Person: Fahmy, Amr
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Fahmy
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Amr
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Fahmy, Amr
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Publication Molecular Signatures of Hemagglutinin Stem-Directed Heterosubtypic Human Neutralizing Antibodies against Influenza A Viruses(Public Library of Science, 2014) Avnir, Yuval; Tallarico, Aimee S.; Zhu, Quan; Bennett, Andrew S.; Connelly, Gene; Sheehan, Jared; Sui, Jianhua; Fahmy, Amr; Huang, Chiung-yu; Cadwell, Greg; Bankston, Laurie A.; McGuire, Andrew T.; Stamatatos, Leonidas; Wagner, Gerhard; Liddington, Robert C.; Marasco, WayneRecent studies have shown high usage of the IGHV1-69 germline immunoglobulin gene for influenza hemagglutinin stem-directed broadly-neutralizing antibodies (HV1-69-sBnAbs). Here we show that a major structural solution for these HV1-69-sBnAbs is achieved through a critical triad comprising two CDR-H2 loop anchor residues (a hydrophobic residue at position 53 (Ile or Met) and Phe54), and CDR-H3-Tyr at positions 98±1; together with distinctive V-segment CDR amino acid substitutions that occur in positions sparse in AID/polymerase-η recognition motifs. A semi-synthetic IGHV1-69 phage-display library screen designed to investigate AID/polη restrictions resulted in the isolation of HV1-69-sBnAbs that featured a distinctive Ile52Ser mutation in the CDR-H2 loop, a universal CDR-H3 Tyr at position 98 or 99, and required as little as two additional substitutions for heterosubtypic neutralizing activity. The functional importance of the Ile52Ser mutation was confirmed by mutagenesis and by BCR studies. Structural modeling suggests that substitution of a small amino acid at position 52 (or 52a) facilitates the insertion of CDR-H2 Phe54 and CDR-H3-Tyr into adjacent pockets on the stem. These results support the concept that activation and expansion of a defined subset of IGHV1-69-encoded B cells to produce potent HV1-69-sBnAbs does not necessarily require a heavily diversified V-segment acquired through recycling/reentry into the germinal center; rather, the incorporation of distinctive amino acid substitutions by Phase 2 long-patch error-prone repair of AID-induced mutations or by random non-AID SHM events may be sufficient. We propose that these routes of B cell maturation should be further investigated and exploited as a pathway for HV1-69-sBnAb elicitation by vaccination.Publication On the Transportation and Distribution of Data Structures in Parallel and Distributed Systems(1995) Fahmy, Amr; Wagner, Robert A.We present algorithms for the transportation of data in parallel and distributed systems that would enable programmers to transport or distribute a data structure by issuing a function call. Such a functionality is needed if programming distributed memory systems is to become commonplace. The distribution problem is defined as follows. We assume that n records of a data structure are scattered among p processors where processor qi holds ri records, 1 ≤ i ≤ p. The problem is to redistribute the records so that each processor holds [n/p] records. We solve the problem in the minimum number of parallel data-permutation operations possible, for the given initial record distribution. This means that we use max(mxr - [n/p], [n/p] - mnr) parallel data transfer steps, where mxr = max(ri) and mnr = min(ri) for 1 ≤ i ≤ p. Having solved the distribution problem, it then remains to transport the data structure from the memory of one processor to another. In the case of dynamically allocated data structures, we solve the problem of renaming pointers by creating an intermediate name space. We also present a transportation algorithm that attempts to hide the cost of making a local copy for the data structure which, is necessary since the data structure could be scattered in the memory of the sender.Publication Bulk Synchronous Parallel Computing - A Paradigm for Transportable Software(1994) Cheatham, Thomas; Fahmy, Amr; Stefanescu, Dan C.; Valiant, LeslieA necessary condition for the establishment, on a substantial basis, of a parallel software industry would appear to be the availability of technology for generating transportable software, i.e. architecture independent software which delivers scalable performance for a wide variety of applications on a wide range of multiprocessor computers. This paper describes H-BSP - a general purpose parallel computing environment for developing transportable algorithms. H-BSP is based on the Bulk Synchronous Parallel Model (BSP), in which a computation involves a number of supersteps, each having several parallel computational threads that synchronize at the end of the superstep. The BSP Model deals explicitly with the notion of communication among computational threads and introduces parameters g and L that quantify the ratio of communication throughput to computation throughput, and the synchronization period, respectively. These two parameters, together with the number of processors and the problem size, are used to quantify the performance and, therefore, the transportability of given classes of algorithms across machines having different values for these parameters. This paper describes the role of unbundled compiler technology in facilitating the development of such a parallel computer environment.Publication Efficient Learning of Real Time One-Counter Automata(1995) Fahmy, Amr; Roos, RobertWe present an efficient learning algorithm for languages accepted by deterministic real time one counter automata (ROCA). The learning algorithm works by first learning an initial segment, Bn, of the infinite state machine that accepts the unknown language and then decomposing it into a complete control structure and a partial counter. A new efficient ROCA decomposition algorithm, which will be presented in detail, allows this result. The decomposition algorithm works in O(n2log(n)) where nc is the number of states of Bn for some constant c. If Angluin's algorithm for learning regular languages is used to learn Bn and the complexity of this step is h(n, m) where m is the length of the longest counter example necessary for Angluin's algorithm, the complexity of our algorithm is thus O(h(n, m) + n2log(n)).Publication Communicable Memory and Lazy Barriers for Bulk Synchronous Parallelism in BSPk(1996) Fahmy, Amr; Heddaya, AbdelsalamCommunication and synchronization stand as the dual bottlenecks in the performance of parallel systems, and especially those that attempt to alleviate the programming burden by incurring overhead in these two domains. We formulate the notions of communicable memory and lazy barriers to help achieve efficient communication and synchronization. These concepts are developed in the context of BSPk, a toolkit library for programming networks of workstations|and other distributed memory architectures in general|based on the Bulk Synchronous Parallel (BSP) model. BSPk emphasizes efficiency in communication by minimizing local memory-to-memory copying, and in barrier synchronization by not forcing a process to wait unless it needs remote data. Both the message passing (MP) and distributed shared memory (DSM) programming styles are supported in BSPk. MP helps processes efficiently exchange short-lived unnamed data values, when the identity of either the sender or receiver is known to the other party. By contrast, DSM supports communication through between processes that may be mutually anonymous, so long as they can agree on variable names in which to store shared temporary or long-lived data.Publication Ensemble Quantum Computing by Nuclear Magnetic Resonance Spectroscopy(1996) Cory, David G.; Fahmy, Amr; Havel, Timothy F.A quantum computer (QC) can operate in parallel on all its possible inputs at once, but the amount of information that can be extracted from the result is limited by the phenomenon of wave function collapse. We present a new computational model, which differs from a QC only in that the result of a measurement is the expectation value of the observable, rather than a random eigenvalue thereof. Such an expectation value QC can solve nondeterministic polynomialtime complete problems in polynomial time. This observation is significant precisely because the computational model can be realized, to a certain extent, by NMR spectroscopy on macroscopic ensembles of quantum spins, namely molecules in a test tube. This is made possible by identifying a manifold of statistical spin states, called pseudo-pure states, the mathematical description of which is isomorphic to that of an isolated spin system. The result is a novel NMR computer that can be programmed much like a QC, but in other respects more closely resembles a DNA computer. Most notably, when applied to intractable combinatorial problems, an NMR computer can use an amount of sample, rather than time, which grows exponentially with the size of the problem. Although NMR computers will be limited by current technology to exhaustive searches over only 15 to 20 bits, searches over as much as 50 bits are in principle possible, and more advanced algorithms could greatly extend the range of applicability of such machines.