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Frasca, R. (2006). Columbia, MO: University of Missouri Press, 295 pp. $44.95 (hardcover). In his conclusion, Ralph Frasca recalls that Benjamin Franklin advised Tom Paine “not to attempt unchainin...

In this paper we present a model in which individuals act in their own best interest, to explain many behaviors associated with cigarette addiction. There are two key features of the model. First, there is an explicit representation of the withdrawal effects experienced when smokers attempt to quit smoking. Second, there is explicit recognition that the negative effects of smoking generally appear late in an individual's life. Among the things we use the model to explain are: (1) how individuals can become trapped in their decision to smoke; (2) the conditions under which cold-turkey quitting and gradual quitting may occur; and (3) a reason for the existence of quit-smoking treatments.

Appropriate tyrosine kinase signaling depends on coordinated sequential coupling of protein-protein interactions with catalytic activation. Focal adhesion kinase (FAK) integrates signals from integrin and growth factor receptors to regulate cellular responses including cell adhesion, migration, and survival. Here, we describe crystal structures representing both autoinhibited and active states of FAK. The inactive structure reveals a mechanism of inhibition in which the N-terminal FERM domain directly binds the kinase domain, blocking access to the catalytic cleft and protecting the FAK activation loop from Src phosphorylation. Additionally, the FERM domain sequesters the Tyr397 autophosphorylation and Src recruitment site, which lies in the linker connecting the FERM and kinase domains. The active phosphorylated FAK kinase adopts a conformation that is immune to FERM inhibition. Our biochemical and structural analysis shows how the architecture of autoinhibited FAK orchestrates an activation sequence of FERM domain displacement, linker autophosphorylation, Src recruitment, and full catalytic activation.

The interactions of oligonucleotide analogs, 12-mers, which contain deoxyribo- or 2'-O-methylribose sugars and methylphosphonate internucleotide linkages with complementary 12-mer DNA and RNA targets and the effect of chirality of the methylphosphonate linkage on oligomer-target interactions was studied. Oligomers containing a single Rp or Sp methylphosphonate linkage (type 1) or oligomers containing a single phosphodiester linkage at the 5'-end followed by 10 contiguous methylphosphonate linkages of random chirality (type 2) were prepared. The deoxyribo- and 2'-O-methylribo- type 1 12-mers formed stable duplexes with both the RNA and DNA as determined by UV melting experiments. The melting temperatures, Tms, of the 2'-O-methylribo-12-mer/RNA duplexes (49-53 degrees C) were higher than those of the deoxyribo-12mer/RNA duplexes (31-36 degrees C). The Tms of the duplexes formed by the Rp isomers of these oligomers were approximately 3-5 degrees C higher than those formed by the corresponding Sp isomers. The deoxyribo type 2 12-mer formed a stable duplex, Tm 34 degrees C, with the DNA target and a much less stable duplex with the RNA target, Tm < 5 degrees C. In contrast, the 2'-O-methylribo type 2 12-mer formed a stable duplex with the RNA target, Tm 20 degrees C, and a duplex of lower stability with the DNA target, Tm < 5 degrees C. These results show that the previously observed greater stability of oligo-2'-O-methylribonucleotide/RNA duplexes versus oligodeoxyribonucleotide/RNA duplexes extends to oligomers containing methylphosphonate linkages and that the configuration of the methylphosphonate linkage strongly influences the stability of the duplexes.

Knowing is nothing but working with one's favorite metaphors. Friedrich Nietzsche Indeed, as the documents of science pile up, are we not coming to see that whole works of scientific research, even entire schools, are hardly more than the patient repetition, in all its ramifications, of a fertile metaphor? Kenneth Burke Until 1983, when Donald McCloskey invited literary criticism to the table of economics, the very notion of metaphor was virtually absent from economic discourse. Arguing in “The Rhetoric of Economics,” McCloskey proposed taking metaphor seriously. Since his article appeared in the Journal of Economic Literature , metaphor has acquired some currency among economists; its mention is no longer a show-stopping non sequitur. The currency of the term “metaphor” does not, however, imply a general acceptance of its importance. On the contrary, suspicion and indifference still rule the day, if we may speak metaphorically. The average economist would be unable to locate “metaphor” in the economic lexicon. Many of our colleagues will grant the existence of metaphor, perhaps even conceding its ubiquity, but they then rejoin with the debater's bogey – “So what?” The suspicion rests, we surmise, on the impression that metaphors introduce ambiguity. The imprecision created by ambiguous meaning is presumably fine for poets, but anathema for scientists. When McCloskey equates economics with poetry because it too relies on metaphors, scientifically minded economists are offended. “What matters is that we, as scientists, write down in a precise way what we mean. Precision is one of the standards by which we measure science.

Previous studies in rats have shown that a single oral dose of alpha-naphthylisothiocyanate (ANIT), but not the regioisomer beta-naphthylisothiocyanate (BNIT), results in intrahepatic cholestasis. The present studies were designed to evaluate the intrinsic cholestatic potential of ANIT and BNIT in the isolated perfused rat liver. Livers from male Sprague-Dawley rats (300-450 g) were isolated and perfused with Krebs-Henseleit buffer supplemented with 50 microM taurocholate and ANIT or BNIT (0, 5, 15 or 50 microM). Rates of bile flow, bile acid uptake and bile acid excretion were monitored for up to 70 min. Permeability of tight junctions also was evaluated. At concentrations of 5 microM, neither ANIT nor BNIT altered hepatobiliary function or tight junction permeability. In contrast, perfusion with 50 microM ANIT or BNIT for 35 min resulted in decreases in bile flow rates of 19 +/- 8 and 13 +/- 4%, respectively. After 70 min of perfusion with ANIT or BNIT, rates of bile flow were decreased by 78 +/- 5 and 71 +/- 4%, respectively. Bile acid excretion also was decreased following perfusion with 50 microM ANIT or BNIT. Perfusion with 50 microM ANIT or BNIT decreased bile acid uptake by 51 +/- 13 and 46 +/- 6%, respectively, at 60 min. Bile/plasma (B/P) ratios of [3H]sucrose were not affected by ANIT or BNIT at any time during perfusion, indicating that changes in bile flow and bile acid excretion in the isolated perfused liver were not associated with increased hepatocyte tight junction permeability. These data demonstrate that the direct portal infusion of a 50 microM concentration of either ANIT or BNIT produced marked decreases in bile flow, indicating that these isomers have a comparable intrinsic cholestatic potential in the isolated perfused liver.

The results of past BRDF round robin comparisons precipitated the establishment of ASTM committee E12.09 on Optical Techniques and the promulgation of the standard E1392, `Standard Practice for Angle Resolved Optical Scatter Measurements on Specular or Diffuse Surfaces.' A recent 10.6 micrometers BRDF round robin tested the utility of this standard practice document. The master sample set included two IR diffuse surfaces, two metal mirrors, one glass mirror and an IR grating. The in-plane BRDF was measured for 10 degree(s) angle-of- incidence, s polarized light at ten optical scatter facilities in the United States. These measurement results are compared.

A flexible class of prior distributions is proposed, for the covariance matrix of a multivariate normal distribution, yielding much more general hierarchical and empirical Bayes smoothing and inference, when compared with a conjugate analysis involving an inverted Wishart distribution. A likelihood approximation is obtained for the matrix logarithm of the covariance matrix, via Bellman's iterative solution to a Volterra integral equation. Exact and approximate Bayesian, empirical and hierarchical Bayesian estimation and finite sample inference techniques are developed. Some risk and asymptotic frequency properties are investigated. A subset of the Project Talent American High School data is analyzed. Applications and extensions to multivariate analysis, including a generalized linear model for covariance matrices, are indicated.

There is increasing interest in the American marketplace for mushrooms other than the common white button mushroom. The trend is toward species with more flavor. Among the new mushrooms making common appearances are the oyster mushroom and shiitake, more formally known as Pleurotus spp. and Lentinula (=Lentinus) edodes, respectively. A third type of mushroom, although less common, is the morel, Morchella spp, which is just beginning to be developed commercially. Since morels and shiitake are the more flavorful of the three mushrooms and are more difficult to produce, we focus our discussion on commercial cultivation practices for these two mushrooms and the challenges ahead for making them more readily available.

Background: Orazol™(MER-101) tablets utilize GIPET® to formulate an oral alternative to intravenous zoledronic acid (ZA) IV (Zometa®). Orazol's enteric coating and high bioavailability decreases GI exposure and provides a tablet with an excellent safety profile. Three clinical trials on doses from 10 to 20mg demonstrated that a weekly 20mg tablet delivers systemic ZA doses equivalent to 4mg infusions given every 4 weeks. Therapeutic equivalence of 20mg tablets and the 4mg infusion has been demonstrated in prostate cancer patients with bone metastatic disease based on change from baseline values for biomarkers of bone metabolism, including uNTX and sCTX. Methods: Safety information from three open label studies is presented here. MER-101-01 was a pilot single weekly dose, 3-way crossover study in 13 osteoporotic women. Orazol tablets 10mg and 20mg were administered versus a 1mg IV infusion after an overnight fast (and 4 hours fast post-dose). Absorption was determined by LCMS urine assay over 48 hours post-dose. MER-101-02 was a single-dose, 5-way crossover study in 30 postmenopausal women and examined Orazol 15mg and 20mg tablets versus 1mg IV infusion. Absorption was determined by serum LCMS assay over 36 hours post-dose. Treatments:(a) Orazol 15mg, overnight fast, breakfast 30 minutes later.(b) Orazol 20mg, overnight fast, breakfast 30 minutes later.(c) Orazol 20mg, FDA standardized breakfast.(d) Orazol 20mg, bedtime, following a 4-hour fast.(e) ZA 1mg IV infusion. MER-101-03 was a multi-center, 8 week, Phase II study comparing two regimens of Orazol tablets 20mg to the standard dose of ZA 4mg infusion in male bisphosphonate-naive hormone-refractory prostate cancer patients with bone metastases. The cohorts were:Cohort A: ZA 4mg infusion, Day 0 & 28.Cohort B: Orazol tablets 20mg, Days 0, 7, 14, 21, 28, 35, 42 & 49.Cohort C: Orazol tablets 20mg, Days 0, 1, 2, 3, 28, 35, 42 & 49. Safety assessments included AE monitoring, PE, hematology, urinalysis, and blood chemistry panels. Results: Orazol tablets yielded a very acceptable safety profile. In MER-101-03, which evaluated Orazol tablets directly against the 4mg infusion, the greatest incidence of AEs occurred in patients on the ZA infusion (75%). Half of the patients in this cohort experienced fever following administration, which lasted up to 72 hours post-dose. The incidence of bone pain was twice that in patients on oral Orazol therapy. There was a consistent decrease in mean diastolic blood pressure, and a greater number of abnormal hematology laboratory results for patients on IV than for Orazol. In analyzing MER-101-01 and MER-101-02 together, which compared Orazol tablets to a 1mg Zometa infusion, AEs were evenly distributed across groups. GI related AEs were similar with the Orazol treatments compared to the ZA infusions. Conclusions: Based on data collected thus far, Orazol tablets offer a substantial improvement over IV infusion in bisphosphonate therapy for oncological uses. The results of these studies combined with the excellent safety profile of Orazol tablets 20mg administered weekly support further development as a preferred route of ZA administration. Results to date indicate Orazol is an effective and potentially safer alternative to IV ZA, which may substantially improve patients’ quality of life. Orazol offers a new treatment paradigm for patients with metastatic bone cancer. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B57.

Nationwide BRDF round robin results in the visible and infrared showed the need for standardized scatter measurement and reporting procedures within the optical community. ASTM Subcommittee E12.09 was formed in 1988 to address this need. This presentation reviews the round robin results, the work of E12.09 to promulgate a BRDF Standard Practice, and work on infrared BRDF reference samples.

The results of a nationwide CO2 BRDF round robin are presented. This study was conducted as a follow -on to a 1988 0.6328 ,um BRDF round robin.t1 Four master samples ranging in roughness from a diffuse surface to a 45 A rmsmirror were measured at six scatter facilities. BRDF data in the forward direction for an incidence angle of 10 ° is compared from all participating facilities for the four samples. Unfortunately, the samples were lost during shipmentbetween scatter facilities, and it was not possible to complete measurements at the 14 planned facilities.1. INTRODUCTIONA previous BRDF round robin conducted in 1988 at 0.6328 pm showed the need for confirmation of BRDFmeasurements to assure accuracy. Infrared radiometry holds more subtle pitfalls than visible radiometry, so this roundrobin was conducted to assess level of confidence in CO2 laser BRDF measurements. The master sample set consisted of four, two -inch diameter samples. WH - diffuse white surface with THR =0.70 (experimental lambertian from a commerical vendor).BL - diffuse black surface made by sandblasting, etching and anodizing aluminum.BE - polished Beryllium mirror, 90 A rms.MO - polished Molybdenum mirror(M14) used in 0.6328 µm round robin, 45 A rms.Unfortunately, the sample case was lost by Federal Express after measurements were made at six facilities. Two ofthe facilities also spun the diffuse samples for a total of eight measurement sets for the diffuse samples. This providedsufficient data to make comparisons, draw conclusions about some of the error sources and make recommendations to

This paper discusses methods of predicting the BRDF of smooth surfaces from profile measurements of their surface finish. The conversion of optical profile data to the BRDF at the same wavelength is essentially independent of scattering models, while the conversion of mechanical measurements, and wavelength scaling in general, are model dependent. Procedures are illustrated for several surfaces, including two from the recent HeNe BRDF round robin, and results are compared with measured data. Reasonable agreement is found except for surfaces which involve significant scattering from isolated surface defects which are poorly sampled in the profile data.

Nation-Wide BRDF round robin results at 0.6328 and 10.6 um showed the need for standardized scatter measurement/reporting procedures within the optical community. ASTM subcommittee E12.09 was formed in 1988 to address this need. This presentation reviews the round robin results, the work of E12.09 to promulgate a BRDF Standard Practice and work on a 10.6 um physical scatter reference.

BRDF measurements made using a 10.6 wavelength laser on low reflectance, diffuse Al samples, showed the BRDF was spatially uniform and smoothly varying with scatter angle.