals produced during ethanol oxidation), enolase isoenzymes (markers of nerve cell maturation), and alcohol and aldehyde dehydrogenase (the main alcohol degradating enzymes). These enzymatic activities were measured at their subcellular level. In these animals never directly exposed to alcohol, superoxide dismutase activity was decreased mainly in the liver cytosol. Only the nonneuronal form of enolase activity was modified. Alcohol dehydrogenase was decreased in the liver as well as in the brain. Aldehyde dehydrogenase was also decreased in the liver and in the brain, mainly in the mitochondria. Behavioral observations showed decreased emotional reactivity as well as an increase in locomotor activity. Our results suggest that long-lasting biochemical and behavioral effects of alcohol may occur in the offspring starting at the earliest stage of development.

Theoretical calculations based on a linear Jahn-Teller effect are performed for the cases of the wurtzite-structure compounds CdS:Fe 2+ and CdSe:Fe 2+ . Vibronic functions with vibrational quantum number N up to 14 are used in order to study the stability of the solutions. Predicted lines that would appear in absorption experiments, Jahn-Teller energies and other parameters are discussed and compared with available experimental and theoretical information.

All of the type I collagen in connective tissue is the product of one structural gene for the pro alpha 1(I) chain and another for the pro alpha 2(I) chain of type I procollagen. An intriguing question therefore is how the expression of the two genes differs in mineralizing and non-mineralizing tissues. One approach that our laboratory has pursued to answer this and related questions is to develop a new system whereby one can examine the self-assembly of collagen fibrils de novo by controlled enzymic cleavage of procollagen to collagen under physiological conditions. The system has made it possible for the first time to define thermodynamic parameters for the self-assembly process. We are now using the system to define the normal kinetics for fibril formation. The results should make it possible to study the effects of other components of extracellular matrix on fibril assembly, including the effects of bone-specific components that initiate mineralization. A second approach has been to define mutations in type I procollagen genes that cause increased brittleness of bone. Over a dozen mutations in type I procollagen genes have been found in probands with osteogenesis imperfecta. One of the surprises has been that at least 25% of the probands with lethal variants of osteogenesis imperfecta have mutations in type I procollagen genes. Another surprise has been the observation that a number of the mutations are tissue specific in terms of their phenotypic manifestations even though the same abnormal pro alpha chains are being synthesized in a variety of tissues.