bluuebunny/crossref_metadata_2025 huggingface dataset:
New insights into pediatric idiopathic pulmonary hemosiderosis: the French RespiRare® cohort
Authors: Taytard Jessica , Nathan Nadia , de Blic Jacques , Fayon Mickael , Epaud Ralph , Deschildre Antoine , Troussier Françoise , Lubrano Marc , Chiron Raphaël , Reix Philippe , Cros Pierrick , Mahloul Malika , Michon Delphine , Clement Annick , Corvol Harriet ,   for the French RespiRare® group
Published: October 2013

Background

Idiopathic pulmonary hemosiderosis (IPH) is a rare cause of alveolar hemorrhage in children and its pathophysiology remains obscure. Classically, diagnosis is based on a triad including hemoptysis, diffuse parenchymal infiltrates on chest X-rays, and iron-deficiency anemia. We present the French pediatric cohort of IPH collected through the French Reference Center for Rare Lung Diseases (RespiRare®,http://www.respirare.fr).

Methods

Since 2008, a national network/web-linked RespiRare® database has been set up in 12 French pediatric respiratory centres. It is structured as a medical recording tool with extended disease-specific datasets containing clinical information relevant to all forms of rare lung diseases including IPH.

Results

We identified 25 reported cases of IPH in children from the database (20 females and 5 males). Among them, 5 presented with Down syndrome. Upon diagnosis, median age was 4.3 [0.8-14.0] yrs, and the main manifestations were: dyspnea (n = 17, 68%), anemia (n = 16, 64%), cough (n = 12, 48%), febrile pneumonia (n = 11, 44%) and hemoptysis (n = 11, 44%). Half of the patients demonstrated diffuse parenchymal infiltrates on chest imaging, and diagnosis was ascertained either by broncho-alveolar lavage indicating the presence of hemosiderin-laden macrophages (19/25 cases), or lung biopsy (6/25). In screened patients, initial auto-immune screening revealed positive antineutrophilic cytoplasmic antibodies (ANCA) (n = 6, 40%), antinuclear antibodies (ANA) (n = 5, 45%) and specific coeliac disease antibodies (n = 4, 28%). All the patients were initially treated by corticosteroids. In 13 cases, immunosuppressants were introduced due to corticoresistance and/or major side effects. Median length of follow-up was 5.5 yrs, with a satisfactory respiratory outcome in 23/25 patients. One patient developed severe pulmonary fibrosis, and another with Down syndrome died as a result of severe pulmonary hemorrhage.

Conclusion

The present cohort provides substantial information on clinical expression and outcomes of pediatric IPH. Analysis of potential contributors supports a role of auto-immunity in disease development and highlights the importance of genetic factors.
Number of glioma polyploid giant cancer cells (PGCCs) associated with vasculogenic mimicry formation and tumor grade in human glioma
Authors: Qu Yang , Zhang Li , Rong Zhe , He Tao , Zhang Sai
Published: October 2013

Background

Polyploid giant cancer cells (PGCCs) contribute to solid tumor heterogeneity. This study investigated the relationships among PGCCs numbers, vasculogenic mimicry (VM) formation, and tumor grades in glioma.

Methods

A total of 76 paraffin-embedded glioma tissue samples, including 28 cases of low grade and 48 cases of high grade gliomas, were performed with H&E and immunohistochemical staining for Ki-67 and hemoglobin. The size of PGCCs nuclei was measured by a micrometer using H&E section and defined as at least three times larger than the nuclei of regular diploid cancer cells. The number of PGCCs and different blood supply patterns were compared in different grade gliomas. Microcirculation patterns in tumors were assessed using CD31 immunohistochemical and PAS histochemical double staining. Human glioma cancer cell line C6 was injected into the chicken embryonating eggs to form xenografts, which was used to observe the PGCCs and microcirculation patterns.

Results

In human glioma, the number of PGCCs increased with the grade of tumors (χ
2 = 4.781, P = 0.015). There were three kinds of microcirculation pattern in human glioma including VM, mosaic vessel (MV) and endothelium dependent vessel. PGCCs were able to generate erythrocytes via budding to form VM. The walls of VM were positive (or negative) for PAS staining and negative for CD31 staining. There were more VM and MVs in high grade gliomas than those in low grade gliomas. The differences have statistical significances for VM (t = 3.745, P = 0.000) and MVs (t = 4.789, P = 0.000). PGCCs, VM and MVs can also be observed in C6 chicken embryonating eggs xenografts.

Conclusions

The data demonstrated presence of PGCCs, VM and MVs in glioma and PGCCs generating erythrocytes contribute the formation of VM and MVs.
The interplay between inflammation, physical activity and metabolic syndrome in a remote male geriatric community in Southern Taiwan: the Tianliao Old People (TOP) study 03
Authors: Chang Chia-Ling , Lee Po-Tseng , Chang Wei-Ting , Chang Chin-Sung , Chen Jyh-Hong , Tsai Liang-Miin , Wu Chih-Hsing , Liu Ping-Yen
Published: October 2013

Background

Both physical activity and inflammation are important in the pathophysiology of metabolic syndrome (MetS). Our study aim is to explore their associations in an elderly male (≥ 65 years old) cohort.

Methods

We enrolled 309 elderly male residents (mean age: 74.4 ± 6.0 years) in a remote southern Taiwan community. The physical activity was recorded by a standard questionnaire. A high-sensitivity C-reactive protein (hsCRP) level > 3.0 mg/L indicated a high inflammatory status.

Results

The total prevalence rate of MetS was 27.8% in this male geriatric cohort. Median hsCRP levels were significantly higher in the MetS group (1.60 ± 0.7 vs. 1.0 ± 0.3 mg/L,p < 0.01), and the risk of elevated hsCRP increased with escalating MetS components (pfor trend < 0.001). The non-MetS group had higher amount of median weekly physical activity (183.1 ± 19.0 vs. 173.5 ± 10.6 MET-hr/week,p = 0.029), which was also higher among those with lower hsCRP levels (186.1 ± 14.1 vs. 167.8 ± 38.5 MET-hr/week,p = 0.013). Multivariate analysis showed that higher body mass index (ORs: 1.527, 95% CI: 1.319-1.768,p < 0.01) insulin (OR: 1.128, 95% CI: 1.045-1.218,p < 0.01) and physical activity (ORs: 0.997, 95% IC: 0.994-0.999,p < 0.05) were independent predictors of MetS, but not hsCRP level (p > 0.05).

Conclusions

Reduced physical activity was one major pathophysiological MetS factor in our Asian geriatric participants.
NMR studies of a Glutaredoxin 2 from Clostridium oremlandii
Authors: Lee Eun Hye , Cheong Hae-Kap , Kim Hye-Yeon
Published: October 2013

Background

Grx2 is a glutaredoxin from gram positive bacterium Clostridium oremlandii (strain OhILAs), which is Cys-homolog of selenoprotein Grx1. Grx2 is a poor reductant of selenoprotein MsrA not like Grx1 while the reducing activity is reversed in two Grxs for Cys version of MsrA.

Methods

The wild-type Grx2 and the C15S mutant were overexpressed in E.coli and purified by affinity chromathography and gel filtration. The 3D NMR spectra was collected and assigned all the backbone chemical shifts including Cα, Cβ, CΟ, HN, and N of Grx2 and C15S mutant. The protein folding of two proteins were evaluated by circular dichroism.

Results

Here we report the protein purification and NMR spectroscopic study of recombinant Grx2 and the C15S mutant. The HSQC spectrum of two proteins show chemical shift difference for residues 8-19, 52-55,66. The circular dichroism result shows that recombinant proteins are well folded.

Conclusion

The conformation of two proteins resembles the oxidized form (wild-type Grx2) and the reduced form (the C15S mutant). The residues showing chemical shift difference will join the conformational change of Grx2 upon a disulfide formation.
Proteomic and bioinformatic analysis of recurrent anaplastic oligodendroglioma
Authors: Hong Yeonhee , Park Edmond Changkyun , Shin Eun-Young , Kwon Sang-Oh , Oh Young-Taek , Choi Byung-Ock , Kim Giwon , Kim Gun-Hwa
Published: October 2013

Background

Anaplastic oligodendroglioma (AO) is a type of glioma that is believed to originate from oligodendrocytes in the brain or from glial precursor cells. Recurrence of AO reduces the overall survival rate of patients and causes meningeal or even systemic spread/metastasis more frequently than other types of gliomas. We performed proteomic analysis of recurrent AO tumors to identify the proteins significantly expressed in recurrent AO and to understand biological characteristics of recurrent AO.

Findings

Using human brain tissues, we identified 401 proteins that were significantly expressed in recurrent AO. Through bioinformatic analysis, we determined that the majority of the identified proteins are involved in anti-apoptotic pathway and cell proliferation. In addition, our findings suggest that epidermal growth factor (EGF) signaling may be responsible for the development of recurrent AO.

Conclusions

These results will aid researchers in understanding the pathology of recurrent AO and identifying the therapeutic targets for the treatment of recurrent AO.
Cerebellar Aspergillosis in an Infant: Case Report
Authors: Mohindra Sandeep , Gupta Rahul , Mohindra Satyawati , Gupta Sunil Kumar , Vaiphei Kim
Published: October 2013

OBJECTIVE AND IMPORTANCE:

Intracranial aspergillosis is occasionally seen among immunocompromised patients, the incidence increasing in consequence to large-scale use of chemotherapy against malignancies and immunosuppression after organ transplantation. Immunocompetent patients harboring invasive intracranial fungal infections still remain an elusive diagnosis.

CLINICAL PRESENTATION:

A 7-month-old immunocompetent infant who developed and harbored cerebellar aspergillosis until 3 years of age is reported.

INTERVENTION:

Radical surgical resection of posterior fossa mass (aspergilloma) and parenteral administration of Amphotericin B led to a successful outcome.

CONCLUSION:

The differential diagnosis at both stages of presentation and the possible mode of infection are discussed according to the radiological images. Preoperative diagnosis on the basis of imaging is difficult. The pathogenesis of such an infection remains uncertain. Parenteral Amphotericin B, followed by prolonged itraconazole therapy, remains the “gold standard” modality for central nervous system fungal infections in adjunct to aggressive surgical debridement.
Magnetic Force-Based Microarray Chips on Soda Lime Glass Prepared by Plating Method for Medical Application
Authors: Arakawa Tomiyuki , Watanabe Nobuaki , Takeda Hiroshi , Haijima Yuki , Takanashi Hiroshi , Obata Tsutomu , Koiwa Ichiro
Published: October 2013

In medicine, microarray chips are desired in order to improve personal medicine. In this paper, we propose a fabrication method for microarray chips using electroplated soft magnetic films on glass substrates using a simple process. Electroless plated Ni–P films were formed on soda lime glass as conductive substrates and were subsequently annealed at 150 °C for 30 min to improve adhesion strength between the films and glass substrates. Microspot array photoresists were patterned on the Ni–P films by photolithography. Co–Ni–Fe alloy films were then electroplated and finely the photoresist removed. As determined by electron probe microanalysis, the Co–Ni–Fe films were composed of 15–74 atom % Co, 12–72 atom % Fe, and 1.6–24 atom % Ni under several plating bath compositions. Vibrating sample magnetometry showed saturation magnetic flux density of 1400–2200 emu cm−3, residual magnetic flux density of 1100–1600 emu cm−3 and coercive force of 90–100 Oe on the Co–Ni–Fe films. A microspot array prepared by electroplated Co–Ni–Fe soft magnetic films/electroless plated Ni–P films on soda lime glass with simple patterning successfully trapped pseudo B-lymphocytes conjugated with magnetic beads.
Quantum Mechanical Theory of Electrochemical Kinetics: Analysis by Electron Transfer Distance and Transition Probability
Authors: Sakata Tadayoshi , Azuma Masashi
Published: October 2013

Quantum mechanical theory of electrochemical kinetics based on Fermi’s golden rule was formulated by introducing the concept of electron-transfer distance. The expressions for the exchange current density and standard rate constant in electrochemistry were derived in analytical form, as well as exponential current overpotential dependence. The theory corresponds well to the electrode kinetics based on the transition state theory that is familiar at present with many electrochemists. It was applied to various kinds of electrode reactions to analyze the standard rate constants and the exchange current densities reported in past literature. The evaluated magnitudes of the electron exchange energy were very small, being in the order of 10−3–10−5 eV. This theory supports the ordinary electron-transfer mechanism due to the overlap of wave functions between the electrode and redox species, denying tunneling mechanism.
Synthesis and Solvatochromic Behavior of Pyrene Derivatives with 4-Hydroxyphenyl and 4-Hydroxyphenylethynyl Groups
Authors: Yamaguchi Isao , Sato Katsuhiko
Published: October 2013

1-(4-Methoxyphenyl)pyrene (PyrPhOMe(1)), 1,3,6,8-tetrakis(4-methoxyphenyl)pyrene (PyrPhOMe(4)), 1-(4-methoxyphenylethynyl)pyrene (PyrC≡CPhOMe(1)), 1,3,6,8-tetrakis(4-methoxyphenylethynyl)pyrene (PyrC≡CPhOMe(4)), 1-(4-hydroxyphenylethynyl)pyrene (PyrC≡CPhOH(1)), and 1,3,6,8-tetrakis(4-hydroxyphenylethynyl)pyrene (PyrC≡CPhOH(4)) were synthesized via organometallic complex catalysis. Deprotection of the methoxy groups of PyrPhOMe(1) and PyrPhOMe(4) was conducted by treatment with BBr3. Deprotonation of the OH groups of PyrPhOH(1), PyrPhOH(4), PyrC≡CPhOH(1), and PyrC≡CPhOH(4) through treatment with NaH caused a bathochromic shift in the absorption and photoluminescence (PL) peaks. The bathochromic shift of the deprotonated species increased with the donor number (DN) of the solvents. These observations can be explained as the consequence of intramolecular charge transfer (ICT) from the ONa groups to the pyrene core.
Hearsay Evidence in South Africa: Should Courts Add the ‘Sole and Decisive Rule’ to Their Arsenal?
Authors: Mujuzi Jamil Ddamulira
Published: October 2013

The South African Law of Evidence Amendment Act (LEAA) recognises the fact that as a general rule hearsay evidence is inadmissible but creates exceptions to this general rule. South African courts are reluctant to convict accused in cases where hearsay evidence plays a decisive or even significant role in the accused's conviction. However, while relying on the LEAA the Supreme Court of Appeal held that the true test of the admission of hearsay evidence is whether it is in the interest of justice to admit such evidence irrespective of its role in the accused's conviction. Relying on the jurisprudence of the European Court of Human Rights, the author argues that the introduction of a sole and decisive rule would strengthen the accused's right to a fair trial in hearsay evidence cases.
Solubility phenomena studies concerning brines in China
Authors: Song Pengsheng , Sun Bai , Zeng Dewen
Published: October 2013

Solubility equilibria are relevant to many aspects of chemistry and chemical engineering. Studies on solubility phenomena are of importance in understanding chemistry and in the development of chemical technology. Solubility equilibria are especially useful for geochemists investigating the formation and evolution of natural salt deposits. China possesses an enormous variety of such resources, including salt lakes, underground brines, oilfield brines, and natural soda and borate deposits, etc. With the ongoing economic development of China, the exploitation and comprehensive utilization of these kinds of mineral resources are making great progress. Although much research on aqueous salt systems has been published, solubility equilibria studies have long been an active research field in China. This paper presents a review of solubility research on salt/water systems, encompassing more than 200 papers from Chinese researchers.
Gut neuroendocrine tumor blood qPCR fingerprint assay: characteristics and reproducibility
Authors: Modlin Irvin M. , Drozdov Ignat , Kidd Mark
Published: October 2013

Background: We have developed a PCR-based tool that measures a 51-gene panel for identification of gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) in peripheral blood. This manuscript assesses the robustness (performance metrics) of this tool with a specific focus on the effects of individual parameters including collection, storage, acid suppressive medication [proton pump inhibitor (PPI)], age, sex, race and food on accuracy.

Methods: Performance metrics were evaluated using a gold standard (mRNA derived from three individual human neuroendocrine tumor cell lines) and clinical samples using qPCR.

Results: One hundred percent of the 51 transcripts were amplified in the gold standard (NEN cell line-derived mRNA) (CQ<35, average efficiency 1.94). The inter- and intra-assay variations were 1%–2%. In clinical samples, 50 of 51 targets (98%) were amplified. The inter- and intra-assay reproducibility ranged between 0.4% and 1.2%. The coefficient of variation (CV) was 5.3%. Expression of the reference gene, ALG9, was robust [low variation, low M-value, high (99.5%) PCR efficiency] and unaffected by sample processing. Test meals, long-term PPI use (>1 year), age, sex and ethnicity had no effect on the signature. Expression of two genes, ALP2 and CD59 correlated strongly with RNA integrity (R=0.72, p<0.001) and could be used to assess storage and processing.

Conclusions: The 51 marker gene signature was robust and reproducible, exhibiting acceptable inter- and intra-assay metrics (<5%). Feeding, PPI intake, age, sex and ethnicity do not affect the signature. Expression levels of APLP2 and CD59 are effective surrogate markers of proper sample collection and processing.
The role of oxidative stress during inflammatory processes
Authors: Lugrin Jérôme , Rosenblatt-Velin Nathalie , Parapanov Roumen , Liaudet Lucas
Published: October 2013

The production of various reactive oxidant species in excess of endogenous antioxidant defense mechanisms promotes the development of a state of oxidative stress, with significant biological consequences. In recent years, evidence has emerged that oxidative stress plays a crucial role in the development and perpetuation of inflammation, and thus contributes to the pathophysiology of a number of debilitating illnesses, such as cardiovascular diseases, diabetes, cancer, or neurodegenerative processes. Oxidants affect all stages of the inflammatory response, including the release by damaged tissues of molecules acting as endogenous danger signals, their sensing by innate immune receptors from the Toll-like (TLRs) and the NOD-like (NLRs) families, and the activation of signaling pathways initiating the adaptive cellular response to such signals. In this article, after summarizing the basic aspects of redox biology and inflammation, we review in detail the current knowledge on the fundamental connections between oxidative stress and inflammatory processes, with a special emphasis on the danger molecule high-mobility group box-1, the TLRs, the NLRP-3 receptor, and the inflammasome, as well as the transcription factor nuclear factor-κB.
Chemical and pharmacological standardization of Ashwagandhadi lehyam: an ayurvedic formulation
Authors: Rasheed Arun , Satyanarayana K.V. , Gulabi P. Swetha , Rao M. Sindhura
Published: October 2013

Standardization is an important measurement for ensuring the quality control of herbal drugs. It has become essential to develop reliable, specific and sensitive quality control methods. One of the prime ingredients of Ashwagandhadi lehyam is Withania somnifera L. Dunal (Solanaceae) (ashwagandha). In the present study, Ashwagandhadi lehyam was formulated and the quality assessment of the formulation was based on phytochemical screening and physico-chemical evaluation. Ashwagandhadi lehyam was formulated according to a working formula and subjected to phytochemical screening by FTIR analysis and HPTLC fingerprinting, heavy metal determination by AAS, determination of alcohol content, tested for Escherichia coli, Staphylococcus aureus, aerobic bacteria, yeasts and mould, oral toxicity studies and anti-epileptic activity by MES method. The physico-chemical studies showed total ash content as 6.45%, extractive values and some trace elements such as lead, mercury, cadmium and arsenic with 3.2, 0.05, 0.18 and 0.48 ppm, respectively. FTIR and HPTLC studies revealed the presence of functional groups of withanolides in Ashwagandhadi lehyam, resulting in its chemical standardization. The formulation exhibited less epileptic seizures in various phases when compared with that of standard phenytoin and found to possess better anti-inflammatory activity, thus making it biologically standardized. The physico-chemical and pharmacological analysis to standardize Ashwagandhadi lehyam confirmed its use as a safe anti-inflammatory agent and for various seizure disorders.
Questioning size effects as predicted by strain gradient plasticity
Authors: Forest Samuel
Published: October 2013

The analytical solution of the elastic-plastic response of a two-phase laminate microstructure subjected to periodic simple shear loading conditions is derived considering strain gradient and micromorphic plasticity models successively. One phase remains purely elastic, whereas the second one displays an isotropic elastic-plastic behavior. Although no classic hardening is introduced at the individual phase level, the laminate is shown to exhibit an overall linear hardening scaling with the inverse of the square of the cell size. The micromorphic model leads to a saturation of the hardening at small length scales in contrast to Aifantis strain gradient plasticity model displaying unlimited hardening. The models deliver qualitatively relevant size effects from the physical metallurgical point of view, but fundamental quantitative discrepancy is pointed out and discussed, thus requiring the development of more realistic nonlinear equations in strain gradient plasticity.
Holey fibers for low bend loss
Authors: Nakajima Kazuhide , Saito Kotaro , Yamada Yusuke , Kurokawa Kenji , Shimizu Tomoya , Fukai Chisato , Matsui Takashi
Published: October 2013

Bending-loss insensitive fiber (BIF) has proved an essential medium for constructing the current fiber to the home (FTTH) network. By contrast, the progress that has been made on holey fiber (HF) technologies provides us with novel possibilities including non-telecom applications. In this paper, we review recent progress on hole-assisted type BIF. A simple design consideration is overviewed. We then describe some of the properties of HAF including its mechanical reliability. Finally, we introduce some applications of HAF including to high power transmission. We show that HAF with a low bending loss has the potential for use in various future optical technologies as well as in the optical communication network.
Genomic Sequence Diversity and Population Structure ofSaccharomyces cerevisiaeAssessed by RAD-seq
Authors: Cromie Gareth A , Hyma Katie E , Ludlow Catherine L , Garmendia-Torres Cecilia , Gilbert Teresa L , May Patrick , Huang Angela A , Dudley Aimée M , Fay Justin C
Published: October 2013

The budding yeast Saccharomyces cerevisiae is important for human food production and as a model organism for biological research. The genetic diversity contained in the global population of yeast strains represents a valuable resource for a number of fields, including genetics, bioengineering, and studies of evolution and population structure. Here, we apply a multiplexed, reduced genome sequencing strategy (restriction site−associated sequencing or RAD-seq) to genotype a large collection of S. cerevisiae strains isolated from a wide range of geographical locations and environmental niches. The method permits the sequencing of the same 1% of all genomes, producing a multiple sequence alignment of 116,880 bases across 262 strains. We find diversity among these strains is principally organized by geography, with European, North American, Asian, and African/S. E. Asian populations defining the major axes of genetic variation. At a finer scale, small groups of strains from cacao, olives, and sake are defined by unique variants not present in other strains. One population, containing strains from a variety of fermentations, exhibits high levels of heterozygosity and a mixture of alleles from European and Asian populations, indicating an admixed origin for this group. We propose a model of geographic differentiation followed by human-associated admixture, primarily between European and Asian populations and more recently between European and North American populations. The large collection of genotyped yeast strains characterized here will provide a useful resource for the broad community of yeast researchers.
Coupling Between Noise and Plasticity in E. coli
Authors: Singh Gajinder Pal
Published: October 2013

Expression levels of genes vary not only between different environmental conditions (“plasticity”) but also between genetically identical cells in constant environment (“noise”). Intriguingly, these two measures of gene expression variability correlate positively with each other in yeast. This coupling was found to be particularly strong for genes with specific promoter architecture (TATA box and high nucleosome occupancy) but weak for genes in which high noise may be detrimental (e.g., essential genes), suggesting that noise–plasticity coupling is an evolvable trait in yeast and may constrain evolution of gene expression and promoter usage. Recently, similar genome-wide data on noise and plasticity have become available for Escherichia coli, providing the opportunity to study noise–plasticity correlation and its mechanism in a prokaryote, which follows a fundamentally different mode of transcription regulation than a eukaryote such as yeast. Using these data, I found significant positive correlation between noise and plasticity in E. coli. Furthermore, this coupling was highly influenced by the following: level of expression; essentiality and dosage sensitivity of genes; regulation by specific nucleoid-associated proteins, transcription factors, and sigma factors; and involvement in stress response. Many of these features are analogous to those found to influence noise–plasticity coupling in yeast. These results not only show the generality of noise–plasticity coupling across phylogenetically distant organisms but also suggest that its mechanism may be similar.
RNA-Guided Genome Editing for Target Gene Mutations in Wheat
Authors: Upadhyay Santosh Kumar , Kumar Jitesh , Alok Anshu , Tuli Rakesh
Published: October 2013

The clustered, regularly interspaced, short palindromic repeats (CRISPR) and CRISPR-associated protein (Cas) system has been used as an efficient tool for genome editing. We report the application of CRISPR-Cas–mediated genome editing to wheat (Triticum aestivum), the most important food crop plant with a very large and complex genome. The mutations were targeted in the inositol oxygenase (inox) and phytoene desaturase (pds) genes using cell suspension culture of wheat and in the pds gene in leaves of Nicotiana benthamiana. The expression of chimeric guide RNAs (cgRNA) targeting single and multiple sites resulted in indel mutations in all the tested samples. The expression of Cas9 or sgRNA alone did not cause any mutation. The expression of duplex cgRNA with Cas9 targeting two sites in the same gene resulted in deletion of DNA fragment between the targeted sequences. Multiplexing the cgRNA could target two genes at one time. Target specificity analysis of cgRNA showed that mismatches at the 3′ end of the target site abolished the cleavage activity completely. The mismatches at the 5′ end reduced cleavage, suggesting that the off target effects can be abolished in vivo by selecting target sites with unique sequences at 3′ end. This approach provides a powerful method for genome engineering in plants.
The efficacy of the bio-electro-magnetic-regulation therapy and pentoxifylline treatment in peripheral arterial stenosis
Authors: Bernát Sándor Iván
Published: October 2013

Introduction: There are limited therapeutic options to improve microcirculation. Aim: The question of the study was to investigate any potential beneficial effect of bio-electro-magnetic-regulation therapy on microcirculation in patients suffering from peripheral arterial stenosis including the circulation of lower extremities, as well as intermittent claudication. Method: Thirty patients suffering from peripheral arterial stenosis (Fontaine IIa and IIb) were recruited. The first step of the study was to determine the pain free and maximal walking distance with a treadmill unit. After the placebo period patients received 8 and 20 minutes bio-electro-magnetic-regulation treatment 16 times. After the treatment the pain free and maximal walking distance were measured again. In the second stage of the study the patients were treated by pentoxifylline infusions. Results: bio-electro-magnetic-regulation treatment increased the pain free period by 57.4% (p = 0.005) and the maximal walking distance by 36.6% (p = 0.042). The two forms of therapy together increased the pain free and maximal walking distance by 81.9% and by 84.0%, respectively. The combined therapy was very effective in contrast to placebo and bio-electro-magnetic-regulation treatment (p = 0.000373 and p = 0.00741, respectively). Conclusions: The bio-electro-magnetic-regulation therapy mainly affected the microvessels and pentoxifylline therapy rather had beneficial effects on hemoreology. The clinical effectiveness of combined therapy was good or excellent in 70% of patients. Orv. Hetil., 154 (42), 1674–1679.
Cellular and intracellular transport of vitamin C. The physiologic aspects
Authors: Szarka András , Lőrincz Tamás
Published: October 2013

Vitamin C requirement is satisfied by natural sources and vitamin C supplements in the ordinary human diet. The two major forms of vitamin C in the diet are L-ascorbic acid and L-dehydroascorbic acid. Both ascorbate and dehydroascorbate are absorbed along the entire length of the human intestine. The reduced form, L-ascorbic acid is imported by an active mechanism, requiring two sodium-dependent vitamin C transporters (SVCT1 and SVCT2). The transport of the oxidized form, dehydroascorbate is mediated by glucose transporters GLUT1, GLUT3 and possibly GLUT4. Initial rate of uptake of both ascorbate and dehydroascorbate is saturable with increasing external substrate concentration. Vitamin C plasma concentrations are tightly controlled when the vitamin is taken orally. It has two simple reasons, on the one hand, the capacity of the transporters is limited, on the other hand the two Na+-dependent transporters can be down-regulated by an elevated level of ascorbate. Orv. Hetil., 154 (42), 1651–1656.
Advantages of ramipril/amlodipin fixed combination therapy. When should we use it?
Authors: Simonyi Gábor
Published: October 2013

Hypertension is one of the most frequent chronic disease in Hungary and one of the most important cardiovascular risk factor. Treatment of blood pressure to target value lowers significantly the risk of coronary artery disease, stroke and chronic renal disease as well as it decreases mortality. Blood pressure control has a great importance in high risk patients. In addition to life style changes, drug treatment plays an essential role in the management of hypertensive patients. The complexity of drug regimen, characteristics of drug class, age and gender are all exert impacts on patient adherence. Antihypertensive drugs should preferably have metabolically neutral properties and cardiovascular protective effects. Ramipril/amlodipine fixed combination meets these criteria and adherence of patients is favorable. Orv. Hetil., 154 (42), 1658–1664.
Biogeochemical impacts of the northward expansion of kudzu under climate change: the importance of ecological context
Authors: Hickman Jonathan E. , Lerdau Manuel T.
Published: October 2013

Climate change is generally expected to push plant species to higher latitudes and elevations; how the climate‐induced migrations of disruptive invasive species may affect higher‐latitude ecosystems has not been widely examined. Kudzu (Pueraria montana) has large impacts on nitrogen (N) cycling and trace N gas emissions in the southeastern United States. To understand how its projected northward migration under climate change will impact ecosystems in the northeastern United States, we examine the impacts of kudzu in the Mid‐Atlantic region, near kudzu's northern invasion front. We pair plots invaded by kudzu with adjacent uninvaded plots, and examine rates of leaf litter decomposition, soil nitrogen pools and net cycling rates, N trace gas emissions, and microbial dynamics. Kudzu litter has more N and decomposes faster than litter from co‐occurring species. Unlike in Georgia, near the center of kudzu's current range in the United States, kudzu invasion in the Mid‐Atlantic has very small ecosystem impacts, causing significant increases only in the sizes of soil nitrate pools. These Mid‐Atlantic ecosystems may be buffered against invasion impacts, creating a lag between changes in the plant community and biogeochemical changes. A combination of factors, including time since establishment, soil types, growing season length, and temperatures, may limit kudzu's biogeochemical impacts along its invasion front.
The Design and Execution of an Alkaline/Surfactant/Polymer Pilot Test
Authors: Sharma A.. , Azizi-Yarand A.. , Clayton B.. , Baker G.. , McKinney P.. , Britton C.. , Delshad M.. , Pope G..
Published: October 2013

A tertiary alkaline/surfactant/polymer (ASP) pilot flood was implemented during 2010 in the Illinois basin of the US, and is continuing currently. With initial discovery of the Bridgeport sandstone formation in the early 1900s and more than 60 years of waterflooding, the pilot was designed to demonstrate that ASP flooding could produce sufficient quantities of incremental oil to sanction a commercial project. Laboratory experiments, including corefloods, were performed to determine the optimal chemical formulation for the pilot and to provide essential parameters for a numerical-simulation model. Polymer-injectivity tests, single well chemical tracer tests (SWCTTs), and an interwell-tracer-test (IWTT) program were all performed to prepare for and support a full interpretation of the pilot results. A field laboratory was run through the duration of the pilot to monitor the quality of the injection and production fluids, which turned out to be critical to the success of the pilot. We present the results and interpretation of the ASP pilot to date, the challenges faced during the project, and the lessons learned from the field perspective.
The Impact of Thermogas Technologies on the Bazhenov Formation Studies Results
Authors: Kokorev V. I. , Darischev V. I. , Ahmadeyshin I. A. , Schekoldin K. A. , Bokserman A. A.
Published: October 2013

At present time; there is change in the structure of Russian oil raw materials production by increasing the share of hard and unconventional hydrocarbons.

The main reserves of unconventional hydrocarbon deposits in Russia are concentrated in Bazhenov Formation (BF). BF deposits occur at depths 2500–3000 m, the thickness is from 10 to 44 meters. Reservoir temperature varies from 80 º C to 134 º C. BF deposits are similar to the oil shale, but their distinguishing feature is that the process of converting organic matter into oil is not complete yet. So alongside with light oil, collector contains hydrocarbons directly in the form of the rock-forming constituent parts, called kerogen.

Thus, the organic part of the BF is presented in two forms: liquid hydrocarbons – light oil with an average grade of 7.2% of the volume of rock and kerogen with an average grade of 23.3% of the rock volume.

Kerogen is the main part of the organic material in the sediments of the Bazhenov Formation and is considered as a substance that generates on stage katagenesis major amount of oil and gas.

BF Hydrocarbon resources are estimated in 50 to 150 billion tonnes according to many experts.

At the present time BF hydrocarbon resources is used inefficiently. Experience shows that the use of traditional methods of development has led to the recovery of only 3–5% of oil contained in the pore space.

OJSC "RITEK" is developing thermogas technology, taking into account the huge potential of the production of hydrocarbons from the BF.

The most important condition for applying thermogas impact on the rocks of the BF is based on the field and laboratory results that the filtration and capacitive characteristics of rocks of the BF is largely determined by the level of temperature (Fig.1).

For all types of kerogenic rocks noted an increase in porosity and permeability, the initial flow rate, cumulative production, hence the drainage area with the increase in temperature.

Numerous experimental studies have shown that increasing the micropore (matrix) temperature to 250–350 not only allow to produce 70–80% of the initially contained therein light oil but to convert part of kerogen in hydrocarbons (Fig.2).
The importance of local events in enriching the cultural and tourism offer
Authors: Spasojevic Bojana , Beric Dejan , Jovicic Ana
Published: October 2013

In the municipality of Ruma twenty five events take place per year. Most of
these events have local or regional character. The event "Christmas Street"
is the youngest event which is being organized in Ruma, the first time was
held in late 2011. The subject of this paper is to study this event that
complements the existing tourism offer of Ruma as potential tourist
destination of Vojvodina. The aim of this paper is to highlight the
importance of this event in the cultural enrichment of Ruma and its
surroundings as well as the development of event tourism and positive
presentation of the Municipality of Ruma. The significance of local events
for enrichment of cultural-tourism offer will be presented as Case study of
?Christmas street? in the city of Ruma.
Nanostructured Fe2O3/TiO2 thick films prepared by screen printing
Authors: Aleksic Obrad , Djuric Zorka , Nikolic Maria , Tasic Nikola , Vukovic Marina , Marinkovic-Stanojevic Zorica , Nikolic Nenad , Nikolic Pantelija
Published: October 2013

Nanostructured single layered (pure TiO2 , pure ?-Fe2O3 and mixed Fe2O3 /TiO2
with two different oxide ratios, 2 : 3 and 3 : 2) and double layered (TiO2
layer over a Fe2O3 layer) thick films have been fabricated by screen printing
technology on a glass substrate. The pastes used for film preparation were
obtained by adding an organic vehicle to the oxide powders together with a
small percentage of binding glass frit. Samples were dried up to 100 ?C and
sintered at 650 ?C/60 minutes. Structural, morphological and optical studies
have been carried out using XRD, SEM analyses and UV/Vis spectroscopy. The
prepared pure and mixed Fe2O3 /TiO2 thick films had a homogenous
nanostructure without secondary phases. Indirect band gaps were determined
from the measured transmission spectra and the obtained values are in the
range of literature data.
Radiocarbon Calibration/Comparison Records Based on Marine Sediments from the Pakistan and Iberian Margins
Authors: Bard Edouard , Ménot Guillemette , Rostek Frauke , Licari Laetitia , Böning Philipp , Edwards R Lawrence , Cheng Hai , Wang Yongjin , Heaton Timothy J
Published: October 2013

We present a new record of radiocarbon ages measured by accelerator mass spectrometry (AMS) on a deep-sea core collected off the Pakistan Margin. The 14C ages measured on the planktonic foraminifera Globigerinoides ruber from core MD04-2876 define a high and stable sedimentation rate on the order of 50 cm/kyr over the last 50 kyr. The site is distant from the main upwelling zone of the western Arabian Sea where 14C reservoir age is large and may be variable. Many independent proxies based on elemental analyses, mineralogy, biomarkers, isotopic proxies, and foraminiferal abundances show abrupt changes correlative with Dansgaard-Oeschger and Heinrich events. It is now common knowledge that these climatic events also affected the Arabian Sea during the last glacial period through changes in the Indian monsoon and in ventilation at intermediate depths. The stratigraphic agreement between all proxies, from fine- to coarse-size fractions, indicates that the foraminiferal 14C ages are representative of the different sediment fractions.

To build a calendar age scale for core MD04-2876, we matched its climate record to the oxygen isotopic (δ18O) profile of Hulu Cave stalagmites that have been accurately dated by U-Th (Wang et al. 2001; Southon et al. 2012; Edwards et al., submitted). Both archives exhibit very similar signatures, even for century-long events linked to monsoonal variations. For comparison, we have also updated our previous work on core MD95-2042 from the Iberian Margin (Bard et al. 2004a,b,c), whose climate record has likewise been tuned to the high-resolution δ18O Hulu Cave profile. Sophisticated and novel statistical techniques were used to interpolate ages and calculate uncertainties between chronological tie-points (Heaton et al. 2013, this issue). The data from the Pakistan and Iberian margins compare well even if they come from distant sites characterized by different oceanic conditions. Collectively, the data also compare well with the IntCal09 curve, except for specific intervals around 16 cal kyr BP and from 28 to 31 cal kyr BP. During these intervals, the data indicate that 14C is somewhat older than indicated by the IntCal09 curve. Agreement between the data from both oceanic sites suggests that the discrepancy is not due to local changes of sea-surface 14C reservoir ages, but rather that the IntCal09 curve needed to be updated in these intervals as has been done in the framework of IntCal13 (Reimer et al. 2013a, this issue).
The well-posedness of a swimming model in the 3-D incompressible fluid governed by the nonstationary Stokes equation
Authors: Khapalov Alexander
Published: October 2013

We introduce and investigate the well-posedness of a model describing the self-propelled motion of a small abstract swimmer in the 3-D incompressible fluid governed by the nonstationary Stokes equation, typically associated with low Reynolds numbers. It is assumed that the swimmer’s body consists of finitely many subsequently connected parts, identified with the fluid they occupy, linked by rotational and elastic Hooke forces. Models like this are of interest in biological and engineering applications dealing with the study and design of propulsion systems in fluids.
Decentralized design of interconnected H∞ feedback control systems with quantized signals
Authors: Zhai Guisheng , Chen Ning , Gui Weihua
Published: October 2013

In this paper, we consider the design of interconnected H∞ feedback control systems with quantized signals. We assume that a decentralized dynamic output feedback has been designed for an interconnected continuous-time LTI system so that the closed-loop system is stable and a desired H∞ disturbance attenuation level is achieved, and that the subsystem measurement outputs are quantized before they are passed to the local controllers. We propose a local-output-dependent strategy for updating the parameters of the quantizers, so that the overall closed-loop system is asymptotically stable and achieves the same H∞ disturbance attenuation level. Both the pre-designed controllers and the parameters of the quantizers are constructed in a decentralized manner, depending on local measurement outputs.
Convergence analysis of piecewise continuous collocation methods for higher index integral algebraic equations of the Hessenberg type
Authors: Shiri Babak , Shahmorad Sedaghat , Hojjati Gholamreza
Published: October 2013

In this paper, we deal with a system of integral algebraic equations of the Hessenberg type. Using a new index definition, the existence and uniqueness of a solution to this system are studied. The well-known piecewise continuous collocation methods are used to solve this system numerically, and the convergence properties of the perturbed piecewise continuous collocation methods are investigated to obtain the order of convergence for the given numerical methods. Finally, some numerical experiments are provided to support the theoretical results.
Random projections and Hotelling’s T2 statistics for change detection in high-dimensional data streams
Authors: Skubalska-Rafajłowicz Ewa
Published: October 2013

The method of change (or anomaly) detection in high-dimensional discrete-time processes using a multivariate Hotelling chart is presented. We use normal random projections as a method of dimensionality reduction. We indicate diagnostic properties of the Hotelling control chart applied to data projected onto a random subspace of Rn. We examine the random projection method using artificial noisy image sequences as examples.
Design of unknown input fractional-order observers for fractional-order systems
Authors: N’Doye Ibrahima , Darouach Mohamed , Voos Holger , Zasadzinski Michel
Published: October 2013

This paper considers a method of designing fractional-order observers for continuous-time linear fractional-order systems with unknown inputs. Conditions for the existence of these observers are given. Sufficient conditions for the asymptotical stability of fractional-order observer errors with the fractional order α satisfying 0 < α < 2 are derived in terms of linear matrix inequalities. Two numerical examples are given to demonstrate the applicability of the proposed approach, where the fractional order α belongs to 1≤α<2 and 0<α≤1, respectively. A stability analysis of the fractional-order error system is made and it is shown that the fractional-order observers are as stable as their integer order counterpart and guarantee better convergence of the estimation error.
Nonlinear state observers and extended Kalman filters for battery systems
Authors: Rauh Andreas , Butt Saif S. , Aschemann Harald
Published: October 2013

The focus of this paper is to develop reliable observer and filtering techniques for finite-dimensional battery models that adequately describe the charging and discharging behaviors. For this purpose, an experimentally validated battery model taken from the literature is extended by a mathematical description that represents parameter variations caused by aging.

The corresponding disturbance models account for the fact that neither the state of charge, nor the above-mentioned parameter variations are directly accessible by measurements. Moreover, this work provides a comparison of the performance of different observer and filtering techniques as well as a development of estimation procedures that guarantee a reliable detection of large parameter variations. For that reason, different charging and discharging current profiles of batteries are investigated by numerical simulations. The estimation procedures considered in this paper are, firstly, a nonlinear Luenberger-type state observer with an offline calculated gain scheduling approach, secondly, a continuous-time extended Kalman filter and, thirdly, a hybrid extended Kalman filter, where the corresponding filter gains are computed online.
Robust nonlinear observer design for actuator fault detection in diesel engines
Authors: Boulkroune Boulaid , Djemili Issam , Aitouche Abdel , Cocquempot Vincent
Published: October 2013

This paper is concerned with actuator fault detection in nonlinear systems in the presence of disturbances. A nonlinear unknown input observer is designed and the output estimation error is used as a residual for fault detection. To deal with the problem of high Lipschitz constants, a modified mean-value theorem is used to express the nonlinear error dynamics as a convex combination of known matrices with time-varying coefficients. Moreover, the disturbance attenuation is performed using a modified H∞ criterion. A sufficient condition for the existence of an unknown input observer is obtained using a linear matrix inequality formula, and the observer gains are obtained by solving the corresponding set of inequalities. The advantages of the proposed method are that no a priori assumption on the unknown input is required and that it can be applied to a large class of nonlinear systems. Performances of the proposed approach are shown through the application to a diesel engine model.