bluuebunny/crossref_metadata_2025 huggingface dataset:
Conformation of coenzyme pyrroloquinoline quinone and role of Ca
2+
in the catalytic mechanism of quinoprotein methanol dehydrogenase
Authors: Zheng Ya-Jun , Bruice Thomas C.
Published: July 2002

The
ab initio
structures of
2,7,9-tricarboxypyrroloquinoline quinone (PQQ), semiquinone (PQQH), and
dihydroquinone (PQQH2) have been determined and compared with
ab
initio
structures of the (PQQ)Ca
2+
,
(PQQH)Ca
2+
, and (PQQH2)Ca
2+
complexes as well
as the x-ray structure of (PQQ)Ca
2+
bound at the active
site of the methanol dehydrogenase (MDH) of methyltropic bacteria.
Plausible mechanisms for the MDH oxidation of methanol involving the
(PQQ)Ca
2+
complex are explored via
ab initio
computations and discussed. Considering the reaction of methanol with
PQQ in the absence of Ca
2+
, nucleophilic addition of
methanol to the PQQ C-5 carbonyl followed by a retro-ene elimination is
deemed unlikely due to large energy barrier. A much more favorable
disposition of the methanol C-5 adduct to provide formaldehyde involves
proton ionization of the intermediate followed by elimination of
methoxide concerted with hydride transfer to the oxygen of the C-4
carbonyl. Much the same transition state is reached if one searches for
the transition state beginning with
Asp-303–CO
2
−
general-base removal of the methanol
proton of the (PQQ)Ca
2+
O(H)CH
3
complex
concerted with hydride transfer to the oxygen at C-4. For such a
mechanism the role of the Ca
2+
moiety would be to
(
i
) contribute to the formation of the ES complex
(
ii
) provide a modest decrease in the pK
a
of
methanol substrate,; and (
iii
) polarize the oxygen at
C-5.
Expression of the mousecerberus-related gene,Cerr1, suggests a role in anterior neural induction and somitogenesis
Authors: Shawlot William , Deng Jian Min , Behringer Richard R.
Published: July 2002

TheXenopus cerberusgene encodes a secreted factor that is expressed in the anterior endomesoderm of gastrula stage embryos and can induce the formation of ectopic heads when its mRNA is injected intoXenopusembryos [Bouwmeester, T., Kim, S., Lu, B. & De Robertis, E. M. (1996)Nature (London)382, 595–601]. Here we describe the existence of acerberus-related gene,Cerr1, in the mouse.Cerr1encodes a putative secreted protein that is 48% identical tocerberusover a 110-amino acid region. Analysis of a mouse interspecific backcross panel demonstrated thatCerr1mapped to the central portion of mouse chromosome 4. In early gastrula stage mouse embryos,Cerr1is expressed in the anterior visceral endoderm and in the anterior definitive endoderm. In somite stage embryos,Cerr1expression is restricted to the most recently formed somites and in the anterior presomitic mesoderm. Germ layer explant recombination assays demonstrated thatCerr1-expressing somitic-presomitic mesoderm, but not olderCerr1-nonexpressing somitic mesoderm, was able to mimic the anterior neuralizing ability of anterior mesendoderm and maintainOtx2expression in competent ectoderm. In mostLim1−/− headless embryos,Cerr1expression in the anterior endoderm was weak or absent. These results suggest thatCerr1may play a role in anterior neural induction and somite formation during mouse development.
A novel glutamine–RNA interaction identified by screening libraries in mammalian cells
Authors: Tan Ruoying , Frankel Alan D.
Published: July 2002

The arginine-rich motif provides a versatile framework for RNA recognition in which few amino acids other than arginine are needed to mediate specific binding. Using a mammalian screening system based on transcriptional activation by HIV Tat, we identified novel arginine-rich peptides from combinatorial libraries that bind tightly to the Rev response element of HIV. Remarkably, a single glutamine, but not asparagine, within a stretch of polyarginine can mediate high-affinity binding. These results, together with the structure of a Rev peptide-Rev response element complex, suggest that the carboxamide groups of glutamine or asparagine are well-suited to hydrogen bond to G-A base pairs and begin to establish an RNA recognition code for the arginine-rich motif. The screening approach may provide a relatively general method for screening expression libraries in mammalian cells.
Leukotriene D
4
and cystinyl-bis-glycine metabolism in membrane-bound dipeptidase-deficient mice
Authors: Habib Geetha M. , Shi Zheng-Zheng , Cuevas Allan A. , Guo Qiuxia , Matzuk Martin M. , Lieberman Michael W.
Published: July 2002

We have developed mice deficient in membrane-bound dipeptidase (MBD, EC
3.4.13.19
), the enzyme believed to be responsible for the conversion of leukotriene D
4
(LTD
4
) to leukotriene E
4
(LTE
4
). The MBD mutation generated by us was demonstrated to be a null mutation by Northern blot analysis and the absence of β-lactamase activity in lung, kidney, small intestine, and heart. MBD gene deletion had no effect on viability or fertility. The mutant mice retain partial ability to convert LTD
4
to LTE
4
, ranging from 80–90% of the wild-type values in small intestine and liver to 16% in kidney and 40% in lung, heart, and pancreas. MBD is also believed to function consecutively after γ-glutamyl transpeptidase to cleave cystinyl-bis-glycine (cys-bis-gly) generated from glutathione cleavage. Our data indicate that kidney homogenates from MBD-deficient mice retain ∼40% of their ability to cleave cys-bis-gly, consistent with only modest elevations (3–5-fold) of cys-bis-gly in urine from MBD-deficient mice. These observations demonstrate that the conversion of LTD
4
to LTE
4
and the degradation of cys-bis-gly are catalyzed by at least two alternative pathways (one of which is MBD) that complement each other to varying extents in different tissues.
C-terminal DNA binding stimulates N-terminal phosphorylation of the outer membrane protein regulator OmpR from
Escherichia coli
Authors: Ames Sharla K. , Frankema Nanja , Kenney Linda J.
Published: July 2002

Expression of the porin genes of
Escherichia coli
is regulated in part by the osmolarity of the growth medium. The process is controlled by the histidine kinase EnvZ and the response regulator OmpR. We have previously shown that phosphorylation of OmpR increases its affinity for the upstream regulatory regions of
ompF
and
ompC
. We now report that, in the presence of DNA, there is a dramatic stimulation in the level of phospho-OmpR. This effect is independent of the source of phosphorylation, i.e., stimulation of phosphorylation is observed with a small phosphorylating agent such as acetyl phosphate or with protein-catalyzed phosphorylation by the kinase EnvZ. The dephosphorylation rate of phospho-OmpR is affected only slightly by the presence of DNA; thus, the increased level is largely caused by an increased rate of phosphorylation. Stimulation of phosphorylation requires specific binding of DNA by OmpR. Occupancy of the DNA binding domain exposes a trypsin cleavage site in the linker, which connects the phosphorylation domain with the DNA binding domain. Our results indicate that when DNA binds in the C terminus, it enhances phosphorylation in the N terminus, and the linker undergoes a conformational change. A generalized mechanism involving a four-state model for response regulators is proposed.
Drosophila
head segmentation factor Buttonhead interacts with the same TATA box-binding protein-associated factors and
in vivo
DNA targets as human Sp1 but executes a different biological program
Authors: Schöck Frieder , Sauer Frank , Jäckle Herbert , Purnell Beverly A.
Published: July 2002

The
Drosophila
gene buttonhead (
btd
) is required for the establishment of three embryonic head segments. It encodes a zinc-finger-type transcription factor expressed in the corresponding head segment anlagen in the blastoderm stage embryo. The DNA-binding properties of the
btd
protein (BTD) are indistinguishable from the human transcription factor Sp1. Furthermore, BTD and Sp1 are capable of activating transcription in transfected cultured cells through interaction with the same DNA target sites. Herein we show that BTD and Sp1 functionally interact with the same TATA box-binding protein-associated factors and support
in vitro
transcription activation through these contacts. Transgene expression of BTD results in the rescue of the head segments that fail to develop in
btd
mutant embryos, whereas Sp1 or Sp1 containing the zinc finger region of BTD rescues mandibular segment development. The results suggest that BTD contains functional domains other than an equivalent DNA-binding region and interaction sites of the TATA box-binding protein-associated factors, which are necessary to establish head segments that fail to develop in response to Sp1.
Building the Road to the Temple: Religion and National Revival in the Chuvash Republic
Authors: Vovina Olessia P.
Published: July 2002

In June 1996, the newly reconstructed waterfront in Cheboksary, the capital of the Chuvash Republic, was officially opened with a formal ceremony led by the President of the Republic, Nikolai Fedorov, and attended by the Patriarch of All Russia, Alexei II. “We have built a road to the temple,” the President declared. In a literal sense, he was referring to the construction of an embankment leading to one of the city's oldest Orthodox churches. But his phrase had a symbolic meaning as well. Metaphorically the phrase equated the physical reconstruction of the capital city with the cultural and spiritual revival of the Chuvash nation.
Expression of a P-selectin Ligand in Zona Pellucida of Porcine Oocytes and P-selectin on Acrosomal Membrane of Porcine Sperm Cells. Potential Implications for Their Involvement in Sperm–Egg Interactions
Authors: Geng Jian-Guo , Raub Thomas J. , Baker Carolyn A. , Sawada Geri A. , Ma Li , Elhammer Åke P.
Published: July 2002

The selectin family of cell adhesion molecules mediates initial leukocyte adhesion to vascular endothelial cells at sites of inflammation. O-glycan structural similarities between oligosaccharides from human leukocyte P-selectin glycoprotein ligand-1 (PSGL-1) and from zona pellucida glycoproteins of porcine oocytes indicate the possible existence of a P-selectin ligand in the zona pellucida. Here, using biochemical as well as morphological approaches, we demonstrate that a P-selectin ligand is expressed in the porcine zona pellucida. In addition, a search for a specific receptor for this ligand leads to the identification of P-selectin on the acrosomal membrane of porcine sperm cells. In vitro binding of porcine acrosome-reacted sperm cells to oocytes was found to be Ca2+ dependent and inhibitable with either P-selectin, P-selectin receptor–globulin, or leukocyte adhesion blocking antibodies against P-selectin and PSGL-1. Moreover, porcine sperm cells were found to be capable of binding to human promyeloid cell line HL-60. Taken together, our findings implicate a potential role for the oocyte P-selectin ligand and the sperm P-selectin in porcine sperm– egg interactions.
The hrp23 Protein in the Balbiani Ring Pre-mRNP Particles Is Released Just before or at the Binding of the Particles to the Nuclear Pore Complex
Authors: Sun Xin , Alzhanova-Ericsson Alla T. , Visa Neus , Aissouni Youssef , Zhao Jian , Daneholt Bertil
Published: July 2002

Balbiani ring (BR) pre-mRNP particles reside in the nuclei of salivary glands of the dipteran Chironomus tentans and carry the message for giant-sized salivary proteins. In the present study, we identify and characterize a new protein component in the BR ribonucleoprotein (RNP) particles, designated hrp23. The protein with a molecular mass of 20 kD has a single RNA-binding domain and a glycine-arginine-serine–rich auxiliary domain. As shown by immunoelectron microscopy, the hrp23 protein is added to the BR transcript concomitant with transcription, is still present in the BR particles in the nucleoplasm, but is absent from the BR particles that are bound to the nuclear pore complex or are translocating through the central channel of the complex. Thus, hrp23 is released just before or at the binding of the particles to the nuclear pore complex. It is noted that hrp23 behaves differently from two other BR RNP proteins earlier studied: hrp36 and hrp45. These proteins both reach the nuclear pore complex, and hrp36 even accompanies the RNA into the cytoplasm. It is concluded that each BR RNA-binding protein seems to have a specific flow pattern, probably related to the particular role of the protein in gene expression.
A Cell-Free Assay System for β-Catenin Signaling That Recapitulates Direct Inductive Events in the Early Xenopus laevis Embryo
Authors: Nelson Richard W. , Gumbiner Barry M.
Published: July 2002

In vertebrate embryos, signaling via the β-catenin protein is known to play an essential role in the induction of the dorsal axis. In its signaling capacity, β-catenin acts directly to affect target gene transcription, in concert with transcription factors of the TCF/LEF family. We have developed a cell-free in vitro assay for β-catenin signaling activity that utilizes transcriptionally active nuclei and cytoplasm from cleavage-blocked Xenopus laevis embryos. Under these assay conditions, we demonstrate that either addition of β-catenin protein or upstream activation of the β-catenin signaling pathway can induce the expression of developmentally relevant target genes. Addition of exogenous β-catenin protein induced expression of Siamois, XTwin, Xnr3, and Cerberus mRNAs in a protein synthesis independent manner, whereas a panel of other Spemann organizer-specific genes did not respond to β-catenin. Lithium induction of the β-catenin signaling pathway, which is thought to cause β-catenin accumulation by inhibiting its proteasome-dependent degradation, caused increased expression of Siamois in a protein synthesis independent fashion. This result suggests that β-catenin derived from a preexisting pool can be activated to signal, and that accumulation of this activated form does not require ongoing synthesis. Furthermore, activation of the signaling pathway with lithium did not detectably alter cytoplasmic β-catenin levels and was insensitive to inhibition of the proteasome- dependent degradation pathway. Taken together, these results suggest that activation of β-catenin signaling by lithium in this system may occur through a distinct activation mechanism that does not require modulation of levels through regulation of proteasomal degradation.
Mek and Cdc2 Kinase Are Sequentially Required for Golgi Disassembly in Mdck Cells by the MitoticXenopusExtracts
Authors: Kano Fumi , Takenaka Katsuya , Yamamoto Akitsugu , Nagayama Kuniaki , Nishida Eisuke , Murata Masayuki
Published: July 2002

At the onset of mitosis, the Golgi apparatus, which consists of several cisternae, disperses throughout the cell to be partitioned into daughter cells. The molecular mechanisms of this process are now beginning to be understood. To investigate the biochemical requirements and kinetics of mitotic Golgi membrane dynamics in polarized cells, we have reconstituted the disassembly of the Golgi apparatus by introducing Xenopus egg extracts into permeabilized Mardin-Darby canine kidney (MDCK) cells. We used green fluorescence protein (GFP)-tagged galactosyltransferase-expressing MDCK cells to analyze the morphological changes of the Golgi membrane in the semi-intact system. Analyses by fluorescence and electron microscopies showed that the Golgi disassembly can be dissected into two elementary processes morphologically. In the first process, the perinuclear Golgi stacks break into punctate structures, intermediates, which are comprised of mini-stacks of cisternae associating with apical microtubule networks. In the second process, the structures fragment more thoroughly or substantially relocate to the ER. Our analyses further showed that cdc2 kinase and mitogen-activated protein kinase kinase (MAPKK = MEK) are differently involved in these two processes: the first process is mainly regulated by MEK and the second mainly by cdc2.
Experimental Transmission of Kaposi's Sarcoma–Associated Herpesvirus (Kshv/Hhv-8) to Scid-Hu Thy/Liv Mice
Authors: Dittmer D. , Stoddart C. , Renne R. , Linquist-Stepps V. , Moreno M.E. , Bare C. , McCune J.M. , Ganem D.
Published: July 2002

Kaposi's sarcoma–associated herpesvirus (KSHV/HHV-8) is a novel human lymphotropic herpesvirus linked to several human neoplasms. To date, no animal model for infection by this virus has been described. We have examined the susceptibility of C.B-17 scid/scid mice implanted with human fetal thymus and liver grafts (SCID-hu Thy/Liv mice) to KSHV infection. KSHV virions were inoculated directly into the implants, and viral DNA and mRNA production was assayed using real-time quantitative polymerase chain reaction. This revealed a biphasic infection, with an early phase of lytic replication accompanied and followed by sustained latency. Ultraviolet irradiation of the inoculum abolished all DNA- and mRNA-derived signals, and infection was inhibited by ganciclovir. Viral gene expression was most abundant in CD19+ B lymphocytes, suggesting that this model faithfully mimics the natural tropism of this virus. Short-term coinfection with HIV-1 did not alter the course of KSHV replication, nor did KSHV alter levels of HIV-1 p24 during the acute phase of the infection. Although no disease was evident in infected animals, SCID-hu Thy/Liv mice should allow the detailed study of KSHV tropism, latency, and drug susceptibility.
Deficiency in the Transcription Factor Interferon Regulatory Factor (Irf)-2 Leads to Severely Compromised Development of Natural Killer and T Helper Type 1 Cells
Authors: Lohoff Michael , Duncan Gordon S. , Ferrick David , Mittrücker Hans-Willi , Bischof Susi , Prechtl Stefan , Röllinghoff Martin , Schmitt Edgar , Pahl Andreas , Mak Tak W.
Published: July 2002

Interferon (IFN) regulatory factor (IRF)-2 was originally described as an antagonist of IRF-1–mediated transcriptional regulation of IFN-inducible genes. IRF-1−/− mice exhibit defective T helper type 1 (Th1) cell differentiation. We have used experimental leishmaniasis to show that, like IRF-1−/− mice, IRF-2−/− mice are susceptible to Leishmania major infection due to a defect in Th1 differentiation. Natural killer (NK) cell development is compromised in both IRF-1−/− and IRF-2−/− mice, but the underlying mechanism differs. NK (but not NK+ T) cell numbers are decreased in IRF-2−/− mice, and the NK cells that are present are immature in phenotype. Therefore, like IRF-1, IRF-2 is required for normal generation of Th1 responses and for NK cell development in vivo. In this particular circumstance the absence of IRF-2 cannot be compensated for by the presence of IRF-1 alone. Mechanistically, IRF-2 may act as a functional agonist rather than antagonist of IRF-1 for some, but not all, IFN-stimulated regulatory element (ISRE)-responsive genes.
Essential Requirement for C-KIT and Common γ Chain in Thymocyte Development Cannot Be Overruled by Enforced Expression of Bcl-2
Authors: Rodewald Hans-Reimer , Waskow Claudia , Haller Corinne
Published: July 2002

The thymus in mice lacking both the receptor tyrosine kinase c-kit and the common cytokine receptor γ chain (γc) is alymphoid because these receptors provide essential signals at the earliest stages of thymocyte development. The signals transduced by these receptors potentially regulate proliferation, survival, or differentiation, but the contribution of each receptor to distinct intracellular signaling cascades is only poorly defined. Here, we have examined whether enforced expression of Bcl-2 can rescue thymocyte development in c-kit and γc single or double mutant mice. A bcl-2 transgene (Eμ-bcl-2-25; expressed in the T cell lineage) was introduced into (a) c-kit and γc wild-type (c-kit+γc+bcl+), (b) c-kit–deficient (c-kit−γc+bcl+), (c) γc-deficient (c-kit+γc−bcl+), or (d) c-kit and γc double-deficient mice (c-kit−γc−bcl+). The bcl-2 transgene was functionally active in wild-type and c-kit or γc single mutants, as it promoted survival of ex vivo isolated thymocytes, including pro-T cells. In vivo, however, transgenic Bcl-2 did not release T cell precursors from their phenotypic block and failed to increase progenitor or total thymocyte cellularity in c-kit or γc single or double mutants. These data argue strongly against a role for Bcl-2 as a key mediator in signaling pathways linked to cytokine and growth factor receptors driving early thymocyte development.
Subconductance States of a Mutant NMDA Receptor Channel Kinetics, Calcium, and Voltage Dependence
Authors: Premkumar Louis S. , Qin Feng , Auerbach Anthony
Published: July 2002

The kinetic properties of main and subconductance states of a mutant mouse N-methyl-d-aspartate (NMDA) receptor channel were examined. Recombinant receptors made of ζ-ε2 (NR1-NR2B) subunits having asparagine-to-glutamine mutations in the M2 segment (ζN598Q /ε2N589Q) were expressed in Xenopus oocytes. Single channel currents recorded from outside-out patches were analyzed using hidden Markov model techniques. In Ca2+-free solutions, an open receptor channel occupies a main conductance (93 pS) and a subconductance (62 pS) with about equal probability. There are both brief and long-lived subconductance states, but only a single main level state. At −80 mV, the lifetime of the main and the longer-lived sub level are both ∼3.3 ms. The gating of the pore and the transition between conductance levels are essentially independent processes. Surprisingly, hyperpolarization speeds both the sub-to-main and main-to-sub transition rate constants (∼120 mV/e-fold change), but does not alter the equilibrium occupancies. Extracellular Ca2+ does not influence the transition rate constants. We conclude that the subconductance levels arise from fluctuations in the energetics of ion permeation through a single pore, and that the voltage dependence of these fluctuations reflects the modulation by the membrane potential of the barrier between the main and subconductance conformations of the pore.
On the Mechanisms Whereby Temperature Affects Excitation-Contraction Coupling in Smooth Muscle
Authors: Burdyga Theodor V. , Wray Susan
Published: July 2002

Moderate cooling of smooth muscle can modulate force production and may contribute to pathophysiological conditions, but the mechanisms underlying its effects are poorly understood. Interestingly, cooling increases force in rat ureter, but decreases it in guinea pigs. Therefore, this study used ureteric smooth muscle as a model system to elucidate the mechanisms of the effects of cooling on excitation-contraction coupling. Simultaneous recordings of force, intracellular [Ca2+], and electrical activity were made in intact ureter and ionic currents measured in isolated cells. The increase in force amplitude in rat ureter with cooling was found to be due to a significant increase in the duration of the Ca2+ transient. This in turn was due to a marked prolongation of the action potential. In guinea pigs, both these parameters were much less affected by cooling. Examination of membrane currents revealed that differences in ion channel contribution to the action potential underlie these differences. In particular, cooling potentiated Ca2+-activated Cl− currents, which are present in rat but not guinea pig ureteric smooth muscle, and prolonged the plateau of the action potential and Ca2+ entry. The force-Ca2+ relationship revealed that the increased duration of the Ca2+ transient was sufficient in the rat, but not in the guinea pig, to overcome kinetic lags produced in both species by cooling and potentiate force. Ca2+ entry and release processes were largely temperature-insensitive, but the rate of relaxation was very temperature-sensitive. Effects of cooling on myosin light chain phosphatase, confirmed in experiments using calyculin A, appear to be the predominant mechanisms affecting relaxation. Thus, smooth muscle is diverse in its response to temperature, even when experimental variables, such as the mode of stimulation, are removed. Although the biochemical and mechanical events accompanying contraction are likely to be affected in similar ways by temperature, differences in electrical events lead to subsequent differences in these processes between smooth muscles.
Voltage-dependence of Ion Permeation in Cyclic GMP–gated Ion Channels Is Optimized for Cell Function in Rod and Cone Photoreceptors
Authors: Ohyama Tsuyoshi , Picones Arturo , Korenbrot Juan I.
Published: July 2002

The kinetics of the photocurrent in both rod and cone retinal photoreceptors are independent of membrane voltage over the physiological range (−30 to −65 mV). This is surprising since the photocurrent time course is regulated by the influx of Ca2+ through cGMP-gated ion channels (CNG) and the force driving this flux changes with membrane voltage. To understand this paradigm, we measured Pf, the fraction of the cyclic nucleotide–gated current specifically carried by Ca2+ in intact, isolated photoreceptors. To measure Pf we activated CNG channels by suddenly increasing free 8-Br-cGMP in the cytoplasm of rods or cones loaded with a caged ester of the cyclic nucleotide. Simultaneous with the uncaging flash, we measured the cyclic nucleotide–dependent changes in membrane current and fluorescence of the Ca2+ binding dye, Fura-2, also loaded into the cells. We determined Pf under physiological solutions at various holding membrane voltages between −65 and −25 mV. Pf is larger in cones than in rods, but in both photoreceptor types its value is independent of membrane voltage over the range tested. This biophysical feature of the CNG channels offers a functional advantage since it insures that the kinetics of the phototransduction current are controlled by light, and not by membrane voltage. To explain our observation, we developed a rate theory model of ion permeation through CNG channels that assumes the existence of two ion binding sites within the permeation pore. To assign values to the kinetic rates in the model, we measured experimental I-V curves in membrane patches of rods and cones over the voltage range −90 to 90 mV in the presence of simple biionic solutions at different concentrations. We optimized the fit between simulated and experimental data. Model simulations describe well experimental photocurrents measured under physiological solutions in intact cones and are consistent with the voltage-independence of Pf, a feature that is optimized for the function of the channel in photoreceptors.
On a nonlinear congruential pseudorandom number generator
Authors: Kato Takashi , Wu Li-Ming , Yanagihara Niro
Published: July 2002

A nonlinear congruential pseudorandom number generator with modulus

M
=

2
w

M = 2^w

is proposed, which may be viewed to comprise both linear as well as inversive congruential generators. The condition for it to generate sequences of maximal period length is obtained. It is akin to the inversive one and bears a remarkable resemblance to the latter.
Non-primitive number fields of degree eight and of signature (2,3), (4,2), and (6,1) with small discriminant
Authors: Selmane Schehrazad
Published: July 2002

We give the lists of all non-primitive number fields of degree eight having two, four and six real places of discriminant less than 6688609, 24363884 and 92810082, respectively, in absolute value. For each field in the lists, we give its discriminant, the discriminant of its subfields, a relative polynomial generating the field over one of its subfields and its discriminant, the corresponding polynomial over

Q

\mathbb {Q}

, and the Galois group of its Galois closure.
Higher rank case of Dwork’s conjecture
Authors: Wan Daqing
Published: July 2002

In this paper, we study the higher rank case of Dwork’s conjecture on the

p
p

-adic meromorphic continuation of the pure slope L-functions arising from the slope decomposition of an overconvergent F-crystal. Our main result is to reduce the general case of the conjecture to the special case when the pure slope part has rank one and when the base space is the simplest affine

n
n

-space.
On a correspondence between cuspidal representations of 𝐺𝐿_{2𝑛} and 𝑆𝑝̃_{2𝑛}
Authors: Ginzburg David , Rallis Stephen , Soudry David
Published: July 2002

Let

η
\eta

be an irreducible, automorphic, self-dual, cuspidal representation of

GL

2
n

⁡
(

A

)

\operatorname {GL}_{2n}(\mathbb A)

, where

A

\mathbb A

is the adele ring of a number field

K
K

. Assume that

L
S

(
η
,

Λ
2

,
s
)

L^S(\eta ,\Lambda ^2,s)

has a pole at

s
=
1

s=1

and that

L
(
η
,

1
2

)
≠
0

L(\eta , \frac 12)\neq 0

. Given a nontrivial character

ψ
\psi

of

K
∖

A

K\backslash \mathbb A

, we construct a nontrivial space of genuine and globally

ψ

−
1

\psi ^{-1}

-generic cusp forms

V

σ

ψ

(
η
)

V_{\sigma _{\psi }(\eta )}

on

Sp
~

2
n

(

A

)

\widetilde {\operatorname {Sp}}_{2n}(\mathbb A)

—the metaplectic cover of

Sp

2
n

(

A

)

{\operatorname {Sp}}_{2n}(\mathbb A)

.

V

σ

ψ

(
η
)

V_{\sigma _{\psi }(\eta )}

is invariant under right translations, and it contains all irreducible, automorphic, cuspidal (genuine) and

ψ

−
1

\psi ^{-1}

-generic representations of

Sp
~

2
n

(

A

)

\widetilde {\operatorname {Sp}}_{2n}(\mathbb A)

, which lift (“functorially, with respect to

ψ
\psi

") to

η
\eta

. We also present a local counterpart. Let

τ
\tau

be an irreducible, self-dual, supercuspidal representation of

GL

2
n

⁡
(
F
)

\operatorname {GL}_{2n}(F)

, where

F
F

is a

p
p

-adic field. Assume that

L
(
τ
,

Λ
2

,
s
)

L(\tau ,\Lambda ^2,s)

has a pole at

s
=
0

s=0

. Given a nontrivial character

ψ
\psi

of

F
F

, we construct an irreducible, supercuspidal (genuine)

ψ

−
1

\psi ^{-1}

-generic representation

σ
ψ

(
τ
)

\sigma _\psi (\tau )

of

Sp
~

2
n

(
F
)

\widetilde {\operatorname {Sp}}_{2n}(F)

, such that

γ
(

σ
ψ

(
τ
)
⊗
τ
,
s
,
ψ
)

\gamma (\sigma _\psi (\tau )\otimes \tau ,s,\psi )

has a pole at

s
=
1

s=1

, and we prove that

σ
ψ

(
τ
)

\sigma _\psi (\tau )

is the unique representation of

Sp
~

2
n

(
F
)

\widetilde {\operatorname {Sp}}_{2n}(F)

satisfying these properties.
Quasiconformal stability of Kleinian groups and an embedding of a space of flat conformal structures
Authors: Izeki Hiroyasu
Published: July 2002

We show the quasiconformal stability for torsion-free convex cocompact Kleinian groups acting on higher dimensional hyperbolic spaces. As an application, we prove an embedding theorem of a space of flat conformal structures on a certain class of compact manifolds.
p19ARF‐independent induction of p53 and cell cycle arrest by Raf in murine keratinocytes
Authors: Roper Elizabeth , Weinberg Wendy , Watt Fiona M , Land Hartmut
Published: July 2002

In tumorigenesis of the skin, activated Ras co‐operates with mutations that inactivate the tumour suppressor p53, but the molecular basis for this co‐operation remains unresolved. Here we show that activation of the Raf/MAP kinase pathway in primary mouse keratinocytes leads to a p53 and p21Cip1‐dependent cycle arrest and to terminal differentiation. Raf activation in keratinocytes lacking p53 or p21Cip1 genes leads to expression of differentiation markers, but the cells do not cease to proliferate. Thus, loss of p53 or p21Cip1 function is necessary to disable growth‐inhibitory Raf/MAP kinase signalling. Activation of oncogenes, including Ras, has been reported to stabilize and activate p53 via induction of the tumour suppressor p19ARF. However, the response to Raf in p19ARF−/− keratinocytes was indistinguishable from wild‐type controls. Thus, p19ARF is not essential for Raf‐induced p53 induction and cell cycle arrest in keratinocytes, indicating that oncogenes engage p53 activity via multiple mechanisms.
Hiding the Scars: A History of Post-Mastectomy Breast Prostheses, 1945–2000
Authors: Gardner Kirsten E.
Published: July 2002

As the public discussion of all cancers, and of breast cancer in particular, expanded after World War II, capitalist ventures emerged to meet the demands of those affected by the disease. For women who had mastectomies this meant a greater choice of breast prostheses but also a clearer message that the scars from surgery should be hidden from public view. This work analyzes the breast prosthesis industry as a beauty business. Considering the use of breast prostheses as a contested part of cancer recovery, the article traces the evolution and expansion of the breast prosthesis industry from 1945 to 2000 and examines how the industry has responded to consumer demand, created a niche for itself within the “healing process,“ and capitalized on notions of feminine beauty.
A role for Ddc1 in signaling meiotic double-strand breaks at the pachytene checkpoint
Authors: Hong Eun-Jin Erica , Roeder G. Shirleen
Published: July 2002

The pachytene checkpoint prevents meiotic cell cycle progression in response to unrepaired recombination intermediates. We show that Ddc1 is required for the pachytene checkpoint in Saccharomyces cerevisiae. During meiotic prophase, Ddc1 localizes to chromosomes and becomes phosphorylated; these events depend on the formation and processing of double-strand breaks (DSBs). Ddc1 colocalizes with Rad51, a DSB-repair protein, indicating that Ddc1 associates with sites of DSB repair. The Rad24 checkpoint protein interacts with Ddc1 and with recombination proteins (Sae1, Sae2, Rad57, and Msh5) in the two-hybrid protein system, suggesting that Rad24 also functions at DSB sites. Ddc1 phosphorylation and localization depend on Rad24 and Mec3, consistent with the hypothesis that Rad24 loads the Ddc1/Mec3/Rad17 complex onto chromosomes. Phosphorylation of Ddc1 depends on the meiosis-specific kinase Mek1. In turn, Ddc1 promotes the stable association of Mek1 with chromosomes and is required for Mek1-dependent phosphorylation of the meiotic chromosomal protein Red1. Ddc1 therefore appears to operate in a positive feedback loop that promotes Mek1 function.
An investigation on the use of removal‐diffusion theory for BNCT treatment planning: A method for determining proper removal‐diffusion parameters
Authors: Albertson B. J. , Blue T. E. , Niemkiewicz J.
Published: July 2002

This paper outlines a method for determining proper removal‐diffusion parameters to be used in removal‐diffusion theory calculations for the purpose of BNCT treatment planning. Additionally, this paper demonstrates that, given the proper choice of removal‐diffusion parameters, removal‐diffusion theory may provide an accurate calculation technique for determining absorbed dose distributions for the purpose of BNCT treatment planning. For a four‐group, one‐dimensional calculation in water, this method was used to determine values for the neutron scattering cross sections, neutron removal cross sections, neutron diffusion coefficients, and extrapolation distances. These values were then used in a one‐dimensional DIF3D calculation. The results of the DIF3D calculation showed a maximum deviation of 2.5% from a MCNP calculation performed for the same geometry.
Yttrium‐90 biodistribution by yttrium‐87 imaging: A theoretical feasibility analysis
Authors: Sgouros George
Published: July 2002

Yttrium‐90 is widely used in radioimmunotherapy but does not emit photons for imaging. Indium‐111, a chemically similar atom has been used instead as a tracer for the distribution of ‐labeled antibodies. Recent advances in gamma camera technology have made it possible to image at energies higher than 364 keV. This work provides a theoretical analysis of the feasibility of using (485 keV, 92.2% yield) as a tracer for in vivo imaging of ‐labeled antibodies. Yttrium‐87 may be produced by the reaction in a cyclotron and has a 3.3 day half‐life. This reaction also yields a metastable state of Yttrium‐87, itself decays to a metastable state of The level of these contaminants and their anticipated impact on the utility of as a tracer for are examined theoretically. Dosimetry is performed to assess the absorbed dose associated with using A 100 h delay following the end of bombardment of an isotopically enriched target reduces the activity of the metastable state of in the product by 10‐ to 15‐fold, with greater delays resulting in a further reduction. A rapid equilibration between and its daughter, is expected, in vivo. Although strontium is known to concentrate in bone, the electron emissions of are short range, thereby making possible biologic effects highly position dependent; the photon emissions allow for independent imaging which may be used to perform dosimetry and thereby directly assess potential toxicity. merits further consideration as an imaging tracer for
Development of an apparatus for two-dimensional collision experiment using a cycloidal slide
Authors: Ha Myung-hyun , Kim Yang-kie , Lee Sang Bub
Published: July 2002

An apparatus has been developed that enables one to investigate the conservation of a linear momentum in a two-dimensional collision experiment. It was found that a cycloidal slide yields a constant rolling time of the ball, independent of the release position on the slide. The two balls, released on two slides of the same size at any desired angle, produce a two-dimensional collision. The initial velocity of the ball before the collision is determined by the height of the release position, and the final velocity after collision is determined from the height of the collision point from the ground and the horizontal distance that the ball travels before it reaches the ground. With this apparatus, the performance of a high precision experiment for momentum conservation during the collision process was achieved.
Solving boundary-value electrostatics problems using Green’s reciprocity theorem
Authors: Hu Ben Yu-Kuang
Published: July 2002

Formal solutions to electrostatics boundary-value problems are derived using Green’s reciprocity theorem. This method provides a more transparent interpretation of the solutions than the standard Green’s function derivation. An energy-based argument for the reciprocity theorem is also presented.
Klopsteg Memorial Lecture (August, 1998): Physics at the breakfast table—or waking up to physics
Authors: Nagel Sidney R.
Published: July 2002

There are many complex phenomena that are so familiar to us that we forget to ask whether or not they are understood. In this lecture, I will discuss several familiar cases of effects that are so ubiquitous that we hardly realize that they defy our normal intuition about why they happen. The examples of poorly understood classical physics that I will choose can all be viewed at a breakfast table. I will mention the long tendrils left behind by honey spooned from one dish to another, the anomalous flow behavior of granular material, and the annoying rings deposited by spilled coffee on a table after the liquid evaporates. These are all nonlinear hydrodynamic phenomena which not only are of technological importance but can also lead the inquisitive into new realms of physics.
Improvements in intelligibility of noisy reverberant speech using a binaural subband adaptive noise-cancellation processing scheme
Authors: Shields Paul W. , Campbell Douglas R.
Published: July 2002

This article reports on the performance of an adaptive subband noise cancellation scheme, which performs binaural preprocessing of speech signals for a hearing-aid application. The multi-microphone subband adaptive (MMSBA) signal processing scheme uses the least mean squares (LMS) algorithm in frequency-limited subbands. The use of subbands enables a diverse processing mechanism to be employed, splitting the two-channel wide-band signal into smaller frequency-limited subbands, which can be processed according to their individual signal characteristics. The frequency delimiting used a linear- or cochlear-spaced subband distribution. The effect of the processing scheme on speech intelligibility was assessed in a trial involving 15 hearing-impaired volunteers with moderate sensorineural hearing loss. The acoustic material consisted of speech and speech-shaped noise signals, generated using simulated and real-room acoustic environments, at signal-to-noise ratios (SNRs) in the range −6 to +3 dB. The results show that the MMSBA scheme delivered average speech intelligibility improvements of 11.5%, with a maximum of 37.25%, in noisy reverberant conditions. There was no significant reduction in mean speech intelligibility due to processing, in any of the test conditions.
Comments on “A unitary model of pitch perception” [J. Acoust. Soc. Am. 102, 1811–1820 (1997)]
Authors: Carlyon Robert P.
Published: July 2002

Meddis and O’Mard have recently presented a revised autocorrelogram model of pitch perception, which they claim can account for the different pattern of experimental results obtained for complex tones consisting of resolved and unresolved harmonics. This Letter demonstrates that, in contrast to the experimental data, important features of the model’s output and predictions vary with frequency region rather than with resolvability.
The auditory evoked potential difference tone and cubic difference tone measured from the inferior colliculus of the chinchilla
Authors: Arnold Sally , Burkard Robert
Published: July 2002

The auditory evoked potential f2−f1 difference tone (DT) and the 2 f1−f2 cubic difference tone (CDT) were recorded from electrodes implanted in the inferior colliculus in a group of chinchillas. The purpose of this study was to measure normative aspects of AEP distortion products in awake chinchillas, by comparing the DT and CDT under a variety of stimulus conditions. For experiment 1, f1 was held constant at 1998 Hz, while the f2/f1 ratio was varied from 1.05 to 1.50. Input–output functions were measured over a range of primary tone levels up to 80 dB SPL. The amplitude of the DT was greatest for the smallest f2/f1 ratio, and decreased systematically as f2/f1 ratio increased. DT amplitude was greater than CDT amplitude for all primary tone pairs. Experiment 2 was conducted to determine the effect of f1 frequency upon the DT and CDT for a constant f1−f2 difference frequency of 102 Hz (f1=999, 1998, 4999, and 9998 Hz). The DT input–output functions were overlapping for all f1 frequencies. For the CDT, amplitude decreased with increasing f1 frequency, which corresponded to an increase in CDT frequency. In experiment 3, the relationship between ear of stimulation and inferior colliculus recorded from was investigated. DT input–output functions (f1=1998 Hz, DT=102 Hz) were measured for monaural contralateral, monaural ipsilateral, and dichotic stimulus conditions. DT amplitude was largest for the contralateral condition, followed by the ipsilateral condition. A smaller, dichotic component to the DT was observed as well.
Examination of time-reversal acoustics and applications to underwater communications
Authors: Abrantes Antonio A. M. , Smith Kevin B. , Larraza Andres
Published: July 2002

Recent experimental work [Roux et al., Appl. Phys. Lett. 70, 1811–1813 (1997); Kuperman et al., J. Acoust. Soc. Am. 103, 25–40 (1998)] has shown that the novel technique of time-reversal acoustics (TRA) can be applied in shallow-water environments to focus energy back at a source location from a transmitted signal received at a distant receiver array. This refocusing produces a local intensification of the field as well as a convergence of the signal in time. These two aspects of TRA techniques suggest it may be a viable approach for use in underwater communication systems. Because TRA techniques rely on the reconvergence of multipath information into focused arrivals at the original source locations, the influence of multipath spreading is removed. The energy transmitted is then enhanced by the focusing, thereby increasing the SNR. Specifically of interest in this study will be an analysis of how well the signal can be refocused in typical shallow-water environments and what type of data transfer rates can be achieved using TRA on realistic systems. [Work supported by ONR.]
Love-theoretical analysis of periodic system of rods
Authors: Ravindra B.
Published: July 2002

Love-theoretical analysis of periodic system of rods is presented. It is shown that the proposed theory enables an extension of Snowdon’s theory of vibration isolation. An example of a periodic vibration isolator, consisting of sandwiched rubber springs, is studied.
Forward masking recovery and peripheral compression in normal-hearing and cochlear-impaired ears
Authors: Nelson David A. , Schroder Anna C.
Published: July 2002

Iso-response temporal masking curves are obtained from normal-hearing subjects at a probe frequency of 1000 Hz for masker frequencies between 500 and 1200 Hz. Time constants calculated from the temporal masking curves varied with masker frequency, from around 70 ms for low off-frequency maskers (500–600 Hz) to around 36 ms for on-frequency maskers (close to the probe frequency). Continuing Bilger’s earlier pursuits of nonlinearities in hearing, estimates of peripheral compression were calculated under the assumption that the response to a low off-frequency masker is linear at the probe frequency place. Average compression exponents varied from close to 1.0 for remote off-frequency maskers (both below and above the probe) to below 0.4 for on-frequency maskers. Input–output transfer functions derived from the compression exponents were consistent with BM transfer functions recorded in animals with normal cochlear function. Comparisons of iso-response temporal masking curves in subjects with sizable cochlear hearing losses at the probe frequency yielded linear transfer functions consistent with BM data from cochlear-damaged animals. It is concluded that time constants for recovery from forward masking in ears with cochlear hearing loss are no different than those obtained from normal-hearing ears, once differences in peripheral compression are taken into account. [Work supported by NIH-NIDCD Grant DC00149 and the Lion’s 5M International Hearing Foundation.]
Spectral characterization of jitter, shimmer, and additive noise in synthetically generated voice signals
Authors: Murphy Peter J.
Published: July 2002

Alteration of the harmonic structure in voice source spectra, taken over at least two periods of the waveform, may occur due to the presence of fundamental frequency (f0) perturbation, amplitude perturbation, additive noise, or changes within the glottal source signal itself. In order to make accurate inferences regarding glottal-flow dynamics or perceptual evaluations based on spectral measurements taken from the acoustic speech waveform, investigation of the spectral features of each aperiodic component is required. Based on a heuristic development involving a consideration of the partial sum of the Fourier series taken for two periods of a jittered, shimmered, and (additive, random) noise-contaminated signal, the corresponding spectral characteristics are hypothesized. Subsequent to this, the Fourier series coefficients are calculated for the two periods in order to test the hypotheses. Definite spectral differences are found for each aperiodic component; based on these findings differential quantitative spectral measurements are suggested. Further supportive evidence is obtained through use of Fourier transform and periodogram-averaged calculations. The analysis is carried out on synthetically generated glottal-pulse waveforms and on radiated speech waveforms. A discussion of the results is given in terms of voice aperiodicity in general and in terms of their implication for future studies involving human voice signals.