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Modern Out-of-Order (OoO) CPUs are complex systems with many components interleaved in non-trivial ways. Pinpointing performance bottlenecks and understanding the underlying causes of program performance issues are critical tasks to make the most of hardware resources. We provide an in-depth overview of performance bottlenecks in recent OoO microarchitectures and describe the difficulties of detecting them. Techniques that measure resources utilization can offer a good understanding of a program's execution, but, due to the constraints inherent to Performance Monitoring Units (PMU) of CPUs, do not provide the relevant metrics for each use case. Another approach is to rely on a performance model to simulate the CPU behavior. Such a model makes it possible to implement any new microarchitecture-related metric. Within this framework, we advocate for implementing modeled resources as parameters that can be varied at will to reveal performance bottlenecks. This allows a generalization of bottleneck analysis that we call sensitivity analysis. We present Gus, a novel performance analysis tool that combines the advantages of sensitivity analysis and dynamic binary instrumentation within a resource-centric CPU model. We evaluate the impact of sensitivity on bottleneck analysis over a set of high-performance computing kernels.

Secure applications implement software protections against side-channel and physical attacks. Such protections are meaningful at machine code or micro-architectural level, but they typically do not carry observable semantics at source level. To prevent optimizing compilers from altering the protection, security engineers embed input/output side-effects into the protection. These side-effects are error-prone and compiler-dependent, and the current practice involves analyzing the generated machine code to make sure security or privacy properties are still enforced. Vu et al. recently demonstrated how to automate the insertion of volatile side-effects in a compiler [52], but these may be too expensive in fined-grained protections such as control-flow integrity. We introduce observations of the program state that are intrinsic to the correct execution of security protections, along with means to specify and preserve observations across the compilation flow. Such observations complement the traditional input/output-preservation contract of compilers. We show how to guarantee their preservation without modifying compilation passes and with as little performance impact as possible. We validate our approach on a range of benchmarks, expressing the secure compilation of these applications in terms of observations to be made at specific program points.

In a super-scalar architecture, the scheduler dynamically assigns micro-operations ($\mu$OPs) to execution ports. The port mapping of an architecture describes how an instruction decomposes into $\mu$OPs and lists for each $\mu$OP the set of ports it can be mapped to. It is used by compilers and performance debugging tools to characterize the performance throughput of a sequence of instructions repeatedly executed as the core component of a loop. This paper introduces a dual equivalent representation: The resource mapping of an architecture is an abstract model where, to be executed, an instruction must use a set of abstract resources, themselves representing combinations of execution ports. For a given architecture, finding a port mapping is an important but difficult problem. Building a resource mapping is a more tractable problem and provides a simpler and equivalent model. This paper describes Palmed, a tool that automatically builds a resource mapping for pipelined, super-scalar, out-of-order CPU architectures. Palmed does not require hardware performance counters, and relies solely on runtime measurements. We evaluate the pertinence of our dual representation for throughput modeling by extracting a representative set of basic-blocks from the compiled binaries of the SPEC CPU 2017 benchmarks. We compared the throughput predicted by existing machine models to that produced by Palmed, and found comparable accuracy to state-of-the art tools, achieving sub-10 % mean square error rate on this workload on Intel's Skylake microarchitecture.

Seventy-one 7-oxycoumarins, 66 synthesized and 5 commercially sourced, were tested for their ability to inhibit growth in murine PAM212 keratinocytes. Forty-nine compounds from the library demonstrated light-induced lethality. None was toxic in the absence of UVA light. Structure-activity correlations indicate that the ability of the compounds to inhibit cell growth was dependent not only on their physiochemical characteristics, but also on their ability to absorb UVA light. Relative lipophilicity was an important factor as was electron density in the pyrone ring. Coumarins with electron withdrawing moieties – cyano and fluoro at C3 – were considerably less active while those with bromines or iodine at that location displayed enhanced activity. Coumarins that were found to inhibit keratinocyte growth were also tested for photo-induced DNA plasmid nicking. A concentration-dependent alteration in migration on neutral gels caused by nicking was observed., SCOPUS: ar.j, info:eu-repo/semantics/published

Nowadays, engineers have to develop software often without even knowing which hardware it will eventually run on in numerous mobile phones, tablets, desktops, laptops, data centers, supercomputers and cloud services. Unfortunately, optimizing compilers are not keeping pace with ever increasing complexity of computer systems anymore and may produce severely underperforming executable codes while wasting expensive resources and energy. We present our practical and collaborative solution to this problem via light-weight wrappers around any software piece when more than one implementation or optimization choice available. These wrappers are connected with a public Collective Mind autotuning infrastructure and repository of knowledge (c-mind.org/repo) to continuously monitor various important characteristics of these pieces (computational species) across numerous existing hardware configurations together with randomly selected optimizations. Similar to natural sciences, we can now continuously track winning solutions (optimizations for a given hardware) that minimize all costs of a computation (execution time, energy spent, code size, failures, memory and storage footprint, optimization time, faults, contentions, inaccuracy and so on) of a given species on a Pareto frontier along with any unexpected behavior. The community can then collaboratively classify solutions, prune redundant ones, and correlate them with various features of software, its inputs (data sets) and used hardware either manually or using powerful predictive analytics techniques. Our approach can then help create a large, realistic, diverse, representative, and continuously evolving benchmark with related optimization knowledge while gradually covering all possible software and hardware to be able to predict best optimizations and improve compilers and hardware depending on usage scenarios and requirements., Comment: Presented at the 18th International Workshop on Compilers for Parallel Computing (CPC'15), London, UK

Psoralens such as 8-methoxypsoralen and 4,5',8-trimethylpsoralen (TMP) are used in photochemotherapy for the treatment of a variety of epidermal proliferative diseases. Sequential treatments of the skin with psoralens plus ultraviolet light in the range of 320-400 nm (UVA light), referred to as PUVA therapy, results in the suppression of abnormal keratinocyte growth. With the recognition that the psoralens are phototoxic and carcinogenic, presumably due to their ability to intercalate into DNA and photo cross-link pyrimidine bases following UVA light activation, it is clear that the development of biologically active analogs lacking this activity would be of significant therapeutic benefit. Towards this goal we have characterized active 4'- and 5'-pyridinium derivatives of 4',5'-dihydro-TMP (H2TMP), a psoralen analog that does not form DNA cross-links. These analogs, which are charged at physiological pH and cannot penetrate cells, are unique in that they retain biological activity as inhibitors of keratinocyte cell growth when activated by UVA light. However, they do not appear to cross-link or damage DNA as determined by plasmid DNA unwinding and nicking experiments, in intact cells using fluorescent analysis of DNA unwinding assays, and by thymidine uptake studies. Reverse transcription-polymerase chain reaction and western blotting demonstrated that, unlike TMP and H2TMP, when activated by UVA light, the pyridinium derivatives were not inhibitors of transcription since interferon-gamma-inducible nitric oxide synthase mRNA and protein in the keratinocytes were unaffected. Taken together, our data suggest that uptake of the compounds by the cells and DNA cross-link formation are not required for growth inhibition. These findings further support the model that the cell membrane is an important target for the psoralens., Journal Article, Research Support, U.S. Gov't, P.H.S., info:eu-repo/semantics/published

FLWIN, info:eu-repo/semantics/published

Muscular microcirculation was studied in seven halothane anaesthetised horses in lateral recumbency using a laser Doppler flowmeter. A significant difference between the dependent and the uppermost triceps brachii was recorded. In the dependent muscles, microflow at first decreased and then increased up to the starting value. In the uppermost muscles, a significant rise of the microflow was measured. © 1986 EVJ Ltd, SCOPUS: ar.j, info:eu-repo/semantics/published