bluuebunny/crossref_metadata_2025 huggingface dataset:
Generation of up-regulated allosteric variants of potato ADP-glucose pyrophosphorylase by reversion genetics
Authors: Greene Thomas W. , Kavakli Ibrahim Halil , Kahn Michael L. , Okita Thomas W.
Published: July 2002

Mutagenesis of the large subunit (LS) of the potato ADP-glucose pyrophosphorylase generated an enzyme, P52L, that was insensitive to 3-phosphoglycerate (3-PGA). To identify additional residues involved in 3-PGA interaction, we subjected P52L LS DNA to a second round of mutagenesis and identified second-site revertants by their ability to restore glycogen accumulation as assessed by iodine (I
2
) staining. Enzymes from class I revertants with normal I
2
-staining had an 11- to 49-fold greater affinity for the activator 3-PGA compared with the P52L mutant and a decreased sensitivity to the inhibitor orthophosphate. Sequence analysis of these class I revertants identified a P66L mutation in R4, an E38K mutation in R20, and a G101N mutation in R10 and R32. These mutations appear to restore 3-PGA binding by counteracting the effect of the P52L mutation because introducing E38K or G101N into the wild-type LS led to enzyme variants with higher affinity for the activator 3-PGA and increased resistance to the inhibitor orthophosphate. The generation of these revertant enzymes provides additional structure-function information on the allosteric regulation of higher plant ADP-glucose pyrophosphorylases and validates a strategy for developing novel variants of the enzyme that may be useful in manipulating starch biosynthesis in higher plants.
Targeted deletion of
Smad4
shows it is required for transforming growth factor β and activin signaling in colorectal cancer cells
Authors: Zhou Shibin , Buckhaults Phillip , Zawel Leigh , Bunz Fred , Riggins Greg , Le Dai Jia , Kern Scott E. , Kinzler Kenneth W. , Vogelstein Bert
Published: July 2002

Smad4
(
DPC4
) is a candidate tumor suppressor gene that has been hypothesized to be critical for transmitting signals from transforming growth factor (TGF) β and related ligands. To directly test this hypothesis, the
Smad4
gene was deleted through homologous recombination in human colorectal cancer cells. This deletion abrogated signaling from TGF-β, as well as from the TGF-β family member activin. These results provide unequivocal evidence that mutational inactivation of
Smad4
causes TGF-β unresponsiveness and provide a basis for understanding the physiologic role of this gene in tumorigenesis.
Direct radiocarbon dates for Vindija G
1
and Velika Pećina Late Pleistocene hominid remains
Authors: Smith Fred H. , Trinkaus Erik , Pettitt Paul B. , Karavanić Ivor , Paunović Maja
Published: July 2002

New accelerator mass spectrometry radiocarbon dates taken directly on human remains from the Late Pleistocene sites of Vindija and Velika Pećina in the Hrvatsko Zagorje of Croatia are presented. Hominid specimens from both sites have played critical roles in the development of current perspectives on modern human evolutionary emergence in Europe. Dates of ≈28 thousand years (ka) before the present (B.P.) and ≈29 ka B.P. for two specimens from Vindija G
1
establish them as the most recent dated Neandertals in the Eurasian range of these archaic humans. The human frontal bone from Velika Pećina, generally considered one of the earliest representatives of modern humans in Europe, dated to ≈5 ka B.P., rendering it no longer pertinent to discussions of modern human origins. Apart from invalidating the only radiometrically based example of temporal overlap between late Neandertal and early modern human fossil remains from within any region of Europe, these dates raise the question of when early modern humans first dispersed into Europe and have implications for the nature and geographic patterning of biological and cultural interactions between these populations and the Neandertals.
Adeno-associated virus (AAV) site-specific integration: Formation of AAV–
AAVS1
junctions in an
in vitro
system
Authors: Dyall Julie , Szabo Paul , Berns Kenneth I.
Published: July 2002

An
in vitro
system to study the mechanism of site-specific integration of adeno-associated virus (AAV) was developed. This system is based on two substrates, a linear or circular AAV donor and a circular acceptor containing the preintegration locus
AAVS1
. In the presence of HeLa extract and the His-Tag-purified Rep68 protein, specific covalent junctions between AAV and
AAVS1
were formed and detected by PCR. The majority of the junctions were located within the Rep binding site of both the AAV and the
AAVS1
substrates, underlining the involvement of the Rep protein. A limited amount of replication and the presence of nuclear factors promoted the efficiency of the reaction. The process was ATP-dependent, indicating that the helicase activity of Rep may be important in the formation of the junctions. According to current models of integration, the formation of the junctions would represent a first step in the process of AAV integration. This step could be crucial for the site specificity of the recombination event that leads to the integration of AAV into human chromosome 19
in vivo
.
Human
PEX19
: cDNA cloning by functional complementation, mutation analysis in a patient with Zellweger syndrome, and potential role in peroxisomal membrane assembly
Authors: Matsuzono Yuji , Kinoshita Naohiko , Tamura Shigehiko , Shimozawa Nobuyuki , Hamasaki Maho , Ghaedi Kamran , Wanders Ronald J. A. , Suzuki Yasuyuki , Kondo Naomi , Fujiki Yukio
Published: July 2002

At least 11 complementation groups (CGs) have been identified for the peroxisome biogenesis disorders (PBDs) such as Zellweger syndrome, for which seven pathogenic genes have been elucidated. We have isolated a human
PEX19
cDNA (
HsPEX19
) by functional complementation of peroxisome deficiency of a mutant Chinese hamster ovary cell line, ZP119, defective in import of both matrix and membrane proteins. This cDNA encodes a hydrophilic protein (Pex19p) comprising 299 amino acids, with a prenylation motif, CAAX box, at the C terminus. Farnesylated Pex19p is partly, if not all, anchored in the peroxisomal membrane, exposing its N-terminal part to the cytosol. A stable transformant of ZP119 with
HsPEX19
was morphologically and biochemically restored for peroxisome biogenesis.
HsPEX19
expression also restored peroxisomal protein import in fibroblasts from a patient (PBDJ-01) with Zellweger syndrome of CG-J. This patient (PBDJ-01) possessed a homozygous, inactivating mutation: a 1-base insertion, A
764
, in a codon for Met
255
, resulted in a frameshift, inducing a 24-aa sequence entirely distinct from normal Pex19p. These results demonstrate that
PEX19
is the causative gene for CG-J PBD and suggest that the C-terminal part, including the CAAX homology box, is required for the biological function of Pex19p. Moreover, Pex19p is apparently involved at the initial stage in peroxisome membrane assembly, before the import of matrix protein.
Inhibition of advanced glycation endproduct formation by acetaldehyde: Role in the cardioprotective effect of ethanol
Authors: Al-Abed Yousef , Mitsuhashi Tomoko , Li Hongwei , Lawson John A. , FitzGerald Garret A. , Founds Hank , Donnelly Thomas , Cerami Anthony , Ulrich Peter , Bucala Richard
Published: July 2002

Epidemiological studies suggest that there is a beneficial effect of moderate ethanol consumption on the incidence of cardiovascular disease. Ethanol is metabolized to acetaldehyde, a two-carbon carbonyl compound that can react with nucleophiles to form covalent addition products. We have identified a biochemical modification produced by the reaction of acetaldehyde with protein-bound Amadori products. Amadori products typically arise from the nonenzymatic addition of reducing sugars (such as glucose) to protein amino groups and are the precursors to irreversibly bound, crosslinking moieties called advanced glycation endproducts, or AGEs. AGEs accumulate over time on plasma lipoproteins and vascular wall components and play an important role in the development of diabetes- and age-related cardiovascular disease. The attachment of acetaldehyde to a model Amadori product produces a chemically stabilized complex that cannot rearrange and progress to AGE formation. We tested the role of this reaction in preventing AGE formation
in vivo
by administering ethanol to diabetic rats, which normally exhibit increased AGE formation and high circulating levels of the hemoglobin Amadori product, HbA
1c
, and the hemoglobin AGE product, Hb-AGE. In this model study, diabetic rats fed an ethanol diet for 4 weeks showed a 52% decrease in Hb-AGE when compared with diabetic controls (
P
< 0.001). Circulating levels of HbA
1c
were unaffected by ethanol, pointing to the specificity of the acetaldehyde reaction for the post-Amadori, advanced glycation process. These data suggest a possible mechanism for the so-called “French paradox,” (the cardioprotection conferred by moderate ethanol ingestion) and may offer new strategies for inhibiting advanced glycation.
Intramolecular control of transcriptional activity by the NK2-specific domain in NK-2 homeodomain proteins
Authors: Watada Hirotaka , Mirmira Raghavendra G. , Kalamaras Julie , German Michael S.
Published: July 2002

The developmentally important homeodomain transcription factors of the NK-2 class contain a highly conserved region, the NK2-specific domain (NK2-SD). The function of this domain, however, remains unknown. The primary structure of the NK2-SD suggests that it might function as an accessory DNA-binding domain or as a protein–protein interaction interface. To assess the possibility that the NK2-SD may contribute to DNA-binding specificity, we used a PCR-based approach to identify a consensus DNA-binding sequences for Nkx2.2, an NK-2 family member involved in pancreas and central nervous system development. The consensus sequence (T
C
T
AAGT
G
A
G
C
TT) is similar to the known binding sequences for other NK-2 homeodomain proteins, but we show that the NK2-SD does not contribute significantly to specific DNA binding to this sequence. To determine whether the NK2-SD contributes to transactivation, we used GAL4-Nkx2.2 fusion constructs to map a powerful transcriptional activation domain in the C-terminal region beyond the conserved NK2-SD. Interestingly, this C-terminal region functions as a transcriptional activator only in the absence of an intact NK2-SD. The NK2-SD also can mask transactivation from the paired homeodomain transcription factor Pax6, but it has no effect on transcription by itself. These results demonstrate that the NK2-SD functions as an intramolecular regulator of the C-terminal activation domain in Nkx2.2 and support a model in which interactions through the NK2-SD regulate the ability of NK-2-class proteins to activate specific genes during development.
Photo-control of helix content in a short peptide
Authors: Kumita Janet R. , Smart Oliver S. , Woolley G. Andrew
Published: July 2002

The α-helix is a key structural element in a wide range of peptides and proteins. We report here the design, synthesis, and characterization of a modified peptide in which the helix content can be reversibly photoregulated. The peptide contains two cysteine residues that are cross-linked by an azobenzene derivative in an intramolecular fashion. In accordance with the design, the photoisomerization of the azobenzene cross-linker from the trans to the cis form causes a large increase in the helix content of the peptide, in water.
Where East Meets West: The Last Stand of Finns and Karelians in Contemporary Karelia?
Authors: Laine Antti
Published: July 2002

The northwestern flank of the Slavic expanse of settlement, the territory of today's Russian Karelia, constitutes an age-old site of Slavic-Baltic-Finnic contact. The Karelians and Vepsians, two Finno-Ugrian groups, are a part of the indigenous population of Karelia. The settlements of the former are found mainly in the western half of the present-day Karelian Republic. The Vepsians live on the southwestern coastal strip of Lake Onega, south of the capital of the republic, Petrozavodsk. Vepsian settlements are also found outside Karelia, in Vologda and Leningrad provinces. For several centuries, the Russians have formed a majority of the inhabitants both near Lake Onega and on the west coast of the White Sea. In contrast to the Karelians, Vepsians and Russians, Finns can be considered newcomers to Karelia.
J. A. Schumpeter, Werner Stark, and the Historiography of Economic Thought
Authors: Szmrecsányi Tamás
Published: July 2002

This article intends to assess and compare the main contributions to our discipline of two major authors and authorities. Both of them originated in Central Europe and, later on, went to work in the United States, where their most important books on the subject were published posthumously during the second half of the twentieth century. At the same time, besides pertaining to different generations, they also were very unlike from each other.

The eldest, Joseph Alois Schumpeter (1883–1950), remains much better known among contemporary economists, although very few of them seem to have read in its entirety his imposing History of Economic Analysis (1954a), still a model of our trade. The same probably also applies to his shorter and previous book on the same subject, Economic Doctrine and Method, which had been initially published in Germany forty years earlier, as well as to the essays collected in his Ten Great Economists: From Marx to Keynes.
Rlp7p is associated with 60S preribosomes, restricted to the granular component of the nucleolus, and required for pre-rRNA processing
Authors: Gadal Olivier , Strauss Daniela , Petfalski Elisabeth , Gleizes Pierre-Emmanuel , Gas Nicole , Tollervey David , Hurt Ed
Published: July 2002

Many analyses have examined subnucleolar structures in eukaryotic cells, but the relationship between morphological structures, pre-rRNA processing, and ribosomal particle assembly has remained unclear. Using a visual assay for export of the 60S ribosomal subunit, we isolated a ts-lethal mutation, rix9-1, which causes nucleolar accumulation of an Rpl25p-eGFP reporter construct. The mutation results in a single amino acid substitution (F176S) in Rlp7p, an essential nucleolar protein related to ribosomal protein Rpl7p. The rix9-1 (rlp7-1) mutation blocks the late pre-RNA cleavage at site C2 in ITS2, which separates the precursors to the 5.8S and 25S rRNAs. Consistent with this, synthesis of the mature 5.8S and 25S rRNAs was blocked in the rlp7-1 strain at nonpermissive temperature, whereas 18S rRNA synthesis continued. Moreover, pre-rRNA containing ITS2 accumulates in the nucleolus of rix9-1 cells as revealed by in situ hybridization. Finally, tagged Rlp7p was shown to associate with a pre-60S particle, and fluorescence microscopy and immuno-EM localized Rlp7p to a subregion of the nucleolus, which could be the granular component (GC). All together, these data suggest that pre-rRNA cleavage at site C2 specifically requires Rlp7p and occurs within pre-60S particles located in the GC region of the nucleolus.
β1 Integrins Are Critically Involved in Neutrophil Locomotion in Extravascular Tissue In Vivo
Authors: Werr Joachim , Xie Xun , Hedqvist Per , Ruoslahti Erkki , Lindbom Lennart
Published: July 2002

Recruitment of leukocytes from blood to tissue in inflammation requires the function of specific cell surface adhesion molecules. The objective of this study was to identify adhesion molecules that are involved in polymorphonuclear leukocyte (PMN) locomotion in extravascular tissue in vivo. Extravasation and interstitial tissue migration of PMNs was induced in the rat mesentery by chemotactic stimulation with platelet-activating factor (PAF; 10−7 M). Intravital time-lapse videomicroscopy was used to analyze migration velocity of the activated PMNs, and the modulatory influence on locomotion of locally administered antibodies or peptides recognizing various integrin molecules was examined. Immunofluorescence flow cytometry revealed increased expression of α4, β1, and β2 integrins on extravasated PMNs compared with blood PMNs. Median migration velocity in response to PAF stimulation was 15.5 ± 4.5 μm/min (mean ± SD). Marked reduction (67 ± 7%) in motility was observed after treatment with mAb blocking β1 integrin function (VLA integrins), whereas there was little, although significant, reduction (22 ± 13%) with β2 integrin mAb. Antibodies or integrin-binding peptides recognizing α4β1, α5β1, or αvβ3 were ineffective in modulating migration velocity.

Our data demonstrate that cell surface expression of β1 integrins, although limited on blood PMNs, is induced in extravasated PMNs, and that members of the β1 integrin family other than α4β1 and α5β1 are critically involved in the chemokinetic movement of PMNs in rat extravascular tissue in vivo.
Cd4+Cd25+ Immune Regulatory Cells Are Required for Induction of Tolerance to Alloantigen via Costimulatory Blockade
Authors: Taylor Patricia A. , Noelle Randolph J. , Blazar Bruce R.
Published: July 2002

Immune regulatory CD4+CD25+ cells play a vital role in the induction and maintenance of self-tolerance and are essential for T cell homeostasis and the prevention of autoimmunity. Induction of tolerance to allogeneic donor grafts is a clinically desirable goal in bone marrow and solid organ transplantation. To determine whether CD4+CD25+ cells regulate T cell responses to alloantigen and are critical for tolerance induction, murine CD4+ T cells were tolerized to alloantigen via ex vivo CD40 ligand (CD40L)/CD40 or CD28/cytotoxic T lymphocyte–associated antigen 4/B7 blockade resulting in secondary mixed leukocyte reaction hyporesponsiveness and tolerance to alloantigen in vivo. CD4+CD25+ T cells were found to be potent regulators of alloresponses. Depletion of CD4+CD25+ T cells from the CD4+ responder population completely abrogated ex vivo tolerance induction to alloantigen as measured by intact responses to alloantigen restimulation in vitro and in vivo. Addback of CD4+CD25+ T cells to CD4+CD25− cultures restored tolerance induction. These data are the first to indicate that CD4+CD25+ cells are essential for the induction of tolerance to alloantigen and have important implications for tolerance-inducing strategies targeted at T cell costimulatory pathways.
The Importation of Hematogenous Precursors by the Thymus Is a Gated Phenomenon in Normal Adult Mice
Authors: Foss Deborah L. , Donskoy Elina , Goldschneider Irving
Published: July 2002

Hematogenous precursors repopulate the thymus of normal adult mice, but it is not known whether this process is continuous or intermittent. Here, two approaches were used to demonstrate that the importation of prothymocytes in adult life is a gated phenomenon. In the first, age-dependent receptivity to thymic chimerism was studied in nonirradiated Ly 5 congenic mice by quantitative intrathymic and intravenous bone marrow (BM) adoptive transfer assays. In the second, the kinetics of importation of blood-borne prothymocytes was determined by timed separation of parabiotic mice. The results showed that >60% of 3–18-wk-old mice developed thymic chimerism after intrathymic injection of BM cells, and that the levels of chimerism (range, 5–90% donor-origin cells) varied cyclically (periodicity, 3 to 5 wk). In contrast, only 11–14% of intravenously injected recipients became chimeric, and chimerism occurred intermittently (receptive period ∼1 wk; refractory period ∼3 wk). In the intravenously injected mice, chimerism occurred simultaneously in both thymic lobes; gate opening occurred only after most intrathymic niches for prothymocytes had emptied; and the ensuing wave of thymocytopoiesis encompassed two periods of gating. These kinetics were confirmed in parabiotic mice, and in cohorts of mice in whom gating was synchronized by an initial intrathymic injection of BM cells. In addition, a protocol was developed by which sequential intravenous injections of BM cells over a 3 to 4 wk period routinely induces thymic chimerism in the apparent absence of stem cell chimerism. Hence, the results not only provide a new paradigm for the regulation of prothymocyte importation during adult life, but may also have applied implications for the selective induction of thymocytopoiesis in nonmyeloablated hosts.
The Exocytosis-Regulatory Protein Synaptotagmin VII Mediates Cell Invasion by Trypanosoma cruzi
Authors: Caler Elisabet V. , Chakrabarti Sabyasachi , Fowler Kimberly T. , Rao Swathi , Andrews Norma W.
Published: July 2002

The intracellular protozoan parasite Trypanosoma cruzi causes Chagas' disease, which affects millions of people in Latin America. T. cruzi enters a large number of cell types by an unusual mechanism that involves Ca2+-triggered fusion of lysosomes with the plasma membrane. Here we show that synaptotagmin VII (Syt VII), a ubiquitously expressed synaptotagmin isoform that regulates exocytosis of lysosomes, is localized on the membranes of intracellular vacuoles containing T. cruzi. Antibodies against the C2A domain of Syt VII or recombinant peptides including this domain inhibit cell entry by T. cruzi, but not by Toxoplasma gondii or Salmonella typhimurium. The C2A domains of other ubiquitously expressed synaptotagmin isoforms have no effect on T. cruzi invasion, and mutation of critical residues on Syt VII C2A abolish its inhibitory activity. These findings indicate that T. cruzi exploits the Syt VII–dependent, Ca2+-regulated lysosomal exocytic pathway for invading host cells.
Interleukin (Il)-18 Promotes the Development of Chronic Gastrointestinal Helminth Infection by Downregulating IL-13
Authors: Helmby Helena , Takeda Kiyoshi , Akira Shizuo , Grencis Richard K.
Published: July 2002

Expulsion of the gastrointestinal nematode Trichuris muris is mediated by a T helper (Th) 2 type response involving interleukin (IL)-4 and IL-13. Here we show that Th1 response–associated susceptibility involves prior activation of IL-18 and caspase-1 followed by IL-12 and interferon (IFN)-γ in the intestine. IL-18–deficient mice are highly resistant to chronic T. muris infection and in vivo treatment of normal mice with recombinant (r)IL-18 suppresses IL-13 and IL-4 secretion but does not affect IFN-γ.

In vivo treatment of T. muris–infected IFN-γ–deficient mice with rIL-18 demonstrated that the inhibitory effect of IL-18 on IL-13 secretion is independent of IFN-γ. Hence, IL-18 does not function as an IFN-γ–inducing cytokine during chronic T. muris infection but rather as a direct regulator of Th2 cytokines. These results provide the first demonstration of the critical role of IL-18 in regulating Th cell responses during gastrointestinal nematode infection.
Fuc-Tvii Is Required for T Helper 1 and T Cytotoxic 1 Lymphocyte Selectin Ligand Expression and Recruitment in Inflammation, and Together with Fuc-Tiv Regulates Naive T Cell Trafficking to Lymph Nodes
Authors: Smithson Glennda , Rogers Clare E. , Smith Peter L. , Scheidegger E. Paul , Petryniak Bronislawa , Myers Jay T. , Kim David S. L. , Homeister Jonathon W. , Lowe John B.
Published: July 2002

To determine how the α(1,3)fucosyltransferases Fuc-TIV and Fuc-TVII, and the selectin ligands they control may contribute to the adaptive immune response, contact hypersensitivity (CHS) was characterized in mice deficient in either or both enzymes. We find a substantial CHS deficiency in Fuc-TVII−/− mice, and a complete deficiency in Fuc-TIV−/−/Fuc-TVII−/− mice. These defects are not accounted for by alterations in the number or function of epidermal Langerhans cells required for cutaneous antigen processing and presentation. By contrast, defective CHS in Fuc-TVII−/− mice or Fuc-TIV−/−/Fuc-TVII−/− mice is attributed in part to prominent, or nearly complete deficiencies, respectively, in the complement of naive T lymphocytes available in lymph nodes for antigen-dependent activation, expansion, differentiation, and dissemination. Fuc-TVII deficiency also deletes expression of E- and P-selectin ligands by Th1 and T cytotoxic 1 (Tc1) lymphocytes, annuls T cell trafficking to inflamed cutaneous sites in vivo, and thereby controls an essential component of the efferent phase of the cutaneous immune response. These observations indicate that collaborative contributions of Fuc-TIV and Fuc-TVII to L-selectin ligand synthesis, and to lymphocyte recruitment, are requisite components of the primary cellular immune response, and assign an essential role to Fuc-TVII in control of E- and P-selectin ligand expression by Th1 and Tc1 lymphocytes.
Absence of Proton Channels in COS-7 Cells Expressing Functional NADPH Oxidase Components
Authors: Morgan Deri , Cherny Vladimir V. , Price Marianne O. , Dinauer Mary C. , DeCoursey Thomas E.
Published: July 2002

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is an enzyme of phagocytes that produces bactericidal superoxide anion (O2−) via an electrogenic process. Proton efflux compensates for the charge movement across the cell membrane. The proton channel responsible for the H+ efflux was thought to be contained within the gp91phox subunit of NADPH oxidase, but recent data do not support this idea (DeCoursey, T.E., V.V. Cherny, D. Morgan, B.Z. Katz, and M.C. Dinauer. 2001. J. Biol. Chem. 276:36063–36066). In this study, we investigated electrophysiological properties and superoxide production of COS-7 cells transfected with all NADPH oxidase components required for enzyme function (COSphox). The 7D5 antibody, which detects an extracellular epitope of the gp91phox protein, labeled 96–98% of COSphox cells. NADPH oxidase was functional because COSphox (but not COSWT) cells stimulated by phorbol myristate acetate (PMA) or arachidonic acid (AA) produced superoxide anion. No proton currents were detected in either wild-type COS-7 cells (COSWT) or COSphox cells studied at pHo 7.0 and pHi 5.5 or 7.0. Anion currents that decayed at voltages positive to 40 mV were the only currents observed. PMA or AA did not elicit detectable H+ current in COSWT or COSphox cells. Therefore, gp91phox does not function as a proton channel in unstimulated cells or in activated cells with a demonstrably functional oxidase.
On sequences of 𝐶^{𝑘,𝛿}_{𝑏} maps which converge in the uniform 𝐶⁰-norm
Authors: ElBialy Mohamed
Published: July 2002

We study maps

f
∈

C

b

k
,
δ

(
U
,
Y
)

f\in C^{k,\delta }_{b}(U,Y)

and give detailed estimates on

‖

D

k

f
(
x
)
‖
,
x
∈
U
,

\|D^{k}f(x)\|,x\in U,

in terms of

‖
f
‖

\|f\|

and

‖
f

‖

k
,
δ

\|f\|_{k,\delta }

. These estimates are used to prove a lemma by D. Henry for the case

k
≥
2

k\geq 2

. Here

U
⊂
X

U\subset X

is an open subset and

X
X

and

Y
Y

are Banach spaces.
The spectra of nonnegative integer matrices via formal power series
Authors: Kim Ki , Ormes Nicholas , Roush Fred
Published: July 2002

We characterize the possible nonzero spectra of primitive integer matrices (the integer case of Boyle and Handelman’s Spectral Conjecture). Characterizations of nonzero spectra of nonnegative matrices over

Z

{\mathbb Z}

and

Q

{\mathbb Q}

follow from this result. For the proof of the main theorem we use polynomial matrices to reduce the problem of realizing a candidate spectrum

(

λ
1

,

λ
2

,
…
,

λ
d

)

(\lambda _1,\lambda _2,\ldots ,\lambda _d)

to factoring the polynomial

∏

i
=
1

d

(
1
−

λ
i

t
)

\prod _{i=1}^d (1-\lambda _it)

as a product
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="left-parenthesis 1 minus r left-parenthesis t right-parenthesis right-parenthesis product Underscript i equals 1 Overscript n Endscripts left-parenthesis 1 minus q Subscript i Baseline left-parenthesis t right-parenthesis right-parenthesis">

(
1
−
r
(
t
)
)

∏

i
=
1

n

(
1
−

q
i

(
t
)
)

(1-r(t))\prod _{i=1}^n (1-q_i(t))

where the

q
i

q_i

’s are polynomials in

t

Z

+

[
t
]

t{\mathbb Z}_+[t]

satisfying some technical conditions and

r
r

is a formal power series in

t

Z

+

[
[
t
]
]

t{\mathbb Z}_+[[t]]

. To obtain the factorization, we present a hierarchy of estimates on coefficients of power series of the form
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="product Underscript i equals 1 Overscript d Endscripts left-parenthesis 1 minus lamda Subscript i Baseline t right-parenthesis slash product Underscript i equals 1 Overscript n Endscripts left-parenthesis 1 minus q Subscript i Baseline left-parenthesis t right-parenthesis right-parenthesis">

∏

i
=
1

d

(
1
−

λ
i

t
)

/

∏

i
=
1

n

(
1
−

q
i

(
t
)
)

\prod _{i=1}^d (1-\lambda _it)/\prod _{i=1}^n (1-q_i(t))

to ensure nonpositivity in nonzero degree terms.
Mating quadratic maps with Kleinian groups via quasiconformal surgery
Authors: Bullett S. , Harvey W.
Published: July 2002

Let

q
:

C

^

→

C

^

q:\hat {\mathbb C} \to \hat {\mathbb C}

be any quadratic polynomial and

r
:

C
2

∗

C
3

→
P
S
L
(
2
,

C

)

r:C_2*C_3 \to PSL(2,{\mathbb C})

be any faithful discrete representation of the free product of finite cyclic groups

C
2

C_2

and

C
3

C_3

(of orders

2
2

and

3
3

) having connected regular set. We show how the actions of

q
q

and

r
r

can be combined, using quasiconformal surgery, to construct a

2
:
2

2:2

holomorphic correspondence

z
→
w

z \to w

, defined by an algebraic relation

p
(
z
,
w
)
=
0

p(z,w)=0

.
Concept and prototype of protein–ligand docking simulator
with force feedback technology
Authors: Nagata Hiroshi , Mizushima Hiroshi , Tanaka Hiroshi
Published: July 2002

A novel concept for a protein–ligand docking simulator using Virtual Reality (VR) technologies, in particular the tactile sense technology, was designed and a prototype was developed. Most conventional docking simulators are based on numerical differential calculations of the total energy between a protein and a ligand. However, the basic concept of our method differs from that of conventional simulators. Our design utilizes the force between a ligand and a protein instead of the total energy. The most characteristic function of the system is its ability to enable the user to ‘touch’ and sense the electrostatic potential field of a protein molecule. The user can scan the surface of a protein using a globular probe, which is given an electrostatic charge, and is controlled by a force feedback device. The electrostatic force between the protein and the probe is calculated in real time and immediately fed back into the force feedback device. The user can easily search interactively for positions where the probe is strongly attracted to the force field. Such positions can be regarded as candidate sites where functional groups of ligands corresponding to the probe can bind to the target protein. Certain limitations remain; for example, only twenty protein atoms can be used to generate the electrostatic field. Furthermore, the system can only use globular probes, preventing drug molecules or small chemical groups from being simulated. These limitations are the result of our insufficient computer resources. However, our prototype system has the potential to become a novel application method as well as being applicable to conventional VR technologies, especially to force feedback technologies.

Contact: hi-nagata@kddilabs.co.jp; hmizushi@ncc.go.jp; tanaka@cim.tmd.ac.jp
Genetic disruption of mineralocorticoid receptor leads to impaired neurogenesis and granule cell degeneration in the hippocampus of adult mice
Authors: Gass Peter , Kretz Oliver , Wolfer David P , Berger Stefan , Tronche Francois , Reichardt Holger M , Kellendonk Christoph , Lipp Hans‐Peter , Schmid Wolfgang , Schütz Günther
Published: July 2002

To dissect the effects of corticosteroids mediated by the mineralocorticoid (MR) and the glucocorticoid receptor (GR) in the central nervous system, we compared MR−/− mice, whose salt loss syndrome was corrected by exogenous NaCl administration, with GR−/− mice having a brain‐specific disruption of the GR gene generated by the Cre/loxP‐recombination system. Neuropathological analyses revealed a decreased density of granule cells in the hippocampus of adult MR−/− mice but not in mice with disruption of GR. Furthermore, adult MR−/− mice exhibited a significant reduction of granule cell neurogenesis to 65% of control levels, possibly mediated by GR due to elevated corticosterone plasma levels. Neurogenesis was unaltered in adult mice with disruption of GR. Thus, we could attribute long‐term trophic effects of adrenal steroids on dentate granule cells to MR. These MR‐related alterations may participate in the pathogenesis of hippocampal changes observed in ageing, chronic stress and affective disorders.
A novel muscle LIM‐only protein is generated from the paxillin gene locus in Drosophila
Authors: Yagi Ryohei , Ishimaru Satoshi , Yano Hajime , Gaul Ulrike , Hanafusa Hidesaburo , Sabe Hisataka
Published: July 2002

Paxillin is a protein containing four LIM domains, and functions in integrin signaling. We report here that two transcripts are generated from the paxillin gene locus in Drosophila; one encodes a protein homolog of the vertebrate Paxillin (DPxn37), and the other a protein with only three LIM domains, partly encoded by its own specific exon (PDLP). At the myotendinous junctions of Drosophila embryos where integrins play important roles, both DPxn37 and PDLP are highly expressed with different patterns; DPxn37 is predominantly concentrated at the center of the junctions, whereas PDLP is highly enriched at neighboring sides of the junction centers, primarily expressed in the mesodermal myotubes. Northern blot analysis revealed that DPxn37 is ubiquitously expressed throughout the life cycle, whereas PDLP expression exhibits a biphasic pattern during development, largely concomitant with muscle generation and remodeling. Our results collectively reveal that a unique system exists in Drosophila for the generation of a novel type of LIM‐only protein, highly expressed in the embryonic musclature, largely utilizing the Paxillin LIM domains.
Trypanosoma cruzi macrophage infectivity potentiator has a rotamase core and a highly exposed α‐helix
Authors: Pereira Pedro José Barbosa , Vega M Cristina , González‐Rey Elena , Fernández‐Carazo Rafael , Macedo‐Ribeiro Sandra , Gomis‐Rüth F Xavier , González Antonio , Coll Miquel
Published: July 2002

The macrophage infectivity potentiator protein from Trypanosoma cruzi (TcMIP) is a major virulence factor secreted by the etiological agent of Chagas' disease. It is functionally involved in host cell invasion. We have determined the three‐dimensional crystal structure of TcMIP at 1.7 Å resolution. The monomeric protein displays a peptidyl‐prolyl cis–trans isomerase (PPIase) core, encompassing the characteristic rotamase hydrophobic active site, thus explaining the strong inhibition of TcMIP by the immunosuppressant FK506 and related drugs. In TcMIP, the twisted β‐sheet of the core is extended by an extra β‐strand, preceded by a long, exposed N‐terminal α‐helix, which might be a target recognition element. An invasion assay shows that the MIP protein from Legionella pneumophila (LpMIP), which has an equivalent N‐terminal α‐helix, can substitute for TcMIP. An additional exposed α‐helix, this one unique to TcMIP, is located in the C‐terminus of the protein. The high‐resolution structure reported here opens the possibility for the design of new inhibitory drugs that might be useful for the clinical treatment of American trypanosomiasis.
Effects of long–term spectral deprivation on the morphological organization of the outer retina of the blue acara (
Aequidens pulcher
)
Authors: Wagner H.–J. , Kröger R.H.H.
Published: July 2002

To investigate the developmental plasticity of colour vision, we reared fish with a trichromatic cone system (
Aequidens pulcher
) under three near–monochromatic lights, differentially stimulating each spectral cone type from the larval stage to the age of at least one year. Control conditions comprised white lights of two intensities. The treatments did not affect the visual pigments, but led to significant changes in cone outer segment lengths. Furthermore, in the blue–reared group the density of single cones within the retina was reduced by two–thirds after 18 months of exposure, while no changes were observed in the other groups. The connectivity of cone horizontal cells with the single cones was influenced by the intensity and spectral composition of the rearing lights: H1 cells were more sensitive to the spectral component, whereas H2 cells responded to intensity cues. In the blue–light group the dynamics of horizontal cell synaptic spinule formation and degradation were severely compromised. These observations show that long–term spectral deprivation leads to significant morphological changes at the level of photoreceptors and horizontal cells. While the reactions of photoreceptors may be interpreted mostly in terms of compensation, the functional consequences of the changes observed on the horizontal cell level remain to be determined electrophysiologically.
A model of the pressure dependence of the enantioselectivity of Candida rugosalipase towards (±)‐menthol
Authors: Kahlow Ulrich H.M. , Schmid Rolf D. , Pleiss Jürgen
Published: July 2002

Transesterification of (±)‐menthol using propionic acid anhydride and Candida rugosa lipase was performed in chloroform and water at different pressures (1, 10, 50, and 100 bar) to study the pressure dependence of enantioselectivity E. As a result, E significantly decreased with increasing pressure from E = 55 (1 bar) to E = 47 (10 bar), E = 37 (50 bar), and E = 9 (100 bar). To rationalize the experimental findings, molecular dynamics simulations of Candida rugosa lipase were carried out. Analyzing the lipase geometry at 1, 10, 50, and 100 bar revealed a cavity in the Candida rugosa lipase. The cavity leads from a position on the surface distinct from the substrate binding site to the core towards the active site, and is limited by F415 and the catalytic H449. In the crystal structure of the Candida rugosa lipase, this cavity is filled with six water molecules. The number of water molecules in this cavity gradually increased with increasing pressure: six molecules in the simulation at 1 bar, 10 molecules at 10 bar, 12 molecules at 50 bar, and 13 molecules at 100 bar. Likewise, the volume of the cavity progressively increased from about 1864 Å3 in the simulation at 1 bar to 2529 Å3 at 10 bar, 2526 Å3 at 50 bar, and 2617 Å3 at 100 bar. At 100 bar, one water molecule slipped between F415 and H449, displacing the catalytic histidine side chain and thus opening the cavity to form a continuous water channel. The rotation of the side chain leads to a decreased distance between the H449‐Nε and the (+)‐menthyl‐oxygen (nonpreferred enantiomer) in the acyl enzyme intermediate, a factor determining the enantioselectivity of the lipase. Although the geometry of the preferred enantiomer is similar in all simulations, the geometry of the nonpreferred enantiomer gets gradually more reactive. This observation correlates with the gradually decreasing enantioselectivity E.
Foreign exchange market as a lattice gauge theory
Authors: Young K.
Published: July 2002

A simple model of the foreign exchange market is exactly a lattice gauge theory. Exchange rates are the exponentials of gauge potentials defined on spatial links while interest rates are related to gauge potentials on temporal links. Arbitrage opportunities are given by nonzero values of the gauge-invariant field tensor or curvature defined on closed loops. Arbitrage opportunities involving cross-rates at one time are “magnetic fields,” while arbitrage opportunities involving future contracts are “electric fields.”
Measurement of the B/A nonlinearity parameter under high pressure: Application to water
Authors: Plantier F. , Daridon J. L. , Lagourette B.
Published: July 2002

An experimental apparatus was developed to measure, over a wide range of pressure, the acoustical nonlinear parameter B/A with an uncertainty of 2.2% in order to study the influence of pressure on the value of this parameter in liquids. The experimental technique rests on an improved thermodynamic method which uses a highly sensitive phase comparison technique to measure the change in speed of sound with pressure. The apparatus was then used to measure B/A in water within the pressure range from 0.1 to 50 MPa and at temperatures of between 303.15 and 373.15 K. The data obtained were compared with those in the literature which come from numerical derivation of speed of sound measurements.
Determination of grain-size distribution from ultrasonic attenuation: Transformation and inversion
Authors: Nicoletti Denise , Anderson Aran
Published: July 2002

Although researchers often describe a particular medium with only a single grain size or an average grain size, distributions of grain sizes can have significant effects on the physical characteristics of the material. Ultrasonic attenuation due to energy scattered at the grain boundaries depends on the ultrasonic wavelength, the grain size, and certain material properties such as elastic constants. This paper examines the relationship between the wavelength dependency of ultrasonic attenuation and grain-size distributions. A transformation is developed which solves a general class of Fredholm equations of the first kind. The equation relating attenuation to grain-size distributions belongs to this class of equations. The transformation allows attenuation to be calculated by discrete convolution, and provides a method for estimating the grain-size distribution directly from attenuation measurements.
Silicon micromachined ultrasonic transducers
Authors: Khuri-Yakub B. T.
Published: July 2002

This paper presents a novel type of ultrasonic transducer that is made by silicon micromachining. Transducers for both air-borne and immersion applications are made from parallel plate capacitors whose dimensions are controlled through traditional integrated circuit manufacturing methods. Typical dimensions of the capacitors are: gap =1 micron (vacuum or air), membrane thickness =1 micron (silicon nitride or polysilicon), and diameter =50 microns. A large number of small elements are connected in parallel to make a transducer. Transducers for air-borne ultrasound applications have been operated in the frequency range of 1–11 MHz, while immersion transducers have been operated in the frequency range of 1–20 MHz. Theoretical modeling calculations of the transducers and their electrical input impedances will be presented. The theory predicts a dynamic range of over 140 dB for both air and immersion applications. Different processing methods for fabricating the transducers and the merits of the different approaches will be presented. Finally, the results of transducer operation both in air and water with over a 100-dB dynamic range will be presented.
Can population density be used to determine ambient noise levels?
Authors: Stewart Catherine M. , Russell William A. , Luz George A.
Published: July 2002

In 1974, the U.S. Environmental Protection Agency (USEPA) published a report endorsing the day–night average sound level (DNL) for nationwide use. Included in this report was an equation predicting DNL from the number of people per square mile. The equation was based on monitoring from 100 sites throughout the U.S. To determine whether the 1974 equation still provided a realistic estimate 25 years later, monitoring was conducted at 50 sites in Baltimore County, Maryland. Population density ranged from 600 to 13000 people per square mile. To explore seasonal differences and test–retest reliability, the monitoring was conducted for 24 h in the summer and 24 h in the winter. The results are compared to those of the USEPA.
Statistical Continuum Theories
Authors: Beran Mark
Published: July 2002

There are presently a large number of problems in continuum physics that may be treated from a statistical point of view. In this paper we shall discuss what is meant by the statistical solution to a continuum problem. We shall initially use the nature of the stress and strain fields in a heterogeneous material as an example. We shall then emphasize the essential similarity of all statistical continuum theories. The more developed statistical continuum theories like the statistical theory of turbulence and the theory of partial coherence will be compared to the statistical theory of heterogeneous materials. For the heterogeneous material problem we shall outline a method for deriving a hierarchy of statistical moment equations from the equations of elasticity for a medium with variable elastic properties. We conclude with a discussion of the use of perturbation procedures in determining bounds for the effective elastic constants.
Time-Dependent Polymer Rheology under Constant Stress and under Constant Shear Conditions
Authors: Lee Kiu H. , Brodkey Robert S.
Published: July 2002

The kinetic rate theory previously presented for describing non-Newtonian phenomena has been further modified to predict the flow behavior of viscoelastic materials under constant stress conditions. The thixotropic shear stress or shear rate is predicted by the kinetic theory, and the experimental stress or shear rate is obtained by modifying the thixotropic value by a stress or shear rate retardation term. The retardation term stems from a Maxwellian approach for stress retardation. In order to test the validity of this approach, transient and steady-state data have been obtained for two solutions of polymethylmethacrylate in diethyl-phthalate. Both constant stress measurements and constant shear rate data have been taken over a broad range. In a systematic manner as suggested by the theory, the parameters were evaluated from constant stress data, and were in turn used to predict constant shear rate data as well as the constant stress measurements. It should be emphasized that the parameters were not obtained from the best empirical fit to the data but were evaluated in a manner suggested by the theory. The agreement between theory and data was good enough to ascertain that the approach is adequate for correlating polymer rheology data. The overall average absolute mean deviation ranged from 4.2% for the steady-state measurements to 11.2% for the constant stress transient measurements. It was further observed that stress overshoot at constant shear rate conditions normally occurred when the Deborah number was greater than unity. Gradual stress growth curves were observed when the number was less than unity.
Numerical simulation of planar entry flow for a polyisobutylene solution using an integral constitutive equation
Authors: Mitsoulis E.
Published: July 2002

Numerical simulations have been undertaken for the entry flow through a 4:1 planar contraction of a well-characterized shear-thinning polymer solution (polyisobutylene in tetradecane) used previously in an experimental study. The fluid has been modeled using an integral constitutive equation of the K-BKZ type with a spectrum of four relaxation times. Numerical values for the constants appearing in the equation have been obtained from fitting linear viscoelastic material functions as well as shear and elongational viscosity data and normal stresses as measured in shear. The numerical solutions for the range of experimental Deborah and Reynolds numbers show a stagnant small corner vortex that slightly decreases with increasing flow rate. The velocity and stress fields are compared with the experimental ones, showing a good general agreement. The constitutive equation overpredicts, however, the maximum centerline birefringence values by as much as 40% for the highest De. The behavior of shear stress and first normal stress difference near the re-entrant corner are also illustrated.