Self-Learning Cloud Controllers: Fuzzy Q-Learning for Knowledge Evolution

Cloud controllers aim at responding to application demands by automatically scaling the compute resources at runtime to meet performance guarantees and minimize resource costs. Existing cloud controllers often resort to scaling strategies that are codified as a set of adaptation rules. However, for a cloud provider, applications running on top of the cloud infrastructure are more or less black-boxes, making it difficult at design time to define optimal or pre-emptive adaptation rules. Thus, the burden of taking adaptation decisions often is delegated to the cloud application. Yet, in most cases, application developers in turn have limited knowledge of the cloud infrastructure. In this paper, we propose learning adaptation rules during runtime. To this end, we introduce FQL4KE, a self-learning fuzzy cloud controller. In particular, FQL4KE learns and modifies fuzzy rules at runtime. The benefit is that for designing cloud controllers, we do not have to rely solely on precise design-time knowledge, which may be difficult to acquire. FQL4KE empowers users to specify cloud controllers by simply adjusting weights representing priorities in system goals instead of specifying complex adaptation rules. The applicability of FQL4KE has been experimentally assessed as part of the cloud application framework ElasticBench. The experimental results indicate that FQL4KE outperforms our previously developed fuzzy controller without learning mechanisms and the native Azure auto-scaling

Cytokine profiles of cord and adult blood leukocytes: differences in expression are due to differences in expression and activation of transcription factors

<p>Abstract</p> <p>Background</p> <p>Stem cell transplantation as therapy for hematological disorders is often hampered by severe graft-versus-host-disease. This may be reduced by umbilical cord blood transplantation, an effect that has been attributed to qualitative differences between neonatal and adult T cells. We compared levels of secreted proteins and cytokine mRNA induced in cord blood leukocytes (CBL) and adult blood leukocytes (ABL) by various stimuli.</p> <p>Results</p> <p>While interleukin-2 (IL-2) levels were similar in CBL and ABL, there was less induction of the Th1 cytokine interferon-γ in CBL. Production of the Th2 cytokines IL-4, IL-5, and IL-13 and the hematopoietic cytokine IL-3 was much lower in CBL versus ABL after T-cell receptor-mediated stimulation, whereas production of GM-CSF was comparable in the 2 cell types. The lower levels of Th1 and Th2 cytokines were maintained in CBL during a 4-day time-course study, while after 12 hours IL-3 and GM-CSF reached in CBL levels similar to those in ABL. For all cytokines except IFNγ, the IC₅₀values for inhibition by cyclosporin A were similar in ABL and CBL. In contrast, there was less expression and activation of transcription factors in CBL. Activation of NF-κB by TPA/ionomycin was detected in ABL but not CBL. Furthermore, there was less expression of the Th subset-specific transcription factors T-bet and c-maf in CBL versus ABL, whereas GATA-3 expression was similar. Expression of T-bet and c-maf correlated with expression of the Th1 and Th2 cytokines, respectively. Time course experiments revealed that T-bet expression was stimulated in both cell types, whereas c-maf and GATA-3 were induced only in ABL.</p> <p>Conclusion</p> <p>The diminished capability of CBL to synthesize cytokines is probably due to decreased activation of NF-κB, whereas differences in Th subsets are due to differences in regulation of Th lineage-specific transcriptions factors. We propose that the reduced incidence and severity of GvHD after allogeneic transplantation of umbilical CB cells is due to lesser activation of specific transcription factors and a subsequent reduction in production of certain cytokines.</p

Das Beobachterkonzept zum Erhalt der Konsistenz in Datenmodellen

Die Aufgaben des Bauingenieurwesens sind dadurch geprägt, daß sowohl die Planung als auch die Ausführung von Bauwerken häufigen Änderungen unterliegen. Beschreibt man das Verhalten der Bauwerke und den Bauprozeß im Computer mit Modellen, so ändern sich Umfang und Struktur der Modelle als Folge der Änderung in Planung und Ausführung. Diesen Vorgang nennt man Dynamisierung des Modells. Die Dynamisierung führt zu Veränderungen und Inkonsistenzen in den Modellen der Anwendungen. Die Aktualisierung und Abstimmung von Beziehungen innerhalb eines Modells sowie die Sicherung der Konsistenz der Modelle untereinander sind daher von zentraler Bedeutung für die Lösung von Bauingenieuraufgaben. Seit den letzten 10 Jahren wird die objektorientierte Methode in der Modellierung für Anwendungen im Bauingenieurwesen intensiv entwickelt und eingesetzt. Es hat sich gezeigt, daß die Anwendung dieser Methode in wichtigen Bereichen der Modellierung zu Verbesserungen führt. Gleichzeitig hat sich aber auch herausgestellt, daß die für das Bauingenieurwesen wichtigen Aspekte der Aktualisierung und der Konsistenz nicht zweckmäßig beschreibbar sind. In diesem Beitrag wird eine einfache Modelliermethode in ihrem Konzept und ihrer Realisierung gezeigt, mit der sich die Aktualisierung von Objekten und Modellen sowie die Sicherstellung der Konsistenz in Systemen des Bauingenieurwesens bearbeiten lassen

Performance of Layer-by-Layer-Modified Multibore® Ultrafiltration Capillary Membranes for Salt Retention and Removal of Antibiotic Resistance Genes

Polyether sulfone Multibore® ultrafiltration membranes were modified using polyelectrolyte multilayers via the layer-by-layer (LbL) technique in order to increase their rejection capabilities towards salts and antibiotic resistance genes. The modified capillary membranes were characterized to exhibit a molecular weight cut-off (at 90% rejection) of 384 Da. The zeta-potential at pH 7 was −40 mV. Laboratory tests using single-fiber modified membrane modules were performed to evaluate the removal of antibiotic resistance genes; the LbL-coated membranes were able to completely retain DNA fragments from 90 to 1500 nt in length. Furthermore, the pure water permeability and the retention of single inorganic salts, MgSO$_{4}$, CaCl$_{2}$ and NaCl, were measured using a mini-plant testing unit. The modified membranes had a retention of 80% toward MgSO$_{4}$ and CaCl$_{2}$ salts, and 23% in case of NaCl. The modified membranes were also found to be stable against mechanical backwashing (up to 80 LMH) and chemical regeneration (in acidic conditions and basic/oxidizing conditions)

The Redshift Evolution of Rest-UV Spectroscopic Properties to z~5

We perform a comprehensive analysis of the redshift evolution of the rest-UV spectra of star-forming galaxies out to z~5. We combine new z~5 measurements of HI Ly$\alpha$ and low- and high-ionization interstellar metal absorption features with comparable measurements at z~2-4. We measure the equivalent widths of interstellar absorption features using stacked spectra in bins of Ly$\alpha$ equivalent width, performing corrections to Ly$\alpha$ strengths based on a model for the transmission of the intergalactic medium. We find a strong correlation between decreasing low-ionization absorption strength and increasing Ly$\alpha$ emission strength over the redshift range z~2-5, suggesting that both of these quantities are fundamentally linked to neutral gas covering fraction. At the highest Ly$\alpha$ equivalent widths, we observe evolution at $z\sim5$ towards greater Ly$\alpha$ emission strength at fixed low-ionization absorption strength. If we interpret the non-evolving relationship of Ly$\alpha$ emission strength and low-ionization line strength at z~2-4 as primarily reflecting the radiative transfer of Ly$\alpha$ photons, this evolution at z~5 suggests a higher intrinsic production rate of Ly$\alpha$ photons than at lower redshift. Our conclusion is supported by the joint evolution of the relationships among Ly$\alpha$ emission strength, interstellar absorption strength, and dust reddening. We perform additional analysis in bins of stellar mass, star-formation rate, UV luminosity, and age, examining how the relationships between galaxy properties and Ly$\alpha$ emission evolve towards higher redshift. We conclude that increasing intrinsic Ly$\alpha$ photon production and strong detection of nebular CIV emission (signaling lower metallicity) at z~5 indicate an elevated ionized photon production efficiency ($\xi_{\rm ion}$).Comment: 20 pages, 17 figures, accepted for publication in MNRA

Spinal inflammatory hyperalgesia is mediated by prostaglandin E receptors of the EP2 subtype

Blockade of prostaglandin (PG) production by COX inhibitors is the treatment of choice for inflammatory pain but is also prone to severe side effects. Identification of signaling elements downstream of COX inhibition, particularly of PG receptor subtypes responsible for pain sensitization (hyperalgesia), provides a strategy for better-tolerated analgesics. Here, we have identified PGE 2 receptors of the EP2 receptor subtype as key signaling elements in spinal inflammatory hyperalgesia. Mice deficient in EP2 receptors (EP2 -/-mice) completely lack spinal PGE 2 -evoked hyperalgesia. After a peripheral inflammatory stimulus, EP2 -/-mice exhibit only short-lasting peripheral hyperalgesia but lack a second sustained hyperalgesic phase of spinal origin. Electrophysiological recordings identify diminished synaptic inhibition of excitatory dorsal horn neurons as the dominant source of EP2 receptor-dependent hyperalgesia. Our results thus demonstrate that inflammatory hyperalgesia can be treated by targeting of a single PG receptor subtype and provide a rational basis for new analgesic strategies going beyond COX inhibition

Targeted immunotherapy for HER2-low breast cancer with 17p loss

The clinical challenge for treating HER2 (human epidermal growth factor receptor 2)-low breast cancer is the paucity of actionable drug targets. HER2-targeted therapy often has poor clinical efficacy for this disease due to the low level of HER2 protein on the cancer cell surface. We analyzed breast cancer genomics in the search for potential drug targets. Heterozygous loss of chromosome 17p is one of the most frequent genomic events in breast cancer, and 17p loss involves a massive deletion of genes including the tumor suppressor TP53 Our analyses revealed that 17p loss leads to global gene expression changes and reduced tumor infiltration and cytotoxicity of T cells, resulting in immune evasion during breast tumor progression. The 17p deletion region also includes POLR2A, a gene encoding the catalytic subunit of RNA polymerase II that is essential for cell survival. Therefore, breast cancer cells with heterozygous loss of 17p are extremely sensitive to the inhibition of POLR2A via a specific small-molecule inhibitor, α-amanitin. Here, we demonstrate that α-amanitin-conjugated trastuzumab (T-Ama) potentiated the HER2-targeted therapy and exhibited superior efficacy in treating HER2-low breast cancer with 17p loss. Moreover, treatment with T-Ama induced immunogenic cell death in breast cancer cells and, thereby, delivered greater efficacy in combination with immune checkpoint blockade therapy in preclinical HER2-low breast cancer models. Collectively, 17p loss not only drives breast tumorigenesis but also confers therapeutic vulnerabilities that may be used to develop targeted precision immunotherapy

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives