This paper proposes a nonuniform subsampling method for finite mixtures of regression models to reduce large data computational tasks. A general estimator based on a subsample is investigated, and its asymptotic normality is established. We assign optimal subsampling probabilities to data points that minimize the asymptotic mean squared errors of the general estimator and linearly transformed estimators. Since the proposed probabilities depend on unknown parameters, an implementable algorithm is developed. We first approximate the optimal subsampling probabilities using a pilot sample. After that, we select a subsample using the approximated subsampling probabilities and compute estimates using the subsample. We evaluate the proposed method in a simulation study and present a real data example using appliance energy data.
The case corresponds to minimization of high eigenvalues of the Dirichlet Laplacian on rectangles, and so our work generalizes a result of Antunes and Freitas. Similarly, we generalize a Neumann eigenvalue maximization result of van den Berg, Bucur and Gittins. Further, Ariturk and Laugesen recently handled by building on our results here.
The case remains open, and is closely related to minimizing energy levels of harmonic oscillators: which right triangles in the first quadrant with two sides along the axes will enclose the most lattice points, as the area tends to infinity?
Powersum varieties, also called varieties of sums of powers, have provided examples of interesting relations between varieties since their first appearance in the 19th century. One of the most useful tools to study them is apolarity, a notion originally related to the action of differential operators on the polynomial ring. In this work, we make explicit how one can see apolarity in terms of the Cox ring of a variety. In this way, powersum varieties are a special case of varieties of apolar schemes; we explicitly describe examples of such varieties in the case of two toric surfaces, when the Cox ring is particularly well-behaved.
A human scFv display library has been constructed from peripheral blood lymphocytes of a patient suffering from Hashimoto's thyroiditis. Upon induction of Cre recombinase, the amplified VH and VL genes were recombined via two loxP sites inserted in amplification primers to construct in vitro scFv genes. Either soluble scFvs or scFvs displayed on phage were screened for binding to human thyroglobulin after two pannings with this antigen. Three scFvs were obtained which showed very similar nucleotidic sequences. The VH genes expressed display 96.4% VH251 gene, one of the two functional members of the small VH5 family and are mutated in sites already described as âselectively neutralâ mutations and the VL genes are close to the germline DPL8 gene. These scFvs bind not only to human thyroglobulin but also to other self and exogenous antigens.
Immunohistochemical analysis of biopsies, cytology specimens or surgical resection specimens using antibodies directed towards tumor-associated antigens, lineage or differentiation antigens is a technique often used by surgical pathologists to aid in establishing the correct histologic classification of malignant tumors. With the proliferation of experimental approaches to cancer treatment using monoclonal antibodies as targeting agents, it is anticipated that surgical pathologists will increasingly be receiving requests from clinicians to define the antigen profile in biopsy specimens, even when not necessary to render the correct tumor classification. Clinicians may use the immunohistochemically delineated antigen profiles provided by surgical pathologists to plan tailored treatment regimens utilizing monoclonal antibodies to the antigens expressed in the tumor biopsy to target anticancer therapeutic agents. Some of the potential problems in such a process might include the differing sensitivities, and perhaps specificities, of the antibodies used for analyzing the surgical pathology biopsy specimens compared to the monoclonal antibodies actually used {\it in vivo}. Our approach to this dilemma is to develop murine monoclonal antibodies to tumor-associated antigens that can reliably be used to detect antigens in routinely processed surgical pathology specimens as a starting point for further therapeutic monoclonal antibody development.
We previously demonstrated the induction of IFN-Îł in polyneuropathy patients associated with monoclonal gammopathy, but not in patients with presumably non-immuno-logical types of neuropathy. We herein examined mechanism involving release of neutralizing autoantibodies (Aabs) to IFN-Îł in sera from those pateints. In contrast to polyneuropathy patients with monoclonal gammopathy, patients with polyneuropathy of presumably non-immunological types showed increased production of neutralizing Aabs specific for IFN-Îł. These results demonstrate a role for autoimmunity in cytokine regulation. However, their association to the clinical manifestations of the disease requires further investigations, which are necessary for future consideration in therapeutic strategies.
Nilpotency for discrete groups can be defined in terms of central extensions. In this paper, the analogous definition for spaces is stated in terms of principal fibrations having infinite loop spaces as fibers, yielding a new invariant between the classical LS cocategory and the more recent notion of homotopy nilpotency introduced by Biedermann and Dwyer. This allows us to characterize finite homotopy nilpotent loop spaces in the spirit of Hubbuckâs Torus Theorem, and obtain corresponding results for p-compact groups and p-Noetherian groups.
A trispecific F(abâČ)3 antibody conjugate (TAC) with specificities for the FcÎł receptor I (FcÎłRI/CD64), the epidermal growth factor receptor (EGFR) and the HER2/neu antigen has been developed to redirect effector cell-mediated cytotoxicity against cancer cells expressing both or either of the tumor-associated antigens. The TAC was constructed in two steps using the sulfhydryl-specific cross-linker o-phenylenedimaleimide (o-PDM). In step one, a bispecific antibody was prepared by linking the FabâČ fragments of mAb m22 (a murine IgG1 specific for FcÎłRI) and mAb H425 (a humanized IgG1 antibody recognizing EGFR). The conjugation efficiency was about 60%. the second step, the FabâČ fragment of mAb 520C9, a murine IgG1 specific for HER2/neu, was coupled to the bispecific antibody made in step one. About 40% antibody. The purity of the TAC was more than 90% purification. The TAC was characterized in vitro for its ability to bind specifically to all the three antigens and to kill target cells expressing the tumor antigens. In contrast to bispecific conjugates that can only target cells expressing either of the tumor antigens, the TAC was able to bind both the antigens more efficiently in cell-binding assays and to kill tumor cells expressing EGFR and HER2/neu antigens.