bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seminumerical calculation of the Hartree–Fock exchange matrix: Application to two‐component procedures and efficient evaluation of local hybrid density functionals
Authors: Plessow Philipp , Weigend Florian 
Published: January 2012

AbstractA two‐component extension of the seminumerical procedure for the calculation of the Hartree–Fock (HF) exchange matrix recently presented by Neese et al. (Chem Phys 2009, 356, 98) was implemented into the program system TURBOMOLE. It is demonstrated that this allows for efficient self‐consistent treatment of spin–orbit coupling at HF and hybrid density functional theory level. One‐component HF calculations were performed to study the accuracy of integration grids and the exploitation of the molecular point group symmetry. The efficiency was tested, and for one‐component calculations compared to the implementation realized by Neese. It was further demonstrated that local hybrid density functionals can be evaluated with this technique. The “prototype” of this class of functionals, Lh‐BLYP, was applied to an organic molecule with more than 150 atoms. © 2012 Wiley Periodicals, Inc. J Comput Chem, 2012
Interactive quantum chemistry: A divide‐and‐conquer ASED‐MO method
Authors: Bosson Mäel , Richard Caroline , Plet Antoine , Grudinin Sergei , Redon Stephane 
Published: January 2012

AbstractWe present interactive quantum chemistry simulation at the atom superposition and electron delocalization molecular orbital (ASED‐MO) level of theory. Our method is based on the divide‐and‐conquer (D&C) approach, which we show is accurate and efficient for this non‐self‐consistent semiempirical theory. The method has a linear complexity in the number of atoms, scales well with the number of cores, and has a small prefactor. The time cost is completely controllable, as all steps are performed with direct algorithms, i.e., no iterative schemes are used. We discuss the errors induced by the D&C approach, first empirically on a few examples, and then via a theoretical study of two toy models that can be analytically solved for any number of atoms. Thanks to the precision and speed of the D&C approach, we are able to demonstrate interactive quantum chemistry simulations for systems up to a few hundred atoms on a current multicore desktop computer. When drawing and editing molecular systems, interactive simulations provide immediate, intuitive feedback on chemical structures. As the number of cores on personal computers increases, and larger and larger systems can be dealt with, we believe such interactive simulations—even at lower levels of theory—should thus prove most useful to effectively understand, design and prototype molecules, devices and materials. © 2012 Wiley Periodicals, Inc.
Oligonucleotide‐mediated gene editing is underestimated in cells expressing mutated green fluorescent protein and is positively associated with target protein expression
Authors: Disterer Petra , Papaioannou Ioannis , Evans Vanessa C. , Paul Simons J. , Owen James S. 
Published: January 2012

AbstractBackgroundSingle‐stranded DNA oligonucleotides (ssODNs) can introduce small, specific sequence alterations into genomes. Potential applications include creating disease‐associated mutations in cell lines or animals, functional studies of single nucleotide polymorphisms and, ultimately, clinical therapy by correcting genetic point mutations. Here, we report feasibility studies into realizing this potential by targeting a reporter gene, mutated enhanced green fluorescent protein (mEGFP).MethodsThree mammalian cell lines, CHO, HEK293T and HepG2, expressing multiple copies of mEGFP were transfected with a 27‐mer ssODN capable of restoring fluorescence. Successful cell correction was quantified by flow cytometry.ResultsGene editing in each isogenic cell line, as measured by percentage of green cells, correlated tightly with target protein levels, and thus gene expression. In the total population, 2.5% of CHO‐mEGFP cells were successfully edited, although, remarkably, in the highest decile producing mEGFP protein, over 20% of the cells had restored green fluorescence. Gene‐edited clones initially selected for green fluorescence lost EGFP expression during cell passaging, which partly reflected G2‐phase cycle arrest and perhaps eventual cell death. The major cause, however, was epigenetic down‐regulation; incubation with sodium butyrate or 5‐aza‐2′‐deoxycytidine reactivated fluorescent EGFP expression and hence established that the repaired genotype was stable.ConclusionsOur data establish that ssODN‐mediated gene editing is underestimated in cultured mammalian cells expressing nonfluorescent mutated EGFP, because of variable expression of this mEGFP target gene in the cell population. This conclusion was endorsed by studies in HEK293T‐mEGFP and HepG2‐mEGFP cells. We infer that oligonucleotide‐directed editing of endogenous genes is feasible, particularly for those that are transcriptionally active. Copyright © 2012 John Wiley & Sons, Ltd.
Antitumor effect of chondroitin sulfate‐coated ternary granulocyte macrophage‐colony‐stimulating factor plasmid complex for ovarian cancer
Authors: Hamada Katsuyuki , Yoshihara Chieko , Ito Tomoko , Tani Kenzaburo , Tagawa Masatoshi , Sakuragawa Norio , Itoh Hiroshi , Koyama Yoshiyuki 
Published: January 2012

AbstractBackgroundAlthough replication‐competent viruses have been developed for treating cancers, their cytotoxic effects are insufficient as a result of infection inhibited by the generation of neutralizing antibodies, and systemic administration is difficult as a result of the life‐threatening serious side‐effects of virus‐induced cytokine surge. To overcome these critical problems, we devised a plasmid/polycation/polyanion complex and assessed the potential of ternary plasmid complexes coated with chondroitin sulfate in gene therapy for ovarian cancer. The antitumor effects of chondroitin sulfate‐coated complex as an anionic component were compared with those of hyaluronic acid on ovarian cancer.MethodsPlasmid harboring the gene of murine granulocyte macrophage‐colony‐stimulating factor (mGM‐CSF) was complexed with polyethyleneimine (PEI) and hyaluronic acid or chondroitin sulfate. Murine ovarian cancer cells were injected into (C57BL/6 × C3H/He) F1 mice to prepare a subcutaneous or intraperitoneal tumor model.ResultsDNA/PEI was charged positively and DNA/PEI/chondroitin sulfate or DNA/PEI/hyaluronic acid was charged negatively. Plasmid‐green fluorescent protein (GFP)/PEI coated with 10‐kilodalton (kDa) chondroitin sulfate increased transfection efficiency compared to coating with chondroitin sulfate of higher‐molecular‐weight or hyaluronic acid. The transfection efficiency of GFP/PEI/10‐kDa chondroitin sulfate in ovarian cancer cells was six‐fold higher than that in normal cells. Intraperitoneal injection of mGM‐CSF/PEI coated with 10‐kDa chondroitin sulfate prolonged survival compared to that coated with hyaluronic acid. Intratumoral injection of mGM‐CSF/PEI coated with 10‐kDa chondroitin sulfate achieved mouse survival rates of 100%, although that with hyaluronic acid did not.ConclusionsThese findings suggest that GM‐CSF/PEI coated with 10‐kDa chondroitin sulfate has the potential for use in gene therapy of ovarian cancer. Copyright © 2012 John Wiley & Sons, Ltd.
CD40‐targeted adenoviral cancer vaccines: the long and winding road to the clinic
Authors: Hangalapura Basav N. , Timares Laura , Oosterhoff Dinja , Scheper Rik J. , Curiel David T. , de Gruijl Tanja D. 
Published: January 2012

SummaryThe ability of dendritic cells (DCs) to orchestrate innate and adaptive immune responses has been exploited to develop potent anti‐cancer immunotherapies. Recent clinical trials exploring the efficacy of ex vivo modified autologous DC‐based vaccines have reported some promising results. However, in vitro generation of autologous DCs for clinical administration, their loading with tumor associated antigens (TAAs) and their activation, is laborious and expensive, and, as a result of inter‐individual variability in the personalized vaccines, remains poorly standardized. An attractive alternative approach is to load resident DCs in vivo by targeted delivery of TAAs, using viral vectors and activating them simultaneously. To this end, we have constructed genetically‐modified adenoviral (Ad) vectors and bispecific adaptor molecules to retarget Ad vectors encoding TAAs to the CD40 receptor on DCs. Pre‐clinical human and murine studies conducted so far have clearly demonstrated the suitability of a ‘two‐component’ (i.e. Ad and adaptor molecule) configuration for targeted modification of DCs in vivo for cancer immunotherapy. This review summarizes recent progress in the development of CD40‐targeted Ad‐based cancer vaccines and highlights pre‐clinical issues in the clinical translation of this approach. Copyright © 2012 John Wiley & Sons, Ltd.
EphrinA1–EphA2 interaction‐mediated apoptosis and FMS‐like tyrosine kinase 3 receptor ligand‐induced immunotherapy inhibit tumor growth in a breast cancer mouse model
Authors: Tandon Manish , Vemula Sai V. , Sharma Anurag , Ahi Yadvinder S. , Mittal Shalini , Bangari Dinesh S. , Mittal Suresh K. 
Published: January 2012

AbstractBackgroundThe receptor tyrosine kinase EphA2 is overexpressed in several types of cancers and is currently being pursued as a target for breast cancer therapeutics. The EphA2 ligand EphrinA1 induces EphA2 phosphorylation and intracellular internalization and degradation, thus inhibiting tumor progression. The hematopoietic growth factor, FMS‐like tyrosine kinase 3 receptor ligand (Flt3L), promotes expansion and mobilization of functional dendritic cells.MethodsWe tested the EphrinA1–EphA2 interaction in MDA‐MB‐231 breast cancer cells focusing on the receptor‐ligand‐mediated apoptosis of breast cancer cells. To determine whether EphrinA1–EphA2 interaction‐associated apoptosis and Flt3L‐mediated immunotherapy would have an additive effect in inhibiting tumor growth, we used an immunocompetent mouse model of breast cancer to evaluate intratumoral (i.t.) inoculation strategies with human adenovirus (HAd) vectors expressing either EphrinA1 (HAd‐EphrinA1‐Fc), Flt3L (HAd‐Flt3L) or a combination of EphrinA1‐Fc + Flt3L (HAd‐EphrinA1‐Fc + HAd‐Flt3L).ResultsIn vitro analysis demonstrated that an EphrinA1–EphA2 interaction led to apoptosis‐related changes in breast cancer cells. In vivo, three i.t. inoculations of HAd‐EphrinA1‐Fc showed potent inhibition of tumor growth. Furthermore, increased inhibition in tumor growth was observed with the combination of HAd‐EphrinA1‐Fc and HAd‐Flt3L accompanied by the generation of an anti‐tumor adaptive immune response.ConclusionsThe results obtained in the present study, indicating the induction of apoptosis and inhibition of mammary tumor growth, show the potential therapeutic benefits of HAd‐EphrinA1‐Fc. In combination with HAd‐Flt3L, this represents a promising strategy for effectively inducing mammary tumor regression by HAd vector‐based therapy. Copyright © 2012 John Wiley & Sons, Ltd.
Preventive Effects of Hesperidin, Glucosyl Hesperidin and Naringin on Hypertension and Cerebral Thrombosis in Stroke‐prone Spontaneously Hypertensive Rats
Authors: Ikemura Miyako , Sasaki Yasuto , Giddings John C. , Yamamoto Junichiro 
Published: January 2012

The effects of hesperidin, glucosyl hesperidin (G‐hesperidin), a water‐soluble derivative of hesperidin, and naringin on blood pressure and cerebral thrombosis were investigated using stroke‐prone spontaneously hypertensive rats (SHRSP). Hesperidin, G‐hesperidin and naringin were mixed with diet and fed to the animals for 4 weeks. No effect was evident on body weight, but the supplements significantly suppressed the age related increase in blood pressure. Thrombotic tendency, as assessed using a He‐Ne laser technique in the cerebral blood vessels, was significantly decreased in the treated animals compared with the control animals. Measurements of 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG) demonstrated that the supplements had strong antioxidant activity. Furthermore, these supplements significantly increased the production of nitric oxide (NO) metabolites in urine measured with Griess reagent. Vasodilation induced by acetylcholine‐mediated NO production in the endothelium was assessed using thoracic aortic ring preparations and indicated that endothelial function was significantly improved by the administration of these supplements.These findings suggest that the strong antioxidant properties of hesperidin, G‐hesperidin and naringin could modulate the inactivation of NO and protect endothelial function from reactive oxygen species (ROS). In this manner, the flavonoids could contribute beneficial effects on the mechanisms of hypertension and thrombosis by increasing the bioavailability of NO. Copyright © 2012 John Wiley & Sons, Ltd.
Extending science beyond the classroom door: Learning from students' experiences with the Choice, Control and Change (C3) curriculum
Authors: Mallya Aarti , Mensah Felicia Moore , Contento Isobel R. , Koch Pamela A. , Barton Angela Calabrese 
Published: January 2012

AbstractThis article describes the experiences of seventh‐grade students living in high poverty areas of New York City who participated in the Choice, Control and Change (C3) science curriculum. Data were collected from eight case study students in the form of individual interviews, classroom observations, and student artifacts. Analysis of these data revealed that students were able to extend their C3 science understandings beyond the classroom door by developing and expressing science agency in the following ways: (1) critically analyze the conditions of their food environment, (2) purposefully make healthier choices, and (3) expand the food and activity options available to themselves and others. Through participation in the C3 curriculum, and the science content and practices addressed therein, students began to view their worlds with a more critical mindset and to devise ways to transform themselves and the conditions of their own and others' lives. Based on the findings, we propose taking a closer look at how we might create meaningful and relevant learning opportunities for students through connecting school science with issues of personal and social significance in students' lives outside of school. © 2011 Wiley Periodicals, Inc. J Res Sci Teach 49: 244–269, 2012
Expression of Enzymes and Transcription Factors Involved in n‐3 Long Chain PUFA Biosynthesis in Limousin Bull Tissues
Authors: Cherfaoui Maya , Durand Denys , Bonnet Muriel , Cassar‐Malek Isabelle , Bauchart Dominique , Thomas Agnès , Gruffat Dominique 
Published: January 2012

AbstractThe current low consumption of n‐3 long chain polyunsaturated fatty acids (n‐3 LCPUFA) led scientists to wonder about the possible enrichment of human food, including meats such as beef, with n‐3 LCPUFA. However, their biosynthesis from dietary n‐3 PUFA seems limited in mammalian tissues implying that a better understanding of the molecular mechanisms responsible for this down regulation is needed. This study aimed at identifying and comparing the limiting steps of n‐3 LCPUFA synthesis in liver, intermuscular adipose tissue (IM‐AT) and semitendinosus muscle (ST) from six Limousin bulls. Tissue FA composition was analysed by GLC and mRNA abundance of enzymes and transcription factors involved in n‐3 LCPUFA synthesis was assessed by RT‐qPCR. In liver, mRNA encoding proteins involved in n‐3 LCPUFA synthesis were present in agreement with the significant high content of n‐3 LCPUFA (8.4 mol% of total FA, 257 mg/100 g of fresh tissue) in this organ. In IM‐AT, these mRNA were all present, but at a tenfold lower intensity than in liver in agreement with the low contents of n‐3 LCPUFA in this tissue. In ST muscle, these mRNA were all present except elongase 5 mRNA which was only present as trace, the corresponding protein being undetectable, probably inducing a break of n‐3 LCPUFA synthesis from 18:4n‐3. In conclusion, Limousin bull ST muscle seemed unable to synthesize n‐3 LCPUFA. However, the presence of 20:5n‐3 (EPA) and 22:5n‐3 (DPAn‐3) in muscle raised the question of the origin of these n‐3 LCPUFA.
Effect of Enzymatic Trans‐ and Interesterification on the Thermal Properties of Groundnut and Linseed Oils and Their Blends
Authors: Sharma Meesha , Lokesh Belur Ramaswamy 
Published: January 2012

AbstractThe present study was undertaken to compare the alterations observed in the triacylglycerol (TAG) molecular species of blended and interesterified oils containing groundnut oil (GNO) and linseed oil (LIN). The blended oil (BLE) was subjected to a lipase catalyzed reaction to prepare transesterified oil (TRA). A structured lipid (STR) was also prepared by a lipase catalyzed acidolysis reaction of GNO and free fatty acids concentrate from LIN. The changes in the molecular species of modified lipids were determined by high performance liquid chromatography. The thermal profiles were determined by differential scanning calorimetry. In comparison with GNO, the triunsaturated triacylglycerols were increased and the disaturated triacylglycerol molecular species were decreased in TRA and STR. Both BLE and TRA showed a decrease in the onset temperature for crystallization as compared to that observed with GNO. The total transitional enthalpy for crystallization was higher for BLE, TRA and STR as compared to GNO. The melting temperature of TRA and STR showed a decrease in comparison to GNO, reflecting on the changes in the TAG molecules species present in the oil. Thus, interesterification of oils introduced changes in the physical properties of oils, even though the overall fatty acid composition of blended and interesterified oils remained similar.
When Spandrels Become Arches: Neural crosstalk and the evolution of consciousness
Authors: Wallace Rodrick 
Published: January 2012

AbstractOnce cognition is recognized as having a 'dual' information source, the information theory chain rule implies that isolating coresident information sources from crosstalk requires more metabolic free energy than permitting correlation. This provides conditions for an evolutionary exaptation leading to the rapid, shifting global neural broadcasts of consciousness. The argument is quite analogous to the well-studied exaptation of noise to trigger stochastic resonance amplification in neurons and neuronal subsystems. Astrobiological implications are obvious.
Long double stranded RNA is present in scrapie infected cells and tissues
Authors: Karapetyan Yervand 
Published: January 2012

AbstractThe nature of the infectious agent causing scrapie and other Transmissible Spongiform Encephalopathies remains an enigma despite decades of research efforts. The protein-only prion hypothesis posits that abnormal conformer of a host protein is the infectious agent. Virus and virino theories include host-independent nucleic acid as the genome of the infectious agent in addition to protein component (in case of virino a host protein and in case of virus a viral protein). Viral or sub-viral nucleic acids have long been sought in scrapie to explain the existence of multiple agent strains. Many different approaches were undertaken to find such nucleic acid. Despite that no scrapie specific nucleic acid sequences have been found in infected cells or tissues. Most viruses induce synthesis of long double stranded RNA (dsRNA) during their replication in cells. Therefore the presence of long dsRNA would be an indication of viral infection in cells. J2 monoclonal antibody against long dsRNA is a great tool for easy screening of cells and tissues for the presence of suspected unknown viral infection. This antibody has not been used for testing of scrapie infected tissues.Evidence is presented here for long dsRNA in scrapie infected cells and tissues. Such dsRNA is also found in scrapie free tissue culture cells.
Full-length myosin Va exhibits altered gating during processive movement on actin
Authors: Armstrong Jessica M. , Krementsova Elena , Michalek Arthur J. , Heaslip Aoife T. , Nelson Shane R. , Trybus Kathleen M. , Warshaw David M. 
Published: January 2012

Myosin Va (myoV) is a processive molecular motor that transports intracellular cargo along actin tracks with each head taking multiple 72-nm hand-over-hand steps. This stepping behavior was observed with a constitutively active, truncated myoV, in which the autoinhibitory interactions between the globular tail and motor domains (i.e., heads) that regulate the full-length molecule no longer exist. Without cargo at near physiologic ionic strength (100 mM KCl), full-length myoV adopts a folded (approximately 15 S), enzymatically-inhibited state that unfolds to an extended (approximately 11 S), active conformation at higher salt (250 mM). Under conditions favoring the folded, inhibited state, we show that Quantum-dot-labeled myoV exhibits two types of interaction with actin in the presence of MgATP. Most motors bind to actin and remain stationary, but surprisingly, approximately 20% are processive. The moving motors transition between a strictly gated and hand-over-hand stepping pattern typical of a constitutively active motor, and a new mode with a highly variable stepping pattern suggestive of altered gating. Each head of this partially inhibited motor takes longer-lived, short forward (35 nm) and backward (28 nm) steps, presumably due to globular tail-head interactions that modify the gating of the individual heads. This unique mechanical state may be an intermediate in the pathway between the inhibited and active states of the motor.
Policy Risk in the Canadian Dairy Industry
Authors: Nogueira Lia , Barichello Richard R. , Baylis Kathy , Chouinard Hayley H. 
Published: January 2012

AbstractCanadian dairy farmers purchase a marketing quota through the Provincial Marketing Boards to sell milk in Canada. That quota captures rents created by regulations and is subject to policy risk. We define policy risk as the farmers' expectation that quota rents will decline or disappear over time. We calculate the effect of perceived policy risk to determine whether the Uruguay Round Agreement affected the amount of protection given to farmers. Calculated policy risk ranged from 14‐29%. Policy risk increased in the years leading up to the Uruguay Round Agreement, but decreased after the WTO was established and remains at a historic low.