Heptaphyrins: expanded porphyrins with seven heterocyclic rings

Expanded porphyrins containing seven pyrrole/heterocyclic rings linked in a cyclic fashion are termed heptaphyrins. The number of π-electrons in heptaphyrins depends on the number ofmeso carbon bridges used to link the heterocyclic rings, accordingly heptaphyrins with 28π-electrons and 30π-electrons are reported to date. Both condensation reactions of the appropriate precursors and acid-catalysed oxidative coupling reactions have been utilized to synthesise the heptaphyrins. The 30π heptaphyrins exhibit rich structural diversity where some of the heterocyclic rings in the macrocycle undergo a 180° ring flipping. An overview of the synthetic methods employed for the synthesis of heptaphyrins, their spectroscopic properties, structural behaviour and aromatic properties are highlighted in this paper

Core modified oxybenziporphyrins: new aromatic ligands for metalcarbon bond activation

Successful syntheses of two new aromatic core modified oxybenziporphyrins by a simple 3 + 1 methodology and the first aromatic core modified oxybenziporphyrin palladium complex are reported

Tumor-vascular interactions promote STING-driven inflammation in the tumor microenvironment

The recruitment of T cells following intratumoral administration of Stimulation of Interferon Genes (STING) agonists in the tumor microenvironment (TME) is a critical event in the STING-driven antitumor immune response, a pathway with great relevance in the context of cancer immunotherapy. We have previously demonstrated that LKB1 mutation is associated with suppression of tumor cell STING levels and reduced production of T-cell chemoattractants such as CXCL10 in KRAS-driven non-small cell lung cancer (NSCLC). Consistent with this, immunohistochemical staining of patient samples showed poor infiltration of CD3, CD4, and CD8 T cells into LKB1 negative versus LKB1 intact cancer epithelium, and instead, retention of T-cells in stroma. To examine how LKB1 alters immune cell recruitment in a STING-dependent manner, we used a 3-D microfluidic co-culture system to study interactions between vasculature and tumor spheroids derived from a KRAS/LKB1 mutated (KL) cell line with LKB1 reconstitution +/- STING deletion. To form the vasculature, we co-cultured tumor spheroids with fibroblasts and endothelial cells for 7 days, and identified changes in morphology, cytokine production, and gene expression that occur in co-culture. We first observed that co-culture induced synergistic production of multiple immune cell chemo-attractants such as CXCL10, CCL2, CCL5, and G-CSF. Interestingly, this more physiologic ex vivo tumor model of LKB1 reconstitution revealed particularly strong cooperative production of STING-dependent cytokines such as CXCL10 in the vasculature. Moreover, STING depletion in LKB1 reconstituted tumor cells did not significantly attenuate production of CXCL10 and other cytokines in co-culture, suggesting that tumor/vessel interaction may promote STING activation in the vasculature regardless of cancer cell-intrinsic STING function. Furthermore, although there was no appreciable response after treatment of KL cancer cells with cGAMP based STING agonists, treatment of isolated 3-D vascular networks with cGAMP enhanced vascular permeability and increased production of CXCL10 and CCL5, possibly contributing to defective chemokine gradients that retain T cells near the vasculature. Thus, developing these more complex models that incorporate the vasculature may elucidate important aspects of STING biology and may ultimately aid further development of effective immunotherapies targeting this signaling axi

Protein complex directs hemoglobin-to-hemozoin formation in Plasmodium falciparum

Malaria parasites use hemoglobin (Hb) as a major nutrient source in the intraerythrocytic stage, during which heme is converted to hemozoin (Hz). The formation of Hz is essential for parasite survival, but to date, the underlying mechanisms of Hb degradation and Hz formation are poorly understood. We report the presence of a ∼200-kDa protein complex in the food vacuole that is required for Hb degradation and Hz formation. This complex contains several parasite proteins, including falcipain 2/2', plasmepsin II, plasmepsin IV, histo aspartic protease, and heme detoxification protein. The association of these proteins is evident from coimmunoprecipitation followed by mass spectrometry, coelution from a gel filtration column, cosedimentation on a glycerol gradient, and in vitro protein interaction analyses. To functionally characterize this complex, we developed an in vitro assay using two of the proteins present in the complex. Our results show that falcipain 2 and heme detoxification protein associate with each other to efficiently convert Hb to Hz. We also used this in vitro assay to elucidate the modes of action of chloroquine and artemisinin. Our results reveal that both chloroquine and artemisinin act during the heme polymerization step, and chloroquine also acts at the Hb degradation step. These results may have important implications in the development of previously undefined antimalarials

Building inclusive health innovation systems: lessons from India

This article presents an overview of the changes that are taking place within the public and private health innovation systems in India including delivery of medical care, pharmaceutical products, medical devices, and Indian traditional medicine. The nature of the flaws that exist in the health innovation system is pinpointed. The response by the government, the health, technology and medical institutions, and the evolving industry is addressed on a national level. The article also discusses how the alignment of policies and institutions was developed within the scope of national health innovation systems, and how the government and the industry are dealing with the challenges to integrate health system, industry, and social policy development processes

STANDARDIZATION OF A SIDDHA FORMULATION AMUKKARA CURANAM BY HPTLC

Amukkara curanam, a Siddha formulation, currently used in all types of gastric disorders, rheumatic pain, insomnia and sexual insufficiency, was investigated for the estimation of the marker compounds, withaferine A and piperine contents in a prepared standard formulation and a commercial formulation by using HPTLC method of analysis. The two formulations were subjected to methanol, ethyl acetate and chloroform extractions by using Soxhhlet apparatus The chromatogram was developed using chloroform: methanol (8.5:1.5 v/v) and toluene: ethyl acetate (7:3 v/v) as mobile phases for the estimation of withferine A and piperine respectively. The detection and quantification were performed at a wavelength of 220 nm for withaferine A and 254 nm for piperine. The linear regression analysis of calibration plots of withferine A and piperine exhibited linear relationship in the range of 5 – 15 µg and 50 – 150 ng respectively, while the % recovery was found to be 94.52% w/w of withaferine A and 98.73%w/w of piperine, thus proving the accuracy and precision of the analysis. Methanol and ethyl acetate were found to be the suitable solvents for the extraction of withaferin A and piperine respectively. The withaferine A content in standard formulation was found to be much higher in all the three extracts than that of the commercial sample. However, the piperine content in all the three extracts of standard formulation was slightly lower than the respective extracts of commercial formulation. The proposed HPTLC method was found to be rapid, simple and accurate for quantitative estimation of withferine A and piperine in different formulation extracts

Detection of short-period coronal oscillations during the total solar eclipse of 24 october, 1995

An experiment to search for short-period oscillations in the solar corona was conducted during the total solar eclipse of 1995 October 24 at Kalpi, India. The intensity in the continuum, centred around 5500 Å and with a passband having a half-width of 240 Å, was recorded at a counting rate of 20 Hz using a thermoelectric-liquid cooled photomultiplier. The power-spectrum analysis of the data reveals that most of the power is contained in 6 frequencies below 0.2 Hz. A least-square analysis gives the periods of the 6 frequency components to be 56.5, 19.5, 13.5, 8.0, 6.1, and 5.3 s. These oscillations are found to be sinusoidal, and their amplitudes are found to lie in the range 0.2-1.3% of the coronal brightness. Assuming these oscillations to be fast magnetosonic modes, the calculations indicate the availability of enough flux for the heating of the active regions in the solar corona

Modelling Clock Synchronization in the Chess gMAC WSN Protocol

We present a detailled timed automata model of the clock synchronization algorithm that is currently being used in a wireless sensor network (WSN) that has been developed by the Dutch company Chess. Using the Uppaal model checker, we establish that in certain cases a static, fully synchronized network may eventually become unsynchronized if the current algorithm is used, even in a setting with infinitesimal clock drifts

Structure and vibrational properties of carbon tubules

The structure of multilayered carbon tubules has been investigated by electron microscopy and X-ray diffraction. The structure of tubules is characterized by disorder in the stacking of cylindrical graphene sheets. Raman scattering measurements have been carried out in tubules and compared with graphite. The observed features in the Raman spectra in tubules can be understood in terms of the influence of disorder. The additional Raman modes predicted for single layer carbon tubules have not been observed