Probing the ultimate limits of plasmonic enhancement.

Metals support surface plasmons at optical wavelengths and have the ability to localize light to subwavelength regions. The field enhancements that occur in these regions set the ultimate limitations on a wide range of nonlinear and quantum optical phenomena. We found that the dominant limiting factor is not the resistive loss of the metal, but rather the intrinsic nonlocality of its dielectric response. A semiclassical model of the electronic response of a metal places strict bounds on the ultimate field enhancement. To demonstrate the accuracy of this model, we studied optical scattering from gold nanoparticles spaced a few angstroms from a gold film. The bounds derived from the models and experiments impose limitations on all nanophotonic systems.

Quantification of biological aging in young adults.

Antiaging therapies show promise in model organism research. Translation to humans is needed to address the challenges of an aging global population. Interventions to slow human aging will need to be applied to still-young individuals. However, most human aging research examines older adults, many with chronic disease. As a result, little is known about aging in young humans. We studied aging in 954 young humans, the Dunedin Study birth cohort, tracking multiple biomarkers across three time points spanning their third and fourth decades of life. We developed and validated two methods by which aging can be measured in young adults, one cross-sectional and one longitudinal. Our longitudinal measure allows quantification of the pace of coordinated physiological deterioration across multiple organ systems (e.g., pulmonary, periodontal, cardiovascular, renal, hepatic, and immune function). We applied these methods to assess biological aging in young humans who had not yet developed age-related diseases. Young individuals of the same chronological age varied in their "biological aging" (declining integrity of multiple organ systems). Already, before midlife, individuals who were aging more rapidly were less physically able, showed cognitive decline and brain aging, self-reported worse health, and looked older. Measured biological aging in young adults can be used to identify causes of aging and evaluate rejuvenation therapies.

Menthol attenuates respiratory irritation and elevates blood cotinine in cigarette smoke exposed mice.

Addition of menthol to cigarettes may be associated with increased initiation of smoking. The potential mechanisms underlying this association are not known. Menthol, likely due to its effects on cold-sensing peripheral sensory neurons, is known to inhibit the sensation of irritation elicited by respiratory irritants. However, it remains unclear whether menthol modulates cigarette smoke irritancy and nicotine absorption during initial exposures to cigarettes, thereby facilitating smoking initiation. Using plethysmography in a C57Bl/6J mouse model, we examined the effects of L-menthol, the menthol isomer added to cigarettes, on the respiratory sensory irritation response to primary smoke irritants (acrolein and cyclohexanone) and smoke of Kentucky reference 2R4 cigarettes. We also studied L-menthol's effect on blood levels of the nicotine metabolite, cotinine, immediately after exposure to cigarette smoke. L-menthol suppressed the irritation response to acrolein with an apparent IC₅₀ of 4 ppm. Suppression was observed even at acrolein levels well above those necessary to produce a maximal response. Cigarette smoke, at exposure levels of 10 mg/m³ or higher, caused an immediate and marked sensory irritation response in mice. This response was significantly suppressed by L-menthol even at smoke concentrations as high as 300 mg/m³. Counterirritation by L-menthol was abolished by treatment with a selective inhibitor of Transient Receptor Potential Melastatin 8 (TRPM8), the neuronal cold/menthol receptor. Inclusion of menthol in the cigarette smoke resulted in roughly a 1.5-fold increase in plasma cotinine levels over those observed in mice exposed to smoke without added menthol. These findings document that, L-menthol, through TRPM8, is a strong suppressor of respiratory irritation responses, even during highly noxious exposures to cigarette smoke or smoke irritants, and increases blood cotinine. Therefore, L-menthol, as a cigarette additive, may promote smoking initiation and nicotine addiction.

A miR-34a-Numb Feedforward Loop Triggered by Inflammation Regulates Asymmetric Stem Cell Division in Intestine and Colon Cancer.

Emerging evidence suggests that microRNAs can initiate asymmetric division, but whether microRNA and protein cell fate determinants coordinate with each other remains unclear. Here, we show that miR-34a directly suppresses Numb in early-stage colon cancer stem cells (CCSCs), forming an incoherent feedforward loop (IFFL) targeting Notch to separate stem and non-stem cell fates robustly. Perturbation of the IFFL leads to a new intermediate cell population with plastic and ambiguous identity. Lgr5+ mouse intestinal/colon stem cells (ISCs) predominantly undergo symmetric division but turn on asymmetric division to curb the number of ISCs when proinflammatory response causes excessive proliferation. Deletion of miR-34a inhibits asymmetric division and exacerbates Lgr5+ ISC proliferation under such stress. Collectively, our data indicate that microRNA and protein cell fate determinants coordinate to enhance robustness of cell fate decision, and they provide a safeguard mechanism against stem cell proliferation induced by inflammation or oncogenic mutation.

Efficacy of Pharmacokinetics-Directed Busulfan, Cyclophosphamide, and Etoposide Conditioning and Autologous Stem Cell Transplantation for Lymphoma: Comparison of a Multicenter Phase II Study and CIBMTR Outcomes.

Busulfan, cyclophosphamide, and etoposide (BuCyE) is a commonly used conditioning regimen for autologous stem cell transplantation (ASCT). This multicenter, phase II study examined the safety and efficacy of BuCyE with individually adjusted busulfan based on preconditioning pharmacokinetics. The study initially enrolled Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients ages 18 to 80 years but was amended due to high early treatment-related mortality (TRM) in patients > 65 years. BuCyE outcomes were compared with contemporaneous recipients of carmustine, etoposide, cytarabine, and melphalan (BEAM) from the Center for International Blood and Marrow Transplant Research. Two hundred seven subjects with HL (n = 66) or NHL (n = 141) were enrolled from 32 centers in North America, and 203 underwent ASCT. Day 100 TRM for all subjects (n = 203), patients > 65 years (n = 17), and patients ≤ 65 years (n = 186) were 4.5%, 23.5%, and 2.7%, respectively. The estimated rates of 2-year progression-free survival (PFS) were 33% for HL and 58%, 77%, and 43% for diffuse large B cell lymphoma (DLBCL; n = 63), mantle cell lymphoma (MCL; n = 29), and follicular lymphoma (FL; n = 23), respectively. The estimated rates of 2-year overall survival (OS) were 76% for HL and 65%, 89%, and 89% for DLBCL, MCL, and FL, respectively. In the matched analysis rates of 2-year TRM were 3.3% for BuCyE and 3.9% for BEAM, and there were no differences in outcomes for NHL. Patients with HL had lower rates of 2-year PFS with BuCyE, 33% (95% CI, 21% to 46%), than with BEAM, 59% (95% CI, 52% to 66%), with no differences in TRM or OS. BuCyE provided adequate disease control and safety in B cell NHL patients ≤ 65 years but produced worse PFS in HL patients when compared with BEAM.

Evaluación de la respuesta a la fertilización con nitrógeno en girasol, en un hapludol típico del partido de Vedia, Provincia de Buenos Aires

p.289-296

HyperJoseph: the hypertextual organization. Epistemological considerations

HYPERJOSEPH combines hypertext, information retrieval, literary studies, Biblical scholarship, and linguistics. Dialectically, this paper contrasts hypertextual form (the extant tool) and AI-captured content (a desideratum), in the HYPERJOSEPH project. The discussion is more general and oriented to epistemology.

From ALIBI to COLUMBUS. The long march to self-aware, reflective computational models of humor

One thing is (a) to develop a system that handles some task to one's satisfaction, and also has a universally recognized myrthful side to its output. Another thing is (b) to provide an analysis of why you are getting such a byproduct. Yet another thing is (c) to develop a model that incorporates reflection about some phenomenon in humor for its own sake. This paper selects for discussion especially Alibi, going on to describe the preliminaries of Columbus. The former, which fits in (a), is a planner with an explanatory capability. It invents pretexts. It's no legal defense, but it is relevant to evidential thinking in AI & Law. Some of the output pretext are myrthful. Not in the sense they are silly: they are not. A key factor seems to be the very alacrity at explaining out detail after detail of globally damning evidence. I attempt a reanalysis of Alibi in respect of (b). As to Columbus, it fits instead in (c). We introduce here the basics of this (unimplemented) model, developed to account for a sample text in parody.

Temporal structure and enablement representation for mutual wills: A Petri net approach

Those temporal formalisms that are sporadically found nowadays in the literature of AI & Law are based on temporal logic. We claim a revived role for another major class of temporal representation: Petri nets. This formalism, popular in computing from the 1970s, had its potential recognized on occasion in the literature of legal computing as well, but apparently the discipline has lost sight of it, and its practitioners on average need be tutored into this kind of representation. Asynchronous, concurrent processes—for which the approach is well‐suited—are found in the legal domain, in disparate contexts. We develop an example for Mutual Wills.

Temporal representation of state transitions

This paper describes a knowledge-based temporal representation of state transitions for industrial real-time systems. To allow expression of uncertainty, we shall define fluents as disjuncts of positive/negative time-varying properties. A state of the world is represented as a collection of fluents, which is usually incomplete in the sense that neither the positive form nor the negative form of some properties can be implied from it. The world under consideration is assumed to persist in a given state until an action(s) takes place to effect a transition of it into another state, where actions may either be instantaneous or durative. High-level causal laws are characterized in terms of relationships between actions and the involved world states. An effect completion axiom is imposed on each causal law to guarantee that all the fluents that can be affected by the performance of the corresponding action are governed. This completion requirement is practical for most industrial real-time applications and in fact provides a simple and effective treatment to the so-called frame problem.

Guest Editorial. Special Issue: Temporal logic in engineering

Logic-based models are thriving within artificial intelligence. A great number of new logics have been defined, and their theory investigated. Epistemic logics introduce modal operators for knowledge or belief; deontic logics are about norms, and introduce operators of deontic necessity and possibility (i.e., obligation or prohibition). And then we have a much investigated class—temporal logics—to whose application to engineering this special issue is devoted. This kind of formalism deserves increased widespread recognition and application in engineering, a domain where other kinds of temporal models (e.g., Petri nets) are by now a fairly standard part of the modelling toolbox.

Reified temporal logics: an overview

There are three main approaches to the representation of temporal information in AI literature: the so-called method of temporal arguments that simply extends functions and predicates of first-order language to include time as the additional argument; modal temporal logics which are extensions ofthe propositional or predicate calculus with modal temporal operators; and reified temporal logics which reify standard propositions of some initial language (e.g., the classical first-order or modal logic) as objects denoting propositional terms. The objective of this paper is to provide an overview onthe temporal reified approach by looking closely atsome representative existing systems featuring reified propositions, including those of Allen, McDermott, Shoham, Reichgelt, Galton, and Ma and Knight. We shall demonstrate that, although reified logics might be more complicated in expressing assertions about some given objects with respect to different times, they accord a special status to time and therefore have several distinct advantages in talking about some important issues which would be difficult (if not impossible) to express in other approaches.

Culture-bound technological solutions: An artificial theoretic insight

Sometimes, technological solutions to practical problems are devised that conspicuously take into account the constraints to which a given culture is subjecting the particular task or the manner in which it is carried out. The culture may be a professional culture (e.g., the practice of law), or an ethnic-cum-professional culture (e.g., dance in given ethnic cultures from South-East Asia), or, again, a denominational culture prescribing an orthopraxy impinging on everyday life through, for example, prescribed abstinence from given categories of workday activities, or dietary laws. Massimo Negrotti's Theory of the artificial is a convenient framework for discussing some of these techniques. We discuss a few examples, but focus on the contrast of two that are taken from the same cultural background, namely, technological applications in compliance with Jewish Law orthopraxy. •Soya-, mycoprotein- or otherwise derived meat surrogates are an example ofnaturoid; they emulate the flavours and olfactory properties, as well as the texture and the outer and inner appearance, of the meat product (its kind, cut, form) they set out to emulate (including amenability to cooking in the usual manner for the model), while satisfying cultural dietary prohibitions. •In contrast, the Sabbath Notebook, a writing surrogate we describe in this paper, is atechnoid: it emulates a technique (writing to store alphanumeric information), while satisfying the prohibition of writing at particular times of the liturgical calendar (the Sabbath and the major holidays).

The Jama legal narrative. Part II: A foray into concepts of improbability

In judicial decision making, the doctrine of chances takes explicitly into account the odds. There is more to forensic statistics, as well as various probabilistic approaches which taken together form the object of an enduring controversy in the scholarship of legal evidence. In this paper, we reconsider the circumstances of the Jama murder and inquiry (dealt with in Part I of this paper: "The Jama Model. On Legal Narratives and Interpretation Patterns"), to illustrate yet another kind of probability or improbability. What is improbable about the Jama story, is actually a given, which contributes in terms of dramatic underlining. In literary theory, concepts of narratives being probable or improbable date back from the eighteenth century, when both prescientific and scientific probability was infiltrating several domains, including law. An understanding of such a backdrop throughout the history of ideas is, I claim, necessary for AI researchers who may be tempted to apply statistical methods to legal evidence. The debate for or against probability (and especially bayesian probability) in accounts of evidence has been flouishing among legal scholars. Nowadays both the the Bayesians (e.g. Peter Tillers) and Bayesioskeptics (e.g. Ron Allen) among those legal scholars whoare involved in the controversy are willing to give AI researchers a chance to prove itself and strive towards models of plausibility that would go beyond probability as narrowly meant. This debate within law, in turn, has illustrious precedents: take Voltaire, he was critical of the application or probability even to litigation in civil cases; take Boole, he was a starry-eyed believer in probability applications to judicial decision making (Rosoni 1995). Not unlike Boole, the founding father of computing, nowadays computer scientists approaching the field may happen to do so without full awareness of the pitfalls. Hence, the usefulness of the conceptual landscape I sketch here.