bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of alcohol on respiratory variables in normal humans
Authors: WOLFF C. B. , PETERS T. J. , KEATING J. , GARDNER W. N.
Published: July 2002

The study is designed to clarify the effect of low doses of alcohol on respiratory variables in air breathing normal subjects. Each subject was given an initial loading dose of alcohol (0.270 g/kg) followed, half an hour later, by a second dose (0.135 g/kg). Blood alcohol increased to a mean value of 52.0 ± 3.0 (SEM) mg/100 ml at 1 hour. Resting ventilation increased significantly from a mean value of 6.25 ± 0.41 litres min−1 to 7.20 ± 0.31 litres min−1 1 hour after alcohol (p= 0.025). Mean inspiratory flow was also increased (p= 0.045). Endtidal PCO2 (PET CO2) showed a highly significant fall (1.87 ± 0.35 mm Hg; p < 0.001) without a significant change in CO2 production rate (p > 0.05). PET CO2 variability (100 × SD/mean) was low (mean 2.4%) and unaffected by alcohol. The longest end‐expiratory pauses (apnoeas) observed for each subject were shortened significantly by alcohol (1.030 ± 0.194 s and 0.690 ± 0.138 s; p = 0.01). Moderate doses of alcohol in normal subjects, therefore lower PET CO2 and shorten end‐expiratory pauses (apnoeic periods) but do not affect PET CO2 variability.
The corticosteroid synthesis inhibitor metyrapone markedly enhances the behavioural effects of d‐amphetamine
Authors: MARROW LYNNE , STATHAM ALISON , OVERTON PAUL G. , BRAIN PAUL F. , CLARK DAVID
Published: July 2002

The clinically utilized corticosteroid synthesis inhibitor metyrapone attenuates the behavioural effects of cocaine in the rat. Given the potential therapeutic implications of this interaction, we felt it important to determine if metyrapone's action would generalize to another widely abused psychostimulant, namely d‐amphetamine. However, rather than producing attenuation, metyrapone preadministration (3 100 mg/kg) markedly enhanced both the locomotor activating and stereotypy‐inducing actions of d‐amphetamine (dose equivalent to 2.5 mg/kg free base). The fact that the corticosteroid synthesis inhibitor trilostane did not affect the behavioural action of d‐amphetamine suggests that inhibition of corticoid synthesis does not underlie the action of metyrapone. Instead, it is argued that inhibition of debrisoquine hydroxylase (cytochrome p450 2D1), an enzyme involved in the metabolism of d‐amphetamine, represents the critical mechanism of action.
Oral reading in Chinese: evidence from dementia of the Alzheimer's type
Authors: Weekes Brendan
Published: July 2002

The traditional view of oral reading ability in patients with dementia holds that it is a preserved skill even if there is a general impairment to lexico‐semantic processing ability. Recently, this view has been challenged by studies showing that the oral reading ability of patients with dementia can deteriorate over the course of the disease. These studies have found that the oral reading of irregular English words is more prone to error than the oral reading of regular words by patients with dementia suggesting that the oral reading of irregular words depends upon support from semantic memory. Relatively little is known about the oral reading abilities of Chinese‐speaking dementia patients. This paper reports on the results of a study of the language processing and the oral reading ability of Chinese speakers with probable dementia of the Alzheimer's type (DAT). DAT patients displayed impairment on tests of oral reading as well as impairment on tests of semantic memory, confrontation naming and word comprehension. The results also show significant effects of regularity, frequency and imageability on the oral reading of DAT patients. It is argued that Chinesespeaking DAT patients display a pattern of language impairment similar to their English‐speaking counterparts and, moreover, that normal oral reading of Chinese characters may depend critically upon the integrity of semantic memory.
Risk factors for speech disorders in children
Authors: Fox A. V. , Dodd Barbara , Howard David
Published: July 2002

The study evaluated the relationship between risk factors and speech disorders. The parents of 65 children with functional speech disorders (aged 2;7−7;2) and 48 normally speaking controls (aged 3;4−6;1) completed a questionnaire investigating risk factors associated in the literature with developmental communication disorders. The findings indicated that some risk factors (pre‐ and perinatal problems, ear, nose and throat (ENT) problems, and sucking habits and positive family history) distinguished speech‐disordered from normally speaking control populations. The present study also investigated whether specific risk factors were associated with three subgroups of speech disorders identified according to their surface error patterns as suggested by Dodd (1995). No risk factor apart from pre‐ and perinatal factors could be found that differentiated these subgroups of speech disorder, so that none of the subgroups exhibited a specific profile of risk factor involvement. Neither was it possible to classify the children according to the risk factor categories suggested by Shriberg's classification system (Shriberg 1994). The relevance of risk factor identification for functional speech disorders is discussed.
Partial Recovery of Light‐Independent Chlorophyll Biosynthesis in the chlL ‐Deletion Mutant of Synechocystis sp. PCC 6803
Authors: Wu Qingyu , Yu Jiujiu , Zhao Nanming
Published: July 2002

A chlL ‐deletion mutant of Synechocystis sp. PCC 6803 designated as chlL ‐ was unable to make significant amounts of chlorophyll in darkness. However, an apparent pseudorevertant has been generated spontaneously that can synthesize an increased amount of chlorophyll under light‐activated heterotrophic growth conditions. Under these conditions, the chlorophyll content in this pseudorevertant was about 20% of that in the wild‐type strain and about 4 times more than that in the original and in the recently recreated chlL ‐deletion mutant. This is paralleled by increased performance of dark‐grown cells in terms of chlorophyll fluorescence induction and oxygen evolution rates in the pseudorevertant versus in the original mutant. PCR analysis confirmed that the chlL ‐ pseudorevertant mutant still lacked the chlL gene. These results imply that the light‐independent chlorophyll biosynthesis pathway was partly recovered.
Extracellular Fibrillar Structure of Latent TGFβ Binding Protein-1: Role in TGFβ-dependent Endothelial-Mesenchymal Transformation during Endocardial Cushion Tissue Formation in Mouse Embryonic Heart
Authors: Nakajima Yuji , Miyazono Kohei , Kato Mitsuyasu , Takase Masao , Yamagishi Toshiyuki , Nakamura Hiroaki
Published: July 2002

Transforming growth factor-β (TGFβ) is a dimeric peptide growth factor which regulates cellular differentiation and proliferation during development. Most cells secrete TGFβ as a large latent TGFβ complex containing mature TGFβ, latency associated peptide, and latent TGFβ-binding protein (LTBP)-1. The biological role of LTBP-1 in development remains unclear. Using a polyclonal antiserum specific for LTBP-1 (Ab39) and three-dimensional collagen gel culture assay of embryonic heart, we examined the tissue distribution of LTBP-1 and its functional role during the formation of endocardial cushion tissue in the mouse embryonic heart. Mature TGFβ protein was required at the onset of the endothelial-mesenchymal transformation to initiate endocardial cushion tissue formation. Double antibody staining showed that LTBP-1 colocalized with TGFβ1 as an extracellular fibrillar structure surrounding the endocardial cushion mesenchymal cells. Immunogold electronmicroscopy showed that LTBP-1 localized to 40–100 nm extracellular fibrillar structure and 5–10-nm microfibrils. The anti–LTBP-1 antiserum (Ab39) inhibited the endothelial-mesenchymal transformation in atrio-ventricular endocardial cells cocultured with associated myocardium on a three-dimensional collagen gel lattice. This inhibitory effect was reversed by administration of mature TGFβ proteins in culture. These results suggest that LTBP-1 exists as an extracellular fibrillar structure and plays a role in the storage of TGFβ as a large latent TGFβ complex.
The Role of Xgrip210 in γ-Tubulin Ring Complex Assembly and Centrosome Recruitment
Authors: Zhang Lijun , Keating Thomas J. , Wilde Andrew , Borisy Gary G. , Zheng Yixian
Published: July 2002

The γ-tubulin ring complex (γTuRC), purified from the cytoplasm of vertebrate and invertebrate cells, is a microtubule nucleator in vitro. Structural studies have shown that γTuRC is a structure shaped like a lock-washer and topped with a cap. Microtubules are thought to nucleate from the uncapped side of the γTuRC. Consequently, the cap structure of the γTuRC is distal to the base of the microtubules, giving the end of the microtubule the shape of a pointed cap. Here, we report the cloning and characterization of a new subunit of Xenopus γTuRC, Xgrip210. We show that Xgrip210 is a conserved centrosomal protein that is essential for the formation of γTuRC. Using immunogold labeling, we found that Xgrip210 is localized to the ends of microtubules nucleated by the γTuRC and that its localization is more distal, toward the tip of the γTuRC-cap structure, than that of γ-tubulin. Immunodepletion of Xgrip210 blocks not only the assembly of the γTuRC, but also the recruitment of γ-tubulin and its interacting protein, Xgrip109, to the centrosome. These results suggest that Xgrip210 is a component of the γTuRC cap structure that is required for the assembly of the γTuRC.
Molecular Characterization and Functional Analysis of Murine Interleukin 4 Receptor Allotypes
Authors: Schulte T. , Kurrle R. , Röllinghoff M. , Gessner A.
Published: July 2002

The murine interleukin 4 receptor (IL-4R) exists as a transmembrane protein transducing pleiotropic IL-4 functions, or as soluble (s)IL-4–binding molecule with potent immunoregulatory effects. In this study we identified and characterized a murine IL-4R allotype. Sequence analysis of the IL-4R cDNA of BALB/c mice revealed 18 base substitutions leading to three extracellular and five cytoplasmic amino acid changes when compared with the published IL-4R sequence of C57BL/6 mice. Analyses with allotype-specific mAbs revealed that AKR/J and SJL/J mice possess the newly identified BALB/c IL-4R allotype whereas the IL-4Rs of C3H, CBA, DBA-2, and FVB/N mice are identical to that of the C57BL/6 mouse. The extracellular Thr49 to Ile substitution abrogates one N-glycosylation site in the naturally occurring BALB/c IL-4R as well as in the experimentally point mutated C57BL/6-T49I sIL-4R, and both molecules display a nearly threefold reduction in IL-4–neutralizing activity compared to the C57BL/6 sIL-4R. In line with this, a significantly enhanced dissociation rate of IL-4 was detected for the BALB/c IL-4R allotype by surface plasmon resonance and in radioligand binding studies with IL-4R–transfected cell lines. These findings suggest that the altered ligand binding behavior of the newly described IL-4R allotype may influence the IL-4 responsiveness, thus contributing to the diverse phenotypes of inbred mouse strains in IL-4–dependent diseases.
The Class I Antigen-processing Pathway for the Membrane Protein Tyrosinase Involves Translation in the Endoplasmic Reticulum and Processing in the Cytosol
Authors: Mosse Claudio A. , Meadows Leslie , Luckey Chance J. , Kittlesen David J. , Huczko Eric L. , Slingluff Craig L. , Shabanowitz Jeffrey , Hunt Donald F. , Engelhard Victor H.
Published: July 2002

Formation of major histocompatibility complex class I–associated peptides from membrane proteins has not been thoroughly investigated. We examined the processing of an HLA-A*0201–associated epitope, YMDGTMSQV, that is derived from the membrane protein tyrosinase by posttranslational conversion of the sequence YMNGTMSQV. Only YMDGTMSQV and not YMNGTMSQV was presented by HLA-A*0201 on cells expressing full-length tyrosinase, although both peptides have similar affinities for HLA-A*0201 and are transported by TAP. In contrast, translation of YMNGTMSQV in the cytosol, as a minigene or a larger fragment of tyrosinase, led to the presentation of the unconverted YMNGTMSQV. This was not due to overexpression leading to saturation of the processing/conversion machinery, since presentation of the converted peptide, YMDGTMSQV, was low or undetectable. Thus, presentation of unconverted peptide was associated with translation in the cytosol, suggesting that processing of the full-length tyrosinase occurs after translation in the endoplasmic reticulum. Nevertheless, presentation of YMDGTMSQV in cells expressing full-length tyrosinase was TAP (transporter associated with antigen processing) and proteasome dependent. After inhibition of proteasome activity, tyrosinase species could be detected in the cytosol. We propose that processing of tyrosinase involves translation in the endoplasmic reticulum, export of full-length tyrosinase to the cytosol, and retransport of converted peptides by TAP for association with HLA-A*0201.
Characterization of the 4C8 Antigen Involved in Transendothelial Migration of CD26hi T Cells after Tight Adhesion to Human Umbilical Vein Endothelial Cell Monolayers
Authors: Masuyama Jun-ichi , Yoshio Taku , Suzuki Kenichi , Kitagawa Seiichi , Iwamoto Masahiro , Kamimura Takeshi , Hirata Daisuke , Takeda Akira , Kano Shogo , Minota Seiji
Published: July 2002

In extravasation of T cells, little is known about the mechanisms of transendothelial migration subsequent to the T cells' tight adhesion to endothelium. To investigate these mechanisms, we developed a monoclonal antibody (mAb), termed anti-4C8, that blocks transmigration but not adhesion in a culture system in which high CD26–expressing (CD26hi) T cells preferentially migrate through human umbilical vein endothelial cell (HUVEC) monolayers cultured on collagen gels. Anti-4C8 reacted with all CD3+ T cells and monocytes but not neutrophils or HUVECs. The structure defined by this antibody was an 80-kD molecule. The mAb at 1 μg/ml inhibited 80–90% of migration of CD3+ T cells through unstimulated and interferon γ–stimulated HUVEC monolayers without interfering with adhesion and cell motility. When added to the cultures after the adhesion, anti-4C8 completely blocked subsequent transmigration of adherent T cells. Phase–contrast and electron microscopy revealed that T cells are arrested at the intercellular junctions of HUVECs in the presence of anti-4C8. Anti-4C8 exhibited agonistic effects on resting T cells without other stimuli under culture conditions in which anti-4C8 can stimulate T cells. First, in the checkerboard assay using collagen gels, the antibody promoted chemokinetic migration of the cells in a dose-dependent manner from 0.1 to 10 μg/ml. The predominant population of T cells that migrated into collagen gels with impregnated anti-4C8 were CD26hi. Second, solid-phase–immobilized anti-4C8 induced adhesion of T cells to the substrate, often with polarizations in cell shape and large pseudopods rich in filamentous (F-) actin. Third, soluble anti-4C8 augmented F-actin content preferentially in CD26hi T cells when added to T cells at a high dose of 10 μg/ml. Finally, both anti-4C8–induced chemokinetic migration and transendothelial migration were inhibited by pretreatment of T cells with pertussis toxin. These findings suggest that stimulation via the 4C8 antigen increases cell motility of CD26hi cells with profound cytoskeletal changes through signaling pathways including G proteins. The 4C8 antigen may be involved in preferential transmigration of CD26hi cells adherent to HUVECs.
Human Transporters Associated with Antigen Processing (Taps) Select Epitope Precursor Peptides for Processing in the Endoplasmic Reticulum and Presentation to T Cells
Authors: Lauvau Grégoire , Kakimi Kazuhiro , Niedermann Gabriele , Ostankovitch Marina , Yotnda Patricia , Firat Hüseyin , Chisari Francis V. , van Endert Peter M.
Published: July 2002

Antigen presentation by major histocompatibility complex (MHC) class I molecules requires peptide supply by the transporters associated with antigen processing (TAPs), which select substrates in a species- and, in the rat, allele-specific manner. Conflicts between TAPs and MHC preferences for COOH-terminal peptide residues in rodent cells strongly reduce the efficiency of MHC class I antigen presentation. Although human TAP is relatively permissive, some peptide ligands for human histocompatibility leukocyte antigen class I molecules are known to possess very low TAP affinities; the significance of these in vitro findings for cellular antigen presentation is not known. We studied two naturally immunodominant viral epitopes presented by HLA-A2 that display very low affinities for human TAP. Low TAP affinities preclude minimal epitope access to the endoplasmic reticulum (ER) and assembly with HLA-A2 in vitro, as well as presentation by minigene-expressing cells to cytotoxic T lymphocytes. However, NH2-terminally but not COOH-terminally extended epitope variants with higher TAP affinities assemble in vitro and are presented to cytotoxic T lymphocytes with high efficiency. Thus, human TAP can influence epitope selection and restrict access to the ER to epitope precursors. Analysis of TAP affinities of a panel of viral epitopes suggests that TAP selection of precursors may be a common phenomenon for HLA-A2–presented epitopes. We also analyzed HLA-A2–eluted peptides from minigene-expressing cells and show that an NH2-terminally extended variant with low A2 binding affinity undergoes ER processing, whereas another with high affinity is presented unmodified. Therefore, the previously reported aminopeptidase activity in the ER can also act on TAP-translocated peptides.
Precursor B Cell Receptor–Dependent B Cell Proliferation and Differentiation Does Not Require the Bone Marrow or Fetal Liver Environment
Authors: Rolink Antonius G. , Winkler Thomas , Melchers Fritz , Andersson Jan
Published: July 2002

The capacity of precursor B (pre-B) I cells from fetal liver and bone marrow to proliferate and differentiate into surface immunoglobulin–positive immature B cells in vitro was analyzed. Both fetal liver– and bone marrow–derived progenitors do so in a pre-B cell receptor (pre-BCR)–dependent manner in tissue culture medium alone, without addition of other cells or cytokines. Approximately 20% of the initial pre-B I cells enter more than one division. Analyses at the single-cell level show that ∼15% divide two to five times. Coculture of pre-B I cells with stromal cells did not enhance proliferation or differentiation, whereas the presence of interleukin 7, especially in combination with stromal cells, resulted mainly in the expansion of pre-B I cells and prevented their further differentiation. Thus, the environment of fetal liver or bone marrow is not required for the pre-BCR to exert its function, which is to select and expand cells that have undergone an inframe VH-DHJH rearrangement that produces a pre-BCR–compatible μH chain. It appears unlikely that a ligand for the pre-BCR drives this pre-B cell proliferation.
The Interleukin 7 Receptor Is Required for T Cell Receptor γ Locus Accessibility to the V(D)j Recombinase
Authors: Schlissel Mark S. , Durum Scott D. , Muegge Kathrin
Published: July 2002

Defects in the interleukin (IL)-7 signal transduction pathway lead to severe immunodeficiency in humans and in mice. In IL-7 receptor–deficient (IL-7R−/−) mice, lymphoid precursors show a reduced survival rate and variable/diversity/joining region V(D)J recombination is variously affected in different loci, being arrested in the T cell receptor (TCR)-γ locus, aberrant in the immunoglobulin heavy chain (IgH) locus, and delayed in the TCR-β locus. Here, we analyze the recombination defect of the TCR-γ locus. Using ligation-mediated polymerase chain reaction, we sought intermediates of the recombination process. In the absence of the IL-7 signal, no initiation of recombination of the TCR-γ locus was observed, whereas recombination intermediates at the TCR-β locus could be detected. Thus, the failure to rearrange the TCR-γ locus is due to a failure to initiate cleavage rather than a failure to religate broken DNA ends. V(D)J recombination was previously thought to begin at the pro-T2 stage of T cell development after the arrest of IL-7R−/− thymocytes at the pro-T1 stage. However, here we show that both TCR-γ and -β recombination intermediates are readily detectable in normal T1 cells, but only TCR-β intermediates were detected in IL-7R−/− T1 cells, supporting a mechanistic role for IL-7 in TCR-γ locus rearrangement. Since reduced recombination activating gene (rag) expression has been reported in the absence of the IL-7 signal, we directly tested whether the TCR-γ locus is accessible to cleavage by recombinant Rag proteins in vitro. We found a reduction in chromatin accessibility for Rag-mediated cleavage in IL-7R−/− thymocytes compared with wild-type. Thus, IL-7 controls recombination at the TCR-γ locus by regulating locus accessibility.
Regulation of Interleukin (Il)-18 Receptor α Chain Expression on Cd4+ T Cells during T Helper (Th)1/Th2 Differentiation
Authors: Smeltz Ronald B. , Chen June , Hu-Li Jane , Shevach Ethan M.
Published: July 2002

Interleukin (IL)-18 has been well characterized as a costimulatory factor for the induction of IL-12–mediated interferon (IFN)-γ production by T helper (Th)1 cells, but also can induce IL-4 production and thus facilitate the differentiation of Th2 cells. To determine the mechanisms by which IL-18 might regulate these diametrically distinct immune responses, we have analyzed the role of cytokines in the regulation of IL-18 receptor α chain (IL-18Rα) expression. The majority of peripheral CD4+ T cells constitutively expressed the IL-18Rα. Upon antigen stimulation in the presence of IL-12, marked enhancement of IL-18Rα expression was observed. IL-12–mediated upregulation of IL-18Rα required IFN-γ. Activated CD4+ T cells that expressed low levels of IL-18Rα could produce IFN-γ when stimulated with the combination of IL-12 and IL-18, while CD4+ cells which expressed high levels of IL-18Rα could respond to IL-18 alone. In contrast, T cell stimulation in the presence of IL-4 resulted in a downregulation of IL-18Rα expression. Both IL-4−/− and signal transducer and activator of transcription (Stat)6−/− T cells expressed higher levels of IL-18Rα after TCR stimulation. Furthermore, activated T cells from Stat6−/− mice produced more IFN-γ in response to IL-18 than wild-type controls. Thus, positive/negative regulation of the IL-18Rα by the major inductive cytokines (IL-12 and IL-4) determines the capacity of IL-18 to polarize an immune response.
Calcium Site Specificity
Authors: Lacaz-Vieira Francisco
Published: July 2002

The molecular mechanisms by which Ca2+ and metal ions interact with the binding sites that modulate the tight junctions (TJs) have not been fully described. Metal ions were used as probes of these sites in the frog urinary bladder. Basolateral Ca2+ withdrawal induces the opening of the TJs, a process that is abruptly terminated when Ca2+ is readmitted, and is followed by a complete recovery of the TJ seal. Mg2+ and Ba2+ were incapable of keeping the TJ sealed or of inducing TJ recovery. In addition, Mg2+ causes a reversible concentration-dependent inhibition of the Ca2+-induced TJ recovery. The effects of extracellular Ca2+ manipulation on the TJs apparently is not mediated by changes of cytosolic Ca2+ concentration. The transition elements, Mn2+ and Cd2+, act as Ca2+ agonists. In the absence of Ca2+, they prevent TJ opening and almost immediately halt the process of TJ opening caused by Ca2+ withdrawal. In addition, Mn2+ promotes an almost complete recovery of the TJ seal. Cd2+, in spite of stabilizing the TJs in the closed state and halting TJ opening, does not promote TJ recovery, an effect that apparently results from a superimposed toxic effect that is markedly attenuated by the presence of Ca2+. The interruption of TJ opening caused by Ca2+, Cd2+, or Mn2+, and the stability they confer to the closed TJs, might result from the interaction of these ions with E-cadherin. Addition of La3+ (2 μM) to the basolateral Ca2+-containing solution causes an increase of TJ permeability that fully reverses when La3+ is removed. This effect of La3+, observed in the presence of Ca2+ (1 mM), indicates a high La3+ affinity for the Ca2+-binding sites. This ability of La3+ to open TJs in the presence of Ca2+ is a relevant aspect that must be considered when using La3+ in the evaluation of TJ permeability of epithelial and endothelial membranes, particularly when used during in vivo perfusion or in the absence of fixatives.
Error bounds for quasi-Monte Carlo integration with nets
Authors: Lécot Christian
Published: July 2002

We analyze the error introduced by approximately calculating the

s
s

-dimensional Lebesgue measure of a Jordan-measurable subset of

I
s

=
[
0
,
1

)
s

I^s=[0,1)^s

. We give an upper bound for the error of a method using a

(
t
,
m
,
s
)

(t,m,s)

-net, which is a set with a very regular distribution behavior. When the subset of

I
s

I^s

is defined by some function of bounded variation on

I
¯

s
−
1

{\bar I}^{s-1}

, the error is estimated by means of the variation of the function and the discrepancy of the point set which is used. A sharper error bound is established when a

(
t
,
m
,
s
)

(t,m,s)

-net is used. Finally a lower bound of the error is given, for a method using a

(
0
,
m
,
s
)

(0,m,s)

-net. The special case of the 2-dimensional Hammersley point set is discussed.
The serial test for a nonlinear pseudorandom number generator
Authors: Kato Takashi , Wu Li-Ming , Yanagihara Niro
Published: July 2002

Let

M
=

2

w

,

M = 2^{w},

and

G

M

=
{
1
,
3
,
.
.
.
,
M
−
1
}
.

G_{M} = \{1,3,...,M-1 \}.

A sequence

{

y

n

}
,

y

n

∈

G

M

,

\{y_{n} \}, y_{n} \in G_{M},

is obtained by the formula

y

n
+
1

≡
a

y
¯

n

+
b
+
c

y

n

m
o
d

M
.

y_{n+1} \equiv a{\overline {y}_{n}} + b + cy_{n} \; \mathrm {mod} \; M.

The sequence

{

x

n

}
,

x

n

=

y

n

/

M
,

\{x_{n} \}, x_{n}=y_{n}/M,

is a sequence of pseudorandom numbers of the maximal period length

M

/

2

M/2

if and only if

a
+
c
≡
1

a+c \equiv 1

(mod 4),

b
≡
2

b \equiv 2

(mod 4). In this note, the uniformity is investigated by the 2-dimensional serial test for the sequence. We follow closely the method of papers by Eichenauer-Herrmann and Niederreiter.
Inversive congruential pseudorandom numbers: distribution of triples
Authors: Eichenauer-Herrmann Jürgen , Niederreiter Harald
Published: July 2002

This paper deals with the inversive congruential method with power of two modulus

m
m

for generating uniform pseudorandom numbers. Statistical independence properties of the generated sequences are studied based on the distribution of triples of successive pseudorandom numbers. It is shown that, on the average over the parameters in the inversive congruential method, the discrepancy of the corresponding point sets in the unit cube is of an order of magnitude between

m

−
1

/

2

m^{-1/2}

and

m

−
1

/

2

(
log
⁡
m

)
3

m^{-1/2}(\log m)^3

. The method of proof relies on a detailed discussion of the properties of certain exponential sums.
The size of the first eigenfunction of a convex planar domain
Authors: Grieser Daniel , Jerison David
Published: July 2002

This paper estimates the size of the first Dirichlet eigenfunction of a convex planar domain. The eigenfunction is shown to be well-approximated, uniformly for all convex domains, by the first Dirichlet eigenfunction of a naturally associated ordinary differential (Schrödinger) operator. In particular, the place where the eigenfunction attains its maximum is located to within a distance comparable to the inradius.
The Hilbert-Smith conjecture for quasiconformal actions
Authors: Martin Gaven
Published: July 2002

This note announces a proof of the Hilbert–Smith conjecture in the quasiconformal case: A locally compact group

G
G

of quasiconformal homeomorphisms acting effectively on a Riemannian manifold is a Lie group. The result established is true in somewhat more generality.
Disruption of C-Terminal Cytoplasmic Domain of βPS Integrin Subunit Has Dominant Negative Properties in DevelopingDrosophila
Authors: Jannuzi Alison L. , Bunch Thomas A. , Brabant Marc C. , Miller Steven W. , Mukai Leona , Zavortink Michael , Brower Danny L.
Published: July 2002

We have analyzed a set of new and existing strong mutations in themyospheroid gene, which encodes the βPS integrin subunit of Drosophila. In addition to missense and other null mutations, three mutants behave as antimorphic alleles, indicative of dominant negative properties. Unlike null alleles, the three antimorphic mutants are synthetically lethal in double heterozygotes with an inflated (αPS2) null allele, and they fail to complement very weak, otherwise viable alleles of myospheroid. Two of the antimorphs result from identical splice site lesions, which create a frameshift in the C-terminal half of the cytoplasmic domain of βPS. The third antimorphic mutation is caused by a stop codon just before the cytoplasmic splice site. These mutant βPS proteins can support cell spreading in culture, especially under conditions that appear to promote integrin activation. Analyses of developing animals indicate that the dominant negative properties are not a result of inefficient surface expression, or simple competition between functional and nonfunctional proteins. These data indicate that mutations disrupting the C-terminal cytoplasmic domain of integrin β subunits can have dominant negative effects in situ, at normal levels of expression, and that this property does not necessarily depend on a specific new protein sequence or structure. The results are discussed with respect to similar vertebrate β subunit cytoplasmic mutations.
HIV-1 genotypic resistance: automated sequence analysis and interpretation.
Authors: Goujon C P , Schneider V M , Jacomet C , Nicolas J C
Published: July 2002

SUMMARY: We present here GRANT ( G enotypic R esistance An alysis T ool), a program that automatically detects resistance-related mutations in HIV-1 protein sequences, and comments on the degree of resistance conferred when possible. This program is easily user-customizable, allowing immediate updates as new resistance mutations are discovered, or use with an organism other than HIV. AVAILABILITY: The package is available free of charge over the internet, either directly from the authors, or by anonymous ftp (ftp. infobiogen.fr/pub/logiciels/mac/biology or windows as appropriate). Versions exist for PPC and 68K Apple Macintosh running MacOS 7.5 or higher. Microsoft Excel 5.0 is required for quality output. A PC version is in progress. CONTACT: goujon@infobiogen.fr
Post-processing long pairwise alignments
Authors: Zhang Zheng , Berman Piotr , Wiehe Thomas , Miller Webb
Published: July 2002

Motivation: The local alignment problem for two sequences requires determining similar regions, one from each sequence, and aligning those regions. For alignments computed by dynamic programming, current approaches for selecting similar regions may have potential flaws. For instance, the criterion of Smith and Waterman can lead to inclusion of an arbitrarily poor internal segment. Other approaches can generate an alignment scoring less than some of its internal segments.

Results: We develop an algorithm that decomposes a long alignment into sub-alignments that avoid these potential imperfections. Our algorithm runs in time proportional to the original alignment’s length. Practical applications to alignments of genomic DNA sequences are described.

Availability: Software is available at http://globin.cse.psu.edu/

Contact: webb@cse.psu.edu
DNA motif associated with meiotic double‐strand break regions in Saccharomyces cerevisiae
Authors: Blumental‐Perry A , Zenvirth D , Klein S , Onn I , Simchen G
Published: July 2002

Meiotic recombination in yeast is initiated by DNA double‐strand breaks (DSBs) that occur at preferred sites, distributed along the chromosomes. These DSB sites undergo changes in chromatin structure early in meiosis, but their common features at the level of DNA sequence have not been defined until now. Alignment of 1 kb sequences flanking six well‐mapped DSBs has allowed us to define a flexible sequence motif, the CoHR profile, which predicts the great majority of meiotic DSB locations. The 50 bp profile contains a poly(A) tract in its centre and may have several gaps of unrelated sequences over a total length of up to 250 bp. The major exceptions to the correlation between CoHRs and preferred DSB sites are at telomeric regions, where DSBs do not occur. The CoHR sequence may provide the basis for understanding meiosis‐induced chromatin changes that enable DSBs to occur at defined chromosomal sites.
Molecular and cytological analysis of a 5.5 Mb minichromosome
Authors: Auriche Cristina , Donini Pierluigi , Ascenzioni Fiorentina
Published: July 2002

Mammalian artificial chromosomes (MACs) provide a new tool for the improvement of our knowledge of chromosome structure and function. Moreover, they constitute an alternative and potentially powerful tool for gene delivery both in cultured cells and for the production of transgenic animals. In the present work we describe the molecular structure of MC1, a human minichromosome derived from chromosome 1. By means of restriction and hybridization analysis, satellite‐PCR, in situ hybridization on highly extended chromatin fibres, and indirect immunofluorescence, we have established that: (i) MC1 has a size of 5.5 Mb; (ii) it consists of 1.1 Mb alphoid, 3.5 Mb Sat2 DNA, and telomeric and subtelomeric sequences at both ends; (iii) it contains an unusual region of interspersed Sat2 and alphoid DNAs at the junction of the alphoid and the Sat2 blocks; and (iv) the two alphoid blocks and the Sat2‐alphoid region bind centromeric proteins suggesting that they participate in the formation of a functional kinetochore.
Monotremes and the evolution of rapid eye movement sleep
Authors: Siegel J. M. , Manger P. R. , Nienhuis R. , Fahringer H. M. , Pettigrew J. D.
Published: July 2002

Early studies of the echidna led to the conclusion that this monotreme did not have rapid eye movement (REM) sleep. Because the monotremes had diverged from the placental and marsupial lines very early in mammalian evolution, this finding was used to support the hypothesis that REM sleep evolved after the start of the mammalian line. The current paper summarizes our recent work on sleep in the echidna and platypus and leads to a very different interpretation. By using neuronal recording from mesopontine regions in the echidna, we found that despite the presence of a high–voltage cortical electroencephalogram (EEG), brainstem units fire in irregular bursts intermediate in intensity between the regular non–REM sleep pattern and the highly irregular REM sleep pattern seen in placentals. Thus the echidna displays brainstem activation during sleep with high–voltage cortical EEG. This work encouraged us to do the first study of sleep, to our knowledge, in the platypus. In the platypus we saw sleep with vigorous rapid eye, bill and head twitching, identical in behaviour to that which defines REM sleep in placental mammals. Recording of the EEG in the platypus during natural sleep and waking states revealed that it had moderate and high–voltage cortical EEGs during this REM sleep state. The platypus not only has REM sleep, but it had more of it than any other animal. The lack of EEG voltage reduction during REM sleep in the platypus, and during the REM sleep–like state of the echidna, has some similarity to the sleep seen in neonatal sleep in placentals. The very high amounts of REM sleep seen in the platypus also fit with the increased REM sleep duration seen in altricial mammals.

Our findings suggest that REM sleep originated earlier in mammalian evolution than had previously been thought and is consistent with the hypothesis that REM sleep, or a precursor state with aspects of REM sleep, may have had its origin in reptilian species.
Interesting times on Krakatau: stand dynamics in the 1990s
Authors: Whittaker Robert J. , Partomihardjo Tukirin , Jones Stephen H.
Published: July 2002

The Krakatau Islands, Indonesia, have provided an opportunity for ecologists to track primary succession from the ‘clean slate’ of 1883, through forest closure in the 1920s, to the contemporary period, in which successional changes take the form of alterations in composition and stature of forest stands rather than gross changes in ecosystem type. This paper reports on permanent forest plots established on the islands in 1989, and fully surveyed again in both 1992 and 1997. Since 1989, the plots have been subject to natural disturbance phenomena in the form of varying combinations of, for example, deposition of volcanic ejecta, landslides, lightning strikes, storm damage and drought. These effects have been concentrated between 1992 and 1997, during which the volcano Anak Krakatau has deposited ash on the islands of Sertung and Panjang, but not on Rakata. Data on stand responses are presented for growth rates (dbh (diameter at breast height, 1.3 m) increment), stem recruitment and mortality, biomass changes (partitioned into mortality, ingrowth and growth of established trees), and compositional shifts. The discussion focuses on evaluation of questions and successional models framed earlier in the programme. One general finding is that the stand dominants as of 1989 have tended to decline in number within the plots, generally through low levels of recruitment failing to balance rates of mortality. The effects of disturbance to the plots appear to be evident in terms of mortality and recruitment, dbh increment, and changes in biomass. The patterns of change in the eight plots are quite varied, such that relatively few generalizations are possible. The difficulties of establishing meaningful baseline rates for tree growth and stand biomass are discussed.
Past, present and future experiments on muscle
Authors: Huxley H. E.
Published: July 2002

Since the basic outline of the sliding filament mechanism became apparent some 45 years ago, the principal challenge, an experimental one, has been to produce definitive evidence about the detailed molecular mechanisms by which myosin cross–bridges produce force and movement in a muscle. More recently, similar questions could be posed about other molecular motors, in non–muscle cells. This problem proved unexpectedly difficult to solve, in part because of the technical difficulty of obtaining the structural and mechanical information required about rapid events within macromolecules, especially in a working system, and this triggered many remarkable technical developments. There is now very strong evidence for a large change in shape of the myosin heads during ATP hydrolysis, consistent with a leverarm mechanism. Whether this does indeed provide the driving force for contraction and movement— and, if so, exactly how—and whether some other processes could also play a significant role, is discussed in the light of the experimental and theoretical findings presented at this meeting, and other recent and long–term evidence.
Establishment of Polycomb silencing requires a transient interaction between PC and ESC
Authors: Poux Sylvain , Melfi Raffaella , Pirrotta Vincenzo
Published: July 2002

Two distinct types of Polycomb complexes have been identified in flies and in vertebrates, one containing ESC and one containing PC. Using LexA fusions, we show that PC and ESC can establish silencing of a reporter gene but that each requires the presence of the other. In early embryonic extracts, we find PC transiently associated with ESC in a complex that includes EZ, PHO, PH, GAGA, and RPD3 but not PSC. In older embryos, PC is found in a complex including PH, PSC, GAGA, and RPD3, whereas ESC is in a separate complex including EZ, PHO, and RPD3.
Absorbed‐dose beam quality conversion factors for cylindrical chambers in high energy photon beams
Authors: Seuntjens J. P. , Ross C. K. , Shortt K. R. , Rogers D. W. O.
Published: July 2002

Recent working groups of the AAPM [Almond et al., Med. Phys. 26, 1847 (1999)] and the IAEA (Andreo et al., Draft V.7 of “An International Code of Practice for Dosimetry based on Standards of Absorbed Dose to Water,” IAEA, 2000) have described guidelines to base reference dosimetry of high energy photon beams on absorbed dose to water standards. In these protocols use is made of the absorbed‐dose beam quality conversion factor, which scales an absorbed‐dose calibration factor at the reference quality to a quality Q, and which is calculated based on state‐of‐the‐art ion chamber theory and data. In this paper we present the measurement and analysis of beam quality conversion factors for cylindrical chambers in high‐energy photon beams. At least three chambers of six different types were calibrated against the Canadian primary standard for absorbed dose based on a sealed water calorimeter at 10 MV 20 MV and 30 MV The uncertainty on the calorimetric determination of for a single chamber is typically 0.36% and the overall 1σ uncertainty on a set of chambers of the same type is typically 0.45%. The maximum deviation between a measured and the TG‐51 protocol value is 0.8%. The overall rms deviation between measurement and the TG‐51 values, based on 20 chambers at the three energies, is 0.41%. When the effect of a 1 mm PMMA waterproofing sleeve is taken into account in the calculations, the maximum deviation is 1.1% and the overall rms deviation between measurement and calculation 0.48%. When the beam is specified using and measurements are compared with values calculated using the version of TG‐21 with corrected formalism and data, differences are up to 1.6% when no sleeve corrections are taken into account. For the NE2571 and the NE2611A chamber types, for which the most literature data are available, using all published data show a spread of 0.4% and 0.6%, respectively, over the entire measurement range, compared to spreads of up to 1.1% for both chambers when the values are expressed as a function of For the PR06‐C chamber no clear preference of beam quality specifier could be identified. When comparing the differences of our measurements and calculations with an analysis in terms of air‐kerma protocols with the same underlying calculations but expressed in terms of a compound conversion factor we observe that a system making use of absorbed‐dose calibrations and calculated values, is more accurate than a system based on air‐kerma calibrations in combination with calculated (rms deviation of 0.48% versus 0.67%, respectively).
Parker weights revisited
Authors: Wesarg Stefan , Ebert Matthias , Bortfeld Thomas
Published: July 2002

The short‐scan case in fan‐beam computed tomography requires the introduction of a weighting function to handle redundant data. Parker introduced such a weighting function for a scan over π plus the opening angle of the fan. In this article we derive a general class of weighting functions for arbitrary scan angles between π plus fan angle and 2π (over‐scan). These weighting functions lead to mathematically exact reconstructions in the continuous case. Parker weights are a special case of a weighting function that belongs to this class. It will be shown that Parker weights are not generally the best choice in terms of noise reduction, especially when there is considerable overscan. We derive a new weighting function that has a value of 0.5 for most of the redundant data and is smooth at the boundaries.
A new frame‐based registration algorithm
Authors: Yan Chye Hwang , Whalen Robert T. , Beaupre Gary S. , Sumanaweera Thilaka S. , Yen Shin Y. , Napel Sandy
Published: July 2002

This paper presents a new algorithm for frame registration. Our algorithm requires only that the frame be comprised of straight rods, as opposed to the structures or an accurate frame model required by existing algorithms. The algorithm utilizes the full 3D information in the frame as well as a least squares weighting scheme to achieve highly accurate registration. We use simulated CT data to assess the accuracy of our algorithm. We compare the performance of the proposed algorithm to two commonly used algorithms. Simulation results show that the proposed algorithm is comparable to the best existing techniques with knowledge of the exact mathematical frame model. For CT data corrupted with an unknown in‐plane rotation or translation, the proposed technique is also comparable to the best existing techniques. However, in situations where there is a discrepancy of more than 2 mm (0.7% of the frame dimension) between the frame and the mathematical model, the proposed technique is significantly better than the existing techniques. The proposed algorithm can be applied to any existing frame without modification. It provides better registration accuracy and is robust against model mis‐match. It allows greater flexibility on the frame structure. Lastly, it reduces the frame construction cost as adherence to a concise model is not required.
Analysis of the axial transmission technique for the assessment of skeletal status
Authors: Camus Estelle , Talmant Maryline , Berger Geneviève , Laugier Pascal
Published: July 2002

Ultrasonic wave propagation in human cortical bone has been investigated in vitro using the so-called axial transmission technique. This technique, which relies on velocity measurement of the first arriving signal, has been used in earlier investigations to study bone status during fracture healing or osteoporosis. Two quasi-point-source elements, one transmitter and one receiver (central frequency 0.5 MHz), were used to generate a wide ultrasonic beam, part of which strikes the sample surface at the longitudinal critical angle, and to receive the signals reflected from the sample surface. The analysis of the field reflected from a fluid–solid interface for an incident spherical wave predicts the existence of a lateral wave propagating along the sample surface at a velocity close to the longitudinal velocity, in addition to the ordinary reflected wave and vibration modes. The transducer–sample and the transmitter–receiver distances were chosen such that the lateral wave is the first arriving signal. Validation of the measuring technique was performed on test materials and was followed by experiments on human cortical bones. Experimental results (arrival time and velocity) strongly suggest that the first detected signal corresponds to the lateral wave predicted by theory.
Generalization of tactile perceptual skills to new context following tactile-alone word recognition training with the Tickle Talker™
Authors: Galvin Karyn L. , Blamey Peter J. , Cowan Robert S. C. , Oerlemans Michael , Clark Graeme M.
Published: July 2002

The Tickle Talker™ is an electrotactile speech perception device. Subjects were evaluated using the device in various tactile-alone and tactile–visual contexts to assess the generalization to other contexts of tactile-alone perceptual skills. The subjects were from a group of six normally hearing subjects who had previously received 12 to 33 h of tactile-alone word recognition training and had learned an average vocabulary of 50 words [Galvin et al., J. Acoust. Soc. Am. 106, 1084–1089 (1999)]. The tactile-alone evaluation contexts were sentences, unfamiliar talkers, and untrained words. The tactile–visual evaluation contexts were closed-set words, open-set words, and open-set sentences. Tactile-alone perceptual skills were generalized to unfamiliar speakers, sentences, and untrained words, though scores indicated that generalization was not complete. In contrast, the generalization of skills to tactile–visual contexts was minimal or absent. The potential value of tactile-alone training for hearing-impaired users of the Tickle Talker™ is discussed.