A rare cryptic translation product is presented by Kb major histocompatibility complex class I molecule to alloreactive T cells.

The identity of allogeneic peptide/major histocompatibility complex (MHC) complexes that elicit vigorous T cell responses has remained an interesting problem for both practical and theoretical reasons. Although a few abundant MHC class I-bound peptides have been purified and sequenced, identifying the unique T cell-stimulating peptides from among the thousands of existing peptides is still a very difficult undertaking. In this report, we identified the antigenic peptide that is recognized by an alloreactive bm1 anti-B6 T cell clone using a novel genetic strategy that is based upon measurement of T cell receptor occupancy in single T cells. Using lacZ-inducible T cells as a probe, we screened a splenic cDNA library in transiently transfected antigen-presenting cells (APCs) and isolated a cDNA clone that allowed expression of the appropriate peptide/Kb MHC complex in APC. The antigenic octapeptide (SVVEFSSL) exactly matched the consensus Kb MHC motif, but was surprisingly encoded by a non-ATG defined translation reading frame. Furthermore, the abundance of the naturally processed analog in untransfected cells was estimated to be <10 copies per cell. These results illustrate a novel strategy for identifying T cell-stimulating antigens in general and directly show that alloreactive T cells can respond to rather rare peptide/MHC complexes. These results also suggest that the total pool of processed peptides expressed on the APC surface may include those generated by cryptic translation of normally expressed transcripts

Neuroprotective role of statins in treating Alzheimer's disease: a comparative study of biomedical and clinical trials

Thesis (M.A.)--Boston UniversityAlzheimer’s disease is a neurodegenerative disorder that occurs most commonly in the elderly. The formation of amyloid plaques and neurofibrillary tangles affects the brain tissue, causing mental deficits ranging in severity from memory loss to incontinence and feeding problems. Currently, the only approved treatments are designed to treat the symptoms of the disease, rather than prevention or slowing the progression. Yet, over the course of the last few decades, researchers have sought new ways of treating the condition. One such drug with promising effects is the cholesterol lowering statin medication. Yet the efficacy shown in the laboratory has not translated to clinical trials to treat AD patients. Therefore, this study analyzed various important biomedical and clinical studies in the literature to elucidate why this disparity exists. On examination of biomedical studies, there was a wide range of support for statins due to its many pleiotropic effects. This drug was shown to be permeable through the blood brain barrier, helping to reverse the damage caused by amyloid plaque formation in brain vessel walls. Other studies showed the link between high cholesterol and AD by analyzing the effects of memory deficits in mice while they attempted various tasks. They used analogs to simulate the disease and found that statins helped delay or reverse some of these changes. On examination of clinical studies, the majority of studies could not find a statistically significant correlation between statin use and neuroprotection against AD. Those that did find a positive correlation needed further study to account for any confounding variables. After examination of these papers it became clear that the disparity between the two realms of study was due to the design of the experiments themselves. The biomedical studies focused on various effects of statins rather than on how the mechanisms of action directly affected AD progression. As of yet not all of the pleiotropic effects have been examined and definitely not within the context of how they effect and complement one another. Thus clinical trials trying to integrate this information have been very discouraging and the designs of these studies, both prospective trials and epidemiological studies further complicate the answers sought. They all varied in the age groups they examined, how early treatment was initiated, which statin was used, and how other confounding variables (such as sociodemographics and smoking) were accounted for. After analyzing the literature, it is in our opinion that statins play a protective role if initiated much earlier than the first clinical signs. However the only way to know how it biochemically may help AD patients is through further study. So, it is our recommendation for more in depth study on the pleiotropic effects of statins on AD, before further clinical intervention occurs

Multi-wavelength Observations of the Giant X-ray Flare Galaxy NGC 5905: signatures of tidal disruption

NGC 5905 is one of the few galaxies with no prior evidence for an AGN in which an X-ray flare, due to the tidal disruption of a star by the massive black hole in the center of the galaxy, was detected by the RASS in 1990-91. Here we present analysis of late-time follow-up observations of NGC 5905 using Chandra, Spitzer VLA 3 GHz and 8 GHz archival data and GMRT 1.28 GHz radio observations. The X-ray image shows no compact source that could be associated with an AGN. Instead, the emission is extended -- likely due to nuclear star formation and the total measured X-ray luminosity is comparable to the X-ray luminosity determined from the 2002 Chandra observations. Diffuse X-ray emission was detected close to the circum-nuclear star forming ring. The Spitzer 2006 mid-infrared spectrum also shows strong evidence of nuclear star formation but no clear AGN signatures. The semi-analytical models of Tommasin et. al. 2010 together with the measured [OIV]/[NeII] line ratio suggest that at most only 5.6% of the total IR Flux at 19 $\mu$m is being contributed by the AGN. The GMRT 1.28 GHz observations reveal a nuclear source. In the much higher resolution VLA 3 GHz map, the emission has a double lobed structure of size 2.7'' due to the circumnuclear star forming ring. The GMRT 1.28 GHz peak emission coincides with the center of the circumnuclear ring. We did not detect any emission in the VLA 8 GHz (1996) archival data. The 3 $\sigma$ upper limits for the radio afterglow of the TDE at 1.28 GHz, 3 GHz and 8 GHz are 0.17 mJy, 0.09 mJy and 0.09 mJy, respectively. Our studies thus show that (i) NGC 5905 has a declining X-ray flux consistent with a TDE, (ii) the IR flux is dominated by nuclear star formation, (iii) the nuclear radio emission observed from the galaxy is due to circumnuclear star formation, (iv) no compact radio emission associated with a radio afterglow from the TDE is detected.Comment: 12 pages, 8 figures, accepted to be published in Astrophysics and Space Scienc

SIMPEL: Circuit model for photonic spike processing laser neurons

We propose an equivalent circuit model for photonic spike processing laser neurons with an embedded saturable absorber---a simulation model for photonic excitable lasers (SIMPEL). We show that by mapping the laser neuron rate equations into a circuit model, SPICE analysis can be used as an efficient and accurate engine for numerical calculations, capable of generalization to a variety of different laser neuron types found in literature. The development of this model parallels the Hodgkin--Huxley model of neuron biophysics, a circuit framework which brought efficiency, modularity, and generalizability to the study of neural dynamics. We employ the model to study various signal-processing effects such as excitability with excitatory and inhibitory pulses, binary all-or-nothing response, and bistable dynamics.Comment: 16 pages, 7 figure

Dynamical laser spike processing

Novel materials and devices in photonics have the potential to revolutionize optical information processing, beyond conventional binary-logic approaches. Laser systems offer a rich repertoire of useful dynamical behaviors, including the excitable dynamics also found in the time-resolved "spiking" of neurons. Spiking reconciles the expressiveness and efficiency of analog processing with the robustness and scalability of digital processing. We demonstrate that graphene-coupled laser systems offer a unified low-level spike optical processing paradigm that goes well beyond previously studied laser dynamics. We show that this platform can simultaneously exhibit logic-level restoration, cascadability and input-output isolation---fundamental challenges in optical information processing. We also implement low-level spike-processing tasks that are critical for higher level processing: temporal pattern detection and stable recurrent memory. We study these properties in the context of a fiber laser system, but the addition of graphene leads to a number of advantages which stem from its unique properties, including high absorption and fast carrier relaxation. These could lead to significant speed and efficiency improvements in unconventional laser processing devices, and ongoing research on graphene microfabrication promises compatibility with integrated laser platforms.Comment: 13 pages, 7 figure

Principles of Neuromorphic Photonics

In an age overrun with information, the ability to process reams of data has become crucial. The demand for data will continue to grow as smart gadgets multiply and become increasingly integrated into our daily lives. Next-generation industries in artificial intelligence services and high-performance computing are so far supported by microelectronic platforms. These data-intensive enterprises rely on continual improvements in hardware. Their prospects are running up against a stark reality: conventional one-size-fits-all solutions offered by digital electronics can no longer satisfy this need, as Moore's law (exponential hardware scaling), interconnection density, and the von Neumann architecture reach their limits. With its superior speed and reconfigurability, analog photonics can provide some relief to these problems; however, complex applications of analog photonics have remained largely unexplored due to the absence of a robust photonic integration industry. Recently, the landscape for commercially-manufacturable photonic chips has been changing rapidly and now promises to achieve economies of scale previously enjoyed solely by microelectronics. The scientific community has set out to build bridges between the domains of photonic device physics and neural networks, giving rise to the field of \emph{neuromorphic photonics}. This article reviews the recent progress in integrated neuromorphic photonics. We provide an overview of neuromorphic computing, discuss the associated technology (microelectronic and photonic) platforms and compare their metric performance. We discuss photonic neural network approaches and challenges for integrated neuromorphic photonic processors while providing an in-depth description of photonic neurons and a candidate interconnection architecture. We conclude with a future outlook of neuro-inspired photonic processing.Comment: 28 pages, 19 figure

A study of vaginal misoprostol tablet versus intra cervical dinoprostone gel for the induction of labour

Background: This was a comparative study conducted to compare the effectiveness of 25 microgram of intravaginal misoprostol with intracervical dinoprostone gel in terms of efficacy of drug, feto-maternal outcome, side effects and complications of drugs.Methods: 400 nulliparas at term, admitted for induction of labor were included in this study. They were randomly selected to receive either intravaginal misoprostol or intracervical dinoprostone gel. Group A (200 women) recieved tablet misoprostol 25 micrograms vaginally 4 hrly to a maximum of 3 doses and Group B (200 women) received dinoprostone gel 0.5mg intracervically 6 hrly to a maximum of 3 doses. Comparison was done in terms of Induction to delivery interval, need for augmentation, LSCS and instrumentation rate, need for NICU admissions and cost effectiveness.Results: The mean induction to delivery interval was less in the misoprostol group than dinoprostone group (12.5 hrs vs. 20 hrs). 78% patients delivered in the first 24 hrs in misoprostol group compared to 52 % patients in dinoprostone group. Group A had a higher success rate (81% vs.76%) and also required less augmentation of labor ( 30% vs. 60%) compared to group B. Need for LSCS was also lower in misoprostol group (11% vs. 16%). Need for instrumentation and incidence of NICU admission was similar in both groups. Misoprostol was more cost effective compared to dinoprostone.Conclusions: The misoprostol group had a shorter induction to delivery interval, more number of deliveries in the first 24 hrs of induction and a reduced need of augmentation of labor with oxytocin. There was no significant difference in the rate of caesarean section, hyper-stimulation syndrome, neonatal and maternal morbidity between the two groups. Thus, misoprosol appears to be safer, cheaper and more efficacious alternative for induction of labor especially for non-fetal indications as compared to dinoprostone gel