Formulation Development and Evaluation of Aqueous Injection of Poorly Soluble Drug Made by Novel Application of Mixed Solvency Concept

It is commonly recognized in the pharmaceutical industry that on average more than 40% of newly discovered drug candidates are poorly water-soluble. The objective of present research is to explore the application of mixed solvency technique in the injection formulation of poorly soluble drugs and to reduce concentration of individual solubilizers (used for solubility enhancement) to minimize the toxic effects of solubilizers. In the present work poorly soluble drugs Ofloxacin are selected as model drugs. Ofloxacin is an antibiotic drug tried to formulate the aqueous injection by the use of various physiologically compatible solubilizing agent like Lignocaine Hydrochloride, Niacinamide, Sodium benzoate, Sodium citrate, PEG 400, PEG 4000, PVP 40000, Ethanol, and Propylene Glycol. For expected synergistic enhancement effect on solubility of these poorly soluble drugs various blends of solubilizers shall be tried to decrease the amounts of Solubilizer employed for a desired solubility enhancement ratio. The study further opens the chances of preparing dry powders for injection of drug which are not stable in aqueous solution, ready to use injection. Key word- Mixed solvency solubilization, Ofloxacin, solubility enhancement, synergistic enhancement effect

LHX2 Interacts with the NuRD Complex and Regulates Cortical Neuron Subtype Determinants Fezf2 and Sox11

In the developing cerebral cortex, sequential transcriptional programs take neuroepithelial cells from proliferating progenitors to differentiated neurons with unique molecular identities. The regulatory changes that occur in the chromatin of the progenitors are not well understood. During deep layer neurogenesis, we show that transcription factor LHX2 binds to distal regulatory elements of Fezf2 and Sox11, critical determinants of neuron subtype identity in the mouse neocortex. We demonstrate that LHX2 binds to the nucleosome remodeling and histone deacetylase histone remodeling complex subunits LSD1, HDAC2, and RBBP4, which are proximal regulators of the epigenetic state of chromatin. When LHX2 is absent, active histone marks at the Fezf2 and Sox11 loci are increased. Loss of LHX2 produces an increase, and overexpression of LHX2 causes a decrease, in layer 5 Fezf2 and CTIP2-expressing neurons. Our results provide mechanistic insight into how LHX2 acts as a necessary and sufficient regulator of genes that control cortical neuronal subtype identity

Co-infection of wilt-resistant chickpeas by Fusarium oxysporum f. sp. ciceri and Meloidogyne javanica

Fusarium oxysporum f.sp. ciceri and Meloidogynejavanica are important pathogens of chickpea. Interrelationships between F. oxysporum f.sp. ciceri and M. javanica were investigated on 53 Fusarium wilt-resistant chickpea genotypes in pot experiments. All of the genotypes were susceptible to M. javanica. Fusarium wilt resistance in one genotype (ICC 12275) was ineffective in the presence of M. javanica, and all the plants completely wilted. Resistance in four genotypes (ICCs 11319, 11322, 12254, 12272) was reduced in the presence of the nematode. Vascular discoloration above the collar region of the plants, an indication of susceptibility to the fungus, was observed. Wilt resistance in 48 genotypes was not modified by M. javanica. The effects of interactions between the pathogens on shoot and root weights, gall index, and galled area of root were significant only on 10-28% of the genotypes. Presence of the fungus reduced the adverse effects of nematodes on growth of 15% of the genotypes. Appraisal of wilt-resistant chickpea genotypes for their reactions to combinations of the two pathogens would help to identify and develop chickpea cultivars with wilt resistance stable in presence of M. javanica

Formulation Development and Evaluation of Aqueous Injection of Poorly Soluble Drug Made by Novel Application of Mixed Solvency Concept

It is commonly recognized in the pharmaceutical industry that on average more than 40% of newly discovered drug candidates are poorly water-soluble. The objective of present research is to explore the application of mixed solvency technique in the injection formulation of poorly soluble drugs and to reduce concentration of individual solubilizers (used for solubility enhancement) to minimize the toxic effects of solubilizers. In the present work poorly soluble drugs Ofloxacin are selected as model drugs. Ofloxacin is an antibiotic drug tried to formulate the aqueous injection by the use of various physiologically compatible solubilizing agent like Lignocaine Hydrochloride, Niacinamide, Sodium benzoate, Sodium citrate, PEG 400, PEG 4000, PVP 40000, Ethanol, and Propylene Glycol. For expected synergistic enhancement effect on solubility of these poorly soluble drugs various blends of solubilizers shall be tried to decrease the amounts of Solubilizer employed for a desired solubility enhancement ratio. The study further opens the chances of preparing dry powders for injection of drug which are not stable in aqueous solution, ready to use injection. Key word- Mixed solvency solubilization, Ofloxacin, solubility enhancement, synergistic enhancement effect

Genome-wide identification and expression profile analysis of nuclear factor Y family genes in Sorghum bicolor L. (Moench)

Members of the plant Heme Activator Protein (HAP) or NUCLEAR FACTOR Y (NF-Y) are trimeric transcription factor complexes composed of the NF-YA, NF-YB and NF-YC subfamilies. They bind to the CCAAT box in the promoter regions of the target genes and regulate gene expressions. Plant NF-Ys were reported to be involved in adaptation to several abiotic stresses as well as in development. In silico analysis of Sorghum bicolor genome resulted in the identification of a total of 42 NF-Y genes, among which 8 code for the SbNF-YA, 19 for SbNF-YB and 15 for the SbNF-YC subunits. Analysis was also performed to characterize gene structures, chromosomal distribution, duplication status, protein subcellular localizations, conserved motifs, ancestral protein sequences, miRNAs and phylogenetic tree construction. Phylogenetic relationships and ortholog predictions displayed that sorghum has additional NF-YB genes with unknown functions in comparison with Arabidopsis. Analysis of promoters revealed that they harbour many stress-related cis-elements like ABRE and HSE, but surprisingly, DRE and MYB elements were not detected in any of the subfamilies. SbNF-YA1, 2, and 6 were found upregulated under 200 mM salt and 200 mM mannitol stresses. While NF-YA7 appeared associated with high temperature (40˚C) stress, NF-YA8 was triggered by both cold (4˚C) and high temperature stresses. Among NF-YB genes, 7, 12, 15, and 16 were induced under multiple stress conditions such as salt, mannitol, ABA, cold and high temperatures. Likewise, NF-YC 6, 11, 12, 14, and 15 were enhanced significantly in a tissue specific manner under multiple abiotic stress conditions. Majority of the mannitol (drought)-inducible genes were also induced by salt, high temperature stresses and ABA. Few of the high temperature stress-induced genes are also induced by cold stress (NF-YA2, 4, 6, 8, NF-YB2, 7, 10, 11, 12, 14, 16, 17, NF-YC4, 6, 12, and 13) thus suggesting a cross talk among them. This work paves the way for investigating the roles of diverse sorghum NF-Y proteins during abiotic stress responses and provides an insight into the evolution of diverse NF-Y members

A QUALITATIVE INVESTIGATION OF TECHNOLOGY TRANSFER* A CASE STUDY

ECHNOLOGY transfer is an issue of national importance and i

A new differential configuration suitable for realization of high CMRR, all-pass/notch filters

#yayıncısurumuyok# ; Tam metin hakemden geçmiş kopyadır.In this paper, a new configuration suitable for realization of differential input-differential output first order, second order all-pass and notch filters with high CMRR is given. The proposed configuration uses two negative type second-generation current conveyors (CCII-), and three admittances. Two first order and one second order all-pass filters and a notch filter (tunable if current controlled conveyor CCCII is used) are extracted from the proposed configuration. Tracking error, element mismatch, sensitivity analysis, simulation and experimental results are included

A project for future life—Swedish women's thoughts on childbearing lacking experience of giving birth and parenthood

A lifeworld hermeneutic approach was used in order to understand Swedish women's thoughts on childbearing. Nine women were interviewed, and they ranged in age from 22 to 28 years and represented diverse socioeconomic, educational, sexual, and fertility backgrounds. All women were similar in that they lacked experience of giving birth and parenthood. The analysis showed that childbearing includes dimensions of both immanence and transcendence. Immanence, as childbearing is seen as stagnant to women's freedom in present life. Transcendence, as childbearing is thought of as a project for future life, a part of female identity, and a conscious standpoint for which the woman wants to be prepared and for which she wants to create the best conditions

Diagnostic classification of childhood cancer using multiscale transcriptomics

The causes of pediatric cancers’ distinctiveness compared to adult-onset tumors of the same type are not completely clear and not fully explained by their genomes. In this study, we used an optimized multilevel RNA clustering approach to derive molecular definitions for most childhood cancers. Applying this method to 13,313 transcriptomes, we constructed a pediatric cancer atlas to explore age-associated changes. Tumor entities were sometimes unexpectedly grouped due to common lineages, drivers or stemness profiles. Some established entities were divided into subgroups that predicted outcome better than current diagnostic approaches. These definitions account for inter-tumoral and intra-tumoral heterogeneity and have the potential of enabling reproducible, quantifiable diagnostics. As a whole, childhood tumors had more transcriptional diversity than adult tumors, maintaining greater expression flexibility. To apply these insights, we designed an ensemble convolutional neural network classifier. We show that this tool was able to match or clarify the diagnosis for 85% of childhood tumors in a prospective cohort. If further validated, this framework could be extended to derive molecular definitions for all cancer types