Drivers and prediction of organic search engine ctr - the effects of serp features and their business implications

33% of web traffic in the $5.7 trillion e-commerce industry originates from organic search engine results. Thus, website providers benefit from a holistic understanding of the drivers of click-through rates (CTR) on organic searches to increase traffic. However, providers face a knowledge gap, as existing literature focuses on position as the primary CTR influence, disregarding other result page characteristics. To solve this problem, we use an extensive dataset comprising organic Google result page information. We conduct an elaborate data analysis highlighting the impact of four categories of result page characteristics before determining suitable CTR prediction modeling techniques. We discover novel patterns impacting CTR for each category and find tree-based models to outperform state-of-the-art deep-learning models. Furthermore, we reveal particular SERP feature effects on CTR and highlight their possible business implications

Applied techniques for mining natural proteasome inhibitors

AbstractIn eukaryotic cells, the ubiquitin–proteasome-system (UPS) is responsible for the non-lysosomal degradation of proteins and plays a pivotal role in such vital processes as protein homeostasis, antigen processing or cell proliferation. Therefore, it is an attractive drug target with various applications in cancer and immunosuppressive therapies. Being an evolutionary well conserved pathway, many pathogenic bacteria have developed small molecules, which modulate the activity of their hosts' UPS components. Such natural products are, due to their stepwise optimization over the millennia, highly potent in terms of their binding mechanisms, their bioavailability and selectivity. Generally, this makes bioactive natural products an ideal starting point for the development of novel drugs. Since four out of the ten best seller drugs are natural product derivatives, research in this field is still of unfathomable value for the pharmaceutical industry. The currently most prominent example for the successful exploitation of a natural compound in the UPS field is carfilzomib (Kyprolis®), which represents the second FDA approved drug targeting the proteasome after the admission of the blockbuster bortezomib (Velcade®) in 2003. On the other hand side of the spectrum, ONX 0914, which is derived from the same natural product as carfilzomib, has been shown to selectively inhibit the immune response related branch of the pathway. To date, there exists a huge potential of UPS inhibitors with regard to many diseases. Both approved drugs against the proteasome show severe side effects, adaptive resistances and limited applicability, thus the development of novel compounds with enhanced properties is a main objective of active research. In this review, we describe the techniques, which can be utilized for the discovery of novel natural inhibitors, which in particular block the 20S proteasomal activity. In addition, we will illustrate the successful implementation of a recently published methodology with the example of a highly potent but so far unexploited group of proteasome inhibitors, the syrbactins, and their biological functions. This article is part of a Special Issue entitled: Ubiquitin–Proteasome System. Guest Editors: Thomas Sommer and Dieter H. Wolf

Dust storms, dust transfer and depositions in the southern Aral Sea region

Land surfaces poor in vegetation coverage and dried out soils are accelerating factors of sand and dust transport. Dust transport also has considerable impact on the human society if highly populated regions are on the transport pathway or sink areas as dust transport can bring pollutants into residence areas. The quantitative prediction of dust storms is impossible unless the entire dust cycle, consisting of dust emission, transport and deposition, can be correctly assessed. In recent years, dust emission schemes have been developed that account reasonably well for the impacts of atmospheric forcing and land-surface properties on dust emission. The Aral Sea disaster has been caused by the overexploitation of the water and land resources and is related to problems of polluted surface and ground water bodies, the loss of agricultural productivity and biodiversity, the regional climate change and also the human health, especially within the disaster zone. Major consequences of the Aral Sea shrinkage, apart from the decrease of its water volume and area, an increase of the water salinity and a modification of the salinity pattern is the formation of a vast saline desert with the area of almost 3.6 mln ha on the exposed seabed. The main factors of dust storm occurrences are the frequency of strong winds and availability of source material in dust emission sites. During the last decades the total area of dust emission sites in the Aral Sea region increased significantly because of the shrinking of the Aral Sea and consequent drying of its exposed bottom and deltaic areas of Amudarya and Syrdarya Rivers

Ecological, socio-economic and demographic analyses as prerequisites for sewage treatment problem solutions in rural areas. The case study of Dirlammen, Vogelsberg, Germany

The municipal sewage treatment in Germany is traditionally centralized and allows for a high disposal security. The implementation of the EU Water Framework Directive (EU-WFD) showed that the central target, the so-called ‘good ecological state’ has not yet been reached in 90% of all surface water bodies. A common and widespread measure to reach said target is the improvement of sewage treatment plants (STP). A large part of the expenses for that has to be shouldered by local communities. But many rural communities already have to manage high costs caused by the modernization of the sewage pipe system. And as the size of the rural population decreases continuously, the per capita burden increases. This raises the question whether the construction of a new sewage treatment plant is the most efficient way to improve the water quality in rural areas. A comprehensive approach has been developed for answering this question, consisting of 1) biological and physico-chemical wastewater analyses, 2) a modified eco-balance for the construction of a new STP and 3) socio-economic and demographic population analyses. The results show that the water quality of the studied creek is good with exception of the sewage disposal point. The eco-balance for the construction, the operation, and the environmental side effects show that the continued operation of the existing STP is more effective than the construction of a modern facility. This conclusion is supported by the aging and general decrease of the rural population. The diminishing potential to shoulder additional costs is in contrast to the reduced future demand for a modern STP

Beziehungen zwischen der Gewässermorphologie und dem Makrozoobenthos an renaturierten Abschnitten der Lahn

Die europäischen Fließgewässer unterliegen seit Jahrhunderten einem starken anthropogenen Nutzungsdruck, welcher den morphologischen und faunistischen Charakter der Gewässer nachhaltig verändert hat. In den vergangenen Jahrzehnten rückten die Defizite der Fließgewässer zunehmend in das Blickfeld der Öffentlichkeit und erste Bestrebungen der Zustandsverbesserung durch die Renaturierung von Gewässerabschnitten wurden unternommen. Maßgeblich vorangetrieben wird dieser Prozess durch die EU-Wasserrahmenrichtlinie. Um die Ziele der Wasserrahmenrichtlinie sowohl fristgerecht als auch kosteneffizient erreichen zu können, bedarf es genauer Kenntnisse über die Wirksamkeit konkreter Maßnahmen, die durch die detaillierte Evaluation bereits umgesetzter Maßnahmen gewonnen werden könnten. In der Praxis erfolgt eine wissenschaftliche Auseinandersetzung mit renaturierten Gewässerabschnitten jedoch ausgesprochen selten oder oberflächlich und auch die Monitoringprogramme der EU-Wasserrahmenrichtlinie können die bestehenden Wissenslücken nicht füllen. Speziell für das Makrozoobenthos als einer der vier Qualitätskomponenten für die Bewertung der Fließgewässer kann die zentrale Frage „Welche morphologischen Prozesse und Strukturen können gefördert werden, um einen guten ökologischen Zustand zu erreichen?“ trotz mehr als 100-jähriger limnologischer Forschung noch immer nicht befriedigend beantwortet werden. Zwar existieren zahlreiche Untersuchungen, die die Abhängigkeit des Makrozoobenthos’ von verschiedenen Umweltfaktoren auf der Makro- und Mesoskala analysieren. Die als Hauptlebensraum relevante Ebene der Mikrohabitate (Choriotope) jedoch ist diesbezüglich kaum untersucht, was zumindest teilweise darin begründet liegt, dass bislang kaum Verfahren existierten, welche die Strukturen des Gewässerbetts in der erforderlichen räumlichen Auflösung erfassen können. In diesem Spannungsfeld zwischen angewandter Wissenschaft und Grundlagenforschung wurden von 2006 bis 2008 intensive Untersuchungen am Mittelauf der Lahn (Fließgewässertyp 9.2) durchgeführt. In drei Untersuchungsgebieten (zwei davon durch eigendynamische Entwicklungsmaßnahmen renaturiert) erfolgten hochaufgelöste Kartierungen der Gewässersohle unter Verwendung des TRiSHa-Verfahrens („Typology of Riverbed Structures and Habitats“) sowie detaillierte Aufnahmen des Makrozoobenthos’ nach dem PERLODES-Verfahren. Analysiert wurde neben der räumlichen Verteilung der Strukturparameter in den renaturierten und nicht renaturierten Untersuchungsabschnitte auch deren zeitliche Dynamik unter besonderer Berücksichtung eines HQ50. Die Zusammenhänge zwischen der Mikrostruktur der Gewässersohle und der Besiedelung durch das Makrozoobenthos wurden statistisch ausgewertet und eine Bewertung der Renaturierungsmaßnahmen wurde durchgeführt. Hierbei konnten unter anderem Lücken in der Fließgewässertypologie und dem PERLODES-Verfahren aufgezeigt werden, die einer breiteren wissenschaftlichen Diskussion bedürfen

Structural Analysis of Spiro β-Lactone Proteasome Inhibitors

Spiro β-lactone-based proteasome inhibitors were discovered in the context of an asymmetric catalytic total synthesis of the natural product (+)-lactacystin (1). Lactone 4 was found to be a potent inhibitor of the 26S proteasome, while its C-6 epimer (5) displayed weak activity. Crystallographic studies of the two analogues covalently bound to the 20S proteasome permitted characterization of the important stabilizing interactions between each inhibitor and the proteasome’s key catalytic N-terminal threonine residue. This structural data support the hypothesis that the discrepancy in potency between 4 and 5 may be due to differences in the hydrolytic stabilities of the resulting acyl enzyme complexes.Chemistry and Chemical Biolog

Azobenzene-based inhibitors of human carbonic anhydrase II

Aryl sulfonamides are a widely used drug class for the inhibition of carbonic anhydrases. In the context of our program of photochromic pharmacophores we were interested in the exploration of azobenzene-containing sulfonamides to block the catalytic activity of human carbonic anhydrase II (hCAII). Herein, we report the synthesis and in vitro evaluation of a small library of nine photochromic sulfonamides towards hCAII. All molecules are azobenzene-4-sulfonamides, which are substituted by different functional groups in the 4 '-position and were characterized by X-ray crystallography. We aimed to investigate the influence of electrondonating or electron-withdrawing substituents on the inhibitory constant Ki. With the aid of an hCAII crystal structure bound to one of the synthesized azobenzenes, we found that the electronic structure does not strongly affect inhibition. Taken together, all compounds are strong blockers of hCAII with K-i = 25-65 nM that are potentially photochromic and thus combine studies from chemical synthesis, crystallography and enzyme kinetics