Parametric Estimation of Harmonically Related Sinusoids

Mud-pulse telemetry is a method used for measurement-while-drilling (MWD)in the oil industry. The telemetry signals are corrupted by spurious mud pump noise consisting of a large number of harmonically related sinusoids. In order to denoise the signal, the noise parameters have to be tracked accurately in real time. There are well established parametric estimation techniques for determining various parameters of independent sinusoids. The iterative methods based on the linear prediction properties of the sinusoids provide a computationally e±cient way of solving the non linear optimization problem presented by these methods. However, owing to the large number of these sinusoids, incorporating the harmonic relationship in the problem becomes important. This thesis is aimed at solving the problem of estimating parameters of harmonically related sinusoids. We examine the efficacy of IQML algorithm in estimating the parameters of the telemetry signal for varying SNRs and data lengths. The IQML algorithm proves quite robust and successfully tracks both stationary and slowly varying frequency signals. Later, we propose an algorithm for fundamental frequency estimation which relies on the initial harmonic frequency estimate. The results of tests performed on synthetic data that imitates real field data are presented. The analysis of the simulation results shows that the proposed method manages to remove noise causing sinusoids in the telemetry signal to a great extent. The low computational complexity of the algorithm also makes for an easy implementation on field where computational power is limited

Rhinocerebral mucormycosis: report of a rare case

Background: Mucormycosis is one of the rapidly progressing and lethal form of fungal infection which involves the nose and paranasal sinuses of the head and the neck regions. Mucormycosis also remains a threat to patients with uncontrolled diabetes or other predisposing systemic conditions. It manifests as rhinocerebral, pulmonary, gastrointestinal, cutaneous or disseminated form. The underlying conditions can influence clinical presentation and often delay diagnosis, with resultant poor outcomes.Case Details: We report a case of rhinocerebral mucormycosis in a 75 year-old diabetic patient with emphasise on diagnosis, treatment and survival options of patient from this potentially fatal fungal infection. Extra oral examination revealed mild non-tender swelling on the face, unable to see from left eye, impaired sense of smell, difficulty in speech and nasal stuffiness. Intra-oral examination showed necrosis of mucosa and underlying bone in relation to canine to the tuberosity area of the left vestibular region of the maxilla.Conclusion: Timely diagnosis is critical to survival and minimization of morbidity. Institution of surgical and medical therapy is critical in maximizing the likelihood of good outcome.Keywords: Mucormycosis, fungal, systemic, maxillary sinu

Encapsulation of Recombinant MOMP in Extended-Releasing PLGA 85:15 Nanoparticles Confer Protective Immunity Against a Chlamydia muridarum Genital Challenge and Re-Challenge

Recently we reported the immune-potentiating capacity of a Chlamydia nanovaccine (PLGA-rMOMP) comprising rMOMP (recombinant major outer membrane protein) encapsulated in extended-releasing PLGA [poly (D, L-lactide-co-glycolide) (85:15)] nanoparticles. Here we hypothesized that PLGA-rMOMP would bolster immune-effector mechanisms to confer protective efficacy in mice against a Chlamydia muridarum genital challenge and re-challenge. Female BALB/c mice received three immunizations, either subcutaneously (SC) or intranasally (IN), before receiving an intravaginal challenge with C. muridarum on day 49 and a re-challenge on day 170. Both the SC and IN immunization routes protected mice against genital challenge with enhanced protection after a re-challenge, especially in the SC mice. The nanovaccine induced robust antigen-specific Th1 (IFN-γ, IL-2) and IL-17 cytokines plus CD4+ proliferating T-cells and memory (CD44high CD62Lhigh) and effector (CD44high CD62Llow) phenotypes in immunized mice. Parallel induction of antigen-specific systemic and mucosal Th1 (IgG2a, IgG2b), Th2 (IgG1), and IgA antibodies were also noted. Importantly, immunized mice produced highly functional Th1 avidity and serum antibodies that neutralized C. muridarum infectivity of McCoy fibroblasts in-vitro that correlated with their respective protection levels. The SC, rather than the IN immunization route, triggered higher cellular and humoral immune effectors that improved mice protection against genital C. muridarum. We report for the first time that the extended-releasing PLGA 85:15 encapsulated rMOMP nanovaccine confers protective immunity in mice against genital Chlamydia and advances the potential towards acquiring a nano-based Chlamydia vaccine.Fil: Sahu, Rajnish. University of Alabama at Birmingahm; Estados UnidosFil: Dixit, Saurabh. University of Alabama at Birmingahm; Estados UnidosFil: Verma, Richa. University of Alabama at Birmingahm; Estados UnidosFil: Duncan, Skyla A.. University of Alabama at Birmingahm; Estados UnidosFil: Smith, Lula. University of Alabama at Birmingahm; Estados UnidosFil: Giambartolomei, Guillermo Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Singh, Shree R.. University of Alabama at Birmingahm; Estados UnidosFil: Dennis, Vida A.. University of Alabama at Birmingahm; Estados Unido

A Comparative Study of Digital City Development Using the Data-Driven Smart City Index

This research compares and contrasts the evolution of smart cities using a comparative analysis based on the Data-Driven Smart City Index. The study includes four important tables: the Digital City Development Index, which shows City D as a model smart city because of its high Infrastructure, Data Utilization, and Connectivity Scores, offers a thorough summary of the development of smart cities. The three components of the Data-Driven Smart City Index are Environmental Sustainability, Governance, and Quality of Life. City D excels in all three areas. The importance of big data analytics, IoT adoption, and open data usage—all of which City D leads—is emphasized in Data Utilization in Digital City Development. Lastly, Connectivity Infrastructure in Digital Cities emphasizes the significance of cutting-edge technology, with City D leading the way in terms of availability of public Wi-Fi, 5G network connectivity, and fiber broadband coverage. These results provide insightful information that will help stakeholders, politicians, and urban planners advance cities into the digital age and improve the quality of life for citizens

The Chlamydia M278 Major Outer Membrane Peptide Encapsulated in the Poly(lactic acid)-Poly(ethylene glycol) Nanoparticulate Self-Adjuvanting Delivery System Protects Mice Against a Chlamydia muridarum Genital Tract Challenge by Stimulating Robust Systemic and Local Mucosal Immune Responses

Recently, we reported that our PPM chlamydial nanovaccine [a biodegradable co-polymeric PLA-PEG (poly(lactic acid)-poly(ethylene glycol))-encapsulated M278 peptide (derived from the major outer membrane protein (MOMP) of Chlamydia)] exploits the caveolin-mediated endocytosis pathway for endosomal processing and MHC class II presentation to immune-potentiate Chlamydia-specific CD4+ T-cell immune effector responses. In the present study, we employed the Chlamydia muridarum mouse infection model to evaluate the protective efficacy of PPM against a genital tract challenge. Our results show that mice immunized with PPM were significantly protected against a homologous genital tract challenge evidently by reduced vaginal bacterial loads. Protection of mice correlated with enhanced Chlamydia-specific adaptive immune responses predominated by IFN-γ along with CD4+ T-cells proliferation and their differentiation to CD4+ memory (CD44high CD62Lhigh) and effector (CD44high CD62Llow) T-cell phenotypes. We observed the elevation of M278- and MOMP-specific serum antibodies with high avidity in the ascending order IgG1 > IgG2b > IgG2a. A key finding was the elevated mucosal IgG1 and IgA antibody titers followed by an increase in MOMP-specific IgA after the challenge. The Th1/Th2 antibody titer ratios (IgG2a/IgG1 and IgG2b/IgG1) revealed that PPM evoked a Th2-directed response, which skewed to a Th1-dominated antibody response after the bacterial challenge of mice. In addition, PPM immune sera neutralized the infectivity of C. muridarum in McCoy cells, suggesting the triggering of functional neutralizing antibodies. Herein, we reveal for the first time that subcutaneous immunization with the self-adjuvanting biodegradable co-polymeric PPM nanovaccine immune-potentiated robust CD4+ T cell-mediated immune effector responses; a mixed Th1 and Th2 antibody response and local mucosal IgA to protect mice against a chlamydial genital tract challenge

Insights into Hox Protein Function from a Large Scale Combinatorial Analysis of Protein Domains

Protein function is encoded within protein sequence and protein domains. However, how protein domains cooperate within a protein to modulate overall activity and how this impacts functional diversification at the molecular and organism levels remains largely unaddressed. Focusing on three domains of the central class Drosophila Hox transcription factor AbdominalA (AbdA), we used combinatorial domain mutations and most known AbdA developmental functions as biological readouts to investigate how protein domains collectively shape protein activity. The results uncover redundancy, interactivity, and multifunctionality of protein domains as salient features underlying overall AbdA protein activity, providing means to apprehend functional diversity and accounting for the robustness of Hox-controlled developmental programs. Importantly, the results highlight context-dependency in protein domain usage and interaction, allowing major modifications in domains to be tolerated without general functional loss. The non-pleoitropic effect of domain mutation suggests that protein modification may contribute more broadly to molecular changes underlying morphological diversification during evolution, so far thought to rely largely on modification in gene cis-regulatory sequences

How to prevent the next Marathon Pharmaceuticals [version 1; referees: 2 approved, 1 approved with reservations]

In recent years, several drug companies have exploited U.S. regulatory policies to acquire exclusive rights to cheap therapies and substantially raise their prices, and Federal agencies and state governments are exploring various ways to prevent or punish such behavior in the future. Among these cases, however, Marathon Pharmaceuticals’ handling of Emflaza (deflazacort) is unique, because the drug was previously only available abroad, and was never previously sold in the U.S. before the company obtained FDA approval for it. Thus, laws and policies designed to address price hikes on already-marketed drugs are unlikely to prevent additional Marathon-like scenarios. In this article, we describe in more detail the unique features of Emflaza compared with these other recent cases of drug price increases, determine the likelihood that similar situations will arise in the future, and explore legislative and administrative options to specifically prevent such behavior

Hox genes and the regulation of movement in Drosophila

Many animals show regionally specialized patterns of movement along the body axis. In vertebrates, spinal networks regulate locomotion, while the brainstem controls movements of respiration and feeding. Similarly, amongst invertebrates diversification of appendages along the body axis is tied to the performance of characteristically different movements such as those required for feeding, locomotion, and respiration. Such movements require locally specialized networks of nerves and muscles. Here we use the regionally differentiated movements of larval crawling in Drosophila to investigate how the formation of a locally specialized locomotor network is genetically determined. By loss and gain of function experiments we show that particular Hox gene functions are necessary and sufficient to dictate the formation of a neuromuscular network that orchestrates the movements of peristaltic locomotion

Caveolin-mediated endocytosis of the Chlamydia M278 outer membrane peptide encapsulated in poly(lactic acid)-Poly(ethylene glycol) nanoparticles by mouse primary dendritic cells enhances specific immune effectors mediated by MHC class II and CD4+ T cells

We previously developed a Chlamydia trachomatis nanovaccine (PPM) by encapsulating a chlamydial M278 peptide within poly(lactic acid)-poly(ethylene glycol) biodegradable nanoparticles that immunopotentiated Chlamydia-specific immune effector responses in mice. Herein, we investigated the mechanistic interactions of PPM with mouse bone marrow-derived dendritic cells (DCs) for its uptake, trafficking, and T cell activation. Our results reveal that PPM triggered enhanced expression of effector cytokines and chemokines, surface activation markers (Cd1d2, Fcgr1), pathogen-sensing receptors (TLR2, Nod1), co-stimulatory (CD40, CD80, CD86) and MHC class I and II molecules. Co-culturing of PPM-primed DCs with T cells from C. muridarum vaccinated mice yielded an increase in Chlamydia-specific immune effector responses including CD3+ lymphoproliferation, CD3+CD4+ IFN-γ-secreting cells along with CD3+CD4+ memory (CD44high and CD62Lhigh) and effector (CD44high and CD62Llow) phenotypes. Intracellular trafficking analyses revealed an intense expression and colocalization of PPM predominantly in endosomes. PPM also upregulated the transcriptional and protein expression of the endocytic mediator, caveolin-1 in DCs. More importantly, the specific inhibition of caveolin-1 led to decreased expression of PPM-induced cytokines and co-stimulatory molecules. Our investigation shows that PPM provided enhancement of uptake, probably by exploiting the caveolin-mediated endocytosis pathway, endosomal processing, and MHC II presentation to immunopotentiate Chlamydia-specific immune effector responses mediated by CD4+ T cells.Fil: Dixit, Saurabh. Alabama State University; Estados UnidosFil: Sahu, Rajnish. Alabama State University; Estados UnidosFil: Verma, Richa. Alabama State University; Estados UnidosFil: Duncan, Skyla. Alabama State University; Estados UnidosFil: Giambartolomei, Guillermo Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Singh, Shree R.. Alabama State University; Estados UnidosFil: Dennis, Vida A.. Alabama State University; Estados Unido