Some historical extracts relevant to the discovery and application of the diffraction of X-rays by crystals to contribute to the centennial celebration and the International Year of Crystallography

Illustrative extracts from the writings of Paul P. Ewald and of Max von Laue are presented. The latter in turn contains extensive text contributions from William Lawrence Bragg. These selections we have chosen so as to indicate the nature of the discovery of X-ray diffraction from crystals (experiments undertaken by Friedrich, Knipping and von Laue) and its early and prompt application in crystal structure analyses (by William Henry Bragg and William Lawrence Bragg). The platform for these discoveries was provided by a macroscopic physics problem dealt with by Ewald in his doctoral thesis with Arnold Sommerfeld in the Munich Physics Department, which is also where von Laue was based. W.L. Bragg was a student in Cambridge who used Trinity College Cambridge as his address on his early papers; experimental work was done by him in the Cavendish Laboratory, Cambridge, and also with his father, W.H. Bragg, in the Leeds University Physics Department. Of further historical interest is the award of an Honorary DSc (Doctor of Science) degree in 1936 to Max von Laue by the University of Manchester, UK, while William Lawrence Bragg was Langworthy Professor of Physics there. © 2012 Copyright Taylor and Francis Group, LLC.

Applications of Nonclassical Logic Methods for Purposes of Knowledge Discovery and Data Mining

* The work is partially supported by Grant no. NIP917 of the Ministry of Science and Education – Republic of Bulgaria.

Defining Moments: A Cuban Exile's Story about Discovery and the Search for a Better Future, Lecture by José I. Ramírez

This flyer promotes the event "Defining Moments: A Cuban Exile's Story about Discovery and the Search for a Better Future, Lecture by José I. Ramírez",sponsored by the FlU Libraries and the Cuban Research Institute.

Discovery and Characterization of a Novel Fatty Acid Synthase Inhibitor with Antineoplastic Activity against Breast Cancer

During oncogenesis, cancer cells go through metabolic reprogramming to maintain their high growth rates and adapt to changes in the microenvironment and the lack of essential nutrients. Several types of cancer are dependent on de novo fatty acid synthesis to sustain their growth rates by providing precursors to construct membranes and produce vital signaling lipids. Fatty acid synthase (FASN) catalyze the terminal step of de novo fatty acid synthesis and it is highly expressed in many types of cancers where it’s up-regulation is correlated with cancer aggressiveness and low therapeutic outcome. Many FASN inhibitors were developed and showed potent anticancer activity however, only one inhibitor advanced to early stage clinical trials with some dose limiting toxicities. Using a modified fluorescence-linked enzyme chemoproteomic strategy (FLECS) screen, we identified HS-106, a thiophenopyrimiden FASN inhibitor that has anti-neoplastic activity against breast cancer in vitro and in vivo. HS-106 was able to inhibit both; purified human FASN activity and cellular fatty acid synthesis activity as evaluated by radioactive tracers incorporation into lipids experiments. In proliferation and apoptosis assays, HS-106 was able to block proliferation and induce apoptosis in several breast cancer cell lines. Several rescue experiment and global lipidome analysis were performed to probe the mechanism by which HS-106 induces apoptosis. HS-106 was found to induce several changes in lipids metabolism: (i) inhibit fatty acids synthesis. (ii) Inhibit fatty acids oxidation as indicated by the ability of inhibiting Malonyl CoA accumulation to block HS-106 induced apoptosis and the increase in the abundance of ceramides. (iii) Increase fatty acids uptake and neutral lipids formation as confirmed 14C Palmitate uptake assay and neutral lipids staining. (iv)Inhibit the formation of phospholipids by inhibiting de novo fatty acid synthesis and diverting exogenous fatty acids to neutral lipids. All of these events would lead to disruption in membranes structure and function. HS-106 was also tested in Lapatinib resistant cell lines and it was able to induce apoptosis and synergizes Lapatinib activity in these cell lines. This may be due the disruption of lipid rafts based on the observation that HS-106 reduces the expression of both HER2 and HER3. HS-106 was found to be well tolerated and bioavailable in mice with high elimination rate. HS-106 efficacy was tested in MMTV neu mouse model. Although did not significantly reduced tumor size (alone), HS-106 was able to double the median survival of the mice and showed potent antitumor activity when combined with Carboplatin. Similar results were obtained when same combinations and dosing schedule was used in C3Tag mouse model except for the inability of HS-106 affect mice survival.

From the above, HS-106 represent a novel FASN inhibitor that has anticancer activity both in vivo and in vitro. Being a chemically tractable molecule, the synthetic route to HS-106 is readily adaptable for the preparation of analogs that are similar in structure, suggesting that, the pharmacological properties of HS-106 can be improved.

Interpretation and typology Spanish indefinite pronoun uno in three discoursive genres

This study investigates the Spanish indefinite pronoun uno (“one”). After a detailed analysis of its occurrences in authentic language, we find that its interpretation varies depending on the linguistic context. Therefore, we examine which elements of the context - we focus on the broader context, beyond the sentence – have an impact on its interpretation and develop a typology of the indefinite pronoun as to its interpretation. The pronoun may be interpreted as completely generic or specific (referring to the speaker, the listener or a third person). Its interpretation can also be located in an intermediate position between these interpretive extremes.In addition, we compare its use in various discursive genres - spontaneous conversations, academic essays and web forum - which are distinguished by the presence or absence of interactivity and of more or less subjectivity / intersubjectivity. The comparison shows that pronoun use depends on these characteristics.

Cooperative Mapping and Exploration using Counter-rotational Potential Fields

This paper presents a novel technique for mapping and exploration using cooperating autonomous underwater vehicles. Rather than using the typical lawnmower sweep pattern to search an entire area, the proposed navigational plan involves guiding the formation directly towards each object of interest in turn, before arriving at a final goal position. This is achieved by the use of traditional artificial potential fields alongside counter-rotational potential fields. These clockwise and counter-clockwise fields are employed simultaneously by vehicles to ensure that the entire object is scanned rather than simply avoided as is the case with traditional collision avoidance techniques. The proposed methodology allows a formation to have fluid-like motion whilst a separation distance between cooperating agents (free of angular constraints) is maintained with a greater degree of flexibility than traditional formation control approaches. Owing to its nature, this technique is suited for applications such as exploration, mapping and underwater inspection to name a few. Simulation results demonstrate the efficacy of the proposed approach.

Black-White Wage Gap Among Restaurant Servers: A Replication, Extension, and Exploration of Consumer Racial Discrimination in Tipping

There is a rich history of social science research centering on racial inequalities that continue to be observed across various markets (e.g., labor, housing, and credit markets) and social milieus. Existing research on racial discrimination in consumer markets, however, is relatively scarce and that which has been done has disproportionately focused on consumers as the victims of race-based mistreatment. As such, we know relatively little about how consumers contribute to inequalities in their roles as perpetrators of racial discrimination. In response, in this paper we elaborate on a line of research that is only in its’ infancy stages of development and yet is ripe with opportunities to advance the literature on consumer racial discrimination and racial earnings inequities among tip dependent employees in the United States. Specifically, we analyze data derived from a large exit survey of restaurant consumers (n=378) in an attempt to replicate, extend, and further explore the recently documented effect of service providers’ race on restaurant consumers’ tipping decisions. Our results indicate that both White and Black restaurant customers discriminate against Black servers by tipping them less than their White coworkers. Importantly, we find no evidence that this Black tip penalty is the result of interracial differences in service skills possessed by Black and White servers. We conclude by delineating directions for future research in this neglected but salient area study.

Discovery and efficient reuse of technology pictures using Wikimedia infrastructures. A proposal

Multimedia objects, especially images and figures, are essential for the visualization and interpretation of research findings. The distribution and reuse of these scientific objects is significantly improved under open access conditions, for instance in Wikipedia articles, in research literature, as well as in education and knowledge dissemination, where licensing of images often represents a serious barrier. Whereas scientific publications are retrievable through library portals or other online search services due to standardized indices there is no targeted retrieval and access to the accompanying images and figures yet. Consequently there is a great demand to develop standardized indexing methods for these multimedia open access objects in order to improve the accessibility to this material. With our proposal, we hope to serve a broad audience which looks up a scientific or technical term in a web search portal first. Until now, this audience has little chance to find an openly accessible and reusable image narrowly matching their search term on first try - frustratingly so, even if there is in fact such an image included in some open access article.

Discovery and validation of serologic biomarkers for the diagnosis and prognosis of invasive candidiasis by computational immunomics

Invasive candidiasis (IC) is an opportunistic systemic mycosis caused by Candida species (commonly Candida albicans) that continues to pose a significant public health problem worldwide. Despite great advances in antifungal therapy and changes in clinical practices, IC remains a major infectious cause of morbidity and mortality in severely immunocompromised or critically ill patients, and further accounts for substantial healthcare costs. Its impact on patient clinical outcome and economic burden could be ameliorated by timely initiation of appropriate antifungal therapy. However, early detection of IC is extremely difficult because of its unspecific clinical signs and symptoms, and the inadequate accuracy and time delay of the currently available diagnostic or risk stratification methods. In consequence, the diagnosis of IC is often attained in advanced stages of infection (leading to delayed therapeutic interventions and ensuing poor clinical outcomes) or, unfortunately, at autopsy. In addition to the difficulties encountered in diagnosing IC at an early stage, the initial therapeutic decision-making process is also hindered by the insufficient accuracy of the currently available tools for predicting clinical outcomes in individual IC patients at presentation. Therefore, it is not surprising that clinicians are generally unable to early detect IC, and identify those IC patients who are most likely to suffer fatal clinical outcomes and may benefit from more personalized therapeutic strategies at presentation. Better diagnostic and prognostic biomarkers for IC are thus needed to improve the clinical management of this life-threatening and costly opportunistic fungal infection...

Building partnership for drug and ag discovery and conservation of the natural resources in Brazil.

2009

Nonparametric discovery and analysis of learning patterns and autism subgroups from therapeutic data

The spectrum nature and heterogeneity within autism spectrum disorders (ASD) pose as a challenge for treatment. Personalisation of syllabus for children with ASD can improve the efficacy of learning by adjusting the number of opportunities and deciding the course of syllabus. We research the data-motivated approach in an attempt to disentangle this heterogeneity for personalisation of syllabus. With the help of technology and a structured syllabus, collecting data while a child with ASD masters the skills is made possible. The performance data collected are, however, growing and contain missing elements based on the pace and the course each child takes while navigating through the syllabus. Bayesian nonparametric methods are known for automatically discovering the number of latent components and their parameters when the model involves higher complexity. We propose a nonparametric Bayesian matrix factorisation model that discovers learning patterns and the way participants associate with them. Our model is built upon the linear Poisson gamma model (LPGM) with an Indian buffet process prior and extended to incorporate data with missing elements. In this paper, for the first time we have presented learning patterns deduced automatically from data mining and machine learning methods using intervention data recorded for over 500 children with ASD. We compare the results with non-negative matrix factorisation and K-means, which being parametric, not only require us to specify the number of learning patterns in advance, but also do not have a principle approach to deal with missing data. The F1 score observed over varying degree of similarity measure (Jaccard Index) suggests that LPGM yields the best outcome. By observing these patterns with additional knowledge regarding the syllabus it may be possible to observe the progress and dynamically modify the syllabus for improved learning.

Industrial lab-on-a-chip: design, applications and scale-up for drug discovery and delivery

Microfluidics is an emerging and promising interdisciplinary technology which offers powerful platforms for precise production of novel functional materials (e.g., emulsion droplets, microcapsules, and nanoparticles as drug delivery vehicles- and drug molecules) as well as high-throughput analyses (e.g., bioassays, detection, and diagnostics). In particular, multiphase microfluidics is a rapidly growing technology and has beneficial applications in various fields including biomedicals, chemicals, and foods. In this review, we first describe the fundamentals and latest developments in multiphase microfluidics for producing biocompatible materials that are precisely controlled in size, shape, internal morphology and composition. We next describe some microfluidic applications that synthesize drug molecules, handle biological substances and biological units, and imitate biological organs. We also highlight and discuss design, applications and scale up of droplet- and flow-based microfluidic devices used for drug discovery and delivery.

Price discovery and asset pricing

This paper tests the hypothesis that price discovery influences asset pricing. Our innovations are twofold. First, we estimate time-varying price discovery for a large number (21) of Islamic stock portfolios. Second, we test using a predictive regression model whether or not price discovery predicts stock excess returns. We find from both in-sample and out-of-sample tests that all 21 portfolio excess returns are predictable. We show that a mean-variance investor by tracking price discovery is able to devise profitable trading strategies.