bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is conformational sampling of drug‐like molecules a solved problem?
Authors: Chen I‐Jen , Foloppe Nicolas 
Published: December 2010

AbstractWith computational tools, it has become straightforward to obtain three‐dimensional (3D) conformers for drug‐like molecules, even for large numbers of compounds. This underpins many downstream molecular modeling activities. We summarize the principles behind the methods, explain why considering multiple conformers per compound is necessary, and discuss the tests used to assess the computed conformers. It leads us to suggest that conformational sampling per se is essentially a solved problem for small drug‐like compounds, and that efforts should focus on improving the energy models. Drug Dev Res 72: 85–94, 2011. © 2010 Wiley‐Liss, Inc.
Fragment and protein simulation methods in fragment based drug design
Authors: Klon Anthony E. , Konteatis Zenon , Meshkat Siavash N. , Zou Jinming , Reynolds Charles H. 
Published: December 2010

AbstractFragment‐based drug design (FBDD) has become an important and successful approach to drug discovery. In this review, we discuss two classes of simulation technologies that we routinely employ as part our of computational FBDD efforts. The first class centers on simulation methods in torsion space to develop high‐quality protein models suitable for FBDD. These algorithms allow for fast molecular dynamics and modal Monte Carlo simulations. The torsion space dynamics techniques have been applied to develop models for the bound conformations of a variety of proteins including the HIV‐1 protease, p38 MAP kinase, and the 5′‐AMP‐activated protein kinase. The second class of simulations is comprised of the Grand Canonical Monte Carlo and systematic sampling methods, which are used to explore the interactions of individual fragments with the protein target. Previously published validation studies for the binding of molecules to T4 lysozyme and the p38 MAP kinase are discussed. We review previous work to computationally assemble whole molecules from fragment binding data, a potential bottleneck in the FBDD approach. One effect of the fragment simulations is that an approximate value for the free energy of binding of a given molecule with the protein may be computed from the fragment simulations, with an estimated standard error approaching 1 kcal/mol, which is comparable to the performance of a variety of other methods reported in the literature. Drug Dev Res 72:130–137, 2011.  © 2010 Wiley‐Liss, Inc.
In silico subtractive genomics for target identification in human bacterial pathogens
Authors: Barh Debmalya , Tiwari Sandeep , Jain Neha , Ali Amjad , Santos Anderson Rodrigues , Misra Amarendra Narayan , Azevedo Vasco , Kumar Anil 
Published: December 2010

AbstractTarget identification is the first step in the drug and vaccine discovery process;in silicosubtractive genomics is widely used in this process. Using this approach, in recent years, a large number of targets have been identified for bacterial pathogens that are either drug resistant or for which no suitable vaccine is available; most such reports concern a specific pathogen. Thein silicomethod reduces the time as well as the cost of target screening. Although a powerful technique that can be applied to a wide range of pathogens, there are many pitfalls in the analysis and interpretation of the data. We review this approach, including targets that have been identified with this technique and various other aspects, including advantages and disadvantages. We also discuss our own experiences using this technology. Drug Dev Res 72: 162–177, 2011. © 2010 Wiley‐Liss, Inc.
Scientific literature mining for drug discovery: a case study on obesity
Authors: Rajpal Deepak K. , Kumar Vinod , Agarwal Pankaj 
Published: December 2010

AbstractObesity is currently an epidemic that affects almost 15% of the global adult population. The complex metabolic processes involved in energy homeostasis, which are regulated by signals from multiple sources, present a challenging problem for drug discovery. In the current analysis, we present bibliometric and data‐mining approaches based on categorizing literature according to medical subject headings (MeSH) to examine “hot” and “cold” trends, which indicate emerging areas of scientific research within obesity. This trend analysis corrects for increase in the overall size of obesity publications. A “hot” trend within obesity research is a concept on which publications are growing statistically faster than the background rise in obesity publications. In addition to growth in the number of publications associated with gastrointestinal weight‐loss surgery and clinical studies in obesity, there is increasing research in the fields of adipose tissue, islet cell, and enteroendocrine biology as observed by a significant increase in the number of publications during the period 2005–2009, when compared to 2000–2004. However, the number of the publications in the area of hypothalamic and nervous system research in obesity appears to be cooling off. Extending the same concept of trend analysis to genes, we present a list of obesity‐related genes that show “hot” trends suggesting emerging molecular mechanisms for obesity. Finally, we present a list of key scientific publications associated with obesity, one from each year over the last decade, which have the highest number of citations. Drug Dev Res 72: 201–208, 2011. © 2010 Wiley‐Liss, Inc.
Mapping drug architecture by MoStBioDat: rapid screening of intramolecular hydrogen bonded motifs in catechols
Authors: Bak Andrzej , Magdziarz Tomasz , Kurczyk Agata , Polanski Jaroslaw 
Published: December 2010

AbstractComputer‐assisted simulations are important for present‐day chemical investigations, producing large amount of structural data. In molecular design, we calculate molecular descriptors for factual or virtual structures in chemical space attempting to predict their chemical properties and evaluate potential biological effects. In the current study, we investigated the application of the MoStBiodat software platform for the extensive screening of spatial arrangement and conformational analysis locating intramolecular hydrogen‐bonded motifs in catechols. We compared the experimentally determined structural data to those that are simulated using virtual structural data. The relevant topological incoherence among structural and molecular data coming from different sources is thus revealed. Drug Dev Res 72: 209–218, 2011.  © 2010 Wiley‐Liss, Inc.
Heterogeneous Catalytic Reactions “On Water” by Using Stable Polymeric Alkynylcopper(I) Pre‐Catalysts: Alkyne/Azide Cycloaddition Reactions
Authors: Buckley Benjamin R. , Dann Sandra E. , Heaney Harry , Stubbs Emma C. 
Published: December 2010

AbstractDinuclear alkynylcopper(I) complexes have been found to be the active pre‐catalysts in copper‐catalysed cycloaddition of azides and terminal alkynes (CuAAC). These copper(I) ladderane polymers are used in “on water” CuAAC reactions, with loadings as low as 1 mol‐%.
Population dynamics of methanogens during acidification of biogas fermenters fed with maize silage
Authors: Munk Bernhard , Bauer Christoph , Gronauer Andreas , Lebuhn Michael 
Published: December 2010

AbstractLimitations in the supply of essential trace elements for methanogenic Archaea can arise in biogas production from renewable resources in flow‐through systems particularly when no manure is added. Without compensating supplementation, primarily Co and Na+ can become limiting in long‐term mono‐digestion of maize silage at threshold values of ca. 0.03 and 10 mg/L, respectively. These deficiencies apparently triggered process acidification. Using molecular biological methods (PCR‐SSCP and quantitative real‐time PCR), microbial population dynamics were monitored qualitatively and quantitatively at distinct stages during the experiments, investigating mcrA/mrtA, coding for a subunit of the key enzyme of methanogenesis. An exponential correlation between mcrA/mrtA copies and methane productivity was obtained. Members of obligatley acetoclastic Methanosaetaceae were found only at low acetate concentrations (below 1 g/L). At organic loading rates>1 g volatile solids/(L×d) and without acidification symptoms, obligately hydrogenotrophic (oh) Methanobacteriales and versatile Methanosarcinaceae were dominating, and an abundance of up to 1010 methanogens per mL fermenter content was determined. In the acidified process, however, ca. 4 orders of magnitude less methanogens were detected, and Methanomicrobiales (oh), more specifically Methanospirillum hungatei or Methanoculleus spp., were dominating. Species diversity at the DNA level was highest at efficient process performance without stress symptoms and at a relatively low organic loading rate (1–2 g volatile solids/(L×d)). According to the quantitative real‐time PCR data, the process was not sustained below an availability of 10−8 to 10−9 μg Co per methanogenic cell.
Operational modeling of a sustainable gas supply chain
Authors: Bekkering Jan , Broekhuis Ton A. , van Gemert Wim J. T. 
Published: December 2010

AbstractBiogas production from codigestion of cattle manure and biomass can have a significant contribution to a sustainable gas supply when this gas is upgraded to specifications prescribed for injection into the national gas grid and injected into this grid. In this study, we analyzed such a gas supply chain in a Dutch situation. A model was developed with which the cost price per m was presented as a function of scale level (m/hr). The hypothesis that transport costs increase with increasing scale level was confirmed although this is not the main factor influencing the cost price for the considered production scales. For farm‐scale gas supply chains (approximately 150–250 m/h green gas), a significant improvement is expected from decreasing costs of digesters and upgrading installations, and efficiency improvement of digesters. In this study also practical sustainability criteria for such a supply chain were investigated. For this reason, the digestate from the digester should be used as a fertilizer. For larger scale levels, the number of transport movements and energy use in the supply chain seem to become a limiting factor with respect to sustainability.
Energy balance of a two‐phase anaerobic digestion process for energy crops
Authors: Zielonka Simon , Lemmer Andreas , Oechsner Hans , Jungbluth Thomas 
Published: December 2010

AbstractThis article deals with the digestion of energy crops in a two‐phase biogas process based on an anaerobic leach‐bed reactor combined with an anaerobic filter. The biogas process is a microbiological conversion of biomass into methane and carbon dioxide. This process is carried out by different microorganisms and can be divided into four steps which normally take place in only one digester. To be able to digest difficult energy crops by mono‐digestion and to meet the different needs of the several bacteria, which take part in the four‐step process of the methane production, the process was divided into two phases: (i) an anaerobic batch leach‐bed phase, where the leachate was produced and (ii) an anaerobic filter, where the organic fraction of the leachate was converted into biogas. Considering the results of the experiments, the two‐phase digestion of energy crops exhibited stable digestion behavior. No biological imbalance of the process, e.g. due to a sudden change of substrate, was detected either in the leach bed or in the anaerobic filter. Variation in suitability for two‐phase fermentation with an anaerobic batch leach‐bed reactor was observed for various substrates. The different substrates varied in their influence on acid formation and concentration as well as an influence on the course of the pH value.Therefore, an effect on the distribution of energy to the phases could be observed.
Combined mechanical enzymatic pretreatment for an improved substrate conversion when fermenting biogenic resources
Authors: Ellenrieder Johannes , Schieder Doris , Mayer Wolfgang , Faulstich Martin 
Published: December 2010

AbstractAnaerobic digestion of lignocellulosic fractions of biogenic resources in biogas plants performs slowly and incompletely leaving fibrous residues. Thus, this work focused on a combined mechanical and enzymatic pretreatment of maize and grass silage to achieve a partial hydrolysis of the substrates and a higher biogas yield. To get an intensive disintegration, the refiner technology was used. For subsequent enzymatic hydrolysis, several commercially available enzyme preparations were tested, and their effect on solid substrate degradation, viscosity and pumpability of the suspensions was investigated. Experiments were performed in laboratory fermenters as well as in pilot scale (1 m3) at a biogas plant. The most promising enzymatic pretreatments with respect to their effect on the fermentation process were tested in 20‐L semicontinuously operated laboratory scale digesters. On maize silage, a dry mass (DM) reduction up to 40% with an amylase‐based preparation was achieved. Equal results were obtained with a cellulase preparation on grass silage. Yet, due to the high demand of enzyme, the economical feasibility was doubtful. Laboratory semicontinuous fermentation experiments, therefore, were performed on maize silage. At a substrate load of 1.5–2.0 kg organic DM (oDM)/(m3 d), a good biogas yield of about 0.7 LN (liter norm)/g oDM and methane yield of about 0.4 LN/g oDM were obtained. However, at the chosen fermentation conditions at 37°C and 25 days hydraulic retention time, no positive effect of the enzymatic prehydrolysis on the biogas yield of fine grinded substrate could be established.
Factors controlling sediment yield in China's Loess Plateau
Authors: Xin Zhongbao , Yu Xinxiao , Lu X. X. 
Published: December 2010

AbstractThe Loess Plateau in China, an area with some of the highest sediment yield in the world, contributes predominant proportion of the sediments found in the Yellow River. We examined sediment yield and its control variables in the plateau based on a multi‐year dataset from 180 gauging stations in areas varying in size from 102 to 104 km2. Various morphometric, hydrologic, climatic and land cover variables were estimated in order to understand and predict the variations in sediment yield. The results show a spatial pattern of sediment yield exhibiting an obvious zonal distribution and a coupling between precipitation and vegetation cover that fits the Langbein–Schumm law. A critical threshold of precipitation and vegetation cover was observed among the relationships of sediment yield and precipitation/vegetation cover. A multiple regression equation with three control variables, i.e. vegetation cover, percentage of cultivated loess and annual runoff, explains 65% of the total variation in sediment yield. For the loess dominated basins, where the cultivated loess accounts for more than 60% of the total area, annual runoff was the dominant variable, explaining 76% of the observed variation in sediment yield. The established equation could be a valuable tool for predicting total sediment yield in the Loess Plateau. Copyright © 2010 John Wiley & Sons, Ltd.
ICI mitigation and diversity gain for OFDM systems in time‐varying multipath fading channels
Authors: Chen Shaoping , Dai Guangfa , Rao Wengui 
Published: December 2010

AbstractIn orthogonal frequency division multiplexing (OFDM) systems, channels' rapid variations cause intercarrier interference (ICI), resulting in performance degradation. Although ICI caused by channels' variations makes the reliable signal detection difficult, it also introduces Doppler diversity, which can be exploited to improve the system performance. In this paper, an ICI mitigation and Doppler‐multipath diversity technique based on fractionally sampling at the receiver is proposed for OFDM systems over time‐varying multipath fading channels. To reduce the computation burden of minimum mean‐square error (MMSE) equaliser with successive detection (SD), an efficient algorithm is presented by using the property of matrix decomposition. The algorithm avoids direct or recursive computation of matrix inversion, thereby reducing the computation complexity and ensuring numerical stability. Simulations show that the proposed techniques can collect both Doppler and multipath diversity gains with moderate complexities. Copyright © 2010 John Wiley & Sons, Ltd.
The present status of the NATM in contracts – tendering / Gegenwart der NÖT im Bauvertrag – Ausschreibung
Authors: Herdina Johann 
Published: December 2010

AbstractAlthough the expert circle of NATM users has demonstrated that they are technically capable of using the NATM successfully under almost any conditions, there are repeated difficulties concerning the handling of contracts. The construction contract with flexible provisions regarding classification and the invoicing of common costs as the basis for a collaborative project implementation has been subjected to extreme stress recently by various construction companies. The expectations of the contractor concerning tendering are not identical to the tender documents currently in use in the market. The article explains the differences and proposes a way of overcoming such problems in the future. The author maintains that in his view three main points could lead to an improvement of contract implementation:· The appointment of contractors only for a plausible total price,· Consultants as a partner of the client and· The provision of a behaviour code for NATM construction measures.Während die Fachgemeinschaft der NÖT‐Anwender bewiesen hat, dass sie technisch in der Lage ist, bei fast allen Randbedingungen die NÖT erfolgreich anzuwenden, ergeben sich auf der vertraglichen Seite immer wieder Abwicklungsschwierigkeiten. Der flexible Bauvertrag bezüglich Klassifizierung und Gemeinkostenabrechnung als Grundlage für eine partnerschaftliche Projektabwicklung zwischen Bauherren und Auftragnehmern wurde in letzter Zeit bei verschiedenen Baumaßnahmen äußerst strapaziert. Die Erwartungshaltung des Auftragnehmers zur Ausschreibung ist nicht ident mit den aktuell am Markt befindlichen Ausschreibungsunterlagen. Im Artikel werden die Unterschiede dargelegt, und es wird versucht, einen Weg aufzuzeigen, wie in Zukunft die Probleme überwunden werden können, wobei der Autor festhält, dass aus seiner Sicht drei wesentliche Punkte zur Verbesserung der vertraglichen Abwicklung führen können:· Beauftragung von Firmen nur zur einem plausiblen Gesamtpreis,· Planer als Partner des Bauherrn und· Festlegen eines Verhaltenskodex für NÖT‐Baumaßnahmen.
The present status of the NATM in contracts – construction / Gegenwart der NÖT im Bauvertrag – Ausführung
Authors: Sachs Manfred 
Published: December 2010

AbstractSince the start of the worldwide success of the new Austrian tunnelling method in the middle 1960s, not only our society but also tunnelling have experienced fundamental change in many areas. The increasing influence of law and bureaucracy have led to the situation where today's tunnelling contracts have become extensive, intricate and disputed compared to former times. Collaboration as among colleagues has been replaced by the collective shedding of responsibility. The creation of tender documents, processing of the tenders and the construction of the works are all subject to the principle of lowest price, which is forced on the clients by law. Tender documents often contain errors and the tenders are not seldom speculative and under‐priced. This inevitably leads to disputes during the construction phase.The NATM is, however, a construction method, which needs flexible contract arrangements between partners, competent professionals, slender structures and short decision routes on the tunnel site in order to fulfil its entire potential. In contrast to this, tunnel sites today are often characterised by senseless administrative work and irrelevant reciprocal controls. The rapid development and increasing automation of machines and the development of construction materials still offer great chances for the NATM in the future. The future of the tendering and award arrangements, however, should be reconsidered and the training of managers capable of making decisions should be encouraged, in order to recreate the old team spirit of tunnellers on the site.Seit der Einführung der Neuen Österreichischen Tunnelbauweise in der Mitte der 1960er Jahre erlebt der Tunnelbau in vielen Bereichen eine grundlegende Veränderung. Die zunehmende Verrechtlichung und die fortschreitende Bürokratisierung haben dazu geführt, dass die heutigen Tunnelbauverträge im Vergleich zu früher umfangreich, umständlich und widersprüchlich geworden sind. Sowohl die Erstellung der Ausschreibungsplanung als auch die Angebotsbearbeitung bis hin zur Ausführung leiden unter dem Billigstbieterprinzip, dem die Bauherrn gesetzlich unterworfen sind. Die Ausschreibungen sind meist mangelhaft, die Angebote nicht selten spekulativ und unterpreisig. Die NÖT aber ist eine Bauweise, die zur vollen Entfaltung ihres Potenzials eine flexible partnerschaftliche Vertragsgestaltung, kompetente Mitarbeiter, schlanke Strukturen und kurze Entscheidungswege auf der Baustelle benötigt. Im Gegensatz dazu sind die Baustellen heute von sinnlosem Verwaltungsaufwand und oft unsinniger gegenseitiger Kontrolle geprägt. Die rasante Entwicklung und die zunehmende Automatisierung von Maschinen und die Weiterentwicklung von Baustoffen bieten auch in Zukunft große Chancen für die NÖT. Allerdings ist in Zukunft der Vergabemodus zu überdenken und die Ausbildung entscheidungskompetenter Führungskräfte zu fördern, um den alten Teamgeist der Tunnelbauer auf den Baustellen wieder herzustellen.
A road tunnel in difficult geology with cross‐sections up to 300 m2 / Straßentunnel in schwieriger Geologie mit Querschnitten bis zu 300 m2
Authors: Längle Thomas , Käppeli Lukas 
Published: December 2010

AbstractThe 4.2 km Eyholz tunnel is part of the autobahn A9 and is the essential element in the bypass of Visp in the canton Valais, Switzerland. The tunnel passes through geologically problematic and also tectonically highly stressed zones (Rhone‐Simplon fault).The excavation of the two two‐lane bores is being performed conventionally, by blasting and also in loose material. The interesting structures include the underground junction caverns, where slip roads to join and leave the autobahn are included in the tunnel, resulting in cross‐sections of up to 300m2 having to be excavated.The overburden areas near the portals were excavated with tunnel excavators under the protection of elaborate jetted canopies. The two tunnel bores are being excavated in parallel and are connected with crosscuts every 270 m. As is typical for recent Swiss autobahn tunnels, a service duct is constructed under the carriageway. The inner lining of the main bores is progressing at the same time as the excavation and also the lining of the cavern with in‐situ concrete. The first bore should open for traffic in 2013.Der 4,2 km lange Autobahntunnel Eyholz ist Teil der Autobahn A9 und bildet das Kernstück der Umfahrung Visp im Kanton Wallis, CH. Der Tunnel befindet sich in geologisch schwierigen, und zusätzlich tektonisch stark beanspruchten Zonen (Rhone‐Simplon Störung).Die Ausbruchsarbeiten der beiden Doppelspurröhren werden konventionell, sowohl im Spreng‐ als auch im Lockermaterialvortrieb ausgeführt. Bautechnisch interessante Bauwerke sind unter anderem die unterirdischen Verzweigungskavernen. Hier wurden aus Platzgründen Ein‐ und Ausfahrtsspuren in den Tunnel verlegt, wodurch Ausbruchsquerschnitte bis 300m2 aufzufahren waren.Die Überlagerungsbereiche der Portalstrecken wurden teilweise mit aufwändigen Jettschirmen gesichert und im Baggervortrieb ausgebrochen. Beide Tunnelröhren werden parallel ausgebrochen und sind alle 270 m mit Querschlägen miteinander verbunden. Typisch für die Schweizer Autobahnen in jüngerer Zeit ist ein, unter der Fahrbahn angeordneter Werkleitungskanal. Gleichzeitig zum Vortrieb laufen der Innenausbau der Hauptröhren sowie der Ausbau der Kavernen in Ortbeton. 2013 soll die erste Röhre ans Netz gehen.