Trading bits in the readout from a genetic network.

In the regulation of gene expression, information of relevance to the organism is represented by the concentrations of transcription factor molecules. To extract this information the cell must effectively "measure" these concentrations, but there are physical limits to the precision of these measurements. We use the gap gene network in the early fly embryo as an example of the tradeoff between the precision of concentration measurements and the transmission of relevant information. For thresholded measurements we find that lower thresholds are more important, and fine tuning is not required for near-optimal information transmission. We then consider general sensors, constrained only by a limit on their information capacity, and find that thresholded sensors can approach true information theoretic optima. The information theoretic approach allows us to identify the optimal sensor for the entire gap gene network and to argue that the physical limitations of sensing necessitate the observed multiplicity of enhancer elements, with sensitivities to combinations rather than single transcription factors.

How does an organism extract relevant information from transcription factor concentrations?

How does an organism regulate its genes? The involved regulation typically occurs in terms of a signal processing chain: an externally applied stimulus or a maternally supplied transcription factor leads to the expression of some downstream genes, which, in turn, are transcription factors for further genes. Especially during development, these transcription factors are frequently expressed in amounts where noise is still important; yet, the signals that they provide must not be lost in the noise. Thus, the organism needs to extract exactly relevant information in the signal. New experimental approaches involving single-molecule measurements at high temporal precision as well as increased precision in manipulations directly on the genome are allowing us to tackle this question anew. These new experimental advances mean that also from the theoretical side, theoretical advances should be possible. In this review, I will describe, specifically on the example of fly embryo gene regulation, how theoretical approaches, especially from inference and information theory, can help in understanding gene regulation. To do so, I will first review some more traditional theoretical models for gene regulation, followed by a brief discussion of information-theoretical approaches and when they can be applied. I will then introduce early fly development as an exemplary system where such information-theoretical approaches have traditionally been applied and can be applied; I will specifically focus on how one such method, namely the information bottleneck approach, has recently been used to infer structural features of enhancer architecture.

Delays in Fitness Adjustment Can Lead to Coexistence of Hierarchically Interacting Species.

Organisms that exploit different environments may experience a stochastic delay in adjusting their fitness when they switch habitats. We study two such organisms whose fitness is determined by the species composition of the local environment, as they interact through a public good. We show that a delay in the fitness adjustment can lead to the coexistence of the two species in a metapopulation, although the faster-growing species always wins in well-mixed competition experiments. Coexistence is favored over wide parameter ranges and is independent of spatial clustering. It arises when species are heterogeneous in their fitness and can keep each other balanced.

Exploiting ecology in drug pulse sequences in favour of population reduction.

A deterministic population dynamics model involving birth and death for a two-species system, comprising a wild-type and more resistant species competing via logistic growth, is subjected to two distinct stress environments designed to mimic those that would typically be induced by temporal variation in the concentration of a drug (antibiotic or chemotherapeutic) as it permeates through the population and is progressively degraded. Different treatment regimes, involving single or periodical doses, are evaluated in terms of the minimal population size (a measure of the extinction probability), and the population composition (a measure of the selection pressure for resistance or tolerance during the treatment). We show that there exist timescales over which the low-stress regime is as effective as the high-stress regime, due to the competition between the two species. For multiple periodic treatments, competition can ensure that the minimal population size is attained during the first pulse when the high-stress regime is short, which implies that a single short pulse can be more effective than a more protracted regime. Our results suggest that when the duration of the high-stress environment is restricted, a treatment with one or multiple shorter pulses can produce better outcomes than a single long treatment. If ecological competition is to be exploited for treatments, it is crucial to determine these timescales, and estimate for the minimal population threshold that suffices for extinction. These parameters can be quantified by experiment.

Universal equation of state and pseudogap in the two-dimensional Fermi gas.

We determine the thermodynamic properties and the spectral function for a homogeneous two-dimensional Fermi gas in the normal state using the Luttinger-Ward, or self-consistent T-matrix, approach. The density equation of state deviates strongly from that of the ideal Fermi gas even for moderate interactions, and our calculations suggest that temperature has a pronounced effect on the pressure in the crossover from weak to strong coupling, consistent with recent experiments. We also compute the superfluid transition temperature for a finite system in the crossover region. There is a pronounced pseudogap regime above the transition temperature: the spectral function shows a Bogoliubov-like dispersion with backbending, and the density of states is significantly suppressed near the chemical potential. The contact density at low temperatures increases with interaction and compares well with both experiment and zero-temperature Monte Carlo results.

Closing the patient-oncologist communication gap: a review of historic and current efforts.

Effective communication is essential in developing any relationship--this is particularly true between oncologists and their patients. The patient-oncologist relationship is one of the most delicate in medicine, and given the strong emotions associated with cancer, successful communication plays a paramount role in the wellbeing of patients and oncologists. Significant advances to close the communication gap have occurred over the past several decades, largely by addressing deficiencies in the various stages of an oncologist's lengthy training: undergraduate medical education, residency and fellowship, and continuing medical education. Stemming from several milestones achieved by highly motivated groups of individuals, including the creation of consensus statements and guidelines by communication education experts, progress has been made to improve patient-oncologist communication. This progress is marked by the development of evidence-based communication skills training programs, such as Oncotalk and Comskil, in addition to the creation of distant-learning modalities, such as the Studying Communication in Oncologist-Patient Encounters trial. This review article outlines the history of communication education during medical education and training, and brings to light more recent efforts to promote competent, communication-minded physicians necessary for effective cancer care.

Dipolar gases in coupled one-dimensional lattices.

We consider dipolar bosons in two tubes of one-dimensional lattices, where the dipoles are aligned to be maximally repulsive and the particle filling fraction is the same in each tube. In the classical limit of zero intersite hopping, the particles arrange themselves into an ordered crystal for any rational filling fraction, forming a complete devil's staircase like in the single tube case. Turning on hopping within each tube then gives rise to a competition between the crystalline Mott phases and a liquid of defects or solitons. However, for the two-tube case, we find that solitons from different tubes can bind into pairs for certain topologies of the filling fraction. This provides an intriguing example of pairing that is purely driven by correlations close to a Mott insulator.

Formation of ß-sheets in glutamine and alanine tripeptides.

The misfolding and aggregation of proteins is associated with many different diseases including the trinucleotide repeat disorders and Prion diseases. We have studied three residue peptides comprising alanine and glutamine in order to understand the short range interactions affecting the formation of ß-rich aggregates. Using infrared spectroscopy, we have found that trialanine and triglutamine form significant amounts of ß-sheet, but that tripeptides containing alanine and glutamine are only able to form ß-sheet if the glutamine side-chains extend outward on both faces of the sheet. From our data, we conclude that different stabilizing interactions are responsible for ß-sheet formation in trialanine and triglutamine.

Interpolation schemes for peptide rearrangements.

A variety of methods (in total seven) comprising different combinations of internal and Cartesian coordinates are tested for interpolation and alignment in connection attempts for polypeptide rearrangements. We consider Cartesian coordinates, the internal coordinates used in CHARMM, and natural internal coordinates, each of which has been interfaced to the OPTIM code and compared with the corresponding results for united-atom force fields. We show that aligning the methylene hydrogens to preserve the sign of a local dihedral angle, rather than minimizing a distance metric, provides significant improvements with respect to connection times and failures. We also demonstrate the superiority of natural coordinate methods in conjunction with internal alignment. Checking the potential energy of the interpolated structures can act as a criterion for the choice of the interpolation coordinate system, which reduces failures and connection times significantly.

Multiple scales in metapopulations of public goods producers.

Multiple scales in metapopulations can give rise to paradoxical behavior: in a conceptual model for a public goods game, the species associated with a fitness cost due to the public good production can be stabilized in the well-mixed limit due to the mere existence of these scales. The scales in this model involve a length scale corresponding to separate patches, coupled by mobility, and separate time scales for reproduction and interaction with a local environment. Contrary to the well-mixed high mobility limit, we find that for low mobilities, the interaction rate progressively stabilizes this species due to stochastic effects, and that the formation of spatial patterns is not crucial for this stabilization.