[Review of] Carmelo Mesa-lago, The Economy of Socialist Cuba: A Two-Decade Appraisal

It\u27s not unusual for partisans of opposing viewpoints about Cuba to spark each other to flaming argument, while those who prefer less heat and more light can easily find adventure enough just in following the course of the Western Hemisphere\u27s most important social experiment since the Mexican Revolution. Shouldn\u27t a book about twenty years of post-revolutionary Cuba be exciting, especially when it comes to us from Carmelo Mesa-Lago, Cuban native, an early supporter of the revolution and also an early emigre to the United States, and now, as Professor of Economics at the University of Pittsburgh, one of only a handful of distinguished students of Cuba in this country? His book is a product of a good deal of effort over a long period of time. It is detailed, precise, balanced, and informative. It is easily understood, so that non-experts can profit from reading it even though its wealth of hard-to-get data makes it an indispensable reference work for professional Latin Americanists. It is all this, but it is not exciting

g/u(1)dg/u(1)^d parafermions from constrained WZNW theories

The conformal field theory based on the $g/u(1)^d$ coset construction is treated as the WZNW theory for the affine Lie algebra $\hat g$ with the constrained $\hat u(1)^d$ subalgebra.Using a modification of the generalized canonical quantization method generators and primary fields of an extended symmetry algebra are found for arbitrary d.Comment: 14 pages,latex,misprints in formulas 26,40,45 corrected,a reference adde

Discovering transcriptional modules by Bayesian data integration

Motivation: We present a method for directly inferring transcriptional modules (TMs) by integrating gene expression and transcription factor binding (ChIP-chip) data. Our model extends a hierarchical Dirichlet process mixture model to allow data fusion on a gene-by-gene basis. This encodes the intuition that co-expression and co-regulation are not necessarily equivalent and hence we do not expect all genes to group similarly in both datasets. In particular, it allows us to identify the subset of genes that share the same structure of transcriptional modules in both datasets. Results: We find that by working on a gene-by-gene basis, our model is able to extract clusters with greater functional coherence than existing methods. By combining gene expression and transcription factor binding (ChIP-chip) data in this way, we are better able to determine the groups of genes that are most likely to represent underlying TMs

The neurotoxin DSP-4 dysregulates the locus coeruleus-norepinephrine system and recapitulates molecular and behavioral aspects of prodromal neurodegenerative disease

The noradrenergic locus coeruleus (LC) is among the earliest sites of tau and α-synuclein pathology in Alzheimer\u27s disease (AD) and Parkinson\u27s disease (PD), respectively. The onset of these pathologies coincides with loss of noradrenergic fibers in LC target regions and the emergence of prodromal symptoms including sleep disturbances and anxiety. Paradoxically, these prodromal symptoms are indicative of a noradrenergic hyperactivity phenotype, rather than the predicted loss of norepinephrine (NE) transmission following LC damage, suggesting the engagement of complex compensatory mechanisms. Because current therapeutic efforts are targeting early disease, interest in the LC has grown, and it is critical to identify the links between pathology and dysfunction. We employed the LC-specific neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), which preferentially damages LC axons, to model early changes in the LC-NE system pertinent to AD and PD in male and female mice. DSP-4 (two doses of 50 mg/kg, one week apart) induced LC axon degeneration, triggered neuroinflammation and oxidative stress, and reduced tissue NE levels. There was no LC cell death or changes to LC firing, but transcriptomics revealed reduced expression of genes that define noradrenergic identity and other changes relevant to neurodegenerative disease. Despite the dramatic loss of LC fibers, NE turnover and signaling were elevated in terminal regions and were associated with anxiogenic phenotypes in multiple behavioral tests. These results represent a comprehensive analysis of how the LC-NE system responds to axon/terminal damage reminiscent of early AD and PD at the molecular, cellular, systems, and behavioral levels, and provides potential mechanisms underlying prodromal neuropsychiatric symptoms

Irrational Conformal Field Theory

This is a review of irrational conformal field theory, which includes rational conformal field theory as a small subspace. Central topics of the review include the Virasoro master equation, its solutions and the dynamics of irrational conformal field theory. Discussion of the dynamics includes the generalized Knizhnik-Zamolodchikov equations on the sphere, the corresponding heat-like systems on the torus and the generic world- sheet action of irrational conformal field theory.Comment: 195 pages, Latex, 12 figures, to appear in Physics Reports. Typos corrected in Sections 13 and 14, and a footnote added in Section 1

On Global Aspects Of Gauged Wess-Zumino-Witten Model

This is a thesis for Rigaku-Hakushi($\simeq$ Ph. D.). It clarifies the geometric meaning and field theoretical consequences of the spectral flows acting on the space of states of the `$G/H$ coset model'. As suggested by Moore and Seiberg, the spectral flow is realized as the response of states to certain change of background gauge field together with the gauge transformation on a circle. Applied to the boundary circle of a disc with field insertion, such a realization leads to a certain relation among correlators of the gauged WZW model for various principal $H$-bundles. In the course of derivation, we find an expression of a (dressed) gauge invariant field as an integral over the flag manifold of $H$ and an expression of a correlator as an integral over a certain moduli space of holomorphic $H_{\bf C}$-bundles with quasi-flag structure at the insertion point. We also find that the gauge transformation on the circle corresponding to the spectral flow determines a bijection of the set of isomorphism classes of holomorphic $H_{\bf C}$-bundles with quasi-flag structure of one topological type to that of another. As an application, it is pointed out that problems arising from the field identification fixed points may be resolved by taking into account of all principal $H$-bundles.Comment: (Thesis) 125 pages, UT-Komaba/94-3 (Latex errors are corrected

Skeletal muscle specific genes networks in cattle

While physiological differences across skeletal muscles have been described, the differential gene expression underlying them and the discovery of how they interact to perform specific biological processes are largely to be elucidated. The purpose of the present study was, firstly, to profile by cDNA microarrays the differential gene expression between two skeletal muscle types, Psoas major (PM) and Flexor digitorum (FD), in beef cattle and then to interpret the results in the context of a bovine gene coexpression network, detecting possible changes in connectivity across the skeletal muscle system. Eighty four genes were differentially expressed (DE) between muscles. Approximately 54% encoded metabolic enzymes and structural-contractile proteins. DE genes were involved in similar processes and functions, but the proportion of genes in each category varied within each muscle. A correlation matrix was obtained for 61 out of the 84 DE genes from a gene coexpression network. Different groups of coexpression were observed, the largest one having 28 metabolic and contractile genes, up-regulated in PM, and mainly encoding fast-glycolytic fibre structural components and glycolytic enzymes. In FD, genes related to cell support seemed to constitute its identity feature and did not positively correlate to the rest of DE genes in FD. Moreover, changes in connectivity for some DE genes were observed in the different gene ontologies. Our results confirm the existence of a muscle dependent transcription and coexpression pattern and suggest the necessity of integrating different muscle types to perform comprehensive networks for the transcriptional landscape of bovine skeletal muscle

ORIGINAL ARTICLES Assessment of Jeopardized Myocardium in Patients with One-vessel Disease

SUMMARY The size of the perfusion defect was assessed from a quantitative analysis of exercise thallium-201 images. Quantitative analysis was determined by measuring the area and the perimeter of the perfusion defect and expressing it as a percentage of the total left ventricular area or perimeter in three projections. Using this technique, we studied 50 patients with one-vessel disease of 50% or greater diameter narrowing. The planimetric and the perimetric methods correlated well (p < 0.001, r = 0.97). Of the 11 patients with less than 70% diameter narrowing, only one patient had abnormal exercise thallium-201 images. Of the remaining 39 patients with 70% or greater diameter narrowing, 35 circumflex disease. Mortality rates undoubtedly depend on left ventricular function: The worse the function, the poorer the prognosis. Therefore, the extent of jeopardized myocardium may have prognostic importance in patients with one-vessel disease; patients with more jeopardized myocardium may be at a higher risk of developing severe left ventricular dysfunction in the event of myocardium infarction. The purpose of this study was to assess the extent of jeopardized myocardium in patients with one-vessel disease by using quantitative analysis of exercise images, a simple technique that does not require computer manipulation, and to define the factors that affect the size of the defects in these patients. Materials and Methods We reviewed our records of exercise thallium-201 imaging and identified 50 patients with one-vessel disease who had undergone exercise perfusion imaging within 3 months of coronary angiography. There were 46 men and four women, ages 32-63 years (mean 52 years). Patients with associated cardiac diseases such as valvular heart disease or idiopathic hypertrophic subaortic stenosis and patients who had had previous bypass surgery were excluded. All patients were evaluated for symptoms of angina pectoris. No patient had unstable angina or historic or electrocardiographic evidence of myocardial infarction. Left-and right-heart catheterization, left ventriculography and coronary arteriography were per- formed with standard techniques. Each coronary vessel was visualized in multiple projections, including the sagittal oblique projection. Each patient had at least 50% diameter narrowing of one coronary artery. The lesion in the left anterior descending artery was classified as either proximal or distal to the first septal perforator and diagonal branches. In each patient with left circumflex artery disease, the lesion was before or involved the major posterolateral branch. In each patient with right coronary artery disease, the lesion was before the crux. The coronary circulation was rightdominant in patients with left circumflex or right coronary artery disease. The remaining vessels were either free of disease or had only slight luminal irregularities. Collaterals were considered present and significant if the collateral flow partially or completely opacified the diseased vessel beyond the site of occlusion or narrowing. The left ventriculograms, which were assessed qualitatively for wall-motion abnormalities, showed that none of these patients had akinetic or dyskinetic segments. The angiograms were reviewed by two experienced angiographers, and the consensus of both reviewers was used in the final interpretation. Exercise treadmill testing was performed according to the Bruce protocol. The end points of exercise were 2 2 mm of horizontal or downsloping ST depression (with or without angina), excessive fatigue or leg weakness, hypotension, frequent ventricular premature complexes, or attainment of at least 85% of the predicted maximal heart rate. Three electrocardiographic leads (V1, V, and aVF) were continuously monitored; lead V5 was used for interpretation. Blood pressure was obtained by the cuff method every 2 minutes. At peak exercise, 2 mCi of thallium-201 were injected intravenously and flushed with dextrose and water. The patient continued to exercise for 1 more minute. Within 10 minutes after injection, images were obtained in the anterior, left anterior oblique and left lateral projections by means of a commercially available scintillation camera (Baird Atomic System-77) equipped with a high-resolution, parallel-hole, 11/2-inch-thick collimator. Redistribution images were obtained 4 hours after exercise in the projections that showed the perfusion abnormalities. All patients in the study with initial abnormal images showed partia'L or complete redistribution in the delayed images. Our method for obtaining the exercise thallium-201 scintigrams has been described." 6 8 21-24 In brief, images were accumulated for a preset count (750,000 to 1,250,000 total counts), which required 8-12 minutes per projection. All images were corrected for background and for detector nonuniformity. Images were displayed on a television screen on a scale of 16 gray shades or 16 colors. The highest count displayed represents 100% on the scale and all other counts are digitally normalized to the maximum. Each of the 16 shades or colors represents a 6.25% increment in counts within the image. Depending on the visual in--spection of the background contribution, 20-30% background subtraction is used and the 16 colors are displayed over the remaining count range. In addition, the images were processed using an algorithm that weighs and spatially averages five adjacent data points in the matrix. The net result is a color-coded isocount contour display of the myocardial thallium-201 distribution. Polaroid pictures were obtained of the computer-smoothed images. We and others7' 25 have found that the color-coded display of the images improve the interpretation. Segments of the myocardium showing 25% decrease in counts (four-color shift) are considered abnormal. The borders of the defects are outlined by two independent observers and minor disagreements were settled by arbitration between the two observers. Quantitative analysis was done by two methods. In the first method, the size of the thallium-201 defect was determined by the method of Niess et al.26 with a computerized planimetry system (Hewlett-Packard 982A calculator and digitizer). This method expresses the size of thallium-201 perfusion defects as a percentage of total potential thallium uptake. The size of the defect was computed in each projection and expressed as a percentage of the total area of the myocardium, excluding the left ventricular cavity and the region of the valves. The average of the three projections was also determined ( In the second method, the perimeter of the defect was measured and expressed as a percentage of the total left ventricular perimeter in each projection ( Statistical analysis was performed using the t test or the analysis of variance when appropriate

Probabilistic Inference of Transcription Factor Binding from Multiple Data Sources

An important problem in molecular biology is to build a complete understanding of transcriptional regulatory processes in the cell. We have developed a flexible, probabilistic framework to predict TF binding from multiple data sources that differs from the standard hypothesis testing (scanning) methods in several ways. Our probabilistic modeling framework estimates the probability of binding and, thus, naturally reflects our degree of belief in binding. Probabilistic modeling also allows for easy and systematic integration of our binding predictions into other probabilistic modeling methods, such as expression-based gene network inference. The method answers the question of whether the whole analyzed promoter has a binding site, but can also be extended to estimate the binding probability at each nucleotide position. Further, we introduce an extension to model combinatorial regulation by several TFs. Most importantly, the proposed methods can make principled probabilistic inference from multiple evidence sources, such as, multiple statistical models (motifs) of the TFs, evolutionary conservation, regulatory potential, CpG islands, nucleosome positioning, DNase hypersensitive sites, ChIP-chip binding segments and other (prior) sequence-based biological knowledge. We developed both a likelihood and a Bayesian method, where the latter is implemented with a Markov chain Monte Carlo algorithm. Results on a carefully constructed test set from the mouse genome demonstrate that principled data fusion can significantly improve the performance of TF binding prediction methods. We also applied the probabilistic modeling framework to all promoters in the mouse genome and the results indicate a sparse connectivity between transcriptional regulators and their target promoters. To facilitate analysis of other sequences and additional data, we have developed an on-line web tool, ProbTF, which implements our probabilistic TF binding prediction method using multiple data sources. Test data set, a web tool, source codes and supplementary data are available at: http://www.probtf.org

Role of Serine Racemase in Behavioral Sensitization in Mice after Repeated Administration of Methamphetamine

BACKGROUND: The N-methyl-D-aspartate (NMDA) receptors play a role in behavioral abnormalities observed after administration of the psychostimulant, methamphetamine (METH). Serine racemase (SRR) is an enzyme which synthesizes D-serine, an endogenous co-agonist of NMDA receptors. Using Srr knock-out (KO) mice, we investigated the role of SRR on METH-induced behavioral abnormalities in mice. METHODOLOGY/PRINCIPAL FINDINGS: Evaluations of behavior in acute hyperlocomotion, behavioral sensitization, and conditioned place preference (CPP) were performed. The role of SRR on the release of dopamine (DA) in the nucleus accumbens after administration of METH was examined using in vivo microdialysis technique. Additionally, phosphorylation levels of ERK1/2 proteins in the striatum, frontal cortex and hippocampus were examined using Western blot analysis. Acute hyperlocomotion after a single administration of METH (3 mg/kg) was comparable between wild-type (WT) and Srr-KO mice. However, repeated administration of METH (3 mg/kg/day, once daily for 5 days) resulted in behavioral sensitization in WT, but not Srr-KO mice. Pretreatment with D-serine (900 mg/kg, 30 min prior to each METH treatment) did not affect the development of behavioral sensitization after repeated METH administration. In the CPP paradigm, METH-induced rewarding effects were demonstrable in both WT and Srr-KO mice. In vivo microdialysis study showed that METH (1 mg/kg)-induced DA release in the nucleus accumbens of Srr-KO mice previously treated with METH was significantly lower than that of the WT mice previously treated with METH. Interestingly, a single administration of METH (3 mg/kg) significantly increased the phosphorylation status of ERK1/2 in the striatum of WT, but not Srr-KO mice. CONCLUSIONS/SIGNIFICANCE: These findings suggest first, that SRR plays a role in the development of behavioral sensitization in mice after repeated administration of METH, and second that phosphorylation of ERK1/2 by METH may contribute to the development of this sensitization as seen in WT but not Srr-KO mice