Miracle-dz/UniFAR-FTUs huggingface dataset:
Total Synthesis of Vinblastine, Related Natural Products, and Key Analogues and Development of Inspired Methodology Suitable for the Systematic Study of Their Structure–Function Properties

Conspectus Biologically active natural products composed of fascinatingly complex structures are often regarded as not amenable to traditional systematic structure–function studies enlisted in medicinal chemistry for the optimization of their properties beyond what might be accomplished by semisynthetic modification. Herein, we summarize our recent studies on the Vinca alkaloids vinblastine and vincristine, often considered as prototypical members of such natural products, that not only inspired the development of powerful new synthetic methodology designed to expedite their total synthesis but have subsequently led to the discovery of several distinct classes of new, more potent, and previously inaccessible analogues. With use of the newly developed methodology and in addition to ongoing efforts to systematically define the importance of each embedded structural feature of vinblastine, two classes of analogues already have been discovered that enhance the potency of the natural products >10-fold. In one instance, remarkable progress has also been made on the refractory problem of reducing Pgp transport responsible for clinical resistance with a series of derivatives made accessible only using the newly developed synthetic methodology. Unlike the removal of vinblastine structural features or substituents, which typically has a detrimental impact, the additions of new structural features have been found that can enhance target tubulin binding affinity and functional activity while simultaneously disrupting Pgp binding, transport, and functional resistance. Already analogues are in hand that are deserving of full preclinical development, and it is a tribute to the advances in organic synthesis that they are readily accessible even on a natural product of a complexity once thought refractory to such an approach.
High-purity isolation of bullfrog hair bundles and subcellular and topological localization of constituent proteins

The small number of hair cells in auditory and vestibular organs severely impedes the biochemical characterization of the proteins involved in mechano-electrical transduction. By developing an efficient and clean "twist-off" method of hair bundle isolation, and by devising a sensitive, nonradioactive method to detect minute quantities of protein, we have partially overcome this limitation and have extensively classified the proteins of the bundles. To isolate hair bundles, we glue the saccular macula of the bullfrog to a glass coverslip, expose the tissue to a molten agarose solution, and allow the agarose to solidify to a firm gel. By rotating the gel disk with respect to the fixed macula, we isolate the hair bundles by shearing them at their mechanically weak bases. The plasma membranes of at least 80% of the stereocilia reseal. To visualize the proteins of the hair bundle, we covalently label them with biotin, separate them by SDS- PAGE, and transfer them to a charged nylon membrane. We can detect less than 500 fg of protein by probing the membrane with streptavidin- alkaline phosphatase and detecting the chemiluminescent product from the hydrolysis of the substrate 3-(4-methoxyspiro-(1,2-dioxetane-3,2'- tricyclo-[3.3.1. 1(3.7)]decan)-4-yl) phenyl phosphate (AMPPD). These techniques reveal a distinct constellation of proteins in and associated with hair bundles. Several proteins, such as calmodulin, calbindin, actin, tubulin, and fimbrin, have previously been described. A second class of proteins in the preparation appears to be derived from extracellular sources. Finally, several heretofore undescribed bundle proteins are identified and characterized by their membrane topology, subcellular localization, and glycosidase and protease sensitivities.
The European Monetary Union: A Political Time Bomb

On January 1, 1999, the exchange rate parities for the countries forming the European Monetary Union were irrevocably fixed. That was the start of the final phase of a process initially aimed at introducing a single currency in Europe, but that now has the final goal of creating a United States of Europe. What are the benefits and potential costs of the European Monetary Union? And will the long transition process between the irrevocable setting of exchange rate parities on January 1, 1999, and the replacement of the various national currencies by the euro in 2002 be a period filled with uncertainty?
Semiautomated Alignment of High-Throughput Metabolite Profiles with Chemometric Tools

The rapid increase in the use of metabolite profiling/fingerprinting techniques to resolve complicated issues in metabolomics has stimulated demand for data processing techniques, such as alignment, to extract detailed information. In this study, a new and automated method was developed to correct the retention time shift of high-dimensional and high-throughput data sets. Information from the target chromatographic profiles was used to determine the standard profile as a reference for alignment. A novel, piecewise data partition strategy was applied for the determination of the target components in the standard profile as markers for alignment. An automated target search (ATS) method was proposed to find the exact retention times of the selected targets in other profiles for alignment. The linear interpolation technique (LIT) was employed to align the profiles prior to pattern recognition, comprehensive comparison analysis, and other data processing steps. In total, 94 metabolite profiles of ginseng were studied, including the most volatile secondary metabolites. The method used in this article could be an essential step in the extraction of information from high-throughput data acquired in the study of systems biology, metabolomics, and biomarker discovery.
The Relationship Between Financial Variables and Real Economic Activity: Evidence From Spectral and Wavelet Analyses

Many empirical studies find that financial variables possess a predictive power over real economic activity. To examine this relationship, we adopt two time-series techniques: spectral analysis and a newly developed method, wavelet analysis. The major innovation of this paper is to apply wavelet analysis to the investigation of the relationship between various financial variables and real economic activity. Spectral analysis reports that US industrial production and financial variables have a common component in the long run and a varying lead-lag relationship, depending on the cycles. It implies that the relationship between US industrial production and the financial variables is not constant over time. This result is consistently confirmed by wavelet analysis. The lead-lag relationship, in the sense of Granger causality, varies over time, depending on the wavelet time scale.
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Interaction among actors involved in a Web-based learning environment is widely thought of as a valuable process, in that it stimulates collaborative work and augments the effectiveness of learning itself. This may be extensively achieved by the integration of groupware tools and techniques, originally coming from the Computer-Supported Cooperative Work discipline. This paper reports on MEDIT, a Web-based environment that addresses various pedagogical issues and has been developed in line with the above. Offering complementary support, and not substituting traditional practices, our approach distinguishes three virtual workspaces and provides appropriate services for each of them. The paper focuses on the presentation of the innovative tools MEDIT is composed of. These concern the multiple view representation of a course, the creation and maintenance of student customised courses , everal exercise methods , argumentative discourse between teachers and students, and group decision making . MEDIT has already been used in five undergraduate courses demonstrating promising evaluation results.
A Type-safe Macro System for XML

XML is originally designed for the use in document processing. Every classical document processing system supports a mechanism which is called macro. In general, a macro is a named collection of actions. These actions are executed whenever the name of the macro appears in a document instance. We describe a very small but powerful macro language for XML. The presented language supports macros with arguments. As a main result we will show that for a macro expansion H and a recognizable set R the set H-1(R) of trees t, whose macro expansion H(t) are in R, is recognizable. This implies that the typechecking problem for macro expansion is decidable. A major drawback of this approach is the time complexity. Therefore we designed a practical typechecking discipline. We equip every macro definition with a type expression describing the input forests. On the basis of this type information the macro processor computes an output type for the macro. Having inferred this output type, we aim at extending the given output DTD to a DTD for admissible input possibly containing unexpanded macros.
Supporting Self-Directed Learning Process in a Virtual Collaborative Problem Based Learning Environment

The PBL process is a self-directed learning process. In the light of self-directed learning theory, the author argues that computational mechanisms can be used to support selfdirected learning for PBL groups in virtual learning environments. In this paper, an approach to the support of self-directed learning is proposed. This approach supports self-directed learning in a virtual PBL environment in two ways. Firstly, the shared workspaces together with their accompanying tools and documents allow students to actively engage in collaborative, creative, and unstructured PBL activities. Secondly, the process support tool helps students to organize, execute, and coordinate structured parts of PBL processes. This approach has been adopted to develop our prototype system CROCODILE.
Reaching Out: Donating and Volunteering in the Republic of Ireland. The 1997/98 Survey.

This Report presents an in-depth picture of the extent and nature of donating and volunteering behaviour over a 12-month period from February 1997 to January 1998. The findings are based on data collected in face-to-face interviews with a national, random sample of 1,181 respondents. The Report is the third in a series; the first two carried out in 1992 and 1994. The series of studies is designed to provide accurate systematic data over time and is intended to be of value to managers and staff of voluntary organisations, policy makers and researchers interested in the voluntary sector.
Hypertext Summary Extraction for Fast Document Browsing

This article describes an application of Natural Langnage Processing (NLP) techniques to enable fast browsing of on-line documents by automatically generating Hypertext s~lmmaries of one or more documents. Unlike previous w~k on summarization, the system described here, HyperGen, does not produce plain-text snmmaries and does not throw away parts of the document that weren’t included in the summary. HyperGen is based on the view that snmmarization is essentially the task of synthesizing Hypertext structure in a document so that parts of the document "important" to the user are accessible up front while other parts are hidden in multiple layers of increasing detail. In fact, HyperGen generates short descriptions of the contents and rhetorical purposes of the hidden parts to label the Hypertext links between the s~lmmary and the different layers of detail that it generates. A prototype HyperGen system has been implemented to illustrate the techniques and demonstrate its usefulness in browsing World Wide Web documents.
The ethics of tax evasion : perspectives in theory and practice

Why do people evade paying taxes? This is the central question addressed in this volume by Robert McGee and a multidisciplinary group of contributors from around the world. Applying insights from economics, public finance, political science, law, philosophy, theology and sociology, the authors consider the complex motivations for not paying taxes and the conditions under which this behavior might be rationalized. Applying theoretical approaches as well as empirical research, The Ethics of Tax Evasion considers three general arguments for tax evasion: (1) in cases where the government is corrupt or engaged in human rights abuses; (2) where citizens claim inability to pay, unfairness in the tax system, paying for things that do not benefit the taxpayer, excessively high tax rates, or where taxes are used to support an unpopular war; and (3) through philosophical, moral, or religious opposition. The authors further explore these issues by asking whether attitudes toward tax evasion differ by country or other demographic variables such as gender, age, ethnicity, income level, marital status, education or religion. The result is a multi-faceted analysis of tax evasion in cultural and institutional context, and, more generally, a study in ethical dilemmas and rational decision making.
DNA Repair and the Evolution of Transformation in Haemophilus influenxae

Under certain environmental conditions, naturally transforming bacteria are induced to pick up DNA released into the environment by other cells of the same or closely related species and, by homologous recombination, integrate that DNA into their chromosome. The selective pressures responsible for the evolution and maintenance of this form of genetic outcrossing, or sex, in bacteria are not known. A prominent hypothesis is that transformation, and sex in general, evolved as a means of obtaining DNA templates to repair damaged regions of the chromosome. Previous results obtained with Bacillus subtilis were consistent with the repair hypothesis. In an effort to explore the generality of those results, I have tested the repair hypothesis with Haemophilus influenrue, a naturally transforming, gram-negative species of bacteria. The results of UV damage-survivorship experiments with H. influenzae were also consistent with that hypothesis. However, additional experiments demonstrate that the higher survival of transformed cultures cannot be accounted for by use of the transforming DNA as templates for repair. I consider alternative hypotheses for the means by which transformation can increase cell survival following UV exposure and discuss the implications of these results with respect to the DNA repair hypothesis and the evolution of transformation.
Medical Image Fusion in Compressed Sensing Based on Non-subsampled Contourlet Transform

In order to get better results and faster speed on medical image fusion, a method based on non-sub sampled contour let transform in compressed sensing was proposed. Because of the large sparsity and sharp contrast between the black and the white of medical images, the energy and average gradient were utilized to design the fusion rules to fuse the low-frequency components and the high-frequency components respectively. The image entropy, relative quality, average gradient, standard deviation and spatial frequency were used to evaluate the fusion results objectively. Experiments show that under the premise of maintaining a certain reconstruction quality the sample rates and calculation amounts are lower, the convergence can be sped up and the fusion results can be improved.
The Flesh of Words: The Politics of Writing

This new collection of challenging literary studies plays with a foundational definition of Western culture: the word become flesh. But the word become flesh is not, or no longer, a theological already-given. It is a millennial goal or telos toward which each text strives. Both witty and immensely erudite, Jacques Ranciere leads the critical reader through a maze of arrivals toward the moment, perhaps always suspended, when the word finds its flesh. That is what he, a valiant and good-humored companion to these texts, goes questing for through seven essays examining a wide variety of familiar and unfamiliar works. A text is always a commencement, the word setting out on its excursions through the implausible vicissitudes of narrative and the bizarre phantasmagorias of imagery, Don Quixote's unsent letter reaching us through generous Balzac, lovely Rimbaud, demonic Althusser. The word is on its way to an incarnation that always lies ahead of the writer and the reader both, in this anguished democracy of language where the word is always taking on its flesh.
Synthesizing Accurate Formulas for the Floating-Point Arithmetic

Many critical embedded systems perform ﬂoating-point computations yet their accuracy is difﬁcult to assert and strongly depending on how formulas are written in programs. In this article, we focus on the synthesis of accurate formulas mathematically equal to the original formulas occurring in source codes. In general, an expression may be rewritten in many ways using associativity, distributivity, etc. To consider as many rewritings as possible while avoiding any combinatorial explosion, we use a new intermediate representation, called APEG, enabling to represent many equivalent expressions in the same structure. In this article, we speciﬁcally address the problem of selecting an accurate formula among all the expressions of an APEG. This is necessary to synthesize an expression which minimizes the roundoff errors in the worst case. To validate our approach, we present experimental results showing how APEGs, combined with proﬁtability analysis, make it possible to improve signiﬁcantly the accuracy of ﬂoating-point computations.
Secure communication in IP-based wireless sensor networks via a trusted gateway

As the IP-integration of wireless sensor networks enables end-to-end interactions, solutions to appropriately secure these interactions with hosts on the Internet are necessary. At the same time, burdening wireless sensors with heavy security protocols should be avoided. While Datagram TLS (DTLS) strikes a good balance between these requirements, it entails a high cost for setting up communication sessions. Furthermore, not all types of communication have the same security requirements: e.g. some interactions might only require authorization and do not need confidentiality. In this paper we propose and evaluate an approach that relies on a trusted gateway to mitigate the high cost of the DTLS handshake in the WSN and to provide the flexibility necessary to support a variety of security requirements. The evaluation shows that our approach leads to considerable energy savings and latency reduction when compared to a standard DTLS use case, while requiring no changes to the end hosts themselves.
Critical Role of Spns2, a Sphingosine-1-Phosphate Transporter, in Lung Cancer Cell Survival and Migration

The sphingosine-1-phosphate (S1P) transporter Spns2 regulates myocardial precursor migration in zebrafish and lymphocyte trafficking in mice. However, its function in cancer has not been investigated. We show here that ectopic Spns2 expression induced apoptosis and its knockdown enhanced cell migration in non-small cell lung cancer (NSCLC) cells. Metabolically, Spns2 expression increased the extracellular S1P level while its knockdown the intracellular. Pharmacological inhibition of S1P synthesis abolished the augmented cell migration mediated by Spns2 knockdown, indicating that intracellular S1P plays a key role in this process. Cell signaling studies indicated that Spns2 expression impaired GSK-3β and Stat3 mediated pro-survival pathways. Conversely, these pathways were activated by Spns2 knockdown, which explains the increased cell migration since they are also crucial for migration. Alterations of Spns2 were found to affect several enzymes involved in S1P metabolism, including sphingosine kinases, S1P phosphatases, and S1P lyase 1. Genetically, Spns2 mRNA level was found to be reduced in advanced lung cancer (LC) patients as quantified by using a small scale qPCR array. These data show for the first time that Spns2 plays key roles in regulating the cellular functions in NSCLC cells, and that its down-regulation is a potential risk factor for LC.
Query optimization in star computer networks

Query processing is investigated for relational databases distributed over several computers organized in a star network. Minimal response-time processing strategies are presented for queries involving the select, project, and join commands. These strategies depend on system parameters such as communication costs and different machine processing speeds; database parameters such as relation cardinality and file size; and query parameters such as estimates of the size and number of tuples in the result relation. The optimal strategies specify relation preparation processes, the shipping strategy, serial or parallel processing, and, where applicable, the site of join filtering and merging. Strategies for optimizing select and join queries have been implemented and tested.
Throughput improvement method exploiting capture effect in densely placed WLANs

Portable wireless LAN (WLAN) systems by using mobile routers and tethering terminals have been increasing. Then, it is expected that a lot of WLAN systems densely coexist. The capture effect is one of the most important factors that impact the throughput of multiple WLANs in such environment. This study aims to improve the throughput exploiting the capture effect when multiple WLANs are densely placed. Especially, in order to achieve the goal, this paper modifies the configuration of backoff time. First, we show the modification of Contention Window (CW) for the capture effect can improve the throughput by experimental evaluations. Next, we propose a method that each station dynamically changes their CWmin. The proposed method not only improves the throughput of multiple WLANs, but also avoids the throughput degradation caused by collision among stations belonging a same WLAN.
Recruitment in small firms: Processes, methods and problems

The article summarises findings from recent case study research into recruitment in small firms. The research aims to ascertain whether small firms follow the procedures outlined in the prescriptive literature on recruitment, and to what extent they rely on informal recruitment methods. It finds little evidence of the adoption of the recommended systematic procedures and a high use of “tried and trusted” methods including word‐of‐mouth recruitment and the hiring of “known quantities”. The implications of this are examined. While these methods have certain advantages, they may also give rise to a number of problems. The study argues that the adoption of more formal procedures and methods could reduce staff turnover in small firms and its associated costs. However, it concludes that many small employers would remain unconvinced by the case for opening up recruitment channels, and may find their existing approaches more cost effective in the short term.
Bayesian approach to segmentation of statistical parametric maps

A contextual segmentation technique to detect brain activation from functional brain images is presented in the Bayesian framework. Unlike earlier similar approaches [Holmes and Ford (1993) and Descombes et al. (1998)], a Markov random field (MRF) is used to represent configurations of activated brain voxels, and likelihoods given by statistical parametric maps (SPM's) are directly used to find the maximum a posteriori (MAP) estimation of segmentation. The iterative segmentation algorithm, which is based on a simulated annealing scheme, is fully data-driven and capable of analyzing experiments involving multiple-input stimuli. Simulation results and comparisons with the simple thresholding and the statistical parametric mapping (SPM) approaches are presented with synthetic images, and functional MR images acquired in memory retrieval and event-related working memory tasks. The experiments show that an MRF Is a valid representation of the activation patterns obtained in functional brain images, and the present technique renders a superior segmentation scheme to the context-free approach and the SPM approach.