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Since ibrutinib was approved by the FDA as an effective monotherapy for chronic lymphocytic leukemia (CLL) and multilymphoma, more and more FDA-approved covalent drugs are coming back into the market. On this occasion, the resurgence of interest in covalent drugs calls for more hit discovery techniques. However, the limited numbers of covalent libraries prevent the development of this area. Herein, we report the design of covalent DNA-encoded library (DEL) and its selection method for the discovery of covalent inhibitors for target proteins. These triazine-based covalent DELs yielded potent compounds after covalent selection against target proteins, including Bruton's Tyrosine Kinase (BTK), Janus kinase 3 (JAK3), and peptidyl-prolyl cis/trans isomerase NIMA-interacting-1 (Pin1).

Transcription factor LEF1 is a downstream mediator of the Wnt/β-Catenin signaling pathway. It is expressed in dermal papilla and surrounding cells in the hair follicle, promoting cell proliferation and differentiation.Here we report that LEF1 is also expressed all through the hair cycle in the terminal Schwann cells (TSCs), a component of the lanceolate complex located at the isthmus. The timing of LEF1 appearance at the isthmus coincides with that of hair follicle innervation. LEF1 is not found at the isthmus in the aberrant hair follicles in nude mice. Instead, LEF1 in TSCs is found in the de novo hair follicles reconstituted on nude mice by stem cells chamber graft assay. Cutaneous denervation experiment demonstrates that the LEF1 expression in TSCs is independent of nerve endings. At last, LEF1 expression in the interfollicular epidermis during the early stage of skin development is significantly suppressed in transgenic mice with TCF3 overexpression.We reveal the expression dynamics of LEF1 in skin during development and hair cycle. LEF1 expression in TSCs indicates that the LEF1/Wnt signal might help to establish a niche at the isthmus region for the lanceolate complex, the bulge stem cells and other neighboring cells. This article is protected by copyright. All rights reserved.

An accurate geoid model is needed for surveyors and engineers who require orthometric heights on a common datum, and environment scientists who require elevations relative to present sea level. Airborne gravity data has been collected by the National Geodetic Survey (NGS) under the Gravity for the Redefinition of the American Vertical Datum (GRAV-D) project and is available along the coasts of the Gulf of Mexico. For this study we obtained a set of absolute gravity data derived from full-field gravity at altitude/elevation. We used the data to derive free-air gravity anomalies to establish gravity on the geoid. For spatial interpolation we used the kriging method to estimate gravity on the geoid in any location and kriging of the difference between gravity on the ellipsoid of reference and the geoid. Various kriging methods were used for evaluation of errors calculated in this study. The mean precision of the predicted values is around 1.23 cm, a very good result for coastal regions, which traditionally have sparse gravity data sets. ResumenLos agrimensores e ingenieros necesitan un modelo preciso del geoide ya que requieren alturas ortométricas de datos comunes, y los científicos del ambiente requieren de elevaciones reales del nivel del mar. La Encuesta Nacional Geodética (NGS por sus siglas en inglés) del proyecto Gravedad para la Redefinición del Datum Vertical Americano (GRAV-D, por sus siglas en inglés) ha recogido datos de gravedad en el aire para las costas del Golfo de México. Para este estudio obtuvimos un conjunto de datos de gravedad absoluta derivados de gravedad completa de campo en altitud/elevación. Usamos los datos para derivar anomalías de gravedad de aire libre con el fin de establecer gravedad en el geoide. En la interpolación espacial usamos el método de kriging para estimar la gravedad en el geoide en cualquier lugar y kriging de la diferencia entre gravedad del elpsoide de referencia y el geoide. Varios métodos de kriging se usaron para evaluar los errores calculados en este estudio. La precisión media de los valores predicho ande alrededor de 1.23 cm, un resultado muy bueno para regiones costeras, que tradicionalmente tienen conjuntos de datos de gravedad dispersos.

This paper deals with the application of kriging technique to find the continuous map of gravity on the geoid in the coastal areas and to evaluate its precision.

An accurate geoid model is needed for surveyors and engineers who require orthometric heights on a common datum, and environ- ment scientists who require elevations relative to present sea level. Airborne gravity data has been collected by the National Geodetic Survey (NGS) under the Gravity for the Redefinition of the Amer- ican Vertical Datum (GRAV-D) project and is available along the coasts of the Gulf of Mexico. For this study we obtained a set of abso- lute gravity data derived from full-field gravity at altitude/elevation. We used the data to derive free-air gravity anomalies to establish gravity on the geoid. For spatial interpolation we used the kriging method to estimate gravity on the geoid in any location and krig- ing of the difference between gravity on the ellipsoid of reference and the geoid. Various kriging methods were used for evaluation of errors calculated in this study. The mean precision of the predicted val- ues is around 1.23 cm, a very good result for coastal regions, which traditionally have sparse gravity data sets.

Revisiting web pages is common when using web browsers. Commercial browsers provide some revisitation tools for users, for example, back and forward buttons, bookmarks and history lists. However, these tools still have some limitations. In this paper, we presented the design and implementation of a novel thumbnail-based web revisitation tool (TRT). TRT employs enhanced thumbnail and treemaps for improving user experience. Comparing to the other graphical revisitation tools, TRT has three new features. First, TRT display thumbnails and titles in a panel, not a list box. Second, logo-enhanced thumbnails are used as an option by the user. Third, treemaps visualization method is used to change the layout of the panel.

Mobile devices are getting more and more popular in people's daily life, but their usability becomes a key issue that affects their acceptance by users. Traditional usability testing methods and platforms cannot easily fit into the mobile environment, because the lab settings are not the same as the real environment where they are used. However, the advances in computing power and wireless network bring new opportunities to the usability research. This paper discusses the challenges and presents a new method for testing the usability of mobile phones. This method utilizes the computing power of the so-called “Smart Phone” to record the user's activities, such as actions, sound and screen. The recorded data are then transferred via the Wi-Fi network to the observer's side in a silent manner without disturbing the user. Experiments were conducted to see whether this method meets the requirement of remote usability testing. The results showed that the data recording could work efficiently without disturbing the user, and the data transfer could be timeliness in an environment with good signal. We believe that this method can be a practical way to study the usability of mobile phones.

With the development of Computer Supported Cooperative Work (CSCW), groupware systems that support collaborative editing have been developing rapidly. Real-time collaborative editing system is groupware systems that allow groups of users from different sites to view and edit the same documents at the same time. Consistency maintenance is one of the most important challenges in the design of these systems. Many algorithms for consistency maintenance which have good performance with Client/Server mode can't work in Peer-to-Peer (P2P) environments. In this paper, we propose an operational transformation algorithm with conflict detection and awareness methods for real-time collaborative editing in P2P environments, where conflict awareness is a reasonable way to help users to solve conflict problems. We designed and implemented a real-time collaborative editor using our algorithm. The experiment results showed that our algorithm is viable and feasible.

With the development of Computer Supported Cooperative Work (CSCW), people's work has become much more efficient by using groupware systems that support collaborative editing. However, many collaborative editing systems only support one type of documents and are sometimes even more difficult to use than traditional software. As a result, we designed and implemented a general collaborative editing platform, which supports collaborative editing of any type of documents by using users' familiar software. The platform is designed in Client/Server style, where the shared document is stored on the server and the users access the document from the client side. File locking mechanism is used to solve the concurrency problem in our platform. Three modules of concurrency control and the design of our platform are described in this paper. The experiment results showed that our platform made a good performance for collaborative editing.

Image retargeting addresses the problem of adapting images to display on devices with small sizes and different aspect ratios. A fisheye warping method for image retargeting is presented in this paper. Our method emphasizes important aspects of images without completely discarding the remaining parts and can solve the multi-focus problem. We have designed and implemented two fisheye transformation algorithms and three multi-focus conflict solution schemes. The results of usability testing show that our method is appropriate for image retargeting.

Graphical fisheye view is an effective technique for visualizing and navigating large information structures. However, there are still technical difficulties that hinder its broader applications. One of the prominent problems is the varying length effect seen in most fisheye views. The varying length effect refers to a phenomenon that the length (or height) of a fisheye component is not fixed, but it varies with the location of the focal point. This effect may bring some disadvantages that reduce the usability of a fisheye component. To overcome this defect, sporadical solutions have been seen for specific implementations, but a systematic method has not been seen yet. This paper proposes a length compensation method to eliminate the varying length defect for one dimensional fisheye components. The method provides solutions for handling both discrete and continuous magnifications respectively. The mathematical foundation of the method is given, and the implemented prototype proves that it is effective.

Multi-clock is commonly used in complex systems. So if synchronous signals in one clock domain are transferred to another clock domain, they will become asynchronous signals. Asynchronous signals will cause metastable state, which will lead to unpredictable results. How metastabilities led to errors in a system is described first. Then a simulation of RS flip flop using pspice is to show the detail procedure of metastability. To demonstrate how often metastabilities will happen, a FPGA based experimentation is realized by changing the internal layout of flip flop manually, which changes the propagation delay between them.

List is a widely used graphical user interface (GUI) component for organizing linearly structured information. It is simple and useful when containing only a few elements. However long lists are difficult to use because only a small part of the list is shown each time, to gain an overview or select elements from a long list the user usually needs to scroll the list many times. This paper tackles this problem by applying the fisheye strategy to the view of the list. The fisheye view dynamically changes the elements to bigger sizes to form a focal area around the mouse cursor while keeping the elements in the peripheral area in smaller sizes as context. This enables it to display a longer list within the same screen area. Therefore navigating the list can be more efficient. Moreover to further increase the information density, graphical representation of the elements' features is used. By doing so the list can be changed into a visualization tool.

Second Life is one of the most popular 3-D multiplayer online games. It's a virtual environment with the features of immersion, interaction and imagination. Some educational communities were built in SL to enhance the traditional teaching way. One would expect the same phenomenon to be true in design and build museum in the virtual world. The discoveries in design and build museum for educational purpose were present, and the related works about design and build museum are discussed.

Automated species identification based on image processing and pattern recognition, as a small but growing domain, has been actively researched in recent years. Feature extraction is always the key step. This paper proposes a hybrid moment invariants method to extract the features of image. The main idea of this method is to combine Hu's invariants and blur- affine moment invariants to identify winged insects obtained under unknown illumination and blurring conditions and it is exemplified by left forewing images of dragonflies. The new method has more advantages such as insensitive to translation, scale change, rotation, as well as affine transform and blurring. The experimental results on a small set of samples showed that the method can achieve higher identification rate.