Miracle-dz/UniFAR-FTUs huggingface dataset:
Research advances in basic mechanisms of seizures and antiepileptic drug action W 3 adys 3

Epilepsy is a common neurological disease but the mechanism of seizure generation has been only partially unraveled. Furthermore, almost 30% of epileptic patients are resistant to pharmacological treatment. Therefore, elucidation of the basic mechanism of seizures and search for new antiepileptics in order to treat the drug-resistant form of epilepsy and to improve the efficacy of current therapies seem justified. The aim of this overview is a brief presentation of some new concepts and research directions in pathogenesis and pharmacotherapy of epilepsy. Development of ideas on the mechanisms of seizures and antiepileptic drugs reflects the progress in our understanding of the central nervous system physiology, particularly of neurotransmission. Hyperactivity of excitatory amino acid systems, insufficient GABAA receptor-mediated neurotransmission, and disturbances in intrinsic properties of neuronal membranes are still regarded as the most important mechanisms of seizures. New data add to the complexity of GABA-glutamate interaction showing both excitatory and inhibitory role of GABA and glutamatergic neurons in the central nervous system. Moreover, besides synaptic NMDA and GABAA receptors, also extrasynaptic receptors for the amino acid transmitters have been recently implicated in the pathomechanism of epilepsy. Changes in expression, polymorphisms, lostor gain-function mutations as well as cellular energetic imbalance can contribute to the disturbed function of the ligandand voltage-dependent sodium, potassium, chloride and calcium channels, resulting in epileptiform activity. Voltage-dependent sodium and calcium channel blockers, and GABA mimetics are the most clinically useful groups of antiepileptic drugs and the newest research in this field is focused on more selective and subtle regulations of their molecular targets. Of interest is an emerging role of extrasynaptic GABAA receptors, various kinds of potassium ion channels, hyperpolarization-activated cyclic nucleotide gated (HCN) channels, acid-sensing ion channels, and gap junctions in the regulation of neuronal excitability and seizures. Ionoand metabotropic glutamate receptors used to be viewed as an attractive target for new anticonvulsants, however, opinions are now less enthusiastic, since their competitive and non-competitive antagonists possess undesired side effects. Positive or negative allosteric modulators of glutamate receptors with fewer side-effects can be more promising. The introduction of new compounds acting through novel pharmacological mechanisms gives hope that the proportion of patients with uncontrolled epilepsy will substantially decrease. However, this may be possible if molecular background of the pharmacoresistance in epilepsy is deciphered.
FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study.

PURPOSE In metastatic colorectal cancer, phase III studies have demonstrated the superiority of fluorouracil (FU) with leucovorin (LV) in combination with irinotecan or oxaliplatin over FU + LV alone. This phase III study investigated two sequences: folinic acid, FU, and irinotecan (FOLFIRI) followed by folinic acid, FU, and oxaliplatin (FOLFOX6; arm A), and FOLFOX6 followed by FOLFIRI (arm B). PATIENTS AND METHODS Previously untreated patients with assessable disease were randomly assigned to receive a 2-hour infusion of l-LV 200 mg/m(2) or dl-LV 400 mg/m(2) followed by a FU bolus 400 mg/m(2) and 46-hour infusion 2,400 to 3,000 mg/m(2) every 46 hours every 2 weeks, either with irinotecan 180 mg/m(2) or with oxaliplatin 100 mg/m(2) as a 2-hour infusion on day 1. At progression, irinotecan was replaced by oxaliplatin (arm A), or oxaliplatin by irinotecan (arm B). RESULT Median survival was 21.5 months in 109 patients allocated to FOLFIRI then FOLFOX6 versus 20.6 months in 111 patients allocated to FOLFOX6 then FOLFIRI (P =.99). Median second progression-free survival (PFS) was 14.2 months in arm A versus 10.9 in arm B (P =.64). In first-line therapy, FOLFIRI achieved 56% response rate (RR) and 8.5 months median PFS, versus FOLFOX6 which achieved 54% RR and 8.0 months median PFS (P =.26). Second-line FOLFIRI achieved 4% RR and 2.5 months median PFS, versus FOLFOX6 which achieved 15% RR and 4.2 months PFS. In first-line therapy, National Cancer Institute Common Toxicity Criteria grade 3/4 mucositis, nausea/vomiting, and grade 2 alopecia were more frequent with FOLFIRI, and grade 3/4 neutropenia and neurosensory toxicity were more frequent with FOLFOX6. CONCLUSION Both sequences achieved a prolonged survival and similar efficacy. The toxicity profiles were different.
Atmospheric dust aerosol over the Tibetan Plateau

Cascade impactor and bulk samples of atmospheric aerosol particles were collected at three sites on the Tibetan Plateau: Udaoliang (September 1993 to May 1994) and Lhasa and Gongga (May 1998). The average dust concentration at these groundbased sites was 82 μg m−3; this is lower than the lowest average concentration observed over the nine major Chinese deserts (arithmetic mean value of 270 μg m−3), and it also is lower than that over the Loess Plateau (170 μg m−3). The elemental mass-particle size distributions for several major dust-derived elements (Al, Ca, Fe, K, Mn, Si, and Ti) were approximately lognormal, but those for Al, Fe, and Ti differed from Ca, K, and Si. Dry deposition velocities calculated from the observed size distributions and a two-layer deposition model averaged 2.7 cm−1 for Al, Fe, and Ti. For Ca, K, and Si, which appear to be more strongly affected by local Tibetan sources, the average calculated dry deposition velocity was 4.3 cm s−1. Wet deposition fluxes estimated from scavenging ratios indicate that less than 10% of the total deposition on the Tibetan Plateau is attributable to wet removal during the 9 months for which data are available. The yearly mean dust deposition rate (local plus remote and dry plus wet) is estimated to be of the order of ∼100 g m−2 yr−1, which is lower than that onto the Chinese desert regions (320 g m−2 yr−1) or the Loess Plateau (250 g m−2 yr−1), suggesting that the sources upwind of China, and the Tibetan Plateau itself, are not major sources for Asian dust.
Geochemical contrasts between late Caledonian granitoid plutons of northern, central and southern Scotland

ABSTRACT New major- and trace-element data for granitoid plutons from the Grampian Highlands, the Midland Valley and the Southern Uplands of Scotland are presented and discussed. The study is restricted to ‘late granitoids’ (all younger than 430 Ma); the term ‘granitoid’ is used in a wide sense to encompass all plutonic components of a zoned intrusion of this age, sometimes including diorites and ultrabasic cumulate rocks. The data indicate that as a whole the province is chemically high-K calc-alkalic. Other notable enrichments are in Sr and Ba, and a marked geographical difference in these trace-elements is found between plutons of the SW Grampian Highlands and those of the Southern Highlands, the Midland Valley, and the Southern Uplands. Plutons of the NE Highlands tend to be more geochemically evolved than those further SW and those of the Midland Valley and Southern Uplands. When petrographical and geochemical data are considered, three plutonic suites are recognised: (1) the Cairngorm suite comprising plutons of the NE Highlands, (2) the Argyll suite comprising plutons from the SW Highlands, and (3) the S of Scotland suite comprising plutons from the Southern Highlands, Midland Valley and the Southern Uplands excluding Criffell and the Cairnsmore of Fleet. It is proposed that the more acidic granitoids are dominantly the products of I-type crustal sources, but certain diorites and the more basic members of zoned plutons have a substantial mantle component. The elevated Sr and Ba levels in granitoids of the Argyll suite may reflect the influence of incompatible-element-rich fluids from the mantle in the petrogenesis of this suite. The relatively anhydrous pyroxene-mica diorites of the S of Scotland suite are richer in Ni and Cr and appear to represent mantle-derived melts. The relationships between these data and already published isotopic data are discussed.
Biochemical and genetic insights into asukamycin biosynthesis

vii CHAPTER ONE: GENERAL INTRODUCTION . 1 CHAPTER TWO: IDENTIFICATION AND CHARACTERIZATION OF THE ASUKAMYCIN BIOSYNTHETIC GENE CLUSTER . 21 CHAPTER THREE: FORMATION OF THE ASUKAMYCIN LOWER CHAIN . 32 CHAPTER FOUR: ASSEMBLY OF THE ASUKAMYCIN UPPER CHAIN . 41 CHAPTER FIVE: ASUKAMYCIN C5N MOIETY FORMATION . 52 CHAPTER SIX: POST-ASSEMBLY OXYGENATION OF PROTOASUKAMYCIN . 60 CHAPTER SEVEN: A TYPE TWO THIOESTERASE AND OTHER ASUKAMYCIN BIOSYNTHETIC GENES . 68 CHAPTER EIGHT: SUMMARY AND FUTURE PROSPECT . 77 CHAPTER NINE: MATERIALS AND METHODS . 88 REFERENCES . 102 APPENDIX: PERMISSIONS . 117 VITA . 118
Internet-Based GIS in an Inductive Learning Environment: A Case Study of Ninth-Grade Geography Students

Abstract This article reports the results of a qualitative case study that explored the use of Internet-based geographic information systems (IGIS) with ninth-grade geography students. The students worked in teams to examine the geography of Africa using IGIS resources with the instructional goal of developing a presentation on a significant issue facing one region or country. The purpose of this study was to explore the use of IGIS as a tool for integrating geospatial technologies into ninth-grade geography curriculum and instruction within an inductive learning environment. The findings for this study indicate that IGIS can be a successful tool for geography education in an inductive learning environment. Based on qualitative data collected through classroom observations, focus group interviews with students, student work samples, and a teacher journal, two assertions are offered: students perceived expanded freedom as a positive aspect of this IGIS project and IGIS projects such as this can lead to gains in students' cultural awareness and empathy for distant others.
Multi-lane detection based on multiple vanishing points detection

Lane detection plays a significant role in Advanced Driver Assistance Systems (ADAS) for intelligent vehicles. In this paper we present a multi-lane detection method based on multiple vanishing points detection. A new multi-lane model assumes that a single lane, which has two approximately parallel boundaries, may not parallel to others on road plane. Non-parallel lanes associate with different vanishing points. A biological plausibility model is used to detect multiple vanishing points and fit lane model. Experimental results show that the proposed method can detect both parallel lanes and non-parallel lanes.
Atmospheric water balance in the Amazon basin: An isotopic evapotranspiration model

An increase of 3‰ in the “d” value of the isotopic composition of precipitation over the Amazon Basin suggests that an isotopically fractionated evapotranspiration flux contributes to the atmospheric water balance over the region. A steady state evapotranspiration model for the Amazon Basin was developed, and it is shown that the observed increase in the “d” value corresponds to a situation where 20–40% of the total evapotranspiration flux is accompanied by an isotopic fractionation, such as by evaporation from an open water surface. The site of this fractionation, whether by evaporation from the flood plains, canopy interception or lakes, cannot be resolved with the presently available data set.
Neutrophil elastase increases MUC5AC mRNA and protein expression in respiratory epithelial cells

Neutrophil elastase increases MUC5AC mRNA and protein expression in respiratory epithelial cells. Am. J. Physiol. 276 ( Lung Cell. Mol. Physiol. 20): L835–L843, 1999. — Chronic neutrophil-predominant inﬂammation and hypersecretion of mucus are common pathophysiological features of cystic ﬁbrosis, chronic bronchitis, and viral- or pollution-triggered asthma. Neutrophils release elastase, a serine protease, that causes increased mucin production and secretion. The molecular mechanisms of elastase-induced mucin production are unknown. We hypothesized that as part of this mechanism, elastase upregulates expression of a major respiratory mucin gene, MUC5AC . A549, a human lung carcinoma cell line that expresses MUC5AC mRNA and protein, and normal human bronchial epithelial cells in an air-liquid interface culture were stimulated with neutrophil elastase. Neutrophil elastase increased MUC5AC mRNA levels in a time-dependent manner in both cell culture systems. Neutrophil elastase treatment also increased MUC5AC protein levels in A549 cells. The mechanism of MUC5AC gene regulation by elastase was determined in A549 cells. The induction of MUC5AC gene expression required serine protease activity; other classes of proteases had no effect on MUC5AC gene expression. Neutrophil elastase increased MUC5AC mRNA levels by enhancing mRNA stability. This is the ﬁrst report of mucin gene regulation by this mechanism. and proteins were transferred under pressure to a polyvinyl- idene diﬂuoride membrane as previously described (9). The membrane was blocked with milk blocking agent (1:10 dilu- tion) and incubated with a rabbit polyclonal monospeciﬁc anti-MUC5AC antibody (1:500 dilution) (9). Membranes were developed with horseradish peroxidase-conjugated goat anti-rabbit IgG (1:5,000 dilution) and 10 mg of 4-chloro-1- naphthol-10 mg of 3,3 8 -diaminobenzidine tetrahydrochloride-0.006% hydrogen peroxide substrate. To determine whether NE digested MUC5AC glycoprotein, conditioned serum-free medium from A549 cells (48-h culture) was treated with 100 nM NE (22 h) or with vehicle control, and 25 µg of total protein from each treatment condition were evaluated for MUC5AC glycoprotein with Western analysis. Statistical analysis . Analysis data was performed with the Kruskal-Wallis one-way nonparametric analysis of vari-ance and post hoc comparisons by Mann-Whitney’s rank sum test. Differences were considered signiﬁcant at P , 0.05.
T cell memory.

Typical immune responses lead to prominent clonal expansion of antigen-specific T and B cells followed by differentiation into effector cells. Most effector cells die at the end of the immune response but some of these cells survive and form long-lived memory cells. The factors controlling the formation and survival of memory T cells are reviewed.
North American Precipitation and Temperature Patterns Associated with the El Niño/Southern Oscillation (ENSO)

Abstract This paper describes an investigation of the “typical” North American precipitation and temperature patterns associated with the El Nino/Southern Oscillation (ENSO). Monthly surface temperature and precipitation data are analyzed using a method designed to identify regions of the globe that have responses associated with ENSO. Monthly composites, covering idealized two-year ENSO episodes, are computed for temperature and precipitation at all stations with data spanning seven or more ENSO events. The firm harmonic is extracted from the 24 monthly composite values and plotted in the form of a two-year harmonic dial vector. When plotted on a map of North America, these vectors reveal both the regions of coherent response and the phase of the responses with respect to the evolution of the ENSO episode. Time series of temperature and precipitation for the regions identified in the harmonic vector maps are examined to determine the magnitudes of the responses and the percentage of the time that the ide.
Analysis of Lymph Node Metastasis and Risk Factors in 975 Patients with FIGO 2009 Stage A- A Cervical Cancer

Lina Cao Beijing Medical College: Capital Medical University https://orcid.org/0000-0002-9151-0959 Weimin Kong (  kwm1967@ccmu.edu.cn ) Beijing Medical College: Capital Medical University https://orcid.org/0000-0002-3283-8620 Jing Li Beijing Medical College: Capital Medical University Dan Song Beijing Medical College: Capital Medical University Bixia Jin Beijing Medical College: Capital Medical University Tingting Liu Beijing Medical College: Capital Medical University Chao Han Beijing Medical College: Capital Medical University
The interaction of a magnetic cloud with the Earth: Ionospheric convection in the northern and southern hemispheres for a wide range of quasi‐steady interplanetary magnetic field conditions

This is the second of three papers which study a large interplanetary magnetic cloud, and its interaction with the earth's magnetosphere. Here the authors study flows within the ionosphere during the passage of the magnetic cloud on Jan 13-15, 1988. This is the first study of ionospheric convections during prolonged periods of stable and different IMF orientations, which result from the stable, but spatially varying field structure within the magnetic cloud. Data from IMP-8 and DMSP-F8 are analyzed for this work. This observation gave information on ionospheric responses to greater than 10 hour period of northward and southward IMF, with a gradual change from one to the other. Issues studied included strengths of peak flows for north and south IMF; changes in cross polar cap potential with IMF B[sub z]; types and variations of convective patterns vs IMF; variations in size of the polar cap; etc.
Temperature gradient and initial snow density as controlling factors in the formation and structure of hard depth hoar

Abstract We investigate how temperature gradient and initial density influence depth-hoar growth in snow and seek to better define the range of conditions under which cohesive, or hard, depth hoar forms. Samples of 400 kg m−3 sieved snow were exposed to temperature gradients of 20–80°C m−1, and samples of four different densities were exposed to a 40°C m temperature gradient. Following exposure to temperature gradients, penetrometer tests were made on samples to determine the presence of solid and/or hard depth hoar. Grain bond orientation was analyzed in section planes by two-dimensional stereological techniques where hard depth hoar developed. Results indicate that hard cohesive depth hoar forms from rounded-grain snow having a density of 400 kg m−3 or greater, following exposure to a temperature gradient of 20°C m−1 or greater. Hard depth hoar appears to consist of solid-type depth-hoar grains connected by necks, with vertically preferred directions of grain elongation and organization of grain-to-grain chains. This work corroborates Atikaya’s (1974) results, but extends his observation of formation of hard depth hoar to weaker temperature gradients for high-density snow. Our results also indicate that hard depth hoar is composed of faceted solid-type (anhedral) grains.
Understanding the ways and the dynamics of collaborative innovation processes: the case of the maritime cluster of the Algarve region (Portugal)

The Algarve region has always showed a close relationship with the sea as a result of its excellent natural conditions, historical and cultural reasons, and notorious know-how related with traditional maritime activities, such as fisheries and fish processing, and naval industry; more recently, nautical activities, such as tourism and recreational boating, have been gaining increased importance. The region is also well infrastructured in terms of public R&D institutions which are important cornerstones of the regional and national innovation systems. Through surveys carried out over a population of firms related to fisheries, aquaculture, fish processing and trade, nautical tourism, naval construction, and repair and shipping, we intend to: (1) characterize the innovation processes adopted by the Algarve’s firms of the maritime economy and evaluate some of the main outputs generated by R&D activities promoted by the regional innovation centers; (2) analyze the potential externalities linked to the production and dissemination of information from knowledge spillovers and knowledge networks; and (3) assess the strategic interest associated with the use of knowledge-intensive service activities regarding their role as sources and/or facilitators of innovation in customer organizations, or as carriers of innovation, when they help in transferring knowledge between or within organizations.
Streamflow trends in Nepal

Abstract This study presents the first comprehensive nationwide trend detection of streamflow in Nepal, a country that has been historically understudied despite its critical location as the southern pathway for most of the Himalayan snowpack melt and torrential seasonal monsoon rains. We applied Mann-Kendall and Sen's trend tests using trend-free pre-whitening and bootstrap approaches to two streamflow data sets to deal with serial and cross-correlation. The two data sets comprised 23–33 hydrometric stations with 31 years and more than 20 years of published data, respectively. The test on the 33 stations data set showed that 23% of the streamflow variables studied had statistically significant trends, evenly divided between upward and downward trends. Similarly, in the second, relatively smaller data set, 24% of variables exhibited trends, of which 41% were downward and 59% upward. The higher percentage of observed upward trends in pre-monsoon and winter seasonal average flow is noteworthy given the potential snowmelt contribution in many of the studied sites. Trends were mostly absent in stations draining the larger basins. However, some spatial patterns were seen in the observed trend directions, specifically, a downward trend in the Karnali-Mahakali River basin and an upward trend in the West Rapti River basin, as well as a nationwide absence of trend in the post-monsoon season. Editor Z.W. Kundzewicz Citation Gautam, M.R. and Acharya, K. , 2011. Streamflow trends in Nepal. Hydrological Sciences Journal, 57 (2), 344–357.
Polar stratospheric clouds climatology over Dumont d'Urville between 1989 and 1993 and the influence of volcanic aerosols on their formation

The first polar stratospheric clouds (PSCs) climatology ever established from lidar data and relative to a specific site is presented here. It is based on lidar backscatter and depolarization measurements of PSCs carried out between 1989 and 1993 at Dumont d'Urville (66°S, 140°E), which is a primary station of the Network for Detection of Stratospheric Changes (NDSC). The climatology was subdivided based on the stratospheric sulphuric acid aerosol content (background aerosols in 1989-1991 and volcanic aerosols in 1992-1993 following the Mount Pinatubo eruption). PSCs were mainly observed in July and August. Very few water ice clouds (type II) were detected. Most of the PSCs tended to form around the peak in sulphuric acid aerosol, between 17 and 23 km in 1989-1991 and between 11 and 20 km in 1992-1993. This tendency suggests that sulphuric acid aerosols are very likely to act as condensation nuclei for PSCs. As shown by previous lidar studies [Browell et al., 1990], two type I subclasses were identified: depolarizing (nonspherical) particles (type Ia) and nondepolarizing (spherical) particles (type Ib). No type Ia PSCs were detected above the nitric acid trihydrate (NAT) saturation temperature, T NAT , lending support to the theory that NAT is the main component of type Ia PSCs. There was also no evidence of the existence of sulphuric acid tetrahydrate (SAT) in the data. Some type It PSCs were observed close to the frost point, showing that supersaturation with respect to NAT is a necessary, but not sufficient, condition for the existence of solid PSCs. No type It PSCs were clearly detected above T NAT in 1989-1991 whereas 18% of the PSCs seem to be found at temperatures above T NAT in 1992-1993. This difference might be linked to the HNO 3 uptake by volcanic sulphuric acid particles starting at higher temperatures. The fraction of type Ia out of the total PSCs observations was lower in 1992-1993 than in 1989-1991. This difference was not found to be highly statistically significant.