Kleinian groups and the rank problem

We prove that the rank problem is decidable in the class of torsion-free word-hyperbolic Kleinian groups. We also show that every group in this class has only finitely many Nielsen equivalence classes of generating sets of a given cardinality.Comment: Published by Geometry and Topology at http://www.maths.warwick.ac.uk/gt/GTVol9/paper12.abs.htm

Stability of asymmetric tetraquarks in the minimal-path linear potential

The linear potential binding a quark and an antiquark in mesons is generalized to baryons and multiquark configurations as the minimal length of flux tubes neutralizing the color, in units of the string tension. For tetraquark systems, i.e., two quarks and two antiquarks, this involves the two possible quark--antiquark pairings, and the Steiner tree linking the quarks to the antiquarks. A novel inequality for this potential demonstrates rigorously that within this model the tetraquark is stable in the limit of large quark-to-antiquark mass ratio.Comment: 8 pages, 6 figures, pdflate

Functional Brain Network Characterization and Adaptivity during Task Practice in Healthy Volunteers and People with Schizophrenia1

Cognitive remediation involves task practice and may improve deficits in people suffering from schizophrenia, but little is known about underlying neurophysiological mechanisms. In people with schizophrenia and controls, we used magnetoencephalography (MEG) to examine accuracy and practice-related changes in parameters indexing neural network structure and activity, to determine whether these might be useful assays of the efficacy of cognitive remediation. Two MEG recordings were acquired during performance of a tone discrimination task used to improve the acuity of auditory processing, before and after ∼2.5 h of task practice. Accuracy before practice was negatively correlated with beta-band cost efficiency, a graph theoretical measure of network organization. Synthetic aperture magnetometry was used to localize brain oscillations with high spatial accuracy; results demonstrated sound and sensorimotor modulations of the beta band in temporo-parietal regions and the sensorimotor cortex respectively. High-gamma activity also correlated with sensorimotor processing during the task, with activation of auditory regions following sound stimulation, and activation of the left sensorimotor cortex preceding the button press. High-gamma power in the left frontal cortex was also found to correlate with accuracy. Following practice, sound-induced broad-band power in the left angular gyri increased. Accuracy improved and was found to correlate with increased mutual information (MI) between sensors in temporal–parietal regions in the beta band but not global cost efficiency. Based on these results, we conclude that hours of task practice can induce meso-scale changes such as increased power in relevant brain regions as well as changes in MI that correlate with improved accuracy

PET scan investigations of Huntington's disease: Cerebral metabolic correlates of neurological features and functional decline

Fifteen drug-free patients with early to midstage Huntington's disease were evaluated with quantitative neurological examinations, scales for functional capacity, computed tomographic (CT) scans, and positron emission tomographic (PET) scans of 18 F-2-fluoro-2-deoxyglucose ( 18 F-FDG) uptake. All patients had abnormal indices of caudate metabolism on PET scanning, whereas in patients with early disease indices of putamen metabolism and CT measures of caudate atrophy were normal. Indices of caudate metabolism correlated highly with the patients' overall functional capacity ( r = 0.906; p < 0.001) and bradykinesia/rigidity ( r = −0.692; p < 0.01). Indices of putamen metabolism correlated highly with motor functions: Chorea ( r = −0.841; p < 0.01), oculomotor abnormalities ( r = −0.849; p < 0.01), and fine motor coordination ( r = −0.866; p < 0.01). Indices of thalamic metabolism correlated positively with dystonia ( r = 0.559; p < 0.05). The data suggest that PET scanning with 18 F-FDG is a sensitive measure of brain dysfunction in Huntington's disease and that basal ganglia metabolism is highly correlated with the overall functional capacity of individual patients and with the degree of their motor abnormalities.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50317/1/410200305_ftp.pd

Analysis of 16S rRNA genes reveals reduced Fusobacterial community diversity when translocating from saliva to GI sites

Fusobacterium nucleatum is a Gram-negative oral commensal anaerobe which has been increasingly implicated in various gastrointestinal (GI) disorders, including inflammatory bowel disease,appendicitis, GI cancers. The oral cavity harbors a diverse group of Fusobacterium, and it ispostulated that F. nucleatum in the GI tract originate from the mouth. It is not known, however, ifall oral Fusobacterium translocate to the GI sites with equal efficiencies. Therefore, we amplified 16SrRNA genes of F. nucleatum and F. periodonticum, two closely related oral species from matchedsaliva, gastric aspirates, and colon or ileal pouch aspirates of three patients with inflammatorybowel disease (IBD) and three healthy controls, and saliva alone from seven patients with eitheractive IBD or IBD in remission. The 16S rRNA gene amplicons were cloned, and the DNA sequencesdetermined by Sanger sequencing. The results demonstrate that fusobacterial community composition differs more significantly between the oral and GI sites than between different individuals.The oral communities demonstrate the highest level of variation and have the richest pool ofunique sequences, with certain nodes/strains enriched in the GI tract and others diminished duringtranslocation. The gastric and colon/pouch communities exhibit reduced diversity and are moreclosely related, possibly due to selective pressure in the GI tract. This study elucidates selectivetranslocation of oral fusobacteria to the GI tract. Identification of specific transmissible clones willfacilitate risk assessment for developing Fusobacterium-implicated GI disorders.Fil: Richardson, Miles. Columbia University; Estados UnidosFil: Ren, Jihui. Columbia University; Estados UnidosFil: Rubinstein Guichon, Mara Roxana. Columbia University; Estados Unidos. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Taylor, Jamila A.. Columbia University; Estados UnidosFil: Friedman, Richard A.. Columbia University; Estados UnidosFil: Shen, Bo. No especifíca;Fil: Han, Yiping W.. Columbia University; Estados Unido

Analysis of 16S rRNA genes reveals reduced Fusobacterial community diversity when translocating from saliva to GI sites

Fusobacterium nucleatum is a Gram-negative oral commensal anaerobe which has been increasingly implicated in various gastrointestinal (GI) disorders, including inflammatory bowel disease,appendicitis, GI cancers. The oral cavity harbors a diverse group of Fusobacterium, and it ispostulated that F. nucleatum in the GI tract originate from the mouth. It is not known, however, ifall oral Fusobacterium translocate to the GI sites with equal efficiencies. Therefore, we amplified 16SrRNA genes of F. nucleatum and F. periodonticum, two closely related oral species from matchedsaliva, gastric aspirates, and colon or ileal pouch aspirates of three patients with inflammatorybowel disease (IBD) and three healthy controls, and saliva alone from seven patients with eitheractive IBD or IBD in remission. The 16S rRNA gene amplicons were cloned, and the DNA sequencesdetermined by Sanger sequencing. The results demonstrate that fusobacterial community composition differs more significantly between the oral and GI sites than between different individuals.The oral communities demonstrate the highest level of variation and have the richest pool ofunique sequences, with certain nodes/strains enriched in the GI tract and others diminished duringtranslocation. The gastric and colon/pouch communities exhibit reduced diversity and are moreclosely related, possibly due to selective pressure in the GI tract. This study elucidates selectivetranslocation of oral fusobacteria to the GI tract. Identification of specific transmissible clones willfacilitate risk assessment for developing Fusobacterium-implicated GI disorders.Fil: Richardson, Miles. Columbia University; Estados UnidosFil: Ren, Jihui. Columbia University; Estados UnidosFil: Rubinstein Guichon, Mara Roxana. Columbia University; Estados Unidos. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Taylor, Jamila A.. Columbia University; Estados UnidosFil: Friedman, Richard A.. Columbia University; Estados UnidosFil: Shen, Bo. No especifíca;Fil: Han, Yiping W.. Columbia University; Estados Unido

Diffusion in a generalized Rubinstein-Duke model of electrophoresis with kinematic disorder

Using a generalized Rubinstein-Duke model we prove rigorously that kinematic disorder leaves the prediction of standard reptation theory for the scaling of the diffusion constant in the limit for long polymer chains $D \propto L^{-2}$ unaffected. Based on an analytical calculation as well as Monte Carlo simulations we predict kinematic disorder to affect the center of mass diffusion constant of an entangled polymer in the limit for long chains by the same factor as single particle diffusion in a random barrier model.Comment: 29 pages, 3 figures, submitted to PR

HIV Clustering in Mississippi: Spatial Epidemiological Study to Inform Implementation Science in the Deep South

Background: In recent years, more than half of new HIV infections in the United States occur among African Americans in the Southeastern United States. Spatial epidemiological analyses can inform public health responses in the Deep South by identifying HIV hotspots and community-level factors associated with clustering. Objective: The goal of this study was to identify and characterize HIV clusters in Mississippi through analysis of state-level HIV surveillance data. Methods: We used a combination of spatial epidemiology and statistical modeling to identify and characterize HIV hotspots in Mississippi census tracts (n=658) from 2008 to 2014. We conducted spatial analyses of all HIV infections, infections among men who have sex with men (MSM), and infections among African Americans. Multivariable logistic regression analyses identified community-level sociodemographic factors associated with HIV hotspots considering all cases. Results: There were HIV hotspots for the entire population, MSM, and African American MSM identified in the Mississippi Delta region, Southern Mississippi, and in greater Jackson, including surrounding rural counties (P \u3c .05). In multivariable models for all HIV cases, HIV hotspots were significantly more likely to include urban census tracts (adjusted odds ratio [AOR] 2.01, 95% CI 1.20-3.37) and census tracts that had a higher proportion of African Americans (AOR 3.85, 95% CI 2.23-6.65). The HIV hotspots were less likely to include census tracts with residents who had less than a high school education (AOR 0.95, 95% CI 0.92-0.98), census tracts with residents belonging to two or more racial/ethnic groups (AOR 0.46, 95% CI 0.30-0.70), and census tracts that had a higher percentage of the population living below the poverty level (AOR 0.51, 95% CI 0.28-0.92). Conclusions: We used spatial epidemiology and statistical modeling to identify and characterize HIV hotspots for the general population, MSM, and African Americans. HIV clusters concentrated in Jackson and the Mississippi Delta. African American race and urban location were positively associated with clusters, whereas having less than a high school education and having a higher percentage of the population living below the poverty level were negatively associated with clusters. Spatial epidemiological analyses can inform implementation science and public health response strategies, including improved HIV testing, targeted prevention and risk reduction education, and tailored preexposure prophylaxis to address HIV disparities in the South

DHODH modulates transcriptional elongation in the neural crest and melanoma

Melanoma is a tumour of transformed melanocytes, which are originally derived from the embryonic neural crest. It is unknown to what extent the programs that regulate neural crest development interact with mutations in the BRAF oncogene, which is the most commonly mutated gene in human melanoma1. We have used zebrafish embryos to identify the initiating transcriptional events that occur on activation of human BRAF(V600E) (which encodes an amino acid substitution mutant of BRAF) in the neural crest lineage. Zebrafish embryos that are transgenic for mitfa:BRAF(V600E) and lack p53 (also known as tp53) have a gene signature that is enriched for markers of multipotent neural crest cells, and neural crest progenitors from these embryos fail to terminally differentiate. To determine whether these early transcriptional events are important for melanoma pathogenesis, we performed a chemical genetic screen to identify small-molecule suppressors of the neural crest lineage, which were then tested for their effects on melanoma. One class of compound, inhibitors of dihydroorotate dehydrogenase (DHODH), for example leflunomide, led to an almost complete abrogation of neural crest development in zebrafish and to a reduction in the self-renewal of mammalian neural crest stem cells. Leflunomide exerts these effects by inhibiting the transcriptional elongation of genes that are required for neural crest development and melanoma growth. When used alone or in combination with a specific inhibitor of the BRAF(V600E) oncogene, DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies. Taken together, these studies highlight developmental pathways in neural crest cells that have a direct bearing on melanoma formation