bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and In Vitro Antiproliferative Activity of Amido and Amino Analogues of the Marine Alkaloid Isogranulatimide
Authors: Lavrard Hubert , Salvetti Béatrice , Mathieu Véronique , Rodriguez Frédéric , Kiss Robert , Delfourne Evelyne
Published: March 2015

Marine organisms have proven to be a promising source of new compounds with activity against tumor cell lines. Granulatimide and isogranulatimide are marine alkaloids that have been shown to inhibit checkpoint kinase 1 (Chk1), a key protein in the DNA damage response and an emerging target for anticancer therapeutics. Here, we describe the synthesis and preliminary evaluation of amido and amino analogues of isogranulatimide. The new derivatives were prepared in three steps from 2‐imidazol‐1‐yl‐1H‐indol‐5‐ylamine. Two of the compounds synthesized exhibited more potent in vitro antiproliferative activity (single‐digit micromolar concentration range), by at least one log of magnitude, than the natural product isogranulatimide when evaluated in six human tumor cell lines: non‐small‐cell lung cancer (A549), colon cancer (LoVo), breast cancer (MCF7), oligodendroglioma (Hs683), glioblastoma (U373), and melanoma (SKMEL28). The mechanism of action of these derivatives remains to be elucidated, given that they did not significantly inhibit Chk1, however these compounds are easily synthesized and exhibit potent anticancer activity and are thus worthy of further study.
Cognitive predictors of understanding treatment decisions in patients with newly diagnosed brain metastasis
Authors: Gerstenecker Adam , Meneses Karen , Duff Kevin , Fiveash John B. , Marson Daniel C. , Triebel Kristen L.
Published: March 2015

BACKGROUND

Medical decision‐making capacity is a higher‐order functional skill that refers to a patient's ability to make informed, sound decisions related to care and treatment. In a medical context, understanding is the most cognitively demanding consent standard and refers to a patient's ability to comprehend information to the extent that informed decisions can be made.

METHODS

The association between reasoning and cognition was examined using data from 41 patients with diagnosed brain metastasis. All diagnoses were made by a board‐certified radiation oncologist and were verified histologically. In total, 41 demographically matched, cognitively healthy controls were also included to aid in classifying patients with brain metastasis according to reasoning status (ie, intact or impaired).

RESULTS

Results indicate that measures of simple attention, verbal fluency, verbal memory, processing speed, and executive functioning were all associated with understanding, and that verbal memory and phonemic fluency were the primary cognitive predictors. Using these two primary predictors, equations can be constructed to predict the ability to understand treatment decisions in patients with brain metastasis.

CONCLUSIONS

Although preliminary, these data demonstrate how cognitive measures can estimate understanding as it relates to medical decision‐making capacities in these patients. Clinically, these findings suggest that poor verbal memory and expressive language function could serve as “red flags” for reduced consent capacity in this patient population, thus signaling that a more comprehensive medical decision‐making capacity evaluation is warranted. Cancer 2015;121:2013–2019. © 2015 American Cancer Society.
Luminescent Carbon Dots for Logic Operations in Two Phases
Authors: Sk Md Palashuddin , Sailapu Sunil Kumar , Chattopadhyay Arun
Published: March 2015

The front cover artwork is provided by the group of Prof. Arun Chattopadhyay (Indian Institute of Technology Guwahati, India). The cover picture depicts luminescent carbon dot based logic operations that occur in liquid media and the solid phase with organic molecules and metal ions as inputs. Read the full text of the article at 10.1002/cphc.201402747.
The successful binomium of multivariate strategies and electrophoresis for the Quality by Design separation of a class of drugs: the case of triptans
Authors: Pasquini Benedetta , Orlandini Serena , Del Bubba Massimo , Bertol Elisabetta , Furlanetto Sandra
Published: March 2015

Quality by Design (QbD) approach was followed having as analytical target profile the determination of different antimigraine drugs (seven triptans, TRP) available on the market. Multivariate strategies were used for defining the design space and solvent‐modified MEKC was the selected analytical method. The versatility of electrophoretic technique, allowing a fine modulation of experimental parameters, made it possible to define the design space (DS). The DS limited a suitable range of experimental parameters in which all possible combinations of variables led to an electrokinetic method able to determine all the considered analytes with a predefined quality. Design of experiments and risk analysis fully assisted the method development from the initial investigation of MEKC knowledge space to the DS definition and finally to the control strategy. Applying the working operative conditions, the baseline separation of TRP was obtained in less than 9 min. The method was finally used for the quantification of three TRP in different pharmaceutical products.
Microchip electrophoresis‐single wall carbon nanotube press‐transferred electrodes for fast and reliable electrochemical sensing of melatonin and its precursors
Authors: Gomez Federico José Vicente , Martín Aída , Silva María Fernanda , Escarpa Alberto
Published: March 2015

In the current work, single‐wall carbon nanotube press‐transferred electrodes (SW‐PTEs) were used for detection of melatonin (MT) and its precursors tryptophan (Trp) and serotonin (5‐HT) on microchip electrophoresis (ME). SW‐PTEs were simply fabricated by press transferring a filtered dispersion of single‐wall carbon nanotubes on a nonconductive PMMA substrate, where single‐wall carbon nanotubes act as exclusive transducers. The coupling of ME–SW‐PTEs allowed the fast detection of MT, Trp, and 5‐HT in less than 150 s with excellent analytical features. It exhibited an impressive antifouling performance with RSD values of ≤2 and ≤4% for migration times and peak heights, respectively (n = 12). In addition, sample analysis was also investigated by analysis of 5‐HT, MT, and Trp in commercial samples obtaining excellent quantitative and reproducible recoveries with values of 96.2 ± 1.8%, 101.3 ± 0.2%, and 95.6 ± 1.2% for 5‐HT, MT, and Trp, respectively. The current novel application reveals the analytical power of the press‐transfer technology where the fast and reliable determination of MT and its precursors were performed directly on the nanoscale carbon nanotube detectors without the help of any other electrochemical transducer.
Development of a toxicogenomics signature for genotoxicity using a dose‐optimization and informatics strategy in human cells
Authors: Li Heng‐Hong , Hyduke Daniel R. , Chen Renxiang , Heard Pamela , Yauk Carole L. , Aubrecht Jiri , Fornace Albert J.
Published: March 2015

The development of in vitro molecular biomarkers to accurately predict toxicological effects has become a priority to advance testing strategies for human health risk assessment. The application of in vitro transcriptomic biomarkers promises increased throughput as well as a reduction in animal use. However, the existing protocols for predictive transcriptional signatures do not establish appropriate guidelines for dose selection or account for the fact that toxic agents may have pleiotropic effects. Therefore, comparison of transcriptome profiles across agents and studies has been difficult. Here we present a dataset of transcriptional profiles for TK6 cells exposed to a battery of well‐characterized genotoxic and nongenotoxic chemicals. The experimental conditions applied a new dose optimization protocol that was based on evaluating expression changes in several well‐characterized stress‐response genes using quantitative real‐time PCR in preliminary dose‐finding studies. The subsequent microarray‐based transcriptomic analyses at the optimized dose revealed responses to the test chemicals that were typically complex, often exhibiting substantial overlap in the transcriptional responses between a variety of the agents making analysis challenging. Using the nearest shrunken centroids method we identified a panel of 65 genes that could accurately classify toxicants as genotoxic or nongenotoxic. To validate the 65‐gene panel as a genomic biomarker of genotoxicity, the gene expression profiles of an additional three well‐characterized model agents were analyzed and a case study demonstrating the practical application of this genomic biomarker‐based approach in risk assessment was performed to demonstrate its utility in genotoxicity risk assessment. Environ. Mol. Mutagen. 56:505–519, 2015. © Wiley Periodicals, Inc.
Dendritic cell‐based autologous tumor vaccines for head and neck squamous cell carcinoma
Authors: Whiteside Theresa L. , Ferris Robert L. , Szczepanski Miroslaw , Tublin Mitchell , Kiss Joseph , Johnson Rita , Johnson Jonas T.
Published: March 2015

Background

An autologous vaccine of apoptotic tumor cells (ATCs) and dendritic cells (DCs) was administered to patients with stage III/IV head and neck squamous cell carcinoma (HNSCC) to study safety and feasibility.

Methods

Autologous DCs were generated from monocytes, loaded with ATCs, and delivered intranodally. Delayed‐type hypersensitivity (DTH) and immunological endpoints were measured prevaccination and postvaccination. Clinical follow‐up was required.

Results

Tumors obtained from 30 patients yielded 2 × 106 to 2 × 108 tumor cells. Only 19 of 30 (63%) were sterile. Ten of 30 patients (33%) had ≥1 × 107 sterile tumor cells required for vaccine production. Eight of 10 patients had positive recall DTH. Five of 10 patients were leukapheresed to generate DCs. Four of 5 patients were vaccinated. ATC‐reactive T cells were detected in 3 of 4 patients. All 4 patients survived >5 years. The trial failed to enroll the projected 12 patients and was terminated.

Conclusion

This vaccine was safe and immunogenic but feasible only in patients with HNSCC with positive prevaccine DTH and ≥1 × 107 sterile tumor cells. All vaccinated patients were long‐term disease‐free survivors. © 2015 Wiley Periodicals, Inc. Head Neck 38: E494–E501, 2016
Possible Impact of RET Polymorphism and Its Haplotypic Association Modulates the Susceptibility to Thyroid Cancer
Authors: Khan Mosin S. , Pandith Arshad A. , Iqbal Mohammad , Naykoo Niyaz A. , Khan Shoukat H. , Rather Tanveer A. , Mudassar Syed
Published: March 2015

Rearranged during Transfection (RET) gene polymorphisms act to influence thyroid cancer in a polygenic and low‐penetrance manner and no study regarding RET alterations in thyroid cancer has undergone from this part of the world (North India). We evaluated RET G691S (rs1799939), L769L (rs1800861), and S904S (rs1800863) polymorphisms to elucidate their possible role as risk factors in papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC). Polymorphic analysis of RET gene was performed by polymerase chain reaction (PCR), followed by restriction fragment length polymorphism (RFLP). In RET G691S polymorphism, the overall distribution of variant alleles (GA + AA) in cases was 62.9% as against 44.5% in controls (P < 0.05) whereas frequency of RET L769L variant alleles (TG + GG) in cases was 70% versus 88% in controls (P < 0.05). In RET S904S, frequency of variant alleles (CG + GG) in cases was 56% versus 44% in controls (P < 0.05). Interestingly, G691S/L769L variant showed increased risk for the non‐smokers (P < 0.05). RET S904S variant showed association with benign thyroid disease as against those with no history. The over‐representation of homozygotes in G691S and L769L polymorphic variants was not observed, which suggest a “Dominant mode of inheritance.” The S904S polymorphism heterozygote lies almost in the middle of the two homozygotes confirming an “Additive mode of inheritance.” In conclusion, RET gene G691S/S904S polymorphisms were over‐represented and L769L polymorphism was under‐represented in PTC and FTC patients. RET polymorphic variants could act synergistically in the development or progression of PTC and FTC. J. Cell. Biochem. 116: 1712–1718, 2015. © 2015 Wiley Periodicals, Inc.
Photoactivation of Akt1/GSK3β Isoform‐Specific Signaling Axis Promotes Pancreatic β‐Cell Regeneration
Authors: Huang Lei , Jiang Xiaoxiao , Gong Longlong , Xing Da
Published: March 2015

Promotion of insulin‐secreting β‐cell regeneration in patients with diabetes is a promising approach for diabetes therapy, which can contribute to rescue the uncontrolled hyperglycemia. Low‐power laser irradiation (LPLI) has been demonstrated to regulate multiple physiological processes both in vitro and in vivo through activation of various signaling pathways. In the present study, we showed that LPLI promoted β‐cell replication and cell cycle progression through activation of Akt1/GSK3β isoform‐specific signaling axis. Inhibition of PI3‐K/Akt or GSK3 with specific inhibitors dramatically reduced or increased LPLI‐induced β‐cell replication, revealing Akt/GSK3 signaling axis was involved in β‐cell replication and survival upon LPLI treatment. Furthermore, the results of shRNA‐mediated knock down of Akt/GSK3 isoforms revealed that Akt1/GSK3β isoform‐specific signaling axis regulated β‐cell replication and survival in response to LPLI, but not Akt2/GSK3α. The mechanism by which LPLI promoted β‐cell replication through Akt1/GSK3β signaling axis involved activation of β‐catenin and down‐regulation of p21. Taken together, these observations suggest that Akt1/GSK3β isoform signaling axis play a key role in β‐cell replication and survival induced by LPLI. Moreover, our findings suggest that activation of Akt1/GSK3β isoform signaling axis by LPLI may provide guidance in practical applications for β‐cell regenerative therapies. J. Cell. Biochem. 116: 1741–1754, 2015. © 2015 Wiley Periodicals, Inc.
Transcription Factor Tfe3 Directly Regulates Pgc‐1alpha in Muscle
Authors: Salma Nunciada , Song Jun S. , Arany Zoltan , Fisher David E.
Published: March 2015

The microphthalmia (MiT) family of transcription factors is an important mediator of metabolism. Family members Mitf and Tfeb directly regulate the expression of the master regulator of metabolism, peroxisome‐proliferator activated receptor gamma coactivator‐1 alpha (Pgc‐1alpha), in melanomas and in the liver, respectively. Pgc‐1alpha is enriched in tissues with high oxidative capacity and plays an important role in the regulation of mitochondrial biogenesis and cellular metabolism. In skeletal muscle, Pgc‐1alpha affects many aspects of muscle functionally such as endurance, fiber‐type switching, and insulin sensitivity. Tfe3 also regulates muscle metabolic genes that enhance insulin sensitivity in skeletal muscle. Tfe3 has not yet been shown to regulate Pgc‐1alpha expression. Our results reported here show that Tfe3 directly regulates Pgc‐1alpha expression in myotubes. Tfe3 ectopic expression induces Pgc‐1alpha, and Tfe3 silencing suppresses Pgc‐1alpha expression. This regulation is direct, as shown by Tfe3's binding to E‐boxes on the Pgc‐1alpha proximal promoter. We conclude that Tfe3 is a critical transcription factor that regulates Pgc‐1alpha gene expression in myotubes. Since Pgc‐1alpha coactivates numerous biological programs in diverse tissues, the regulation of its expression by upstream transcription factors such Tfe3 implies potential opportunities for the treatment of diseases where modulation of Pgc‐1alpha expression may have important clinical outcomes. J. Cell. Physiol. 230: 2330–2336, 2015. © 2015 Wiley Periodicals, Inc.
Fluorescent dye incorporation causes weakened gene association and intracellular aggregate formation in nonviral carriers
Authors: Foster Abbygail A. , Ross Nikki L. , Sullivan Millicent O.
Published: March 2015

Background

The successful application of nonviral gene transfer technologies requires both improved understanding and control with respect to intracellular trafficking and release. However, the intracellular space is highly complex and hence well‐defined, stable structures are necessary to probe the stages of the delivery pathway. Fluorescent labeling is a regularly used approach to monitor nonviral delivery and release, yet few studies investigate the effects of label incorporation on the structure and activity of gene‐containing vehicles.

Methods

In the present study, the impacts of label incorporation on the assembly and gene transfer capacity of DNA polyplexes were determined through the utilization of a model DNA‐polyethylenimine (PEI) delivery system. PEI was fluorescently labeled with the Oregon Green® dye prior to polyplex formation and delivery to CHO‐K1 cells.

Results

The present study provides evidence showing that routine labeling strategies for polyplexes weakened DNA binding affinity, produced large quantities of extracellular structures and significantly increased intracellular polyplex aggregation. Additionally, cellular internalization studies showed that increased labeling fractions led to reductions in polyplex uptake as a result of weakened complexation.

Conclusions

These results not only provide insight into the assembly of these structures, but also help to identify labeling strategies sufficient to preserve activity at the same time as enabling detailed studies of trafficking and disassembly. Copyright © 2015 John Wiley & Sons, Ltd.
Heterocyclic amines. A convenient synthesis of 3,5‐diamino‐1,2,4‐triazine derivatives
Authors: Settepani Joseph A. , Bořkovec A. B.
Published: March 2015

A facile synthesis of 3, 5‐diamino‐1, 2,4‐triazines (I) via condensations in acidic media of acylnitriles with aminoguanidine and subsequent base‐catalyzed cyclization of the resulting acylnitrile amidinohydrazones (IV) is described.
High‐frequency modeling of Cu‐graphene heterogeneous interconnects
Authors: Zhao Wen‐Sheng , Zhang Rui , Fang Yuan , Yin Wen‐Yan , Wang Gaofeng , Kang Kai
Published: March 2015

One novel interconnect scheme consisting of both Cu and graphene sheet is proposed in this paper, with the advantages of both materials exploited greatly. It is shown that the introduction of graphene layers in such heterogeneous interconnect scheme can reduce its effective resistance and thereby improve its transmission performance. On the other hand, it is also demonstrated that both coated and double‐coated structures possess better electrical performance than that of the sandwich one at high frequencies, because the graphene is placed at the interconnect surface where current is crowded. With the help of Partial Element Equivalent Circuit method, together with equivalent circuit technique, the transmission characteristics of some Cu‐graphene interconnects are captured and compared with that of Cu wire, and the advantages of such heterogeneous interconnects can be enlarged with the advanced technology. Copyright © 2015 John Wiley & Sons, Ltd.
Morphology Control in Biphasic Hybrid Systems of Semiconducting Materials
Authors: Mathias Florian , Fokina Ana , Landfester Katharina , Tremel Wolfgang , Schmid Friederike , Char Kookheon , Zentel Rudolf
Published: March 2015

Simple blends of inorganic nanocrystals and organic (semiconducting) polymers usually lead to macroscopic segregation. Thus, such blends typically exhibit inferior properties than expected. To overcome the problem of segregation, polymer coated nanocrystals (nanocomposites) have been developed. Such nanocomposites are highly miscible within the polymer matrix. In this Review, a summary of synthetic approaches to achieve stable nanocomposites in a semiconducting polymer matrix is presented. Furthermore, a theoretical background as well as an overview concerning morphology control of inorganic NCs in polymer matrices are provided. In addition, the morphologic behavior of highly anisotropic nanoparticles (i.e. liquid crystalline phase formation of nanorod‐composites) and branched nanoparticles (spatial orientation of tetrapods) is described. Finally, the morphology requirements for the application of inorganic/organic hybrid systems in light emitting diodes and solar cells are discussed, and potential solutions to achieve the required morphologies are provided.

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Superovulation induces alterations in the epigenome of zygotes, and results in differences in gene expression at the blastocyst stage in mice
Authors: Huffman Sarah Rose , Pak Youngju , Rivera Rocío Melissa
Published: March 2015

Gamete and embryo manipulations can result in alterations to the epigenome, and are associated with altered gene expression. The initial objective of this study was to determine the transcript level of several epigenetic modifiers in embryos that had been cultured from the 2‐cell stage until the late‐blastocyst stage in four culture conditions. Cultured embryos were compared to control, in vivo‐produced late blastocysts to ascertain if differences in gene expression existed among the culture conditions; none were observed. As all of the embryos used were produced in females that had undergone superovulation, we next compared the transcript level of the same epigenetic modifiers between superovulated, in vivo‐produced embryos and embryos produced from natural ovulation. Following in vitro culturing, expression of the genes analyzed was increased in all superovulation groups. We therefore hypothesized that the superovulation procedure—used to increase the number of embryos obtained for experimentation—may have caused an inappropriate acquisition of epigenetic modifications in the maternal genome prior to ovulation, which in turn caused misexpression of genes at the blastocyst stage. To test this hypothesis, we compared the level of global DNA methylation and histone 3 lysine‐9 or ‐14 acetylation in zygotes obtained by natural‐ or superovulation. Indeed, superovulation decreased global DNA methylation on the maternal pronucleus of zygotes, which inversely correlated with H3K9/14 acetylation. In conclusion, superovulation alters the epigenome of the oocyte, resulting in the dysregulation of gene expression at the blastocyst stage. Mol. Reprod. Dev. 82: 207–217, 2015. © 2015 Wiley Periodicals, Inc.
Rotating frame relaxation imaging of prostate cancer: Repeatability, cancer detection, and Gleason score prediction
Authors: Jambor Ivan , Pesola Marko , Taimen Pekka , Merisaari Harri , Boström Peter J. , Minn Heikki , Liimatainen Timo , Aronen Hannu J.
Published: March 2015

Purpose

To investigate relaxation along a fictitious field (RAFF) and continuous wave (cw) T1ρ imaging of prostate cancer (PCa) in the terms of repeatability, PCa detection, and characterization.

Methods

Thirty‐six patients (PSA 11.6 ± 7.6 ng/mL, mean ± standard deviation) with histologically confirmed PCa underwent two repeated 3T MR examinations using surface array coils before prostatectomy. Relaxation along fictitious field, cw T1ρ, and T2 relaxation times (TRAFF, T1ρcw, T2) were measured and averaged over regions of interest placed in PCa, normal peripheral zone (PZ), and normal central gland (CG) positioned using whole‐mount prostatectomy sections and anatomical T2‐weighted images. Receiver operating characteristic curve analysis with area under the curve (AUC) was calculated to distinguish PCa from PZ/CG and PCa with Gleason score (GS) of 3+3 from GS of 3+4/≥3+4.

Results

TRAFF and T1ρcw relaxation times were repeatable with coefficients of repeatability as a percentage of median value in the range of 7.8–23.2%. AUC (mean, 95% confidence interval) in the differentiation of PCa with GS of 3+3 from PCa with CS of ≥3+4 were 0.88 (0.72–0.99), 0.69 (0.46–0.90), and 0.68 (0.45–0.88), for TRAFF, T1ρcw, and T2, respectively.

Conclusion

In quantitative region of interest based analysis, TRAFF outperformed T1ρcw and T2 in PCa detection and characterization. Magn Reson Med 75:337–344, 2016. © 2015 Wiley Periodicals, Inc.
The impact of demand uncertainty on product line design under endogenous substitution
Authors: Rong Ying , Chen Ying‐Ju , Shen Zuo‐Jun Max
Published: March 2015

The existing product line design literature devotes little attention to the effect of demand uncertainty. Due to demand uncertainty, the supply‐demand mismatch is inevitable which leads to different degrees of lost sales depending on the configuration of product lines. In this article, we adopt a stylized two‐segment setup with uncertain market sizes and illustrate the interplay between two effects: risk pooling that mitigates the impact of demand uncertainty and market segmentation that facilitates consumer differentiation. Compared to downward substitution, inducing bidirectional substitution through product line decisions including quality levels and prices can yield greater risk pooling effects. However, we show that the additional benefit from the risk pooling effect cannot compensate for the reduced market segmentation effect. We demonstrate that the presence of demand uncertainty can reduce the benefit of market segmentation and therefore the length of product lines in terms of the difference between products. We also propose three heuristics that separate product line and production decisions; each of these heuristics corresponds to one particular form of demand substitution. Our numerical studies indicate that the best of the three heuristics yields performance that is close to optimality. © 2015 Wiley Periodicals, Inc. Naval Research Logistics 62: 143–157, 2015
Partially penalized immersed finite element methods for parabolic interface problems
Authors: Lin Tao , Yang Qing , Zhang Xu
Published: March 2015

We present partially penalized immersed finite element methods for solving parabolic interface problems on Cartesian meshes. Typical semidiscrete and fully discrete schemes are discussed. Error estimates in an energy norm are derived. Numerical examples are provided to support theoretical analysis. © 2015 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 31: 1925–1947, 2015
Proteomic and network analysis of proteins regulated by REX1 in human embryonic stem cells
Authors: Son Mi‐Young , Kwak Jae Eun , Kim Young‐Dae , Cho Yee Sook
Published: March 2015

Recent studies have suggested that REX1 (reduced expression 1) plays an important role in pluripotency, proliferation, and differentiation. However, the molecular mechanisms involved in REX1‐dependent regulation of diverse cellular processes remain unclear. To elucidate the regulatory functions of REX1 in human embryonic stem cells (hESCs), comparative proteomic analysis was performed on REX1 RNAi specifically silenced hESCs. Analysis of the proteome via nano‐LC‐MS/MS identified 140 differentially expressed proteins (DEPs) displaying a >2‐fold difference in expression level between control and REX1 knockdown (KD) hESCs, which were then compared with transcriptome data and validated by quantitative real‐time RT‐PCR and Western blotting. These DEPs were analyzed by GO, pathway, and functional clustering analyses to determine the molecular functions of the proteins and pathways regulated by REX1. The REX1 KD‐mediated DEPs mapped to major biological processes involved in the regulation of ribosome‐mediated translation and mitochondrial function. Functional network analysis revealed a highly interconnected network among these DEPs and indicated that these interconnected proteins are predominantly involved in translation and the regulation of mitochondrial organization. These findings regarding REX1‐mediated regulatory network have revealed the contributions of REX1 to maintaining the status of hESCs and have improved our understanding of the molecular events that underlie the fundamental properties of hESCs.
Orientation control in nanoparticle filled block copolymer cold zone annealed films
Authors: Samant Saumil , Hailu Shimelis T. , Al‐Enizi Abdullah M. , Karim Alamgir , Raghavan Dharmaraj
Published: March 2015

Nanoparticles provide an attractive route to modifying polymer thin film properties, yet controlling the dispersion and morphology of functionalized nanoparticle filled films is often difficult. Block copolymers can provide an ideal template for directed assembly of nanoparticles under controlled nanoparticle‐polymer interactions. Previously we observed that neat films of cylinder forming poly(styrene‐b‐methyl methacrylate) PS‐b‐PMMA block copolymer (c‐BCP) orient vertically with dynamic sharp thermal cold zone annealing (CZA‐S) over wide range of CZA‐S speed (0.1–10) μm/s. Here, we introduce a low concentration (1–5 wt %) of nanoparticles of phenolic group functionalized CdS (fCdS‐NP), to PMMA cylinder forming polystyrene‐b‐poly (methyl methacrylate) block copolymer (c‐BCP) films. Addition of the fCdS‐NP induces a vertical to horizontal orientation transition at low CZA‐S speed, V = 5 μm/s. The orientation flip studies were analyzed using AFM and GISAXS. These results confirm generality of our previously observed orientation transition in c‐BCP under low speed CZA‐S with other nanoparticles (gold [Au‐NP], fulleropyrrolidine [NCPF‐NP]) in the same concentration range, but reveal new aspects not previously examined: (1) A novel observation of significant vertical order recovery from 5–10% vertical cylindrical fraction at V = 5 μm/s to 46–63% vertical cylindrical fraction occurring at high CZA‐S speed, V = 10 μm/s for the fCdS nanoparticle filled films. (2) We rule out the possibility that a nanoparticle wetting layer on the substrate is responsible for the vertical to horizontal flipping transition. (3) We demonstrate that the orientation flipping results can be achieved in a nanoparticle block copolymer system where the nanoparticles are apparently better‐dispersed within only one (matrix PS) domain unlike our previous nanoparticle system studied. We consider facile processing conditions to fabricate functionalized nanoparticles filled PS‐PMMA block copolymer films with controlled anisotropy, a useful strategy in the design of next generation electronic and photonic materials. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2015, 53, 604–614
Surface photovoltage behavior of GaN columns
Authors: Deeb Manal Ali , Wei Jiandong , Hartmann Jana , Wehmann Hergo‐Heinrich , Waag Andreas
Published: March 2015

GaN columns are grown by metal organic vapor phase epitaxy (MOVPE) with a high silane flow, which often leads to rough sidewalls and related problems during a subsequent shell overgrowth by e.g., InGaN/GaN quantum wells. In order to get more information on the surface of GaN columns before overgrowth, surface photovoltage (SPV) measurements have been performed by photo‐assisted Kelvin probe force microscopy (KPFM) before and after chemical etching of the surface. Its electronic properties are demonstrated to be influenced by the silane injection during the samples' growth. Distinct differences are shown in the SPV behavior of GaN columns before and after etching with phosphoric acid. SPV decreases before etching, whereas after etching it increases like that on GaN bulk material. Silicon related surface states introduced during the growth are considered as the origin of the SPV behavior of the as grown samples. The change of this behavior after etching is attributed to the removal of the Si containing surface coating. Our investigations not only show the important role of silane injection during the growth on the SPV behavior of GaN columns, but it also reveals that the photo‐assisted KPFM technique is an easy and quick method to analyze surfaces.
Context and Implications Document for: Who you know, what you know and knowing the ropes: a review of evidence about access to higher education institutions in England
Authors: Whitty Geoff , Hayton Annette , Tang Sarah
Published: March 2015

This guide accompanies the following article: G. Whitty, A. Hayton and S. Tang. Who you know, what you know and knowing the ropes: a review of evidence about access to higher education institutions in England. Review of Education, DOI:10.1002/rev3.3038
Comparative evaluation of root canal preparations of maxillary first molars with self‐adjusting file, reciproc single file, and revo‐s rotary file: A micro‐computed tomography study
Authors: Ahmetoglu Fuat , Keles Ali , Simsek Neslihan , Ocak M.Sinan , Yologlu Saim
Published: March 2015

This study was aimed to use micro‐computed tomography (μ‐CT) to evaluate the canal shaping properties of three nickel‐titanium instruments, Self‐Adjusting File (SAF), Reciproc, and Revo‐S rotary file, in maxillary first molars. Thirty maxillary molars were scanned preoperatively by using micro‐computed tomography (μ‐CT) scans at 13,68 μm resolution. The teeth were randomly assigned to three groups (n = 10). The root canals were shaped with SAF, Reciproc, and Revo‐S, respectively. The shaped root canals were rescanned. Changes in canal volumes and surface areas were compared with preoperative values. The data were analyzed using Kruskal‐Wallis and Conover's post hoc tests, with p < .05 denoting a statistically significant difference. Preoperatively canal volumes and surface area were statistically similar among the three groups (p > .05). There were statistically significant differences in all measures comparing preoperative and postoperative canal models (p = 0.0001). These differences occurred after instrumentation among the three experimental groups showed no statistically significant difference for volume (p > .05). Surface area showed the similar activity in buccal canals in each of the three techniques whereas no statistically significant difference was detected among surface area, the SAF, and the Revo‐S in the palatal (P) canal. Each of three shaping system showed the similar volume activity in all canals, but SAF and Revo‐S provided more effectively root planning in comparison with Reciproc in P canal. SCANNING 37:218–225, 2015. © 2015 Wiley Periodicals, Inc.
Signal transduction in inherited metabolic disorders: a model for a possible pathogenetic mechanism
Authors: Boneh Avihu
Published: March 2015

Signal transduction is the process by which external or internal signals exert their intracellular biological effects and by which intracellular communication is regulated. An important component of the signalling pathway is the second messenger, which is produced upon stimulation of the cell and mediates its effects downstream through phosphorylation and dephosphorylation of target proteins. Intracellular accumulation or deficiency of metabolites that serve as second messengers, due to inborn errors of their metabolism, may lead to perturbation of signalling pathways and disruption of the balance between them, serving as a missing link between the genotype, biochemical phenotype and clinical phenotype. The main second messengers that are putatively associated with the pathogenesis of IEM are ‘bioactive lipids’ (complex lipids and long‐chain fatty acids), ‘calcium’, ‘stress’ (osmotic, reactive oxygen/nitorgen species, misfolded proteins and others) and ‘metabolic’ (AMP/ATP ratio, leucine, glutamine). They act through protein kinase C, calcium dependent kinases (CamK) and phosphatase (CN), ‘stress‐mediated’ kinases (MAPK) and AMP/ATP‐dependent kinase (AMPK). These signalling pathways lead to cell proliferation, inflammatory response, autophagy (and mitophagy) and apoptosis, suggesting that there are only few final common pathways involved in this pathogenetic mechanism. Questions remain regarding the complexity of the effects of the accumulating metabolites on different signalling pathways, and regarding the relative role and origin of ‘proxy’ second messengers such as reactive oxygen species. A better understanding of the signalling pathways in IEM may enhance the development of novel therapies in situations where normalising intracellular concentrations of the second messenger is impossible or impractical.
Identification of minimum Rpn4‐responsive elements in genes related to proteasome functions
Authors: Shirozu Ryohei , Yashiroda Hideki , Murata Shigeo
Published: March 2015

The proteasome is an essential, 66‐subunit protease that mediates ubiquitin‐dependent proteolysis. The transcription factor Rpn4 regulates concerted expression of proteasome subunits to increase the proteasome by recognizing nonamer proteasome‐associated control element (PACE) elements on the promoter regions. However, the genes for proteasome assembly chaperones and some of the subunits have no PACEs. Here we identified a minimal hexamer “PACE‐core” sequence that responds to Rpn4. PACE‐cores are found in many genes related to proteasome function including the assembly chaperones, but cannot substitute for PACE of the subunits. Our results add a new layer of complexity in transcriptional regulation of genes involved in protein degradation.
Improved O2‐tolerance in variants of a H2‐evolving [NiFe]‐hydrogenase from Klebsiella oxytoca HP1
Authors: Huang Gang-Feng , Wu Xiao-Bing , Bai Li-Ping , Liu Ke , Jiang Li-Jing , Long Min-Nan , Chen Qing-Xi
Published: March 2015

In this study, we investigated the mechanism of O2 tolerance of Klebsiella oxytoca HP1 H2‐evolving hydrogenase 3 (KHyd3) by mutational analysis and three‐dimensional structure modeling. Results revealed that certain surface amino acid residues of KHyd3 large subunit, in particular those at the outer entrance of the gas channel, have a visible effect on its oxygen tolerance. Additionally, solution pH, immobilization and O2 partial pressure also affect KHyd3 O2‐tolerance to some extent. We propose that the extent of KHyd3 O2‐tolerance is determined by a balance between the rate of O2 access to the active center through gas channels and the deoxidation rate of the oxidized active center. Based on our findings, two higher O2‐tolerant KHyd3 mutations G300E and G300M were developed.
The histone acetyltransferase Myst2 regulates Nanog expression, and is involved in maintaining pluripotency and self‐renewal of embryonic stem cells
Authors: Kim Min Seong , Cho Hye In , Park Su Hyung , Kim Joo Hyuk , Chai Young Gyu , Jang Yeun Kyu
Published: March 2015

The histone acetyltransferase Myst2 plays an important role in embryogenesis, but its function in undifferentiated ES cells remains poorly understood. Here, we show that Myst2 plays a role in pluripotency and self‐renewal of ES cells. Myst2 deficiency results in loss of characteristic morphology, decreased alkaline phosphatase staining and reduced histone acetylation, as well as aberrant expression of pluripotency and differentiation markers. Our ChIP data reveal a direct association of Myst2 with the Nanog promoter and Myst2‐dependent Oct4 binding on the Nanog promoter. Together our data suggest that Myst2‐mediated histone acetylation may be required for recruitment of Oct4 to the Nanog promoter, thereby regulating Nanog transcription in ES cells.
Acquiring snapshots of the orientation of trans‐membrane protein domains using a hybrid FRET pair
Authors: Gahl Robert F. , Tekle Ephrem , Zhu Gefei Alex , Taraska Justin W. , Tjandra Nico
Published: March 2015

One challenge in studying the function of membrane‐embedded proteins is determining the orientation of key domains in the context of the changing and dynamic membrane environment. We describe a confocal microscopy setup that utilizes external electric field pulses to direct dipicrylamine (DPA) to a membrane leaflet. The detection of FRET between DPA and a fluorescent probe attributes it to the inner or outer leaflet of a membrane. By utilizing short acquisition times and confocal imaging, this attribution could be made even in changing membrane environments. Our setup adds versatility to the study of the biological activity of membrane‐embedded proteins.
The Perennial Problem of Variability In Adenosine Triphosphate (ATP) Tests for Hygiene Monitoring Within Healthcare Settings
Authors: Whiteley Greg S. , Derry Chris , Glasbey Trevor , Fahey Paul
Published: March 2015

OBJECTIVE

To investigate the reliability of commercial ATP bioluminometers and to document precision and variability measurements using known and quantitated standard materials.

METHODS

Four commercially branded ATP bioluminometers and their consumables were subjected to a series of controlled studies with quantitated materials in multiple repetitions of dilution series. The individual dilutions were applied directly to ATP swabs. To assess precision and reproducibility, each dilution step was tested in triplicate or quadruplicate and the RLU reading from each test point was recorded. Results across the multiple dilution series were normalized using the coefficient of variation.

RESULTS

The results for pure ATP and bacterial ATP from suspensions ofStaphylococcus epidermidisandPseudomonas aeruginosaare presented graphically. The data indicate that precision and reproducibility are poor across all brands tested. Standard deviation was as high as 50% of the mean for all brands, and in the field users are not provided any indication of this level of imprecision.

CONCLUSIONS

The variability of commercial ATP bioluminometers and their consumables is unacceptably high with the current technical configuration. The advantage of speed of response is undermined by instrument imprecision expressed in the numerical scale of relative light units (RLU).

Infect Control Hosp Epidemiol2015;00(0):1–6
Mixed convection in a periodically heated channel
Authors: Hossain M. Z. , Floryan J. M.
Published: March 2015

Mixed convection in a channel with flow driven by a pressure gradient and subject to spatially periodic heating along one of the walls has been studied. The pattern of the heating is characterized by the wavenumber${\it\alpha}$and its intensity is expressed in terms of the Rayleigh number$\mathit{Ra}_{p}$. The primary convection has the form of counter-rotating rolls with the wavevector parallel to the wavevector of the heating. The resulting net heat flow between the walls increases proportionally to$\mathit{Ra}_{p}$but the growth saturates when$\mathit{Ra}_{p}=O(10^{3})$. The most effective heating pattern corresponds to${\it\alpha}\approx 1$, as this leads to the most intense transverse motion. The primary convection is subject to transition to secondary states with the onset conditions depending on${\it\alpha}$. The conditions leading to transition between different forms of secondary motion have been determined using the linear stability theory. Three patterns of secondary motion may occur at small Reynolds numbers$\mathit{Re}$, i.e. longitudinal rolls, transverse rolls and oblique rolls, with the critical conditions varying significantly as a function of${\it\alpha}$. An increase of${\it\alpha}$leads to the elimination of the longitudinal rolls and, eventually, to the elimination of the oblique rolls, with the transverse rolls assuming the dominant role. For large${\it\alpha}$, the transition is driven by the Rayleigh–Bénard mechanism; while for${\it\alpha}=O(1)$, the spatial parametric resonance dominates. The global flow characteristics are identical regardless of whether the heating is applied at the lower or the upper wall.
Contingencies between verbs, body parts, and argument structures in maternal and child speech: a corpus study
Authors: MAOUENE JOSITA C. , SETHURAMAN NITYA , MAOUENE MOUNIR M. , OTIENO SANGO
Published: March 2015

abstract

Prior work on argument structure development has shown connections between abstract verb meaning and argument structure; neuroimaging and behavioral studies have shown connections between verb meaning and body effectors. Here we examine the contingencies between verbs, their most likely body region pairing, and argument structure. We ask whether the verbs used in six common syntactic frames are specifically linked to one of three main regions of the body:head, arm, leg.The speech of 20-month-olds (N= 67), 28-month-olds (N= 27), and their mothers (N= 54) (CHILDES: MacWhinney, 2000) was examined for the use of early-learned verbs (MCDI: Fenson, Dale, Reznick, Bates, Thal, & Pethick, 1994). In total, 89 verb types in 3321 utterances were coded for their associations with thehead, arm, andlegbody regions (associations taken from Maouene, Hidaka, & Smith, 2008). Significant non-random relations are found both overall and for each age group in analyses using multiple chi-square tests of independence and goodness-of-fit. These results are discussed in terms of their relevance for both argument structure development and embodied cognition, as evidence supporting a developmental path that has not been previously examined, in which the infant can use early and concrete perception-action information to learn later abstract syntactic achievements.
Competing for Transparency: Political Competition and Institutional Reform in Mexican States
Authors: BERLINER DANIEL , ERLICH AARON
Published: March 2015

Why do political actors undertake reforms that constrain their own discretion? We argue that uncertainty generated by political competition is a major driver of such reforms, and test this argument using subnational data on Mexican states’ adoption of state-level access to information (ATI) laws. Examining data from 31 Mexican states plus the Federal District, we find that more politically competitive states passed ATI laws more rapidly, even taking into account the party in power, levels of corruption, civil society, and other factors. The fine-grained nature of our data, reflecting the staggered timing of elections, inauguration dates, and dates of passage, allows us to distinguish between different theoretical mechanisms. We find the greatest evidence in favor of an insurance mechanism, by which incumbent parties who face uncertainty over future political control seek to ensure access to government information, and means of monitoring incumbents, in the future in case they lose power.
Civic Origins of Progressive Policy Change: Combating Violence against Women in Global Perspective, 1975–2005—CORRIGENDUM
Authors: HTUN MALA , WELDON S. LAUREL
Published: March 2015

On page 556 of the article by Htun and Weldon (2012) it is stated that, “Before Vienna [the 1993 World Conference on Human Rights], mainstream human rights organizations such as Human Rights Watch and Amnesty International did not treat rape and domestic violence as core issues of human rights. (These organizations now have women's rights projects.)”
Evaluation of different lactation curve models fitted for milk viscosity recorded by an automated on-line California Mastitis Test
Authors: Neitzel Anne-Christin , Stamer Eckhard , Junge Wolfgang , Thaller Georg
Published: March 2015

Laboratory somatic cell count (LSCC) records are usually recorded monthly and provide an important information source for breeding and herd management. Daily milk viscosity detection in composite milking (expressed as drain time) with an automated on-line California Mastitis Test (CMT) could serve immediately as an early predictor of udder diseases and might be used as a selection criterion to improve udder health. The aim of the present study was to clarify the relationship between the well-established LSCS and the new trait,‘drain time’, and to estimate their correlations to important production traits. Data were recorded on the dairy research farm Karkendamm in Germany. Viscosity sensors were installed on every fourth milking stall in the rotary parlour to measure daily drain time records. Weekly LSCC and milk composition data were available. Two data sets were created containing records of 187 692 milkings from 320 cows (D1) and 25 887 drain time records from 311 cows (D2). Different fixed effect models, describing the log-transformed drain time (logDT), were fitted to achieve applicable models for further analysis. Lactation curves were modelled with standard parametric functions (Ali and Schaeffer, Legendre polynomials of second and third degree) of days in milk (DIM). Random regression models were further applied to estimate the correlations between cow effects between logDT and LSCS with further important production traits. LogDT and LSCS were strongest correlated in mid-lactation (r = 0·78). Correlations between logDT and production traits were low to medium. Highest correlations were reached in late lactation between logDT and milk yield (r = −0·31), between logDT and protein content (r = 0·30) and in early as well as in late lactation between logDT and lactose content (r = −0·28). The results of the present study show that the drain time could be used as a new trait for daily mastitis control.