Beyond rules: The next generation of expert systems

The PARAGON Representation, Management, and Manipulation system is introduced. The concepts of knowledge representation, knowledge management, and knowledge manipulation are combined in a comprehensive system for solving real world problems requiring high levels of expertise in a real time environment. In most applications the complexity of the problem and the representation used to describe the domain knowledge tend to obscure the information from which solutions are derived. This inhibits the acquisition of domain knowledge verification/validation, places severe constraints on the ability to extend and maintain a knowledge base while making generic problem solving strategies difficult to develop. A unique hybrid system was developed to overcome these traditional limitations

A Selective Irreversible Inhibitor of Furin Does Not Prevent Pseudomonas Aeruginosa Exotoxin A-Induced Airway Epithelial Cytotoxicity

Many bacterial and viral pathogens (or their toxins), including Pseudomonas aeruginosa exotoxin A, require processing by host pro-protein convertases such as furin to cause disease. We report the development of a novel irreversible inhibitor of furin (QUB-F1) consisting of a diphenyl phosphonate electrophilic warhead coupled with a substrate-like peptide (RVKR), that also includes a biotin tag, to facilitate activity-based profiling/visualisation. QUB-F1 displays greater selectivity for furin, in comparison to a widely used exemplar compound (furin I) which has a chloromethylketone warhead coupled to RVKR, when tested against the serine trypsin-like proteases (trypsin, prostasin and matriptase), factor Xa and the cysteine protease cathepsin B. We demonstrate QUB-F1 does not prevent P. aeruginosa exotoxin A-induced airway epithelial cell toxicity; in contrast to furin I, despite inhibiting cell surface furin-like activity to a similar degree. This finding indicates additional proteases, which are sensitive to the more broad-spectrum furin I compound, may be involved in this process

Increased accuracy of ligand sensing by receptor internalization

Many types of cells can sense external ligand concentrations with cell-surface receptors at extremely high accuracy. Interestingly, ligand-bound receptors are often internalized, a process also known as receptor-mediated endocytosis. While internalization is involved in a vast number of important functions for the life of a cell, it was recently also suggested to increase the accuracy of sensing ligand as the overcounting of the same ligand molecules is reduced. Here we show, by extending simple ligand-receptor models to out-of-equilibrium thermodynamics, that internalization increases the accuracy with which cells can measure ligand concentrations in the external environment. Comparison with experimental rates of real receptors demonstrates that our model has indeed biological significance.Comment: 9 pages, 4 figures, accepted for publication in Physical Review

The current practice of intra-aortic balloon counterpulsation: results from the Benchmark Registry

OBJECTIVES This study presents clinical data from the first large registry of aortic counterpulsation, a computerized database that incorporates prospectively gathered data on indications for intra-aortic balloon counterpulsation (IABP) use, patient demographics, concomitant medication and in-hospital outcomes and complications. BACKGROUND The intra-aortic balloon pump (IABP) is widely used to provide circulatory support for patients experiencing hemodynamic instability due to myocardial infarction, cardiogenic shock, or in very high risk patients undergoing angioplasty or coronary artery bypass grafting. METHODS Between June 1996 and August 2000, 203 hospitals worldwide (90% U.S., 10% non-U.S.) collected 16,909 patient case records (68.8% men, 31.2% women; mean age 65.9 ± 11.7 years). RESULTS The most frequent indications for use of IABP were as follows: to provide hemodynamic support during or after cardiac catheterization (20.6%), cardiogenic shock (18.8%), weaning from cardiopulmonary bypass (16.1%), preoperative use in high risk patients (13.0%) and refractory unstable angina (12.3%). Major IABP complications (major limb ischemia, severe bleeding, balloon leak, death directly due to IABP insertion or failure) occurred in 2.6% of cases; in-hospital mortality was 21.2% (11.6% with the balloon in place). Female gender, high age and peripheral vascular disease were independent predictors of a serious complication. CONCLUSIONS This registry provides a useful tool for monitoring the evolving practice of IABP. In the modern-day practice of IABP, complication rates are generally low, although in-hospital mortality remains high. There is an increased risk of major complications in women, older patients and patients with peripheral vascular disease

Combustion Joining of Regolith Tiles for In-Situ Fabrication of Launch/Landing Pads on the Moon and Mars

To mitigate dust problems during launch-landing operations in lunar and Mars missions, it is desired to build solid pads on the surface. Recently, strong tiles have been fabricated from lunar regolith simulants using high-temperature sintering. The present work investigates combustion joining of these tiles through the use of exothermic intermetallic reactions. Specifically, nickel aluminum (1:1 mole ratio) mixture was placed in a gap between the tiles sintered from JSC-1A lunar regolith simulant. Upon ignition by a laser, a self-sustained propagation of the combustion front over the mixture occurred. Joining was improved with increasing the tile thickness from 6.3 mm to 12.7 mm. The temperatures sufficient for melting the glass phase of JSC-1A were recorded for 12.7-mm tiles, which explains the observed better joining

Incidence and Severity of Lymphoedema following Limb Salvage of Extremity Soft Tissue Sarcoma

Background and Purpose. Lymphoedema is a serious complication following limb salvage for extremity soft tissue sarcomas (STSs) for which little is known. We aimed to evaluate its incidence, its, severity and its associated risk factors. Material and Method. Patient and tumor characteristics, treatment modalities and complications and functional outcomes (MSTS 1987, TESS), and lymphoedema severity (Stern) were all collected from prospective databases. Charts were retrospectively abstracted for BMI and comorbidities. Results. There were 289 patients (158 males). Mean age was 53 (16–88). Followup ranged between 12 and 60 months with an average of 35 and a median of 36 months. Mean BMI was 27.4 (15.8–52.1). 72% had lower extremity tumors and 38% upper extremity. Mean tumor size was 8.1 cm (1.0–35.6 cm). 27% had no adjuvant radiation, 62% had 50 Gy, and 11% received 66 Gy. The incidence of lymphoedema was 28.8% (206 none, 58 mild, 22 moderate, 3 severe, and 0 very severe). Mean MSTS score was 32 (11–35) and TESS was 89.4 (32.4–100). Radiation dose was significantly correlated with tumor size > 5 cm (P = 0.0001) and TESS score (P = 0.001), but not MSTS score (P = 0.090). Only tumor size > 5 cm and depth were found to be independent predictors of significant lymphoedema. Conclusion. Nine percent of STS patients in our cohort developed significant (grade ≥ 2) lymphoedema. Tumor size > 5 cm and deep tumors were associated with an increased occurrence of lymphoedema but not radiation dosage

Adverse Impact of a History of Violence for Women with Breast, Cervical, Endometrial, or Overian Cancer

The experience of physical and sexual violence (victimization) is common among U.S. women and is associated with adverse health consequences. The study objectives were to estimate the prevalence of victimization in women with cancer and to examine associations with demographics, cancer screening, and cancer stage. METHODS: From 2004 to 2005, 101 women with breast, cervical, endometrial, or ovarian cancer were interviewed to collect demographics, cancer screening history, health care access/use, and violence history. Chisquare and Fisher exact tests were used test risk-factor associations. A multinomial logistic regression model was used for multivariable analysis. RESULTS: The prevalence of a history of violence was 48.5% (49/101 women), and within that group, 46.9% (23/49) had a positive childhood violence screen, 75.5% (37/49) had a positive adult screen, and 55% (27/49) reported sexual violence at any age. Women with a positive violence screen differed significantly from women with a negative screen in that they were younger (P .031), more often divorced (P.012), more likely to smoke (P.010), more often lacked commercial insurance (P.036), and had more advanced stage of disease (P.013), but they did not differ with regard to race, cancer type, education level, alcohol or drug use, or cancer screening compliance. Multivariable analysis revealed that only stage remained significant; women with a history of violence had a 2.6-fold increased chance of diagnosis in later stages (odds ratio 2.61, 95% confidence interval 1.03– 6.59). CONCLUSION: A history of violence in breast, ovarian, endometrial, and ovarian cancer patients was extremely common and correlated with advanced stage at diagnosis

Photospheric Abundances of the Hot Stars in NGC1399 and Limits on the Fornax Cluster Cooling Flow

We present far-UV spectroscopy of the giant elliptical galaxy NGC 1399, obtained with the Far Ultraviolet Spectroscopic Explorer. Of all quiescent ellipticals, NGC 1399 has the strongest known ``UV upturn'' -- a sharp spectral rise shortward of 2500 A. It is now well-established that this emission comes from hot horizontal branch (HB) stars and their progeny; however, the chemical composition of these stars has been the subject of a long-standing debate. For the first time in observations of any elliptical galaxy, our spectra clearly show photospheric metallic absorption lines within the UV upturn. The abundance of N is at 45% solar, Si is at 13% solar, and C is at 2% solar. Such abundance anomalies are a natural consequence of gravitational diffusion. These photospheric abundances fall in the range observed for subdwarf B stars of the Galactic field. Although NGC1399 is at the center of the Fornax cluster, we find no evidence for O VI cooling flow emission. The upper limit to 1032,1038 emission is 3.9E-15 erg/s/cm2, equivalent to 0.14 M_sun/yr, and less than that predicted by simple cooling flow models of the NGC 1399 X-ray luminosity.Comment: 4 pages, Latex. 2 figures. Uses corrected version of emulateapj.sty and apjfonts.sty (included). Accepted for publication in ApJ Letters. Revised figure placemen