Systems approaches to modelling pathways and networks.

Peer reviewedPreprin

The Lantern Vol. 47, No. 2, May 1981

• Festival • Ode to Old Tom • Living Room • Writing a Poem • Mission Impossible • The Hinge is Oiled • The Potter\u27s Field at Malvern • Points of Time • Attempted Autonomy • My Love • Love, not War • Death Comes Quickly • You Can\u27t Always Get What You Don\u27t Really Want • You See (Johnny\u27s Tale): An Elegy • Sanguine Hopeshttps://digitalcommons.ursinus.edu/lantern/1118/thumbnail.jp

Stochasticity and traffic jams in the transcription of ribosomal RNA: Intriguing role of termination and antitermination

In fast growing bacteria, ribosomal RNA (rRNA) is required to be transcribed at very high rates to sustain the high cellular demand on ribosome synthesis. This results in dense traffic of RNA polymerases (RNAP). We developed a stochastic model, integrating results of single-molecule and quantitative in vivo studies of E. coli, to evaluate the quantitative effect of pausing, termination, and antitermination on rRNA transcription. Our calculations reveal that in dense RNAP traffic, spontaneous pausing of RNAP can lead to severe "traffic jams", as manifested in the broad distribution of inter-RNAP distances and can be a major factor limiting transcription and hence growth. Our results suggest the suppression of these pauses by the ribosomal antitermination complex to be essential at fast growth. Moreover, unsuppressed pausing by even a few non-antiterminated RNAPs can already reduce transcription drastically under dense traffic. However, the termination factor Rho can remove the non-antiterminated RNAPs and restore fast transcription. The results thus suggest an intriguing role by Rho to enhance rather than attenuate rRNA transcription.Comment: includes Supporting Informatio

Mutational Analysis of the SOX9 Gene in Campomelic Dysplasia and Autosomal Sex Reversal: Lack of Genotype/Phenotype Correlations

It has previously been shown that, in the heterozygous state, mutations in the SOX9 gene cause campomelic dysplasia (CD) and the often associated autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one recurrent mutation were characterized in one SOX9 allele each, and in one case, no mutation was found. Four missense mutations are all located within the high mobility group (HMG) domain. They either reduce or abolish the DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense and three frameshift mutations identified, two leave the C-terminal transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or almost completely intact. When tested in cell transfection experiments, the recurrent nonsense mutation Y440X, found in two patients who survived for four and more than 9 years, respectively, exhibits some residual transactivation ability. In contrast, a frameshift mutation extending the protein by 70 residues at codon 507, found in a patient who died shortly after birth, showed no transactivation. This is apparently due to instability of the mutant SOX9 protein as demonstrated by Western blotting. Amino acid substitutions and nonsense mutations are found in patients with and without XY sex reversal, indicating that sex reversal in CD is subject to variable penetrance. Finally, none of 18 female patients with XY gonadal dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP assays, providing evidence that SOX9 mutations do not usually result in XY sex reversal without skeletal malformation

A Spatial Analysis of Rift Valley Fever Virus Seropositivity in Domestic Ruminants in Tanzania

Rift Valley fever (RVF) is an acute arthropod-borne viral zoonotic disease primarily occurring in Africa. Since RVF-like disease was reported in Tanzania in 1930, outbreaks of the disease have been reported mainly from the eastern ecosystem of the Great Rift Valley. This cross-sectional study was carried out to describe the variation in RVF virus (RVFV) seropositivity in domestic ruminants between selected villages in the eastern and western Rift Valley ecosystems in Tanzania, and identify potential risk factors. Three study villages were purposively selected from each of the two Rift Valley ecosystems. Serum samples from randomly selected domestic ruminants (n = 1,435) were tested for the presence of specific immunoglobulin G (IgG) and M (IgM), using RVF enzyme-linked immunosorbent assay methods. Mixed effects logistic regression modelling was used to investigate the association between potential risk factors and RVFV seropositivity. The overall RVFV seroprevalence (n = 1,435) in domestic ruminants was 25.8% and species specific seroprevalence was 29.7%, 27.7% and 22.0% in sheep (n = 148), cattle (n = 756) and goats (n = 531), respectively. The odds of seropositivity were significantly higher in animals sampled from the villages in the eastern than those in the western Rift Valley ecosystem (OR = 1.88, CI: 1.41, 2.51; p<0.001), in animals sampled from villages with soils of good than those with soils of poor water holding capacity (OR = 1.97; 95% CI: 1.58, 3.02; p< 0.001), and in animals which had been introduced than in animals born within the herd (OR = 5.08, CI: 2.74, 9.44; p< 0.001). Compared with animals aged 1-2 years, those aged 3 and 4-5 years had 3.40 (CI: 2.49, 4.64; p< 0.001) and 3.31 (CI: 2.27, 4.82, p< 0.001) times the odds of seropositivity. The findings confirm exposure to RVFV in all the study villages, but with a higher prevalence in the study villages from the eastern Rift Valley ecosystem

Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations

It has previously been shown that, in the heterozygous state, mutations in the SOX9 gene cause campomelic dysplasia (CD) and the often associated autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one recurrent mutation were characterized in one SOX9 allele each, and in one case, no mutation was found. Four missense mutations are all located within the high mobility group (HMG) domain. They either reduce or abolish the DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense and three frameshift mutations identified, two leave the C-terminal transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or almost completely intact. When tested in cell transfection experiments, the recurrent nonsense mutation Y440X, found in two patients who survived for four and more than 9 years, respectively, exhibits some residual transactivation ability. In contrast, a frameshift mutation extending the protein by 70 residues at codon 507, found in a patient who died shortly after birth, showed no transactivation. This is apparently due to instability of the mutant SOX9 protein as demonstrated by Western blotting. Amino acid substitutions and nonsense mutations are found in patients with and without XY sex reversal, indicating that sex reversal in CD is subject to variable penetrance. Finally, none of 18 female patients with XY gonadal dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP assays, providing evidence that SOX9 mutations do not usually result in XY sex reversal without skeletal malformations

Joint Endeavor Toward Sustainable Mountain Development: Research at the Institute for Interdisciplinary Mountain Research of the Austrian Academy of Sciences

The sustainable development of mountain regions requires inter-and transdisciplinary knowledge. The Institute for Interdisciplinary Mountain Research contributes to this global endeavor as part of the Austrian Academy of Sciences and as a member of international scientific networks, together with local partners and stakeholders. As a joint effort of individual researchers covering multiple fields, this article highlights our views on mountains as research objects, the phenomena we investigate as parts of entire mountain systems, and the synergies and differences of the disciplinary frames within which we work

Nus transcription elongation factors and RNase III modulate small ribosome subunit biogenesis in E scherichia coli

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96334/1/mmi12105.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/96334/2/mmi12105-sup-0001-si.pd

Quantum Transport in Semiconductor Nanostructures

I. Introduction (Preface, Nanostructures in Si Inversion Layers, Nanostructures in GaAs-AlGaAs Heterostructures, Basic Properties). II. Diffusive and Quasi-Ballistic Transport (Classical Size Effects, Weak Localization, Conductance Fluctuations, Aharonov-Bohm Effect, Electron-Electron Interactions, Quantum Size Effects, Periodic Potential). III. Ballistic Transport (Conduction as a Transmission Problem, Quantum Point Contacts, Coherent Electron Focusing, Collimation, Junction Scattering, Tunneling). IV. Adiabatic Transport (Edge Channels and the Quantum Hall Effect, Selective Population and Detection of Edge Channels, Fractional Quantum Hall Effect, Aharonov-Bohm Effect in Strong Magnetic Fields, Magnetically Induced Band Structure).Comment: 111 pages including 109 figures; this review from 1991 has retained much of its usefulness, but it was not yet available electronicall

Precise measurement of the W-boson mass with the CDF II detector

We have measured the W-boson mass MW using data corresponding to 2.2/fb of integrated luminosity collected in proton-antiproton collisions at 1.96 TeV with the CDF II detector at the Fermilab Tevatron collider. Samples consisting of 470126 W->enu candidates and 624708 W->munu candidates yield the measurement MW = 80387 +- 12 (stat) +- 15 (syst) = 80387 +- 19 MeV. This is the most precise measurement of the W-boson mass to date and significantly exceeds the precision of all previous measurements combined