bluuebunny/crossref_metadata_2025 huggingface dataset:
The proapoptotic function ofDrosophilaHid is conserved in mammalian cells
Authors: Haining W. N. , Carboy-Newcomb C. , Wei C. L. , Steller H.
Published: July 2002

Three genes—reaper,grim, andhid—are crucial to the regulation of programmed cell death inDrosophila melanogaster. Mutations involving all three genes virtually abolish apoptosis during development, and homozygoushidmutants die as embryos with extensive defects in apoptosis. Although Hid is central to apoptosis inDrosophila, it has no mammalian homologue identified to date. We present evidence that expression ofDrosophilaHid in mammalian cells induces apoptosis. This activity is subject to regulation by inhibitors of mammalian cell death. We show that the N terminus of Hid, which is a region of homology with Reaper and Grim, is essential for Hid’s function in mammalian cells. We demonstrate that Hid is localized to the mitochondria via a hydrophobic region at its C terminus and functionally interacts with BclXL. This study shows that the function of Hid as a death inducer inDrosophilais conserved in mammalian cells and argues for the existence of a mammalian homologue of this critical regulator of apoptosis.
Suramin inhibits initiation of defense signaling by systemin, chitosan, and a β-glucan elicitor in suspension-cultured
Lycopersicon peruvianum
cells
Authors: Stratmann Johannes , Scheer Justin , Ryan Clarence A.
Published: July 2002

Systemin-mediated defense signaling in tomato (
Lycopersicon
esculentum
) plants is analogous to the cytokine-mediated
inflammatory response in animals. Herein, we report that the initiation
of defense signaling in suspension-cultured cells of
Lycopersicon peruvianum
by the peptide systemin, as well
as by chitosan and β-glucan elicitor from
Phytophtora
megasperma,
is inhibited by the polysulfonated naphtylurea
compound suramin, a known inhibitor of cytokine and growth factor
receptor interactions in animal cells. Using a radioreceptor assay, we
show that suramin interfered with the binding of the systemin analog
125
I-Tyr-2,Ala-15-systemin to the systemin receptor with an
IC
50
of 160 μM. Additionally, labeling of the systemin
receptor with a photoaffinity analog of systemin was inhibited in the
presence of suramin. Receptor-mediated tyrosine phosphorylation of a
48-kDa mitogen-activated protein kinase and alkalinization of the
medium of suspension-cultured cells in response to systemin and
carbohydrate elicitors were also inhibited by suramin. The inhibition
of medium alkalinization by suramin was reversible in the presence of
high concentrations of systemin and carbohydrate elicitors. Calyculin A
and erythrosin B, intracellular inhibitors of phosphatases and plasma
membrane proton ATPases, respectively, both induce medium
alkalinization, but neither response was inhibited by suramin. The
polysulfonated compound heparin did not inhibit systemin-induced medium
alkalinization. NF 007, a suramin derivative, induced medium
alkalinization, indicating that neither NF 007 nor heparin interact
with elicitor receptors like suramin. The data indicate that
cell-surface receptors in plants show some common structural features
with animal cytokine and growth factor receptors that can interact with
suramin to interfere with ligand binding.
Yin6, a fission yeast Int6 homolog, complexes with Moe1 and plays a role in chromosome segregation
Authors: Yen Hsueh-Chi S. , Chang Eric C.
Published: July 2002

The
INT6
gene has been implicated in human
breast cancer formation, but its function is unknown. We isolated an
Int6 homolog from fission yeast, Yin6, by its binding to a conserved
protein in the Ras pathway, Moe1. Yin6 and Moe1 converge on the same
protein complex to promote microtubule instability/disassembly.
Yin6 and Moe1 interact cooperatively: when either protein is absent,
the other becomes mislocalized with decreased protein levels.
Furthermore, whereas full-length human Int6 rescues the phenotypes of
the
yin6
-null (
yin6
Δ
)
mutant cells and binds human Moe1, truncated Int6 proteins found in
tumors do not. Importantly,
yin6
Δ alone impairs
chromosome segregation weakly, but
yin6
Δ together with
ras1
Δ causes severe chromosome missegregation. These
data support a model in which
INT6
mutations in humans
either alone or together with additional mutations, such as a
RAS
mutation
,
may contribute to
tumorigenesis by altering genome stability.
The role of rigidity in DNA looping-unlooping by AraC
Authors: Harmer Tara , Wu Martin , Schleif Robert
Published: July 2002

We applied two experiments useful in the study of
ligand-regulated DNA binding proteins to AraC, the dimeric regulator of
the
Escherichia coli
l
-arabinose operon. In
the absence of arabinose, AraC prefers to loop DNA by binding to two
half-sites that are separated by 210 base pairs, and in the presence of
arabinose it prefers to bind to adjacently located half-sites. The
basis for this ligand-regulated shift in binding appears to result from
a shift in the rigidity of the system, where rigidity both in AraC
protein in the absence of arabinose, and in the DNA are required to
generate the free energy differences that produce the binding
preferences. Eliminating the dimerization domains and connecting the
two DNA binding domains of AraC by a flexible peptide linker should
provide a protein whose behavior mimics that of AraC when there is no
interaction between its dimerization and DNA binding domains. The
resulting protein bound to adjacent half-sites on the DNA, like AraC
protein in the presence of arabinose. When the two double-stranded DNA
half-sites were connected by 24 bases of single-stranded, flexible DNA,
wild-type AraC protein bound to the DNA in the presence and absence of
arabinose with equal affinity, showing that AraC modulates its DNA
binding affinity in response to arabinose by shifting the relative
positions of its DNA binding domains. These results are consistent with
the light switch mechanism for the action of AraC, refine the model,
and extend the range of experimental tests to which it has been
subjected.
Transcript leader regions of two
Saccharomyces cerevisiae
mRNAs contain internal ribosome entry sites that function in living cells
Authors: Zhou Wei , Edelman Gerald M. , Mauro Vincent P.
Published: July 2002

In higher eukaryotes, translation of some mRNAs occurs by
internal initiation. It is not known, however, whether this mechanism
is used to initiate the translation of any yeast mRNAs. In this report,
we identify naturally occurring nucleotide sequences that function as
internal ribosome entry sites (IRESes) within the 5′ leader sequences
of
Saccharomyces cerevisiae
YAP1 and p150 mRNAs. When
tested in the 5′ untranslated regions of monocistronic reporter genes,
both leader sequences enhanced translation efficiency in vegetatively
growing yeast cells. Moreover, when tested in the intercistronic region
of dicistronic mRNAs, both sequences were shown to contain IRESes that
functioned in living cells. The activity of the p150 leader was much
greater than that of the YAP1 leader. The second cistron was not
expressed in control dicistronic constructs that lacked these sequences
or contained the 5′ leader sequence of the CLN3 mRNA in the
intercistronic region. Further analyses of the p150 IRES revealed that
it contained several nonoverlapping segments that were able
independently to mediate internal initiation. These results suggested a
modular composition for the p150 IRES that resembled the composition of
IRESes contained within some cellular mRNAs of higher eukaryotes. Both
YAP1 and p150 leaders contain several complementary sequence matches to
yeast 18S rRNA. The findings are discussed in terms of our
understanding of internal initiation in higher eukaryotes.
Anti‐inflammatory response of IL‐4, IL‐10 and TGF‐β in patients with systemic inflammatory response syndrome
Authors: Torre Donato , Tambini Roberto , Aristodemo Silvana , Gavazzeni Giovanna , Goglio Antonio , Cantamessa Carla , Pugliese Agostino , Biondi Gilberto
Published: July 2002

The systemic inflammatory response syndrome (SIRS) is an inflammatory process seen in association with a large number of clinical infective and noninfective conditions.

The aim of this study was to investigate the role of anti‐inflammatory cytokines such as interleukin–4 (IL–4), interleukin–10 (IL–10), and transforming growth factor‐beta (TGF‐beta). Serum levels of IL–4, IL–10 and TGF‐β were determined in 45 patients with SIRS: 38 patients had SIRS of infectious origin, whereas seven patients had non‐infectious SIRS. Twenty healthy subjects were used as controls.

Serum levels of IL–4, IL–10 and TGFg were determined by an immunoenzyme assay. A significant increase of IL–4 was observed in these patients at the time of diagnosis and 5 days later. In contrast, serum levels of IL–10 were not increased at the time of diagnosis, but a slight decrease was noted after 5 days. Serum levels of TGF‐β were not increased at time of diagnosis, and a slight increase was observed after 5 days. Serum levels of IL–4 were significantly higher in patients with infectious SIRS at the time of diagnosis, whereas no significant difference between infectious and non‐infectious SIRS was noted for serum levels of IL–10 and TGF‐β at the time of diagnosis and 5 days later.

During SIRS, serum levels of IL–4 were significantly increased with a significant correlation between IL–4 and mortality, and only levels of IL–4 were significantly increased in the SIRS caused by infectious stimuli.
Pex20p of the Yeast Yarrowia lipolytica Is Required for the Oligomerization of Thiolase in the Cytosol and for Its Targeting to the Peroxisome
Authors: Titorenko Vladimir I. , Smith Jennifer J. , Szilard Rachel K. , Rachubinski Richard A.
Published: July 2002

Pex mutants are defective in peroxisome assembly. In the pex20-1 mutant strain of the yeast Yarrowia lipolytica, the peroxisomal matrix protein thiolase is mislocalized exclusively to the cytosol, whereas the import of other peroxisomal proteins is unaffected. The PEX20 gene was isolated by functional complementation of the pex20-1 strain and encodes a protein, Pex20p, of 424 amino acids (47,274 D). Despite its role in the peroxisomal import of thiolase, which is targeted by an amino-terminal peroxisomal targeting signal-2 (PTS2), Pex20p does not exhibit homology to Pex7p, which acts as the PTS2 receptor. Pex20p is mostly cytosolic, whereas 4–8% is associated with high-speed (200,000 g) pelletable peroxisomes. In the wild-type strain, all newly synthesized thiolase is associated with Pex20p in a heterotetrameric complex composed of two polypeptide chains of each protein. This association is independent of PTS2. Pex20p is required for both the oligomerization of thiolase in the cytosol and its targeting to the peroxisome. Our data suggest that monomeric Pex20p binds newly synthesized monomeric thiolase in the cytosol and promotes the formation of a heterotetrameric complex of these two proteins, which could further bind to the peroxisomal membrane. Translocation of the thiolase homodimer into the peroxisomal matrix would release Pex20p monomers back to the cytosol, thereby permitting a new cycle of binding-oligomerization-targeting-release for Pex20p and thiolase.
Neurolin Ig Domain 2 Participates in Retinal Axon Guidance and Ig Domains 1 and 3 in Fasciculation
Authors: Leppert Christian A. , Diekmann Heike , Paul Claudia , Laessing Ute , Marx Monika , Bastmeyer Martin , Stuermer Claudia A.O.
Published: July 2002

The optic disk–directed growth of retinal ganglion cell axons is markedly disturbed in the presence of polyclonal antineurolin antibodies, which mildly affect fasciculation (Ott, H., M. Bastmeyer, and C.A.O. Stuermer, 1998. J. Neurosci. 18:3363–3372).

New monoclonal antibodies (mAbs) against goldfish neurolin, an immunoglobulin (Ig) superfamily cell adhesion/recognition molecule with five Ig domains, were generated to assign function (guidance versus fasciculation) to specific Ig domains. By their ability or failure to recognize Chinese hamster ovary cells expressing recombinant neurolin with deletions of defined Ig domains, mAbs were identified as being directed against Ig domains 1, 2, or 3, respectively. Repeated intraocular injections of a mAb against Ig domain 2 disturb the disk-directed growth: axons grow in aberrant routes and fail to reach the optic disk, but remain fasciculated. mAbs against Ig domains 1 and 3 disturb the formation of tight fascicles.

mAb against Ig domain 2 significantly increases the incidence of growth cone departure from the disk-oriented fascicle track, while mAbs against Ig domains 1 and 3 do not. This was demonstrated by time-lapse videorecording of labeled growth cones.

Thus, Ig domain 2 of neurolin is apparently essential for growth cone guidance towards the disk, presumably by being part of a receptor (or complex) for an axon guidance component.
Virus-induced Transient Bone Marrow Aplasia: Major Role of Interferon-α/β during Acute Infection with the Noncytopathic Lymphocytic Choriomeningitis Virus
Authors: Binder Daniel , Fehr Jörg , Hengartner Hans , Zinkernagel Rolf M.
Published: July 2002

The hematologic consequences of infection with the noncytopathic lymphocytic choriomeningitis virus (LCMV) were studied in wild-type mice with inherent variations in their interferon (IFN)-α/β responder ability and in mutant mice lacking α/β (IFN-α/β R0/0) or γ IFN (IFN-γ R0/0) receptors. During the first week of infection, wild type mice demonstrated a transient pancytopenia. Within a given genetic background, the extent of the blood cell abnormalities did not correlate with the virulence of the LCMV isolate but variations were detected between different mouse strains; they were found to depend on their IFN-α/β responder phenotype. Whereas IFN-γ R0/0 mice were comparable to wild-type mice, IFN-α/β R0/0 mice exhibited unchanged peripheral blood values during acute LCMV infection. In parallel, the bone marrow (BM) cellularity, the pluripotential and committed progenitor compartments were up to 30-fold reduced in wild type and IFN-γ R0/0, but remained unchanged in IFN-α/β R0/0 mice. Viral titers in BM 3 d after LCMV infection were similar in these mice, but antigen localization was different. Viral antigen was predominantly confined to stromal BM in normal mice and IFN-γ R0/0 knockouts, whereas, in IFN-α/β R0/0 mice, LCMV was detected in >90% of megakaryocytes and 10–15% of myeloid precursors, but not in erythroblasts. Although IFN-α/β efficiently prevented viral replication in potentially susceptible hematopoietic cells, even in overwhelming LCMV infection, unlimited virus multiplication in platelet and myeloid precursors in IFN-α/β R0/0 mice did not interfere with the number of circulating blood cells. Natural killer (NK) cell expansion and activity in the BM was comparable on day 3 after infection in mutant and control mice. Adaptive immune responses did not play a major role because comparable kinetics of LCMV-induced pancytopenia and transient depletion of the pluripotential and committed progenitor compartments were observed in CD80/0 and CD40/0 mice, in mice depleted of NK cells, in lpr mice, and in perforin-deficient (P0/0) mice lacking lytic NK cells. Thus, the reversible depression of hematopoiesis during early LCMV infection was not mediated by LCMV-WE–specific cytotoxic T lymphocyte, cytolysis, or secreted IFN-γ from virally induced NK cells but was a direct effect of IFN-α/β.
Augmented Expression of a Human Gene for 8-oxoguanine DNA Glycosylase (MutM) in B Lymphocytes of the Dark Zone in Lymph Node Germinal Centers
Authors: Kuo Frank C. , Sklar Jeffrey
Published: July 2002

B cells that mediate normal, T cell–dependent, humoral immune responses must first pass through germinal centers (GCs) within the cortex of antigenically stimulated lymph nodes. As they move through the dark zone and then the light zone in the GC, B cells are subjected to somatic hypermutation and switch recombination within their rearranged immunoglobulin genes and also participate in a number of other processes that control development into memory cells or cells specialized for antibody secretion. To investigate the molecular mechanisms that contribute to B cell development within GCs, we constructed a recombinant DNA library enriched for cDNAs derived from human genes expressed in B cells at this site. This library was found to contain a cDNA structurally and functionally related to genes in bacteria and yeast for the DNA repair enzyme 8-oxoguanine DNA glycosylase. Northern blot analysis indicated that the human gene is expressed as two alternatively spliced messenger RNAs within GC B cells at levels greatly exceeding that found in other tissues. In situ hybridization studies revealed that expression of this gene is most abundant within the dark zones of GCs. Both the function and localized expression of this gene suggest that it may play a role in somatic hypermutation of immunoglobulin genes.
Induction of Protective Cytotoxic T Cell Responses in the Presence of High Titers of  Virus-neutralizing Antibodies: Implications for Passive and Active Immunization
Authors: Seiler Peter , Bründler Marie-Anne , Zimmermann Christine , Weibel Doris , Bruns Michael , Hengartner Hans , Zinkernagel Rolf M.
Published: July 2002

The effect of preexistent virus-neutralizing antibodies on the active induction of antiviral T cell responses was studied in two model infections in mice. Against the noncytopathic lymphocytic choriomeningitis virus (LCMV), pretreatment with neutralizing antibodies conferred immediate protection against systemic virus spread and controlled the virus below detectable levels. However, presence of protective antibody serum titers did not impair induction of antiviral cytotoxic T lymphocyte (CTL) responses after infection with 102 PFU of LCMV. These CTLs efficiently protected mice independent of antibodies against challenge with LCMV–glycoprotein recombinant vaccinia virus; they also protected against otherwise lethal lymphocytic choriomeningitis caused by intracerebral challenge with LCMV-WE, whereas transfused antibodies alone did not protect, and in some cases even enhanced, lethal lymphocytic choriomeningitis. Against the cytopathic vesicular stomatitis virus (VSV), specific CTLs and Th cells were induced in the presence of high titers of VSV-neutralizing antibodies after infection with 106 PFU of VSV, but not at lower virus doses. Taken together, preexistent protective antibody titers controlled infection but did not impair induction of protective T cell immunity. This is particularly relevant for noncytopathic virus infections since both virus-neutralizing antibodies and CTLs are essential for continuous virus control. Therefore, to vaccinate against such viruses parallel or sequential passive and active immunization may be a suitable vaccination strategy to combine advantages of both virus-neutralizing antibodies and CTLs.
Processing of a Multiple Membrane Spanning Epstein-Barr Virus Protein for Cd8+T Cell Recognition Reveals a Proteasome-Dependent, Transporter Associated with Antigen Processing–Independent Pathway
Authors: Lautscham Georg , Mayrhofer Sabine , Taylor Graham , Haigh Tracey , Leese Alison , Rickinson Alan , Blake Neil
Published: July 2002

Epstein-Barr virus (EBV) latent membrane protein (LMP)2 is a multiple membrane spanning molecule which lacks ectodomains projecting into the lumen of the endoplasmic reticulum (ER). Human CD8+ cytotoxic T lymphocytes (CTL)s recognize a number of epitopes within LMP2. Assays with epitope-specific CTLs in two different cell backgrounds lacking the transporter associated with antigen processing (TAP) consistently show that some, but not all, LMP2 epitopes are presented in a TAP-independent manner. However, unlike published examples of TAP-independent processing from endogenously expressed antigens, presentation of TAP-independent LMP2 epitopes was abrogated by inhibition of proteasomal activity. We found a clear correlation between hydrophobicity of the LMP2 epitope sequence and TAP independence, and experiments with vaccinia minigene constructs expressing cytosolic epitope peptides confirmed that these more hydrophobic peptides were selectively able to access the HLA class I pathway in TAP-negative cells. Furthermore, the TAP-independent phenotype of particular epitope sequences did not require membrane location of the source antigen since (i) TAP-independent LMP2 epitopes inserted into an EBV nuclear antigen and (ii) hydrophobic epitope sequences native to EBV nuclear antigens were both presented in TAP-negative cells. We infer that there is a proteasome-dependent, TAP-independent pathway of antigen presentation which hydrophobic epitopes can selectively access.
African Journals Online: improving awareness and access
Authors: Rosenberg Diana
Published: July 2002

Indigenous journal publication is vital to the well‐being of the African research enterprise in ways that the high‐profile initiatives of Western publishers have, so far, failed to address. This paper describes the scope and development of African Journals Online, a free service which provides online access to the tables of contents and abstracts of scholarly journals published in Africa, backed by a document delivery service and managed by the International Network for the Availability of Scientific Publications.
Positive definiteness and commutativity of operators
Authors: Stochel Jan
Published: July 2002

It is shown that an

n
n

–tuple of bounded linear operators on a complex Hilbert space, which is positive definite in the sense of Halmos, must be commutative. Some generalizations of this result to the case of pairs of unbounded operators are obtained.
𝑆𝐿_{𝑛}-character varieties as spaces of graphs
Authors: Sikora Adam
Published: July 2002

An

S

L
n

SL_n

-character of a group

G
G

is the trace of an

S

L
n

SL_n

-representation of

G
.

G.

We show that all algebraic relations between

S

L
n

SL_n

-characters of

G
G

can be visualized as relations between graphs (resembling Feynman diagrams) in any topological space

X
,

X,

with

π
1

(
X
)
=
G
.

\pi _1(X)=G.

We also show that all such relations are implied by a single local relation between graphs. In this way, we provide a topological approach to the study of

S

L
n

SL_n

-representations of groups.

The motivation for this paper was our work with J. Przytycki on invariants of links in 3-manifolds which are based on the Kauffman bracket skein relation. These invariants lead to a notion of a skein module of

M
M

which, by a theorem of Bullock, Przytycki, and the author, is a deformation of the

S

L
2

SL_2

-character variety of

π
1

(
M
)
.

\pi _1(M).

This paper provides a generalization of this result to all

S

L
n

SL_n

-character varieties.
Remarks on the Schoof-Elkies-Atkin algorithm
Authors: Dewaghe L.
Published: July 2002

Schoof’s algorithm computes the number

m
m

of points on an elliptic curve

E
E

defined over a finite field

F

q

{\Bbb F}_q

. Schoof determines

m
m

modulo small primes

ℓ
\ell

using the characteristic equation of the Frobenius of

E
E

and polynomials of degree

O
(

ℓ
2

)

O(\ell ^2)

. With the works of Elkies and Atkin, we have just to compute, when

ℓ
\ell

is a “good" prime, an eigenvalue of the Frobenius using polynomials of degree

O
(
ℓ
)

O(\ell )

. In this article, we compute the complexity of Müller’s algorithm, which is the best known method for determining one eigenvalue and we improve the final step in some cases. Finally, when

ℓ
\ell

is “bad", we describe how to have polynomials of small degree and how to perform computations, in Schoof’s algorithm, on

x
x

-values only.
The incipient infinite cluster in high-dimensional percolation
Authors: Hara Takashi , Slade Gordon
Published: July 2002

We announce our recent proof that, for independent bond percolation in high dimensions, the scaling limits of the incipient infinite cluster’s two-point and three-point functions are those of integrated super-Brownian excursion (ISE). The proof uses an extension of the lace expansion for percolation.
EDITtoTrEMBL: a distributed approach to high-quality automated protein sequence annotation.
Authors: M√∂ller S , Leser U , Fleischmann W , Apweiler R
Published: July 2002

SUMMARY: Many databases in molecular biology face the problem that the ever increasing rate of data production can no longer be handled by traditional methods, especially human curation. Therefore, a number of projects are currently investigating methods for automated sequence annotation. This paper describes the EBI's approach to this problem for protein sequences by integration of arbitrary analysis programs into a distributed and highly flexible environment. Our software framework allows an individual treatment of sequences depending on their particular properties, which is achieved through a high-level description of the preconditions and capabilities of analysing modules. This not only improves the overall performance of the annotation process, as unnecessary steps are avoided, but also enhances its quality since dependencies between different modules are taken into account. We have implemented a prototype and use it in the production of TrEMBL releases. AVAILABILITY: Upon request.
STAR/mmCIF: An ontology for macromolecular structure
Authors: Westbrook John D. , Bourne Philip E.
Published: July 2002

Motivation: Crystallographers were motivated 10 years ago to develop a simple and consistent data representation for the exchange and archiving of data associated with the crystallographic experiment and the final structure. As this process evolved (and the data grew at near exponential rates) came the recognition that this representation should also facilitate the automated management of the data and, with the aid of additional software for verification and validation, provide improved consistency and accuracy and hence improved scientific inquiry. This realization led to a new Dictionary Definition Language (DDL) and an extensive dictionary based on this DDL for describing macromolecular structure. In broad terms this could be considered an ontology. An important feature in the development of the ontology was the endorsement and ongoing maintenance and support of the International Union of Crystallography (IUCr). While the description of macromolecular structure and the x-ray crystallographic experiment used to derive it represent explicit data, the ontology is extensible and applicable to other less well- characterized data domains.

Results: Details of the DDL, the dictionaries that have been developed, and software for reading and using this ontology are presented.

Availability: Extensive documentation, software tools and the DDL and dictionaries are available from http://ndbserver.rutgers.edu/mmcifand associated mirror sites.

Contact: Bourne: bourne@sdsc.eduand Westbrook: jwest@rcsb.rutgers.edu
Thioguanine substitution alters DNA cleavage mediated by topoisomerase II
Authors: Krynetskaia Natalia F. , Cai Xiangjun , Nitiss John L. , Krynetski Eugene Y. , Relling Mary V.
Published: July 2002

Thiopurines and topoisomerase II‐targeted drugs (e.g., etoposide) are widely used anticancer drugs. However, topoisomerase II‐targeted drugs can cause acute myeloid leukemia, with the risk of this secondary leukemia linked to a genetic defect in thiopurine catabolism. Chronic thiopurines result in thioguanine substitution in DNA. The effect of these substitutions on DNA topoisomerase II activity is not known. Our goal was to determine whether deoxythioguanosine substitution alters DNA cleavage stabilized by human topoisomerase II. We studied four variations of a 40 mer oligonucleotide with a topoisomerase II cleavage site, each with a single deoxythioguanosine in a different position relative to the cleavage site (‐1 or +2 in the top and +2 or +4 in the bottom strand). Deoxythioguanosine substitution caused position‐dependent quantitative effects on cleavage. With the ‐ 1 or + 2 top and + 2 or+ 4 bottom substitutions, mean topoisomerase II‐induced cleavage was 0.6‐, 2.0‐, 1.1‐, and 3.3‐fold that with the wild‐type substrate (P=0.011, < 0.008, 0.51, and < 0.001, respectively). In the presence of 100 µ? etoposide, cleavage was enhanced for wild‐type and all thioguanosine‐modified substrates relative to no etoposide, with the + 4 bottom substitution showing greater etoposide‐induced cleavage than the wild‐type substrate (P=0.015). We conclude that thioguanine incorporation alters the DNA cleavage induced by topoisomerase II in the presence and absence of etoposide, providing new insights to the mechanism of thiopurine effect and on the leukemogenesis of thiopurines, with or without topoisomerase inhibitors.—Krynetskaia, N. F., Cai, X., Nitiss, J. L., Krynetski, E. Y., Relling, M. V. Thioguanine substitution alters DNA cleavage mediated by topoisomerase II. FASEB J. 14, 2339‐2344 (2000)
A comparison of the effectiveness of thermoluminescent crystals LiF:Mg,Ti, and LiF:Mg,Cu,P for clinical dosimetry
Authors: Harris Christie K. , Elson Howard R. , Lamba Michael A. S. , Foster Alvis E.
Published: July 2002

This study compared the relative effectiveness of TLD crystals LiF:Mg,Ti (TLD‐100) and LiF:Mg,Cu,P (TLD‐700H) for clinical dosimetry, focusing on reproducibility, linearity, and energy response. Experimental results indicated that TLD‐700H was superior to TLD‐100 with regard to reproducibility, lack of supralinearity, and the absence of variation in TL signal with radiation quality. TLD‐700H also had the additional advantages of higher sensitivity and immediate readability. The investigators concluded that this relatively new TLD crystal shows promising potential for clinical dosimetry.
Filter material selection for region of interest radiologic imaging
Authors: Massoumzadeh Parinaz , Rudin Stephen , Bednarek Daniel R.
Published: July 2002

Region of interest (ROI) fluoroscopic techniques have the potential for improving image quality and greatly reducing radiation dose. The utility of ROI imaging depends on the material used for the filter. Various materials for x‐ray beam shaping ROI filters are evaluated using a computer simulation to determine their transmission and effect on radiographic image quality as a function of kVp. Selected measurements were also performed to verify the results of the simulation. Rare earth materials such as gadolinium (Gd) showed distinct advantages over conventional filter materials such as copper (Cu). The effects of Gd and Cu filters on transmission, contrast, and contrast to noise ratio using a CsI image receptor were investigated for beams of 40 to 100 kVp for a broad range of thicknesses of iodine, barium, bone, fat, and for a range of phantom thicknesses. The results were the following: (1) Gd generally increases image contrast while Cu substantially decreases contrast for all materials at all kVp's; (2) Gd has much less variation in transmission with kVp than Cu; and (3) for the same signal in the ROI and with thicknesses of filters which provides the same entrance phantom kerma, Gd provides higher contrast to noise ratio than Cu for lower kVp values while Cu provides higher contrast to noise ratio at higher kVp values. Analytical results of transmission and contrast improvement as a function of iodine concentration, filter thickness, and kVp compared favorably with experimental values. In conclusion, Gd appears to be the filter material of choice when it is important to maintain a higher level of image contrast in the periphery, such as during angiography, since image contrast is not degraded with Gd while it is degraded substantially with Cu. Although contrast is degraded with Cu, Cu may be the preferred filter material for higher kVp procedures such as GI exams since the detected signal in the periphery would be substantially higher permitting either greater reduction in patient dose or a decrease in image noise for the same dose reduction.
How to distinguish identical particles
Authors: Herbut Fedor
Published: July 2002

Usually fermions and bosons behave very differently. Regarding distinguishability, they behave in one and the same way. Two-identical-particle quantum theory is discussed on the example of the deuteron and that of distant correlations, as well as on the example of the real interference and quantum erasure experiments in the Hong–Ou–Mandel two-photon interferometer (with and without polarizers and analyzers). Distinguishability and indistinguishability of two identical photons in the experiments are illustrated. It is demonstrated, using a simple formalism valid simultaneously for fermions and for bosons, that there exists an isomorphism giving theoretical foundation to distinguishing two identical particles. But the distinguishing has a limited range of exact applicability. In most cases of interest, only the indistinguishability approach has a first-principle (and universal) validity.
The dynamics of a massless hoop
Authors: Theron W. F. D. , du Plessis N. M.
Published: July 2002

For many years it was believed that a rigid, massless hoop which is loaded with a heavy particle on its rim and rolling on a rough surface would hop when the normal reaction became zero. This is a hypothetical model that raises a number of very interesting and subtle aspects of dynamics. In this paper the motion of such hoops is analyzed in detail, and a new motion with unusual characteristics is found.
The physics of golf: The optimum loft of a driver
Authors: Penner A. Raymond
Published: July 2002

The impact between a clubhead and a golf ball along with the resulting flight and run of the ball after landing is considered. The clubhead loft which results in the maximum drive distance and its dependence on the initial clubhead speed is then determined.
Underwater source detection using a spatial stationarity test
Authors: Ephraty A. , Tabrikian J. , Messer H.
Published: July 2002

The problem of detecting a source in shallow water is addressed. The complexity of such a propagation channel makes precise modeling practically impossible. This lack of accuracy causes a deterioration in the performance of the optimal detector and motivates the search for suboptimal detectors which are insensitive to uncertainties in the propagation model. A novel, robust detector which measures the degree of spatial stationarity of a received field is presented. It exploits the fact that a signal propagating in a bounded channel induces spatial nonstationarity to a higher degree than mere background noise. The performance of the proposed detector is evaluated using both simulated data and experimental data collected in the Mediterranean Sea. This performance is compared to those of three other detectors, employing different extents of prior information. It is shown that when the propagation channel is not completely known, as is the case of the experimental data, the novel detector outperforms the others in terms of threshold signal-to-noise ratio (SNR). In the presence of environmental mismatch, the threshold SNR of the novel detector for the experimental data appears 2–5 dB lower than the other detectors. That is, this detector couples good performance with robustness to propagation uncertainties.
The effects of production and presentation level on the auditory distance perception of speech
Authors: Brungart Douglas S. , Scott Kimberly R.
Published: July 2002

Although both perceived vocal effort and intensity are known to influence the perceived distance of speech, little is known about the processes listeners use to integrate these two parameters into a single estimate of talker distance. In this series of experiments, listeners judged the distances of prerecorded speech samples presented over headphones in a large open field. In the first experiment, virtual synthesis techniques were used to simulate speech signals produced by a live talker at distances ranging from 0.25 to 64 m. In the second experiment, listeners judged the apparent distances of speech stimuli produced over a 60-dB range of different vocal effort levels (production levels) and presented over a 34-dB range of different intensities (presentation levels). In the third experiment, the listeners judged the distances of time-reversed speech samples. The results indicate that production level and presentation level influence distance perception differently for each of three distinct categories of speech. When the stimulus was high-level voiced speech (produced above 66 dB SPL 1 m from the talker’s mouth), the distance judgments doubled with each 8-dB increase in production level and each 12-dB decrease in presentation level. When the stimulus was low-level voiced speech (produced at or below 66 dB SPL at 1 m), the distance judgments doubled with each 15-dB increase in production level but were relatively insensitive to changes in presentation level at all but the highest intensity levels tested. When the stimulus was whispered speech, the distance judgments were unaffected by changes in production level and only decreased with increasing presentation level when the intensity of the stimulus exceeded 66 dB SPL. The distance judgments obtained in these experiments were consistent across a range of different talkers, listeners, and utterances, suggesting that voice-based distance cueing could provide a robust way to control the apparent distances of speech sounds in virtual audio displays.
Membrane waves on a cylindrical shell with an axial rib
Authors: Manning Patricia A.
Published: July 2002

A test facility has been set up to study the effect of structural modifications on membrane waves in cylindrical shells. Previous research on submerged shells has shown the importance of membrane waves in the mid-frequency, high aspect angle regimes. These shear and compressional waves are important because they are the principle determinants of the shell’s radiation and scattering properties. Flexural waves serve mainly as modifiers of the membrane waves because they are poorly coupled to the acoustic medium. The current test structure is a thin plastic shell. The advantages of plastic include higher damping, a lower compressional wave speed, and easy machining. Single modes up to n=6 are generated using an axisymmetric source array and the resulting accelerations are measured with an axial line array. The measured accelerations are separated into flexural, compressional and shear waves. Data collected on the unmodified plastic shell show excellent agreement with theory. Membrane and flexural waves in both forward and backward propagation directions are clearly seen. The experimental dispersion curves closely match theoretical predictions. Recent modifications to the shell involve the addition of an axial rib. Data from the modified shell will be presented. [Work supported by ONR.]
A simple technique for converting a conventional processor to a fluctuation-based processor and enhancing performance
Authors: Wagstaff Ronald A. , Kooney S. F.
Published: July 2002

It has been shown [R. A. Wagstaff, J. Acoust. Soc. Am. 100, 2853(A) (1996)] that extraordinary gains can be achieved in signal-to-noise ratio enhancement, spatial and spectral resolution can be increased, clutter can be reduced, and submerged sources can be detected by exploiting the natural amplitude fluctuations of the signal and noise. Natural amplitude fluctuations are those fluctuations induced during propagation through the undersea acoustic environment. The gains were achieved by biasing the signal processor, through the WISPR and AWSUM controlling equations, to operate at very low percentiles in the distributions. It is shown in this paper that it is not only possible to achieve additional fluctuation exploitation gains for fluctuation-based processors, such as WISPR and AWSUM, but it is also possible to convert conventional processors to fluctuation-based processors by appropriate modification using a fluctuation sensitive parameter such as the standard deviation. The method is discussed and examples are presented that demonstrate the gains that have been achieved. [Work supported by ONR and NRL.]
Nonlinear acoustic modulation technique for nondestructive flaw detection
Authors: Kim J. P. , Kim E. J. , Yoon S. W. , Sutin A.
Published: July 2002

A new nonlinear acoustic modulation technique was developed to determine flaw locations in a material as a nondestructive evaluation method. Nonlinear interaction of two primary low-frequency continuous and high-frequency burst-type acoustic waves in the material can generate modulated signals. Such modulated signals show significant difference in the material with flaws. The experimental measurements were performed with steel and aluminum rods. Two PZT ceramic elements attached at the ends of rods were driven with two primary frequencies by separate functiongenerators through power amplifiers. Modulated signals detected at a receiving sensor were analyzed by a digital storage oscilloscope with the function of fast Fourier transformation. The second harmonic amplitude was observed 20 dB higher in a sample material with crack than that without crack. The crack location was also very accurately estimated by this nonlinear acoustic modulation technique at the sum and difference frequencies of the primary waves.
Loss factors of a complex composed of a number of coupled harmonic oscillators
Authors: Maidanik G.
Published: July 2002

Investigation of the response of a complex composed of a number of coupled harmonic oscillators is conducted. One of the harmonic oscillators is designed as the master, the others as the satellites. The expression for the loss factor of the coupled master harmonic oscillator is sought. Two distinct loss factors are defined; the prevailing loss factor and the effective loss factor. The first is defined in terms of the real part of the inverse of the normalized in situ admittance of the master harmonic oscillator. The second is defined in terms of the ratio of the normalized input power onto the master harmonic oscillator to the normalized stored energy in the complex due to that power injection. The relationship and the contrast between these two loss factors are revealed. It is argued that, with the exception of an isolated master harmonic oscillator, the prevailing loss factor is apparent; it is the effective loss factor that is real. Whereas the prevailing loss factor invokes the question, ‘‘Where did the energy go?,’’ the effective loss factor renders this question moot.
Array element localization for a horizontal hydrophone array in the Arctic Ocean
Authors: Dosso Stan E. , Fallat Mark R. , Sotirin Barbara J.
Published: July 2002

In 1996, an acoustic research array with both horizontal and vertical components was deployed through the polar ice pack north of Ellesmere Island. The horizontal components consist of a 2.4-km horizontal line array (HLA) of 80 hydrophones on the seafloor and a 240-m secondary HLA of 8 hydrophones perpendicular to the main HLA. To accurately localize these hydrophones, a series of recordings were made immediately after deployment. Glass light bulbs were imploded at 50-m depth at eight locations surrounding the array. Source locations were known to within approximately 2 m; however, to invert the travel time data to within their estimated uncertainties, it was necessary to include corrections to the source locations as unknowns. Source instants were not measured, and were also included as unknowns. An iterative inversion algorithm was formulated by expanding the ray-tracing equations and neglecting second-order terms to yield a linear system of equations. The system was solved by minimizing the HLA curvature and source-location corrections subject to fitting the data to a statistically meaningful level. Minimizing HLA curvature produces a minimum-structure solution in which any deviations from a straight array are absolutely required by the data, and are not artifacts of the starting model.
Generic beamforming structure for adaptive schemes implemented in two- and three-dimensional arrays of sensors
Authors: Tawfik Ayman , Dhanantwari Amar C. , Stergiopoulos Stergios
Published: July 2002

The concept for implementing successfully adaptive schemes in two-dimensional (2-D) and three-dimensional (3-D) arrays of sensors, such as planar, circular, cylindrical, and spherical arrays, is similar to that of line arrays. In particular, the basic step is to minimize the number of degrees of freedom associated with the adaptation process. The present investigation has been centered on the definition of a generic beamforming structure that decomposes the beamforming process of 2- and 3-D sensor arrays into subsets of coherent processes. The approach is to separate the computationally intensive multidimensional beamforming into two simple modules, which are line and circular array beamformers. Thus the multidimensional beamforming process can now be divided into coherent subprocesses which lead to efficient implementation in real-time sonar and radar systems. Furthermore, the application of spatial shading to reduce the side-lobe structures can now be easily incorporated. Moreover, the new approach makes the implementation of adaptive schemes in multidimensional sensor arrays practically achievable. The investigation includes also the definition of generic sub-aperture schemes for 2- and 3-D sensor arrays. This approach leads to minimization of the associated convergence period and makes the implementation of adaptive schemes in multidimensional sensor arrays practically feasible. [Work supported by NSERC-STR181039.]
Acoustic tomography at basin scales and clock errors
Authors: Silivra Anisim A. , Spiesberger John L. , Fabrikant Anatoly , Hurlburt Harley
Published: July 2002

A basin scale underwater acoustic tomography simulation is carried out for the northeast Pacific Ocean to determine the accuracy with which time must be kept at the sources when clocks at the receivers are accurate. A sequential Kalman filter is used to estimate sound-speed perturbation and clock errors. Using an acoustic array of 4 fixed sources and 20 drifting receivers, it is found that the percentage of the modeled ocean’s sound-speed variance accounted for with tomography is 92% at 400-km resolution, practically regardless of the accuracy of the clocks. Clocks which drift up to hundreds of seconds of error (or even more) for a year do not degrade tomographic reconstruction of the model ocean. It is shown that tomographic reconstructions of the sound-speed field are insensitive to clock errors primarily because of a wide variety of distances between the receivers and each particular source. Every receiver ‘‘sees’’ the same clock error from the source, regardless of section length, but changes of travel time associated with the sound-speed perturbation depend on the section length. The Kalman filter is thus able to reconstruct clock error and to map the sound-speed field accurately. [Work supported by ARPA, ♯MDA972-931-0004.]