Safe Computing

So-called worms, viruses, and Trojan horses that attack computer systems are defined. The vehicle that allows these attacks to occur, namely, the open computer internetwork, is examined. The problem of providing protection against attack in an internetwork environment is discussed. The need for professional responsibility on the part of the scientific and engineering community in enforcing strong ethical practices and neither tolerating nor condoning such practices is stressed

A Statistical Mechanical Load Balancer for the Web

The maximum entropy principle from statistical mechanics states that a closed system attains an equilibrium distribution that maximizes its entropy. We first show that for graphs with fixed number of edges one can define a stochastic edge dynamic that can serve as an effective thermalization scheme, and hence, the underlying graphs are expected to attain their maximum-entropy states, which turn out to be Erdos-Renyi (ER) random graphs. We next show that (i) a rate-equation based analysis of node degree distribution does indeed confirm the maximum-entropy principle, and (ii) the edge dynamic can be effectively implemented using short random walks on the underlying graphs, leading to a local algorithm for the generation of ER random graphs. The resulting statistical mechanical system can be adapted to provide a distributed and local (i.e., without any centralized monitoring) mechanism for load balancing, which can have a significant impact in increasing the efficiency and utilization of both the Internet (e.g., efficient web mirroring), and large-scale computing infrastructure (e.g., cluster and grid computing).Comment: 11 Pages, 5 Postscript figures; added references, expanded on protocol discussio

The PARSE Programming Paradigm. Part I: Software Development Methodology. Part II: Software Development Support Tools

The programming methodology of PARSE (parallel software environment), a software environment being developed for reconfigurable non-shared memory parallel computers, is described. This environment will consist of an integrated collection of language interfaces, automatic and semi-automatic debugging and analysis tools, and operating system —all of which are made more flexible by the use of a knowledge-based implementation for the tools that make up PARSE. The programming paradigm supports the user freely choosing among three basic approaches /abstractions for programming a parallel machine: logic-based descriptive, sequential-control procedural, and parallel-control procedural programming. All of these result in efficient parallel execution. The current work discusses the methodology underlying PARSE, whereas the companion paper, “The PARSE Programming Paradigm — II: Software Development Support Tools,” details each of the component tools

Experimental Benchmarks and Initial Evaluation of the Performance of the PASM System Prototype

The work reported here represents experiences with the PASM parallel processing system prototype during its first operational year. Most of the experiments were performed by students in the Fall semester of 1987. The first programming, and the first timing measurements, were made during the summer of 1987 by Sam Fineberg. The goal of the collection of experiments presented here was to undertake an Application-driven Architecture Study of the PASM system as a paradigm for parallel architecture evaluation in general. PASM was an excellent vehicle for experimenting with this evaluation technique due to its unique architectural features. Among these are: 1. A reconfigurable, partitionable multistage circuit-switched network. 2. Support for both SIMD and MIMD programs. 3. Ability to execute hybrid SIMD/MIMD programs. 4. An instruction queue which allows overlap of control-flow and data manipulation between micro-control (MC) units and processing elements (PE). It had been hypothesized that superlinear speed-up over the number of PEs could be attained with this feature, and experimental results verified this. 5. Support for barrier synchronization of MIMD tasks. This feature was exploited in some non-standard ways to show the ability to decouple variant length SIMD instructions into multiple MIMD streams for an overall performance benefit. This type of study is expected to continue in the future on PASM and other parallel machines at Purdue. This report should serve as a guide for this future work as well

Bioinformatic Analysis of Gene Sets Regulated by Ligand-Activated and Dominant-Negative Peroxisome Proliferator-Activated Receptor in Mouse Aorta

Drugs that activate PPARγ improve glucose sensitivity and lower blood pressure, whereas dominant negative mutations in PPARγ cause severe insulin resistance and hypertension. We hypothesize that these PPARγ mutants regulate target genes opposite to that of ligand-mediated activation and tested this hypothesis on a genome-wide scale

Microfluidics with fluid walls

Microfluidics has great potential, but the complexity of fabricating and operating devices has limited its use. Here we describe a method - Freestyle Fluidics - that overcomes many key limitations. In this method, liquids are confined by fluid (not solid) walls. Aqueous circuits with any 2D shape are printed in seconds on plastic or glass Petri dishes; then, interfacial forces pin liquids to substrates, and overlaying an immiscible liquid prevents evaporation. Confining fluid walls are pliant and resilient; they self-heal when liquids are pipetted through them. We drive flow through a wide range of circuits passively by manipulating surface tension and hydrostatic pressure, and actively using external pumps. Finally, we validate the technology with two challenging applications - triggering an inflammatory response in human cells and chemotaxis in bacterial biofilms. This approach provides a powerful and versatile alternative to traditional microfluidics.The complexity of fabricating and operating microfluidic devices limits their use. Walsh et al. describe a method in which circuits are printed as quickly and simply as writing with a pen, and liquids in them are confined by fluid instead of solid walls

Microenvironment alters epigenetic and gene expression profiles in Swarm rat chondrosarcoma tumors

<p>Abstract</p> <p>Background</p> <p>Chondrosarcomas are malignant cartilage tumors that do not respond to traditional chemotherapy or radiation. The 5-year survival rate of histologic grade III chondrosarcoma is less than 30%. An animal model of chondrosarcoma has been established - namely, the Swarm Rat Chondrosarcoma (SRC) - and shown to resemble the human disease. Previous studies with this model revealed that tumor microenvironment could significantly influence chondrosarcoma malignancy.</p> <p>Methods</p> <p>To examine the effect of the microenvironment, SRC tumors were initiated at different transplantation sites. Pyrosequencing assays were utilized to assess the DNA methylation of the tumors, and SAGE libraries were constructed and sequenced to determine the gene expression profiles of the tumors. Based on the gene expression analysis, subsequent functional assays were designed to determine the relevancy of the specific genes in the development and progression of the SRC.</p> <p>Results</p> <p>The site of transplantation had a significant impact on the epigenetic and gene expression profiles of SRC tumors. Our analyses revealed that SRC tumors were hypomethylated compared to control tissue, and that tumors at each transplantation site had a unique expression profile. Subsequent functional analysis of differentially expressed genes, albeit preliminary, provided some insight into the role that thymosin-β4, c-fos, and CTGF may play in chondrosarcoma development and progression.</p> <p>Conclusion</p> <p>This report describes the first global molecular characterization of the SRC model, and it demonstrates that the tumor microenvironment can induce epigenetic alterations and changes in gene expression in the SRC tumors. We documented changes in gene expression that accompany changes in tumor phenotype, and these gene expression changes provide insight into the pathways that may play a role in the development and progression of chondrosarcoma. Furthermore, specific functional analysis indicates that thymosin-β4 may have a role in chondrosarcoma metastasis.</p

Chinese herb related molecules of cancer-cell-apoptosis: a minireview of progress between Kanglaite injection and related genes

Many kinds of Chinese herb had been confirmed to have the character of anti-tumor, clinical reports about anti-tumor effects of Chinese herb had also been found in recent years, but most of the reports were focused on the clinical treatment of effectiveness for Chinese herb, on the other hand, review about Chinese herbal related with molecules on cancer-cell-apoptosis was seldom, many scientists could not believe such kinds of clinical describes about anti-tumor effects for Chinese herb, because these describes were lack of molecular biology evidence. Kanglaite(KLT) injection is an anti-tumor new drug which extracts from Chinese medicine-coix seed with modern advanced pharmaceutical technology, it is also a new biphase extended-spectrum anticancer medicine, the food and drug administration(FDA) of United States also approved a phase II trial of KLT to test its efficacy in treating non-small-cell lung cancer. Some studies show it could inhibit some anti-apoptotic gene and activate some pro-apoptotic gene, its injection solution is one of the new anticancer medicine that can significantly inhibit a various kinds of tumor cells, so it has become the core of research that how to further explore KLT injection to promote tumor cell apoptosis by impacting on related genes. In this review, the relationship between KLT and some tumor cell apoptosis molecules had been discussed and reviewed generally

An E2F1-Mediated DNA Damage Response Contributes to the Replication of Human Cytomegalovirus

DNA damage resulting from intrinsic or extrinsic sources activates DNA damage responses (DDRs) centered on protein kinase signaling cascades. The usual consequences of inducing DDRs include the activation of cell cycle checkpoints together with repair of the damaged DNA or induction of apoptosis. Many DNA viruses elicit host DDRs during infection and some viruses require the DDR for efficient replication. However, the mechanism by which DDRs are activated by viral infection is poorly understood. Human cytomegalovirus (HCMV) infection induces a DDR centered on the activation of ataxia telangiectasia mutated (ATM) protein kinase. Here we show that HCMV replication is compromised in cells with inactivated or depleted ATM and that ATM is essential for the host DDR early during infection. Likewise, a downstream target of ATM phosphorylation, H2AX, also contributes to viral replication. The ATM-dependent DDR is detected as discrete, nuclear γH2AX foci early in infection and can be activated by IE proteins. By 24 hpi, γH2AX is observed primarily in HCMV DNA replication compartments. We identified a role for the E2F1 transcription factor in mediating this DDR and viral replication. E2F1, but not E2F2 or E2F3, promotes the accumulation of γH2AX during HCMV infection or IE protein expression. Moreover, E2F1 expression, but not the expression of E2F2 or E2F3, is required for efficient HCMV replication. These results reveal a novel role for E2F1 in mediating an ATM-dependent DDR that contributes to viral replication. Given that E2F activity is often deregulated by infection with DNA viruses, these observations raise the possibility that an E2F1-mediated mechanism of DDR activation may be conserved among DNA viruses