Miracle-dz/UniFAR-FTUs huggingface dataset:
An Allelic Mutant Series of ATM3 Reveals Its Key Role in the Biogenesis of Cytosolic Iron-Sulfur Proteins in Arabidopsis1[C][W][OA]

The ATP-binding cassette transporters of mitochondria (ATMs) are highly conserved proteins, but their function in plants is poorly defined. Arabidopsis (Arabidopsis thaliana) has three ATM genes, namely ATM1, ATM2, and ATM3. Using a collection of insertional mutants, we show that only ATM3 has an important function for plant growth. Additional atm3 alleles were identified among sirtinol-resistant lines, correlating with decreased activities of aldehyde oxidases, cytosolic enzymes that convert sirtinol into an auxin analog, and depend on iron-sulfur (Fe-S) and molybdenum cofactor (Moco) as prosthetic groups. In the sirtinol-resistant atm3-3 allele, the highly conserved arginine-612 is replaced by a lysine residue, the negative effect of which could be mimicked in the yeast Atm1p ortholog. Arabidopsis atm3 mutants displayed defects in root growth, chlorophyll content, and seedling establishment. Analyses of selected metal enzymes showed that the activity of cytosolic aconitase (Fe-S) was strongly decreased across the range of atm3 alleles, whereas mitochondrial and plastid Fe-S enzymes were unaffected. Nitrate reductase activity (Moco, heme) was decreased by 50% in the strong atm3 alleles, but catalase activity (heme) was similar to that of the wild type. Strikingly, in contrast to mutants in the yeast and mammalian orthologs, Arabidopsis atm3 mutants did not display a dramatic iron homeostasis defect and did not accumulate iron in mitochondria. Our data suggest that Arabidopsis ATM3 may transport (1) at least two distinct compounds or (2) a single compound required for both Fe-S and Moco assembly machineries in the cytosol, but not iron.
Initiation Factor 2 of Myxococcus xanthus, a Large Version of Prokaryotic Translation Initiation Factor 2

ABSTRACT We have isolated the structural gene for translation initiation factor IF2 (infB) from the myxobacterium Myxococcus xanthus. The gene (3.22 kb) encodes a 1,070-residue protein showing extensive homology within its G domain and C terminus to the equivalent regions of IF2 from Escherichia coli. The protein cross-reacts with antibodies raised against E. coliIF2 and was able to complement an E. coli infB mutant. TheM. xanthus protein is the largest IF2 known to date. This is essentially due to a longer N-terminal region made up of two characteristic domains. The first comprises a 188-amino-acid sequence consisting essentially of alanine, proline, valine, and glutamic acid residues, similar to the APE domain observed in Stigmatella aurantiaca IF2. The second is unique to M. xanthusIF2, is located between the APE sequence and the GTP binding domain, and consists exclusively of glycine, proline, and arginine residues.
Community mobilization as an HIV prevention strategy: challenges and obstacles (South Africa).

This paper explores on the challenges and obstacles confronting the Mothusimpilo Project, a program designed to develop ways of responding to HIV/AIDS in a gold mining community in South Africa. The project utilized participatory approaches to promote active involvement of local groups and the community in designing and implementing the program. It employs 3 full-time workers who were recruited locally. The 2 major components of the program include improved prevention of sexually transmitted diseases and community-based condom distribution and peer education, whose particular targets involve migrant mine workers, commercial sex workers and the young people. It seeks to maximize community involvement through stakeholder management of the program and through grassroots involvement in program implementation. Despite the number of accesses in mobilizing the different components of the community, enormous obstacles, and challenges still remains. Some of these obstacles include poverty, women's lack of background of a male-dominated culture, and their sense of fatalism, which reduces their motivation to protect their sexual health.
Alloglossidium floridense n. sp. (Digenea: Macroderoididae) from a Spring Run in North Central Florida

Abstract: A new species of Alloglossidium is described from the intestines of 2 madtom species (Noturus leptacanthus and Noturus gyrinus) that were collected from the run of a small, unnamed spring system that drains into the Santa Fe River, Florida. Alloglossidium floridense n. sp. is morphologically very similar to other nonprecocious Alloglossidium spp. that use ictalurids as definitive hosts, but can be distinguished by a combination of its smaller overall size (length and width), large eggs in relation to its small body size, position of the vitellaria, ovary shape, and position of the ovary in relation to the cirrus sac. A comparison of nuclear rDNA sequences (spanning partial 18s, complete ITS1, 5.8s, ITS2, and partial 28s regions) showed that A. floridense n. sp. diverged by 0.70–3.17% from the other 4, nonprecocious species that infect ictalurids (Alloglossidium corti, Alloglossidium fonti, Alloglossidium geminum, and Alloglossidium kenti). The new species of Alloglossidium, described herein, is the first of the genus to be reported from Florida and the first to be recorded from N. leptacanthus. In light of the subtle morphological differences among the nonprecocious species that infect ictalurids, we discuss how previous descriptions of species traits that are not supported with genetic data are difficult to interpret because of the possible past nonrecognition of distinct species.
Analysis of Social Group Dynamics

The continuous interest in the social network area contributes to the fast development of this field. New possibilities of obtaining and storing data allows for more and more deeper analysis of the network in general, as well as groups and individuals within it. Especially interesting is studying the dynamics of changes in social groups over time. Having such knowledge ones may attempt to predict the future of the group, and then manage it properly in order to achieve presumed goals. Such ability would be a powerful tool in the hands of human resource managers, personnel recruitment, marketing, etc. The thesis presents a new method for exploring the evolution of social groups, called Group Evolution Discovery (GED). Next, the results of its use are provided together with comparison to two other algorithms in terms of accuracy, execution time, flexibility and ease of implementation. Moreover, the method was evaluated with various measures of user importance within a group. Obtained results suggest that GED is the best method for analyzing social group dynamics.
Toward High-Speed 40-Gbit/s Transponders

Today a 40-Gbit/s data rate is agreed by major optical telecommunication players as the next step in the network evolution, with an actual deployment foreseen in the 2007-2008 timeframe. R&D activities on technologies for 40-Gbit/s products are currently active but the path to 40-Gbit/s transponders is not yet fully settled. In this paper, we review the different component technologies currently considered for the actual development and the implementation of future 40-Gbit/s transponders. Dedicated paragraphs are devoted to electronic ICs and electrooptical devices, along with considerations on the technical solutions ensuring suitable interconnections or integration of the different components. Such advanced transponders should be compliant with the requirements of the different segments of the optical transport market. Solutions derived from choices made at lower data rates are projected for the shortest transmission paths, based on conventional nonreturn to zero modulation. In the peculiar case of long-haul transmission, signal distortion resulting from fiber propagation impairments calls for the generation of alternative modulation formats at the transmitter side and the potential need for electronic processing at the receiver side. This obviously has a clear impact on both the transponder design and the individual components features. Finally, recent advances in the field of innovative "all-optical" transponders implementing optical regeneration are also reported
The Bayer-Activities of Daily Living Scale (B-ADL): Results from a Validation Study in Three European Countries

The Bayer-Activities of Daily Living Scale (B-ADL) is a 25-item, informant-rated questionnaire which was developed as a brief and internationally applicable instrument for assessing functional disabilities. The scale’s target group are elderly patients suffering from mild to moderate dementia or cognitive impairment. To investigate the reliability and validity of different language versions, the B-ADL was administered in the UK, Germany, and Spain to a total of 1,433 subjects with a wide range of cognitive decline. The results from the three country samples were very similar, with internal consistency being above 0.98 (Cronbach alpha). A factor analysis revealed that a one-factor solution accounted for most of the variance. The B-ADL total score significantly increased between adjacent Global Deterioration Scale (GDS) stages 1 to 5. A second factor analysis entering additional variables (GDS stage, Mini-Mental State Examination or MMSE subscores, age, years of education, gender, and country) revealed that all B-ADL items loaded on the same factor, ‘dementia severity’, and that they were not related to age, education, gender, or country. In the identification of subjects with clinically manifest dementia symptoms (GDS stages 4 and 5), the B-ADL proved to be as efficient as the MMSE in the UK and German samples and superior to the MMSE in the Spanish sample.
A novel switch-mode DC-to-AC inverter with nonlinear robust control

A switch-mode DC-to-AC inverter based on a DC-to-DC converter topology using a novel nonlinear robust control to generate a sinusoidal output waveform is presented. The control scheme is based on simultaneous feedback of the output voltage and feedforward of the input voltage and inductor voltage. As a result, the output voltage remains dynamically unchanged when there are large disturbances in input voltage or load current. The nature of the control law is explained. Computer simulation results show the robustness and fast dynamical response of the control system. The experimental results are presented to verify the analysis and demonstrate the feasibility of the control strategy.
Antiangiogenic therapy with bevacizumab in recurrent malignant gliomas: analysis of the response and core pathway aberrations.

BACKGROUND Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor, has shown promising activity in recurrent malignant gliomas. We reported the treatment response for the combination of bevacizumab and chemotherapy in a series of six patients with recurrent malignant glioma and investigated the molecular alterations in cancer pathways using the surgical biopsies from these patients. METHODS Standard therapy with primary resection followed by adjuvant chemoradiotherapy had failed in all patients. Bevacizumab was administered at a dose of 10 mg/kg every 2 weeks. Concomitantly, four patients received temozolomide (50 mgxm(-2)xd(-1)), one patient irinotecan (125 mg/m(2) every 2 weeks) and one patient topotecan (1.2 mgxm(-2)xd(-1)). Response to therapy was mainly determined by magnetic resonance imaging. The expression of Ras, phosphorylated mitogen activated protein kinase (p-MAPK), phosphorylated AKT (p-AKT), phosphorylated mammalian target of rapamycin (p-mTOR) and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) were semiquantitatively assessed by immunohistochemistry using surgical biopsies before the initial treatment. RESULTS Five of the six patients had a radiographic response. Three were complete response, and two were partial response. Only one patient had progressive disease. The 6-month progession-free survival (PFS) was 33% and the median PFS was 15 weeks, with a range of 6 to more than 60 weeks. Of the three core pathways analyzed in this study, the Ras/MAPK and phosphatidylinositol-3-kinase (PI3K)/AKT/mTOR pathways were more likely to be associated with the treatment response to bevacizumab. In two younger patients (ages < 50) with complete response, simultaneous overexpression of p-MAPK, p-AKT and p-mTOR might be the crucial feature. CONCLUSIONS Bevacizumab in combination with chemotherapeutic agents may be an effective strategy for patients with recurrent malignant glioma. Activated MAPK and AKT might be possible biomarkers for selecting suitable patients for this targeted therapy.
Functionally conserved architecture of hepatitis C virus RNA genomes

Significance Plus-sense RNA viruses cause diverse pathologies in humans. Viral RNA genomes are selected to encode information both in their primary sequences and in their higher-order tertiary structures required to replicate and to evade host immune responses. We interrogated the physical structures of three evolutionarily divergent hepatitis C virus (HCV) RNA genomes using high-throughput chemical probing and found, along with all previously known RNA-structure–based regulatory elements, diverse previously uncharacterized structures that impact viral replication. We also characterized strategies by which the HCV genomic RNA structure masks detection by innate immune sensors. This structure-first strategy for comparative analysis of genome-wide RNA structure can be broadly applied to understand the contributions of higher-order genome structure to viral replication and pathogenicity. Hepatitis C virus (HCV) infects over 170 million people worldwide and is a leading cause of liver disease and cancer. The virus has a 9,650-nt, single-stranded, messenger-sense RNA genome that is infectious as an independent entity. The RNA genome has evolved in response to complex selection pressures, including the need to maintain structures that facilitate replication and to avoid clearance by cell-intrinsic immune processes. Here we used high-throughput, single-nucleotide resolution information to generate and functionally test data-driven structural models for three diverse HCV RNA genomes. We identified, de novo, multiple regions of conserved RNA structure, including all previously characterized cis-acting regulatory elements and also multiple novel structures required for optimal viral fitness. Well-defined RNA structures in the central regions of HCV genomes appear to facilitate persistent infection by masking the genome from RNase L and double-stranded RNA-induced innate immune sensors. This work shows how structure-first comparative analysis of entire genomes of a pathogenic RNA virus enables comprehensive and concise identification of regulatory elements and emphasizes the extensive interrelationships among RNA genome structure, viral biology, and innate immune responses.
Endarterectomy or Stenting in Severe Asymptomatic Carotid Stenosis.

BACKGROUND Stroke is a major cause of death in the western world, and carotid endarterectomy has been shown to be effective in treating both symptomatic and asymptomatic carotid stenosis. Carotid stenting is a relatively new form of treatment for carotid stenosis and few studies have looked specifically at asymptomatic patients. OBJECTIVES To retrospectively examine short- and long-term results in the treatment of asymptomatic carotid artery stenosis with surgery or stenting. METHODS We retrospectively collected data of all patients with asymptomatic carotid stenosis treated by carotid artery stenting or carotid endarterectomy in our department from 2006-2007. The primary endpoints were stroke, myocardial infarction, or death during the periprocedural period; or any ipsilateral stroke, restenosis, or death within 4 years after the procedure. RESULTS The study comprised 409 patients who were treated by either stenting or surgery. There was a low morbidity rate in both treatment groups with no significant difference in morbidity or mortality between the treatment groups in both in the short-term as well as long-term. CONCLUSIONS Both treatment methods have a low morbidity and mortality rate and should be considered for patients with few risk factors and a long life expectancy. Treatment method should be selected according to the patient's individual risk factors and imaging data.
Localization and Targeting of an Unusual Pyridine Nucleotide Transhydrogenase in Entamoeba histolytica

ABSTRACT Pyridine nucleotide transhydrogenase (PNT) catalyzes the direct transfer of a hydride-ion equivalent between NAD(H) and NADP(H) in bacteria and the mitochondria of eukaryotes. PNT was previously postulated to be localized to the highly divergent mitochondrion-related organelle, the mitosome, in the anaerobic/microaerophilic protozoan parasite Entamoeba histolytica based on the potential mitochondrion-targeting signal. However, our previous proteomic study of isolated phagosomes suggested that PNT is localized to organelles other than mitosomes. An immunofluorescence assay using anti-E. histolytica PNT (EhPNT) antibody raised against the NADH-binding domain showed a distribution to the membrane of numerous vesicles/vacuoles, including lysosomes and phagosomes. The domain(s) required for the trafficking of PNT to vesicles/vacuoles was examined by using amoeba transformants expressing a series of carboxyl-terminally truncated PNTs fused with green fluorescent protein or a hemagglutinin tag. All truncated PNTs failed to reach vesicles/vacuoles and were retained in the endoplasmic reticulum. These data indicate that the putative targeting signal is not sufficient for the trafficking of PNT to the vesicular/vacuolar compartments and that full-length PNT is necessary for correct transport. PNT displayed a smear of >120 kDa on SDS-PAGE gels. PNGase F and tunicamycin treatment, chemical degradation of carbohydrates, and heat treatment of PNT suggested that the apparent aberrant mobility of PNT is likely attributable to its hydrophobic nature. PNT that is compartmentalized to the acidic compartments is unprecedented in eukaryotes and may possess a unique physiological role in E. histolytica.
The Causes And Consequences Of Income Tax Noncompliance

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Truncated beta‐amyloid peptide species in pre‐clinical Alzheimer's disease as new targets for the vaccination approach

Vaccination against human beta‐amyloid peptide (Aβ) has been shown to remove the amyloid burden produced in transgenic mice overexpressing the mutated human amyloid precursor protein (APP) gene. For human beings, the efficiency of this therapeutic strategy has to take into account the specificities of human amyloid, especially at the early stages of ‘sporadic’ Alzheimer's disease (AD). Aβ 40/42 were previously quantified in tissues from our well‐established brain bank, including non‐demented individuals with both mild amyloid and tau pathologies, hence corresponding to the earliest stages of Alzheimer pathology. Herein, we have adapted a proteomic method combined with western blotting and mass spectrometry for the characterization of insoluble Aβ extracted in pure‐formic acid. We demonstrated that amino‐truncated Aβ species represented more than 60% of all Aβ species, not only in full blown AD, but also, and more interestingly, at the earliest stage of Alzheimer pathology. At this stage, Aβ oligomers were exclusively made of Aβ‐42 species, most of them being amino‐truncated. Thus, our results strongly suggest that amino‐truncated Aβ‐42 species are instrumental in the amyloidosis process. In conclusion, a vaccine specifically targeting these pathological amino‐truncated species of Aβ‐42 are likely to be doubly beneficial, by inducing the production of specific antibodies against pathological Aβ products that are, in addition, involved in the early and basic mechanisms of amyloidosis in humans.
Lobe‐specific lineages of carcinogenesis in the transgenic adenocarcinoma of mouse prostate and their responses to chemopreventive selenium

The transgenic adenocarcinoma of mouse prostate (TRAMP) model is by far the most practical transgenic model for preclinical prostate cancer chemoprevention studies. It is critical to characterize the prostate lobe‐specificity of lesion lineages to consolidate the advantages of this model and minimize its limitations for chemoprevention studies.
DOES EXCHANGE RATE VOLATILITY DEPRESS TRADE FLOWS IN A SMALL OPEN ECONOMY? EVIDENCE FROM NEW ZEALAND 1

This paper empirically investigates the impact of real exchange rate volatility on the real bilateral export flows of New Zealand by using quarterly data over 1991Q1-2007Q1 period. Cointegration and error-correction models are employed to obtain the estimates of the long run equilibrium and the short-run dynamics, respectively. We analysis the ignored potential structure breaks which might bias the results, and provide evidence that real exchange rate volatility has a significant negative effect on real exports in the long run, but a weak positive effect in the short run for New Zealand.
Highly sialylated recombinant human erythropoietin production in large‐scale perfusion bioreactor utilizing CHO‐gmt4 (JW152) with restored GnT I function

Therapeutic glycoprotein drugs require a high degree of sialylation of their N‐glycans for a better circulatory half‐life that results in greater efficacy. It has been demonstrated that Chinese hamster ovary (CHO) glycosylation mutants lacking N‐acetylglucosaminyltransferase I (GnT I), when restored by introduction of a functional GnT I, produced highly sialylated erythropoietin (EPO). We have now further engineered one of such mutants, JW152, by inactivating the dihydrofolate reductase (DHFR) gene to allow for the amplification of the EPO gene with methotrexate (MTX). Several MTX‐amplified clones maintained the ability to produce highly sialylated EPO and one was selected for culture in a perfusion bioreactor that is used in an existing industrial EPO‐production bioprocess. Extensive characterization of the EPO produced was performed using total sialic quantification, HPAEC‐PAD and MALDI‐TOF MS analyses. Our results demonstrated that the EPO produced by the mutant line exhibits superior sialylation compared to the commercially used EPO‐producing CHO clone cultured under the same conditions. Therefore, this mutant has the industrial potential for producing highly sialylated recombinant EPO and potentially other recombinant glycoprotein therapeutics.