bluuebunny/crossref_metadata_2025 huggingface dataset:
The GOME-2 instrument on the Metop series of satellites: instrument design, calibration, and level 1 data processing – an overview
Authors: Munro R. , Lang R. , Klaes D. , Poli G. , Retscher C. , Lindstrot R. , Huckle R. , Lacan A. , Grzegorski M. , Holdak A. , Kokhanovsky A. , Livschitz J. , Eisinger M.
Published: August 2015

Abstract. The Global Ozone Monitoring Experiment-2 (GOME-2) flies on the Metop series of satellites, the space component of the EUMETSAT Polar System. In this paper we will provide an overview of the instrument design, the on-ground calibration and characterisation activities, in-flight calibration, and level 0 to 1 data processing. The quality of the level 1 data is presented and points of specific relevance to users are highlighted. Long-term level 1 data consistency is also discussed and plans for future work are outlined. The information contained in this paper summarises a large number of technical reports and related documents containing information that is not currently available in the published literature. These reports and documents are however made available on the EUMETSAT web pages (http://www.eumetsat.int) and readers requiring more details than can be provided in this overview paper will find appropriate references at relevant points in the text.
Statistical detection and modeling of the over-dispersion of winter storm occurrence
Authors: Raschke M.
Published: August 2015

Abstract. In this communication, I improve the detection and modeling of the over-dispersion of winter storm occurrence. For this purpose, the generalized Poisson distribution and the Bayesian information criterion are introduced; the latter is used for statistical model selection. Moreover, I replace the frequently used dispersion statistics by an over-dispersion parameter which does not depend on the considered return period of storm events. These models and methods are applied in order to properly detect the over-dispersion in winter storm data for Germany, carrying out a joint estimation of the distribution models for different samples.
“Esses chamados intelectuais de esquerda”: o IPM do PCB e o fenômeno do comunismo na produção cultural do pósgolpe
Authors: Czajka Rodrigo
Published: August 2015

Entre as muitas ações de investigação adotadas pelos militares com a intenção de coletar informação sobre a chamada “subversão comunista” no pó-golpe, em 1964, uma das formas que muito se destacou foi o Inquérito Policial-Militar (IPM). Esse instrumento de investigação tinha por finalidade a coleta de provas e indícios que, posteriormente, serviriam de base para processos penais com base na Lei de Segurança Nacional (JSN). Entre os IPMs que ganharam maior repercussão estava o do Partido Comunista Brasileiro (PCB), sobretudo porque ele serviu de ponto de partida para outros inquéritos que se desdobraram em investigações específicas. Uma delas, que será abordada nesse artigo, diz respeito à organização de uma intelectualidade de esquerda que, se antes do golpe fundamentou um debate sobre o pensamento político e social no Brasil, após o golpe ganhará projeção ainda maior pela sua atuação na resistência ao regime militar. No IPM do PCB o “intelectual de esquerda” ou o “intelectual comunista” são definidos pelos relatórios militares como elementos portadores de um discurso sofisticado de propaganda soviética, logo, deveriam ser investigados em profundidade pelos serviços de informações.
Efectos de la afluencia humana durante la etapa de auge algodonero en el Chaco (1920-1944). Un abordaje a partir de información oficial, y testimonios de época
Authors: Mari Oscar Ernesto
Published: August 2015

Durante as décadas de 20 e 30 do século XX, o Chaco, que foi um dos Territórios Nacionais da Argentina, foi um dos processos socioeconômicos mais marcantes do país após o sucesso da cultura primária e da industrialização do algodão. Isso foi motivado pela atração de fortes cotas de imigração interna e externa que chegaram a esta jurisdição para o mercado de trabalho de benefício do demandante. Incluídos nessas cotas estavam milhares de trabalhadores temporários que entravam regularmente no Território para participar da colheita manual de têxteis. Essas receitas maciças causaram o estouro de um governo local, que não conseguiu atender de forma eficaz às necessidades de uma população crescente. Algumas consequências desse fenômeno, principalmente aquelas relacionadas ao controle social, devem ser analisadas neste artigo a partir de referências de governantes e jogadores hábeis da época.
Sabiá no III Festival Internacional da Canção: vaia e ocaso da estética bossa novista de Tom Jobim
Authors: Poletto Fabio Guilherme
Published: August 2015

Este artigo aborda a canção Sabiá, composição de Tom Jobim e Chico Buarque. Mobiliza diferentes séries de fontes com o objetivo de reconstituir historicamente a vaia à apresentação da canção durante o III Festival Internacional da Canção, realizado em 1968 na cidade do Rio de Janeiro. Procura evidenciar como este episódio catalisou a existência de diferentes expectativas sobre a canção popular e seu papel como veículo para ideais de modernidade em meio às interferências do ambiente autoritário no campo cultural e político. Em seguida, com base na análise dos parâmetros constitutivos da canção, sugere possibilidades de compreensão de sua construção poético musical em diálogo crítico com suas reverberações no plano cultural.
Ultrasonographic Biometrical Studies on Reproductive Organs of rbST Treated Pregnant Kundhi Buffaloes
Authors: Kachiwal A.B. , Sheikh B.A. , Sheikh S.A. , Memon K.H. , Memon S. , Qureshi T.A.
Published: August 2015

Biometrical studies were conducted on sixty four gravid uteri with estimated gestation period of 1st, 2nd, 3rd and 4th month of pregnancy in Kundhi buffaloes. Sixteen specimens for each month of gestation were collected from Hyderabad slaughterhouse to evaluate techniques for measurement of reproductive organs. The measurements for fetometry and morphometry of reproductive organs by ultrasound machine and manually (by measuring tape and vernier caliper) were performed and compared. The Ultrasound examinations were performed through diagnostic ultrasound machine equipped with multi-frequency 5-10MHz transrectal linear array transducer. Analysis revealed that the ovary, foetus, foetal fluid and uterus progressively increased significantly (P<0.01) in weight during 4th month of the gestation than 1st, 2nd and 3rd month of gestation period in rbST treated Kundhi buffaloes. Ovaries with CL were significantly (P<0.01) heavier than the ovary in which CL was absent. Corpus leutum was significantly lighter (P<0.01) during 1st month of pregnancy than 2nd, 3rd and 4th month of pregnancy in rbST treated Kundhi buffaloes. Gravid uterus was significantly heavier (P<0.01) during 4th month of pregnancy than 1st, 2nd and 3rd month of pregnancy in rbST treated Kundhi buffaloes. There was no significant difference between the measurements of oviduct, cervix and vagina during 1st to 4th month of pregnancy. The placenta, foetal fluid and foetus progressively increased significantly in size as gestation period progressed. The ultrasonographic fetometric and morphometric threshold of CRL, TD and UD and foetal weight was steadily increased in rbST treated Kundhi buffaloes. There was significant increase (P<0.05) in the CRL, TD, UD and foetus weight/volume at 4th month of pregnancy than 1st , 2nd and 3rd month of pregnancy in rbST treated Kundhi buffaloes. In conclusion, the overall data indicated that the examination for ultrasonographic fetometry and morphometry of reproductive organs of kundhi buffaloes for evaluation of fetal development, estimation of gestational age and formulation of fetal chart through reproductive organs were more suitable as compare to manual biometrical evaluation
Warfighter Skills
Authors: Morrill Peter O.
Published: August 2015

In this article, the author identifies skills that are needed for coping with sudden decisions that must be made in an ever‐changing world that we all live in. This veteran of the U.S. Marine Corps shares skill sets that he learned while serving in the Corps. He uses a lively approach to stimulate those responsible for dynamic management leadership. The key ideas come from the battlefields faced in every life arena. They are: improvise, adapt, and overcome. © 2015 Wiley Periodicals, Inc.
Topical diclofenac does not affect the antiplatelet properties of aspirin as compared to the intermediate effects of oral diclofenac: A prospective, randomized, complete crossover study
Authors: Rowcliffe M. , Nezami B. , Westphal E. S. , Rainka M. , Janda M. , Bates V. , Gengo F.
Published: August 2015

Nonsteroidal anti‐inflammatory drugs (NSAIDs) adversely interact with aspirin, diminishing its antiplatelet effect and potentially placing patients at an increased risk for recurrent thrombotic events. This crossover study aimed to determine whether the topical NSAID diclofenac epolamine 1.3% patch or oral diclofenac 50 mg interfered with the antiplatelet effects of aspirin 325 mg. Twelve healthy men and women aged 18‐50 were included. Participants were randomized into 5 treatment arms: aspirin, diclofenac potassium 50 mg, diclofenac patch, diclofenac potassium plus ASA 325 mg, and diclofenac patch plus aspirin. Platelet responsiveness was determined using whole‐blood impedance aggregation (WBA) to collagen 1 μg/mL and arachidonic acid (AA) 0.5 mM and was sampled every 2 hours. No significant difference in platelet function was observed following the diclofenac patch and aspirin vs aspirin alone. Oral diclofenac produced a mixed effect with significant reduction in platelet inhibition at hour 2 and hour 8 following aspirin administration. Topical diclofenac does not significantly interfere with the antiplatelet effects of aspirin and may be a safer alternative to the oral formulation.
Real‐time histological imaging of kidneys stained with food dyes using multiphoton microscopy
Authors: Nagao Yasuaki , Kimura Kazushi , Wang Shujie , Fujiwara Takeshi , Mizoguchi Akira
Published: August 2015

We have developed a real‐time imaging technique for diagnosis of kidney diseases which is composed of two steps, staining renal cells safely with food dyes and optical sectioning of living renal tissue to obtain histological images by multiphoton microscopy (MPM). Here, we demonstrated that the MPM imaging with food dyes, including erythrosine and indigo carmine, could be used as fluorescent agents to visualize renal functions and structures such as glomerular bloodstreams, glomerular filtration, and morphology of glomeruli and renal tubules. We also showed that the kidneys of IgA nephropathy model‐mice stained with the food dyes presented histopathological characteristics different from those observed in normal kidneys. The use of the food dyes enhances the quality of tissue images obtained by MPM and offers the potential to contribute to a clinical real‐time diagnosis of kidney diseases. Microsc. Res. Tech. 78:847–858, 2015. © 2015 Wiley Periodicals, Inc.
Robot‐assisted hepatic mobilization and control of suprahepatic infradiaphragmatic inferior vena cava for level 3 vena caval thrombectomy: An IDEAL stage 0 study
Authors: Sood Akshay , Jeong Wooju , Barod Ravi , Bahnson Eamonn , Kirura Parfait , Abdollah Firas , Bhandari Mahendra , Bahnson Robert , Menon Mani
Published: August 2015

Robot‐assisted level 1/2 inferior vena caval (IVC) thrombectomy techniques have been recently described for clinical use. Following the IDEAL recommendations on safe surgical innovation, we here describe a robotic approach for level 3 IVC thrombectomy in fresh frozen cadavers (IDEAL stage 0). In all cadavers (n = 3), hepatic mobilization with control of short hepatic veins, contralateral renal vein, infrarenal IVC and suprahepatic‐infradiaphragmatic IVC could be achieved successfully, without converting to open surgery. Clinical feasibility of our technique remains to be tested. J. Surg. Oncol. 2015;112:741–745. © 2015 Wiley Periodicals, Inc.
Präventive operative Optionen für Frauen mit einer familiären Brust- und Eierstockkrebsbelastung
Authors: Rhiem Kerstin
Published: August 2015

Für das familiäre Mamma- und Ovarialkarzinom ist seit der Entdeckung der beiden Hochrisikogene BRCA1 und BRCA2 in den 1990er-Jahren die genetische Testung und die damit einhergehende individuelle Risikobestimmung möglich. In den zurückliegenden 20 Jahren waren im Rahmen der Betreuung von BRCA-Mutationsträgerinnen und ihren Familien die Bestimmung der Inzidenz und des Phänotyps der Karzinome sowie der Nachweis der Effizienz von prophylaktischen Operationen, intensivierter Brustkrebsfrüherkennung und zielgerichteter Therapieverfahren möglich. Dies versetzt uns heute in die Lage, bei Ratsuchenden individuelle Risikokalkulationen durchzuführen und sie im Rahmen nicht direktiver Beratungsgespräche auf dem Weg zu einer informierten und präferenzsensiblen Entscheidung in Bezug auf die Inanspruchnahme risikoadaptierter Präventionsmaßnahmen zu begleiten. Aktuell und zukünftig gilt es die Herausforderungen z. B. im Zusammenhang mit der Zulassung des ersten PARP-Inhibitors sowie mit der Entdeckung neuer Risikogene zu bewältigten. Schwerpunkt dieses Artikels ist der Nachweis, dass v. a. Frauen mit Mutationen in den Hochrisikogenen BRCA1/2 von operativen Maßnahmen profitieren.
Reciprocal longitudinal associations between substance use and child‐to‐parent violence in adolescents
Authors: Calvete Esther , Orue Izaskun , Gámez‐Guadix Manuel
Published: August 2015

Child‐to‐parent violence (CPV) is a type of violence that has received little attention despite its increasing rates in Western countries. Several models state that substance abuse constitutes a risk factor for aggressive behavior and that relationships among these variables can be reciprocal. In this study, the temporal relationships among substance use and physical and psychological CPV were examined. A sample of 981 adolescents (mean age = 15.22 years, SD = 1.2 years) completed measures of substance use and CPV at three time points (T1, T2, and T3) spaced 6 months apart. The results indicated that T1 levels of substance use predicted an increase in psychological CPV at T2 and that T2 levels of substance use predicted an increase in physical CPV at T3. Additionally, several mediational mechanisms emerged between substance use at T1 and CPV at T3. Neither physical nor psychological CPV predicted an increase in substance use at any time. Multiple comparisons indicated that the predictive association between substance use and physical aggression against parents was significant only in boys. These findings suggest that preventive programs for CPV should include specific components for reducing substance use.
Endoscopic balloon‐based radiofrequency ablation for long‐segment early esophageal squamous cell neoplasia
Authors: Tsai Ying‐Nan , Lee Ching‐Tai , Tang Tao‐Qian , Chang I‐Wei , Chang Chi‐Yang , Mo Lein‐Ray , Wang Wen‐Lun
Published: August 2015

Esophageal cancer is a common and highly lethal disease. In the Asia‐Pacific region, esophageal squamous cell neoplasias are the major forms of the disease. Recent advances in endoscopic therapy enable curative treatment of early esophageal squamous cell neoplasias, however, the technique is complicated and requires a high level of expertise, especially for those with long‐segment lesions. Endoscopic radiofrequency ablation is a rapidly evolving treatment modality and has been shown to have good efficacy and safety for the treatment of dysplasia in cases of Barrett's esophagus. Theoretically, it can also be used to treat squamous dysplasia. We report a case of a 48‐year‐old man with an 8‐cm‐long circumferential squamous high‐grade dysplasia over the esophagus (from 21 cm to 29 cm below the incisor) that was treated successfully and safely with balloon‐based radiofrequency ablation. The procedure took only around 30 minutes to complete. There were no major adverse events during and after the procedure. In addition, we examined the histology of the esophageal coagulum, which showed an extensive cauterization effect with focal dysplasia within the ablated epithelium. Follow‐up endoscopy at 1 month, 3 months, and 6 months showed no residual lesion, and biopsies also confirmed complete remission.
Blue silica nanoparticle-based colorimetric immunoassay for detection of Salmonella pullorum
Authors: Sun Qian , Zhao Guangying , Dou Wenchao
Published: August 2015

A colorimetric immunoassay based on blue silica nanoparticles (blue-SiNPs) was developed for quantitative detection of Salmonella pullorum (S. pullorum).
Mn3O4 nanoparticles anchored to multiwall carbon nanotubes: a distinctive synergism for high-performance supercapacitors
Authors: Mondal Chanchal , Ghosh Debasis , Aditya Teresa , Sasmal Anup Kumar , Pal Tarasankar
Published: August 2015

A modified hydrothermal (MHT) route has been adopted for the synthesis of a MWCNT/Mn3O4 composite to attain enhanced supercapacitive performance.
A simple and greener approach for the amide bond formation employing FeCl3as a catalyst
Authors: Basavaprabhu Basavaprabhu , Muniyappa Krishnamurthy , Panguluri Nageswara Rao , Veladi Panduranga , Sureshbabu Vommina V.
Published: August 2015

A protocol employing FeCl3in the presence of glacial AcOH is described for the less nucleophilic aniline and its variants, bromoacetic acid and sterically hindered amino acids.
Superacid mediated intramolecular condensation: facile synthesis of indenones and indanones
Authors: Ramulu Bokka Venkat , Satyanarayana Gedu
Published: August 2015

Superacid promoted intramolecular acylation is described for the synthesis of indenones.
Generic model for tunable colloidal aggregation in multidirectional fields
Authors: Kogler Florian , Velev Orlin D. , Hall Carol K. , Klapp Sabine H. L.
Published: August 2015

Based on Brownian dynamics simulations we investigate the non-equilibrium aggregation of colloidal particles in external fields.
Intracellular growth and pathogenesis of Leishmania parasites
Authors: Naderer Thomas , McConville Malcolm J.
Published: August 2015

Parasitic protozoa belonging to the genus Leishmania are the cause of a spectrum of diseases in humans, as well as chronic long-term infections. These parasites exhibit a remarkable capacity to survive and proliferate within the phagolysosome compartment of host macrophages. Studies with defined Leishmania mutants in mouse models of infection have highlighted processes that are required for parasite survival in macrophages. Parasite mutants have been identified that (i) are poorly virulent when the insect (promastigote) stage is used to initiate infection, but retain wild-type virulence following transformation to the obligate intracellular amastigote stage, (ii) are highly attenuated when either promastigotes or amastigotes are used, and (iii) are unable to induce characteristic lesion granulomas, but can persist within macrophages in other tissues. From these analyses it can be concluded that promastigote stages of some species require the surface expression of lipophosphoglycan, but not other surface components. Survival and subsequent proliferation of Leishmania in macrophages requires the activation of heat-shock responses (involving the up-regulation and/or phosphorylation of heat-shock proteins), the presence of oxidative and nitrosative defence mechanisms, and uptake and catabolism of carbon sources (glycoproteins, hexoses and amino acids) and essential nutrients (purines, amino acids and vitamins). Parasite mutants with defects in specific kinase/phosphatase-dependent signalling pathways are also severely attenuated in amastigote virulence, highlighting the potential importance of post-translational regulatory mechanisms in parasite adaptation to this host niche.
Calcium storage and function in apicomplexan parasites
Authors: Moreno Silvia N.J. , Ayong Lawrence , Pace Douglas A.
Published: August 2015

Calcium is relevant for several vital functions in apicomplexan parasites, including host cell invasion, parasite motility and differentiation. The ER (endoplasmic reticulum) and calcium-rich acidocalcisomes have been identified as major calcium stores. Other potential calcium-storage organelles include the Golgi, the mitochondrion, the apicoplast and the recently described plant-like vacuole in Toxoplasma gondii. Compared with most eukaryotic systems, apicomplexan parasites contain a reduced number of calcium-related genes, a vast majority of which remain uncharacterized. Several Ca2+-ATPases have been described in apicomplexans, several of which are annotated in the different genomes. There is experimental evidence for an IP3 (inositol 1,4,5-trisphosphate)-dependent calcium response in Plasmodium spp. and T. gondii, although no IP3 or ryanodine receptors have been identified. Genes encoding potential calcium channels are present in T. gondi, but not in Plasmodium spp. and Cryptosporidium spp. Effector calcium-binding proteins including calmodulins and CDPK (calcium-dependent protein kinase) genes mainly found in plants have also been described. The characterized CDPKs were found to play important roles in protein secretion, host cell invasion and parasite differentiation. Taken together, the available information on calcium storage and function in apicomplexans, although fragmented, suggest the existence of unique calcium-mediated pathways in these parasites. An in-depth functional characterization of the apicomplexan calcium-related genes could lead to the identification of novel therapeutic targets, and will improve our understanding of the role of calcium in parasite development and virulence.
Structure of mammalian DNA methyltransferase as deduced from the inferred amino acid sequence and direct studies of the protein
Authors: BESTOR TIMOTHY
Published: August 2015

Abstract

DNA (cytosine-5)-methyltransferase (DNA MeTase) establishes and maintains methylation patterns in the genome of higher eukaryotes. This enzyme has been purified, and the cDNA which encodes it has been cloned and sequenced. DNA MeTase appears to contain a large (1000 amino acid) N-terminal domain that contains potential metal-binding sites. This domain appears to contain a series of five to seven structural units of Mr about 20 000, since post-translational processing in vivo or partial proteolysis of the purified protein in vitro leads to the production of a series of catalytically active species differing in Mr by units of 20 000. The N-terminal domain is fused to a smaller (570 amino acid) C-terminal domain that is related to bacterial type II cytosine methyltransferases. The relevance of these findings for the biological function of DNA MeTase is discussed.
Rapid antibody biosensor assays for environmental analysis
Authors: Killard A. J. , Smyth M. R. , Grennan K. , Micheli L. , Palleschi G.
Published: August 2015

Traditionally, biosensor development has focused on molecules with a defined metabolic role that can be exploited by enzyme-based systems. Antibodies have the ability to move beyond this range of analytes, and are particularly useful in detecting small, hapten molecules. Electrochemically based biosensor developments have been less fruitful in this regard, as enzyme labelling is required, and such assays require the separation from bound and unbound species. These separations and the removal of background signals result in the increased complexity of the assay format, making it unsuitable for rapid sensor analysis. We have developed an electrochemical sensor based on anti-bodies that does not require the separation of bound and unbound molecules in a competition immunoassay format. This removes the need for several washing and separation steps as is normally employed in this type of assay. This allows single-step immunoassays to be performed using this system, and also allows for the real-time monitoring of antibody—antigen interactions. We have shown that such assays are possible in both batch and flow-injection formats and we are currently developing an assay for the pesticide atrazine. Tentative results show that analysis with this system is possible in the p.p.m. to p.p.b. range.
Corneal epithelial migration: Up-regulation of Galactose-linked glycoproteins
Authors: Ahmed Asifa , Ahmed Nikhat , Siddiqui Anwar Ali
Published: August 2015

Plasma membrane glycoprotein of corneal epithelium have been found to play a vital role in the migratory process of the corneal epithelium during woujd healing. In the present study we have focussed on rates of glycoprotein synthesis as monitored by [C] - glucosanine, 3[H] - mannose and 3[H] - galactose incorporation in organ cultures of rabbit corneal epithelium during migration. The amount of incorporation of the radiolabeled sugar into TCA -precipitable proteins from normal and migrating corneal epithelium was determined. Migrating epithelium incorporated glucosanine, mannose and galaactose at rates 1.05, 4.92 and 3.95 times that of normal epithelium respectively. Incorporation of mannose was highest in samples taken at 18 hrs. and was observed to decrease as the wound defect closed indicating that as cell-cell contact develops there is a reduced synthesis of mannose - linked glycoproteins. However, incorporation of galactose was seen to increase with time and was highest at 72 hrs., the wound closure time. Thus galactose-linked glycoproteins were observed to be up-regulated in the migratory process.
Similarities between ATP-dependent and ion-coupled multidrug transporters
Authors: Venter H. , Shahi S. , Balakrishnan L. , Velamakanni S. , Bapna A. , Woebking B. , van Veen H.W.
Published: August 2015

The movement of drugs across biological membranes is mediated by two major classes of membrane transporters. Primary-active, ABC (ATP-binding cassette) multidrug transporters are dependent on ATP-binding/hydrolysis, whereas secondary-active multidrug transporters are coupled to the proton (or sodium)-motive force that exists across the plasma membrane. Recent work on LmrA, an ABC multidrug transporter in Lactococcus lactis, suggests that primary- and secondary-active multidrug transporters share functional and structural features. Some of these similarities and their implications for the mechanism of transport by ABC multidrug transporters will be discussed.
Role of malonyl-CoA in the hypothalamic control of food intake and energy expenditure
Authors: Lane M.D. , Hu Z. , Cha S.-H. , Dai Y. , Wolfgang M. , Sidhaye A.
Published: August 2015

The brain plays an important role in the regulation of energy balance in higher animals. Global energy balance is monitored by sets of neurons in the hypothalamus that respond to peripheral hormonal and afferent neural signals that sense the energy status. Malonyl-CoA, an intermediate in the biosynthesis of fatty acids, appears to function in this hypothalamic energy-sensing system. The steady-state level of malonyl-CoA is determined by its rate of synthesis catalysed by ACC (acetyl-CoA carboxylase) relative to its rate of turnover catalysed by FAS (fatty acid synthase). Changes in the level of malonyl-CoA in the hypothalamus alter the expression/secretion of key hypothalamic orexigenic and anorexigenic neuropeptides that regulate the feeding behaviour and energy expenditure. Inhibitors of FAS, administered i.c.v. (intracerebroventricularly) to lean or obese mice, cause a rapid rise in hypothalamic malonyl-CoA level, suppression of food intake, increased fatty acid oxidation in skeletal muscle and profound weight loss. Stereotactic delivery of a viral MCD (malonyl-CoA decarboxylase) expression vector into the ventral hypothalamus lowers malonyl-CoA levels and reverses the anorectic effect of the FAS inhibitors. Fasting decreases, whereas refeeding increases, hypothalamic malonyl-CoA and alters subsequent feeding behaviour accordingly. The level of malonyl-CoA in the hypothalamus appears to be under the control of 5′-AMP kinase, which phosphorylates and thereby inactivates ACC under conditions of energy surplus. Thus malonyl-CoA appears to link the energy-responsive fatty acid synthesis in the hypothalamus to feeding behaviour and peripheral energy expenditure.
Inhibition of pro-inflammatory cytokine receptor signalling by cAMP in vascular endothelial cells
Authors: Sands W.A. , Palmer T.M.
Published: August 2015

The anti-inflammatory effects of the prototypical second messenger cAMP have been extensively documented in multiple cell types. However, in many instances, the molecular mechanisms by which cAMP elevation disrupts specific pro-inflammatory signalling cascades are unknown. In this review, we will describe the importance of the JAK–STAT (where JAK stands for Janus kinase and STAT for signal transducer and activator of transcription) signalling pathway in vascular endothelial cell function, outline key inhibitory processes that serve to reduce cytokine-stimulated tyrosine phosphorylation and activation of STAT proteins, and discuss possible mechanisms by which intracellular cAMP sensors could interact with these inhibitory processes to diminish cytokine receptor-mediated pro-inflammatory signalling.
Single amino acid exchanges in FAD-binding domains of squalene epoxidase of Saccharomyces cerevisiae lead to either loss of functionality or terbinafine sensitivity
Authors: Ruckenstuhl C. , Eidenberger A. , Lang S. , Turnowsky F.
Published: August 2015

Squalene epoxidase (Erg1p) is an essential enzyme in the ergosterol biosynthesis pathway in yeast. For its enzymatic activity, Erg1p requires molecular oxygen, NAD(P)H and FAD. Amino acid analysis and sequence alignment with other squalene epoxidases revealed two highly conserved FAD-binding domains, FAD I and FAD II. By random PCR mutagenesis of the ERG1 gene, one erg1 allele was isolated that carries a mutation leading to a single amino acid exchange in the FAD I domain close to the N-terminus of Erg1p. This erg1 allele codes for functional squalene epoxidase and renders yeast cells hypersensitive to terbinafine. Amino acid exchanges of other conserved residues in the FAD I and FAD II regions either led to non-functional squalene epoxidase or to the formation of squalene epoxidase with wild-type properties. These results describe the importance of specific amino acids for enzymatic activity in the yeast squalene epoxidase Erg1p.
High-throughput subcellular protein localization using cell arrays
Authors: Hu Y.-H. , Vanhecke D. , Lehrach H. , Janitz M.
Published: August 2015

Accomplishment of the human and mouse genome projects resulted in accumulation of extensive gene sequence information. However, the information about the biological functions of the identified genes remains a bottleneck of the post-genomic era. Hence, assays providing simple functional information, such as localization of the protein within the cell, can be very helpful in the elucidation of its function. Transfected cell arrays offer a robust platform for protein localization studies. Open reading frames of unknown genes can be linked to a His6-tag or GFP (green fluorescent protein) reporter in expression vectors and subsequently transfected using the cell array. Cellular localization of the transfected proteins is detected either by specific anti-His-tag antibodies or directly by fluorescence of the GFP fusion protein and by counterstaining with organelle-specific dyes. The high throughput of the method in terms of information provided for every single experiment makes this approach superior to classical immunohistological methods for protein localization.
Enhancing crop yield in Solanaceous species through the genetic manipulation of energy metabolism
Authors: Nunes-Nesi A. , Carrari F. , Lytovchenko A. , Fernie A.R.
Published: August 2015

The improvement of crop yield has been endeavoured for centuries; whereas traditional breeding strategies have achieved this, until recently transgenic approaches to yield improvement have generally been less successful. In this mini-review, we discuss metabolic engineering strategies specifically targeting energy metabolism as a strategy for yield enhancement.
An in silico analysis of trypanosomatid RNA polymerases: insights into their unusual transcription
Authors: Kelly S. , Wickstead B. , Gull K.
Published: August 2015

African trypanosomes employ both Pol I (RNA polymerase I) and Pol II to transcribe protein-coding genes in large polycistronic units of up to 50 genes. Subsequent processing produces mature capped mRNAs. Evidence suggests that regulation of gene expression is primarily exerted post-transcriptionally. Here, we use the recently completed genome sequences of three trypanosomatids, Trypanosoma brucei, Trypanosoma cruzi and Leishmania major, in an in silico analysis of their fundamental RNA polymerase complexes. The core complement of Pol II subunits, including those that are shared with Pol I and Pol III are present. However, both Pol I and Pol III complexes are missing members of the rpoE-rpoF subunit groups. Out of the five shared subunits, both RPB5 and RPB6 have two isoforms in the three trypanosomes. One represents the canonical polymerase subunit and the other differs by insertion or deletion of stretches of charged residues. We propose that these alternative isoforms function in distinct polymerase complexes, and may influence recruitment of the trypanosome RPB4–RPB7 heterodimer.
Helicases that interact with replication forks: new candidates from archaea
Authors: Bolt E.L.
Published: August 2015

Overcoming DNA replication fork blocks is essential for completing genome duplication and cell division. Archaea and eukaryotes drive replication using essentially the same protein machinery. Archaea may be a valuable resource for identifying new helicase components at advancing forks and/or in replication-restart pathways. As described here, these may be relevant to understanding genome instability in metazoans.
Applying science to drug discovery
Authors: McCormack J.G.
Published: August 2015

Scientists and science in the pharmaceutical industry rely heavily on the more academically orientated basic research carried out at Universities, for first of all training, but also as a source of new ideas and approaches to drug discovery. Progress in the discovery and development of novel therapeutics benefits from a healthy alliance with, and the output from, more basic research institutions, and the reverse is also true, with many advances in understanding of physiological and pathological processes being as the result of the application of novel targeted molecules. To illustrate this, some examples related to the themes of this meeting from my experiences in three different companies will be described. The first involves a metabolic angle in the unravelling of the mechanism of the novel anti-anginal agent ranolazine. The second describes the application of detailed knowledge of insulin structure and action to then use recombinant approaches to design novel molecules to be able to offer the Type I (insulin-dependent) diabetic patient therapies allowing a more physiological treatment regime, and also the further application of learned technology to then discover a means of harnessing the potential of GLP-1 (glucagon-like polypeptide 1) for treating Type II (non-insulin-dependent) diabetes. The last illustrates how findings of novel binding sites on glycogen phosphorylase and glucokinase as the result of drug discovery programmes have led to increased understanding of these key metabolic enzymes and also potential new therapies for Type II diabetes.
CRISPR adaptation in Escherichia coli subtypeI-E system
Authors: Kiro Ruth , Goren Moran G. , Yosef Ido , Qimron Udi
Published: August 2015

The CRISPRs (clustered regularly interspaced short palindromic repeats) and their associated Cas (CRISPR-associated) proteins are a prokaryotic adaptive defence system against foreign nucleic acids. The CRISPR array comprises short repeats flanking short segments, called ‘spacers’, which are derived from foreign nucleic acids. The process of spacer insertion into the CRISPR array is termed ‘adaptation’. Adaptation allows the system to rapidly evolve against emerging threats. In the present article, we review the most recent studies on the adaptation process, and focus primarily on the subtype I-E CRISPR–Cas system of Escherichia coli.
The spatiotemporal regulation of the Keap1–Nrf2 pathway and its importance in cellular bioenergetics
Authors: Dinkova-Kostova Albena T. , Baird Liam , Holmström Kira M. , Meyer Colin J. , Abramov Andrey Y.
Published: August 2015

The Kelch-like ECH associated protein 1 (Keap1)–NF-E2 p45-related factor 2 (Nrf2) pathway regulates networks of proteins that protect against the cumulative damage of oxidants, electrophiles and misfolded proteins. The interaction between transcription factor Nrf2 and its main negative cytoplasmic regulator Keap1 follows a cycle whereby the protein complex sequentially adopts two conformations: ‘open’, in which Nrf2 binds to one monomer of Keap1, followed by ‘closed’, in which Nrf2 interacts with both members of the Keap1 dimer. Electrophiles and oxidants (inducers) are recognized by cysteine sensors within Keap1, disrupting its ability to target Nrf2 for ubiquitination and degradation. Consequently, the protein complex accumulates in the ‘closed’ conformation, free Keap1 is not regenerated and newly synthesized Nrf2 is stabilized to activate target-gene transcription. The prevailing view of the Keap1–Nrf2 pathway, for which there exists a wealth of experimental evidence, is that it lies at the heart of cellular defence, playing crucial roles in adaptation and survival under conditions of stress. More recently, the significance of Nrf2 in intermediary metabolism and mitochondrial physiology has also been recognized, adding another layer of cytoprotection to the repertoire of functions of Nrf2. One way by which Nrf2 influences mitochondrial activity is through increasing the availability of substrates (NADH and FADH2) for respiration. Another way is through accelerating fatty acid oxidation (FAO). These findings reinforce the reciprocal relationship between oxidative phosphorylation and the cellular redox state, and highlight the key role of Nrf2 in regulating this balance.
From molecular systems to continuum solids: A multiscale structure and dynamics
Authors: Tong Qi , Li Shaofan
Published: August 2015

We propose a concurrent multiscale molecular dynamics for molecular systems in order to apply macroscale mechanical boundary conditions such as traction and average displacement for solid state materials, which is difficult to do in traditional molecular dynamics where boundary conditions are applied in terms of forces and displacements on selected particles. The multiscale model is systematically constructed in terms of multiscale structures of kinematics, force field, and dynamical equations. The idea is to extend the Anderson-Parrinello-Rahman molecular dynamics to the cases that have arbitrary finite domain and boundary, thus the model is capable of solving inhomogeneous, non-equilibrium problems. The macroscale stress loading on a representative volume element with periodic boundary condition is generalized to all kinds of macroscale mechanical boundary conditions. Unlike most multiscale techniques, our theory is aimed at understanding fundamental physics rather than achieving computing efficiency. Examples of problems with prescribed average displacements and surface tractions are presented to demonstrate the validity of the proposed multiscale molecular dynamics.
Facile time-of-flight methods for characterizing pulsed superfluid helium droplet beams
Authors: He Yunteng , Zhang Jie , Li Yang , Freund William M. , Kong Wei
Published: August 2015

We present two facile time-of-flight (TOF) methods of detecting superfluid helium droplets and droplets with neutral dopants. Without an electron gun and with only a heated filament and pulsed electrodes, the electron impact ionization TOF mass spectrometer can resolve ionized helium clusters such as He2+ and He4+, which are signatures of superfluid helium droplets. Without ionizing any helium atoms, multiphoton non-resonant laser ionization of CCl4 doped in superfluid helium droplets at 266 nm generates complex cluster ions of dopant fragments with helium atoms, including (He)nC+, (He)nCl+, and (He)nCCl+. Using both methods, we have characterized our cryogenic pulsed valve—the Even-Lavie valve. We have observed a primary pulse with larger helium droplets traveling at a slower speed and a rebound pulse with smaller droplets at a faster speed. In addition, the pickup efficiency of dopant is higher for the primary pulse when the nozzle temperature is higher than 13 K, and the total time duration of the doped droplet pulse is only on the order of 20 μs. These results stress the importance of fast and easy characterization of the droplet beam for sensitive measurements such as electron diffraction of doped droplets.
A method for measuring the Néel relaxation time in a frozen ferrofluid
Authors: Tackett Ronald J. , Thakur Jagdish , Mosher Nathaniel , Perkins-Harbin Emily , Kumon Ronald E. , Wang Lihua , Rablau Corneliu , Vaishnava Prem P.
Published: August 2015

We report a novel method of determining the average Néel relaxation time and its temperature dependence by calculating derivatives of the measured time dependence of temperature for a frozen ferrofluid exposed to an alternating magnetic field. The ferrofluid, composed of dextran-coated Fe3O4 nanoparticles (diameter 13.7 nm ± 4.7 nm), was synthesized via wet chemical precipitation and characterized by x-ray diffraction and transmission electron microscopy. An alternating magnetic field of constant amplitude (H0=20 kA/m) driven at frequencies of 171 kHz, 232 kHz, and 343 kHz was used to determine the temperature dependent magnetic energy absorption rate in the temperature range from 160 K to 210 K. We found that the specific absorption rate of the ferrofluid decreased monotonically with temperature over this range at the given frequencies. From these measured data, we determined the temperature dependence of the Néel relaxation time and estimate a room-temperature magnetocrystalline anisotropy constant of 40 kJ/m3, in agreement with previously published results.
Ion implantation for manufacturing bent and periodically bent crystals
Authors: Bellucci Valerio , Camattari Riccardo , Guidi Vincenzo , Mazzolari Andrea , Paternò Gianfranco , Mattei Giovanni , Scian Carlo , Lanzoni Luca
Published: August 2015

Ion implantation is proposed to produce self-standing bent monocrystals. A Si sample 0.2 mm thick was bent to a radius of curvature of 10.5 m. The sample curvature was characterized by interferometric measurements; the crystalline quality of the bulk was tested by X-ray diffraction in transmission geometry through synchrotron light at ESRF (Grenoble, France). Dislocations induced by ion implantation affect only a very superficial layer of the sample, namely, the damaged region is confined in a layer 1 μm thick. Finally, an elective application of a deformed crystal through ion implantation is here proposed, i.e., the realization of a crystalline undulator to produce X-ray beams.
STIM1 enhances SR Ca
2+
content through binding phospholamban in rat ventricular myocytes
Authors: Zhao Guiling , Li Tianyu , Brochet Didier X. P. , Rosenberg Paul B. , Lederer W. J.
Published: August 2015

Significance

Calcium ions play a central role in controlling contraction in heart muscle cells. We have investigated the function of a calcium ion signaling protein found in the heart called STIM1 (stromal interaction molecule 1) that has a known function in many other cells. We discovered, however, that in the heart STIM1 works completely differently. Instead of enabling Ca
2+
entry into the cell, STIM1 enhances the rate and amount of Ca
2+
stored and released from intracellular organelles in the steady state. Hence, more STIM1 expression increases the magnitude of the calcium signal, and this increases contraction. STIM1 thus may play an important and novel role in ventricular myocytes under physiological conditions by regulating the [Ca
2+
]
i
transient and contraction.
Single-sensor multispeaker listening with acoustic metamaterials
Authors: Xie Yangbo , Tsai Tsung-Han , Konneker Adam , Popa Bogdan-Ioan , Brady David J. , Cummer Steven A.
Published: August 2015

Significance

Combining acoustic metamaterials and compressive sensing, we demonstrate here a single-sensor multispeaker listening system that functionally mimics the selective listening and sound separation capabilities of human auditory systems. Different from previous research efforts that generally rely on signal and speech processing techniques to solve the “cocktail party” listening problem, our proposed method is a unique hardware-based approach by exploiting carefully designed acoustic metamaterials. We not only believe that the results of this work are significant for communities of various disciplines that have been pursuing the understanding and engineering of cocktail party listening over the past decades, but also that the system design approach of combining physical layer design and computational sensing will impact on traditional acoustic sensing and imaging modalities.
Glassin, a histidine-rich protein from the siliceous skeletal system of the marine sponge
Euplectella
, directs silica polycondensation
Authors: Shimizu Katsuhiko , Amano Taro , Bari Md. Rezaul , Weaver James C. , Arima Jiro , Mori Nobuhiro
Published: August 2015

Significance

Hexactinellid sponges of the genus
Euplectella
produce highly ordered and mechanically robust skeletal systems of amorphous hydrated silica. The high damage tolerance of their constituent skeletal elements and the environmentally benign conditions under which these sponges form have prompted additional investigations into the characterization of the proteins driving the synthesis of these materials. In the present report, we describe a previously unidentified protein, named “glassin,” extracted from the demineralized skeletal elements of
Euplectella
. Glassin is a histidine-, aspartic acid-, threonine-, and proline-rich protein and directs silica polycondensation at neutral pH and room temperature.
Adaptive evolution of malaria parasites in French Guiana: Reversal of chloroquine resistance by acquisition of a mutation in
pfcrt
Authors: Pelleau Stéphane , Moss Eli L. , Dhingra Satish K. , Volney Béatrice , Casteras Jessica , Gabryszewski Stanislaw J. , Volkman Sarah K. , Wirth Dyann F. , Legrand Eric , Fidock David A. , Neafsey Daniel E. , Musset Lise
Published: August 2015

Significance

This study addresses the evolutionary dynamics of antimalarial drug resistance after changes in drug use. We show that chloroquine resistance in
Plasmodium falciparum
from French Guiana was lost after sustained drug removal, whereas the resistance marker PfCRT K76T remained fixed in the parasite population. This phenotypic reversion was caused by the acquisition of a single additional C350R substitution in PfCRT. This genetic change also impaired susceptibility to piperaquine, suggesting that piperaquine pressure drove the expansion of this allele. These findings have important implications for understanding drug resistance evolution when standard resistance alleles reach fixation and can lose their utility as markers because of adaptive changes at other amino acid positions or loci in the genome.
Breakthrough of SIV strain smE660 challenge in SIV strain mac239-vaccinated rhesus macaques despite potent autologous neutralizing antibody responses
Authors: Burton Samantha L. , Kilgore Katie M. , Smith S. Abigail , Reddy Sharmila , Hunter Eric , Robinson Harriet L. , Silvestri Guido , Amara Rama R. , Derdeyn Cynthia A.
Published: August 2015

Significance

It is widely believed that if an HIV vaccine elicits moderate in vitro titers of serum neutralizing antibodies (nAbs) against a challenge virus, it will prevent infection. This paradigm is based on studies in which passive transfer of HIV-specific nAbs protected rhesus macaques from mucosal challenge with a chimeric simian/human immunodeficiency virus. However, it is unknown whether this direct relationship can be extrapolated to protection in the setting of active immunization. Our data suggest that the relationship between serum in vitro nAb titers and protection from mucosal SIV challenge is more complex than previously recognized in the setting of active immunization, warranting further studies to understand the balance between immune activation, target cell availability, and protective antibody responses.