Approximations and Bounds for (n, k) Fork-Join Queues: A Linear Transformation Approach

Compared to basic fork-join queues, a job in (n, k) fork-join queues only needs its k out of all n sub-tasks to be finished. Since (n, k) fork-join queues are prevalent in popular distributed systems, erasure coding based cloud storages, and modern network protocols like multipath routing, estimating the sojourn time of such queues is thus critical for the performance measurement and resource plan of computer clusters. However, the estimating keeps to be a well-known open challenge for years, and only rough bounds for a limited range of load factors have been given. In this paper, we developed a closed-form linear transformation technique for jointly-identical random variables: An order statistic can be represented by a linear combination of maxima. This brand-new technique is then used to transform the sojourn time of non-purging (n, k) fork-join queues into a linear combination of the sojourn times of basic (k, k), (k+1, k+1), ..., (n, n) fork-join queues. Consequently, existing approximations for basic fork-join queues can be bridged to the approximations for non-purging (n, k) fork-join queues. The uncovered approximations are then used to improve the upper bounds for purging (n, k) fork-join queues. Simulation experiments show that this linear transformation approach is practiced well for moderate n and relatively large k.Comment: 10 page

Response and resistance to BET inhibitors in triple negative breast cancer

Introduction: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, and urgently needs new potent therapies. Bromodomain and extra-terminal proteins (BET) are primary regulators of RNA polymerase II, which also regulate gene transcription. For cancer patients, numerous BET inhibitors are now undergoing clinical trials. Unfortunately, the responses to BET inhibitors varied between preclinical and clinical investigations, necessitating more research into their functions in cancer. Materials and methods: Gene expression data were acquired from The Cancer Genome Atlas the (TCGA), Cancer Cell Line Encyclopedia (CCLE), and the Human Protein Atlas (HPA) to analyze the gene and protein expression of BET family members in TNBC patients and cell lines. One cell line (MDA-MB-231R) resistant to the BET inhibitor JQ1 was established from the parental cell line MDA-MB-231. The cytotoxicity of the medications following treatments was assessed using the MTT test. The cell cycle, cell apoptosis, and BH3 profiling analyses were carried out using FACS analysis. Western blotting was used to detect protein expression before and after treatments. Results: Particularly in TNBC tissues and cell lines with the low rate of mutations, BRD4 was overexpressed in breast cancer. The BET inhibitor JQ1 could induce cell cycle G1 arrest, senescence, and minor cell apoptosis in TNBC. When combined with CDK9 inhibitors, JQ1 showed a strong synergistic effect in TNBC cell lines by inducing apoptosis. It was discovered through the use of the BH3 profiling assay and the MTT assay that BCL-xL was necessary for the survival of MDA-MB-231 and MDA-MB-231R cells, whereas that of MDA-MB-436 cells was dependent on BCL-xL and MCL-1. According to Western blot analysis the combination of JQ1 and CDK9 inhibitor dramatically reduced the expression of BCL-xL and MCL-1 in TNBC cell lines. Therefore it is likely that apoptosis induced by combination of both substances is a result of reduction of BCL-xL and/or MCL-1. Summary/conclusions: Promising Targets in TNBC include BET proteins, particularly BRD4. The BET inhibitor JQ1 is a potential therapeutic agent in treatment of TNBC treatment. Moreover, the combination of BET and CDK9 inhibitors has a synergistic inhibitory effect in TNBC treatment not only in JQ1-sensitive cell but also in primary and secondary resistant cell lines by inducing cell apoptosis possibly through suppressing MCL-1 and BCL-xL.Zusammenfassung Einleitung: Das triple-negative Mammakarzinom (triple negative breast cancer, TNBC) gilt als der aggressivste Subtyp von Mammakarzinomen und es werden für diese Entität dringend neue wirksamere Therapieansätze gesucht. Bromodomain und Extra-Terminal (BET)-Proteine sind Schlüsselregulatoren der RNA-Polymerase II und kontrollieren die Gentranskription. Derzeit werden BET-Inhibitoren in klinischen Studien für Krebspatienten untersucht. BET-Inhibitoren zeigten bis dato unterschiedlichen Ergebnissen in präklinischen Studien untersucht, weshalb ihre Rolle bei Tumortherapien, insbesondere beim TNBC, weiter erforscht und definiert sollte. Material und Methoden: Genexpressionsdaten wurden vom Cancer Genome Atlas (TCGA), der Cancer Cell Line Encyclopedia (CCLE) und dem Human Protein Atlas (HPA) heruntergeladen, um die Expression der BET-Familie bei TNBC-Patienten und Zelllinien zu analysieren. Eine Zelllinie (MDA-MB-231R), die gegen den BET-Inhibitor JQ1 resistent war, wurde aus der ursprünglichen Zelllinie MDA-MB-231 entwickelt. An TNBC-Zelllinien wurde die Zytotoxizität der Substanzen mittels MTT-Assay untersucht. Zellzyklus, Zellapoptose und BH3-Profiling wurden mittels FACS analysiert. Die Proteinexpression nach der Behandlung wurde mittels Western Blot analysiert. Ergebnisse: BRD4 wird bei Brustkrebs überexprimiert, besonders in TNBC-Gewebe und Zelllinien mit zugleich niedriger Mutationsrate. Der BET-Inhibitor JQ1 induzierte Zellzyklus-G1-Arrest, Seneszenz und geringe Zellapoptose in TNBC. In Kombination mit CDK9-Inhibitoren zeigte der Bromodomain-Inhibitor JQ1 jedoch einen starken synergistischen Effekt auf TNBC-Zelllinien bei der Apoptose-Induktion. Mit Hilfe des BH3-Profiling-Assays und MTT-Assays konnte gezeigt werden, dass das Überleben von MDA-MB-231- und MDA-MB-231R-Zellen von BCL-xL abhängt, während die Überlebensrate der MDA-MB-436-Zellen von BCL-xL und MCL-1 abhängig ist. Die Western-Blot-Analyse zeigte, dass die Kombination von JQ1 und CDK9-Inhibitoren eine signifikante Herabregulierung der BCL-xL- und MCL-1-Expression in TNBC-Zelllinien bewirkte. Daher wat es wahrscheinlich, dass die durch die Kombination der beiden Substanzen induzierte Apoptose auf eine Verringerung von BCL-xL und/oder MCL-1 zurückzuführen ist. Zusammenfassung/Schlussfolgerungen: BET-Proteine, insbesondere BRD4, sind vielversprechende therapeutische Zielstrukturen beim TNBC. Der BET-Inhibitor JQ1 erwies sich als effektiv in die Behandlung von TNBC-Zelllinien. Darüber hinaus hat die Kombination von BET- und CDK9-Inhibitoren eine synergistische hemmende Wirkung bei TNBC, nicht nur bei JQ1-empfindlichen Zellen, sondern auch bei primär und sekundär resistenten Zelllinien, möglicherweise durch Apoptoseinduktion über die Unterdrückung von MCL-1 und BCL-xL

Studies in hydrocarboxylation of styrene and derivatives using palladium complex catalysts

Carbonylation of aryl olefins and alcohols using homogeneous Pd catalysts has gained considerable interest due to their important applications in the synthesis the non-steroidal anti-inflammatory drugs consisting of 2-arylpropionic acids (e.g. Ibuprofen®, Naproxen®). In this work, different homogeneous palladium catalysts were compared for their performances in the hydrocarboxylation of styrene to identify the best performing catalyst system using Pd(pyca)(PPh3)(OTs) as a precursor, which shows above 99% regio-selectivity to 2-phenylpropionic acid as well as high activity. Therefore, this work mainly investigated the kinetics of hydrocarboxylation of styrene using Pd(pyca)(PPh3)(OTs)/PPh3/TsOH/LiCl catalyst system. Particularly, parametric study was carried out to understand the effects of different reaction parameters on the rate of hydrocarboxylation in a batch reactor as well as the concentration-time profiles. For interpretation of the reaction kinetics, a molecular level description of the reaction mechanism (catalytic cycle) was proposed to explain the unique observation of induction period at lower pressures of CO. The experimental concentration-time data for styrene, water and acid products were used to simulate the intrinsic rate parameters using an optimization program. The proposed reaction mechanism based on a Pd-hydride complex as an intermediate active species well explains the experimental data at different temperatures. The approach of micro-kinetic modeling does not require assumption of a rate determining step and provides good description of the complex trends with respect to reaction and catalyst parameters over a wide range of conditions. The approach is also useful to discriminate different reaction mechanisms and obtain intrinsic kinetic parameters for design and scale-up of reactors

Zero-Shot Certified Defense against Adversarial Patches with Vision Transformers

Adversarial patch attack aims to fool a machine learning model by arbitrarily modifying pixels within a restricted region of an input image. Such attacks are a major threat to models deployed in the physical world, as they can be easily realized by presenting a customized object in the camera view. Defending against such attacks is challenging due to the arbitrariness of patches, and existing provable defenses suffer from poor certified accuracy. In this paper, we propose PatchVeto, a zero-shot certified defense against adversarial patches based on Vision Transformer (ViT) models. Rather than training a robust model to resist adversarial patches which may inevitably sacrifice accuracy, PatchVeto reuses a pretrained ViT model without any additional training, which can achieve high accuracy on clean inputs while detecting adversarial patched inputs by simply manipulating the attention map of ViT. Specifically, each input is tested by voting over multiple inferences with different attention masks, where at least one inference is guaranteed to exclude the adversarial patch. The prediction is certifiably robust if all masked inferences reach consensus, which ensures that any adversarial patch would be detected with no false negative. Extensive experiments have shown that PatchVeto is able to achieve high certified accuracy (e.g. 67.1% on ImageNet for 2%-pixel adversarial patches), significantly outperforming state-of-the-art methods. The clean accuracy is the same as vanilla ViT models (81.8% on ImageNet) since the model parameters are directly reused. Meanwhile, our method can flexibly handle different adversarial patch sizes by simply changing the masking strategy.Comment: 12 pages, 5 figure

Search and Delivery of Standardized Learning Resources Based on SOAP Messaging and Native XML Databases

With the progress of Web-based learning technologies, standardized digital repositories and learning management systems are becoming prevalent over time. The heterogeneity in underlying databases and access methods, however, makes it difficult to share and exchange the learning resources between them. In this paper, we propose an architecture for the search and delivery of learning resources. Based on the SOAP transmission protocol, the architecture seeks to improve interoperability between heterogeneous E-Learning implementations. We also present a general-purpose query language as a building block of the architecture. The language provides a unified query interface for resource repositories, thereby shielding the users from the differences in underlying databases and metadata schemas. To highlight our design, an implementation using LOM, native XML database and XPath is presented. The last part of this paper discusses technical and pedagogical issues of concern regarding the launching of contents from within standardized LMSs