Principles of Knowledge Representation and Reasoning in the FRAPPE System

The purpose of this paper is to elucidate the following four important architectural principles of knowledge representation and reasoning with the example of an implemented system: limited reasoning, truth maintenance, hybrid architecture, and many sorted logic.MIT Artificial Intelligence Laborator

The Interaction Between Truth Maintenance, Equality, and Pattern-Directed Invocation: Issues of Completeness and Efficiency

We have implemented a reasoning system, called BREAD, which includes truth maintenance, equality, and pattern-directed invocation. This paper reports on the solution of two technical problems arising out of the interaction between these mechanisms. The first result is an algorithm which ensures the completeness of pattern-directed invocation with respect to equality. The second result is an algorithm which reduces a class of redundant proofs.MIT Artificial Intelligence Laborator

Naked Price and Pharmaceutical Trade Secret Overreach

Trade secret has drifted from a quiet backwater doctrine to a pervasive force in intellectual property. As always, the risk of distortion is great when a legal arena is developing and expanding rapidly. Nowhere do the theoretical tensions of trade secret law appear in such stark relief as in the modern pharmaceutical debates, where the heart of the theoretical question involves whether pricing is a proper subject for trade secrecy claims. We aim to bring trade secret into greater harmony with broad concepts that reach across all intellectual property regimes. As with other areas of intellectual property law, trade secret law is not a mere contest of private commercial interests. Rather, it embeds substantial dedication to the public interest, reflecting utilitarian balancing of key societal interests. In this context, we develop the concept of “thin” trade secret, looking to the analogous concepts in other intellectual property regimes. Such approaches embody the recognition that intellectual property rights are not solid monoliths, presenting an impenetrable wall through which no party but the rights holder may pass. Rather, they are brilliantly nimble and subtle systems, deftly threading their way among various societal goals. This Article offers the potential of anchoring trade secret more firmly to its theoretical base, as well as bringing trade secret closer to the family of other intellectual property regimes. Although squabbling, chaotic, and somewhat dispersed, all members of this time-honored family can learn from each other, sharing their battleworn wisdom with the newest, young upstart

A Stream of Prospects or a Prospect of Streams: On the Evaluation of Intertemporal Risks

Recent debate has identified important gaps in the understanding of intertemporal risks. Critical to closing these gaps is evidence on which dimension of intertemporal risk – the risk or the time – is evaluated first. Though under discounted expected utility this ordering is of no consequence, under discounted non-expected utility models the order of evaluation is critical. We provide experimental tests in which different orderings of evaluation generate different predictions for behavior. We find more support for the notion that the risk dimension is evaluated first

A Stream of Prospects or a Prospect of Streams: On the Evaluation of Intertemporal Risks

Recent debate has identified important gaps in the understanding of intertemporal risks. Critical to closing these gaps is evidence on which dimension of intertemporal risk – the risk or the time – is evaluated first. Though under discounted expected utility this ordering is of no consequence, under discounted non-expected utility models the order of evaluation is critical. We provide experimental tests in which different orderings of evaluation generate different predictions for behavior. We find more support for the notion that the risk dimension is evaluated first

Exposure of a 23F serotype strain of <i>Streptococcus pneumoniae</i> to cigarette smoke condensate is associated with selective upregulation of genes encoding the two-component regulatory system 11 (TCS11)

Alterations in whole genome expression profiles following exposure of the pneumococcus (strain 172, serotype 23F) to cigarette smoke condensate (160 μg/mL) for 15 and 60 min have been determined using the TIGR4 DNA microarray chip. Exposure to CSC resulted in the significant (P &#60; 0.014–0.0006) upregulation of the genes encoding the two-component regulatory system 11 (TCS11), consisting of the sensor kinase, hk11, and its cognate response regulator, rr11, in the setting of increased biofilm formation. These effects of cigarette smoke on the pneumococcus may contribute to colonization of the airways by this microbial pathogen

An overview of tenofovir and renal disease for the HIV-treating clinician

Tenofovir disoproxil fumarate (TDF, commonly termed ‘tenofovir’) is the antiretroviral most commonly implicated in antiretroviral-induced nephrotoxicity. As patients on successful antiretroviral therapy (ART) age, their risk for developing renal disease may increase in part because of ART itself, but more importantly, because of HIV-associated and non-HIVassociated comorbidity. Therefore, clinicians need an approach to managing renal disease in people on TDF. TDF as a cause of acute kidney injury (AKI) or chronic kidney disease (CKD) is uncommon, and clinicians should actively exclude other causes (Box 1). In TDF-associated AKI, TDF should be interrupted in all cases, and replaced, or ART interrupted altogether. Tenofovir disoproxil fumarate toxicity can present as AKI or CKD, and as a full or partial Fanconi’s syndrome. TDF has a small but definite negative impact on kidney function (up to a 10% decrease in glomerular filtration rate [GFR]). This occurs because of altered tubular function in those exposed to TDF for treatment and as pre-exposure prophylaxis. Renal function should be assessed using creatinine-based estimated GFR at the time of initiation of TDF, if ART is changed, at 1–3 months, and then ideally every 6–12 months if stable. Specific tests of tubular function are not routinely recommended; in the case of clinical concern, a spot protein or albumin: creatinine ratio is preferable, but in resource-limited settings, urine dipstick can be used. More frequent monitoring may be required in those with established CKD (estimated glomerular filtration rate [eGFR] &lt; 50 mL/min/1.73 m2) or risk factors for kidney disease. The most common risk factors are comorbid hypertension, diabetes, HIV associated kidney disease, hepatitis B or C co-infection, and TDF in combination with a ritonavir-boosted protease inhibitor. Management of these comorbid conditions must be prioritised in this group. If baseline screening eGFR is &lt; 50 mL/min/1.73 m2, abacavir (the preferred option), and dose-adjusted TDF (useful if concomitant hepatitis B), zidovudine or stavudine (d4T) remain alternatives to full-dose TDF. If there is a rapid decline in kidney function (eGFR drops by more than 25% and decreases to &lt; 50 mL/min/1.73 m2 from of baseline function), or there is new onset or worsening of proteinuria or albuminuria, clinicians should review ART and other potentially nephrotoxic medications and comorbidity and conduct further testing if indicated. If kidney function does not improve after addressing reversible causes of renal failure, then referral to a nephrologist is appropriate. In the case of severe CKD, timeous referral for planning for renal replacement therapy is recommended. Tenofovir alafenamide, a prodrug of tenofovir, appears to have less renal toxicity and is likely to replace TDF in future