Molecular Subtyping of Invasive Breast Cancer Using a PAM50-Based Multigene Expression Test-Comparison with Molecular-Like Subtyping by Tumor Grade/Immunohistochemistry and Influence on Oncologist’s Decision on Systemic Therapy in a Real-World Setting

In intermediate risk hormone receptor (HR) positive, HER2 negative breast cancer (BC), the decision regarding adjuvant chemotherapy might be facilitated by multigene expression tests. In all, 142 intermediate risk BCs were investigated using the PAM50-based multigene expression test Prosigna® in a prospective multicentric study. In 119/142 cases, Prosigna® molecular subtyping was compared with local and two central (C1 and C6) molecular-like subtypes relying on both immunohistochemistry (IHC; HRs, HER2, Ki-67) and IHC + tumor grade (IHC+G) subtyping. According to local IHC, 35.4% were Luminal A-like and 64.6% Luminal B-like subtypes (local IHC+G subtype: 31.9% Luminal A-like; 68.1% Luminal B-like). In contrast to local and C1 subtyping, C6 classified >2/3 of cases as Luminal A-like. Pairwise agreement between Prosigna® subtyping and molecular-like subtypes was fair to moderate depending on molecular-like subtyping method and center. The best agreement was observed between Prosigna® (53.8% Luminal A; 44.5% Luminal B) and C1 surrogate subtyping (Cohen’s kappa = 0.455). Adjuvant chemotherapy was suggested to 44.2% and 88.6% of Prosigna® Luminal A and Luminal B cases, respectively. Out of all Luminal A-like cases (locally IHC/IHC+G subtyping), adjuvant chemotherapy was recommended if Prosigna® testing classified as Prosigna® Luminal A at high / intermediate risk or upgraded to Prosigna® Luminal B.     

A straightforward design technique for narrowband multi‐stage low‐noise amplifiers with I/O conjugate match

Low‐noise amplifier (LNA) designers often struggle to simultaneously satisfy gain, noise, stability, and I/O matching requirements. In this article, a novel design technique, tailored for two‐stage low‐noise amplifiers, is presented. The proposed design method is completely deterministic and exploits inductive source degeneration to obtain a two‐stage LNA featuring perfect input and output match together with low noise figure (NF) and a pre‐determined gain, including stability analysis. A novel flowchart is provided together with the corresponding design chart that contains gain, matching, and stability information, therefore addressing all key figures‐of‐merit of a linear amplifier. The design chart is easily implementable in commercial Electronic Design Automation software, to aid designers in the difficult task of selecting the appropriate source degeneration inductor value. The noise performance, on the other hand, is the best possible since the matching networks are designed to provide the input of the two Field Effect Transistors with the optimum termination for noise. The design method is validated with two separate test vehicles operating respectively at Ka‐band (26.5‐31.5 GHz) and K‐band (20.0‐24.0 GHz). The realized Monolithic Microwave Integrated Circuits exhibit 18 dB gain for both versions, NF of 1.5 and 1.2 dB, respectively for the Ka‐band and K‐band version. Input and output matching are typically better than 12 and 15 dB.     

JavAdaptor—Flexible runtime updates of Java applications

Software is changed frequently during its life cycle. New requirements come, and bugs must be fixed. To update an application, it usually must be stopped, patched, and restarted. This causes time periods of unavailability, which is always a problem for highly available applications. Even for the development of complex applications, restarts to test new program parts can be time consuming and annoying. Thus, we aim at dynamic software updates to update programs at runtime. There is a large body of research on dynamic software updates, but so far, existing approaches have shortcomings either in terms of flexibility or performance. In addition, some of them depend on specific runtime environments and dictate the program's architecture. We present JavAdaptor , the first runtime update approach based on Java that (a) offers flexible dynamic software updates, (b) is platform independent, (c) introduces only minimal performance overhead, and (d) does not dictate the program architecture. JavAdaptor combines schema changing class replacements by class renaming and caller updates with Java HotSwap using containers and proxies. It runs on top of all major standard Java virtual machines. We evaluate our approach's applicability and performance in non‐trivial case studies and compare it with existing dynamic software update approaches. Copyright © 2012 John Wiley & Sons, Ltd.     

Investigation of Dipicolinic Acid Isosteres for the Inhibition of Metallo-β-Lactamases

New Delhi metallo-β-lactamase-1 (NDM-1) poses an immediate threat to our most effective and widely prescribed drugs, the β-lactam-containing class of antibiotics. There are no clinically relevant inhibitors to combat NDM-1, despite significant efforts toward their development. Inhibitors that use a carboxylic acid motif for binding the Zn^II ions in the active site of NDM-1 make up a large portion of the >500 inhibitors reported to date. New and structurally diverse scaffolds for inhibitor development are needed urgently. Herein we report the isosteric replacement of one carboxylate group of dipicolinic acid (DPA) to obtain DPA isosteres with good inhibitory activity against NDM-1 (and related metallo-β-lactamases, IMP-1 and VIM-2). It was determined that the choice of carboxylate isostere influences both the potency of NDM-1 inhibition and the mechanism of action. Additionally, we show that an isostere with a metal-stripping mechanism can be re-engineered into an inhibitor that favors ternary complex formation. This work provides a roadmap for future isosteric replacement of routinely used metal binding motifs (i.e., carboxylic acids) for the generation of new entities in NDM-1 inhibitor design and development.     

Dendritic Zinc Growth in Acid Electrolyte: Effect of the pH

In this paper, dendritic growth at the edges of electrogalvanized steel strip has been studied using a specially designed rotating washer electrode which simulates the fluid dynamic conditions and the current density distribution at the steel strip edge found in a production line. The effect of electrolyte pH and current density on dendritic growth in an acidic zinc plating bath (ZnSO₄ and H₂SO₄) was addressed. The temperature was kept constant at 60 °C. Solution pH was adjusted to 1, 2 or 3 using different amounts of H₂SO₄. In addition, the influence of temperature on the pH of the solution was determined. The current density was set at 40 or 60 A/dm², similar to that used in the industry. Deposits were characterized using SEM and XRD. The results showed that pH strongly affects dendrites shape, length and texture. Furthermore, the morphology of dendrites at the washer edge and of deposits on the flat portion of the washer changed considerably as solution pH was increased from 1 to 3. It was found that the morphology of dendrites at the washer edge stems from the morphology of the deposit on its flat portion, which in turn determines their shape.     

Dielectric and structural studies of ferroelectric phase evolution in dipole-pair substituted barium titanate ceramics

Ba{[Ga_x,Ta_x]Ti_(1−2x)}O₃ ceramics with x equal to 0, 0.0025, 0.005, 0.01, 0.025, and 0.05 have been prepared by conventional solid-state reaction. Structural and dielectric characterization have been performed to investigate the effect of dipole-pair substitution concentration on the macroscopic dielectric properties. Ba{[Ga_x,Ta_x]Ti_(1−2x)}O₃ evolves from a classic ferroelectric to a diffuse phase transition (DPT) as x increases. Ba{[Ga_x,Ta_x]Ti_(1−2x)}O₃ for x ≥ 0.01 possesses diffuseness parameters comparable to Pb(Mg_1/3Nb_2/3)O₃-PbTiO₃ (PMN-PT) and recently reported (Ba_0.97Pr_0.03)(Ti_0.9425Ce_0.05)O₃ (BPTC), yet it lacks the frequency and temperature dependence of T_m necessary to be a strictly defined relaxor ferroelectric. Additionally, Ba{[Ga_0.05,Ta_0.05]Ti_0.9}O₃ possesses a relative permittivity, ɛ_r, of 700 ± 16% and dissipation factor less than 0.05 at 10 kHz within the temperature range [−75°C, 120°C]. In comparison to BaTiO₃, Ba{[Ga_x,Ta_x]Ti_(1−2x)}O₃ possesses enhanced electrical resistivity at and above room temperature. In situ XRD, including Rietveld refinement, have been performed to determine the lattice parameter, coefficient of thermal expansion, and phase transition temperature (T_c) of each composition within the temperature range [RT, 1000°C], thus linking the dielectric properties with the material's structure. These studies have been corroborated by temperature-dependent Raman spectroscopy to compare the T_c determined by electrical and structural characterization. The properties of Ba{[Ga_x,Ta_x]Ti_(1−2x)}O₃ are discussed in context with available models that describe donor and acceptor dopants spatially separated in the parent matrix, inter-relating lattice parameter, Curie temperature, and other material properties.     

Policy effectiveness on emissions and cost reduction for hydrogen supply chains: The case for British Columbia

Hydrogen-specific policies are required to accelerate the adoption of low-carbon hydrogen. In this study, a range of economic instruments and regulations were incorporated explicitly to optimize a hydrogen supply chain. The effectivenes of policies aiming to enhance the financial viability of low-carbon hydrogen production was quantified. A spatially explicit, multi-period cost optimization model was developed for light duty hydrogen hydrogen vehicle deployment in British Columbia under three demand scenarios. Subsidies and regulations were coupled to current provincial policies (a carbon tax and a low carbon fuel standard). The results indicated that production tax credits and electricity incentives were up to 24 times more effective in facilitating low-carbon hydrogen production compared to capital subsidies, bans on steam methane reforming or the adoption of higher carbon taxes. The strategic deployment of policies over time was found to be more effective than cumulative subsidies.     

Influence of in-plane and out-of-plane machining on the surface topography,the removal mechanism and the flexural strength of 2D C/C-SiC composites

Ceramic Matrix Composites (CMCs) are increasingly demanded especially for the production of structural components for several industries such as aerospace because of their excellent thermo-mechanical and fatigue properties. As one of the last production steps final machining is necessary to meet the required tolerances. From the economic point of view final machining of CMCs is highly critical and special knowledge is assumed to avoid irreparable damage, because of their heterogeneous, anisotropic and brittle nature. In this work diamond grinding and diamond milling have been applied to a 2D C/C-SiC composite at various feed rates and cutting speeds and in both main laminate directions, in-plane and out-of-plane. The microstructures of in-plane and out-of-plane machining indicate different material removal mechanisms due to different composite architecture. Increasing feed rate leads generally to more surface defects and consequently to higher roughness. Little influence on the four-point-bending strength was observed when changing the machining speed.     

A flexible framework for evaluating user and item fairness in recommender systems

User Modeling and User-Adapted Interaction - One common characteristic of research works focused on fairness evaluation (in machine learning) is that they call for some form of parity (equality)...