bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sample size for detecting differentially expressed genes in microarray experiments
Authors: Wei Caimiao , Li Jiangning , Bumgarner Roger E 
Published: November 2004

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractAnti-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

Abstract
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

Abstract
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.
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.