bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying the Chemical Composition of Decomposed Residues From Cyanobacterial Bloom Biomass by Pyrolysis‐GC/MS
Authors: Liu Xin , He Rui , Shi Yuan , Yan Zaisheng , Wang Changhui , Jiang Helong
Published: September 2016

The frequent occurrence of cyanobacterial blooms in eutrophic lakes can lead to a high amount of biomass in aquatic systems, and following cell death, this autochthonous organic matter will eventually decompose. In this study, the effect of temperature and sediment on the chemical composition of cyanobacterial biomass residue was investigated by microcosm experiment. The results showed that the lowest cyanobacterial bloom biomass (CBB) removal efficiency was recorded at 32°C regardless of the presence or absence of sediment. Based on total organic carbon, the CBB removal efficiencies were higher than 90% at 20–29°C but less than 87.0% at 32°C. Pyrolysis gas chromatography mass spectrometry and Fourier transform infrared analysis indicated that organic nitrogen compounds (e.g., carbamic acid monoammonium salt) and polysaccharides (e.g., 2‐propanone, 1‐hydroxy‐) were the main components in the residues. Based on the determined components in the residues under different conditions, unweighted pair group clustering method with arithmetic averages and principal components analysis further suggested that sediment and temperature had obvious influence on the chemical composition of CBB decomposition residues. Considering that cyanobacteria biomass is produced annually in eutrophic lakes, residues from CBB may contribute to the nitrogen/carbon cycles and macro‐fauna growth in these ecosystems.
Discovery and Biophysical Evaluation of First Low Nanomolar Hits Targeting CYP125 of M. tuberculosis
Authors: Brengel Christian , Thomann Andreas , Schifrin Alexander , Eberhard Jens , Hartmann Rolf W.
Published: September 2016

Tuberculosis, which is predominantly caused by Mycobacterium tuberculosis (Mtb), is still the most lethal bacterial infection with 1.5 million casualties in 2014. Moreover, the fact that the appearance of resistant mutants and long‐term treatment are coupled with economic problems in developing countries hampers an efficient therapy. Interference with the essential cholesterol metabolism of Mtb could be a promising novel strategy to fight Mtb infections. CYP125, a P450 enzyme in Mtb, has been shown to play an important role in this metabolic pathway. For this reason, we used a combined screening approach involving surface plasmon resonance spectroscopy and a heme coordination assay to identify new CYP125 binders by employing a focused P450‐inhibitor library. We identified the first hits with high affinity and favorable ligand efficiencies. Furthermore, frontrunner compounds also showed selectivity toward CYP121 specific to Mtb and required for its survival. To date, these are the first compounds targeting CYP125 with low nanomolar affinity.
The treatment of childhood acute lymphoblastic leukemia in Guatemala: Biologic features, treatment hurdles, and results
Authors: Antillón Federico G. , Blanco Jessica G. , Valverde Patricia D. , Castellanos Mauricio , Garrido Claudia P. , Girón Veronica , Letona Tomas R. , Osorio Emilia J. , Borrayo Dyna A. , Mack Ricardo A. , Melgar Mario A. , Lorenzana Rodolfo , Ribeiro Raul C. , Metzger Monika , Conter Valentino , Rossi Emanuela , Valsecchi Maria Grazia
Published: September 2016

BACKGROUND

The National Pediatric Oncology Unit (UNOP) is the only pediatric hemato‐oncology center in Guatemala.

METHODS

Patients ages 1 to 17 years with acute lymphoblastic leukemia (ALL) were treated according to modified ALL Intercontinental Berlin‐Frankfurt‐Münster (IC‐BFM) 2002 protocol. Risk classification was based on age, white blood cell count, immunophenotype, genetics (when available), and early response to therapy.

RESULTS

From July 2007 to June 2014, 787 patients were treated, including 160 who had standard‐risk ALL, 450 who had intermediate‐risk ALL, and 177 who had high‐risk ALL. The induction death rate was 6.6%, and the remission rate was 92.9%. The rates of death and treatment abandonment during first complete remission were 4.8% and 2.5%, respectively. At a median observation time of 3.6 years, and with abandonment considered an event, the 5‐year event‐free survival and overall survival estimates ( ± standard error) were 56.2% ± 2.1% and 64.1% ± 2.1%, respectively, with a 5‐year cumulative incidence of relapse of 28.9% ± 2.0%. Twenty‐one of 281 patients (7.5%) investigated were positive for the ets variant 6/runt‐related transcription factor 1 (ETV6/RUNX1) fusion.

CONCLUSIONS

A well organized center in a low‐middle‐income country can overcome the disadvantages of malnutrition and reduce abandonment. Outcomes remain suboptimal because of late diagnosis, early death, and a high relapse rate, which may have a partly genetic basis. Earlier diagnosis, better management of complications, and better knowledge of ALL will improve outcomes. Cancer 2017;123:436–448. © 2016 American Cancer Society.
Prolonged survival with a longer duration of maintenance lenalidomide after autologous hematopoietic stem cell transplantation for multiple myeloma
Authors: Mian Idrees , Milton Denái R. , Shah Nina , Nieto Yago , Popat Uday R. , Kebriaei Partow , Parmar Simrit , Oran Betul , Shah Jatin J. , Manasanch Elisabet E. , Orlowski Robert Z. , Shpall Elizabeth J. , Champlin Richard E. , Qazilbash Muzaffar H. , Bashir Qaiser
Published: September 2016

BACKGROUND

Although lenalidomide maintenance therapy has demonstrated improved outcomes after autologous hematopoietic stem cell transplantation (auto‐HCT) for patients with multiple myeloma (MM), the impact of the duration of this therapy is not clearly known.

METHODS

This study retrospectively analyzed all MM patients who were placed on maintenance lenalidomide after auto‐HCT between January 2007 and December 2013. Progression‐free survival (PFS) and overall survival (OS) were analyzed in multivariate Cox proportional hazards regression models that included the duration of maintenance as a time‐dependent covariate.

RESULTS

Of the 464 patients identified, 46% initiated therapy early (<4 months after auto‐HCT). The median PFS and OS were 38 and 78 months, respectively. Improvements in PFS (hazard ratio [HR], 0.13; 95% confidence interval [CI], 0.04‐0.38; P < .001) and OS (HR, 0.09; 95% CI, 0.03‐0.26; P < .001) were seen for those on maintenance for >2 years versus those on maintenance for ≤2 years. For those on maintenance for >3 versus those on maintenance for ≤3 years, this trend continued with improvements seen in PFS (HR, 0.02; 95% CI, 0.00‐0.44; P = .012) and OS (HR, 0.05; 95% CI, 0.00‐0.83; P = .037). The incidence of second primary malignancies (SPMs) in the entire cohort was 3%. No differences were seen in survival between early and late initiators of maintenance lenalidomide.

CONCLUSIONS

A longer duration of maintenance therapy was associated with longer survival. The incidence of SPMs was low, and they were not associated with the duration of maintenance. The timing of the initiation of maintenance had no effect on survival. Cancer 2016;122:3831–3837. © 2016 American Cancer Society.
IL‐1β, IL‐18, and eicosanoids promote neutrophil recruitment to pore‐induced intracellular traps following pyroptosis
Authors: Jorgensen Ine , Lopez Joseph P. , Laufer Stefan A. , Miao Edward A.
Published: September 2016

Inflammasomes activate caspase‐1, initiating a lytic form of programmed cell death termed pyroptosis, which is an important innate immune defense mechanism against intracellular infections. We recently demonstrated in a mouse infection model of pyroptosis that instead of releasing bacteria into the extracellular space, bacteria remain trapped within the pyroptotic cell corpse, termed the pore‐induced intracellular trap (PIT). This trapping mediates efferocytosis of the PIT and associated bacteria by neutrophils; bacteria are subsequently killed via neutrophil ROS. Using this pyroptosis model, we now show that the pro‐inflammatory cytokines IL‐1β and IL‐18 and inflammatory lipid mediators termed eicosanoids are required for effective clearance of bacteria downstream of pyroptosis. We further show that IL‐1β, IL‐18, and eicosanoids affect this in part by mediating neutrophil recruitment to the PIT. This is in addition to our prior findings that complement is also important to attract neutrophils. Thus, the PIT initiates a robust and coordinated innate immune response involving multiple mediators that attract neutrophils to efferocytose the PIT and its entrapped bacteria.
Electrochemically‐controlled DNA Release under Physiological Conditions from a Monolayer‐modified Electrode
Authors: Honarvarfard Elham , Gamella Maria , Guz Nataliia , Katz Evgeny
Published: September 2016

An indium tin oxide (ITO) electrode prepared on a flexible polymeric support was modified with an amino‐silane and then functionalized with trigonelline and 4‐carboxyphenylboronic acid covalently bound to the amino groups. The trigonelline species containing quarterized ammonium group produced positive charge on the electrode surface regardless of the pH value, while the phenylboronic acid species were neutral below pH 8 and negatively charged above pH 9 (note that their pKa=8.4). The total charge on the monolayer‐modified electrode was positive at the neutral pH and negative at pH>9 (note that 4‐carboxyphenylboronic acid was attached to the electrode surface in excess to trigonelline, thus allowing the negative charge to dominate on the electrode surface at basic pH). Single‐stranded DNA molecules were loaded on the modified electrode at pH 7.0 due to their electrostatic attraction to the positively charged surface. By applying electrolysis at −1.0 V (vs. Ag/AgCl reference) electrochemical oxygen reduction resulted in the consumption of hydrogen ions and local pH increase in the vicinity of the electrode surface. The process resulted in the transition to the total negative charge due to the negative charges formed on the phenylboronic acid species. This resulted in the electrostatic repulsion and release of the loaded DNA. The developed approach allowed the electrochemically‐triggered DNA release not only in the aqueous solutions, but also in human serum solution, thus giving promise for future biomedical applications.
Effects of dietary methylmercury on the dopaminergic system of adult fathead minnows and their offspring
Authors: Nielsen Kristin M. , Venables Barney , Roberts Aaron
Published: September 2016

Mercury (Hg) is a ubiquitous environmental contaminant and potent neurotoxin, which may be transformed by bacteria in aquatic ecosystems to methylmercury (MeHg), an organic form which bioaccumulates and biomagnifies. Consequently, long-lived organisms at the top of the food web are at risk of dietary MeHg exposure, which can be actively transferred from mother to offspring. Exposure during neurodevelopment can lead to serious, irreversible neurological dysfunction, associated with a variety of cognitive and motor abnormalities. At low dietary concentrations, MeHg exposure has been associated with deficits in attention and hyperactivity in multiple species. Pathways associated with cognitive function and motor activity are primarily associated with the dopaminergic system. The present study used a model fish species, Pimephales promelas, to examine the effects of MeHg exposure on dopamine concentrations and monoamine oxidase activity in embryos and adult brains. Adult fatheads were exposed for 30 d to either a control or a treated diet (0.72 ppm Hg). Embryonic and larval exposures were a result of maternal transfer of dietary MeHg. The authors confirmed hyperactive behaviors in embryos and detected significant changes in embryonic dopamine concentrations. Similar effects on dopamine concentrations were seen in the telencephalon of adult brains. Exposure to MeHg also corresponded with a significant decrease in monoamine oxidase activity in both embryos and brain tissue. Collectively, these results suggest that current exposure scenarios in North America are sufficient to induce alterations to this highly conserved neurochemical pathway in offspring, which may have adverse effects on fish behavior and cognition. Environ Toxicol Chem 2017;36:1077–1084. © 2016 SETAC
Major prognostic value of complex karyotype in addition to TP53 and IGHV mutational status in first‐line chronic lymphocytic leukemia
Authors: Le Bris Yannick , Struski Stéphanie , Guièze Romain , Rouvellat Caroline , Prade Naïs , Troussard Xavier , Tournilhac Olivier , Béné Marie C. , Delabesse Eric , Ysebaert Loïc
Published: September 2016

Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disorder of remarkable heterogeneity as demonstrated by cytogenetics and molecular analyses. Complex karyotype (CK), TP53 deletions and/or mutations (TP53 disruption), IGVH mutational status, and, more recently, recurrent somatic mutations have been identified as prognostic markers in CLL. On a cohort of 110 patients with CLL treated with first‐line fludarabin, cyclophosphamide, and rituximab treatment compared with 33 untreated (watch and wait) patients with CLL, we report more frequent complex karyotypes (34 vs 15%; P = .05), unmutated IGHV (70 vs 21%; P < .0001), ATM deletion (25 vs 6%, P = .02), and NOTCH mutation (3 vs 17%, P = .04). Among treated patients, 39 relapsed during the follow‐up period. These patients were characterized before treatment by a higher incidence of trisomy 12 (38 vs 11%, P < .001) and TP53 disruption (31 vs 4%, P = .0002). A significantly shorter 5‐year overall survival was found for treated patients with CK (72.4 vs 85.8%; P = .007), unmutated IGHV (70 vs 100%; P = .04), or TP53 disruption (55.7 vs 82.7%; P < .0001). Three risk groups were defined based on the status of TP53 disruption or unmutated IGVH, which differed significantly in terms of 5‐year overall survival. Moreover, the presence of CK impacted pejoratively 5‐year overall survival and progression‐free survival in all these 3 groups. Conventional karyotyping therefore appears to be of value, CK being an additional factor, undetectable in classical FISH, in patients with CLL at the stage when therapy becomes required.
The influence of fiscal rules on healthcare policy in the United States and the Netherlands
Authors: Schakel H. Christiaan , Jeurissen Patrick , Glied Sherry
Published: September 2016

Governments use fiscal rules to put a framework and limits on how budgetary challenges are addressed, but the rules themselves are still an understudied area among health policy scholars. For a long time, healthcare held a somewhat separate status because of the reliance on entitlements and dedicated revenue streams. However, the combined forces of advocates for integral decision‐making, central budget control and the increasing costs might shift healthcare towards budgetary frameworks that currently apply to other spending categories. In this paper, we study fiscal rules that the US and the Netherlands have adopted since 2010 and their impact on healthcare policy. Our analysis shows that fiscal rules can have an impact on the rationing of healthcare. In the studied timeframe, the rules seem to have more impact on budget outcomes than on the budget process itself. In addition, the convergence of fiscal and program policy objectives seems to be better accomplished in a budgetary system that applies enforceable budget ceilings. Budgeting for health entitlements requires a comprehensive and tailor‐made approach and the composition of traditional rules might not fully answer to the complexities of healthcare policy. This paper aims to contribute to that debate and the way we think about healthcare budgeting. Copyright © 2016 John Wiley & Sons, Ltd.
Dalotuzumab in chemorefractory KRAS exon 2 mutant colorectal cancer: Results from a randomised phase II/III trial
Authors: Sclafani Francesco , Kim Tae Y. , Cunningham David , Kim Tae W. , Tabernero Josep , Schmoll Hans J. , Roh Jae K. , Kim Sun Y. , Park Young S. , Guren Tormod K. , Hawkes Eliza , Clarke Stephen J. , Ferry David , Frodin Jan‐Erik , Ayers Mark , Nebozhyn Michael , Peckitt Clare , Loboda Andrey , Watkins David J.
Published: September 2016

Limited data are available on the efficacy of anti‐IGF‐1R agents in KRAS mutant colorectal cancer (CRC). We analysed the outcome of 69 chemorefractory, KRAS exon 2 mutant CRC patients who were enrolled in a double‐blind, randomised, phase II/III study of irinotecan and cetuximab plus dalotuzumab 10 mg/kg once weekly (arm A), dalotuzumab 7.5 mg/kg every second week (arm B) or placebo (arm C). Objective response rate (5.6% vs. 3.1% vs. 4.8%), median progression‐free survival (2.7 vs. 2.6 vs. 1.4 months) and overall survival (7.8 vs. 10.3 vs. 7.8 months) were not statistically significantly different between treatment groups. Most common grade ≥3 treatment‐related toxicities included neutropenia, diarrhoea, hyperglycaemia, fatigue and dermatitis acneiform. Expression of IGF‐1R, IGF‐1, IGF‐2 and EREG by quantitative real‐time polymerase chain reaction was assessed in 351 patients from the same study with available data on KRAS exon 2 mutational status. Median cycle threshold values for all biomarkers were significantly lower (i.e., higher expression, p < 0.05) among patients with KRAS wild‐type compared to those with KRAS exon 2 mutant tumours. No significant changes were found according to location of the primary tumour with only a trend towards lower expression of IGF‐1 in colon compared to rectal cancers (p = 0.06). Albeit limited by the small sample size, this study does not appear to support a potential role for anti‐IGF‐1R agents in KRAS exon 2 mutant CRC. Data on IGF‐1R, IGF‐1 and IGF‐2 expression here reported may be useful for patient stratification in future trials with inhibitors of the IGF pathway.
Symmetry‐based Study of MoS2 and WS2 Nanotubes
Authors: Damnjanović Milan , Vuković Tatjana , Milošević Ivanka
Published: September 2016

The symmetry‐based study of MS2 (M=Mo, W) single‐wall nanotubes (SWNTs) is reviewed. First, the structure and symmetry of MS2 NTs is determined. Then, conserved quantum numbers and general forms of potentials are derived. The valence force‐field method implemented into the POLSym code is used to calculate phonon dispersions. Phonons characterized by a zero angular‐momentum quantum number are studied in detail. The functional dependence of the frequency of rigid layer modes on NT diameter and chirality are found, and Raman‐ and infrared‐active modes are singled out. Electronic band structure calculations are performed by the symmetry‐based density functional tight‐binding (DFTB) method. Changes in the band‐gap type and size with NT chirality and diameter are evaluated. Optical absorption spectra of individual NTs are calculated using DFTB wave functions for exact transition matrix element calculations. Diffraction patterns of MS2 are predicted and NT characterization by different diffraction methods is discussed.
New Insights on the Regulation of Ca2+‐Activated Chloride Channel TMEM16A
Authors: Ma Ke , Wang Hui , Yu Jiankun , Wei Minjie , Xiao Qinghuan
Published: September 2016

TMEM16A, also known as anoctamin 1, is a recently identified Ca2+‐activated chloride channel and the first member of a 10‐member TMEM16 family. TMEM16A dysfunction is implicated in many diseases such as cancer, hypertension, and cystic fibrosis. TMEM16A channels are well known to be dually regulated by voltage and Ca2+. In addition, recent studies have revealed that TMEM16A channels are regulated by many molecules such as calmodulin, protons, cholesterol, and phosphoinositides, and a diverse range of stimuli such as thermal and mechanical stimuli. A better understanding of the regulatory mechanisms of TMEM16A is important to understand its physiological and pathological role. Recently, the crystal structure of a TMEM16 family member from the fungus Nectria haematococcaten (nhTMEM16) is discovered, and provides valuable information for studying the structure and function of TMEM16A. In this review, we discuss the structure and function of TMEM16A channels based on the crystal structure of nhTMEM16A and focus on the regulatory mechanisms of TMEM16A channels. J. Cell. Physiol. 232: 707–716, 2017. © 2016 Wiley Periodicals, Inc.
Green synthesis of silver nanoparticles using Pongamia pinnata seed: Characterization, antibacterial property, and spectroscopic investigation of interaction with human serum albumin
Authors: Beg Maidul , Maji Anukul , Mandal Amit Kumar , Das Somnath , Aktara Mt Nasima , Jha Pradeep K. , Hossain Maidul
Published: September 2016

In recent years, green synthesized nanoparticles from plant extract have drawn a great interest due to their prospective nanomedicinal application. This study investigates a proficient, safer, and sustainable way for the preparation of AgNPs using medicinal plant Pongamia pinnata (family: Leguminoseae, species: Pinnata) seeds extract without using any external reducing and stabilizing agent. Both ultraviolet‐visible spectrum at λmax = 439 nm and energy dispersive X‐ray spectra proof the formation of AgNPs. An average diameter of the AgNPs was 16.4 nm as revealed from transmission electron microscope. Hydrodynamic size (d = ~19.6 nm) was determined by dynamic light scattering (DLS). Zeta potential of AgNPs was found to be −23.7 mV, which supports its dispersion and stability. Fourier transform infrared study revealed that the O ─ H, C ═ O, and C‐O‐C groups were responsible for the formation of AgNPs. The antibacterial activity of the synthesized AgNPs was checked against Escherichia coli ATCC 25922. AgNPs at its LD50 dose exhibited synergistic effect with ampicillin. Because protein‐AgNPs association greatly affects its adsorption, distribution, and functionality and can also influence the functions of biomolecules. So in order to understand the adsorption and bioavailability, we investigated by fluorescence, ultraviolet‐visible, and circular dichroism spectroscopic methods the interaction of synthesized AgNPs toward human serum albumin. The binding affinity and binding sites of human serum albumin toward AgNPs were measured by using the fluorescence quenching data. The circular dichroism spectroscopic results revealed that there was a negligible change of α‐helical content in their native structure. Overall, these AgNPs show versatile biological activities and may be applied in the field of nanomedicine.
Effectiveness of Prolonged Exposure and Cognitive Processing Therapy for U.S. Veterans With a History of Traumatic Brain Injury
Authors: Ragsdale Katie A. , Voss Horrell Sarah C.
Published: September 2016

This retrospective analysis of previously existing nonrandomized clinical data examined the effectiveness of completing prolonged exposure (PE) or cognitive processing therapy (CPT) in a sample of 41 U.S. veterans at a Veterans Affairs medical center. The sample included 19 veterans with diagnoses of posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) and 22 veterans with PTSD only. Diagnostic groups did not significantly differ on PTSD and depression symptom reduction, F(2, 36) = 0.05, p = .951; Pillai's trace = 0.00, partial η2= .00. Veterans who completed PE showed greater symptom reduction than those who completed CPT, F(2, 36) = 12.10, p < .001; Pillai's trace = 0.40, partial η2 = .40, regardless of TBI status. Overall, our results suggested that TBI status should not preclude individuals from being offered trauma‐focused PTSD treatment.
Mechanically Robust and Transparent N‐Halamine Grafted PVA‐co‐PE Films with Renewable Antimicrobial Activity
Authors: Si Yang , Cossu Andrea , Nitin Nitin , Ma Yue , Zhao Cunyi , Chiou Bor‐sen , Cao Trung , Wang Dong , Sun Gang
Published: September 2016

Antimicrobial polymeric films that are both mechanically robust and function renewable would have broad technological implications for areas ranging from medical safety and bioengineering to foods industry; however, creating such materials has proven extremely challenging. Here, a novel strategy is reported to create high‐strength N‐halamine incorporated poly(vinyl alcohol‐co‐ethylene) films (HAF films) with renewable antimicrobial activity by combining melt radical graft polymerization and reactive extrusion technique. The approach allows here the intrinsically rechargeable N‐halamine moieties to be covalently incorporated into polymeric films with high biocidal activity and durability. The resulting HAF films exhibit integrated properties of robust mechanical strength, high transparency, rechargeable chlorination capability (>300 ppm), and long‐term durability, which can effectively offer 3–5 logs CFU reduction against typical pathogenic bacterium Escherichia coli within a short contact time of 1 h, even at high organism conditions. The successful synthesis of HAF films also provides a versatile platform for exploring the applications of antimicrobial N‐halamine moieties in a self‐supporting, structurally adaptive, and function renewable form.

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Fabrication of Robust Hydrophobic and Super‐Hydrophobic Polymer Films with Onefold or Dual Inverse Opal Structures
Authors: Wu Yi , Zhou Shuxue , Wu Limin
Published: September 2016

Hydrophobic and super‐hydrophobic materials have many important applications, but most of the artificially hydrophobic and super‐hydrophobic surfaces suffer from poor durability. Herein, a facile method is reported to fabricate robust hydrophobic and super‐hydrophobic polymer films through backfilling the silica colloidal crystal templates with the mixture of fluoropolymer, thermoset hydroxyl acrylate resins, and curing agent. After removal of the template, 3D ordered porous structures are obtained. The obtained polymer films have not only excellent hydrophobic or super‐hydrophobic properties but also good stability against temperatures, acids, and alkalis. Dual ordered porous structure can obviously enhance the hydrophobicity of polymer films compared to unitary one.

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Multitargeting Gene Delivery Systems for Enhancing the Transfection of Endothelial Cells
Authors: Yang Jing , Li Qian , Yang Xiao , Feng Yakai , Ren Xiangkui , Shi Changcan , Zhang Wencheng
Published: September 2016

Gene therapy demonstrates promising prospects on cardiovascular diseases. However, nonviral gene delivery system has relatively low transfection efficiency, especially for endothelial cells (ECs). Herein, typical cell‐penetrating peptide (TAT), nuclear localization signals (NLSs), and REDV functional peptide have been used to prepare multitargeting complexes. These complexes exhibit higher transfection efficiency owing to the targeting sequences of REDV and NLSs as well as the cell‐penetrating function of TAT. The multifunction of the complexes provides high cell uptake, endo/lysosomal escape, and nucleus accumulation of the encapsulated DNA. Thus these multitargeting complexes can provide a potential platform for gene delivery, especially for EC transfection.

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Advancement of Sialyltransferase Inhibitors: Therapeutic Challenges and Opportunities
Authors: Szabo Rémi , Skropeta Danielle
Published: September 2016

Hypersialylation of tumor cell surface proteins along with a marked upregulation of sialyltransferase (ST) activity is a well‐established hallmark of cancer. Due to the critical role of STs in tumor growth and progression, ST inhibition has emerged as a potential new antimetastatic strategy for a range of cancers including pancreatic and ovarian. Human STs are divided into subtypes based on their linkage and acceptor molecule, with each subtype controlling the synthesis of specific sialylated structures with unique biological roles. This has important implications for inhibitor development, as STs also play significant roles in immune responses, inflammation, viral infection, and neurological disorders. Thus, the current goal in order to advance to the clinic is the development of subtype selective, cell‐permeable and synthetically accessible, small‐molecule ST inhibitors. Herein is a comprehensive review of the latest developments in ST inhibitors from design, Nature, and high‐throughput screening, addressing both the challenges and opportunities in targeting cell surface sialylation. The review features an overview of the biological evaluation methods, computational and imaging tools, inhibitor molecular diversity, and selectivity toward ST subtypes, along with the emerging role of ST inhibitors as diagnostic tools for disease imaging.
Safety and pain in electrodiagnostic studies
Authors: London Zachary N.
Published: September 2016

Discomfort is an unavoidable part of electrodiagnostic (EDX) studies. The most readily modifiable mediator of electromyography (EMG)‐associated pain is muscle selection. Interventions that may reduce pain include vapocoolant spray, ibuprofen, and techniques such as slapping or stretching the skin. Needlestick injuries to health care workers carry the risk of transmitting bloodborne illnesses, but other infectious complications of EDX studies are very rare. EMG probably contributes to asymptomatic hemorrhage in approximately 1% of patients, but clinically significant bleeding has only been reported a few times. Therapeutic anticoagulation does not significantly increase this risk. With standard procedures, there have been no reports of patients developing cardiac arrhythmia from nerve conduction studies. No special precautions are necessary in patients with implantable cardiac devices or intravenous lines. There is a small risk of pneumothorax associated with EMG of the diaphragm and chest wall muscles. Several techniques have been suggested to improve the safety of diaphragm EMG. Muscle Nerve 55: 149–159, 2017
Three‐dimensional thermal annealing: An unconventional method to fabricate monodisperse polymer nanoparticles from polymer films
Authors: Chiu Yu‐Jing , Kuo Tyng‐Yow , Cheng Ming‐Hsiang , Tseng Hsiao‐Fan , Lo Yu‐Ching , Chen Jiun‐Tai
Published: September 2016

We develop a simple and feasible method to fabricate polymer nanoparticles by annealing polymer films in a uniform environment. Different from the conventional methods, no extra additive or emulsifier is needed in the preparation processes. Poly(methyl methacrylate) (PMMA) films are used as a model system and annealed at elevated temperatures in ethylene glycol, which provides a uniform three‐dimensional annealing environment and acts as stabilizers once the nanoparticles are formed. After the annealing process, PMMA nanoparticles with monodisperse diameters are formed. By examining the remaining films after the annealing process, the formation mechanism, which involves surface undulation and detachment of polymer nanoparticles, is proposed. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016, 54, 2471–2475
The flagellar motor adapts, optimizing bacterial behavior
Authors: Berg Howard C.
Published: September 2016

A short review is given of recent work showing that the flagellar rotary motor of the bacterium Escherichia coli remodels to match its operating point (the fraction of time that it spins clockwise) to the requirements of the chemotaxis signaling network, and to provide the torque necessary to operate at different viscous loads.
A network based approach to envisage potential accidents in offshore process facilities
Authors: Baksh Al‐Amin , Abbassi Rouzbeh , Garaniya Vikram , Khan Faisal
Published: September 2016

Envisaging potential accidents in large scale offshore process facilities such as Floating Liquefied Natural Gas (FLNG) is complex and could be best characterized through evolving scenarios. In the present work, a new methodology is developed to incorporate evolving scenarios in a single model and predicts the likelihood of accident. The methodology comprises; (a) evolving scenario identification, (b) accident consequence framework development, (c) accident scenario likelihood estimation, and (d) ranking of the scenarios. Resulting events in the present work are modeled using a Bayesian network approach, which represents accident scenarios as cause‐consequences networks. The methodology developed in this article is compared with case studies of ammonia and Liquefied Natural Gas from chemical and offshore process facility, respectively. The proposed method is able to differentiate the consequence of specific events and predict probabilities for such events along with continual updating of consequence probabilities of fire and explosion scenarios taking into account. The developed methodology can be used to envisage evolving scenarios that occur in the offshore oil and gas process industry; however, with further modification it can be applied to different sections of marine industry to predict the likelihood of such accidents. © 2016 American Institute of Chemical Engineers Process Saf Prog 36: 178–191, 2017
Synthesis of polypyrrole on nanodiamonds with hydrogenated and oxidized surfaces
Authors: Miliaieva Daria , Stehlik Stepan , Stenclova Pavla , Rezek Bohuslav
Published: September 2016

Composite nanoparticles of detonation nanodiamond (DND) and polypyrrole (PPy) were produced in colloidal solution and on surfaces by wet chemical process. Changes of vibrational bands (in particular > CO and CH) in Fourier‐transform infrared spectroscopy revealed the DND/PPy composite formation and tight interaction of PPy with hydrogenated DND (H‐DND) and oxidized DND (O‐DND). Atomic force microscopy showed uniform PPy coating but different PPy thickness on H‐DND (7.0 nm) and O‐DND (3.5 nm). These results suggest different bonding nature and arrangement of PPy on H‐DND and O‐DND surfaces.
A comparison of five approaches to decision‐making for a first clinical trial of efficacy
Authors: Kirby Simon , Chuang‐Stein Christy
Published: September 2016

The first trial of clinical efficacy is an important step in the development of a compound. Such a trial gives the first indication of whether a compound is likely to have the efficacy needed to be successful. Good decisions dictate that good compounds have a large probability of being progressed and poor compounds have a large probability of being stopped. In this paper, we consider and contrast five approaches to decision‐making that have been used. To illustrate the use of the five approaches, we conduct a comparison for two plausible scenarios with associated assumptions for sample sizing. The comparison shows some large differences in performance characteristics of the different procedures. Which decision‐making procedures and associated performance characteristics are preferred will depend on the focus of interest and the decision maker's attitude to risk. Copyright © 2016 John Wiley & Sons, Ltd.
Surface acting and exhaustion: The moderating role of eudaimonia
Authors: Pătraş Luminiţa , Martínez‐Tur Vicente , Gracia Esther , Moliner Carolina
Published: September 2016

Surface acting (faking emotions) is one of the stressors experienced by contact employees during service interactions with customers, and it has implications for workers' exhaustion. One challenge of research and practice is to identify moderators that help to better understand the positive relationships between surface acting and exhaustion. The present study proposes the two dimensions of eudaimonia beliefs about well‐being (self‐development and contribution‐to‐others beliefs) as moderators between surface acting and exhaustion. We performed regression analyses with 817 contact employees working in 118 health‐care organizations providing services to people with intellectual disability. Results confirmed the hypotheses, showing that contribution‐to‐others strengthens the link from surface acting to exhaustion, whereas self‐development weakens this relationship. Therefore, self‐development beliefs act as a protector for workers when they have to deal with situations that require surface acting.
Refactoring technical support to reduce interrupts of developers
Authors: Kelemen Zádor Dániel , Tódor Balázs , Hodosi Sándor , Somfai Ákos
Published: September 2016

In this paper an analysis of a technical support data with the goal of identifying process improvement actions for reducing interrupts is presented. A technical support chat is established and used to provide internal developer support to other development teams, which use the software code developed by a core team. The paper shows how data analysis of a 6‐month support time helped to identify gaps and action items for improving the technical support process to minimize interrupts from other developer teams. We show that developers are interrupted through the investigated technical support chat multiple times a day and the interruptions come during the peak working hours. We also show that these interruptions can be prevented with the introduction of multiple tools such as a dispatcher service policy, a dispatcher role, and an FAQ page among others. The paper also shows effects (advantages and drawbacks) of the technical support refactor actions taken on the basis of this analysis.
Turbulence-particle interactions under surface gravity waves
Authors: Paskyabi Mostafa Bakhoday
Published: September 2016

The dispersion and transport of single inertial particles through an oscillatory turbulent aquatic environment are examined numerically by a Lagrangian particle tracking model using a series of idealised test cases. The turbulent mixing is incorporated into the Lagrangian model by the means of a stochastic scheme in which the inhomogeneous turbulent quantities are governed by a one-dimensional k- ε turbulence closure scheme. This vertical mixing model is further modified to include the effects of surface gravity waves including Coriolis-Stokes forcing, wave breaking, and Langmuir circulations. To simplify the complex interactions between the deterministic and the stochastic phases of flow, we assume a time-invariant turbulent flow field and exclude the hydrodynamic biases due to the effects of ambient mean current. The numerical results show that the inertial particles acquire perturbed oscillations traced out as time-varying sinking/rising orbits in the vicinity of the sea surface under linear and cnoidal waves and acquire a non-looping single arc superimposed with the high-frequency fluctuations beneath the nonlinear solitary waves. Furthermore, we briefly summarise some recipes through the course of this paper on the implementation of the stochastic particle tracking models to realistically describe the drift and suspension of inertial particles throughout the water column.
Predictive Genetic Testing of Children for Adult‐Onset Conditions: Negotiating Requests with Parents
Authors: Fenwick Angela , Plantinga Mirjam , Dheensa Sandi , Lucassen Anneke
Published: September 2016

Healthcare professionals (HCPs) regularly face requests from parents for predictive genetic testing of children for adult‐onset conditions. Little is known about how HCPs handle these test requests, given that guidelines recommend such testing is deferred to adulthood unless there is medical benefit to testing before that time. Our study explored the process of decision‐making between HCPs and parents. Semi‐structured interviews were conducted with 34 HCPs in 8 regional genetic services across the UK, and data were thematically analysed. We found that instead of saying ‘yes’ or ‘no’ to such requests, many HCPs framed the consultation as an opportunity to negotiate the optimal time of testing. This, they argued, facilitates parents’ considered decision‐making, since parents’ eventual decisions after requesting a test was often to defer testing their child. In cases where parents’ requests remained a sustained wish, most HCPs said they would agree to test, concluding that not testing would not serve the child's wider best interest. As a strategy for determining the child's best interest and for facilitating shared decision‐making, we recommend that HCPs re‐frame requests for testing from parents as a discussion about the optimal time of testing for adult‐onset disease.
Decisions Regarding Pregnancy Termination Due to β‐Thalassemia Major: a Mixed‐Methods Study in Sistan and Baluchestan, Iran
Authors: Moudi Zahra , Miri‐Moghaddam Ebrahim
Published: September 2016

In the present study, an embedded design was applied in order to conduct a one‐year cross‐sectional audit of chorionic villus sampling (CVS) and foetal outcomes affected by β‐thalassemia major (β‐TM) in a prenatal diagnosis (PND) setting. In addition, we explored the decisions regarding pregnancy termination among women whose pregnancy (or child) was affected by β‐TM. In the quantitative phase, the available data in the clients’ medical records were analysed, while the qualitative phase was performed using a grounded theory method. Interviews were performed with nine pregnant women who had decided against pregnancy termination despite positive CVS results, 11 mothers who had admitted their child to the thalassemia ward for blood transfusion, and 19 mothers who had received positive CVS results and had decided against pregnancy termination in the preceding year. Over one year, 18.6 % of women decided against pregnancy termination despite positive CVS results. Two main themes related to decisions against pregnancy termination emerged from the qualitative data: 1) Cognitive factors (questioning the reliability of the tests or doubts about the accuracy of the results, understanding disease recurrence, curability, perceived severity of the disease, and lack of “real‐life experiences”); and 2) Sociocultural responsiveness (family opposition, responsibility before God, and self‐responsiveness). All of the mentioned factors could intensify fear of abortion in couples due to possible regret, and encourage a decision against pregnancy termination.
Taking the Devil at his Word: The Devil and Language in the Dialogues of Gregory the Great
Authors: KINGSTON CHARLOTTE
Published: September 2016

In the Dialogues of Gregory the Great (590–604), the devil is sometimes given direct speech in which he is shown protesting his innocence. The devil in these stories is frequently interpreted as comical, trivial and somewhat underwhelming. However, when re-read through the lens of Gregory's exegesis of Genesis iii, and his ideas regarding the devil, sin and language, what emerges is that it is the devil's verbal skill and appearance of harmlessness that make him dangerous. This failure to see the devil's words as a deceptive recapitulation of Genesis iii cannot be separated from the Dialogues’ complex historiography.
Two Unpublished Letters of Stephen Gardiner, August–September 1547 (Bodleian Library, Oxford, ms Eng. th. b. 2)
Authors: WEINREICH SPENCER J.
Published: September 2016

This note is a transcription of two hitherto unknown letters of Stephen Gardiner, bishop of Winchester (c.1497–1555), found in an early seventeenth-century Catholic commonplace book (Bodleian Library, Oxford, ms Eng. th. b. 2). Composed in late August or early September 1547 and addressed to several of the royal Visitors of Winchester, the letters are a delaying tactic in Gardiner's ongoing resistance to the Edwardian Injunctions and the ‘Book of homilies’, an attempt to win time until the calling of the parliamentary session. The strongly theological content of the letters challenges traditional characterisations of Gardiner as primarily a legalist.
Reason and Justice: The Optimal and the Maximal
Authors: Sen Amartya
Published: September 2016

This paper is a revised version of the Royal Institute of Philosophy’s Annual Lecture, 2016. It discusses the demands of critical reasoning in ethical arguments, and focuses in particular on the assessment of justice. It disputes the belief that reasoning about choice remains unfinished until an optimal alternative has been identified. A successful closure of a reasoning may identify a maximal alternative, which is not judged to be worse than any other available option. A maximal alternative need not be optimal in the sense of being ‘best’ (that is, at least as good as every other alternative). Critically sound reasoning can lead us to a partial ordering yielding a maximal alternative that is not optimal. The compulsive search for an optimal alternative needlessly limits the reach of reasoning in ethics.
Philosophy (and Athens) in Decay: Timon of Athens
Authors: Blits Jan H.
Published: September 2016

Pericles famously described the Athenians as “lovers of the beautiful with thrift, and lovers of wisdom without softness.” Yet he cautioned that Athens's pursuit of boundless empire and glory could corrupt the citizens and destroy Athenian brilliance. Timon of Athens, the counterpart of A Midsummer Night's Dream, depicts what Pericles had warned against. The Athenians' love of the noble has given way to a voracious love of gold. With artists looking upon their work as merchandise to be sold at the highest price, the only thing considered beautiful is a line of salacious chorus-girls. Flattery and utility prevail throughout. The lowest form of friendship is thought to be the highest. Athens has disintegrated as a community of citizens sharing a common heritage. And philosophy, no longer a speculative inquiry, has become a shameless way of life, based on a fixed doctrine and virtually indistinguishable from misanthropy.
The Philosopher's Literary Critic
Authors: Alvis John
Published: September 2016

Leon Craig's five books are interrelated by a common approach: Craig writes of philosophic matters juxtaposing them with literary works, or one may reverse the order—whichever way, the exegesis proceeds in tandem. Moreover, he has intertwined the books in a sequential development. One can perceive Craig discovered his fountainhead in Plato. His first book, in 1993, The War Lover: A Study of Plato's “Republic,” has left its genetic pattern upon the next four, Of Philosophers and Kings: Political Philosophy in Shakespeare's “Macbeth” and “King Lear” (2001), The Platonian Leviathan (2010), Philosophy and the Puzzles of “Hamlet” (2014), and his latest, The Philosopher's English King: Shakespeare's “Henriad” as Political Philosophy (2015). In this latest effort, Shakespeare is the philosopher and Henry V the best of Shakespeare's English kings. But you will not appreciate the extent and intricacy of Craig's web unless you recognize that Plato's thought, especially as that thought has been conveyed in The Republic, runs through every filament. To be precise, taking such themes of that dialogue as Socrates's notion of a tripartite human soul, his taxonomy of defective regimes, his all but best regime of “Guardians,” and Socrates's ultimately best constitution, rule by a philosopher become king or king become philosopher, or only somewhat less improbably, a king become an understanding student of a counselor philosopher. Then, best self-government within the individual soul is likewise worked out in The Republic as Craig reads it. To my mind he has read Plato aright.
HERE COMES NEWER DESPAIR: AN AESTHETIC PRIMER FOR THE NEW CONCEPTUALISM OF JOHANNES KREIDLER
Authors: Erwin Max
Published: September 2016

This article seeks to clarify the aesthetic precedents for New Conceptualism generally, and Johannes Kreidler's work in particular. Pursuant to this end, I examine how Kreidler's approaches to musical and political material are ideologically indebted to his teacher, Mathias Spahlinger, whose dictum that New Music can be socially relevant without resorting to political clichés is taken by Kreidler into the digital age. Finally, by means of a conclusion, I attempt to provide a broad examination of how Kreidler's aesthetic concerns differ from – and sometimes radically conflict with – those other composers who are grouped under the New Conceptualism letterhead.