bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic effects of ethanol on muscarinic acetylcholine receptors are modulated by protein kinase C
Authors: CARON MURIELLE , LARSSON CHRISTER , ALLING CHRISTER
Published: July 2002

We have previously demonstrated that long‐term ethanol treatment increased the number and function of muscarinic acetylcholine receptors (mAChRs) in human neuroblastoma cells, but the molecular mechanisms involved in these changes are unknown. In the present study, the effect of protein kinase C (PKC) on these events was investigated in human neuroblastoma SH‐SY5Y cells. Following exposure to 100 mM ethanol for 2 days, both [3H]N‐methylscopolamine binding and carbachol‐stimulated I(1,4,5)P3 formation were increased. When cells were cultured in the presence of 12‐O‐tetradecanoylphorbol 13‐acetate (TPA), a potent activator of PKC, the effects of ethanol on mAChR number were totally inhibited but ethanol still potentiated carbacholstimulated I(1,4,5)P3 formation in TPA treated cells. TPA dose‐dependently inhibited carbochol‐stimulated I(1,4,5)P3 formation and this effect appeared to be independent of PKC phosphorylating activity. On the other hand, PKC inhibitors mimicked ethanol effects on mAChR number and function. Selective inhibition of classical PKC isozymes with 1 μM Gö 6976 for 2 days caused an increase in mAChR number and function, suggesting a role for these isozymes in ethanol‐induced upregulation of mAChRs. These data indicate that longterm ethanol treatment may upregulate the number of mAChRs by counteracting PKC‐mediated phosphorylation. The effects of ethanol on receptor‐coupled phosphoinositide hydrolysis appear to be independent of PKC activity.
The urinary MHPG/creatinine ratio and its relationship to platelet monoamine oxidase activity in abstinent alcoholics
Authors: FARREN CONOR K. , TIPTON KEITH F.
Published: July 2002

This study was designed to assess the baseline noradrenergic turnover of subgroups of postwithdrawal abstinent alcoholics and healthy controls. The method chosen was an overnight fasting urine sample of the breakdown product of norepinephrine, MHPG, related to urinary creatinine. A comparison was made with platelet monoamine oxidase activity and also within subgroups of the study population. This study found no difference between alcoholics and controls, nor between subgroups of postwithdrawal alcoholics in their level of urinary MHPG corrected for creatinine, and no significant correlation with major subject characteristics or with platelet monoamine oxidase. There was a trend, however, towards a significant correlation with duration of abstinence from alcohol, and there was a correlation with a history of fighting when drinking alcohol, but not with sociopathic traits overall. Within the type 2 alcoholics there was a significant correlation with a history of fighting when drinking and a negative correlation with behavioral tolerance to alcohol. It is possible that only the subset of type 2 alcoholics with certain antisocial characteristics have noradrenergic abnormalities. Although no statistical difference was found between the different groups under study, the information is helpful in increasing understanding of the noradrenergic system in abstinent alcoholics.
Use of the speech pattern audiometer and the electropalatograph to explore the speech production/perception relationship in a profoundly deaf child
Authors: Parsloe Rachael
Published: July 2002

The use of electropalatography (EPG) in the teaching of new speech skills to deaf speakers, is not widely researched. Whether these skills can be maintained, or whether they can become fully automatic, without enough speech perception to enable auditory self‐monitoring is therefore unclear. Most approaches to increasing speech intelligibility in deaf speakers, rightly, place an emphasis on maximizing residual hearing and listening skills. However, a small amount of evidence exists which suggests that speech production can aid speech perception. This research aimed to measure change in speech perception, through use of the speech pattern audiometer (SPA), whilst working on speech production with the electropalatograph. Intervention took place over a year. The issues of maintenance and generalization are discussed.
Tic20 and Tic22 Are New Components of the Protein Import Apparatus at the Chloroplast Inner Envelope Membrane
Authors: Kouranov Andrei , Chen Xuejun , Fuks Bruno , Schnell Danny J.
Published: July 2002

Two components of the chloroplast envelope, Tic20 and Tic22, were previously identified as candidates for components of the general protein import machinery by their ability to covalently cross-link to nuclear-encoded preproteins trapped at an intermediate stage in import across the envelope (Kouranov, A., and D.J. Schnell. 1997. J. Cell Biol. 139:1677–1685). We have determined the primary structures of Tic20 and Tic22 and investigated their localization and association within the chloroplast envelope. Tic20 is a 20-kD integral membrane component of the inner envelope membrane. In contrast, Tic22 is a 22-kD protein that is located in the intermembrane space between the outer and inner envelope membranes and is peripherally associated with the outer face of the inner membrane. Tic20, Tic22, and a third inner membrane import component, Tic110, associate with import components of the outer envelope membrane. Preprotein import intermediates quantitatively associate with this outer/inner membrane supercomplex, providing evidence that the complex corresponds to envelope contact sites that mediate direct transport of preproteins from the cytoplasm to the stromal compartment. On the basis of these results, we propose that Tic20 and Tic22 are core components of the protein translocon of the inner envelope membrane of chloroplasts.
Fission Yeast Bub1 Is a Mitotic Centromere Protein Essential for the Spindle Checkpoint and the Preservation of Correct Ploidy through Mitosis
Authors: Bernard Pascal , Hardwick Kevin , Javerzat Jean-Paul
Published: July 2002

The spindle checkpoint ensures proper chromosome segregation by delaying anaphase until all chromosomes are correctly attached to the mitotic spindle. We investigated the role of the fission yeast bub1 gene in spindle checkpoint function and in unperturbed mitoses. We find that bub1+ is essential for the fission yeast spindle checkpoint response to spindle damage and to defects in centromere function. Activation of the checkpoint results in the recruitment of Bub1 to centromeres and a delay in the completion of mitosis. We show that Bub1 also has a crucial role in normal, unperturbed mitoses. Loss of bub1 function causes chromosomes to lag on the anaphase spindle and an increased frequency of chromosome loss. Such genomic instability is even more dramatic in Δbub1 diploids, leading to massive chromosome missegregation events and loss of the diploid state, demonstrating that bub1+ function is essential to maintain correct ploidy through mitosis. As in larger eukaryotes, Bub1 is recruited to kinetochores during the early stages of mitosis. However, unlike its vertebrate counterpart, a pool of Bub1 remains centromere-associated at metaphase and even until telophase. We discuss the possibility of a role for the Bub1 kinase after the metaphase–anaphase transition.
Coupling Assembly of the E-Cadherin/β-Catenin Complex to Efficient Endoplasmic Reticulum Exit and Basal-lateral Membrane Targeting of E-Cadherin in Polarized MDCK Cells
Authors: Chen Yih-Tai , Stewart Daniel B. , Nelson W. James
Published: July 2002

The E-cadherin/catenin complex regulates Ca++-dependent cell–cell adhesion and is localized to the basal-lateral membrane of polarized epithelial cells. Little is known about mechanisms of complex assembly or intracellular trafficking, or how these processes might ultimately regulate adhesion functions of the complex at the cell surface. The cytoplasmic domain of E-cadherin contains two putative basal-lateral sorting motifs, which are homologous to sorting signals in the low density lipoprotein receptor, but an alanine scan across tyrosine residues in these motifs did not affect the fidelity of newly synthesized E-cadherin delivery to the basal-lateral membrane of MDCK cells. Nevertheless, sorting signals are located in the cytoplasmic domain since a chimeric protein (GP2CAD1), comprising the extracellular domain of GP2 (an apical membrane protein) and the transmembrane and cytoplasmic domains of E-cadherin, was efficiently and specifically delivered to the basal-lateral membrane. Systematic deletion and recombination of specific regions of the cytoplasmic domain of GP2CAD1 resulted in delivery of <10% of these newly synthesized proteins to both apical and basal-lateral membrane domains. Significantly, >90% of each mutant protein was retained in the ER. None of these mutants formed a strong interaction with β-catenin, which normally occurs shortly after E-cadherin synthesis. In addition, a simple deletion mutation of E-cadherin that lacks β-catenin binding is also localized intracellularly. Thus, β-catenin binding to the whole cytoplasmic domain of E-cadherin correlates with efficient and targeted delivery of E-cadherin to the lateral plasma membrane. In this capacity, we suggest that β-catenin acts as a chauffeur, to facilitate transport of E-cadherin out of the ER and the plasma membrane.
Centromeres Are Specialized Replication Domains in Heterochromatin
Authors: Ahmad Kami , Henikoff Steven
Published: July 2002

The properties that define centromeres in complex eukaryotes are poorly understood because the underlying DNA is normally repetitive and indistinguishable from surrounding noncentromeric sequences. However, centromeric chromatin contains variant H3-like histones that may specify centromeric regions. Nucleosomes are normally assembled during DNA replication; therefore, we examined replication and chromatin assembly at centromeres in Drosophila cells. DNA in pericentric heterochromatin replicates late in S phase, and so centromeres are also thought to replicate late. In contrast to expectation, we show that centromeres replicate as isolated domains early in S phase. These domains do not appear to assemble conventional H3-containing nucleosomes, and deposition of the Cid centromeric H3-like variant proceeds by a replication-independent pathway. We suggest that late-replicating pericentric heterochromatin helps to maintain embedded centromeres by blocking conventional nucleosome assembly early in S phase, thereby allowing the deposition of centromeric histones.
Replacement of Pre-T Cell Receptor Signaling Functions by the CD4 Coreceptor
Authors: Norment Anne M. , Forbush Katherine A. , Nguyen Nhan , Malissen Marie , Perlmutter Roger M.
Published: July 2002

An important checkpoint in early thymocyte development ensures that only thymocytes with an in-frame T cell receptor for antigen β (TCR-β) gene rearrangement will continue to mature. Proper assembly of the TCR-β chain into the pre-TCR complex delivers signals through the src-family protein tyrosine kinase p56lck that stimulate thymocyte proliferation and differentiation to the CD4+CD8+ stage. However, the biochemical mechanisms governing p56lck activation remain poorly understood. In more mature thymocytes, p56lck is associated with the cytoplasmic domain of the TCR coreceptors CD4 and CD8, and cross-linking of CD4 leads to p56lck activation. To study the effect of synchronously inducing p56lck activation in immature CD4−CD8− thymocytes, we generated mice expressing a CD4 transgene in Rag2−/− thymocytes. Remarkably, without further experimental manipulation, the CD4 transgene drives maturation of Rag2−/− thymocytes in vivo. We show that this process is dependent upon the ability of the CD4 transgene to bind Lck and on the expression of MHC class II molecules. Together these results indicate that binding of MHC class II molecules to CD4 can deliver a biologically relevant, Lck-dependent activation signal to thymocytes in the absence of the TCR-α or -β chain.
Lineage Relationships and Differentiation of Natural Killer (NK) T Cells: Intrathymic Selection and Interleukin (IL)-4 Production in the Absence of NKR-P1 and Ly49 Molecules
Authors: Lantz Olivier , Sharara Lama I. , Tilloy Florence , Andersson Åsa , DiSanto James P.
Published: July 2002

In this report, we have assessed the lineage relationships and cytokine dependency of natural killer (NK) T cells compared with mainstream TCR-αβ T cells and NK cells. For this purpose, we studied common γ chain (γc)-deficient mice, which demonstrate a selective defect in CD3− NK cell development relative to conventional TCR-αβ T cells. NK thymocytes differentiate in γc− mice as shown by the normal percentage of TCR Vβ8+ CD4−CD8− cells and the normal quantity of thymic Vα14–Jα281 mRNA that characterize the NK T repertoire. However, γc-deficient NK thymocytes fail to coexpress the NK-associated markers NKR-P1 or Ly49, yet retain characteristic expression of the cytokine receptors interleukin (IL)-7Rα and IL-2Rβ. Despite these phenotypic abnormalities, γc− NK thymocytes could produce normal amounts of IL-4. These results define a maturational progression of NK thymocyte differentiation where intrathymic selection and IL-4–producing capacity can be clearly dissociated from the acquisition of the NK phenotype. Moreover, these data suggest a closer ontogenic relationship of NK T cells to TCR-αβ T cells than to NK cells with respect to cytokine dependency. We also failed to detect peripheral NK T cells in these mice, demonstrating that γc-dependent interactions are required for export and/or survival of NK T cells from the thymus. These results suggest a stepwise pattern of differentiation for thymically derived NK T cells: primary selection via their invariant TCR to confer the IL-4–producing phenotype, followed by acquisition of NK-associated markers and maturation/export to the periphery.
Signaling Efficiency of the T Cell Receptor Controlled by a Single Amino Acid in the β Chain Constant Region
Authors: Bäckström B. Thomas , Hausmann Barbara T. , Palmer Ed
Published: July 2002

A single amino acid residue, Gln136, located within the connecting peptide domain of Cβ controls the ability of the α/β TCR to transmit a full signal. TCRs in which this Cβ residue is mutated to Phe, the residue found in TCR-γ, are unresponsive to antigenic ligands. Interestingly, this Cβ residue is either polar or charged in every species studied thus far, including the trout and the skate. In contrast, the analogous residue in Cγ is always hydrophobic. In spite of their compromised antigen responsiveness, the mutant TCR complex contains the CD3-γ, -δ, -ε, and -ζ chains, and undergoes ζ chain phosphorylation and ZAP-70 recruitment. However, the biological response of the mutant TCR could be rescued with a calcium ionophore, implying that mutant TCRs are defective in generating a calcium-mediated signal. The implications of the differences between Cβ and Cγ are considered.
1α,25-Dihydroxyvitamin D3–Induced Myeloid Cell Differentiation Is Regulated by a Vitamin D Receptor–Phosphatidylinositol 3-Kinase Signaling Complex
Authors: Hmama Zakaria , Nandan Devki , Sly Laura , Knutson Keith L. , Herrera-Velit Patricia , Reiner Neil E.
Published: July 2002

1α,25-dihydroxyvitamin D3 (D3) promotes the maturation of myeloid cells and surface expressions of CD14 and CD11b, markers of cell differentiation in response to D3. To examine how these responses are regulated, THP-1 cells were grown in serum-free medium and incubated with D3. This was associated with rapid and transient increases in phosphatidylinositol 3-kinase (PI 3-kinase) activity. Furthermore, induction of CD14 expression in response to D3 was abrogated by (a) the PI 3-kinase inhibitors LY294002 and wortmannin; (b) antisense oligonucleotides to mRNA for the p110 catalytic subunit of PI 3-kinase; and (c) a dominant negative mutant of PI 3-kinase. In THP-1 cells, induction of CD11b expression by D3 was also abrogated by LY294002 and wortmannin. Similarly, LY294002 and wortmannin inhibited D3-induced expression of both CD14 and CD11b in peripheral blood monocytes. In contrast to CD14 and CD11b, hormone-induced expression of the Cdk inhibitor p21 in THP-1 cells was unaffected by either wortmannin or LY294002. These findings suggest that PI 3-kinase selectively regulates D3-induced monocyte differentiation, independent of any effects on p21.
Abrogation of Experimental Colitis Correlates with Increased Apoptosis in Mice Deficient for Cd44 Variant Exon 7 (Cd44v7)
Authors: Wittig Bianca M. , Johansson Britt , Zöller Margot , Schwärzler Christoph , Günthert Ursula
Published: July 2002

Experimental colitis in mice is characterized by infiltration of activated T helper (Th) cells and macrophages into the lamina propria. Particularly, these cells expressed CD44 variant exon 7 (CD44v7)-containing isoforms. Upregulation of CD44v7 isoforms was induced by CD40 ligation, an inflammation-driving interaction between activated Th cells and macrophages. To define the role of CD44v7 in colitis, mice bearing a targeted deletion for exon v7 were generated. In trinitrobenzene sulfonic acid–induced colitis, wild-type mice developed severe signs of persistent inflammation. Mice lacking CD44v7 initially showed unspecific inflammation, then recovered completely. The pathogenic origin was shown to reside in bone marrow–derived CD44v7+ cells, because adoptive transfer experiments demonstrated an absolute requirement for CD44v7 on hematopoietic cells for maintenance of colitis. Interleukin (IL)-10–deficient mice, which develop a chronic Th1-driven enterocolitis, were crossbred with CD44v6/v7 null mice. In IL-10 × CD44v6/v7 double deficient mice, intestinal inflammation developed only weakly and at an older age. Analysis of cell death in the inflamed lesions revealed that mononuclear cells in the CD44v7 null infiltrates had higher rates of apoptosis than those from wild-type mice. Thus, the region encoded by CD44v7 appears to be essential for survival of effector lymphocytes, resulting in persistence of inflammation.
Localization of Distinct Peyer's Patch Dendritic Cell Subsets and Their Recruitment by Chemokines Macrophage Inflammatory Protein (Mip)-3α, Mip-3β, and Secondary Lymphoid Organ Chemokine
Authors: Iwasaki Akiko , Kelsall Brian L.
Published: July 2002

We describe the anatomical localization of three distinct dendritic cell (DC) subsets in the murine Peyer's patch (PP) and explore the role of chemokines in their recruitment. By two-color in situ immunofluorescence, CD11b+ myeloid DCs were determined to be present in the subepithelial dome (SED) region, whereas CD8α+ lymphoid DCs are present in the T cell–rich interfollicular region (IFR). DCs that lack expression of CD8α or CD11b (double negative) are present in both the SED and IFR. By in situ hybridization, macrophage inflammatory protein (MIP)-3α mRNA was dramatically expressed only by the follicle-associated epithelium overlying the SED, while its receptor, CCR6, was concentrated in the SED. In contrast, CCR7 was expressed predominantly in the IFR. Consistent with these findings, reverse transcriptase polymerase chain reaction analysis and in vitro chemotaxis assays using freshly isolated DCs revealed that CCR6 was functionally expressed only by DC subsets present in the SED, while all subsets expressed functional CCR7. Moreover, none of the splenic DC subsets migrated toward MIP-3α. These data support a distinct role for MIP-3α/CCR6 in recruitment of CD11b+ DCs toward the mucosal surfaces and for MIP-3β/CCR7 in attraction of CD8α+ DCs to the T cell regions. Finally, we demonstrated that all DC subsets expressed an immature phenotype when freshly isolated and maintained expression of subset markers upon maturation in vitro. In contrast, CCR7 expression by myeloid PP DCs was enhanced with maturation in vitro. In addition, this subset disappeared from the SED and appeared in the IFR after microbial stimulation in vivo, suggesting that immature myeloid SED DCs capture antigens and migrate to IFR to initiate T cell responses after mucosal microbial infections.
Natural Proteolytic Processing of Hemofiltrate Cc Chemokine 1 Generates a Potent Cc Chemokine Receptor (Ccr)1 and Ccr5 Agonist with Anti-HIV Properties
Authors: Detheux Michel , Ständker Ludger , Vakili Jalal , Münch Jan , Forssmann Ulf , Adermann Knut , Pöhlmann Stefan , Vassart Gilbert , Kirchhoff Frank , Parmentier Marc , Forssmann Wolf-Georg
Published: July 2002

Hemofiltrate CC chemokine (HCC)-1 is a recently described human chemokine that is constitutively expressed in numerous tissues and is present at high concentrations in normal plasma. Using a cell line expressing CC chemokine receptor (CCR)5 as a bioassay, we isolated from human hemofiltrate an HCC-1 variant lacking the first eight amino acids. HCC-1[9–74] was a potent agonist of CCR1, CCR3, and CCR5 and promoted calcium flux and chemotaxis of T lymphoblasts, monocytes, and eosinophils. It also blocked entry of HIV-1 strains using CCR5 as coreceptor. Limited tryptic digestion of HCC-1 generated the active variant. Conditioned media from several tumor cell lines activated HCC-1 with a high efficiency, and this activity could be inhibited by serine protease inhibitors. Our results indicate that HCC-1 represents a nonfunctional precursor that can be rapidly converted to the active chemokine by proteolytic processing. This process represents an additional mechanism by which tumor cells might generate chemoattractant molecules and recruit inflammatory cells. It might also affect HIV-1 replication in infected individuals and play an important role in AIDS pathogenesis.
Smorodinsky’s conjecture on rank-one mixing
Authors: Adams Terrence
Published: July 2002

We prove Smorodinsky’s conjecture: the rank-one transformation, obtained by adding staircases whose heights increase consecutively by one, is mixing.
Braid groups are linear
Authors: Bigelow Stephen
Published: July 2002

The braid group

B
n

B_n

can be defined as the mapping class group of the

n
n

-punctured disk. A group is said to be linear if it admits a faithful representation into a group of matrices over

R

\mathbf R

. Recently Daan Krammer has shown that a certain representation of the braid groups is faithful for the case

n
=
4

n=4

. In this paper, we show that it is faithful for all

n
n

.
Boundary behavior of quasi-regular maps and the isodiametric profile
Authors: Hanson Bruce , Koskela Pekka , Troyanov Marc
Published: July 2002

We study obstructions for a quasi-regular mapping

f
:
M
→
N

f:M\rightarrow N

of finite degree between Riemannian manifolds to blow up on or collapse on a non-trivial part of the boundary of

M
M

.
JaDis: computing distances between nucleic acid sequences.
Authors: Gon√ßalves I , Robinson M , Perri√®re G , Mouchiroud D
Published: July 2002

SUMMARY: JaDis is a Java application for computing evolutionary distances between nucleic acid sequences and G+C base frequencies. It allows specific comparison of coding sequences, of non-coding sequences or of a non-coding sequence with coding sequences. AVAILABILITY: http://pbil.univ-lyon1.fr/software/jadis.html
Molecular taphonomy of animal and plant cuticles: selective preservation and diagenesis
Authors: Briggs Derek E. G.
Published: July 2002

The nature of organic material and the environment in which it is deposited exert a major influence on the extent to which biomacromolecules are preserved in the fossil record. The role of these factors is explored with a particular focus on the cuticle of arthropods and leaves. Preservation of the original chemistry of arthropod cuticles is favoured by their thickness and degree of sclerotization, and the presence of biominerals. Decay and burial in terrestrial as opposed to marine, and anoxic rather than oxygenated conditions, likewise appear to enhance preservation. The most important factor in the long–term preservation of the chemistry of both animal and plant cuticles, however, is diagenetic alteration to an aliphatic composition. This occurs even in amber, which encapsulates the fossil, eliminating almost all external factors. Some plants contain an original decay–resistant macromolecular aliphatic component but this is not the case in arthropods. It appears that the aliphatic components of many plant as well as animal fossils may be the result of diagenetic polymerization. Selective preservation as a result of decay resistance may explain the initial survival of organic materials in sediments, but in many cases longer–term preservation relies on chemical changes. Selective preservation is only a partial explanation for the origin of kerogen.
Preservation of key biomolecules in the fossil record: current knowledge and future challenges
Authors: Bada Jeffrey L. , Wang Xueyun S. , Hamilton Healy
Published: July 2002

We have developed a model based on the analyses of modern and Pleistocene eggshells and mammalian bones which can be used to understand the preservation of amino acids and other important biomolecules such as DNA in fossil specimens. The model is based on the following series of diagenetic reactions and processes involving amino acids: the hydrolysis of proteins and the subsequent loss of hydrolysis products from the fossil matrix with increasing geologic age; the racemization of amino acids which produces totally racemized amino acids in 105–106years in most environments on the Earth; the introduction of contaminants into the fossil that lowers the enantiomeric (D/L) ratios produced via racemization; and the condensation reactions between amino acids, as well as other compounds with primary amino groups, and sugars which yield humic acid–like polymers. This model was used to evaluate whether useful amino acid and DNA sequence information is preserved in a variety of human, amber entombed insect and dinosaur specimens. Most skeletal remains of evolutionary interest with respect to the origin of modern humans are unlikely to preserve useful biomolecular information although those from high latitude sites may be an exception. Amber entombed insects contain well preserved unracemized amino acids, apparently because of the anhydrous nature of the amber matrix, and thus may contain DNA fragments which have retained meaningful genetic information. Dinosaur specimens contain mainly exogenous amino acids, although traces of endogenous amino acids may be present in some cases. Future ancient biomolecule research which takes advantage of new methologies involving, for example, humic acid cleaving reagents and microchip–based DNA–protein detection and sequencing, along with investigations of very slow biomolecule diagenetic reactions such as the racemization of isoleucine at the β–carbon, will lead to further enhancements of our understanding of biomolecule preservation in the fossil record.
Functional neuroimaging in psychiatry
Authors: Fu Cynthia H. Y. , McGuire Philip K.
Published: July 2002

Functional neuroimaging is one of the most powerful means available for investigating the pathophysiology of psychiatric disorders. In this review, we shall focus on the different ways that it can be employed to this end, describing the major findings in the field in the context of different methodological approaches. We will also discuss practical issues that are particular to studying psychiatric disorders and the potential contribution of functional neuroimaging to future psychiatric research.
The water–water cycle as alternative photon and electron sinks
Authors: Asada Kozi
Published: July 2002

The water–water cycle in chloroplasts is the photoreduction of dioxygen to water in photosystem I (PS I) by the electrons generated in photosystem II (PS II) from water. In the water–water cycle, the rate of photoreduction of dioxygen in PS I is several orders of magnitude lower than those of the disproportionation of superoxide catalysed by superoxide dismutase, the reduction of hydrogen peroxide to water catalysed by ascorbate peroxidase, and the reduction of the resulting oxidized forms of ascorbate by reduced ferredoxin or catalysed by either dehydroascorbate reductase or monodehydroascorbate reductase. The water–water cycle therefore effectively shortens the lifetimes of photoproduced superoxide and hydrogen peroxide to suppress the production of hydroxyl radicals, their interactions with the target molecules in chloroplasts, and resulting photoinhibition. When leaves are exposed to photon intensities of sunlight in excess of that required to support the fixation of CO
2
, the intersystem electron carriers are over–reduced, resulting in photoinhibition. Under such conditions, the water–water cycle not only scavenges active oxygens, but also safely dissipates excess photon energy and electrons, in addition to downregulation of PS II and photorespiration. The dual functions of the water–water cycle for protection from photoinhibition under photon excess stress are discussed, along with its functional evolution.
The murine winged helix transcription factors, Foxc1 and Foxc2, are both required for cardiovascular development and somitogenesis
Authors: Kume Tsutomu , Jiang HaiYan , Topczewska Jolanta M. , Hogan Brigid L.M.
Published: July 2002

The murine Foxc1/Mf1 and Foxc2/Mfh1 genes encode closely related forkhead/winged helix transcription factors with overlapping expression in the forming somites and head mesoderm and endothelial and mesenchymal cells of the developing heart and blood vessels. Embryos lacking either Foxc1 or Foxc2, and most compound heterozygotes, die pre- or perinatally with similar abnormal phenotypes, including defects in the axial skeleton and cardiovascular system. However, somites and major blood vessels do form. This suggested that the genes have similar, dose-dependent functions, and compensate for each other in the early development of the heart, blood vessels, and somites. In support of this hypothesis, we show here that compound Foxc1; Foxc2 homozygotes die earlier and with much more severe defects than single homozygotes alone. Significantly, they have profound abnormalities in the first and second branchial arches, and the early remodeling of blood vessels. Moreover, they show a complete absence of segmented paraxial mesoderm, including anterior somites. Analysis of compound homozygotes shows thatFoxc1 and Foxc2 are both required for transcription in the anterior presomitic mesoderm of paraxis, Mesp1,Mesp2, Hes5, and Notch1, and for the formation of sharp boundaries of Dll1, Lfng, and ephrinB2expression. We propose that the two genes interact with the Notch signaling pathway and are required for the prepatterning of anterior and posterior domains in the presumptive somites through a putative Notch/Delta/Mesp regulatory loop.
A Human cDNA Expression Library in Yeast Enriched for Open Reading Frames
Authors: Holz Caterina , Lueking Angelika , Bovekamp Lara , Gutjahr Claudia , Bolotina Natalia , Lehrach Hans , Cahill Dolores J.
Published: July 2002

We developed a high-throughput technique for the generation of cDNA libraries in the yeast Saccharomyces cerevisiae which enables the selection of cloned cDNA inserts containing open reading frames (ORFs). For direct screening of random-primed cDNA libraries, we have constructed a yeast shuttle/expression vector, the so-called ORF vector pYEXTSH3, which allows the enriched growth of protein expression clones. The selection system is based on the HIS3 marker gene fused to the C terminus of the cDNA insert. The cDNAs cloned in-frame result in histidine prototrophic yeast cells growing on minimal medium, whereas clones bearing the vector without insert or out-of-frame inserts should not grow on this medium. A randomly primed cDNA library from human fetal brain tissue was cloned in this novel vector, and using robot technology the selected clones were arrayed in microtiter plates and were analyzed by sequencing and for protein expression. In the constructed cDNA expression library, about 60% of clones bear an insert in the correct reading frame. In comparison to unselected libraries it was possible to increase the clones with inserts in the correct reading frame more than fourfold, from 14% to 60%. With the expression system described here, we could avoid time-consuming and costly techniques for identification of clones expressing protein by using antibody screening on high-density filters and subsequently rearraying the selected clones in a new “daughter” library. The advantage of this ORF vector is that, in a one-step screening procedure, it allows the generation of expression libraries enriched for clones with correct reading frames as sources of recombinant proteins.
Side‐chain modeling with an optimized scoring function
Authors: Liang Shide , Grishin Nick V.
Published: July 2002

Modeling side‐chain conformations on a fixed protein backbone has a wide application in structure prediction and molecular design. Each effort in this field requires decisions about a rotamer set, scoring function, and search strategy. We have developed a new and simple scoring function, which operates on side‐chain rotamers and consists of the following energy terms: contact surface, volume overlap, backbone dependency, electrostatic interactions, and desolvation energy. The weights of these energy terms were optimized to achieve the minimal average root mean square (rms) deviation between the lowest energy rotamer and real side‐chain conformation on a training set of high‐resolution protein structures. In the course of optimization, for every residue, its side chain was replaced by varying rotamers, whereas conformations for all other residues were kept as they appeared in the crystal structure. We obtained prediction accuracy of 90.4% for χ1, 78.3% for χ1 + 2, and 1.18 Å overall rms deviation. Furthermore, the derived scoring function combined with a Monte Carlo search algorithm was used to place all side chains onto a protein backbone simultaneously. The average prediction accuracy was 87.9% for χ1, 73.2% for χ1 + 2, and 1.34 Å rms deviation for 30 protein structures. Our approach was compared with available side‐chain construction methods and showed improvement over the best among them: 4.4% for χ1, 4.7% for χ1 + 2, and 0.21 Å for rms deviation. We hypothesize that the scoring function instead of the search strategy is the main obstacle in side‐chain modeling. Additionally, we show that a more detailed rotamer library is expected to increase χ1 + 2 prediction accuracy but may have little effect on χ1 prediction accuracy.
Automated computerized scheme for distinction between benign and malignant solitary pulmonary nodules on chest images
Authors: Aoyama Masahito , Li Qiang , Katsuragawa Shigehiko , MacMahon Heber , Doi Kunio
Published: July 2002

A novel automated computerized scheme has been developed to assist radiologists for their distinction between benign and malignant solitary pulmonary nodules on chest images. Our database consisted of 55 chest radiographs (33 primary lung cancers and 22 benign nodules). In this method, the location of a nodule was indicated first by a radiologist. The difference image with a nodule was produced by use of filters and then represented in a polar coordinate system. The nodule was segmented automatically by analysis of contour lines of the gray‐level distribution based on the polar‐coordinate representation. Two clinical parameters (age and sex) and 75 image features were determined from the outline, the image, and histogram analysis for inside and outside regions of the segmented nodule. Linear discriminant analysis (LDA) and knowledge about benign and malignant nodules were used to select initial feature combinations. Many combinations for subgroups of 77 features were evaluated as input to artificial neural networks (ANNs). The performance of ANNs with the selected 7 features by use of the round‐robin test showed which was greater than obtained previously with the manual method The performance of LDA was slightly improved compared to that of ANNs and was greater than that of the manual method reported previously The high level of its performance indicates the potential usefulness of this automated computerized scheme in assisting radiologists as a second opinion for distinction between benign and malignant solitary pulmonary nodules on chest images.
Classical analog of electromagnetically induced transparency
Authors: Garrido Alzar C. L. , Martinez M. A. G. , Nussenzveig P.
Published: July 2002

We present a classical analog of electromagnetically induced transparency (EIT). In a system of just two coupled harmonic oscillators subject to a harmonic driving force, we reproduce the phenomenology observed in EIT. We also describe a simple experiment with two linearly coupled RLC circuits which can be incorporated into an undergraduate laboratory.
Anamorphic images
Authors: Hunt J. L. , Nickel B. G. , Gigault Christian
Published: July 2002

Anamorphic images are images of objects which have been distorted in some way so that only by viewing them from some particular direction or in some particular optical surface do they become recognizable. Artists have been fascinated with these transformations since the 16th century, but there seems to be no modern explication of the mathematics of these transforms. In this paper we describe the most common of the anamorphic images found in art and derive the transform equations for plane, conical, and cylindrical cases. With these equations it is possible to analyze early anamorphs, and with computation to create modern ones with ease.
Time normalization of voice signals using functional data analysis
Authors: Lucero Jorge C. , Koenig Laura L.
Published: July 2002

The harmonics-to-noise ratio (HNR) has been used to quantify the waveform irregularity of voice signals [Yumoto et al., J. Acoust. Soc. Am. 71, 1544–1550 (1982)]. This measure assumes that the signal consists of two components: a harmonic component, which is the common pattern that repeats from cycle-to-cycle, and an additive noise component, which produces the cycle-to-cycle irregularity. It has been shown [J. Qi, J. Acoust. Soc. Am. 92, 2569–2576 (1992)] that a valid computation of the HNR requires a nonlinear time normalization of the cycle wavelets to remove phase differences between them. This paper shows the application of functional data analysis to perform an optimal nonlinear normalization and compute the HNR of voice signals. Results obtained for the same signals using zero-padding, linear normalization, and dynamic programming algorithms are presented for comparison. Functional data analysis offers certain advantages over other approaches: it preserves meaningful features of signal shape, produces differentiable results, and allows flexibility in selecting the optimization criteria for the wavelet alignment. An extension of the technique for the time normalization of simultaneous voice signals (such as acoustic, EGG, and airflow signals) is also shown. The general purpose of this article is to illustrate the potential of functional data analysis as a powerful analytical tool for studying aspects of the voice production process.
Concurrent vowel identification. I. Effects of relative amplitude and F difference
Authors: de Cheveigné Alain , Kawahara Hideki , Tsuzaki Minoru , Aikawa Kiyoaki
Published: July 2002

Subjects identified concurrent synthetic vowel pairs that differed in relative amplitude and fundamental frequency (F0). Subjects were allowed to report one or two vowels for each stimulus, rather than forced to report two vowels as was the case in previously reported experiments of the same type. At all relative amplitudes, identification was better at a fundamental frequency difference (ΔF0) of 6% than at 0%, but the effect was larger when the target vowel amplitude was below that of the competing vowel (−10 or −20 dB). The existence of a ΔF0 effect when the target is weak relative to the competing vowel is interpreted as evidence that segregation occurs according to a mechanism of cancellation based on the harmonic structure of the competing vowel. Enhancement of the target based on its own harmonic structure is unlikely, given the difficulty of estimating the fundamental frequency of a weak target. Details of the pattern of identification as a function of amplitude and vowel pair were found to be incompatible with a current model of vowel segregation.
Lamb waves generated by complex harmonic inhomogeneous plane waves
Authors: Poncelet O. , Deschamps M.
Published: July 2002

This paper presents a theoretical investigation of the generation of Lamb waves inside an immersed plate by complex harmonic inhomogeneous plane waves. Whereas free modes of a fluid-loaded plate are classically assumed to be formed by inhomogeneous plane waves with real frequency (leaky waves), the nature of Lamb waves is searched in this study in terms of combinations of transient inhomogeneous plane waves characterized by a complex slowness vector and a complex frequency. It is shown that dispersion curves of transient Lamb waves (only the frequency is complex) can be very different from the dispersion curves of permanent leaky waves (only the slowness is complex), especially for the A0 and S0 modes for which there exists a cut-off frequency beyond which these modes do not exist. In the general case, when both the frequency and the slowness are complex, connections between modes clearly appear from the calculation of dispersion curves.
Developmental changes in the precedence effect: Estimates of minimum audible angle
Authors: Litovsky Ruth Y.
Published: July 2002

The precedence effect refers to an auditory phenomenon which occurs when two similar sounds are presented from different locations with a brief delay, and only one sound is heard whose perceived location is dominated by the first source. Although the lagging source is not localized as an independent event, under some conditions, adults are able to extract its directional cues. Developmental studies suggest that this ability changes during development. However, those studies have used stimulus configurations which minimize the measurement of that ability. In the present study adults were first tested under several conditions, and the one which produced optimal performance was chosen for testing children. Using the minimum audible angle (MAA) task in the azimuthal plane, performance was compared for a single-source condition and two precedence conditions: in lag discrimination the lagging source changed location while the lead remained at midline, and in lead discrimination the reverse occurred. Subjects were 18 months old, 5 years old, and adult. Significant improvements in MAA occurred with an increase in age, especially in the precedence conditions. Within each group, performance was significantly better in single-source condition, followed by the lead and the lag discrimination.
Electromagnetic exposure safety of the Carstens Aerticulograph AG100
Authors: Hasegawa-Johnson Mark
Published: July 2002

Extremely strong magnetic fields at the frequencies used in an electromagnetic articulometer (EMA) system may pose a risk to the health of a subject. To avoid such risks, the field strengths produced by any EMA system should be measured, and compared to published permissible exposure standards. This Letter reports measurements of the 2–50 kHz magnetic field strength of the Carstens Articulograph AG100. The measured field strength (35 μT at a distance of 7.5 cm) is permissible under local standards in Austria, Germany, the UK, and the USA (except Massachusetts), but may be impermissible under the 1995 European Community Prestandard, and in Canada.
Computational model of an individual head-related transfer function using the BEM
Authors: Katz Brian F. G.
Published: July 2002

The head-related transfer function (HRTF), determined by the complex geometry of the pinnae and head, is the primary research and commercial tool for exploring and exploiting 3-D auralization and auditory localization. Research into the determining characteristics of the HRTF is difficult, as the anatomical variations between individuals are many. These variations make comparisons between individuals less than ideal for determining the relation between structure of the individual and components of the HRTF. This paper will discuss an investigation into the use of a geometrical model of an individual to calculate the HRTF. The calculation utilizes the boundary element method (BEM). As a tool, the use of a computer model allows for selected variations in the individual’s anatomy and direct observation of the results, a difficult task in experimental measures. Previous work by the author discussed the variability in experimental measurement techniques of the HRTF. Comparisons are made between the model results and these HRTF measurements for the same individual. Some preliminary variations to the model and their effects are also discussed. Computational results show good agreement with the general trends of the measurements and the frequency limitations of the computation. a)Currently at Artec Consultants, Inc., 114 W. 26th St., New York, NY 10001.
Perception of complex tones and its analogy to echo spectral analysis in the bat,Megaderma lyra
Authors: Krumbholz Katrin , Schmidt Sabine
Published: July 2002

The gleaning bat Megaderma lyra emits broadband echolocation sounds consisting of multiple frequency components. The present study investigates into which perceptual qualities the spectral characteristics of echoes may be translated in the auditory system of M. lyra. Three bats were trained in a 2-AFC behavioral experiment to classify nine complex tones, which spectrally resembled M. lyra’s sonar calls, into two perceptual categories. Then the bats’ spontaneous responses to unknown complex tones were recorded. The results show that the animals based their classifications of the complex tones on a sound quality which was mediated by their broadband frequency spectra. The bats used the training stimuli as spectral templates and classified the test stimuli according to their broadband spectral similarity with the learned patterns. Assuming that passive hearing and echo processing are governed by similar perceptual qualities and subject to similar limitations, the perceptual mode which was used by the bats to compare the multicomponent spectral patterns in the reported experiments could serve as a powerful tool for the spectral analysis of M. lyra’s multicomponent echoes. The analogy between the perception of complex tones and echo spectral analysis in M. lyra is theoretically elaborated in the “formant-mode” model.
Tinnitus and 2f1−f2 distortion product otoacoustic emissions following salicylate overdose
Authors: Janssen Thomas , Boege Paul , Oestreicher Elmar , Arnold Wolfgang
Published: July 2002

A 22-year-old woman consumed approximately 10 g of salicylate with suicidal intent. She had a severe hearing loss and a strong tinnitus within 22 h of the overdose, and then 24 h later a subsequent hearing restoration and tinnitus abolishment. Transiently evoked otoacoustic emissions (TEOAEs) and 2f1−f2 distortion product otoacoustic emissions (DPOAEs) were measured in both states. In the state of intoxication DPOAEs could be recorded well in the frequency range that corresponded to the appearance of the tinnitus despite the 50-dB hearing loss. The corresponding DPOAE I/O-functions were linearized, indicating loss of outer hair cell compression. After recovery, DPOAE level and DPOAE growth were within the normal range and showed normal physiological compression. The TEOAEs were missing in the acute state of intoxication. This case supports the hypothesis that aspirin-induced tinnitus is generated at the outer hair cell level. Whereas TEOAEs only give evidence that something might have changed in the cochlea, DPOAEs are a more useful and robust quantitative indicator of the underlying mechanism of some forms of cochlear tinnitus.