bluuebunny/crossref_metadata_2025 huggingface dataset:
Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand (Trail) Is an Inhibitor of Autoimmune Inflammation and Cell Cycle Progression
Authors: Song Kaimei , Chen Yiguang , Göke Rüdiger , Wilmen Andreas , Seidel Cheryl , Göke Alexandra , Hilliard Brendan , Chen Youhai
Published: July 2002

The tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) induces apoptosis of tumor cells but not normal cells; its role in normal nontransformed tissues is unknown. We report here that chronic blockade of TRAIL in mice exacerbated autoimmune arthritis, and that intraarticular TRAIL gene transfer ameliorated the disease. In vivo, TRAIL blockade led to profound hyperproliferation of synovial cells and arthritogenic lymphocytes and heightened the production of cytokines and autoantibodies. In vitro, TRAIL inhibited DNA synthesis and prevented cell cycle progression of lymphocytes. Interestingly, TRAIL had no effect on apoptosis of inflammatory cells either in vivo or in vitro. Thus, unlike other members of the tumor necrosis factor superfamily, TRAIL is a prototype inhibitor protein that inhibits autoimmune inflammation by blocking cell cycle progression.
Platelet Glycoprotein Ibα Is a Counterreceptor for the Leukocyte Integrin Mac-1 (Cd11b/Cd18)
Authors: Simon Daniel I. , Chen Zhiping , Xu Hui , Li Chester Q. , Dong Jing-fei , McIntire Larry V. , Ballantyne Christie M. , Zhang Li , Furman Mark I. , Berndt Michael C. , López José A.
Published: July 2002

The firm adhesion and transplatelet migration of leukocytes on vascular thrombus are both dependent on the interaction of the leukocyte integrin, Mac-1, and a heretofore unknown platelet counterreceptor. Here, we identify the platelet counterreceptor as glycoprotein (GP) Ibα, a component of the GP Ib-IX-V complex, the platelet von Willebrand factor (vWf) receptor. THP-1 monocytic cells and transfected cells that express Mac-1 adhered to GP Ibα–coated wells. Inhibition studies with monoclonal antibodies or receptor ligands showed that the interaction involves the Mac-1 I domain (homologous to the vWf A1 domain), and the GP Ibα leucine-rich repeat and COOH-terminal flanking regions. The specificity of the interaction was confirmed by the finding that neutrophils from wild-type mice, but not from Mac-1–deficient mice, bound to purified GP Ibα and to adherent platelets, the latter adhesion being inhibited by pretreatment of the platelets with mocarhagin, a protease that specifically cleaves GP Ibα. Finally, immobilized GP Ibα supported the rolling and firm adhesion of THP-1 cells under conditions of flow. These observations provide a molecular target for disrupting leukocyte–platelet complexes that promote vascular inflammation in thrombosis, atherosclerosis, and angioplasty-related restenosis.
Caspase Activation Is Required for Terminal Erythroid Differentiation
Authors: Zermati Yael , Garrido Carmen , Amsellem Sophie , Fishelson Serge , Bouscary Didier , Valensi Françoise , Varet Bruno , Solary Eric , Hermine Olivier
Published: July 2002

The cysteine proteases known as caspases play a central role in most apoptotic pathways. Here, we show that caspase inhibitors arrest the maturation of human erythroid progenitors at early stages of differentiation, before nucleus and chromatin condensation. Effector caspases such as caspase-3 are transiently activated through the mitochondrial pathway during erythroblast differentiation and cleave proteins involved in nucleus integrity (lamin B) and chromatin condensation (acinus) without inducing cell death and cleavage of GATA-1. These observations indicate a new function for caspases as key proteases in the process of erythroid differentiation.
Structural Features of Peptide Analogs of Human Histocompatibility Leukocyte Antigen Class I Epitopes That Are More Potent and Immunogenic than Wild-Type Peptide
Authors: Tangri Shabnam , Ishioka Glenn Y. , Huang Xiuqing , Sidney John , Southwood Scott , Fikes John , Sette Alessandro
Published: July 2002

Certain peptide analogs that carry substitutions at residues other than the main major histocompatibility complex anchors and are surprisingly much more antigenic than wild-type peptide (heteroclitic analogs). To date, it was unknown how frequently wild-type epitopes could be modified to obtain heteroclitic activity. In this study, we analyzed a large panel of analogs of two different human histocompatibility leukocyte antigen (HLA)-A2.1–restricted epitopes and found that heteroclitic analogs were associated with higher magnitude responses and increased (up to 107-fold) sensitivity to antigen, and corresponded to conservative or semiconservative substitutions at odd-numbered positions in the middle of the peptide (positions 3, 5, or 7). These findings were validated by performing additional immunogenicity studies in murine and human systems with four additional epitopes. The biological relevance of heteroclitic analogs was underlined when predicted analogs of the p53.261 epitope was shown to induce cytotoxic T lymphocytes (CTLs) that recognize low concentrations of peptide (high avidity) in vivo and demonstrate in vitro antitumor recognition. Finally, in vitro immunization of human peripheral blood mononuclear cells with two heteroclitic analogs resulted in recruitment of more numerous CTLs which were associated with increased antigen sensitivity. In conclusion, heteroclitic analogs were identified in each of the six cases studied and structural features were defined which allow identification of such analogs. The strong CTL immunity elicited by heteroclitic epitopes suggest that they could be of significant value in vaccination against tolerant or weakly immunogenic tumor-associated and viral antigens.
Rabphilin-3A: A Multifunctional Regulator of Synaptic Vesicle Traffic
Authors: Burns M.E. , Sasaki T. , Takai Y. , Augustine G.J.
Published: July 2002

We have investigated the function of the synaptic vesicle protein Rabphilin-3A in neurotransmitter release at the squid giant synapse. Presynaptic microinjection of recombinant Rabphilin-3A reversibly inhibited the exocytotic release of neurotransmitter. Injection of fragments of Rabphilin-3A indicate that at least two distinct regions of the protein inhibit neurotransmitter release: the NH2-terminal region that binds Rab3A and is phosphorylated by protein kinases and the two C2 domains that interact with calcium, phospholipid, and β-adducin. Each of the inhibitory fragments and the full-length protein had separate effects on presynaptic morphology, suggesting that individual domains were inhibiting a subset of the reactions in which the full-length protein participates. In addition to inhibiting exocytosis, constructs containing the NH2 terminus of Rabphilin-3A also perturbed the endocytotic pathway, as indicated by changes in the membrane areas of endosomes, coated vesicles, and the plasma membrane. These results indicate that Rabphilin-3A regulates synaptic vesicle traffic and appears to do so at distinct stages of both the exocytotic and endocytotic pathways.
Actions of Genistein on Cystic Fibrosis Transmembrane Conductance Regulator Channel Gating
Authors: Wang Fei , Zeltwanger Shawn , Yang Iris C.-H. , Nairn Angus C. , Hwang Tzyh-Chang
Published: July 2002

Previous studies have shown that genistein increased cystic fibrosis transmembrane conductance regulator (CFTR) channel activity in the presence of saturating concentrations of forskolin and calyculin A in intact cells. Possible molecular mechanisms for genistein's action include inhibition of tyrosine kinases, inhibition of serine/threonine protein phosphatases, or direct binding of genistein to CFTR. Since genistein inhibits several enzymes that hydrolyze ATP, and ATP hydrolysis is an intrinsic property of CFTR, we examined the effect of genistein on CFTR gating in excised inside-out patches from Hi-5 insect cells and NIH3T3 cells expressing recombinant CFTR. Genistein (50 μM) did not open phosphorylated CFTR channels by itself, but increased the ATP- induced CFTR channel current by approximately twofold. A similar magnitude of enhancement was observed when genistein was applied with PKI, a specific inhibitor of protein kinase A, or vanadate, a tyrosine phosphatase inhibitor, suggesting that inhibition of protein phosphatases or tyrosine kinases does not account for genistein's effects. The enhancement of channel current increased with increasing concentrations of genistein and reached a maximum at 35 μM genistein. At higher concentrations of genistein concentration, CFTR channel current decreased, resulting in a bell-shaped dose–response relationship. In the absence of genistein, both open- and closed-time histograms could be fitted with a single exponential function, yielding a mean open time (τO) of 0.302 ± 0.002 s, and a mean closed time (τC) of 0.406 ± 0.003 s. In the presence of 50 μM genistein, the open time histogram could be fitted with a double exponential function with τO1 = 0.429 ± 0.003 s and τO2 = 2.033 ± 0.173 s. Thus, genistein induced a prolonged open state, an effect that mimics that of nonhydrolyzable ATP analogs. Closed time analysis showed that 50 μM genistein caused a prolonged closed state with a time constant of 2.410 ± 0.035 s. We thus conclude that (a) the effects of genistein are likely caused by a direct binding of the drug to the CFTR protein, and (b) at least two binding sites are required to explain the effects of genistein: a high affinity site that decreases the closing rate and a low affinity site that reduces the opening rate.
A Combinatorial Proof of Bass’s Evaluations of the Ihara-Selberg Zeta Function for Graphs
Authors: Foata Dominique , Zeilberger Doron
Published: July 2002

We derive combinatorial proofs of the main two evaluations of the Ihara-Selberg zeta function associated with a graph. We give three proofs of the first evaluation all based on the algebra of Lyndon words. In the third proof it is shown that the first evaluation is an immediate consequence of Amitsur’s identity on the characteristic polynomial of a sum of matrices. The second evaluation of the Ihara-Selberg zeta function is first derived by means of a sign-changing involution technique. Our second approach makes use of a short matrix-algebra argument.
On wavewise entropy inequalities for high-resolution schemes. I: The semidiscrete case
Authors: Yang Huanan
Published: July 2002

We develop a new approach, the method of wavewise entropy inequalities for the numerical analysis of hyperbolic conservation laws. The method is based on a new extremum tracking theory and Vol′pert’s theory of BV solutions. The method yields a sharp convergence criterion which is used to prove the convergence of generalized MUSCL schemes and a class of schemes using flux limiters previously discussed in 1984 by Sweby.
Tables of maximally equidistributed combined LFSR generators
Authors: L’Ecuyer Pierre
Published: July 2002

We give the results of a computer search for maximally equidistri- buted combined linear feedback shift register (or Tausworthe) random number generators, whose components are trinomials of degrees slightly less than 32 or 64. These generators are fast and have good statistical properties.
Complex earthquakes and Teichmüller theory
Authors: McMullen Curtis
Published: July 2002

It is known that any two points in Teichmüller space are joined by an earthquake path. In this paper we show any earthquake path

R

→
T
(
S
)

\mathbb R \rightarrow T(S)

extends to a proper holomorphic mapping of a simply-connected domain

D
D

into Teichmüller space, where

R

⊂
D
⊂

C

\mathbb R \subset D \subset \mathbb C

. These complex earthquakes relate Weil-Petersson geometry, projective structures, pleated surfaces and quasifuchsian groups. Using complex earthquakes, we prove grafting is a homeomorphism for all 1-dimensional Teichmüller spaces, and we construct bending coordinates on Bers slices and their generalizations. In the appendix we use projective surfaces to show the closure of quasifuchsian space is not a topological manifold.
On the image of the 𝑙-adic Abel-Jacobi map for a variety over the algebraic closure of a finite field
Authors: Schoen Chad
Published: July 2002

Let

Y
Y

be a smooth projective variety of dimension at most 4 defined over the algebraic closure of a finite field of characteristic

>
2

>2

. It is shown that the Tate conjecture implies the surjectivity of the

l
l

-adic Abel-Jacobi map,
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="bold a Subscript upper Y comma l Superscript r Baseline colon upper C upper H Subscript h o m Superscript r Baseline left-parenthesis upper Y right-parenthesis right-arrow upper H Superscript 2 r minus 1 Baseline left-parenthesis upper Y comma double-struck upper Z Subscript l Baseline left-parenthesis r right-parenthesis right-parenthesis circled-times double-struck upper Q Subscript l Baseline slash double-struck upper Z Subscript l Baseline">

a

Y
,
l

r

:
C

H

h
o
m

r

(
Y
)
→

H

2
r
−
1

(
Y
,

Z

l

(
r
)
)
⊗

Q

l

/

Z

l

\mathbf {a}^{r}_{Y,l}:CH^{r}_{hom}(Y)\to H^{2r-1}(Y,\mathbb Z_l (r))\otimes \mathbb Q_l /\mathbb Z_l

, for all

r
r

and almost all

l
l

. For a special class of threefolds the surjectivity of

a

Y
,
l

2

\mathbf {a}^{2}_{Y,l}

is proved without assuming any conjectures.
Symmetric spectra
Authors: Hovey Mark , Shipley Brooke , Smith Jeff
Published: July 2002

The stable homotopy category, much studied by algebraic topologists, is a closed symmetric monoidal category. For many years, however, there has been no well-behaved closed symmetric monoidal category of spectra whose homotopy category is the stable homotopy category. In this paper, we present such a category of spectra; the category of symmetric spectra. Our method can be used more generally to invert a monoidal functor, up to homotopy, in a way that preserves monoidal structure. Symmetric spectra were discovered at about the same time as the category of

S
S

-modules of Elmendorf, Kriz, Mandell, and May, a completely different symmetric monoidal category of spectra.
On certain small representations of indefinite orthogonal groups
Authors: Zhu Chen-bo , Huang Jing-Song
Published: July 2002

For any

n
∈

N

n\in \mathbb {N}

such that

2
n
≤
min
(
p
,
q
)

2n\leq \min (p,q)

, we construct a representation

π

n

\pi _{n}

of

O
(
p
,
q
)

O(p,q)

with

p
+
q

p+q

even as the kernel of a commuting set of

n
(
n
+
1
)

2

\frac {n(n+1)}{2}

number of

O
(
p
,
q
)

O(p,q)

-invariant differential operators in the space of

C

∞

C^{\infty }

functions on an isotropic cone with a distinguished

G

L

n

(

R

)

GL_{n}(\mathbb {R})

-homogeneity degree. By identifying

π

n

\pi _{n}

with a certain representation constructed via the formalism of the theta correspondence, we show (except when

p
=
q
=
2
n

p=q=2n

) that the space of

K
K

-finite vectors of

π

n

\pi _{n}

is the

(

g

,
K
)

(\mathfrak {g},K)

-module of an irreducible unitary representation of

O
(
p
,
q
)

O(p,q)

with Gelfand-Kirillov dimension

n
(
p
+
q
−
2
n
−
1
)

n(p+q-2n-1)

. Our construction generalizes the work of Binegar and Zierau (Unitarization of a singular representation of

S

O

e

(
p
,
q
)

SO_{e}(p,q)

, Commun. Math. Phys. 138 (1991), 245–258) for

n
=
1

n=1

.
Fission Yeast Rad26 Is a Regulatory Subunit of the Rad3 Checkpoint Kinase
Authors: Wolkow Tom D. , Enoch Tamar
Published: July 2002

Fission yeast Rad3 is a member of a family of phosphoinositide 3-kinase -related kinases required for the maintenance of genomic stability in all eukaryotic cells. In fission yeast, Rad3 regulates the cell cycle arrest and recovery activities associated with the G2/M checkpoint. We have developed an assay that directly measures Rad3 kinase activity in cells expressing physiological levels of the protein. Using the assay, we demonstrate directly that Rad3 kinase activity is stimulated by checkpoint signals. Of the five other G2/M checkpoint proteins (Hus1, Rad1, Rad9, Rad17, and Rad26), only Rad26 was required for Rad3 kinase activity. Because Rad26 has previously been shown to interact constitutively with Rad3, our results demonstrate that Rad26 is a regulatory subunit, and Rad3 is the catalytic subunit, of the Rad3/Rad26 kinase complex. Analysis of Rad26/Rad3 kinase activation in rad26.T12, a mutant that is proficient for cell cycle arrest, but defective in recovery, suggests that these two responses to checkpoint signals require quantitatively different levels of kinase activity from the Rad3/Rad26 complex.
COFFEE: an objective function for multiple sequence alignments.
Authors: Notredame C , Holm L , Higgins D G
Published: July 2002

MOTIVATION: In order to increase the accuracy of multiple sequence alignments, we designed a new strategy for optimizing multiple sequence alignments by genetic algorithm. We named it COFFEE (Consistency based Objective Function For alignmEnt Evaluation). The COFFEE score reflects the level of consistency between a multiple sequence alignment and a library containing pairwise alignments of the same sequences. RESULTS: We show that multiple sequence alignments can be optimized for their COFFEE score with the genetic algorithm package SAGA. The COFFEE function is tested on 11 test cases made of structural alignments extracted from 3D_ali. These alignments are compared to those produced using five alternative methods. Results indicate that COFFEE outperforms the other methods when the level of identity between the sequences is low. Accuracy is evaluated by comparison with the structural alignments used as references. We also show that the COFFEE score can be used as a reliability index on multiple sequence alignments. Finally, we show that given a library of structure-based pairwise sequence alignments extracted from FSSP, SAGA can produce high-quality multiple sequence alignments. The main advantage of COFFEE is its flexibility. With COFFEE, any method suitable for making pairwise alignments can be extended to making multiple alignments. AVAILABILITY: The package is available along with the test cases through the WWW: http://www. ebi.ac.uk/cedric CONTACT: cedric.notredame@ebi.ac.uk
Extending the method of mathematically controlled comparison to
include numerical comparisons
Authors: Alves Rui , Savageau Michael A.
Published: July 2002

Motivation: The method of mathematically controlled comparison has been used for some time to determine which of two alternative regulatory designs is better according to specific quantitative criteria for functional effectiveness. In some cases, the results obtained using this technique are general and independent of parameter values and the answers are clear-cut. In others, the result might be general, but the demonstration is difficult and numerical results with specific parameter values can help to clarify the situation. In either case, numerical results with specific parameter values can also provide an answer to the question of how much larger the values might be. In contrast, a more ambiguous result is obtained when either of the alternatives can have the larger value for a given systemic property, depending on the specific values of the parameters. In any case, introduction of specific values for the parameters reduces the generality of the results. Therefore, we have been motivated to develop and apply statistical methods that would permit the use of numerical values for the parameters and yet retain some of the generality that makes mathematically controlled comparison so attractive.

Results: We illustrate this new numerical method in a step-by-step application using a very simple didactic example. We also validate the results by comparison with the corresponding results obtained using the previously developed analytical method. The analytical approach is briefly present for reference purposes, since some of the same key concepts are needed to understand the numerical method and the results are needed for comparison. The numerical method confirms the qualitative differences between the systemic behavior of alternative designs obtained from the analytical method. In addition, the numerical method allows for quantification of the differences and it provides results that are general in a statistical sense. For example, the older analytical method showed that overall feedback inhibition in an unbranched pathway makes the system more robust whereas it decreases the stability margin of the steady state. The numerical method shows that the magnitudes of these differences are not comparable. The differences in stability margins (1–2% on average) are small when compared to the differences in robustness (50–100% on average). Furthermore, the numerical method shows that the system with overall feedback responds more quickly to change than the otherwise equivalent system without overall feedback. These results suggest reasons why overall feedback inhibition is such a prevalent regulatory pattern in unbranched biosynthetic pathways.

Contact: savageau@umich.edu

To whom correspondence should be addressed.
Point mutation of bacterial artificial chromosomes by ET recombination
Authors: Muyrers Joep P P , Zhang Youming , Benes Vladimir , Testa Giuseppe , Ansorge Wilhelm , Stewart A Francis
Published: July 2002

Bacterial artificial chromosomes (BACs) offer many advantages for functional studies of large eukaryotic genes. To utilize the potential applications of BACs optimally, new approaches that allow rapid and precise engineering of these large molecules are required. Here, we describe a simple and flexible two‐step approach based on ET recombination, which permits point mutations to be introduced into BACs without leaving any other residual change in the recombinant product. Introduction of other modifications, such as small insertions or deletions, is equally feasible. The use of ET recombination to achieve site‐directed mutagenesis opens access to a powerful use of BACs and is extensible to DNA molecules of any size in Escherichia coli, including the E. coli chromosome.
Aggresomes and Russell bodies
Authors: Kopito Ron R , Sitia Roberto
Published: July 2002

All cells are equipped with a proteolytic apparatus that eliminates damaged, misfolded and incorrectly assembled proteins. The principal engine of cytoplasmic proteolysis, the 26S proteasome, requires that substrates be unfolded to gain access to the active site; consequently, it is relatively ineffective at degrading aggregated proteins. Cellular indigestion occurs when the production of aggregation‐prone proteins exceeds the cell's (or organelle's) capacity to eliminate them. Cellular pathways that resolve this indigestion exist, but appear to have limited capacities. Russell bodies and aggresomes are manifestations of cellular indigestion in the endoplasmic reticulum and cytoplasmic compartments, respectively, and are often associated with disease.
Requirement of functional telomeres for metaphase chromosome alignments and integrity of meiotic spindles
Authors: Liu Lin , Blasco Maria A , Keefe David L
Published: July 2002

Telomerase deficiency in the mouse eventually leads to loss of telomeric repeats from chromosome ends and to end‐to‐end chromosome fusions, which result in defects in highly proliferative tissues. We show that telomere dysfunction resulting from telomerase deficiency leads to disruption of functional meiotic spindles and misalignment of chromosomes during meiotic division of oocytes in late‐generation (G4) mice. However, oocytes from first‐generation (G1) mice lacking telomerase showed no appreciable telomere dysfunction and exhibited chromosome alignment at the metaphase plates of meiotic spindles, in a manner similar to that of wild‐type mouse oocytes. These findings suggest that telomerase does not directly influence chromosome alignment and spindle integrity. Rather, functional telomeres may be involved in mediating metaphase chromosome alignment and maintaining functional spindles during meiotic division.
An episomally replicating vector binds to the nuclear matrix protein SAF‐A in vivo
Authors: Jenke Bok Hee C , Fetzer Christian P , Stehle Isa M , Jönsson Franziska , Fackelmayer Frank O , Conradt Harald , Bode Jürgen , Lipps Hans J
Published: July 2002

pEPI‐1, a vector in which a chromosomal scaffold/matrix‐attached region (S/MAR) is linked to the simian virus 40 origin of replication, is propagated episomally in CHO cells in the absence of the virally encoded large T‐antigen and is stably maintained in the absence of selection pressure. It has been suggested that mitotic stability is provided by a specific interaction of this vector with components of the nuclear matrix. We studied the interactions of pEPI‐1 by crosslinking with cis‐diamminedichloroplatinum II, after which it is found to copurify with the nuclear matrix. In a south‐western analysis, the vector shows exclusive binding to hnRNP‐U/SAF‐A, a multifunctional scaffold/matrix specific factor. Immunoprecipitation of the crosslinked DNA–protein complex demonstrates that pEPI‐1 is bound to this protein in vivo. These data provide the first experimental evidence for the binding of an artificial episome to a nuclear matrix protein in vivo and the basis for understanding the mitotic stability of this novel vector class.
The Extensive Side of Nineteenth-Century Military Economy: The Tent Industry in the Northern United States during the Civil War
Authors: Wilson Mark R.
Published: July 2002

Because most histories of military-industrial relations have rested on the examples of arms production and shipbuilding, balanced accounts of military procurement and technologies during the nineteenth century are difficult to find. In fact, weapons and ships accounted for a relatively small fraction of all the goods and services consumed by nineteenth-century armed forces. This article, which describes the tent industry in the United States during the Civil War, suggests that many military enterprises of the period were characterized by an industrial dynamic that was relatively extensive rather than intensive. In the U.S. tent industry, the leading military contractors were mercantile firms, which stood at the center of disintegrated production and distribution networks. Featuring relatively low-capital production arrangements, large numbers of women workers, and powerful mercantile intermediaries who linked manufacturers and army purchasing agents, the Civil War tent business is an example that challenges traditional accounts of the economic foundations of nineteenth-century military capability.
Fluoroquinolone phototoxicity: a comparison of moxifloxacin and lomefloxacin in normal volunteers
Authors: Man I. , Murphy J. , Ferguson J.
Published: July 2002

Moxifloxacin, a broad-spectrum fluoroquinolone with the methoxy group at position 8 of the quinolone structure that is believed to confer reduced phototoxicity, was investigated in 32 healthy human male volunteers by a randomized double-blind placebo and positive control (lomefloxacin) phototest technique. A comparison of pre- and on-drug photosensitivity levels tested with an irradiation monochromator using relevant sunlight wavelengths, failed to demonstrate phototoxicity after administration of either placebo or moxifloxacin (200 mg or 400 mg/day) for 7 days. As expected, lomefloxacin (400 mg/day) phototoxicity was revealed at the UVA wavebands 335 ± 30 nm and 365 ± 30 nm (maximal at 24 h), with a phototoxic index of 3–4. The susceptibility to this effect rapidly normalized within 48 h of stopping the drug. No special protection from UVA wavelengths is necessary for those taking moxifloxacin.
Leptin‐induced lipolysis opposes the tonic inhibition of endogenous adenosine in white adipocytes
Authors: FRÜHBECK GEMA , GÓMEZ‐AMBROSI JAVIER , SALVADOR JAVIER
Published: July 2002

The aim of the present study was to gain insight into the signaling pathway used by leptin to stimulate lipolysis. The lipolytic rate of white adipocytes from sex‐ and age‐matched lean (+/+) and fa/fa rats was determined in the absence or presence of leptin together with a number of agents acting at different levels of the signaling cascade. Leptin did not modify FSK‐, dbcAMP‐, and IBMX‐stimulated lipolysis. Lipolysis can also be maximally stimulated by lowering media adenosine levels with adenosine deaminase (ADA), i.e., in the ligand‐free state. Although ADA produced near maximal lipolysis in adipocytes of lean animals, only half of the maximal lipolytic rate (50.9±3.2%) was achieved in fat cells from fa/fa rats (P=0.0034). In adipocytes from lean animals preincubated with ADA, leptin caused a concentration‐related stimulation of lipolysis (P=0.0001). However, leptin had no effect on the lipolytic activity of adipocytes in the ligand‐free state from fa/fa rats. The adenosine A1 receptor agonist CPA effectively inhibited basal lipolysis in both lean and obese adipocytes (P=0.0001 and P=0.0090, respectively). Leptin had no effect on the lipolytic rate of adipocytes isolated from fa/fa rats and preincubated with CPA. When adipocytes were incubated with the A1 receptor antagonist DPCPX, a significant increase in glycerol release was observed in fa/fa fat cells (P=0.009), whereas cells isolated from lean rats showed no differences to ADA‐stimulated lipolysis. After pretreatment with PTX, which inactivates receptor‐mediated Gi function, adipocytes of obese rats became as responsive to the stimulatory actions of ISO as cells from lean rats (P= 0.0090 vs. ISO in fa/fa rats;P=0.2416 vs. lean rats, respectively). PTX treatment of lean cells, however, did not alter their response to this lipolytic agent. It can be concluded that the lipolytic effect of leptin is located at the adenylate cyclase/Gi proteins level and that leptin‐induced lipolysis opposes the tonic inhibition of endogenous adenosine in white adipocytes.—Frühbeck, G., Gómez‐Ambrosi, J., Salvador, J. Leptin‐induced lipolysis opposes the tonic inhibition of endogenous adenosine in white adipocytes. FASEB J. 15, 333‐340 (2001)
Mate-finding behaviour in Calanus marshallae Frost
Authors: Tsuda Atsushi , Miller Charles B.
Published: July 2002

Mate-finding behaviour byCalanus marshallaeFrost, 1974, was observed and video recorded in a 1 m diameter kreisel. Newly moulted females signal to males by depositing vertical pheromone trails many tens of centimetres long. Males search for trails along primarily horizontal trajectories. The orthogonality of signal trace and search trail trajectory maximizes the chance of intersection. Males often initiate a dance of rapid, tight turns upon encountering a pheromone trail, then waggle down it (chase swimming) to the signalling female. She jumps away after initial contact, and the male follows. Many successive approach, bump and jump sequences follow, with mating eventually ensuing. The actual copulatory clasp and spermatophore transfer were not observed, although a few instances of brief attachment and tandem swimming were seen. Male dances occur at times when chase swimming does not follow, and the function of dances is not yet known.
Place cells, navigational accuracy, and the human hippocampus
Authors: O'Keefe John , Burgess Neil , Donnett James G. , Jeffery Kathryn J. , Maguire Eleanor A.
Published: July 2002

The hippocampal formation in both rats and humans is involved in spatial navigation. In the rat, cells coding for places, directions, and speed of movement have been recorded from the hippocampus proper and/or the neighbouring subicular complex. Place fields of a group of the hippocampal pyramidal cells cover the surface of an environment but do not appear to do so in any systematic fashion. That is, there is no topographical relation between the anatomical location of the cells within the hippocampus and the place fields of these cells in an environment. Recent work shows that place cells are responding to the summation of two or more Gaussian curves, each of which is fixed at a given distance to two or more walls in the environment. The walls themselves are probably identified by their allocentric direction relative to the rat and this information may be provided by the head direction cells. The right human hippocampus retains its role in spatial mapping as demonstrated by its activation during accurate navigation in imagined and virtual reality environments. In addition, it may have taken on wider memory functions, perhaps by the incorporation of a linear time tag which allows for the storage of the times of visits to particular locations. This extended system would serve as the basis for a spatio–temporal event or episodic memory system.
Control of cell elongation and stress responses by steroid hormones and carbon catabolic repression in plants
Authors: Salchert Klaus , Bhalerao Rishikesh , Koncz–Kálmán Zsuzsanna , Koncz Csaba
Published: July 2002

Molecular analysis of
Arabidopsis
mutants displaying hypocotyl elongation defects in both the dark and light revealed recently that steroids play an essential role as hormones in plants. Deficiencies in brassinosteroid biosynthesis and signalling permit photomorphogenic development and light––regulated gene expression in the dark, and result in severe dwarfism, male sterility and de–repression of stress–induced genes in the light. A cytochrome P450 steroid hydroxylase (CYP90) controls a rate limiting step in brassinosteroid biosynthesis and appears to function as a signalling factor in stress responses. Another key step in steroid biosynthesis is controlled by the
Arabidopsis
SNF1 kinases that phosphorylate the 3–hydroxy–3methylglutaryl–CoA reductase. The activity of SNF1 kinases is regulated by PRL1, an evolutionarily conserved α–importin–binding nuclear WD–protein. The
prl1
mutation results in cell elongation defects, de–repression of numerous stress–induced genes, and augments the sensitivity of plants to glucose, cold stress and several hormones, including cytokinin, ethylene, auxin, and abscisic acid.
Consensus Promoter Identification in the Human Genome Utilizing Expressed Gene Markers and Gene Modeling
Authors: Liu Rongxiang , States David J.
Published: July 2002

Deciphering the human genome includes locating the promoters that initiate transcription and identifying the exons of genes. Many promoter prediction programs have been proposed, but when they are applied to extended regions of the genome, most of their predictions are false-positives. The extensive collection of gene transcript sequences is an important new source of information, which has not been used previously in promoter predictions. Our approach is to enhance the specificity of predictions by restricting the genomic regions that are searched using gene transcript alignments as anchors in the genome for gene modeling. We developed a consensus promoter prediction method combining previously developed algorithms with theGENSCAN gene modeling program. Our method,CONPRO (CONsensus PROmoter), identifies promoters with very high confidence, and the predicted promoters are guaranteed to be associated with genes. On our test data set, the method correctly detects promoters for approximately half of all human genes (37%–71%), and most predictions are true promoters (85%–90%). Applying our method to the human genome and human genes from the Unigene data set, we find the promoters for 13,744 genes. Of these, 6440 are genes with a functionally cloned mRNA, and 7304 are novel genes for which only expressed sequence tags (ESTs) are available. Candidate promoters for many novel genes will be a useful resource in elucidating complex biological response mechanisms. CONPRO is available for searching promoters in the human genome (http://stl.bioinformatics.med.umich.edu/conpro).
Image distortion in MRI‐based polymer gel dosimetry of Gamma Knife stereotactic radiosurgery systems
Authors: Watanabe Yoichi , Perera Gerard M. , Mooij Robertus B.
Published: July 2002

We have studied effects of MR (magnetic resonance) image distortion on polymer gel dosimetry of Gamma Knife stereotactic radiosurgery systems. MR images of BANG polymer gel phantoms were acquired by using a Hahn spin‐echo sequence and a fast 3D imaging GRASS sequence. Image artifacts were studied by varying the directions of frequency encoding and the receiver bandwidth. The phantoms were also CT (computed tomography) scanned. The studies showed that the measured dose distributions are shifted by (2 pixels) in the frequency encoding direction. The magnitude of the shift is inversely proportional to the receiver bandwidth in agreement with theory. Comparison of MRI with CT showed the same image shift. We concluded that the discrepancy is caused by MR image distortion due to a difference in susceptibility effects between the phantom and the fiducial markers of the Leksell localization box.
Effective doses to patients undergoing thoracic computed tomography examinations
Authors: Huda Walter , Scalzetti Ernest M , Roskopf Marsha
Published: July 2002

The purpose of this study was to investigate how x‐ray technique factors and effective doses vary with patient size in chest CT examinations. Technique factors (kVp, mAs, section thickness, and number of sections) were recorded for 44 patients who underwent a routine chest CT examination. Patient weights were recorded together with dimensions and mean Hounsfield unit values obtained from representative axial CT images. The total mass of directly irradiated patient was modeled as a cylinder of water to permit the computation of the mean patient dose and total energy imparted for each chest CT examination. Computed values of energy imparted during the chest CT examination were converted into effective doses taking into account the patient weight. Patient weights ranged from 4.5 to 127 kg, and half the patients in this study were children under 18 years of age. All scans were performed at 120 kVp with a 1 s scan time. The selected tube current showed no correlation with patient weight indicating that chest CT examination protocols do not take into account for the size of the patient. Energy imparted increased with increasing patient weight, with values of energy imparted for 10 and 70 kg patients being 85 and 310 mJ, respectively. The effective dose showed an inverse correlation with increasing patient weight, however, with values of effective dose for 10 and 70 kg patients being 9.6 and 5.4 mSv, respectively. Current CT technique factors (kVp/mAs) used to perform chest CT examinations result in relatively high patient doses, which could be reduced by adjusting technique factors based on patient size.
On the partial wave amplitude of Coulomb scattering in three dimensions
Authors: Lin Qiong-gui
Published: July 2002

The partial wave series for the Coulomb scattering amplitude in three dimensions is evaluated in a very simple way to give the closed result.
Time-development operator method in quantum mechanics
Authors: Balasubramanian S.
Published: July 2002

We discuss the time-development operator method in quantum mechanics. The equivalence of this method and the usual method of expansion in terms of energy eigenfunctions discussed in textbooks is pointed out. As examples of cases of time-dependent Hamiltonians, we discuss the time development of a Gaussian wave packet for a charged particle subject to a time-dependent electric field using an operator differential equation. We also consider a spin in a time-dependent magnetic field through a time-development operator.
The hidden symmetry for a quantum system with an infinitely deep square-well potential
Authors: Dong Shi-Hai , Ma Zhong-Qi
Published: July 2002

An infinitely deep square-well potential is studied by an SU(1,1) algebra, not by an SO(2) algebra. The creation and annihilation operators for the system are obtained from the factorization method. Closed analytical expressions for the matrix elements of some relevant functions are evaluated.
Parametric instability of two coupled nonlinear oscillators
Authors: Denardo Bruce , Earwood John , Sazonova Vera
Published: July 2002

One of the two normal modes of a system of two coupled nonlinear oscillators is subject to an instability. Several demonstration apparatus of weakly coupled oscillators that exhibit the instability are described. The effect is due to one normal mode parametrically driving the other, and occurs for the broad range of systems where the nonlinearity has a cubic contribution to the restoring force of each oscillator, which includes pendulums. The instability has an amplitude threshold that increases as the coupling is increased. A naive physical approach predicts that the mode opposite to that observed should be unstable. This is resolved by a weakly nonlinear analysis which reveals that the nonlinearity causes the linear frequency of a normal mode to depend upon the finite amplitude of the other mode. Numerical simulations confirm the theory, and extend the existence of the instability and the accuracy of the theoretical amplitude threshold beyond the regime of weak nonlinearity and weak coupling.
The explicit secular equation for surface acoustic waves in monoclinic elastic crystals
Authors: Destrade Michel
Published: July 2002

The secular equation for surface acoustic waves propagating on a monoclinic elastic half-space is derived in a direct manner, using the method of first integrals. Although the motion is at first assumed to correspond to generalized plane strain, the analysis shows that only two components of the mechanical displacement and of the tractions on planes parallel to the free surface are nonzero. Using the Stroh formalism, a system of two second order differential equations is found for the remaining tractions. The secular equation is then obtained as a quartic for the squared wave speed. This explicit equation is consistent with that found in the orthorhombic case. The speed of subsonic surface waves is then computed for 12 specific monoclinic crystals.
Summary of recent NASA studies of human response to sonic booms
Authors: Leatherwood Jack D. , Sullivan Brenda M. , Shepherd Kevin P. , McCurdy David A. , Brown Sherilyn A.
Published: July 2002

NASA Langley Research Center has conducted three groups of studies on human response to sonic booms: laboratory, “inhome,” and field. The laboratory studies were designed to: (1) quantify loudness and annoyance response to a wide range of shaped sonic boom signatures and (2) assess several noise descriptors as estimators of sonic boom subjective effects. The studies were conducted using a sonic boom simulator capable of generating and playing, with high fidelity, both user-prescribed and recorded boom waveforms to test subjects. Results showed that sonic boom waveform shaping provided substantial reductions in loudness and annoyance and that perceived level was the best estimator of subjective effects. Booms having asymmetrical waveforms were found to be less loud than symmetrical waveforms of equivalent perceived level. Subjective responses to simulated ground-reflected waveforms were fully accounted for by perceived level. The inhome study presented participants with simulated sonic booms played within their normal home environment. The results showed that the equal energy theory of annoyance applied to a variety of multiple sonic boom exposures. The field studies concluded that sonic boom annoyance is greater than that in a conventional aircraft noise environment with the same continuous equivalent noise exposure.
Quasisteady aero-acoustic response of orifices
Authors: Durrieu P. , Hofmans G. , Ajello G. , Boot R. , Aurégan Y. , Hirschberg A. , Peters M. C. A. M.
Published: July 2002

The low frequency response of orifices (slit, circular diaphragm, and perforated plate) in the presence of mean flow is well predicted by a quasisteady theory. A refinement is brought to the theory by considering a Mach number dependent vena contracta coefficient. The measurements of the vena contracta coefficient of a slit agree well with the simple analytical expression existing in the case of the Borda tube orifice. The measured scattering matrix coefficients do not depend strongly on the geometry of the element. If the frequency is increased the moduli remain relatively unaffected while the arguments exhibit a complex behavior which depends on the geometry. From these considerations an anechoic termination efficient at high mass flow is designed.
The effect of exit radii on intraglottal pressure distributions in the convergent glottis
Authors: Scherer Ronald C. , De Witt Kenneth J. , Kucinschi Bogdan R.
Published: July 2002

Phonation depends upon the dynamic distribution of glottal air pressures that act upon the vocal folds, as well as tissue properties of the vocal folds. The glottal wall pressures depend upon the shape, size, and diameter of the glottis for a given flow. This study examined how the radius of curvature of the glottal exit in the converging glottis affects the wall pressures in the glottis. The following exit radii were used: 0.0908 cm, 0.0454 cm, and 0.0050 cm for the 10° case, and 0.0841 cm, 0.021 025 cm, and 0.0050 cm for the 20° case. Minimal glottal diameter and flow were held constant at 0.02 cm and 73.2 cm3/s, respectively. The computational fluid dynamics code FLUENT was used to obtain the pressure profiles. Both the transglottal and intraglottal pressures increased as the exit radius decreased, resulting in an increase in flow resistance and an increase in the outward pressure forces on the vocal folds. The results suggest that the glottal exit curvature should be well specified when building computational or physical models of the vocal folds.
Efficient prediction methods for the micro-pressure wave from a high-speed train entering a tunnel using the Kirchhoff formulation
Authors: Yoon Taeseok , Lee Soogab
Published: July 2002

The compression wave generated by a high-speed train emerging from the exit portal of a tunnel gives rise to an impulsive noise called a micro-pressure wave. In this study, new methods for the prediction of sonic-boom noise are proposed. The first method combines acoustic monopole analysis and the method of characteristics with the Kirchhoff method. The compression wave from a train entering a tunnel is calculated by an approximate compact Green’s function, and the resultant noise at the tunnel exit is predicted by a linear Kirchhoff formulation. The second method couples the Kirchhoff formulation with the Euler equation, which is solved numerically for the generation and propagation of the compression wave. Numerical prediction of the compression wave, the propagation in the tunnel, and the micro-pressure wave obtained by the present methods are compared with measured data. The numerical results exhibit a reasonable agreement with the experimental data. The proposed methods in this study are shown to be very useful design tools for the nose shape of trains and the geometry of tunnels, and they can be utilized to minimize the pressure fluctuation in the tunnel and the corresponding booming noise.
Mapping ear canal movement using area-based surface matching
Authors: Grenness Malcolm J. , Osborn Jon , Weller W. Lee
Published: July 2002

Movement of the external ear canal, associated with jaw motion, relative to the concha region of the pinna has been studied. Pairs of open-jaw and closed-jaw impressions were taken of 14 ears from 10 subjects. Three-dimensional coordinate data were obtained from the concha and the anterior surface of the canal using a reflex microscope. Proprietary area-based matching software was used to evaluate distortion of the two surfaces between the two jaw positions. The canal data from each pair were placed into the same coordinate system with their respective concha regions aligned. Difference maps of the canal data were used to demonstrate the amount of anterior–posterior (A–P), superior–inferior (S–I), and medial–lateral (M–L) movement, relative to the concha, that occurred between the open- and closed-jaw impressions. The concha regions did not undergo significant deformation. The canal regions underwent varying amounts of deformation with all canals conforming within an rms of 136 μm across the entire surface. The majority of canals underwent significant movement relative to the concha. M–L movement ranged from +2.0 to −3.8 mm; eight canals moved laterally, five moved medially, and two showed no movement. S–I movement ranged from +3.7 to −2.7 mm; nine canals moved inferiorly, two moved superiorly, and three showed no movement. A–P movement ranged between +7.5 and −8.5 mm, with five canals moving anteriorly, three posteriorly, and four in a mixed fashion. This study has shown the variability of canal movement relative to the concha and does not support previous reports that suggest that the ear canal only widens with jaw opening.