pinecone/core-2020-05-10-deduplication huggingface dataset:
The Design and Cytotoxic Evaluation of Some 1-Aryl-3-
isopropylamino-1-propanone Hydrochlorides towards Human
Huh-7 Hepatoma Cells

Cataloged from PDF version of article.A series of 1-aryl-3-isopropylamino-1-propanone hydrochlorides 1 and a related heterocyclic analog 2 as candidate antineoplastic agents were prepared and the rationale for designing these compounds is presented. A specific objective in this study is the discovery of novel compounds possessing growth-inhibiting properties of hepatoma cells. The compounds in series 1 and 2 were prepared and their structures established unequivocally. X-ray crystallography of two representative compounds 1d and 1g were achieved. Over half of the compounds are more potent than 5-fluorouracil which is an established drug used in treating liver cancers. QSAR evaluations and molecular modeling studies were undertaken with a view to detecting some physicochemical parameters which govern cytotoxic potencies. A number of guidelines for amplification of the project have been formulated. A number of Mannich bases displayed greater potency than the reference drug 5-fluorouracil against human Huh-7 hepatoma cells. In particular, 1i emerged as a lead compound possessing 2.8 fold higher activity than that of the reference drug. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Novel pyrazole and indazole derivatives: synthesis and evaluation of their anti-proliferative and anti-angiogenic activities

The synthesis of several new pyrazole and indazole derivatives from acetophenone and tetralone substrates is reported. The bioactivities of the new compounds were evaluated through in vitro assays for endothelial cell proliferation and tube formation. Results herein indicate that the easily prepared compounds containing the indazole structural framework exhibit potent cytostatic properties against all cell lines tested, with compounds 13 and 14 being the most active displaying IC(50) values of 1.5 ± 0.4 µM and 5.6 ± 2.5 µM, respectively, against MCF-7 cells. In addition, the indazole derivative 16 was assessed as a competent inhibitor of endothelial tube formation at 30 µM.status: publishe
Synthesis and Evaluation of 3-[(2,4-Dioxo-1,3,8-triazaspiro[4.6]undec-3-yl)methyl]benzonitrile Derivatives as Potential Anticonvulsants.

New 3-[(2,4-dioxo-1,3,8-triazaspiro[4.6]undec-3-yl)methyl]benzonitrile derivs. 8-37 were synthesized and their pharmacol. activities were detd. with the objective to better understand their structure-activity relationship (SAR) for anticonvulsant activity.  All the compds. were evaluated for their possible anticonvulsant activity by maximal electroshock seizure (MES) and pentylenetetrazole (PTZ) test.  Compds. 11, 18, 31, and 32 showed significant and protective effect on seizure, when compared with the std. drug valproate.  The same compds. were found to exhibit advanced anticonvulsant activity as well as lower neurotoxicity than the ref. drug.  From this study, it is quite apparent that there are at least three parameters for the activity of anticonvulsant drugs, i.e., a lipophilic domain, a hydrophobic center, and a two-electron donor. [on SciFinder(R)
Design, synthesis, and antiviral activity of novel ribonucleosides of 1,2,3-triazolylbenzyl-aminophosphonates

A novel series of ribonucleosides of 1,2,3-triazolylbenzyl-aminophosphonates was synthesized through the Kabachnik-Fields reaction using I2 as catalyst followed by copper-catalyzed cycloaddition of the azide-alkyne reaction (CuAAC). All structures of the newly prepared compounds were characterized by (1) H NMR, (13) C NMR, and HRMS spectra. The structures of 2e, 2f, 3d, and 3g were further confirmed by X-ray diffraction analysis. These compounds were tested against various strains of DNA and RNA viruses; compounds 4b and 4c showed a modest inhibitory activity against respiratory syncytial virus (RSV) and compound 4h displayed modest inhibitory activity against Coxsackie virus B4.status: publishe
Ontologies on the semantic web

As an informational technology, the World Wide Web has enjoyed spectacular success. In just ten years it has transformed the way information is produced, stored, and shared in arenas as diverse as shopping, family photo albums, and high-level academic research. The “Semantic Web” was touted by its developers as equally revolutionary but has not yet achieved anything like the Web’s exponential uptake. This 17 000 word survey article explores why this might be so, from a perspective that bridges both philosophy and IT
Low Altitude Thermal Survey by Means of an Automated Unmanned Aerial Vehicle for the Detection of Archaeological Buried Structures

International audienceAirborne thermal prospecting is based on the principle that there is a fundamental difference between the thermal characteristics of buried remains and the environment in which they are buried. The French 'Archéodrone' project aims to combine the flexibility and low cost of using an airborne drone with the accuracy of the registration of a thermal digital camera. This combination allows the use of thermal prospection for archaeological detection at low altitude with high-resolution information, from a microregional scale to the site scale. The first results have allowed us to assess the contribution of this technique for the detection of ancient roads, land plots boundaries, site plans and underground caves. Copyright © 2013 John Wiley & Sons, Ltd
Geophysical Survey in Sub-Saharan Africa: magnetic and Electromagnetic Investigation of the UNESCO World Heritage Site of Songo Mnara, Tanzania

Magnetometry and Slingram electromagnetic surveys were conducted at the UNESCO World Heritage Site of Songo Mnara, Tanzania, as part of a multinational programme of investigation to examine the uses of space within and outside of this stonetown. The town was a major Islamic trading port during the fourteenth and fifteenth centuries. The surveys detected significant evidence for the containment of activities within the town walls, and previously unknown anthropogenic activity was revealed between the existing coral rag buildings, as well as within the open areas inside the town. Over 40 areas of magnetic disturbance were identified that corresponded directly with areas of high magnetic susceptibility in the Slingram electromagnetic in-phase responses. On excavation many of these anomalies were found to correlate with wattle and daub structures, indicating a hitherto unidentified population, and the location of the anomalies also suggests a potentially deliberate delineation of space within the open areas of the stonetown. The combined results of the three geophysical data sets indicate that there are clear delineations in the use of space within Songo Mnara. This, coupled with the presence of industrial activities and evidence of more ephemeral occupation, neither of which had previously been recorded at the site, indicates that the pre-existing town plan is in need of significant reappraisal. The current plan, based upon the remains of extant and collapsed coral buildings, can now be updated to incorporate the more ephemeral aspects of Swahili sites, including activity areas, and notably, the homes of the ‘hidden majority’ of the population. The results establish the benefit of a combined approach at these sites, and demonstrate that further invasive and non-invasive exploration is required in order to fully exploit the significance of the role of geophysical techniques in understanding Swahili towns
Palaeogeographic reconstruction in the transition zone : the role of geophysical forward modelling in ground investigation surveys

Geophysical survey techniques are commonly used as part of studies to reconstruct past geographies in archaeological and palaeoenvironmental landscape investigations onshore and offshore. However, their use across the intertidal zone for constructing contiguous models is far more challenging. In order to enhance the interpretation of the recovered data forward modelling is used here to demonstrate the effective use of a staged approach to site investigation. Examples of data from electrical and electromagnetic techniques have been modelled and tested with ground truth measurements including trial pits, coring and cone penetrometer testing. This combination of forward modelling and testing has proved to be particularly effective at mapping key geological situations of archaeological interest. The approach is demonstrated by reference to varying sub-surface sediment types exemplified by two field examples from the UK coast where typical palaeolandscape features, namely incised channels and deeply buried topographies are encountered. These palaeogeographic features were chosen as they have high potential for association with the evidence of past human activity.PostprintPeer reviewe
Geochemical survey and evaluation excavations at Alderley Edge: recognising anthropogenic signatures within a mining site-scape

Archaeological science and archaeological field investigations are making greater use of multi-element geochemical survey as a tool for site prospection and intra-excavation analysis. This increasing use of geochemical survey is allowing a new field of geoprospection to develop, a technique that has specific relevance to the investigation of sites containing archaeometallurgical evidence, due to the high geochemical loadings within archaeological contexts produced from past metalworking activities. Correspondingly, there have been relatively few published examples that compare the results of these geochemical surveys against excavation data. This study reports the use of geochemical data to investigate a multi-period mining site-scape at Alderley Edge, Cheshire, UK. The geochemical data is analysed using Principle Components Analysis, which facilitates the identification of a number of geochemical anomalies. The site taphonomy and stratigraphic evolution of this mining site-cape is complex, with naturally occurring areas of lead and copper mineralisation’s that have been previously been mined. The geochemical anomalies were compared to the results of excavation within the survey area and this combination of excavation and prospection data allowed the reasons for the different geochemical anomalies to be explained. The paper highlights the potential of using multi-element geochemical survey to investigate sites containing archaeometallurgical remains and provides a discussion of why context specificity is essential to correctly interpret multi-element geochemical data
Reconstructing Palaeogeography and Inter-island Visibility in the Wallacean Archipelago During the Likely Period of Sahul Colonization, 65-45000 Years Ago

The palaeogeography of the Wallacea Archipelago is a significant factor in understanding early modern human colonization of Sahul (Australia and New Guinea), and models of colonization patterns, as well as archaeological survey and site interpretation, are all heavily dependent on the specific palaeogeographic reconstruction employed. Here we present five reconstructions for the periods 65, 60, 55, 50, and 45 000 years ago, using the latest bathometric chart and a sea-level model that is adjusted to account for the average uplift rate known from Wallacea. Using this data we also reconstructed island areal extent as well as topography for each time period. These reconstructions were then used to estimate visibility for each island in the archipelago, and finally to model how intervisible each island was during the period of likely human colonization. Our models provide the first evidence for intervisibility between Timor and Australia at ca. 65–62 ka and 47–12 ka, the second of which is notable for its overlap with the oldest radiocarbon dates from Timor-Leste and Australia. Based on intervisibility alone, however, our study suggests that the northern route into Papua New Guinea was the most parsimonious route for first modern human entry into Sahul. Our study provides archaeologists with an important baseline from which to conduct physical surveys, interpret archaeological data, and theorize the colonization of Wallacea and Sahul.Full Tex
Integrated geophysical survey to recognize ancient Picentia’s buried walls, in the Archaeological Park of Pontecagnano – Faiano (Southern Italy)

There is no information on previous geophysical prospections carried out in the Archaeological Park of Pontecagnano-
Faiano, in order to reconstruct the ancient settlement of Picentia, an Etrusco-Campanian and Roman
settlement near Salerno (Southern Italy). Therefore, an integrated geophysical survey based on magnetic, geoelectric
and ground-penetrating radar (GPR) prospections was executed in the Park. The methods provided a
basic map of buried ancient structures at depth from 0.1-0.2 to about 1.5 meters. Magnetic data were processed
analyzing the analytical signal of the vertical derivative of the measured gradient and this substantially reduced
a strong fence effect. The results of the geophysical prospections showed archaeological structures located close
to those discovered in the excavated areas. The shape of the anomalies are usually elongated with well-defined
geometrical characteristics. Many anomalies are arranged along orthogonal directions and they are very coherent
with the excavated structures, namely the quarters structures of the ancient Picentia
Immunosuppressive therapy in lupus nephritis: the Euro‐Lupus Nephritis Trial, a randomized trial of low‐dose versus high‐dose intravenous cyclophosphamide.

Arthritis Rheum. 2002 Aug;46(8):2121-31.

Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide.
Houssiau FA, Vasconcelos C, D'Cruz D, Sebastiani GD, Garrido Ed Ede R, Danieli MG, Abramovicz D, Blockmans D, Mathieu A, Direskeneli H, Galeazzi M, Gül A, Levy Y, Petera P, Popovic R, Petrovic R, Sinico RA, Cattaneo R, Font J, Depresseux G, Cosyns JP, Cervera R.

Cliniques Universitaires St. Luc, Université Catholique de Louvain, Brussels, Belgium. houssiau@ruma.ucl.ac.be

Comment in:

Arthritis Rheum. 2003 May;48(5):1466; author reply 1466-7. 

Abstract
OBJECTIVE: Glomerulonephritis is a severe manifestation of systemic lupus erythematosus (SLE) that is usually treated with an extended course of intravenous (IV) cyclophosphamide (CYC). Given the side effects of this regimen, we evaluated the efficacy and the toxicity of a course of low-dose IV CYC prescribed as a remission-inducing treatment, followed by azathioprine (AZA) as a remission-maintaining treatment.

METHODS: In this multicenter, prospective clinical trial (the Euro-Lupus Nephritis Trial [ELNT]), we randomly assigned 90 SLE patients with proliferative glomerulonephritis to a high-dose IV CYC regimen (6 monthly pulses and 2 quarterly pulses; doses increased according to the white blood cell count nadir) or a low-dose IV CYC regimen (6 fortnightly pulses at a fixed dose of 500 mg), each of which was followed by AZA. Intent-to-treat analyses were performed.

RESULTS: Followup continued for a median of 41.3 months in the low-dose group and 41 months in the high-dose group. Sixteen percent of those in the low-dose group and 20% of those in the high-dose group experienced treatment failure (not statistically significant by Kaplan-Meier analysis). Levels of serum creatinine, albumin, C3, 24-hour urinary protein, and the disease activity scores significantly improved in both groups during the first year of followup. Renal remission was achieved in 71% of the low-dose group and 54% of the high-dose group (not statistically significant). Renal flares were noted in 27% of the low-dose group and 29% of the high-dose group. Although episodes of severe infection were more than twice as frequent in the high-dose group, the difference was not statistically significant.

CONCLUSION: The data from the ELNT indicate that in European SLE patients with proliferative lupus nephritis, a remission-inducing regimen of low-dose IV CYC (cumulative dose 3 gm) followed by AZA achieves clinical results comparable to those obtained with a high-dose regimen.

PMID: 12209517 [PubMed - indexed for MEDLINE
Ciprofloxacin enhances the stimulation of matrix metalloproteinase 3 expression by interleukin-1beta in human tendon-derived cells

To determine whether the fluoroquinolone antibiotic ciprofloxacin, which can cause tendon pain and rupture in a proportion of treated patients, affects the expression of matrix metalloproteinases (MMPs) in human tendon-derived cells in culture. Cell cultures were derived from 6 separate tendon explants, and were incubated in 6-well culture plates for 2 periods of 48 hours each, with ciprofloxacin (or DMSO in controls) and interleukin-1ß (IL-1ß), alone and in combination. Samples of supernatant medium from the second 48-hour incubation were assayed for MMPs 1, 2, and 3 by Western blotting. RNA was extracted from the cells and assayed for MMP messenger RNA (mRNA) by semiquantitative reverse transcription–polymerase chain reaction, with normalization for GAPDH mRNA. Unstimulated tendon cells expressed low or undetectable levels of MMP-1 and MMP-3, and substantial levels of MMP-2. IL-1ß induced a substantial output of both MMP-1 and MMP-3 into cell supernatants, reflecting increases (typically 100-fold) in MMP mRNA, but had only minor effects on MMP-2 expression. Ciprofloxacin had no detectable effect on MMP output in unstimulated cells. Preincubation with ciprofloxacin potentiated IL-1ß–stimulated MMP-3 output, reflecting a similar effect on MMP-3 mRNA expression. Ciprofloxacin also potentiated IL-1ß–stimulated MMP-1 mRNA expression, but did not potentiate the output of MMP-1, and had no significant effects on MMP-2 mRNA expression or output. Ciprofloxacin can selectively enhance MMP expression in tendon-derived cells. Such effects might compromise tendon microstructure and integrity
Somatostatin receptor imaging: The presence of somatostatin receptors in rheumatoid arthritis

Objective. To investigate the in vivo and in vitro expression of somatostatin receptors (SS-R) on synovial membranes of patients with rheumatoid arthritis (RA).\ud
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Methods. The joints of 14 consecutive patients with active RA, 4 patients with severe osteoarthritis (OA), and 30 control patients were studied. The somatostatin analog [111In-DTPA-D-Phe1]-octreotide was used for in vivo SS-R scintigraphy, and the somatostatin analog [125I-Tyr3]-octreotide for in vitro SS-R autoradiography.\ud
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Results. Seventy-six percent (220 of 290) of the painful joints and 76% (207 of 274) of the swollen joints of the patients with RA were visualized by SS-R scintigraphy. The degree of pain and swelling correlated well with positive scintigraphy findings in the joints (P < 0.0001). In 2 of the RA patients who underwent scintigraphy, as well as in 4 of 5 other patients, in vitro studies of the synovial membranes showed the presence of specific SS-R. In patients with OA, uptake of radioactivity in the affected joints was significantly lower than that in patients with RA. None of the joints of the control patients demonstrated uptake of radioactivity.\ud
\ud
Conclusion. SS-R are present in the synovial tissue of patients with active RA, as demonstrated by both in vivo and in vitro techniques. The potential value of SS-R scintigraphy in the clinical evaluation of patients with active RA is presently unknown
Prednisone treatment of elderly-onset rheumatoid arthritis: Disease activity and bone mass in comparison with chloroquine treatment

Objective. Prednisone is frequently used in the treatment of elderly-onset rheumatoid arthritis (RA), but the balance between efficacy and toxicity, including the effect on bone mass, has not been investigated in long-term studies. This prospective, randomized study was undertaken to compare disease activity and bone mass during long-term treatment with prednisone versus chloroquine in this patient population.\ud
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Methods. Patients with active RA diagnosed at age ≥ 60 were randomized to receive prednisone (15 mg/day for 1 month, with the dosage tapered as low as possible thereafter) (n = 28) or chloroquine (n = 28). Patients who did not show a response received other second-line drugs as an adjunct to prednisone or as a replacement for chloroquine. Bone mass was measured by dual-energy x-ray absorptiometry. The study duration was 2 years.\ud
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Results. During the 2 years, treatment with other second-line drugs was needed for 12 patients in the prednisone group (43%) and 8 in the chloroquine group (29%). Functional capacity and disease activity improved significantly in both groups and did not differ significantly between the groups, except for a greater improvement in the prednisone group at 1 month. Radiographic scores for joint destruction progressed similarly in both groups. There was a nonsignificant excess bone loss of 1.8% in the spine and 1.5% in the hip in the prednisone group, compared with the chloroquine group.\ud
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Conclusion. Neither treatment was entirely satisfactory since a significant number of patients needed an additional second-line drug over the 2-year period
Risk factors for septic arthritis in patients with joint disease: A prospective study

Objective. To quantify potential risk factors for septic arthritis, in order to identify a basis for prevention.  \ud
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Methods. The occurrence of potential risk factors for septic arthritis in patients with joint diseases attending a rheumatic disease clinic was prospectively monitored at 3-m onth intervals over a period of 3 years. Potential risk factors investigated were type of joint disease, comorbidity, medication, joint prosthesis, infections, and invasive procedures. The frequencies of risk factors in patients with and those without septic arthritis were compared using multiple logistic regression analysis.  \ud
\ud
Results. There were 37 patients with and 4,870 without septic arthritis. Risk factors for developing septic arthritis were age ≥80 years (odds ratio [OR] = 3.5, 95% confidence interval [95% CI] 1.4–8.6), diabetes mellitus (OR = 3.3, 95% CI 1.1–10.1), rheumatoid arthritis (OR = 4.0, 95% CI 1.9–8.3), hip and/or knee prosthesis (OR = 15, 95% CI 4.1–54.3), joint surgery (OR = 5.1, 95% CI 2.2–11.9), and skin infection (OR = 27.2, 95% CI 7.6–97.1)  \ud
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Conclusion. These findings indicate that preventive measures against septic arthritis in patients with joint diseases should mainly be directed at those with joint prostheses and/or skin infection
Investigation of the association of the CRTM and CRTL1 genes with radiographically evident osteoarthritis in subjects from the Rotterdam study

__Objective:__ To investigate whether radiographically evident osteoarthritis (ROA) in 55-65-year-old men and women is associated with specific alleles or genotypes of the cartilage matrix protein (CRTM) and cartilage link protein (CRTLl) genes.  \ud
__Methods:__ Cases were selected from a populationbased study on the presence of ROA of the knee or hip. Further radiographic analysis included scoring for spine and hand ROA. Controls, selected from the same population, were free of ROA in all joints.  \ud
__Results:__ The CRTM locus was significantly associated with hip ROA in men (odds ratio 0.50, 95% confidence interval 0.26-0.95). A significant association between ROA and the CRTLl gene was not observed.  \ud
__Conclusion:__ These results suggest that the CRTM locus may play a role in the sex- and joint site-specific pattern of ROA development