bluuebunny/crossref_metadata_2025 huggingface dataset:
The global burden of HIV-1 drug resistance in the past 20 years
Authors: Zazzi Maurizio , Hu Hui , Prosperi Mattia
Published: May 2018

Genotypic drug resistance testing has been an integral part of the clinical management of HIV patients for almost 20 years, not only assisting treatment choices but also informing drug development. Accurate estimations on the worldwide circulation of drug resistance are difficult to obtain, particularly in low/middle-income countries. In this work, we queried two of the largest public HIV sequence repositories in the world—Los Alamos and Stanford HIVdb—to derive global prevalence, time trends and geodemographic predictors of HIV drug resistance. Different genotypic interpretation systems were used to ascertain resistance to reverse transcriptase and protease inhibitors. Continental, subtype-specific (including circulating recombinant forms) stratification as well as analysis on drug-naïve isolates were performed. Geographic information system analysis correlated country-specific drug resistance to sociodemographic and health indicators obtained from the World Bank. By looking at over 33,000 sequences worldwide between 1996 and 2016, increasing drug resistance trends with non-B subtypes and recombinants were found; transmitted drug resistance appeared to remain stable in the last decade. While an increase in drug resistance is expected with antiretroviral therapy rollout in resource-constrained areas, the plateau effect in areas covered by the most modern drug regimens warns against the downgrading of the resistance issue.
Physical fitness predicts technical-tactical and time-motion profile in simulated Judo and Brazilian Jiu-Jitsu matches
Authors: Coswig Victor S. , Gentil Paulo , Bueno João C.A. , Follmer Bruno , Marques Vitor A. , Del Vecchio Fabrício B.
Published: May 2018

Background

Among combat sports, Judo and Brazilian Jiu-Jitsu (BJJ) present elevated physical fitness demands from the high-intensity intermittent efforts. However, information regarding how metabolic and neuromuscular physical fitness is associated with technical-tactical performance in Judo and BJJ fights is not available. This study aimed to relate indicators of physical fitness with combat performance variables in Judo and BJJ.

Methods

The sample consisted of Judo (n = 16) and BJJ (n = 24) male athletes. At the first meeting, the physical tests were applied and, in the second, simulated fights were performed for later notational analysis.

Results

The main findings indicate: (i) high reproducibility of the proposed instrument and protocol used for notational analysis in a mobile device; (ii) differences in the technical-tactical and time-motion patterns between modalities; (iii) performance-related variables are different in Judo and BJJ; and (iv) regression models based on metabolic fitness variables may account for up to 53% of the variances in technical-tactical and/or time-motion variables in Judo and up to 31% in BJJ, whereas neuromuscular fitness models can reach values up to 44 and 73% of prediction in Judo and BJJ, respectively. When all components are combined, they can explain up to 90% of high intensity actions in Judo.

Discussion

In conclusion, performance prediction models in simulated combat indicate that anaerobic, aerobic and neuromuscular fitness variables contribute to explain time-motion variables associated with high intensity and technical-tactical variables in Judo and BJJ fights.
Effect of Sofosbuvir plus Ribavirin therapy on hepatitis C patients in Pakistan: a retrospective study
Authors: Jamil Zubia , Waheed Yasir , Malik Maryam , Durrani Asghar A.
Published: May 2018

Background

The annual global deaths from viral hepatitis is 1.4 million. Pakistan has the second highest burden of hepatitis C in the world. There is dire need to evaluate the response of new direct acting antivirals for the treatment of hepatitis C patients in Pakistan. World Health Organization has developed a strategy to treat 80% of HCV patients by 2030. In Pakistan, HCV treatment rate is 1%. The aim of the study was to analyze the effect of Sofosbuvir plus Ribavirin therapy on HCV patients in Pakistan.

Methods

An observational study was conducted at Fauji Foundation Hospital Rawalpindi from November-2016 to July-2017. All the drugs were administered according to the guidelines of Asia Pacific Association for the Study of Liver (APASL) for the treatment of HCV patients. A total 327 chronic HCV patients were enrolled in the study and 304 completed the treatment. Patients belonged to three different groups including treatment: Naïve patients (n = 107), Non-Responder patients (n = 126) and patients who relapsed to Interferon therapy (n = 71).All the patients were given Sofosbuvir plus Ribavirin therapy for 24 weeks and the early virological response (EVR) and end treatment response (ETR) was calculated. Different parameters including patient age, viral load, viral genotype, blood picture, ultrasound findings and liver function tests were also studied.

Results

Out of 304 patients, 301 (99%) achieved EVR and 300 achieved ETR (98.7%). End treatment response was 95.6% in HCV genotype 1 and 98.9% in HCV genotype 3 patients. ETR was 99.06% in treatment Naïve, 99.20% in non-responders and 97.18% in previously relapsed patients. We did not find the association of any host and viral factor in the determination of EVR and ETR.

Conclusion

The Sofosbuvir plus Ribavirin treatment is highly effective, safe and cost-effective for the treatment of hepatitis C patients in Pakistan.
Factors that distinguish aggression toward animals from other antisocial behaviors: Evidence from a community sample
Authors: Alleyne Emma , Parfitt Charlotte
Published: May 2018

Animal cruelty is a form of passive and active aggression that is largely undocumented and unreported. Given that animals are voiceless victims, we have to rely on witnesses and frontline staff (e.g., veterinarians) to report incidents of abuse, which suggests the number of convicted animal abusers is an under‐representation of actual perpetrators. The primary aim of the current study was to identify the static and dynamic factors that distinguish animal abusers from non‐abuse offenders (i.e., individuals who self‐reported antisocial behavior, but not animal abuse), and non‐offenders (i.e., individuals who have not engaged in any antisocial behavior) in a community sample. The secondary aim was to identify the potential pathways that distinguish animal abuse perpetration from other types of antisocial behavior. Three hundred and eighty‐four participants took part in this retrospective, correlational study. We found that animal abusers share similar socio‐demographic characteristics to other offenders but are distinct in their exposure to animal harm/killing during childhood. Low animal‐oriented empathy and low self‐esteem distinguished animal abusers from non‐abuse offenders when controlling for confound variables and other psychological characteristics. We also found that low animal‐oriented empathy mediated the relationship between childhood exposure to animal killing and animal abuse perpetration, and that this relationship was stronger among participants with anger regulation issues. This is the first study to examine similarities and differences between animal abusers, non‐abuse offenders, and non‐offenders on socio‐demographic and psychological characteristics. The findings highlight potential treatment targets that are unique to animal abusers with implications for prevention and intervention strategies.
Participation in Regular Physical Activity After Total Knee or Hip Arthroplasty for Osteoarthritis: Prevalence, Associated Factors, and Type
Authors: Naylor Justine M. , Pocovi Natasha , Descallar Joseph , Mills Kathryn A.
Published: May 2018

Objective

To describe the rates of participation in regular physical activity presurgery and at 3 years follow‐up after knee or hip arthroplasty, and to describe factors associated with participation postsurgery and types of activity undertaken.

Methods

A previously acquired multicenter, prospective cohort of knee or hip arthroplasty recipients was followed up for 3 years postsurgery. Regular participation in physical activity was defined as participation in physical activity ≥1 time/week, excluding incidental activities. Participants were interviewed about current participation as well as participation in the year presurgery. Joint‐specific and health‐related quality‐of‐life scores and information on experience of major complications were obtained. Information about comorbidity and body weight were updated. Factors associated with 3‐year physical activity participation were determined using multivariable logistic regression modeling.

Results

In total, 73.4% of the eligible cohort (1,289 of 1,757) were followed up (718 patients with total knee arthroplasty, and 571 patients with total hip arthroplasty). Participation profiles were similar regardless of the joint replaced. Participation in physical activity increased postsurgery in the combined cohort (from 45.2% to 63.5%; P < 0.001). Participation at 3 years was associated with participation presurgery (P < 0.0001), better 3‐year quality of life (P < 0.001), younger age (P = 0.002), better 3‐year joint scores (P = 0.01), >1 lifetime arthroplasty (P = 0.02), and higher education level (P = 0.04). Low‐impact and nonambulatory activities significantly increased postsurgery with no change in high‐impact activities.

Conclusion

Participation rates increased postsurgery when recovery was stable, but approximately one‐third of arthroplasty recipients did not engage in physical activity at least once per week. Because participation is associated with habitual activity presurgery, a potential role for behavior change interventions is suggested. The increase in nonambulatory activities indicates that current devices measuring ambulatory activity alone are inadequate for capturing physical activity.
Subsequent Cardiovascular Events Among Patients With Rheumatoid Arthritis, Psoriatic Arthritis, or Psoriasis: Patterns of Disease‐Modifying Antirheumatic Drug Treatment
Authors: Sparks Jeffrey A. , Lesperance Tamara , Accortt Neil A. , Solomon Daniel H.
Published: May 2018

Objective

To examine disease‐modifying antirheumatic drug (DMARD) treatments and estimate the risk of a subsequent cardiovascular (CV) event following an initial CV event in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or psoriasis.

Methods

We analyzed data from MarketScan claims databases (January 1, 2006 to June 30, 2015) for adults with RA, PsA, or psoriasis and an initial/index CV event (acute myocardial infarction, stroke, or coronary revascularization) while receiving DMARDs (tumor necrosis factor inhibitor [TNFi] biologic DMARDs [bDMARDs], conventional synthetic DMARDs [csDMARDs], or non‐TNFi bDMARDs). We studied DMARD treatment patterns following the index event and rates of subsequent CV events. We used Cox regression to investigate predictors of DMARD discontinuation and risk factors for subsequent CV events.

Results

Among 10,254 patients, 15.3% discontinued and 15.5% switched DMARD therapy after the index CV event. Independent predictors of DMARD discontinuation included a psoriasis diagnosis, renal disease, hypertension, heart failure, diabetes mellitus, older age, and baseline csDMARD or non‐TNFi bDMARD use (versus TNFi bDMARDs). Rates per 1,000 patient‐years of subsequent events were 75.2 (95% confidence interval [95% CI] 54.4–96.0) for patients taking TNFi bDMARDs, 83.6 (95% CI 53.3–113.9) for csDMARDs, and 122.4 (95% CI 60.6–184.3) for non‐TNFi bDMARDs. A diagnosis of RA (versus psoriasis) and heart failure at baseline, but not a DMARD pattern after the index event, were independently associated with an increased risk of subsequent CV event.

Conclusion

In this large nationwide study, nearly one‐third of patients with RA, PsA, or psoriasis switched or discontinued DMARD therapy following a CV event. There was no association between DMARD class and the risk of a subsequent CV event.
Dilatometric and Calorimetric Short‐Term Characterization Methods on 100Cr6 Micro Samples for High‐Throughput Investigations
Authors: Cramer Lena , Toenjes Anastasiya , Steinbacher Matthias , von Hehl Axel , Zoch Hans‐Werner
Published: May 2018

Combining new processes for solidification, forming, and heat treatment on the micro as well as on the macro scale, the Collaborative Research Center “Farbige Zustände” develops a novel high‐throughput method for the research of new steel and aluminum alloys with advanced structural properties. These material scientific processes are accompanied by sample logistics and mathematical and computer science based methods for the analysis of large amounts of data. The presented subproject “thermal and thermo‐mechanical treatment” is intended to contribute to a wide range of multiscale adjustment of material properties by technical and, beyond this, novel heat treatment processes and process combinations. Therefore, fast dilatometric and calorimetric characterization methods are developed on the micro scale to act as high‐throughput descriptors for macroscopic material properties. First results compare experimental data of these two thermal analysis methods in which spherical steel samples of 100Cr6 (AISI 52100) with a diameter of 1 mm have been investigated.
Rhodium(III)‐Catalyzed Synthesis of Cinnolinium Salts from Azobenzenes and Diazo Compounds
Authors: Chen Xiaohong , Zheng Guangfan , Song Guoyong , Li Xingwei
Published: May 2018

A Rh(III)‐catalyzed C−H activation of azobenzenes in the coupling with diazo compounds has been realized, providing a straightforward strategy to access functionalized cinnolinium triflates in high yields. This protocol features silver free mild reaction conditions and compatibility with diverse functional groups. The coupling proceeds via initial Rh(III)‐catalyzed C−H alkylation, followed by zinc triflate‐mediated cyclization, where zinc triflate acts as a Lewis acid as well as a triflate source.

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In Situ Analysis of Solvent and Additive Effects on Film Morphology Evolution in Spin‐Cast Small‐Molecule and Polymer Photovoltaic Materials
Authors: Manley Eric F. , Strzalka Joseph , Fauvell Thomas J. , Marks Tobin J. , Chen Lin X.
Published: May 2018

To elucidate the details of film morphology/order evolution during spin‐coating, solvent and additive effects are systematically investigated for three representative organic solar cell (OSC) active layer materials using combined in situ grazing incidence wide angle x‐ray scattering (GIWAXS) and optical reflectance. Two archetypical semiconducting donor (p‐type) polymers, P3HT and PTB7, and semiconducting donor small‐molecule, p‐DTS(FBTTh2)2 are studied using three neat solvents (chloroform, chlorobenzene, 1,2‐dichlorobenzene) and four processing additives (1‐chloronaphthalene, diphenyl ether, 1,8‐diiodooctane, and 1,6‐diiodohexane). In situ GIWAXS identifies several trends: 1) for neat solvents, rapid crystallization occurs that risks kinetically locking the material into multiple crystal structures or crystalline orientations; and 2) for solvent + additive processed films, morphology evolution involves sequential transformations on timescales ranging from seconds to hours, with key divergences dependent on additive/semiconductor molecular interactions. When π‐planes dominate the additive/semiconductor interactions, both polymers and small molecule films follow similar evolutions, completing in 1–5 min. When side chains dominate the additive/semiconductor interactions, polymer film maturation times are up to 9 h, while initial crystallization times <10 s are observed for small‐molecule films. This study offers guiding information on OSC donor intermediate morphologies, evolution timescales, and divergent evolutions that can inform OSC manufacture.
On the Stability of DNA Origami Nanostructures in Low‐Magnesium Buffers
Authors: Kielar Charlotte , Xin Yang , Shen Boxuan , Kostiainen Mauri A. , Grundmeier Guido , Linko Veikko , Keller Adrian
Published: May 2018

DNA origami structures have great potential as functional platforms in various biomedical applications. Many applications, however, are incompatible with the high Mg2+ concentrations commonly believed to be a prerequisite for maintaining DNA origami integrity. Herein, we investigate DNA origami stability in low‐Mg2+ buffers. DNA origami stability is found to crucially depend on the availability of residual Mg2+ ions for screening electrostatic repulsion. The presence of EDTA and phosphate ions may thus facilitate DNA origami denaturation by displacing Mg2+ ions from the DNA backbone and reducing the strength of the Mg2+–DNA interaction, respectively. Most remarkably, these buffer dependencies are affected by DNA origami superstructure. However, by rationally selecting buffer components and considering superstructure‐dependent effects, the structural integrity of a given DNA origami nanostructure can be maintained in conventional buffers even at Mg2+ concentrations in the low‐micromolar range.
Direct Participation of a Peripheral Side Chain of a Corrin Ring in Coenzyme B12 Catalysis
Authors: Shibata Naoki , Sueyoshi Yui , Higuchi Yoshiki , Toraya Tetsuo
Published: May 2018

The crystal structures of the B12‐dependent isomerases (eliminating) diol dehydratase and ethanolamine ammonia‐lyase complexed with adenosylcobalamin were solved with and without substrates. The structures revealed that the peripheral a‐acetamide side chain of the corrin ring directly interacts with the adenosyl group to maintain the group in the catalytic position, and that this side chain swings between the original and catalytic positions in a synchronized manner with the radical shuttling between the coenzyme and substrate/product. Mutations involving key residues that cooperatively participate in the positioning of the adenosyl group, directly or indirectly through the interaction with the a‐side chain, decreased the turnover rate and increased the relative rate of irreversible inactivation caused by undesirable side reactions. These findings guide the engineering of enzymes for improved catalysis and producing useful chemicals by utilizing the high reactivity of radical species.
Selective Solid–Liquid and Liquid–Liquid Extraction of Lithium Chloride Using Strapped Calix[4]pyrroles
Authors: He Qing , Williams Neil J. , Oh Ju Hyun , Lynch Vincent M. , Kim Sung Kuk , Moyer Bruce A. , Sessler Jonathan L.
Published: May 2018

LiCl is a classic “hard” ion salt that is present in lithium‐rich brines and a key component in end‐of‐life materials (that is, used lithium‐ion batteries). Its isolation and purification from like salts is a recognized challenge with potential strategic and economic implications. Herein, we describe two ditopic calix[4]pyrrole‐based ion‐pair receptors (2 and 3), that are capable of selectively capturing LiCl. Under solid–liquid extraction conditions, using 2 as the extractant, LiCl could be separated from a NaCl/KCl salt mixture containing as little as 1 % LiCl with circa 100 % selectivity, while receptor 3 achieved similar separations when the LiCl level was as low as 200 ppm. Under liquid–liquid extraction conditions using nitrobenzene as the non‐aqueous phase, the extraction preference displayed by 2 is KCl>NaCl>LiCl. In contrast, 3 exhibits high selectivity towards LiCl over NaCl and KCl, with no appreciable extraction being observed for the latter two salts.
Ethylene diamine post‐synthesis modification on open metal site Cr‐MOF to access efficient bifunctional catalyst for the Hantzsch condensation reaction
Authors: Rostamnia Sadegh , Alamgholiloo Hassan , Jafari Maryam
Published: May 2018

Ethylene diamine functionalized MIL‐101(Cr) was established to be an efficient organocatalyst for single‐pot synthesis of polyhydroquinolines via four‐component condensation reaction between aldehydes, dimedone, β‐ketoecters and ammonium acetate in aqueous medium. Ethylene diamine of the parent open metal site MIL‐101(Cr) has been carried out through a post‐synthetic modification (PSM) technique. Efficient transformation, mild condition, easy product isolation and the potential high recycbility of the organocatalyst are the key feature of this protocol.
Palladium complexes of bidentate pyridine N‐heterocyclic carbenes: Optical resolution, antimicrobial and cytotoxicity studies
Authors: Choo Kar Bee , Mah Wee Li , Lee Sui Mae , Lee Wai Leng , Cheow Yuen Lin
Published: May 2018

A series of bidentate pyridine‐functionalized palladium N‐heterocyclic carbene (Pd NHC) complexes with various wingtip substituents (R = methyl, phenyl and tert‐butyl) have been synthesized and evaluated for their potential biomedical applications as antimicrobials and antiproliferative drug candidates. The obtained Pd NHC complexes were applied in a standard broth microdilution assay for determination of their antimicrobial activities against thirteen strains of pathogenic microorganisms. In addition to that, cytotoxic activities of the Pd NHC complexes were also evaluated against three human cancer cell lines, namely breast (MCF‐7), colon (HCT116) and oral (H103) cancer cells, using a standard MTT assay. Upon coordination to palladium, the Pd NHC complexes show significant antimicrobial activities with minimum inhibitory concentrations in the micromolar range, and they are cytotoxic to the tested carcinomas with IC50 ranging from 13 to 38 μM. Evidences for influence of both wingtip substituents and optical isomerism on the biological activities of the complexes have been found.
Thermodynamic and structural study of complexation of phenylboronic acid with salicylhydroxamic acid and related ligands
Authors: Martínez‐Aguirre Mayte A. , Flores‐Alamo Marcos , Yatsimirsky Anatoly K.
Published: May 2018

Stability constants of boronate complexes with a highly efficient bioconjugation ligand salicylhydroxamic acid, its derivatives and some structurally related compounds were determined by potentiometric and spectroscopic titrations at variable pH allowing one to obtain detailed stability – pH profiles and to identify the optimum pH for complexation with each ligand. The N,O‐binding of salicylhydroxamic acid via condensation of boronic acid with phenolic OH and hydroxamic NH groups was established by crystal structure determination of isolated complexes with phenylboronic and 4‐nitrophenylboronic acids. Although this type of binding is impossible for N‐methylated salicylhydroxamic acid it still forms stable boronate complexes supposedly involving unusual 7‐membered –O‐B‐O‐ cycle supported by 1H NMR studies. Hydroxamic acids lacking ortho‐OH group and salicyloyl hydrazide form less stable boronate complexes, which nevertheless possess stabilities similar to those of catechole complexes and may be useful for conjugation applications. In contrast to other ligands, which form tetrahedral anionic complexes, salicylamidoxime forms tetrahedral, but neutral boronate complex with high stability in weakly acid solutions. The highest affinity in neutral and acid solutions surpassing that of salicylhydroxamic acid is observed with 2,6‐dihydroxybenzhydroxamic acid (Kobs = 5.2 × 104 at pH 7.4). Fairly stable mono‐ and bisboronate complexes are formed with 2,5‐dihydroxy‐1,4‐benzdihydroxamic acid, which also possesses intense fluorescence and may serve as a boronic acid sensor with detection limit 4 μM. Results presented in this study provide quantitative basis for rational applications of hydroxamic acid derivatives in bioconjugation and sensing.
Synthesis, Structural, Biological Evaluation, Molecular Docking and DFT Studies of Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II) Complexes bearing Heterocyclic Thiosemicarbazone ligand
Authors: Konakanchi Ramaiah , Haribabu Jebiti , Prashanth Jyothi , Nishtala Venkata Bharat , Mallela Ramachary , Manchala Saikumar , Gandamalla Durgaiah , Karvembu Ramasamy , Reddy Byru Venkatram , Yellu Narsimha Reddy , Kotha Laxma Reddy
Published: May 2018

A new ligand, 2‐aminonicotinaldehyde N‐methyl thiosemicarbazone (ANMTSC) and its metal complexes [Co(II) (1); Ni(II) (2); Cu(II) (3); Zn(II) (4); Cd(II) (5) or Hg(II) (6)] were synthesized. The compounds were characterized by analytical methods and various spectroscopic (infrared, magnetic, thermal, 1H, 13C NMR, electronic and ESR) tools. The structure of ANMTSC ligand was confirmed by single crystal X‐ray diffraction study. The spectral data of metal complexes indicate that the ligand acts as mononegative, bidentate coordination through imine nitrogen (N) and thiocarbonyl sulphur (S−) atoms. The proposed geometries for complexes were octahedral (1–2), distorted octahedral (3) and tetrahedral (4–6). Computational details of theoretical calculations (DFT) of complexes have been discussed. The compounds were subjected to antimicrobial, antioxidant, antidiabetic, anticancer, ROS, studies and EGFR targeting molecular docking analysis. Complex 5 has shown excellent antibacterial activity and the complexes 2 and 5 have shown good antifungal activity. The complexes 1 and 4 displayed good antioxidant property with IC50 values of 11.17 ± 1.92 μM and 10.79 ± 1.85 μM, respectively compared to standard. In addition, in vitro anticancer activity of the compounds was investigated against HeLa, MCF‐7, A549, IMR‐32 and HEK 293 cell lines. Among all the compounds, complex 4 was more effective against HeLa (IC50 = 10.28 ± 0.69 μM), MCF‐7 (IC50 = 9.80 ± 0.83 μM), A549 (IC50 = 11.08 ± 0.57 μM) and IMR‐32 (10.41 ± 0.60 μM) exhibited superior anticancer activity [IC50 = 9.80 ± 0.83 (4) and 9.91 ± 0.37 μM (1)] against MCF‐7 compared with other complexes.
Synthesis and biological evaluation of novel 99mTc‐oxo and 99mTc‐tricarbonyl complexes with C3′‐functionalized thymidine dithiocarbamate for tumor imaging
Authors: Duan Xiaojiang , Gan Qianqian , Song Xiaoqing , Fang Si'an , Zhang Xuran , Ruan Qing , Zhang Junbo
Published: May 2018

A novel C3′‐functionalized thymidine dithiocarbamate derivative (3’DTC‐TdR) was successfully synthesized and labelled using [99mTcO]3+ core and [99mTc(CO)3(H2O)3]+ core with high yields. The structures of the 99mTc complexes were verified by preparation and characterization of the corresponding stable rhenium complexes. Both of the complexes were lipophilic and stable in vitro. Cell internalization experiments indicated that the uptakes of 99mTcO‐3’DTC‐TdR were related to nucleoside transporters. Biodistribution of these complexes in mice bearing tumor showed that they had high tumor uptakes, good tumor/muscle ratios and tumor/blood ratios. Especially for 99mTcO‐3’DTC‐TdR, it exhibited the highest tumor/muscle ratio and tumor/blood ratio at 4 h post‐injection. SPECT/CT imaging studies indicated clear accumulation in tumor, suggesting 99mTcO‐3’DTC‐TdR would be a promising candidate for tumor imaging.
Expanding the chemical space of anti‐HCV NS5A inhibitors by stereochemical exchange and peptidomimetic approaches
Authors: Ramsis Triveena M. , Abdel Karim Shereen E. , Vassilaki Niki , Frakolaki Efseveia , Kamal Ahmed A. M. , Zoidis Grigoris , Ahmed Nermin S. , Abadi Ashraf H.
Published: May 2018

Here we report a series of potent anti‐HCV agents bearing a symmetrical benzidine l‐prolinamide backbone with different capping groups including alkyl/aryl carbamates of natural and unnatural valine and leucine amino acids. All compounds were investigated for their inhibitory activity in an HCV replicon assay on genotype 1b. The novel compounds share some chemical and clinical attributes of commercially available NS5A inhibitors. Compounds 5 and 6 with unnatural capping residue and ethyl and isobutyl carbamates showed EC50 values in the picomolar range with a low toxicity profile and selectivity indices of several orders of magnitude. These findings enlarge the chemical space from which NS5A inhibitors may be discovered by adopting unnatural amino acids, amino acids other than valine and carbamates other than methyl as the capping groups.
Complex prospection of medieval underground salt chambers in the village of Wiślica, Poland
Authors: Gołębiowski Tomisław , Pasierb Bernadetta , Porzucek Sławomir , Łój Monika
Published: May 2018

In the period of its great boom, i.e. between the fourteenth and the sixteenth centuries, Wiślica (a village in the southeast part of Poland) was one of the administrative capitals of Poland, an important centre of commerce and trade, as well as one of the most important centres of salt trade in the country. There is a hypothesis that underground chambers previously existed in Wiślica where salt was stored. This paper delineates archaeological, geological, and hydrogeological studies conducted in Wiślica and presents historical background with a particular focus on the salt trade. The main part of the paper consists of the results of geophysical studies carried out in the Solny Square, and the objective of the investigations was verification of the hypothesis of the existence of underground salt chambers. Three geophysical techniques were employed, i.e. ground penetrating radar (GPR), electrical resistivity tomography (ERT), and a micro‐gravimetric method. The GPR method was applied for examination of the near‐surface zone to find the remains of medieval shafts located over the underground chambers facilities. ERT and micro‐gravimetric methods were applied for detection of chambers or their remains located at depths from a few to a dozen or so metres. The results of geophysical surveys were correlated with information from boreholes. ERT and micro‐gravimetric data were correlated, which allowed the determination of three main anomalous regions located several metres under Solny Square. A control borehole was drilled in the central part of the largest geophysical anomaly and samples were collected to establish pH; the borehole data confirmed the existence of a depression in the rock mass filled with Quaternary material with alkaline pH. It is likely that two of three anomalies indicated the locations of remains of medieval underground salt chambers.
Feedback Linearization Control for Systems with Mismatched Uncertainties via Disturbance Observers
Authors: Kayacan Erkan , Fossen Thor I.
Published: May 2018

This paper focuses on a novel feedback linearization control (FLC) law based on a self‐learning disturbance observer (SLDO) to counteract mismatched uncertainties. The FLC based on BNDO (FLC‐BNDO) demonstrates robust control performance only against mismatched time‐invariant uncertainties while the FLC based on SLDO (FLC‐SLDO) demonstrates robust control performance against mismatched time‐invariant and ‐varying uncertainties, and both of them maintain the nominal control performance in the absence of mismatched uncertainties. In the estimation scheme for the SLDO, the BNDO is used to provide a conventional estimation law, which is used as the learning error for the type‐2 neuro‐fuzzy system (T2NFS), and T2NFS learns mismatched uncertainties. Thus, the T2NFS takes the overall control of the estimation signal entirely in a very short time and gives unbiased estimation results for the disturbance. A novel learning algorithm established on sliding mode control theory is derived for an interval type‐2 fuzzy logic system. The stability of the overall system is proven for a second‐order nonlinear system with mismatched uncertainties. The simulation results show that the FLC‐SLDO demonstrates better control performance than the traditional FLC, FLC with an integral action (FLC‐I), and FLC‐BNDO.
Towards Versatile Continuous‐Flow Chemistry and Process Technology Via New Conceptual Microreactor Systems
Authors: Ramanjaneyulu Bandaru T. , Vishwakarma Niraj K. , Vidyacharan Shinde , Adiyala Praveen Reddy , Kim Dong‐Pyo
Published: May 2018

In the past decade, microreaction technology has been attracted much attention to the scientific community as one of the subareas in chemical synthesis. The microreactor improves the yield with higher selectivity, and also facilitates the reactions by simple, safe, fast, and green approaches. This review gives an overview on our contributions to develop versatile continuous‐flow syntheses and process technology by exampling gas–liquid binary phase in modified PDMS microreactors, and process intensification for safe operation of toxic/hazardous chemistry by generating hazardous chemicals to end utilization via various separation techniques in newly devised systems as well as ordinary capillary reactors. Furthermore, it covers process technology for ultrafast organic synthesis such as submillisecond control of short‐lived intermediates in a polyimide chip reactor. These works provide outlooks for integrated and automated flow chemistry via one‐flow/feed to end concept, i.e., useful in pharmaceutical industry, toward enabling new and innovative chemistry beyond limits of a batch reactor.
Morphological Abnormalities in True Bugs (Heteroptera) near Swiss Nuclear Power Stations
Authors: Körblein Alfred , Hesse‐Honegger Cornelia
Published: May 2018

After the nuclear accidents of Chernobyl and Fukushima, several studies reported adverse health effects on wildlife animals. Epidemiological studies in humans found significant increases of leukemia rates in young children residing within 5 km from nuclear power plants. This study investigates morphological abnormalities in true bugs (Heteroptera), collected in the environs of three Swiss nuclear power stations (NPS). The objective of the study is to test whether there is an increased frequency of abnormalities in the vicinity of NPS. We found a frequency of abnormalities of 14.1% at distances r < 5 km and a frequency of 6.8% for distances r > 5 km, a rate ratio of 2.1 (P < 0.0001). The corresponding odds ratio was 2.26 (95% CI: 1.59, 3.18). We also conducted logistic regression of abnormality rates on reciprocal distance for each NPS site. The trend was significant for NPS Beznau (regression coefficient β = 1.5 ± 0.3, P < 0.0001) but not significant for NPS Gösgen und NPS Leibstadt with little samples within 5 km. To the best of our knowledge, this study is the first to find adverse health effects on insects near operating nuclear power plants. Due to its ecological design, however, it cannot answer the question whether the effect is caused by radiation from nuclear power plants.
Osmium Tag for Post‐transcriptionally Modified RNA
Authors: Debnath Turja Kanti , Okamoto Akimitsu
Published: May 2018

5‐Methylcytidine (m5C) and 5‐methyluridine (m5U) are highly abundant post‐transcriptionally modified nucleotides that are observed in various natural RNAs. Such nucleotides were labeled through a chemical approach, as both underwent oxidation at the C5=C6 double bond, leading to the formation of osmium–bipyridine complexes, which could be identified by mass spectrometry. This osmium tag made it possible to distinguished m5C and m5U from their isomers, 2′‐O‐methylcytidine and 2′‐O‐methyluridine, respectively. Queuosine and 2‐methylthio‐N6‐isopentenyladenosine in tRNA were also tagged through complex formation.
A novel unbalanced translocation between the short arms of chromosomes 6 and 16 in a newborn girl: Clinical features and management
Authors: de Sousa Paula , Kennedy Alasdair , Lalani Heva H. S.
Published: May 2018

Key Clinical Message

The reporting of previously undescribed genetic mutations and resulting clinical phenotypes guides management and enables a more accurate prognosis for clinicians treating newborns with similar features. Previous cases of 6p deletions and 16p duplications have been described as separate entities. This patient presents with both and has a unique phenotype.
Protein‐Assisted Formation and Stabilization of Catalytically Active Polyoxometalate Species
Authors: Vandebroek Laurens , De Zitter Elke , Ly Hong Giang Thi , Conić Dragan , Mihaylov Tzvetan , Sap Annelies , Proost Paul , Pierloot Kristine , Van Meervelt Luc , Parac‐Vogt Tatjana N.
Published: May 2018

The effect of the protein environment on the formation and stabilization of an elusive catalytically active polyoxometalate (POM) species, K6[Hf(α2‐P2W17O61)] (1), is reported. In the co‐crystal of hen egg‐white lysozyme (HEWL) with 1, the catalytically active monomeric species is observed, originating from the dimeric 1:2 POM form, while it is intrinsically unstable under physiological pH conditions. The protein‐assisted dissociation of the dimeric POM was rationalized by means of DFT calculations. The dissociation process is unfavorable in bulk water, but becomes favorable in the protein–POM complex due to the low dielectric response at the protein surface. The crystal structure shows that the monomeric form is stabilized by electrostatic and water‐mediated hydrogen bonding interactions with the protein. It interacts at three distinct sites, close to the aspartate‐containing hydrolysis sites, demonstrating high selectivity towards peptide bonds containing this residue.
Synthesis of ZIF‐93/11 Hybrid Nanoparticles via Post‐Synthetic Modification of ZIF‐93 and Their Use for H2/CO2 Separation
Authors: Sánchez‐Laínez Javier , Zornoza Beatriz , Orsi Angelica F. , Łozińska Magdalena M. , Dawson Daniel M. , Ashbrook Sharon E. , Francis Stephen M. , Wright Paul A. , Benoit Virginie , Llewellyn Philip L. , Téllez Carlos , Coronas Joaquín
Published: May 2018

The present work shows the synthesis of nano‐sized hybrid zeolitic imidazolate frameworks (ZIFs) with the rho topology based on a mixture of the linkers benzimidazole (bIm) and 4‐methyl‐5‐imidazolecarboxaldehyde (4‐m‐5‐ica). The hybrid ZIF was obtained by post‐synthetic modification of ZIF‐93 in a bIm solution. The use of different solvents, MeOH and N,N‐dimethylacetamide (DMAc), and reaction times led to differences in the quantity of bIm incorporated to the framework, from 7.4 to 23 % according to solution‐state NMR spectroscopy. XPS analysis showed that the mixture of linkers was also present at the surface of the particles. The inclusion of bIm to the ZIF‐93 nanoparticles improved the thermal stability of the framework and also increased the hydrophobicity according to water adsorption results. N2 and CO2 adsorption experiments revealed that the hybrid material has an intermediate adsorption capacity, between those of ZIF‐93 and ZIF‐11. Finally, ZIF‐93/11 hybrid materials were applied as fillers in polybenzimidazole (PBI) mixed matrix membranes (MMMs). These MMMs were used for H2/CO2 separation (at 180 °C) reaching values of 207 Barrer of H2 and a H2/CO2 selectivity of 7.7 that clearly surpassed the Robeson upper bound (corrected for this temperature).
Access to Functionalized Imidazolidin‐2‐one Derivatives by Iron‐Catalyzed Oxyamination of Alkenes
Authors: Manick Anne‐Doriane , Aubert Sidonie , Yalcouye Boubacar , Prangé Thierry , Berhal Farouk , Prestat Guillaume
Published: May 2018

Functionalized imidazolidin‐2‐one were prepared by using an iron‐catalyzed alkene oxyamination reaction. Hydroxylamine derivatives were used in this atom‐economical process, and the addition of an external oxidant was not required. The conditions developed were shown to be efficient for mono‐, di‐, and trisubstituted double bonds, and a large scope of diamino alcohol precursors were delivered in good yields with good diastereoselectivities. The mechanistic pathway was studied and appears to involve both a fused aziridine and a carbocationic species.
Toward Cleavable Metabolic/pH Sensing “Double Agents” Hyperpolarized by NMR Signal Amplification by Reversible Exchange
Authors: Kidd Bryce E. , Mashni Jamil A. , Limbach Miranda N. , Shi Fan , Chekmenev Eduard Y. , Hou Yuqing , Goodson Boyd M.
Published: May 2018

We show the simultaneous generation of hyperpolarized 13C‐labeled acetate and 15N‐labeled imidazole following spin‐relay of hyperpolarization and hydrolysis of the acetyl moiety on 1–13C‐15N2‐acetylimidazole. Using SABRE‐SHEATH (Signal Amplification by Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei), transfer of spin order occurs from parahydrogen to acetylimidazole 15N atoms and the acetyl 13C site (≈263‐fold enhancement), giving rise to relatively long hyperpolarization lifetimes at 0.3 T (T1≈52 s and ≈149 s for 13C and 15N, respectively). Immediately following polarization transfer, the 13C‐labeled acetyl group is hydrolytically cleaved to produce hyperpolarized 13C‐acetate/acetic acid (≈140‐fold enhancement) and 15N‐imidazole (≈180‐fold enhancement), the former with a 13C T1 of ≈14 s at 0.3 T. Straightforward synthetic routes, efficient spin‐relay of SABRE hyperpolarization, and facile bond cleavage open a door to the cheap and rapid generation of long‐lived hyperpolarized states within a wide range of molecular targets, including biologically relevant carboxylic acid derivatives, for metabolic and pH imaging.
Impact of lung‐function measures on cardiovascular disease events in older adults with metabolic syndrome and diabetes
Authors: Lee Hwa Mu , Zhao Yanglu , Liu Michael A. , Yanez David , Carnethon Mercedes , Graham Barr R. , Wong Nathan D.
Published: May 2018

Background

Individuals with metabolic syndrome (MetS) and diabetes (DM) are more likely to have decreased lung function and are at greater risk of cardiovascular disease (CVD).

Hypothesis.

Lung‐function measures can predict CVD events in older persons with MetS, DM, and neither condition.

Methods

We followed 4114 participants age ≥ 65 years with and without MetS or DM in the Cardiovascular Health Study. Cox regression examined the association of forced vital capacity (FVC) and 1‐second forced expiratory volume (FEV1; percent of predicted values) with incident coronary heart disease and CVD events over 12.9 years.

Results

DM was present in 537 (13.1%) and MetS in 1277 (31.0%) participants. Comparing fourth vs first quartiles for FVC, risk of CVD events was 16% (HR: 0.84, 95% CI: 0.59–1.18), 23% (HR: 0.77, 95% CI: 0.60–0.99), and 30% (HR: 0.70, 95% CI: 0.58–0.84) lower in DM, MetS, and neither disease groups, respectively. For FEV1, CVD risk was lower by 2% (HR: 0.98, 95% CI: 0.70–1.37), 26% (HR: 0.74, 95% CI: 0.59–0.93), and 31% (HR: 0.69, 95% CI: 0.57–0.82) in DM. Findings were strongest for predicting congestive heart failure (CHF) in all disease groups. C‐statistics increased significantly with addition of FEV1 or FVC over risk factors for CVD and CHF among those with neither MetS nor DM.

Conclusions

FEV1 and FVC are inversely related to CVD in older adults with and without MetS, but not DM (except for CHF); however, their value in incremental risk prediction beyond standard risk factors is limited mainly to metabolically healthier persons.
Predicted airway obstruction distribution based on dynamical lung ventilation data: A coupled modeling‐machine learning methodology
Authors: Pozin N. , Montesantos S. , Katz I. , Pichelin M. , Vignon‐Clementel I. , Grandmont C.
Published: May 2018

In asthma and chronic obstructive pulmonary disease, some airways of the tracheobronchial tree can be constricted, from moderate narrowing up to closure. Those pathological patterns of obstructions affect the lung ventilation distribution. While some imaging techniques enable visualization and quantification of constrictions in proximal generations, no noninvasive technique exists to provide the airway morphology and obstruction distribution in distal areas. In this work, we propose a method that exploits lung ventilation measures to access positions of airway obstructions (restrictions and closures) in the tree. This identification approach combines a lung ventilation model, in which a 0D tree is strongly coupled to a 3D parenchyma description, along with a machine learning approach. On the basis of synthetic data generated with typical temporal and spatial resolutions as well as reconstruction errors, we obtain very encouraging results of the obstruction distribution, with a detection rate higher than 85%.
A server consolidation method with integrated deep learning predictor in local storage based clouds
Authors: Zhang Guoliang , Bao Weidong , Zhu Xiaomin , Zhao Weiwei , Yan Huining
Published: May 2018

Server consolidation is one of the critical techniques for energy‐efficiency in cloud data centers. As it is often assumed that cloud service instances (eg, Amazon EC2 instances) utilize the shared storage only. In recent years, however, cloud service providers have been providing local storage for cloud users, since local storage can offer a better performance with identified price. However, these cloud instances usually contain much more data than shared storage cloud instances. Thus, in such local storage based cloud center, the migration cost can be really high and is in dire need of an efficient resource pre‐allocation. If we can predict the resource demand in advance, the migration oscillation will be reduced to minify the migration cost. We have found that there are some related work about server consolidation based on forecasting. Unfortunately, their latest work did not consider the background of “local storage” as we mentioned above. At the same time, some research about local storage did not involve the prediction strategy, which plays a significant part in server consolidation. To address this issue, this paper proposes Losari, a consolidation method, which takes numeric forecasting and local storage architecture into consideration. Losari consolidates servers on the basis of the resource demand predicted value using a statistical learning method. We model the workload from real cloud production environment as a time series. Taking deep learning as a frame of reference, multiple deep belief networks integrated with ARIMA model was trained to study the feature of historical workload. The experimental results have showed that its average predicted error is only 10.7% in the short term, which is much lower than the most common model based on threshold (19.8%) on the same dataset. What is more, the results show that Losari not only simulates the true sequences in high accuracy but also scales the compute resource well, which demonstrated the validity of this integrated deep learning model.
Research on index weight of logistics integration based on cloud models
Authors: Qian Guo
Published: May 2018

Accurate evaluation on development of logistics integration is conducive to the coordinated development in Beijing‐Tianjin‐Hebei region. Results of the index weight setting directly influence the accuracy of the evaluation results. Weight is cognition and evaluation of objective things made by human based on aspect of important degree of objective things. People's subjective initiative in setting index weight, in a sense, leads to the natural language having obvious fuzziness and randomness, uncertainty. In this paper, based on the research of weight setting in China and abroad, the weight system is designed qualitatively and quantitatively by using the cloud models so that the weight results are close to human cognition and easy to understand and accept.
A full‐duplex relay selection strategy based on potential game in cognitive cooperative networks
Authors: Zhanjun Liu , Zhaoyi Li , Yuxia Cheng , Xiaoge Huang , Qianbin Chen
Published: May 2018

In this paper, we study the full‐duplex relay selection strategy based on a potential game in a cognitive cooperative network under the interference power constraint from secondary users to the primary receivers, the total available transmission power constraint for the secondary system, and the self‐interference constraint at each secondary relay. The relay selection problem is modeled as a non‐cooperative game where the total rate of a cognitive cooperative network has common utility. Then, we prove that the game is a potential game that has at least a pure strategy Nash equilibrium (NE), and the optimal strategy set that able to maximize cognitive cooperative system rate is also a pure strategy NE of the proposed game model. On the premise of having no information of infeasible strategy sets, we solve the feasibility conditions of the pure NE in the proposed game. Furthermore, we propose a cognitive full‐duplex relay iterative algorithm that can achieve a pure strategy NE, and the complexity and the convergence of the proposed algorithm are studied. Simulation results show that the proposed algorithm can achieve optimal or near optimal rate performance with low complexity and offers significant performance gain compared with the traditional half‐duplex mode.