Opportunistic soaring by birds suggests new opportunities for atmospheric energy harvesting by flying robots.

The use of flying robots (drones) is increasing rapidly, but their utility is limited by high power demand, low specific energy storage and poor gust tolerance. By contrast, birds demonstrate long endurance, harvesting atmospheric energy in environments ranging from cluttered cityscapes to open landscapes, coasts and oceans. Here, we identify new opportunities for flying robots, drawing upon the soaring flight of birds. We evaluate mechanical energy transfer in soaring from first principles and review soaring strategies encompassing the use of updrafts (thermal or orographic) and wind gradients (spatial or temporal). We examine the extent to which state-of-the-art flying robots currently use each strategy and identify several untapped opportunities including slope soaring over built environments, thermal soaring over oceans and opportunistic gust soaring. In principle, the energetic benefits of soaring are accessible to flying robots of all kinds, given atmospherically aware sensor systems, guidance strategies and gust tolerance. Hence, while there is clear scope for specialist robots that soar like albatrosses, or which use persistent thermals like vultures, the greatest untapped potential may lie in non-specialist vehicles that make flexible use of atmospheric energy through path planning and flight control, as demonstrated by generalist flyers such as gulls, kites and crows.

Rosai dorfman disease - an unusual presentation: A case report.

Rosai Dorfman Disease (Sinus Histiocytosis with massive lymphadenopathy) is a rare self-limiting histiocytic disorder of unknown etiology usually presenting with cervical lymphadenopathy and haematological abnormalities. Extra-nodal presentation is rare . This ease is such a rare presentation of Rosai Dorfman Disease.

Adjuvant sequential dose-dense doxorubicin, paclitaxel, and cyclophosphamide (ATC) for high-risk breast cancer is feasible in the community setting.

PURPOSE: This study evaluated the feasibility, when given in the community, of dose-dense, sequential ATC (doxorubicin, paclitaxel, cyclophosphamide) as adjuvant therapy for breast cancer with four or more metastatic axillary lymph nodes. PATIENTS AND METHODS: Patients were recruited after definitive breast cancer surgery if four or more axillary nodes were involved by metastatic cancer and if distant metastases were not present on computed tomographic scan or bone scan. Forty patients received doxorubicin, 90 mg/m2 every 14 days for three cycles; paclitaxel, 250 mg/m2 every 14 days for three cycles; and cyclophosphamide, 3 g/m2 every 14 days for three cycles with filgrastim support. Chemotherapy was administered by the referring physician. RESULTS: Mean dose intensity was 99% for doxorubicin, 96% for paclitaxel, and 99% for cyclophosphamide. Grade 3 toxicities included mucositis (13%), nausea/vomiting (10%), neuropathy (13%), and myalgia/arthralgia (10%). Thirteen patients had neutropenic fever. One patient developed acute leukemia. Three relapses have occurred. Ninety percent of patients are alive and disease-free at a median follow-up of 24 months. DISCUSSION: ATC can be administered in the community at full doses with acceptable toxicity. Preliminary efficacy data suggest that this high-dose, intensively scheduled regimen warrants comparison with standard therapy for high-risk patients.

Omega-3 fatty acids alter lipoprotein subfraction distributions and the in vitro conversion of very low density lipoproteins to low density lipoproteins.

The purpose of this study was to determine the effects of a fish oil concentrate (FOC) on the in vitro conversion of very low density lipoproteins (VLDL) to intermediate (IDL) and low density lipoproteins (LDL). Six hypertriglyceridemic patients were randomly allocated to receive either placebo (olive oil) or FOC (1 g/14 kg body weight/day) for 4 weeks in a crossover study with a 4-week washout period. The FOC provided 3 g of eicosapentaenoic + docosahexaenoic acid per 70 kg of body weight, and it lowered plasma triglyceride and VLDL cholesterol levels by 35% and 42%, respectively. Decreases in the largest particles (VLDL(1)) were primarily responsible, with no effect noted in smaller VLDL particles (VLDL(2) and VLDL(3)). The FOC increased LDL cholesterol levels by 25% (P < 0.06) but did not affect LDL particle size. VLDL(1) and VLDL(3) were incubated in vitro with human postheparin lipases. Although triglycerides from both types of VLDL were hydrolyzed to the same extent with both treatments, particles isolated during the FOC phase were more readily converted into IDL and LDL than were control particles. These data suggest that the marine omega3 fatty acids may enhance the propensity of VLDL to be converted to LDL, partly explaining the decreased VLDL and increased LDL levels in FOC-treated patients.

Influence of n-3 fatty acid supplementation on the endogenous activities of plasma lipases.

The aim of these studies was to explore the possibility that enhanced triacylglycerol clearance may contribute to the hypotriacylglycerolemic effect of n-3 fatty acids in humans. Healthy subjects (n = 20) and hypertriacylglycerolemic patients (n = 6) were given a placebo (olive oil, OO) or a fish-oil concentrate (FOC; 41% eicosapentaenoic acid and 23% docosahexaenoic acid) in two, independent, randomized, blind trials. For the healthy subjects, the FOC treatment period was 3 wk long and FOC intakes were 5 g/d. For the patients, treatment periods were 4 wk long and dosages were 5 g.70 kg body wt-1.d-1. Washout periods were 2-4 wk for both groups. Blood samples were drawn at the end of each phase and analyzed for plasma lipids, lipoproteins, and endogenous (nonheparin-stimulated) activities of lipoprotein lipase (LPL) and hepatic lipase (HL). In the healthy subjects the FOC decreased plasma triacylglycerol concentrations by 18% (P < 0.01), whereas in the patients concentrations were reduced by 35% (P < 0.05). Low-density-lipoprotein-cholesterol concentrations increased by 25% in the latter group (P = 0.06). FOC increased the endogenous activities of LPL and HL by 62% and 68%, respectively (P < 0.0001), in the healthy subjects, but only LPL in the patients (65%, P < 0.005). These data suggest that endogenous lipase activities may be altered by nutritional interventions, and further, that accelerated lipolysis could contribute, at least in part, to the observed effects of n-3 fatty acids on human lipoprotein metabolism.

Inhibiting cholesterol absorption with CP-88,818 (beta-tigogenin cellobioside; tiqueside): studies in normal and hyperlipidemic subjects.

CP-88,818 (beta-tigogenin cellobioside; tiqueside) is a synthetic saponin developed to treat hypercholesterolemia by inhibiting the absorption of biliary and dietary cholesterol. Two studies are reported here: one in patients to assess safety and efficacy, and one in normal volunteers to explore the mechanism of action. The former included 15 hypercholesterolemic outpatients [low-density lipoprotein cholesterol (LDL-C) > or = 160 mg/dl] treated with 1, 2, and 3 g of tiqueside daily (b.i.d.) in a crossover design for three 2-week treatment periods, each separated by a 3-week placebo period. The mechanistic study was conducted with 24 healthy male subjects who were randomized in a parallel group design to either placebo (n = 6) or tiqueside (2 or 4 g/day; n = 9 each) once daily for 3 weeks. All subjects in this study were fed a low-fat, low-cholesterol diet [National Cholesterol Education Program (NCEP) Step 1]. Fecal steroid excretion rates and plasma lipid levels were determined at baseline and after 3 weeks of treatment. Fractional cholesterol absorption was measured before and after treatment by the continuous feeding, dual-isotope method. Tiqueside produced a dose-dependent reduction in plasma LDL cholesterol levels in the hypercholesterolemic patients. In the mechanistic study, it decreased fractional cholesterol absorption rates and increased fecal neutral sterol excretion rates, changes associated with trends toward lower LDL cholesterol levels. Other lipoprotein levels were unaffected, as were fecal fat and bile acid excretion and fat-soluble vitamin absorption. Thus tiqueside dose-dependently inhibits cholesterol absorption in humans, resulting in a reduction in serum LDL cholesterol levels.

Inhibition of cholesterol absorption with CP-148,623 lowers serum cholesterol in humans.

OBJECTIVE: To determine the effects of the reduction of intestinal cholesterol absorption with CP-148,623 on serum cholesterol levels in men with mild hyperlipidemia. METHODS: In an outpatient study in a university medical center, healthy male volunteers (n = 25) with borderline-high serum cholesterol levels participated in a double-blind, placebo-controlled parallel-group study. A 3-week dietary run-in period was followed by 2 weeks of treatment with either CP-148,623 (300 mg twice a day; n = 12) or placebo (n = 13). RESULTS: Fractional cholesterol absorption (by the dual-isotope, continuous-feeding technique), fecal neutral sterol excretion, and serum lipids were measured after the diet run-in and after the treatment periods. CP-148,623 caused a marked inhibition (by 38%) of fractional cholesterol absorption (50% +/- 2% [baseline] to 31% +/- 1%) and a 71% increase in fecal neutral sterol excretion (481 +/- 39 mg/day [baseline] to 804 +/- 55 mg/day), compared with negligible changes in the placebo group (p < 0.0001 for both). Mean percent reductions from baseline in serum low-density lipoprotein (LDL) cholesterol levels were 11.6% with CP-148,623 (119 +/- 17 mg/dl to 104 +/- 13 mg/dl) versus a nonsignificant 1.8% reduction with placebo (change with CP-148,623 versus placebo, p < 0.0002). CONCLUSIONS: In healthy male volunteers with mild hypercholesterolemia, treatment for 2 weeks with 600 mg/day CP-148,623 inhibited fractional cholesterol absorption by 35% to 40%, increased fecal neutral sterol excretion by 60% to 70%, and reduced serum LDL cholesterol by 10% to 12%.

n-3 fatty acids and urinary excretion of nitric oxide metabolites in humans.

Fish oils rich in n-3 fatty acids have been shown to augment endothelium-dependent vasodilation in human peripheral and coronary arteries. This suggests that n-3 fatty acids may enhance arterial nitric oxide production. To explore this hypothesis we measured total urinary nitrate output in healthy volunteers supplemented with a fish oil concentrate (FOC; n = 15) or purified eicosapentaenoic acid (EPA; n = 14) in a placebo-controlled, parallel-group study. The FOC contained 41% EPA and 23% docosahexaenoic acid (DHA) ethyl esters, whereas EPA was 91% pure; the placebo contained olive oil ethyl esters. Doses were 5 g placebo, 5 g FOC, and 3 g EPA to keep the total n-3 fatty acid content equal in the latter two groups. The placebo period was 2 wk long and was followed by a 3-wk n-3 fatty acid phase. At the end of each period, 24-h urine collections and fasting blood samples were obtained. Serum and urinary nitrate concentrations were measured in a blinded fashion. The FOC produced a 43% increase in daily, creatinine-adjusted, nitrate excretion rates (P < 0.029). Because serum nitrate concentrations were not different, these findings suggest that FOC supplementation may stimulate systemic nitric oxide synthesis. The lack of effect with EPA supplementation suggests that this component of the FOC is not likely to be an active component. If confirmed, these observations suggest another mechanism whereby n-3 fatty acids may be antiatherogenic.

Safety and efficacy of Omacor in severe hypertriglyceridemia.

BACKGROUND: Severe hypertriglyceridemia is a risk factor for acute pancreatitis, therefore decreasing serum triglyceride concentrations is an important component of risk management. Omega-3 fatty acids are well known hypotriglyceridemic agents, but their efficacy in severe forms of the disorder is not well documented. Our objective was to examine the effects of Omacor, a drug composed of 85% omega-3 fatty acid ethyl esters. METHODS: Forty-two patients with triglyceride concentrations between 5.65 and 22.60 mmol/l (500 and 2000 mg/dl) were studied in a prospective, double-blind, placebo-controlled trial of Omacor (4 g/day for 4 months). RESULTS: Compared with baseline values, Omacor significantly reduced mean triglyceride concentrations by 45% (P<0.00001), cholesterol by 15% (P< 0.001), very-low-density lipoprotein cholesterol by 32% (P< 0.0001) and cholesterol:high density lipoprotein (HDL) cholesterol ratio by 20% (P=0.0013), and increased HDL cholesterol by 13% (P=0.014) and low-density lipoprotein cholesterol by 31% (P=0.0014). The placebo had no effect on these parameters. Omacor was well tolerated and no patient discontinued medication because of side effects. CONCLUSIONS: Four capsules of Omacor per day markedly decreased triglyceride concentrations in patients with severe hypertriglyceridemia. The availability of a potent and safe omega-3 fatty acid preparation for this patient population should diminish the risk for acute pancreatitis, and may also reduce the long-term risk for cardiovascular disease.

Studies of the binding of diolepoxide metabolites of polycyclic aromatic hydrocarbons to DNA using electrofluorescence polarization spectroscopy.

In the electrofluorescence method, a solution of DNA with covalently bound polycyclic hydrocarbons is placed in an electric field, and changes in the intensity of polarized fluorescence are observed. Under the correct conditions, these charges can be used to determine a value for the angle psi between the long axis of the hydrocarbon molecule and the axis of the DNA helix. For DNA or poly(dA-dT) treated with each stereoisomer of anti-benzo[c]phenanthrene diolepoxide, psi ranged from 55 degrees to 61 degrees, consistent with a mixture of quasi-intercalated adenine adducts and externally bound guanine adducts. Similar results were obtained with another set of 'fjord-region' diolepoxides, derived from benzo[c]chrysene. Adducts in DNA treated with diolepoxides derived from chrysene, 5-methylchrysene or 6-methylchrysene gave psi of about 53 degrees, so the predominant adducts are externally bound, probably in the minor groove of DNA.

Eicosapentaenoic acid is primarily responsible for hypotriglyceridemic effect of fish oil in humans.

The aim of this study was to determine whether eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), or both, were responsible for the triglyceride (TG)-lowering effects of fish oil. EPA (91% pure) and DHA (83% pure), a fish oil concentrate (FOC; 41% EPA and 23% DHA) and an olive oil (OO) placebo (all ethyl esters) were tested. A total of 49 normolipidemic subjects participated. Each subject was given placebo for 2-3 wk and one of the n-3 supplements for 3 wk in randomized, blinded trials. The target n-3 fatty acid (FA) intake was 3 g/day in all studies. Blood samples were drawn twice at the end of each supplementation phase and analyzed for lipids, lipoproteins, and phospholipid FA composition. In all groups, the phospholipid FA composition changed to reflect the n-3 FA given. On DHA supplementation, EPA levels increased to a small but significant extent, suggesting that some retroconversion may have occurred. EPA supplementation did not raise DHA levels, however. FOC and EPA produced significant decreases in both TG and very low density lipoprotein (VLDL) cholesterol (C) levels (P < 0.01) and increases in low density lipoprotein (LDL) cholesterol levels (P < 0.05). DHA supplementation did not affect cholesterol, triglyceride, VLDL, LDL, or high density lipoprotein (HDL) levels, but it did cause a significant increase in the HDL2/HDL3 cholesterol ratio. We conclude that EPA appears to be primarily responsible for TG-lowering (and LDL-C raising) effects of fish oil.

Binding of biologically important molecules to DNA, probed using electro-fluorescence polarization spectroscopy.

When small fluorescent tag molecules are bound with a single geometry to larger carrier molecules the fluorescence excited using polarized light may itself be partially polarized. If this is the case then alignment of the carrier molecules changes the fluorescence polarization. Electro-fluorescence polarization spectrometry (EFPS) makes use of the fluorescence polarization changes which occur when the carrier molecules are aligned by an electric field. EFPS allows the determination of the binding geometry of the small tag molecules to the larger carrier molecules. In this study, EFPS has been used to probe the interactions between DNA and a series of chromosomal stains and anti-neoplastic (anti-cancer) agents. Results are presented for calf thymus DNA, treated with the dyes acridine orange, ethidium bromide, proflavine, Hoechst 33258, Hoechst 33342, 4',6-diamidino-2-phenylindole and the anti-tumour agents, doxorubicin, daunomycin, actinomycin C and actinomycin V.

Effects of pravastatin with niacin or magnesium on lipid levels and postprandial lipemia.

This study was designed to evaluate the therapeutic effectiveness of 3 different pharmacologic lipid-lowering regimens in the treatment of patients with clustered lipid risk factors. Sixty-five patients with low high-density lipoprotein (HDL) levels and hypertriglyceridemia were randomized to 1 of 3 treatment arms: pravastatin/niacin, pravastatin/magnesium, or pravastatin/placebo. After 18 weeks, patients in the pravastatin/niacin group had a -41% change in the total cholesterol/HDL ratio compared with -13% in the pravastatin/magnesium arm and -16% in the pravastatin/placebo group. The HDL2 and HDL3 subfractions, as well as the apolipoprotein A-I levels, were increased significantly only in the pravastatin/niacin arm. The levels of small dense low-density lipoprotein (LDL) cholesterol (LDL3) were decreased to a greater extent in the pravastatin/niacin arm (-43%) than in either the pravastatin/magnesium (-13%) or the pravastatin/placebo (-20%) arm. Only the pravastatin/niacin regimen significantly diminished postprandial lipemia (-32% change in the remnant particle triglyceride concentration and decreased very-low-density lipoprotein remnant levels). Thus, in this group of patients with clustered risk factors, the combination of pravastatin and niacin resulted in significant improvements in HDL and triglyceride levels, total cholesterol to HDL ratio, small dense LDL levels, and postprandial lipemia. Pravastatin alone or in combination with magnesium resulted in less significant changes that were largely limited to LDL cholesterol reduction.

Factor VIII gene inversions in severe hemophilia A: results of an international consortium study.

Twenty-two molecular diagnostic laboratories from 14 countries participated in a consortium study to estimate the impact of Factor VIII gene inversions in severe hemophilia A. A total of 2,093 patients with severe hemophilia A were studied; of those, 740 (35%) had a type 1 (distal) factor VIII inversion, and 140 (7%) showed a type 2 (proximal) inversion. In 25 cases, the molecular analysis showed additional abnormal or polymorphic patterns. Ninety-eight percent of 532 mothers of patients with inversions were carriers of the abnormal factor VIII gene; when only mothers of nonfamilial cases were studied, 9 de novo inversions in maternal germ cells were observed among 225 cases (approximately 1 de novo maternal origin of the inversion in 25 mothers of sporadic cases). When the maternal grandparental origin was examined, the inversions occurred de novo in male germ cells in 69 cases and female germ cells in 1 case. The presence of factor VIII inversions is not a major predisposing factor for the development of factor VIII inhibitors; however, slightly more patients with severe hemophilia A and factor VIII inversions develop inhibitors (130 of 642 [20%]) than patients with severe hemophilia A without inversions (131 of 821 [16%]).

Severe haemophilia A in a female resulting from two de novo factor VIII mutations.

A 2-year-old girl is described with severe haemophilia A (factor VIII: C < 0.01 units/ml). Both of her parents were phenotypically normal. Cytogenetic analysis on the proband demonstrated an interstitial X chromosome deletion encompassing Xq26-q28. Molecular studies with several polymorphic markers close to and within the factor VIII gene showed that the proband had inherited only the paternal factor VIII gene, indicating that the X chromosome deletion had occurred de novo in the maternal germ line. Further study of the factor VIII gene inherited by the proband from her father showed the presence of a de novo gene inversion mutation (a type 1, distal pattern inversion). Neither parent showed any evidence of the factor VIII inversion in their somatic DNA. The severe haemophilia A documented in this girl is therefore the result of two de novo mutations affecting the factor VIII gene, a maternally derived X chromosome deletion and a paternal factor VIII inversion mutation.

Characterization of infectious type D retrovirus from baboons.

Infectious virus resembling type D simian retrovirus (SRV) was isolated from Ethiopian baboons (Papio cynocephalus) (SRV-Pc) housed at the University of Washington Regional Primate Research Center. When baboon peripheral blood mononuclear cells (PBMC) or tissues were cocultured with the H-9 human T-cell line or the Raji human B-cell line, large multinucleated syncytia positive for SRV-2 antigens were observed microscopically. Immunoblot analysis of purified SRV-Pc from cell culture supernatants demonstrated that the viral core and envelope proteins reacted with rabbit anti-SRV-2 serum. Fresh PBMC and cocultured cells were positive by polymerase chain reaction using two different sets of SRV-2 primers. Preliminary sequence analysis of two separate isolates from portions of the SRV-Pc p27 and gp20 regions revealed homology with SRV-1, SRV-2, and Mason-Pfizer monkey virus. The homologies in the p27 segment were 91-94% and the homologies in the gp20 segment were 72-75%.

Direct detection of a common inversion mutation in the genetic diagnosis of severe hemophilia A.

Two recent reports suggest that approximately 50% of the cases of severe hemophilia A (factor VIII:C < 0.01 U/mL) may be caused by a gross rearrangement of the factor VIII gene. The mutation involves genomic sequence from exon 1 to within intron 22 of the gene in an inversion event. This rearrangement can be detected on a Southern blot using a probe that is complementary to sequence from within intron 22. In this report, we describe the analysis of 71 severe hemophilia A patients for the presence of this mutation. Thirty-two of the patients (45%) showed evidence of the rearrangement, a figure that confirms the initial reports on 28 patients. Five different patterns of rearrangement have been noted, although two of these patterns (pattern 1 [70%] and pattern 2 [16%]) account for the majority of cases. The other patterns of rearrangement appear to be confined to individual families and may represent the result of additional sequence variation within the region of the genome to which the proximal 22 exons of factor VIII are translocated. Analysis of this patient population for the factor VIII inversion mutation has been extremely useful in a molecular diagnostic sense. In 23 of the cases studied (72%), the affected individual was the only documented hemophiliac in the family and, thus, previous linkage analysis had been limited to the provision of exclusion testing only. In conclusion, it appears that testing for the factor VIII inversion mutation will be positive in approximately 45% of severe hemophiliacs and as such should constitute the initial stage in the genetic testing protocol for these patients' families.