Synthesis and comparative molecular field analysis (CoMFA) of antitumor 3-arylisoquinoline derivatives

In this study a series of 3-arylisoquinoline derivatives were synthesized and cytotoxicity against human melanoma tumor cell evaluated, and a three dimensional quantitative structure-activity relationship was investigated using the comparative molecular field analysis (CoMFA). The results suggested that the electrostatic, steric and hydrophobic factors of 3-arylisoquinolines were strongly correlated with the antitumor activity. Considerable predictive ability (cross-validated r2 as high as 0.721) was obtained through CoMFA.     

Suppression of in vitro IgM rheumatoid factor production by diphtheria toxin interleukin 2 recombinant fusion protein (DAB 486IL-2) in patients with refractory rheumatoid arthritis

OBJECTIVE: To investigate the effect of diphtheria toxin interleukin 2 recombinant fusion protein (DAB 486IL-2) on in vitro synthesis of immunoglobulin and rheumatoid factor (RF) in patients with severe refractory rheumatoid arthritis (RA) enrolled in a phase II, double blind, placebo controlled study. METHODS: Anticoagulated venous blood samples were obtained before (Day 1) and after (Day 28) intravenous infusion of either DAB 486IL-2 at 0.075 mg/kg/day (12 patients) or saline placebo (10 patients) on Days 1-5. Peripheral blood leukocytes (PBL) were prepared by density gradient centrifugation, cultured in the presence and absence of pokeweed mitogen (PWM) for one week, and culture supernatants assayed for immunoglobulins and IgM RF by ELISA. RESULTS: Compared to placebo treated patients, PWM induced IgM RF synthesis by PBL decreased after treatment with DAB 486IL-2 (p = 0.043). However, there was no apparent correlation with clinical improvement. PWM induced IgM, IgA, and IgG synthesis also tended to decrease, although the changes did not attain statistical significance. In contrast, PWM induced IgM RF, IgM, IgA, and IgG synthesis by PBL from patients treated with placebo tended to increase during the observation period. Spontaneous immunoglobulin and IgM RF production by PBL from either the DAB 486IL-2 or placebo patients remained stable. CONCLUSION: These observations raise the possibility that DAB 486IL-2 may diminish B cell function either directly or indirectly through effects on T cell function, but the change may not correspond to clinical response.     

Limb salvage surgery for widely infiltrating bony sarcomas

OBJECTIVE: To determine whether neoadjuvant chemotherapy and radiotherapy for bony sarcomas extending into soft tissues would allow limb salvage yet maintain local disease control. DESIGN: A prospective cohort study. SETTING: A university-affiliated cancer centre in Alberta. PATIENTS: All patients with potentially curable, widely infiltrating bony sarcomas of the extremity without neurologic deficit, referred to the centre in the 6 years from January 1984 to December 1990. There were 11 patients; 1 did not complete the protocol. The mean follow-up was 24 months. INTERVENTIONS: Adriamycin (doxorubicin) was infused for 3 days at a rate of 30 mg/d. A few days later radiotherapy was given 5 days a week for 10 doses at a rate of 3.0 Gy per dose. Four to 5 weeks later the tumour was excised surgically, with placement of a bone allograft or prosthesis, allowing a 1-cm margin of healthy soft tissue and a 5-cm margin of healthy bone and marrow cavity whenever possible. MAIN OUTCOME MEASURES: Need for limb amputation, infectious complications, recurrence of local or regional disease. RESULTS: One patient underwent amputation after fracture through the tumour site. There were two postoperative infections, one acute and one chronic. All patients had full neurologic function of the distal limb. There was no local or regional recurrence of disease. CONCLUSION: Neoadjuvant chemotherapy followed by radiotherapy and tumour excision provides control of aggressive local bone sarcomas while maintaining limb integrity.     

Long-term information collection with energy harvesting wireless sensors: a multi-armed bandit based approach

This paper reports on the development of a multi-agent approach to long-term information collection in networks of energy harvesting wireless sensors. In particular, we focus on developing energy management and data routing policies that adapt their behaviour according to the energy that is harvested, in order to maximise the amount of information collected given the available energy budget. In so doing, we introduce a new energy management technique, based on multi-armed bandit learning, that allows each agent to adaptively allocate its energy budget across the tasks of data sampling, receiving and transmitting. By using this approach, each agent can learn the optimal energy budget settings that give it efficient information collection in the long run. Then, we propose two novel decentralised multi-hop algorithms for data routing. The first proveably maximises the information throughput in the network, but can sometimes involve high communication cost. The second algorithm provides near-optimal performance, but with reduced computational and communication costs. Finally, we demonstrate that, by using our approaches for energy management and routing, we can achieve a 120% improvement in long-term information collection against state-of-the-art benchmarks.     

Thrombospondin-1 CD47 Signalling: From Mechanisms to Medicine

Recent advances provide evidence that the cellular signalling pathway comprising the ligand-receptor duo of thrombospondin-1 (TSP1) and CD47 is involved in mediating a range of diseases affecting renal, vascular, and metabolic function, as well as cancer. In several instances, research has barely progressed past pre-clinical animal models of disease and early phase 1 clinical trials, while for cancers, anti-CD47 therapy has emerged from phase 2 clinical trials in humans as a crucial adjuvant therapeutic agent. This has important implications for interventions that seek to capitalize on targeting this pathway in diseases where TSP1 and/or CD47 play a role. Despite substantial progress made in our understanding of this pathway in malignant and cardiovascular disease, knowledge and translational gaps remain regarding the role of this pathway in kidney and metabolic diseases, limiting identification of putative drug targets and development of effective treatments. This review considers recent advances reported in the field of TSP1-CD47 signalling, focusing on several aspects including enzymatic production, receptor function, interacting partners, localization of signalling, matrix-cellular and cell-to-cell cross talk. The potential impact that these newly described mechanisms have on health, with a particular focus on renal and metabolic disease, is also discussed.     

HEAT TRANSFER BETWEEN ROUGH SURFACES IN CONTACT OVER A HIGHLY ELLIPTICAL CONTOUR AREA: COMPARISON OF EXPERIMENTAL AND NUMERICAL RESULTS

This paper describes experimental and numerical studies of heat transfer between surfaces in contact over a highly elliptical area in a gas or in vacuum. Measurements of the steady-state thermal resistance of a high aspect ratio contact formed between cylindrical steel surfaces with widely different radii of curvature (76 cm vs 0.95 cm) are reported for two levels of surface roughness (0.05 μm and 1.0 μm rms) and compared to 3-D numerical results obtained with the multigrid method. Theoretical results obtained by evaluating the contact conductance acting over each surface element within the contour area with a method developed previously for rough but nominally flat surfaces are shown to be in excellent agreement with the rough surface experimental data.     

Stability of nonlinear 2D systems described by the continuous-time Roesser model

This paper considers systems with two-dimensional dynamics (2D systems) described by the continuous-time nonlinear state-space Roesser model. The sufficient conditions of exponential stability in terms of vector Lyapunov functions are established. These conditions are then applied to analysis of the absolute stability of a certain class of systems comprising a linear continuous-time plant in the form of the Roesser model with a nonlinear characteristic in the feedback loop, which satisfies quadratic constraints. The absolute stability conditions are reduced to computable expressions in the form of linear matrix inequalities. The obtained results are extended to the class of continuous-time systems governed by the Roesser model with Markovian switching. The problems of absolute stability and stabilization via state- and output-feedback are solved for linear systems of the above class. The solution procedures for these problems are in the form of algorithms based on linear matrix inequalities.     

Dis-Bond Detection and the Possibility of Interfacial Stiffness Measurement with Real-Time Impulsive Stimulated Thermal Scattering

We describe a new, real-time, noninvasive method for dis-bond (delamination) detection which is based on a technique known as impulsive stimulated thermal scattering (ISTS). We first explain the ISTS technique and compare data from polyimide films tightly bound to silicon substrates with data from unsupported polyimide films. The observed differences in the data from these two cases are readily understandable and offer an unmistakable signature for delaminations. We demonstrate ISTS dis-bond detection by locating and mapping out randomly-distributed and spatially-fine regions of delamination in a polyimide film-silicon substrate system. Finally, we present two simple physical models of the interfacial region which comprehensively describe acoustic data from the tightly-bound and the unsupported samples. With insight from simulations using these models, we suggest how ISTS might be used to determine interfacial adhesion quality and we show how ISTS sensitivity to interfacial effects can be adjusted.     

The composition of volatile oils derived from oleoresins

Essential oils and oleoresins derived from spices and herbs, by steam distillation in the former case or by solvent extraction in the latter case, are increasingly more important as flavoring constituents in heat-processed foods. Steam-distilled oils, when used for such purposes, tend to steam-distill during the heat processing due to moisture that is present. Oleoresins that contain the essential oil and natural fixatives tend to depress this volatilization and are preferred as flavoring materials in such cases. Subjective flavor panel evaluations are reported, showing the significance between oleoresins and essential oils as well as the corresponding spice or herb. Instrumental evaluation, primarily gas chromatography, will compare essential oils produced by direct steam distillation vs. those isolated form oleoresins. The difference in composition which can be related to the improved flavor effect from oleoresins is discussed. One of 13 papers presented in the symposium “Flavor Research in Fats and Fat Bearing foods,” AOCS Meeting, Atlantic City, October 1971.     

The Effects of Experience and Strategy on Visual Attention Allocation in an Automated Multiple-Task Environment

Operators and users interacting with computer environments often have to deal with multiple tasks at once, responding to each in series. Diagnostic automation, that is, automation that alerts users when and where to look, has been suggested to support the unique challenges of multiple task environments: activating tasks, switching between tasks, and tasks interfering with each other. Automation is not always reliable, however. Because of the common interaction with novel systems and the importance of training, the Simultaneous Task Environment Platform program—a multiple-task environment—was developed to understand the effects of experience on interaction with these automation-supported systems, as well as what strategies were developed. It was found that participants became more efficient with experience only when they interacted with higher reliability automation. Furthermore, the strategies participants developed focused on the differences between tasks and patterns across those tasks. Automated systems training should be sure to employ these findings.