Miracle-dz/UniFAR-FTUs huggingface dataset:
Parasite Mitochondria as a Target of Chemotherapy: Inhibitory Effect of Licochalcone A on the Plasmodium falciparum Respiratory Chain

Parasites have exploited unique energy metabolic pathways as adaptations to the natural host habitat. In fact, the respiratory systems of parasites typically show greater diversity in electron transfer pathways than do those of host animals. These unique aspects of parasite mitochondria and related enzymes may represent promising targets for chemotherapy. Natural products have been recognized as a source of the candidates of the specific inhibitors for such parasite respiratory chains. Chalcones was recently evaluated for its antimalarial activity in vitro and in vivo. However, its target is still unclear in malaria parasites. In this study, we investigated that licochalcone A inhibited the bc1 complex (ubiquinol‐cytochrome c reductase) as well as complex II (succinate ubiquinone reductase, SQR) of Plasmodium falciparum mitochondria. In particular, licochalcone A inhibits bc1 complex activity at very low concentrations. Because the property of the P. falciparum bc1 complex is different from that of the mammalian host, chalcones would be a promising candidate for a new antimalarial drug.
CSF myelin basic protein, IgG and IgM levels in 101 MS patients before and after treatment with high‐dose intravenous methylprednisolone

A total of 101 patients (62 women; 39 men) with definite MS were treated with 1000 mg methylprednisolone (MP) intravenously for 10 consecutive days. Immediately before and after MP treatment clinical scoring (Kurtzke's Expanded Disability Status Scale) and CSF analysis were performed. Before MP treatment CSF MBP, IgG and IgM immunoglobulin levels (CSF Ig, index and intrathecal synthesis) were significantly elevated. The mean CSF MBP levels were significantly higher in the relapsing‐remitting (RR) and chronic progressive MS patients with relapses (CP + RR) than in the CP group without a RR disease course, respectively 2.1, 2.3 and 1.5 μg/1. A weak positive correlation was found between CSF MBP level and EDSS in the RR MS group (r = 0.34). CSF MBP was significantly correlated with IgM index (r = 0.36), IgM synthesis (r = 0.26), but not with the IgG levels. Therefore demyelination seems to be related to intrathecal IgM production. After MP treatment mean (median) EDSS decreased from 4.4 (4.0) to 3.3 (3.0). Except for Q albumin and IgM index, all CSF immunoglobulin levels decreased significantly after MP. The mean CSF MBP returned to reference values. In the RR group the decrease in CSF MBP was significantly correlated with the change in EDSS (r = 0.39). CSF MBP seems to be a good parameter for disease activity in relapsing MS. Following treatment CSF MBP was found to be related with the change in IgM index (r = 0.30). MP treatment reduces CSF MBP and intrathecal IgM in a similar way indicating a relation between these 2 parameters.
Comparison of Serological Markers of Inflammatory Bowel Disease with Clinical Diagnosis in Children

Background:Our purpose was to study the concordance of serological tests for inflammatory bowel disease with clinical diagnosis established by traditional testing in children. Methods:All children seen in our division who had IBD Diagnostic System (ie, pANCA, ASCA IgA, and ASCA IgG) performed over a 21-month period (June 1998 to February 2000) were identified. Their medical records were reviewed for basic demographics, test results (endoscopy, histology, and radiology), IBD Diagnostic System results, and patient symptoms/medications. Results of the IBD Diagnostic System were compared with several patient characteristics including age, sex, absence/presence of symptoms, medication use, disease activity and duration. Results:One hundred seven patients were divided into 6 groups based on clinical diagnosis and IBD Diagnostic System results. The sensitivity, specificity and +/− predictive values of the IBD Diagnostic System for ulcerative colitis were 69.2, 95.1, 90.0, and 87.1%, respectively, and for Crohn's disease were 54.1, 96.8, 90.9, and 80.8%, respectively. Overall, the results of the IBD Diagnostic System were concordant with the clinical diagnosis in 76 of the 107 (71%) patients. Conclusions:In our experience, the specificity of IBD Diagnostic System is better than the sensitivity; the sensitivity is better for ulcerative colitis than Crohn's disease (69.2% vs 54.1%). The low sensitivity, especially for Crohn's disease, precludes the possibility that the IBD Diagnostic System can replace traditional studies when evaluating for inflammatory bowel disease. Though we do not exclude inflammatory bowel disease solely by IBD Diagnostic System results, it is reassuring to note that all patients without clinical evidence of inflammatory bowel disease also had negative IBD Diagnostic System results.
Contributions of Electron Microscopy to Understand Secretion of Immune Mediators by Human Eosinophils

Abstract Mechanisms governing secretion of proteins underlie the biologic activities and functions of human eosinophils, leukocytes of the innate immune system, involved in allergic, inflammatory, and immunoregulatory responses. In response to varied stimuli, eosinophils are recruited from the circulation into inflammatory foci, where they modulate immune responses through the release of granule-derived products. Transmission electron microscopy (TEM) is the only technique that can clearly identify and distinguish between different modes of cell secretion. In this review, we highlight the advances in understanding mechanisms of eosinophil secretion, based on TEM findings, that have been made over the past years and that have provided unprecedented insights into the functional capabilities of these cells.
Association of HER2 status with prognosis in gastric cancer patients undergoing R0 resection: A large-scale multicenter study in China.

AIM To determine whether the positive status of human epidermal growth receptor 2 (HER2) can be regarded as an effective prognostic factor for patients with gastric cancer (GC) undergoing R0 resection. METHODS A total of 1562 GC patients treated by R0 resection were recruited. HER2 status was evaluated in surgically resected samples of all the patients using immunohistochemical (IHC) staining. Correlations between HER2 status and clinicopathological characteristics were retrospective analyzed. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard model, stratified by age, gender, tumor location and tumor-node-metastasis (TNM) stage, with additional adjustment for potential prognostic factors. RESULTS Among 1562 patients, 548 (positive rate = 35.08%, 95%CI: 32.72%-37.45%) were HER2 positive. Positive status of HER2 was significantly correlated with gender (P = 0.004), minority (P < 0.001), tumor location (P = 0.001), pathological grade (P < 0.001), TNM stage (P < 0.001) and adjuvant radiotherapy (74.67% vs 23.53%, P = 0.011). No significant associations were observed between HER2 status and disease free survival (HR = 0.19, 95%CI: 0.96-1.46, P = 0.105) or overall survival (HR = 1.19, 95%CI: 0.96-1.48, P = 0.118) using multivariate analysis, although stratified analyses showed marginally statistically significant associations both in disease free survival and overall survival, especially among patients aged < 60 years or with early TNM stages (I and II). Categorical age, TNM stage, neural invasion, and adjuvant chemotherapy were, as expected, independent prognostic factors for both disease free survival and overall survival. CONCLUSION The positive status of HER2 based on IHC staining was not related to the survival in patients with GC among the Chinese population.
Neutron diffraction investigation of the magnetic structure and magnetoelastic effects in NdMnO3

We investigated the evolution of the magnetic structure and magnetoelastic effects of NdMnO3 by neutron powder diffraction. We confirmed the A-type antiferromagnetic (AF) structure of NdMnO3 below TN≈82 K with magnetic moments parallel to the b axis of the orthorhombic crystal structure (space group Pbnm). We found that the magnetic moments of Nd order below about TN(Nd)≈20 K in a ferromagnetic structure with moments parallel to the c axis. At the same temperature the magnetic moments of Mn develop a ferromagnetic component parallel to the c axis. We found strong magnetoelastic effects associated with the AF transition at TN≈82 K. The effect is very prominent for the b lattice parameter. All three lattice parameters and therefore the unit cell volume contracts at TN≈82 K. We treated quantitatively the magnetoelastic effect of the b lattice parameter and found that the extra change in the lattice parameter Δb due to the magnetoelastic effect is proportional to the magnetic moment of the Mn ion. We also determined the critical exponent of the AF phase transition to be β = 0.296 ± 0.008.
Link between single-particle properties and macroscopic properties in particulate assemblies: role of structures within structures

The prevalence of particulate materials in modern industrial processes and products provides a significant motivation to achieve fundamental understanding of the bulk behaviour of particulate media. The rapid progress being made with atomic force microscopy and related particle characterization techniques pushes the limits of micro- and nanotechnologies such that interparticle interactions can be engineered to fabricate particulate assemblies to deliver specific functionalities. In this paper, primarily based on discrete element method simulations that we performed over the past 10 years, we summarize the key findings on the role of force transmission networks in dense particulate systems subjected to shearing. In general, the macroscopic strength characteristics in particulate systems is dictated by the distribution of heavily loaded contacts, also referred to as ‘strong’ force chains. Surprisingly, they constitute only a limited proportion of all contacts in particulate systems. They act like a ‘granular brain’ (memory networks) at particle scale. We show that the structural arrangement of the force chains and their evolution during loading depends on the single-particle properties and the initial packing condition in particulate assemblies. Further, the ‘nature’ of force chains in sheared granular media induces larger ‘solid’ grains to behave like ‘fluid’ particles, retarding their breakage. Later, we probe for ways by which we can control the signature of memory networks in packed beds, for example by applying an external electrical field in a densely packed particulate bed subjected to shearing (combined electromechanical loading). Though further research is required to account for more realistic conditions and preferably to allow particles to self-organize to strength specifications, understanding the hidden memory networks in particulate materials could be exploited to optimize their collective strength.
The Seven Secrets of Germany: Economic Resilience in an Era of Global Turbulence

German economic performance has astonished the world. At the turn of the century, Germany had been written off as the sick man of Europe. No more. Even as most of its European neighbors and OECD trading partners have struggled in the face of a turbulent global economy, the German economy has thrived. How does Germany do it? What is the secret? In The Seven Secrets of Germany, authors David Audretsch and Erik Lehmann answer these very questions. This book reveals, explains, and analyzes seven key aspects of Germany, its economy, and its society that have provided the nation with considerable buoyance in an era of global turbulence. These seven features range from the key and strategic role played by small firms to world leadership in its skilled and trained labor force, an ability to harness global opportunities through leveraging local resources, public infrastructure, the capacity to deal with change and confront challenges in a flexible manner, and the emergence of a remarkably positive identity and image. The Seven Secrets of Germany have insulated the country from long-term economic deterioration and enabled it to take advantage of the opportunities afforded from globalization rather than succumbing as a victim to globalization. This insights can be instructive to other countries and refute the defeatist view that globalization leads to an inevitable deterioration of the standard of living, quality of life, and degree of economic prosperity. Available in OSO:
Scalability and electrical properties of germanium oxynitride MOS dielectrics

In this letter, we present a fundamental study on the scalability and electrical properties of germanium oxynitride dielectrics for metal-oxide-semiconductor device applications. The nitrogen depth profile within the oxynitride dielectric layers was first monitored using angle-resolved x-ray photoemission spectroscopy and the dielectric permittivity variation was therefore identified. After thinning down the lower permittivity portion of these dielectrics, we successfully scaled down the capacitance-based equivalent SiO/sub 2/ thickness, in Ge MOS capacitors, to 1.9 nm without suffering from gate leakage. We have also investigated the effects of thermal annealing on various capacitor electrical properties. For instance, we measured a flat-band voltage shift of as much as -0.8 V from the ideal value on as-deposited capacitors and the recovery of the theoretical value, with acceptably small amount of oxide fixed charge, after subsequent thermal annealing. Lastly, we have benchmarked the performance of these oxynitride insulators with the advanced high-/spl kappa/ dielectrics on Ge and discussed the impacts on future scaling.
Influenza-Like Illness Responsible for Severe Exacerbations in Asthmatic Children During H1N1 Pandemic: A Survey Before Vaccination

Background. Asthma seems to be the more prevalent underlying condition in patients hospitalized for H1N1-related flu. Methods. A prospective survey was conducted during the early phase of H1N1 pandemic in France in asthmatic children before vaccination to assess whether severe exacerbations in childhood asthma are associated with influenza-like illness (ILI, the definition of H1N1-related flu in a pandemic). Eight pediatricians in primary care distributed in three localities (Paris, south suburb, and west suburb) conducted the survey (4 weeks/locality from week 36 to 47). At each visit, the pediatrician filled a questionnaire entering the information regarding asthma treatment, severe exacerbation (at least 3 days' use of systemic corticosteroids), and ILI (temperature ≥37.8°C, cough, and/or sore throat, in the absence of a known cause other than influenza) during the past 3 weeks. Results. The survey included 1155 asthmatic children (mean age [SD]: 7.5 years [4.1]); almost all visits were scheduled (99%). A severe exacerbation was recorded in 121 children [10.5%; 95% confidence interval (CI): 8.7–12.2%], which was concomitant with ILI in 20 children (16.5%; 95% CI: 9.9–23.2%), whereas 1034 children did not exhibit any exacerbation. In these latter children, 40 ILI were observed (3.9%; 95% CI: 2.7–5.0%), which constituted a significantly lesser percentage as compared with children with both exacerbation and ILI (p < .0001). This result remained significant in each locality. Overall, 60/1155 (5.2%; 95% CI: 3.9–6.5%) asthmatic children had an ILI. Conclusions. Our survey shows that severe exacerbation and ILI are strongly associated during the H1N1 pandemic in asthmatic children.
Practical barriers to timely primary care access: impact on adult use of emergency department services.

BACKGROUND Most Americans report having a usual source of medical care, but many also report significant barriers to timely access to such care. This can lead patients to use the emergency department (ED) as a ready alternative to their usual source of medical care, even when such care could be provided more cost-effectively in a primary care setting. The purpose of this study was to examine the relationship between ED visits and perceived barriers to receiving timely primary care. METHODS Among 30,677 adults 18 years or older participating in the adult sample section of the National Health Interview Survey, 23,413 who reported having a usual source of medical care other than the ED and answered the questions related to barriers were included in our analyses. Associations between perceived timely access barriers and reported use of ED in the previous 12 months were examined using logistic regression to control for covariates that also affect ED use. RESULTS For those reporting no access barriers, 1 in 5 adult Americans in the noninstitutionalized civilian population visited an ED at least once during the preceding year. For those reporting 1 or more barriers, the proportion having an ED visit was 1 in 3. Four of the 5 following timely access barriers was independently associated with ED use, even after adjusting for other socioeconomic and health-related factors: (1) "couldn't get through on phone" (OR [odds ratio], 1.27; 95% confidence interval [CI], 1.02-1.59); (2) "couldn't get appointment soon enough" (OR, 1.45; 95% CI, 1.21-1.75); (3) "waiting too long in doctor's office" (OR, 1.20; 95% CI, 1.02-1.41); (4) "not open when you could go" (OR, 1.24; 95% CI, 0.99-1.55); and (5) "no transportation" (OR, 1.88; 95% CI, 1.50-2.35). CONCLUSIONS The benefits of having a usual source of medical care are diminished by barriers that limit effective and timely access to such care. Interventions to improve effective access to medical care such as open access scheduling might have benefits not only for individual patients and practices but also for health policy related to cost-effective health care delivery systems and our need to relieve overcrowded conditions at EDs.
Conjugation of the 15-kDa Interferon-induced Ubiquitin Homolog Is Distinct from That of Ubiquitin (*)

The biological effect of type 1 interferons is proposed to arise in part from the conjugation of ubiquitin cross-reactive protein (UCRP), the ISG15 gene product, to intracellular target proteins in a process analogous to that of its sequence homolog ubiquitin, a highly conserved 8.6-kDa polypeptide whose ligation marks proteins for degradation via the 26 S proteasome. Inclusion of CoCl during the purification of recombinant UCRP blocks the proteolytic inactivation of the polypeptide occurring by cleavage of the carboxyl-terminal glycine dipeptide required for activation and subsequent ligation. Intact UCRP supports a low rate of ubiquitin-activating enzyme (E1)-dependent ATP:PP exchange but fails to form a stoichiometric E1-UCRP thiol ester or undergo transfer to ubiquitin carrier protein (E2). The binding affinity of E1 for UCRP is significantly diminished relative to that of ubiquitin. These results suggest that UCRP conjugation proceeds through an enzyme pathway distinct from that of ubiquitin, at least with respect to the step of activation. This was confirmed for an in vitro conjugation assay in which I-UCRP could be ligated in an ATP-dependent reaction to proteins present within an A549 human lung carcinoma cell extract and could be competitively inhibited by excess unlabeled UCRP but not ubiquitin. Other results demonstrate that I-UCRP conjugation is significantly increased in cell extracts after 24 h of incubation in the presence of interferon-β, consistent with the late induction of UCRP conjugating activity. Thus, interferon-responsive cells contain a pathway for UCRP ligation that is parallel but distinct from that of ubiquitin.
Beyond Information: College Choice as a Literacy Practice

iv Acknowledgments . vi Preface . ix Table of
Efferent projections of the ectostriatum in the pigeon (Columba livia)

The ectostriatum is a major visual component of the avian telencephalon. The core region of the ectostriatum (Ec) receives visual input from the optic tectum through thalamic nuclei. In the present study, the efferent projections of the ectostriatum were investigated by using the anterograde tracers Phaseolus vulgaris leucoagglutinin and biotinylated dextran amine. Projection patterns resulting from these tracers were confirmed by the retrograde tracer cholera toxin subunit B. When anterograde tracers were injected in Ec, primary projections were seen traveling dorsolaterally to the belt region of the ectostriatum (Ep) and the neostriatal area immediately surrounding Ep (Ep2). Neurons in Ep sent projections primarily to the overlying Ep2. The efferents of Ep2 traveled dorsolaterally to terminate in three telencephalic regions, from anterior to posterior: (1) neostriatum frontale, pars lateralis (NFL), (2) area temporo‐parieto‐occipitalis (TPO), and (3) neostriatum intermedium, pars lateralis (NIL). A part of the archistriatum intermedium and the lateral part of the neostriatum caudale also received somewhat minor projections. In addition, some neurons in Ec were also the source of direct, but minor, projections to the NFL, TPO, NIL, and archistriatum intermedium. The topographical relationship among the primary (Ec), secondary (Ep and Ep2), and tertiary (NFL, TPO, NIL) areas indicate that the neural populations for visual processing are organized along the rostral‐caudal axis. Thus, the anterior Ec sent efferents to the anterior Ep, which in turn sent projections to anterior Ep2. Neurons in the anterior Ep2 sent projections to NFL and the anterior TPO. Similarly, the intermediate and posterior Ec sent projections to corresponding parts of Ep, whose efferents projected to intermediate and posterior Ep2, respectively. The intermediate Ep2 gave rise to major projections to TPO, whereas posterior Ep2 neurons sent efferents primarily to NIL. The organization of this neural circuit is compared with those of other sensory circuits in the avian telencephalon, as well as the laminar arrangement of the mammalian isocortex. J. Comp. Neurol. 406:329–345, 1999. © 1999 Wiley‐Liss, Inc.
Bacterial Toxin RelE Mediates Frequent Codon-independent mRNA Cleavage from the 5′ End of Coding Regions in Vivo*

The enzymatic activity of the RelE bacterial toxin component of the Escherichia coli RelBE toxin-antitoxin system has been extensively studied in vitro and to a lesser extent in vivo. These earlier reports revealed that 1) RelE alone does not exhibit mRNA cleavage activity, 2) RelE mediates mRNA cleavage through its association with the ribosome, 3) RelE-mediated mRNA cleavage occurs at the ribosomal A site and, 4) Cleavage of mRNA by RelE exhibits high codon specificity. More specifically, RelE exhibits a preference for the stop codons UAG and UGA and sense codons CAG and UCG in vitro. In this study, we used a comprehensive primer extension approach to map the frequency and codon specificity of RelE cleavage activity in vivo. We found extensive cleavage at the beginning of the coding region of five transcripts, ompA, lpp, ompF, rpsA, and tufA. We then mapped RelE cleavage sites across one short transcript (lpp) and two long transcripts (ompF and ompA). RelE cut all of these transcripts frequently and efficiently within the first ∼100 codons, only occasionally cut beyond this point, and rarely cut at sites in proximity to the 3′ end. Among 196 RelE sites in these five transcripts, there was no preference for CAG or UCG sense codons. In fact, bioinformatic analysis of the RelE cleavage sites failed to identify any sequence preferences. These results suggest a model of RelE function distinct from those proposed previously, because RelE directed frequent codon-independent mRNA cleavage coincident with the commencement of translation elongation.