On compile time Knuth-Morris-Pratt precomputation

Many keyword pattern matching algorithms use precomputation subroutines to produce lookup tables, which in turn are used to improve performance during the search phase. If the keywords to be matched are known at compile time, the precomputation subroutines can be implemented to be evaluated at compile time versus at run time. This will provide a performance boost to run time operations. We have started an investigation into the use of metaprogramming techniques to implement such compile time evaluation, initially for the Knuth-Morris-Pratt (KMP) algorithm. We present an initial experimental comparison of the performance of the traditional KMP algorithm to that of an optimised version that uses compile time precomputation. During implementation and benchmarking, it was discovered that C++ is not well suited to metaprogramming when dealing with strings, while the related D language is. We therefore ported our implementation to the latter and performed the benchmarking with that version. We discuss the design of the benchmarks, the experience in implementing the benchmarks in C++ and D, and the results of the D benchmarks. The results show that under certain circumstances, the use of compile time precomputation may significantly improve performance of the KMP algorithm

On compile time Knuth-Morris-Pratt precomputation

Many keyword pattern matching algorithms use precomputation subroutines to produce lookup tables, which in turn are used to improve performance during the search phase. If the keywords to be matched are known at compile time, the precomputation subroutines can be implemented to be evaluated at compile time versus at run time. This will provide a performance boost to run time operations. We have started an investigation into the use of metaprogramming techniques to implement such compile time evaluation, initially for the Knuth-Morris-Pratt (KMP) algorithm. We present an initial experimental comparison of the performance of the traditional KMP algorithm to that of an optimised version that uses compile time precomputation. During implementation and benchmarking, it was discovered that C++ is not well suited to metaprogramming when dealing with strings, while the related D language is. We therefore ported our implementation to the latter and performed the benchmarking with that version. We discuss the design of the benchmarks, the experience in implementing the benchmarks in C++ and D, and the results of the D benchmarks. The results show that under certain circumstances, the use of compile time precomputation may significantly improve performance of the KMP algorithm

Triple-negative breast cancer: Current perspective on the evolving therapeutic landscape

Triple-negative breast cancer (TNBC) is known to have a poor prognosis and limited treatment options, namely chemotherapy. Different molecular studies have recently classified TNBC into different subtypes opening the door to potential new-targeted treatment options. In this review, we discuss the current standard of care in the treatment of TNBC in the neoadjuvant, adjuvant and metastatic settings. In addition, we summarize the ongoing phase III clinical trials evaluating different associations between the 3 pillars of anticancer treatment: chemotherapy, targeted therapy and immunotherapy

On compile time Knuth-Morris-Pratt precomputation

Abstract. Many keyword pattern matching algorithms use precomputation subroutines to produce lookup tables, which in turn are used to improve performance during the search phase. If the keywords to be matched are known at compile time, the precomputation subroutines can be implemented to be evaluated at compile time versus at run time. This will provide a performance boost to run time operations. We have started an investigation into the use of metaprogramming techniques to implement such compile time evaluation, initially for the Knuth-Morris-Pratt (KMP) algorithm. We present an initial experimental comparison of the performance of the traditional KMP algorithm to that of an optimised version that uses compile time precomputation. During implementation and benchmarking, it was discovered that C++ is not well suited to metaprogramming when dealing with strings, while the related D language is. We therefore ported our implementation to the latter and performed the benchmarking with that version. We discuss the design of the benchmarks, the experience in implementing the benchmarks in C++ and D, and the results of the D benchmarks. The results show that under certain circumstances, the use of compile time precomputation may significantly improve performance of the KMP algorithm

Predicting the response to CTLA-4 blockade by longitudinal noninvasive monitoring of CD8 T cells

Immunotherapy using checkpoint-blocking antibodies against targets such as CTLA-4 and PD-1 can cure melanoma and non-small cell lung cancer in a subset of patients. The presence of CD8 T cells in the tumor correlates with improved survival. We show that immuno-positron emission tomography (immuno-PET) can visualize tumors by detecting infiltrating lymphocytes and, through longitudinal observation of individual animals, distinguish responding tumors from those that do not respond to therapy. We used 89 Zr-labeled PEGylated single-domain antibody fragments (VHHs) specific for CD8 to track the presence of intratumoral CD8 + T cells in the immunotherapy-susceptible B16 melanoma model in response to checkpoint blockade. A 89 Zr-labeled PEGylated anti-CD8 VHH detected thymus and secondary lymphoid structures as well as intratumoral CD8 T cells. Animals that responded to CTLA-4 therapy showed a homogeneous distribution of the anti-CD8 PET signal throughout the tumor, whereas more heterogeneous infiltration of CD8 T cells correlated with faster tumor growth and worse responses. To support the validity of these observations, we used two different transplantable breast cancer models, yielding results that conformed with predictions based on the antimelanoma response. It may thus be possible to use immuno-PET and monitor antitumor immune responses as a prognostic tool to predict patient responses to checkpoint therapies.National Institutes of Health (U.S.) (Grant R01-AI087879-06)National Institutes of Health (U.S.) (Grant DP1-GM106409-03)National Institutes of Health (U.S.) (Grant R01-GM100518-04)National Institutes of Health (U.S.) (Grant P01 CA080111

Proteome analysis of human gastric cardia adenocarcinoma by laser capture microdissection

<p>Abstract</p> <p>Background</p> <p>The incidence of gastric cardiac adenocarcinoma (GCA) has been increasing in the past two decades in China, but the molecular changes relating to carcinogenesis have not been well characterised.</p> <p>Methods</p> <p>In this study, we used a comparative proteomic approach to analyse the malignant and nonmalignant gastric cardia epithelial cells isolated by navigated laser capture microdissection (LCM) from paired surgical specimens of human GCA.</p> <p>Results</p> <p>Twenty-seven spots corresponding to 23 proteins were consistently differentially regulated. Fifteen proteins were shown to be up-regulated, while eight proteins were shown to be down-regulated in malignant cells compared with nonmalignant columnar epithelial cells. The identified proteins appeared to be involved in metabolism, chaperone, antioxidation, signal transduction, apoptosis, cell proliferation, and differentiation. In addition, expressions of HSP27, 60, and Prx-2 in GCA specimens were further confirmed by immunohistochemical and western blot analyses.</p> <p>Conclusion</p> <p>These data indicate that the combination of navigated LCM with 2-DE provides an effective strategy for discovering proteins that are differentially expressed in GCA. Such proteins may contribute in elucidating the molecular mechanisms of GCA carcinogenesis. Furthermore, the combination provides potential clinical biomarkers that aid in early detection and provide potential therapeutic targets.</p

All-d-Enantiomer of β-Amyloid Peptide Forms Ion Channels in Lipid Bilayers

Alzheimer’s disease (AD) is the most common type of senile dementia in aging populations. Amyloid β (Aβ)-mediated dysregulation of ionic homeostasis is the prevailing underlying mechanism leading to synaptic degeneration and neuronal death. Aβ-dependent ionic dysregulation most likely occurs either directly via unregulated ionic transport through the membrane or indirectly via Aβ binding to cell membrane receptors and subsequent opening of existing ion channels or transporters. Receptor binding is expected to involve a high degree of stereospecificity. Here, we investigated whether an Aβ peptide enantiomer, whose entire sequence consists of d-amino acids, can form ion-conducting channels; these channels can directly mediate Aβ effects even in the absence of receptor–peptide interactions. Using complementary approaches of planar lipid bilayer (PLB) electrophysiological recordings and molecular dynamics (MD) simulations, we show that the d-Aβ isomer exhibits ion conductance behavior in the bilayer indistinguishable from that described earlier for the l-Aβ isomer. The d isomer forms channel-like pores with heterogeneous ionic conductance similar to the l-Aβ isomer channels, and the d-isomer channel conductance is blocked by Zn2+, a known blocker of l-Aβ isomer channels. MD simulations further verify formation of β-barrel-like Aβ channels with d- and l-isomers, illustrating that both d- and l-Aβ barrels can conduct cations. The calculated values of the single-channel conductance are approximately in the range of the experimental values. These findings are in agreement with amyloids forming Ca2+ leaking, unregulated channels in AD, and suggest that Aβ toxicity is mediated through a receptor-independent, nonstereoselective mechanism