An efficient new route to dihydropyranobenzimidazole inhibitors of HCV replication.

A class of dihydropyranobenzimidazole inhibitors was recently discovered that acts against the hepatitis C virus (HCV) in a new way, binding to the IRES-IIa subdomain of the highly conserved 5' untranslated region of the viral RNA and thus preventing the ribosome from initiating translation. However, the reported synthesis of these compounds is lengthy and low-yielding, the intermediates are troublesome to purify, and the route is poorly structured for the creation of libraries. We report a streamlined route to this class of inhibitors in which yields are far higher and most intermediates are crystalline. In addition, a key variable side chain is introduced late in the synthesis, allowing analogs to be easily synthesized for optimization of antiviral activity

Mass spectrometer analysis of solid materials with the ion-microprobe sputter source

Sputter ion source mass spectrometer for analysis of solid material

Towards White Box Deep Learning

Deep neural networks learn fragile "shortcut" features, rendering them difficult to interpret (black box) and vulnerable to adversarial attacks. This paper proposes semantic features as a general architectural solution to this problem. The main idea is to make features locality-sensitive in the adequate semantic topology of the domain, thus introducing a strong regularization. The proof of concept network is lightweight, inherently interpretable and achieves almost human-level adversarial test metrics - with no adversarial training! These results and the general nature of the approach warrant further research on semantic features. The code is available at https://github.com/314-Foundation/white-box-nnComment: 16 pages, 12 figures, independent research, v5 changes: Expanded Abstract and Related Work section; minor wording improvement

The Bigger Picture

The Bigger Picture series is inspired by the saying when you are too focused on the finer details, you forget about the bigger picture, which my grandma always said to me when I was growing up. I tend to focus on details in the world such as the cracks in the road, the pebble in my shoe, and many other seemingly insignificant details in the world, instead of looking at the bigger picture and thinking about things wholistically. When I look at every detail, I become consumed. This feeling of being overwhelmed by all the little stuff takes a toll on many people in todays world. My series is a reminder to pause, take a deep breath, and look at the bigger picture. For this series, I photographed common everyday objects under a microscope. Focusing on the small details, similar to how people look at situations in their life in minutiae. The groups of images of the micro world spark curiosity in the viewer about the identity of the item photographed. Discovering the whole object is the first step everyone needs to take to be able to see the bigger picture in their everyday life

David Christian. \u3ci\u3eMaps of Time: An Introduction to Big History\u3c/i\u3e. University of California Press, New Edition, 2004. Leonid E. Grinin, Andrey V. Korotayev, Barry H. Rodrigue, eds. \u3ci\u3eEvolution: A Big History Perspective\u3c/i\u3e. Volgograd: Uchitel Publishing House, 2011.

What is history? Or rather, what are the appropriate time-scales that can be constituted as “history”? The general consensus among scholars is that history is the study of approximately the last 5,000 years or so due to the existence of written records. Anything prior to that is generally considered pre-history, at least as far as it concerns the existence of human beings on earth. As for the creation of the earth we live upon, or the solar system our planet dwells within, or the universe as a whole these are considered outside the formal domain of historical research. That is, until the advent of the field of Big History that has emerged within the past few decades to challenge these distinctions as merely arbitrary and encourage scholars to think on much larger timescales. David Christian is generally attributed as the father of the field, and he outlines his vision for it in his monumental book Maps of Time: An Introduction to Big History

Civilizational Dynamics of Hybrid Warfare

Since the end of the Cold War, analysts have struggled to make sense of the proliferation of smaller scale conflicts. Several labels have been used to describe this phenomenon, the most recent being “Hybrid Warfare.” This paper attempts to analyze them through the perspective of civilizational theory. Very rarely, however, have the civilizational dimensions to these Hybrid Wars been extensively addressed. Considering that civilizations represent collective identities on perhaps the most macro-scale, they play an important potential dimension in this ongoing debate. Avoiding any gross simplified variation of a clash of civilizations type thesis, a civilizational perspective into this debate can also shed significant insight into the nature of intra-civilizational conflicts and how they might also overlap with any inter-civilizational conflicts. A civilizational perspective also raises the critical issue of the persistence of collective identities, even in an increasingly globalized world

On Civilizational Strategic Studies

Given the on-going crises around the world, especially the current war in Ukraine, it has become imperative to analyze the strategic interests of the major geopolitical players in the world. Samuel P. Huntington formulated his controversial “Clash of Civilizations” thesis almost thirty years ago, but this topic has received a resurgence of interest due to Christopher Coker’s research on “civilizational states.” Coker takes this concept a bit further by arguing that different geopolitical actors disagree on how the world should be ordered. Now is perhaps the most opportune time to examine the relevance of civilizations as well as civilizational theory to the inter-disciplinary field of Strategic Studies. This would bring together insights from such fields as geopolitics, grand strategy, military analysis, and global security analysis to bear upon civilizational science and analysis. This would be further achieved through the study of Civilizational Ontology, to determine how best to understand civilizational contexts regarding geopolitical and strategic actors. It would expand previous research conducted regarding civilizations and threats of “hybrid warfare.” Although a major goal of this synthesis of Civilizational Sciences and Strategic Studies would be to assist in the proper analysis of on-going current (and possible future) events, it would also be vitally important to the study of historical case studies. Carl von Clausewitz famously declared “War is a continuation of politics by other means.” This paper builds upon the argument that strategy and civilizations are reflections and continuations of one another

Formal and semantic factors in the distribution of Polish decclension forms

The problem can be very well illustrated with the results of the analysis of the distribution of masculine noun endings (Norn. Pl.) and the results of the discussion on the position of the ending -owie in the form system of that particular case. It appears that, contrary to previous findings, the distribution of that ending is based on a formal rather than semantic principle (it is added to nouns belonging to only two categories: 1) Christian names and surnames, and 2) names of family relationship). The use of this ending is limited to those word classes in which Nominative forms and other endings would increase the number of homonymic unite of the language. The changes in distribution of this case have not finished yet but they require a certain modification in the description of Polish decciension system.Zadanie pt. Digitalizacja i udostępnienie w Cyfrowym Repozytorium Uniwersytetu Łódzkiego kolekcji czasopism naukowych wydawanych przez Uniwersytet Łódzki nr 885/P-DUN/2014 zostało dofinansowane ze środków MNiSW w ramach działalności upowszechniającej nauk