Imidazole aldoximes effective in assisting butyrylcholinesterase catalysis of organophosphate detoxification.

Intoxication by organophosphate (OP) nerve agents and pesticides should be addressed by efficient, quickly deployable countermeasures such as antidotes reactivating acetylcholinesterase or scavenging the parent OP. We present here synthesis and initial in vitro characterization of 14 imidazole aldoximes and their structural refinement into three efficient reactivators of human butyrylcholinesterase (hBChE) inhibited covalently by nerve agent OPs, sarin, cyclosarin, VX, and the OP pesticide metabolite, paraoxon. Rapid reactivation of OP-hBChE conjugates by uncharged and nonprotonated tertiary imidazole aldoximes allows the design of a new OP countermeasure by conversion of hBChE from a stoichiometric to catalytic OP bioscavenger with the prospect of oral bioavailability and central nervous system penetration. The enhanced in vitro reactivation efficacy determined for tertiary imidazole aldoximes compared to that of their quaternary N-methyl imidazolium analogues is attributed to ion pairing of the cationic imidazolium with Asp 70, altering a reactive alignment of the aldoxime with the phosphorus in the OP-hBChE conjugate

Forecasting of arecanut market price in north eastern India: ARIMA modelling approach

The paper deals with forecasting of minimum, maximum and average arecanut (Areca catechu L.) prices in the major arecanut markets of the Assam as well as Meghalaya based on the monthly price data. Monthly minimum, maximum, and average market price data of arecanut (in Rs./quintal) for the period May-2003 to March-2012 (for Assam) and February-2003 to March-2012 (for Meghalaya) were used. Box-Jenkins autoregressive integrated moving average (ARIMA) methodology was adopted for developing the models. An interrupted time-series model was also applied to resolve the problem of intervention point (October-2011) for Meghalaya price data. The proposed models were ARIMA (1, 0, 1), ARIMA (1, 1, 1), ARIMA (0, 1, 1) (for Assam market price data series) and, log ARIMA (0, 1, 1), log ARIMA (1, 0, 1) with linear trend and a man-made intervention (Oct-2011) and log ARIMA (0, 1, 1) with linear trend and a manmade intervention (Oct-2011) (for Meghalaya market price data series) for minimum, maximum, and average monthly price series, respectively

Metagenomic characterization of swine slurry in a North American swine farm operation

Abstract Modern day large-scale, high-density farming environments are inherently susceptible to viral outbreaks, inadvertently creating conditions that favor increased pathogen transmission and potential zoonotic spread. Metagenomic sequencing has proven to be a useful tool for characterizing the microbial burden in both people, livestock, and environmental samples. International efforts have been successful at characterizing pathogens in commercial farming environments, especially swine farms, however it is unclear whether the full extent of microbial agents have been adequately captured or is representative of farms elsewhere. To augment international efforts we performed metagenomic next-generation sequencing on nine swine slurry and three environmental samples from a United States of America (U.S.A.) farm operation, characterized the microbial composition of slurry, and identified novel viruses. We assembled a remarkable total of 1792 viral genomes, of which 554 were novel/divergent. We assembled 1637 Picobirnavirus genome segments, of which 538 are novel. In addition, we discovered 10 new viruses belonging to a novel taxon: porcine Statoviruses; which have only been previously reported in human, macaques, mouse, and cows. We assembled 3 divergent Posaviruses and 3 swine Picornaviruses. In addition to viruses described, we found other eukaryotic genera such as Entamoeba and Blastocystis, and bacterial genera such as Listeria, Treponema, Peptoclostridium and Bordetella in the slurry. Of these, two species Entamoeba histolytica and Listeria monocytogenes known to cause human disease were detected. Further, antimicrobial resistance genes such as tetracycline and MLS (macrolide, lincosamide, streptogramin) were also identified. Metagenomic surveillance in swine fecal slurry has great potential for novel and antimicrobial resistant pathogen detection

On the generalised Ritt problem as a computational problem

The Ritt problem asks if there is an algorithm that tells whether one prime differential ideal is contained in another one if both are given by their characteristic sets. We give several equivalent formulations of this problem. In particular, we show that it is equivalent to testing if a differential polynomial is a zero divisor modulo a radical differential ideal. The technique used in the proof of equivalence yields algorithms for computing a canonical decomposition of a radical differential ideal into prime components and a canonical generating set of a radical differential ideal. Both proposed representations of a radical differential ideal are independent of the given set of generators and can be made independent of the ranking.Comment: 9 page

Global-local dynamics in the transformation of the Jakarta Metropolitan Area into a global city-region

This paper investigates the way in which factors at the global and local level interact in the emergence and development of “global city-regions”, which are deemed to be the contemporary growth machines of the global economy. To this end, this paper takes the Jakarta metropolitan area (JMA) as a case to investigate its evolution in the context of the intertwined dynamics of foreign direct investment (FDI) inflow and state intervention over the past three decades. The findings indicate that from a macro-level perspective the JMA has maintained its position as the country’s hotspot for manufacturing investment embedded in East Asian production networks. In addition, we find that the national state has continuously privileged the JMA as the main grounds for national economic development in spite of the country’s shifting political system. We reveal how the nexus between “global” forces (incoming FDI) and “local” conditions (the state’s strategic intervention) has led to the development and restructuring of the JMA as a global city-region

Systematic reconstruction of RNA functional motifs with high-throughput microfluidics

We present RNA-MITOMI, a microfluidic platform for integrated synthesis and functional assays across thousands of RNAs. The interaction of a comprehensive library of RNA mutants with stem loop binding protein precisely defined the RNA structural and sequence features that govern affinity. The functional motif reconstructed in a single experiment on our platform uncovers novel binding specificities and enriches interpretation of phylogenetic data

Symptom Monitoring With Patient-Reported Outcomes During Routine Cancer Treatment: A Randomized Controlled Trial

There is growing interest to enhance symptom monitoring during routine cancer care using patient-reported outcomes, but evidence of impact on clinical outcomes is limited

Feasibility of Long-Term Patient Self-Reporting of Toxicities From Home via the Internet During Routine Chemotherapy

Patient-reported outcomes are increasingly used in routine outpatient cancer care to guide clinical decisions and enhance communication. Prior evidence suggests good patient compliance with reporting at scheduled clinic visits, but there is limited evidence about compliance with long-term longitudinal reporting between visits

Total ozone variability and trends over the South Pole during the wintertime

The Antarctic polar vortex creates unique chemical and dynamical conditions when the stratospheric air over Antarctica is isolated from the rest of the stratosphere. As a result, stratospheric ozone within the vortex remains largely unchanged for a 5-month period from April until late August when the sunrise and extremely cold temperatures create favorable conditions for rapid ozone loss. Such prolonged stable conditions within the vortex make it possible to estimate the total ozone levels there from sparse wintertime ozone observations at the South Pole. The available records of focused Moon (FM) observations by Dobson and Brewer spectrophotometers at the Amundsen–Scott South Pole Station (for the periods 1964–2022 and 2008–2022, respectively) as well as integrated ozonesonde profiles (1986–2022) and MERRA-2 reanalysis data (1980–2022) were used to estimate the total ozone variability and long-term changes over the South Pole. Comparisons with MERRA-2 reanalysis data for the period 1980–2022 demonstrated that the uncertainties of Dobson and Brewer daily mean FM values are about 2.5 %–4 %. Wintertime (April–August) MERRA-2 data have a bias with Dobson data of −8.5 % in 1980–2004 and 1.5 % in 2005–2022. The mean difference between wintertime Dobson and Brewer data in 2008–2022 was about 1.6 %; however, this difference can be largely explained by various systematic errors in Brewer data. The wintertime ozone values over the South Pole during the last 20 years were about 12 % below the pre-1980s level; i.e., the decline there was nearly twice as large as that over southern midlatitudes. It is probably the largest long-term ozone decline aside from the springtime Antarctic ozone depletion. While wintertime ozone decline over the pole has hardly any impact on the environment, it can be used as an indicator to diagnose the state of the ozone layer, particularly because it requires data from only one station. Dobson and ozonesonde data after 2001 show a small positive, but not statistically significant, trend in ozone values of about 1.5 % per decade that is in line with the trend expected from the concentration of the ozone-depleting substances in the stratosphere.</p