Bis(Benzofuran–1,3-N,N-heterocycle)s as Symmetric and Synthetic Drug Leads against Yellow Fever Virus

The yellow fever virus (YFV) is an emerging RNA virus and has caused large outbreaks in Africa and Central and South America. The virus is often transmitted through infected mosquitoes and spreads from area to area because of international travel. Being an acute viral hemorrhagic disease, yellow fever can be prevented by an effective, safe, and reliable vaccine, but not be eliminated. Currently, there is no antiviral drug available for its cure. Thus, two series of novel bis(benzofuran–1,3-imidazolidin-4-one)s and bis(benzofuran–1,3-benzimidazole)s were designed and synthesized for the development of anti-YFV lead candidates. Among 23 new bis-conjugated compounds, 4 of them inhibited YFV strain 17D (Stamaril) on Huh-7 cells in the cytopathic effect reduction assays. These conjugates exhibited the most compelling efficacy and selectivity with an EC₅₀ of <3.54 μM and SI of >15.3. The results are valuable for the development of novel antiviral drug leads against emerging diseases.     

Reversible Platelet Integrin αIIbβ3 Activation and Thrombus Instability

Integrin αIIbβ3 activation is essential for platelet aggregation and, accordingly, for hemostasis and arterial thrombosis. The αIIbβ3 integrin is highly expressed on platelets and requires an activation step for binding to fibrinogen, fibrin or von Willebrand factor (VWF). A current model assumes that the process of integrin activation relies on actomyosin force-dependent molecular changes from a bent-closed and extended-closed to an extended-open conformation. In this paper we review the pathways that point to a functional reversibility of platelet αIIbβ3 activation and transient aggregation. Furthermore, we refer to mouse models indicating that genetic defects that lead to reversible platelet aggregation can also cause instable thrombus formation. We discuss the platelet agonists and signaling pathways that lead to a transient binding of ligands to integrin αIIbβ3. Our analysis points to the (autocrine) ADP P2Y₁ and P2Y₁₂ receptor signaling via phosphoinositide 3-kinases and Akt as principal pathways linked to reversible integrin activation. Downstream signaling events by protein kinase C, CalDAG-GEFI and Rap1b have not been linked to transient integrin activation. Insight into the functional reversibility of integrin activation pathways will help to better understand the effects of antiplatelet agents.     

低IQ DC/DC控制器帮助延长汽车电池运行时间

尽管开关模式电源效率很高,但是所有开关模式电源都需要一定量的功率,以在甚至没有输出负载或输出负载非常小时工作.尽管这一功率可能很低,但是在能量稀缺和多个始终保持接通电路处于体眠模式的应用中,这一功率却可能高得不可接受.为了解决这个问题,凌力尔特公司提供的LTC3857/-1双输出同步降压型控制器采用了突发模式(Burst Mode)工作,这种工作模式在DC/DC转换器轻负载时最大限度地降低了功耗     

Study of the bias of the MTC estimate by noise analysis due to the presence of feedback

This paper discusses the bias of the non-parametric Moderator Temperature Coefficient (MTC) estimate due to the presence of feedback. Up to now the non-parametric estimation of the Frequency Response Function (FRF) is the most commonly used method to estimate the MTC by noise analysis. This estimation method is proportional to the Cross Power Spectral Density between the total neutron flux variation and total temperature variation divided by the auto power spectral density of the total temperature variation. The estimation method is very popular since feedback is considered to be negligible in the frequency band of interest. Unfortunately this is not the case in practice. Measurements at a Nuclear Power Plant in Belgium will be used to confirm that this feedback cannot be neglected. In case of feedback the chosen estimator always results in a biased estimate when there are external neutron flux variations present. It will be seen that the ratio between the external neutron flux and external temperature variation in combination with the amplitude of the feedback determines the bias. The theoretical analysis of the bias is based on a simplified scheme of the MTC measurement setup. A simulation in MATLAB is used to confirm the theoretical results. In order to avoid a biased estimate due to the feedback we will advise to measure the external temperature variation and to use another non-parametric estimator.     

The Yield Stress of Gas/Liquid/Fibre Suspensions

Yield stress measurements of gas/liquid/fibre suspensions, were conducted to examine the effect of gas concentration as well as fibre concentration. Obtaining a well mixed stable pulp suspension with gas was difficult. A transparent model system consisting of glass fibres submersed in refractive index matched liquid gave stable suspensions and had the additional advantage of allowing visual observations. The measurements were performed in a baffled shear tester and concentrations were in the range of 0–12.5% vol. gas and 8–14% wt. fibres. Results show that yield stress decreases with increasing gas fraction for constant fibre concentrations. Since the fibre concentration is defined in the liquid phase, the amount of fibres decreases with increasing gas concentration. This fact alone partly explains the decrease in yield stress, but the gas also has a direct impact on the decrease in yield stress. Further, as expected, the yield stress increases with increasing fibre concentrations when the gas fraction is kept constant.     

An annotated corpus for the analysis of VP ellipsis

Verb Phrase Ellipsis (VPE) has been studied in great depth in theoretical linguistics, but empirical studies of VPE are rare. We extend the few previous corpus studies with an annotated corpus of VPE in all 25 sections of the Wall Street Journal corpus (WSJ) distributed with the Penn Treebank. We annotated the raw files using a stand-off annotation scheme that codes the auxiliary verb triggering the elided verb phrase, the start and end of the antecedent, the syntactic type of antecedent (VP, TV, NP, PP or AP), and the type of syntactic pattern between the source and target clauses of the VPE and its antecedent. We found 487 instances of VPE (including predicative ellipsis, antecedent-contained deletion, comparative constructions, and pseudo-gapping) plus 67 cases of related phenomena such as do so anaphora. Inter-annotator agreement was high, with a 0.97 average F-score for three annotators for one section of the WSJ. Our annotation is theory neutral, and has better coverage than earlier efforts that relied on automatic methods, e.g. simply searching the parsed version of the Penn Treebank for empty VP’s achieves a high precision (0.95) but low recall (0.58) when compared with our manual annotation. The distribution of VPE source–target patterns deviates highly from the standard examples found in the theoretical linguistics literature on VPE, once more underlining the value of corpus studies. The resulting corpus will be useful for studying VPE phenomena as well as for evaluating natural language processing systems equipped with ellipsis resolution algorithms, and we propose evaluation measures for VPE detection and VPE antecedent selection. The stand-off annotation is freely available for research purposes.     

Catalyst Design by NH4OH Treatment of USY Zeolite

Hierarchical zeolites are a class of superior catalysts which couples the intrinsic zeolitic properties to enhanced accessibility and intracrystalline mass transport to and from the active sites. The design of hierarchical USY (Ultra‐Stable Y) catalysts is achieved using a sustainable postsynthetic room temperature treatment with mildly alkaline NH₄OH (0.02 m ) solutions. Starting from a commercial dealuminated USY zeolite (Si/Al = 47), a hierarchical material is obtained by selective and tuneable creation of interconnected and accessible small mesopores (2–6 nm). In addition, the treatment immediately yields the NH₄⁺ form without the need for additional ion exchange. After NH₄OH modification, the crystal morphology is retained, whereas the microporosity and relative crystallinity are decreased. The gradual formation of dense amorphous phases throughout the crystal without significant framework atom leaching rationalizes the very high material yields (>90%). The superior catalytic performance of the developed hierarchical zeolites is demonstrated in the acid‐catalyzed isomerization of α‐pinene and the metal‐catalyzed conjugation of safflower oil. Significant improvements in activity and selectivity are attained, as well as a lowered susceptibility to deactivation. The catalytic performance is intimately related to the introduced mesopores, hence enhanced mass transport capacity, and the retained intrinsic zeolitic properties.     

Incremental method evolution in global software product management: A retrospective case study

Company growth in a global setting causes challenges in the adaptation and maintenance of an organization’s methods. In this paper, we will analyze incremental method evolution in software product management in a global environment. We validate a method increment approach, based on method engineering principles, by applying it to a retrospective case study conducted at a large ERP vendor. The results show that the method increment types cover all increments that were found in the case study. Also, we identified the following lessons learned for company growth in a global software product management context: method increment drivers, such as the change of business strategy, vary during evolution; a shared infrastructure is critical for rollout; small increments facilitate gradual process improvement; and global involvement is critical. We then claim that method increments enable software companies to accommodate evolutionary adaptations of development process in agreement with the overall company expansion.     

Electromagnetic MEMS microspeaker for portable electronic devices

This work presents the conception, the microfabrication, and the electroacoustic characterization of a new electromagnetic microspeaker based on silicon. The objectives are to get improved sound quality compared to that of conventional microspeakers, while keeping the electroacoustic efficiency as high as possible. An optimized stiffening silicon microstructure let the sound radiator be extremely light and rigid. The mobile part is suspended to the fixed part by silicon suspension springs, which enable large out-of-plane displacement. The acoustic radiator is actuated by an electromagnetic motor, composed of a fixed permanent magnet and a planar coil located on top of the silicon radiator. The piston-like motion of the radiator favored by this structure is very beneficial for the sound quality. Electro–mechano–acoustic characterization of the microfabricated microspeaker showed that the radiator surface could run out-of-plane with displacements higher than ±400 μm, with no mechanical and electrical failure. For an electrical power of 0.5 W, the microspeaker was capable to generate a sound pressure level of 80 dB at 10 cm, from 330 Hz up to 20 kHz frequency. The efficiency reaches 3 × 10^?5, that is to say three times more than typical efficiency of conventional microspeakers. Moreover, as characterization results showed, the existence of very few structural modes and the low electroacoustic distortions evidence the high sound quality of the microspeaker.     

Platinum particle size and support effects in NO(x) mediated carbon oxidation over platinum catalysts

Platinum metal was dispersed on microporous, mesoporous, and nonporous support materials including the zeolites Na-Y, Ba-Y, Ferrierite, ZSM-22, ETS-10, and AIPO-11, alumina, and titania. The oxidation of carbon black loosely mixed with catalyst powder was monitored gravimetrically in a gas stream containing nitric oxide, oxygen, and water. The carbon oxidation activity of the catalysts was found to be uniquely related to the Pt dispersion and little influenced by support type. The optimum dispersion is around 3-4% corresponding to relatively large Pt particle sizes of 20-40 nm. The carbon oxidation activity reflects the NO oxidation activity of the platinum catalyst, which reaches an optimum in the 20-40 nm Pt particle size range. The lowest carbon oxidation temperatures were achieved with platinum loaded ZSM-22 and AIPO-11 zeolite crystallites bearing platinum of optimum dispersion on their external surfaces.