Miracle-dz/UniFAR-FTUs huggingface dataset:
Some Physical Properties of Vernonia amygdalina and Garcinia kola Microspheres Prepared with High Molecular Weight Polyethylene Glycols

: The effect of polymer concentrations on some of the physicochemical properties of Vernonia amygdalina (Linn) and Garcinia kola (Heckel) extracts loaded microspheres was evaluated. Microspheres of the aqueous extracts was prepared by emulsion solvent evaporation using polyethylene glycol (PEG) mixtures of molecular weight 4000 and 6000 at different ratios of 1:0, 0:1, 1:1, 1:2 and 2:1 while the amounts of the extracts incorporated was constant for all ratios. The microspheres were evaluated for their particles sizes, yield, flavonoid content, loading efficiency, moisture loss and flow properties. In-vitro release studies were carried out by monitoring flavonoid release rate from the microspheres. The microspheres were spherical and uniformly shaped and exhibited good flow characteristics. Their size range, yield, loading efficiency, moisture loss and flavonoid content were 76 - 83 μm, 49 - 76 %, 47 - 82 %, 2.18 - 4.60 % and 17.10 - 23.80 mg%, respectively for V. amygdalina and 144 - 160 μm, 50 - 68 %, 51 - 68 %, 3.00 - 4.41 % and 20.00 - 28.70 mg%, respectively for G. kola . Flavonoids release from the microsphere was up to 90 % within 1 h and it followed a matrix release kinetic model with a super case-II transport mechanism. The concentrations of the polymers affected the yield, loading efficiency, moisture loss and the extent of flavonoid release of the microspheres but had no effect on their particle sizes and flavonoid content. These results may find useful application in the delivery of V. amygdalina and G. kola extracts since the combination of PEG of different molecular weights resulted in microspheres with good physicochemical and release properties.
Integrating Knowledge Sources for the Speci(cid:12)cation of a Task-Oriented Dialogue System

We show how the speci(cid:12)cation of a dialoguesys-tem can be divided into domain-dependent and domain-independent parts. We demonstrate how comparisons of actual representations in the dialogue history can help to infer hierarchical dialogue structure. The principles guiding the inference can be expressed in domain independent rules. Using typed feature structures as the only representation formalism we retain the simplicity of frame-based systems in terms of gathering necessary information to ful(cid:12)l a task. On the other hand, being able to easily integrate a type hierarchy into the representations and describing the systems behavior in clauses quantifying over feature structures in the dialogue history, we not only achieve a compact speci(cid:12)cation of the system’s behavior. The described implementation is a (cid:12)rst step towards the implementation of domain-independent task-oriented dialogue processing systems.
Long‐term seismicity and ground deformation at Axial Volcano, Juan de Fuca Ridge

Seismicity along the Juan de Fuca Ridge (JdFR) has been monitored since August 1991 using U.S. Navy hydrophones in the northeast Pacific Ocean. During this time, the focus of JdFR seismicity has been Axial Volcano, where a total of 9055 earthquakes have been detected (1669 located). This activity occurred within 48 discrete swarms along the summit caldera and flank rift zones. From August 1991 to May 1996, Axial Volcano exhibited only one swarm with ≥50 earthquakes. From May 1996 to November 1997 swarm activity increased significantly with five swarms of ≥50 earthquakes. Activity culminated at the volcano in January 1998 with an 11‐day, 8247‐event swarm that was the result of a major eruption along the summit and southern flank. Seafloor deformation sensors indicated pre‐eruption swarms in October 1995, May 1996, and June 1996 coincided with subsidence of the caldera floor. The 1996–1997 swarm activity increase also coincided with horizontal extension of the north rift zone, consistent with pre‐eruption deformation of the volcano. Following the 1998 eruption, swarm activity dramatically decreased and no earthquakes have been detected since April 1998. This is the longest aseismic period (∼1 yr) observed at the volcano since acoustic monitoring began, suggesting the January 1998 swarm marked the end of an eruptive cycle at Axial Volcano.
The Problem of Cure in Kala-Azar

can be considered cured and the antimony treatment discontinued. From time to time since the introduction of the treatment with the antimony tartrates various rules have been suggested for the course of treatment that is necessary to effect a cure; these rules have become more and more elastic and there is usually a very decided tendency towards prolongation of the course. Sir Leonard Rogers first suggested that the injections
Nutrients in the gully, Scotian shelf, Canada

Abstract The Gully is a large shelf‐edge submarine canyon located on the eastern Scotian Shelf which has long been recognized as an area rich in marine life. This paper analyses the available nutrient (nitrate, silicate and phosphate) data for The Gully, including the new information collected since The Gully was designated a potential Marine Protected Area in 1998, and reports on nutrient climatology, nutrient transports and transport mechanisms, and surface nutrient distributions with a focus on how nutrient behaviour may or may not be different in The Gully than observed elsewhere on the Scotian Shelf. Seasonal cycles for nutrients in The Gully show the general patterns expected for nutrients in temperate coastal waters. The concentrations of all three nutrients in the surface layer (z ≤ 50 m) are relatively high in late fall and winter. Nitrate and silicate levels fall rapidly during the spring bloom and remain low during the summer and fall. Nitrate is more severely depleted than silicate. Phosphate levels are also lower in summer than in winter, but not depleted in summer, which is consistent with a nitrogen limited ecosystem. Attenuated versions of these seasonal cycles for the three nutrients are evident in the intermediate layer (50 < z ≤ 100 m), with substantial quantities of nutrients remaining in the summer. Little evidence of a seasonal cycle is seen in deeper waters (z > 100 m). These nutrient concentrations and seasonal cycles are similar to those found elsewhere on the shelf. A more detailed examination of nutrient concentrations in The Gully shows that higher nitrate, silicate and phosphate levels occur at the head of The Gully compared to the mouth, and on the Sable Bank side of The Gully compared to the Banquereau side. These observations are consistent with a trapping of nutrients associated with the counter‐clockwise circulation within The Gully, which could fuel more primary productivity in The Gully than on the adjacent shelf. Nutrient levels determined from surface samples collected at high frequency while survey vessels were underway showed anomalously high surface concentrations of nitrate and silicate that were consistent with the areas where the interaction of gully currents with the bottom topography at the head of The Gully and breaking internal waves along the north‐east edge of The Gully would enhance vertical mixing. Calculations of transports of nutrients through The Gully show that ∼5% of the external inputs of nitrate to the eastern Scotian Shelf are supplied through The Gully in winter, and ∼25% flow through The Gully in summer. Calculations based on these physical processes and the observed nutrient levels show that such mechanisms have the potential to increase production substantially in The Gully compared to other areas of the shelf.
Staining of Tissue Sections for Electron Microscopy with Heavy Metals

Descriptions of three heavy metal stains and methods of application to tissue sections for electron microscopy are presented. Lead hydroxide stains rather selectively two types of particles in liver: those associated with the endoplasmic reticulum and containing ribonucleic acid and other somewhat larger particles. Barium hydroxide emphasizes certain bodies within vesicles of the Golgi region of hepatic cells. Alkalized lead acetate is useful as a general stain, as are also lead and barium hydroxides.
Alternatively activated macrophages induced by nematode infection inhibit proliferation via cell‐to‐cell contact

The cytokine microenvironment is thought to play an important role in the generation of immunoregulatory cells. Nematode infections are commonly associated with Th2 cytokines and hyporesponsive T cells. Here we show that IL‐4‐dependent macrophages recruited in vivo by the nematode parasite Brugia malayi actively suppress the proliferation of lymphocytes on co‐culture in vitro. These alternatively activated macrophages block proliferation by cell‐to‐cell contact, implicating a receptor‐mediated mechanism. Further, the proliferative block is reversible and is not a result of apoptosis. Suppressed cells accumulate in the G1 and G2 / M phase of the cell cycle. Interestingly, the G1 and G2 / M block correlates with increased levels of Ki‐67 protein, suggesting a mechanism that affects degradation of cell cycle proteins. We also show that, in addition to lymphocyte cell lines of murine origin, these suppressive cells can inhibit proliferation of a wide range of transformed human carcinoma lines. Our data reveal a novel mechanism of proliferative suppression induced by a parasitic nematode that acts via IL‐4‐dependent macrophages. These macrophages may function as important immune regulatory cells in both infectious and noninfectious disease contexts.
Insulin-Like Growth Factor-1 and Neuroinflammation

Insulin-like growth factor-1 (IGF-1) effects on aging and neurodegeneration is still controversial. However, it is widely admitted that IGF-1 is involved in the neuroinflammatory response. In peripheral tissues, several studies showed that IGF-1 inhibited the expression of inflammatory markers, although other studies concluded that IGF-1 has proinflammatory functions. Furthermore, proinflammatory cytokines such as TNF-α impaired IGF-1 signaling. In the brain, there are controversial results on effects of IGF-1 in neuroinflammation. In addition to direct protective effects on neurons, several studies revealed anti-inflammatory effects of IGF-1 acting on astrocytes and microglia, and that IGF-1 may also inhibit blood brain barrier permeability. Altogether suggests that the aging-related decrease in IGF-1 levels may contribute to the aging-related pro-inflammatory state. IGF-1 inhibits the astrocytic response to inflammatory stimuli, and modulates microglial phenotype (IGF-1 promotes the microglial M2 and inhibits of M1 phenotype). Furthermore, IGF-1 is mitogenic for microglia. IGF-1 and estrogen interact to modulate the neuroinflammatory response and microglial and astrocytic phenotypes. Brain renin-angiotensin and IGF-1 systems also interact to modulate neuroinflammation. Induction of microglial IGF-1 by angiotensin, and possibly by other pro-inflammatory inducers, plays a major role in the repression of the M1 microglial neurotoxic phenotype and the enhancement of the transition to an M2 microglial repair/regenerative phenotype. This mechanism is impaired in aged brains. Aging-related decrease in IGF-1 may contribute to the loss of capacity of microglia to undergo M2 activation. Fine tuning of IGF-1 levels may be critical for regulating the neuroinflammatory response, and IGF-1 may be involved in inflammation in a context-dependent mode.
Methyl donors change the germline epigenetic state of the Avy allele

Waterland and colleagues conclude that the epigenetic effect of methyl donors in A mice is not inherited (1), and contrast their result with our report of induced germline epigenetic change in A (2). There is a simple explanation for the discrepancy. A mice are epigenetic mosaics: the A allele is active and unmethylated in some cells, silent and methylated in others (3, 4; and J.C. and D.M., unpublished). Methyl donors increase the proportion of silent A alleles (2, 5–7); inheritance of this silent state is at issue here. Yellow mice have no silent A alleles, mottled mice as few as 5%. Waterland et al. bred mostly females that were either yellow or lightly mottled (i.e., in most of their cells the A allele had not been silenced by methyl donors). Germ cells in these mice will reflect the somatic state of A (mostly active), but epigenetic inheritance at A results from germline maintenance of the silent state (4, 8). Heavily mottled mice, which are more likely to have silent A alleles in their germline cells, were minor contributors to the breeding population. Thus, in most of the mice bred by Waterland et al. there was little or nothing in the germline to be inherited. Our experiment (2) maximized the chances of observing epigenetic inheritance at A, by breeding only pseudoagouti females (in which A is completely silent in somatic cells) with or without a history of methyl donor supplementation. The result was unambiguously consistent with our conclusion that “. methyl donors can change the epigenetic state of the A allele in the germline (2). ” We expect that Waterland and colleagues would have observed a small degree of inheritance, attributable largely to passage of silent A through heavily mottled and pseudoagouti mice, if they had carried out their experiment with very large numbers of mice.
- mutated cutaneous melanoma successfully rechallenged after initial progression

DNA and RNA extraction DNA was extracted from tumor and germline samples using the Gentra kit (Qiagen) following manufacturer’s instructions. For FFPE samples, tissue was scraped from slides (10μm sections) and deparaffinized with xylene (twice 5 min at room temperature) followed by ethanol rinses prior to digestion with proteinase K (overnight at 55°C). RNA was extracted using guanidinium thiocyanate/CsCl gradient (frozen samples and cultured cells) or the ExtractAll RNA extraction kit (FFPE sample, Ambion, Life technologies).
Novel therapeutic opportunities for Alzheimer's disease: focus on nonsteroidal anti‐inflammatory drugs

Alzheimer's disease (AD) is the most common form of neurodegenerative disorder with dementia in the elderly. The AD brain pathology is characterized by deposits of amyloid‐β (Aβ) peptides and neurofibrillary tangles but also (among other aspects) by signs of a chronic inflammatory process. Epidemiological studies have shown that long‐term use of nonsteroidal anti‐inflammatory drugs (NSAIDs) reduces the risk of developing AD and delays its onset. Classical targets of NSAIDs include cycloxygenase, nuclear factor κB, and peroxisome proliferator‐activated receptors. Modulation of these pathways, all of which have been implicated in AD pathogenesis, could explain the NSAID effect on AD progression. However, recent studies indicate that a subset of NSAIDs such as ibuprofen, indomethacin, and flurbiprofen may have direct Aβ‐lowering properties in cell cultures as well as transgenic models of AD‐like amyloidosis. A renewed interest in the old and a discovery of new pharmacological properties of these drugs are providing vital insight for future clinical trials. In this review we will summarize how the combination of traditional (anti‐inflammatory) and new (anti‐amyloidogenic) properties of some NSAIDs is providing unprecedented opportunities for drug discovery and could potentially result in novel therapeutic approaches for the treatment of AD. Townsend K. P., Praticò D. Novel therapeutic opportunities for Alzheimer's disease: focus on nonsteroidal anti‐inflammatory drugs. FASEB J. 19, 1592–1601 (2005)
Decomposing Effects of Time on Task Reveals an Anteroposterior Gradient of Perceptual Decision Regions

In perceptual decision making, the selection of an appropriate action depends critically on an organism’s ability to use sensory inputs to accumulate evidence for a decision. However, differentiating decision-related processes from effects of “time on task” can be difficult. Here we combine the response signal paradigm, in which the experimenter rather than the subject dictates the time of the response, and independent components analysis (ICA) to search for signatures consistent with time on task and decision making, respectively, throughout the brain. Using this novel approach, we identify two such independent components from BOLD activity related to a random dot motion task: one sensitive to the main effect of stimulus duration, and one to both the main effect of motion coherence and its interaction with duration. Furthermore, we demonstrate that these two components are expressed differently throughout the brain, with activity in occipital regions most reflective of the former, activity within intraparietal sulcus modulated by both factors, and more anterior regions including the anterior insula, pre-SMA, and inferior frontal sulcus driven almost exclusively by the latter. Consistent with these ICA findings, cluster analysis identifies a posterior-to-anterior gradient that differentiates regions sensitive to time on task from regions whose activity is strongly tied to motion coherence. Together, these findings demonstrate that progressively more anterior regions are likely to participate in progressively more proximate decision-related processes.
Acetylcholine receptor-aggregating activity of agrin isoforms and mapping of the active site

Agrin is a basal lamina protein that induces aggregation of acetylcholine receptors (AChRs) and other molecules at the developing neuromuscular junction. Alternative splicing of chick agrin mRNA at two sites, A and B, gives rise to eight possible isoforms of which five are expressed in vivo. Motor neurons express high levels of isoforms with inserts at sites A and B, muscle cells synthesize isoforms that lack amino acids at the B-site. To obtain further insights into the mechanism of agrin-induced AChR aggregation, we have determined the EC50 (effective concentration to induce half-maximal AChR clustering) of each agrin isoform and of truncation mutants. On chick myotubes, EC50 of the COOH-terminal, 95-kD fragment of agrinA4B8 was approximately 35 pM, of agrinA4B19 approximately 110 pM and of agrinA4B11 approximately 5 nM. While some AChR clusters were observed with 64 nM of agrinA4B0, no activity was detected for agrinA0B0. Recombinant full-length chick agrin and a 100-kD fragment of ray agrin showed similar EC50 values. A 45-kD, COOH-terminal fragment of agrinA4B8 retained high activity (EC50 approximately equal to 130 pM) and a 21-kD fragment was still active, but required higher concentrations (EC50 approximately equal to 13 nM). Unlike the 45-kD fragment, the 21-kD fragment neither bound to heparin nor did heparin inhibit its capability to induce AChR aggregation. These data show quantitatively that agrinA4B8 and agrinA4B19, expressed in motor neurons, are most active, while no activity is detected in agrinA0B0, the dominant isoform synthesized by muscle cells. Furthermore, our results show that a fragment comprising site B8 and the most COOH- terminal G-like domain is sufficient for this activity, and that agrin domains required for binding to heparin and those for AChR aggregation are distinct from each other.
Large floods, alluvial overprint, and bedrock erosion

Depending on their behaviour during extreme floods, streams can be divided into two distinct classes, which derive from a simple threshold model of transport dynamics. ‘Flood‐cleaning’ streams erode during high flows and deposit during small and medium flows. ‘Flood‐depositing’ streams deposit during high flows and erode during small and medium flows. Using published descriptions of the geomorphic effects of large floods, rivers with a wide range of drainage areas and other characteristics are classified as either ‘flood‐cleaning’ or ‘flood‐depositing’. In bedrock channels, this behaviour can lead to a feedback effect, the ‘overprint effect’, between sediment transport processes and bedrock erosion, which can modulate long‐term bedrock erosion rates. The ‘overprint effect’ arises when alluvium covers the bedrock and typical alluvial channel forms (e.g. meandering or braiding patterns, armour layers or bedforms) develop, which influence sediment transport rates. This effect may accelerate or decelerate sediment export from a reach, causing increased or decreased long‐term bedrock erosion rates. The ‘overprint effect’ is illustrated using field data from the Erlenbach, Switzerland, and its implications for channel dynamics and bedrock erosion are discussed. Copyright © 2012 John Wiley & Sons, Ltd.
Effects of Hypericum perforatum extract on rat irritable bowel syndrome

Context: In irritable bowel syndrome (IBS), disturbance of bowel motility is associated with infiltration of inflammatory mediators and cytokines into the intestine, such as neutrophils, myeloperoxidase (MPO), tumor necrosis factor alfa (TNF-α), and lipid peroxide. Aims: Regarding promising anti-inflammatory and anti-oxidative effects of Hypericum perforatum (HP) extract, besides its anti-depressant effect, this study was designed to evaluate the effects of HP in an experimental model of IBS. Settings and Design: IBS was induced by a 5-day restraint stress in rats. The HP extract was administered by gavage in doses of 150, 300, and 450 mg/kg for 26 days. Fluoxetine and loperamide were used as positive controls. Gastric emptying and small bowel and colon transit, besides the levels of TNF-α, MPO, lipid peroxidation, and antioxidant power, were determined in colon homogenates. Statistical Analysis Used: Data were analyzed by one-way ANOVA followed by Tukey's post hoc test for multiple comparisons. Results: A significant reduction in small bowel and colonic transit (450 mg/kg), TNF-α, MPO, and lipid peroxidation and an increase in antioxidant power in all HP-treated groups (150, 300, and 450 mg/kg) were seen as compared with the control group. Gastric emptying did not alter significantly when compared with the control group. Treatment with loperamide (10 mg/kg) significantly inhibited gastric emptying and small bowel and colonic transit, while flouxetine (10 mg/kg) decreased gastric emptying, TNF-α, MPO, and lipid peroxidation and increased the antioxidant power of the samples in comparison with the control group. Conclusions: HP diminished the recruitment of inflammatory cells and TNF-α following restraint stress not in a dose-dependent manner, possibly via inhibition of MPO activity and increasing colon antioxidant power, without any difference with fluoxetine. The HP extract inhibits small bowel and colonic transit acceleration like loperamide but has minimal effect on gastric emptying.
Undifferentiated arthritis in an early synovitis out-patient clinic.

OBJECTIVE To describe the features of undifferentiated arthritis in an early synovitis out-patient clinic. METHODS In a two-year prospective cohort study 320 patients with rheumatic symptoms of less than one year were investigated in an early synovitis out-patient clinic. Besides the clinical parameters, an intensive laboratory program was performed, including routine blood and serum parameters, immunological investigations (CRP, IgG,A,M,C3C4,RF,ANA, DNA, HLA B-27), and a microbiological program to search for reactive arthritis-inducing infections. RESULTS 217 patients had inflammatory rheumatic diseases, of whom only 100 (46%) could be given a definite diagnosis, whereas 117 (54%) were considered as having undifferentiated arthritis (UA). Patients with UA had a mean age of 41 +/- 15 years, the sex-ratio was 1.8:1.0 (f/m), joint manifestations were oligoarticular in 68%, monarticular in 14%, and polyarticular in 18%. Rheumatoid factor was positive in 17%, HLA-B27 was found in 27%, and 21% of the patients had a history of recent infection. Follow up over 26 (range 4-38) months of 28 (24%) patients with UA revealed complete remission in 15 patients (54%), while 10 patients (36%) had further UA with partial remission, unchanged activity or progressive disease, and only 2 (7%) developed rheumatoid arthritis (RA) and 1 (4%) was diagnosed as having ankylosing spondylitis. CONCLUSION Most patients with early synovitis followed at our clinic remain unclassified with a good prognosis.