Sesquiterpene Lactones Isolated from Elephantopus scaber L. Inhibits Human Lymphocyte Proliferation and the Growth of Tumour Cell Lines and Induces Apoptosis In Vitro

This study was designed to isolate the compounds responsible for the cytotoxic properties of South Indian Elephantopus scaber L. and further investigate their effects on quiescent and proliferating cells. Bioassay-guided isolation of the whole plant of chloroform extract of South Indian Elephantopus scaber afforded the known sesquiterpene lactone, deoxyelephantopin, and isodeoxyelephantopin whose structures were determined by spectroscopic methods. These compounds caused a dose dependent reduction in the viability of L-929 tumour cells in 72 h culture (IC50 value of 2.7 μg/mL and 3.3 μg/mL) by the cell viability assay. Both the compounds act selectively on quiescent and PHA-stimulated proliferating human lymphocytes and inhibited tritiated thymidine incorporation into cellular DNA of DLA tumour cells. The compound deoxyelephantopin at a concentration of 3 μg/mL caused maximum apoptotic cells. It also exhibited significant in vivo antitumour efficacy against DLA tumour cells. The results, therefore, indicate that the antiproliferative property of deoxyelephantopin and isodeoxyelephantopin could be used in regimens for treating tumors with extensive proliferative potencies

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Oxidative addition of dimethyl malonate to styrenes mediated by cerium(IV) ammonium nitrate: some novel observations

The oxidative addition of dimethyl malonate to ring substituted styrenes leads to the formation of substituted dimethyl (2-oxo-2-phenylethyl) malonate and methyl 2-oxo-5-phenyltetrahydrofuran-3-carboxylate along with small amounts of substituted dimethyl [2-(nitrooxy)-2-phenylethyl] malonate and dimethyl 2-methoxy-2-phenylethyl) malonate. A tentative mechanism which supports the formation of these products is also presented

An exceedingly mild and efficient CAN mediated method for the deprotection of acetals

1234-1236<span style="font-size:12.0pt;font-family: " times="" new="" roman";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-in;mso-fareast-language:en-in;mso-bidi-language:ar-sa"="" lang="EN-IN">An efficient and mild procedure for the deprotection of acetals using CAN(Cerium(IV) Ammonium Nitrate) has been described.</span

Oxidative addition of 1,3-dicarbonyl compounds to dienes mediated by CAN:Formation of dihydrofuran derivatives

352-356Oxidative addition of 1,3-dicarbonyl compounds to dienes constitutes a facile method for the synthesis of dihydrofuran derivatives

Cerium(IV) ammonium nitrate mediated thiocyanation of dienes: some interesting observations

Various 1,3-dienes when treated with a solution of cerium(IV) ammonium nitrate and ammonium thiocyanate in acetonitrile afforded the isothiocyanatothiocyanates via a [3,3] sigmatropic rearrangement. Electron rich dienes afforded the γ-thiocyanato-α,β-unsaturated carbonyl compounds under similar experimental conditions

Large Diameter Triaxial Tests on Geosynthetic-Reinforced Granular Subbases

The estimation of strength and stiffness of reinforced aggregates is very important for the design and construction of reinforced unpaved/paved road sections. This paper presents the experimental results from static and cyclic triaxial tests carried out on granular subbase samples reinforced with multiple layers of geogrid reinforcement. Aggregates of different size ranges were mixed in calculated proportions by weight to obtain the gradation specified for rural roads. Triaxial samples of 300 mm diameter and 600 mm height were prepared using this sampled aggregate. The strength and stiffness characteristics of this aggregate reinforced with geogrids at different elevations were determined from static and cyclic triaxial tests. Triaxial tests were also carried out on geocell encased aggregates, and the results are compared. From the experimental results it is observed that reinforced systems carried more stresses than unreinforced systems at the same strain level. The beneficial effect increased with increase in the quantity of reinforcement, whereas for geocell reinforcement, the advantage was evident only at higher strains. (C) 2014 American Society of Civil Engineers

Taming of large diameter triaxial setup

Triaxial tests are essential to estimate the shear strength properties of the soil or rock. Normally triaxial tests are carried out on samples of 38 mm diameter and 76 mm height. Granular materials, predominantly used in base/sub-base construction of pavements or in railways have size range of 60-75 mm. Determination of shear strength parameters of those materials can be made possible only through triaxial tests on large diameter samples. This paper describes a large diameter cyclic triaxial testing facility set up in the Geotechnical Engineering lab of Indian Institute of Science. This setup consists of 100 kN capacity dynamic loading frame, which facilitates testing of samples of up to 300 mm diameter and 600 mm height. The loading ram can be actuated up to a maximum frequency of 10 Hz, with maximum amplitude of 100 mm. The setup is capable of carrying out static as well as dynamic triaxial tests under isotropic, anisotropic conditions with a maximum confining pressure of 1 MPa. Working with this setup is a difficult task because of the size of the sample. In this paper, a detailed discussion on the various problems encountered during the initial testing using the equipment, the ideas and solutions adopted to solve them are presented. Pilot experiments on granular sub-base material of 53 mm down size are also presented