bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamics of embryonic stem cell differentiation inferred from single-cell transcriptomics show a series of transitions through discrete cell states
Authors: Jang Sumin , Choubey Sandeep , Furchtgott Leon , Zou Ling-Nan , Doyle Adele , Menon Vilas , Loew Ethan B , Krostag Anne-Rachel , Martinez Refugio A , Madisen Linda , Levi Boaz P , Ramanathan Sharad
Published: February 2017

The complexity of gene regulatory networks that lead multipotent cells to acquire different cell fates makes a quantitative understanding of differentiation challenging. Using a statistical framework to analyze single-cell transcriptomics data, we infer the gene expression dynamics of early mouse embryonic stem (mES) cell differentiation, uncovering discrete transitions across nine cell states. We validate the predicted transitions across discrete states using flow cytometry. Moreover, using live-cell microscopy, we show that individual cells undergo abrupt transitions from a naïve to primed pluripotent state. Using the inferred discrete cell states to build a probabilistic model for the underlying gene regulatory network, we further predict and experimentally verify that these states have unique response to perturbations, thus defining them functionally. Our study provides a framework to infer the dynamics of differentiation from single cell transcriptomics data and to build predictive models of the gene regulatory networks that drive the sequence of cell fate decisions during development.
Compacting and correcting Trinity and Oases RNA-Seq de novo assemblies
Authors: Cabau Cédric , Escudié Frédéric , Djari Anis , Guiguen Yann , Bobe Julien , Klopp Christophe
Published: February 2017

Background

De novo transcriptome assembly of short reads is now a common step in expression analysis of organisms lacking a reference genome sequence. Several software packages are available to perform this task. Even if their results are of good quality it is still possible to improve them in several ways including redundancy reduction or error correction. Trinity and Oases are two commonly used de novo transcriptome assemblers. The contig sets they produce are of good quality. Still, their compaction (number of contigs needed to represent the transcriptome) and their quality (chimera and nucleotide error rates) can be improved.

Results

We built a de novo RNA-Seq Assembly Pipeline (DRAP) which wraps these two assemblers (Trinity and Oases) in order to improve their results regarding the above-mentioned criteria. DRAP reduces from 1.3 to 15 fold the number of resulting contigs of the assemblies depending on the read set and the assembler used. This article presents seven assembly comparisons showing in some cases drastic improvements when using DRAP. DRAP does not significantly impair assembly quality metrics such are read realignment rate or protein reconstruction counts.

Conclusion

Transcriptome assembly is a challenging computational task even if good solutions are already available to end-users, these solutions can still be improved while conserving the overall representation and quality of the assembly. The de novo RNA-Seq Assembly Pipeline (DRAP) is an easy to use software package to produce compact and corrected transcript set. DRAP is free, open-source and available under GPL V3 license at http://www.sigenae.org/drap.
Effects of Prophylactic Ozone Therapy on General Anesthesia and Surgical Stress Response: Neutrophil/Lymphocyte Ratio and Ischemia-Modified Albumin
Authors: Toman Huseyin , Sahin Hasan , Erbas Mesut , Turkon Hakan , Simsek Tuncer , Kiraz Hasan Ali , Özkan Muhammed Turgut Alper
Published: February 2017

General anesthesia and surgical stress cause an acute endocrine, metabolic, and immunologic inflammatory response in organisms and an increase in neutrophil lymphocyte ratio (NLR) and ischemia-modified albumin (IMA) levels. Ozone, other than inhalation administration, reduces the release of antioxidants and some proinflammatory cytokines and has been shown to have an anti-inflammatory effect. Our aim is to research how the NLR and IMA response is affected in rabbits undergoing surgical intervention with general anesthesia given prophylactic with ozone therapy. We divided 12 New Zealand rabbits into 2 groups: group O was given 70 μg/mL 10 mL ozone by the rectal route in 6 sessions on alternate days, and group C was given air by the rectal route. The rabbits underwent surgical intervention under general anesthesia. Blood samples were taken at basal, preoperation, 30 minutes postanesthesia, and 24 hours postoperation and were examined for hemogram and IMA. At 24 hours postoperation, an increase in NLR was observed in both groups, more clearly in group C (P < 0.05). In both groups, comparisons within the groups showed a significant increase in NLR only at 24 hours postoperation compared to other times (P < 0.05).When IMA values were compared, differences between the groups were observed between preoperative values and those at the 30 minutes postanesthesia and 24 hours postoperation (P < 0.05). When general anesthesia and surgical stress response were evaluated using inflammatory parameters of both NLR and IMA, there was significantly less of an increase in levels in rabbits given ozone compared to the control group.
Elevated atmospheric CO2 negatively impacts photosynthesis through radiative forcing and physiology‐mediated climate feedback
Authors: Zhu Peng , Zhuang Qianlai , Ciais Philippe , Welp Lisa , Li Wenyu , Xin Qinchuan
Published: February 2017

Increasing atmospheric CO2 affects photosynthesis involving directly increasing leaf carboxylation rates, stomatal closure, and climatic effects. The direct effects are generally thought to be positive leading to increased photosynthesis, while its climatic effects can be regionally positive or negative. These effects are usually considered to be independent from each other, but they are in fact coupled through interactions between land surface exchanges of gases and heat and the physical climate system. In particular, stomatal closure reduces evapotranspiration and increases sensible heat emissions from ecosystems, leading to decreased atmospheric moisture and precipitation and local warming. We use a coupled earth system model to attribute the influence of the increase in CO2 on gross primary productivity (GPP) during the period of 1930–2011. In our model, CO2 radiative effects cause climate change that has only a negligible effect on global GPP (a reduction of 0.9 ± 2% during the last 80 years) because of opposite responses between tropical and northern biomes. On the other hand, CO2 physiological effects on GPP are both positive, by increased carboxylation rates and water use efficiency (7.1 ± 0.48% increase), and negative, by vegetation‐climate feedback reducing precipitation, as a consequence of decreased transpiration and increased sensible heat in areas without water limitation (2.7 ± 1.76% reduction).When considering the coupled atmosphere‐vegetation system, negative climate feedback on photosynthesis and plant growth due to the current level of CO2 opposes 29–38% of the gains from direct fertilization effects.
Evidence of erosional self‐channelization of pyroclastic density currents revealed by ground‐penetrating radar imaging at Mount St. Helens, Washington (USA)
Authors: Gase Andrew C. , Brand Brittany D. , Bradford John H.
Published: February 2017

The causes and effects of erosion are among the least understood aspects of pyroclastic density current (PDC) dynamics. Evidence is especially limited for erosional self‐channelization, a process whereby PDCs erode a channel that confines the body of the eroding flow or subsequent flows. We use ground‐penetrating radar imaging to trace a large PDC scour and fill from outcrop to its point of inception and discover a second, larger PDC scour and fill. The scours are among the largest PDC erosional features on record, at >200 m wide and at least 500 m long; estimated eroded volumes are on the order of 106 m3. The scours are morphologically similar to incipient channels carved by turbidity currents. Erosion may be promoted by a moderate slope (5–15°), substrate pore pressure retention, and pulses of increased flow energy. These findings are the first direct evidence of erosional self‐channelization by PDCs, a phenomenon that may increase flow velocity and runout distance through confinement and substrate erosion.
Right Node Raising
Authors: Citko Barbara
Published: February 2017

This chapter examines a construction known as Right Node Raising (RNR). There are many questions that RNR raises, and perhaps the most widely debated ones concern the position of the ‘right node raised’ element: is it located outside both conjuncts, inside only one of them, or perhaps inside both conjuncts simultaneously? All three possibilities have been explored in the literature. On some accounts, RNR initially involves two copies of the shared element, one in each conjunct, which undergo rightward across‐the‐board movement to a position above the coordination level. On other accounts, one of the copies undergoes deletion; and yet, on others, a single copy is literally shared between the two conjuncts, resulting in a multidominant structure. After introducing the existing accounts of RNR, this chapter turns to the diagnostics that have been used to weigh in on the choice between them. These include constituency, case, agreement, reconstruction effects, binding, islandhood, scope, compatibility with relational modifiers, vehicle change effects, and the availability of strict versus sloppy identity readings. Interestingly, with respect to some of these diagnostics, the shared element behaves as if it were inside both conjuncts; with respect to others, it behaves as if it were outside both of them; and with respect to still others, it behaves as if it were only in one.
On the adaptive control of cooperative robots with time‐variant holonomic constraints
Authors: Pliego‐Jimenez Javier , Arteaga‐Perez Marco
Published: February 2017

In this work, we consider the problem of 2 robots handling a rigid object, while model‐parameter uncertainties are assumed. It is also assumed that the manipulators can push but not pull the object. Several control schemes proposed in the literature attempt to control the position of the object rather than its orientation. However, many industrial tasks require to move and to rotate the object. To this end, we propose an adaptive hybrid position/force control law based on time‐variant holonomic constraints, which allow for object position and orientation control. Our approach guarantees that the force error asymptotically converges to 0; therefore, a stable grasp can be accomplished by means of a proper definition of the desired pushing force. In addition, a dynamic model of the cooperative system based on the load distribution and joint‐space orthogonalization principles is developed. Experimental results are presented to validate the proposed dynamic model and control scheme.
Euler–euler anisotropic gaussian mesoscale simulation of homogeneous cluster‐induced gas–particle turbulence
Authors: Kong Bo , Fox Rodney O. , Feng Heng , Capecelatro Jesse , Patel Ravi , Desjardins Olivier , Fox Rodney O.
Published: February 2017

An Euler–Euler anisotropic Gaussian approach (EE‐AG) for simulating gas–particle flows, in which particle velocities are assumed to follow a multivariate anisotropic Gaussian distribution, is used to perform mesoscale simulations of homogeneous cluster‐induced turbulence (CIT). A three‐dimensional Gauss–Hermite quadrature formulation is used to calculate the kinetic flux for 10 velocity moments in a finite‐volume framework. The particle‐phase volume‐fraction and momentum equations are coupled with the Eulerian solver for the gas phase. This approach is implemented in an open‐source CFD package, OpenFOAM, and detailed simulation results are compared with previous Euler–Lagrange simulations in a domain size study of CIT. The results demonstrate that the proposed EE‐AG methodology is able to produce comparable results to EL simulations, and this moment‐based methodology can be used to perform accurate mesoscale simulations of dilute gas–particle flows. © 2017 American Institute of Chemical Engineers AIChE J, 63: 2630–2643, 2017
Changing the surgical dogma in frontal sinus trauma: transnasal endoscopic repair
Authors: Grayson Jessica W. , Jeyarajan Hari , Illing Elisa A. , Cho Do‐Yeon , Riley Kristen O. , Woodworth Bradford A.
Published: February 2017

Background

Management of frontal sinus trauma includes coronal or direct open approaches through skin incisions to either ablate or obliterate the frontal sinus for posterior table fractures and openly reduce/internally fixate fractured anterior tables. The objective of this prospective case‐series study was to evaluate outcomes of frontal sinus anterior and posterior table trauma using endoscopic techniques.

Methods

Prospective evaluation of patients undergoing surgery for frontal sinus fractures was performed. Data were collected regarding demographics, etiology, technique, operative site, length involving the posterior table, size of skull base defects, complications, and clinical follow‐up.

Results

Forty‐six patients (average age, 42 years) with frontal sinus fractures were treated using endoscopic techniques from 2008 to 2016. Mean follow‐up was 26 (range, 0.5 to 79) months. Patients were treated primarily with a Draf IIb frontal sinusotomies. Draf III was used in 8 patients. Average fracture defect (length vs width) was 17.1 × 9.1 mm, and the average length involving the posterior table was 13.1 mm. Skull base defects were covered with either nasoseptal flaps or free tissue grafts. One individual required Draf IIb revision, but all sinuses were patent on final examination and all closed reductions of anterior table defects resulted in cosmetically acceptable outcomes.

Conclusion

Frontal sinus trauma has traditionally been treated using open approaches. Our findings show that endoscopic management should become part of the management algorithm for frontal sinus trauma, which challenges current surgical dogma regarding mandatory open approaches.
Clinical outcomes of sinonasal squamous cell carcinomas based on tumor etiology
Authors: Yan Carol H. , Newman Jason G. , Kennedy David W. , Palmer James N. , Adappa Nithin D.
Published: February 2017

Background

Squamous cell carcinoma (SCC) of the sinonasal cavity is a rare entity that arises as either de‐novo tumors or from inverted papillomas (IPs). In this study we evaluate and compare oncologic outcomes of sinonasal SCCs based on their etiology and treatment strategy.

Methods

This investigation was a single‐center, retrospective review comparing de‐novo SCCs (n = 28) and those associated with IPs (n = 38) resected during the period from 2000 to 2015. Demographic and tumor data, surgical approach, recurrence, and clinical outcomes were analyzed.

Results

There was no statistical difference when comparing age, smoking history, tumor origin, or tumor stage of our patients with de‐novo sinonasal SCC (DN‐SCC) vs IP‐transformed SCC (IP‐SCC). IP‐SCC tumors demonstrated better overall survival (p = 0.065) and disease‐specific survival (p = 0.041) compared with DN‐SCC. Early T‐stage IP‐SCC tumors had better disease‐free survival compared with early T‐stage DN‐SCC tumors (p = 0.002). Distant metastasis was an independent prognostic factor of worse disease‐specific survival (p = 0.002). SCC disease‐specific survival was not affected by surgical resection technique.

Conclusion

SCC tumors arising from IPs appear to have improved disease‐specific survival compared with de‐novo sinonasal SCC tumors. The oncologic differences between the 2 groups are found primarily among the early‐stage tumors.
Palladium‐Mediated Arylation of Lysine in Unprotected Peptides
Authors: Lee Hong Geun , Lautrette Guillaume , Pentelute Bradley L. , Buchwald Stephen L.
Published: February 2017

A mild method for the arylation of lysine in an unprotected peptide is presented. In the presence of a preformed biarylphosphine‐supported palladium(II)–aryl complex and a weak base, lysine amino groups underwent C−N bond formation at room temperature. The process generally exhibited high selectivity for lysine over other amino acids containing nucleophilic side chains and was applicable to the conjugation of a variety of organic compounds, including complex drug molecules, with an array of peptides. Finally, this method was also successfully applied to the formation of cyclic peptides by macrocyclization.
Outer‐Sphere 2 e−/2 H+ Transfer Reactions of Ruthenium(II)‐Amine and Ruthenium(IV)‐Amido Complexes
Authors: Cattaneo Mauricio , Ryken Scott A. , Mayer James M.
Published: February 2017

A diverse set of 2 e−/2 H+ reactions are described that interconvert [RuII(bpy)(en*)2]2+ and [RuIV(bpy)(en‐H*)2]2+ (bpy=2,2′‐bipyridine, en*=H2NCMe2CMe2NH2, en*‐H=H2NCMe2CMe2NH−), forming or cleaving different O−H, N−H, S−H, and C−H bonds. The reactions involve quinones, hydrazines, thiols, and 1,3‐cyclohexadiene. These proton‐coupled electron transfer reactions occur without substrate binding to the ruthenium center, but instead with precursor complex formation by hydrogen bonding. The free energies of the reactions vary over more than 90 kcal mol−1, but the rates are more dependent on the type of X−H bond involved than the associated ΔG°. There is a kinetic preference for substrates that have the transferring hydrogen atoms in close proximity, such as ortho‐tetrachlorobenzoquinone over its para‐isomer and 1,3‐cyclohexadiene over its 1,4‐isomer, perhaps hinting at the potential for concerted 2 e−/2 H+ transfers.
Patchy Nanofibers from the Thin Film Self‐Assembly of a Conjugated Diblock Copolymer
Authors: Kynaston Emily L. , Fang Yuan , Manion Joseph G. , Obhi Nimrat K. , Howe Jane Y. , Perepichka Dmitrii F. , Seferos Dwight S.
Published: February 2017

An unexpected morphology comprising patchy nanofibers can be accessed from the self‐assembly of an all‐conjugated, polyselenophene‐block‐polythiophene copolymer. This morphology consists of very small (<10 nm), polythiophene‐ and polyselenophene‐rich domains and is unprecedented for both conjugated polymers and diblock copolymers in general. We propose that the patchy morphology occurs from the enhanced miscibility of the blocks arising from the longer alkyl chains in comparison to similar block copolymers with shorter alkyl chains, which fully phase separate, as well as the difference in rigidity between the polythiophene and polyselenophene blocks. This work demonstrates a facile way to tune the self‐assembly behavior of conjugated block copolymers by modification of the side chain substituents.
Carbon nanospheres with well‐controlled nano‐morphologies as support for palladium‐catalyzed Suzuki coupling reaction
Authors: Dong Wenhuan , Cheng Saisai , Feng Cheng , Shang Ningzhao , Gao Shutao , Wang Chun , Wang Zhi
Published: February 2017

Uniform carbon nanospheres (UCS) with well‐controlled nano‐morphologies were fabricated by hydrothermal carbonization of sucrose in the presence of kayexalate. Highly dispersed and ultrafine palladium nanoparticles were supported on the UCS through a facile co‐reduction process with NaBH4 as reducing agent. The obtained Pd@UCS exhibited efficient catalytic activity for the Suzuki coupling reaction. Moreover, the as‐prepared catalyst could be recycled and reused at least five times without significant loss of its catalytic activity.
Effect of side‐chain functionality on the organic field‐effect transistor performance of oligo(p‐phenylenevinylene) derivatives
Authors: Chini Mrinmoy Kumar , Chatterjee Shyambo
Published: February 2017

In order to observe the effects of the substitution of electronegative flourine with aromatic groups in oligo(p‐phenylenevinylene) compounds on their packing, morphology, and charge carrier mobility, we have synthesized napthol‐substituted oligo(p‐phenylenevinylene) compounds and examined their solubility, redox properties, thin film morphologies, and charge carrier properties. To date, very few examples of conjugated oligomers bearing napthol side groups have been reported in the literature. After annealing at 150 °C, the mobility of S1, S2, and S3 was 4.0 × 10−2 cm2 V−1 s−1, 1.2 × 10−2 cm2 V−1 s−1, and 2.6 × 10−3 cm2 V−1 s−1, respectively. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 44825.
Effects of ultrasonic vibration on the rheological behavior of high‐density polyethylene composites filled with flash aluminum flake pigments
Authors: Hong Xinmi , Xiao Xiaoting , Zhang Zhengrong , Zhang J. J.
Published: February 2017

The metallic effect of polymer composites was produced through the loading of flash aluminum flake pigments (FAFPs) into polymers. This production method could eliminate postprocessing techniques, such as spray coating, painting, or metallization. We used a self‐improved, ultrasound‐assisted capillary rheometer to explore the rheological behavior of high‐density polyethylene composites filled with FAFPs in the absence and presence of ultrasound treatment. The effects of the ultrasound intensity, experimental temperature, filler content, and particle size on the composite viscosity were studied. The results show that the composite viscosity not only decreased as the ultrasound intensity, experimental temperature, and particle size increased but also decreased as the filler content decreased. A viscosity model of the polymer melts was proposed to illustrate the relationship between the viscosity and ultrasonic intensity. The viscosity obeyed the equations under ultrasonic vibration. The predicted results for the composite viscosity complied greatly with the experimental values. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 44906.
Irradiation dose control for polymer‐matrix composites fabricated by in situ curing with low‐energy electron beam
Authors: Zhang Jingjing , Duan Yugang , Zhao Xinming , Wang Ben
Published: February 2017

The electron beam (EB) with emitting energies lower than 150 keV is applicable in in situ curing of polymer‐matrix composites; however, being poor in penetration ability, it leads to significant attenuation of irradiation dose along the prepreg thickness. In this study, polymer‐matrix composites were fabricated by low‐energy EB irradiation curing, and the effect of dose control of double‐sided irradiation was systematically investigated. Experimental results showed that laminates fabricated by single‐sided irradiated prepregs were low in interlaminar shear strength (ILSS) owing to incomplete curing after being post cured at 180 °C for 30 min. A double‐sided irradiation method which included irradiation of equal dose and different doses on both sides of the prepreg was proposed to overcome this difficulty. Analysis showed that under a total dose of 70 and 100 kGy, the ILSS results were high owing to the low curing degree of two adhesive surfaces; under a total dose of 130 and 160 kGy, laminates fabricated with different EB irradiation doses on both sides exhibited enhanced ILSS compared to those with equal dose on both sides, owing to physical adhesion and chemical crosslinking between layers. The ILSS results exhibited the largest increase of 18.9 and 60.5%, respectively, by tuning the dose differences between both sides of the prepregs. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 44944.
Differential responses of Helicoverpa armigera C‐type immunlectin genes to the endoparasitoid Campoletis chlorideae
Authors: Wang Xiong‐Ya , Bai Su‐Fen , Li Xin , An Shi‐Heng , Yin Xin‐Ming , Li Xian‐Chun
Published: February 2017

The C‐type lectins mediate nonself recognition in insects. The previous studies focused on host immunlectin response to bacterial infection; however, the molecular basis of immunlectin reactions to endoparasitoids has not been elucidated. The present study investigated the effect of parasitization by Campoletis chlorideae on hemagglutination activity (HA; defined as the ability of lectin to agglutinate erythrocytes or other cells), and transcriptional expression of C‐type immunlectin genes in the larval host, Helicoverpa armigera. Parasitization induced four‐ to eightfold higher HA in the parasitized larvae, compared to nonparasitized larvae at days 2 and 6 postparasitization (PP), however inhibited HA at other days PP. Eight C‐type lectins were differentially expressed in different host developmental stages, from feeding to wandering stage. The mRNA levels of HaCTL1, HaCTL3, HaCTL4, and HaCTL5 were upregulated and HaCTL2 and HaCTL7 were downregulated. Tissue analysis showed that HaCTLs were mainly expressed in fat body or hemocytes, while HaCTL5 was highly expressed in testes. The effects of parasitization on the lectin expression patterns differed. Lectins except HaCTL6 or HaCTL5 were significantly down‐ or upregulated in parasitized larvae at day 4 or 6 PP compared with that of nonparasitized larvae. We infer from our results that C‐type immunlectins are involved in host–parasitoid interactions, and parasitization alter host immunlectin levels both in inhibiting and promoting host immune defenses to endoparasitoids. These immunlectin genes indicated an altered physiological status of the host insect, depending on developmental stage, tissue, and parasitization.
A novel freeze‐dried storage and preparation method for the determination of mycophenolic acid in plasma by high‐performance liquid chromatography
Authors: Wang Lei , Qiang Wei , Li Ying , Cheng Zeneng , Xie Mengmeng
Published: February 2017

Plasma samples were conventionally stored at freezing conditions until the time of detection. Such a technique, when carried out over an extended period, is energy consuming; in addition, preparation and transportation of stored samples is inconvenient. In this study, a freeze‐dried storage and preparation method was proposed to determine the presence of mycophenolic acid (MPA) in plasma. Fresh plasma samples were freeze‐dried using a device, and then stored at ambient temperature. After the stored samples were soaked with methanol spiked with the internal standard, high‐performance liquid chromatography was conducted to detect MPA. The proposed method was demonstrated to be precise and accurate over the linear range of 0.5–50 μg mL−1, with both intra‐ and inter‐day precision being <7% and biases <10%. The freeze‐dried samples were stable at ambient temperature for at least 40 days. This method was also successfully applied to the pharmacokinetic study of MPA in healthy volunteers. Pharmacokinetic parameters, such as maximum plasma concentration, time point of maximum plasma concentration and elimination half‐life, among others, were consistent with the results in the published study. This proposed technique was proved to be simple, reproducible and energy saving. This approach could also simplify the storage and analysis of samples in clinical and scientific drug research.
Inhibitory Activities of Butanol Fraction from Butea monosperma (Lam.) Taub. Bark Against Free Radicals, Genotoxins and Cancer Cells
Authors: Kaur Varinder , Kumar Manish , Kaur Paramjeet , Kaur Sandeep , Kaur Satwinderjeet
Published: February 2017

The present study was undertaken to investigate antioxidant, antigenotoxic, and antiproliferative activity of butanol fraction (Bmbu) from bark of medicinal plant Butea monosperma. Antioxidant potency of Bmbu was examined by various in vitro assays. It was also investigated for antigenotoxic activity using Escherichia coli. PQ37 employing SOS chromotest. Further, cytotoxic and apoptosis inducing activity of Bmbu was evaluated in MCF‐7 breast cancer cells. Bmbu showed potent free radical scavenging ability in ABTS assay (IC50 56.70 μg/ml) and anti‐lipid peroxidation ability (IC50 40.39 μg/ml). 4NQO and H2O2 induced genotoxicity was suppressed by Bmbu in SOS chromotest by 74.26% and 82.02% respectively. It also inhibited the growth of MCF‐7 cells with GI50 value of 158.71 μg/ml. Induction of apoptosis in MCF‐7 cells by Bmbu treatment was deciphered using confocal microscopy, flow cytometry, and neutral comet assay. Bmbu treatment increased cell population in sub‐G1 phase (69.6%) indicating apoptotic cells. Further, Bmbu treatment resulted in increased reactive oxygen species generation and decreased mitochondrial membrane potential indicating involvement of mitochondrial dependent pathway of apoptosis. HPLC profiling showed the presence of polyphenols such as ellagic acid, catechin, quercetin, and gallic acid as its major constituents. Consequently, it is suggested that the phytoconstituents from this plant may be further exploited for development of novel drug formulation with possible therapeutic implication.
Student success and retention using new definitions created for nonterm, direct assessment CBE
Authors: Mayeshiba M. , Brower A.
Published: February 2017

Background

Nonterm, direct assessment competency‐based education gives students unique options for tailoring their coursework to fit their individual needs. These options invalidate traditional measures of student retention and success (such as such as yearly retention, grade point average, or 4‐year graduation rates) that assume all students will complete courses at the same rate and will remain continuously enrolled from admission to graduation. In this article, we propose a new measure of retention, reenrollment within 6 months, and explore its relationship to student success in the University of Wisconsin Flexible Option.

Methods

We examined data for the 1,311 subscriptions that occurred during the first 2 years of the program: from January 2014 through December 2015. These subscriptions represented 565 unique students who each enrolled between one and eight times. Using each subscription's academic outcomes, we conducted a series of logistic regressions to describe students’ likelihood to retain.

Results

We found that academic outcomes strongly predict a student's likelihood to reenroll within 6 months. Students who mastered at least one competency set during their first subscription were particularly more likely to reenroll. Furthermore, we found that academic outcomes from the previous subscription and the student's longevity in the program also significantly predicted retention.

Conclusion

While further research is needed, these definitions provide a starting point to understand student behavior in nonterm, direct assessment CBE, and suggest the educational value to using 6‐month reenrollment as the measure for retention. The results also suggest possible best educational practices in this unique environment.
Structural Basis of Microtubule Stabilization by Discodermolide
Authors: Prota Andrea E. , Bargsten Katja , Redondo‐Horcajo Mariano , Smith Amos B. , Yang Chia‐Ping H. , McDaid Hayley M. , Paterson Ian , Horwitz Susan B. , Fernando Díaz José , Steinmetz Michel O.
Published: February 2017

Microtubule‐stabilizing agents (MSAs) are widely used in chemotherapy. Using X‐ray crystallography we elucidated the detailed binding modes of two potent MSAs, (+)‐discodermolide (DDM) and the DDM–paclitaxel hybrid KS‐1‐199‐32, in the taxane pocket of β‐tubulin. The two compounds bind in a very similar hairpin conformation, as previously observed in solution. However, they stabilize the M‐loop of β‐tubulin differently: KS‐1‐199‐32 induces an M‐loop helical conformation that is not observed for DDM. In the context of the microtubule structure, both MSAs connect the β‐tubulin helices H6 and H7 and loop S9–S10 with the M‐loop. This is similar to the structural effects elicited by epothilone A, but distinct from paclitaxel. Together, our data reveal differential binding mechanisms of DDM and KS‐1‐199‐32 on tubulin.
Effect of heme oxygenase‐1 transduced bone marrow mesenchymal stem cells on damaged intestinal epithelial cells in vitro
Authors: Cao Yi , Wu Ben‐Juan , Zheng Wei‐Ping , Yin Ming‐Li , Liu Tao , Song Hong‐Li
Published: February 2017

In this study, we explored the effects of mesenchymal stem cells (MSCs) from bone marrow overexpressing heme oxygenase‐1 (HO‐1) on the damaged human intestinal epithelial barrier in vitro. Rat MSCs were isolated from bone marrow and transduced with rat HO‐1 recombinant adenovirus (HO‐MSCs) for stable expression of HO‐1. Colorectal adenocarinoma 2 (Caco2) cells were treated with tumor necrosis factor‐α (TNF‐α) to establish a damaged colon epithelial model. Damaged Caco2 were cocultured with MSCs, Ad‐MSCs, Ad‐HO + MSCs or HO‐MSCs. mRNA and protein expression of Zona occludens‐1 (ZO‐1) and human HO‐1 and the release of cytokines were measured. ZO‐1 and human HO‐1 in Caco2 were significantly decreased after treatment with TNF‐α; and this effect was reduced when coculture with MSCs from bone marrow. Expression of ZO‐1 was not significantly affected by Caco2 treatment with TNF‐α, Ad‐HO, and MSCs. In contrast, ZO‐1 and human HO‐1 increased significantly when the damaged Caco2 was treated with HO‐MSCs. HO‐MSCs showed the strongest effect on the expression of ZO‐1 in colon epithelial cells. Coculture with HO‐MSCs showed the most significant effects on reducing the expression of IL‐2, IL‐6, IFN‐γ and increasing the expression of IL‐10. HO‐MSCs protected the intestinal epithelial barrier, in which endogenous HO‐1 was involved. HO‐MSCs play an important role in the repair process by reducing the release of inflammatory cytokines and increasing the release of anti‐inflammatory factors. These results suggested that HO‐MSCs from bone marrow were more effective in repairing the damaged intestinal epithelial barrier, and the effectiveness of MSCs was improved by HO‐1 gene transduction, which provides favorable support for the application of stem cell therapy in the intestinal diseases.
It's getting better all the time
Authors: Butman Samuel M.
Published: February 2017

Key Points

The risk of target lesion revascularization increases when extensive numbers or lengths of cobalt chromium everolimus‐eluting stents are deployed.

There is no relationship between the risk of stent thrombosis to total stent length.

Newer stent materials and designs do result in better long‐term outcomes.
Atrial baffle stenting
Authors: Parekh Dhaval , Krajcer Zvonimir
Published: February 2017

Key Points

Adult survivors of the atrial switch operation contend with a multitude of complications, including systemic and pulmonary venous baffle obstruction, baffle leak, arrhythmia, and failure of the systemic right ventricle.

Hybrid or intravascular interventions may be indicated for baffle obstruction, baffle leak, pacing lead revision, and clinical symptoms.

Despite the complexity of these procedures, high procedural success rates can be achieved, with limited complications and improvement of clinical symptoms, at experienced centers.
Time is muscle and every minute counts
Authors: Ahmad Tariq Ali , Gilchrist Ian C.
Published: February 2017

Key Points

Prehospital 12‐lead electrocardiogram should be considered as a part of the initial assessment in patients with symptoms concerning for acute coronary syndrome without causing undue delays in care. A significant amount of evidence confirms the prehospital electrocardiogram as an active contributor to the patients’ clinical outcomes.

Systematic protocols including prehospital electrocardiograms should be designed within certain healthcare networks to facilitate the timely transport of the patients to primary‐PCI capable facilities.

Regulatory and technological challenges exist that require a change to fully implement routine 12‐lead electrocardiograms at first contact with patients before the full potential of this technology can be demonstrated.
Silver‐Promoted Dehydroaromatization of Ethylene over ZSM‐5 Catalysts
Authors: Hsieh Ming‐Feng , Zhou Yunwen , Thirumalai Hari , Grabow Lars C. , Rimer Jeffrey D.
Published: February 2017

The shape selectivity of ZSM‐5 (MFI type) catalysts is ideal for the production of C6–C8 aromatics. Developing high‐performance zeolite catalysts with improved selectivity to aromatics, particularly from diversified (non‐petroleum) feedstocks, has broad commercial appeal. Non‐oxidative coupling (NOC) of ethylene was examined over Ag‐ZSM‐5 catalysts at 400 °C and shows that Ag+ sites promote dehydroaromatization with enhanced selectivity to toluene and xylenes. Metal exchange of H‐ZSM‐5 results in Ag zoning wherein Ag+ site density is higher on the exterior of ZSM‐5 particles. Catalyst performance was characterized with varying Ag loading as well as the use of methane co‐feed. Aromatic selectivity is about 60 % on Ag‐ZSM‐5 compared to 20 % on H‐ZSM‐5, which is qualitatively consistent with density functional theory (DFT) showing that ethylene forms strong complexes with Ag+ (Lewis acid) sites. DFT calculations also reveal that ethylene activation on H+ (Brønsted acid) sites is more energetically favorable, and likely constitutes the first mechanistic step in ethylene‐to‐liquids (ETL) reactions. Ag‐ZSM‐5 is thus identified as an effective catalyst for low‐temperature ETL reactions that has the potential to outperform conventional metal‐exchanged zeolites.
Design of Allosteric Stimulators of the Hsp90 ATPase as New Anticancer Leads
Authors: D'Annessa Ilda , Sattin Sara , Tao Jiahui , Pennati Marzia , Sànchez‐Martìn Carlos , Moroni Elisabetta , Rasola Andrea , Zaffaroni Nadia , Agard David A. , Bernardi Anna , Colombo Giorgio
Published: February 2017

Allosteric compounds that stimulate Hsp90 adenosine triphosphatase (ATPase) activity were rationally designed, showing anticancer potencies in the low micromolar to nanomolar range. In parallel, the mode of action of these compounds was clarified and a quantitative model that links the dynamic ligand–protein cross‐talk to observed cellular and in vitro activities was developed. The results support the potential of using dynamics‐based approaches to develop original mechanism‐based cancer therapeutics.
Homometallic DyIII Complexes of Varying Nuclearity from 2 to 21: Synthesis, Structure, and Magnetism
Authors: Biswas Sourav , Das Sourav , Acharya Joydev , Kumar Vierandra , van Leusen Jan , Kögerler Paul , Herrera Juan Manuel , Colacio Enrique , Chandrasekhar Vadapalli
Published: February 2017

The synthesis, structure, and magnetic properties of four DyIII coordination compounds isolated as [Dy2(LH2)2(μ2‐η1:η1‐Piv)]Cl⋅2 MeOH⋅H2O (1), [Dy4(LH)2(μ3‐OH)2(Piv)4(MeOH)2]⋅4 MeOH⋅2 H2O (2), [Dy6(LH2)3(tfa)3(O3PtBu)(Cl)3]Cl4⋅15.5 H2O⋅4 MeOH⋅5 CHCl3 (3) and [Dy21(L)7(LH)7(tfa)7]Cl7⋅15 H2O⋅7 MeOH⋅12 CHCl3 (4) are reported (Piv=pivalate, tfa=1,1,1‐trifluoroacetylacetone, O3PtBu=tert‐butylphosphonate). Among these, 3 displays an equilateral triangle topology with a side length of 9.541 Å and a rare pentagonal‐bipyramidal Dy3+ environment, whereas complex 4 exhibits a single‐stranded nanowheel structure with the highest nuclearity known for a homometallic lanthanide cluster structure. A tentative model of the dc magnetic susceptibility and the low‐temperature magnetization of compounds 1 and 2 indicates that the former exhibits weak ferromagnetic intramolecular exchange interaction between the Dy3+ ions, whereas in the latter both intramolecular ferromagnetic and antiferromagnetic magnetic exchange interactions are present. Compounds 1, 3, and 4 exhibit frequency‐dependent ac signals below 15 K at zero bias field, but without exhibiting any maximum above 2 K at frequencies up to 1400 Hz. The observed slow relaxation of the magnetization suggests that these compounds could exhibit single molecule magnet (SMM) behavior with either a thermal energy barrier for the reversal of the magnetization that is not high enough to block the magnetization above 2 K, or there exists quantum tunneling of the magnetization (QTM).
Radical‐Enabled Bicyclization Cascades of Oxygen‐Tethered 1,7‐Enynes Leading to Skeletally Diverse Polycyclic Chromen‐2‐ones
Authors: Jiang Bo , Li Jie , Pan Yuanyuan , Hao Wenjuan , Li Guigen , Tu Shujiang
Published: February 2017

Catalytic bicyclization cascades of oxygen‐tethered 1,7‐enynes with simple cycloalkanes or aryl sulfonhydrazides have been established via subsequent multiple C‐C bond‐forming events from alkynyl/alkenyl functions, delivering a series of densely functionalized tetracyclic chromen‐2‐ones in a functional‐group‐compatible manner. In the former, Fe‐catalyzed spiro‐bicyclization involves radical addition, 6‐exo‐dig cyclization, H‐abstraction and 5‐endo‐trig cyclization sequences under mild conditions, resulting in new spiro‐fused cyclopenta[c]chromen‐2‐ones via dual α,α‐C(sp3)‐H abstractions. The latter enables in‐situ sulfonylation and desulfonylation of oxygen‐tethered 1,7‐enynes to realize the construction of multiple C‐C bonds, thereby leading to the formation of naphtho[2,3‐c]chromen‐6‐ones.
Differential diagnosis of well‐differentiated squamous cell carcinoma from non‐neoplastic oral mucosal lesions: New cytopathologic evaluation method dependent on keratinization‐related parameters but not nuclear atypism
Authors: Hara Hitoshi , Misawa Tsuneo , Ishii Eri , Nakagawa Miki , Koshiishi Saki , Amemiya Kenji , Oyama Toshio , Tominaga Kazuya , Cheng Jun , Tanaka Akio , Saku Takashi
Published: February 2017

Background

The cytology of oral squamous cell carcinoma (SCC) is challenging because oral SCC cells tend to be well differentiated and lack nuclear atypia, often resulting in a false negative diagnosis. The purpose of this study was to establish practical cytological parameters specific to oral SCCs.

Methods

We reviewed 123 cases of malignancy and 53 of non‐neoplastic lesions of the oral mucosa, which had been diagnosed using both cytology and histopathology specimens. From those, we selected 12 SCC and 4 CIS cases that had initially been categorized as NILM to ASC‐H with the Bethesda system, as well as 4 non‐neoplastic samples categorized as LSIL or ASC‐H as controls, and compared their characteristic findings. After careful examinations, we highlighted five cytological parameters, as described in Results. Those 20 cytology samples were then reevaluated by 4 independent examiners using the Bethesda system as well as the 5 parameters.

Results

Five cytological features, (i) concentric arrangement of orangeophilic cells (indicating keratin pearls), (ii) large number of orangeophilic cells, (iii) bizarre‐shaped orangeophilic cells without nuclear atypia, (iv) keratoglobules, and (v) uneven filamentous cytoplasm, were found to be significant parameters. All malignant cases contained at least one of those parameters, while none were observed in the four non‐neoplastic cases with nuclear atypia. In reevaluations, the Bethesda system did not help the screeners distinguish oral SCCs from non‐neoplastic lesions, while use of the five parameters enabled them to make a diagnosis of SCC.

Conclusion

Recognition of the present five parameters is useful for oral SCC cytology. Diagn. Cytopathol. 2017;45:406–417. © 2017 Wiley Periodicals, Inc.
Cribriform adenocarcinoma of the minor salivary gland arising in the tonsil with metastasis to a cervical lymph node: A case report with description of fine needle aspiration cytology
Authors: Pagano Alexa , Dennis Katie
Published: February 2017

Cribriform adenocarcinoma of minor salivary gland (CAMSG) is a rare tumor of the head and neck. We report a case of a 70‐year‐old female who presented with a 4–5‐month history of a left neck mass. CT scan of the neck showed a left neck mass just inferior to the angle of the mandible and left tonsillar prominence. Fine‐needle aspiration (FNA) of the neck mass showed epithelial groups with focal cribriform architecture. The cells had round to oval nuclei and fine chromatin. The background contained scattered lymphocytes. A preliminary diagnosis of low grade adenocarcinoma with cribriform features metastatic to a lymph node was made. Subsequent biopsy of the tonsil mass showed a tumor with a combination of tubular, solid, and papillary architecture containing round to ovoid nuclei with very fine chromatin, consistent with cribriform adenocarcinoma of the minor salivary gland. Cribriform adenocarcinoma of minor salivary gland has a documented tendency to metastasize to cervical lymph nodes. Since this neoplasm can cytologically and histologically resemble other neoplasms of the head and neck, including polymorphous low‐grade adenocarcinoma (PLGA), papillary thyroid carcinoma (PTC), and occasionally adenoid cystic carcinoma, being aware of and familiar with the cytologic features of CAMSG on FNA smears is important for patient management. Diagn. Cytopathol. 2017;45:468–471. © 2017 Wiley Periodicals, Inc.
Pancreatic involvement by metastasizing neoplasms as determined by endoscopic ultrasound‐guided fine needle aspiration: A clinicopathologic characterization
Authors: Sekulic Miroslav , Amin Khalid , Mettler Tetyana , Miller Lizette K. , Mallery Shawn , Stewart Jimmie
Published: February 2017

Background

Pancreatic tumors often represent primary neoplasms, however organ involvement with metastatic disease can occur. The use of endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) to determine the underlying pathology provides guidance of clinical management.

Methods

25 cases were identified in a retrospective review of our institution's records from 2006 to 2016. Clinical parameters and prognosis are described.

Results

Metastatic lesions to the pancreas diagnosed by EUS‐FNA accounted for 4.2% of all pancreatic neoplastic diagnoses, each lesion had a median greatest dimension of 1.5 cm, were most often located in the head of the pancreas, and by EUS were typically hypoechoic masses with variably defined borders. Patients were of a median age of 64 years old at diagnosis of the metastatic lesion(s) and the mean interval from primary diagnosis to the diagnosis of metastasis to the pancreas was 58.7 months (95% confidence interval, CI, 35.4 to 82.0 months). The rates of 24‐month overall survival after diagnoses of metastatic renal cell carcinoma or all other neoplasms to the pancreas were 90% and 7% respectively. The origin of the neoplasms included the kidney (n = 10), colon (n = 4), ovary (n = 3), lung (n = 2), et al. Smear‐based cytomorphology, and a combination of histomorphology and immunohistochemical studies from cell block preparations showed features consistent with the neoplasm of derivation.

Conclusion

Metastases to the pancreas can be diagnosed via EUS‐FNA, with enough specimen to conduct immunohistochemical studies if necessary to delineate origin. The determination of metastatic disease to the pancreas alters management and prognosis of the patient. Diagn. Cytopathol. 2017;45:418–425. © 2017 Wiley Periodicals, Inc.
Increasing the linear dynamic range in LC–MS: is it valid to use a less abundant isotopologue?
Authors: Trobbiani Stephen , Stockham Peter , Scott Timothy
Published: February 2017

Liquid chromatography‐mass spectrometry (LC–MS) has quickly become the analytical method of choice in forensic toxicology laboratories due to its ability to detect a very wide range of compounds in a single analysis. One of the major limitations of LC–MS however, is a relatively limited linear dynamic range for quantitation. A new approach to combating this problem is to use the [+1M + H]+ isotope mass peak for quantitation, thereby reducing saturation at the detector and extending the linear range. This is particularly useful in full‐scan applications, such as quadrupole‐time‐of‐flight (QTOF) mass spectrometry, where the isotopic mass peaks are acquired as a matter of course. Due to the variation in abundance of naturally occurring isotopes for common elements, especially 13C, this technique has the potential to lead to additional quantitative error. Through a review of published isotope ratio mass spectrometry data, we have assessed this potential for error and found that it is likely to be less than 2% and unlikely to be more than 4%, although this may not apply to compounds containing high numbers of nitrogen or sulphur atoms. This additional potential error must be considered before using this technique as it may not be appropriate for all applications. We have deemed it fit for purpose for our application and demonstrate the applicability of this technique to a quantitative LC‐TOF method. © 2017 Commonwealth of Australia. Drug Testing and Analysis © 2017 John Wiley & Sons, Ltd.