bluuebunny/crossref_metadata_2025 huggingface dataset:
The importance of size and growth in infancy: integrated findings from systematic reviews of scientific evidence and lay perspectives
Authors: Lucas P. J. , Roberts H. M. , Baird J. , Kleijnen J. , Law C. M.
Published: January 2007

Background  Associations between growth and size during infancy and adult disease have led some to recommend that interventions in infancy might benefit lifelong health. Any such recommendations should be informed by both the scientific evidence for relationships between infancy and later outcomes and the views and opinions of those who care for babies.

Methods  Separate, but interlinked, systematic reviews were conducted of the epidemiological evidence relating infant size or growth to later health and of lay perspectives on infant size and growth. Findings were compared and integrated to consider policy implications.

Results  Lay and scientific perspectives both cast infant growth and size as an indicator of other aspects of an infant’s life, rather than being of fundamental importance. While the scientific literature is most often concerned with infants at the extreme ends of the population distribution, and towards long‐term outcomes, the literature on lay perspectives suggests a focus on defining the ‘normal’ range, and on current health.

Conclusions  Differences and similarities between scientific and lay perspectives on health can highlight areas of agreement, as well as areas of potential misunderstanding or miscommunication.
Tectonic control on peritidal carbonate parasequence formation: an investigation using forward tectono‐stratigraphic modelling
Authors: BENEDICTIS DARIO DE , BOSENCE DAN , WALTHAM DAVE
Published: January 2007

Studies of Quaternary extensional faults indicate that they have instantaneous amounts of throw (0·4 to 4 m), average slip rates (0·05 to 2·8 m kyr−1) and frequency of recurrence (<40 000 years) accounting for the accommodation space required for the accumulation of peritidal carbonate parasequences (PCPs). Hangingwall sites and graben are characterized by fault down‐dropping together with regional subsidence, and footwall sites and horsts by fault‐related uplift alternating with periods of regional subsidence. The relative sea‐level curves generated by these processes operating in a maritime rift setting are used as inputs to a forward stratigraphic modelling program SedTec2000 to simulate how fault‐related changes in accommodation space can account for high‐frequency PCP formation. Each instantaneous fault slip generates a flooding surface or aggradation in hangingwall and graben settings. High‐frequency cycles in hangingwall sites are either symmetric (deepening then shallowing upward) or asymmetric (shallowing‐upward). The major factor controlling cycle types is the balance between rates of carbonate accumulation and generation of accomodation space. High‐frequency cycles in footwall sites and horsts comprise shallow subtidal facies, with no distinctive bathymetric trends, capped by erosional boundaries generated by footwall uplift. The modelled cycles are of the same thickness, with bathymetric trends and frequency to cycles commonly interpreted to be due to orbitally driven eustatic sea‐level changes or autocyclic processes. These numerical experiments demonstrate that high‐frequency PCPs can be generated by tectonic, fault‐related processes, a hypothesis that is frequently discounted.
Effect of processing parameters on static strength of dissimilar friction stir spot welds between different aluminium alloys
Authors: TOZAKI Y. , UEMATSU Y. , TOKAJI K.
Published: January 2007

The effect of processing parameters on static strength and fracture mechanisms of dissimilar friction stir spot welds between different aluminium alloys was studied. Tensile shear strength increased with decreasing tool rotational speed and increasing tool holding time, while cross tension strength decreased with increasing both parameters. Two fracture modes were observed: nugget shear fracture and mixed mode fracture under tensile shear loading, and debonding and pull‐out of the nugget under cross tension loading. Based on experimental observation, the dependence of static strength on processing parameters and the occurrence of different fracture modes were discussed.
Repeat prostate biopsy in the Prostate, Lung, Colorectal and Ovarian cancer screening trial
Authors: Pinsky Paul F. , Crawford E. David , Kramer Barnett S. , Andriole Gerald L. , Gelmann Edward P. , Grubb Robert , Greenlee Robert , Gohagan John K.
Published: January 2007

OBJECTIVE

To determine patterns of repeat prostate biopsy in a cohort of men undergoing prostate cancer screening who have a negative initial biopsy.

SUBJECTS AND METHODS

The Prostate, Colorectal, Lung, and Ovarian (PLCO) cancer screening trial is an ongoing study the prostate component of which consists of six annual screens with measurements of prostate‐specific antigen (PSA) level and a digital rectal examination (DRE). The diagnostic follow‐up of positive screening results is done by the subject’s healthcare provider outside the purview of the PLCO. We analysed the experience of repeat biopsy in men in the PLCO with an initial negative biopsy. Men were divided by indication for initial biopsy into those with suspicious PSA levels and those with suspicious DRE findings.

RESULTS

The probability of having a repeat biopsy within 3 years of initial biopsy was 43% for 1736 men with suspicious PSA levels and 13% for 1025 men with suspicious DRE findings. Rates of third and fourth biopsy after a previous negative biopsy were similar to the initial repeat biopsy rate in PSA‐positive men. Most men had a repeat biopsy only after having an additional round of screening. The PSA level and PSA velocity determined after initial biopsy were independent risk factors for a repeat biopsy, both in PSA‐positive and DRE‐positive men. High‐grade prostatic intraepithelial neoplasia was a risk factor for repeat biopsy before any repeat PSA or DRE testing.

CONCLUSION

The experience of this cohort should be generally representative of patterns of care for repeat biopsy in men undergoing periodic screening. These data can provide context to the debate over optimum practices for repeat biopsy.
The Collaborative Study of Obesity and Diabetes in Adults (CODA) project: meta‐analysis design and description of participating studies
Authors: Duval S. , Vazquez G. , Baker W. L. , Jacobs D. R. ,   for the CODA Study Group
Published: January 2007

The Collaborative Study of Obesity and Diabetes in Adults (CODA) project was formed to establish an international database of studies of abdominal obesity and type 2 diabetes mellitus (T2DM), and to provide analyses of these associations using individual participant data (IPD) meta‐analytic techniques. The collaboration involves obtaining raw data from existing studies. The main objectives of the collaboration are to assess which simple anthropometric indices most closely predict the risk of T2DM in adults, and to investigate ethnicity and other factors that potentially modify that prediction. A second task related to primary prevention of diabetes subsequently evolved, the CODA‐2 project, and is concerned with population‐based methods to identify people most likely to benefit from diabetes interventions. This article describes the meta‐analysis design and the studies involved. The collaboration currently has 37 studies enrolled, providing data on 260 000 participants. The proposed IPD meta‐analyses will help resolve several outstanding issues in diabetes.
Direct Modelling of Regression Effects for Transition Probabilities in Multistate Models
Authors: SCHEIKE THOMAS H. , ZHANG MEI‐JIE
Published: January 2007

Abstract. A simple and standard approach for analysing multistate model data is to model all transition intensities and then compute a summary measure such as the transition probabilities based on this. This approach is relatively simple to implement but it is difficult to see what the covariate effects are on the scale of interest. In this paper, we consider an alternative approach that directly models the covariate effects on transition probabilities in multistate models. Our new approach is based on binomial modelling and inverse probability of censoring weighting techniques and is very simple to implement by standard software. We show how to do flexible regression models with possibly time‐varying covariate effects.
Use of Cohort Information in the Design and Analysis of Case‐Control Studies
Authors: LANGHOLZ BRYAN
Published: January 2007

Abstract. Four case studies are presented to illustrate how information available on cohort members can be used to inform the control selection in epidemiologic case‐control studies. The basic framework is the nested case‐control paradigm and accompanying analysis methods. Emphasis is on development of intuition for choosing study design candidates, the form of the estimators, and extensions of the basic theory to solve design and analysis problems.
Perturbations of Soliton Solutions to the Unstable Nonlinear Schrödinger and Sine‐Gordon Equations
Authors: Swaters Gordon E.
Published: January 2007

The adiabatic evolution of soliton solutions to the unstable nonlinear Schrödinger (UNS) and sine‐Gordon (SG) equations in the presence of small perturbations is reconsidered. The transport equations describing the evolution of the solitary wave parameters are determined by a direct multiple‐scale asymptotic expansion and by phase‐averaged conservation relations for an arbitrary perturbation. The evolution associated with a dissipative perturbation is explicitly determined and the first‐order perturbation fields are also obtained.
Asymptotic Solutions of a Fourth Order Differential Equation
Authors: Wong R. , Zhang H. Y.
Published: January 2007

In this paper, we derive uniform asymptotic expansions of solutions to the fourth order differential equation
image

where x is a real variable and λ is a large positive parameter. The solutions of this differential equation can be expressed in the form of contour integrals, and uniform asymptotic expansions are derived by using the cubic transformation introduced by Chester, Friedman, and Ursell in 1957 and the integration‐by‐part technique suggested by Bleistein in 1966. There are two advantages to this approach: (i) the coefficients in the expansion are defined recursively, and (ii) the remainder is given explicitly. Moreover, by using a recent method of Olde Daalhuis and Temme, we extend the validity of the uniform asymptotic expansions to include all real values of x.
DNA barcoding using chitons (genus Mopalia)
Authors: KELLY RYAN P. , SARKAR INDRA NEIL , EERNISSE DOUGLAS J. , DESALLE ROB
Published: January 2007

Incorporating substantial intraspecific genetic variation for 19 species from 131 individual chitons, genus Mopalia (Mollusca: Polyplacophora), we present rigorous DNA barcodes for this genus as per the currently accepted approaches to DNA barcoding. We also have performed a second kind of analysis that does not rely on blast or the distance‐based neighbour‐joining approach as currently resides on the Barcode of Life Data Systems website. Our character‐based approach, called characteristic attribute organization system, returns fast, accurate, character‐based diagnostics and can unambiguously distinguish between even closely related species based on these diagnostics. Using statistical subsampling approaches with our original data matrix, we show that the method outperforms blast and is equally effective as the neighbour‐joining approach. Our approach differs from the neighbour‐joining approach in that the end‐product is a list of diagnostic nucleotide positions that can be used in descriptions of species. In addition, the diagnostics obtained from this character‐based approach can be used to design oligonucleotides for detection arrays, polymerase chain reaction drop off diagnostics, TaqMan assays, and design of primers for generating short fragments that encompass regions containing diagnostics in the cytochrome oxidase I gene.
Development of simple sequence repeat markers for the plant pathogenic rust fungus Puccinia triticina
Authors: SZABO LES J. , KOLMER JAMES A.
Published: January 2007

Eighteen polymorphic di‐ and trinucleotide simple sequence repeat markers were developed for the phytopathogenic rust fungus Puccinia triticina. The allelic diversity varied from two to nine alleles per locus. Levels of observed heterozygosity ranged from 0.095 to 0.952. Seven of the loci deviated significantly from Hardy–Weinberg equilibrium (P < 0.002) with 70% having levels of observed heterozygosity higher than expected heterozygosity. Null allele(s) were observed for locus PtSSR76 with a frequency of 9%. A preliminary screen of other cereal rust fungi (P. coronata, P. graminis, P. recondita and P. striiformis) indicated that these primer pairs are specific to P. triticina.
Effect of the o2 time‐averaging interval on the reproducibility of o2max in healthy athletic subjects
Authors: Midgley Adrian W. , McNaughton Lars R. , Carroll Sean
Published: January 2007

Aims:  Limited research has investigated the most appropriate oxygen uptake (o2) data averaging method to obtain reliable and valid maximal oxygen uptake (o2max) values. This study investigated the effect of the o2 time‐averaging interval on the reproducibility of o2max.

Methods and results:  Twenty‐two competitive distance runners (six female) performed two identical incremental treadmill tests to their limit of exercise tolerance separated by at least 48 h. Commencing at 7 km h−1, running speed was increased by 1 km h−1 per minute for five stages and 0·5 km h−1 thereafter. Breath‐by‐breath o2 data collected during each incremental test were time‐averaged over 10‐, 15‐, 20‐, 30‐ and 60‐s and the highest averaged o2 value was regarded as o2max for each time‐averaging interval. The o2max values derived from different o2 time‐averaging intervals were significantly different for the first (F = 39·6; P<0·001) and second (F = 68·9; P<0·001) incremental test. There was a tendency for o2max to significantly increase as the time‐averaging interval became shorter. The reproducibility of o2max was similar for all five o2 time‐averages, with no significant differences between the within‐subject variance (F = 0·4; P = 0·6).

Conclusion:  The results of this study suggests that the reproducibility of o2max is not affected by the length of the o2 time‐average interval. However, o2max was significantly altered by changing the o2 time‐averaging interval between 10 and 60 s. Consistency in the o2 time‐averaging interval is therefore an important methodological consideration for repeated determinations of o2max.
Longitudinal progression of behavioral and psychological symptoms of dementia: a pilot study from India
Authors: PINTO Charles , SEETHALAKSHMI Ramanathan
Published: January 2007

Introduction:  Behavioral and psychological symptoms of dementia (BPSD) vary across different types, stages and different time spans of dementia. BPSD form an important determinant in the effective management of dementia as they contribute significantly to the prognosis and outcome of dementia.

Methods:  Thirty‐three individuals with dementia were assessed across three different time periods for changes in behavioral problems as noted on the BEHAV‐AD. Of the 33 individuals, eight had received medications that primarily consisted of low‐dose typical antipsychotics.

Results:  Although, it was noted that behavioral problems fluctuate over time; significant variations in intensity were noted only in delusions. BPSD variations were similar in both Alzheimer’s and vascular dementia. Individuals on medications showed significant improvement in nearly all behavioral problems and a decrease in caregiver distress.

Discussion:  Behavioral symptoms vary across different time spans and follow a general pattern. Detailed analyses of these longitudinal variations in BPSD can be useful in planning cost‐effective treatment strategies.
Lack of genetic association between cholesteryl ester transfer protein and Japanese sporadic Alzheimer’s disease
Authors: KITAJIMA Akiyoshi , SHIBATA Nobuto , OHNUMA Tohru , HIGASHI Shinji , OHKUBO Taku , USUI Chie , WATANABE Tomoko , KAWASHIMA Ritsuko , OHTSUKA Mieko , UEKI Akira , NAGAO Masatsugu , ARAI Heii
Published: January 2007

Background:  Cholesteryl ester transfer protein regulates the plasma high density lipoprotein cholesterol level, which is considered to play an antiatherogenic role in humans. The presence of apolipoprotein E epsilon4 allele is a strong risk factor for developing Alzheimer’s disease (AD). Since apolipoprotein E is a regulator of lipid metabolism, it is reasonable to assume that lipids play important roles in the pathogenesis of AD.

Methods:  We studied the relationship between polymorphisms of the cholesteryl ester transfer protein gene and risk for AD, analyzing two common polymorphisms of the gene and the relationship between them and plasma cholesterol level control samples.

Results:  These polymorphisms showed no association with risk for AD. In rs5882, there was no significant difference in the mean plasma cholesterol concentrations found between patients with the A/A, A/G and G/G genotype. For rs2303790, no significant difference in the mean baseline cholesterol concentrations was found between patients with the A/A genotype and carriers of the G allele.

Conclusion:  Our study indicates that these polymorphisms, rs5882 and rs2303790 were not associated with risk for AD. We also pointed out that these two polymorphisms do not affect plasma cholesterol levels in our Japanese AD samples.
Neuropsychological test for the detection of dementia in elderly individuals: the Nishimura Dementia Test
Authors: FUKUNAGA Tomoko , UKAI Satoshi , KOBAYASHI Toshiko , NISHIMURA Tsuyoshi , TAKEDA Masatoshi
Published: January 2007

Background:  Progression of the core and accessory symptoms of dementia can be slowed if drug therapies and psychosocial interventions are administered at an early stage. The aim of this study was to develop and standardize a neuropsychological test for the elderly that can detect dementia at an early stage with high sensitivity and can evaluate a wide range of severities of dementia based on assessments of various cognitive functions.

Methods:  A preliminary test consisting of 23 items and the Nishimura Mental State Scale for the Elderly (NM Scale), which evaluates the mental functions of elderly individuals by observing their actual behaviors in daily life, were administered to 448 elderly subjects. After applying Hayashi’s quantification theory type I to the results, we revised the preliminary test to construct a neuropsychological test for the elderly, which we named the Nishimura Dementia Test (ND Test), and standardized it. Then, we examined its validity and test–retest reliability.

Results:  Among the 448 subjects, there was a strong correlation between the ND Test scores and NM Scale scores. The ND Test showed a good general agreement rate for the discrimination of the severity of dementia, and good sensitivity and specificity of discrimination of dementia when compared with the actual NM Scale. Using different groups of elderly subjects, the ND Test showed validity and test–retest reliability, and the ND Test scores showed strong correlations with the Revised Hasegawa Dementia Scale scores and the Mini‐Mental State Examination scores.

Conclusions:  The ND Test is based on assessment of a variety of cognitive functions and can evaluate a wide range of severities of dementia with good validity and reliability.
Temperature compensation through systems biology
Authors: Ruoff Peter , Zakhartsev Maxim , Westerhoff Hans V.
Published: January 2007

Temperature has a strong influence on most individual biochemical reactions. Despite this, many organisms have the remarkable ability to keep certain physiological fluxes approximately constant over an extended temperature range. In this study, we show how temperature compensation can be considered as a pathway phenomenon rather than the result of a single‐enzyme property. Using metabolic control analysis, it is possible to identify reaction networks that exhibit temperature compensation. Because most activation enthalpies are positive, temperature compensation of a flux can occur when certain control coefficients are negative. This can be achieved in networks with branching reactions or if the first irreversible reaction is regulated by a feedback loop. Hierarchical control analysis shows that networks that are dynamic through regulated gene expression or signal transduction may offer additional possibilities to bring the apparent activation enthalpies close to zero and lead to temperature compensation. A calorimetric experiment with yeast provides evidence that such a dynamic temperature adaptation can actually occur.
Effect of acetazolamide on pulmonary and muscle gas exchange during normoxic and hypoxic exercise
Authors: Jonk Amy M. , Van Den Berg Irene P. , Olfert I. Mark , Wray D. Walter , Arai Tatsuya , Hopkins Susan R. , Wagner Peter D.
Published: January 2007

Acetazolamide (ACZ) is used to prevent acute mountain sickness at altitude. Because it could affect O2 transport in several different and potentially conflicting ways, we examined its effects on pulmonary and muscle gas exchange and acid–base status during cycle exercise at ∼30, 50 and 90% in normoxia (F= 0.2093) and acute hypoxia (F= 0.125). In a double‐blind, order‐balanced, crossover design, six healthy, trained men (normoxic = 59 ml kg−1 min−1) exercised at both F values after ACZ (3 doses of 250 mg, 8 h apart) and placebo. One week later this protocol was repeated using the other drug (placebo or ACZ). We measured cardiac output , leg blood flow (LBF), and muscle and pulmonary gas exchange, the latter using the multiple inert gas elimination technique. ACZ did not significantly affect , , LBF or muscle gas exchange. As expected, ACZ led to lower arterial and venous blood [HCO3−], pH and lactate levels (P < 0.05), and increased ventilation (P < 0.05). In both normoxia and hypoxia, ACZ resulted in higher arterial PO2 and saturation and a lower alveolar–arterial PO2 difference (AaDO2) due to both less mismatch and less diffusion limitation (P < 0.05). In summary, ACZ improved arterial oxygenation during exercise, due to both greater ventilation and more efficient pulmonary gas exchange. However, muscle gas exchange was unaffected.
Fetal body weight and the development of the control of the cardiovascular system in fetal sheep
Authors: Frasch M. G. , Müller T. , Wicher C. , Weiss C. , Löhle M. , Schwab K. , Schubert H. , Nathanielsz P. W. , Witte O. W. , Schwab M.
Published: January 2007

Reduced birth weight predisposes to cardiovascular diseases in later life. We examined in fetal sheep at 0.76 (n= 18) and 0.87 (n= 17) gestation whether spontaneously occurring variations in fetal weight affect maturation of autonomic control of cardiovascular function. Fetal weights at both gestational ages were grouped statistically in low (LW) and normal weights (NW) (P < 0.01). LW fetuses were within the normal weight span showing minor growth dysproportionality at 0.76 gestation favouring heart and brain, with a primary growth of carcass between 0.76 and 0.87 gestation (P < 0.05). While twins largely contributed to LW fetuses, weight differences between singletons and twins were absent at 0.76 and modest at 0.87 gestation, underscoring the fact that twins belong to normality in fetal sheep not constituting a major malnutritive condition. Mean fetal blood pressure (FBP) of all fetuses was negatively correlated to fetal weight at 0.76 but not 0.87 gestation (P < 0.05). At this age, FBP and baroreceptor reflex sensitivity were increased in LW fetuses (P < 0.05), suggesting increased sympathetic activity and immaturity of circulatory control. Development of vagal modulation of fetal heart rate depended on fetal weight (P < 0.01). These functional associations were largely independent of twin pregnancies. We conclude, low fetal weight within the normal weight span is accompanied by a different trajectory of development of sympathetic blood pressure and vagal heart rate control. This may contribute to the development of elevated blood pressure in later life. Examination of the underlying mechanisms and consequences may contribute to the understanding of programming of cardiovascular diseases.
CRAC channel activity in C. elegans is mediated by Orai1 and STIM1 homologues and is essential for ovulation and fertility
Authors: Lorin‐Nebel Catherine , Xing Juan , Yan Xiaohui , Strange Kevin
Published: January 2007

The Ca2+ release‐activated Ca2+ (CRAC) channel is a plasma membrane Ca2+ entry pathway activated by endoplasmic reticulum (ER) Ca2+ store depletion. STIM1 proteins function as ER Ca2+ sensors and regulate CRAC channel activation. Recent studies have demonstrated that CRAC channels are encoded by the human Orai1 gene and a homologous Drosophila gene. C. elegans intestinal cells express a store‐operated Ca2+ channel (SOCC) regulated by STIM‐1. We cloned a full‐length C. elegans cDNA that encodes a 293 amino acid protein, ORAI‐1, homologous to human and Drosophila Orai1 proteins. ORAI‐1 GFP reporters are co‐expressed with STIM‐1 in the gonad and intestine. Inositol 1,4,5‐trisphosphate (IP3)‐dependent Ca2+ signalling regulates C. elegans gonad function, fertility and rhythmic posterior body wall muscle contraction (pBoc) required for defecation. RNA interference (RNAi) silencing of orai‐1 expression phenocopies stim‐1 knockdown and causes sterility and prevents intestinal cell SOCC activation, but has no effect on pBoc or intestinal Ca2+ signalling. Orai‐1 RNAi suppresses pBoc defects induced by intestinal expression of a STIM‐1 Ca2+‐binding mutant, indicating that the proteins function in a common pathway. Co‐expression of stim‐1 and orai‐1 cDNAs in HEK293 cells induces large inwardly rectifying cation currents activated by ER Ca2+ depletion. The properties of this current recapitulate those of the native SOCC current. We conclude that C. elegans expresses bona fide CRAC channels that require the function of Orai1‐ and STIM1‐related proteins. CRAC channels thus arose very early in animal evolution. In C. elegans, CRAC channels do not play obligate roles in all IP3‐dependent signalling processes and ER Ca2+ homeostasis. Instead, we suggest that CRAC channels carry out highly specialized and cell‐specific signalling roles and that they may function as a failsafe mechanism to prevent Ca2+ store depletion under pathophysiological and stress conditions.
The physiology of a local renin–angiotensin system in the pancreas
Authors: Leung Po Sing
Published: January 2007

The systemic renin–angiotensin system (RAS) plays an important role in regulating blood pressure, electrolyte and fluid homeostasis. However, local RASs also exist in diverse tissues and organs, where they play a multitude of autocrine, paracrine and intracrine physiological roles. The existence of a local RAS is now recognized in pancreatic acinar, islet, duct, endothelial and stellate cells, the expression of which is modulated in response to physiological and pathophysiological stimuli such as hypoxia, pancreatitis, islet transplantation, hyperglycaemia, and diabetes mellitus. This pancreatic RAS has been proposed to have important endocrine and exocrine roles in the pancreas, regulating local blood flow, duct cell sodium bicarbonate secretion, acinar cell digestive enzyme secretion, islet beta‐cell (pro)insulin biosynthesis, and thus, glucose‐stimulated insulin release, delta‐cell somatostatin secretion, and pancreatic cell proliferation and differentiation. It may further mediate oxidative stress‐induced cell inflammation, apoptosis and fibrosis. Further exploration of this system would probably offer new insights into the pathogenesis of pancreatitis, diabetes, cystic fibrosis and pancreatic cancer formation. New therapeutic targets and strategies might thus be suggested.
Stimulation‐induced changes in NADH fluorescence and mitochondrial membrane potential in lizard motor nerve terminals
Authors: Talbot Janet , Barrett John N. , Barrett Ellen F. , David Gavriel
Published: January 2007

To investigate mitochondrial responses to repetitive stimulation, we measured changes in NADH fluorescence and mitochondrial membrane potential (Ψm) produced by trains of action potentials (50 Hz for 10–50 s) delivered to motor nerve terminals innervating external intercostal muscles. Stimulation produced a rapid decrease in NADH fluorescence and partial depolarization of Ψm. These changes were blocked when Ca2+ was removed from the bath or when N‐type Ca2+ channels were inhibited with ω‐conotoxin GVIA, but were not blocked when bath Ca2+ was replaced by Sr2+, or when vesicular release was inhibited with botulinum toxin A. When stimulation stopped, NADH fluorescence and Ψm returned to baseline values much faster than mitochondrial [Ca2+]. In contrast to findings in other tissues, there was usually little or no poststimulation overshoot of NADH fluorescence. These findings suggest that the major change in motor terminal mitochondrial function brought about by repetitive stimulation is a rapid acceleration of electron transport chain (ETC) activity due to the Ψm depolarization produced by mitochondrial Ca2+ (or Sr2+) influx. After partial inhibition of complex I of the ETC with amytal, stimulation produced greater Ψm depolarization and a greater elevation of cytosolic [Ca2+]. These results suggest that the ability to accelerate ETC activity is important for normal mitochondrial sequestration of stimulation‐induced Ca2+ loads.
The kinetics of inhibition of rat recombinant heteromeric α1β glycine receptors by the low‐affinity antagonist SR‐95531
Authors: Beato Marco , Burzomato Valeria , Sivilotti Lucia G.
Published: January 2007

The GABAAantagonist SR‐95531 (gabazine) is known to block glycine receptors, albeit with low affinity. We have studied the effect of SR‐95531 on rat recombinant α1β glycine receptors expressed in human embryonic kidney (HEK293) cells by recording macroscopic currents elicited by rapid glycine application to outside‐out patches. SR‐95531 has a fast unbinding rate (koffSR, about 3000 s−1) and this means that the time course of its unbinding is comparable to the expected time course of the transmitter in the cleft. We also found that equilibrium applications of SR‐95531 reduced the response to brief glycine applications by an amount inversely proportional to the duration of glycine application. The fast unbinding rate of SR‐95531 from the glycine receptor will make it useful for establishing the time course of glycine concentration at glycinergic synapses.
Molecular basis of the T‐ and L‐type Ca2+ currents in canine Purkinje fibres
Authors: Rosati Barbara , Dun Wen , Hirose Masanori , Boyden Penelope A. , McKinnon David
Published: January 2007

This study examines the molecular basis for the T‐type and L‐type Ca2+ currents in canine Purkinje cells. The ICaT in Purkinje cells was completely suppressed by 200 nm kurtoxin, a specific blocker of both Cav3.1 and Cav3.2 channels. Since only Cav3.2 mRNA is expressed at high levels in Purkinje fibres, being approximately 100‐fold more abundant than either Cav3.1 or Cav3.3 mRNAs, it is concluded that the Cav3.2 gene encodes the bulk of the T‐type Ca2+ channels in canine Purkinje cells. This conclusion is consistent with the sensitivity of the current to blockade by Ni2+ ions (KD= 32 μm). For L‐type channels, Cav1.2 mRNA was most abundant in Purkinje fibres but a significant level of Cav1.3 mRNA expression was also found. A comparison of the sensitivity to blockade by isradipine of the L‐type currents in Purkinje cells and ventricular epicardial myocytes, which only express Cav1.2, suggests that the Cav1.3 channels make, at most, a minor contribution to the L‐type current in canine Purkinje cells.
Comment on "A Common Genetic Variant Is Associated with Adult and Childhood Obesity"
Authors: Dina Christian , Meyre David , Samson Chantal , Tichet Jean , Marre Michel , Jouret Beatrice , Charles Marie Aline , Balkau Beverley , Froguel Philippe
Published: January 2007

Herbert
et al
. (Reports, 14 April 2006, p. 279) reported an association between the
INSIG2
gene variant rs7566605 and obesity in four sample populations, under a recessive model. We attempted to replicate this result in 10,265 Caucasian individuals, combining family-based, case-control, and general population studies, but found no support for a major role of this variant in obesity.
Comment on "A Common Genetic Variant Is Associated with Adult and Childhood Obesity"
Authors: Loos Ruth J. F. , Barroso Inês , O'Rahilly Stephen , Wareham Nicholas J.
Published: January 2007

Herbert
et al
. (Reports, 14 April 2006, p. 279) found that the rs7566605 genetic variant, located upstream of the
INSIG2
gene, was consistently associated with increased body mass index. However, we found no evidence of association between rs7566605 and body mass index in two large ethnically homogeneous population-based cohorts. On the contrary, an opposite tendency was observed.
Early Upper Paleolithic in Eastern Europe and Implications for the Dispersal of Modern Humans
Authors: Anikovich M. V. , Sinitsyn A. A. , Hoffecker John F. , Holliday Vance T. , Popov V. V. , Lisitsyn S. N. , Forman Steven L. , Levkovskaya G. M. , Pospelova G. A. , Kuz'mina I. E. , Burova N. D. , Goldberg Paul , Macphail Richard I. , Giaccio Biagio , Praslov N. D.
Published: January 2007

Radiocarbon and optically stimulated luminescence dating and magnetic stratigraphy indicate Upper Paleolithic occupation—probably representing modern humans—at archaeological sites on the Don River in Russia 45,000 to 42,000 years ago. The oldest levels at Kostenki underlie a volcanic ash horizon identified as the Campanian Ignimbrite Y5 tephra that is dated elsewhere to about 40,000 years ago. The occupation layers contain bone and ivory artifacts, including possible figurative art, and fossil shells imported more than 500 kilometers. Thus, modern humans appeared on the central plain of Eastern Europe as early as anywhere else in northern Eurasia.
Stabilization of Platinum Oxygen-Reduction Electrocatalysts Using Gold Clusters
Authors: Zhang J. , Sasaki K. , Sutter E. , Adzic R. R.
Published: January 2007

We demonstrated that platinum (Pt) oxygen-reduction fuel-cell electrocatalysts can be stabilized against dissolution under potential cycling regimes (a continuing problem in vehicle applications) by modifying Pt nanoparticles with gold (Au) clusters. This behavior was observed under the oxidizing conditions of the O
2
reduction reaction and potential cycling between 0.6 and 1.1 volts in over 30,000 cycles. There were insignificant changes in the activity and surface area of Au-modified Pt over the course of cycling, in contrast to sizable losses observed with the pure Pt catalyst under the same conditions. In situ x-ray absorption near-edge spectroscopy and voltammetry data suggest that the Au clusters confer stability by raising the Pt oxidation potential.
Bringing Down the House to Add a (Nice) Room
Authors: Sassen Saskia
Published: January 2007

Deflecting Immigration
. Networks, Markets, and Regulation in Los Angeles.
By Ivan Light
. Russell Sage Foundation, New York, 2006. 262 pp. $35. ISBN 9780871545381.

Exploring the fates of immigrants in late 20th-century Los Angeles, the author argues that local enforcement of employment and housing standards has encouraged newcomers to go elsewhere in the United States.
Late Pleistocene Human Skull from Hofmeyr, South Africa, and Modern Human Origins
Authors: Grine F. E. , Bailey R. M. , Harvati K. , Nathan R. P. , Morris A. G. , Henderson G. M. , Ribot I. , Pike A. W. G.
Published: January 2007

The lack of Late Pleistocene human fossils from sub-Saharan Africa has limited paleontological testing of competing models of recent human evolution. We have dated a skull from Hofmeyr, South Africa, to 36.2 ± 3.3 thousand years ago through a combination of optically stimulated luminescence and uranium-series dating methods. The skull is morphologically modern overall but displays some archaic features. Its strongest morphometric affinities are with Upper Paleolithic (UP) Eurasians rather than recent, geographically proximate people. The Hofmeyr cranium is consistent with the hypothesis that UP Eurasians descended from a population that emigrated from sub-Saharan Africa in the Late Pleistocene.
Clustering by Passing Messages Between Data Points
Authors: Frey Brendan J. , Dueck Delbert
Published: January 2007

Clustering data by identifying a subset of representative examples is important for processing sensory signals and detecting patterns in data. Such “exemplars” can be found by randomly choosing an initial subset of data points and then iteratively refining it, but this works well only if that initial choice is close to a good solution. We devised a method called “affinity propagation,” which takes as input measures of similarity between pairs of data points. Real-valued messages are exchanged between data points until a high-quality set of exemplars and corresponding clusters gradually emerges. We used affinity propagation to cluster images of faces, detect genes in microarray data, identify representative sentences in this manuscript, and identify cities that are efficiently accessed by airline travel. Affinity propagation found clusters with much lower error than other methods, and it did so in less than one-hundredth the amount of time.
Role of Cell Culture for Virus Detection in the Age of Technology
Authors: Leland Diane S. , Ginocchio Christine C.
Published: January 2007

Viral disease diagnosis has traditionally relied on the isolation of viral pathogens in cell cultures. Although this approach is often slow and requires considerable technical expertise, it has been regarded for decades as the “gold standard” for the laboratory diagnosis of viral disease. With the development of nonculture methods for the rapid detection of viral antigens and/or nucleic acids, the usefulness of viral culture has been questioned. This review describes advances in cell culture-based viral diagnostic products and techniques, including the use of newer cell culture formats, cryopreserved cell cultures, centrifugation-enhanced inoculation, precytopathogenic effect detection, cocultivated cell cultures, and transgenic cell lines. All of these contribute to more efficient and less technically demanding viral detection in cell culture. Although most laboratories combine various culture and nonculture approaches to optimize viral disease diagnosis, virus isolation in cell culture remains a useful approach, especially when a viable isolate is needed, if viable and nonviable virus must be differentiated, when infection is not characteristic of any single virus (i.e., when testing for only one virus is not sufficient), and when available culture-based methods can provide a result in a more timely fashion than molecular methods.
Modes and Modulations of Antibiotic Resistance Gene Expression
Authors: Depardieu Florence , Podglajen Isabelle , Leclercq Roland , Collatz Ekkehard , Courvalin Patrice
Published: January 2007

Since antibiotic resistance usually affords a gain of function, there is an associated biological cost resulting in a loss of fitness of the bacterial host. Considering that antibiotic resistance is most often only transiently advantageous to bacteria, an efficient and elegant way for them to escape the lethal action of drugs is the alteration of resistance gene expression. It appears that expression of bacterial resistance to antibiotics is frequently regulated, which indicates that modulation of gene expression probably reflects a good compromise between energy saving and adjustment to a rapidly evolving environment. Modulation of gene expression can occur at the transcriptional or translational level following mutations or the movement of mobile genetic elements and may involve induction by the antibiotic. In the latter case, the antibiotic can have a triple activity: as an antibacterial agent, as an inducer of resistance to itself, and as an inducer of the dissemination of resistance determinants. We will review certain mechanisms, all reversible, that bacteria have elaborated to achieve antibiotic resistance by the fine-tuning of the expression of genetic information.
Current Therapeutics, Their Problems, and Sulfur-Containing-Amino-Acid Metabolism as a Novel Target against Infections by “Amitochondriate” Protozoan Parasites
Authors: Ali Vahab , Nozaki Tomoyoshi
Published: January 2007

The “amitochondriate” protozoan parasites of humansEntamoeba histolytica,Giardia intestinalis, andTrichomonas vaginalisshare many biochemical features, e.g., energy and amino acid metabolism, a spectrum of drugs for their treatment, and the occurrence of drug resistance. These parasites possess metabolic pathways that are divergent from those of their mammalian hosts and are often considered to be good targets for drug development. Sulfur-containing-amino-acid metabolism represents one such divergent metabolic pathway, namely, the cysteine biosynthetic pathway and methionine γ-lyase-mediated catabolism of sulfur-containing amino acids, which are present inT. vaginalisandE. histolyticabut absent inG. intestinalis. These pathways are potentially exploitable for development of drugs against amoebiasis and trichomoniasis. For instance,l-trifluoromethionine, which is catalyzed by methionine γ-lyase and produces a toxic product, is effective againstT. vaginalisandE. histolyticaparasites in vitro and in vivo and may represent a good lead compound. In this review, we summarize the biology of these microaerophilic parasites, their clinical manifestation and epidemiology of disease, chemotherapeutics, the modes of action of representative drugs, and problems related to these drugs, including drug resistance. We further discuss our approach to exploit unique sulfur-containing-amino-acid metabolism, focusing on development of drugs againstE. histolytica.
Global Dissemination of
Vibrio parahaemolyticus
Serotype O3:K6 and Its Serovariants
Authors: Nair G. Balakrish , Ramamurthy Thandavarayan , Bhattacharya Sujit K. , Dutta Basabjit , Takeda Yoshifumi , Sack David A.
Published: January 2007

Vibrio parahaemolyticus
is recognized as a cause of food-borne gastroenteritis, particularly in the Far East, where raw seafood consumption is high. An unusual increase in admissions of
V. parahaemolyticus
cases was observed at the Infectious Diseases Hospital in Calcutta, a city in the northeastern part of India, beginning February 1996. Analysis of the strains revealed that a unique serotype, O3:K6, not previously isolated during the surveillance in Calcutta accounted for 50 to 80% of the infections in the following months. After this report, O3:K6 isolates identical to those isolated in Calcutta were reported from food-borne outbreaks and from sporadic cases in Bangladesh, Chile, France, Japan, Korea, Laos, Mozambique, Peru, Russia, Spain, Taiwan, Thailand, and the United States. Other serotypes, such as O4:K68, O1:K25, and O1:KUT (untypeable), that had molecular characteristics identical to that of the O3:K6 serotype were subsequently documented. These serotypes appeared to have diverged from the O3:K6 serotype by alteration of the O:K antigens and were defined as “serovariants” of the O3:K6 isolate. O3:K6 and its serovariants have now spread into Asia, America, Africa, and Europe. This review traces the genesis, virulence features, molecular characteristics, serotype variants, environmental occurrence, and global spread of this unique clone of
V. parahaemolyticus
.
Histoplasmosis: a Clinical and Laboratory Update
Authors: Kauffman Carol A.
Published: January 2007

Infection with
Histoplasma capsulatum
occurs commonly in areas in the Midwestern United States and Central America, but symptomatic disease requiring medical care is manifest in very few patients. The extent of disease depends on the number of conidia inhaled and the function of the host's cellular immune system. Pulmonary infection is the primary manifestation of histoplasmosis, varying from mild pneumonitis to severe acute respiratory distress syndrome. In those with emphysema, a chronic progressive form of histoplasmosis can ensue. Dissemination of
H. capsulatum
within macrophages is common and becomes symptomatic primarily in patients with defects in cellular immunity. The spectrum of disseminated infection includes acute, severe, life-threatening sepsis and chronic, slowly progressive infection. Diagnostic accuracy has improved greatly with the use of an assay for
Histoplasma
antigen in the urine; serology remains useful for certain forms of histoplasmosis, and culture is the ultimate confirming diagnostic test. Classically, histoplasmosis has been treated with long courses of amphotericin B. Today, amphotericin B is rarely used except for severe infection and then only for a few weeks, followed by azole therapy. Itraconazole is the azole of choice following initial amphotericin B treatment and for primary treatment of mild to moderate histoplasmosis.
GEOMETRICAL PARTICLE MODELS ON 3D LIGHTLIKE CURVES
Authors: HUANG RONGPEI , LIAO CAISHENG
Published: January 2007

The (2+1)-dimensional mechanical systems associated with lightlike curves are considered. We studied the action whose Lagrangian depends quadratically on the Cartan curvature (torsion). Some conservation laws are given and the motion equation for a special case is completely solved by using geometrical methods.
ELASTIC SCATTERING AND THE PROTON FORM FACTOR
Authors: CARVALHO F. , NATALE A. A. , ZANETTI C. M.
Published: January 2007

We use the QCD pomeron model proposed by Landshoff and Nachtmann to compute the differential and the total cross-sections for pp scattering in order to discuss a QCD-based approach to the proton form factor. This model is quite dependent on the experimental electromagnetic form factor, and it is not totally clear why this form factor gives good results even at moderate transferred momentum. We exchange the electromagnetic form factor by the asymptotic QCD proton form factor determined by Brodsky and Lepage (BL) plus a prescription for its low energy behavior dictated by the existence of a dynamically generated gluon mass. We fit the data with this QCD inspired form factor and a value for the dynamical gluon mass consistent with the ones determined in the literature. Our results also provide a determination of the proton wave function at the origin, which appears in the BL form factor.
ETERNALLY ACCELERATING SPACELIKE BRANEWORLD COSMOLOGIES
Authors: MOCHIZUKI RIUJI
Published: January 2007

We construct an eternally inflating spacelike brane world model. If the space dimension of the brane is three (SM2) or six (SM5) for M theory or four (SD3) for superstring theory, a time-dependent n-form field would supply a constant energy density and cause exponentially expansion of the spacelike brane. In these cases, the hyperbolic space perpendicular to the brane would keep its scale factor constant. In the other cases, however, the extra space would vary in size.
GRAVITATIONAL COLLAPSE OF A SELF-INTERACTING SCALAR FIELD
Authors: GOSWAMI RITUPARNO , JOSHI PANKAJ S.
Published: January 2007

We construct and study here a class of collapsing scalar field models with a nonzero potential. The weak energy condition is satisfied by the collapsing configuration and it is shown that the end state of collapse could be either a black hole or a naked singularity. It is seen that physically it is the rate of collapse that governs these outcomes of the dynamical evolution. The implications for the cosmic censorship conjecture are discussed.
ANALYTICITY AND THE Nc COUNTING RULE OF S MATRIX POLES
Authors: XIAO Z. G. , ZHENG H. Q.
Published: January 2007

By studying ππ scattering amplitudes in the large-N c limit, we clarify the N c dependence of the S matrix pole position. It is demonstrated that analyticity and the N c counting rule exclude the existence of S-matrix poles with [Formula: see text]. Especially the properties of σ and f0(980) with respect to the 1/N c expansion are discussed. We point out that in general tetra-quark resonances do not exist.