Low-Level HIV-I Replication and the Dynamics of the Resting CD4(+) T Cell Reservoir for HIV-I in the Setting of HAART

In the setting of highly active antiretroviral therapy (HAART), plasma levels of human immunodeficiency type-I (HIV-I) rapidly decay to below the limit of detection of standard clinical assays. However, reactivation of remaining latently infected memory CD4(+) T cells is a source of continued virus production, forcing patients to remain on HAART despite clinically undetectable viral loads. Unfortunately, the latent reservoir decays slowly, with a half-life of up to 44 months, making it the major known obstacle to the eradication of HIV-I infection. However, the mechanism underlying the long half-life of the latent reservoir is unknown. The most likely potential mechanisms are low-level viral replication and the intrinsic stability of latently infected cells. Methods: Here we use a mathematical model of T cell dynamics in the setting of HIV-I infection to probe the decay characteristics of the latent reservoir upon initiation of HAART. We compare the behavior of this model to patient derived data in order to gain insight into the role of low-level viral replication in the setting of HAART. Results: By comparing the behavior of our model to patient derived data, we find that the viral dynamics observed in patients on HAART could be consistent with low-level viral replication but that this replication would not significantly affect the decay rate of the latent reservoir. Rather than low-level replication, the intrinsic stability of latently infected cells and the rate at which they are reactivated primarily determine the observed reservoir decay rate according to the predictions of our model. Conclusion: The intrinsic stability of the latent reservoir has important implications for efforts to eradicate HIV-I infection and suggests that intensified HAART would not accelerate the decay of the latent reservoir.NIH AI 065960, AI 143222, AI 51178Doris Duke Charitable FoundationThe Howard Hughes Medical InstituteIntegrative Biolog

Kinetics of the viral cycle influence pharmacodynamics of antiretroviral therapy

<p>Abstract</p> <p>Background</p> <p>More and more antiretroviral therapies are being developed for treatment of HIV infection. The <it>in-vivo </it>efficacy of these drugs is commonly predicted based on <it>in-vitro </it>measures of antiviral effect. One primary <it>in-vitro </it>measure is the IC50, the amount of drug required for 50% inhibition of viral replication. We have previously shown that HIV life-cycle kinetics impact clinically observed HIV viral dynamics. Here we present a mathematical model of how they affect the pharmacodynamics of antiretroviral drugs.</p> <p>Results</p> <p>We find that experimentally measured antiretroviral IC50s are determined by three factors: (i) intrinsic drug properties (e.g. drug-target binding), (ii) kinetics of the HIV life cycle, and (iii) kinetics of drug-inhibited infected cells. Our model predicts that the IC50 is a declining function of the duration of the drug-susceptible stage in the host cell. We combine our model with known viral life-cycle kinetics to derive a measure of intrinsic properties, reflecting drug action, for known antiretroviral drugs from previously measured IC50s. We show that this measure of intrinsic drug property correlates very well with <it>in vitro</it>-measured antiviral activity, whereas experimentally measured IC50 does not.</p> <p>Conclusions</p> <p>Our results have implications for understanding pharmacodynamics of and improving activity of antiretroviral drugs. Our findings predict that drug activity can be improved through co-administration of synergistic drugs that delay the viral life cycle but are not inhibitory by themselves. Moreover, our results may easily extend to treatment of other pathogens.</p> <p>This article was reviewed by Dr. Ruy Ribeiro, Dr. Ha Youn Lee, Dr. Alan Perelson and Dr. Christoph Adami.</p

Error Estimation of Numerical Integration Methods

We compare the accuracy of numerical integral methods like Newton-Cotes method and Gaussian Quadrature Rule (GQR) for the model problem and tested for another problem to verify the results. From results we notice that error of GQR is about 10 times less than Newton-Cotes formulas. For this reason we prefer GQR over other methods. But GQR uses nodes and weights which is a tedious work. This difficulty can overcome by using the idea of  ”three-term recurrence” relation. We can transform the problem of finding the nodes and weights for GQR to one of finding eigenvalues and eigenvectors of a symmetric tridiagonal matrix. Keywords: Numerical integration; Gaussian Quadrature rules; error estimate; convergence rate

Pengaruh Perbandingan Eceng Gondok dan Air terhadap Kestabilan Sistem pada Produksi Biogas secara Fermentasi Anaerob Tahap Metanogenesis

Hyacinth (Eichhorhia crassipes) is a weed on waters which is a big problem for damage the environment but it contains materials that can be fermented and produce biogas, there are hemicellulose and cellulose. This research head for produce biogas from hyacinth by anaerob fermentation process with microorganizm on batch system and determine optimum ratio of hyacinth and water along with the effect to the stability of system. There were stages on this research, including seeding, acclimatization, and anaerob batch fermentation. Seeding was doing in ten days with ratio hyacinth and water was 75%:25%, then continued to acclimatization in 48 days. The anaerob batch fermentation was doing with variation of ratio hyacinth and water 1:2, 1:3, 1:4, and 1:5 in anaerob batch bioreactor during 32 days. Analysis of pH, biogas volume, volatile acid, and alkalinity was analized every two days during anaerob batch fermentation. The result of this research showed that in 48 days acclimatization process was produced biogas about 75.840 mL. In the fermentation process was resulted biogas about 23.300 mL with methane contents was 11.924,56 ppm or 1,19%; pH optimum 6,8-7,2; volatile acid concentration 145,8 mg/L; alkalinity concentration 1684,13 mg/L, and ratio of AV/alkalinity 0,087 on the rasio of hyacinth and water at 1:2. In conclusion, the stability of system will decrease along with increasing amount of water in the substrat of anaerob batch fermentation

Pengaruh Laju Alir terhadap Substrat pada Fermentasi Reject Nanas Menjadi Bioetanol secara Kontinu

Today, the world's need for energy is increasing while the supply of energy from fossil fuels that have been relied upon a limited number. Therefore, it is necessary that alternative energy sources are able to overcome the energy crisis. One of the alternative energy sources are being developed is bioethanol. Bioethanol can be produced by fermentation of glucose using the yeast Saccharomyces cerevisiae. One of source of glucose is pineapple. This research aims to make bioethanol from pineapple fruit skin using continuous fermentation method with a flow rate variations. Fixed variable used is the 5-liter, pH 4.5, inoculum levels of 0.3%, 0.5% urea, phosphorus levels and temperature fermentation 0.08% used is room temperature. Variable changes used are changes in feed flow rate is 5 L / day; 2.5 L / day; 1.67 L / day; 1:25 L / day and 1L / day. Experimental procedure includes pretreatment, inoculation, fermentation and purification using a vacuum evaporator. Analysis performed is analyzing glucose and ethanol concentration analysis. The results were obtained concentration of ethanol in the steady state condition for the flow rate of 5L / day as much as 5% v / v; 2.5 L / day by 7% v / v; 1.67 L / day as much as 6.5% v / v; 1.25 L / day as much as 6% v / v; and 1 L / day as much as 4% v / v. The highest ethanol concentration was obtained at a flow rate of 2.5L / day as much as 7%. This study suggests that the concentration of ethanol fermentation results increases with the flow rate of the substrate to achieve the optimal flow rate then decreased after reaching the optimum flow rate

Continuing Nursing Education: Best Practice Initiative in Nursing Practice Environment

AbstractContinuing Nursing Education (CNE) within the Nursing Practice Environment (NPE) is important in determining issues associated with unsafe practice, unproductiveness or incompetent nurses. A descriptive correlational study was designed to determine the best practice initiative in NPE whereby 395 (94.3%) nurses participated. This study showed that the highest mean score was 2.91 on ‘Nursing Foundations for Quality of Care’ of which 314 (79.5%) nurses highly agreed that CNE programs are the most important. In conclusion, CNE program is the best practice initiative and it is recommended that CNE will encourage lifelong and transformational learning in the nursing career

Low-level HIV-1 replication and the dynamics of the resting CD4+ T cell reservoir for HIV-1 in the setting of HAART

<p>Abstract</p> <p>Background</p> <p>In the setting of highly active antiretroviral therapy (HAART), plasma levels of human immunodeficiency type-1 (HIV-1) rapidly decay to below the limit of detection of standard clinical assays. However, reactivation of remaining latently infected memory CD4⁺T cells is a source of continued virus production, forcing patients to remain on HAART despite clinically undetectable viral loads. Unfortunately, the latent reservoir decays slowly, with a half-life of up to 44 months, making it the major known obstacle to the eradication of HIV-1 infection. However, the mechanism underlying the long half-life of the latent reservoir is unknown. The most likely potential mechanisms are low-level viral replication and the intrinsic stability of latently infected cells.</p> <p>Methods</p> <p>Here we use a mathematical model of T cell dynamics in the setting of HIV-1 infection to probe the decay characteristics of the latent reservoir upon initiation of HAART. We compare the behavior of this model to patient derived data in order to gain insight into the role of low-level viral replication in the setting of HAART.</p> <p>Results</p> <p>By comparing the behavior of our model to patient derived data, we find that the viral dynamics observed in patients on HAART could be consistent with low-level viral replication but that this replication would not significantly affect the decay rate of the latent reservoir. Rather than low-level replication, the intrinsic stability of latently infected cells and the rate at which they are reactivated primarily determine the observed reservoir decay rate according to the predictions of our model.</p> <p>Conclusion</p> <p>The intrinsic stability of the latent reservoir has important implications for efforts to eradicate HIV-1 infection and suggests that intensified HAART would not accelerate the decay of the latent reservoir.</p

Lepton-nucleus scattering in the impulse approximation regime

We discuss theoretical calculations of electron- and neutrino-nucleus scattering, carried out using realistic nuclear spectral functions and including the effect of final state interactions. Comparison between electron scattering data and the calculated inclusive cross sections off oxygen shows that the Fermi gas model fails to provide a satisfactory description of the measured cross sections, and inclusion of nuclear dynamics is needed. The role of Pauli blocking in charged-current neutrino induced reactions at low $Q^2$ is also analyzed.Comment: To be published in the Proceedings of NUFACT05 (Nucl. Phys. B, Proceedings Supplements

Studi Manajemen Pengelolaan Obat di Puskesmas Lawa Kabupaten Muna Barat Tahun 2015

Pengelolaan obat merupakan suatu rangkaian kegiatan yang menyangkut aspekperencanaan, pengadaan, penyimpanan, pendistribusian dan penghapusan obat yangdikelola secara optimal untuk menjamin tercapainya ketepatan jumlah dan jenis perbekalanfarmasi. Pada pengelolaan obat di Puskesmas tingkat ketersediaan obat masih belum sesuaidengan kebutuhan pelayanan kesehatan karena masih sering terjadi kekurangan dankekosongan obat disisi lain terjadi pula kelebihan obat. Penelitian ini bertujuan untukmendapatkan informsi lebih mendalam tentang studi manajemen pengelolaan obat diPuskesmas Lawa Kabubaten Muna Barat tahun 2015 ditinjau dari perencanaan, pengadaan,penyimpanan, pendistribusian dan penghapusan. Jenis penelitian adalah kualitatif denganpendekatan deskriptif. Informan dalam penelitian ini berjumlah 4 orang, yang terdiri dari 2orang informan kunci dan 2 orang informan biasa. Hasil penelitian menunjukan bahwaperencanaan pengelolaan obat berdasarkan metode epidemiologi dengan pengadaan obatdi sesuaikan pola penyakit dengan mengajukan LPLPO (Lembar Permintaan Dan LembarPemakaian Obat) ke Dinas Kesehatan Kabupaten Muna Barat dan GFK (Gudang FarmasiKota). Tempat penyimpanan obat di puskesmas masih kurang memadai, namunpenyusunannya sudah memenuhi standar penyimpanan obat di puskesmas. Pendistribusianobat yang dilakukan sesuai dengan prosedur pengelolaan obat, serta mengadakanpemusnahan pada obat yang kadaluarsa