Using Early Data to Illuminate the Pioneer Anomaly

Analysis of the radio tracking data from the Pioneer 10/11 spacecraft at distances between about 20 - 70 AU from the Sun has consistently indicated the presence of an unmodeled, small, constant, Doppler blue shift drift of order 6 \times 10^{-9} Hz/s. After accounting for systematics, this drift can be interpreted as a constant acceleration of a_P= (8.74 \pm 1.33) \times 10^{-8} cm/s^2 directed towards the Sun, or perhaps as a time acceleration of a_t = (2.92 \pm 0.44)\times 10^{-18} s/s^2. Although it is suspected that there is a systematic origin to this anomaly, none has been unambiguously demonstrated. We review the current status of the anomaly, and then point out how the analysis of early data, which was never analyzed in detail, could allow a more clear understanding of the origin of the anomaly, be it a systematic or a manifestation of unsuspected physics.Comment: 19 pages, 6 figures, 2 tables, additional materia

Reproducibility of CSF quantitative culture methods for estimating rate of clearance in cryptococcal meningitis.

Quantitative cerebrospinal fluid (CSF) cultures provide a measure of disease severity in cryptococcal meningitis. The fungal clearance rate by quantitative cultures has become a primary endpoint for phase II clinical trials. This study determined the inter-assay accuracy of three different quantitative culture methodologies. Among 91 participants with meningitis symptoms in Kampala, Uganda, during August-November 2013, 305 CSF samples were prospectively collected from patients at multiple time points during treatment. Samples were simultaneously cultured by three methods: (1) St. George's 100 mcl input volume of CSF with five 1:10 serial dilutions, (2) AIDS Clinical Trials Group (ACTG) method using 1000, 100, 10 mcl input volumes, and two 1:100 dilutions with 100 and 10 mcl input volume per dilution on seven agar plates; and (3) 10 mcl calibrated loop of undiluted and 1:100 diluted CSF (loop). Quantitative culture values did not statistically differ between St. George-ACTG methods (P= .09) but did for St. George-10 mcl loop (P< .001). Repeated measures pairwise correlation between any of the methods was high (r≥0.88). For detecting sterility, the ACTG-method had the highest negative predictive value of 97% (91% St. George, 60% loop), but the ACTG-method had occasional (∼10%) difficulties in quantification due to colony clumping. For CSF clearance rate, St. George-ACTG methods did not differ overall (mean -0.05 ± 0.07 log10CFU/ml/day;P= .14) on a group level; however, individual-level clearance varied. The St. George and ACTG quantitative CSF culture methods produced comparable but not identical results. Quantitative cultures can inform treatment management strategies

A genomic survey of the fish parasite Spironucleus salmonicida indicates genomic plasticity among diplomonads and significant lateral gene transfer in eukaryote genome evolution

BACKGROUND: Comparative genomic studies of the mitochondrion-lacking protist group Diplomonadida (diplomonads) has been lacking, although Giardia lamblia has been intensively studied. We have performed a sequence survey project resulting in 2341 expressed sequence tags (EST) corresponding to 853 unique clones, 5275 genome survey sequences (GSS), and eleven finished contigs from the diplomonad fish parasite Spironucleus salmonicida (previously described as S. barkhanus). RESULTS: The analyses revealed a compact genome with few, if any, introns and very short 3' untranslated regions. Strikingly different patterns of codon usage were observed in genes corresponding to frequently sampled ESTs versus genes poorly sampled, indicating that translational selection is influencing the codon usage of highly expressed genes. Rigorous phylogenomic analyses identified 84 genes – mostly encoding metabolic proteins – that have been acquired by diplomonads or their relatively close ancestors via lateral gene transfer (LGT). Although most acquisitions were from prokaryotes, more than a dozen represent likely transfers of genes between eukaryotic lineages. Many genes that provide novel insights into the genetic basis of the biology and pathogenicity of this parasitic protist were identified including 149 that putatively encode variant-surface cysteine-rich proteins which are candidate virulence factors. A number of genomic properties that distinguish S. salmonicida from its human parasitic relative G. lamblia were identified such as nineteen putative lineage-specific gene acquisitions, distinct mutational biases and codon usage and distinct polyadenylation signals. CONCLUSION: Our results highlight the power of comparative genomic studies to yield insights into the biology of parasitic protists and the evolution of their genomes, and suggest that genetic exchange between distantly-related protist lineages may be occurring at an appreciable rate in eukaryote genome evolution

Novel method of estimating volume of distribution of a drug obeying Michaelis-Menten elimination kinetics

The novel method of estimating the volume of distribution involves (a) administering an appropriate bolus intravenous dose of the drug, (b) starting a constant-rate intravenous infusion of the drug at the same time, (c) maintaining the infusion for a given number of hours, (a) measuring the drug concentration over the entire time course, (e) computer-fitting the post-infusion data to obtain estimates of V m and K m , (f) estimating the total area under the concentration-time curve from zero time to infinity, and (g) iteratively solving a cubic equation to obtain the estimate of the volume of distribution. The method was applied to ethanol in the cat and yielded an average value of 635ml/kg (63.5% of body weight) with a coefficient of variation of 23.0%. This is equivalent to total body water in the cat.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45074/1/10928_2005_Article_BF01312262.pd

Enzyme-Nanoporous Gold Biocomposite: Excellent Biocatalyst with Improved Biocatalytic Performance and Stability

Background: Applications involving biomolecules, such as enzymes, antibodies, and other proteins as well as whole cells, are often hampered by their unstable nature at extremely high temperature and in organic solvents. Methodology/Principal Findings: We constructed enzyme-NPG biocomposites by assembling various enzymes onto the surface of nanoporous gold (NPG), which showed much enhanced biocatalytic performance and stability. Various enzymes with different molecular sizes were successfully tethered onto NPG, and the loadings were 3.6, 3.1 and 0.8 mg g 21 for lipase, catalase and horseradish peroxidase, respectively. The enzyme-NPG biocomposites exhibited remarkable catalytic activities which were fully comparable to those of free enzymes. They also presented enhanced stability, with 74, 78 and 53 % of enzymatic activity retained after 20 successive batch reactions. Moreover, these novel biocomposites possessed significantly enhanced reaction durability under various thermal and in organic solvent systems. In a sample transesterification reaction, a high conversion rate was readily achieved by using the lipase-NPG biocomposite. Conclusion/Significance: These nano-biocomposite materials hold great potential in applications such as biosensing, molecular electronics, catalysis, and controlled delivery

The Effect of Iron Oxide Magnetic Nanoparticles on Smooth Muscle Cells

Recently, magnetic nanoparticles of iron oxide (Fe3O4, γ-Fe2O3) have shown an increasing number of applications in the field of biomedicine, but some questions have been raised about the potential impact of these nanoparticles on the environment and human health. In this work, the three types of magnetic nanoparticles (DMSA-Fe2O3, APTS-Fe2O3, and GLU-Fe2O3) with the same crystal structure, magnetic properties, and size distribution was designed, prepared, and characterized by transmission electronic microscopy, powder X-ray diffraction, zeta potential analyzer, vibrating sample magnetometer, and Fourier transform Infrared spectroscopy. Then, we have investigated the effect of the three types of magnetic nanoparticles (DMSA-Fe2O3, APTS-Fe2O3, and GLU-Fe2O3) on smooth muscle cells (SMCs). Cellular uptake of nanoparticles by SMC displays the dose, the incubation time and surface property dependent patterns. Through the thin section TEM images, we observe that DMSA-Fe2O3is incorporated into the lysosome of SMCs. The magnetic nanoparticles have no inflammation impact, but decrease the viability of SMCs. The other questions about metabolism and other impacts will be the next subject of further studies

Anthropogenic Space Weather

Anthropogenic effects on the space environment started in the late 19th century and reached their peak in the 1960s when high-altitude nuclear explosions were carried out by the USA and the Soviet Union. These explosions created artificial radiation belts near Earth that resulted in major damages to several satellites. Another, unexpected impact of the high-altitude nuclear tests was the electromagnetic pulse (EMP) that can have devastating effects over a large geographic area (as large as the continental United States). Other anthropogenic impacts on the space environment include chemical release ex- periments, high-frequency wave heating of the ionosphere and the interaction of VLF waves with the radiation belts. This paper reviews the fundamental physical process behind these phenomena and discusses the observations of their impacts.Comment: 71 pages, 35 figure

Total cardiovascular or fatal events in people with type 2 diabetes and cardiovascular risk factors treated with dulaglutide in the REWIND trail:a post hoc analysis

Abstract Background The Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) double blind randomized trial demonstrated that weekly subcutaneous dulaglutide 1.5 mg, a glucagon like peptide-1 receptor agonist, versus matched placebo reduced the first outcome of major adverse cardiovascular event (MACE), cardiovascular death, nonfatal myocardial infarction or nonfatal stroke (594 versus 663 events) in 9901 persons with type 2 diabetes and either chronic cardiovascular disease or risk factors, and followed during 5.4 years. These findings were based on a time-to-first-event analysis and preclude relevant information on the burden of total major events occurring during the trial. This analysis reports on the total cardiovascular or fatal events in the REWIND participants Methods We compared the total incidence of MACE or non-cardiovascular deaths, and the total incidence of expanded MACE (MACE, unstable angina, heart failure or revascularization) or non-cardiovascular deaths between participants randomized to dulaglutide and those randomized to placebo. Incidences were expressed as number per 1000 person-years. Hazard ratios (HR) were calculated using the conditional time gap and proportional means models. Results Participants had a mean age of 66.2 years, 46.3% were women and 31% had previous cardiovascular disease. During the trial there were 1972 MACE or non-cardiovascular deaths and 3673 expanded MACE or non-cardiovascular deaths. The incidence of total MACE or non-cardiovascular deaths in the dulaglutide and placebo groups was 35.8 and 40.3 per 1000 person-years, respectively [absolute reduction = 4.5 per 1000 person-years; conditional time gap HR 0.90 (95% CI, 0.82–0.98) p = 0.020, and proportional means HR 0.89 (95% CI, 0.80–0.98) p = 0.022]. The incidence of total expanded MACE or non-cardiovascular deaths in the dulaglutide and placebo groups was 67.1 and 74.7 per 1000 person-years, respectively [absolute reduction = 7.6 per 1000 person-years; conditional time gap HR 0.93 (95% CI, 0.87–0.99) p = 0.023, and proportional means HR 0.90 (95% CI, 0.82–0.99) p = 0.028]. Conclusions These findings suggest that weekly subcutaneous dulaglutide reduced total cardiovascular or fatal event burden in people with type 2 diabetes at moderate cardiovascular risk. Clinical Trial Registration: https://www.clinicaltrials.gouv . Unique Identifier NCT01394952)

The Pioneer Anomaly

Radio-metric Doppler tracking data received from the Pioneer 10 and 11 spacecraft from heliocentric distances of 20-70 AU has consistently indicated the presence of a small, anomalous, blue-shifted frequency drift uniformly changing with a rate of ~6 x 10^{-9} Hz/s. Ultimately, the drift was interpreted as a constant sunward deceleration of each particular spacecraft at the level of a_P = (8.74 +/- 1.33) x 10^{-10} m/s^2. This apparent violation of the Newton's gravitational inverse-square law has become known as the Pioneer anomaly; the nature of this anomaly remains unexplained. In this review, we summarize the current knowledge of the physical properties of the anomaly and the conditions that led to its detection and characterization. We review various mechanisms proposed to explain the anomaly and discuss the current state of efforts to determine its nature. A comprehensive new investigation of the anomalous behavior of the two Pioneers has begun recently. The new efforts rely on the much-extended set of radio-metric Doppler data for both spacecraft in conjunction with the newly available complete record of their telemetry files and a large archive of original project documentation. As the new study is yet to report its findings, this review provides the necessary background for the new results to appear in the near future. In particular, we provide a significant amount of information on the design, operations and behavior of the two Pioneers during their entire missions, including descriptions of various data formats and techniques used for their navigation and radio-science data analysis. As most of this information was recovered relatively recently, it was not used in the previous studies of the Pioneer anomaly, but it is critical for the new investigation.Comment: 165 pages, 40 figures, 16 tables; accepted for publication in Living Reviews in Relativit

Foliar epidermis morphology in Quercus (subgenus Quercus, section Quercus) in Iran

The foliar morphology of trichomes, epicuticular waxes and stomata in Quercus cedrorum, Q. infectoria subsp. boissieri, Q. komarovii, Q. longipes, Q. macranthera, Q. petraea subsp. iberica and Q. robur subsp. pedunculiflora were studied by scanning electron microscopy. The trichomes are mainly present on abaxial leaf surface in most species, but rarely they appear on adaxial surface. Five trichome types are identified as simple uniseriate, bulbous, solitary, fasciculate and stellate. The stomata of all studied species are of the anomocytic type, raised on the epidermis. The stomata rim may or may not be covered with epicuticular. The epicuticular waxes are mostly of the crystalloid type but smooth layer wax is observed in Q. robur subsp. pedunculiflora. Statistical analysis revealed foliar micromorphological features as been diagnostic characters in Quercus