Pynamic: the Python Dynamic Benchmark

Python is widely used in scientific computing to facilitate application development and to support features such as computational steering. Making full use of some of Python's popular features, which improve programmer productivity, leads to applications that access extremely high numbers of dynamically linked libraries (DLLs). As a result, some important Python-based applications severely stress a system's dynamic linking and loading capabilities and also cause significant difficulties for most development environment tools, such as debuggers. Furthermore, using the Python paradigm for large scale MPI-based applications can create significant file IO and further stress tools and operating systems. In this paper, we present Pynamic, the first benchmark program to support configurable emulation of a wide-range of the DLL usage of Python-based applications for large scale systems. Pynamic has already accurately reproduced system software and tool issues encountered by important large Python-based scientific applications on our supercomputers. Pynamic provided insight for our system software and tool vendors, and our application developers, into the impact of several design decisions. As we describe the Pynamic benchmark, we will highlight some of the issues discovered in our large scale system software and tools using Pynamic

Report on New Capabilities for the Purple Development Environment

As part of the deliverables for the Development Environment for Purple, additional capabilities to improve the tools offerings and to address unique Purple system requirements, such as increased processor count, were expected. This report details some of the new capabilities that have been incorporated into the development environment tools for Purple. The shift on Purple to 64-bit applications (from 32-bit on White) initially broke many debugging and memory tools. Most tools were updated to support 64 bit well before Purple was delivered to LLNL, but the company that provided the popular heavy-weight 32-bit AIX memory tool, ZeroFault, was reluctant to port to 64 bit due to perceived lack of market. LLNL tried offering financial incentives to the ZeroFault developers, which were turned down, but eventually they did give vague promises to try to port to AIX 64-bit mode when they got time. The ZeroFault developers have been making intermittent and very slow progress over the last two plus years, but despite getting close, have not released a version of ZeroFault that yet meets our needs for 64-bit applications. However, given the critical need for memory tools and the uncertainty of ZeroFault development, other memory tool options were actively pursued and delivered

Report on Challenges and Resolutions for the Purple Development Environment

Previous AIX development environment experience with ASC White and Early Delivery systems UV and UM was leveraged to provide a smooth and robust transition to the Purple development environment. Still, there were three major changes that initially caused serious problems for Purple users. The first was making 64-bit builds of executables the default instead of 32-bit. The second was requiring all executables to use large page memory. The third was the phase-out of the popular, but now defunct, third-party C++ compiler KCC, which required the migration of many codes to IBM's xlC C++ compiler. On Purple, the default build environment changed from 32-bit builds to 64-bit builds in order to enable executables to use the 4GB per processor (32GB per node) memory available, and in order for the MPI library to do collective optimizations that required the larger 64-bit address space. The 64-bit build environment was made default by setting the IBM environment variable OBJECT{_}MODE to 64 and wrapping third-party software (mainly the gnu compilers) in order to make them handle OBJECT{_}MODE properly. Because not all applications could port to 64-bit right away, (usually due to third-party constraints, such as python not supporting 64-bit AIX builds until very recently), 32-bit builds of the major common third-party libraries also had be supported. This combined 32/64 bit build support was accomplished fairly seamlessly using the AIX feature that allows both 32-bit and 64-bit versions of the code to appear in the same library file, and documentation with clear examples helped our library developers generate the required combined 32-bit and 64-bit libraries for Purple. In general, the port to 64-bit AIX executables went smoothly. The most common problem encountered with 64-bit was that many C codes didn't prototype malloc everywhere, via ''include <stdlib.h>'', which caused invalid pointers to be returned by unprototyped malloc calls. This was usually seen in old crusty C libraries, leading to segfault on first use of the invalid pointer. Users had not encountered this prototype issue on other 64-bit Operating Systems (Tru64 and SUN) because those vendors worked around this issue by ''auto-prototyping'' malloc for the user. IBM instead required a compiler option to be thrown for autoprototyping. This issue was resolved with user education, and often a quick recognition of the symptoms by support personnel. This addresses a requirement for a report on problems encountered with the tools and environment, and the resolution or status

Designing a broad-spectrum integrative approach for cancer prevention and treatment

Abstract not availableKeith I. Block ... Sarah K. Thompson ... et al

Designing a broad-spectrum integrative approach for cancer prevention and treatment

Targeted therapies and the consequent adoption of "personalized" oncology have achieved notablesuccesses in some cancers; however, significant problems remain with this approach. Many targetedtherapies are highly toxic, costs are extremely high, and most patients experience relapse after a fewdisease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistantimmortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are notreliant upon the same mechanisms as those which have been targeted). To address these limitations, aninternational task force of 180 scientists was assembled to explore the concept of a low-toxicity "broad-spectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspectsof relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a widerange of high-priority targets (74 in total) that could be modified to improve patient outcomes. For thesetargets, corresponding low-toxicity therapeutic approaches were then suggested, many of which werephytochemicals. Proposed actions on each target and all of the approaches were further reviewed forknown effects on other hallmark areas and the tumor microenvironment. Potential contrary or procar-cinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixedevidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of therelationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. Thisnovel approach has potential to be relatively inexpensive, it should help us address stages and types ofcancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for futureresearch is offered

Designing a broad-spectrum integrative approach for cancer prevention and treatment

Targeted therapies and the consequent adoption of “personalized” oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity “broad-spectrum” therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested; many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment. Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to help us address disease relapse, which is a substantial and longstanding problem, so a proposed agenda for future research is offered