He Scattering from Random Adsorbates, Disordered Compact Islands and Fractal Submonolayers: Intensity Manifestations of Surface Disorder

A theoretical study is made on He scattering from three fundamental classes of disordered ad-layers: (a) Translationally random adsorbates, (b) disordered compact islands and (c) fractal submonolayers. The implications of the results to experimental studies of He scattering from disordered surfaces are discussed, and a combined experimental-theoretical study is made for Ag submonolayers on Pt(111). Some of the main theoretical findings are: (1) Structural aspects of the calculated intensities from translationally random clusters were found to be strongly correlated with those of individual clusters. (2) Low intensity Bragg interference peaks appear even for scattering from very small ad-islands, and contain information on the ad-island local electron structure. (3) For fractal islands, just as for islands with a different structure, the off-specular intensity depends on the parameters of the He/Ag interaction, and does not follow a universal power law as previously proposed in the literature. In the experimental-theoretical study of Ag on Pt(111), we use first experimental He scattering data from low-coverage (single adsorbate) systems to determine an empirical He/Ag-Pt potential of good quality. Then, we carry out He scattering calculations for high coverage and compare with experiments. The conclusions are that the actual experimental phase corresponds to small compact Ag clusters of narrow size distribution, translationally disordered on the surface.Comment: 36 double-spaced pages, 10 figures; accepted by J. Chem. Phys., scheduled to appear March 8. More info available at http://www.fh.huji.ac.il/~dani

Histamine production during the anti-allograft response. Demonstration of a new lymphokine enhancing histamine synthesis

Histamine production is greatly increased during culture of allograft recipient spleen cells in the presence of immunizing cells (secondary mixed leukocyte cultures [MLC]) as compared to that found in primary MLC (i.e., without previous allograft). This phenomenon appears after 24 h of culture and reaches its maximum at 48 h. Optimal increased histamine production is observed when MLC is performed with spleen cells removed from mice during rejection. This increased production of histamine during secondary MLC results from the action of a lymphokine: the histamine-producing cell stimulating factor (HCSF). This factor is released by T lymphocytes. Its production requires specific stimulation of the recipient lymphocytes because increase in histamine production during secondary MLC can be only observed when recipient cells are cultured with stimulating cells bearing at least one homology at K or D loci with immunizing cells. HCSF acts on a cell which is present in bone marrow, spleen, blood, and peritoneal cells but absent in thymus or lymph node cells. This target cell is found in the less-dense layer of a discontinuous Ficoll-gradient of bone marrow cells. HCSF is heat stable, destroyed by trypsin treatment, and has a molecular weight between 50,000 and 100,000. It acts on its target cells by increasing histidine decarboxylase activity

Modulation of tumour colony growth by irradiated accessory cells.

The ability of human tumour cells to form colonies in soft agar is enhanced by the presence of autologous phagocytic/adherent cells. We investigated the effect of irradiation on the ability of the adherent cells to support human tumour colony formation. Relatively low doses of irradiation significantly increased the growth enhancing ability of adherent cells in 17/19 cases. The possibility that the enhancement was mediated by inactivation of radiosensitive contaminating lymphocytes was explored. Depletion of T lymphocytes from unirradiated adherent cells by a monoclonal antibody and complement resulted in little overall change in tumour colony growth. However, elimination of only the suppressor subset (OKT8+) of T lymphocytes resulted in increased colony growth relative to control values obtained with unirradiated adherent cells. In contrast, depletion of T lymphocytes from irradiated adherent cells by a pan T monoclonal antibody and complement decreased colony formation. Thus, the ability of irradiated macrophages to enhance tumour colony growth appeared to be mediated by a T lymphocyte. The effect of irradiation on isolated populations of macrophages and T lymphocytes was also examined. The enhanced ability of irradiated adherent cells to support tumor colony growth appeared to have been due to treatment of T lymphocytes alone. The results indicate that both adherent macrophages and lymphocytes may influence the growth of clonogenic human tumour cells

Elastic Scattering by Deterministic and Random Fractals: Self-Affinity of the Diffraction Spectrum

The diffraction spectrum of coherent waves scattered from fractal supports is calculated exactly. The fractals considered are of the class generated iteratively by successive dilations and translations, and include generalizations of the Cantor set and Sierpinski carpet as special cases. Also randomized versions of these fractals are treated. The general result is that the diffraction intensities obey a strict recursion relation, and become self-affine in the limit of large iteration number, with a self-affinity exponent related directly to the fractal dimension of the scattering object. Applications include neutron scattering, x-rays, optical diffraction, magnetic resonance imaging, electron diffraction, and He scattering, which all display the same universal scaling.Comment: 20 pages, 11 figures. Phys. Rev. E, in press. More info available at http://www.fh.huji.ac.il/~dani

Double Threshold Digraphs

A semiorder is a model of preference relations where each element x is associated with a utility value alpha(x), and there is a threshold t such that y is preferred to x iff alpha(y) - alpha(x) > t. These are motivated by the notion that there is some uncertainty in the utility values we assign an object or that a subject may be unable to distinguish a preference between objects whose values are close. However, they fail to model the well-known phenomenon that preferences are not always transitive. Also, if we are uncertain of the utility values, it is not logical that preference is determined absolutely by a comparison of them with an exact threshold. We propose a new model in which there are two thresholds, t_1 and t_2; if the difference alpha(y) - alpha(x) is less than t_1, then y is not preferred to x; if the difference is greater than t_2 then y is preferred to x; if it is between t_1 and t_2, then y may or may not be preferred to x. We call such a relation a (t_1,t_2) double-threshold semiorder, and the corresponding directed graph G = (V,E) a (t_1,t_2) double-threshold digraph. Every directed acyclic graph is a double-threshold digraph; increasing bounds on t_2/t_1 give a nested hierarchy of subclasses of the directed acyclic graphs. In this paper we characterize the subclasses in terms of forbidden subgraphs, and give algorithms for finding an assignment of utility values that explains the relation in terms of a given (t_1,t_2) or else produces a forbidden subgraph, and finding the minimum value lambda of t_2/t_1 that is satisfiable for a given directed acyclic graph. We show that lambda gives a useful measure of the complexity of a directed acyclic graph with respect to several optimization problems that are NP-hard on arbitrary directed acyclic graphs

Nanoscale integration of single cell biologics discovery processes using optofluidic manipulation and monitoring.

The new and rapid advancement in the complexity of biologics drug discovery has been driven by a deeper understanding of biological systems combined with innovative new therapeutic modalities, paving the way to breakthrough therapies for previously intractable diseases. These exciting times in biomedical innovation require the development of novel technologies to facilitate the sophisticated, multifaceted, high-paced workflows necessary to support modern large molecule drug discovery. A high-level aspiration is a true integration of "lab-on-a-chip" methods that vastly miniaturize cellulmical experiments could transform the speed, cost, and success of multiple workstreams in biologics development. Several microscale bioprocess technologies have been established that incrementally address these needs, yet each is inflexibly designed for a very specific process thus limiting an integrated holistic application. A more fully integrated nanoscale approach that incorporates manipulation, culture, analytics, and traceable digital record keeping of thousands of single cells in a relevant nanoenvironment would be a transformative technology capable of keeping pace with today's rapid and complex drug discovery demands. The recent advent of optical manipulation of cells using light-induced electrokinetics with micro- and nanoscale cell culture is poised to revolutionize both fundamental and applied biological research. In this review, we summarize the current state of the art for optical manipulation techniques and discuss emerging biological applications of this technology. In particular, we focus on promising prospects for drug discovery workflows, including antibody discovery, bioassay development, antibody engineering, and cell line development, which are enabled by the automation and industrialization of an integrated optoelectronic single-cell manipulation and culture platform. Continued development of such platforms will be well positioned to overcome many of the challenges currently associated with fragmented, low-throughput bioprocess workflows in biopharma and life science research