Medicare and the Philadelphia Market: The Gathering Storm

No abstract available

Navigating the Third Offset Strategy

This article suggests adding a “craftsman” at lower ranks to steer private-sector projects through the Third Offset Strategy. This strategy was established by experienced leadership at the Pentagon to increase military acquisitions of automation and artificial intelligence technology

Images in Christmas Balls

We describe light-reflection properties of spherically curved mirrors, like balls in the Christmas tree. In particular, we study the position of the image which is formed somewhere beyond the surface of a spherical mirror, when an eye observes the image of a pointlike light source. The considered problem, originally posed by Abu Ali Hasan Ibn al-Haitham -- alias Alhazen -- more than a millennium ago, turned out to have the now well known analytic solution of a biquadratic equation, being still of great relevance, e.g. for the aberration-free construction of telescopes. We do not attempt to perform an exhaustive survey of the rich historical and engineering literature on the subject, but develop a simple pedagogical approach to the issue, which we believe to be of continuing interest in view of its maltreating in many high-school textbooks.Comment: 13 pages, 7 figures plain LaTeX; Also see http://cft.fis.uc.pt/eef/mirrors.htm, revised version has simplified formulas, more transparent for a wider audience, one reference adde

Viticultural Climate Indexes and Their Role in The Prediction of Anthocyanins and Other Flavonoids Content in Seedless Table Grapes

Background: Viticulture bioclimatic indexes like the Heliothermal Index (HI), Cool Night Index (CI), and Dryness Index (DI), can be used to assess the influence of climate on grapes’ quality. Methods: HI, CI, and DI + total seasonal irrigation were utilized to assess the effect of climate on the flavonoids content and composition of two Vitis vinifera seedless varieties, ‘Summer Royal’ and ‘Crimson Seedless’, both grown in Apulia (Southern Italy). Results: The flavonoids content was significantly affected by variety and climate conditions on the base of HI, CI, and DI + total seasonal irrigation. Factor analysis applied to climate indexes and flavonoids showed that anthocyanins and flavonols were negatively and positively correlated to CI in both varieties, respectively. Additionally, warmer night temperatures determined higher fla-van-3-ols. HI increase promoted anthocyanins, flavonols, and flavan-3-ols content in Crimson Seedless, whilst it induced an opposite trend in Summer Royal. Finally, DI + total seasonal irrigation showed to be positively linked to flavonols content and negatively linked to anthocyanins content just in the case of Crimson Seedless. Significant regression models were also determined between climate indexes and productive parameters (i.e., yield, TSS, TA, pH, bunch, and berry weight). Conclusions: Climate indexes HI, CI, and DI + total seasonal irrigation showed an effect on quality grape parameters like flavonoids and contributed to building predictive models when new climatic zones are going to be evaluated for the production of table grapes

An all-endo Approach to Complete Ureteral Duplications Complicated by Ureterocele and/or Vesicoureteral Reflux: Feasibility, Limitations, and Results

Purpose. Totally endoscopic management (all-endo) of patients with a duplicated renal system (DS) associated with severe vesicoureteral reflux (VUR) or obstructive ureterocele (UC) is an attractive alternative to traditional open procedures. The authors discuss feasibility and results of an all-endo approach on a consecutive series of patients. Methods. From 1999 to 2009, all patients with a complete DS associated with UC and/or VUR were proposed for primary all-endo approach. UC puncture was performed using a 3 Fr Bugbee electrode. Deflux (dextranomer/hyaluronic acid copolymer) injection was administered for VUR. The need for secondary surgery was evaluated on followup. Results. Of the 62 patients recruited, 46 were treated using a primary all-endo approach and 16 patients received no treatment. Of the 46 treated patients with 56 affected renal units, 32 (97%) UCs collapsed following puncture and 29 (63%) VURs were resolved or downgraded. Secondary VUR occurred in 13 (39%) renal units. Secondary surgery was performed on 23 (41%) renal units. Conclusion. The all-endo approach for VUR in DS is an effective therapeutic option. UC collapse was achieved by puncture in most of the patients; secondary VUR was the main complication in a small group of extravesical UC

Folding mechanisms steer the amyloid fibril formation propensity of highly homologous proteins

Significant advances in the understanding of the molecular determinants of fibrillogenesis can be expected from comparative studies of the aggregation propensities of proteins with highly homologous structures but different folding pathways. Here, we fully characterize, by means of stopped-flow, T-jump, CD and DSC experiments, the unfolding mechanisms of three highly homologous proteins, zinc binding Ros87 and Ml153-149 and zinc-lacking Ml452-151. The results indicate that the three proteins significantly differ in terms of stability and (un)folding mechanisms. Particularly, Ros87 and Ml153-149 appear to be much more stable to guanidine denaturation and are characterized by folding mechanisms including the presence of an intermediate. On the other hand, metal lacking Ml452-151 folds according to a classic two-state model. Successively, we have monitored the capabilities of Ros87, Ml452-151 and Ml153-149 to form amyloid fibrils under native conditions. Particularly, we show, by CD, fluorescence, DLS, TEM and SEM experiments, that after 168 hours, amyloid formation of Ros87 has started, while Ml153-149 has formed only amorphous aggregates and Ml452-151 is still monomeric in solution. This study shows how metal binding can influence protein folding pathways and thereby control conformational accessibility to aggregation-prone states, which in turn changes aggregation kinetics, shedding light on the role of metal ions in the development of protein deposition diseases

A small organic compound enhances the religation reaction of human topoisomerase I and identifies crucial elements for the religation mechanism

The different steps of the human Top1 (topoisomerase I) catalytic cycle have been analysed in the presence of a pentacyclic-diquinoid synthetic compound. The experiments indicate that it efficiently inhibits the cleavage step of the enzyme reaction, fitting well into the catalytic site. Surprisingly the compound, when incubated with the binary topoisomerase–DNA cleaved complex, helps the enzyme to remove itself from the cleaved DNA and close the DNA gap, increasing the religation rate. The compound also induces the religation of the stalled enzyme–CPT (camptothecin)– DNA ternary complex. Analysis of the molecule docked over the binary complex, together with its chemical properties, suggests that the religation enhancement is due to the presence on the compound of two oxygen atoms that act as hydrogen acceptors. This property facilitates the deprotonation of the 5 DNA end, suggesting that this is the limiting step in the topoisomerase religation mechanism

Hydrogen sulfide-induced dual vascular effect involves arachidonic acid cascade in rat mesenteric arterial bed.

Hydrogen sulfide (H(2)S), a novel gaseous transmitter, is considered a physiological regulator of vascular homeostasis. Recent evidence suggests H(2)S as an endothelium-hyperpolarizing factor (EDHF) candidate. To address this issue, we evaluated the vascular effect of sodium hydrogen sulfide (NaHS), an H(2)S donor, on the rat mesenteric arterial bed. NaHS concentration-response curve was performed on preconstricted mesenteric arterial bed. To assess the contribution of EDHF, we performed a pharmacologic dissection using indomethacin, N(G)-nitro-L-arginine methyl ester (L-NAME), or apamin and charybdotoxin as cyclooxygenase, nitric-oxide synthase, and calcium-dependent potassium channel inhibitors, respectively. In another set of experiments, we used 4-(4-octadecylphenyl)-4-oxobutenoic acid, baicalein, or proadifen as phospholipase A(2) (PLA(2)), lipoxygenase, and cytochrome P450 inhibitors, respectively. Finally, an immunofluorescence study was performed to support the involvement of PLA(2) in mesenteric artery challenged by NaHS. NaHS promoted a dual vascular effect (i.e., vasoconstriction and vasodilation). L-NAME or baicalein administration affected neither NaHS-mediated vasodilation nor vasoconstriction, whereas apamin and charybdotoxin significantly inhibited NaHS-induced relaxation. Pretreatment with PLA(2) inhibitor abolished both the contracting and the relaxant effect, whereas P450 cytochrome blocker significantly reduced NaHS-mediated relaxation. The immunofluorescence study showed that NaHS caused a migration of cytosolic PLA(2) close to the nucleus, which implicates activation of this enzyme. Our data indicate that H(2)S could activate PLA(2), which in turn releases arachidonic acid leading, initially, to vasoconstriction followed by vasodilation mediated by cytochrome P450-derived metabolites. Because EDHF has been presumed to be a cytochrome P450 derivative of the arachidonic acid, our results suggest that H(2)S acts through EHDF release