ELUCIDATION OF THE MECHANISM OF ACTION OF A RESPIRATORY SYNCYTIAL VIRUS SUBUNIT VACCINE CANDIDATE CONTAINING A POLYMER-BASED COMBINATION ADJUVANT

Human respiratory syncytial virus (RSV) is the primary cause of respiratory illnesses in infants, young children, elderly and immunocompromised individuals. Supportive care is the mainstay of RSV treatment. Currently no licensed vaccine against RSV is available. We have developed a subunit RSV vaccine candidate (ΔF/TriAdj) consisting of a truncated version of the RSV fusion protein (ΔF) formulated with a combination adjuvant (TriAdj) comprised of low molecular weight (LMW) polyinosinic:polycytidylic acid [poly(I:C)], an innate defense regulator (IDR) peptide and poly[di(sodium carboxylatoethylphenoxy)]-phosphazene (PCEP). We previously demonstrated the safety and protective efficacy of ΔF/TriAdj in several animal models. The overall objective of this thesis was to elucidate the mechanism of action of ΔF/TriAdj in BALB/c mice. First, we determined that ΔF/TriAdj when delivered intranasally plays a crucial role in stimulating innate immune responses in both upper and lower respiratory tracts of immunized mice as demonstrated by local production of cytokines, chemokines and interferons, as well as infiltration and activation of immune cells. Innate activation subsequently led to robust adaptive immunity and protection against RSV. Next, we elucidated the mechanisms of action of ΔF/TriAdj at the cell-signaling level in macrophages. Macrophages responded directly to in vitro stimulation with ΔF/TriAdj with induction of both endosomal and cytosolic pattern recognition receptors (PRRs). Based on inhibition studies, we determined that multiple signal transduction pathways are involved in ΔF/TriAdj-mediated activation of macrophages. Finally, we conducted a comprehensive chemical isotope labeling liquid chromatography-mass spectrometry (CIL LC-MS) analysis of the lung tissues from vaccinated and unvaccinated, RSV-infected mice as well as healthy controls, to understand the underlying mechanisms of action of ΔF/TriAdj at the further downstream metabolomic level. Metabolomic profiling revealed alterations of tryptophan metabolism (including kynurenine pathway), biosynthesis of amino acids (including arginine biosynthesis), urea cycle and tyrosine metabolism due to RSV infection. Interestingly, ΔF/TriAdj was found to a play a critical role in modulating alterations in the concentrations of the metabolites of the above-mentioned pathways in response to RSV infection. Ultimately, information on the mechanism of action of this RSV vaccine candidate may serve to identify potential biomarkers for immunogenicity and protective efficacy of ΔF/TriAdj in future

A New Blind DOA Estimation Using Two Uniform Linear Array for Low Side Lobe Adaptive Array

312-314Suitably designed Adaptive algorithm can collect the main signals’ multipath and add them constructively with main signal with very low side lobe level in all other directions, hence eliminating the jamming signal from other directions. A new technique for DOA estimation of signals impinging on Two Uniform Linear Array (ULA) offset with each other by a known angle also has been proposed for further analysis and discussions

Two-temperature accretion flows around strongly magnetized stars and their spectral analysis

We investigate two-temperature accretion flows onto strongly magnetized compact stars. Matter is accreted in the form of an accretion disc upto the disc radius ($r_{\rm d}$), where, the magnetic pressure exceeds both the gas and ram pressure and thereafter the matter is channelled along the field lines onto the poles. We solve the equations of motion self-consistently along the field lines, incorporating radiative processes like bremsstrahlung, synchrotron and inverse-Comptonization. For a given set of constants of motion, the equations of motion do not produce unique transonic solution. Following the second law of thermodynamics the solution with the highest entropy is selected and thereby eliminating the degeneracy in solution. We study the properties of these solutions and obtain corresponding spectra as a function of the magnetic field ($B_*$), spin period ($P$) and accretion rate of the star ($\dot{M}$). A primary shock is always formed just near the surface. The enhanced radiative processes in this post-shock region slows down the matter and it finally settles on the surface of the star. This post-shock region contributes to $\gtrsim 99.99\%$ of the total luminosity obtained from the accretion flow. It is still important to study the full accretion flow because secondary shocks may be present for some combination of $B_*$, $P$ and ${\dot{M}}$ in addition to primary shocks. We find that secondary shocks, if present, produce an extended emission at higher energies in the spectra.Comment: 18 pages, 17 figures and accepted for publication in MNRA

More assistance of entanglement, less rounds of classical communication

Classical communication plays a crucial role to distinguish locally a class of quantum states. Despite considerable advances, we have very little knowledge about the number of measurement and communication rounds needed to implement a discrimination task by local quantum operations and classical communications (in short, LOCC). In this letter, we are able to show the relation between round numbers with the local discrimination of a set of pure bipartite orthogonal quantum states. To demonstrate the possible strong dependence on the round numbers, we consider a class of orthogonal product states in $d\otimes d$, which require at least $2d-2$ round of classical communications. Curiously the round number can be reduced to $d$ by the assistance of one-ebit of entanglement as resource and can be reduced further by assistance of more entanglement. We are also able to show that the number of LOCC rounds needed for a discrimination task may depend on the amount of entanglement assistances.Comment: 11 pages, 3 figures, revtex, comments welcom

Impact of Auditory Verbal Therapy in Children with Cochlear Implant

Introduction Auditory Verbal Therapy (AVT) is considered as most successful therapeutic approach for cochlear implant children. The impact of auditory verbal therapy has been studied vividly in Indian context. The number of cochlear implantees receiving AVT has been increased nationwide but there is no structured protocol that is used to assess the efficacy of AVT on children with cochlear implant. Hence, it is important to develop a structured protocol consisting of established tools to study the effectiveness of AVT. Materials and Methods          The study was conducted on 62 (male-38, female-24) bilaterally profound sensorineural hearing impaired children with cochlear implant done under ADIP (Assistance to Disabled Persons for Purchase/ Fitting of Aids and Appliances) scheme. Pre-therapy assessments were done before 2 weeks of cochlear implantation using Functional Auditory Performance Indicator (FAPI), Assessment of language development, Speech intelligibility rating scales, Brown’s (1973) stages of mean length of utterance (MLU) assessment, and Overall rating of parental satisfaction on a visual analog scale of 0 to 10. Auditory verbal therapy (AVT) was given for 6-8 months, twice per week under video-monitoring of the sessions. Post therapeutic scores were obtained by assessing with the same tools through observation and interaction with the children and interviewing the caregivers.  Results Independent Sample’s T-test in SPSS -16 software were used and significant differences between pre and post therapy scores were obtained (p<0.005). Conclusion These tools can be used further as a protocol for assessment of baseline skills before AVT, then develop an individualized management program and finally to assess the improvement after AVT

A New Blind DOA Estimation Using Two Uniform Linear Array for Low Side Lobe Adaptive Array

Suitably designed Adaptive algorithm can collect the main signals’ multipath and add them constructively with main signal with very low side lobe level in all other directions, hence eliminating the jamming signal from other directions. A new technique for DOA estimation of signals impinging on Two Uniform Linear Array (ULA) offset with each other by a known angle also has been proposed for further analysis and discussions

Dual role of nanoparticles as drug carrier and drug.

The conventional chemotherapeutic agents used in the treatment of human malignancies are directed nonspecifically against both malignant and nonmalignant cells, often limiting their efficacy with having serious side effects. Recent development of drug delivery vehicles has opened up the possibility of targeted drug delivery systems with the potential of achieving maximum efficacy with minimal toxicity. The possibility of using a nanomaterial as a combinational drug component is intuitively evident as it would compensate the toxicity level by enhancing drug delivery efficiency. Additionally, cell-specific cytotoxicity (reported earlier by our group) of the nanovehicle itself may potentiate a more effective targeted cell killing. In this paper, we explore the possibility of using gold nanoparticles playing the dual role of an anticancer agent and a carrier of a chemotherapeutic drug. This is demonstrated using vincristine sulfate (VS), salt of an alkaloid often used in the treatment of multiple myeloma (MM), and U266 as a test MM cell line. The drug VS shows the expected G2-M-phase arrest of cells. Notably, bare gold nanoparticle shows arrest of the S phase cells that may be particularly important in case of slow-growing malignancies like MM where most of the cells remain in G1 phase of the cell cycle. The VS conjugated gold retains the activity of both gold nanoparticle and VS leading to a synergistic rise of the apoptotic cell population