FORMULATION AND IMMUNOSTIMULANT STABILITY POLYSACCHARIDE SYRUP OF FRACTION NONI (MORINDA CITRIFOLIA L.) FRUITS

Objective: The study aimed to formulate standardized polysaccharide fraction of Noni (SPFN) fruit into syrup preparations to fulfill the acceptability requirement of National Agency of Drugs and Food Control [Badan Pengawas Obat dan Makanan Republik of Indonesia (BPOM RI)] so that it can be used in the community as an immunostimulant. Methods: The optimization of the formula A and B were done using Simplex Lattice Design (SLD) method and its stability tested under extreme temperature change effect using thaw cycling method by evaluating the physical properties, microbial contamination and immunostimulant activity. MTT method was used to determine the immunostimulant activity of syrup against lymphocyte proliferation in vitro. Results: Based on the results of stability tests of formula A using pH (4.45), viscosity (81.03 mPas), taste (good taste), pouring power (2.31 s), amount of bacteria (68 colonies/ml), total yeast and mold (269 colonies/ml) parameters and fulfilled the acceptability requirement of BPOM RI. Formula A could maintain better stability than formula B. Formula A syrup used for immunostimulant activity testing that could increase lymphocyte proliferation at a concentration of 13.33 to 106.64 μg/μl and it’s stable under the influence of extreme temperature changes. Conclusion: Formula A could be used to produce SPFN syrup, which has stable physical properties and immunostimulant activity beside no microbial contamination that fulfill requirements of BPOM RI

Hubble Space Telescope Angular Velocity Estimation During the Robotic Servicing Mission

In 2004 NASA began investigation of a robotic servicing mission for the Hubble Space Telescope (HST). Such a mission would require estimates of the HST attitude and rates in order to achieve a capture by the proposed Hubble robotic vehicle (HRV). HRV was to be equipped with vision-based sensors, capable of estimating the relative attitude between HST and HRV. The inertial HST attitude is derived from the measured relative attitude and the HRV computed inertial attitude. However, the relative rate between HST and HRV cannot be measured directly. Therefore, the HST rate with respect to inertial space is not known. Two approaches are developed to estimate the HST rates. Both methods utilize the measured relative attitude and the HRV inertial attitude and rates. First, a non-linear estimator is developed. The nonlinear approach estimates the HST rate through an estimation of the inertial angular momentum. Second, a linearized approach is developed. The linearized approach is a pseudo-linear Kalman filter. Simulation test results for both methods are given. Even though the development began as an application for the HST robotic servicing mission, the methods presented are applicable to any rendezvous/capture mission involving a non-cooperative target spacecraft

On the Relationship between the Uniqueness of the Moonshine Module and Monstrous Moonshine

We consider the relationship between the conjectured uniqueness of the Moonshine Module, ${\cal V}^\natural$, and Monstrous Moonshine, the genus zero property of the modular invariance group for each Monster group Thompson series. We first discuss a family of possible $Z_n$ meromorphic orbifold constructions of ${\cal V}^\natural$ based on automorphisms of the Leech lattice compactified bosonic string. We reproduce the Thompson series for all 51 non-Fricke classes of the Monster group $M$ together with a new relationship between the centralisers of these classes and 51 corresponding Conway group centralisers (generalising a well-known relationship for 5 such classes). Assuming that ${\cal V}^\natural$ is unique, we then consider meromorphic orbifoldings of ${\cal V}^\natural$ and show that Monstrous Moonshine holds if and only if the only meromorphic orbifoldings of ${\cal V}^\natural$ give ${\cal V}^\natural$ itself or the Leech theory. This constraint on the meromorphic orbifoldings of ${\cal V}^\natural$ therefore relates Monstrous Moonshine to the uniqueness of ${\cal V}^\natural$ in a new way.Comment: 53 pages, PlainTex, DIAS-STP-93-0

Researching the use of force: The background to the international project

This article provides the background to an international project on use of force by the police that was carried out in eight countries. Force is often considered to be the defining characteristic of policing and much research has been conducted on the determinants, prevalence and control of the use of force, particularly in the United States. However, little work has looked at police officers’ own views on the use of force, in particular the way in which they justify it. Using a hypothetical encounter developed for this project, researchers in each country conducted focus groups with police officers in which they were encouraged to talk about the use of force. The results show interesting similarities and differences across countries and demonstrate the value of using this kind of research focus and methodology

Expression of Regulatory Platelet MicroRNAs in Patients with Sickle Cell Disease

Background: Increased platelet activation in sickle cell disease (SCD) contributes to a state of hypercoagulability and confers a risk of thromboembolic complications. The role for post-transcriptional regulation of the platelet transcriptome by microRNAs (miRNAs) in SCD has not been previously explored. This is the first study to determine whether platelets from SCD exhibit an altered miRNA expression profile. Methods and Findings: We analyzed the expression of miRNAs isolated from platelets from a primary cohort (SCD = 19, controls = 10) and a validation cohort (SCD = 7, controls = 7) by hybridizing to the Agilent miRNA microarrays. A dramatic difference in miRNA expression profiles between patients and controls was noted in both cohorts separately. A total of 40 differentially expressed platelet miRNAs were identified as common in both cohorts (p-value 0.05, fold change>2) with 24 miRNAs downregulated. Interestingly, 14 of the 24 downregulated miRNAs were members of three families - miR-329, miR-376 and miR-154 - which localized to the epigenetically regulated, maternally imprinted chromosome 14q32 region. We validated the downregulated miRNAs, miR-376a and miR-409-3p, and an upregulated miR-1225-3p using qRT-PCR. Over-expression of the miR-1225-3p in the Meg01 cells was followed by mRNA expression profiling to identify mRNA targets. This resulted in significant transcriptional repression of 1605 transcripts. A combinatorial approach using Meg01 mRNA expression profiles following miR-1225-3p overexpression, a computational prediction analysis of miRNA target sequences and a previously published set of differentially expressed platelet transcripts from SCD patients, identified three novel platelet mRNA targets: PBXIP1, PLAGL2 and PHF20L1. Conclusions: We have identified significant differences in functionally active platelet miRNAs in patients with SCD as compared to controls. These data provide an important inventory of differentially expressed miRNAs in SCD patients and an experimental framework for future studies of miRNAs as regulators of biological pathways in platelets. © 2013 Jain et al

Natural Host Genetic Resistance to Lentiviral CNS Disease: A Neuroprotective MHC Class I Allele in SIV-Infected Macaques

Human immunodeficiency virus (HIV) infection frequently causes neurologic disease even with anti-retroviral treatment. Although associations between MHC class I alleles and acquired immunodeficiency syndrome (AIDS) have been reported, the role MHC class I alleles play in restricting development of HIV-induced organ-specific diseases, including neurologic disease, has not been characterized. This study examined the relationship between expression of the MHC class I allele Mane-A*10 and development of lentiviral-induced central nervous system (CNS) disease using a well-characterized simian immunodeficiency (SIV)/pigtailed macaque model. The risk of developing CNS disease (SIV encephalitis) was 2.5 times higher for animals that did not express the MHC class I allele Mane-A*10 (P = 0.002; RR = 2.5). Animals expressing the Mane-A*10 allele had significantly lower amounts of activated macrophages, SIV RNA, and neuronal dysfunction in the CNS than Mane-A*10 negative animals (P<0.001). Mane-A*10 positive animals with the highest CNS viral burdens contained SIV gag escape mutants at the Mane-A*10-restricted KP9 epitope in the CNS whereas wild type KP9 sequences dominated in the brain of Mane-A*10 negative animals with comparable CNS viral burdens. These concordant findings demonstrate that particular MHC class I alleles play major neuroprotective roles in lentiviral-induced CNS disease

Humanization and Characterization of an Anti-Human TNF-α Murine Monoclonal Antibody

A murine monoclonal antibody, m357, showing the highly neutralizing activities for human tumor necrosis factor (TNF-α) was chosen to be humanized by a variable domain resurfacing approach. The non-conserved surface residues in the framework regions of both the heavy and light chain variable regions were identified via a molecular modeling of m357 built by computer-assisted homology modeling. By replacing these critical surface residues with the human counterparts, a humanized version, h357, was generated. The humanized h357 IgG1 was then stably expressed in a mammalian cell line and the purified antibody maintained the high antigen binding affinity as compared with the parental m357 based on a soluble TNF-α neutralization bioassay. Furthermore, h357 IgG1 possesses the ability to mediate antibody-dependent cell-mediated cytotoxicity and complement dependent cytotoxicity upon binding to cells bearing the transmembrane form of TNF-α. In a mouse model of collagen antibody-induced arthritis, h357 IgG significantly inhibited disease progression by intra-peritoneal injection of 50 µg/mouse once-daily for 9 consecutive days. These results provided a basis for the development of h357 IgG as therapeutic use

PRPF8-mediated dysregulation of hBrr2 helicase disrupts human spliceosome kinetics and 5\ub4-splice-site selection causing tissue-specific defects

\ua9 The Author(s) 2024.The carboxy-terminus of the spliceosomal protein PRPF8, which regulates the RNA helicase Brr2, is a hotspot for mutations causing retinitis pigmentosa-type 13, with unclear role in human splicing and tissue-specificity mechanism. We used patient induced pluripotent stem cells-derived cells, carrying the heterozygous PRPF8 c.6926 A &gt; C (p.H2309P) mutation to demonstrate retinal-specific endophenotypes comprising photoreceptor loss, apical-basal polarity and ciliary defects. Comprehensive molecular, transcriptomic, and proteomic analyses revealed a role of the PRPF8/Brr2 regulation in 5’-splice site (5’SS) selection by spliceosomes, for which disruption impaired alternative splicing and weak/suboptimal 5’SS selection, and enhanced cryptic splicing, predominantly in ciliary and retinal-specific transcripts. Altered splicing efficiency, nuclear speckles organisation, and PRPF8 interaction with U6 snRNA, caused accumulation of active spliceosomes and poly(A)+ mRNAs in unique splicing clusters located at the nuclear periphery of photoreceptors. Collectively these elucidate the role of PRPF8/Brr2 regulatory mechanisms in splicing and the molecular basis of retinal disease, informing therapeutic approaches