Realization of an all-optical zero to pi cross-phase modulation jump.

We report on the experimental demonstration of an all-optical pi cross-phase modulation jump. By performing a preselection, an optically induced unitary transformation, and then a postselection on the polarization degree of freedom, the phase of the output beam acquires either a zero or pi phase shift (with no other possible values). The postselection results in optical loss in the output beam.

Discordant genotypic interpretation and phenotypic role of protease mutations in HIV-1 subtypes B and G.

Objectives: HIV-1 group M is classified into nine different subtypes. Most antiretroviral (ARV) drugs have been developed for subtype B, and the response of non-B subtypes in terms of susceptibility and the acquisition of drug resistance when facing those drugs is largely unknown. In this study, we aimed to address differences in the impact of protease inhibitor (PI)-selected mutations on subtypes B and G.

The rise and fall of K65R in a Portuguese HIV-1 Drug Resistance database, despite continuously increasing use of tenofovir.

Objective: The overall prevalence of the K65R mutation in HIV-1 reverse transcriptase has increased in treatment-experienced patients, mostly attributed to the increasing use of tenofovir (TDF). A number of TDF-based regimens are associated with high rate of early virological failure. In this study, we evaluated the impact of these combinations on K65R selection over time.

Hypothalamic control of hepatic glucose production and its potential role in insulin resistance.

The liver plays a pivotal role in the regulation of glucose metabolism because it is the key organ that maintains glucose levels during fasting. An emerging body of literature has demonstrated the important role of the hypothalamus in controlling hepatic glucose production (HGP). The hypothalamus senses circulating nutrients and hormones, conveying the energy status to the central nervous system, which, in turn, controls HGP in part by way of the autonomic nervous system.

Bayesian network analyses of resistance pathways against efavirenz and nevirapine.

Objective: To clarify the role of novel mutations selected by treatment with efavirenz or nevirapine, and investigate the influence of HIV-1 subtype on nonnucleoside reverse transcriptase inhibitor (nNRTI) resistance pathways.

Design: By finding direct dependencies between treatment-selected mutations, the involvement of these mutations as minor or major resistance mutations against efavirenz, nevirapine, or coadministrated nucleoside analogue reverse transcriptase inhibitors (NRTIs) is hypothesized. In addition, direct dependencies were investigated between treatment-selected mutations and polymorphisms, some of which are linked with subtype, and between NRTI and nNRTI resistance pathways.

Modelled in vivo HIV fitness under drug selective pressure and estimated genetic barrier towards resistance are predictive for virological response.

Background: A method has been developed to estimate a fitness landscape experienced by HIV-1 under treatment selective pressure as a function of the genotypic sequence thereby also estimating the genetic barrier to resistance.

Methods: We evaluated the performance of two estimated fitness landscapes (nelfinavir [NFV] and zidovudine [AZT] plus lamivudine [3TC]) to predict week 12 viral load (VL) change for 176 treatment change episodes (TCEs) and probability of week 48 virological failure for 90 TCEs, in treatment experienced patients starting these drugs in combination.

Results: A higher genetic barrier for AZT plus 3TC, (quantified per additional mutation required to develop resistance against these drugs) was associated with a 0.

Preservation of energy-time entanglement in a slow light medium.

We demonstrate the preservation of entanglement of an energy-time entangled biphoton through a slow light medium. Using the D(1) and D(2) fine structure resonances of Rubidium, we delay one photon of the 1.5 THz biphoton by approximately 1.

Storage and retrieval of multimode transverse images in hot atomic Rubidium vapor.

We report on the experimental realization of the storage of images in a hot vapor of Rubidium atoms. The images are stored in and retrieved from the long-lived ground state atomic coherences. We show that an image impressed onto a 500 ns pulse can be stored and retrieved up to 30 mus later.

Impact of HIV-1 protease mutations A71V/T and T74S on M89I/V-mediated protease inhibitor resistance in subtype G isolates.

Objectives: Non-B human immunodeficiency virus (HIV)-1 subtypes possess several amino acid signatures in the viral protease that distinguish them from subtype B, some of which are reported as secondary drug-related mutations. We have previously shown a strong statistical interdependency of residues 71, 89 and 90 in subtype G, but the impact of substitutions on protease inhibitor (PI) resistance is unknown.

Patients And Methods: We selected subtype G viruses from patients with diverse amino acid combinations at codons 71 (A/T), 74 (T/S), 89 (I/L/M/V) and 90 (L/M).

The incidence of multidrug and full class resistance in HIV-1 infected patients is decreasing over time (2001-2006) in Portugal.

Despite improvements in HIV treatment, the prevalence of multidrug resistance and full class resistance is still reported to be increasing. However, to investigate whether current treatment strategies are still selecting for multidrug and full class resistance, the incidence, instead of the prevalence, is more informative. Temporal trends in multidrug resistance (MDR defined as at most 1 drug fully susceptible) and full class resistance (FCR defined as no drug in this class fully susceptible) in Portugal based on 3394 viral isolates genotyped from 2000 to 2006 were examined using the Rega 6.

Slow-light fourier transform interferometer.

We describe a new type of Fourier transform (FT) interferometer in which the tunable optical delay between the two arms is realized by using a continuously variable slow-light medium instead of a moving arm as in a conventional setup. The spectral resolution of such a FT interferometer exceeds that of a conventional setup of comparable size by a factor equal to the maximum group index of the slow-light medium. The scheme is experimentally demonstrated by using a rubidium atomic vapor cell as the tunable slow-light medium, and the spectral resolution is enhanced by a factor of approximately 100.

Estimation of an in vivo fitness landscape experienced by HIV-1 under drug selective pressure useful for prediction of drug resistance evolution during treatment.

Motivation: HIV-1 antiviral resistance is a major cause of antiviral treatment failure. The in vivo fitness landscape experienced by the virus in presence of treatment could in principle be used to determine both the susceptibility of the virus to the treatment and the genetic barrier to resistance. We propose a method to estimate this fitness landscape from cross-sectional clinical genetic sequence data of different subtypes, by reverse engineering the required selective pressure for HIV-1 sequences obtained from treatment naive patients, to evolve towards sequences obtained from treated patients.

Characterization of a novel and selective cannabinoid CB1 receptor inverse agonist, Imidazole 24b, in rodents.

We document in vitro and in vivo effects of a novel, selective cannabinoid CB(1) receptor inverse agonist, Imidazole 24b (5-(4-chlorophenyl)-N-cyclohexyl-4-(2,4-dichlorophenyl)-1-methyl-imidazole-2-carboxamide). The in vitro binding affinity of Imidazole 24b for recombinant human and rat CB(1) receptor is 4 and 10 nM, respectively. Imidazole 24b binds to human cannabinoid CB(2) receptor with an affinity of 297 nM; in vitro, it is a receptor inverse agonist at both cannabinoid CB(1) and CB(2) receptors as it causes a further increase of forskolin-induced cAMP increase.

Estimating the relative contribution of dNTP pool imbalance and APOBEC3G/3F editing to HIV evolution in vivo.

The human immunodeficiency virus (HIV) has a genome that is rich in adenine, and its rapid evolution shows an observed bias of guanine (G) to adenine (A) mutations. Two mechanisms have been proposed to explain these properties: (1) an imbalance in dNTP pool concentrations which drives the misincorporation process during reverse transcription, and (2) cytidine deamination by the APOBEC3G/3F restriction factor, causing G to A mutations most notably in specific dinucleotide contexts. Although crucial to understanding HIV evolution, current estimates on misincorporation bias during the replication cycle are based on scarce in vitro measurements.

Characterization of the NOD/scid-[Tg]DR1 mouse expressing HLA-DRB1*01 transgene: a model of SCID-hu mouse for vaccine development.

Objective: We previously showed enhanced engraftment of human T cells in the transgenic NonObese Diabetic/severe combined immunodeficient (NOD/scid)-DR1 mice, compared to NOD/scid mice. We now characterize their immunobiology, innate immunity, and intrahepatic neonatal engraftment of cord blood mononuclear cells (CBMNC), and test immune responses of these chimeric mice to an experimental cancer vaccine.

Methods: Fluorescence in situ hybridization analysis, blood biochemistry, hematology, and fluorescein-activated cell sorting analyses of cellular subsets were performed on NOD/scid-DR1 mice, in comparison to parental NOD/scid mice.

Amino acid pairing at the N- and C-termini of helical segments in proteins.

A systematic survey was carried out in an unbiased sample of 815 protein chains with a maximum of 20% homology selected from the Protein Data Bank, whose structures were solved at a resolution higher than 1.6 A and with a R-factor lower than 25%. A set of 5556 subsequences with alpha-helix or 3(10)-helix motifs was extracted from the protein chains considered.

Recombination confounds the early evolutionary history of human immunodeficiency virus type 1: subtype G is a circulating recombinant form.

Human immunodeficiency virus type 1 (HIV-1) is classified in nine subtypes (A to D, F, G, H, J, and K), a number of subsubtypes, and several circulating recombinant forms (CRFs). Due to the high level of genetic diversity within HIV-1 and to its worldwide distribution, this classification system is widely used in fields as diverse as vaccine development, evolution, epidemiology, viral fitness, and drug resistance. Here, we demonstrate how the high recombination rates of HIV-1 may confound the study of its evolutionary history and classification.

Wide-bandwidth, tunable, multiple-pulse-width optical delays using slow light in cesium vapor.

We demonstrate an all-optical delay line in hot cesium vapor that tunably delays 275 ps input pulses up to 6.8 ns and 740 input ps pulses up to 59 ns (group index of approximately 200) with little pulse distortion. The delay is made tunable with a fast reconfiguration time (hundreds of ns) by optically pumping out of the atomic ground states.

Endothelial dysfunction is related to insulin resistance and inflammatory biomarker levels in obese prepubertal children.

Background: The metabolic syndrome (MS) is associated with insulin resistance (IR), a systemic low-grade inflammatory state and endothelial dysfunction. These disorders may arise at a very early age in obese children. This study aimed to investigate the relationship between endothelial dysfunction and both IR and inflammation in prepubertal obese children.

Molecular epidemiology and prevalence of drug resistance-associated mutations in newly diagnosed HIV-1 patients in Portugal.

Background: Drug resistance transmission in newly diagnosed, drug-naïve HIV-1 infected individuals has been previously reported, with rates ranging from 5 to 27%. The aim of this study is to investigate the prevalence of resistance-associated mutations in drug-naïve, newly diagnosed patients, as well as monitoring the diversity of HIV-1 strains circulating in Portugal.

Methods: One hundred eighty samples from newly diagnosed patients were prospectively collected during 2003, according to the distribution of HIV-1 infections in Portugal.

All-optical delay of images using slow light.

Two-dimensional images carried by optical pulses (2 ns) are delayed by up to 10 ns in a 10 cm cesium vapor cell. By interfering the delayed images with a local oscillator, the transverse phase and amplitude profiles of the images are shown to be preserved. It is further shown that delayed images can be well preserved even at very low light levels, where each pulse contains on average less than one photon.

Antiretroviral resistance in different HIV-1 subtypes: impact on therapy outcomes and resistance testing interpretation.

Purpose Of Review: This review summarizes our knowledge of HIV-1 subtype-related differences associated with antiretroviral drug resistance and its interpretation, and with clinical, immunological and virological therapy outcomes. It also addresses the problem that subtypes are only a crude classification of the genetic diversity relevant to these topics.

Recent Findings: Subtype-related variability is responsible for differences in drug resistance.

Bayesian network analysis of resistance pathways against HIV-1 protease inhibitors.

Interpretation of Human Immunodeficiency Virus 1 (HIV-1) genotypic drug resistance is still a major challenge in the follow-up of antiviral therapy in infected patients. Because of the high degree of HIV-1 natural variation, complex interactions and stochastic behaviour of evolution, the role of resistance mutations is in many cases not well understood. Using Bayesian network learning of HIV-1 sequence data from diverse subtypes (A, B, C, F and G), we could determine the specific role of many resistance mutations against the protease inhibitors (PIs) nelfinavir (NFV), indinavir (IDV), and saquinavir (SQV).