Development of Nanocomposites for Solid Freeform Fabrication

Nanocomposites in which the constituents are mixed on a nanorneter scale can provide important advantages in the Selective Laser Sintering (SLS) and Selective Laser Reactive Sintering (SLRS) processes. The larger surface area and grain boundaries in the nanocolnposites compared to that in the conventional microcomposites are expected to enhance the solid state diffusion during laser irradiation as well as during any other subsequent processes. Our strategy is to design and develop nanocomposites in which one nanosize cOlnponent has a lower melting point than the other nanosize component, either of which can serve as the matrix phase. The nanoscale dispersion of the low melting component can aid the sintering process during SLS or SLRS. Nanocomposite powders of AI203-COOx, Ab03-NiO, A1203-CO and A1203-Ni have been synthesized by sol-gel processing and are evaluated by SLS.Mechanical Engineerin

Process simulation based decisional tool to evaluate strategies for continuous downstream bioprocess implementation - A CDMO perspective

To maintain a competitive space in the rapidly expanding and highly competitive market, many biopharmaceutical companies are outsourcing to contract development and manufacturing organizations (CDMOs) to accelerate research and development, shorten the time to market, alleviate internal capacity and technical constraints, and reduce risks associated with production [1]. To acquire new and maintain current clients, CDMOs must have strong, diverse technical offerings for development, manufacture, and testing of products with competitive pricing and timelines [2]. Adopting innovative technologies like continuous downstream processing can help debottleneck the process and reduce processing time, which is the most appealing to CDMOs as it translates to an increased number of batches per year. The majority of continuous processing assessments to date have focused on cost of goods and not on the time reduction potential [3-7]. End-to-end continuous downstream processing is not always practical as CDMOs must accommodate a wide range of molecules and processes. Hence, it is imperative to evaluate and customize continuous production based on client needs. Application of process simulation as a decisional tool to select an appropriate downstream processing strategy was evaluated. Two modelling programs were evaluated: BioSolve Process and SuperPro Designer®. Fully continuous and hybrid (continuous Protein A operation only) downstream processing were assessed for a 2000 L fed-batch bioreactor producing 1, 5, and 10 g/L of monoclonal antibody at 40 and 200 kg production demands. Hybrid and continuous processing decreased batch duration by 20% and 60%, respectively. Continuous processing was more favorable for higher titer processes (≥ 5 g/L). The largest cost reductions were observed for 5 and 10 g/L titer processes during 40 kg production. The results highlight the business case for continuous downstream bioprocessing especially at a CDMO. Selection of a processing method will be influenced by a range of factors and the impact can easily be assessed using process simulation. Therefore, it is recommended that CDMOs use process simulation to ensure the most favorable processing strategy is selected. [1] O. Gassmann, A. Schuhmacher, M. von Zedtwitz, G. Reepmeyer, The Make-or-Buy Challenge: How to In-and Outsource Innovation, Leading Pharmaceutical Innovation, Springer2018, pp. 79-110. [2] R. Hernandez, Contract Biomanufacturing Firms Become More Specialized, BioPharm International, 28 (2015) 22-27. [3] D. Pollard, M. Brower, Y. Abe, A.G. Lopes, Standardized Economic Cost Modeling for Next-Generation MAb Production, BioProcess Int, (2016). [4] A. Xenopoulos, A new, integrated, continuous purification process template for monoclonal antibodies: process modeling and cost of goods studies, Journal of biotechnology, 213 (2015) 42-53. [5] J. Hummel, M. Pagkaliwangan, X. Gjoka, T. Davidovits, R. Stock, T. Ransohoff, R. Gantier, M. Schofield, Modeling the Downstream Processing of Monoclonal Antibodies Reveals Cost Advantages for Continuous Methods for a Broad Range of Manufacturing Scales, Biotechnology journal, (2018) 1700665. [6] J. Pollock, J. Coffman, S.V. Ho, S.S. Farid, Integrated continuous bioprocessing: Economic, operational, and environmental feasibility for clinical and commercial antibody manufacture, Biotechnology progress, 33 (2017) 854-866. [7] S. Klutz, L. Holtmann, M. Lobedann, G. Schembecker, Cost evaluation of antibody production processes in different operation modes, Chemical Engineering Science, 141 (2016) 63-74

A novel autotransporter of uropathogenic Proteus mirabilis is both a cytotoxin and an agglutinin

One of the six predicted Proteus mirabilis autotransporters (ATs), ORF c2341, is predicted to contain a serine protease motif and was earlier identified as an immunogenic outer membrane protein in P. mirabilis . The 3.2 kb gene encodes a 117 kDa protein with a 58-amino-acid-long signal peptide, a 75-kDa-long N-terminal passenger domain and a 30-kDa-long C-terminal translocator. Affinity-purified 110 kDa AT exhibited chymotrypsin-like activity and hydrolysed N -Suc–Ala–Ala–Pro–Phe– p Na and N -Suc–Ala–Ala–Pro–Leu– p Na with a K M of 22 μM and 31 μM, respectively, under optimal pH of 8.5–9.0 in a Ca 2+ -dependent manner. Activity was inhibited by subtilase-specific inhibitors leupeptin and chymostatin. Both the cell-associated and purified form elicited cytopathic effects on cultured kidney and bladder epithelial cells. Substrate hydrolysis as well as cytotoxicity was associated with the passenger domain and was compromised upon mutation of any of the catalytic residues (Ser366, His147 and Asp533). At alkaline pH and optimal cell density, the AT also promoted autoaggregation of P. mirabilis and this function was independent of its protease activity. Cytotoxicity, autoaggregation and virulence were significantly reduced in an isogenic pta mutant of P. mirabilis . Proteus toxic agglutinin (Pta) represents a novel autotransported cytotoxin with no bacterial homologues that works optimally in the alkalinized urinary tract, a characteristic of urease-mediated urea hydrolysis during P. mirabilis infection.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73221/1/j.1365-2958.2008.06199.x.pd

Visual motherese? Signal-to-noise ratios in toddler-directed television

Younger brains are noisier information processing systems; this means that information for younger individuals has to allow clearer differentiation between those aspects that are required for the processing task in hand (the ‘signal’) and those that are not (the ‘noise’). We compared toddler-directed and adult-directed TV programmes (TotTV/ATV). We examined how low-level visual features (that previous research has suggested influence gaze allocation) relate to semantic information, namely the location of the character speaking in each frame. We show that this relationship differs between TotTV and ATV. First, we conducted Receiver Operator Characteristics analyses and found that feature congestion predicted speaking character location in TotTV but not ATV. Second, we used multiple analytical strategies to show that luminance differentials (flicker) predict face location more strongly in TotTV than ATV. Our results suggest that TotTV designers have intuited techniques for controlling toddler attention using low-level visual cues. The implications of these findings for structuring childhood learning experiences away from a screen are discussed

Missed opportunities in full immunization coverage:findings from low- and lower-middle-income countries

Background: An estimated 23 million infants are still not being benefitted from routine immunization services. We assessed how many children failed to be fully immunized even though they or their mothers were in contact with health services to receive other interventions. Design: Fourteen countries with Demographic and Health Surveys and Multiple Indicator Cluster Surveys carried out after 2000 and with coverage for DPT (Diphtheria-tetanus-pertussis) vaccine below 70% were selected. We defined full immunization coverage (FIC) as having received one dose of BCG (bacille Calmette-Guérin), one dose of measles, three doses of polio, and three doses of DPT vaccines. We tabulated FIC against: antenatal care (ANC), skilled birth attendance (SBA), postnatal care for the mother (PNC), vitamin A supplementation (VitA) for the child, and sleeping under an insecticide-treated bed-net (ITN). Missed opportunities were defined as the percentage of children who failed to be fully immunized among those receiving one or more other interventions. Results: Children who received other health interventions were also more likely to be fully immunized. In nearly all countries, FIC was lowest among children born to mothers who failed to attend ANC, and highest when the mother had four or more ANC visits Côte d'Ivoire presented the largest difference in FIC: 54 percentage points (pp) between having four or more ANC visits and lack of ANC. SBA was also related with higher FIC. For instance, the coverage in children without SBA was 36 pp lower than for those with SBA in Nigeria. The largest absolute difference on FIC in relation to PNC was observed for Ethiopia: 31 pp between those without and with PNC. FIC was also positively related with having received VitA. The largest absolute difference was observed in DR Congo: 41 pp. The differences in FIC among whether or not children slept under ITN were much smaller than for other interventions. Haiti presented the largest absolute difference: 16 pp. Conclusions: Our results show the need to develop and implement strategies to vaccinate all children who contact health services in order to receive other interventions

A new type of reconstruction on the InSb() surface determined by grazing incidence X-ray diffraction

The (3×3) reconstruction of the InSb( ) surface has been investigated by grazing incidence X-ray diffraction and scanning tunneling microscopy. The structure is characterized by 6-atom rings on top of a slightly buckled InSb top double layer. Two types of rings have been found, an elliptic ring consisting of 4 In and 2 Sb atoms and a trigonal ring with 3 In and 3 Sb atoms. The bond angles and lengths are consistent with the concept of rehybridization and depolarization which explains the reconstructions of the (111) and (110) surfaces

Invasive Allele Spread under Preemptive Competition

We study a discrete spatial model for invasive allele spread in which two alleles compete preemptively, initially only the "residents" (weaker competitors) being present. We find that the spread of the advantageous mutation is well described by homogeneous nucleation; in particular, in large systems the time-dependent global density of the resident allele is well approximated by Avrami's law.Comment: Computer Simulation Studies in Condensed Matter Physics XVIII, edited by D.P. Landau, S.P. Lewis, and H.-B. Schuttler, (Springer, Heidelberg, Berlin, in press

The KMOS Deep Survey (KDS) – I. Dynamical measurements of typical star-forming galaxies at z ≃ 3.5

We present dynamical measurements from the KMOS (K-band Multi-Object Spectrograph) Deep Survey (KDS), which is comprised of 77 typical star-forming galaxies at z z ≃ 3.5 in the mass range 9.0 1), with the sample average VC/σint value much smaller than at lower redshift. After carefully selecting comparable star-forming samples at multiple epochs, we find that the rotation-dominated fraction evolves with redshift with a z−0.2 dependence. The rotation-dominated KDS galaxies show no clear offset from the local rotation velocity-stellar mass (i.e. VC − M⋆) relation, although a smaller fraction of the galaxies are on the relation due to the increase in the dispersion-dominated fraction. These observations are consistent with a simple equilibrium model picture, in which random motions are boosted in high-redshift galaxies by a combination of the increasing gas fractions, accretion efficiency, specific star-formation rate and stellar feedback and which may provide significant pressure support against gravity on the galactic disk scale

High-precision determination of transition amplitudes of principal transitions in Cs from van der Waals coefficient C_6

A method for determination of atomic dipole matrix elements of principal transitions from the value of dispersion coefficient C_6 of molecular potentials correlating to two ground-state atoms is proposed. The method is illustrated on atomic Cs using C_6 deduced from high-resolution Feshbach spectroscopy. The following reduced matrix elements are determined < 6S_{1/2} || D || 6P_{1/2} > =4.5028(60) |e| a0 and =6.3373(84) |e| a0 (a0= 0.529177 \times 10^{-8} cm.) These matrix elements are consistent with the results of the most accurate direct lifetime measurements and have a similar uncertainty. It is argued that the uncertainty can be considerably reduced as the coefficient C_6 is constrained further.Comment: 4 pages; 3 fig

Cluster Monte Carlo study of multi-component fluids of the Stillinger-Helfand and Widom-Rowlinson type

Phase transitions of fluid mixtures of the type introduced by Stillinger and Helfand are studied using a continuum version of the invaded cluster algorithm. Particles of the same species do not interact, but particles of different types interact with each other via a repulsive potential. Examples of interactions include the Gaussian molecule potential and a repulsive step potential. Accurate values of the critical density, fugacity and magnetic exponent are found in two and three dimensions for the two-species model. The effect of varying the number of species and of introducing quenched impurities is also investigated. In all the cases studied, mixtures of $q$-species are found to have properties similar to $q$-state Potts models.Comment: 25 pages, 5 figure