bluuebunny/crossref_metadata_2025 huggingface dataset:
Sample size for detecting differentially expressed genes in microarray experiments
Authors: Wei Caimiao , Li Jiangning , Bumgarner Roger E
Published: November 2004

Background

Microarray experiments are often performed with a small number of biological replicates, resulting in low statistical power for detecting differentially expressed genes and concomitant high false positive rates. While increasing sample size can increase statistical power and decrease error rates, with too many samples, valuable resources are not used efficiently. The issue of how many replicates are required in a typical experimental system needs to be addressed. Of particular interest is the difference in required sample sizes for similar experiments in inbred vs. outbred populations (e.g. mouse and rat vs. human).

Results

We hypothesize that if all other factors (assay protocol, microarray platform, data pre-processing) were equal, fewer individuals would be needed for the same statistical power using inbred animals as opposed to unrelated human subjects, as genetic effects on gene expression will be removed in the inbred populations. We apply the same normalization algorithm and estimate the variance of gene expression for a variety of cDNA data sets (humans, inbred mice and rats) comparing two conditions. Using one sample, paired sample or two independent sample t-tests, we calculate the sample sizes required to detect a 1.5-, 2-, and 4-fold changes in expression level as a function of false positive rate, power and percentage of genes that have a standard deviation below a given percentile.

Conclusions

Factors that affect power and sample size calculations include variability of the population, the desired detectable differences, the power to detect the differences, and an acceptable error rate. In addition, experimental design, technical variability and data pre-processing play a role in the power of the statistical tests in microarrays. We show that the number of samples required for detecting a 2-fold change with 90% probability and a p-value of 0.01 in humans is much larger than the number of samples commonly used in present day studies, and that far fewer individuals are needed for the same statistical power when using inbred animals rather than unrelated human subjects.
An information integration theory of consciousness
Authors: Tononi Giulio
Published: November 2004

Background

Consciousness poses two main problems. The first is understanding the conditions that determine to what extent a system has conscious experience. For instance, why is our consciousness generated by certain parts of our brain, such as the thalamocortical system, and not by other parts, such as the cerebellum? And why are we conscious during wakefulness and much less so during dreamless sleep? The second problem is understanding the conditions that determine what kind of consciousness a system has. For example, why do specific parts of the brain contribute specific qualities to our conscious experience, such as vision and audition?

Presentation of the hypothesis

This paper presents a theory about what consciousness is and how it can be measured. According to the theory, consciousness corresponds to the capacity of a system to integrate information. This claim is motivated by two key phenomenological properties of consciousness: differentiation – the availability of a very large number of conscious experiences; and integration – the unity of each such experience. The theory states that the quantity of consciousness available to a system can be measured as the Φ value of a complex of elements. Φ is the amount of causally effective information that can be integrated across the informational weakest link of a subset of elements. A complex is a subset of elements with Φ>0 that is not part of a subset of higher Φ. The theory also claims that the quality of consciousness is determined by the informational relationships among the elements of a complex, which are specified by the values of effective information among them. Finally, each particular conscious experience is specified by the value, at any given time, of the variables mediating informational interactions among the elements of a complex.

Testing the hypothesis

The information integration theory accounts, in a principled manner, for several neurobiological observations concerning consciousness. As shown here, these include the association of consciousness with certain neural systems rather than with others; the fact that neural processes underlying consciousness can influence or be influenced by neural processes that remain unconscious; the reduction of consciousness during dreamless sleep and generalized seizures; and the time requirements on neural interactions that support consciousness.

Implications of the hypothesis

The theory entails that consciousness is a fundamental quantity, that it is graded, that it is present in infants and animals, and that it should be possible to build conscious artifacts.
Morphological correlates of injury-induced reorganization in primate somatosensory cortex
Authors: Churchill James D , Tharp Jason A , Wellman Cara L , Sengelaub Dale R , Garraghty Preston E
Published: November 2004

Background

Topographic reorganization of central maps following peripheral nerve injury has been well characterized. Despite extensive documentation of these physiological changes, the underlying anatomical correlates have yet to be fully explored. In this study, we used Golgi impregnation and light microscopy to assess dendritic morphology following denervation of the glabrous hand surface in adult primates.

Results

After survival durations that permit complete physiologically-defined reorganization, we find a systematic change in the dendritic arborization pattern of both layer II/III pyramidal and layer IV spiny stellate cells in the contralateral hand region of area 3b, compared to unaffected cortical areas. In general, our analyses indicate a progressive expansion of distal regions of the dendritic arbor with no appreciable changes proximally. This pattern of distal dendritic elaboration occurs for both basilar and apical dendrites.

Conclusions

These observations are consistent with the notion that latent inputs gain expression in reorganized cortex after nerve injury via their influence through contacts with more distally located termination sites.
Increased deep sleep in a medication-free, detoxified female offender with schizophrenia, alcoholism and a history of attempted homicide: Case report
Authors: Lindberg Nina , Tani Pekka , Takala Pirjo , Sailas Eila , Putkonen Hanna , Eronen Markku , Virkkunen Matti
Published: November 2004

Background

Psychiatric sleep research has attempted to identify diagnostically sensitive and specific sleep patterns associated with particular disorders. Both schizophrenia and alcoholism are typically characterized by a severe sleep disturbance associated with decreased amounts of slow wave sleep, the physiologically significant, refreshing part of the sleep. Antisocial behaviour with severe aggression, on the contrary, has been reported to associate with increased deep sleep reflecting either specific brain pathology or a delay in the normal development of sleep patterns. The authors are not aware of previous sleep studies in patients with both schizophrenia and antisocial personality disorder.

Case presentation

The aim of the present case-study was to characterize the sleep architecture of a violent, medication-free and detoxified female offender with schizophrenia, alcoholism and features of antisocial personality disorder using polysomnography. The controls consisted of three healthy, age-matched women with no history of physical violence. The offender's sleep architecture was otherwise very typical for patients with schizophrenia and/or alcoholism, but an extremely high amount of deep sleep was observed in her sleep recording.

Conclusions

The finding strengthens the view that severe aggression is related to an abnormal sleep pattern with increased deep sleep. The authors were able to observe this phenomenon in an antisocially behaving, violent female offender with schizophrenia and alcohol dependence, the latter disorders previously reported to be associated with low levels of slow wave sleep. New studies are, however, needed to confirm and explain this preliminary finding.
Mucosal delivery of anti-inflammatory IL-1Ra by sporulating recombinant bacteria
Authors: Porzio Stefano , Bossù Paola , Ruggiero Paolo , Boraschi Diana , Tagliabue Aldo
Published: November 2004

Background

Mucosal delivery of therapeutic protein drugs or vaccines is actively investigated, in order to improve bioavailability and avoid side effects associated with systemic administration. Orally administered bacteria, engineered to produce anti-inflammatory cytokines (IL-10, IL-1Ra), have shown localised ameliorating effects in inflammatory gastro-intestinal conditions. However, the possible systemic effects of mucosally delivered recombinant bacteria have not been investigated.

Results

B. subtilis was engineered to produce the mature human IL-1 receptor antagonist (IL-1Ra). When recombinant B. subtilis was instilled in the distal colon of rats or rabbits, human IL-1Ra was found both in the intestinal lavage and in the serum of treated animals. The IL-1Ra protein in serum was intact and biologically active. IL-1-induced fever, neutrophilia, hypoglycemia and hypoferremia were inhibited in a dose-dependent fashion by intra-colon administration of IL-1Ra-producing B. subtilis. In the mouse, intra-peritoneal treatment with recombinant B. subtilis could inhibit endotoxin-induced shock and death. Instillation in the rabbit colon of another recombinant B. subtilis strain, which releases bioactive human recombinant IL-1β upon autolysis, could induce fever and eventually death, similarly to parenteral administration of high doses of IL-1β.

Conclusions

A novel system of controlled release of pharmacologically active proteins is described, which exploits bacterial autolysis in a non-permissive environment. Mucosal administration of recombinant B. subtilis causes the release of cytoplasmic recombinant proteins, which can then be found in serum and exert their biological activity in vivo systemically.
Protective role of Scoparia dulcis plant extract on brain antioxidant status and lipidperoxidation in STZ diabetic male Wistar rats
Authors: Pari Leelavinothan , Latha Muniappan
Published: November 2004

Background

The aim of the study was to investigate the effect of aqueous extract of Scoparia dulcis on the occurrence of oxidative stress in the brain of rats during diabetes by measuring the extent of oxidative damage as well as the status of the antioxidant defense system.

Methods

Aqueous extract of Scoparia dulcis plant was administered orally (200 mg/kg body weight) and the effect of extract on blood glucose, plasma insulin and the levels of thiobarbituric acid reactive substances (TBARS), hydroperoxides, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and reduced glutathione (GSH) were estimated in streptozotocin (STZ) induced diabetic rats. Glibenclamide was used as standard reference drug.

Results

A significant increase in the activities of plasma insulin, superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and reduced glutathione was observed in brain on treatment with 200 mg/kg body weight of Scoparia dulcis plant extract (SPEt) and glibenclamide for 6 weeks. Both the treated groups showed significant decrease in TBARS and hydroperoxides formation in brain, suggesting its role in protection against lipidperoxidation induced membrane damage.

Conclusions

Since the study of induction of the antioxidant enzymes is considered to be a reliable marker for evaluating the antiperoxidative efficacy of the medicinal plant, these findings suggest a possible antiperoxidative role for Scoparia dulcis plant extract. Hence, in addition to antidiabetic effect, Scoparia dulcis possess antioxidant potential that may be used for therapeutic purposes.
Results of a planned interim toxicity analysis with trimodality therapy, including carboplatin AUC = 4, paclitaxel, 5-fluorouracil, amifostine, and radiation for locally advanced esophageal cancer: preliminary analyses and treatment recommendations from the North Central Cancer Treatment Group
Authors: Jatoi Aminah , Martenson James , Mahoney Michelle R , Lair Bradley S , Brindle Jeffrey S , Nichols Frank , Caron Normand , Rowland Kendrith , Tschetter Loren , Alberts Steven
Published: November 2004

Purpose

An aggressive trimodality approach from the Minnie Pearl Cancer Research Network [carboplatin AUC = 6, days 1 and 22; 5-fluorouracil 225 mg/m2 continuous infusion, days 1–42, paclitaxel 200 mg/m2, days 1 and 22; 45 Gy] has resulted in remarkable pathologic response rates but notable toxicity. This trial was designed to mitigate this toxicity by starting with a lower carboplatin dose, AUC = 4, and by adding subcutaneous amifostine.

Methods

This phase II trial included patients with locally advanced, potentially resectable esophageal cancer. All were to receive the above regimen with modifications of carboplatin AUC = 4 and amifostine 500 mg subcutaneously before radiation. All were then to undergo an esophagectomy. A planned interim toxicity analysis after the first 10 patients was to determine whether the carboplatin dose should escalate to AUC = 6.

Results

Ten patients were enrolled, and all required dose reductions/omissions during neoadjuvant therapy. One patient died from paclitaxel anaphylaxis. Six patients manifested a complete pathologic response.

Conclusion

With this regimen, carboplatin AUC = 4 for patients with locally advanced esophageal cancer is appropriate.
Identification of a SmD3 epitope with a single symmetrical dimethylation of an arginine residue as a specific target of a subpopulation of anti-Sm antibodies
Authors: Mahler Michael , Fritzler Marvin J , Blüthner Martin
Published: November 2004

Anti-Sm antibodies, identified in 1966 by Tan and Kunkel, are highly specific serological markers for systemic lupus erythrematosus (SLE). Anti-Sm reactivity is found in 5–30% of SLE patients, depending on the autoantibody detection system and the racial background of the SLE population. The Sm autoantigen complex comprises at least nine different polypeptides. All of these core proteins can serve as targets of the anti-Sm B-cell response, but most frequently the B and D polypeptides are involved. Because the BB'Sm proteins share cross-reactive epitopes (PPPGMRPP) with U1 specific ribonucleoproteins, which are more frequently targeted by antibodies that are present in patients with mixed connective tissue disease, the SmD polypeptides are regarded as the Sm autoantigens that are most specific to SLE. It was recently shown that the polypeptides D1, D3 and BB' contain symmetrical dimethylarginine, which is a component of a major autoepitope within the carboxyl-terminus of SmD1. In one of those studies, a synthetic dimethylated peptide of SmD1 (amino acids 95–119) exhibited significantly increased immunoreactivity as compared with unmodified SmD1 peptide. Using immobilized peptides, we confirmed that the dimethylated arginine residues play an essential role in the formation of major SmD1 and SmD3 autoepitopes. Moreover, we demonstrated that one particular peptide of SmD3 represents a more sensitive and more reliable substrate for the detection of a subclass of anti-Sm antibodies. Twenty-eight out of 176 (15.9%) SLE patients but only one out of 449 (0.2%) control individuals tested positive for the anti-SmD3 peptide (SMP) antibodies in a new ELISA system. These data indicate that anti-SMP antibodies are exclusively present in sera from SLE patients. Thus, anti-SMP detection using ELISA represents a new serological marker with which to diagnose and discriminate between systemic autoimmune disorders.
Bispectral index versus COMFORT score to determine the level of sedation in paediatric intensive care unit patients: a prospective study
Authors: Triltsch Andreas E , Nestmann Grit , Orawa Helmut , Moshirzadeh Maryam , Sander Michael , Große Joachim , Genähr Arka , Konertz Wolfgang , Spies Claudia D
Published: November 2004

Introduction

Most clinicians give sedatives and analgesics according to their professional experience and the patient's estimated need for sedation. However, this approach is prone to error. Inadequate monitoring of sedation and analgesia may contribute to adverse outcomes and complications. With this in mind, data obtained continuously using nonstimulating methods such as bispectral index (BIS) may have benefits in comparison with clinical monitoring of sedation. The aim of this prospective observational trial was to evaluate the use of electroencephalographic (EEG) BIS for monitoring sedation in paediatric intensive care unit (PICU) patients.

Methods

Forty paediatric patients (<18 years) were sedated for mechanical ventilation in a cardiac surgical and general PICU. In each paediatric patient BIS and COMFORT score were obtained. The study protocol did not influence ongoing PICU therapy. BIS and corresponding COMFORT score were collected three times for each patient. Measurements with the best starting EEG impedances were analyzed further. Deep sedation was defined as a COMFORT score between 8 and 16, and light sedation as a score between 17 and 26. Biometric and physiological data, and Pediatric Risk of Mortality III scores were also recorded.

Results

There was a good correlation (Spearman's rho 0.651; P = 0.001) between BIS and COMFORT score in the presence of deep sedation and low starting impedance. Receiver operating characteristic (ROC) analysis revealed best discrimination between deep and light sedation at a BIS level of 83.

Conclusion

In the presence of deep sedation, BIS correlated satisfactorily with COMFORT score results if low EEG impedances were guaranteed.
Cellular infiltrates and injury evaluation in a rat model of warm pulmonary ischemia–reperfusion
Authors: Van Putte Bart P , Kesecioglu Jozef , Hendriks Jeroen MH , Persy Veerle P , van Marck Erik , Van Schil Paul EY , De Broe Marc E
Published: November 2004

Introduction

Beside lung transplantation, cardiopulmonary bypass, isolated lung perfusion and sleeve resection result in serious pulmonary ischemia–reperfusion injury, clinically known as acute respiratory distress syndrome. Very little is known about cells infiltrating the lung during ischemia–reperfusion. Therefore, a model of warm ischemia–reperfusion injury was applied to differentiate cellular infiltrates and to quantify tissue damage.

Methods

Fifty rats were randomized into eight groups. Five groups underwent warm ischemia for 60 min followed by 30 min and 1–4 hours of warm reperfusion. An additional group was flushed with the use of isolated lung perfusion after 4 hours of reperfusion. One of two sham groups was also flushed. Neutrophils and oedema were investigated by using samples processed with hematoxylin/eosin stain at a magnification of ×500. Immunohistochemistry with antibody ED-1 (magnification ×250) and antibody 1F4 (magnification ×400) was applied to visualize macrophages and T cells. TdT-mediated dUTP nick end labelling was used for detecting apoptosis. Statistical significance was accepted at P < 0.05.

Results

Neutrophils were increased after 30 min until 4 hours of reperfusion as well as after flushing. A doubling in number of macrophages and a fourfold increase in T cells were observed after 30 min until 1 and 2 hours of reperfusion, respectively. Apoptosis with significant oedema in the absence of necrosis was seen after 30 min to 4 hours of reperfusion.

Conclusions

After warm ischemia–reperfusion a significant increase in infiltration of neutrophils, T cells and macrophages was observed. This study showed apoptosis with serious oedema in the absence of necrosis after all periods of reperfusion.
Protective effect of Emblica officinalis ethanolic extract against 7,12-dimethylbenz(a)anthracene (DMBA) induced genotoxicity in Swiss albino mice
Authors: Banu S Mumtaz , Selvendiran K , Singh J Prince Vijeya , Sakthisekaran D
Published: November 2004

Ethanolic extract of Emblica officinalis (EO) fruit extract was evaluated for protection against genotoxicity induced by the rodent carcinogen, 7,12-dimethylbenz(a)anthracene (DMBA). Oral administration of EO fruit extract in various concentrations (100, 250, 500mg/kg b.wt) for seven consecutive days prior to a single intraperitoneal injection of DMBA decreased the frequency of bone marrow micronuclei induced in Swiss albino mice. Significant increases in the liver antioxidants, such as glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR) and detoxifying enzyme glutathione-S-transferase (GST), were found in the fruit extract treated group. The extract also reduced the hepatic levels of the activating enzymes cytochrome (CYt) P450 and Cyt b5. These increased in the carcinogen treated group, which emphasizes its protective effect against the carcinogen. There was a dose-dependent effect of the extract against the genotoxin with the maximum effect at 500 mg/kg b.wt. The protection afforded by EO may be associated with its antioxidant capacity and through its modulatory effect on hepatic activation and detoxifying enzymes.
Spatial and temporal regulation of ventral spinal cord precursor specification by Hedgehog signaling
Authors: Park Hae-Chul , Shin Jimann , Appel Bruce
Published: November 2004

Graded Hedgehog (Hh) signaling patterns the spinal cord dorsoventral axis by inducing and positioning distinct precursor domains, each of which gives rise to a different type of neuron. These domains also generate glial cells,but the full range of cell types that any one precursor population produces and the mechanisms that diversify cell fate are unknown. By fate mapping and clonal analysis in zebrafish, we show that individual ventral precursor cells that express olig2 can form motoneurons, interneurons and oligodendrocytes. However, olig2+ precursors are not developmentally equivalent, but instead produce subsets of progeny cells in a spatially and temporally biased manner. Using genetic and pharmacological manipulations, we provide evidence that these biases emerge from Hh acting over time to set, maintain, subdivide and enlarge the olig2+ precursor domain and subsequently specify oligodendrocyte development. Our studies show that spatial and temporal differences in Hh signaling within a common population of neural precursors can contribute to cell fate diversification.
Epsin potentiatesNotchpathway activity inDrosophilaandC. elegans
Authors: Tian Xiaolin , Hansen Dave , Schedl Tim , Skeath James B.
Published: November 2004

Endocytosis and trafficking within the endocytosis pathway are known to modulate the activity of different signaling pathways. Epsins promote endocytosis and are postulated to target specific proteins for regulated endocytosis. Here, we present a functional link between the Notchpathway and epsins. We identify the Drosophila ortholog of epsin, liquid facets (lqf), as an inhibitor of cardioblast development in a genetic screen for mutants that affect heart development. We find that lqf inhibits cardioblast development and promotes the development of fusion-competent myoblasts, suggesting a model in which lqf acts on or in fusion-competent myoblasts to prevent their acquisition of the cardioblast fate. lqf and Notch exhibit essentially identical heart phenotypes, and lqf genetically interacts with the Notch pathway during multiple Notch-dependent events in Drosophila. We extended the link between the Notch pathway and epsin function to C. elegans, where the C. elegans lqf ortholog acts in the signaling cell to promote the glp-1/Notch pathway activity during germline development. Our results suggest that epsins play a specific, evolutionarily conserved role to promote Notch signaling during animal development and support the idea that they do so by targeting ligands of the Notch pathway for endocytosis.
INCOMPOSITA: a MADS-box gene controlling prophyll development and floral meristem identity inAntirrhinum
Authors: Masiero Simona , Li Ming-Ai , Will Isa , Hartmann Ulrike , Saedler Heinz , Huijser Peter , Schwarz-Sommer Zsuzsanna , Sommer Hans
Published: November 2004

INCOMPOSITA (INCO) is a MADS-box transcription factor and member of the functionally diverse StMADS11 clade of the MADS-box family. The most conspicuous feature of inco mutant flowers are prophylls initiated prior to first whorl sepals at lateral positions of the flower primordium. The developing prophylls physically interfere with subsequent floral organ development that results in aberrant floral architecture. INCO, which is controlled by SQUAMOSA, prevents prophyll formation in the wild type, a role that is novel among MADS-box proteins, and we discuss evolutionary implications of this function. Overexpression of INCO or SVP, a structurally related Arabidopsis MADS-box gene involved in the negative control of Arabidopsis flowering time,conditions delayed flowering in transgenic plants, suggesting that SVP and INCO have functions in common. Enhanced flowering of squamosa mutants in the inco mutant background corroborates this potential role of INCO as a floral repressor in Antirrhinum. One further,hitherto hidden, role of INCO is the positive control of Antirrhinumfloral meristem identity. This is revealed by genetic interactions between inco and mutants of FLORICAULA, a gene that controls the inflorescence to floral transition, together with SQUAMOSA. The complex regulatory and combinatorial relations between INCO, FLORICAULA and SQUAMOSA are summarised in a model that integrates observations from molecular studies as well as analyses of expression patterns and genetic interactions.
Conservation of B-class floral homeotic gene function between maize andArabidopsis
Authors: Whipple Clinton J. , Ciceri Pietro , Padilla Christopher M. , Ambrose Barbara A. , Bandong Simona L. , Schmidt Robert J.
Published: November 2004

The ABC model of flower development, established through studies in eudicot model species, proposes that petal and stamen identity are under the control of B-class genes. Analysis of B- and C-class genes in the grass species rice and maize suggests that the C- and B-class functions are conserved between monocots and eudicots, with B-class genes controlling stamen and lodicule development. We have undertaken a further analysis of the maize B-class genes Silky1, the putative AP3 ortholog, and Zmm16, a putative PI ortholog, in order to compare their function with the Arabidopsis B-class genes. Our results show that maize B-class proteins interact in vitro to bind DNA as an obligate heterodimer, as do Arabidopsis B-class proteins. The maize proteins also interact with the appropriate Arabidopsis B-class partner proteins to bind DNA. Furthermore, we show that maize B-class genes are capable of rescuing the corresponding Arabidopsis B-class mutant phenotypes. This demonstrates B-class activity of the maize gene Zmm16, and provides compelling evidence that B-class gene function is conserved between monocots and eudicots.
α3β1 integrin modulates neuronal migration and placement during early stages of cerebral cortical development
Authors: Schmid Ralf S. , Shelton Stephanie , Stanco Amelia , Yokota Yukako , Kreidberg Jordan A. , Anton E. S.
Published: November 2004

We show that α3 integrin mutation disrupts distinct aspects of neuronal migration and placement in the cerebral cortex. The preplate develops normally in α3 integrin mutant mice. However, time lapse imaging of migrating neurons in embryonic cortical slices indicates retarded radial and tangential migration of neurons, but not ventricular zone-directed migration. Examination of the actin cytoskeleton of α3 integrin mutant cortical cells reveals aberrant actin cytoskeletal dynamics at the leading edges. Deficits are also evident in the ability of developing neurons to probe their cellular environment with filopodial and lamellipodial activity. Calbindin or calretinin positive upper layer neurons as well as the deep layer neurons ofα3 integrin mutant mice expressing EGFP were misplaced. These results suggest that α3β1 integrin deficiency impairs distinct patterns of neuronal migration and placement through dysregulated actin dynamics and defective ability to search and respond to migration modulating cues in the developing cortex.
Repression of Dpp targets in theDrosophilawing by Brinker
Authors: Winter Stephanie E. , Campbell Gerard
Published: November 2004

Patterning along developing body axes is regulated by gradients of transcription factors, which activate or repress different genes above distinct thresholds. Understanding differential threshold responses requires knowledge of how these factors regulate transcription. In the Drosophila wing, expression of genes such as omb and sal along the anteroposterior axis is restricted by lateral-to-medial gradients of the transcriptional repressor Brinker (Brk). omb is less sensitive to repression by Brk than sal and is consequently expressed more laterally. Contrary to previous suggestions, we show that Brk cannot repress simply by competing with activators, but requires specific repression domains along with its DNA-binding domain. Brk possesses at least three repression domains, but these are not equivalent; one, 3R, is sufficient to repress omb but not sal. Thus, although sal and omb show quantitative differences in their response to Brk, there are qualitative differences in the mechanisms that Brk uses to repress them.
The Strength of Weak Ties You Can Trust: The Mediating Role of Trust in Effective Knowledge Transfer
Authors: Levin Daniel Z. , Cross Rob
Published: November 2004

Research has demonstrated that relationships are critical to knowledge creation and transfer, yet findings have been mixed regarding the importance of relational and structural characteristics of social capital for the receipt of tacit and explicit knowledge. We propose and test a model of two-party (dyadic) knowledge exchange, with strong support in each of the three companies surveyed. First, the link between strong ties and receipt of useful knowledge (as reported by the knowledge seeker) was mediated by competence- and benevolence-based trust. Second, once we controlled for these two trustworthiness dimensions, the structural benefit of weak ties emerged. This finding is consistent with prior research suggesting that weak ties provide access to nonredundant information. Third, competence-based trust was especially important for the receipt of tacit knowledge. We discuss implications for theory and practice.
Innovation and Attention to Detail in the Quality Improvement Paradigm
Authors: Naveh Eitan , Erez Miriam
Published: November 2004

This study asserted that quality improvement (QI) requires the coexistence of two cultural values of innovation and attention to detail and proposed that their coexistence depends on the implementation of multiple QI practices. A longitudinal QI intervention, with five phases, consisting of multiple QI practices—ISO 9000, QI teams, quality goals, and coaching and communication by top management—was implemented.

Participants were 425 employees working in 18 departments of four manufacturing plants. The QI practices were implemented in a different order in each one of the plants. Measures were assessed five times, at the end of each implementation phase. We used hierarchical linear models (HLM) to account for the nested structure of departments within the plants and the five repeated measures.

Findings demonstrated that the above-mentioned QI practices had differential effects on innovation and attention to detail: ISO 9000 positively affected attention to detail but negatively affected innovation. Both QI teams and quality goals positively affected innovation. Thus, the multiple QI initiative enabled the coexistence of the two aforementioned cultural values. Both cultural values had a positive impact on performance quality and productivity and partially mediated the effects of ISO 9000 on productivity.
Selfish Routing in Capacitated Networks
Authors: Correa José R. , Schulz Andreas S. , Stier-Moses Nicolás E.
Published: November 2004

According to Wardrop's first principle, agents in a congested network choose their routes selfishly, a behavior that is captured by the Nash equilibrium of the underlying noncooperative game. A Nash equilibrium does not optimize any global criterion per se, and so there is no apparent reason why it should be close to a solution of minimal total travel time, i.e., the system optimum. In this paper, we offer positive results on the efficiency of Nash equilibria in traffic networks. In contrast to prior work, we present results for networks with capacities and for latency functions that are nonconvex, nondifferentiable, and even discontinuous.

The inclusion of upper bounds on arc flows has early been recognized as an important means to provide a more accurate description of traffic flows. In this more general model, multiple Nash equilibria may exist and an arbitrary equilibrium does not need to be nearly efficient. Nonetheless, our main result shows that the best equilibrium is as efficient as in the model without capacities. Moreover, this holds true for broader classes of travel cost functions than considered hitherto.
On Houseswapping, the Strict Core, Segmentation, and Linear Programming
Authors: Quint Thomas , Wako Jun
Published: November 2004

We consider the n-player houseswapping game of Shapley and Scarf (1974), with indifferences in preferences allowed. It is well known that the strict core of such a game may be empty, single valued, or multi valued. We define a condition on such games called segmentability, which means that the set of players can be partitioned into a top trading segmentation. It generalizes Gale's well-known idea of the partition of players into top trading cycles (which is used to find the unique strict core allocation in the model with no indifference). We prove that a game has a nonempty strict core if and only if it is segmentable. We then use this result to devise an O(n 3) algorithm which takes as input any houseswapping game, and returns either a strict core allocation or a report that the strict core is empty. Finally, we are also able to construct a linear inequality system whose feasible region's extreme points precisely correspond to the allocations of the strict core. This last result parallels the results of Vande Vate (1989) and Rothblum (1992) for the marriage game of Gale and Shapley (1962).
The Cost Effects of Component Commonality: A Literature Review Through a Management-Accounting Lens
Authors: Labro Eva
Published: November 2004

In this paper I review the component commonality literature through a management-accounting lens, focusing on the cost effects of an increase in the use of the same version of a component across multiple products. The bulk of this literature is of a theoretical nature, for example, analytical models, programming models, or conjectures based on casual observations of practice. Some of this literature purports, especially in introductions to the topic, that cost generally decreases with increasing commonality. However, based on a review of the theoretical literature using an activity-based costing framework and distinguishing between cost-driver and cost-rate effects, I conclude that the cost picture is more subtle. In other words, it is too early to make any general statement about the effect of increasing commonality on total costs. Moving to the limited empirical literature on the topic, consisting of case studies (sometimes combined with simulation) and empirical research on larger data sets, the conclusion that there is even more room for future research becomes evident.
Value Creation in Service Delivery: Relating Market Segmentation, Incentives, and Operational Performance
Authors: Güneş Evrim D. , Akşin O. Zeynep
Published: November 2004

This paper studies service-delivery design in settings where firms engage in value-creation activities that have the objective of generating additional revenue from customer interactions. The paper provides a general modelling framework to analyze the ties between market segmentation decisions, incentives, and process performance in such service-delivery systems. The firm is modelled as a single-server queue, in a principal-agent framework. Customers have different value-generation potentials whose realizations are observed by the server but not by the manager of the firm. The manager determines a market segmentation scheme given an overall customer value-generation profile, which divides customers into two groups (high and low), and also determines a service level for each segment. The server decides which of the two available service levels (high and low) to provide for each customer, given a compensation scheme offered by the manager. The optimal market segmentation decision, optimal service-level choice, and a set of optimal linear incentive contracts that enable their implementation are characterized. The robustness of these strategies is explored with respect to model parameters and assumptions. It is shown that a market segmentation scheme that combines revenue generation concerns with their process implications is essential for success. Characteristics of appropriate incentive schemes are identified.
New Product Introduction: Timing, Design, and Pricing
Authors: Klastorin Ted , Tsai Weiyu
Published: November 2004

In this paper, we consider the case when two profit-maximizing firms enter a new market with a competing product that has a finite (and known) life cycle. Both firms make design decisions simultaneously without information about the other firm's decisions. The order of entry is a function of the two firms' product design levels and design capabilities. The first firm entering the market sets a monopoly price for its product and enjoys a monopoly situation until the second firm enters the market. When the second firm enters the market, both firms simultaneously set (or reset) their product prices knowing the design of both products at that time (and we assume those prices are fixed for the remainder of the product's life).

We develop a game-theoretic model that represents the new product introduction process and show that a subgame-perfect Nash equilibrium occurs under certain conditions defined by the expected product life span, product cost, development time, and customer preferences. Our model shows that product differentiation always arises at equilibrium due to the joint effects of resource utilization, price competition, and product life cycle.

A critical parameter for our model is a product-specific index B that we define; we show how it can be easily calculated from existing data. We then use a numerical example to illustrate managerial implications for a new product development process when the product life span is finite. We show that the strategy of time-based competition is the natural result of firms' improving development capability, reducing product cost, and increasing customer preference. In other words, it is not wise for profit-maximizing firms to arbitrarily shorten product life cycle for the sake of competition, because all firms are worse off. Our results also indicate that the first entrant into the market does not necessarily earn the greatest profit, and that a firm with low-cost advantage or fast design capability might not choose to come to market first to maximize its profit in the product life cycle.
Dynamic Vehicle Routing Based on Online Traffic Information
Authors: Fleischmann Bernhard , Gnutzmann Stefan , Sandvoß Elke
Published: November 2004

With the increasing availability of real-time information and communication systems in logistics, the need for appropriate planning algorithms, which make use of this technology, arises. Customers in transport markets increasingly expect quicker and more flexible fulfillment of their orders, especially in the electronic marketplace. This paper considers a dynamic routing system that dispatches a fleet of vehicles according to customer orders arriving at random during the planning period. Each customer order requires a transport from a pickup location to a delivery location in a given time window. The system disposes of online communication with all drivers and customers and, in addition, disposes of online information on travel times from a traffic management center. This paper presents a planning framework for this situation which, to our knowledge, has not yet been addressed in the literature. It then describes three routing procedures for event-based dispatching, which differ in the length of the planning horizon per event. We focus on the use of dynamic travel time information, which requires dynamic shortest path calculations. The procedures are tested and compared using real-life data of an urban traffic management center and a logistics service provider.
Absolute rate summability domains
Authors: Dağadur I.
Published: November 2004

In this paper we show that for ℓπA, E and E′ are equivalent, and that if either Λ┴πA or IπA is invariant they both are, and then Λ┴πA = IπA = lπA.
Study of Jet‐Cooled Bis(η6‐Benzene)Chromium by Multiphoton Zero Kinetic Energy—Mass‐Analyzed Threshold Ionization Spectroscopy
Authors: Ketkov Sergey Yu. , Selzle Heinrich L. , Schlag Edward W.
Published: November 2004

Zero kinetic energy‐mass‐analyzed threshold ionization (ZEKE‐MATI) spectra of jet‐cooled (η6‐C6H6)2Cr have been obtained for the first time with use of the 3dz2 → R4px,y Rydberg transition as the initial step of the electronic excitation. The ionization potential of (η6‐C6H6)2Cr determined on the basis of the ZEKE‐MATI experiment is 44087 ± 3 cm−1 (5.4661 ± 0.0004 eV). The binding energy of the R4px,y electron is 17333 ± 3 cm−1. The frequencies of the symmetric metal‐ring stretching vibration and CH umbrella vibration in the gas‐phase ground‐state molecular cation (η6‐C6H6)2Cr+ are 262 ± 5 and 788 ± 4 cm−1, respectively.
Conical Intersections: Relaxation, Dephasing, and Dynamics in a Simple Model
Authors: Katz Gil , Kosloff Ronnie , Ratner Mark A.
Published: November 2004

Conical intersections occur on potential energy surfaces of many medium‐sized and larger molecules. Their investigation, which has been ongoing for more than six decades, shows that vibronic coupling and relaxation behaviors at conical intersections can become quite complex and show large quantum effects. We present calculations of dynamical behavior in very simple (two‐dimensional, degenerate, non‐displaced) conical intersection models. The focus is placed on the effects of bath interactions on conical behavior—that is, the extent to which electronic dephasing, nuclear relaxation, and electronic relaxation affect the initially excited wave packet evolving on conical intersection surface. The calculations are carried through using a density matrix picture, with a Lindblad semi‐group formalism to characterize relaxation. We observe large quantum effects that act particularly on true conical structures (anti‐symmetric with respect to the mixing coordinate), as opposed to comparable‐strength interactions without this symmetry. Significant changes in excited‐state population decay, and even larger and more striking changes in the (observable) bleach recovery signal, are found.
Ultrafast Charge Separation Due to Excited State Symmetry Breaking in Dimers of Push‐Pull Perylenes
Authors: Fuller Michael J. , Gusev Alexey V. , Wasielewski Michael R.
Published: November 2004

Photoexcitation of chromophoric dimers constrained to a symmetric π‐stacked geometry by their molecular structure usually produce excimers independent of solvent polarity, while dimers with edge‐to‐edge perpendicular π systems undergo excited‐state symmetry breaking in highly polar solvents leading to intradimer charge separation. We present direct evidence for symmetry breaking in the lowest excited singlet state of a symmetric cofacial dimer of 9‐(N‐pyrrolidinyl)‐1,6‐bis(3,5‐di‐tert‐butylphenoxy)perylene‐3,4‐dicarboximide (5PMI) in the low‐polarity solvent toluene to produce a radical ion pair quantitatively. This dimer, cof‐5PMI2, was synthesized by attaching two 5PMI chromophores via imide groups to a xanthene spacer. For comparison, a linear symmetric dimer, lin‐5PMI2, was prepared in which the 5PMI chromophores are linked end‐to‐end via a N‐N single bond between their imides. The edge‐to‐edge π systems of the 5PMI chromophores within lin‐5PMI2 are perpendicular to one another. Ground‐state absorption spectra of both 5PMI dimers show exciton coupling, which is consistent with the orientation of the 5PMI chromophores relative to one another. Ultrafast transient absorption spectroscopy following excitation of the dimers with 400‐nm, 80‐fs laser pulses shows that quantitative intradimer electron transfer occurs in cof‐5PMI2 in toluene with τ = 0.9 ps, followed by charge recombination to ground state with τ = 780 ps. Similar measurements on lin‐5PMI2 reveal that photoinduced electron transfer does not occur in toluene, but occurs in more polar solvents such as 2‐methyltetra‐hydrofuran, wherein τ = 4.5 ps for charge separation and τ = 660 ps for charge recombination. Excited‐state symmetry breaking in 5PMI dimers provides new routes to biomimetic charge separation and storage assemblies that can be more easily prepared and modified than those based on multiple tetrapyrrole macrocycles.
Electronic Circular Dichroism Spectroscopy of 1‐(R)‐Phenylethanol: The “Sector Rule” Revisited and an Exploration of Solvent Effects
Authors: Macleod Neil A. , Butz Patrick , Simons John P. , Grant Guy H. , Baker Christopher M. , Tranter George E.
Published: November 2004

The sensitivity of the electronic circular dichroism (ECD) of a chiral molecule to structural and environmental changes has been investigated using 1‐(R)‐phenylethanol (1‐PE) as the benchmark solute and cyclohexane and water as the trial solvents. Rotatory strengths associated with the π → π* (1Lb) electronic transition have been calculated ab initio for: (a) isolated 1‐PE, as a function of the dihedral angles within its chiral side chain and between the side chain and the aromatic ring: these confirm the validity of the empirical “sector rule” but with the signs reversed; (b) the singly and doubly hydrated clusters of 1‐PE, isolated in the gas phase; (c) 1‐PE and its singly and doubly hydrated clusters embedded in a polarizable dielectric continuum; and (d) 1‐PE in an aqueous solution interacting with the local hydration shell and with the polarizable dielectric continuum, using averaged solute structures computed from the fluctuating solute and solvent configurations generated via molecular dynamics simulations.

The ab initio calculations (conducted with GAUSSIAN 98) employed configuration interaction singles (CIS) or time‐dependent density functional theory (TD‐DFT) procedures using basis sets of double‐ and triple‐zeta quality. The results have been related to experimental observations and discussed in terms of changes in the molecular geometry and solvent‐induced perturbations.
Isotope Effects in the High‐Overtone Spectrum of C‐H Stretches in HCN
Authors: Sage Martin L.
Published: November 2004

The same Morse potential predicts the vibrational overtone spectra for the various isotopomers of HCl. However, the C‐H stretching overtones of HCN require different Morse parameters for different isotopomers. This paper considers how the other vibrational coordinates change the frequency of the C‐H overtones. A simple model is used that considers the C‐H to be a Morse oscillator and the other motions to be harmonic oscillators. The change in bending frequency with overtone level and kinetic coupling between the two stretching motions accounts for the observed C‐H overtone spectrum. The simple Morse potential that accounts for a single isotopomer is only an effective potential.