Activation of mating type genes by transposition in Saccharomyces cerevisiae

Yeast Saccharomyces cerevisiae may express an a or alpha mating type. These cells types may be interconverted as a consequence of heritable genetic alteractions at the mating type locus (MAT). According to the more general controlling element model [Oshima, U. & Takano, I. (1971) Genetics 67, 327--335] and the specific cassette model [Hicks, J., Strathern, J. & Herskowitz, I. (1977) in DNA Insertion Elements, Plasmids and Episomes, eds. Bukhari, A. I., Shapiro, J.A. & Adhya, S. L.(Cold Spring Harbor Laboratory, Cold Spring Harbor, NY), pp. 457--462], the regulatory information required for switching the MAT locus exists at two other loosely linked loci, HMa and HMalpha. Specifically, the HMa and HMalpha loci are proposed to carry silent alpha and silent a genes, respectively. According to these models, switching occurs when a replica of a silent gene replaces the resident information at the mating type locus and is thereby expressed. These models predict that mutations at the silent ("storage") loci would generate defective MAT loci subsequent to the switching process. Therefore, the behavior of HMalpha mutants during the mating type interconversion was investigated. The results demonstrate that defective MATa alleles are generated by switching the MATalpha locus in HMalpha mutants. Thus, the genetic information from HMalpha is transposed to the mating type locus. These results provide genetic evidence in support of these models

Optimizing the Stark-decelerator beamline for the trapping of cold molecules using evolutionary strategies

We demonstrate feedback control optimization for the Stark deceleration and trapping of neutral polar molecules using evolutionary strategies. In a Stark-decelerator beamline pulsed electric fields are used to decelerate OH radicals and subsequently store them in an electrostatic trap. The efficiency of the deceleration and trapping process is determined by the exact timings of the applied electric field pulses. Automated optimization of these timings yields an increase of 40 % of the number of trapped OH radicals.Comment: 7 pages, 4 figures (RevTeX) (v2) minor corrections (v3) no changes to manuscript, but fix author list in arXiv abstrac

Kink stability, propagation, and length scale competition in the periodically modulated sine-Gordon equation

We have examined the dynamical behavior of the kink solutions of the one-dimensional sine-Gordon equation in the presence of a spatially periodic parametric perturbation. Our study clarifies and extends the currently available knowledge on this and related nonlinear problems in four directions. First, we present the results of a numerical simulation program which are not compatible with the existence of a radiative threshold, predicted by earlier calculations. Second, we carry out a perturbative calculation which helps interpret those previous predictions, enabling us to understand in depth our numerical results. Third, we apply the collective coordinate formalism to this system and demonstrate numerically that it accurately reproduces the observed kink dynamics. Fourth, we report on a novel occurrence of length scale competition in this system and show how it can be understood by means of linear stability analysis. Finally, we conclude by summarizing the general physical framework that arises from our study.Comment: 19 pages, REVTeX 3.0, 24 figures available from A S o

HIV-1 Evolutionary Patterns Associated with Metastatic Kaposi's Sarcoma during AIDS.

Kaposi's sarcoma (KS) in HIV-infected individuals can have a wide range of clinical outcomes, from indolent skin tumors to a life-threatening visceral cancer. KS tumors contain endothelial-related cells and inflammatory cells that may be HIV-infected. In this study we tested if HIV evolutionary patterns distinguish KS tumor relatedness and progression. Multisite autopsies from participants who died from HIV-AIDS with KS prior to the availability of antiretroviral therapy were identified at the AIDS and Cancer Specimen Resource (ACSR). Two patients (KS1 and KS2) died predominantly from non-KS-associated disease and KS3 died due to aggressive and metastatic KS within one month of diagnosis. Skin and visceral tumor and nontumor autopsy tissues were obtained (n = 12). Single genome sequencing was used to amplify HIV RNA and DNA, which was present in all tumors. Independent HIV tumor clades in phylogenies differentiated KS1 and KS2 from KS3, whose sequences were interrelated by both phylogeny and selection. HIV compartmentalization was confirmed in KS1 and KS2 tumors; however, in KS3, no compartmentalization was observed among sampled tissues. While the sample size is small, the HIV evolutionary patterns observed in all patients suggest an interplay between tumor cells and HIV-infected cells which provides a selective advantage and could promote KS progression

Towards hardware acceleration of neuroevolution for multimedia processing applications on mobile devices

This paper addresses the problem of accelerating large artificial neural networks (ANN), whose topology and weights can evolve via the use of a genetic algorithm. The proposed digital hardware architecture is capable of processing any evolved network topology, whilst at the same time providing a good trade off between throughput, area and power consumption. The latter is vital for a longer battery life on mobile devices. The architecture uses multiple parallel arithmetic units in each processing element (PE). Memory partitioning and data caching are used to minimise the effects of PE pipeline stalling. A first order minimax polynomial approximation scheme, tuned via a genetic algorithm, is used for the activation function generator. Efficient arithmetic circuitry, which leverages modified Booth recoding, column compressors and carry save adders, is adopted throughout the design

Renormalization Group Theory for a Perturbed KdV Equation

We show that renormalization group(RG) theory can be used to give an analytic description of the evolution of a perturbed KdV equation. The equations describing the deformation of its shape as the effect of perturbation are RG equations. The RG approach may be simpler than inverse scattering theory(IST) and another approaches, because it dose not rely on any knowledge of IST and it is very concise and easy to understand. To the best of our knowledge, this is the first time that RG has been used in this way for the perturbed soliton dynamics.Comment: 4 pages, no figure, revte

Annealing schedule from population dynamics

We introduce a dynamical annealing schedule for population-based optimization algorithms with mutation. On the basis of a statistical mechanics formulation of the population dynamics, the mutation rate adapts to a value maximizing expected rewards at each time step. Thereby, the mutation rate is eliminated as a free parameter from the algorithm.Comment: 6 pages RevTeX, 4 figures PostScript; to be published in Phys. Rev.

Eluxadoline Benefits Patients With Irritable Bowel Syndrome With Diarrhea in a Phase 2 Study

Background & AimsSimultaneous agonism of the μ-opioid receptor and antagonism of the δ-opioid receptor can reduce abdominal pain and diarrhea in patients with irritable bowel syndrome with diarrhea (IBS-D) without constipating side effects. We evaluated the efficacy and safety of a minimally absorbed, μ-opioid receptor agonist and δ-opioid receptor antagonist (eluxadoline) in a phase 2 study in patients with IBS-D.MethodsWe randomly assigned 807 patients to groups that received oral placebo twice daily or 5, 25, 100, or 200 mg oral eluxadoline for 12 weeks. The primary end point was clinical response at week 4, defined by a mean reduction in daily pain score from baseline of ≥30%, and of at least 2 points on 0−10 scale, as well as a stool consistency score of 3 or 4 on the Bristol Stool Scale (1–7) for at least 66% of daily diary entries during that week.ResultsSignificantly more patients receiving 25 mg (12.0%) or 200 mg (13.8%) eluxadoline met the primary end point of clinical response than patients given placebo (5.7%; P < .05). Patients receiving eluxadoline at 100 mg and 200 mg also had greater improvements in bowel movement frequency and urgency, global symptoms, quality of life, and adequate relief assessments (P < .05). Additionally, patients receiving 100 mg (28.0%) or 200 mg (28.5%) eluxadoline were significantly more likely than those receiving placebo (13.8%; P < .005) to meet the US Food and Drug Administration response end point during the full 12 weeks of the study. Eluxadoline was well tolerated with a low incidence of constipation.ConclusionsIn a phase 2 study of the mixed μ-opioid receptor agonist/δ-opioid receptor antagonist eluxadoline vs placebo in patients with IBS-D, patients given eluxadoline were significantly more likely to be clinical responders, based on a composite of improvement in abdominal pain and stool consistency. Further study of eluxadoline is warranted to assess its potential as a treatment for IBS-D. ClinicalTrials.gov number, NCT0113027

Virtual Immortality: Reanimating Characters from TV Shows.

The objective of this work is to build virtual talking avatars of characters fully automatically from TV shows. From this unconstrained data, we show how to capture a character's style of speech, visual appearance and language in an e ort to construct an interactive avatar of the person and e ectively immortalize them in a computational model. We make three contributions (i) a complete framework for producing a generative model of the audiovisual and language of characters from TV shows; (ii) a novel method for aligning transcripts to video using the audio; and (iii) a fast audio segmentation system for silencing nonspoken audio from TV shows. Our framework is demonstrated using all 236 episodes from the TV series Friends [34] ( 97hrs of video) and shown to generate novel sentences as well as character specific speech and video