bluuebunny/crossref_metadata_2025_split huggingface dataset:
Directed OmniChange Evolution Converts P450 BM3 into an Alkyltrimethylammonium Hydroxylase
Authors: Ji Yu , Mertens Alan Maurice , Gertler Christoph , Fekiri Sallama , Keser Merve , Sauer Daniel F. , Smith Kilian E. C. , Schwaneberg Ulrich 
Published: August 2018

AbstractCetyl‐trimethylammonium bromide (CTAB) is a widely used cationic surfactant that is biodegradable in nature. CTAB biodegradation requires hydroxylation in the first step, which is rate‐limiting and crucial for solubility in water. In this study, the OmniChange multi‐site mutagenesis method was applied to reengineer the P450 BM3 substrate specificity towards the hydroxylation of CTAB by simultaneous mutagenesis of four previously reported positions (R47, Y51, F87, and L188). 1740 clones from the P450 BM3 OmniChange library were screened with the NADPH depletion assay. A total of 696 clones were rescreened with the NADPH depletion and an Ampliflu™ Red/ horseradish peroxidase based H2O2 detection assay. Several improved P450 BM3 variants were identified and finally four were kinetically characterized with respect to CTAB hydroxylation, based on both performance and coupling efficiency. Based on NADPH consumption, the P450 BM3 variant P3A8 (R47E/Y51M/F87V/L188E) displayed an initial activity (64.9±4.8 s−1, 13.5‐fold increased activity compared with wild‐type P450 BM3), which nearly matches the specific activity for its natural fatty acid substrate (palmitic acid (32–122 s−1)). Variant P3A8 showed high coupling efficiency (92.5 %), whereas wild‐type P450 BM3 displayed a low coupling efficiency (0.5 %). HPLC‐MS/MS detection confirmed that P3A8 and P2E7 (R47D/Y51L/F87V/L188A) form 13 and 35 times more 2‐hydroxylated CTAB than P450 BM3. In addition, di‐hydroxylated CTAB products were detected for all four investigated P450 BM3 variants (up to a yield of 77 %; P3A8). Di‐hydroxylated quaternary amines are highly interesting bolaform surfactants with a high hydrophilicity (surface contact angle: θ=16.7°).
Prodrugs of Nucleoside Triphosphates as a Sound and Challenging Approach: A Pioneering Work That Opens a New Era in the Direct Intracellular Delivery of Nucleoside Triphosphates
Authors: Camarasa María‐José 
Published: August 2018

AbstractSynthetic nucleosides, designed to mimic naturally occurring nucleosides, are important antiviral and anticancer chemotherapeutic agents. However, nucleosides are not active as such and need to be metabolized, step by step, to their corresponding active nucleoside triphosphates (NTPs). This is mediated by phosphorylating enzymes, mainly host cellular kinases with strong specificity for their substrates; in many cases, this specificity prevents efficient conversion into the NTPs. To circumvent this metabolic handicap, successful nucleo(s/t)ide prodrugs have been developed as a valuable concept in the design of effective drugs. The unique concept of the TriPPPro approach, developed by Chris Meier and colleagues, is a powerful tool for the intracellular delivery of active NTPs, bypassing all the phosphorylation steps required by nucleosides to yield the active NTP metabolites. This concept is illustrated herein with general examples.
Folates in Trypanosoma brucei: Achievements and Opportunities
Authors: Cullia Gregorio , Tamborini Lucia , Conti Paola , De Micheli Carlo , Pinto Andrea 
Published: August 2018

AbstractTrypanosoma brucei is the agent of human African trypanosomiasis (HAT), a neglected disease that threatens the lives of 65 million people in sub‐Saharan Africa every year. Unfortunately, available therapies are unsatisfactory, due primarily to safety issues and development of drug resistance. Over the last decades significant effort has been made in the discovery of new potential anti‐HAT agents, with help from the World Health Organization (WHO) and private–public partnerships such as the Drugs for Neglected Diseases Initiative (DNDi). Whereas antifolates have been a valuable source of drugs against bacterial infections and malaria, compounds effective against T. brucei have not yet been identified. Considering the relatively simple folate metabolic pathway in T. brucei, along with results obtained in this research field so far, we believe that further investigations might lead to effective chemotherapeutic agents. Herein we present a selection of the more promising results obtained so far in this field, underlining the opportunities that could lead to successful therapeutic approaches in the future.
A comparative study of porous medium CFD models for flow diverter stents: Advantages and shortcomings
Authors: Dazeo Nicolás , Dottori Javier , Boroni Gustavo , Larrabide Ignacio 
Published: August 2018

AbstractIn computational fluid dynamics, there is a high interest in modeling flow diverter stents as porous media due to its reduced computational loads. One of the main difficulties of such models is proper parameter setup. Most authors assume flow diverter's wire screen as an isotropic and homogeneous medium, while others proposes anisotropic configurations, yet very little is discussed about the effect of these assumptions on model's accuracy. In this paper, we compare the effect of different models on hemodynamics in relation to their parameters. The fidelity and efficiency of the different models to capture wire screen effect on fluid flow are quantitatively analyzed and compared.
cuThomasBatch and cuThomasVBatch, CUDA Routines to compute batch of tridiagonal systems on NVIDIA GPUs
Authors: Valero‐Lara Pedro , Martínez‐Pérez Ivan , Sirvent Raül , Martorell Xavier , Peña Antonio J. 
Published: August 2018

SummaryThe solving of tridiagonal systems is one of the most computationally expensive parts in many applications, so that multiple studies have explored the use of NVIDIA GPUs to accelerate such computation. However, these studies have mainly focused on using parallel algorithms to compute such systems, which can efficiently exploit the shared memory and are able to saturate the GPUs capacity with a low number of systems, presenting a poor scalability when dealing with a relatively high number of systems. The gtsvStridedBatch routine in the cuSPARSE NVIDIA package is one of these examples, which is used as reference in this article. We propose a new implementation (cuThomasBatch) based on the Thomas algorithm. Unlike other algorithms, the Thomas algorithm is sequential, and so a coarse‐grained approach is implemented where one CUDA thread solves a complete tridiagonal system instead of one CUDA block as in gtsvStridedBatch. To achieve a good scalability using this approach, it is necessary to carry out a transformation in the way that the inputs are stored in memory to exploit coalescence (contiguous threads access to contiguous memory locations). Different variants regarding the transformation of the data are explored in detail. We also explore some variants for the case of variable batch, when the size of the systems of the batch has different size (cuThomasVBatch). The results given in this study prove that the implementations carried out in this work are able to beat the reference code, being up to 5× (in double precision) and 6× (in single precision) faster using the latest NVIDIA GPU architecture, the Pascal P100.
MADPTM: Mix zones and dynamic pseudonym trust management system for location privacy
Authors: Memon Imran , Mirza Hamid Turab 
Published: August 2018

SummaryIn intelligent transportation systems, the messages transmitted and received from one vehicle to another vehicle may enhance location privacy scheme; falsification message forwarding collusion attack, timing, and transition attacks all are serious issues and must be addressed in event trust management. Without which, decision making on event message may endanger the whole transportation system and may even threat the human life. In addition, pseudonym expiry is another critical issue of location privacy. The time interval of decision waiting even has been the critical accident response time. In this paper, we proposed a new novel mix zones and dynamic pseudonym trust management system, called MADPTM, which aims to prevent against attackers under privacy‐enhanced road networks. On shortening the pseudonym expiry, we propose dynamic pseudonym trust management system, with the assistance of reported server. We performed a set of simulations under many trust attack models to evaluate the performance and efficiency of the proposed system. Our proposed MADPTM method proved to be highly resilient to various attacks, and simulation results verified that our method outperforms other existing methods.
Synthesis and pharmacology of new psychoactive substance 5F‐CUMYL‐P7AICA, a scaffold‐ hopping analog of synthetic cannabinoid receptor agonists 5F‐CUMYL‐PICA and 5F‐CUMYL‐PINACA
Authors: Banister Samuel D. , Adams Axel , Kevin Richard C. , Macdonald Christa , Glass Michelle , Boyd Rochelle , Connor Mark , McGregor Iain S. , Havel Christopher M. , Bright Stephen J. , Vilamala Mireia Ventura , Lladanosa Cristina Gil , Barratt Monica J. , Gerona Roy R. 
Published: August 2018

AbstractSynthetic cannabinoid receptor agonists (SCRAs) are a dynamic class of new psychoactive substances (NPS), with novel chemotypes emerging each year. Following the putative detection of 5F‐CUMYL‐P7AICA in Australia in 2016, the scaffold‐hopping SCRAs 5F‐CUMYL‐PICA, 5F‐CUMYL‐PINACA, and 5F‐CUMYL‐P7AICA were synthesized and characterized by nuclear magnetic resonance (NMR) spectroscopy, gas chromatography–mass spectrometry (GC–MS), and liquid chromatography–quadrupole time‐of‐flight–MS (LC–QTOF–MS). Since little is known of the pharmacology of 7‐azaindole SCRAs like 5F‐CUMYL‐P7AICA, the binding affinities and functional activities of all compounds at cannabinoid type 1 and type 2 receptors (CB1 and CB2, respectively) were assessed using tritiated radioligand competition experiments and fluorescence‐based plate reader membrane potential assays. Despite CB1 binding affinities differing by over two orders of magnitude (Ki = 2.95–174 nM), all compounds were potent and efficacious CB1 agonists (EC50 = 0.43–4.7 nM), with consistent rank order for binding and functional activity (5F‐CUMYL‐PINACA >5F‐CUMYL‐PICA >5F‐CUMYL‐P7AICA). Additionally, 5F‐CUMYL‐P7AICA was found to exert potent cannabimimetic effects in mice, inducing hypothermia (6°C, 3 mg/kg) through a CB1‐dependent mechanism.
Pre‐fire drought and competition mediate post‐fire conifer mortality in western U.S. National Parks
Authors: van Mantgem Phillip J. , Falk Donald A. , Williams Emma C. , Das Adrian J. , Stephenson Nathan L. 
Published: August 2018

AbstractTree mortality is an important outcome of many forest fires. Extensive tree injuries from fire may lead directly to mortality, but environmental and biological stressors may also contribute to tree death. However, there is little evidence showing how the combined effects of two common stressors, drought and competition, influence post‐fire mortality. Geographically broad observations of three common western coniferous trees subjected to prescribed fire showed the likelihood of post‐fire mortality was related to intermediate‐term (10 yr) pre‐fire average radial growth, an important component of tree vigor. Path analysis showed that indices of competition and drought stress prior to fire can be described in terms of joint effects on growth, indirectly affecting post‐fire mortality. Our results suggest that the conditions that govern the relationship between growth and mortality in unburned stands may also apply to post‐fire environments. Thus, biotic and abiotic changes that affect growth negatively (e.g., drought stress) or positively (e.g., growth releases following thinning treatments) prior to fire may influence expressed fire severity, independent of fire intensity (e.g., heat flux, residence time). These relationships suggest that tree mortality may increase under stressful climatic or stand conditions even if fire behavior remains constant.
Chemical and Electrochemical Oxidation of Tris(3,5‐di‐tert‐butylphenyl)phosphine – High Z′ Crystal Structures and Conformational Effects Associated with Bulky meta Substituents
Authors: Dimbarre Lao Guimarães Ivelise , Garcia Jarem Raul , Wohnrath Karen , Boeré René T. 
Published: August 2018

AbstractInvited for the cover of this issue is the group of Karen Wohnrath of Universidade Estadual de Ponta Grossa, Paraná, Brazil, and collaborator René Boeré of the University of Lethbridge, Alberta, Canada, focused on enhancing ruthenium metallodrug design for antiproliferative and antibacterial agents. The cover image shows the shape of a highly lipophilic organophosphine ligand used in these studies.
Mechanical characterization of HIV‐1 with a solid‐state nanopore sensor
Authors: Darvish Armin , Lee Jung Soo , Peng Bin , Saharia Jugal , VenkatKalyana Sundaram Ramalingam , Goyal Gaurav , Bandara Nuwan , Ahn Chi Won , Kim Jungsuk , Dutta Prashanta , Chaiken Irwin , Kim Min Jun 
Published: August 2018

AbstractEnveloped viruses fuse with cells to transfer their genetic materials and infect the host cell. Fusion requires deformation of both viral and cellular membranes. Since the rigidity of viral membrane is a key factor in their infectivity, studying the rigidity of viral particles is of great significance in understating viral infection. In this paper, a nanopore is used as a single molecule sensor to characterize the deformation of pseudo‐type human immunodeficiency virus type 1 at sub‐micron scale. Non‐infective immature viruses were found to be more rigid than infective mature viruses. In addition, the effects of cholesterol and membrane proteins on the mechanical properties of mature viruses were investigated by chemically modifying the membranes. Furthermore, the deformability of single virus particles was analyzed through a recapturing technique, where the same virus was analyzed twice. The findings demonstrate the ability of nanopore resistive pulse sensing to characterize the deformation of a single virus as opposed to average ensemble measurements.
Inhibition of CYP2E1 With Propylene Glycol Does Not Protect Against Hepatocellular Injury in Human Acetaminophen Daily‐Dosing Model
Authors: Ganetsky Michael , Berg Anders H. , Solano Joshua J. , Salhanick Steven 
Published: August 2018

AbstractAcetaminophen (APAP)‐induced liver injury is initiated by metabolism of APAP by the cytochrome P‐450 (CYP) system, primarily CYP2E1. We previously demonstrated CYP inhibition following administration of a liquid APAP formulation containing propylene glycol, a CYP2E1 inhibitor, and other excipients. This study was undertaken to determine if propylene glycol specifically inhibits production of CYP‐derived metabolites and if propylene glycol reduces the rise in alanine aminotransferase (ALT) seen following prolonged APAP dosing. Human subjects were randomized to receive 4 g of APAP daily in one arm of the study or 4 g of APAP with 5 mL of 99% propylene glycol in the other arm, both for 14 days. After a washout period of at least 14 days, subjects were crossed over between arms. Outcomes were rise of ALT greater than 2 times baseline (responders) and proportion of randomly sampled CYP‐derived metabolites relative to total metabolites produced. There was no difference in percentage of responders between treatment groups: 6 of 21 in the APAP group (29%) compared with 8 of 20 in the APAP + propylene glycol group (40%); chi‐square, P = .59. For all subjects, the mean percentage of CYP‐derived metabolites produced was 5.8% (APAP) versus 4.3% (APAP + propylene glycol); P = .018. This effect was solely attributable to the responders: the mean percentage of CYP metabolites of responders was 7.7% (APAP) versus 4.6% (APAP + propylene glycol), P = .050, whereas there was no difference for the nonresponders. Five subjects were responders in both arms (2% probability of random occurrence). Our data indicates that propylene glycol inhibits CYP2E1 metabolism of APAP in some subjects but does not effect hepatocellular indury at the dose given.
The effects of different land uses on soil hydraulic properties in the Loess Plateau, Northern China
Authors: Kalhoro Shahmir Ali , Xu Xuexuan , Ding Kang , Chen Wenyuan , Shar Abdul Ghaffar , Rashid Muhammad 
Published: August 2018

AbstractSome agriculture practices are unsuitable in the northern hilly region of the Chinese Loess Plateau and have resulted in the degradation of the native vegetation ecosystems and unfavorable soil hydraulic properties, which cause serious soil losses. The objective of this study was to ascertain the influence of land use changes on soil infiltration rate and other related soil properties in this region. A total of 90 infiltration tests were run on six different land uses (natural grassland, apple orchard, abandoned apple orchard, farmland wheat, farmland maize, and scrub grassland). For studying the infiltration rate, a triplicate of infiltration tests had been taken using a disc permeameter with different pressure heads. Infiltration rate was high in abandoned apple orchard (10 mm min−1) whereas very low in apple orchard (0.6 mm min−1). The statistical analysis showed that the main soil properties were affected by changes of land use types or vegetation cover. Compared with that in the natural grassland and abandoned apple orchard sites, a notable reduction of soil root biomass, infiltration, and bulk density in apple orchard was recorded. The root image analysis showed that the natural grassland and abandoned apple orchard have strong root systems, that is, root length density 6.97 ± 0.344 cm cm−3, root surface area 1.56 ± 0.24 cm2 cm−3, and average root diameter 0.814 ± 0.24 mm, in comparison with other sites. The limited root length density, root surface area, and average diameter were recorded in apple orchard 0.51 ± 0.03 cm cm−3, 0.49 ± 0.12 cm2 cm−3, and 1.88 ± 0.24 mm. Conclusively, our study suggests that converting farmland apple orchard into grassland or scrubland may change soil hydraulic properties, which may help to reduce soil losses in the Loess Plateau.
Seasonal similarity in rates of protistan herbivory in fjords along the Western Antarctic Peninsula
Authors: Morison F. , Menden‐Deuer S. 
Published: August 2018

AbstractWe quantified phytoplankton growth and protistan grazing rates during late austral autumn 2013 and late austral spring 2014, in several glacio‐marine fjords and connecting channels along the Western Antarctic Peninsula (WAP). During austral autumn, low and declining chlorophyll a (Chl a) concentrations (≤ 0.4 μg L−1) were almost entirely composed of pico/nanophytoplankton, whereas during austral spring, high but patchy Chl a concentrations in the fjords (up to 18.5 μg L−1) reflected a diatom bloom. These contrasting dynamics were associated with high seasonal differences in irradiance, but not temperature, and were consistent with the balance resulting from lower phytoplankton growth rates in autumn (−0.01 d−1 to 0.19 d−1) than in spring (0.06–0.93 d−1) but similar magnitudes of herbivorous grazing in both seasons. Grazing was either absent or low (0.11–0.26 d−1) and restricted to the picophytoplankton and nanophytoplankton. In the productive fjords lining the WAP, a fraction of primary production was channelled through a persistent and across‐seasons equally active microbial food web, while during spring an increasing fraction of organic carbon shifted from trophic transfer and recycling to an export pathway.
Onset of Donor Warm Ischemia Time in Donation After Circulatory Death Liver Transplantation: Hypotension or Hypoxia?
Authors: Kalisvaart Marit , de Haan Jubi E. , Polak Wojciech G. , N. M. IJzermans Jan , Gommers Diederik , Metselaar Herold J. , de Jonge Jeroen 
Published: August 2018

Abstract
The aim of this study was to investigate the impact of hypoxia and hypotension during the agonal phase of donor warm ischemia time (DWIT) on hepatic ischemia/reperfusion injury (IRI) and complications in donation after circulatory death (DCD) liver transplantation. A retrospective single‐center study of 93 DCD liver transplants (Maastricht type III) was performed. DWIT was divided into 2 periods: the agonal phase (from withdrawal of treatment [WoT] until circulatory arrest) and the asystolic phase (circulatory arrest until cold perfusion). A drop to <80% in peripheral oxygenation (SpO2) was considered as hypoxia in the agonal phase (SpO2‐agonal) and a drop to <50 mm Hg as hypotension in the agonal phase (SBP‐agonal). Peak postoperative aspartate transaminase level >3000 U/L was considered as severe hepatic IRI. SpO2 dropped within 2 minutes after WoT <80%, whereas the systolic blood pressure dropped to <50 mm Hg after 9 minutes, resulting in a longer SpO2‐agonal (13 minutes) than SBP‐agonal (6 minutes). In multiple logistic regression analysis, only duration of SpO2‐agonal was associated with severe hepatic IRI (P = 0.006) and not SBP‐agonal (P = 0.32). Also, recipients with long SpO2‐agonal (>13 minutes) had more complications with a higher Comprehensive Complication Index during hospital admission (43.0 versus 32.0; P = 0.002) and 90‐day graft loss (26% versus 6%; P = 0.01), compared with recipients with a short SpO2‐agonal (≤13 minutes). Furthermore, Cox proportional hazard modeling identified a long SpO2‐agonal as a risk factor for longterm graft loss (hazard ratio, 3.30; 95% confidence interval, 1.15‐9.48; P = 0.03). In conclusion, the onset of hypoxia during the agonal phase is related to the severity of hepatic IRI and postoperative complications. Therefore, SpO2 <80% should be considered as the start of functional DWIT in DCD liver transplantation.
Stimuli‐Responsive Supramolecular Gels Constructed by Hierarchical Self‐Assembly Based on Metal‐Ligand Coordination and Host–Guest Recognition
Authors: Lee Yin‐Hsuan , He Lipeng , Chan Yi‐Tsu 
Published: August 2018

AbstractMetal‐ligand coordination and host–guest recognition are introduced into the hybrid system in order to prepare supramolecular gels, which can be responsive to multiple external stimuli such as metal ions, competitive guest/host molecules, and oxidants. To this end, the triangular terpyridine‐based metallocycles functionalized with 1‐adamantyl and ferrocenyl groups are constructed through self‐assembly, and further used as supramolecular cross‐linkers for gelation of β‐CD‐containing copolymers. Their gelation and stimuli‐response tests are discussed, and an application of the metallotriangles for serving as supramolecular glue is demonstrated through a series of adhesion experiments. This approach enables facile access to construction of multifunctional metallosupramolecules as well as functional hybrid materials.
Hereditary cancer screening: Case reports and review of literature on ten Ashkenazi Jewish founder mutations
Authors: Cox Devin M. , Nelson Katherine L. , Clytone Meera , Collins Debra L. 
Published: August 2018

AbstractBackgroundHistorically, three founder mutations in the BRCA1/2 (OMIM 113705; OMIM 600185) genes have been the focus of cancer risks within the Ashkenazi Jewish (AJ) population. However, there are several additional mutations associated with increased susceptibility to cancer in individuals of AJ ancestry.MethodsWe report three patients who exemplify the need to keep these additional founder mutations in mind when pursuing hereditary cancer genetic testing of individuals in this population. All gene sequences in this paper were aligned to reference sequences based on human genome build GRCh37/UCSC hg19.Resultsreview of the literature discusses that the combined risk is 12.36%–20.83% forhaving 1 of the 10 hereditary cancer AJ founder mutations in the BRCA1, BRCA2, CHEK2 (OMIM 604373), APC (OMIM 611731), MSH2 (OMIM 609309), MSH6 (OMIM 600678), and GREM1 (OMIM 603054) genes for individuals of AJ ancestry.ConclusionWe recommend testing for all 10 of these AJ founder cancer susceptibility mutations for individuals within this population as standard screening in order to ensure appropriate cancer risk management and cascade testing.