Internal flows and energy circulation in light beams

We review optical phenomena associated with the internal energy redistribution which accompany propagation and transformations of monochromatic light fields in homogeneous media. The total energy flow (linear-momentum density, Poynting vector) can be divided into spin part associated with the polarization and orbital part associated with the spatial inhomogeneity. We give general description of the internal flows in the coordinate and momentum (angular spectrum) representations for both nonparaxial and paraxial fields. This enables one to determine local densities and integral values of the spin and orbital angular momenta of the field. We analyse patterns of the internal flows in standard beam models (Gaussian, Laguerre-Gaussian, flat-top beam, etc.), which provide an insightful picture of the energy transport. The emphasize is made to the singular points of the flow fields. We describe the spin-orbit and orbit-orbit interactions in the processes of beam focusing and symmetry breakdown. Finally, we consider how the energy flows manifest themselves in the mechanical action on probing particles and in the transformations of a propagating beam subjected to a transverse perturbation.Comment: 50 pages, 21 figures, 173 references. This is the final version of the manuscript (v1) modified in accord to the referee's remarks and with allowance for the recent development. The main changes are: additional discussion of the energy flows in Bessel beams (section 4.1), a lot of new references are added and the Conclusion is shortened and made more accurat

Retropubic, laparoscopic and mini-laparoscopic radical prostatectomy : a prospective assessment of patient scar satisfaction

Published online: 26 October 2014PURPOSE: To compare patient scar satisfaction after retropubic, standard laparoscopic, mini-laparoscopic (ML) and open radical prostatectomy (RP). METHODS: Patients undergoing RP for a diagnosis of localized prostate cancer at a single academic hospital between September 2012 and December 2013 were enrolled in this prospective nonrandomized study. The patients were included in three study arms: open surgery, VLP and ML. A skin stapler was used for surgical wound closure in all cases. Demographic and main surgical outcomes, including perioperative complications, were analyzed. Surgical scar satisfaction was measured using the Patient and Observer Scar Assessment Questionnaire (POSAS) and the two Body Image Questionnaire (BIQ) scales, respectively, recorded at skin clips removal and either at 6 months after surgery. RESULTS: Overall, 32 patients were enrolled and completed the 6 month of follow-up. At clips removal, laparoscopic approaches offered better scar result than open surgery according to the POSAS. However, at 6 months, no differences were detected between VLP and open, whereas ML was still associated with a better scar outcome (p = 0.001). This finding was also confirmed by both BIQ scales, including the body image score (ML 9.8 ± 1.69, open 15.73 ± 3.47, VLP 13.27 ± 3.64; p = 0.001) and the cosmetic score (ML 16.6 ± 4.12, open 10 ± 1.9, LP 12.91 ± 3.59; p = 0.001). Small sample size and lack of randomization represent the main limitations of this study. CONCLUSIONS: ML RP offers a better cosmetic outcome when compared to both open and standard laparoscopic RP, representing a step toward minimal surgical scar. The impact of scar outcome on RP patients' quality of life remains to be determined

Candidate Vaccine Sequences to Represent Intra- and Inter-Clade HIV-1 Variation

A likely key factor in the failure of a HIV-1 vaccine based on cytotoxic T lymphocytes (CTL) is the natural immunodominance of epitopes that fall in variable regions of the proteome, which both increases the chance of epitope sequence mismatch with the incoming challenge strain and replicates the pathogenesis of early CTL failure due to epitope escape mutation during natural infection. To identify potential vaccine sequences to focus the CTL response on highly conserved epitopes, the whole proteomes of HIV-1 clades A1, B, C, and D were assessed for Shannon entropy at each amino acid position. Highly conserved regions in Gag (cGag-1, Gag 148–214, and cGag-2, Gag 253–331), Env (cEnv, Env 521–606), and Nef (cNef, Nef 106–148) were identified across clades. Inter- and intra-clade variability of amino acids within the regions tended to overlap, suggesting that polyvalent representation of consensus sequences for the four clades would allow broad HIV-1 strain representation. These four conserved regions were rich in both known and predicted CTL epitopes presented by a breadth of HLA types, and screening of 54 persons with chronic HIV-1 infection revealed that these regions are commonly immunogenic in the context of natural infection. These data suggest that vaccine delivery of a 16-valent mixture of these regions could focus the CTL response against conserved epitopes that are broadly representative of circulating HIV-1 strains

Multiplex RT-PCR Amplification of HIV Genes to Create a Completely Autologous DC-Based Immunotherapy for the Treatment of HIV Infection

BACKGROUND: Effective therapy for HIV-infected individuals remains an unmet medical need. Promising clinical trials with dendritic cell (DC)-based immunotherapy consisting of autologous DC loaded with autologous virus have been reported, however, these approaches depend on large numbers of HIV virions to generate sufficient doses for even limited treatment regimens. METHODOLOGY/PRINCIPAL FINDINGS: The present study describes a novel approach for RT-PCR amplification of HIV antigens. Previously, RT-PCR amplification of autologous viral sequences has been confounded by the high mutation rate of the virus which results in unreliable primer-template binding. To resolve this problem we developed a multiplex RT-PCR strategy that allows reliable strain-independent amplification of highly polymorphic target antigens from any patient and requires neither viral sequence data nor custom-designed PCR primers for each individual. We demonstrate the application of our RT-PCR process to amplify translationally-competent RNA encoding regions of Gag, Vpr, Rev and Nef. The products amplified using this method represent a complex mixture of autologous antigens encoded by viral quasispecies. We further demonstrate that DCs electroporated with in vitro-transcribed HIV RNAs are capable of stimulating poly-antigen-specific CD8+ T cell responses in vitro. CONCLUSION/SIGNIFICANCE: This study describes a strategy to overcome patient to patient viral diversity enabling strain-independent RT-PCR amplification of RNAs encoding sequence divergent quasispecies of Gag, Vpr, Rev and Nef from small volumes of infectious plasma. The approach allows creation of a completely autologous therapy that does not require advance knowledge of the HIV genomic sequences, does not have yield limitations and has no intact virus in the final product. The simultaneous use of autologous viral antigens and DCs may provoke broad patient-specific immune responses that could potentially induce effective control of viral loads in the absence of conventional antiretroviral drug therapy

HLA Alleles Associated with Slow Progression to AIDS Truly Prefer to Present HIV-1 p24

Background: The mechanism behind the association between human leukocyte antigen (HLA) molecules and the rate of HIV-1 disease progression is still poorly understood. Recent data suggest that ‘‘protective’’ HLA molecules, i.e. those associated with a low HIV-1 viral load and relatively slow disease progression, tend to present epitopes from the Gag capsid protein. Although this suggests that preferential targeting of Gag delays disease progression, the apparent preference for Gag could also be a side-effect of the relatively high immunogenicity of the protein. Methods and Findings: To separate cause and effect, we predicted HIV-1 epitopes from the whole genome of HIV-1, and found that protective HLA alleles have a true preference for the p24 Gag protein, while non-protective HLA alleles preferentially target HIV-1 Nef. In line with this, we found a significant negative correlation between the predicted affinity of the best-binding p24 epitopes and the relative hazard of HIV-1 disease progression for a large number of HLA molecules. When the epitopes targeted by protective HLA alleles were mapped to the known p24 structure, we found that mutations in these epitopes are likely to disturb the p24 dimer structure, which is expected to severely reduce the fitness of the virus. Conclusions: Our results suggest that the intrinsic preference of different HLA molecules to present p24 peptides explains why some HLA molecules are more protective than others

Unique CRF01_AE Gag CTL Epitopes Associated with Lower HIV-Viral Load and Delayed Disease Progression in a Cohort of HIV-Infected Thais

Cytotoxic T Lymphocytes (CTLs) play a central role in controlling HIV-replication. Although numerous CTL epitopes have been described, most are in subtype B or C infection. Little is known about CTL responses in CRF01_AE infection. Gag CTL responses were investigated in a cohort of 137 treatment-naïve HIV-1 infected Thai patients with high CD4+ T cell counts, using gIFN Enzyme-Linked Immunospot (ELISpot) assays with 15-mer overlapping peptides (OLPs) derived from locally dominant CRF01_AE Gag sequences. 44 OLPs were recognized in 112 (81.8%) individuals. Both the breadth and magnitude of the CTL response, particularly against the p24 region, positively correlated with CD4+ T cell count and inversely correlated with HIV viral load. The breadth of OLP response was also associated with slower progression to antiretroviral therapy initiation. Statistical analysis and single peptide ELISpot assay identified at least 17 significant associations between reactive OLP and HLA in 12 OLP regions; 6 OLP-HLA associations (35.3%) were not compatible with previously reported CTL epitopes, suggesting that these contained new CTL Gag epitopes. A substantial proportion of CTL epitopes in CRF01_AE infection differ from subtype B or C. However, the pattern of protective CTL responses is similar; Gag CTL responses, particularly against p24, control viral replication and slow clinical progression