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

Myths and Realities about Online Forums in Open Source Software Development: An Empirical Study

The use of free and open source software (OSS) is gaining momentum due to the ever increasing availability and use of the Internet. Organizations are also now adopting open source software, despite some reservations, in particular regarding the provision and availability of support. Some of the biggest concerns about free and open source software are post release software defects and their rectification, management of dynamic requirements and support to the users. A common belief is that there is no appropriate support available for this class of software. A contradictory argument is that due to the active involvement of Internet users in online forums, there is in fact a large resource available that communicates and manages the provision of support. The research model of this empirical investigation examines the evidence available to assess whether this commonly held belief is based on facts given the current developments in OSS or simply a myth, which has developed around OSS development. We analyzed a dataset consisting of 1880 open source software projects covering a broad range of categories in this investigation. The results show that online forums play a significant role in managing software defects, implementation of new requirements and providing support to the users in open source software and have become a major source of assistance in maintenance of the open source projects

Event by Event Analysis of High Multiplicity Events Produced in 158 A GeV/c 208 Pb- 208 Pb Collisions

An extensive analysis of individual high multiplicity events produced in 158 A GeV /c 208Pb- 208Pb collisions is carried by adopting different methods to examine the anomalous behavior of these rare events. A method of selecting the events with densely populated narrow regions or spikes out of a given sample of collision events is discussed.Employing this approach two events with large spikes in their eta- and phi- distributions are selected for further analysis. For the sake of comparison, another two events which do not exhibit such spikes are simultaneously analyzed. The findings suggest that the systematic studies of particle density fluctuations in one- and two-dimensional phase-spaces and comparison with those obtained from the studies of correlation free Monte Carlo events, would be useful for identifying the events with large dynamical fluctuations. Formation of clusters or jet like phenomena in multihadronic final states in individual events is also discussed and the experimental findings are compared with the independent particle emission hypothesis by carrying out Monte Carlo simulations

Modulation of corticospinal excitability induced by paired associative stimulation combined with movement

An essential feature of the brain is its capacity to undergo long-lasting morphological or functional changes in response to experiences or trauma. Advances in noninvasive brain stimulation techniques have led to increased interest in understanding neural mechanisms of neuroplasticity at the network level. Paired associative stimulation (PAS) is one of the most commonly used applications for noninvasive brain stimulation because of its clinical potential as an adjuvant rehabilitative intervention. However, the optimal method for incorporating PAS into rehabilitative activities remains unknown. This dissertation explores different approaches to combining PAS with movement and investigates the enhancement of the specificity of conventional PAS-induced effects. A fundamental aspect in combining PAS and voluntary movement is the timing of stimuli with respect to muscle activation onset. Therefore, this dissertation first focuses on determining the effect of PAS on the primary motor cortex (M1) excitability when the stimuli are delivered during preparation or execution of a voluntary finger extension in a reaction time setup. The results of this investigation show that applying PAS during voluntary contraction or at rest increases the corticospinal excitability (CSE), while PAS delivered during movement preparation decreases CSE. This suggests that the direction of PAS-induced plasticity is dependent on the order of stimulation and the phase of the movement. Next, combining PAS with the movement of the stimulated limb may further increase the enhancement of CSE. However, individuals with moderate to severe motor function impairment due to stroke may not be able to engage in the necessary repetitive voluntary movements of the paretic limb. The objective of this study is to investigate the feasibility of contralaterally coordinated PAS applied to the resting hand’s extensors during fast extension of the contralateral hand in healthy individuals. PAS delivered during the muscle contraction of the left hand, and PAS delivered at rest both increase the CSE. Delivering PAS during the preparation phase of the left-hand movement leads to a decrease in the CSE. Thus, PAS-induced bidirectional plasticity effects that are dependent on the phase of the movement of the opposite hand. Additionally, given the noted topographical specificity of the somatosensory cortex and reported muscle-specific PAS-induced changes, this dissertation also evaluates the feasibility of enhancing the specificity of PAS-induced effects through a simultaneous application of facilitatory PAS to hand extensor muscles and inhibitory PAS to flexor muscles while at rest in healthy individuals. The simultaneous application of PAS, targeting the hand extensor muscle with facilitatory PAS and hand flexor muscle with inhibitory PAS leads to a consistent and significant increase in CSE of the extensor muscle. Finally, in a pilot study, two scenarios combining PAS with dynamic hand movements in a reaction time paradigm are explored in people with stroke. PAS of the ipsilesional M1 is combined with a voluntary activation of finger extensors of the paretic limb or during a nonparetic finger extension. This is done to evaluate the feasibility of combining PAS with voluntary movement in chronic stroke patients. Although there were no notable changes in the CSE, recruited stroke patients are able to tolerate and perform a motor task with both their affected and less affected hand while PAS is applied

Wali Nikah dalam Pemikiran Fuqaha dan Muhadditsin Kontemporer

This article deals with wali nikah (relative legally responsible for a bride) as a requirement in a wedding process. Majority of Islamic scholars (fuqaha), and also Indonesian Islamic law, always refers to male relative when they talk about wali nikah. On the other hand, contemporary Islamic scholars even give a bride a freedom to get married without a wali nikah. While the first opinion may lead to gender inequality and injustice, the latter opinion is very dangerous. From historical approach, the opinion that wali nikah always refers to male relative can be traced from Islamic legislation prescribed in the Qur\u27an and hadits. Referring to some contemporary Islamic scholars and muhadditsin, the writer contends that wali nikah is not an obligatory rule (rukun) of a marriage, but only serves as a monitoring apparatus. Suppose wali nikah must exist, it does not necessarily come from a bride side, but may come from a bridegroom side. Moreover, the order of wali nikah may differ from what is compiled in Islamic legal thought (fiqh)