CiteULike: Author Freeman

Twenty-five years of quantitative PCR for gene expression analysis.

H Vanguilder — 2008-07-25T07:55:24-00:00

BioTechniques, Vol. 44, No. 5. (April 2008), pp. 619-626.

Following its invention 25 years ago, PCR has been adapted for numerous molecular biology applications. Gene expression analysis by reverse-transcription quantitative PCR (RT-qPCR) has been a key enabling technology of the post-genome era. Since the founding of BioTechniques, this journal has been a resource for the improvements in qPCR technology, experimental design, and data analysis. qPCR and, more specifically, real-time qPCR has become a routine and robust approach for measuring the expression of genes of interest, validating microarray experiments, and monitoring biomarkers. The use of real-time qPCR has nearly supplanted other approaches (e.g., Northern blotting, RNase protection assays). This review examines the current state of qPCR for gene expression analysis now that the method has reached a mature stage of development and implementation. Specifically, the different fluorescent reporter technologies of real-time qPCR are discussed as well as the selection of endogenous controls. The conceptual framework for data analysis methods is also presented to demystify these analysis techniques. The future of qPCR remains bright as the technology becomes more rapid, cost-effective, easier to use, and capable of higher throughput.

The Sorcerer II Global Ocean Sampling Expedition: Northwest Atlantic through Eastern Tropical Pacific

Douglas Rusch — 2007-03-13T17:06:35-00:00

PLoS Biology, Vol. 5, No. 3. (1 March 2007), e77.

The world's oceans contain a complex mixture of micro-organisms that are for the most part, uncharacterized both genetically and biochemically. We report here a metagenomic study of the marine planktonic microbiota in which surface (mostly marine) water samples were analyzed as part of the Sorcerer II Global Ocean Sampling expedition. These samples, collected across a several-thousand km transect from the North Atlantic through the Panama Canal and ending in the South Pacific yielded an extensive dataset consisting of 7.7 million sequencing reads (6.3 billion bp). Though a few major microbial clades dominate the planktonic marine niche, the dataset contains great diversity with 85% of the assembled sequence and 57% of the unassembled data being unique at a 98% sequence identity cutoff. Using the metadata associated with each sample and sequencing library, we developed new comparative genomic and assembly methods. One comparative genomic method, termed “fragment recruitment,” addressed questions of genome structure, evolution, and taxonomic or phylogenetic diversity, as well as the biochemical diversity of genes and gene families. A second method, termed “extreme assembly,” made possible the assembly and reconstruction of large segments of abundant but clearly nonclonal organisms. Within all abundant populations analyzed, we found extensive intra-ribotype diversity in several forms: (1) extensive sequence variation within orthologous regions throughout a given genome; despite coverage of individual ribotypes approaching 500-fold, most individual sequencing reads are unique; (2) numerous changes in gene content some with direct adaptive implications; and (3) hypervariable genomic islands that are too variable to assemble. The intra-ribotype diversity is organized into genetically isolated populations that have overlapping but independent distributions, implying distinct environmental preference. We present novel methods for measuring the genomic similarity between metagenomic samples and show how they may be grouped into several community types. Specific functional adaptations can be identified both within individual ribotypes and across the entire community, including proteorhodopsin spectral tuning and the presence or absence of the phosphate-binding gene PstS.

Funding pharmaceutical innovation through direct tax credits

Kristina Lybecker — 2008-07-23T12:38:20-00:00

Health Economics, Policy and Law, Vol. 2, No. 03. (2007), pp. 267-284.

Rising pharmaceutical prices, increasing demand for more effective innovative drugs and growing public outrage have heightened criticism of the pharmaceutical industry. The public debate has focused on drug prices and access. As a consequence, the patent system is being reexamined as an efficient mechanism for encouraging pharmaceutical innovation and drug development. We propose an alternative to the existing patent system, instead rewarding the innovating firm with direct tax credits in exchange for marginal cost pricing. This concept is based on the fundamental assumption that innovation that benefits society at large may be financed publicly. As an industry which produces a social good characterized by high fixed costs, high information and regulatory costs, and relatively low marginal costs of production, pharmaceuticals are well-suited to such a mechanism. Under this proposal, drug prices fall, consumer surplus increases, access is enhanced, and the incentives to innovate are preserved.

Inter-hospital variations in length of hospital stay following hip fracture

Martyn Parker — 2008-07-23T11:52:09-00:00

Age Ageing, Vol. 27, No. 3. (1 May 1998), pp. 333-337.

OBJECTIVE:: to investigate differences in length of hospital stay after hip fracture. DESIGN:: prospective survey of a consecutive series of patients admitted with an acute hip fracture and followed-up for 90 days after admission. SETTING:: eight hospitals in the East Anglian region. SUBJECTS:: 580 patients admitted with a hip fracture. MAIN OUTCOME MEASURES:: mortality, length of hospital stay, place of discharge and transfer of patients between hospitals. RESULTS:: there was a significant difference in the median lengths of hospital stay between centres (range 13-28 days). A prolonged hospital stay was associated with increased age, decreased activities of daily living score and delay from surgery to mobilization. Hospitals which had a policy of transferring patients to other wards prior to discharge tended to have a longer length of hospital stay. CONCLUSIONS:: large differences in the duration of inpatient stay exist between hospitals. Centres which transferred a high proportion of patients before discharge had a longer length of stay. 10.1093/ageing/27.3.333

Centrality in social networks: Conceptual clarification

Linton Freeman — 2005-08-11T15:39:34-00:00

Social Networks, Vol. 1, No. 3. (1979), pp. 215-239.

The intuitive background for measures of structural centrality in social networks is reviewed and existing measures are evaluated in terms of their consistency with intuitions and their interpretability.Three distinct intuitive conceptions of centrality are uncovered and existing measures are refined to embody these conceptions. Three measures are developed for each concept, one absolute and one relative measure of the centrality of positions in a network, and one reflecting the degree of centralization of the entire network. The implications of these measures for the experimental study of small groups is examined.

Pigeons combine compass and landmark guidance in familiar route navigation.

Dora Biro — 2007-04-25T14:27:40-00:00

Proc Natl Acad Sci U S A (23 April 2007)

How do birds orient over familiar terrain? In the best studied avian species, the homing pigeon (Columba livia), two apparently independent primary mechanisms are currently debated: either memorized visual landmarks provide homeward guidance directly, or birds rely on a compass to home from familiar locations. Using miniature Global Positioning System tracking technology and clock-shift procedures, we set sun-compass and landmark information in conflict, showing that experienced birds can accurately complete their memorized routes by using landmarks alone. Nevertheless, we also find that route following is often consistently offset in the expected compass direction, faithfully reproducing the shape of the track, but in parallel. Thus, we demonstrate conditions under which compass orientation and landmark guidance must be combined into a system of simultaneous or oscillating dual control.

Exploiting Low-Dimensional Structure in Astronomical Spectra

Joseph Richards — 2008-07-21T16:17:49-00:00

(18 Jul 2008)

Dimension-reduction techniques can greatly improve statistical inference in astronomy. A standard approach is to use Principal Components Analysis (PCA). In this work we apply a recently-developed technique, diffusion maps, to astronomical spectra for data parameterization and dimensionality reduction, and develop a robust, eigenmode-based framework for regression. We show how our framework provides a computationally efficient means by which to predict redshifts of galaxies, and thus could inform more expensive redshift estimators such as template cross-correlation. It also provides a natural means by which to identify outliers (e.g., misclassified spectra, spectra with anomalous features). We analyze 3835 SDSS spectra and show how our framework yields a more than 95% reduction in dimensionality. Finally, we show that the prediction error of the diffusion map-based regression approach is markedly smaller than that of a similar approach based on PCA, clearly demonstrating the superiority of diffusion maps over PCA for this regression task.

STAT3 mutations in the hyper-IgE syndrome.

SM Holland — 2008-07-19T22:05:20-00:00

The New England journal of medicine, Vol. 357, No. 16. (18 October 2007), pp. 1608-1619.

BACKGROUND: The hyper-IgE syndrome (or Job's syndrome) is a rare disorder of immunity and connective tissue characterized by dermatitis, boils, cyst-forming pneumonias, elevated serum IgE levels, retained primary dentition, and bone abnormalities. Inheritance is autosomal dominant; sporadic cases are also found. METHODS: We collected longitudinal clinical data on patients with the hyper-IgE syndrome and their families and assayed the levels of cytokines secreted by stimulated leukocytes and the gene expression in resting and stimulated cells. These data implicated the signal transducer and activator of transcription 3 gene (STAT3) as a candidate gene, which we then sequenced. RESULTS: We found increased levels of proinflammatory gene transcripts in unstimulated peripheral-blood neutrophils and mononuclear cells from patients with the hyper-IgE syndrome, as compared with levels in control cells. In vitro cultures of mononuclear cells from patients that were stimulated with lipopolysaccharide, with or without interferon-gamma, had higher tumor necrosis factor alpha levels than did identically treated cells from unaffected persons (P=0.003). In contrast, the cells from patients with the hyper-IgE syndrome generated lower levels of monocyte chemoattractant protein 1 in response to the presence of interleukin-6 (P=0.03), suggesting a defect in interleukin-6 signaling through its downstream mediators, one of which is STAT3. We identified missense mutations and single-codon in-frame deletions in STAT3 in 50 familial and sporadic cases of the hyper-IgE syndrome. Eighteen discrete mutations, five of which were hot spots, were predicted to directly affect the DNA-binding and SRC homology 2 (SH2) domains. CONCLUSIONS: Mutations in STAT3 underlie sporadic and dominant forms of the hyper-IgE syndrome, an immunodeficiency syndrome involving increased innate immune response, recurrent infections, and complex somatic features.

Causes of death in hyper-IgE syndrome.

AF Freeman — 2008-07-19T22:10:08-00:00

The Journal of allergy and clinical immunology, Vol. 119, No. 5. (May 2007), pp. 1234-1240.

BACKGROUND: Hyper-IgE syndrome (HIES) is characterized by recurrent pyogenic infections, eczema, increased serum IgE levels, and a variety of connective tissue and skeletal system abnormalities. Little has been published regarding the causes of death in these patients or pathologic findings. OBJECTIVE: To identify the cause of death in patients with HIES and to describe pathologic findings in fatal HIES. METHODS: We reviewed the medical records and autopsy slides of 6 patients with HIES with autopsies performed at our institution. RESULTS: All 6 patients with HIES were women and ranged in age from 24 to 40 years. All patients had a history of cystic lung disease and had pneumonia at the time of death, with Pseudomonas aeruginosa and fungal organisms predominating. Pulmonary fungal vascular invasion with fatal hemorrhage was observed in 3 patients, and metastatic fungal disease to the brain was observed in 2 patients caused by Aspergillus fumigatus and Scedosporium prolificans. Four patients had evidence of renal tubular injury, which was likely from amphotericin B toxicity; 3 patients had glomerulosclerosis; and 1 patient had 2 kidney angiomyolipomas. CONCLUSIONS: Our series highlights the important role Pseudomonas and Aspergillus species play in patients with HIES with cystic lung disease. Intensified antifungal and gram-negative bacterial prophylaxis need evaluation as possible strategies to prevent these infectious complications in patients with cystic lung disease. CLINICAL IMPLICATIONS: Fungal and Pseudomonas infection of cystic lung disease in HIES may be life threatening, and the proper management and prevention of these infections need continued investigation.

What makes one person paranoid and another person anxious? The differential prediction of social anxiety and persecutory ideation in an experimental situation

D Freeman — 2008-07-19T21:21:40-00:00

Psychological Medicine, Vol. 38, No. 08. (2008), pp. 1121-1132.

Background In recent years a close association between anxiety and persecutory ideation has been established, contrary to the traditional division of neurosis and psychosis. Nonetheless, the two experiences are distinct. The aim of this study was to identify factors that distinguish the occurrence of social anxiety and paranoid thoughts in an experimental situation.

Learning Low-Level Vision

William Freeman — 2006-08-15T19:43:28-00:00

International Journal of Computer Vision, Vol. 40, No. 1. (2000), pp. 25-47.

We describe a learning-based method for low-level vision problems#estimating scenes from images. We generate a synthetic world of scenes and their corresponding rendered images, modeling their relationships with a Markov network.

Model for end-stage liver disease (MELD) and allocation of donor livers.

R Wiesner — 2008-07-11T05:51:33-00:00

Gastroenterology, Vol. 124, No. 1. (January 2003), pp. 91-96.

BACKGROUND & AIMS: A consensus has been reached that liver donor allocation should be based primarily on liver disease severity and that waiting time should not be a major determining factor. Our aim was to assess the capability of the Model for End-Stage Liver Disease (MELD) score to correctly rank potential liver recipients according to their severity of liver disease and mortality risk on the OPTN liver waiting list. METHODS: The MELD model predicts liver disease severity based on serum creatinine, serum total bilirubin, and INR and has been shown to be useful in predicting mortality in patients with compensated and decompensated cirrhosis. In this study, we prospectively applied the MELD score to estimate 3-month mortality to 3437 adult liver transplant candidates with chronic liver disease who were added to the OPTN waiting list at 2A or 2B status between November, 1999, and December, 2001. RESULTS: In this study cohort with chronic liver disease, 412 (12%) died during the 3-month follow-up period. Waiting list mortality increased directly in proportion to the listing MELD score. Patients having a MELD score <9 experienced a 1.9% mortality, whereas patients having a MELD score > or =40 had a mortality rate of 71.3%. Using the c-statistic with 3-month mortality as the end point, the area under the receiver operating characteristic (ROC) curve for the MELD score was 0.83 compared with 0.76 for the Child-Turcotte-Pugh (CTP) score (P < 0.001). CONCLUSIONS: These data suggest that the MELD score is able to accurately predict 3-month mortality among patients with chronic liver disease on the liver waiting list and can be applied for allocation of donor livers.

Refinement types for ML

Tim Freeman — 2008-07-10T06:42:38-00:00

SIGPLAN Not., Vol. 26, No. 6. (June 1991), pp. 268-277.

Web content management by self-organization

RT Freeman — 2008-07-09T08:40:49-00:00

Neural Networks, IEEE Transactions on, Vol. 16, No. 5. (2005), pp. 1256-1268.

We present a new method for content management and knowledge discovery using a topology-preserving neural network. The method, termed topological organization of content (TOC), can generate a taxonomy of topics from a set of unannotated, unstructured documents. The TOC consists of a hierarchy of self-organizing growing chains (GCs), each of which can develop independently in terms of size and topics. The dynamic development process is validated continuously using a proposed entropy-based Bayesian information criterion (BIC). Each chain meeting the criterion spans child chains, with reduced vocabularies and increased specializations. This results in a topological tree hierarchy, which can be browsed like a table of contents directory or web portal. A brief review is given on existing methods for document clustering and organization, and clustering validation measures. The proposed approach has been tested and compared with several existing methods on real world web page datasets. The results have clearly demonstrated the advantages and efficiency in content organization of the proposed method in terms of computational cost and representation. The TOC can be easily adapted for large-scale applications. The topology provides a unique, additional feature for retrieving related topics and confining the search space.

Cytokine gene polymorphisms in hemodialysis patients: association with comorbidity, functionality, and serum albumin.

VS Balakrishnan — 2008-07-08T03:02:21-00:00

Kidney international, Vol. 65, No. 4. (April 2004), pp. 1449-1460.

BACKGROUND: Cytokine-orchestrated chronic inflammation plays a major role in long-term morbidity and mortality in patients with end-stage renal disease (ESRD) on hemodialysis (HD). In this cross-sectional study, we evaluated the association between specific alleles/genotypes and combinations of genotypes of interleukin (IL)-6, tumor necrosis factor-alpha (TNF-alpha), and IL-10 with indices of comorbidity, functional status, and other biological markers in a cohort of 183 ESRD patients recruited to the Hemodialysis (HEMO) Study from two Boston centers. METHODS: Genotyping was performed for single nucleotide polymorphisms in the promoter region of IL-6 (-174 G-->C), TNF-alpha (-308 G-->A), and IL-10 (-1082 G-->A). The relationship of specific genotypes to the index of coexistent disease (ICED) score (an index of comorbidity), Karnofsky Index (a measure of functional status), serum albumin, and nutritional indices (anthropometric measurements, body mass index, normalized protein catabolic ratio) were studied. Plasma IL-6 levels, as well as TNF-alpha and IL-10 production by endotoxin-stimulated peripheral blood mononuclear cells (PBMC), were also measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Patients with the high producer genotypes for the proinflammatory cytokines IL-6 (G/G and G/C) and TNF-alpha (G/A and A/A) had significantly higher comorbidity (ICED scores of > or =2) and lower functional scores (Karnofsky Index) compared with patients with the low producer genotypes for these cytokines (C/C and G/G, respectively). In contrast, patients with the high and intermediate producer genotypes (G/G and G/A) for the anti-inflammatory cytokine IL-10 had a higher Karnofsky Index compared with those with the low producer genotype (A/A). Serum albumin levels were lower in patients with the TNF-alpha high producer genotype (G/A and A/A) compared with those with the low producer genotype (G/A and A/A). On multivariate analysis, the IL-6 high producer genotypes were associated with an odds ratio (OR) of 4.87 for higher comorbidity (ICED scores > or =2) (P= 0.02), and 4.9 for lower Karnofsky Index (lower functional status) (P= 0.04) compared with patients with the low IL-6 producer genotypes. Similarly, the TNF-alpha high producer genotype was associated with increased odds for a higher ICED score, lower Karnofsky Index, and lower serum albumin compared with patients with the low producer genotype for this cytokine. In contrast, the IL-10 high/intermediate producer genotype was associated with increased odds for a higher Karnofsky Index (P= 0.05). Cytokine genotype combinations-the TNF-alpha high producer and IL-6 high producer genotype combination, and the IL-6 high producer and IL-10 low producer genotype combination-were independently associated with a higher ICED score. These genotype combinations, as well as the TNF-alpha high producer and IL-10 low producer genotype combination, were also associated with a lower Karnofsky Index. CONCLUSION: In ESRD patients on long-term HD, single nucleotide polymorphisms in the promoter region of the proinflammatory cytokines IL-6 and TNF-alpha, and the regulatory monokine IL-10, show a strong association with indices of comorbidity and function, and biological and nutritional markers.

Reduced atherosclerosis in MyD88-null mice links elevated serum cholesterol levels to activation of innate immunity signaling pathways.

H Björkbacka — 2006-03-13T21:39:19-00:00

Nat Med, Vol. 10, No. 4. (April 2004), pp. 416-421.

Atherosclerosis, the leading cause of death in developed countries, has been linked to hypercholesterolemia for decades. More recently, atherosclerotic lesion progression has been shown to depend on persistent, chronic inflammation in the artery wall. Although several studies have implicated infectious agents in this process, the role of infection in atherosclerosis remains controversial. Because the involvement of monocytes and macrophages in the pathogenesis of atherosclerosis is well established, we investigated the possibility that macrophage innate immunity signaling pathways normally activated by pathogens might also be activated in response to hyperlipidemia. We examined atherosclerotic lesion development in uninfected, hyperlipidemic mice lacking expression of either lipopolysaccharide (LPS) receptor CD14 or myeloid differentiation protein-88 (MyD88), which transduces cell signaling events downstream of the Toll-like receptors (TLRs), as well as receptors for interleukin-1 (IL-1) and IL-18. Whereas the MyD88-deficient mice evinced a marked reduction in early atherosclerosis, mice deficient in CD14 had no decrease in early lesion development. Inactivation of the MyD88 pathway led to a reduction in atherosclerosis through a decrease in macrophage recruitment to the artery wall that was associated with reduced chemokine levels. These findings link elevated serum lipid levels to a proinflammatory signaling cascade that is also engaged by microbial pathogens.

Contrast gain control in the kitten's visual system

G Sclar — 2008-07-04T13:54:16-00:00

J Neurophysiol, Vol. 54, No. 3. (1 September 1985), pp. 668-675.

Using the SF-36 measure to compare the health impact of multiple sclerosis and Parkinson's disease with normal population health profiles.

A Riazi — 2008-07-04T10:16:48-00:00

Journal of neurology, neurosurgery, and psychiatry, Vol. 74, No. 6. (June 2003), pp. 710-714.

OBJECTIVE: To examine the relative impact of two chronic neurological disorders, multiple sclerosis and Parkinson's disease, by comparing patients' scores on the medical outcomes study 36-item short form health survey (SF-36) with the health profile of the United Kingdom population norms. METHODS: 638 people representing the full spectrum of multiple sclerosis and 227 patients with Parkinson's disease were studied. Health status was measured by the SF-36. Scores for the eight health domains were compared after controlling for age, sex, disease duration, mobility, social class, ethnicity, education, marital status, and employment status. RESULTS: People with multiple sclerosis and those with Parkinson's disease had significantly worse health than the general population on all eight domains measured by the SF-36. The relative impact of multiple sclerosis and Parkinson's disease were similar, but multiple sclerosis resulted in poorer scores on physical functioning and better scores in mental health. People with mild multiple sclerosis who walked without an aid also had significantly worse scores in all dimensions than the general UK population. CONCLUSIONS: The results highlight the need for further research into aspects of health measured by the SF-36. Nevertheless, generic measures that are applicable across multiple diseases may fail to address clinically important aspects of the impact of specific disorders.

An international scoring system for self-reported health complaints in adolescents

Ulrike Ravens-Sieberer — 2008-07-04T07:55:03-00:00

Eur J Public Health, Vol. 18, No. 3. (1 June 2008), pp. 294-299.

Background: Aimed to develop a unitary scoring system for the Health Behaviour in school-aged Children' (HBSC) symptom checklist that would facilitate cross-national comparisons and interpretation. Rasch measurement analysis and investigation of differential item functioning (DIF) were conducted. Methods: Data were obtained from the WHO collaborative study HBSC 2001/2002'. A total of 162 305 students aged 11, 13 and 15 years from 35 European and North American Countries were surveyed. Unidimensionality of the items and local independence were tested using means of confirmatory factor analysis. DIF across countries, age groups and gender was investigated using a logistic regression procedure. Item and person parameters were estimated according to the Rating Scale Model (RSM). Results: All items proved to be unidimensional. One item displayed noticeable DIF across countries and was discarded. The remaining items were functioning equally across subgroups. The RSM analysis resulted in Rasch model conform item parameter estimation. Infit mean square values between 0.84 and 1.35 revealed acceptable item fit. Conclusion: The control of DIF enables comparable and unbiased assessment of subjective health complaints across countries, age groups and gender. A scoring algorithm could be developed which enables a cross-cultural comparable and interval-scaled assessment of subjective health complaints. 10.1093/eurpub/ckn001

Investigations of above-threshold ionization using subpicosecond laser pulses

RR Freeman — 2008-07-04T05:30:23-00:00

Journal of Physics B: Atomic, Molecular and Optical Physics, Vol. 24, No. 2. (1991), pp. 325-347.

At very high light intensities, the electron energy spectrum in multiphoton ionization (MPI) spectroscopy of even the simplest atoms changes from a single, well defined threshold peak into multiple peaks, separated from one another by the photon energy. This phenomenon is generally referred to as 'above-threshold ionization' (ATI). The original experiments investigating ATI used relatively long laser pulses, with the result that amplitudes, energy widths and angular distributions of the individual photoelectron peaks depended on the laser intensity. In addition, the widths of the peaks, as well as their absolute energy positions, changed according to the temporal width of the laser pulse. These dependencies were not intrinsic to the ionization process, but rather were all eventually ascribed to ponderomotive forces exerted on free photoelectrons by the laser focus. The ponderomotive effects frustrated comparisons between theoretical calculations and experimental data.

TNF-alpha and H2O2 induce IL-18 and IL-18R beta expression in cardiomyocytes via NF-kappa B activation.

B Chandrasekar — 2008-07-03T23:54:05-00:00

Biochemical and biophysical research communications, Vol. 303, No. 4. (18 April 2003), pp. 1152-1158.

Myocardial ischemia/reperfusion is characterized by oxidative stress and induction of proinflammatory cytokines. Interleukin (IL)-18, a member of the IL-1 family, acts as a proinflammatory cytokine, and is induced during various immune and inflammatory disorders. Therefore, in the present study we investigated whether IL-18 expression is regulated by cytokines and oxidative stress in cardiomyocytes. TNF-alpha induced rapid and sustained activation of NF-kappaB whereas H(2)O(2) induced delayed and transient activation. Both TNF-alpha and H(2)O(2) induced IL-18 mRNA and precursor protein in cardiomyocytes, and IL-18 release into culture supernatants. However, only TNF-alpha led to sustained expression. Expression of IL-18Rbeta, but not alpha, was induced by both agonists. TNF-alpha and H(2)O(2) induced delayed expression of IL-18 BP. Pretreatment with PDTC attenuated TNF-alpha and H(2)O(2) induced IL-18 and IL-18Rbeta, but not basal expression of IL-18Ralpha. These results indicate that adult cardiomyocytes express IL-18 and its receptors, and proinflammatory cytokines and oxidative stress regulate their expression via activation of NF-kappaB. Presence of both ligand and receptors suggests IL-18 impacts myocardial biology through an autocrine pathway.

Effects of major depression on estimates of intelligence

Harold Sackeim — 2008-07-03T23:45:07-00:00

Journal of Clinical and Experimental Neuropsychology, Vol. 14, No. 2. (1992), pp. 268-288.

This study examined whether patients with major depressive disorder manifest deficits in intelligence during affective episodes and following clinical improvement. WAIS-R scores were contrasted in 100 patients in an episode of major depression with 50 normal controls, matched to the patient sample in terms of demographic variables and estimates of premorbid IQ. The groups were equivalent in verbal IQ, but, in line with previous studies, the depressed patients had a pronounced deficit in performance IQ. A patient subsample was administered the WAIS-R under unlimited time conditions to determine whether the time constraints of performance IQ subtests contributed to the magnitude of the verbal-performance IQ discrepancy. This discrepancy was only slightly reduced with untimed scoring. Subgroups of depressed patients were retested with the WAIS-R within one week (n = 26) or two months (n = 33) following treatment with electroconvulsive therapy. In both subsamples, IQ scores were improved at posttreatment testing relative to pretreatment, but with little change in the verbal-performance IQ discrepancy. These and related findings suggested that a performance IQ deficit is characteristic of depressed patients regardless of affective state.

Interleukin-18 induces human cardiac endothelial cell death via a novel signaling pathway involving NF-kappaB-dependent PTEN activation.

B Chandrasekar — 2008-07-03T21:47:26-00:00

Biochemical and biophysical research communications, Vol. 339, No. 3. (20 January 2006), pp. 956-963.

The tumor suppressor gene PTEN (phosphatase and tensin homologue deleted on chromosome 10) antagonizes the pro-survival signaling of Akt and promotes cell death. Previously, we demonstrated that IL-18 induced apoptosis in human cardiac microvascular endothelial cells (HCMEC). Here we have investigated the role of PTEN in this response. Our results demonstrate that IL-18 reduced phospho-Akt and bcl-2 levels, stimulated NF-kappaB activation, and induced PTEN-promoter-reporter activity, mRNA expression, and protein levels in HCMEC. IL-18-mediated PTEN transcription was enhanced by ectopic expression of wild type p65, but inhibited by dominant negative (dn) IkappaB-alpha, dnp65, and dnIKKbeta. Furthermore, overexpression of constitutively active Akt and wild type bcl-2 blocked IL-18-mediated cell death. While forced expression of PTEN potentiated, expression of catalytically inactive PTEN attenuated IL-18-mediated cell death. IL-18-induced activation of NF-kappaB and PTEN upregulation were mediated by p38MAPK. Together, these studies demonstrate a novel signal transduction pathway involving p38MAPK-NF-kappaB-PTEN in IL-18-mediated HCMEC death, and identify IL-18 as potential therapeutic target to inhibit or reduce myocardial inflammation and injury.

Visual Hand Tracking Using Nonparametric Belief Propagation

Erik Sudderth — 2007-05-04T14:00:44-00:00

(2004)

Global variation in copy number in the human genome

Richard Redon — 2006-11-22T18:14:00-00:00

Nature, Vol. 444, No. 7118. (23 November 2006), pp. 444-454.

Enhancement of Proton Acceleration by Hot-Electron Recirculation in Thin Foils Irradiated by Ultraintense Laser Pulses

AJ Mackinnon — 2008-06-30T16:25:11-00:00

Physical Review Letters, Vol. 88, No. 21. (14 May 2002), 215006.

MeV-proton production from solid targets irradiated by 100-fs laser pulses at intensities above 1×1020 W cm-2 has been studied as a function of initial target thickness. For foils 100 μm thick the proton beam was characterized by an energy spectrum of temperature 1.4 MeV with a cutoff at 6.5 MeV. When the target thickness was reduced to 3 μm the temperature was 3.2±0.3 MeV with a cutoff at 24 MeV. These observations are consistent with modeling showing an enhanced density of MeV electrons at the rear surface for the thinnest targets, which predicts an increased acceleration and higher proton energies.

Is the future for clinical trials internet-based? A cluster randomized clinical trial

Jennifer Litchfield — 2005-02-26T13:19:22-00:00

Clinical Trials, Vol. 2, No. 1. (February 2005), pp. 72-79.

Nonlinear brain dynamics as macroscopic manifestation of underlying many-body field dynamics

Walter Freeman — 2008-06-29T20:56:10-00:00

Physics of Life Reviews, Vol. 3, No. 2. (June 2006), pp. 93-118.

Neural activity patterns related to behavior occur at many scales in time and space from the atomic and molecular to the whole brain. Patterns form through interactions in both directions, so that the impact of transmitter molecule release can be analyzed to larger scales through synapses, dendrites, neurons, populations and brain systems to behavior, and control of that release can be described step-wise through transforms to smaller scales. Here we explore the feasibility of interpreting neurophysiological data in the context of many-body physics by using tools that physicists have devised to analyze comparable hierarchies in other fields of science. We focus on a mesoscopic level that offers a multi-step pathway between the microscopic functions of neurons and the macroscopic functions of brain systems revealed by hemodynamic imaging. We use electroencephalographic (EEG) records collected from high-density electrode arrays fixed on the epidural surfaces of primary sensory and limbic areas in rabbits and cats trained to discriminate conditioned stimuli (CS) in the various modalities. High temporal resolution of EEG signals with the Hilbert transform gives evidence for diverse intermittent spatial patterns of amplitude (AM) and phase modulations (PM) of carrier waves that repeatedly re-synchronize in the beta and gamma ranges in very short time lags over very long distances. The dominant mechanism for neural interactions by axodendritic synaptic transmission should impose distance-dependent delays on the EEG oscillations owing to finite propagation velocities and sequential synaptic delays. It does not. EEGs show evidence for anomalous dispersion: neural populations have a low velocity range of information and energy transfers, and a high velocity range of the spread of phase transitions. This distinction labels the phenomenon but does not explain it. In this report we analyze these phenomena using concepts of energy dissipation, the maintenance by cortex of multiple ground states corresponding to AM patterns, and the exclusive selection by spontaneous breakdown of symmetry (SBS) of single states in sequential phase transitions.

Origin, structure, and role of background EEG activity. Part 2. Analytic phase

Walter Freeman — 2007-01-26T07:32:08-00:00

Clinical Neurophysiology, Vol. 115, No. 9. (September 2004), pp. 2089-2107.

Objective: To explain spontaneous EEG through measurements of spatiotemporal patterns of phase among beta-gamma oscillations. Methods: High-density 8x8 intracranial arrays were fixed over sensory cortices of rabbits. EEGs were spatially low pass filtered, temporally bandpass filtered and segmented in overlapping windows stepped at 2 ms. Phase was measured with the cosine as the temporal basis function, using both Fourier and Hilbert transforms to compensate for their respective limitations. Spatial patterns in 2D phase surfaces were measured with the geometric form of the cone as the spatial basis function. Results: Two fundamental state variables were measured at each digitizing step in the 64 EEGs: the rate of change in phase with time (frequency) and the rate of change in phase with distance (gradient). The parameters of location, diameter, duration, and phase velocity of the cone of phase were derived from these two state variables. Parameter distributions including recurrence intervals extending into the low theta range were fractal; the mean values varied with window duration and interelectrode distance. Conclusions: The formation of spatial amplitude patterns began with state transitions that were documented by phase discontinuities and phase cones. The multiplicity of overlapping cones indicated that sensory neocortices maintained a scale-free state of self-organized criticality (SOC) in each hemisphere as the basis for its rapid integration of sensory input with prior learning stored in cortical synaptic webs. Further evidence came from the fractal properties of the phase parameters and the self-similarity of phase patterns in the ms/mm to m/s ranges. Significance: These EEG data suggest that neocortical dynamics is analogous to the dynamics of self-stabilizing systems, such as a sand pile that maintains its critical angle by avalanches, and a pan of boiling water that maintains its critical temperature by bubbles that release heat. Beta-gamma oscillations stem from the ability of neocortex to maintain its stability under continuous sensory bombardment. Modeling implies that the critical parameter of neocortex (analogous to angle of repose or temperature) is the mean firing rates of neurons that are homeostatically regulated by refractory periods everywhere at all times in cortex. The advantage of SOC in perception may be the ability it gives neocortex to generate instantaneous global state transitions (avalanches, bubbles) large enough to include the multiple sensory areas that are necessary to form gestalts (multisensory percepts).

Origin, structure, and role of background EEG activity. Part 1. Analytic amplitude

Walter Freeman — 2007-01-26T07:33:41-00:00

Clinical Neurophysiology, Vol. 115, No. 9. (September 2004), pp. 2077-2088.

Objective: To explain the neural mechanisms of spontaneous EEG by measuring the spatiotemporal patterns of synchrony among beta-gamma oscillations during perception. Methods: EEGs were measured from 8x8 (5.6x5.6 mm2) arrays fixed on the surfaces of primary sensory areas in rabbits that were trained to discriminate visual, auditory or tactile conditioned stimuli (CSs) eliciting conditioned responses (CRs). EEG preprocessing was by (i) bandpass filtering to extract the beta-gamma range (deleting theta-alpha); (ii) low-pass spatial filtering (not high-pass Laplacians used for localization), (iii) spatial averaging (not time averaging used for evoked potentials), and (iv) close spacing of 64 electrodes for simultaneous recording in each area (not sampling single signals from several areas); (v) novel algorithms were devised to measure synchrony and spatial pattern stability by calculating variances among patterns in 64-space derived from the 8x8 arrays (not by fitting equivalent dipoles). These methodological differences are crucial for the proposed new perspective on EEG. Results: Spatial patterns of beta-gamma EEG emerged following sudden jumps in cortical activity called `state transitions'. Each transition began with an abrupt phase re-setting to a new value on every channel, followed sequentially by re-synchronization, spatial pattern stabilization, and a dramatic increase in pattern amplitude. State transitions recurred at varying intervals in the theta range. A novel parameter was devised to estimate the perceptual information in the beta-gamma EEG, which disclosed 2-4 patterns with high information content in the CS-CR interval on each trial; each began with a state transition and lasted ~0.1 s. Conclusions: The function of each primary sensory neocortex was discontinuous; discrete spatial patterns occurred in frames like those in cinema. The frames before and after the CS-CR interval had low content. Significance: Derivation and interpretation of unit data in studies of perception might benefit from using multichannel EEG recordings to define distinctive epochs that are demarcated by state transitions of neocortical dynamics in the CS-CR intervals, particularly in consideration of the possibility that EEG may reveal recurring episodes of exchange and sharing of perceptual information among multiple sensory cortices. Simultaneously recorded, multichannel beta-gamma EEG might assist in the interpretation of images derived by fMRI, since high beta-gamma EEG amplitudes imply high rates of energy utilization. The spatial pattern intermittency provides a tag to distinguish gamma bursts from contaminating EMG activity in scalp recording in order to establish beta-gamma recording as a standard clinical tool. Finally, EEG cannot fail to have a major impact on brain theory.

The physiology of perception.

WJ Freeman — 2008-06-29T20:13:55-00:00

Scientific American, Vol. 264, No. 2. (February 1991), pp. 78-85.

Cough reflex and oral chemesthesis induced by capsaicin and capsiate in healthy never-smokers

Miyako Yamasaki — 2007-10-31T08:33:39-00:00

Cough, Vol. 3 (31 October 2007), 9.

American Society for Parenteral and Enteral Nutrition and American Dietetic Association: Standards of Practice and Standards of Professional Performance for Registered Dieticians (generalist, specialty, and advanced) in Nutrition Support.

2008-06-28T08:12:29-00:00

Journal of the American Dietetic Association, Vol. 107, No. 10. (October 2007), pp. 1815-1822.

Simulation of chaotic EEG patterns with a dynamic model of the olfactory system

W Freeman — 2008-06-27T21:59:06-00:00

Biological Cybernetics, Vol. 56, No. 2. (7 May 1987), pp. 139-150.

The main parts of the central olfactory system are the bulb (OB), anterior nucleus (AON), and prepyriform cortex (PC). Each part consists of a mass of excitatory or inhibitory neurons that is modelled in its noninteractive state by a 2nd order ordinary differential equation (ODE) having a static nonlinearity. The model is called a KOe or a KOt set respectively; it is evaluated in the “open loop” state under deep anesthesia. Interactions in waking states are represented by coupled KO sets, respectivelyKIe (mutual excitation) andKIi (mutual inhibition). The coupledKIe andKIi sets form aKII set, which suffices to represent the dynamics of theOB, AON, andPC separately. The coupling of these three structures by both excitatory and inhibitory feedback loops forms aKIII set. The solutions to this high-dimensional system ofODEs suffice to simulate the chaotic patterns of the EEG, including the normal low-level background activity, the high-level relatively coherent “bursts” of oscillation that accompany reception of input to the bulb, and a degenerate state of an epileptic seizure determined by a toroidal chaotic attractor. An example is given of the Ruelle-Takens-Newhouse route to chaos in the olfactory system. Due to the simplicity and generality of the elements of the model and their interconnections, the model can serve as the starting point for other neural systems that generate deterministic chaotic activity.

The design and use of steerable filters

WT Freeman — 2007-10-01T01:35:15-00:00

Pattern Analysis and Machine Intelligence, IEEE Transactions on, Vol. 13, No. 9. (1991), pp. 891-906.

The authors present an efficient architecture to synthesize filters of arbitrary orientations from linear combinations of basis filters, allowing one to adaptively steer a filter to any orientation, and to determine analytically the filter output as a function of orientation. Steerable filters may be designed in quadrature pairs to allow adaptive control over phase as well as orientation. The authors show how to design and steer the filters and present examples of their use in the analysis of orientation and phase, angularly adaptive filtering, edge detection, and shape from shading. One can also build a self-similar steerable pyramid representation. The same concepts can be generalized to the design of 3-D steerable filters

Recovering Intrinsic Images from a Single Image

MF Tappen — 2008-06-27T09:42:29-00:00

Pattern Analysis and Machine Intelligence, IEEE Transactions on, Vol. 27, No. 9. (2005), pp. 1459-1472.

Interpreting real-world images requires the ability distinguish the different characteristics of the scene that lead to its final appearance. Two of the most important of these characteristics are the shading and reflectance of each point in the scene. We present an algorithm that uses multiple cues to recover shading and reflectance intrinsic images from a single image. Using both color information and a classifier trained to recognize gray-scale patterns, given the lighting direction, each image derivative is classified as being caused by shading or a change in the surface's reflectance. The classifiers gather local evidence about the surface's form and color, which is then propagated using the Generalized Belief Propagation algorithm. The propagation step disambiguates areas of the image where the correct classification is not clear from local evidence. We use real-world images to demonstrate results and show how each component of the system affects the results.

Assistive technology and handwriting problems: what do occupational therapists recommend?

AR Freeman — 2008-06-26T09:54:07-00:00

Canadian journal of occupational therapy. Revue canadienne d'ergothérapie, Vol. 71, No. 3. (June 2004), pp. 150-160.

BACKGROUND: Handwriting difficulties for students are a common reason for referral to occupational therapy. Little research evidence is available concerning the factors guiding technology recommendations for these children. PURPOSE: The objective of this survey research was to describe the technology-related recommendations and factors involved in the decisions made by Canadian occupational therapists for these students. RESULTS: More therapists recommended the use of keyboard-based strategies (93%) than dictation-based strategies (72%). Experienced therapists were more likely to prescribe technology tools. Dictation to a scribe (93%) and desktop computers (89%) were the strategies most frequently recommended. Equipment cost and availability of funding, and the availability of support in the school for the student were the most influential factors, respectively, on the keyboard and dictation strategy type prescribed. PRACTICE IMPLICATIONS: The results confirmed that occupational therapists prescribe a range of technology solutions. Factors influencing these recommendations differ depending on the nature of the technology, the person, environment or occupation. Knowing the factors guiding occupational therapist technology recommendations will help provide valuable information about the practical implications of the available technologies.

Crowding and eccentricity determine reading rate.

DG Pelli — 2008-06-26T08:59:16-00:00

Journal of vision, Vol. 7, No. 2. (2007)

Bouma's law of crowding predicts an uncrowded central window through which we can read and a crowded periphery through which we cannot. The old discovery that readers make several fixations per second, rather than a continuous sweep across the text, suggests that reading is limited by the number of letters that can be acquired in one fixation, without moving one's eyes. That "visual span" has been measured in various ways, but remains unexplained. Here we show (1) that the visual span is simply the number of characters that are not crowded and (2) that, at each vertical eccentricity, reading rate is proportional to the uncrowded span. We measure rapid serial visual presentation (RSVP) reading rate for text, in both original and scrambled word order, as a function of size and spacing at central and peripheral locations. As text size increases, reading rate rises abruptly from zero to maximum rate. This classic reading rate curve consists of a cliff and a plateau, characterized by two parameters, critical print size and maximum reading rate. Joining two ideas from the literature explains the whole curve. These ideas are Bouma's law of crowding and Legge's conjecture that reading rate is proportional to visual span. We show that Legge's visual span is the uncrowded span predicted by Bouma's law. This result joins Bouma and Legge to explain reading rate's dependence on letter size and spacing. Well-corrected fluent observers reading ordinary text with adequate light are limited by letter spacing (crowding), not size (acuity). More generally, it seems that this account holds true, independent of size, contrast, and luminance, provided only that text contrast is at least four times the threshold contrast for an isolated letter. For any given spacing, there is a central uncrowded span through which we read. This uncrowded span model explains the shape of the reading rate curve. We test the model in several ways. We use a "silent substitution" technique to measure the uncrowded span during reading. These substitutions spoil letter identification but are undetectable when the letters are crowded. Critical spacing is the smallest distance between letters that avoids crowding. We find that the critical spacing for letter identification predicts both the critical spacing and the span for reading. Thus, crowding predicts the parameters that characterize both the cliff and the plateau of the reading rate curve. Previous studies have found worrisome differences across observers and laboratories in the measured peripheral reading rates for ordinary text, which may reflect differences in print exposure, but we find that reading rate is much more consistent when word order is scrambled. In all conditions tested--all sizes and spacings, central and peripheral, ordered and scrambled--reading is limited by crowding. For each observer, at each vertical eccentricity, reading rate is proportional to the uncrowded span.

Understanding belief propagation and its generalizations

Jonathan Yedidia — 2006-12-20T19:06:47-00:00

(2003), pp. 239-269.

Development of an ecological mapping methodology for urban areas in New Zealand

Claire Freeman — 2008-06-25T11:23:18-00:00

Landscape and Urban Planning, Vol. 63, No. 3. (30 April 2003), pp. 161-173.

At present there is no ecologically based mapping system designed for application to urban areas in New Zealand. New Zealand's ecological structure is particularly interesting as it combines indigenous habitats comprising significant numbers of endemic species with a vibrant imported ecology comprising habitats characteristic of their primarily European and Australian origins. In New Zealand, the focus to date in habitat mapping has been on developing vegetation mapping techniques for application to predominantly indigenous habitats in rural areas. Thus, they omit reference to the type of mixed exotic-indigenous vegetation associated with habitats common to urban areas, such as cliff faces, disused quarries, private gardens and grounds, river and rail corridors. A project was undertaken in conjunction with the Dunedin City Council to develop a habitat map of the city. The aim was to produce a map that would accommodate the diverse highly modified habitats characteristic of Dunedin and that would incorporate all types of urban open space ranging from indigenous habitats, such as forest to exotic habitats such as lawns, and residential gardens. The project developed a land use and habitat classification hierarchy applicable to the New Zealand urban context, including a classification system for private gardens. This paper describes the classification system that was developed, its benefits, limitations and application. The map is the first attempt to record all natural land uses, including gardens in any New Zealand city at a detailed level, i.e. at a scale of 1:3000. In all 1100 separate habitat parcels were mapped. The map revealed that whilst Dunedin is a city rich in natural vegetation very little of this is indigenous or even predominantly indigenous vegetation. A Geographic Information System was used to map the urban habitats and store the habitat data. The habitat map and associated data will be used by the council in developing an open space strategy for the city.

LabelMe: A Database and Web-Based Tool for Image Annotation

Bryan Russell — 2008-06-03T00:04:47-00:00

Int. J. Comput. Vision, Vol. 77, No. 1-3. (2008), pp. 157-173.

Gas transport properties of poly(ether-b-amide) segmented block copolymers

VI Bondar — 2008-06-24T00:53:51-00:00

Journal of Polymer Science Part B: Polymer Physics, Vol. 38, No. 15. (2000), pp. 2051-2062.

The permeation properties of H2, N2, and CO2 were determined at 35 °C and pressures up to 15 atm in phase-separated polyether-b-polyamide segmented block copolymers. These polymers contain poly(ethylene oxide) [PEO] or poly(tetramethylene oxide) [PTMEO] as the rubbery polyether phase and nylon-6 [PA6] or nylon-12 [PA12] as the hard polyamide phase. Extremely high values of polar (or quadrupolar)/nonpolar gas selectivities, coupled with high CO2 permeability coefficients, were observed. CO2/H2 selectivities as high as 9.8 and CO2/N2 selectivities as high as 56 were obtained in polymers with CO2 permeability coefficients of approximately 220 × 10-10 cm3(STP) cm/(cm2 s cmHg). As the amount of polyether increases, permeability increases. Gas permeability is higher in polymers with less polar constituents, PTMEO and PA12, than in those containing the more polar PEO and PA6 units. CO2/N2 and CO2/H2 selectivities are higher in polymers with higher concentrations of polar groups. These high selectivity values derive from large solubility selectivities in favor of CO2. Because CO2 is larger than H2 and has, therefore, a lower diffusion coefficient than H2, the weak size-sieving ability of the rubbery polyether phase, which is the locus of most of the gas permeation, also contributes to high CO2/H2 selectivity. © 2000 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 38: 2051-2062, 2000

Quantitative RT-PCR: pitfalls and potential.

WM Freeman — 2008-06-23T20:26:39-00:00

BioTechniques, Vol. 26, No. 1. (January 1999)

Reverse transcription PCR (RT-PCR) represents a sensitive and powerful tool for analyzing RNA. While it has tremendous potential for quantitative applications, a comprehensive knowledge of its technical aspects is required. Successful quantitative RT-PCR involves correction for experimental variations in individual RT and PCR efficiencies. This review addresses the mathematics of RT-PCR, choice of RNA standards (internal vs. external) and quantification strategies (competitive, noncompetitive and kinetic [real-time] amplification). Finally, the discussion turns to practical considerations in experimental design. It is hoped that this review will be appropriate for those undertaking these experiments for the first time or wishing to improve (or validate) a technique in what is frequently a confusing and contradictory field.

Divergent Paths of Immigration Politics in the United States and Australia

Gary Freeman — 2008-06-21T20:43:32-00:00

Population and Development Review, Vol. 27, No. 3. (2001), pp. 525-551.

The United States and Australia converged by the mid-1980s on receptive and expansive immigration policies reflecting "client" politics. Australia has since pursued a more restrictive and selective course while the United States has resisted pressures toward such a stance. The authors account for these differences by assessing the theoretical perspectives of interests, rights, and states. Conflicts among groups with direct interests in policy outcomes are the principal source of immigration politics, but a comparison of the roles of rights and state institutions helps explain peculiarities of the two cases. The distinctive Australian policy trajectory is shaped by greater volatility of public opinion about immigration and multiculturalism, and by political institutions that are more responsive to popular sentiment.

Optical constants of rf sputtered hydrogenated amorphous Si

Eva Freeman — 2008-06-19T14:09:06-00:00

Physical Review B, Vol. 20, No. 2. (15 July 1979), 716.

Drug delivery systems in urology--getting "smarter".

OC Farokhzad — 2008-06-17T23:03:10-00:00

Urology, Vol. 68, No. 3. (September 2006), pp. 463-469.

Stereoscopic depth discrimination in the visual cortex: neurons ideally suited as disparity detectors

I Ohzawa — 2008-06-13T22:27:36-00:00

Science, Vol. 249, No. 4972. (31 August 1990), pp. 1037-1041.

The possibility has been explored that a subset of physiologically identifiable cells in the visual cortex is especially suited for the processing of stereoscopic depth information. First, characteristics of a disparity detector that would be useful for such processing were outlined. Then, a method was devised by which detailed binocular response data were obtained from cortical cells. In addition, a model of the disparity detector was developed that includes a plausible hierarchical arrangement of cortical cells. Data from the cells compare well with the requirements for the archetypal disparity detector and are in excellent agreement with the predictions of the model. These results demonstrate that a specific type of cortical neuron exhibits the desired characteristics of a disparity detector. 10.1126/science.2396096

A sequence-oriented comparison of gene expression measurements across different hybridization-based technologies

Winston Kuo — 2006-07-14T10:57:39-00:00

Nature Biotechnology, Vol. 24, No. 7. (02 July 2006), pp. 832-840.

Constructing free-energy approximations and generalized belief propagation algorithms

JS Yedidia — 2006-02-16T21:45:03-00:00

Information Theory, IEEE Transactions on, Vol. 51, No. 7. (2005), pp. 2282-2312.

Important inference problems in statistical physics, computer vision, error-correcting coding theory, and artificial intelligence can all be reformulated as the computation of marginal probabilities on factor graphs. The belief propagation (BP) algorithm is an efficient way to solve these problems that is exact when the factor graph is a tree, but only approximate when the factor graph has cycles. We show that BP fixed points correspond to the stationary points of the Bethe approximation of the free energy for a factor graph. We explain how to obtain region-based free energy approximations that improve the Bethe approximation, and corresponding generalized belief propagation (GBP) algorithms. We emphasize the conditions a free energy approximation must satisfy in order to be a "valid" or "maxent-normal" approximation. We describe the relationship between four different methods that can be used to generate valid approximations: the "Bethe method", the "junction graph method", the "cluster variation method", and the "region graph method". Finally, we explain how to tell whether a region-based approximation, and its corresponding GBP algorithm, is likely to be accurate, and describe empirical results showing that GBP can significantly outperform BP.

Revisiting Lévy flight search patterns of wandering albatrosses, bumblebees and deer

Andrew Edwards — 2007-10-25T05:11:28-00:00

Nature, Vol. 449, No. 7165., pp. 1044-1048.