Search

Analyses some of the reasons for fatigue and stress among drivers. Contributors to fatigue can be the distance travelled, or sleeping disorders. Contributors to driver stress can include worry and emotional stress, related to work or to life events; or road rage. Identifies ways in which stress, fatigue and road rage can be reduced or avoided. Provides advice for fleet managers on making driving safer.

Saccharomyces cerevisiae alcohol dehydrogenase I crystallized as trigonal plates using 20% 2-propanol and 20% PEG 4000 in 0.1 M sodium citrate buffer pH 5.6 in the presence of 1 mM NAD(+). The crystals diffract to 3.0 A resolution and belong to the trigonal space group P3(1)21 or P3(2)21, with unit-cell parameters a = b = 146.3, c = 68.1 A, alpha = beta = 90, gamma = 120 degrees. X-ray data were collected from frozen crystals at the 17-ID beamline of the Advanced Photon Source. A Zn fluorescence scan of the crystal produced a peak at 9671.6 eV, suggesting the existence of Zn ions in the crystal.

On 1 February 2011 the Kepler Mission released data for 156,453 stars observed from the beginning of the science observations on 2 May through 16 September 2009. There are 1235 planetary candidates with transit like signatures detected in this period. These are associated with 997 host stars. Distributions of the characteristics of the planetary candidates are separated into five class-sizes; 68 candidates of approximately Earth-size (radius < 1.25 Earth radii), 288 super-Earth size (1.25 Earth radii < radius < 2 Earth radii), 662 Neptune-size (2 Earth radii < radius < 6 Earth radii), 165 Jupiter-size (6 Earth radii < radius < 15 Earth radii), and 19 up to twice the size of Jupiter (15 Earth radii < radius < 22 Earth radii). In the temperature range appropriate for the habitable zone, 54 candidates are found with sizes ranging from Earth-size to larger than that of Jupiter. Five are less than twice the size of the Earth. Over 74% of the planetary candidates are smaller than Neptune. The observed number versus size distribution of planetary candidates increases to a peak at two to three times Earth-size and then declines inversely proportional to area of the candidate. Our current best estimates of the intrinsic frequencies of planetary candidates, after correcting for geometric and sensitivity biases, are 6% for Earth-size candidates, 7% for super-Earth size candidates, 17% for Neptune-size candidates, and 4% for Jupiter-size candidates. Multi-candidate, transiting systems are frequent; 17% of the host stars have multi-candidate systems, and 33.9% of all the candidates are part of multi-candidate systems., 106 pages, 15 figures, contains tables of candidates. Submitted to ApJ

The EORTC/NCIC 22981/26981 study demonstrated an improvement in median overall survival (OS) from 12.1 to 14.6 months in patients with glioblastoma (GBM) who received temozolomide with post-operative radiotherapy (RT). The current study was performed to determine if those results translated into a survival benefit in a population-based cohort. Patients diagnosed between 2000 and 2006 with a GBM who underwent surgery and post-operative RT were selected from the Surveillance, Epidemiology and End Results database. Patients were grouped into time periods: 2000-2001, 2002-2003, 2004 and 2005-2006 (which represented those treated after the EORTC/NCIC trial presentation in 2004). Relative survival (RS) was estimated by the Kaplan-Meier method, and Cox multivariable regression modeling was used to estimate proportional hazard ratios (HR). Over time, there was improvement in the median and 2-year RS of 12 months and 15% for 2000-2001, 13 months and 19% for 2002-2003, 14 months and 24% for 2004, and 15 months and 26% for 2005-2006 (P < 0.0001 compared to 2000-2001 and 2002-2003; P = 0.07 compared to 2004). The estimated adjusted HR showed that patients diagnosed in 2005-2006 had significantly improved survival when compared to patients diagnosed in 2000-2001 (HR = 0.648, 95% CI 0.604-0.696). The median and 2 year RS of 15 months and 26% in 2005-2006 was similar to the median and 2 year OS of 14.6 months and 26% seen in the EORTC/NCIC phase III study. These results are encouraging and suggest that the current treatment of glioblastoma nationwide is now associated with an improved survival compared to previous time cohorts.

♦ All children who complain of knee symptoms must be assessed for ipsilateral hip and spine pathology♦ Congenital or persistent lateral dislocation of the patella and obligatory dislocation of the patella have two different clinical presentations: surgical treatment (if required) is often complex♦ The natural history of stable osteochondritis dissecans lesions is generally favourable in a child with open physes.

Single chain Fv (sFv) proteins consist of the variable heavy chain (VH) and variable light chain (VL) domains of an antibody, covalently joined by an engineered polypeptide linker. We report the crystallization of single-chain Fv's with specificities for fluorescein (4-4-20 sFv) and the TAG-72 pancarcinoma glycoprotein antigen (CC49 sFv). Concentration of these proteins, preliminary to crystallization, results in a monomer-multimer equilibrium, causing aggregation which interferes with crystallization. Aggregation has been observed to depend primarily on an intact linker between VL and VH domains, although other factors are likely to modulate this phenomenon as well, including the specific identity of Fv and ligand, presence or absence of the ligand, linker length and possibly sequence. We have found two methods to overcome sFv aggregation, both of which yield X-ray diffraction quality crystals. The first, discovered serendipitously, is by introducing a proteolytic clip into the linker region (effectively yielding an Fv fragment). The second is the purification of the sFv dimer form, with linker regions intact, from an equilibrium mixture of aggregates. The sFv molecular association in a dimer is believed to be unusual in that each VL/VH interface may not be formed by the two linker connected VL and VH domains, but rather by interaction of VL and VH domains from two distinct sFv monomers. Structure determination of the CC49 sFv dimer, with the 14-residue linker designated 212, is underway to test this model. Increasing linker length, to relieve steric strain on the monomer, and inclusion of the appropriate antigen, to slow transitions between monomeric and multimeric forms, may prove valuable strategies with sFv proteins less amenable to crystallization.

Low-bandwidth video has a place in health service delivery. Videoconferencing systems commonly used in telehealth have a high capital cost, take days or weeks to install at specific locations, and have high communications charges. A range of circumstances can be envisaged where video may be of benefit but would not justify the cost of large systems. There are projects in community nursing, home dialysis and post-acute respiratory care where various low-bandwidth video technologies have been added as a supplement to the humble telephone call. It can be expected that at least some of these projects will be able to demonstrate tangible improvements in health outcomes, such as decreased readmission rates, reduced acute episodes of a chronic illness and improved health status from the additional social support.

The End-Stage Renal Disease Network 5 sought to improve the influenza vaccination rate for the period September 1, 2008, to January 31, 2009, through an awareness campaign, coupled with primary data collection in the form of a tracking tool prepopulated with patient names. The latter served as a reminder to staff to determine the immunization status of patients and offer the influenza vaccination, as appropriate. Targets for the intervention were all facilities and their prevalent hemodialysis and peritoneal dialysis patients, with the exclusion of military treatment centers, Veterans Health Administration hospitals, and prisons. The majority of eligible network facilities (86.9%) participated in the project to achieve an overall adult influenza vaccination rate of 82.6% (95% confidence interval = 82.1%, 83.2%), greatly exceeding the project goal of 64.5% and representing substantial progress toward the 2010 goal of 90%. The initiative is reported here using the Standards for Quality Improvement Reporting Excellence (SQUIRE).

Glycocyamine kinase (GK), a member of the phosphagen kinase family, catalyzes the Mg(2+)-dependent reversible phosphoryl group transfer of the N-phosphoryl group of phosphoglycocyamine to ADP to yield glycocyamine and ATP. This reaction helps to maintain the energy homeostasis of the cell in some multicelullar organisms that encounter high and variable energy turnover. GK from the marine worm Namalycastis sp. is heterodimeric, with two homologous polypeptide chains, alpha and beta, derived from a common pre-mRNA by mutually exclusive N-terminal alternative exons. The N-terminal exon of GKbeta encodes a peptide that is different in sequence and is 16 amino acids longer than that encoded by the N-terminal exon of GKalpha. The crystal structures of recombinant GKalphabeta and GKbetabeta from Namalycastis sp. were determined at 2.6 and 2.4 A resolution, respectively. In addition, the structure of the GKbetabeta was determined at 2.3 A resolution in complex with a transition state analogue, Mg(2+)-ADP-NO(3)(-)-glycocyamine. Consistent with the sequence homology, the GK subunits adopt the same overall fold as that of other phosphagen kinases of known structure (the homodimeric creatine kinase (CK) and the monomeric arginine kinase (AK)). As with CK, the GK N-termini mediate the dimer interface. In both heterodimeric and homodimeric GK forms, the conformations of the two N-termini are asymmetric, and the asymmetry is different than that reported previously for the homodimeric CKs from several organisms. The entire polypeptide chains of GKalphabeta are structurally defined, and the longer N-terminus of the beta subunit is anchored at the dimer interface. In GKbetabeta the 24 N-terminal residues of one subunit and 11 N-terminal residues of the second subunit are disordered. This observation is consistent with a proposal that the GKalphabeta amino acids involved in the interface formation were optimized once a heterodimer emerged as the physiological form of the enzyme. As a consequence, the homodimer interface (either solely alpha or solely beta chains) has been corrupted. In the unbound state, GK exhibits an open conformation analogous to that observed with ligand-free CK or AK. Upon binding the transition state analogue, both subunits of GK undergo the same closure motion that clasps the transition state analogue, in contrast to the transition state analogue complexes of CK, where the corresponding transition state analogue occupies only one subunit, which undergoes domain closure. The active site environments of the GK, CK, and AK at the bound states reveal the structural determinants of substrate specificity. Despite the equivalent binding in both active sites of the GK dimer, the conformational asymmetry of the N-termini is retained. Thus, the coupling between the structural asymmetry and negative cooperativity previously proposed for CK is not supported in the case of GK.

Doppler observations from Keck Observatory reveal the presence of a planet with M sin i of 2.1 M_(Jup) orbiting the M3V star HIP 79431. This is the sixth giant planet to be detected in Doppler surveys of M dwarfs and it is one of the most massive planets discovered around an M dwarf star. The planet has an orbital period of 111.7 days and an orbital eccentricity of 0.29. The host star is metal rich, with an estimated [Fe/H] = +0.4. This is the first planet to emerge from our new survey of 1600 M-to-K dwarf stars.

The structure of the B2 immunoglobulin-binding domain of streptococcal protein G has been determined at 1.67-A resolution using a combination of single isomorphous replacement (SIR) phasing and manual fitting of the coordinates of the NMR structure of B 1 domain of streptococcal protein G (Gronenborn, A. M., et al. (1991) Science 253, 657-6611, The final R value was 0.191 for data between 8.0 and 1.67 A. The structure described here has 13 residues preceding the 57-residue Ig-binding domain and 13 additional residues following it, for a total of 83 residues. The 57-residue binding domain is well-determined in the structure, having an average B factor of 18.0. Only residues 8-77 could be located in the electron density maps, with the ends of the structure fading into disorder. Like the B1 domain, the B2 domain consists of four 6-strands and a single helix lying diagonally across the s these globular domains are connected by extended linkers (Fahnestocket al., 1990). Protein G offersseveraladvantages over protein A for the binding of IgG immunoglobins. Protein G binds to all subclasses of human IgG, whereas protein A does not bind the IgG3 subclass (Reis et al., 1984). Protein G binds a number of animal IgGs to which protein A binds only weakly. Protein G has a number of useful applications, including the treatment of diseases and the detection and purification of IgG's. Protein G could be used in the removal of IgGs from plasma, using an extracorporeal column (Tenan et al., 1981). The detection of IgG's is important in screening for hybridoma clones, in quantitative studies of immune response in animals, and in detection of antigens by competition-binding

This article proposes an algorithm to automatically learn useful transformations of data to improve accuracy in supervised classification tasks. These transformations take the form of a mixture of base transformations and are learned by maximizing the kernel alignment criterion. Because the proposed optimization is nonconvex, a semidefinite relaxation is derived to find an approximate global solution. This new convex algorithm learns kernels made up of a matrix mixture of transformations. This formulation yields a simpler optimization while achieving comparable or improved accuracies to previous transformation learning algorithms based on maximizing the margin. Remarkably, the new optimization problem does not slow down with the availability of additional data allowing it to scale to large datasets. One application of this method is learning monotonic transformations constructed from a base set of truncated ramp functions. These monotonic transformations permit a nonlinear filtering of the input to the classifier. The effectiveness of the method is demonstrated on synthetic data, text data and image data.

Frontier Exploration Licence 7/97 is located 115km offshore north-west Ireland and directly overlies the Erris Ridge. The ridge is an enigmatic, narrow, segmented, NE-SW orientated structural high which lies between the Erris Basin to the east and the Irish Rockall Trough to the west and which, to date, remains un-drilled. Seismic data quality across the Erris Ridge is typically poor and correlation with the sparse offset well database is challenging. Zones of poor seismic imaging are associated with combinations of complex shallow volcaniclastics, possible intrusive features and large-scale Tertiary channels/entry points which overlie older strike-slip zones and segment the ridge along its length. Displaying considerable complexity and structural variation along strike, seismic based interpretations provide models ranging from a shallow basement horst to preservation of significant thicknesses of Paleozoic and Mesozoic sediments. Recent work by Eni identifies the potential for prospective section to be preserved on the Erris Ridge resulting in two large prospects, Fiachra and Conn, and a number of leads being identified. The Fiachra Prospect is a large fault assisted four-way dip closure situated within a crestal location on the Erris Ridge and forms the focus of an exploration well planned for 2010. An early Triassic sandstone play (Sherwood Sandstone Group equivalent) is prognosed as the primary reservoir target interval, although several secondary targets also exist. After an intensive evaluation programme the critical geological risk remains modelling the presence of sedimentary section with reservoir potential in areas where the quality of seismic data is very poor. However, it is concluded that Licence 7/97 possesses good potential for deepwater frontier exploration; the Corrib gas field to the south of the licence area and the Dooish gas discovery to the north indicate the potential for a favourable location within an effective petroleum system.

We presented evidence that the WASP-14 exoplanetary system has misaligned orbital and stellar-rotational axes, with an angle of 33.1 plus or minus 7.4 degrees between their sky projections. At the time of this publication, WASP-14 was the third system known to have a significant spin-orbit misalignment, and all three systems had super- Jupiter planets and eccentric orbits. Therefore we hypothesized that the migration and subsequent orbital evolution of massive, eccentric exoplanets is somehow different from that of less massive close-in Jupiters, the majority of which have well-aligned orbits., United States. National Aeronautics and Space Administration (NASA Origins of Solar Systems program, award NNX09AD36G), United States. National Aeronautics and Space Administration (NASA Origins of Solar Systems program, award NNX09AB33G), National Science Foundation (U.S.) (NSF Astronomy and Astrophysics Postdoctoral Fellow, grant AST-0702821), Massachusetts Institute of Technology (Class of 1942), Netherlands Organization for Scientific Research (Rubicon fellowship), United States. National Aeronautics and Space Administration (NASA grant NNG05GK92G), University of California, Berkeley (Space Sciences Laboratory,Townes Postdoctoral Fellowship)

Traffic injuries are an important problem in low income countries. In Uganda road traffic is the largest single cause of injury in Kampala; pedestrians, and children are most affected. Pedestrian injury affects school children in Uganda.To determine the overall risk of pedestrian traffic injury among school children in Kawempe, Uganda.A cohort was assembled at 35 primary schools and followed for 3 terms. Ten of the schools had participated in previous injury programs, others were systematically selected. Injuries were recorded by teachers using a questionnaire. Data collected included ID, school, age, grade, gender, incident date, vehicle type, and injury outcome. Demographic characteristics are described and cumulative incidences calculated.The cohort included 8,165 children (49% male) from 35 primary schools. The mean age was 9 years (Sd=2.78). Of the 35 schools, 92% were day; the others mixed day and boarding. 53 children (27 girls) were involved in a traffic incident. 25% of the injuries reported were serious and warranted care in a health facility. No deaths occurred. Forty % of incidents involved commercial motorcycles, 41% bicycles, 9% cars, 8% taxis, and 2% trucks. The cumulative incidence was 0.168% each term. Over the 3 terms of the year the cumulative incidence was 0.5 +/- 0.02. There were no gender differences in the cumulative incidence.Each school year about 1/2 % of Kawempe school children are involved in a traffic incident. Interventions are necessary to reduce the unacceptably high incidents of pedestrian traffic. Interventions to alleviate this situation including safer routes, teaching skills of road crossing to children as well as better regulation and road safety education to two wheelers could reduce the unacceptably high incidents of pedestrian traffic injury.

Poly(lactide-co-glycolide) (PLGA) has been widely used for bone tissue regeneration. However, it lacks hydrophilicity, bioactivity and sufficient mechanical strength and its acidic degradation by-products can lead to pH decrease in the vicinity of the implants. Mesoporous bioactive glass (MBG) with highly ordered structure (pore size 2-50nm) possesses higher bioactivity than non-mesoporous bioactive glass (BG). The aim of this study is to investigate the effect of MBG on the mechanical strength, in vitro degradation, bioactivity, cellular response and drug release of PLGA films and optimize their physicochemical, biological and drug-delivery properties for bone tissue engineering application. The surface and inner microstructure, mechanical strength and surface hydrophilicity of MBG/PLGA and BG/PLGA films were tested. Results indicated that MBG or BG was uniformly dispersed in the PLGA films. The incorporation of MBG into PLGA films significantly improved their tensile strength, modulus and surface hydrophilicity. MBG/PLGA resulted in an enhanced mechanical strength, in vitro degradation (water absorbance, weight loss and ions release), apatite-formation ability and pH stability in simulated body fluids (SBF), compared to BG/PLGA. MBG/PLGA and BG/PLGA films enhanced human osteoblastic-like cells (HOBs) attachment, spreading and proliferation compared to PLGA. HOBs differentiation was significantly upregulated when cells were cultured on 30 MBG/PLGA for 14 days, compared to 30 BG/PLGA. MBG/PLGA enhanced the accumulative release of dexamethazone (DEX) at early stages (0-200h) compared to BG/PLGA, however, after 200h, DEX-release rates for MBG/PLGA was slower than that of BG/PLGA. The contents of MBG in PLGA films can control the amount of DEX released. Taken together, MBG/PLGA films possessed excellent physicochemical, biological and drug-release properties, indicating their potential application for bone tissue engineering by designing 3D scaffolds according to their corresponding compositions.

The prevalence of food allergy has increased dramatically in recent years. Tremendous research progress has been made in understanding the pathophysiological mechanisms of allergy and in identifying and characterizing food allergens. Peanut is a major food allergen source and Ara h 3 is a major peanut allergen. Using overlapping short peptides, several linear IgE-binding epitopes in Ara h 3 have been defined before. However, the structure of Ara h 3 of the native allergen is not clear and information on conformational epitopes is lacking. Structural characterization of allergens is required for understanding the allergenicity of food allergens and for the development of immunotherapeutic agents. Previously, we have reported the crystallization of Ara h 3 purified from raw peanut. Here we report the crystal structure of Ara h 3 at 1.73A resolution. Mapping of the previously defined linear epitopes on the crystal structure of Ara h 3 indicated that linear epitopes with more solvent exposure were those indicated by the literature to react with more patient sera. The structure of Ara h 3 may be used to assess the importance of conformational epitopes in further investigations.

The 11S globulins from plant seeds account for a number of major food allergens. Because of the interest in the structural basis underlying the allergenicity of food allergens, we sought to crystallize the main 11S seed storage protein from almond ( Prunus dulcis). Prunin-1 (Pru1) was purified from defatted almond flour by water extraction, cryoprecipitation, followed by sequential anion exchange, hydrophobic interaction, and size exclusion chromatography. Single crystals of Pru1 were obtained in a screening with a crystal screen kit, using the hanging-drop vapor diffusion method. Diffraction quality crystals were grown after optimization. The Pru1 crystals diffracted to at least 3.0 A and belong to the tetragonal space group P4(1)22, with unit cell parameters of a = b = 150.912 A, c = 165.248 A. Self-rotation functions and molecular replacement calculations showed that there are three molecules in the asymmetry unit with water content of 51.41%. The three Pru1 protomers are related by a noncrystallographic 3-fold axis and they form a doughnut-shaped trimer. Two prunin trimers form a homohexamer. Elucidation of prunin structure will allow further characterization of the allergenic features of the 11S protein allergens at the molecular level.

Detecting people around unmanned ground vehicles (UGVs) to facilitate safe operation of UGVs is one of the highest priority issues in the development of perception technology for autonomous navigation. Research to date has not achieved the detection ranges or reliability needed in deployed systems to detect upright pedestrians in flat, relatively uncluttered terrain, let alone in more complex environments and with people in postures that are more difficult to detect. Range data is essential to solve this problem. Combining range data with high resolution imagery may enable higher performance than range data alone because image appearance can complement shape information in range data and because cameras may offer higher angular resolution than typical range sensors. This makes stereo vision a promising approach for several reasons: image resolution is high and will continue to increase, the physical size and power dissipation of the cameras and computers will continue to decrease, and stereo cameras provide range data and imagery that are automatically spatially and temporally registered. We describe a stereo vision-based pedestrian detection system, focusing on recent improvements to a shape-based classifier applied to the range data, and present frame-level performance results that show great promise for the overall approach.

Background and objectives: Kidney transplantation is the most desired and cost-effective modality of renal replacement therapy for patients with irreversible chronic kidney failure (end-stage renal disease, stage 5 chronic kidney disease). Despite emerging evidence that the best outcomes accrue to patients who receive a transplant early in the course of renal replacement therapy, only 2.5% of incident patients with end-stage renal disease undergo transplantation as their initial modality of treatment, a figure largely unchanged for at least a decade. Design, setting, participants, & measurements: The National Kidney Foundation convened a Kidney Disease Outcomes Quality Initiative (KDOQI) conference in Washington, DC, March 19 through 20, 2007, to examine the issue. Fifty-two participants representing transplant centers, dialysis providers, and payers were divided into three work groups to address the impact of early transplantation on the chronic kidney disease paradigm, educational needs of patients and professionals, and finances of renal replacement therapy. Results: Participants explored the benefits of early transplantation on costs and outcomes, identified current barriers (at multiple levels) that impede access to early transplantation, and recommended specific interventions to overcome those barriers. Conclusions: With implementation of early education, referral to a transplant center coincident with creation of vascular access, timely transplant evaluation, and identification of potential living donors, early transplantation can be an option for substantially more patients with chronic kidney disease.

Ginkgo biloba, a well known ;living fossil' native to China, is grown worldwide as an ornamental shade plant. Medicinal and nutritional uses of G. biloba in Asia have a long history. However, ginkgo seed proteins have not been well studied at the biochemical and molecular level. In this study, the G. biloba 11S seed storage protein ginnacin was purified by sequential anion-exchange and gel-filtration chromatography. A crystallization screen was performed and well diffracting single crystals were obtained by the vapor-diffusion method. A molecular-replacement structural solution has been obtained. There are six protomers in an asymmetric unit. Structure refinement is currently in progress.

The crystal structure of HI0827 from Haemophilus influenzae Rd KW20, initially annotated "hypothetical protein" in sequence databases, exhibits an acyl-coenzyme A (acyl-CoA) thioesterase "hot dog" fold with a trimer of dimers oligomeric association, a novel assembly for this enzyme family. In studies described in the preceding paper [Zhuang, Z., Song, F., Zhao, H., Li, L., Cao, J., Eisenstein, E., Herzberg, O., and Dunaway-Mariano, D. (2008) Biochemistry 47, 2789-2796], HI0827 is shown to be an acyl-CoA thioesterase that acts on a wide range of acyl-CoA compounds. Two substrate binding sites are located across the dimer interface. The binding sites are occupied by two CoA molecules, one with full occupancy and the second only partially occupied. The CoA molecules, acquired from HI0827-expressing Escherichia coli cells, remained tightly bound to the enzyme through the protein purification steps. The difference in CoA occupancies indicates a different substrate affinity for each of the binding sites, which in turn implies that the enzyme might be subject to allosteric regulation. Mutagenesis studies have shown that the replacement of the putative catalytic carboxylate Asp44 with an alanine residue abolishes activity. The impact of this mutation is seen in the crystal structure of D44A HI0827. Whereas the overall fold and assembly of the mutant protein are the same as those of the wild-type enzyme, the CoA ligands are absent. The dimer interface is perturbed, and the channel that accommodates the thioester acyl chain is more open and wider than that observed in the wild-type enzyme. A model of intact substrate bound to wild-type HI0827 provides a structural rationale for the broad substrate range.

This report describes Team Caltech's technical approach and results for the 2007 DARPA Urban Challenge. Our primary technical thrusts were in three areas: (1) mission and contingency management for autonomous systems; (2) distributed sensor fusion, mapping and situational awareness; and (3) optimization-based guidance, navigation and control. Our autonomous vehicle, Alice, demonstrated new capabilities in each of these areas and drove approximate 300 autonomous miles in preparation for the race. The vehicle completed 2 of the 3 qualification tests, but did not ultimately qualify for the race due to poor performance in the merging tests at the National Qualifying Event.

This paper describes a method for localizing the members of a mobile robot team, using only the robots themselves as landmarks. We assume that robots are equipped with sensors that allow them to measure the relative pose and identity of nearby robots, as well as sensors that allow them to measure changes in their own pose. Using a combination of maximum likelihood estimation and distributed numerical optimization, we can, for each robot, estimate the relative range, bearing, and orientation of every other robot in the team. This paper describes the basic formalism, its distributed implementation, and presents experimental results obtained using a team of four mobile robots.

The peanut is a significant food source, but is responsible for many cases of anaphylaxis. The peanut 11S legumin-like seed storage protein Ara h 3 is one of the best characterized allergens. In this study, Ara h 3 was extracted from peanut kernels and purified by sequential anion-exchange, hydrophobic interaction and gel-filtration chromatography to very high purity to facilitate crystallization and structural studies. Well diffracting single crystals were obtained by the vapor-diffusion method. A molecular-replacement structural solution has been obtained and refinement of the structure is currently under way.

Peanut and tree-nut allergies have attracted considerable attention because of their frequency and their lifelong persistence. Brazil-nut (Bertholletia excelsa) allergies have been well documented and the 11S legumin-like seed storage protein Ber e 2 (excelsin) is one of the two known brazil-nut allergens. In this study, Ber e 2 was extracted from brazil-nut kernels and purified to high purity by crystalline precipitation and gel-filtration chromatography. Well diffracting single crystals were obtained using the hanging-drop vapour-diffusion method. A molecular-replacement structural solution has been obtained. Refinement of the structure is currently under way.

The cupin superfamily of proteins includes the 7S and 11S seed storage proteins. Many members of this family of proteins are known allergens. In this study, the Korean pine (Pinus koraiensis) vicilin-type 7S seed storage protein was isolated from defatted pine-nut extract and purified by sequential gel-filtration and anion-exchange chromatography. Well diffracting single crystals were obtained by the vapor-diffusion method in hanging drops. The crystals belong to the primitive cubic space group P2(1)3, with unit-cell parameters a = b = c = 148.174 A. Two vicilin molecules were present in the asymmetric unit and the Matthews coefficient was determined to be 2.90 A(3) Da(-1), with a corresponding solvent content of approximately 58%. A molecular-replacement structural solution has been obtained using the program Phaser. Refinement of the structure is currently under way.

Functional complementation screens can identify known or novel proteins with important intracellular activities. We have isolated human enhancer of filamentation 2 (HEF2) in a screen to find human genes that promote pseudohyphal growth in budding yeast. HEF2 is identical to enhancer of rudimentary homolog (ERH), a highly conserved protein of 104 amino acids. In silico protein-interaction mapping implies that HEF2/ERH interacts with transcription factors, cell-cycle regulators, and other proteins shown to enhance filamentous growth in S. cerevisiae, suggesting a context for studies of HEF2/ERH function. To provide a mechanistic basis to study of HEF2/ERH, we have determined the crystal structure of HEF2/ERH at 1.55 A. The crystal asymmetric unit contains a HEF2/ERH monomer. The two monomers of the physiological dimer are related by the y, x, –z crystal symmetric operation. The HEF2/ERH structure is characterized by a novel α + β fold, a four-strand antiparallel β-sheet with three α-helixes on one side of the sheet. The β-sheets from the two monomers together constitute a pseudo-β-barrel, and form the center of the functional HEF2/ERH dimer, with a cavity channel at the dimer interface. Docking of this structure to the HEF2/ERH partner protein DCOH/PCD suggests that HEF2/ERH may regulate the oligomeric state of this protein. These data suggest that HEF2/ERH may be an important transcription regulator that also functions in the control of cell-cycle progression. Proteins 2007. © 2007 Wiley-Liss, Inc.

Immunotherapy strives to replace radiation, chemo and surgery in the fight against cancer by reversing cancer’s suppression of the immune system. CTLA-4 and PDL1 checkpoint blockade inhibitors are emerging therapies that release anti-tumor T cells to kill the tumor. However, cancer also alters myeloid activation to systemically suppress the immune system, which may explain the range of responses to checkpoint blockade inhibitors. We strive to better understand myeloid activation in cancer and develop therapies to modulate these altered responses. Through in vitro myeloid activation assays, we investigated the mechanism of action for two established immunomodulatory compounds, lenalidomide and tipifarnib, as well as tested novel small molecule Intramimics, developed by our lab, for immunomodulatory function. We found that lenalidomide and tipifarnib modulate immune responses through their activation of Rho GTPases and their downstream effectors to promote F-actin assembly. Interestingly, Intramimics prove to be better at modulating immune responses as they directly activate the diaphanous related formin effectors of Rho GTPases. We propose that modulation occurs mechanistically through the MADS box transcription factor SRF, which senses actin dynamics within the cell. We intend to confirm the dependency of SRF in immunomodulation and test these therapeutics in combination with checkpoint blockade inhibitors in preclinical cancer models in the future.

Phosphonopyruvate (P-pyr) hydrolase (PPH), a member of the phosphoenolpyruvate (PEP) mutase/isocitrate lyase (PEPM/ICL) superfamily, hydrolyzes P-pyr and shares the highest sequence identity and functional similarity with PEPM. Recombinant PPH from Variovorax sp. Pal2 was expressed in Escherichia coli and purified to homogeneity. Analytical gel filtration indicated that the protein exists in solution predominantly as a tetramer. The PPH pH rate profile indicates maximal activity over a broad pH range. The steady-state kinetic constants determined for a rapid equilibrium ordered kinetic mechanism with Mg2+ binding first (Kd = 140 +/- 40 microM), are kcat = 105 +/- 2 s(-1) and P-pyr Km = 5 +/- 1 microM. PEP (slow substrate kcat = 2 x 10(-4) s(-1)), oxalate, and sulfopyruvate are competitive inhibitors with Ki values of 2.0 +/- 0.1 mM, 17 +/- 1 microM, and 210 +/- 10 microM, respectively. Three PPH crystal structures have been determined, that of a ligand-free enzyme, the enzyme bound to Mg2+ and oxalate (inhibitor), and the enzyme bound to Mg2+ and P-pyr (substrate). The complex with the inhibitor was obtained by cocrystallization, whereas that with the substrate was obtained by briefly soaking crystals of the ligand-free enzyme with P-pyr prior to flash cooling. The PPH structure resembles that of the other members of the PEPM/ICL superfamily and is most similar to the functionally related enzyme, PEPM. Each monomer of the dimer of dimers exhibits an (alpha/beta)8 barrel fold with the eighth helix swapped between two molecules of the dimer. Both P-pyr and oxalate are anchored to the active site by Mg2+. The loop capping the active site is disordered in all three structures, in contrast to PEPM, where the equivalent loop adopts an open or disordered conformation in the unbound state but sequesters the inhibitor from solvent in the bound state. Crystal packing may have favored the open conformation of PPH even when the enzyme was cocrystallized with the oxalate inhibitor. Structure alignment of PPH with other superfamily members revealed two pairs of invariant or conservatively replaced residues that anchor the flexible gating loop. The proposed PPH catalytic mechanism is analogous to that of PEPM but includes activation of a water nucleophile with the loop Thr118 residue.

Purpose: The aim of this study was to investigate the impact of a hybrid fluorodeoxyglucose positron-emission tomography/computed tomography (FDG-PET/CT) scanner in radiotherapy planning for esophageal and non–small-cell lung cancer (NSCLC). Methods and Materials: A total of 30 patients (16 with esophageal cancer, 14 with NSCLC) underwent an FDG-PET/CT for radiotherapy planning purposes. Noncontrast total-body spiral CT scans were obtained first, followed immediately by FDG-PET imaging which was automatically co-registered to the CT scan. A physician not involved in the patients’ original treatment planning designed a gross tumor volume (GTV) based first on the CT dataset alone, while blinded to the FDG-PET dataset. Afterward, the physician designed a GTV based on the fused PET/CT dataset. To standardize PET GTV margin definition, background liver PET activity was standardized in all images. The CT-based and PET/CT-based GTVs were then quantitatively compared by way of an index of conformality, which is the ratio of the intersection of the two GTVs to their union. Results: The mean index of conformality was 0.44 (range, 0.00–0.70) for patients with NSCLC and 0.46 (range, 0.13–0.80) for patients with esophageal cancer. In 10 of the 16 (62.5%) esophageal cancer patients, and in 12 of the 14 (85.7%) NSCLC patients, the addition of the FDG-PET data led to the definition of a smaller GTV. Conclusion: The incorporation of a hybrid FDG-PET/CT scanner had an impact on the radiotherapy planning of esophageal cancer and NSCLC. In future studies, we recommend adoption of a conformality index for a more comprehensive comparison of newer treatment planning imaging modalities to conventional options.

This paper reports on experiments conducted as part of the DARPA SDR (Software for Distributed Robotics) program. The core challenge for this program is to develop a system capable of carrying out 'locate-and-protect' missions: the system must be able to deploy a large number of robots into an unexplored building, map the building interior, locate a valued object, detect and track intruders, and transmit all of the above information to a remote observer/operator. To satisfy these requirements, we have developed a large heterogeneous robot team consisting of approximately 80 robots. This paper sketches the key technical elements of this system, and presents selected results from externally supervised experiments conducted in a 600 m 2 indoor environment.

Simulators have played a critical role in robotics research as tools for quick and efficient testing of new concepts, strategies, and algorithms. To date, most simulators have been restricted to 2D worlds, and few have matured to the point where they are both highly capable and easily adaptable. Gazebo is designed to fill this niche by creating a 3D dynamic multi-robot environment capable of recreating the complex worlds that would be encountered by the next generation of mobile robots. Its open source status, fine grained control, and high fidelity place Gazebo in a unique position to become more than just a stepping stone between the drawing board and real hardware: data visualization, simulation of remote environments, and even reverse engineering of blackbox systems are all possible applications. Gazebo is developed in cooperation with the Player and Stage projects (Gerkey, B. P., et al., July 2003), (Gerkey, B. P., et al., May 2001), (Vaughan, R. T., et al., Oct. 2003), and is available from http://playerstage.sourceforge.net/gazebo/ gazebo.html.

This paper describes work-in-progress aimed at generating dense 3D maps of urban environments using laser range data acquired from a moving platform. These maps display both fine-scale detail (resolving features only a few centimeters across) and large-scale consistency (typical maps are approximately 0.5 km on a side). In this paper, we sketch a basic 3D mapping algorithm (paying particular attention to practical engineering details) and present preliminary results acquired on the USC University Park campus using a Segway RMP vehicle.

The human gene coding for the enhancer of rudimentary homologue (ERH) protein was overexpressed in Escherichia coli. The ERH protein was purified by anion-exchange, hydrophobic interaction and gel-filtration chromatography. Well diffracting single crystals were obtained by the vapour-diffusion method in hanging drops. The crystals belong to the trigonal space group P3(1)21 or its enantiomorph P3(2)21, with unit-cell parameters a = b = 53.74, c = 67.45 A, alpha = beta = 90, gamma = 120 degrees. They diffract to at least 1.75 A. A selenomethionine derivative of the protein was prepared and crystallized for multiwavelength anomalous diffraction (MAD) phasing.

The human gene coding for the spliceosomal protein thioredoxin-like 4B (TXNL4B) was overexpressed in Escherichia coli and the encoded protein was purified and crystallized. Well diffracting single crystals were obtained by the vapor-diffusion method in hanging drops. The crystals belong to the primitive monoclinic space group P2, with unit-cell parameters a = 39.0, b = 63.6, c = 51.0 A, beta = 92.484 degrees,, and diffract to at least 1.50 A. A SeMet derivative of the protein was prepared and crystallized for MAD phasing.

This paper presents an approach to generating compact 3D maps of urban environments using mobile robots and laser range finders. Our algorithm extracts planar information from 3D point cloud maps. The planar representation is very efficient for representing building structures in urban environments when a high level of detail is not required. We also present preliminary results on 3D geometric mapping with incomplete data. Based on previously known models and incomplete data, our system is able to estimate parts of buildings which have never been seen before. As validation, we present experimental results using a Segway RMP vehicle in two environments, both approximately the size of a city block.

The ygfZ gene product of Escherichia coli represents a large protein family conserved in bacteria to eukaryotes. The members of this family are uncharacterized proteins with marginal sequence similarity to the T-protein (aminomethyltransferase) of the glycine cleavage system. To assist with the functional assignment of the YgfZ family, the crystal structure of the E. coli protein was determined by multiwavelength anomalous diffraction. The protein molecule has a three-domain architecture with a central hydrophobic channel. The structure is very similar to that of bacterial dimethylglycine oxidase, an enzyme of the glycine betaine pathway and a homolog of the T-protein. Based on structural superposition, a folate-binding site was identified in the central channel of YgfZ, and the ability of YgfZ to bind folate derivatives was confirmed experimentally. However, in contrast to dimethylglycine oxidase and T-protein, the YgfZ family lacks amino acid conservation at the folate site, which implies that YgfZ is not an aminomethyltransferase but is likely a folate-dependent regulatory protein involved in one-carbon metabolism.

Reduced pteridines are required for a number of important cellular functions. Trypanosomatid parasites, unlike their mammalian hosts, are pteridine auxotrophs and salvage the precursor pteridines from the host and reduce them to the respective biologically active tetrahydro forms using parasite-encoded enzymes. These enzymes may offer selective drug targets. In Leishmania, pteridine reductase 1 (PTR1), the primary enzyme for reducing pterins, is also responsible for resistance to antifolate drugs. Typically, PTR1 is more active with fully oxidized biopterin and folate than with their reduced counterparts. We have identified an enzyme, TcPTR2 of Trypanosoma cruzi, which though very similar to PTR1 in its primary sequence, can reduce only dihydrobiopterin and dihydrofolate and not oxidized pteridines. The structures of an inhibitor (methotrexate) and a substrate (dihydrofolate) complex of this enzyme demonstrate that the orientation of the substrate and the inhibitor in the active site of TcPTR2 are different from each other. However, the orientation of each ligand is similar to that of the corresponding ligand in Leishmania major PTR1 complexes.

We seek to make robot programming more efficient by developing a standard abstract interface for robot hardware, based on familiar techniques from operating systems and network engineering. This paper describes the application of three well known abstractions, the character device model, the interface/driver model, and the client/server model to this purpose. These abstractions underlie Player/Stage, our open source project for rapid development of robot control systems. One product of this project is the Player Abstract Device Interface (PADI) specification, which defines a set of interfaces that capture the functionality of logically similar sensors and actuators. This specification is the central abstraction that enables Player-based controllers to run unchanged on a variety of real and simulated devices. We propose that PADI could be a starting point for development of a standard platform for robot interfacing, independent of Player, to enable code portability and re-use, while still providing access to the unique capabilities of individual devices.

The crystal structure of the Haemophilus influenzae protein HI1480 was determined at 2.1-A resolution. The amino acid sequence of HI1480 is unique, having no homology with other known protein sequences. The protein adopts a novel α+β fold, and associates into a dimer of tightly associated dimers. The tight dimers are formed by intermolecular interactions that are mediated by an antiparallel β-barrel involving both monomers. Helical regions of two dimers mediate the tetramer formation. The helical region contains a four-helix bundle that has been seen only in the anticodon binding domains of class I tRNA synthetases. A cluster of four residues, Tyr18, Arg134, Glu26, and Lys12 is located in a depression formed at the four-helix bundle/ β-barrel interface. The arrangement is suggestive of an active center, possibly a catalytic site. The HI1480 gene is located within the Mu-like prophage region of H. influenzae, has no homology to bacteriophage genes, and is flanked by transposases. Hence, this is an example of horizontal transfer from an unknown organism. Gel mobility shift assays revealed that HI1480 binds DNA and RNA molecules. Double-stranded DNA is favored over single-stranded DNA, and longer DNA molecules are bound better than shorter ones. Proteins 2004. © 2004 Wiley-Liss, Inc.

This paper describes a behavior-based approach to stealth. The specific problem we consider is that of making stealthy traverses, i.e., transiting from one point to another while remaining hidden from an observer. Since we assume that the robot has no a priori model of the environment, our stealthy traverse behavior makes opportunistic use of terrain features to hide from the observer. This behavior has been evaluated in both real and simulated experiments, comparing it against a regular goal-seeking/obstacle-avoidance behavior. These experiments show a clear improvement in the stealthiness of the robot.

This paper describes a cooperative method for relative localization of mobile robot teams; that is, it describes a method whereby every robot in the team can estimate the pose of every other robot, relative to itself. This robot does not require the use of GPS, landmarks, or maps of any kind; instead, robots make direct measurement of the relative pose of nearby robots, and broadcast this information to the team as a whole. Each robot processes this information independently to generate ego-centric estimate for the pose of other robots. Our method uses Bayesian formalism with a particle filter implementation, and is, as a consequence, very robust. It is also completely distributed, yet requires relatively little communication between robots. This paper describes the basic ego-centric formalism, sketches the implementation, and presents experimental results obtained using a team of four mobile robots.