Gene therapy in autoimmune diseases

The influence of "shinrin-yoku" (forest-air bathing and walking) on blood glucose levels in diabetic patients was examined. Eighty-seven (29 male and 58 female) non-insulin-dependent diabetic patients [61 (SEM 1) years old] participated in the present study. Shinrin-yoku was performed nine times over a period of 6 years. The patients were divided into two parties. They then walked in the forest for 3 km or 6 km according to their physical ability and/or the existence of diabetic complications. The mean blood glucose level after forest walking changed from 179 (SEM 4) mg.100 ml-1 to 108 (SEM 2) mg.100 ml-1 (P < 0.0001). The level of glycated haemoglobin A1c also decreased from 6.9 (SEM 0.2)% (before the first shinrin-yoku) to 6.5 (SEM 0.1)% (after the last shinrin-yoku; P < 0.05). Blood glucose values declined by 74 (SEM 9) mg.100 ml-1 and 70 (SEM 4) mg.100 ml-1 after short- and long-distance walking respectively. There was no significant difference between these values. Since the forest environment causes changes in hormonal secretion and autonomic nervous functions, it is presumed that, in addition to the increased calorie consumption and improved insulin sensitivity, walking in a forest environment has other beneficial effects in decreasing blood glucose levels.     

A reactive coordination scheme for a many-robot system

This paper presents a novel approach for coordinating a homogeneous system of mobile robots using implicit communication in the form of broadcasts. The broadcast-based coordination scheme was developed for the Army Ant swarm-a system of small, relatively inexpensive mobile robots that can accomplish complex tasks by cooperating as a team. The primary drawback, however, of the Army Ant system is that the absence of a central supervisor poses difficulty in the coordination and control of the agents. Our coordination scheme provides a global "group dynamic" that controls the actions of each robot using only local interactions. Coordination of the swarm is achieved with signals we call "heartbeats". Each agent broadcasts a unique heartbeat and responds to the collective behavior of all other heartbeats. We generate heartbeats with van der Pol oscillators. In this application, we use the known properties of coupled van der Pol oscillators to create predictable group behavior. Some of the properties and behaviors of coupled van der Pol oscillators are discussed in detail. We emphasize the use of this scheme to allow agents to simultaneously perform an action such as lifting, steering, or changing speed. The results of experiments performed on three actual heartbeat circuits are presented and the behavior of the realized system is compared to simulated results. We also demonstrate the application of the coordination scheme to global speed control.     

Spectroscopic determination of pressure-induced shifts in inclusion complexation equilibria

The effect of modest hydrostatic pressure (<350 bar) on condensed-phase equilibrium processes has been largely overlooked, due in large part to the small compressibility of these phases relative to gases or supercritical fluids. Although the bulk properties of condensed phases are not significantly modified by pressure in this modest regime, the solvation processes driving inclusion complexation may be appreciably affected. In this paper, we examine this hypothesis using steady-state fluorescence spectroscopy to determine the pressure dependence of association constants. The widely used host molecule, β-cyclodextrin, provides an incompressible hydrophobic cavity into which structurally analogous fluorescent probes are encapsulated. By comparing the unique pressure dependencies of these equilibria, the importance of local site solvation and rim interactions in influencing the pressure dependence is demonstrated. The structurally analogous complexes chosen for these studies are expected to have similar pressure-dependent behavior based on comparable solvation structures. However, pressure-induced changes in the association constant for these two analogs are quite distinct, with differences in K(c) ranging from clearly pressure dependent (-14%) to pressure independent over 338 bar. Additional solvation perturbations are observed in the pressure dependence of the quantum efficiency for both complexes (-7.3% and -9.4%). Thus, pressure-induced perturbation in the fluorescence properties of the complex need not be accompanied by simultaneous changes in the complexation equilibrium. Finally, these pressure-induced changes in complexation selectivity are important for all measurements conducted under variable pressure conditions, including liquid chromatography and process monitoring.     

Effect of inflammation on the proliferation of human gingival epithelial cells in vitro

The adaptive or pathologic responses of epithelial cells to inflammation are poorly characterized. The purpose of this study was to determine if epithelial cells cultured from clinically healthy and inflamed human gingival tissues express differences in proliferation rate and viability. Briefly, the inflammation status of individual donor sites from 101 patients was visually assessed at the time of periodontal surgery and categorized as either non-to-slightly inflamed, moderately inflamed, or severely inflamed. Discarded gingival tissues were then processed to obtain primary cell cultures, for which proliferation rates were determined by calculating the ratio of mean population doublings to the number of days required for cultures to become confluent. In general, the cells in the minimally inflamed group exhibited characteristics different than cells in the moderately and severely inflamed groups. Specifically, the cells obtained from clinical sites which exhibited no-to-slight inflammation had a significantly higher mean proliferation rate than cells in either the moderate inflammation group or the severe inflammation group. Based on trypan blue exclusion, the cells obtained from clinical sites which exhibited no-to-slight inflammation also were more viable than cells obtained from sites with moderate inflammation or severe inflammation. Microscopic evaluation showed morphological changes associated with increased inflammation. Cell cycle analysis by fluorescent-activated cell sorting (FACS) revealed a directly proportional relationship between the degree of inflammation and apoptosis, and a strong inversely proportional trend between the degree of inflammation and the numbers of cells undergoing mitosis. Taken together, these data suggest that epithelial cell proliferation and viability are inversely associated with the degree of gingival inflammation, once a putative "adaptive threshold" is exceeded. Elucidation of the underlying mechanisms will likely lead to improvements in clinical diagnosis and treatment.     

Influence of projected complication rates on estimated appropriate use rates for carotid endarterectomy. Appropriateness Project Investigators. Academic Medical Center Consortium

OBJECTIVE: To examine specifically the influence of estimated perioperative mortality and stroke rate on the assessment of appropriateness of carotid endarterectomy. DATA SOURCES/STUDY SETTING: An expert panel convened to rate the appropriateness of a variety of potential indications for carotid endarterectomy based on various rates of perioperative complications. We then applied these ratings to the charts of 1,160 randomly selected patients who had carotid endarterectomy in one of the 12 participating academic medical centers. STUDY DESIGN: An expert panel evaluated indications for carotid endarterectomy using the modified Delphi approach. Charts of patients who received surgery were abstracted, and clinical indications for the procedure as well as perioperative complications were recorded. To examine the impact of surgical risk assessment on the rates of appropriateness, three different definitions of risk strata for combined perioperative death or stroke were used: Definition A, low risk < 3 percent; Definition B, low risk < 5 percent; and Definition C, low risk < 7 percent. PRINCIPAL FINDINGS: Overall hospital-specific mortality ranged from 0 percent to 4.0 percent and major complications, defined as death, stroke, intracranial hemorrhage, or myocardial infarction, varied from 2.0 percent to 11.1 percent. Most patients (72 percent) had surgery for transient ischemic attack or stroke; 24 percent of patients were asymptomatic. Most patients (82 percent) had surgery on the side of a high-grade stenosis (70-99 percent). When the thresholds for operative risk were placed at the values defined by the expert panel (Definition A), only 33.5 percent of 1,160 procedures were classified as "appropriate." When the definition of low risk was shifted upward, the proportion of cases categorized as appropriate increased to 58 percent and 81.5 percent for Definitions B and C, respectively. CONCLUSIONS: Despite the high proportion of procedures performed for symptomatic patients with a high degree of ipsilateral extracranial carotid artery stenosis and generally low rates of surgical complications at the participating institutions, the overall rate of "appropriateness" using a perioperative complication rate of < 3 percent was low. However, the rate of "appropriateness" was extremely sensitive to judgments about a single clinical feature, surgical risk. These data show that before applying such "appropriateness" ratings, it is crucial to perform sensitivity analyses in order to assess the stability of the results. Results that are robust to moderate in variation in surgical risk provide a much sounder basis for policy making than those that are not.     

The geriatric gravida: multifetal pregnancy reduction, donor eggs, and aggressive infertility treatments

OBJECTIVE: Recent technologic advances and societal acceptance have dramatically increased the use of donor eggs for infertile couples who require assisted reproductive technologies. Now many "older" couples can access assisted reproductive technologies to achieve pregnancies. We sought to evaluate the changing pattern of patients referred for multifetal pregnancy reduction as a result of donor eggs and age factors in aggressive infertility treatment. STUDY DESIGN: Patients undergoing multifetal pregnancy reduction from 1986 to 1996 were included and categorized by year groupings, age, and the use of donor eggs. RESULTS: A total of 523 patients were referred for and underwent multifetal pregnancy reduction. Before 1994, only 4 of 226 (1.8%) had received donor eggs, whereas in 1994 to 1996, 29 of 297 (9.8%) had received donor eggs (chi 2 = 12.6, p < 0.001). Eight of 9 patients aged > or = 45 years undergoing multifetal pregnancy reduction received donor eggs. There were no patients aged > or = 45 years before 1994 but 9 in 1994 to 1996. Four of 9 patients aged > or = 45 years with multifetal pregnancies chose reduction to singleton gestation. The proportions of patients aged > or = 40 years have increased from 0% to 11% in the last 8 years. CONCLUSIONS: The availability of donor eggs has dramatically increased the use of assisted reproductive technologies and subsequent use of multifetal pregnancy reduction in older patients. Older patients are more inclined to want reduction to singleton gestation; they cite parental demands, financial issues, and their ability to parent in their 60s and 70s as reasons for reduction to singleton gestation.     

Inhibitory effect of alkylating modulators on the function of P-glycoprotein

Modulators of P-glycoprotein (P-gp) are often themselves transported out of cells, thereby limiting their effectiveness. It may be possible to develop more effective modulators of multidrug resistance by designing drugs that irreversibly block the function of P-gp. Therefore, we studied the effect of the mustard derivatives of fluphenazine (FPN) and trans-flupenthixol (FPT) on P-gp function. Both fluphenazine-mustard (FPN-M) and trans-flupenthixol-mustard (FPT-M) possessed alkylating activity, as assayed using 4-(p-nitrobenzyl) pyridine. Multidrug-resistant MCF-7/AdrR cells were incubated with FPN or FPN-M, or FPT or FPT-M for 1 h, washed for varying number of times in phosphate-buffered saline (PBS), then resuspended in medium containing [3H]vinblastine (VBL), and assayed for steady-state accumulation of the drug. Washing had far less of an effect on the ability of FPN-M and FPT-M to increase VBL accumulation compared to their parent compounds. After eight washes in excess PBS, the cells initially exposed to FPN or FPT accumulated only 30% and 50% of the initially accumulated drug, whereas the FPN-M- or FPT-M-treated cells accumulated approximately 75% and 90% of the control, respectively. FPN-M and FPT-M also increased the uptake and decreased the efflux of VBL from MDR cells despite repeated washing. We also examined the effects of these modulators on sensitivity of MDR cells to cytotoxic agents. FPN-M and FPT-M sensitized MCF-7/AdrR cells to VBL and doxorubicin to a greater extent than their parent compounds. These studies point out the potential of "irreversible" P-gp modulators to produce prolonged chemosensitization.     

Identifying incompleteness in privacy policy goals using semantic frames

Requirements Engineering - Companies that collect personal information online often maintain privacy policies that are required to accurately reflect their data practices and privacy goals. To be...     

Ecologically Driven Ultrastructural and Hydrodynamic Designs in Stomatopod Cuticles

Ecological pressures and varied feeding behaviors in a multitude of organisms have necessitated the drive for adaptation. One such change is seen in the feeding appendages of stomatopods, a group of highly predatory marine crustaceans. Stomatopods include “spearers,” who ambush and snare soft bodied prey, and “smashers,” who bludgeon hard‐shelled prey with a heavily mineralized club. The regional substructural complexity of the stomatopod dactyl club from the smashing predator Odontodactylus scyllarus represents a model system in the study of impact tolerant biominerals. The club consists of a highly mineralized impact region, a characteristic Bouligand architecture (common to arthropods), and a unique section of the club, the striated region, composed of highly aligned sheets of mineralized fibers. Detailed ultrastructural investigations of the striated region within O. scyllarus and a related species of spearing stomatopod, Lysiosquillina maculate show consistent organization of mineral and organic, but distinct differences in macro‐scale architecture. Evidence is provided for the function and substructural exaptation of the striated region, which facilitated redeployment of a raptorial feeding appendage as a biological hammer. Moreover, given the need to accelerate underwater and “grab” or “smash” their prey, the spearer and smasher appendages are specifically designed with a significantly reduced drag force.