Impact of new cancer medicine - real-world evidence from Danish register study of lung cancer patients.

Background: Lung cancer (LC) is the leading cause of cancer deaths worldwide. Several new treatments have become available in recent decades, but little research exists on the impact of these on productivity, early retirement and survival for LC patients and their spouses. This study evaluates the effect of new medicines on productivity, early retirement and survival for LC patients and their spouses.

Tryptophan 2,3-dioxygenase (TDO)-reactive T cells differ in their functional characteristics in health and cancer.

Tryptophan-2,3-dioxygenase (TDO) physiologically regulates systemic tryptophan levels in the liver. However, numerous studies have linked cancer with activation of local and systemic tryptophan metabolism. Indeed, similar to other heme dioxygenases TDO is constitutively expressed in many cancers.

The expression, function and targeting of haem oxygenase-1 in cancer.

Haem oxygenase-1 (HO-1) catalyses the rate-limiting step in haem degradation. All three metabolites resulting from haem degradation (carbon monoxide (CO), biliverdin and free iron) have anti-inflammatory and anti-apoptotic properties. HO-1 is a stress-inducible enzyme found extensively expressed in a vast variety of both human and murine cancers, where it serves as an essential survival molecule by modulating expression of molecules regulating apoptosis and stimulating angiogenesis.

High frequency of T cells specific for cryptic epitopes in melanoma patients.

A number of cytotoxic T-cell epitopes are cryptic epitopes generated from non-conventional sources. These include epitopes that are encoded by alternative open reading frames or in generally non-coding genomic regions, such as introns. We have previously observed a frequent recognition of cryptic epitopes by tumor infiltrating lymphocytes isolated from melanoma patients.

Construction of a cytosolic firefly luciferase reporter cassette for use in PCR-mediated gene deletion and fusion in Saccharomyces cerevisiae.

Monitoring promoter response to environmental changes using reporter systems has provided invaluable information regarding cellular state. With the development of in vivo luciferase reporter systems, inexpensive, sensitive and accurate promoter assays have been developed without the variability reported between in vitro samplings. Current luciferase reporter systems, however, are largely inflexible to modifications to the promoter of interest.

Indoleamine 2,3-dioxygenase specific, cytotoxic T cells as immune regulators.

Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme that is implicated in suppressing T-cell immunity in normal and pathologic settings. Here, we describe that spontaneous cytotoxic T-cell reactivity against IDO exists not only in patients with cancer but also in healthy persons. We show that the presence of such IDO-specific CD8(+) T cells boosted T-cell immunity against viral or tumor-associated antigens by eliminating IDO(+) suppressive cells.

Cell population modeling and parameter estimation for continuous cultures of Saccharomyces cerevisiae.

Saccharomyces cerevisiae is known to exhibit sustained oscillations in chemostats operated under aerobic and glucose-limited growth conditions. The oscillations are reflected both in intracellular and extracellular measurements. Our recent work has shown that unstructured cell population balance models are capable of generating sustained oscillations over an experimentally meaningful range of dilution rates.

Multiple stable states and hysteresis in continuous, oscillating cultures of budding yeast.

The conditions that precede the onset of autonomous oscillations in continuous yeast cultures were studied in three different types of experiments. It was found that the final state of the culture depended on the protocol used to start up the reactor. Batch cultures, switched to continuous operation at different stages of the batch growth curve, all exhibited similar dynamics-ethanol depletion followed by autonomous oscillations.

Statistical analysis of elicitation strategies for thiarubrine A production in hairy root cultures of Ambrosia artemisiifolia.

Elicitation strategies were studied for yield enhancement of thiarubrine A, a secondary metabolite and a potential pharmaceutical, produced by hairy root cultures of Ambrosia artemisiifolia. Abiotic elicitation was performed using vanadyl sulfate solution and biotic elicitation using autoclaved cell wall filtrates of the fungi Protomyces gravidus, a pathogen of A. artemisiifolia and Botrytis cinereae.

Solution and properties of age population balance models which assume discrete division ages.

A solution procedure for models of the transient age distribution which employ the assumption of discrete, constant division ages is developed. The solutions for the final state of the age distribution, the solutions obtained in the limit as time goes to infinity, are found to have properties which do not make biological sense. In particular, the solutions will only approach the steady-state solution for very special initial conditions.

Population balance models of autonomous microbial oscillations.

Autonomous oscillations in continuous microbial cultures is well documented for the case of baker's yeast, Saccharomyces cerevisiae, for which it has been observed under a range of operating conditions. We have found that autonomous microbial oscillations can be modeled by unstructured population balance models in which a key cell cycle parameter is a function of the environmental conditions, e.g.

Control of an Escherichia coli mixed culture via affinity binding.

A chemostat with population specific recycle was employed to alter the dynamics of a competitive mixed culture of Escherichia coli. Based on differential expression of a functional maltoporin, the two populations were separated by specific adhesion on starch-Sepharose. The slower growing population was the recycled to the reactor.

Growth and thiophene accumulation by hairy root cultures of Tagetes patula in media of varying initial pH.

Hairy roots of Tagetes patula were grown for 24 days in modified Murashige and Skoog's liquid medium at different initial pH levels of 4.0, 5.0, 5.

Control of mixed microbial cultures via specific cell adhesion.

A new method for manipulating the steady-state behavior of a mixed culture is introduced. The method makes use of differences in adherence properties between competing populations to maintain a desired population ratio. The very specific nature of some ligand-to-cell interactions allows precise manipulation of even closely related populations.

Periodic forcing of microbial cultures: a model for induction synchrony.

Periodic environmental shifts have been used to induce synchrony in many different microbial populations. In this article, the induction synchrony phenomenon is analyzed using an age distribution model in which the age at which the cells divide is subjected to periodic forcing. It is found that synchrony will occur whenever the period of the forcing lies in the interval between the youngest and the oldest division age that occur in the population during the forcing.

Plasmid stability in budding yeast populations: Steady-state growth with selection pressure.

Plasmid gene product accumulation in a cell population depends on the fraction of plasmid-containing cells and the distribution of single-cell plasmid content. These important population properties have been related to plasmid replication regulation and kinetics and to plasmid segregation rules at the single-cell level using population balance mathematical models. Budding yeast populations are considered in detail because of the practical potential of yeast host-vector systems and because of the model complications introduced by the asymmetric division pattern observed for Saccharomyces cerevisiae at all but the largest growth rates.

Kinetics of product formation and plasmid segregation in recombinant microbial populations.

Experimental and mathematical analysis of productivity of cultures containing recombinant plasmids is based in this work on the following paradigm: molecular controls leads to single cell kinetics leads to cell population dynamics leads to reactor productivity. Mathematical models have been developed for replication control of the lambda dv plasmid and for efficiency of the lac promoter-operator based on the molecular control mechanisms of these systems in Escherichia coli. A special and important attribute of these models is their ability to describe quantitatively a wide range of genetic effects as well as environmental influences on molecular control function.