Studying Lactoferrin N-Glycosylation.

Lactoferrin is a multifunctional glycoprotein found in the milk of most mammals. In addition to its well-known role of binding iron, lactoferrin carries many important biological functions, including the promotion of cell proliferation and differentiation, and as an anti-bacterial, anti-viral, and anti-parasitic protein. These functions differ among lactoferrin homologs in mammals. Although considerable attention has been given to the many functions of lactoferrin, its primary nutritional contribution is presumed to be related to its iron-binding characteristics, whereas the role of glycosylation has been neglected. Given the critical role of glycan binding in many biological processes, the glycan moieties in lactoferrin are likely to contribute significantly to the biological roles of lactoferrin. Despite the high amino acid sequence homology in different lactoferrins (up to 99%), each exhibits a unique glycosylation pattern that may be responsible for heterogeneity of the biological properties of lactoferrins. An important task for the production of biotherapeutics and medical foods containing bioactive glycoproteins is the assessment of the contributions of individual glycans to the observed bioactivities. This review examines how the study of lactoferrin glycosylation patterns can increase our understanding of lactoferrin functionality

Lunar drill footplate and casing

To prevent hole collapse during lunar drilling operations, a casing has been devised of a graphite reinforced polyimide composite which will be able to withstand the lunar environment. Additionally, this casing will be inserted into the ground in segments two meters long which will penetrate the regolith simultaneously with the auger. The vertical action of the mobile platform will provide a downward force to the casing string through a special adaptor, giving the casing the needed impetus to sink the anticipated depth of ten meters. Casing segments will be connected with a simple snap arrangement. Excess casing will be cut off by a cylindrical cutting tool which will also transport the excess casing away from the hole. A footplate will be incorporated to grasp the auger rod string during rod segment additions or removals. The footplate grasping mechanism will consist of a set of vice-like arms, one end of each bearing threaded to a common power screw. The power screw will be threaded such that one end's thread pitch opposes that of the other end. The weight of the auger and rod string will be transmitted through the arms to the power screw and absorbed by a set of three ball bearing assemblies. The power screw will be driven by a one-half horsepower brushless motor actuated by radio control. The footplate will rest on four short legs and be anchored with pins that are an integral part of each leg

Fractal geometry in an expanding, one-dimensional, Newtonian universe

International audienceObservations of galaxies over large distances reveal the possibility of a fractal distribution of their positions. The source of fractal behavior is the lack of a length scale in the two body gravitational interaction. However, even with new, larger, sample sizes from recent surveys, it is difficult to extract information concerning fractal properties with confidence. Similarly, three-dimensional N-body simulations with a billion particles only provide a thousand particles per dimension, far too small for accurate conclusions. With one-dimensional models these limitations can be overcome by carrying out simulations with on the order of a quarter of a million particles without compromising the computation of the gravitational force. Here the multifractal properties of two of these models that incorporate different features of the dynamical equations governing the evolution of a matter dominated universe are compared. For each model at least two scaling regions are identified. By employing criteria from dynamical systems theory it is shown that only one of them can be geometrically significant. The results share important similarities with galaxy observations, such as hierarchical clustering and apparent bifractal geometry. They also provide insights concerning possible constraints on length and time scales for fractal structure. They clearly demonstrate that fractal geometry evolves in the µ (position, velocity) space. The observed patterns are simply a shadow (projection) of higher-dimensional structure

Complexity of Coloring Graphs without Paths and Cycles

Let $P_t$ and $C_\ell$ denote a path on $t$ vertices and a cycle on $\ell$ vertices, respectively. In this paper we study the $k$-coloring problem for $(P_t,C_\ell)$-free graphs. Maffray and Morel, and Bruce, Hoang and Sawada, have proved that 3-colorability of $P_5$-free graphs has a finite forbidden induced subgraphs characterization, while Hoang, Moore, Recoskie, Sawada, and Vatshelle have shown that $k$-colorability of $P_5$-free graphs for $k \geq 4$ does not. These authors have also shown, aided by a computer search, that 4-colorability of $(P_5,C_5)$-free graphs does have a finite forbidden induced subgraph characterization. We prove that for any $k$, the $k$-colorability of $(P_6,C_4)$-free graphs has a finite forbidden induced subgraph characterization. We provide the full lists of forbidden induced subgraphs for $k=3$ and $k=4$. As an application, we obtain certifying polynomial time algorithms for 3-coloring and 4-coloring $(P_6,C_4)$-free graphs. (Polynomial time algorithms have been previously obtained by Golovach, Paulusma, and Song, but those algorithms are not certifying); To complement these results we show that in most other cases the $k$-coloring problem for $(P_t,C_\ell)$-free graphs is NP-complete. Specifically, for $\ell=5$ we show that $k$-coloring is NP-complete for $(P_t,C_5)$-free graphs when $k \ge 4$ and $t \ge 7$; for $\ell \ge 6$ we show that $k$-coloring is NP-complete for $(P_t,C_\ell)$-free graphs when $k \ge 5$, $t \ge 6$; and additionally, for $\ell=7$, we show that $k$-coloring is also NP-complete for $(P_t,C_7)$-free graphs if $k = 4$ and $t\ge 9$. This is the first systematic study of the complexity of the $k$-coloring problem for $(P_t,C_\ell)$-free graphs. We almost completely classify the complexity for the cases when $k \geq 4, \ell \geq 4$, and identify the last three open cases

The Wide Brown Dwarf Binary Oph 1622-2405 and Discovery of A Wide, Low Mass Binary in Ophiuchus (Oph 1623-2402): A New Class of Young Evaporating Wide Binaries?

We imaged five objects near the star forming clouds of Ophiuchus with the Keck Laser Guide Star AO system. We resolved Allers et al. (2006)'s #11 (Oph 16222-2405) and #16 (Oph 16233-2402) into binary systems. The #11 object is resolved into a 243 AU binary, the widest known for a very low mass (VLM) binary. The binary nature of #11 was discovered first by Allers (2005) and independently here during which we obtained the first spatially resolved R~2000 near-infrared (J & K) spectra, mid-IR photometry, and orbital motion estimates. We estimate for 11A and 11B gravities (log(g)>3.75), ages (5+/-2 Myr), luminosities (log(L/Lsun)=-2.77+/-0.10 and -2.96+/-0.10), and temperatures (Teff=2375+/-175 and 2175+/-175 K). We find self-consistent DUSTY evolutionary model (Chabrier et al. 2000) masses of 17+4-5 MJup and 14+6-5 MJup, for 11A and 11B respectively. Our masses are higher than those previously reported (13-15 MJup and 7-8 MJup) by Jayawardhana & Ivanov (2006b). Hence, we find the system is unlikely a ``planetary mass binary'', (in agreement with Luhman et al. 2007) but it has the second lowest mass and lowest binding energy of any known binary. Oph #11 and Oph #16 belong to a newly recognized population of wide (>100 AU), young (<10 Myr), roughly equal mass, VLM stellar and brown dwarf binaries. We deduce that ~6+/-3% of young (<10 Myr) VLM objects are in such wide systems. However, only 0.3+/-0.1% of old field VLM objects are found in such wide systems. Thus, young, wide, VLM binary populations may be evaporating, due to stellar encounters in their natal clusters, leading to a field population depleted in wide VLM systems.Comment: Accepted version V2. Now 13 pages longer (45 total) due to a new discussion of the stability of the wide brown dwarf binary population, new summary Figure 17 now included, Astrophysical Journal 2007 in pres

Saliency Benchmarking Made Easy: Separating Models, Maps and Metrics

Dozens of new models on fixation prediction are published every year and compared on open benchmarks such as MIT300 and LSUN. However, progress in the field can be difficult to judge because models are compared using a variety of inconsistent metrics. Here we show that no single saliency map can perform well under all metrics. Instead, we propose a principled approach to solve the benchmarking problem by separating the notions of saliency models, maps and metrics. Inspired by Bayesian decision theory, we define a saliency model to be a probabilistic model of fixation density prediction and a saliency map to be a metric-specific prediction derived from the model density which maximizes the expected performance on that metric given the model density. We derive these optimal saliency maps for the most commonly used saliency metrics (AUC, sAUC, NSS, CC, SIM, KL-Div) and show that they can be computed analytically or approximated with high precision. We show that this leads to consistent rankings in all metrics and avoids the penalties of using one saliency map for all metrics. Our method allows researchers to have their model compete on many different metrics with state-of-the-art in those metrics: "good" models will perform well in all metrics.Comment: published at ECCV 201

Comparison of insulin detemir and insulin glargine in a Basal-Bolus regimen, with insulin aspart as the mealtime insulin, in patients with type 1 diabetes: A 52-week, multinational, randomized, open-label, parallel-group, treat-to-target noninferiority trial

Objective: The primary study objective was to determine whether insulin detemir (detemir) was noninferior to insulin glargine (glargine) as the basal insulin in a basal-bolus regimen, with insulin aspart as the mealtime insulin, in terms of glycemic control at the end of 52 weeks in patients with type I diabetes mellitus (T1DM). Methods: This multinational, open-label, parallel-group, treat-to-target, noninferiority trial enrolled patients aged >= 18 years who had had T1DM for at least 12 months, had been taking a basal-bolus insulin regimen for at least 3 months, and had a glycosylated hemoglobin (HbA(1c)) value <= 11.0% at screening. Patients were randomized in a 2:1 ratio to receive either detemir or glargine for 52 weeks. The basal insulin was initially administered once daily (in the evening) in both groups; if patients in the detemir group were achieving the plasma glucose (PG) target before breakfast but not before dinner, they were switched to twice-daily administration. Glargine was administered once daily throughout the trial, according to its approved labeling. Each patient attended 13 study visits and received 16 scheduled telephone calls from the trial site. The primary efficacy end point was glycemic control (HbA(1c)) after 52 weeks of treatment. Secondary end points included the number of patients achieving an HbAlc value <= 7.0%, with or without a major hypoglycemic episode in the last month of treatment; fasting PG (FPG); within-patient variation in self-monitored plasma glucose (SMPG) before breakfast and dinner; and 10-point SMPG profiles. The noninferiority margin was 0.4%, consistent with US Food and Drug Administration guidelines. Results: Four hundred forty-three patients (mean [SD] age, 42 [12] years; body mass index, 26.5 [4.0] kg/m(2); duration of diabetes, 17.2 [11.4] years; HbA(1c), 8.1% [1.1%]) received study treatment. After 52 weeks, the estimated mean HbA(1c) did not differ significantly between the detemir and glargine groups (7.57% and 7.56%, respectively; mean difference, 0.01%; 95% CI -0.13 to 0.16), consistent with the noninferiority of detemir to glargine. The corresponding estimated changes in HbA(1c) were -0.53% and -0.54%. In the 90 patients who completed the trial on once-dally detemir and the 173 patients who completed the trial on twice-daily detemir, the estimated changes in HbA(1c) were-0.49% and -0.58%, respectively. After 52 weeks, there were no significant differences in the proportions of those receiving detemir and glargine who achieved an HbA(1c) value <= 7.0% without major hypo-glycemia (31.9% and 28.9%, respectively). In addition, there were no significant differences in estimated mean FPG (8.58 and 8.81 rnmol/L; mean difference, -0.23 mmol/L; 95% CI, -1.04 to 0.58) or in basal insulin doses. The basal insulin dose was numerically higher in patients receiving detemir twice rather than once daily (0.47 vs 0.33 U/kg, respectively). The relative risks for total and nocturnal hypoglycemia with detemir versus glargine were 0.94 and 1.12, respectively (both, P = NS). Six patients (2.0%) randomized to the detemir group and 4 (2.7%) randomized to the glargine group withdrew due to adverse events. Conclusions: During 52 weeks of basal-bolus therapy in patients with T1DM, detemir was noninferior to glargine in terms of overall glycemic control (HbA(1c)). When used according to the approved labeling, detemir and glargine did not differ in tolerability or in terms of the occurrence of hypoglycemia. (Clin Ther. 2009; 31:2086-2097) (C) 2009 Excerpta Medica Inc