bluuebunny/crossref_metadata_2025 huggingface dataset:
Olivocerebellar modulation of motor cortex ability to generate vibrissal movements in rat
Authors: Lang Eric J. , Sugihara Izumi , Llinás Rodolfo
Published: December 2005

The vibrissal movements known as whisking are generated in a pulsatile, or non‐continuous, fashion and comprise sequences of brief regularly spaced movements. These rhythmic timing sequences imply the existence of periodically issued motor commands. As inferior olivary (IO) neurones generate periodic synchronous discharges that could provide the underlying timing signal, this possibility was tested by determining whether the olivocerebellar system modulates motor cortex (MCtx)‐triggered whisker movements in rats. Trains of current pulses were applied to MCtx, and the resulting whisker movements were recorded using a high speed video camera. The evoked movement patterns demonstrated properties consistent with the existence of an oscillatory motor driving rhythm. In particular, movement amplitude showed a bell‐shaped dependence on stimulus frequency, with a peak at 11.5 ± 2.3 Hz. Moreover, movement trajectories showed harmonic and subharmonic entrainment patterns within specific stimulus frequency ranges. By contrast, movements evoked by facial nerve stimulation showed no such frequency‐dependent properties. To test whether the IO was the oscillator in question, IO neuronal properties were modified in vivo by intra‐IO picrotoxin injection, which enhances synchronous oscillatory IO activity and reduces its natural frequency. The ensuing changes in the evoked whisker patterns were consistent with these pharmacological effects. Furthermore, in cerebellectomized rats, oscillatory modulation of MCtx‐evoked movements was greatly reduced, and intra‐IO picrotoxin injections did not affect the evoked movement patterns. Additionally, multielectrode recording of Purkinje cell complex spikes showed a temporal correlation of olivocerebellar activity during MCtx stimulus trains to evoked movement patterns. In sum, the results indicate that MCtx's ability to generate movements is modulated by an oscillatory signal arising in the olivocerebellar system.
The snoRNA HBII-52 Regulates Alternative Splicing of the Serotonin Receptor 2C
Authors: Kishore Shivendra , Stamm Stefan
Published: December 2005

The Prader-Willi syndrome is a congenital disease that is caused by the loss of paternal gene expression from a maternally imprinted region on chromosome 15. This region contains a small nucleolar RNA (snoRNA), HBII-52, that exhibits sequence complementarity to the alternatively spliced exon Vb of the serotonin receptor 5-HT
2C
R. We found that HBII-52 regulates alternative splicing of 5-HT
2C
R by binding to a silencing element in exon Vb. Prader-Willi syndrome patients do not express HBII-52. They have different 5-HT
2C
R messenger RNA (mRNA) isoforms than healthy individuals. Our results show that a snoRNA regulates the processing of an mRNA expressed from a gene located on a different chromosome, and the results indicate that a defect in pre-mRNA processing contributes to the Prader-Willi syndrome.
Femtosecond Multidimensional Imaging of a Molecular Dissociation
Authors: Geßner O. , Lee A. M. D. , Shaffer J. P. , Reisler H. , Levchenko S. V. , Krylov A. I. , Underwood Jonathan G. , Shi H. , East A. L. L. , Wardlaw D. M. , Chrysostom E. t. H. , Hayden C. C. , Stolow Albert
Published: December 2005

The coupled electronic and vibrational motions governing chemical processes are best viewed from the molecule's point of view—the molecular frame. Measurements made in the laboratory frame often conceal information because of the random orientations the molecule can take. We used a combination of time-resolved photoelectron spectroscopy, multidimensional coincidence imaging spectroscopy, and ab initio computation to trace a complete reactant-to-product pathway—the photodissociation of the nitric oxide dimer—from the molecule's point of view, on the femtosecond time scale. This method revealed an elusive photochemical process involving intermediate electronic configurations.
A Stretchable Form of Single-Crystal Silicon for High-Performance Electronics on Rubber Substrates
Authors: Khang Dahl-Young , Jiang Hanqing , Huang Young , Rogers John A.
Published: December 2005

We have produced a stretchable form of silicon that consists of submicrometer single-crystal elements structured into shapes with microscale, periodic, wavelike geometries. When supported by an elastomeric substrate, this “wavy” silicon can be reversibly stretched and compressed to large levels of strain without damaging the silicon. The amplitudes and periods of the waves change to accommodate these deformations, thereby avoiding substantial strains in the silicon itself. Dielectrics, patterns of dopants, electrodes, and other elements directly integrated with the silicon yield fully formed, high-performance “wavy” metal oxide semiconductor field-effect transistors, p-n diodes, and other devices for electronic circuits that can be stretched or compressed to similarly large levels of strain.
Scaling of Connectivity in Marine Populations
Authors: Cowen R. K. , Paris C. B. , Srinivasan A.
Published: December 2005

Defining the scale of connectivity, or exchange, among marine populations and determining the factors driving this exchange are pivotal to our understanding of the population dynamics, genetic structure, and biogeography of many coastal species. Using a high-resolution biophysical model for the Caribbean region, we report that typical larval dispersal distances of ecologically relevant magnitudes are on the scale of only 10 to 100 kilometers for a variety of reef fish species. We also show the importance of the early onset of active larval movement mediating the dispersal potential. In addition to self-recruitment, larval import from outside the local area is required to sustain most populations, although these population subsidies are very limited in particular systems. The results reveal distinct regions of population isolation based on larval dispersal that also correspond to genetic and morphological clines observed across a range of marine organisms.
The role of physical workload and pain related fear in the development of low back pain in young workers: evidence from the BelCoBack Study; results after one year of follow up
Authors: Van Nieuwenhuyse A , Somville P R , Crombez G , Burdorf A , Verbeke G , Johannik K , Van den Bergh O , Masschelein R , Mairiaux Ph , Moens G F
Published: December 2005

Aims:To study the influence of work related physical and psychosocial factors and individual characteristics on the occurrence of low back pain among young and pain free workers.

Methods:The Belgian Cohort Back Study was designed as a prospective cohort study. The study population of this paper consisted of 716 young healthcare or distribution workers without low back pain lasting seven or more consecutive days during the year before inclusion. The median age was 26 years with an interquartile range between 24 and 29 years. At baseline, these workers filled in a questionnaire with physical exposures, work related psychosocial factors and individual characteristics. One year later, the occurrence of low back pain lasting seven or more consecutive days and some of its characteristics were registered by means of a questionnaire. To assess the respective role of predictors at baseline on the occurrence of low back pain in the following year, Cox regression with a constant risk period for all subjects was applied.

Results:After one year of follow up, 12.6% (95% CI 10.1 to 15.0) of the 716 workers had developed low back pain lasting seven or more consecutive days. An increased risk was observed for working with the trunk in a bent and twisted position for more than two hours a day (RR 2.2, 95% CI 1.2 to 4.1), inability to change posture regularly (RR 2.1, 95% CI 1.3 to 3.5), back complaints in the year before inclusion (RR 1.7, 95% CI 1.1 to 2.8), and high scores of pain related fear (RR 1.8, 95% CI 1.0 to 3.1). Work related psychosocial factors and physical factors during leisure time were not predictive.

Conclusion:This study highlighted the importance of physical work factors and revealed the importance of high scores of pain related fear in the development of low back pain among young workers.
Self perceived health and mental health among women flight attendants
Authors: Ballard T J , Romito P , Lauria L , Vigiliano V , Caldora M , Mazzanti C , Verdecchia A
Published: December 2005

Aims:The authors investigated associations of work related risk factors with self perceived health as less than “good” and psychological distress among Italian women flight attendants.

Methods:The authors conducted a cross sectional survey on health and mental health among 1955 former and current flight attendants, using a postal questionnaire.

Results:More current than former flight attendants reported self perceived health as fair to poor and psychological distress measured as a GHQ-12 score of six or more. Among current flight attendants, reporting health as fair to poor was associated with low job satisfaction (OR 1.89) and recent experiences of sexual harassment by passengers (OR 2.83). Psychological distress was associated with low job satisfaction (OR 2.38) and frequent tension with partner over childcare (OR 1.79).

Conclusions:Perceived health as fair to poor and psychological distress were greater among current flight attendants and were related to job characteristics and family difficulties. Perceived poor health has been shown in the literature to be related to mortality, high job strain, and early retirement, and psychological distress is associated with work absence. The effect of sexual harassment by passengers on perceived health of flight attendants may be relevant to other working women dealing with the public. The health effects of family/work conflicts, low job satisfaction, and sexual harassment should be explored more in depth, using qualitative as well as quantitative methods among working women in various occupations.
Lung cancer risk and talc not containing asbestiform fibres: a review of the epidemiological evidence
Authors: Wild P
Published: December 2005

A literature search was done and all epidemiological cancer studies mentioning talc as a risk factor were selected. The talc exposed populations were divided into three groups: (1) populations in which no other occupational carcinogen was mentioned (only talc millers satisfied this criterion); (2) populations of talc miners exposed to talc, quartz, and/or radon; and (3) other industrial populations in which talc is associated with quartz, nitrosamines, and asbestos depending on the study. No excess lung cancer mortality was found for the populations of talc millers exposed to high levels of talc but without any other potential carcinogen (SMR = 0.92, 42 cases) while the summary of mortality of talc miners exposed to quartz and/or radon was in excess (fixed effect SMR = 1.20, random effect RR = 1.85, 40 cases). Six studies in other industrial settings were identified. All reported increased lung cancer mortality among talc exposed workers but the talc exposure was confounded with other carcinogens and only one study was able to adjust on them. In conclusion, no increased lung cancer mortality was observed among talc millers despite their high exposure experience. In populations in which talc was associated with other potential carcinogens, some lung cancer excesses were observed.
Agricultural seed dust as a potential cause of organic dust toxic syndrome
Authors: Smit L A M , Wouters I M , Hobo M M , Eduard W , Doekes G , Heederik D
Published: December 2005

Aims:Episodes of serious work related health problems resembling organic dust toxic syndrome (ODTS) in workers of a grass seed quality inspection laboratory prompted the authors to study personal endotoxin exposure levels in this facility and in the agricultural seed processing industry. In addition, microbial and inflammatory characteristics of agricultural seeds were studied.

Methods:The authors assessed inhalable dust and endotoxin levels in 101 samples from 57 workers in grass, cereal, and vegetable seed plants who were handling mainly grass seeds as bulk product, and horticulture seeds in smaller quantities. Additionally, real-time dust exposure was measured using a DataRAM monitor in 12 grass seed workers to obtain more information on exposure patterns during specific tasks. Endotoxin concentrations in seed extracts were determined by LAL assay and seed samples were analysed by scanning electron microscopy. Release of inflammatory cytokines was measured in supernatants of whole blood samples stimulated with lipopolysaccharide (LPS) or agricultural seed extracts in a human whole blood assay (WBA).

Results:Endotoxin concentrations in personal samples were high (geometric mean 1800 EU/m3), particularly in the grass seed quality inspection lab where endotoxin levels up to 274 000 EU/m3were measured. The recommended health based endotoxin exposure limit of 50 EU/m3was amply exceeded in almost all personal samples. Job tasks dumping and mixing were associated with highest dust and endotoxin exposures, which was confirmed by real-time measurements. Microbial infestation was found in almost all seed samples. WBA results showed that most seed extracts were capable of inducing a pronounced dose dependent cytokine release.

Conclusions:Workers handling grass, cereal, or vegetable seeds are at risk of exposure to high levels of endotoxin containing seed dust. Occupational exposure to inhalable agricultural seed dust can induce inflammatory responses, and is a potential cause of ODTS.
Occupational risk factors for nasopharyngeal cancer among female textile workers in Shanghai, China
Authors: Li W , Ray R M , Gao D L , Fitzgibbons E D , Seixas N S , Camp J E , Wernli K J , Astrakianakis G , Feng Z , Thomas D B , Checkoway H
Published: December 2005

Aims:To investigate whether occupational exposure to dusts and chemicals in the Chinese textile industry are associated with risk of nasopharyngeal cancer.

Methods:Sixty seven nasopharyngeal carcinoma (NPC) cases identified during 1989–98 and a random sample (n = 3188) of women were included in a case cohort study nested in a cohort of 267 400 women textile workers in Shanghai, China. A complete occupational history of work in the textile industry was obtained for each woman. A job exposure matrix developed by experienced industrial hygienists was used to assess exposures to specific dusts and chemicals.

Results:Risk of NPC is associated with cumulative exposure to cotton dust. The hazard ratio for women cumulatively exposed to >143.4 mg/m3× years of cotton dust was 3.6 (95% CI 1.8 to 7.2) compared with unexposed women. Trends of increasing risk were also found with increasing duration of exposure to acids and caustics (p = 0.05), and with years worked in dyeing processes (p = 0.06). Women who worked at least 10 years in dyeing processes had a 3.6-fold excess risk of NPC (95% CI 1.0 to 12.1).

Conclusions:Occupational exposure to cotton dust, acids, and caustics, and work in dyeing and printing jobs in the textile industry may have increased risk of NPC in this cohort.
EMERGENCE OF REGULATORY NETWORKS IN SIMULATED EVOLUTIONARY PROCESSES
Authors: DRASDO DIRK , KRUSPE MATTHIAS
Published: December 2005

Despite spectacular progress in biophysics, molecular biology and biochemistry our ability to predict the dynamic behavior of multicellular systems under different conditions is very limited. An important reason for this is that still not enough is known about how cells change their physical and biological properties by genetic or metabolic regulation, and which of these changes affect the cell behavior. For this reason, it is difficult to predict the system behavior of multicellular systems in case the cell behavior changes, for example, as a consequence of regulation or differentiation. The rules that underlie the regulation processes have been determined on the time scale of evolution, by selection on the phenotypic level of cells or cell populations. We illustrate by detailed computer simulations in a multi-scale approach how cell behavior controlled by regulatory networks may emerge as a consequence of an evolutionary process, if either the cells, or populations of cells are subject to selection on particular features. We consider two examples, migration strategies of single cells searching a signal source, or aggregation of two or more cells within minimal multiscale models of biological evolution. Both can be found for example in the life cycle of the slime mold Dictyostelium discoideum. However, phenotypic changes that can lead to completely different modes of migration have also been observed in cells of multi-cellular organisms, for example, as a consequence of a specialization in stem cells or the de-differentiation in tumor cells. The regulatory networks are represented by Boolean networks and encoded by binary strings. The latter may be considered as encoding the genetic information (the genotype) and are subject to mutations and crossovers. The cell behavior reflects the phenotype. We find that cells adopt naturally observed migration strategies, controlled by networks that show robustness and redundancy. The model simplicity allow us to unambiguously analyze the regulatory networks and the resulting phenotypes by different measures and by knockouts of regulatory elements. We illustrate that in order to maintain a cells' phenotype in case of a knockout, the cell may have to be able to deal with contradictory information. In summary, both the cell phenotype as well as the emerged regulatory network behave as their biological counterparts observed in nature.
NEUTRAL NETWORKS OF INTERACTING RNA SECONDARY STRUCTURES
Authors: STEPHAN-OTTO ATTOLINI CAMILLE , STADLER PETER F.
Published: December 2005

RNA molecules interact by forming inter-molecular base pairs that compete with the intra-molecular base pairs of their secondary structures. We investigate the patterns of neutral mutations in RNAs whose function is the interaction with other RNAs, i.e. the co-folding with one or more other RNA molecules. We find that (i) the degree of neutrality is much smaller in interacting RNAs compared to RNAs that just have to coform to a single externally prescribed target structure, and (ii) strengthening this contraint to the conservation of the co-folded structure with two or more partners essentially eliminates neutrality. It follows that RNAs whose function depends on the formation of a specific interaction complex with a target RNA molecule will evolve much more slowly than RNAs with a function depending only on their own structure.
A NETWORK-BASED THRESHOLD MODEL FOR THE SPREADING OF FADS IN SOCIETY AND MARKETS
Authors: GRÖNLUND ANDREAS , HOLME PETTER
Published: December 2005

We investigate the behavior of a threshold model for the spreading of fads and similar phenomena in society. The model gives the fad dynamics and is intended to be confined to an underlying network structure. We investigate the whole parameter space of the fad dynamics on three types of network models. The dynamics we discover is rich and highly dependent on the underlying network structure. For some range of the parameter space, for all types of substrate networks, there are a great variety of sizes and life-lengths of the fads — what one sees in real-world social and economical systems.
COARSE GRAINING IN SIMULATED CELL POPULATIONS
Authors: DRASDO DIRK
Published: December 2005

The main mechanisms that control the organization of multicellular tissues are still largely open. A commonly used tool to study basic control mechanisms are in vitro experiments in which the growth conditions can be widely varied. However, even in vitro experiments are not free from unknown or uncontrolled influences. One reason why mathematical models become more and more a popular complementary tool to experiments is that they permit the study of hypotheses free from unknown or uncontrolled influences that occur in experiments. Many model types have been considered so far to model multicellular organization ranging from detailed individual-cell based models with explicit representations of the cell shape to cellular automata models with no representation of cell shape, and continuum models, which consider a local density averaged over many individual cells. However, how the different model description may be linked, and, how a description on a coarser level may be constructed based on the knowledge of the finer, microscopic level, is still largely unknown. Here, we consider the example of monolayer growth in vitro to illustrate how, in a multi-step process starting from a single-cell based off-lattice-model that subsumes the information on the sub-cellular scale by characteristic cell-biophysical and cell-kinetic properties, a cellular automaton may be constructed whose rules have been chosen based on the findings in the off-lattice model. Finally, we use the cellular automaton model as a starting point to construct a multivariate master equation from a compartment approach from which a continuum model can be derived by a systematic coarse-graining procedure. We find that the resulting continuum equation largely captures the growth behavior of the CA model. The development of our models is guided by experimental observations on growing monolayers.
CONSUMER BEHAVIOR AND FLUCTUATIONS IN ECONOMIC ACTIVITY
Authors: WESTERHOFF FRANK H.
Published: December 2005

We develop a simple Keynesian type business cycle model in which heterogeneous agents are either optimistic or pessimistic. If the majority of the agents are optimistic, then consumption expenditures are high and the economy booms, otherwise consumption expenditures are low and the economy is in a recession. Within our model, the sentiment of the agents is affected by their social interactions. For instance, people regularly meet each other and thus their mood may change. Overall, our model suggests that swings in consumer confidence may generate irregular fluctuations in economic activity.
DESIGN OF THE STATE OBSERVER WITH D-STABILITY FOR UNCERTAIN SYMMETRIC CIRCULANT COMPOSITE SYSTEMS
Authors: LIU MAN , ZHANG YOU , JING YUAN-WEI , ZHANG SI-YING
Published: December 2005

The design of the state observer for a kind of uncertain symmetric circulant composite systems based on regional pole assignment is studied. The "decentralized observer gain matrices" have been obtained by taking use of the special structure of the system. The central observer gain matrix for such a system has the same block symmetric circulant structure as the original system and can be constructed by the "decentralized observer gain matrices." Thus, the problem of designing state observer for such an uncertain system with n·N dimensions based on regional pole assignment can be transformed into the subproblems for N/2+1 or (N + 1)/2 uncertain systems with n dimensions. The central D-stabilizable state observer is also a symmetric circulant composite system. And the design of the observer makes best use of the advantage of interconnections of the system.
UTILIZING EVOLUTIONARY INFORMATION AND GENE EXPRESSION DATA FOR ESTIMATING GENE NETWORKS WITH BAYESIAN NETWORK MODELS
Authors: TAMADA YOSHINORI , BANNAI HIDEO , IMOTO SEIYA , KATAYAMA TOSHIAKI , KANEHISA MINORU , MIYANO SATORU
Published: December 2005

Since microarray gene expression data do not contain sufficient information for estimating accurate gene networks, other biological information has been considered to improve the estimated networks. Recent studies have revealed that highly conserved proteins that exhibit similar expression patterns in different organisms, have almost the same function in each organism. Such conserved proteins are also known to play similar roles in terms of the regulation of genes. Therefore, this evolutionary information can be used to refine regulatory relationships among genes, which are estimated from gene expression data. We propose a statistical method for estimating gene networks from gene expression data by utilizing evolutionarily conserved relationships between genes. Our method simultaneously estimates two gene networks of two distinct organisms, with a Bayesian network model utilizing the evolutionary information so that gene expression data of one organism helps to estimate the gene network of the other. We show the effectiveness of the method through the analysis on Saccharomyces cerevisiae and Homo sapiens cell cycle gene expression data. Our method was successful in estimating gene networks that capture many known relationships as well as several unknown relationships which are likely to be novel. Supplementary information is available at .
HEURISTIC SEARCH IN CONSTRAINED BIPARTITE MATCHING WITH APPLICATIONS TO PROTEIN NMR BACKBONE RESONANCE ASSIGNMENT
Authors: LIN GUOHUI , TEGOS THEODORE , CHEN ZHI-ZHONG
Published: December 2005

The constrained bipartite matching (CBM) problem is a variant of the classical bipartite matching problem that has been well studied in the Combinatorial Optimization community. The input to CBM is an edge-weighted complete bipartite graph in which there are a same number of vertices on both sides and vertices on one side are sequentially ordered while vertices on the other side are partitioned and connected into disjoint directed paths. In a feasible matching, a path must be mapped to consecutive vertices on the other side. The optimization goal is to find a maximum or a minimum weight perfect matching. Such an optimization problem has its applications to scheduling and protein Nuclear Magnetic Resonance peak assignment. It has been shown to be NP-hard and MAX SNP-hard if the perfectness requirement is dropped. In this paper, more results on the inapproximability are presented and IDA*, a memory efficient variant of the well known A* search algorithm, is utilized to solve the problem. Accordingly, search heuristics and a set of heuristic evaluation functions are developed to assist the search, whose effectiveness is demonstrated by a simulation study using real protein NMR backbone resonance assignment instances.
A WAVELET APPROACH FOR THE ANALYSIS OF FOLDING TRAJECTORY OF PROTEIN TRP-CAGE
Authors: YE LEI , CHEN HUAJUN , LIU TING , WU ZHAOHUI , LI JINGYUAN , ZHOU RUHONG
Published: December 2005

Understanding how protein folds into a functional native structure is arguably one of the most challenging problems remaining in computational biology. Currently, the protein folding mechanism is often characterized by calculating the free energy landscape in terms of various reaction coordinates such as the fraction of native contacts, the radius of gyration, the RMS deviation from the native and so on. In this paper, we present a wavelet approach towards understanding the global state changes during protein folding. The approach is based on the wavelet analysis on the trajectories of various reaction coordinates to identify the significant intermediate states or structural motifs in the folding process. We demonstrate through an example protein Trp-cage that this approach extracts crucial information about protein folding intermediate states as well as the time correlation among these states. Furthermore, the current approach reveals a meaningful structural pattern that had been overlooked in previous works, which provides a better understanding of the folding mechanism as well as the limitation of the current force fields.
LINEAR INDEPENDENCE OF PAIRWISE COMPARISONS OF DNA MICROARRAY DATA
Authors: LONGACRE ANGELIKA , SCOTT L. RIDGWAY , LEVINE JERROLD S.
Published: December 2005

Motivation: For DNA microarrays, the gain in certainty by performing multiple experimental repeats is offset by the high cost of each experiment. In a typical experiment, two independent measurements (that is, data from two separate arrays) are combined to yield a single comparative index per gene. Thus, although one uses 2n arrays and performs 2n independent measurements, one obtains only n comparative measurements. We addressed the question: how many of the potential n2 comparisons derivable from such data are actually independent, and what effect do these additional comparisons have on the false positive rate. Results: We show there are precisely 2n - 1 independent comparisons available from among the n2 possibilities. Applying these additional n - 1 independent comparisons to experimental and simulated data reduced the false positive rate by as much as 10-fold, with excellent agreement between experimental and theoretical false positive rates.
A ROBUST ALGORITHM FOR RATIO ESTIMATION IN TWO-COLOR MICROARRAY EXPERIMENTS
Authors: NOVIKOV EUGENE , BARILLOT EMMANUEL
Published: December 2005

The reliability of the algorithms for ratio estimation in two-color microarray image analysis is very important, as these ratios build up the primary source of information for the subsequent analytical procedures (normalization, clustering, classification, etc). Although various algorithms already exist, there is still a need to develop procedures having higher levels of accuracy and robustness. We present a statistical procedure for the detection and removal of aberrant pixels in two-color microarray images. It is based on a linear regression approach, assuming reasonably high level of correlation between the two color channels. This procedure ensures more robust ratio estimation for the spots in both linear regression and traditional segmentation algorithms. The developed algorithms have been evaluated using simulated artificial images and experimental images of different designs. A demonstration version of the software can be downloaded from .
COVARIATION ANALYSIS OF LOCAL AMINO ACID SEQUENCES IN RECURRENT PROTEIN LOCAL STRUCTURES
Authors: WANG LU-YONG
Published: December 2005

Local structural information is supposed to be frequently encoded in local amino acid sequences. Previous research only indicated that some local structure positions have specific residue preferences in some particular local structures. However, correlated pairwise replacements for interacting residues in recurrent local structural motifs from unrelated proteins have not been studied systematically. We introduced a new method fusing statistical covariation analysis and local structure-based alignment. Systematic analysis of structure-based multiple alignments of recurrent local structures from unrelated proteins in representative subset of Protein Databank indicates that covarying residue pairs with statistical significance exist in local structural motifs, in particular β-turns and helix caps. These residue pairs are mostly linked through polar functional groups with direct or indirect hydrogen bonding. Hydrophobic interaction is also a major factor in constraining pairwise amino acid residue replacement in recurrent local structures. We also found correlated residue pairs that are not clearly linked with through-space interactions. The physical constrains underlying these covariations are less clear. Overall, covarying residue pairs with statistical significance exist in local structures from unrelated proteins. The existence of sequence covariations in local structural motifs from unrelated proteins indicates that many relics of local relations are still retained in the tertiary structures after protein folding. It supports the notion that some local structural information is encoded in local sequences and the local structural codes could play important roles in determining native state protein folding topology.
ON THE HAMILTONIAN FORMULATION OF YANG–MILLS GAUGE THEORIES
Authors: VIGNOLO STEFANO , CIANCI ROBERTO , BRUNO DANILO
Published: December 2005

The Hamiltonian formulation of the theory proposed in [1, 2] is given both in the Hamilton–De Donder and in the multimomentum Hamiltonian geometrical approaches. (3 + 3) Yang–Mills gauge theories are dealt with explicitly in order to restate them in terms of Einstein–Cartan like field theories.
CRITICAL PROBLEMS OF RURAL SMALL BUSINESSES: A COMPARISON OF AFRICAN-AMERICAN AND WHITE-OWNED FORMATION AND EARLY GROWTH FIRMS
Authors: HARRIS MICHAEL L. , GRUBB W. LEE , HEBERT FREDERIC J.
Published: December 2005

This study investigated the critical problems encountered by African American and White-owned formation and early growth firms in rural businesses. Analyses were conducted to determine the most critical types of problems encountered by these businesses and the relationship between the types of problems reported and the owner's race and firm's developmental stage. Strategic problems were the most critical problems by business owners in the sample, regardless of race or developmental stage, followed by administrative and operations. Although no significant relationship was found between the type of problems and the owner's race, a significant relationship was found between problem type and the firm's developmental stage, such that businesses in the formation stage are more likely to encounter strategic problems and early growth firms more often experience administrative problems.
VENTURE CAPITAL INVESTMENTS IN EMERGING ECONOMIES: AN EMPIRICAL ANALYSIS
Authors: SALEHIZADEH MEDHI
Published: December 2005

In the international arena an increasing number of entrepreneurs and venture capitalists have succeeded, yielding both micro-level financial rewards and macro-level prosperity and improved economic conditions for many industrialized countries. The next logical "group," with a potential to reap such benefits, is expected to be the emerging economies. This study tabulates and analyzes an emerging market VC-investment dataset, and then identifying and testing a number of independent economic and financial factors that explain such investments for a selected group of emerging countries. Based on 1990-2003 data covering 19 nations, the regression results show four of the five proposed variables, namely GDP per capita, long-term capital inflows, stock market listings, and a measure of stock market correlations, to be significant in explaining VC investments.
PERSONAL TRAITS OF CEOS, INTER-FIRM NETWORKING AND ENTREPRENEURSHIP IN THEIR FIRMS: INVESTIGATING STRATEGIC SME NETWORK PARTICIPANTS
Authors: WINCENT JOAKIM , WESTERBERG MATS
Published: December 2005

This research tests a model including direct and indirect effects of CEO's personal traits (i.e., tolerance for ambiguity and self-efficacy) on entrepreneurial behavior for firms in a specific context, namely strategic SME networks. Findings indicate no direct relationship between personal traits and entrepreneurial behavior on the firm level but reports positive relationship between CEO's traits and levels of inter-firm networking with other strategic SME network participants. Inter-firm networking, in turn, is positively related to entrepreneurial behavior on the firm level. Our results thus indicate that personal traits of the CEO can be important to study in order to understand small firm behavior and performance. The absence of direct links may hide interesting indirect and mediating influences. Based on this, we argue that it is important for future research in the entrepreneurship domain to consider inclusion of context-specific action-based factors that may link CEO traits to entrepreneurship.
Endophenotypes in the Genetic Analyses of Mental Disorders
Authors: Cannon Tyrone D. , Keller Matthew C.
Published: December 2005

Common mental disorders such as schizophrenia, bipolar disorder, and severe major depression are highly heritable, but differ from single-gene (Mendelian) diseases in that they are the end products of multiple causes. Although this fact may help explain their prevalence from an evolutionary perspective, the complexity of the causes of these disorders makes identification of disease-promoting genes much more difficult. The “endophenotype” approach is an alternative method for measuring phenotypic variation that may facilitate the identification of susceptibility genes for complexly inherited traits. Here we examine the endophenotype construct in context of psychiatric genetics. We first develop an evolutionary theoretical framework for common mental disorders and differentiate them from simpler, single-gene disorders. We then provide a definition and description of endophenotypes, elucidating several features that will make a proposed endophenotype useful in psychiatric genetic research and evaluating the methods for detecting and validating such endophenotypes. We conclude with a review of recent results in the schizophrenia literature that illustrate the usefulness of endophenotypes in genetic analyses of mental disorders, and discuss implications of these findings for models of disease causation and nosology. Given that in mental disorders as in behavior generally, the pathways from genotypes to phenotypes are circuitous at best, discernment of endophenotypes more proximal to the effects of genetic variation will aid attempts to link genes to disorders.
Yin yang 1 (YY1) represseshistidine decarboxylasegene expression with SREBP-1a in part through an upstream Sp1 site
Authors: Ai Wandong , Liu Ying , Wang Timothy C.
Published: December 2005

Histidine decarboxylase (HDC) is the enzyme that converts histidine to histamine, a bioamine that plays an important role in many physiological aspects including allergic responses, inflammation, neurotransmission, and gastric acid secretion. In previous studies, we demonstrated that Kruppel-like factor 4 represses HDC promoter activity in a gastric cell line through both an upstream Sp1-binding GC box (GGGCGG sequence) and downstream gastrin-responsive elements. In the current study, Yin Yang 1 (YY1), a pleiotropic transcriptional factor, was also shown in cotransfection assays to repress HDC promoter activity through the upstream GC box. DNA affinity purification assay demonstrated that YY1 was pulled down specifically by the upstream GC box. In addition, sterol-responsive element-binding protein 1a (SREBP-1a), a transcriptional factor that binds YY1, represses the HDC promoter. Interestingly, deletion analysis and cotransfection assays indicated that mutation of the upstream GC box or truncation of downstream gastrin-responsive elements in the HDC promoter disrupted the inhibitory effect of YY1 and SREBP-1a in an identical fashion. Furthermore, quantitative real-time PCR analysis indicated that gastrin treatment downregulated SREBP-1a gene expression and reduced the DNA binding activity of SREBP in EMSAs. Taken together, these results suggest that YY1 and SREBP-1a form a complex to inhibit HDC gene expression through both the upstream GC box and downstream gastrin-responsive elements and gastrin-induced activation of HDC gene expression is mediated at least partly through downregulation of transcriptional repressors such as SREBPs.
Coordinated induction of bile acid detoxification and alternative elimination in mice: role of FXR-regulated organic solute transporter-α/β in the adaptive response to bile acids
Authors: Zollner Gernot , Wagner Martin , Moustafa Tarek , Fickert Peter , Silbert Dagmar , Gumhold Judith , Fuchsbichler Andrea , Halilbasic Emina , Denk Helmut , Marschall Hanns-Ulrich , Trauner Michael
Published: December 2005

The bile acid receptor farnesoid X receptor (FXR) is a key regulator of hepatic defense mechanisms against bile acids. A comprehensive study addressing the role of FXR in the coordinated regulation of adaptive mechanisms including biosynthesis, metabolism, and alternative export together with their functional significance is lacking. We therefore fed FXR knockout (FXR−/−) mice with cholic acid (CA) and ursodeoxycholic acid (UDCA). Bile acid synthesis and hydroxylation were assessed by real-time RT-PCR for cytochrome P-450 (Cyp)7a1, Cyp3a11, and Cyp2b10 and mass spectrometry-gas chromatography for determination of bile acid composition. Expression of the export systems multidrug resistance proteins (Mrp)4–6 in the liver and kidney and the recently identified basoalteral bile acid transporter, organic solute transporter (Ost-α/Ost-β), in the liver, kidney, and intestine was also investigated. CA and UDCA repressed Cyp7a1 in FXR+/+ mice and to lesser extents in FXR−/− mice and induced Cyp3a11 and Cyp2b10 independent of FXR. CA and UDCA were hydroxylated in both genotypes. CA induced Ost-α/Ost-β in the liver, kidney, and ileum in FXR+/+ but not FXR−/− mice, whereas UDCA had only minor effects. Mrp4 induction in the liver and kidney correlated with bile acid levels and was observed in UDCA-fed and CA-fed FXR−/− animals but not in CA-fed FXR+/+ animals. Mrp5/6 remained unaffected by bile acid treatment. In conclusion, we identified Ost-α/Ost-β as a novel FXR target. Absent Ost-α/Ost-β induction in CA-fed FXR−/− animals may contribute to increased liver injury in these animals. The induction of bile acid hydroxylation and Mrp4 was independent of FXR but could not counteract liver toxicity sufficiently. Limited effects of UDCA on Ost-α/Ost-β may jeopardize its therapeutic efficacy.
Ability of short-time Fourier transform method to detect transient changes in vagal effects on hearts: a pharmacological blocking study
Authors: Martinmäki Kaisu , Rusko Heikki , Saalasti Sami , Kettunen Joni
Published: December 2005

Conventional spectral analyses of heart rate variability (HRV) have been limited to stationary signals and have not allowed the obtainment of information during transient autonomic cardiac responses. In the present study, we evaluated the ability of the short-time Fourier transform (STFT) method to detect transient changes in vagal effects on the heart. We derived high-frequency power (HFP, 0.20–0.40 Hz) as a function of time during active orthostatic task (AOT) from the sitting to standing posture before and after selective vagal (atropine sulfate 0.04 mg/kg) and sympathetic (metoprolol 0.20 mg/kg) blockades. The HFP minimum point during the first 30 s after standing up was calculated and compared with sitting and standing values. Reactivity scores describing the fast and slow HFP responses to AOT were calculated by subtracting the minimum and standing values from the sitting value, respectively. The present results, obtained without controlled respiration, showed that in the drug-free condition, HFP decreased immediately after standing up ( P < 0.001) and then gradually increased toward the level characteristic for the standing posture ( P < 0.001), remaining lower than in the sitting baseline posture ( P < 0.001). The magnitudes of the fast and slow HFP responses to AOT were abolished by the vagal blockade ( P < 0.001) and unaffected by the sympathetic blockade. These findings indicate that HFP derived by the STFT method provided a tool for monitoring the magnitude and time course of transient changes in vagal effects on the heart without the need to interfere with normal control by using blocking drugs.
Adrenal splanchnic innervation contributes to the diurnal rhythm of plasma corticosterone in rats by modulating adrenal sensitivity to ACTH
Authors: Ulrich-Lai Yvonne M. , Arnhold Michelle M. , Engeland William C.
Published: December 2005

Activity of the hypothalamic-pituitary-adrenal axis is characterized by a diurnal rhythm with an AM nadir and PM peak. Splanchnic nerve transection disrupts the diurnal rhythm in plasma corticosterone; however, there is a controversy as to whether the nerve-mediated effect is 1) via inhibition in the AM vs. excitation in the PM, or 2) involves changes in adrenal sensitivity to ACTH. The present studies were designed to address these issues. Adult male rats were anesthetized and underwent bilateral transection of the thoracic splanchnic nerve or sham transection. One week after surgery, rats were killed in the AM or PM with collection of nonstress plasma for measurement of corticosterone and ACTH. Plasma corticosterone was increased in the PM relative to the AM; however, plasma corticosterone in the PM was attenuated by splanchnic nerve transection, without affecting plasma ACTH. This decrease in PM plasma corticosterone after nerve-transection was 1) associated with decreased adrenal responsivity to ACTH, 2) associated with decreased adrenal cAMP content, 3) prevented by adrenal demedullation, and 4) not affected by removal of adrenal capsaicin-sensitive afferent fibers. Repeated serial blood sampling from individual rats confirmed the excitatory effect of splanchnic innervation in the PM. These results support the hypothesis that the adrenal splanchnic innervation modulates the diurnal rhythm in plasma corticosterone by increasing adrenal responsivity to ACTH and augmenting steroidogenesis in the PM and suggest that alterations in adrenal corticosterone secretion obscured by pulsatile secretion are more clearly revealed with repeated serial blood sampling.
Prenatal exposure to interleukin-6 results in inflammatory neurodegeneration in hippocampus with NMDA/GABAA dysregulation and impaired spatial learning
Authors: Samuelsson Anne-Maj , Jennische Eva , Hansson Hans-Arne , Holmäng Agneta
Published: December 2005

During pregnancy, infection or immune responses induce cytokine release, which might influence fetal neurodevelopment, leading to neurodegenerative disease in adulthood. Because the hippocampus is a key area for learning and memory, we evaluated 4- and 24-wk-old rats for the effects of early and late prenatal exposure to interleukin-6 (IL-6) on hippocampal morphology, expression of mRNA for IL-6, the γ-aminobutyric acid receptor (GABAAα5), the NR1 subunit of the N-methyl-d-aspartate receptor, and glial fibrillary acidic protein (GFAP), caspase-3 protein and mRNA levels, and learning abilities. Late exposure increased serum IL-6 and hippocampal expression of IL-6 mRNA at 4 and 24 wk. All adult rats showed neuronal loss in the hilus and astrogliosis; males had losses mainly in the CA2 and CA3 regions, and females in CA1. Expression of GABAAα5, NR1, and GFAP mRNA increased in late-exposed males and females at 4 and 24 wk. mRNA and protein levels of the apoptosis marker caspase-3 were increased in all late-exposed rats except males at 4 wk. Evaluation of hippocampus-dependent working memory in the Morris water maze at 20 wk of age showed increases in escape latency and time spent near the pool wall in all IL-6 adult rats, especially females. These findings suggest that fetal IL-6 exposure, especially in late pregnancy, leads to increased IL-6 levels in the circulation and hippocampus, abnormalities of hippocampal structural and morphology, and decreased learning during adulthood.
Altered mitochondrial apparent affinity for ADP and impaired function of mitochondrial creatine kinase in gluteus medius of patients with hip osteoarthritis
Authors: Eimre Margus , Puhke Raivo , Alev Karin , Seppet Evelin , Sikkut Anneli , Peet Nadezhda , Kadaja Lumme , Lenzner Aleks , Haviko Tiit , Seene Teet , Saks Valdur A. , Seppet Enn K.
Published: December 2005

The cellular energy metabolism in human musculus gluteus medius (MGM) under normal conditions and hip osteoarthritis (OA) was explored. The functions of oxidative phosphorylation and energy transport systems were analyzed in permeabilized (skinned) muscle fibers by oxygraphy, in relation to myosin heavy chain (MHC) isoform distribution profile analyzed by SDS-PAGE, and to creatine kinase (CK) and adenylate kinase (AK) activities measured spectrophotometrically in the intact muscle. The results revealed high apparent Km for ADP in regulation of respiration that decreased after addition of creatine in MGM of traumatic patients (controls). OA was associated with increased sensitivity of mitochondrial respiration to ADP, decreased total activities of AK and CK with major reduction in mi-CK fraction, and attenuated effect of creatine on apparent Km for ADP compared with control group. It also included a complete loss of type II fibers in a subgroup of patients with the severest disease grade. It is concluded that energy metabolism in MGM cells is organized into functional complexes of mitochondria and ATPases. It is suggested that because of degenerative remodeling occurring during development of OA, these complexes become structurally and functionally impaired, which results in increased access of exogenous ADP to mitochondria and dysfunction of CK-phosphotransfer system.