A genetic model for undifferentiated cell tumor formation: similar tumors formed by different cell lines transformed by the E1A oncogene

The activation of oncogenes and the mutation/deletion of suppressor genes may be involved in tumor heterogeneity. In an attempt to study tumor heterogeneity, we transformed cell lines from epithelial (PAM 212), mesenchymal (NIH-3T3), or melanocytic origin (L-BIOBR) with the wild type E1a oncogene. To make the cell lines tumorigenic, cells were infected with Harvey sarcoma virus carrying the v-H-ras oncogene. The transformed cells were injected into nude mice and the tumors studied by optical and electron microscopy. The tumors formed by v-H-ras-transformed cells consisted of epitheliod melanomas, spindle cells sarcomas and poorly-differentiated carcinomas, depending on the cell of origin. In contrast, the tumors obtained from cells also carrying the E1a oncogene showed a predominant small and undifferentiated cell pattern regardless of the cell of origin. We conclude that the E1a oncogene products induce a negative control of differentiation, independent of the cell type, and that tumors formed by cells carrying the E1a oncogene display an undifferentiated cell pattern.     

Cyclic variations in the permeability of the cell wall of Saccharomyces cerevisiae.

To study cell-cycle-related variations in wall permeability of Saccharomyces cerevisiae, two approaches were used. First, an asynchronous culture was fractionated by centrifugal elutriation into subpopulations containing cells of increasing size. The subpopulations represented different stages of the cell cycle as judged by light microscopy. Cell wall porosity increased when these subpopulations became enriched with budded cells. Secondly, synchronous cultures were obtained by releasing MATa cells from alpha-factor induced G1-arrest. These cultures grew synchronously for at least two generations. The cell wall porosity increased sharply in these cultures, shortly before buds became visible and was maximal during the initial stages of bud growth. It decreased in cells which had completed nuclear migration and before abscission of the bud had occurred. The porosity reached its lowest value during abscission and in unbudded cells. We examined the incorporation of mannoproteins into the wall during the cell cycle. SDS-extractable mannoproteins were incorporated continuously. However, the incorporation of glucanase-extractable mannoproteins, which are known to affect cell wall porosity, showed cyclic oscillations and reached its maximum after nuclear migration. This coincided with a rapid decrease in cell wall porosity, indicating that glucanase-extractable mannoproteins might contribute to this decrease.     

Process-based cost modeling of photonics manufacture: the cost competitiveness of monolithic integration of a 1550-nm DFB laser and an electroabsorptive modulator on an InP platform

The monolithic integration of components holds promise to increase network functionality and reduce packaging expense. Integration also drives down yield due to manufacturing complexity and the compounding of failures across devices. Consensus is lacking on the economically preferred extent of integration. Previous studies on the cost feasibility of integration have used high-level estimation methods. This study instead focuses on accurate-to-industry detail, basing a process-based cost model of device manufacture on data collected from 20 firms across the optoelectronics supply chain. The model presented allows for the definition of process organization, including testing, as well as processing conditions, operational characteristics, and level of automation at each step. This study focuses on the cost implications of integration of a 1550-nm DFB laser with an electroabsorptive modulator on an InP platform. Results show the monolithically integrated design to be more cost competitive over discrete component options regardless of production scale. Dominant cost drivers are packaging, testing, and assembly. Leveraging the technical detail underlying model projections, component alignment, bonding, and metal-organic chemical vapor deposition (MOCVD) are identified as processes where technical improvements are most critical to lowering costs. Such results should encourage exploration of the cost advantages of further integration and focus cost-driven technology development.     

A survey on approaches to gridification

The Grid shows itself as a globally distributed computing environment, in which hardware and software resources are virtualized to transparently provide applications with vast capabilities. Just like the electrical power grid, the Grid aims at offering a powerful yet easy‐to‐use computing infrastructure to which applications can be easily ‘plugged’ and efficiently executed. Unfortunately, it is still very difficult to Grid‐enable applications, since current tools force users to take into account many details when adapting applications to run on the Grid. In this paper, we survey some of the recent efforts in providing tools for easy gridification of applications and propose several taxonomies to identify approaches followed in the materialization of such tools. We conclude this paper by describing common features among the proposed approaches, and by pointing out open issues and future directions in the research and development of gridification methods. Copyright © 2007 John Wiley & Sons, Ltd.     

Radiation effects in a model ceramic for nuclear waste disposal

The safe immobilization of nuclear waste in geological repositories is one of the major scientific challenges facing humanity today. Crystalline ceramics hold the promise of locking up actinides from nuclear fuel and excess weapons plutonium in their structure thereby isolating them from the environment. This paper presents the atomistic details of radiation damage in a model ceramic, zircon.     

Confidence voting method ensemble applied to off-line signature verification

In this paper, a new approximation to off-line signature verification is proposed based on two-class classifiers using an expert decisions ensemble. Different methods to extract sets of local and a global features from the target sample are detailed. Also a normalization by confidence voting method is used in order to decrease the final equal error rate (EER). Each set of features is processed by a single expert, and on the other approach proposed, the decisions of the individual classifiers are combined using weighted votes. Experimental results are given using a subcorpus of the large MCYT signature database for random and skilled forgeries. The results show that the weighted combination outperforms the individual classifiers significantly. The best EER obtained were 6.3 % in the case of skilled forgeries and 2.31 % in the case of random forgeries.     

IR and Raman studies and effect of γ radiation on crystallization of some lead borate glasses containing Al2O3

IR and Raman spectra of glass ceramics based on PbO-Cr₂O₃-B₂O₃glass composition system have been studied. The bands characteristic of BO₃. and BO₄ functional groups are present in all the samples. An incorporation of Al₂O₃(up to 5 mol%) in the initial glass composition considerably changes the glass network structure and relative concentrations of BO₃ and BO₄ groups. The composition 50 PbO-20 Cr₂O₃-25 B₂O₃-5 Al₂O₃(in mol%) reveals a maximum fraction of boron in the BO₄ group. A sample of this composition heat treated at 850° C for 25 h shows a maximum crystallization fraction with Pb₂O · CrO₄ as a prominent crystalline phase. The glasses irradiated with rays inhibit the crystallization into the Pb₂O · CrO₄ phase. They also show relatively smaller thermal conductivity.     

Adenovirus-Mediated Inducible Expression of a PD-L1 Blocking Antibody in Combination with Macrophage Depletion Improves Survival in a Mouse Model of Peritoneal Carcinomatosis

Immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy in a growing number of malignancies. However, overcoming primary or secondary resistances is difficult due to pharmacokinetics issues and side effects associated with high systemic exposure. Local or regional expression of monoclonal antibodies (mAbs) using gene therapy vectors can alleviate this problem. In this work, we describe a high-capacity adenoviral vector (HCA-EFZP-aPDL1) equipped with a mifepristone-inducible system for the controlled expression of an anti-programmed death ligand 1 (PD-L1) blocking antibody. The vector was tested in an immune-competent mouse model of colorectal cancer based on implantation of MC38 cells. A single local administration of HCA-EFZP-aPDL1 in subcutaneous lesions led to a significant reduction in tumor growth with minimal release of the antibody in the circulation. When the vector was tested in a more stringent setting (rapidly progressing peritoneal carcinomatosis), the antitumor effect was marginal even in combination with other immune-stimulatory agents such as polyinosinic-polycytidylic acid (pI:C), blocking mAbs for T cell immunoglobulin, mucin-domain containing-3 (TIM-3) or agonistic mAbs for 4-1BB (CD137). In contrast, macrophage depletion by clodronate liposomes enhanced the efficacy of HCA-EFZP-aPDL1. These results highlight the importance of addressing macrophage-associated immunoregulatory mechanisms to overcome resistance to ICIs in the context of colorectal cancer.