bluuebunny/crossref_metadata_2025 huggingface dataset:
E3 Ligases in T Cell Anergy—Turning Immune Responses into Tolerance
Authors: Heissmeyer Vigo , Rao Anjana
Published: September 2004

Peripheral tolerance is an important strategy used by the immune system to prevent self-reactive lymphocytes from attacking host tissues. A variety of mechanisms contribute to peripheral tolerance, among them activation-induced cell death, suppression by regulatory T cells, and T cell anergy or unresponsiveness. Recent work has led to a better understanding of the cell-intrinsic program that establishes T cell anergy. A major insight is that during the induction phase of anergy, incomplete stimulation (T cell receptor stimulation without costimulation) leads via calcium influx to an altered gene expression program that includes up-regulation of several E3 ubiquitin ligases. When the anergic T cells contact antigen-presenting cells, intracellular signaling proteins are monoubiquitinated and targeted for lysosomal degradation, thus decreasing intracellular signaling and also resulting in decreased stability of the T cell–antigen-presenting cell contact. We propose a molecular program leading to T cell anergy and discuss other proteins that may play a role.
14-3-3 Proteins: A Number of Functions for a Numbered Protein
Authors: Bridges Dave , Moorhead Greg B. G.
Published: September 2004

Many signal transduction events are orchestrated by specific interactions of proteins mediated through discrete phosphopeptide-binding motifs. Although several phosphospecific-binding domains are now known, 14-3-3s were the first proteins recognized to specifically bind a discrete phosphoserine or phosphothreonine motif. The 14-3-3 proteins are a family of ubiquitously expressed, exclusively eukaryotic proteins with an astonishingly large number of binding partners. Consequently, 14-3-3s modulate an enormous and diverse group of cellular processes. The effects of 14-3-3 proteins on their targets can be broadly defined using three categories: (i) conformational change; (ii) physical occlusion of sequence-specific or structural protein features; and (iii) scaffolding. This review will describe the current state of knowledge on 14-3-3 proteins, highlighting several important advances, and will attempt to provide a framework by which 14-3-3 functions can be understood.
Cellular Domains That Contribute to Ca
2+
Entry Events
Authors: Ambudkar Indu S.
Published: September 2004

Stimulation of cell surface receptors that increase phosphatidylinositol 4,5-bisphosphate (PIP
2
) hydrolysis leads to intracellular Ca
2+
release and activation of plasma membrane Ca
2+
entry channels. Ca
2+
entry via these channels regulates a wide array of physiological functions. The molecular composition of these channels and the mechanisms that activate or inactivate them have not yet been elucidated. Members of the TRPC subfamily of the TRP (transient receptor potential) family of proteins have been recently suggested as molecular components of these channels. In addition, Ca
2+
signaling proteins and the signals they generate are compartmentalized and spatiotemporally regulated. Thus, the mechanisms involved in the assembly and trafficking of Ca
2+
signaling proteins, including TRPC channels, will determine the regulation of Ca
2+
entry and its effect on cellular function.
Store-Operated Channels: Diversity and Activation Mechanisms
Authors: Bolotina Victoria M.
Published: September 2004

This perspective addresses two questions: How many store-operated channels (SOCs) are there, and how many mechanisms can account for SOC activation by depleted stores? Accumulating evidence suggests that the SOC family is not limited to the calcium-selective SOC that is responsible for
I
CRAC
(Ca
2+
-SOC), but includes poorly selective cation SOCs (cat-SOCs) that may satisfy physiological needs in diverse excitable and nonexcitable cells. A growing number of studies in different cell types support the idea that all the members of SOC family (Ca
2+
-SOC and cat-SOC) may be activated by depletion of the stores through the same mechanism, which is mediated by calcium influx factor (CIF) and calcium-independent phospholipase A
2
(iPLA
2
). A conformational coupling model is also discussed. To account for the most recent findings, we propose that two distinct classes of calcium-conducting channels may exist in plasma membrane, which respond to different signals: SOCs, which are activated by depletion of calcium stores through the CIF-iPLA
2
mechanism [no inositol triphosphate (IP
3
) needed]; and IP
3
receptor–operated channels (IP
3
ROCs), which are activated by IP
3
receptor through a direct coupling mechanism (no store depletion is needed). This model, with two separate mechanisms linked to different channels, may resolve many conflicting findings and interpretations and may give a new perspective on the diversity of calcium influx pathways.
Store-Operated Calcium Entry: A Tough Nut to CRAC
Authors: Penner Reinhold , Fleig Andrea
Published: September 2004

Store-operated or capacitative Ca
2+
entry is a prominent feature of many electrically nonexcitable cell types. It is due to Ca
2+
ion permeation pathways in the plasma membrane that are activated after receptor-mediated Ca
2+
release from intracellular stores. Despite hundreds of publications on the topic of store-operated Ca
2+
entry and intense efforts by many dedicated laboratories, neither the molecular nature of the ion permeation pathway nor its activation mechanism is known. Here we review the progress made on the characterization of store-operated currents and the challenges encountered in identifying the molecular components of store-operated Ca
2+
entry.
Receptor-Activated Calcium Entry Channels—Who Does What, and When?
Authors: Shuttleworth Trevor J.
Published: September 2004

The recent
Science
STKE E-Conference on Defining Calcium Entry Signals highlighted many of the outstanding problems and questions regarding the nature and regulation of the receptor-activated entry of Ca
2+
, particularly as it relates to Ca
2+
signaling in nonexcitable cells. Frequently, these stem from the current lack of any clear candidates for the molecular identity of many of the major conductances involved. Moreover, there is considerable confusion in the field, largely as a result of the use of sometimes inappropriate or imprecise methodologies and inconsistent terminology. Nevertheless, much useful information is beginning to be revealed about the biophysical characterization of the fundamental properties of the channels involved and, at least in some cases, the specific conditions under which they are active. As a result, it is becoming clear that cells often contain various Ca
2+
entry channels in addition to the ubiquitous store-operated, or capacitative, channels. These different channels are activated in distinct ways and operate under different conditions of stimulation.
Molecular and Cellular Determinants of Skeletal Muscle Atrophy and Hypertrophy
Authors: Sartorelli Vittorio , Fulco Marcella
Published: September 2004

The maintenance of adult skeletal muscle mass is ensured by physical exercise. Accordingly, physiological and pathological situations characterized by either impaired motor neuron activity, reduced gravity (microgravity during space flights), or reduced physical activity result in loss of muscle mass. Furthermore, a plethora of clinical conditions, including cancer, sepsis, diabetes, and AIDS, are associated with varying degrees of muscle atrophy. The cellular and molecular pathways responsible for maintaining the skeletal muscle mass are not well defined. Nonetheless, studies aimed at the understanding of the mechanisms underlying either muscular atrophy or hypertrophy have begun to identify the physiological determinants and clarify the molecular pathways responsible for the maintenance of muscle mass.
Ubiquitylation and Isgylation: Overlapping Enzymatic Cascades Do the Job
Authors: Staub Olivier
Published: September 2004

Ubiquitylation—that is, the covalent attachment of ubiquitin polypeptides to target proteins—involves the sequential action of the E1 ubiquitin-activating enzyme, E2 ubiquitin-conjugating enzymes, and E3 ubiquitin-protein ligases. Similarly, the conjugation of ubiquitin-like proteins is thought to occur through parallel, but nonidentical, cascades. This concept of strict separation of these modification pathways is now being challenged by the evidence, showing that there are enzymes that play a role both in ubiquitylation and isgylation.
Quantitative Information Management for the Biochemical Computation of Cellular Networks
Authors: Campagne Fabien , Neves Susana , Chang Chiung-wen , Skrabanek Lucy , Ram Prahlad T. , Iyengar Ravi , Weinstein Harel
Published: September 2004

Understanding complex protein networks within cells requires the ability to develop quantitative models and to numerically compute the properties and behavior of the networks. To carry out such computational analysis, it is necessary to use modeling tools and information management systems (IMSs) where the quantitative data, associated to its biological context, can be stored, curated, and reliably retrieved. We have focused on the biochemical computation of cellular interactions and developed an IMS that stores both quantitative information on the cellular components and their interactions, and the basic reactions governing those interactions. This information can be used to construct pathways and eventually large-scale networks. This system, SigPath, is available on the Internet (
http://www.sigpath.org
). Key features of the approach include (i) the use of background information (for example, names of molecules, aliases, and accession codes) to ease data submission and link this quantitative database with other qualitative databases, (ii) a strategy to allow refinement of information over time by multiple users, (iii) the development of a data representation that stores both qualitative and quantitative information, and (iv) features to assist contributors and users in assembling custom quantitative models from the information stored in the IMS. Currently, models assembled in SigPath can be automatically exported to several computing environments, such as Kinetikit/Genesis, Virtual Cell, Jarnac/JDesigner, and JSim. We anticipate that, when appropriately populated, such a system will be useful for large-scale quantitative studies of cell-signaling networks and other cellular networks. SigPath is distributed under the GNU General Public License.
Signal Transduction and Mechanical Stress
Authors: Hughes-Fulford Millie
Published: September 2004

Bone undergoes a constant process of remodeling in which mass is retained or lost in response to the relative activity of osteoblasts and osteoclasts. Weight-bearing exercise—which is critical for retaining skeletal integrity—promotes osteoblast function, whereas a lack of mechanical stimulation, as seen during spaceflight or prolonged bed rest, can lead to osteoporosis. Thus, understanding mechanotransduction at the cellular level is key to understanding basic bone biology and devising new treatments for osteoporosis. Various mechanical stimuli have been studied as in vitro model systems and have been shown to act through numerous signaling pathways to promote osteoblast activity. Here, we examine the various types of stress and the sequential response of transduction pathways that result in changes in gene expression and the ensuing proliferation of osteoblasts.
On the Fight Between Excitation and Inhibition: Location Is Everything
Authors: Mel Bartlett W. , Schiller Jackie
Published: September 2004

In the intact brain, neurons are constantly subjected to both excitatory and inhibitory inputs to their dendritic trees. Although it is accepted that the overall response of a neuron--its train of output spikes--depends on the balance of excitation and inhibition, we continue to lack specific knowledge of the rules that govern how excitatory and inhibitory inputs interact in space and time within the confines of individual neurons. In a recent paper, Liu starts by providing evidence that the relative locations and numbers of excitatory and inhibitory synapses are tightly regulated in cultured neurons from the hippocampus. This is consistent with findings in other labs that suggest neurons work hard, and in a variety of different ways, to maintain their inputs in proper balance and their outputs within appropriate ranges. On this backdrop, Liu's most important finding of a functional nature is that inhibition appears to act quite locally; that is, an inhibitory synapse effectively opposes an excitatory synapse only when it is very close by within the same dendritic branch (Fig. 1). This finding provides further support for the view--anticipated by neural theorists more than 20 years ago--that the brain's principal neurons contain a potentially large number of separate computational subunits.
A Series of Diaryltriazines and Diarylpyrimidines Are Highly Potent Nonnucleoside Reverse Transcriptase Inhibitors with Possible Applications as Microbicides
Authors: Van Herrewege Yven , Vanham Guido , Michiels Jo , Fransen Katrien , Kestens Luc , Andries Koen , Janssen Paul , Lewi Paul
Published: September 2004

An in vitro model of monocyte-derived dendritic cells (MO-DC) and CD4
+
T cells, representing the primary targets of sexual human immunodeficiency virus (HIV) transmission, was used to evaluate the antiviral and immune suppressive activity of new classes of nonnucleoside reverse transcriptase inhibitors, diaryltriazines (DATAs) and diarylpyrimidines (DAPYs), compared to the reference compounds UC-781 and PMPA. Antiviral activity (as reflected by the 50% effective concentration [EC
50
]) was determined by treating HIV-infected MO-DC/CD4
+
-T-cell cocultures with a dose range of a compound during 14 days, followed by analysis of supernatants in HIV p24 antigen enzyme-linked immunosorbent assay. A limited, 24-h treatment evaluated the compounds as microbicides. Viral rescue was evaluated in a PCR by monitoring proviral DNA in secondary cultures with phytohemagglutinin-interleukin-2 blasts. We determined 50% immunosuppressive concentrations in mixed leukocyte cultures of MO-DC and allogeneic T cells, with compound either continuously present or present only during the first 24 h. The EC
50
values of DATA and DAPY compounds ranged from 0.05 to 3 nM compared to 50 nM for UC-781 and 89 nM for PMPA. When evaluated in the “microbicide” setting, the most potent compounds completely blocked HIV infection at 10 to 100 nM. The immunosuppressive concentrations were well above the EC
50
, resulting in favorable therapeutic indices for all compounds tested. The DATA and DAPY compounds described here are more potent than earlier reverse transcriptase inhibitors and show favorable pharmacological profiles in vitro. They could strengthen the antiretroviral armamentarium and might be useful as microbicides.
Posaconazole Is a Potent Inhibitor of Sterol 14α-Demethylation in Yeasts and Molds
Authors: Munayyer Hanan K. , Mann Paul A. , Chau Andrew S. , Yarosh-Tomaine Taisa , Greene Jonathan R. , Hare Roberta S. , Heimark Larry , Palermo Robert E. , Loebenberg David , McNicholas Paul M.
Published: September 2004

Posaconazole (POS; SCH 56592) is a novel triazole that is active against a wide variety of fungi, including fluconazole-resistant
Candida albicans
isolates and fungi that are inherently less susceptible to approved azoles, such as
Candida glabrata
. In this study, we compared the effects of POS, itraconazole (ITZ), fluconazole (FLZ), and voriconazole (VOR) on sterol biosynthesis in strains of
C. albicans
(both azole-sensitive and azole-resistant strains),
C. glabrata
,
Aspergillus fumigatus
, and
Aspergillus flavus
. Following exposure to azoles, nonsaponifiable sterols were extracted and resolved by liquid chromatography and sterol identity was confirmed by mass spectroscopy. Ergosterol was the major sterol in all but one of the strains;
C. glabrata
strain C110 synthesized an unusual sterol in place of ergosterol. Exposure to POS led to a decrease in the total sterol content of all the strains tested. The decrease was accompanied by the accumulation of 14α-methylated sterols, supporting the contention that POS inhibits the cytochrome P450 14α-demethylase enzyme. The degree of sterol inhibition was dependent on both dose and the susceptibility of the strain tested. POS retained activity against
C. albicans
isolates with mutated forms of the 14α-demethylase that rendered these strains resistant to FLZ, ITZ, and VOR. In addition, POS was a more potent inhibitor of sterol synthesis in
A. fumigatus
and
A. flavus
than either ITZ or VOR.
Emergence and Spread of Three Clonally Related Virulent Isolates of CTX-M-15-Producing
Escherichia coli
with Variable Resistance to Aminoglycosides and Tetracycline in a French Geriatric Hospital
Authors: Leflon-Guibout Véronique , Jurand Cécile , Bonacorsi Stéphane , Espinasse Florence , Guelfi Marie Claude , Duportail Françoise , Heym Beate , Bingen Edouard , Nicolas-Chanoine Marie-Hélène
Published: September 2004

Three types of multidrug-resistant
Escherichia coli
isolates, called GEN S, GEN R, and AMG S, according to their three different aminoglycoside resistance patterns, were responsible for urinary tract colonization or infection in 87, 12, and 13 new patients, respectively, in a French 650-bed geriatric hospital over a 13-month period. The three
E. coli
types belonged to the same clone and phylogenetic group (group B2) and had identical transferable plasmid contents (a 120-kb plasmid), β-lactam and fluoroquinolone resistance genotypes (
bla
TEM-1B
,
bla
CTX-M-15
, and double mutations in both the
gyrA
and the
parC
genes), and virulence factor genotypes (
aer
,
fyuA
, and
irp2
). They disseminated in the geriatric hospital, where the antibiotics prescribed most often were fluoroquinolones and ceftriaxone, but not in the affiliated acute-care hospital, where isolation precautions were applied to the transferred patients. Thus,
E. coli
isolates, both CTX-M-type β-lactamase producers and fluoroquinolone-resistant isolates, might present a new challenge for French health care settings.
Inhibition of Human Cytomegalovirus Replication by Benzimidazole Nucleosides Involves Three Distinct Mechanisms
Authors: Evers David L. , Komazin Gloria , Ptak Roger G. , Shin Dongjin , Emmer Brian T. , Townsend Leroy B. , Drach John C.
Published: September 2004

The benzimidazole nucleosides 2-bromo-5,6-dichloro-1-(β-
d
-ribofuranosyl)benzimidazole (BDCRB) and 2-isopropylamino-5,6-dichloro-1-(β-
l
-ribofuranosyl)benzimidazole (1263W94, or maribavir) are potent and selective inhibitors of human cytomegalovirus (HCMV) replication. These inhibitors act by two different mechanisms: BDCRB blocks the processing and maturation of viral DNA, whereas maribavir prevents viral DNA synthesis and capsid nuclear egress. In order to determine by which of these two mechanisms other benzimidazole nucleosides acted, we performed time-of-addition studies and other experiments with selected new analogs. We found that the erythrofuranosyl analog and the α-lyxofuranosyl analog acted late in the viral replication cycle, similar to BDCRB. In marked contrast, the α-5′-deoxylyxofuranosyl analog of 2,5,6-trichloro-1-(β-
d
-ribofuranosyl)benzimidazole (compound UMJD1311) acted early in the replication cycle, too early to be consistent with either mechanism. Similar to other reports on early acting inhibitors of herpesviruses, compound 1311 was multiplicity of infection dependent, an observation that could not be reproduced with UV-inactivated virus. HCMV isolates resistant to BDCRB and maribavir were sensitive to compound 1311, as were viruses resistant to ganciclovir, cidofovir, and foscarnet. The preincubation of host cells with compound 1311 and removal prior to the addition of HCMV did not produce an antiviral cellular response. We conclude that this newly discovered early mode of action occurs at a stage of viral replication after entry to cells but prior to viral DNA synthesis, thereby strongly suggesting that the trisubstituted benzimidazole nucleoside series possesses three distinct biochemical modes of action for inhibition of HCMV replication.
Combination Therapy Counteracts the Enhanced Transmission of Drug-Resistant Malaria Parasites to Mosquitoes
Authors: Hallett Rachel L. , Sutherland Colin J. , Alexander Neal , Ord Rosalynn , Jawara Musa , Drakeley Chris J. , Pinder Margaret , Walraven Gijs , Targett Geoffrey A. T. , Alloueche Ali
Published: September 2004

Malaria parasites carrying genes conferring resistance to antimalarials are thought to have a selective advantage which leads to higher rates of transmissibility from the drug-treated host. This is a likely mechanism for the increasing prevalence of parasites with resistance to chloroquine (CQ) and sulfadoxine-pyrimethamine in sub-Saharan Africa. Combination therapy is the key strategy being implemented to reduce the impact of resistance, but its effect on the transmission of genetically resistant parasites from treated patients to mosquito vectors has not been measured directly. In a trial comparing CQ monotherapy to the combination CQ plus artesunate (AS) in Gambian children with uncomplicated falciparum malaria, we measured transmissibility by feeding
Anopheles gambiae
mosquitoes with blood from 43 gametocyte-positive patients through a membrane. In the CQ-treated group, gametocytes from patients carrying parasites with the CQ resistance-associated allele
pfcrt
-76T prior to treatment produced infected mosquitoes with 38 times higher
Plasmodium falciparum
oocyst burdens than mosquitoes fed on gametocytes from patients infected with sensitive parasites (
P
< 0.001). Gametocytes from parasites carrying the resistance-associated allele
pfmdr1
-86Y produced 14-fold higher oocyst burdens than gametocytes from patients infected with sensitive parasites (
P
= 0.011). However, parasites carrying either of these resistance-associated alleles pretreatment were not associated with higher mosquito oocyst burdens in the CQ-AS-treated group. Thus, combination therapy overcomes the transmission advantage enjoyed by drug-resistant parasites.
Antibody Mapping of the Linear Epitopes of CMY-2 and SHV-1 β-Lactamases
Authors: Hujer Andrea M. , Bethel Christopher R. , Bonomo Robert A.
Published: September 2004

Knowledge of the amino acids that define recognition of anti-β-lactamase antibodies is critical to the interpretation of sensitivity and specificity of these antibodies when they are used in a clinical or research setting. To this end, we mapped the epitopes of the CMY-2 and SHV-1 β-lactamases by using the SPOT synthesis method. Eight linear epitopes in SHV-1 and seven linear epitopes in CMY-2 were identified by using anti-SHV-1 and anti-CMY-2 polyclonal antibodies, respectively. The epitopes of SHV-1 were mapped to amino acids at the Ambler positions ABL 28 to 38, 42 to 54, 88 to 100, 102 to 114, 170 to 182, 186 to 194, 202 to 210, and 276 to 288. In the epitope spanning amino acids 102 to 114, alanine and X-Scan analysis demonstrated that D104, Y105, P107, and S109 are essential residues for antibody recognition. In the epitope containing amino acids 170 to 182, N170, L173, P174, G175, and D176 were immunodominant. In CMY-2 β-lactamase, amino acids 4 to 16, 70 to 79, 211 to 223, 274 to 286, 289 to 298, 322 to 334, and 343 to 358 of the mature enzyme defined the major linear epitopes. A detailed analysis of the recognition sites that are located in an area analogous to the omega loop of class A β-lactamases (V211 to V223) showed that the amino acids Q215 to E219 are important in antibody binding. Incubation of CMY-2 β-lactamase with a 10-fold molar excess of anti-CMY-2 antibody for 60 min resulted in greater than 80% inhibition of nitrocefin hydrolysis. A 10-fold molar excess of anti-SHV-1 antibody reduced the activity of SHV-1 by 69%. Analysis of the CMY-2 and SHV-1 structures suggest that this reduction of hydrolytic activity may be due in part to the direct binding of antibodies to the omega loop, thereby hindering access of substrate to the active site.
Dual-Action Mechanism of Viramidine Functioning as a Prodrug and as a Catabolic Inhibitor for Ribavirin
Authors: Wu Jim Zhen , Larson Gary , Hong Zhi
Published: September 2004

An investigational nucleoside analogue drug, viramidine, has recently emerged as a potentially safer alternative to ribavirin for the treatment of hepatitis C viral infection. We have reported that viramidine mainly functions as a prodrug of ribavirin that is enriched in the liver. This in vitro study further explores viramidine's activity against nucleoside phosphorylase, a host enzyme that is responsible for phosphorolysis of ribavirin in vivo. Our experiments show that viramidine inhibits ribavirin phosphorolysis with a

K
i

of 2.5 μM. This result suggests that viramidine may act through a dual-action mechanism by serving as a prodrug of ribavirin and concomitantly as an inhibitor for nucleoside phosphorylase catabolism of ribavirin.
Abdominal coarctation in a hypertensive female collegiate basketball player: Figure 1
Authors: Sloan B , Simons S , Stromwall A
Published: September 2004

The purpose of the preparticipation examination is to identify health conditions that might adversely affect an athlete while participating in sport. Hypertension is the most common. This case report details a female basketball player found to be hypertensive, and complaining of fatigue, at her preparticipation physical examination. Presentation, diagnostics, treatment, and final outcome of coarctation involving the abdominal aorta are summarised.
On issues of confidence in determining the time constant for oxygen uptake kinetics
Authors: Markovitz G H , Sayre J W , Storer T W , Cooper C B
Published: September 2004

Background:τV˙o2at the onset of constant work rate (CWR) exercise is a variable of aerobic fitness that shortens with physical training and lengthens with cardiopulmonary disease. Determination of τV˙o2with sufficiently high confidence has typically required multiple exercise transitions limiting its clinical application.

Objectives:To design a protocol to determine τV˙o2reliably but simply.

Methods:On each of three days, five healthy men performed two CWR tests on a cycle ergometer below the metabolic threshold (V˙o2θ) for blood lactate accumulation as determined by gas exchange measurements followed by an incremental work rate (IWR) test. τV˙o2was determined (a) from the on-transit (on-τV˙o2) and off-transit (off-τV˙o2) of six CWR tests both individually and superimposed, using non-linear regression with a monoexponential model, and (b) by geometric analysis of the IWR tests (ramp-τV˙o2).

Results:Group means (SD) were: V˙o2max3.84 (0.44) litres/min, V˙o2θ 1.88 (0.23) litres/min, steady state exercise V˙o21.67 (0.07) litres/min, on-τV˙o238.0 (5.3) seconds, off-τV˙o239.0 (4.3) seconds, and ramp-τV˙o260.8 (15.4) seconds. On-τV˙o2correlated with off-τV˙o2(r =  0.87), V˙o2max(r =  −0.73), and V˙o2θ (r =  0.89). The pooled mean τV˙o2from six superimposed tests agreed with the arithmetic grand mean of the six tests.

Conclusions:The average of on-τV˙o2and off-τV˙o2fell within the 95% confidence interval of the pooled mean by the second test. Ramp-τV˙o2was longer and less reproducible. These findings support the use of both on- and off-transit data for the determination of τV˙o2, an approach that reduces the number of transitions necessary for accurate determination of τV˙o2, potentially enhancing its clinical application.
Relation between physical exertion and heart rate variability characteristics in professional cyclists during the Tour of Spain
Authors: Earnest C P , Jurca R , Church T S , Chicharro J L , Hoyos J , Lucia A
Published: September 2004

Background:Continued exposure to prolonged periods of intense exercise may unfavourably alter neuroendocrine, neuromuscular, and cardiovascular function.

Objective:To examine the relation between quantifiable levels of exertion (TRIMPS) and resting heart rate (HR) and resting supine heart rate variability (HRV) in professional cyclists during a three week stage race.

Method:Eight professional male cyclists (mean (SEM) age 27 (1) years, body mass 65.5 (2.3) kg, and maximum rate of oxygen consumption (V˙o2max) 75.6 (2.2) ml/kg/min) riding in the 2001 Vuelta a España were examined for resting HR and HRV on the mornings of day 0 (baseline), day 10 (first rest day), and day 17 (second rest day). The rest days followed stages 1–9 and 10–15 respectively. HR was recorded during each race stage, and total HR time was categorised into a modified, three phase TRIMPS schema. These phases were based on standardised physiological laboratory values obtained during previous V˙o2maxtesting, where HR time in each phase (phase I  =  light intensity and less than ventilatory threshold (VT; ∼70% V˙o2max); phase II  =  moderate intensity between VT and respiratory compensation point (RCP; ∼90% V˙o2max); phase III  =  high intensity (>RCP)) was multiplied by exertional factors of 1, 2, and 3 respectively.

Results:Multivariate analysis of variance showed that total TRIMPS for race stages 1–9 (2466 (90)) were greater than for stages 10–15 (2055 (65)) (p<0.0002). However, TRIMPS/day were less for stages 1–9 (274 (10)) than for stages 10–15 (343 (11)) (p<0.01). Despite a trend to decline, no difference in supine resting HR was found between day 0 (53.2 (1.8) beats/min), day 10 (49.0 (2.8) beats/min), and day 17 (48.0 (2.6) beats/min) (p  =  0.21). Whereas no significant group mean changes in HR or HRV indices were noted during the course of the race, significant inverse Pearson product-moment correlations were observed between all HRV indices relative to total TRIMPS and TRIMPS/day accumulated in race stages 10–15. Total TRIMPS correlated with square root of mean squared differences of successive RR intervals (r =  −0.93; p<0.001), standard deviation of the RR intervals (r =  −0.94; p<0.001), log normalised total power (r =  −0.97; p<0.001), log normalised low frequency power (r =  −0.79; p<0.02), and log normalised high frequency power (r =  −0.94; p<0.001).

Conclusion:HRV may be strongly affected by chronic exposure to heavy exertion. Training volume and intensity are necessary to delineate the degree of these alterations.
Relation between running injury and static lower limb alignment in recreational runners
Authors: Lun V , Meeuwisse W H , Stergiou P , Stefanyshyn D
Published: September 2004

Objectives:To determine if measurements of static lower limb alignment are related to lower limb injury in recreational runners.

Methods:Static lower limb alignment was prospectively measured in 87 recreational runners. They were observed for the following six months for any running related musculoskeletal injuries of the lower limb. Injuries were defined according to six types: R1, R2, and R3 injuries caused a reduction in running mileage for one day, two to seven days, or more than seven days respectively; S1, S2, and S3 injuries caused stoppage of running for one day, two to seven days, or more than seven days respectively.

Results:At least one lower limb injury was suffered by 79% of the runners during the observation period. When the data for all runners were pooled, 95% confidence intervals calculated for the differences in the measurements of lower limb alignment between the injured and non-injured runners suggested that there were no differences. However, when only runners diagnosed with patellofemoral pain syndrome (n = 6) were compared with non-injured runners, differences were found in right ankle dorsiflexion (0.3 to 6.1), right knee genu varum (−0.9 to −0.3), and left forefoot varus (−0.5 to −0.4).

Conclusions:In recreational runners, there is no evidence that static biomechanical alignment measurements of the lower limbs are related to lower limb injury except patellofemoral pain syndrome. However, the effect of static lower limb alignment may be injury specific.
Orbital emphysema following nose blowing as a sequel of a snowboard related head injury
Authors: Taguchi Y , Sakakibara Y , Uchida K , Kishi H
Published: September 2004

A case of orbital emphysema as a sequel of a snowboard related head injury is reported. It is believed that a fracture of the medial orbital wall was caused by the increased intraorbital pressure when the patient hit his forehead on the snowy ground, allowing air to enter the orbit when he blew his nose. Wearing goggles may prevent this type of sports related injury.
Is lactic acidosis a cause of exercise induced hyperventilation at the respiratory compensation point?: Figure 1
Authors: Meyer T , Faude O , Scharhag J , Urhausen A , Kindermann W
Published: September 2004

Objectives:The respiratory compensation point (RCP) marks the onset of hyperventilation (“respiratory compensation”) during incremental exercise. Its physiological meaning has not yet been definitely determined, but the most common explanation is a failure of the body’s buffering mechanisms which leads to metabolic (lactic) acidosis. It was intended to test this experimentally.

Methods:During a first ramp-like exercise test on a cycle ergometer, RCP (range: 2.51–3.73 l*min–1oxygen uptake) was determined from gas exchange measurements in five healthy subjects (age 26–42; body mass index (BMI) 20.7–23.9 kg*m–2; Vo2peak51.3–62.1 ml*min–1*kg–1). On the basis of simultaneous determinations of blood pH and base excess, the necessary amount of bicarbonate to completely buffer the metabolic acidosis was calculated. This quantity was administered intravenously in small doses during a second, otherwise identical, exercise test.

Results:In each subject sufficient compensation for the acidosis, that is, a pH value constantly above 7.37, was attained during the second test. A delay but no disappearance of the hyperventilation was present in all participants when compared with the first test. RCP occurred on average at a significantly (p = 0.043) higher oxygen uptake (+0.15 l*min–1) compared with the first test.

Conclusions:For the first time it was directly demonstrated that exercise induced lactic acidosis is causally involved in the hyperventilation which starts at RCP. However, it does not represent the only additional stimulus of ventilation during intense exercise. Muscle afferents and other sensory inputs from exercising muscles are alternative triggering mechanisms.
Fracture shaft of clavicle, an indirect injury from bench pressing
Authors: Gill I P S , Mbubaegbu Chima
Published: September 2004

Injuries related to weight training are becoming increasingly common as the trend for body resistance training grows. There have been numerous injuries related to repeated stress, but this appears to be the first reported case of a fracture of the shaft of clavicle related to violent muscular contraction. It occurred in a 28 year old man during bench pressing. He was treated conservatively and the fracture united in six weeks. Resistant trainers should be made aware of the risks of heavy weight training and need proper supervision.
β3-Adrenoceptors: relaxant function and mRNA detection in smooth muscle cells isolated from the human colon
Authors: Severi Carola , Tattoli Ivan , Romano Giovanna , Corleto Vito D , Fave Gianfranco Delle
Published: September 2004

Functional involvement of β3-adrenoceptors in controlling human gastrointestinal motility has not been unequivocally assessed yet. The direct myogenic contribution of these receptors was examined, by in vitro functional studies and analysis of mRNA expression, on smooth muscle cells separately isolated from taenia coli and circular muscle layers of the human colon. Isoproterenol, a nonselective β-adrenoceptor agonist, relaxed, in a concentration-dependent manner, both human taenia coli and circular colonic smooth muscle cells, although displaying a higher intrinsic activity (65.3 ± 2.3 vs. 55.2 ± 1.4% maximal relaxation) and potency (pEC50: 7.41 ± 0.07 vs. 6.32 ± 0.08) were greater on taenia coli than circular cells. In the presence of the β1-antagonist CGP20712A and of the β2-antagonist ICI 118,551, a 25–30% decrease in isoproterenol intrinsic activity was observed on both cell types and on taenia coli, the nonselective β1/β2-antagonist propranolol produced a rightward shift of the isoproterenol concentration-response curve with mean estimated pKB values (8.12 ± 0.27 at 0.1 µM and 6.45 ± 0.13 at 1 µM) lower than that expected for both β1- and β2-adrenoceptors. CGP12177A and SR 58611A, two β3-adrenoceptor agonists, presented an intrinsic activity comparable to that of isoproterenol in the presence of β1- and β2-antagonists, the former being more potent on taenia coli than on circular smooth muscle cells. β3-Adrenoceptor mRNA was detected by reverse transcription PCR on both cell types. These results strongly suggest a direct functional role of β3-adrenoceptors in the human colon.Key words: adrenoceptors, β3-adrenoceptors, smooth muscle cells, taenia coli, human colon.
POLYNOMIALS ASSOCIATED WITH THE HYPERGEOMETRIC FUNCTIONS WITH FINITE MONODROMY GROUPS
Authors: OCHIAI HIROYUKI , YOSHIDA MASAAKI
Published: September 2004

The hypergeometric equations with polyhedral monodromy groups derive 3-integral-parameter families of polynomials.
SMOOTH THREEFOLDS WITH G2,3-DEFECT
Authors: COPPENS MARC
Published: September 2004

Let X be an n-dimensional non-degenerated subvariety of ℙN with N≥2n+1. We give a rough classification for varieties X having Gn-1,n-defect. In case n=3, we give a fine classification for smooth varieties X having G2,3-defect.
OPENING THE FINANCIAL SECTOR TO FOREIGN COMPETITION: ASSESSING THE DYNAMIC MACROECONOMIC CONSEQUENCES USING A TWO-SECTOR GROWTH MODEL
Authors: CHOU YUAN K. , CHIN MARTIN S.
Published: September 2004

This paper uses an economic growth model with a financial sector to examine the conditions under which financial liberalization is desirable from the perspective of a policymaker who cares about the well-being of domestic households. Financial liberalization raises the rate of financial innovation and the efficiency of financial intermediation, but typically causes large foreign firms from leading-edge countries to displace smaller and less efficient domestic firms. Profits are repatriated abroad instead of accruing to domestic households as dividends. This trade-off is further complicated when we allow financial firms to hire talented foreigners once liberalization has taken place. Simulations of the model indicate that the case for financial liberalization is stronger when agents are more impatient, spillover effects of current financial innovation on future innovation are larger, financial innovations are more susceptible to congestion in their use, and when knowledge diffuses more quickly from foreign to domestic workers.
EXPANSIONARY FISCAL CONTRACTION: GOVERNMENT SPENDING FINANCED BY LUMP-SUM TAXES
Authors: TAN KIM-HENG
Published: September 2004

Barry and Devereux (2003) have identified two conditions for permanent fiscal contractions to be expansionary. The first condition is that households do not face an effective infinite horizon. The second is that the wealth effect of reduced tax liabilities on labor supply must be small if labor supply is endogenous. However, Barry and Devereux have not allowed for the possibility that government spending may affect the intertemporal allocation of private consumption. By allowing for the possibility, this paper identifies a third condition for permanent fiscal contractions to be expansionary, namely that public and private consumption must not be too highly substitutable.
GLOBALIZATION, SOCIAL WELFARE, PUBLIC POLICY AND LABOR INEQUALITIES
Authors: TISDELL CLEM , SVIZZERO SERGE
Published: September 2004

Income inequality has increased sharply in higher income and in many lower income countries. Theories attributing this to bifurcation of labor markets in higher income countries are examined. Some theorists attribute this bifurcation primarily to technical change with influence from globalization. Others take an opposite viewpoint. A contrasting view presented here is that globalization is strongly linked with technological change. More significantly even if globalization increases economic efficiency and growth in globalizing countries, it can raise income inequality and reduce social welfare in such countries. International fiscal competitiveness may, it is argued, contribute to income inequality and make all nations worse off. Trends in public social expenditure and in taxation receipts in higher income countries, including Singapore, are examined to determine the extent of empirical support for the theory.
THE PRODUCTIVE EFFICIENCY OF SINGAPORE BANKS: AN APPLICATION AND EXTENSION OF THE BARR ET AL. (1999) APPROACH
Authors: LEONG WAI HO , DOLLERY BRIAN
Published: September 2004

While a voluminous literature exists on the measurement of financial institution efficiency, little work has been directed at investigating the properties of data envelopment analysis (DEA) scores by examining the relationships between these scores and traditional measures of bank performance. Following the seminal work of Barr, Killgo, Siems and Zimmel (1999), this paper employs data on Singapore financial institutions for the period 1993 to 1999 to develop efficiency scores for Singapore banks. It then examines the manner in which derived DEA efficiency scores interact with traditional measures of profitability, size, risk and soundness.
DECAY PROBABILITY RATIO OF PENTAQUARK Θ+ STATE
Authors: CHEN XUN , MAO YAJUN , MA BO-QIANG
Published: September 2004

The pentaquark state of [Formula: see text] has been observed to decay with two decay modes: Θ+→nK+ and Θ+→pK0. The decay probability ratio of the two decay modes is studied with general symmetry consideration of isospin, spin and parity. We arrive at a result of the ratio [Formula: see text], which is valid for the Θ+ state to be a pure isoscalar or isovector state, or an isoscalar and isovector mixing state, or an isotensor state with mixture of isoscalar and isovector components with coefficients α and β. The dependence on spin and parity of the pentaquark Θ+ state is found to be small due to small difference between the center-of-mass decay momenta k1 and k2 of the two decay modes. We also provide an analysis on the constraint of the isospin of Θ+ from the absence of a peak in the pK+ invariant mass distribution in the γp→pK+K- process. Future experimental results about the decay probability ratio may provide information about the properties of the pentaquark Θ+ state.
CHARGING INTERACTING ROTATING BLACK HOLES IN HETEROTIC STRING THEORY
Authors: HERRERA-AGUILAR ALFREDO
Published: September 2004

We present a formulation of the stationary bosonic string sector of the whole toroidally compactified effective field theory of the heterotic string as a double Ernst system which, in the framework of general relativity describes, in particular, a pair of interacting spinning black holes; however, in the framework of low-energy string theory the double Ernst system can in particular be interpreted as the rotating field configuration of two interacting sources of black hole type coupled to dilaton and Kalb–Ramond fields. We clarify the rotating character of the Btφ-component of the antisymmetric tensor field of Kalb–Ramond and discuss on its possible torsion nature. We also recall the fact that the double Ernst system possesses a discrete symmetry which is used to relate physically different string vacua. Therefore we apply the normalized Harrison transformation (a charging symmetry which acts on the target space of the low-energy heterotic string theory preserving the asymptotics of the transformed fields and endowing them with multiple electromagnetic charges) on a generic solution of the double Ernst system and compute the generated field configurations for the 4-D effective field theory of the heterotic string. This transformation generates the U (1)n vector field content of the whole low-energy heterotic string spectrum and gives rise to a pair of interacting rotating black holes endowed with dilaton, Kalb–Ramond and multiple electromagnetic fields where the charge vectors are orthogonal to each other.
NEUTRINO MASSES AND R-PARITY VIOLATION
Authors: RAKSHIT SUBHENDU
Published: September 2004

We review different contributions to the neutrino masses in the context of R-parity violating supersymmetry in a basis independent manner. We comment on the generic spectrum expected in such a scenario comparing different contributions.
CP VIOLATION AND ΔI=1/2 ENHANCEMENT FOR K→ππ, K→ππγ WEAK DECAYS
Authors: SCADRON MICHAEL D. , RUPP GEORGE , VAN BEVEREN EEF
Published: September 2004

Data indicate that ΔI=3/2 transitions account for 4.5–4.7% of both CP conserving and CP violating K→2π decays, as well as CP conserving radiative K→ππγ processes. Observed K→ππγ/ππ branching ratios are shown to scale near α/π or α/2π. The KL–KSmixing angle ϕ and the semileptonic weak-rate asymmetry δ are reviewed, and theory is shown to be consistent with data. Also, K→2π ΔI=1/2 dominance is studied in the context of the chiral constituent quark model, displaying again excellent agreement with data. Finally, indirect and direct kaon CP violation (CPV) are successfully described in the framework of photon-mediated quark-loop graphs. This suggests that kaon CPV can be understood via second-order weak transitions, radiatively corrected.
TIME EVOLUTION OF THE PHASE OPERATOR IN INTERACTING FOCK SPACE
Authors: DAS P. K.
Published: September 2004

Here we discuss interaction of a single two-level atom with a single mode of interacting electromagnetic field in the Jaynes–Cummings model with the rotating wave approximation.
DOPED LEAD TELLURIDE-BASED SEMICONDUCTORS: NEW POSSIBILITIES FOR DETECTION OF TERAHERZ RADIATION
Authors: KHOKHLOV DMITRIY
Published: September 2004

Doping of the lead telluride and related alloys with the group III impurities results in the appearance of unique physical features of the material, such as persistent photoresponse, enhanced responsive quantum efficiency (up to 100 photoelectrons/incident photon), radiation hardness and many others. We review physical principles of operation of the photodetecting devices based on the group III doped IV–VI including possibilities of fast quenching of the persistent photoresponse, construction of a focal-plane array, new readout technique, and others. Comparison of performance of the state of the art Ge ( Ga ) and Si ( Sb ) photodetectors with their lead telluride based analogs shows that the responsivity of PbSnTe ( In ) photodetectors is by several orders of magnitude higher. High photoresponse is detected at the wavelength of 241 μm in PbSnTe ( In ), and it is possible that the photoconductivity spectrum covers all the submillimeter wavelength range.
THE DEPENDENCY ON THE SQUEEZING PARAMETER FOR THE UNCERTAINTY RELATION IN THE SQUEEZED STATES OF THE TIME-DEPENDENT OSCILLATOR
Authors: CHOI JEONG RYEOL
Published: September 2004

We obtained the uncertainty relation in squeezed states for a time-dependent oscillator. The uncertainty relation in coherent states is same as that of the number states with n=0. However, the uncertainty relation in squeezed states does not satisfy this property and depends on squeezing parameter c. For instance, the uncertainty relation is ℏ/2 which is the minimum value as far as quantum mechanics permits for c=1, same as that in coherent state for c=±∞, and infinity for c=-1. If the time-dependency of the Hamiltonian for the system vanishes, the uncertainty relation in squeezed states will no longer depend on c and becomes the same as that in number state with n=0, like the uncertainty relation in coherent states.
S-EQUIVALENCE OF KNOTS
Authors: KEARTON C.
Published: September 2004

S-equivalence of classical knots is investigated, as well as its relationship with mutation and the unknotting number. Furthermore, we identify the kernel of Bredon's double suspension map, and give a geometric relation between slice and algebraically slice knots. Finally, we show that every knot is S-equivalent to a prime knot.