SURVEY ON ADVISOR INTELLIGENCE THROUGH PURCHASE PATTERNS AND SALES ANALYTICS

In mutual fund, an individual or a firm that is in the business of giving advice about securities to clients is an investment advisor. Investment advisers are individuals or firms that receive compensation for giving advice on investing in stocks, bonds, mutual funds, or exchange-traded funds. Investment advisors manage portfolios of securities. Advisors can use new cognitive and analytics capabilities to better understand their clients and needs and have a stronger ability to deepen relationships with a better portfolio. In this paper, we analyze data points foreach advisor, and distinguish the best prospects, obtain insight into their experience and credentials, and learn about their portfolio, in other words, to recognize the pattern of portfolio of the advisors. Such analysis helps the sales people to sell the fund company products to the suitable advisors based on the nature of the product they want to sell. This is done by investigating what kind of products advisors have been buying, and what kind of products they might be looking for. This helps to increase the sales of the products as sales people will be reaching the appropriate advisors

Structure of Cryptosporidium IMP de­hydrogenase bound to an inhibitor with in vivo antiparasitic activity

Inosine 50-monophosphate dehydrogenase (IMPDH) is a promising target for the treatment of Cryptosporidium infections. Here, the structure of C. parvum IMPDH (CpIMPDH) in complex with inosine 50-monophosphate (IMP) and P131, an inhibitor with in vivo anticryptosporidial activity, is reported. P131 contains two aromatic groups, one of which interacts with the hypoxanthine ring of IMP, while the second interacts with the aromatic ring of a tyrosine in the adjacent subunit. In addition, the amine and NO2 moieties bind in hydrated cavities, forming water-mediated hydrogen bonds to the protein. The design of compounds to replace these water molecules is a new strategy for the further optimization of C. parvum inhibitors for both antiparasitic and antibacterial applications

Triazole Inhibitors of Cryptosporidium parvum Inosine 5?-Monophosphate Dehydrogenase

Cryptosporidium parvum is an important human pathogen and potential bioterrorism agent. This protozoan parasite cannot salvage guanine or guanosine and therefore relies on inosine 5?-monophosphate dehydrogenase (IMPDH) for biosynthesis of guanine nucleotides and hence for survival. Because C. parvum IMPDH is highly divergent from the host counterpart, selective inhibitors could potentially be used to treat cryptosporidiosis with minimal effects on its mammalian host. A series of 1,2,3-triazole containing ether CpIMPDH inhibitors are described. A structure?activity relationship study revealed that a small alkyl group on the ?-position of the ether was required, with the (R)-enantiomer significantly more active than the (S)-enantiomer. Electron-withdrawing groups in the 3- and/or 4-positions of the pendent phenyl ring were best, and conversion of the quinoline containing inhibitors to quinoline-N-oxides retained inhibitory activity both in the presence and absence of bovine serum albumin. The 1,2,3-triazole CpIMPDH inhibitors provide new tools for elucidating the role of IMPDH in C. parvum and may serve as potential therapeutics for treating cryptosporidiosis

Selective and potent urea inhibitors of Cryptosporidium parvum inosine 5’-monophosphate dehydrogenase

Cryptosporidium parvum and related species are zoonotic intracellular parasites of the intestine. Cryptosporidium is a leading cause of diarrhea in small children around the world. Infection can cause severe pathology in children and immunocompromised patients. This waterborne parasite is resistant to common methods of water treatment and therefore a prominent threat to drinking and recreation water even in countries with strong water safety systems. The drugs currently used to combat these organisms are ineffective. Genomic analysis revealed that the parasite relies solely on inosine-5?-monophosphate dehydrogenase (IMPDH) for the biosynthesis of guanine nucleotides. Herein, we report a selective urea-based inhibitor of C. parvum IMPDH (CpIMPDH) identified by high-throughput screening. We performed a SAR study of these inhibitors with some analogues exhibiting high potency (IC50 1000-fold versus human IMPDH type 2 and good stability in mouse liver microsomes. A subset of inhibitors also displayed potent antiparasitic activity in a Toxoplasma gondii model

A Screening Pipeline for Antiparasitic Agents Targeting Cryptosporidium Inosine Monophosphate Dehydrogenase

Persistent diarrhea is a leading cause of illness and death among impoverished children, and a growing share of this disease burden can be attributed to the parasite Cryptosporidium. There are no vaccines to prevent Cryptosporidium infection, and the treatment options are limited and unreliable. Critically, no effective treatment exists for children or adults suffering from AIDS. Cryptosporidium presents many technical obstacles for drug discovery; perhaps the most important roadblock is the difficulty of monitoring drug action. Here we have developed a set of methods to accelerate the drug discovery process for cryptosporidiosis. We exploit the opportunities for experimental manipulation in the related parasite Toxoplasma to genetically engineer a Cryptosporidium model. This new model parasite mirrors the metabolism of Cryptosporidium for a particularly promising drug target that supplies the building blocks for DNA and RNA. Drug effectiveness can be assayed through simple fluorescence measurements for many candidates. Using this assay as an initial filter, and adapting other assays to a high throughput format, we identify several novel chemical compounds that exhibit markedly improved anti-cryptosporidial activity and excellent selectivity

Bax-Induced Apoptosis in Leber's Congenital Amaurosis: A Dual Role in Rod and Cone Degeneration

Pathogenesis in the Rpe65−/− mouse model of Leber's congenital amaurosis (LCA) is characterized by a slow and progressive degeneration of the rod photoreceptors. On the opposite, cones degenerate rapidly at early ages. Retinal degeneration in Rpe65−/− mice, showing a null mutation in the gene encoding the retinal pigment epithelium 65-kDa protein (Rpe65), was previously reported to depend on continuous activation of a residual transduction cascade by unliganded opsin. However, the mechanisms of apoptotic signals triggered by abnormal phototransduction remain elusive. We previously reported that activation of a Bcl-2-dependent pathway was associated with apoptosis of rod photoreceptors in Rpe65−/− mice during the course of the disease. In this study we first assessed whether activation of Bcl-2-mediated apoptotic pathway was dependent on constitutive activation of the visual cascade through opsin apoprotein. We then challenged the direct role of pro-apoptotic Bax protein in triggering apoptosis of rod and cone photoreceptors

ROLE OF MAGNETIC RESONANCE IMAGING IN THE EVALUATION OF SPINAL CORD LESIONS IN A TERTIARY CARE HOSPITAL, HYDERABAD

Background: Using other imaging modalities, subtle bone marrow, soft tissue, and spinal cord abnormalities, which may not be apparent, can be readily detected on magnetic resonance imaging (MRI). Prompt and accurate diagnosis, expeditious management, and avoidance of unnecessary procedures are achieved by early detection. Aim: The aim is to study the role of MRI in diagnosing spinal cord lesions. Methods: This study was conducted during the period from November 2018 to November 2020 and it is a prospective descriptive study of 50 patients who were referred to the Department of Radiodiagnosis Osmania General Hospital and MNJ Institute of Oncology and Regional Cancer Centre, Hyderabad, Telangana. Results: In the present study of 50 cases, different spinal cord lesions were found. The most common spinal cord lesions were neoplastic (38%) followed by spinal cord trauma (28%), and congenital lesions (16%). The most common spinal lesions were found in the 20–29 age group (40%), with more male predilection of 72% in comparison to 28% female in the present study. Out of 19 neoplastic lesions, the most common type of intramedullary spinal cord tumor (IMSC) is ependymoma (31.5%). The second most common IMSC tumor is astrocytoma 15.7% of all neoplastic lesions in the present study and the most common tumor among children. The most common location of the lesion is the thoracic cord. Hemangioblastomas constitute 10.5% of all spinal cord tumors in the present study. Meningiomas which are intradural extramedullary lesions constituted 10.5%. Neurofibroma constituted 5.2% which are intradural extramedullary with extradural component noted in NF1. Spinal cord metastasis constituted 26.3%. Intradural intramedullary lesions constituted 48% followed by extradural lesions 40% followed by intradural extramedullary lesions 12%. Conclusion: MRI by virtue of non-invasiveness, lack of radiation hazard, and the ability to demonstrate structural changes is an investigation of choice for spinal cord pathologies. The ability to image the cord directly rather than indirectly as in myelography, the absence of bone artifacts as in computed tomography, and the multiplanar capabilities indicate that MRI is the procedure of choice in the examination of the spinal cord

Subventricular zone involvement in Glioblastoma - A proteomic evaluation and clinicoradiological correlation

Glioblastoma multiforme (GBM), the most malignant of all gliomas is characterized by a high degree of heterogeneity and poor response to treatment. The sub-ventricular zone (SVZ) is the major site of neurogenesis in the brain and is rich in neural stem cells. Based on the proximity of the GBM tumors to the SVZ, the tumors can be further classified into SVZ+ and SVZ-. The tumors located in close contact with the SVZ are classified as SVZ+, while the tumors located distantly from the SVZ are classified as SVZ-. To gain an insight into the increased aggressiveness of SVZ+ over SVZ - tumors, we have used proteomics techniques like 2D-DIGE and LC-MS/MS to investigate any possible proteomic differences between the two subtypes. Serum proteomic analysis revealed significant alterations of various acute phase proteins and lipid carrying proteins, while tissue proteomic analysis revealed significant alterations in cytoskeletal, lipid binding, chaperone and cell cycle regulating proteins, which are already known to be associated with disease pathobiology. These findings provide cues to molecular basis behind increased aggressiveness of SVZ + GBM tumors over SVZ - GBM tumors and plausible therapeutic targets to improve treatment modalities for these highly invasive tumors

Comparative efficacy of different methods in the generation of 12S particles from 146S particles of FMDV serotype A and their detection using serotype (146S) specific monoclonal antibodies

Foot-and-mouth disease [FMD] is a highly infectious and contagious viral disease of domestic and wild cloven hoofed animals. The disease is controlled by vaccination using inactivated vaccine as one of the important options. The integrity of 146S plays an important role in the efficacy of the vaccine. The currently applied methods like density gradient to check the integrity of the 146Sparticles are besotted with certain isadvantages. Therefore, we generated monoclonal antibodies (mAbs) specific to 146S of FMDV serotype A [Indianstrain]. To test these mAbs for their specificity to 146S, conversion of 146S into 12S is a must. Normally, three methods like strong [1N HCl] and weak acid [Na2HPO4] methods; and heat method are followed in the conversion of 146S into 12S. Upon comparison of these methods in the present study, consistent results were obtained using heat method at 560C and 600C each for half an hour and one hour. However, the former two methods were very inconsistent in yielding 12S from 146S particle due to slight variation in the pH. Hence, we optimized heat method for efficient conversion of 146S particle to 12S particle of FMDV serotype A [A/INDIA/40/00], an Indian vaccine strain. The results are ascertained applying serotype specific [146S] monoclonal antibody based double antibody sandwich ELISA. However, the method needs to be evaluated using more number of 146S samples

A Simple Protein Extraction Method for Proteomic Analysis of Diverse Biological Specimens

The success of a proteomic experiment largely depends on the quality and quantity of the protein extract. Currently, various protocols are available for extraction of proteins from different types of samples; however, further optimization is required for every new sample type. Hence, a common protein extraction protocol is desirable. In the present study, soluble proteins were extracted from six diverse samples using TRIzol without any additional clean-up step and subjected to 2-DE and 2D-DIGE analysis for global protein expression profiling. Image analysis using IMP7 and DeCyder showed good coverage, reproducibility and quality of the gel. MS analysis of 24 spots from all the six samples showed good score and coverage for the identified proteins. Additionally, this method facilitated the concurrent isolation of RNA from the same cell lysates with high integrity and quality, suitable for transcriptomic analysis. Thus, we demonstrate the use of a common protein extraction protocol involving TRIzol reagent for 2-DE, 2D-DIGE and MS analysis using six diverse samples and show its suitability for concomitant transcriptomic studies