Computing median and antimedian sets in median graphs

The median (antimedian) set of a profile π = (u1, . . . , uk) of vertices of a graphG is the set of vertices x that minimize (maximize) the remoteness i d(x,ui ). Two algorithms for median graphs G of complexity O(nidim(G)) are designed, where n is the order and idim(G) the isometric dimension of G. The first algorithm computes median sets of profiles and will be in practice often faster than the other algorithm which in addition computes antimedian sets and remoteness functions and works in all partial cubes

Soft Computing Approach for Optimization of siRNA Efficiency Prediction for Post-transcriptional Gene Silencing

Post-transcriptional gene silencing by RNA interference is mediated by small interfering RNA called siRNA. This gene silencing mechanism can be exploited therapeutically to a wide variety of disease-associated targets, especially in AIDS, neurodegenerative diseases, cholesterol and cancer on mice with the hope of extending these approaches to treat humans. Over the recent past, a significant amount of work has been undertaken to understand the gene silencing mediated by exogenous siRNA. The design of efficient exogenous siRNA sequences is challenging because of many issues related to siRNA. While designing efficient siRNA, target mRNAs must be selected such that their corresponding siRNAs are likely to be efficient against that target and unlikely to accidentally silence other transcripts due to sequence similarity. So before doing gene silencing by siRNAs, it is essential to analyze their off-target effects in addition to their inhibition efficiency against a particular target. Hence designing exogenous siRNA with good knock-down efficiency and target specificity is an area of concern to be addressed. Some methods have been developed already by considering both inhibition efficiency and off-target possibility of siRNA against agene. Out of these methods, only a few have achieved good inhibition efficiency, specificity and sensitivity. The main focus of this thesis is to develop computational methods to optimize the efficiency of siRNA in terms of “inhibition capacity and off-target possibility” against target mRNAs with improved efficacy, which may be useful in the area of gene silencing and drug design for tumor development. This study aims to investigate the currently available siRNA prediction approaches and to devise a better computational approach to tackle the problem of siRNA efficacy by inhibition capacity and off-target possibility. The strength and limitations of the available approaches are investigated and taken into consideration for making improved solution. Thus the approaches proposed in this study extend some of the good scoring previous state of the art techniques by incorporating machine learning and statistical approaches and thermodynamic features like whole stacking energy to improve the prediction accuracy, inhibition efficiency, sensitivity and specificity. Here, we propose one Support Vector Machine (SVM) model, and two Artificial Neural Network (ANN) models for siRNA efficiency prediction. In SVM model, the classification property is used to classify whether the siRNA is efficient or inefficient in silencing a target gene. The first ANNmodel, named siRNA Designer, is used for optimizing the inhibition efficiency of siRNA against target genes. The second ANN model, named Optimized siRNA Designer, OpsiD, produces efficient siRNAs with high inhibition efficiency to degrade target genes with improved sensitivity-specificity, and identifies the off-target knockdown possibility of siRNA against non-target genes. The models are trained and tested against a large data set of siRNA sequences. The validations are conducted using Pearson Correlation Coefficient, Mathews Correlation Coefficient, Receiver Operating Characteristic analysis, Accuracy of prediction, Sensitivity and Specificity. It is found that the approach, OpsiD, is capable of predicting the inhibition capacity of siRNA against a target mRNA with improved results over the state of the art techniques. Also we are able to understand the influence of whole stacking energy on efficiency of siRNA. The model is further improved by including the ability to identify the “off-target possibility” of predicted siRNA on non-target genes. Thus the proposed model, OpsiD, can predict optimized siRNA by considering both “inhibition efficiency on target genes and off-target possibility on non-target genes”, with improved inhibition efficiency, specificity and sensitivity. Since we have taken efforts to optimize the siRNA efficacy in terms of “inhibition efficiency and offtarget possibility”, we hope that the risk of “off-target effect” while doing gene silencing in various bioinformatics fields can be overcome to a great extent. These findings may provide new insights into cancer diagnosis, prognosis and therapy by gene silencing. The approach may be found useful for designing exogenous siRNA for therapeutic applications and gene silencing techniques in different areas of bioinformatics.

Rezentralisierung: Server-Based Computing in der Praxis einer Universitätsbibliothek

Der Beitrag beschreibt die Ein- und Durchführung einer Server-basierten Computerinfrastruktur in einer Universitätsbibliothek. Beschrieben wird das so genannte MetaFrame-DV-Konzept der Universitätsbibliothek Kassel, das das dortige Informationsmanagement in den letzten vier Jahren initiiert, konzipiert und umgesetzt hat. Hierbei werden nunmehr nicht mehr nur Applikationsserver z.B. für das CD-Angebot eingesetzt, sondern sämtliche ca. 200 Mitarbeiter- und Funktionsarbeitsplätze über eine Citrix MetaFrame-Installation serverseitig betreut. Besonderes Augenmerk gilt in diesem Beitrag der Konfiguration, der praktischen Administration und den täglichen Arbeitsbedingungen an den Bibliotheksmitarbeiterarbeitsplätzen.

Computing Generators of Free Modules over Orders in Group Algebras

Let E be a number field and G be a finite group. Let A be any O_E-order of full rank in the group algebra E[G] and X be a (left) A-lattice. We give a necessary and sufficient condition for X to be free of given rank d over A. In the case that the Wedderburn decomposition E[G] \cong \oplus_xM_x is explicitly computable and each M_x is in fact a matrix ring over a field, this leads to an algorithm that either gives elements \alpha_1,...,\alpha_d \in X such that X = A\alpha_1 \oplus ... \oplusA\alpha_d or determines that no such elements exist. Let L/K be a finite Galois extension of number fields with Galois group G such that E is a subfield of K and put d = [K : E]. The algorithm can be applied to certain Galois modules that arise naturally in this situation. For example, one can take X to be O_L, the ring of algebraic integers of L, and A to be the associated order A(E[G];O_L) \subseteq E[G]. The application of the algorithm to this special situation is implemented in Magma under certain extra hypotheses when K = E = \IQ.

Strategies towards evaluation beyond scientific impact

Various research fields, like organic agricultural research, are dedicated to solving real-world problems and contributing to sustainable development. Therefore, systems research and the application of interdisciplinary and transdisciplinary approaches are increasingly endorsed. However, research performance depends not only on self-conception, but also on framework conditions of the scientific system, which are not always of benefit to such research fields. Recently, science and its framework conditions have been under increasing scrutiny as regards their ability to serve societal benefit. This provides opportunities for (organic) agricultural research to engage in the development of a research system that will serve its needs. This article focuses on possible strategies for facilitating a balanced research evaluation that recognises scientific quality as well as societal relevance and applicability. These strategies are (a) to strengthen the general support for evaluation beyond scientific impact, and (b) to provide accessible data for such evaluations. Synergies of interest are found between open access movements and research communities focusing on global challenges and sustainability. As both are committed to increasing the societal benefit of science, they may support evaluation criteria such as knowledge production and dissemination tailored to societal needs, and the use of open access. Additional synergies exist between all those who scrutinise current research evaluation systems for their ability to serve scientific quality, which is also a precondition for societal benefit. Here, digital communication technologies provide opportunities to increase effectiveness, transparency, fairness and plurality in the dissemination of scientific results, quality assurance and reputation. Furthermore, funders may support transdisciplinary approaches and open access and improve data availability for evaluation beyond scientific impact. If they begin to use current research information systems that include societal impact data while reducing the requirements for narrative reports, documentation burdens on researchers may be relieved, with the funders themselves acting as data providers for researchers, institutions and tailored dissemination beyond academia.

Asymptotically Zero Energy Computing Using Split-Level Charge Recovery Logic

The dynamic power requirement of CMOS circuits is rapidly becoming a major concern in the design of personal information systems and large computers. In this work we present a number of new CMOS logic families, Charge Recovery Logic (CRL) as well as the much improved Split-Level Charge Recovery Logic (SCRL), within which the transfer of charge between the nodes occurs quasistatically. Operating quasistatically, these logic families have an energy dissipation that drops linearly with operating frequency, i.e., their power consumption drops quadratically with operating frequency as opposed to the linear drop of conventional CMOS. The circuit techniques in these new families rely on constructing an explicitly reversible pipelined logic gate, where the information necessary to recover the energy used to compute a value is provided by computing its logical inverse. Information necessary to uncompute the inverse is available from the subsequent inverse logic stage. We demonstrate the low energy operation of SCRL by presenting the results from the testing of the first fully quasistatic 8 x 8 multiplier chip (SCRL-1) employing SCRL circuit techniques.

Reconfigurable Architectures for General-Purpose Computing

General-purpose computing devices allow us to (1) customize computation after fabrication and (2) conserve area by reusing expensive active circuitry for different functions in time. We define RP-space, a restricted domain of the general-purpose architectural space focussed on reconfigurable computing architectures. Two dominant features differentiate reconfigurable from special-purpose architectures and account for most of the area overhead associated with RP devices: (1) instructions which tell the device how to behave, and (2) flexible interconnect which supports task dependent dataflow between operations. We can characterize RP-space by the allocation and structure of these resources and compare the efficiencies of architectural points across broad application characteristics. Conventional FPGAs fall at one extreme end of this space and their efficiency ranges over two orders of magnitude across the space of application characteristics. Understanding RP-space and its consequences allows us to pick the best architecture for a task and to search for more robust design points in the space. Our DPGA, a fine- grained computing device which adds small, on-chip instruction memories to FPGAs is one such design point. For typical logic applications and finite- state machines, a DPGA can implement tasks in one-third the area of a traditional FPGA. TSFPGA, a variant of the DPGA which focuses on heavily time-switched interconnect, achieves circuit densities close to the DPGA, while reducing typical physical mapping times from hours to seconds. Rigid, fabrication-time organization of instruction resources significantly narrows the range of efficiency for conventional architectures. To avoid this performance brittleness, we developed MATRIX, the first architecture to defer the binding of instruction resources until run-time, allowing the application to organize resources according to its needs. Our focus MATRIX design point is based on an array of 8-bit ALU and register-file building blocks interconnected via a byte-wide network. With today's silicon, a single chip MATRIX array can deliver over 10 Gop/s (8-bit ops). On sample image processing tasks, we show that MATRIX yields 10-20x the computational density of conventional processors. Understanding the cost structure of RP-space helps us identify these intermediate architectural points and may provide useful insight more broadly in guiding our continual search for robust and efficient general-purpose computing structures.

Learning-Based Approach to Estimation of Morphable Model Parameters

We describe the key role played by partial evaluation in the Supercomputing Toolkit, a parallel computing system for scientific applications that effectively exploits the vast amount of parallelism exposed by partial evaluation. The Supercomputing Toolkit parallel processor and its associated partial evaluation-based compiler have been used extensively by scientists at MIT, and have made possible recent results in astrophysics showing that the motion of the planets in our solar system is chaotically unstable.

New Architectural Models for Visibly Controllable Computing: The Relevance of Dynamic Object Oriented Architectures and Plan Based Computing Models

Traditionally, we've focussed on the question of how to make a system easy to code the first time, or perhaps on how to ease the system's continued evolution. But if we look at life cycle costs, then we must conclude that the important question is how to make a system easy to operate. To do this we need to make it easy for the operators to see what's going on and to then manipulate the system so that it does what it is supposed to. This is a radically different criterion for success. What makes a computer system visible and controllable? This is a difficult question, but it's clear that today's modern operating systems with nearly 50 million source lines of code are neither. Strikingly, the MIT Lisp Machine and its commercial successors provided almost the same functionality as today's mainstream sytsems, but with only 1 Million lines of code. This paper is a retrospective examination of the features of the Lisp Machine hardware and software system. Our key claim is that by building the Object Abstraction into the lowest tiers of the system, great synergy and clarity were obtained. It is our hope that this is a lesson that can impact tomorrow's designs. We also speculate on how the spirit of the Lisp Machine could be extended to include a comprehensive access control model and how new layers of abstraction could further enrich this model.

Exploiting the Parallelism Exposed by Partial Evaluation

We describe the key role played by partial evaluation in the Supercomputing Toolkit, a parallel computing system for scientific applications that effectively exploits the vast amount of parallelism exposed by partial evaluation. The Supercomputing Toolkit parallel processor and its associated partial evaluation-based compiler have been used extensively by scientists at MIT, and have made possible recent results in astrophysics showing that the motion of the planets in our solar system is chaotically unstable.

A Privacy Conscious Bluetooth Infrastructure for Location Aware Computing

We present a low cost and easily deployed infrastructure for location aware computing that is built using standard Bluetooth® technologies and personal computers. Mobile devices are able to determine their location to room-level granularity with existing bluetooth technology, and to even greater resolution with the use of the recently adopted bluetooth 1.2 specification, all while maintaining complete anonymity. Various techniques for improving the speed and resolution of the system are described, along with their tradeoffs in privacy. The system is trivial to implement on a large scale – our network covering 5,000 square meters was deployed by a single student over the course of a few days at a cost of less than US$1,000.

Failure-Oblivious Computing and Boundless Memory Blocks

Memory errors are a common cause of incorrect software execution and security vulnerabilities. We have developed two new techniques that help software continue to execute successfully through memory errors: failure-oblivious computing and boundless memory blocks. The foundation of both techniques is a compiler that generates code that checks accesses via pointers to detect out of bounds accesses. Instead of terminating or throwing an exception, the generated code takes another action that keeps the program executing without memory corruption. Failure-oblivious code simply discards invalid writes and manufactures values to return for invalid reads, enabling the program to continue its normal execution path. Code that implements boundless memory blocks stores invalid writes away in a hash table to return as the values for corresponding out of bounds reads. he net effect is to (conceptually) give each allocated memory block unbounded size and to eliminate out of bounds accesses as a programming error. We have implemented both techniques and acquired several widely used open source servers (Apache, Sendmail, Pine, Mutt, and Midnight Commander).With standard compilers, all of these servers are vulnerable to buffer overflow attacks as documented at security tracking web sites. Both failure-oblivious computing and boundless memory blocks eliminate these security vulnerabilities (as well as other memory errors). Our results show that our compiler enables the servers to execute successfully through buffer overflow attacks to continue to correctly service user requests without security vulnerabilities.

Japanese Scientific And Technology Information in the United States - Public Policy and Private Initiatives

In January 1983 a group of US government, industry and university information specialists gathered at MIT to take stock of efforts to monitor, acquire, assess, and disseminate Japanese scientific and technical information (JSTI). It was agreed that these efforts were uncoordinated and poorly conceived, and that a clearer understanding of Japanese technical information systems and a clearer sense of its importance to end users was necessary. That meeting led to formal technology assessments, Congressinal hearings, and legislation; it also helped stimulate several private initiatives in JSTI provision. Four years later there exist better coordinated and better conceived JSTI programs in both the public and private sectors, but there remains much room for improvement. This paper will recount their development and assess future directions.

How to improve the formal analytic reasoning and scientific motivation in the intellectual training of medical students

A review article of the The New England Journal of Medicine refers that almost a century ago, Abraham Flexner, a research scholar at the Carnegie Foundation for the Advancement of Teaching, undertook an assessment of medical education in 155 medical schools in operation in the United States and Canada. Flexner’s report emphasized the nonscientific approach of American medical schools to preparation for the profession, which contrasted with the university-based system of medical education in Germany. At the core of Flexner’s view was the notion that formal analytic reasoning, the kind of thinking integral to the natural sciences, should hold pride of place in the intellectual training of physicians. This idea was pioneered at Harvard University, the University of Michigan, and the University of Pennsylvania in the 1880s, but was most fully expressed in the educational program at Johns Hopkins University, which Flexner regarded as the ideal for medical education. (...)