Search

A qualitative study was conducted to analyze degradation of CO2 capture solvents containing ionic liquids by GC/MS under a variety of conditions representative of the carbon capture process. Aqueous monoethanolamine (MEA) was used as a benchmark for solvent degradation and compared to two advanced CO2 capture solvents containing ionic liquids. Accelerated aging experiments were conducted in the laboratory by exposing solvents to various gases (N2, air, CO2, or SO2) at elevated temperature in sealed cylinders. Degradation products were analyzed by GC/MS and key pathways leading to their formation were elucidated. For all solvents, degradation was most rapid and lead to a wider array of products in the presence of CO2 compared to the other studied gases. The ionic liquid solvents showed enhanced degradation and a different set of degradation products than those observed for MEA. In one case, the anion of the ionic liquid was found to be reactive and led to a unique primary degradation mechanism not seen in ...

Human cytomegalovirus (CMV) is a large enveloped virus that encodes multiple glycoproteins required for virus-cell binding and fusion. To assess the binding properties of antibodies with target glycoprotein in a natural context of infection, we investigated the feasibility of using the surface plasmon resonance (SPR) technique for studying the direct binding of antibodies with CMV virions. Direct immobilization of whole virions to sensor surface and a surface regeneration procedure allowed for quantitative and reproducible measurements of binding affinity and binding kinetics of antibody-whole virion interactions. The conformational and functional integrity of viral particles was not compromised by the regeneration condition as evaluated with antibodies recognizing conformational epitopes and by electron microscopy. Binding of an irrelevant antibody was not observed, indicating the high specificity of the method. A panel of anti-gB antibodies was measured and the binding affinities correlated fairly well with those determined by ELISA. These data demonstrated that the interaction of anti-gB antibody with whole virion of large enveloped CMV can be quantitatively studied using SPR. This method has been successfully applied for screening and selection of anti-CMV antibodies and can be potentially extended to study antibody-glycoprotein interactions of other related herpesviruses.

We recently showed that increasing Wnt/beta-catenin signalling in the bone marrow microenvironment or in multiple myeloma (MM) cells clearly suppresses osteoclastogenesis in SCID-hu mice; however, this regulation of osteoclastogenesis could result directly from activation of Wnt/beta-catenin signalling in osteoclasts or indirectly from effects on osteoblasts. The present studies characterized Wnt/beta-catenin signalling and its potential role in osteoclasts. Systematic analysis of expression of WNT, FZD, LRP and TCF gene families demonstrated that numerous Wnt-signalling components were expressed in human osteoclasts from patients with MM. Functional Wnt/beta-catenin signalling was identified by accumulation of total and active beta-catenin and increases in Dvl-3 protein in response to Wnt3a or LiCl. Furthermore, Wnt-induced increases in beta-catenin and Dvl-3 were attenuated by Wnt antagonists Dkk1 and sFRP1. Finally, Wnt3a-induced TCF/LEF transcriptional activity suggests that canonical Wnt signalling is active in osteoclasts. Supernatants from dominant-negative-beta-catenin-expressing osteoblast clones significantly stimulated tartrate-resistant acid phosphatase-positive osteoclast formation from primary MM-derived osteoclasts, compared with supernatants from control cells. These results suggested that Wnt/beta-catenin signalling is active in osteoclasts in MM and is involved in osteoclastogenesis in bone marrow, where it acts as a negative regulator of osteoclast formation in an osteoblast-dependent manner in MM.

Perhaps no other building combines the fundamentals of structural design and architecture more organically than does the geodesic dome of R. Buckminster Fuller. Sir Harold Kroto, ‘Macro‐, Micro‐ an...

Classification methods for data sets of molecules according to their chemical structure were evaluated for their biological relevance, including rule-based, scaffold-oriented classification methods and clustering based on molecular descriptors. Three data sets resulting from uniformly determined in vitro biological profiling experiments were classified according to their chemical structures, and the results were compared in a Pareto analysis with the number of classes and their average spread in the profile space as two concurrent objectives which were to be minimized. It has been found that no classification method is overall superior to all other studied methods, but there is a general trend that rule-based, scaffold-oriented methods are the better choice if classes with homogeneous biological activity are required, but a large number of clusters can be tolerated. On the other hand, clustering based on chemical fingerprints is superior if fewer and larger classes are required, and some loss of homogeneity in biological activity can be accepted.

The primary goal of this research effort is to develop nondestructive evaluation techniques capable of detecting material damage precursors mainly for turbine engine materials under low and high-cycle fatigue testing. The experimental results presented in this paper show a significant increase of the relative acoustic nonlinearity, βr, in aluminum and Ni-based superalloy fatigued specimens. While in agreement with the prior research, the main advantage of the current technique over the previous methods is that the ultrasonic beam may be focused to inspect the presence of damage precursors at localized stress concentrator site. For example, when the ultrasonic beam travelled through the root of the round-notched specimens, the acoustic nonlinearity exhibited an increase of approximately 450% as compared to the pristine specimens. This procedure will be further developed to detect damage precursors in propulsion components undergoing thermo-mechanically fatigue to quantify their remaining useful life.

The shift toward condition-based monitoring is a key area of research for many military, industrial, and commercial customers who want to lower the overall operating costs of capital equipment and general facilities. Assessing the health of rotating systems such as gearboxes, bearings, pumps and other actuation systems often rely on the need for continuous monitoring to capture transient signals that are evidence of events that could cause (i.e. cavitation), or be the result of (i.e. spalling), damage within a system. In some applications this can be accomplished using line powered analyzers, however for wide-spread monitoring, the use of small-scale embedded electronic systems are more desirable. In such cases the method for powering the electronics becomes a significant design factor. This work presents a multi-source energy harvesting approach meant to provide a robust power source for embedded electronics, capturing energy from vibration, thermal and light sources to operate a low-power sensor node. This paper presents the general design philosophy behind the multi-source harvesting circuit, and how it can be extended from powering electronics developed for periodic monitoring to sensing equipment capable of providing continuous condition-based monitoring.

The application of diversity selection for identification of biologically active molecules is based on the similarity property principle according to which no compound similar to a compound already in the screening needs to be screened since a similar outcome can be expected. However, experimental errors of the screening experiment and the only limited validity of the similarity property principle can lead to the situation that a diversely selected subset does not cover more hit series of a screening summary data set than a random selection. Due to the size bias in chemical similarity functions diversely selected subset can have a reduced complexity, which causes unwanted side effects on the distribution of IC50 values.

The molecular scaffold is an oft-cited concept in medicinal chemistry suggesting that the definition of what makes a scaffold is rigorous and objective. However, this is far from the case with the definition of a scaffold being highly dependent on the particular viewpoint of a given scientist. It follows, therefore, that the definition of scaffold hopping and, more importantly, the detection of what constitutes a scaffold hop, is also ill-defined and highly subjective. Essentially, it is agreed that scaffolds should be substantially different from each other, although significantly similar to each other, to constitute a hop. In the latter, the scaffolds must permit a similar geometric arrangement of functional groups to permit the mode of action. However, this leaves the paradox of how to describe both scaffold similarity and dissimilarity simultaneously. In this paper, the current statuses of scaffolds and scaffold hopping are reviewed based on published examples of scaffold hopping from the literature. An investigation of the degree to which it is possible to formulate a more rigorous definition of scaffolds and hopping in the context of molecular topologies is considered. These techniques are adapted from chemoinformatics to be applied in the design of new medicinal compounds.

Depuis plus de trois siecles, les systemes politiques du Moyen-Orient sont consideres par les auteurs occidentaux comme des exemples de gouvernement arbitraire. La gouvernance dans les societes moyen-orientales, contrairement a l’Etat de droit, est consideree comme s’exercant dans le cadre d’un pouvoir absolu et selon le caprice personnel. Pour de nombreux fondateurs de la tradition liberale occidentale, la pratique gouvernementale orientale a ete un repoussoir bien utile. Les regimes ottoman...

In this paper a new method is defined that encapsulates the geometric information contained in a molecular structure in an alignment-free way within a hash-key fingerprint. A review of fingerprinting technologies is provided followed by a thorough definition of the method by which geometry may be encoded. The paper concludes with comparative QSAR studies to test the efficacy of this new descriptor in comparison with a number of published methods and results with two datasets: 38 D 2 receptor antagonists and 58 estrogen receptors.

ChimeriVax-dengue (DEN) viruses are live attenuated vaccine candidates. They are constructed by replacing the premembrane (prM) and envelope (E) genes of the yellow fever (YF) 17D virus vaccine with the corresponding genes from wild-type DEN viruses (serotypes 1-4) isolated from humans. In this study, the growth kinetics of ChimeriVax-DEN1-4 and parent viruses (wild-type DEN-1-4 and YF 17D) were assessed in human myeloid dendritic cells (DCs) and in three hepatic cell lines (HepG2, Huh7, and THLE-3). In DC, ChimeriVax-DEN-1-4 showed similar growth kinetics to their parent viruses, wild-type DEN virus (propagated in Vero cells), or YF 17D virus (peak titers ~3-4.5 log(10) plaque-forming units (PFU)/mL at 48-72 hours post-infection). Parent wild-type DEN-1-4 viruses derived from C6/36 mosquito cells did not show any growth at a multiplicity of infection of 0.1 in DCs, except for DEN-2 virus, which grew to a modest titer of 2.5 log(10) PFU/mL at 48 hours post-infection. ChimeriVax-DEN1-4 grew to significantly lower titers (2-5 log(10) PFU/mL) than YF 17D virus in hepatic cell lines THLE-3 and HepG2, but not in Huh7 cells. These experiments suggest that ChimeriVax-DEN1-4 viruses replicate similarly to YF-VAX in DCs, but at a lower level than YF 17D virus in hepatic cell lines. The lack of growth of chimeric viruses in human hepatic cells suggests that these viruses may be less hepatotropic than YF 17D virus vaccine in humans.

Acute Oak Decline (AOD) is a new condition affecting both species of native oak, Quercus robur and Quercus petraea, in Great Britain. The decline is characterised by a distinctive set of externally visible stem symptoms; bark cracks that “weep” dark exudate are found above necrotic lesions in the inner bark. Emergence holes of the buprestid beetle, Agrilus biguttatus are often also seen on the stems of oak within affected woodlands. This investigation assesses the extent to which the external symptoms of these two agents co-occur and reveals the spatial and temporal patterns present in affected woodland. Annual monitoring in eight affected woodlands showed that stem bleeding and emergence holes frequently occur on the same trees, with new emergence holes significantly more likely to occur when trees already have stem bleeds. Trials with coloured prism traps confirm A. biguttatus was present at all experimental sites. Beetle emergence is linked primarily to a few heavily declining trees, indicating that susceptibility may vary between hosts and that those with reduced health may be predisposed to AOD. Stem bleeds occur on trees in close proximity to the locations of trees with exit holes.

We study the process e+e−→ψ(2S)π+π− with initial-state-radiation events produced at the PEP-II asymmetric-energy collider. The data were recorded with the BABAR detector at center-of-mass energies at and near the Υ(nS) (n=2,3,4) resonances and correspond to an integrated luminosity of 520 fb−1. We investigate the ψ(2S)π+π− mass distribution from 3.95 to 5.95 GeV/c2, and measure the center-of-mass energy dependence of the associated e+e−→ψ(2S)π+π− cross section. The mass distribution exhibits evidence of two resonant structures. A fit to the ψ(2S)π+π− mass distribution corresponding to the decay mode ψ(2S)→J/ψπ+π− yields a mass value of 4340±16 (stat) ±9 (syst) MeV/c2 and a width of 94±32 (stat) ±13 (syst) MeV for the first resonance, and for the second a mass value of 4669±21 (stat) ±3 (syst) MeV/c2 and a width of 104±48 (stat) ±10 (syst) MeV. In addition, we show the π+π− mass distributions for these resonant regions.

A novel approach to malware classification is introduced based on analysis of instruction traces that are collected dynamically from the program in question. The method has been implemented online in a sandbox environment (i.e., a security mechanism for separating running programs) at Los Alamos National Laboratory, and is intended for eventual host-based use, provided the issue of sampling the instructions executed by a given process without disruption to the user can be satisfactorily addressed. The procedure represents an instruction trace with a Markov chain structure in which the transition matrix, $\mathbf {P}$, has rows modeled as Dirichlet vectors. The malware class (malicious or benign) is modeled using a flexible spline logistic regression model with variable selection on the elements of $\mathbf {P}$, which are observed with error. The utility of the method is illustrated on a sample of traces from malware and nonmalware programs, and the results are compared to other leading detection schemes (both signature and classification based). This article also has supplementary materials available online., Comment: Published in at http://dx.doi.org/10.1214/13-AOAS703 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org)

Imidazoles present a tunable, versatile and economical platform for the development of novel liquid solvents and polymer membranes for CO2 capture. An overview of our studies in this area is presented, with emphasis on characterization of structure-property relationships in imidazole-based materials through both experimental and computational studies. To this end, a growing library of systematically varied imidazole compounds has been synthesized using only commercial available starting materials and straightforward reactions. Using this library of compounds, we have sought to understand and develop predictive models for thermophysical properties relating to process design, including: density, viscosity, vapor pressure, pKa and CO2 absorption capacity. Furthermore, we have discovered that imidazoles are stable in the presence of SO2 and can form reversible 1:1 adducts, which can be beneficial as SO2 is typically present at ppm levels alongside CO2 in flue gas from coal-fired power plants.

Background: There is a global consensus that multiple myeloma patients with high-risk disease require additional monitoring and therapy compared to low/standard risk patients in order to maximize their chances of survival. Current diagnostic guidelines recommend FISH-based assessment of chromosomal aberrations to determine risk status (i.e. t(14;20), t(14;16), t(4;14) and/or Del17p), however, studies show FISH for MM may have a 20-30% QNS rate and is up to 15% discordant between laboratories, even when starting from isolated plasma cells. In this study we demonstrate that MyPRS gene expression profiling reproduces the key high risk translocations for MM risk stratification, in addition to having other significant advantages. Methods: Reproducibility studies show that MyPRS results are less than 1% discordant starting from isolated plasma cells and return successful results in up to 95% of cases. 270 MM patients from Johns Hopkins University (MD) and Weill Cornell Medicine (NY) had both FISH and MyPRS gene expression profiling performed between 2012 and 2016 using standard and previously published methodology, respectively. Results: Retrospective review of the matched FISH and MyPRS results showed: 25/28 (89%) patients wish FISH-identified t(4;14) were classified as MMSET (MS) subtype. 10/10 (100%) patients with t(14;16) or t(14;20) were classified as MAF-like (MF) subtype 62/67 (93%) patients with t(11;14) were assigned to the Cyclin D (1 or 2) subtype. Patients with FISH hyperdiploidy status were classified as the Hyperdiploid (HY) subtype or had multiple gains detected by the separate MyPRS Virtual Karyotype (VK) algorithm, included in MyPRS. TP53del was seen in patients with multiple molecular subtypes, predominantly Proliferation (PR) and MMSET (MS). Assessment of TP53 function by gene expression is a more clinically relevant prognostic marker than TP53del, as dysregulation of the tumor suppressor is affected by mutations as well as deletions. Analysis of the TP53 expression in the 39 patients with delTP53 showed a statistically significant difference, compared to patients without this deletion (P Conclusion: Gene expression profiling is a superior and more reliable method for determining an individual patients' prognostic risk status. The molecular subtypes of MM, as reported by Signal Genetics MyPRS assay, are driven by large-scale changes in gene expression caused by or closely associated with chromosomal changes, including translocations. Physicians who are managing myeloma patients and wishing to base their assessment of risk on R-ISS or mSMART Guidelines may obtain the required data points from either FISH or MyPRS, with the latter offering lower QNS rates, higher reproducibility, assessment of a larger number of cells and a substantially lower price point ($5,480 vs. $1,912; 2016 CMS data). A larger cohort study is now underway to further validate these observations. Figure GEP-based TP53 expression in patients with and without Del17p. P Disclosures Van Laar: Signal Genetics, Inc.: Employment. Borrelo:Sidney Kimmel Cancer Institute: Employment. Jabalayan:Weill Cornell Medical Center: Employment. Niesvizky:Celgene: Consultancy, Research Funding, Speakers Bureau; Takeda: Consultancy, Research Funding, Speakers Bureau; Onyx: Consultancy, Research Funding, Speakers Bureau. Zielinski:Signal Genetics, Inc.: Employment. Leigh:Signal Genetics, Inc.: Employment. Brown:Signal Genetics, Inc.: Employment. Bender:Signal Genetics, Inc.: Employment.

Background: Small-RNAs (including microRNAs) are a novel class of molecules with functions that include the regulation of coding genes as well as development, proliferation, apoptosis and differentiation of myeloma cells. The presence of these genes has been detected inside cells and also in the extracellular environment, suggesting they may be useful for risk stratification and treatment monitoring. We sought to explore the small-RNA profiles of bone marrow specimens submitted for MyPRS analysis and identify candidate molecules associated with a patient's 70-gene (mRNA) prognostic risk score. Method and Results: 32 bone marrow aspirate samples from patients with multiple myeloma, 3 whole-blood control samples and the MM cell line NCI-H929 were included in the present study. Plasma cells were isolated from the bone marrow aspirates as per standard MyPRS protocols. Total RNA was then extracted using the miRNeasy Mini Kit protocol (Qiagen, Canada). All miRNA libraries were prepared using the Illumina TruSeq Small RNA protocol following the manufacturer's instructions with 11-15 cycles of PCR amplification. Individual libraries were prepared using a unique index primer to allow for pooling of multiple samples. After amplification, Novex TBE PAGE gel electrophoresis was used to select for fragments sized 145- 160 nt, corresponding to mature miRNA's and other small RNA molecules. Libraries were validated and quantified using an Agilent 2100 Bioanalyzer High Sensitivity DNA chip, sequenced on an Illumina NextSeq 500 and analyzed using Illumina BaseSpace Onsite. After adapter trimming, an average of 3.7, 17.7 and 0.5 million reads were generated from the multiple myeloma, normal blood and NCI-H929 cell line libraries, respectively. When comparing the MM vs. control data, 757/6041 total miRNA's passed a low-count filter and 535 of these were found to be differentially expressed. The top 10 miRNA families with the largest difference between sample types according to DESEq2 were mir-1285, let-7, mir-1248, mir-1303, mir-1260b, mir-1301, mir-10, mir-128, mir-129 and mir-130. Within the MM sample group, 620 individual miRNAs were reliably detected and compared between GEP70 high and low risk disease, with 14 passing a differential expression filter. Hierarchal clustering of patients using all 620 genes did not separate patients into high and low risk groups and only 2/411 miRNA families (mir-130 and mir-17) were found to differ between these classes. Serum levels of miR-130a in MM patients have been shown to be associated with extramedullary disease and miR-17 is thought to regulate the Myc oncogene. Conclusion: In this study we identified a number of novel microRNAs with patterns of expression in patient bone marrow aspirates associated with the extensively validated 70-gene risk score available commercially as 'MyPRS'. Two particular miRNA's were identified that appear to be associated with high risk behavior, one of which correlates with the Myc oncogene whose relationship to clinically aggressive MM is well described. Further work is planned to expand the number of patients in the study and to investigate whether these microRNA's are present in the extracellular bone marrow environment and peripheral fluids. Disclosures van Laar: Signal Genetics, Inc.: Employment. Leigh:Signal Genetics, Inc.: Employment. Zielinski:Signal Genetics, Inc.: Employment. Brown:Signal Genetics, Inc.: Employment. Bender:Signal Genetics, Inc.: Employment.

The purpose of this project was to evaluate the performance of ION’s lead solvent and determine if ION’s solvent candidate could potentially meet DOE’s target of achieving 90% CO{sub 2} Capture from a 550 MWe Pulverized Coal Plant without resulting in an increase in COE greater than 35%. In this project, ION’s lead solvent demonstrated a 65% reduction in regeneration energy and a simultaneous 35% reduction in liquid to gas ratio (L/G) in comparison to aqMEA at 90% CO{sub 2} capture using actual flue gas at 0.2 MWe. Results have clearly demonstrated that the ION technology is in line with DOE performance expectations and has the potential to meet DOE’s performance targets in larger scale testing environments.

Purpose The aim of this study was to identify the relative anatomic locations of relevant vital structures at risk for injury during posterior iliac crest bone graft procurement. Materials and Methods Twenty-one cadavers yielded 39 intact posterior ilia for dissection. The posterior superior iliac spine (PSIS) was used as the primary reference landmark. Measurements were made to the medial branch of the superior cluneal nerves, the superior branch of the middle cluneal nerves, the sciatic notch, and the superior gluteal vessels. Distances from the spinal midline to the superior cluneal nerves were recorded. Results The average distances from the PSIS to the superior and middle cluneal nerves, greater sciatic notch, and superior gluteal vessels were 5.7 cm (standard deviation, 1.22 cm), 6.55 cm (standard deviation, 1.53 cm), 5.3 cm (standard deviation, 0.71 cm), and 5.4 cm (standard deviation, 0.95 cm), respectively. The most medial superior cluneal nerve was identified at 3.0 to 4.9 cm from the PSIS in 23% of cases, at 5.0 to 6.9 cm from the PSIS in 61.5% of cases, and farther than 7.0 cm from the PSIS in 15.4% of cases. Conclusions This study illustrates that the most medial superior cluneal nerve is often closer to the PSIS than previously described and the same holds true for the greater sciatic notch and superior gluteal vessels. Knowledge of the anatomic locations of these important structures should allow the surgeon to avoid or decrease the complication rate of bone procurement from the posterior ilium.

The ever-growing malware threat in the cyber space calls for techniques that are more effective than widely deployed signature-based detection systems and more scalable than manual reverse engineering by forensic experts. To counter large volumes of malware variants, machine learning techniques have been applied recently for automated malware classification. Despite the successes made from these efforts, we still lack a basic understanding of some key issues, such as what features we should use and which classifiers perform well on malware data. Against this backdrop, the goal of this work is to explore discriminatory features for automated malware classification. We conduct a systematic study on the discriminative power of various types of features extracted from malware programs, and experiment with different combinations of feature selection algorithms and classifiers. Our results not only offer insights into what features most distinguish malware families, but also shed light on how to develop scalable techniques for automated malware classification in practice.

The dielectric response of a charged particle beam to a periodic focusing field enhances the effective focusing strength, reducing the matched beam radius and affecting the motion of halo particles. The change in the effective focusing strength is found for a uniform-density beam with a diffuse halo in a quadrupole channel, giving increases of 2% to 8% for some typical examples. These changes are important for both the production and behavior of halos in intense, high energy beams, in which fractional current losses as small as 10-8 /m can result in radioactivation. The effective focusing strength of a periodic channel is an important factor for accelerator applications requiring high beam intensities, such as heavy ion inertial fusion, radioactive waste transmutation, spallation neutron sources, tritium production and muon production. Limiting currents have been found in the past using the smooth approximation [1] to find the effective focusing strength of a periodic channel which, along with the aperture, determines the current that can be transported through a given channel [2]. Accurate knowledge of the effective focusing strength is also important for matching. Transverse mismatch has been shown to be an important cause of halo production and the resulting particle losses [3-5]. Fractional current losses as small as 10-8 /m can result in radioactivation, inhibiting routine maintenance [6]; this can also be the limiting factor in the transport of intense, high-energy beams [7]. The dielectric response of a plasma to the periodic field of a Paul trap was recently shown to enhance the effective focusing strength of the trap [8]. The dielectric response results from the correlation between the oscillations in the space charge field and the peiodic focusing field [9]. The dielectric response is shown here to increase the effective focusing strength of the channel, by an amount that depends on the shape of the beam, the type of focusing, and the ratio of the plasma frequency of the beam, ω p, to the frequency of the focusing, ω . The dielectric response and the fractional change in the effective focusing strength are found for a uniformdensity continuous beam with a diffuse halo and for a uniformdensity ellipsoidal (bunched) beam, both in a quadrupole channel. The increase in the effective focusing strength results in a higher transverse phase advance per period, a higher average beam density and a lower average beam radius. Since accurate matching is important for beam applications requiring low losses, the effect of the dielectric response on the matched beam parameters can be important for the applications listed above. A beam in a periodic focusing channel experiences a fluctuating electric field Ef (r,s0), which consists of the fluctuating component of the focusing field, Ecf (r, s 0), and small fluctuations in the space charge field, Esf (r, s0). The position relative to the center of the beam is r, and the focusing is periodic in s, the longitudinal distance along the channel. Although particles with different longitudinal positions within the beam are at different phases in the periodic field, it is assumed that the effects of this are negligible so that the fluctuating fields can be written as periodic functions of the longitudinal position of the beam center along the channel, s0. The focusing field and the space charge field are each divided into two parts so that the fluctuating components have an average value of zero and the steady-state components vary slowly or not at all with s0. The frequency of the focusing is ω=2πvB/S, where S is the period of the focusing along the longitudinal direction and vB is the beam velocity. In general there are three periods (Sx , Sy and Sz) and three frequencies (ω x , ω y and ω z), one for each of three directions in Cartesian coordinates (x and y are transverse and z is parallel to the beam axis; for most practical applications Sx = Sy). The focusing field can be the result of electrostatic or magnetic quadrupole lenses, inductionacceleration gaps, and magnetic solenoids (if the beam is considered in the Larmor frame). It can also be the result of focusing by electromagnetic fields which are periodic in time and space, as in the case of radio-frequency quadrupole (RFQ) focusing. The focusing field is written as an electric field with the approximation that particle motion in the beam frame is nonrelativistic, so that magnetic focusing can be represented by equivalent electrostatic fields. The force resulting from the magnetic field of the beam is included in the self electric field (the space charge field) with the same approximation. Unless otherwise stated, all quantities are considered in the lab frame. With RFQ focusing and induction-acceleration gaps, it is assumed that acceleration along the longitudinal direction is slow enough that it can be treated as adiabatic, and that the beam is in phase with the time-varying field so that the focusing field can be treated as periodic only in longitudinal distance along the channel. The effective focusing field can be found from the average field of a particle due to its motion in the periodic field [10]. The motion of a particle in the periodic field is first found with the fluctuating field as a function of position fixed at Ef (r,s0) = Ef (r0,s0), where r0 is the position of the particle averaged over a period. The resulting particle position is r0 + δr; the first-order variation in the position of the particle resulting from the fluctuating field is δr. The effective field that results from the fluctuating field is then found to first order from Eeff = Ef(r ,s0) = δr ⋅ DEL0 ( )Ef (r0 ,s0 ) , (1) where DEL0 is the gradient with respect to r0 and the brackets LINAC 96

The Maxwell–Boltzmann distribution of a bunched charged particle beam is the state toward which every other distribution will relax. For beams with lifetimes much shorter than the time required for relaxation to equilibrium, it is the distribution at injection that minimizes the emittance growth due to relaxation toward equilibrium. Three‐dimensional thermal distributions are found numerically for the case of linear external focusing forces acting on an axially symmetric bunched beam in a conducting pipe. Equations are derived for current loss into the conducting channel due to particle thermal motion in the equilibrium distribution. Relations between parameters such as perveance, emittance, space‐charge tune depression, bunch radius, and bunch length are given over a wide range of conditions from short to long bunches and from space‐charge dominated to emittance‐dominated beams. Comparison is made with previous results of radial density profiles for unbunched beams and line‐charge density profiles for bunched beams [Phys. Rev. Lett. 71, 2911 (1993)].

In the conventional design of rf linear accelerators (linacs) the charged-particle bunches are not in three-dimensional thermal equilibrium. For applications requiring high beam currents, the space charge couples the longitudinal and transverse particle motions. This leads to equipartitioning processes which cause unacceptable emittance growth and halo formation. A new design strategy for high-current rf linacs is proposed in which the bunches are in thermal equilibrium so that these effects do not occur. Analytic relationships and scaling laws for the design of such linacs are presented.

This paper reports the measurement of the [ital B] meson and [ital b] quark cross sections through the decay chain [ital B][sup 0][r arrow][ital J]/[psi] K[sup *](892)[sup 0], [ital J]/[psi][r arrow][mu][sup +][mu][sup [minus]], [ital K][sup *](892)[sup 0][r arrow][ital K][sup +][pi][sup [minus]], using 4.3 pb[sup [minus]1] of data collected at the Collider Detector at Fermilab in [ital [bar p]p] collisions at [ital qrts]=1.8 TeV. We obtain [sigma][sub [ital B]]=1.5[plus minus]0.7(stat)[plus minus]0.6(syst) [mu]b for [ital B][sup 0] mesons with transverse momentum [ital P][sub [ital T]][gt]9.0 GeV/[ital c] and rapidity [vert bar][ital y][vert bar][lt]1.0. Using this result, we find [sigma][sub [ital b]]=3.7[plus minus]1.6(stat)[plus minus]1.5(syst) [mu]b for [ital b] quarks with [ital P][sub [ital T]][gt]11.5 GeV/[ital c] and rapidity [vert bar][ital y][vert bar][lt]1.0. The [ital b] quark cross section is compared to next-to-leading order QCD calculations and previous measurements.

Bacteriophage S-CRM01 has been isolated from a freshwater strain of Synechococcus and shown to be present in the upper Klamath River valley in northern California and Oregon. The genome of this lytic T4-like phage has a 178,563 bp circular genetic map with 297 predicted protein-coding genes and 33 tRNA genes that represent all 20-amino-acid specificities. Analyses based on gene sequence and gene content indicate a close phylogenetic relationship to the 'photosynthetic' marine cyanomyophages infecting Synechococcus and Prochlorococcus. Such relatedness suggests that freshwater and marine phages can draw on a common gene pool. The genome can be considered as being comprised of three regions. Region 1 is populated predominantly with structural genes, recognized as such by homology to other T4-like phages and by identification in a proteomic analysis of purified virions. Region 2 contains most of the genes with roles in replication, recombination, nucleotide metabolism and regulation of gene expression, as well as 5 of the 6 signature genes of the photosynthetic cyanomyophages (hli03, hsp20, mazG, phoH and psbA; cobS is present in Region 3). Much of Regions 1 and 2 are syntenic with marine cyanomyophage genomes, except that a segment encompassing Region 2 is inverted. Region 3 contains a high proportion (85%) of genes that are unique to S-CRM01, as well as most of the tRNA genes. Regions 1 and 2 contain many predicted late promoters, with a combination of CTAAATA and ATAAATA core sequences. Two predicted genes that are unusual in phage genomes are homologues of cellular spoT and nusG.

Human cytomegalovirus (HCMV) enters cells through a complex pathway involving the interaction of multiple viral glycoproteins and cellular receptors. While HCMV clinical isolates enter a wide range of cell types, entry has historically been studied using a laboratory strain of virus that can only infect fibroblasts. Herein, we have constructed a HCMV reporter strain that contains GFP fused to the abundant tegument protein pp65 to allow for the direct visualization of virus attachment and entry. Furthermore, the UL131 gene of this strain was restored to clinical isolate sequence to expand our studies of entry into physiologically relevant epithelial cell types. Using the HCMV-GFP reporter virus, we developed an image-based assay and screened a library containing 65,000 compounds for the inhibition of virus entry into fibroblasts. In addition to assessing the effect on virus entry, automated image analysis provided information on compound toxicity and whether the compounds acted as attachment or post-attachment inhibitors. To identify therapeutically viable inhibitors capable of blocking entry in multiple cell types, the inhibitors were screened further for their ability to inhibit virus entry into epithelial cells. Compounds were identified that were able to inhibit virus entry into both cell types at either attachment or post-attachment steps.

Results of a year-long workshop devoted to a review of the physics opportunities of the BABAR experiment at the PEP-II B Factory, at the Stanford Linear Accelerator Center laboratory are presented.

A live chimeric vaccine virus against Japanese encephalitis (JE), ChimeriVax-JE, was used to define methods for optimal, random insertion of foreign immunologic determinants into flavivirus glycoproteins. The conserved M2e peptide of influenza A virus was randomly inserted into the yellow fever-specific NS1 glycoprotein of ChimeriVax-JE. A technique combining plaque purification with immunostaining yielded a recombinant virus that stably expressed M2e at NS1-236 site. The site was found permissive for other inserts. The insertion inhibited NS1 dimerization in vitro, which had no significant effect on virus replication in vitro and immunogenicity in vivo. Two different NS1-specific monoclonal antibodies and a polyclonal antibody efficiently recognized only the NS1 protein dimer, but not monomer. Adaptation of the virus to Vero cells resulted in two amino acid changes upstream from the insert which restored NS1 dimerization. Immunized mice developed high-titer M2e-specific antibodies predominantly of the IgG2A isotype indicative of a Th1-biased response.

Chemogenomics knowledge-based drug discovery approaches aim to extract the knowledge gained from one target and to apply it for the discovery of ligands and hopefully drugs of a new target which is related to the parent target by homology or conserved molecular recognition. Herein, we demonstrate the potential of knowledge-based virtual screening by applying it to the MDM4-p53 protein-protein interaction where the MDM2-p53 protein-protein interaction constitutes the parent reference system; both systems are potentially relevant to cancer therapy. We show that a combination of virtual screening methods, including homology based similarity searching, QSAR (Quantitative Structure-Activity Relationship) methods, HTD (High Throughput Docking), and UNITY pharmacophore searching provide a successful approach to the discovery of inhibitors. The virtual screening hit list is of the magnitude of 50,000 compounds picked from the corporate compound library of approximately 1.2 million compounds. Emphasis is placed on the facts that such campaigns are only feasible because of the now existing HTCP (High throughput Cherry-Picking) automation systems in combination with robust MTS (Medium Throughput Screening) fluorescence-based assays. Given that the MDM2-p53 system constitutes the reference system, it is not surprising that significantly more and stronger hits are found for this interaction compared to the MDM4-p53 system. Novel, selective and dual hits are discovered for both systems. A hit rate analysis will be provided compared to the full HTS (High-throughput Screening).

The Santa Clara River in Southern California provides beneficial uses that include agricultural water supply, groundwater recharge, and rare and endangered species habitat. Significant urbanization has contributed to elevated chloride concentrations along portions of the river in the Santa Clarita Valley and downstream areas. The affected reaches of the Santa Clara River are included on California's list of impaired waters with respect to chloride. A total maximum daily load for chloride, which was originally adopted by the Los Angeles Regional Water Quality Control Board in 2002 and later amended in 2004 and 2006, required special studies to provide the technical basis for establishing appropriate chloride water quality objectives. As part of these studies, a fully integrated groundwater/surface-water numerical model was developed to facilitate the implementation of the chloride total maximum daily load. Modeling results indicated that implementation of expensive water treatment alternatives at two water reclamation plants would not likely lead to consistent compliance with existing chloride objectives in local streams or underlying groundwater basins. Accordingly, the model was used to develop a cooperative alternative water resources management approach. Once implemented, this approach could protect beneficial uses, aid in managing salinity (specifically chloride concentrations) in the Santa Clara River system, improve salt exportation from the study area, and provide enhanced water-supply benefits to water users in affected areas, while providing flexibility and more feasible chloride compliance solutions.