Deliberately Losing Control of C−H Activation Processes in the Design of Small-Molecule-Fragment Arrays Targeting Peroxisomal Metabolism

Combined photochemical arylation, “nuisance effect” (S_NAr) reaction sequences have been employed in the design of small arrays for immediate deployment in medium-throughput X-ray protein–ligand structure determination. Reactions were deliberately allowed to run “out of control” in terms of selectivity; for example the ortho-arylation of 2-phenylpyridine gave five products resulting from mono- and bisarylations combined with S_NAr processes. As a result, a number of crystallographic hits against NUDT7, a key peroxisomal CoA ester hydrolase, have been identified.     

The thermoelastic behaviour of semicrystalline and of glassy poly(ether-ether-ketone)

A thermoelastic evaluation, based on simultaneous measurements of the mechanical work and of the concomitant heat of deformation by a stretching micro calorimeter, was performed on semicrystalline and glassy PEEK. The objective of this study was to utilize the sensitive technique to detect differences that would account for observed effects of micro structure on mechanical performance. A clear difference was detected beyond a 0.6% strain, where the behaviour of glassy PEEK began to exhibit inelastic features such as yielding and plastic deformation. This difference between the glassy and the semicrystalline polymers was considered the reason for the superior mechanical fatigue and fracture properties produced by the latter micro structure.     

Locally random reductions: Improvements and applications

A (t, n)-locally random reduction maps a problem instancex into a set of problem instancesy ₁,...,y _n in such a way that it is easy to construct the answer tox from the answers toy ₁,...,y _n, and yet the distribution ont-element subsets ofy ₁,...,y _n depends only on |x|. In this paper we formalize such reductions and give improved methods for achieving them. Then we give a cryptographic application, showing a new way to prove in perfect zero knowledge that committed bitsx ₁,...,x _m satisfy some predicateQ. Unlike previous techniques for such perfect zero-knowledge proofs, ours uses an amount of communication that is bounded by a fixed polynomial inm, regardless of the computational complexity ofQ. These results were presented in preliminary form at the 10th Annual Crypto Conference, Santa Barbara, CA, August 1990. The work of D. Beaver was done at Harvard University, supported in part by NSF Grant CCR-870-4513. The work of J. Kilian was done at MIT and Harvard University, supported by an NSF postdoctoral fellowship.     

Liver Lipids of Patients with Hepatitis B and C and Associated Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) still remains a difficult to cure malignancy. In recent years, the focus has shifted to lipid metabolism for the treatment of HCC. Very little is known about hepatitis B virus (HBV) and C virus (HCV)-related hepatic lipid disturbances in non-malignant and cancer tissues. The present study showed that triacylglycerol and cholesterol concentrations were similar in tumor adjacent HBV and HCV liver, and were not induced in the HCC tissues. Higher levels of free cholesterol, polyunsaturated phospholipids and diacylglycerol species were noted in non-tumorous HBV compared to HCV liver. Moreover, polyunsaturated phospholipids and diacylglycerols, and ceramides declined in tumors of HBV infected patients. All of these lipids remained unchanged in HCV-related HCC. In HCV tumors, polyunsaturated phosphatidylinositol levels were even induced. There were no associations of these lipid classes in non-tumor tissues with hepatic inflammation and fibrosis scores. Moreover, these lipids did not correlate with tumor grade or T-stage in HCC tissues. Lipid reprogramming of the three analysed HBV/HCV related tumors mostly resembled HBV-HCC. Indeed, lipid composition of non-tumorous HCV tissue, HCV tumors, HBV tumors and HBV/HCV tumors was highly similar. The tumor suppressor protein p53 regulates lipid metabolism. The p53 and p53S392 protein levels were induced in the tumors of HBV, HCV and double infected patients, and this was significant in HBV infection. Negative correlation of tumor p53 protein with free cholesterol indicates a role of p53 in cholesterol metabolism. In summary, the current study suggests that therapeutic strategies to target lipid metabolism in chronic viral hepatitis and associated cancers have to consider disease etiology.     

Ultra-dense planar metallic nanowire arrays with extremely large anisotropic optical and magnetic properties

A nanofabrication method for the production of ultra-dense planar metallic nanowire arrays scalable to wafer-size is presented. The method is based on an efficient template deposition process to grow diverse metallic nanowire arrays with extreme regularity in only two steps. First, III–V semiconductor substrates are irradiated by a low-energy ion beam at an elevated temperature, forming a highly ordered nanogroove pattern by a “reverse epitaxy” process due to self-assembly of surface vacancies. Second, diverse metallic nanowire arrays (Au, Fe, Ni, Co, FeAl alloy) are fabricated on these III–V templates by deposition at a glancing incidence angle. This method allows for the fabrication of metallic nanowire arrays with periodicities down to 45 nm scaled up to wafer-size fabrication. As typical noble and magnetic metals, the Au and Fe nanowire arrays produced here exhibited large anisotropic optical and magnetic properties, respectively. The excitation of localized surface plasmon resonances (LSPRs) of the Au nanowire arrays resulted in a high electric field enhancement, which was used to detect phthalocyanine (CoPc) in surface-enhanced Raman scattering (SERS). Furthermore, the Fe nanowire arrays showed a very high in-plane magnetic anisotropy of approximately 412 mT, which may be the largest in-plane magnetic anisotropy field yet reported that is solely induced via shape anisotropy within the plane of a thin film.

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Boosted multi-task learning

In this paper we propose a novel algorithm for multi-task learning with boosted decision trees. We learn several different learning tasks with a joint model, explicitly addressing their commonalities through shared parameters and their differences with task-specific ones. This enables implicit data sharing and regularization. Our algorithm is derived using the relationship between ? ₁-regularization and boosting. We evaluate our learning method on web-search ranking data sets from several countries. Here, multi-task learning is particularly helpful as data sets from different countries vary largely in size because of the cost of editorial judgments. Further, the proposed method obtains state-of-the-art results on a publicly available multi-task dataset. Our experiments validate that learning various tasks jointly can lead to significant improvements in performance with surprising reliability.     

A very light and thin liquid hydrogen/deuterium heat pipe target for COSY experiments

A liquid hydrogen/deuterium heat pipe (HP) target is used at the COSY external experiments TOF, GEM and MOMO. The target liquid is produced at a cooled condenser and guided through a central tube assisted by gravitation into the target cell. An aluminum condenser is used instead of copper, which requires less material, improves conductivities and provides shorter cooling down time. Residual condenser temperature fluctuations in the order of ≈0.4 K are reduced by using thermal resistances between the cooling machine and the condenser of the heat pipe combined with a controlled heating power. A new design with only a 7-mm-diameter HP has been developed. The diameter of the condenser part remains at 16 mm to provide enough condensation area. The small amount of material ensures short cooling down times. A cold gas deuterium HP target has been designed and developed which allows protons with energy ?1 MeV to be measured. A 7-mm-diameter HP is used to fill a cooling jacket around the D₂ gas cell with LH₂. The D₂ gas is stabilized at 200 mbar to allow for thin windows. Its density is increased by factor 15 compared to room temperature.     

Studying grain boundary regions in polycrystalline materials using spherical nano-indentation and orientation imaging microscopy

In this article, we report on the application of our spherical nanoindentation data analysis protocols to study the mechanical response of grain boundary regions in as-cast and 30% deformed polycrystalline Fe–3%Si steel. In particular, we demonstrate that it is possible to investigate the role of grain boundaries in the mechanical deformation of polycrystalline samples by systematically studying the changes in the indentation stress–strain curves as a function of the distance from the grain boundary. Such datasets, when combined with the local crystal lattice orientation information obtained using orientation imaging microscopy, open new avenues for characterizing the mechanical behavior of grain boundaries based on their misorientation angle, dislocation density content near the boundary, and their propensity for dislocation source/sink behavior.     

DFC++ Processing Framework Concept

Development of modern Software Defined Radio (SDR) based communication systems can be accelerated significantly by the use of processing frameworks. The evolution of SDR and the involved departure from digital representations of classical radio architecture towards more abstract software systems raises new requirements of increased flexibility and versatility. The proposed Data Flow Control for C++ (DFC++) processing framework concept addresses those requirements by employing modern programming techniques and flow control mechanisms to allow for variable data rates, dynamic paths, and flexible component designs. Another important trend is the integration of various embedded platforms in the software radio domain. The rapidly increasing performance and efficiency of embedded processors enables the deployment of SDR systems in more space and power constrained environments. Therefore covering a heterogeneous hardware selection becomes increasingly important for processing frameworks. By relying exclusively on C++ and minimizing external dependencies, DFC++ is specifically aiming for excellent portability and adaptability to support a wide range of current and future software radio projects while maintaining high performance and ease of use. This paper introduces the key aspects of the DFC++ concept and implementation with focus on the reference pointer based data transport mechanisms responsible for the propagation of user data between different processing components.     

Chemical Biology Tools To Investigate Malaria Parasites

Parasitic diseases like malaria tropica have been shaping human evolution and history since the beginning of mankind. After infection, the response of the human host ranges from asymptomatic to severe and may culminate in death. Therefore, proper examination of the parasite's biology is pivotal to deciphering unique molecular, biochemical and cell biological processes, which in turn ensure the identification of treatment strategies, such as potent drug targets and vaccine candidates. However, implementing molecular biology methods for genetic manipulation proves to be difficult for many parasite model organisms. The development of fast and straightforward applicable alternatives, for instance small-molecule probes from the field of chemical biology, is essential. In this review, we will recapitulate the highlights of previous molecular and chemical biology approaches that have already created insight and understanding of the malaria parasite Plasmodium falciparum. We discuss current developments from the field of chemical biology and explore how their application could advance research into this parasite in the future. We anticipate that the described approaches will help to close knowledge gaps in the biology of P. falciparum and we hope that researchers will be inspired to use these methods to gain knowledge – with the aim of ending this devastating disease.