Breakdown of Ohm's law and nontrivial Berry phase in magnetic Weyl semimetal Co3Sn2S2.

The concept of realization of Weyl points close to the Fermi level in materials with broken time-reversal symmetry has significant theoretical and technological ramifications. Here, we review the investigation of magneto-transport measurements in single crystals of magnetic Weyl semimetal Co3Sn2S2. We see a turn-on like behaviour followed by saturation in resistivity under magnetic field in the low temperature region which is allocated to the topological surface states. A non-saturating magnetoresistance, linear at high fields, is observed at low temperatures where applied magnetic field is transverse to the current direction. The linear negative magnetoresistance at low magnetic fields (B < 0.1 T) provides evidence for time reversal symmetry breaking in Co3Sn2S2. Chiral anomaly in Weyl metallic state in Co3Sn2S2 is confirmed from the breakdown of Ohm's law in the electronic transport. Shubnikov de Haas (SdH) oscillation measurement has unveiled the multiple sub-bands on the Fermi surface that corresponds to a non-trivial Berry phase. The non-linear behaviour in Hall resistivity validates the existence of two type of charge carriers with equal electron and hole densities. Strong temperature dependence of carrier mobilities reflects the systematic violation of Kohler's rule in Co3Sn2S2. Our findings open avenues to study kagome-lattice based magnetic Weyl semimetals that unfurl the basic topological aspects leading to significant ramification for spintronics.

Validation and development of MTH1 inhibitors for treatment of cancer.

BACKGROUND: Previously, we showed cancer cells rely on the MTH1 protein to prevent incorporation of otherwise deadly oxidised nucleotides into DNA and we developed MTH1 inhibitors which selectively kill cancer cells. Recently, several new and potent inhibitors of MTH1 were demonstrated to be non-toxic to cancer cells, challenging the utility of MTH1 inhibition as a target for cancer treatment. MATERIAL AND METHODS: Human cancer cell lines were exposed in vitro to MTH1 inhibitors or depleted of MTH1 by siRNA or shRNA. 8-oxodG was measured by immunostaining and modified comet assay. Thermal Proteome profiling, proteomics, cellular thermal shift assays, kinase and CEREP panel were used for target engagement, mode of action and selectivity investigations of MTH1 inhibitors. Effect of MTH1 inhibition on tumour growth was explored in BRAF V600E-mutated malignant melanoma patient derived xenograft and human colon cancer SW480 and HCT116 xenograft models. RESULTS: Here, we demonstrate that recently described MTH1 inhibitors, which fail to kill cancer cells, also fail to introduce the toxic oxidized nucleotides into DNA. We also describe a new MTH1 inhibitor TH1579, (Karonudib), an analogue of TH588, which is a potent, selective MTH1 inhibitor with good oral availability and demonstrates excellent pharmacokinetic and anti-cancer properties in vivo. CONCLUSION: We demonstrate that in order to kill cancer cells MTH1 inhibitors must also introduce oxidized nucleotides into DNA. Furthermore, we describe TH1579 as a best-in-class MTH1 inhibitor, which we expect to be useful in order to further validate the MTH1 inhibitor concept.

Actions of vitamin D are mediated by the TLR4 pathway in inflammation-induced colon cancer.

Many chronic inflammatory diseases are associated with increased risk of developing cancer. In the colon, strong support for a link between chronic inflammation and cancer extends, in part, from population-based studies of persons with inflammatory bowel disease (IBD). Patients with IBD are at increased risk of developing colorectal cancer (CRC). The general consensus is that IBD results from the combined effects of genetics and environment factors known to affect the immune system. Vitamin D, an important regulator of the immune system, has been linked to IBD. Despite the strong potential reported for 1,25-dihydroxyvitamin D (1,25-OH)2D), its effects on calcium metabolism limits its application. Recently, less active vitamin D metabolites, cholecalciferol and 25-hydroxyvitamin D (25(OH)D), have gained considerable attention as promising agents against IBD-related colon cancer. Yet, their anti-proliferative properties and mechanism of action remain to be better defined. We present several signaling pathways commonly regulated by vitamin D compounds and highlight their regulation on TLR4. The efficacy of 25(OH)D and 1alpha-hydroxyviatmin D5 are evaluated using the azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced IBD-related colon carcinogenesis model. In summary, vitamin D supplementation may provide a cost-effective approach to reduce IBD related colon cancer.

Remediation of contaminated soils using supercritical fluid extraction: a review (1994-2004).

Considerable effort is being made to remediate soils contaminated with petroleum hydrocarbons, polyaromatic hydrocarbons, polychlorinated biphenyls, dioxins, heavy metals and other organic and inorganic compounds that have resulted from industrial activities, accidental spills and improper waste disposal practices. Current remediation technologies may be limited when treating certain types of contaminated soils and therefore new, efficient and cost effective technologies are being investigated. Supercritical fluid extraction is a potential remediation technology for contaminated soils. It is a simple, fast and selective solvent extraction process that uses a supercritical fluid as the solvent. A commonly used fluid is carbon dioxide at pressures and temperatures greater than 7.4 MPa and 31 degrees C, respectively. In supercritical fluid extraction, the extracted contaminants first dissolve into the supercritical solvent and then these contaminants are separated from the supercritical solvent via a simple change in pressure and temperature conditions or by using a separation process. This paper provides a review of supercritical fluid extraction and its application to the remediation of contaminated soils. This review focuses on the removal of organic contaminants (such as petroleum hydrocarbons, polyaromatic hydrocarbons, polychlorinated biphenyls and others) and inorganic contaminants (such as heavy metals and radioactive elements) from soils. Recent data (1994-2004) on the supercritical fluid extraction of spiked soils and field-contaminated soils were collected. The success of supercritical fluid extraction as a method for removing these contaminants from soils is highlighted and some of the future research needed to develop it as a commercial-scale economic remediation technology are discussed.

Comparative study of oral and topical ketoconazole therapy in pityriasis versicolor.

INTRODUCTION: Both topical and systemic ketoconazole are reported to be effective against pityriasis versicolor. MATERIAL AND METHODS: Forty patients suffering from pityriasis versicolor were treated either with oral ketoconazole 200 mg per day or 2% ketoconazole cream topically once daily for 2 weeks. RESULTS: On global assessment, after 2 weeks of start of therapy, 18 (90%) out of 20 patients treated with oral ketoconazole were cured while 2 patients had considerable residual disease. In the ketoconazole cream group, 16 (80%) out of 20 patients were cured and 4 patients had considerable residual disease. CONCLUSION: No significant difference was observed in the response rates in the two groups. Relapse occurred in two patients of the systemic ketoconazole group and six patients of the topical ketoconazole group during the follow-up period of three months.