bluuebunny/crossref_metadata_2025_split huggingface dataset:
Catalytic Asymmetric Synthesis of Enantioenriched Heterocycles Bearing a CCF3 Stereogenic Center
Authors: Huang Yi‐Yong , Yang Xing , Chen Zhuo , Verpoort Francis , Shibata Norio 
Published: March 2015

AbstractGiven the important agricultural and medicinal application of optically pure heterocycles bearing a trifluoromethyl group at the stereogenic carbon center in the heterocyclic framework, the exploration of efficient and practical synthetic strategies to such types of molecules remains highly desirable. Catalytic enantioselective synthesis has one clear advantage that it is more cost‐effective than other synthetic methods, but remains limited by challenges in achieving excellent yield and stereoselectivities with a low catalyst loading. Thus far, numerous models of organo‐ and organometal‐catalyzed asymmetric reactions have been exploited to achieve this elusive goal over the past decade. This review article describes recent progress on this research topic, and focuses on an understanding of the catalytic asymmetric protocols exemplified in the catalytic enantioselective synthesis of a wide range of complex enantioenriched trifluoromethylated heterocycles.
Scaffold Identification of a New Class of Potent and Selective BCRP Inhibitors
Authors: Marighetti Federico , Steggemann Kerstin , Karbaum Maria , Wiese Michael 
Published: March 2015

AbstractWe recently reported the synthesis and quantitative structure–activity relationships of a new breast cancer resistance protein (BCRP) inhibitor class. In the study presented herein, we investigated the possibility to better define the scaffold of this compound class by removing or modifying the aromatic ring A with various substituents selected on the basis of their electronic and lipophilic properties. The results show that this aromatic ring is important, but not essential, for activity. Many of the selected substituents led to compounds with low activity, but in some cases activity was retained. Among these, a phenolic hydroxy group proved to impart as much potency to the molecule as a hydroxyethyl side chain, initially considered necessary for activity. This derivative is one of the most active compounds in this class, maintaining an inhibitory activity similar to that of the reference compound; it is also selective for BCRP.
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

AbstractMarine 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

BACKGROUNDMedical 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.METHODSThe 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).RESULTSResults 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.CONCLUSIONSAlthough 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

AbstractThe 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.
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

AbstractBackgroundAn 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.MethodsAutologous 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.ResultsTumors 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.ConclusionThis 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

ABSTRACTRearranged 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

ABSTRACTPromotion 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

AbstractThe 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

AbstractBackgroundThe 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.MethodsIn 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.ResultsThe 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.ConclusionsThese 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

AbstractA 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

SummaryOne 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

SUMMARYGamete 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

PurposeTo 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.MethodsThirty‐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.ResultsTRAFF 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.ConclusionIn 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

AbstractThe 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