Estimation of Elasticities of Substitution for CES and VES Production Functions using Firm-level Data for Food-processing Industries in Pakistan

This study, based on the time-series data covering the period from 1956 to 1986, estimates production function in the agricultural sector of Pakistan. The strategy for agricultural development in the country has been based on greater utilization of "high pay-off' low-cost technology. The government advanced loans through financial institutions to make it possible for the farmers to acquire this technology. Despite the infusion of seed-fertilizer technology, per acre yield of major crops like wheat, rice, cereal and sugar-cane in Pakistan is lower than in most LDCs in the region. Therefore, it is concluded that the use of present technology has reached a plateau and it is time to look for additional inputs for improvement in productivity

Identifying the oncogenic potential of gene fusions exploiting miRNAs

It is estimated that oncogenic gene fusions cause about 20% of human cancer morbidity. Identifying potentially oncogenic gene fusions may improve affected patients’ diagnosis and treatment. Previous approaches to this issue included exploiting specific gene-related information, such as gene function and regulation. Here we propose a model that profits from the previous findings and includes the microRNAs in the oncogenic assessment. We present ChimerDriver, a tool to classify gene fusions as oncogenic or not oncogenic. ChimerDriver is based on a specifically designed neural network and trained on genetic and post-transcriptional information to obtain a reliable classification. The designed neural network integrates information related to transcription factors, gene ontologies, microRNAs and other detailed information related to the functions of the genes involved in the fusion and the gene fusion structure. As a result, the performances on the test set reached 0.83 f1-score and 96% recall. The comparison with state-of-the-art tools returned comparable or higher results. Moreover, ChimerDriver performed well in a real-world case where 21 out of 24 validated gene fusion samples were detected by the gene fusion detection tool Starfusion. ChimerDriver integrates transcriptional and post-transcriptional information in an ad-hoc designed neural network to effectively discriminate oncogenic gene fusions from passenger ones. ChimerDriver source code is freely available at https://github.com/martalovino/ChimerDriver

Effect of Mn doping on the growth and properties of enstatite single crystals

Millimetric Mn-doped enstatite (MgSiO3) crystals have been grown by slow cooling in MoO3, V2O5, and Li2CO3 flux. Six starting mixture with different amount of manganese were slowly cooled from 1350 °C, 1050 °C and 950 °C down to 750 °C, 650 °C and 600 °C respectively. The enstatite crystals were characterized by X-ray powder diffraction (XRPD) and scanning electron microscopy with energy-dispersive spectrometry (SEM/EDS). Mn-doped enstatite crystals were reddish in color, euhedral and elongate parallel to c-axis. The largest enstatite crystal obtained is 8.5 mm in length. The effects of growth parameters on yield and size of crystals were studied. Variations observed in crystal size were attributed to the amount of Mn doping. Further characterizations by μ-Raman spectroscopy (μ-R) and cathodoluminescence (CL) allowed to study the effect of Mn doping on some chemical/physical characteristics of the enstatite and to assess its potential in advanced technological applications

Pathogenetic and diagnostic significance of microRNA deregulation in peripheral T-cell lymphoma not otherwise specified

Peripheral T-cell lymphomas not otherwise specified (PTCLs/NOS) are rare and aggressive tumours whose molecular pathogenesis and diagnosis are still challenging. The microRNA (miRNA) profile of 23 PTCLs/NOS was generated and compared with that of normal T-lymphocytes (CD4+, CD8+, naive, activated). The differentially expressed miRNA signature was compared with the gene expression profile (GEP) of the same neoplasms. The obtained gene patterns were tested in an independent cohort of PTCLs/NOS. The miRNA profile of PTCLs/NOS then was compared with that of 10 angioimmunoblastic T-cell lymphomas (AITLs), 6 anaplastic large-cell lymphomas (ALCLs)/ALK+ and 6 ALCLs/ALK - . Differentially expressed miRNAs were validated in an independent set of 20 PTCLs/NOS, 20 AITLs, 19 ALCLs/ALK - and 15 ALCLs/ALK+. Two hundred and thirty-six miRNAs were found to differentiate PTCLs/NOS from activated T-lymphocytes. To assess which miRNAs impacted on GEP, a multistep analysis was performed, which identified all miRNAs inversely correlated to different potential target genes. One of the most discriminant miRNAs was selected and its expression was found to affect the global GEP of the tumours. Moreover, two sets of miRNAs were identified distinguishing PTCL/NOS from AITL and ALCL/ALK - , respectively. The diagnostic accuracy of this tool was very high (83.54%) and its prognostic value validated

Large community-acquired Legionnaires’ disease outbreak caused by Legionella pneumophila serogroup 1, Italy, July to August 2018

In July 2018, a large outbreak of Legionnaires\u2019 disease (LD) caused by Legionella pneumophila serogroup 1 (Lp1) occurred in Bresso, Italy. Fifty-two cases were diagnosed, including five deaths. We performed an epidemiological investigation and prepared a map of the places cases visited during the incubation period. All sites identified as potential sources were investigated and sampled. Association between heavy rainfall and LD cases was evaluated in a case-crossover study. We also performed a case\u2013control study and an aerosol dispersion investigation model. Lp1 was isolated from 22 of 598 analysed water samples; four clinical isolates were typed using monoclonal antibodies and sequence-based typing. Four Lp1 human strains were ST23, of which two were Philadelphia and two were France-Allentown subgroup. Lp1 ST23 France-Allentown was isolated only from a public fountain. In the case-crossover study, extreme precipitation 5\u20136 days before symptom onset was associated with increased LD risk. The aerosol dispersion model showed that the fountain matched the case distribution best. The case\u2013control study demonstrated a significant eightfold increase in risk for cases residing near the public fountain. The three studies and the matching of clinical and environmental Lp1 strains identified the fountain as the source responsible for the epidemic

Marked oestrous cycle-dependent regulation of rat arterial KV7.4 channels driven by GPER1

Background and Purpose: Kcnq-encoded KV7 channels (termed KV7.1–5) regulate vascular smooth muscle cell (VSMC) contractility at rest and as targets of receptor-mediated responses. However, the current data are mostly derived from males. Considering the known effects of sex, the oestrous cycle and sex hormones on vascular reactivity, here we have characterised the molecular and functional properties of KV7 channels from renal and mesenteric arteries from female Wistar rats separated into di-oestrus and met-oestrus (F-D/M) and pro-oestrus and oestrus (F-P/E). Experimental Approach: RT-qPCR, immunocytochemistry, proximity ligation assay and wire myography were performed in renal and mesenteric arteries. Circulating sex hormone concentrations were determined by liquid chromatography–tandem mass spectrometry. Whole-cell electrophysiology was undertaken on cells expressing KV7.4 channels in association with G-protein-coupled oestrogen receptor 1 (GPER1). Key Results: The KV7.2–5 activators S-1 and ML213 and the pan-KV7 inhibitor linopirdine were more effective in arteries from F-D/M compared with F-P/E animals. In VSMCs isolated from F-P/E rats, exploratory evidence indicates reduced membrane abundance of KV7.4 but not KV7.1, KV7.5 and Kcne4 when compared with cells from F-D/M. Plasma oestradiol was higher in F-P/E compared with F-D/M, and progesterone showed the converse pattern. Oestradiol/GPER1 agonist G-1 diminished KV7.4 encoded currents and ML213 relaxations and reduced the membrane abundance of KV7.4 and interaction between KV7.4 and heat shock protein 90 (HSP90), in arteries from F-D/M but not F-P/E. Conclusions and Implications: GPER1 signalling decreased KV7.4 membrane abundance in conjunction with diminished interaction with HSP90, giving rise to a ‘pro-contractile state’

Nonpsychotropic plant cannabinoids, cannabidivarin (CBDV) and cannabidiol (CBD), activate and desensitize transient receptor potential vanilloid 1 (TRPV1) channels in vitro: potential for the treatment of neuronal hyperexcitability

Epilepsy is the most common neurological disorder, with over 50 million people worldwide affected. Recent evidence suggests that the transient receptor potential cation channel subfamily V member 1 (TRPV1) may contribute to the onset and progression of some forms of epilepsy. Since the two nonpsychotropic cannabinoids cannabidivarin (CBDV) and cannabidiol (CBD) exert anticonvulsant activity in vivo and produce TRPV1-mediated intracellular calcium elevation in vitro, we evaluated the effects of these two compounds on TRPV1 channel activation and desensitization and in an in vitro model of epileptiform activity. Patch clamp analysis in transfected HEK293 cells demonstrated that CBD and CBDV dose-dependently activate and rapidly desensitize TRPV1, as well as TRP channels of subfamily V type 2 (TRPV2) and subfamily A type 1 (TRPA1). TRPV1 and TRPV2 transcripts were shown to be expressed in rat hippocampal tissue. When tested on epileptiform neuronal spike activity in hippocampal brain slices exposed to a Mg2+-free solution using multielectrode arrays (MEAs), CBDV reduced both epileptiform burst amplitude and duration. The prototypical TRPV1 agonist, capsaicin, produced similar, although not identical effects. Capsaicin, but not CBDV, effects on burst amplitude were reversed by IRTX, a selective TRPV1 antagonist. These data suggest that CBDV antiepileptiform effects in the Mg2+-free model are not uniquely mediated via activation of TRPV1. However, TRPV1 was strongly phosphorylated (and hence likely sensitized) in Mg2+-free solution-treated hippocampal tissue, and both capsaicin and CBDV caused TRPV1 dephosphorylation, consistent with TRPV1 desensitization. We propose that CBDV effects on TRP channels should be studied further in different in vitro and in vivo models of epilepsy