1,145 research outputs found
The failure of radical treatments to cure cancer: can less deliver more?
All too often attempts to deliver improved cancer cure rates by increasing the dose of a particular treatment are not successful enough to justify the accompanying increase in toxicity and reduction in quality of life suffered by a significant number of patients. In part, this drive for using higher levels of treatment derives from the nature of the process for testing and incorporation of new protocols. Indeed, new treatment regimens must now consider the key role of immunity in cancer control, a component that has been largely ignored until very recently. The recognition that some drugs developed for cytotoxicity at higher doses can display alternative anticancer activities at lower doses including through modulation of immune responses is prompting a significant re-evaluation of treatment protocol development. Given that tumours are remarkably heterogeneous and with inherent genetic instability it is probably only the adaptive immune response with its flexibility and extensive repertoire that can rise to the challenge of effecting significant control and ultimately elimination of a patient's cancer. This article discusses some of the elements that have limited higher levels of treatment outcomes and where too much proved less effective. We explore observations that less can often be as effective, if not more effective especially with some chemotherapy regimens, and discuss how this can be exploited in combination with immunotherapies to deliver nontoxic improved tumour responses
Characterizing Long Term Rainfall Data for Estimating Climate Risk in Semi-arid Zimbabwe
There is still a strong disconnect between the parameters and scale of information that farmers prefer and those of the seasonal climate forecasts (SCFs). There is a need to augment SCFs as they are currently presented; to make them more useful for farm decision making. The objective of this study was to use simple statistical methods of analysis to characterise long term rainfall for estimating climate risk in semi-arid Zimbabwe. This study reveals the importance of accessing long-term daily rainfall records to enable āweather-within-climateā analyses that can be tailored to the needs of farmers. The most critical point is to describe the climate in terms of events of direct relevance to farming rather than simple standard measures. Agronomically, the important rainfall events relevant to farmers in rainfed agriculture include the start, end and length of the rainy season, risks of dry spells as well as the distribution of rainfall amounts through the year. There are difficult risks in El Nino compared to Ordinary and La Nina seasons in terms of frequency and length of dry spells, number of rain days, rainfall onset and cessation dates and total rainfall amount. The chance of a dry-spell being broken is also considerably lower in El Nino years, compared to La Nina and Ordinary years. Packaging SCF with historic climate data as well as bringing in the shorter range forecasts, together with the experience of the season as it develops is a way in which value could be added to climate information dissemination. Technologies that enhance water use efficiency could also be one of the major areas of research to be integrated into the semi-arid farmersā existing strategies to cope with climate variability and ultimately change
Species Doublers as Super Multiplets in Lattice Supersymmetry: Exact Supersymmetry with Interactions for D=1 N=2
We propose a new lattice superfield formalism in momentum representation
which accommodates species doublers of the lattice fermions and their bosonic
counterparts as super multiplets. We explicitly show that one dimensional N=2
model with interactions has exact Lie algebraic supersymmetry on the lattice
for all super charges. In coordinate representation the finite difference
operator is made to satisfy Leibnitz rule by introducing a non local product,
the ``star'' product, and the exact lattice supersymmetry is realized. The
standard momentum conservation is replaced on the lattice by the conservation
of the sine of the momentum, which plays a crucial role in the formulation.
Half lattice spacing structure is essential for the one dimensional model and
the lattice supersymmetry transformation can be identified as a half lattice
spacing translation combined with alternating sign structure. Invariance under
finite translations and locality in the continuum limit are explicitly
investigated and shown to be recovered. Supersymmetric Ward identities are
shown to be satisfied at one loop level. Lie algebraic lattice supersymmetry
algebra of this model suggests a close connection with Hopf algebraic exactness
of the link approach formulation of lattice supersymmetry.Comment: 34 pages, 2 figure
Constraining noncommutative field theories with holography
An important window to quantum gravity phenomena in low energy noncommutative
(NC) quantum field theories (QFTs) gets represented by a specific form of UV/IR
mixing. Yet another important window to quantum gravity, a holography,
manifests itself in effective QFTs as a distinct UV/IR connection. In matching
these two principles, a useful relationship connecting the UV cutoff
, the IR cutoff and the scale of
noncommutativity , can be obtained. We show that an effective
QFT endowed with both principles may not be capable to fit disparate
experimental bounds simultaneously, like the muon and the masslessness of
the photon. Also, the constraints from the muon preclude any possibility
to observe the birefringence of the vacuum coming from objects at cosmological
distances. On the other hand, in NC theories without the UV completion, where
the perturbative aspect of the theory (obtained by truncating a power series in
) becomes important, a heuristic estimate of the region
where the perturbative expansion is well-defined , gets affected when holography is applied by providing the energy of the
system a -dependent lower limit. This may affect models
which try to infer the scale by using data from low-energy
experiments.Comment: 4 pages, version to be published in JHE
Adaptation in integrated assessment modeling: where do we stand?
Adaptation is an important element on the climate change policy agenda. Integrated assessment models, which are key tools to assess climate change policies, have begun to address adaptation, either by including it implicitly in damage cost estimates, or by making it an explicit control variable. We analyze how modelers have chosen to describe adaptation within an integrated framework, and suggest many ways they could improve the treatment of adaptation by considering more of its bottom-up characteristics. Until this happens, we suggest, models may be too optimistic about the net benefits adaptation can provide, and therefore may underestimate the amount of mitigation they judge to be socially optimal. Under some conditions, better modeling of adaptation costs and benefits could have important implications for defining mitigation targets. Ā© Springer Science+Business Media B.V. 2009
Searching for Exoplanets Using a Microresonator Astrocomb
Detection of weak radial velocity shifts of host stars induced by orbiting
planets is an important technique for discovering and characterizing planets
beyond our solar system. Optical frequency combs enable calibration of stellar
radial velocity shifts at levels required for detection of Earth analogs. A new
chip-based device, the Kerr soliton microcomb, has properties ideal for
ubiquitous application outside the lab and even in future space-borne
instruments. Moreover, microcomb spectra are ideally suited for astronomical
spectrograph calibration and eliminate filtering steps required by conventional
mode-locked-laser frequency combs. Here, for the calibration of astronomical
spectrographs, we demonstrate an atomic/molecular line-referenced,
near-infrared soliton microcomb. Efforts to search for the known exoplanet HD
187123b were conducted at the Keck-II telescope as a first in-the-field
demonstration of microcombs
Can computational efficiency alone drive the evolution of modularity in neural networks?
Some biologists have abandoned the idea that computational efficiency in processing multipart tasks or input sets alone drives the evolution of modularity in biological networks. A recent study confirmed that small modular (neural) networks are relatively computationally-inefficient but large modular networks are slightly more efficient than non-modular ones. The present study determines whether these efficiency advantages with network size can drive the evolution of modularity in networks whose connective architecture can evolve. The answer is no, but the reason why is interesting. All simulations (run in a wide variety of parameter states) involving gradualistic connective evolution end in non-modular local attractors. Thus while a high performance modular attractor exists, such regions cannot be reached by gradualistic evolution. Non-gradualistic evolutionary simulations in which multi-modularity is obtained through duplication of existing architecture appear viable. Fundamentally, this study indicates that computational efficiency alone does not drive the evolution of modularity, even in large biological networks, but it may still be a viable mechanism when networks evolve by non-gradualistic means
Recurrent Modification of a Conserved Cis-Regulatory Element Underlies Fruit Fly Pigmentation Diversity
The development of morphological traits occurs through the collective action of networks of genes connected at the level of gene expression. As any node in a network may be a target of evolutionary change, the recurrent targeting of the same node would indicate that the path of evolution is biased for the relevant trait and network. Although examples of parallel evolution have implicated recurrent modification of the same gene and cis-regulatory element (CRE), little is known about the mutational and molecular paths of parallel CRE evolution. In Drosophila melanogaster fruit flies, the Bric-Ć -brac (Bab) transcription factors control the development of a suite of sexually dimorphic traits on the posterior abdomen. Female-specific Bab expression is regulated by the dimorphic element, a CRE that possesses direct inputs from body plan (ABD-B) and sex-determination (DSX) transcription factors. Here, we find that the recurrent evolutionary modification of this CRE underlies both intraspecific and interspecific variation in female pigmentation in the melanogaster species group. By reconstructing the sequence and regulatory activity of the ancestral Drosophila melanogaster dimorphic element, we demonstrate that a handful of mutations were sufficient to create independent CRE alleles with differing activities. Moreover, intraspecific and interspecific dimorphic element evolution proceeded with little to no alterations to the known body plan and sex-determination regulatory linkages. Collectively, our findings represent an example where the paths of evolution appear biased to a specific CRE, and drastic changes in function were accompanied by deep conservation of key regulatory linkages. Ā© 2013 Rogers et al
Synthesis and Exciton Dynamics of Donor-Orthogonal Acceptor Conjugated Polymers: Reducing the Singlet-Triplet Energy Gap
The presence of energetically low-lying triplet states is a hallmark of organic semiconductors. Even though they present a wealth of interesting photophysical properties, these optically dark states significantly limit optoelectronic device performance. Recent advances in emissive charge-transfer molecules have pioneered routes to reduce the energy gap between triplets and "bright" singlets, allowing thermal population exchange between them and eliminating a significant loss channel in devices. In conjugated polymers, this gap has proved resistant to modification. Here, we introduce a general approach to reduce the singlet-triplet energy gap in fully conjugated polymers, using a donor-orthogonal acceptor motif to spatially separate electron and hole wave functions. This new generation of conjugated polymers allows for a greatly reduced exchange energy, enhancing triplet formation and enabling thermally activated delayed fluorescence. We find that the mechanisms of both processes are driven by excited-state mixing between Ļ-Ļ*and charge-transfer states, affording new insight into reverse intersystem crossing.Part of this work was funded by EU project 679789 ā 455 CONTREX, EC H2020 SYNCHRONICS (643238), EC H2020 SOLEDLIGHT (643791) and EPSRC (EP/M005143/1) A.J.M. was supported by the EPSRC (EP/456M01083X). J.M.F. was supported by EPSRC (EP/K016288/1). F.C. is a Royal Society Wolfson Research Merit Award holder. H.L.S. was supported by the Winton Programme 457 for the Physics of Sustainability. We are grateful to the Imperial College High Performance Computing Service (doi: 10.14469/hpc/2232)
Reciprocity as a foundation of financial economics
This paper argues that the subsistence of the fundamental theorem of contemporary financial mathematics is the ethical concept āreciprocityā. The argument is based on identifying an equivalence between the contemporary, and ostensibly āvalue neutralā, Fundamental Theory of Asset Pricing with theories of mathematical probability that emerged in the seventeenth century in the context of the ethical assessment of commercial contracts in a framework of Aristotelian ethics. This observation, the main claim of the paper, is justified on the basis of results from the Ultimatum Game and is analysed within a framework of Pragmatic philosophy. The analysis leads to the explanatory hypothesis that markets are centres of communicative action with reciprocity as a rule of discourse. The purpose of the paper is to reorientate financial economics to emphasise the objectives of cooperation and social cohesion and to this end, we offer specific policy advice
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