14,019 research outputs found
Towards Interactive Logic Programming
Linear logic programming uses provability as the basis for computation. In
the operational semantics based on provability, executing the
additive-conjunctive goal from a program simply terminates
with a success if both and are solvable from . This is an
unsatisfactory situation, as a central action of \& -- the action of choosing
either or by the user -- is missing in this semantics.
We propose to modify the operational semantics above to allow for more active
participation from the user. We illustrate our idea via muProlog, an extension
of Prolog with additive goals.Comment: 8 pages. It describes two execution models for interactive logic
programmin
Design Opportunities in Service-Product Combined Systems
This paper aims to examine recent research issues related to the integration of service and product in view of industrial design. Further, it attempts to identify new opportunities for further research regarding “product-servicization” vs. “service-productization”.
In the continued efforts to provide the users with fuller experiences, one major trend is the blending of products and services.
Much existing research seems to either present cases or propose frameworks regarding the ‘connection’, rather than ‘integration’ between products and services. Broadly, two major approaches seem to exist in this area: 1. product-servicization, 2. service-productization. The former generally indicates adding more services to existing products, whereas the latter generally refers to making services tangible and/or visible in the form of a product. However, findings of an extensive literature search conducted for this study suggest one important deficiency in dealing with service issues around the product: the ‘integration’ between the actual product design and service elements for supporting new service-product system. That is the rationale behind this research, an attempt to investigate the possibility for the integration of product design and service factors which could be embedded in the design of product itself in new service-product system.
This paper is largely based on qualitative research. New design research opportunities are identified by qualitatively analyzing relevant literature, synthesizing the information and presenting some cases to support the main argument of the research.
Design-led Service-Productization is not, and should not be re-arranging deck chairs on the Titanic. Rather, it should bring practical and tangible design issues related to new service-product system. Findings suggest that this approach could provide a new model of new product development integrated with a service scheme, which is a more proactive approach than “product-servicization”. Further development of this research could lead to establishing a framework for the Design-led Service-Product Integration.
Keywords:
Product-servicization; Industrial design; Service; Product; Integration</p
Structure analysis of single- and multi-frequency subspace migrations in inverse scattering problems
In this literature, we carefully investigate the structure of single- and
multi-frequency imaging functions, that are usually employed in inverse
scattering problems. Based on patterns of the singular vectors of the
Multi-Static Response (MSR) matrix, we establish a relationship between imaging
functions and the Bessel function. This relationship indicates certain
properties of imaging functions and the reason behind enhancement in the
imaging performance by multiple frequencies. Several numerical simulations with
a large amount of noisy data are performed in order to support our
investigation.Comment: 11 pages, 10 figure
Terahertz quantum plasmonics at nanoscales and angstrom scales
Through the manipulation of metallic structures, light-matter interaction can enter into the realm of quantum mechanics. For example, intense terahertz pulses illuminating a metallic nanotip can promote terahertz field-driven electron tunneling to generate enormous electron emission currents in a subpicosecond time scale. By decreasing the dimension of the metallic structures down to the nanoscale and angstrom scale, one can obtain a strong field enhancement of the incoming terahertz field to achieve atomic field strength of the order of V/nm, driving electrons in the metal into tunneling regime by overcoming the potential barrier. Therefore, designing and optimizing the metal structure for high field enhancement are an essential step for studying the quantum phenomena with terahertz light. In this review, we present several types of metallic structures that can enhance the coupling of incoming terahertz pulses with the metals, leading to a strong modification of the potential barriers by the terahertz electric fields. Extreme nonlinear responses are expected, providing opportunities for the terahertz light for the strong light-matter interaction. Starting from a brief review about the terahertz field enhancement on the metallic structures, a few examples including metallic tips, dipole antenna, and metal nanogaps are introduced for boosting the quantum phenomena. The emerging techniques to control the electron tunneling driven by the terahertz pulse have a direct impact on the ultrafast science and on the realization of next-generation quantum devices
Discrete diffraction managed solitons: Threshold phenomena and rapid decay for general nonlinearities
We prove a threshold phenomenon for the existence/non-existence of energy
minimizing solitary solutions of the diffraction management equation for
strictly positive and zero average diffraction. Our methods allow for a large
class of nonlinearities, they are, for example, allowed to change sign, and the
weakest possible condition, it only has to be locally integrable, on the local
diffraction profile. The solutions are found as minimizers of a nonlinear and
nonlocal variational problem which is translation invariant. There exists a
critical threshold ?cr such that minimizers for this variational problem exist
if their power is bigger than ?cr and no minimizers exist with power less than
the critical threshold. We also give simple criteria for the finiteness and
strict positivity of the critical threshold. Our proof of existence of
minimizers is rather direct and avoids the use of Lions' concentration
compactness argument.
Furthermore, we give precise quantitative lower bounds on the exponential
decay rate of the diffraction management solitons, which confirm the physical
heuristic prediction for the asymptotic decay rate. Moreover, for ground state
solutions, these bounds give a quantitative lower bound for the divergence of
the exponential decay rate in the limit of vanishing average diffraction. For
zero average diffraction, we prove quantitative bounds which show that the
solitons decay much faster than exponentially. Our results considerably extend
and strengthen the results of [15] and [16].Comment: 49 pages, no figure
Cytochrome P450 pharmacogenetics : implications for anticancer and warfarin therapy
There is a pronounced interindividual variability in the drug disposition, response and toxicity.
Pharmacogenetics aims at identifying genetic biomarkers that could help to increase the drug efficacy, reduce
adverse drug reactions and contribute to the development of personalized medicine. Polymorphic cytochrome
P450 genes encoding heme-containing ER membrane bound monooxygenases that metabolize xenobiotics,
drugs and also endogenous compounds, strongly contribute to interindividual variations in drug response. In the
present work we have investigated molecular mechanisms of the adverse drug reactions caused by the
polymorphic changes in the cytochrome P450 2C8 (CYP2C8), CYP2C9 and CYP3A4 genes and, in addition
developed a novel enzymatic assay for CYP2W1.
CYP2W1, a P450 enzyme mainly expressed in colon cancer, has an unknown function and no specific
substrates were previously identified. Despite the unusual inverse membrane topology of CYP2W1 that allows
its glycosylation but prevents interaction with the redox partner, P450 oxidoreductase (POR), we discovered
specific CYP2W1-mediated metabolism of indolines, which indicates the presence of a yet unknown electron
transport chain in the lumen of ER.
CYP2C9 catalyzes the metabolism of anticoagulant drug warfarin. We characterized the newly discovered
rare CYP2C9*35 allele encoding an enzyme with two amino acid changes including Arg125Leu that was found
in a patient with warfarin hypersensitivity. The expression of the variant proteins in the mammalian HEK293
cell system showed abolished activity of the CYP2C9.35 enzyme towards warfarin in NADPH supported
reaction, but the enzyme could be activated when NADPH was replaced by hydroperoxides. This indicates that
CYP2C9.35 is unable to receive electrons from POR because of the impaired interaction with this redox partner.
Indeed, in silico modeling confirmed this conclusion showing disrupted salt bridges between CYP2C9.35 and
POR due to the mutation of key residues involved in such interaction.
CYP3A4 is one of the key enzymes, which metabolizes the anticancer drug paclitaxel. In a cohort of 236
Spanish patients with a paclitaxel induced neuropathy whole exome sequencing revealed the presence of
different rare CYP3A4 gene variants, CYP3A4*8, CYP3A4*20, CYP3A4*25 (p.Pro389Ser) and CYP3A4*27
(p.Leu475Val), the latter two previously not described. The expression of these two novel gene variants in
HEK293 cells revealed that the corresponding enzymes are more unstable than the CYP3A4.1 enzyme and
carriers of these rare CYP3A4 variants had much higher risk for neuropathy and a need in paclitaxel treatment
modifications. The data indicate enrichment of these rare defect CYP3A4 alleles in the group of the paclitaxel
induced neuropathy patients and suggest that genotyping of CYP3A4 defective variants may provide a basis for
paclitaxel treatment individualization.
Based on previous data indicating a role for the defective CYP2C8*3 allele for paclitaxel induced
neuropathy, we also investigated the influence of this polymorphism on paclitaxel induced neuropathy and
neuropathy risk in 148 patients receiving paclitaxel as well as the CYP2C8.3 catalyzed metabolism of paclitaxel
in a mammalian expression system. However, in contrast to many other studies we found no significant effect of
this allele on paclitaxel induced neuropathy or paclitaxel metabolism in vitro.
In conclusion, our data indicate the importance of rare genetic CYP variants for induction of selective drug
induced adverse reactions and emphasize the necessity of more extensive genetic analyses, e.g. whole exome
sequencing, before fully individualized drug therapy can be achieved
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