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.     

Influence of episodic wind events on thermal stratification and bottom water hypoxia in a Great Lakes estuary

Hypoxia formation and breakdown were tracked during 2015 in Muskegon Lake estuary at multiple locations, and five years (2011–2015) of time-series buoy observatory data were evaluated for the effect of episodic wind-events on lake mixing. Bi-weekly water temperature and dissolved oxygen (DO) profiles at four locations revealed that hypoxia occurred at all sites and persisted for 2–3 months during summer 2015. On one date in late-summer, up to 24% of the lake’s volume was estimated to be mildly hypoxic (DO < 4 mg L^?1) as defined by lake sturgeon requirements. Patterns of wind speed and water column stability in late spring indicated that high winds and low stability delayed the onset of hypoxia while in late summer low winds and high stability delayed degradation of hypoxia. Wind speeds appear to play a great role in the interannual variability of stratification and subsequent hypoxia. Water temperature and DO profiles taken before and after one mid-summer mixing event (wind speed >7.7 m s^?1 for 10 h), indicated that while the wind was unable to completely mix the entire water column, it deepened the epilimnion by ～1.5 m and sheared a thin layer from the upper hypolimnion. By entraining internally loaded nutrients, such episodic wind-events may initiate and sustain algal blooms in nutrient limited surface waters. Quantifying the variable role of wind and mixing events will be key to integrating limnological processes into climate models of the future.     

Research on the overall architecture of Internet of Things middleware for intelligent industrial parks

With the continuous development of the Internet of Things technology and the proposal of “Made in China 2025”, the construction of IoT applicat     

Quantitative pharmacophore models with inductive logic programming

Three-dimensional models, or pharmacophores, describing Euclidean constraints on the location on small molecules of functional groups (like hydrophobic groups, hydrogen acceptors and donors, etc.), are often used in drug design to describe the medicinal activity of potential drugs (or ‘ligands’). This medicinal activity is produced by interaction of the functional groups on the ligand with a binding site on a target protein. In identifying structure-activity relations of this kind there are three principal issues: (1) It is often difficult to “align” the ligands in order to identify common structural properties that may be responsible for activity; (2) Ligands in solution can adopt different shapes (or `conformations’) arising from torsional rotations about bonds. The 3-D molecular substructure is typically sought on one or more low-energy conformers; and (3) Pharmacophore models must, ideally, predict medicinal activity on some quantitative scale. It has been shown that the logical representation adopted by Inductive Logic Programming (ILP) naturally resolves many of the difficulties associated with the alignment and multi-conformation issues. However, the predictions of models constructed by ILP have hitherto only been nominal, predicting medicinal activity to be present or absent. In this paper, we investigate the construction of two kinds of quantitative pharmacophoric models with ILP: (a) Models that predict the probability that a ligand is “active”; and (b) Models that predict the actual medicinal activity of a ligand. Quantitative predictions are obtained by the utilising the following statistical procedures as background knowledge: logistic regression and naive Bayes, for probability prediction; linear and kernel regression, for activity prediction. The multi-conformation issue and, more generally, the relational representation used by ILP results in some special difficulties in the use of any statistical procedure. We present the principal issues and some solutions. Specifically, using data on the inhibition of the protease Thermolysin, we demonstrate that it is possible for an ILP program to construct good quantitative structure-activity models. We also comment on the relationship of this work to other recent developments in statistical relational learning. Editors: Tamás Horváth and Akihiro Yamamoto     

不断增强RF功率测量

精确的RF功率管理是现代无线发射器的热点话题，从基站的功率放大器保护到移动应用中的延长电池使用时间，它都有很多的优点。RF功率监测器，比如对数放大器，允许RF功率测量系统在一个较宽的范围监控和动态调整发射功率。尽管近几年来功率监测的精度已经有了很大改进，但是对于像那些需要高功率发射的应用甚至受到0dB功率监测误差微小变化引起的显著影响。因此这也促使检测器性能不断提高。     

Quantitative feedback theory with applications in welding

Two different control systems were developed using quantitative feedback theory for weld quality improvement. The first application to be discussed was designed for the resistance pinch welding process and uses electrode displacement and force as feedback parameters. A correlation between weld quality and electrode displacement is established for constant electrode force. The system is capable of producing repeatable welds of consistent quality, with wide variations in weld parameters. This is the first time feedback control has been successfully applied to pinch welding. The second example presented in this paper was developed for penetration control of the gas-tungsten-arc welding process. The feedback signal is obtained by measuring the amount of light emitted from the back side of the weld. Welds of constant penetration have been demonstrated in tests with travel speeds varying from 1.5 to 6 inches per minute and with 200 per cent changes in part thickness.     

MANAGING DISTRIBUTED COMPUTING Five Practices for Success

Management of distributed environments requires corporate IS managers to shift from being operators of a central utility to facilitators who can recognize the synergy among loosely related groups of users. Success depends on the development of new ways of visualizing and measuring the service delivery process.