bluuebunny/crossref_metadata_2025 huggingface dataset:
Conformational change and enhanced stabilization of the vitamin D receptor by the 1,25-dihydroxyvitamin D3 analog KH1060.
Authors: van den Bemd G C , Pols H A , Birkenhäger J C , van Leeuwen J P
Published: July 2002

The 1,25-dihydroxyvitamin D3 [1,25-(OH)2vitamin D3] analog KH1060 exerts very potent effects on cell proliferation and cell differentiation via the vitamin D receptor (VDR). However, the activities of KH1060 are not associated with an increased affinity for the VDR. We now show that increased stabilization of the VDR-KH1060 complex could be an explanation for its high potencies. VDR half-life studies performed with cycloheximide-translational blocked rat osteoblast-like ROS 17/2.8 cells demonstrated that, in the absence of ligand, VDR levels rapidly decreased. After 2 hr, less than 10% of the initial VDR level could be measured. In the presence of 1,25-(OH)2vitamin D3, the VDR half-life was 15 hr. After 24 hr. less than 20% of the initial VDR content was detectable, whereas, at this time-point, when the cells were incubated with KH1060 80% of the VDR was still present. Differences in 1,25-(OH)2vitamin D3- and KH1060-induced conformational changes of the VDR could underlie the increased VDR stability. As assessed by limited proteolytic digestion analysis, both 1,25-(OH)2vitamin D3 and KH1060 caused a specific conformational change of the VDR. Compared with 1,25-(OH)2vitamin D3, KH1060 induced a conformational change that led to a far more dramatic protection of the VDR against proteolytic degradation. In conclusion, the altered VDR stability and the possibly underlying change in VDR conformation caused by KH1060 could be an explanation for its enhanced bioactivity.
Systematic derivation of partition functions for ligand binding to two-dimensional lattices
Authors: Wang Luyu , Di Cera Enrico
Published: July 2002

The Ising problem consists in finding the analytical solution of
the partition function of a lattice once the interaction geometry among
its elements is specified. No general analytical solution is available
for this problem, except for the one-dimensional case. Using
site-specific thermodynamics, it is shown that the partition function
for ligand binding to a two-dimensional lattice can be obtained from
those of one-dimensional lattices with known solution. The complexity
of the lattice is reduced recursively by application of a
contact transformation
that involves a relatively small
number of steps. The transformation implemented in a computer code
solves the partition function of the lattice by operating on the
connectivity matrix of the graph associated with it. This provides a
powerful new approach to the Ising problem, and enables a systematic
analysis of two-dimensional lattices that model many biologically
relevant phenomena. Application of this approach to finite
two-dimensional lattices with positive cooperativity indicates that the
binding capacity per site diverges as
N

a

(
N
=
number of sites in the lattice) and experiences a phase-transition-like
discontinuity in the thermodynamic limit
N
→ ∞. The
zeroes of the partition function tend to distribute on a slightly
distorted unit circle in complex plane and approach the positive real
axis already for a 5×5 square lattice. When the lattice has negative
cooperativity, its properties mimic those of a system composed of two
classes of independent sites with the apparent population of
low-affinity binding sites increasing with the size of the lattice,
thereby accounting for a phenomenon encountered in many ligand-receptor
interactions.
Human immunodeficiency virus type-1 Tat is an integral component of the activated transcription-elongation complex.
Authors: Keen N J , Gait M J , Karn J
Published: July 2002

The human immunodeficiency virus type 1 transactivator protein, Tat, stimulates transcriptional elongation from the viral long terminal repeat. To test whether Tat associates directly with activated transcription complexes, we have used the lac repressor protein (LacR) to "trap" elongating RNA polymerases. The arrested transcription complexes were purified by binding biotinylated templates to streptaviridin-coated magnetic beads. Transcription complexes were released from the magnetic beads following cleavage of the templates with restriction enzymes and were immunoblotted with antibodies to Tat, LacR and RNA polymerase II. The Tat protein copurified with RNA polymerase bound to wild-type templates but did not copurify with transcription complexes prepared by using templates carrying mutations in the transactivation response element (TAR) RNA. We conclude that Tat and cellular cofactors become attached to the transcription complex during its transit through TAR.
The perception of transparent three-dimensional objects
Authors: Purves Dale , Andrews Timothy J.
Published: July 2002

When the proximal and distal elements of wire-frame cubes are conflated, observers perceive illusory structures that no longer behave veridically. These phenomena suggest that what we normally see depends on visual associations generated by experience. The necessity of such learning may explain why the mammalian visual system is subject to a prolonged period of plasticity in early life, when novel circuits are made in enormous numbers.
The one ancestor per generation rule and three other rules of mitochondrial inheritance
Authors: Ohno Susumu
Published: July 2002

In mammals, at least, a species-specific mechanism exists that eliminates sperm-derived mitochondrial DNA from a fertilized egg. The result is the “one female ancestor per generation” rule and three other rules of mitochondrial inheritance. The second, third, and fourth rules are as follows. (
ii
) Sublineages of a given mitochondrial line can be generated only during the parallel descents from ancestral sisters. (
iii
) In a static population in which the production of one female progeny per mated pair per generation has been a rule, several ancient mitochondrial lineages harking back to the female founders of the speciation may persist side by side. (
iv
) Two or more individuals not related to each other in the recent past may share the identical or nearly identical mitochondrial genome derived from the common female ancestor or ancestral sisters of many generations ago.
Kinematic geometry of mass-triangles and reduction of Schrödinger’s equation of three-body systems to partial differential equations solely defined on triangular parameters
Authors: Hsiang Wu-Yi
Published: July 2002

Schrödinger’s equation of a three-body system is a linear partial differential equation (PDE) defined on the 9-dimensional configuration space, ℝ
9
, naturally equipped with Jacobi’s kinematic metric and with translational and rotational symmetries. The natural invariance of Schrödinger’s equation with respect to the translational symmetry enables us to reduce the configuration space to that of a 6-dimensional one, while that of the rotational symmetry provides the quantum mechanical version of angular momentum conservation. However, the problem of maximizing the use of rotational invariance so as to enable us to reduce Schrödinger’s equation to corresponding PDEs solely defined on triangular parameters—i.e., at the level of ℝ
6
/
SO
(3)—has never been adequately treated. This article describes the results on the orbital geometry and the harmonic analysis of (
SO
(3),ℝ
6
) which enable us to obtain such a reduction of Schrödinger’s equation of three-body systems to PDEs solely defined on triangular parameters.
Direct isolation of human transcribed sequences from yeast artificial chromosomes through the application of RNA fingerprinting
Authors: Still Ivan H. , Vince Pauline , Cowell John K.
Published: July 2002

The identification of cDNA clones from genomic regions known to contain human genes is usually the rate-limiting factor in positional cloning strategies. We demonstrate here that human genes present on yeast artificial chromosomes (YACs) are transcribed in yeast host cells. We have used the arbitrarily primed RNA (RAP) fingerprinting method to identify human-specific, transcribed sequences from YACs located in the 13q12 chromosome region. By comparing the RAP fingerprints generated using defined, arbitrary primers from various fragmented YACs, megaYACs, and host yeast, we were able to identify and map 20 products transcribed from the human YAC inserts. This method, therefore, permits the simultaneous isolation and mapping of novel expressed sequences directly from whole YACs.
Critical transport properties of random metals in large magnetic fields
Authors: Phillips J. C.
Published: July 2002

The threshold behavior of the transport properties of a random metal in the critical region near a metal–insulator transition is strongly affected by the measuring electromagnetic fields. In spite of the randomness, the electrical conductivity exhibits striking phase-coherent effects due to broken symmetry, which greatly sharpen the transition compared with the predictions of effective medium theories, as previously explained for electrical conductivities. Here broken symmetry explains the sign reversal of the
T
→ 0 magnetoconductance of the metal–insulator transition in Si(B,P), also previously not understood by effective medium theories. Finally, the symmetry-breaking features of quantum percolation theory explain the unexpectedly very small electrical conductivity temperature exponent α = 0.22(2) recently observed in Ni(S,Se)
2
alloys at the antiferromagnetic metal–insulator transition below
T
= 0.8 K.
B12-dependent ribonucleotide reductases from deeply rooted eubacteria are structurally related to the aerobic enzyme from
Escherichia coli
Authors: Jordan Albert , Torrents Eduard , Jeanthon Christian , Eliasson Rolf , Hellman Ulf , Wernstedt Christer , Barbé Jordi , Gibert Isidre , Reichard Peter
Published: July 2002

The ribonucleotide reductases from three ancient eubacteria, the hyperthermophilic
Thermotoga maritima
(TM), the radioresistant
Deinococcus radiodurans
(DR), and the thermophilic photosynthetic
Chloroflexus aurantiacus,
were found to be coenzyme-B
12
(class II) enzymes, similar to the earlier described reductases from the archaebacteria
Thermoplasma acidophila
and
Pyrococcus furiosus
. Reduction of CDP by the purified TM and DR enzymes requires adenosylcobalamin and DTT. dATP is a positive allosteric effector, but stimulation of the TM enzyme only occurs close to the temperature optimum of 80–90°C. The TM and DR genes were cloned by PCR from peptide sequence information. The TM gene was sequenced completely and expressed in
Escherichia coli
. The deduced amino acid sequences of the two eubacterial enzymes are homologous to those of the archaebacteria. They can also be aligned to the sequence of the large protein of the aerobic
E. coli
ribonucleotide reductase that belongs to a different class (class I), which is not dependent on B
12
. Structure determinations of the
E. coli
reductase complexed with substrate and allosteric effectors earlier demonstrated a 10-stranded β/α-barrel in the active site. From the conservation of substrate- and effector-binding residues we propose that the B
12
-dependent class II enzymes contain a similar barrel.
Irreversible antagonism of 5HT2c receptors by
N
-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ)
Authors: Ni Y. G. , Camacho N. , Miledi R.
Published: July 2002

To determine if
N
-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), a carboxyl group activating agent, can inactivate 5HT2c receptors, we have examined the effects of EEDQ on 5HT2c receptor-mediated responses to 5-hydroxytryptamine (5HT) in
Xenopus
oocytes, and on the binding of [
3
H]5HT to 5HT2c receptors in transfected HeLa cells. In oocytes expressing rat 5HT2c receptors, EEDQ inhibited the 5HT2c receptor-mediated Cl
−
currents; and the response did not recover more than 24 h after removal of the EEDQ. To see if this effect of EEDQ was on the receptor itself, the binding of 5HT to 5HT2c receptors was studied in transfected HeLa cells. EEDQ decreased the specific binding of [
3
H]5HT to 5HT2c receptors. At ≈22°C, incubating the membranes with 2 × 10
−4
M EEDQ for 1 h caused a 40% decrease in the
B
max
, without changing the
K
d
. At 37°C, the same treatment with EEDQ blocked [
3
H]5HT binding completely. Half-maximal inhibition occurred at 5 μM EEDQ at both temperatures, and washing for 1.5 h did not restore the binding, suggesting that the inactivation of 5HT2c receptor binding was practically irreversible. Results from both systems showed clearly that EEDQ is an irreversible antagonist of 5HT2c receptors and therefore can be used for many studies of this receptor.
Resinless section electron microscopy reveals the yeast cytoskeleton
Authors: Penman Joshua , Penman Sheldon
Published: July 2002

The cytoskeleton of
Saccharomyces cerevisiae
is essentially invisible using conventional microscopy techniques. A similar problem was solved for the mammalian cell cytoskeleton using resinless section electron microscopy, a technique applied here to yeast. In the resinless image, soluble proteins are no longer cloaked by embedding medium and must be removed by selective detergent extraction. In yeast, this requires breaching the cell wall by digesting with Zymolyase sufficiently to allow detergent extraction of the plasma membrane lipids. Gel electropherograms show that the extracted or “soluble” proteins are distinct from the retained or “structural” proteins that presumably comprise the cytoskeleton. These putative cytoskeleton proteins include the major portions of a 43-kDa protein, which is presumably actin, and of proteins in a band appearing at 55 kDa, as well as numerous less abundant, nonactin proteins. Resinless section electron micrographs show a dense, three-dimensional web of anastomosing, polymorphic filaments bounded by the remnant cell wall. Although the filament network is very heterogenous, there appear to be two principal classes of filament diameters—5 nm and 15–20 nm—which may correspond to actin and intermediate filaments, respectively. A large oval region of lower filament density probably corresponds to the vacuole, and an electron dense spheroidal body, 300–500 nm in diameter, is likely the nucleus. The techniques detailed in this report afford new approaches to the study of yeast cytoarchitecture.
Is strong hydrogen bonding in the transition state enough to account for the observed rate acceleration in a mutant of papain?
Authors: Zheng Ya-Jun , Bruice Thomas C.
Published: July 2002

Nitriles are good inhibitors for the cysteine protease papain. However, a single amino acid mutation (Gln-19 → Glu-19) in the active site makes the mutant enzyme a good catalyst for nitrile hydrolysis. A theoretical approach was used to examine the differential transition state stabilization in the papain mutant relative to the wild-type enzyme. Based on this study, we concluded that strong hydrogen bonding in the transition state is responsible for the observed rate enhancement of 4 × 10
5
.
Letter recognition reveals pathways of second-order and third-order motion
Authors: Ho Ching Elizabeth
Published: July 2002

How are second-order (texture-defined) and third-order
(pattern-tracking) motions processed in our brains? As shown here in
the context of an ambiguous motion task involving a nominal
second-order stimuli first devised by Werkhoven
et al
.,
[Werkhoven, P., Sperling, G. & Chubb, C. (1993)
Vision Res.
33, 463–485.], the observers fell into two distinct groups
based on the direction of perceived motion. The differences were
interpreted in terms of the algorithms used to extract motion: one
group by using a second-order motion process and the other by using a
third-order motion process. This was investigated further using a
dual-task paradigm in which the interference between two tasks
indicated the nature of processing involved. Observers who used
third-order motion processing experienced interference with letter
recognition and a more severe interference in dual third-order motion
tasks. Observers who used second-order motion processing experienced
interference with another second-order motion detection but not with
letter recognition. Insofar as task interference implies the need for
attention, the complex interference effects and the apparently
paradoxical interference effects of second-order motion perception
imply that there are multiple forms of attention. Whether two tasks
interfere depends on whether they require the same form of attention.
Insofar as spatio-temporal processing is assumed to be carried out in
the dorsal stream and pattern recognition in the ventral stream, the
interference patterns suggest that second-order motion may be computed
entirely in the dorsal stream, and third-order motion may involve two
computational processes, one of which shares computational resources
with the letter recognition task in the ventral stream.
Comparative analyses of the secondary structures of synthetic and intracellular yeast
MFA
2
mRNAs
Authors: Doktycz Mitchel J. , Larimer Frank W. , Pastrnak Miro , Stevens Audrey
Published: July 2002

The overall folded (global) structure of mRNA may be critical to translation and turnover control mechanisms, but it has received little experimental attention. Presented here is a comparative analysis of the basic features of the global secondary structure of a synthetic mRNA and the same intracellular eukaryotic mRNA by dimethyl sulfate (DMS) structure probing. Synthetic
MFA2
mRNA of
Saccharomyces cerevisiae
first was examined by using both enzymes and chemical reagents to determine single-stranded and hybridized regions; RNAs with and without a poly(A) tail were compared. A folding pattern was obtained with the aid of the
mfold
program package that identified the model that best satisfied the probing data. A long-range structural interaction involving the 5′ and 3′ untranslated regions and causing a juxtaposition of the ends of the RNA, was examined further by a useful technique involving oligo(dT)-cellulose chromatography and antisense oligonucleotides. DMS chemical probing of A and C nucleotides of intracellular
MFA2
mRNA was then done. The modification data support a very similar intracellular structure. When low reactivity of A and C residues is found in the synthetic RNA, ≈70% of the same sites are relatively more resistant to DMS modification
in vivo
. A slightly higher sensitivity to DMS is found
in vivo
for some of the A and C nucleotides predicted to be hybridized from the synthetic structural model. With this small mRNA, the translation process and mRNA-binding proteins do not block DMS modifications, and all A and C nucleotides are modified the same or more strongly than with the synthetic RNA.
A genetic screen for the isolation and characterization of site-specific proteases
Authors: Sices Harry J. , Kristie Thomas M.
Published: July 2002

Site-specific proteolysis is an important regulatory mechanism in basic cellular and viral processes. Using the protease of the HIV as a model, a genetic system has been developed for the isolation and characterization of site-specific proteases. The system utilizes the well defined bacteriophage λ regulatory circuit where the viral repressor, cI, is specifically cleaved to initiate the lysogenic-to-lytic switch. The model system is rapid, highly specific, and demonstrates the ability to isolate and characterize enzymes of limited expression or activity. In addition, the system has a significant potential for the selection of clinically relevant mutant enzymes and in the development of anti-protease therapeutics.
Chromatin structure analysis of the mouse
Xist
locus
Authors: McCabe Veronica , Formstone Emma J. , O’Neill Laura P. , Turner Bryan M. , Brockdorff Neil
Published: July 2002

The
Xist
gene is expressed exclusively from the inactive X chromosome and plays a central role in regulating X chromosome inactivation. Here we describe experiments aimed at defining the extent of the active chromatin domain of the expressed
Xist
allele. By using an allele-specific general DNaseI sensitivity assay we show that there is preferential digestion of the expressed allele at sites within the transcribed locus but not in flanking sites located up to 70 kb 5′. A putative proximal boundary for the
Xist
domain is located within 10 kb upstream of promoter P
1
. Chromatin in the expressed domain was found to be acetylated at H4 in XX somatic cells but also in XY cells, where
Xist
is never expressed. A single clear exception to this was the
Xist
promoter, which is acetylated only in XX cells. These observations concur with the view that H4 acetylation may not be a general marker of active chromatin domains and further support data implicating local promoter acetylation as being of primary functional significance
in vivo
.
Highly efficient endonucleolytic cleavage of RNA by a Cys
2
His
2
zinc-finger peptide
Authors: Lima Walt F. , Crooke Stanley T.
Published: July 2002

We have identified a 30-aa peptide that efficiently cleaves single-stranded RNA. The peptide sequence corresponds to a single zinc finger of the human male-associated ZFY protein; a transcription factor belonging to the Cys
2
His
2
family of zinc-finger proteins. RNA cleavage was observed only in the absence of zinc. Coordination with zinc resulted in complete loss of ribonuclease activity. The ribonuclease active structure was determined to be a homodimeric form of the peptide. Dimerization of the peptide occurred through a single intermolecular disulfide between two of the four cystines. The observed hydrolytic activity was single-stranded RNA-specific. Single-stranded DNA, double-stranded RNA and DNA, and 2′-methoxy-modified sequences were not degraded by the peptide. The peptide specifically cleaved pyrimidines within single-stranded RNA and the dinucleotide sequence 5′-pyr-A-3′ was preferred. The RNA cleavage products consisted of a 3′ phosphate and 5′ hydroxyl. The initial rates of cleavage (
V
0
) observed for the finger peptide were comparable to rates observed for human ribonucleases, and the catalytic rate (
K
cat
) was comparable to rates observed for the group II intron rybozymes. The pH profile exhibited by the peptide is characteristic of general acid–base catalytic mechanisms observed with other ribonucleases. These observations raise interesting questions about the potential biological roles of zinc-finger proteins.
Invariance of brain-wave representations of simple visual images and their names
Authors: Suppes Patrick , Han Bing , Epelboim Julie , Lu Zhong-Lin
Published: July 2002

In two experiments, electric brain waves of 14 subjects were recorded under several different conditions to study the invariance of brain-wave representations of simple patches of colors and simple visual shapes and their names, the words
blue, circle,
etc. As in our earlier work, the analysis consisted of averaging over trials to create prototypes and test samples, to both of which Fourier transforms were applied, followed by filtering and an inverse transformation to the time domain. A least-squares criterion of fit between prototypes and test samples was used for classification. The most significant results were these. By averaging over different subjects, as well as trials, we created prototypes from brain waves evoked by simple visual images and test samples from brain waves evoked by auditory or visual words naming the visual images. We correctly recognized from 60% to 75% of the test-sample brain waves. The general conclusion is that simple shapes such as circles and single-color displays generate brain waves surprisingly similar to those generated by their verbal names. These results, taken together with extensive psychological studies of auditory and visual memory, strongly support the solution proposed for visual shapes, by Bishop Berkeley and David Hume in the 18th century, to the long-standing problem of how the mind represents simple abstract ideas.
On the classification of binary shifts of finite commutant index
Authors: Price Geoffrey L.
Published: July 2002

We provide a complete classification up to conjugacy of the binary shifts of finite commutant index on the hyperfinite
II
1
, factor. There is a natural correspondence between the conjugacy classes of these shifts and polynomials over
GF
(
2
) satisfying a certain duality condition.
The asymptotic distribution of canonical correlations and variates in cointegrated models
Authors: Anderson T. W.
Published: July 2002

The cointegrated model considered here is a nonstationary vector autoregressive process in which some linear functions are stationary and others are random walks. The first difference of the process (the “error-correction form“) is stationary. Statistical inference, such as reduced rank regression estimation of the coefficients of the process and tests of hypotheses of dimensionality of the stationary part, involves the canonical correlations between the difference vector and the relevant vector of the past of the process. The asymptotic distributions of the canonical correlations and the canonical vectors under the assumption that the process is Gaussian are found.
Free entropy and property T factors
Authors: Ge Liming , Shen Junhao
Published: July 2002

We show that a large class of finite factors has free entropy dimension less than or equal to one. This class includes all prime factors and many property T factors.
Macroscopic phase separation in high-temperature superconductors
Authors: Wen Hai-Hu
Published: July 2002

High-temperature superconductivity is recovered by introducing
extra holes to the Cu-O planes, which initially are insulating with
antiferromagnetism. In this paper I present data to show the
macroscopic electronic phase separation that is caused by either mobile
doping or electronic instability in the overdoped region. My results
clearly demonstrate that the electronic inhomogeneity is probably a
general feature of high-temperature superconductors.
Perceived Effects of Exercise and Sport in a Population Defined by Their Injection Drug Use
Authors: Powers Joseph M. , Woody George E. , Sachs Michael L.
Published: July 2002

The role of exercise and sport in the lives of intravenous drug users (n = 45) was assessed, using an interviewer‐administered open‐ended questionnaire. Results demonstrated a high level of exercise and sport interest in this population (64%). Being a sports fan was also found in most of the responses (72%). This study on the role of exercise and sport in an intravenous drug‐using population could be considered when developing rehabilitation measures or as an addition to present therapeutic interventions.
Establishing a Left‐Right Axis in the Embryo
Authors: Ryan Aimee K. , Belmonte Juan Carlos Izpisúa
Published: July 2002

Vertebrates exhibit evolutionarily conserved asymmetries in the pattern of internal organ placement that are essential for their normal physiological function. Left‐right asymmetries in organ situs are dependent upon the formation of an intact left‐right axis during embryogenesis. Recently many of the molecular components involved in the initiation and maintenance of the left‐right axis have been described. These molecules and their function in promoting left‐right asymmetries are reviewed.
The Selection of M3-Restricted T Cells Is Dependent on M3 Expression and Presentation of N-Formylated Peptides in the Thymus
Authors: Chiu Nancy M. , Wang Bin , Kerksiek Kristen M. , Kurlander Roger , Pamer Eric G. , Wang Chyung-Ru
Published: July 2002

The major histocompatibility complex (MHC) class Ib molecule H2-M3 binds N-formylated peptides from mitochondria and bacteria. To explore the role of M3 expression and peptide supply in positive and negative selection, we generated transgenic mice expressing an M3-restricted TCR-α/β from a CD8+ T cell hybridoma (D7) specific for a listerial peptide (LemA). Development of M3-restricted transgenic T cells is impaired in both β2-microglobulin–deficient and transporter associated with antigen processing (TAP)-deficient mice, but is not diminished by changes in the H-2 haplotype. Maturation of M3/LemA-specific CD8+ single positive cells in fetal thymic organ culture was sensitive to M3 expression levels as determined by antibody blocking and use of the castaneus mutant allele of M3. Positive selection was rescued in TAP−/− lobes by nonagonist mitochondrial and bacterial peptides, whereas LemA and a partial agonist variant caused negative selection. Thus, M3-restricted CD8+ T cells are positively and negatively selected by M3, with no contribution from the more abundant class Ia molecules. These results demonstrate that class Ib molecules can function in thymic education like class Ia molecules, despite limited ligand diversity and low levels of expression.
Phosphoinositide 3-Kinase–Dependent Membrane Recruitment of P62dok Is Essential for Its Negative Effect on Mitogen-Activated Protein (Map) Kinase Activation
Authors: Zhao Mingming , Schmitz Arndt A.P. , Qin Yi , Di Cristofano Antonio , Pandolfi Pier Paolo , Van Aelst Linda
Published: July 2002

A major pathway by which growth factors, such as platelet-derived growth factor (PDGF), regulate cell proliferation is via the receptor tyrosine kinase/Ras/mitogen-activated protein kinase (MAPK) signaling cascade. The output of this pathway is subjected to tight regulation of both positive and negative regulators. One such regulator is p62dok, the prototype of a newly identified family of adaptor proteins. We recently provided evidence, through the use of p62dok-deficient cells, that p62dok acts as a negative regulator of growth factor–induced cell proliferation and the Ras/MAPK pathway. We show here that reintroduction of p62dok into p62dok−/− cells can suppress the increased cell proliferation and prolonged MAPK activity seen in these cells, and that plasma membrane recruitment of p62dok is essential for its function. We also show that the PDGF-triggered plasma membrane translocation of p62dok requires activation of phosphoinositide 3-kinase (PI3-kinase) and binding of its pleckstrin homology (PH) domain to 3′-phosphorylated phosphoinositides. Furthermore, we demonstrate that p62dok can exert its negative effect on the PDGFR/MAPK pathway independently of its ability to associate with RasGAP and Nck. We conclude that p62dok functions as a negative regulator of the PDGFR/Ras/MAPK signaling pathway through a mechanism involving PI3-kinase–dependent recruitment of p62dok to the plasma membrane.
Effect of 11-Cis 13-Demethylretinal on Phototransduction in Bleach-Adapted Rod and Cone Photoreceptors
Authors: Corson D.Wesley , Kefalov Vladimir J. , Cornwall M. Carter , Crouch Rosalie K.
Published: July 2002

We used 11-cis 13-demethylretinal to examine the physiological consequences of retinal's noncovalent interaction with opsin in intact rod and cone photoreceptors during visual pigment regeneration. 11-Cis 13-demethylretinal is an analog of 11-cis retinal in which the 13 position methyl group has been removed. Biochemical experiments have shown that it is capable of binding in the chromophore pocket of opsin, forming a Schiff-base linkage with the protein to produce a pigment, but at a much slower rate than the native 11-cis retinal (Nelson, R., J. Kim deReil, and A. Kropf. 1970. Proc. Nat. Acad. Sci. USA. 66:531–538). Experimentally, this slow rate of pigment formation should allow separate physiological examination of the effects of the initial binding of retinal in the pocket and the subsequent formation of the protonated Schiff-base linkage. Currents from solitary rods and cones from the tiger salamander were recorded in darkness before and after bleaching and then after exposure to 11-cis 13-demethylretinal. In bleach-adapted rods, 11-cis 13-demethylretinal caused transient activation of phototransduction, as evidenced by a decrease of the dark current and sensitivity, acceleration of the dim flash responses, and activation of cGMP phosphodiesterase and guanylyl cyclase. The steady state of phototransduction activity was still higher than that of the bleach-adapted rod. In contrast, exposure of bleach-adapted cones to 11-cis 13-demethylretinal resulted in an immediate deactivation of transduction as measured by the same parameters. These results extend the validity of a model for the effects of the noncovalent binding of a retinoid in the chromophore pockets of rod and cone opsins to analogs capable of forming a Schiff-base and imply that the noncovalent binding by itself may play a role for the dark adaptation of photoreceptors.
Fifty years of change in some meteorological instruments
Authors: G D Robinson
Published: July 2002

Meteorological Office, Bracknell, Berks. This year, 1968, is the 50th anniversary of the formation of the Institute of Physics. (The Institute of Physics and The Physical Society was formed from the amalgamation of the two bodies.) In order to celebrate this Jubilee we are publishing a series of articles concerning various aspects of instrumentation over the last 50 years.
Dielectric relaxation spectroscopy of liquids: frequency domain and time domain experimental methods
Authors: U Kaatze  , K Giese
Published: July 2002

Starting from basic principles of dielectric relaxation measurements, an account is given on the present state of the frequency and time domain methods. The relative merits and limitations of the different techniques of measurement are discussed.
Microprocessor system for control and data acquisition in a millimetre-wave spectrometer
Authors: M Bogey  , C Demuynck  , J L Destombes  , J M Lapauw
Published: July 2002

A description is given of a millimetre-wave spectrometer controlled by a dedicated microprocessor system. This system, built around an Intel 8085A microprocessor, samples, digitises and stores the spectroscopic repetitive waveform and executes on the stored data some automatic data processing operations such as smoothing, baseline suppression and frequency calculation. New results on the millimetre-wave spectrum of CO in very high vibrational states (v<or=40) and on the rotational spectrum of C3O are briefly given as an illustration of the use of this system for the study of transient species.
The response time of a surface thermometer employing encapsulated thermochromic liquid crystals
Authors: P T Ireland  , T V Jones
Published: July 2002

A time-varying surface temperature may be measured by a thin film of encapsulated thermochromic liquid crystal applied to the surface. The work reported in this paper has assessed, for engineering purposes, the response of such a film to a rapidly increasing surface temperature. Rates of increase in temperature of greater than 2000 degrees C s-1 were employed in these tests. The experiments show that the delay between the time at which the surfaces reaches the steady-state colour display temperature and the occurrence of the colour display is no more than a few milliseconds. The particular type of film used employed a micro-encapsulated chiral nematic thermochromic liquid crystal which was supplied by BDH and applied to the surface by a screen printing technique to a thickness of approximately 10 mu m. The conduction of heat into the film is analysed, but this would not appear to explain the observed response time of the thermometer.
Measurement of neutron and proton-induced background in germanium gamma-ray spectrometers for use in a space environment
Authors: A K Entwistle  , C S Dyer  , J J Quenby  , A J Evans  , M Joshi
Published: July 2002

Particle-induced background in germanium spectrometers used for astrophysical and remote sensing measurement in a space environment provides an important limitation to the ultimate instrument sensitivity. To aid future experimental design and interpretation, laboratory exposure of typical sensors to known fluences of slow and fast neutrons and energetic protons is carried out to predict the line and continuum background components. Fast neutron elastic scatter is found to be the chief source of background below 100 keV for an unshielded detector inside a heavy spacecraft. At higher energies, comparable contributions are identified from neutron inelastic scattering and neutron- and proton-induced radioactivity. Radiation damage to an n-type high purity Ge detector caused broadening in resolution by a factor of 1.8 after subjection to 1.2*1010 protons of 600 MeV.
Future developments in automotive sensors and their systems
Authors: M H Westbrook
Published: July 2002

The author speculates about some of the new developments in sensor and related technology, in particular intelligent sensors, self-calibrating sensors and new developments in control technology which may permit a reduction in the number of sensors required for future control systems. Some of the latest developments of practical sensor technology for near-future systems within the vehicle are then described as well as some of the sensors which will enable the vehicle and its driver to interact with the world outside the vehicle.
Analogue circuits for luminescence polarization measurements
Authors: F W J Teale
Published: July 2002

Very simple instrumentation, using the properties of balanced resistance bridges, can be used to measure directly the polarization of luminescence, emission anisotropy and other parameters. The incorporation of these circuits into a simple manually operated polarization photometer suitable for routine measurements or teaching purposes, and also into a more elaborate automated instrument for research use, is outlined.
Laser plasma generation from a deuterium ice pellet freely falling within a superconducting magnetic bottle
Authors: M Tanimoto  , A Kitsunezaki  , T Sekiguchi
Published: July 2002

An experimental system is described for the production of an isolated plasma blob from a freely falling, isolated deuterium ice pellet by means of a high power giant laser pulse. A falling pellet which has dimensions ranging from 0.1 to 0.4 mm (with 5*1016-3*1018atoms), is detached from the freezer head by gravity and is captured by the focused high power laser beam pulse after falling freely through about 10 cm. The plasma thus produced in a vacuum chamber is confined in a magnetic cusp or mirror field which is produced by a pair of superconducting coils.
Infrared spectroscopy of adsorbed layers. I. Possible sensitivity improvements
Authors: J C Smith
Published: July 2002

The immense information potential of infrared spectroscopy on adsorbed layers on metal surfaces is difficult to realize since signal strengths lie near to the limits of detection using present techniques. Previous work has been directed at increasing signal strength; a reduction of the noise level is the goal of the present contribution. Two possible methods are suggested, a synchronous differentiating method and a calorimetric technique whereby only absorbed radiation is detected. The first is a common procedure in other similar applications, for example Auger spectroscopy, and a practical approach to the second method is suggested.
Optical isolators for high-power giant-pulse lasers
Authors: K Eidmann  , P Sachsenmaier  , H Salzmann  , R Sigel
Published: July 2002

Describes Faraday rotators acting as optical isolators, which are indispensable to experiments for producing plasmas with high-power giant-pulse lasers. Special attention is paid to the problem of material.
An improved bakeable quartz fibre manometer
Authors: W Nowak
Published: July 2002

An improved quartz-fibre manometer is described which is bakeable to 520 degrees C and is suitable for measurements in ultrahigh vacuum systems. The cell contains no metallic components, so that pressure measurements in corrosive gaseous media within a range of 10- to some 10-6 torr are practicable. Suspension of the vibrating system within a glass bellows tube permits more satisfactory initiation of the oscillations, and the influence of external disturbances on the system is also reduced.
Operational characteristics of a radio-frequency ion source
Authors: M Yar Khan  , S Ali Khan
Published: July 2002

An RF ion source has been constructed which yields a hydrogen ion current of up to 6 mA, consisting of 60-70% protons. The ion current yield has been studied as a function of the discharge parameter, i.e. the oscillator input power, gas pressure, magnetic field, extracting voltage and extracting electrode geometry. The ion current yield is increased by about 50% by the application of an axial magnetic field at a discharge pressure of about 30 mTorr. Mean beam energies of about 250 eV above the extracting voltage up to 4000 V have been observed.
Gas gain measurements in proportional counters
Authors: M W Charles
Published: July 2002

Doubt is cast upon evidence in favour of various theories of gas amplification because of errors in gas gain measurement through amplifier pulse shaping effects. Measurements for a 90:10 Ar:CH4 gas mixture are presented which illustrate this effect.
Photoconductivity-its application in photometry
Authors: S K Guha
Published: July 2002

In appraising the performance of a new photometer using cadmium sulphide cells the principle and operation of the instrument are described. Photoconductivity of a CdS cell is discussed in relation to some limitations of the instrument, as detected during calibration. Difficulties are experienced in keeping the meter in calibration due to some inherent characteristics of dynamic equilibrium of a CdS cell under any condition. To overcome these difficulties some suggestions are outlined for the users, and some modifications proposed in future design.
Tensile test apparatus for brittle materials
Authors: J N Robinson
Published: July 2002

A modified version of previous methods of testing rings of brittle material by internal pressurization is described. The modified version is simpler and cheaper to make and can be used where a pressure vessel capable of high pressures, such as isostatic pressing equipment, is available. The calibration of the apparatus is described and some results for paper-reinforced resin are given.
Instrumental effects in the Raman lineshapes of polaritons
Authors: K H F Ahrens  , G Schaack  , B Unger
Published: July 2002

The instrumental lineshapes of polaritons observed in near forward scattering experiments with the arrangement suggested by Claus have been calculated by means of geometrical optics. The width of the exciting laser beam, the finite apertures of blinds and the acceptance angles of lenses have been considered. The results are compared with experimental lineshapes of a phonon polariton in uniaxial potassium bromate.
A fast gas valve for plasma sampling (in isotope separation study)
Authors: S W Simpson
Published: July 2002

The construction and operation of a fast acting gas valve is described. The valve, which has a measured sampling time of 150 mu s, has been used to extract samples from a transient rotating neon plasma for the purpose of studying isotope separation effects in the plasma. The motion of the valve was investigated optically. The valve sampling time was determined by a novel method, which utilized the discharge itself.
Two new points in the spectrum of the absolute Mahler measure of totally positive algebraic integers
Authors: Flammang V.
Published: July 2002

For totally positive algebraic integers

α
≠
0
,
1

\alpha \ne 0,1

of degree

d
(
α
)

d(\alpha )

, we consider the set

L

\mathcal {L}

of values of

M
(
α

)

1

d
(
α
)

=
Ω
(
α
)

M(\alpha )^{\frac 1{d(\alpha )}}=\Omega (\alpha )

, where

M
(
α
)

M(\alpha )

is the Mahler measure of

α
\alpha

. C. J. Smyth has found the four smallest values of

L

\mathcal {L}

and conjectured that the fifth point is

Ω
(
(
2
cos
⁡

2
π

60

)
2

)

\Omega ((2\cos \frac {2\pi }{60})^2)

. We prove that this is so and, moreover, we give the sixth point of

L

\mathcal {L}

.
Some results on pseudosquares
Authors: Lukes R. , Patterson C. , Williams H.
Published: July 2002

If

p
p

is an odd prime, the pseudosquare

L
p

L_p

is defined to be the least positive nonsquare integer such that

L
p

≡
1

(
mod

8
)

L_p\equiv 1\pmod {8}

and the Legendre symbol

(

L
p

/

q
)
=
1

(L_p/q)=1

for all odd primes

q
≤
p

q\le p

. In this paper we first discuss the connection between pseudosquares and primality testing. We then describe a new numerical sieving device which was used to extend the table of known pseudosquares up to

L

271

L_{271}

. We also present several numerical results concerning the growth rate of the pseudosquares, results which so far confirm that

L
p

>

e

p

/

2

L_p> e^{\sqrt {p/2}}

, an inequality that must hold under the extended Riemann Hypothesis.
The zeros of Faber polynomials generated by an 𝑚-star
Authors: Kuijlaars Arno
Published: July 2002

It is shown that the zeros of the Faber polynomials generated by a regular

m
m

-star are located on the

m
m

-star. This proves a recent conjecture of J. Bartolomeo and M. He. The proof uses the connection between zeros of Faber polynomials and Chebyshev quadrature formulas.
A multiple-precision division algorithm
Authors: Smith David
Published: July 2002

The classical algorithm for multiple

\,

-precision division normalizes digits during each step and sometimes makes correction steps when the initial guess for the quotient digit turns out to be wrong. A method is presented that runs faster by skipping most of the intermediate normalization and recovers from wrong guesses without separate correction steps.
A new algorithm for constructing large Carmichael numbers
Authors: Löh Günter , Niebuhr Wolfgang
Published: July 2002

We describe an algorithm for constructing Carmichael numbers

N
N

with a large number of prime factors

p

1

,

p

2

,
…
,

p

k

p_{1}, p_{2}, \dots , p_{k}

. This algorithm starts with a given number

Λ
=
lcm
⁡
(

p

1

−
1
,

p

2

−
1
,
…
,

p

k

−
1
)

\Lambda =\operatorname {lcm} (p_{1}-1, p_{2}-1, \dots ,p_{k}-1)

, representing the value of the Carmichael function

λ
(
N
)

\lambda (N)

. We found Carmichael numbers with up to

1101518
1101518

factors.
Simple perfect squared squares and 2×1 squared rectangles of order 26
Authors: Duijvestijn A.
Published: July 2002

In this note tables of all simple perfect squared squares and simple

2
×
1

2\times 1

perfect squared rectangles of order 26 are presented.
Unicity in piecewise polynomial 𝐿¹-approximation via an algorithm
Authors: Gayle R. , Wolfe J.
Published: July 2002

Our main result shows that certain generalized convex functions on a real interval possess a unique best

L

1

L^{1}

approximation from the family of piecewise polynomial functions of fixed degree with varying knots. This result was anticipated by Kioustelidis in [Uniqueness of optimal piecewise polynomial

L

1

L_{1}

approximations for generalized convex functions, from “Functional Analysis and Approximation”, Internat. Ser. Numer. Math., vol. 60 (1981), 421–432]; however the proof given there is nonconstructive and uses topological degree as the primary tool, in a fashion similar to the proof the comparable result for the

L

2

L^{2}

case in [J. Chow, On the uniqueness of best

L

2

[
0
,
1
]

L_{2}[0,1]

approximation by piecewise polynomials with variable breakpoints, Math. Comp. 39 (1982), 571–585.]. By contrast, the proof given here proceeds by demonstrating the global convergence of an algorithm to calculate a best approximation over the domain of all possible knot vectors. The proof uses the contraction mapping theorem to simultaneously establish convergence and uniqueness. This algorithm was suggested by Kioustelidis [Optimal segmented polynomial

L

p

L^{p}

-approximation, Computing 26 (1981), 239–246.]. In addition, an asymptotic uniqueness result and a nonuniqueness result are indicated, which analogize known results in the

L

2

L^{2}

case.
Dissections of 𝑝:𝑞 rectangles
Authors: Jepsen Charles
Published: July 2002

We determine all simple perfect dissections of

p
:
q

p:q

rectangles into at most twelve

p
:
q

p:q

rectangular elements. A computer search shows there are only eight such dissections, two of order 10, three of order 11, and three of order 12.
Cyclotomic units and Greenberg’s conjecture for real quadratic fields
Authors: Fukuda Takashi
Published: July 2002

We give new examples of real quadratic fields

k
k

for which the Iwasawa invariant

λ
3

(
k
)

\lambda _3(k)

and

μ
3

(
k
)

\mu _3(k)

are both zero by calculating cyclotomic units of real cyclic number fields of degree 18.