Evolution of replication efficiency following infection with a molecularly cloned feline immunodeficiency virus of low virulence

The development of an effective vaccine against human immunodeficiency virus is considered to be the most practicable means of controlling the advancing global AIDS epidemic. Studies with the domestic cat have demonstrated that vaccinal immunity to infection can be induced against feline immunodeficiency virus (FIV); however, protection is largely restricted to laboratory strains of FIV and does not extend to primary strains of the virus. We compared the pathogenicity of two prototypic vaccine challenge strains of FIV derived from molecular clones; the laboratory strain PET<sub>F14</sub> and the primary strain GL8<sub>414</sub>. PET<sub>F14</sub> established a low viral load and had no effect on CD4<sup>+</sup>- or CD8<sup>+</sup>- lymphocyte subsets. In contrast, GL8<sub>414</sub> established a high viral load and induced a significant reduction in the ratio of CD4<sup>+</sup> to CD8<sup>+</sup> lymphocytes by 15 weeks postinfection, suggesting that PET<sub>F14</sub> may be a low-virulence-challenge virus. However, during long-term monitoring of the PET<sub>F14</sub>-infected cats, we observed the emergence of variant viruses in two of three cats. Concomitant with the appearance of the variant viruses, designated 627<sub>W135</sub> and 628<sub>W135</sub>, we observed an expansion of CD8<sup>+</sup>-lymphocyte subpopulations expressing reduced CD8 ß-chain, a phenotype consistent with activation. The variant viruses both carried mutations that reduced the net charge of the V3 loop (K409Q and K409E), giving rise to a reduced ability of the Env proteins to both induce fusion and to establish productive infection in CXCR4-expressing cells. Further, following subsequent challenge of naïve cats with the mutant viruses, the viruses established higher viral loads and induced more marked alterations in CD8<sup>+</sup>-lymphocyte subpopulations than did the parent F14 strain of virus, suggesting that the E409K mutation in the PET<sub>F14</sub> strain contributes to the attenuation of the virus

Structure Functions are not Parton Probabilities

The common view that structure functions measured in deep inelastic lepton scattering are determined by the probability of finding quarks and gluons in the target is not correct in gauge theory. We show that gluon exchange between the fast, outgoing partons and target spectators, which is usually assumed to be an irrelevant gauge artifact, affects the leading twist structure functions in a profound way. This observation removes the apparent contradiction between the projectile (eikonal) and target (parton model) views of diffractive and small x_{Bjorken} phenomena. The diffractive scattering of the fast outgoing quarks on spectators in the target causes shadowing in the DIS cross section. Thus the depletion of the nuclear structure functions is not intrinsic to the wave function of the nucleus, but is a coherent effect arising from the destructive interference of diffractive channels induced by final state interactions. This is consistent with the Glauber-Gribov interpretation of shadowing as a rescattering effect.Comment: 35 pages, 8 figures. Discussion of physical consequences of final state interactions amplified. Material on light-cone gauge choices adde

Modafinil reduces patient-reported tiredness after sedation/analgesia but does not improve patient psychomotor skills

Background: Early recovery of patients following sedation/analgesia and anesthesia is important in ambulatory practice. The aim of this study was to assess whether modafinil, used for the treatment of narcolepsy, improves recovery following sedation/analgesia. Methods: Patients scheduled for extracorporeal shock wave lithotripsy were randomly assigned to one of four groups. Two groups received a combination of fentanyl/midazolam with either modafinil or placebo. The remaining groups received remifentanil/propofol with either modafinil or placebo. Modafinil 200 mg was administered to the treatment group patients 1 h before sedation/analgesia. Groups were compared using the digital symbol substitution test (DSST), trail making test (TMT), observer scale of sedation and analgesia (OAA/S) and Aldrete score. Verbal rating scale (VRS) scores for secondary outcome variables e.g. energy, tiredness and dizziness were also recorded before and after treatment. Results: Sixty-seven patients successfully completed the study. Groups received similar doses of sedation and analgesic drugs. No statistically significant difference was found for DSST between groups. No significant adverse effects occurred in relation to modafinil. No statistically significant difference between groups was identified for TMT, OAA/S and Aldrete scores. The mean VRS score for tiredness was lesser in the modafinil/fentanyl/midazolam group [1.3 (2.0)] compared with the placebo group [3.8 (2.5)], P=0.02. Such a difference was not found between the remifentanil/propofol groups [placebo 2.6 (2.2) vs. modafinil 3.1(2.7)], p&gt;0.05. Dizziness was greater in the modafinil/remifentanil/propofol group 1.7 (2.0) vs. placebo 0.0 (0.5), p&lt;0.05. Conclusion: Modafinil reduces patient-reported tiredness after sedation/analgesia but does not improve recovery in terms of objective measures of patient psychomotor skills.</p

Modafinil reduces patient-reported tiredness after sedation/analgesia but does not improve patient psychomotor skills

Background: Early recovery of patients following sedation/analgesia and anesthesia is important in ambulatory practice. The aim of this study was to assess whether modafinil, used for the treatment of narcolepsy, improves recovery following sedation/analgesia. Methods: Patients scheduled for extracorporeal shock wave lithotripsy were randomly assigned to one of four groups. Two groups received a combination of fentanyl/midazolam with either modafinil or placebo. The remaining groups received remifentanil/propofol with either modafinil or placebo. Modafinil 200 mg was administered to the treatment group patients 1 h before sedation/analgesia. Groups were compared using the digital symbol substitution test (DSST), trail making test (TMT), observer scale of sedation and analgesia (OAA/S) and Aldrete score. Verbal rating scale (VRS) scores for secondary outcome variables e.g. energy, tiredness and dizziness were also recorded before and after treatment. Results: Sixty-seven patients successfully completed the study. Groups received similar doses of sedation and analgesic drugs. No statistically significant difference was found for DSST between groups. No significant adverse effects occurred in relation to modafinil. No statistically significant difference between groups was identified for TMT, OAA/S and Aldrete scores. The mean VRS score for tiredness was lesser in the modafinil/fentanyl/midazolam group [1.3 (2.0)] compared with the placebo group [3.8 (2.5)], P=0.02. Such a difference was not found between the remifentanil/propofol groups [placebo 2.6 (2.2) vs. modafinil 3.1(2.7)], p&gt;0.05. Dizziness was greater in the modafinil/remifentanil/propofol group 1.7 (2.0) vs. placebo 0.0 (0.5), p&lt;0.05. Conclusion: Modafinil reduces patient-reported tiredness after sedation/analgesia but does not improve recovery in terms of objective measures of patient psychomotor skills.</p

A Two-dimensional Superconductor in a Tilted Magnetic Field - new states with finite Cooper-pair momentum

Varying the angle Theta between applied field and the conducting planes of a layered superconductor in a small interval close to the plane-parallel field direction, a large number of superconducting states with unusual properties may be produced. For these states, the pair breaking effect of the magnetic field affects both the orbital and the spin degree of freedom. This leads to pair wave functions with finite momentum, which are labeled by Landau quantum numbers 0<n<\infty. The stable order parameter structure and magnetic field distribution for these states is found by minimizing the quasiclassical free energy near H_{c2} including nonlinear terms. One finds states with coexisting line-like and point-like order parameter zeros and states with coexisting vortices and antivortices. The magnetic response may be diamagnetic or paramagnetic depending on the position within the unit cell. The structure of the Fulde-Ferrell-Larkin-Ovchinnikov (FFLO) states at Theta=0 is reconsidered. The transition n->\infty of the paramagnetic vortex states to the FFLO-limit is analyzed and the physical reason for the occupation of higher Landau levels is pointed out.Comment: 24 pages, 11 figure

Quantum Lattice Solitons

The number state method is used to study soliton bands for three anharmonic quantum lattices: i) The discrete nonlinear Schr\"{o}dinger equation, ii) The Ablowitz-Ladik system, and iii) A fermionic polaron model. Each of these systems is assumed to have $f$-fold translational symmetry in one spatial dimension, where $f$ is the number of freedoms (lattice points). At the second quantum level $(n=2)$ we calculate exact eigenfunctions and energies of pure quantum states, from which we determine binding energy $(E_{\rm b})$, effective mass $(m^{*})$ and maximum group velocity $(V_{\rm m})$ of the soliton bands as functions of the anharmonicity in the limit $f \to \infty$. For arbitrary values of $n$ we have asymptotic expressions for $E_{\rm b}$, $m^{*}$, and $V_{\rm m}$ as functions of the anharmonicity in the limits of large and small anharmonicity. Using these expressions we discuss and describe wave packets of pure eigenstates that correspond to classical solitons.Comment: 21 pages, 1 figur

Multimodal Highlighting of Structural Abnormalities in Diabetic Rat and Human Corneas.

PURPOSE: This study aimed to highlight structural corneal changes in a model of type 2 diabetes, using in vivo corneal confocal microscopy (CCM). The abnormalities were also characterized by transmission electron microscopy (TEM) and second harmonic generation (SHG) microscopy in rat and human corneas. METHODS: Goto-Kakizaki (GK) rats were observed at age 12 weeks (n = 3) and 1 year (n = 6), and compared to age-matched controls. After in vivo CCM examination, TEM and SHG microscopy were used to characterize the ultrastructure and the three-dimensional organization of the abnormalities. Human corneas from diabetic (n = 3) and nondiabetic (n = 3) patients were also included in the study. RESULTS: In the basal epithelium of GK rats, CCM revealed focal hyper-reflective areas, and histology showed proliferative cells with irregular basement membrane. In the anterior stroma, extracellular matrix modifications were detected by CCM and confirmed in histology. In the Descemet's membrane periphery of all the diabetic corneas, hyper-reflective deposits were highlighted using CCM and characterized as long-spacing collagen fibrils by TEM. SHG microscopy revealed these deposits with high contrast, allowing specific detection in diabetic human and rat corneas without preparation and characterization of their three-dimensional organization. CONCLUSION: Pathologic findings were observed early in the development of diabetes in GK rats. Similar abnormalities have been found in corneas from diabetic patients. TRANSLATIONAL RELEVANCE: This multidisciplinary study highlights diabetes-induced corneal abnormalities in an animal model, but also in diabetic donors. This could constitute a potential early marker for diagnosis of hyperglycemia-induced tissue changes

Edge states of graphene bilayer strip

The electronic structure of the zig-zag bilayer strip is analyzed. The electronic spectra of the bilayer strip is computed. The dependence of the edge state band flatness on the bilayer width is found. The density of states at the Fermi level is analytically computed. It is shown that it has the singularity which depends on the width of the bilayer strip. There is also asymmetry in the density of states below and above the Fermi energy.Comment: 9 page

Connectivity in MEG resting-state networks increases after resective surgery for low-grade glioma and correlates with improved cognitive performance☆

Purpose Low-grade glioma (LGG) patients often have cognitive deficits. Several disease- and treatment related factors affect cognitive processing. Cognitive outcome of resective surgery is unpredictable, both for improvement and deterioration, especially for complex domains such as attention and executive functioning. MEG analysis of resting-state networks (RSNs) is a good candidate for presurgical prediction of cognitive outcome. In this study, we explore the relation between alterations in connectivity of RSNs and changes in cognitive processing after resective surgery, as a stepping stone to ultimately predict postsurgical cognitive outcome. Methods: Ten patients with LGG were included, who had no adjuvant therapy. MEG recording and neuropsychological assessment were obtained before and after resective surgery. MEG data were recorded during a no-task eyes-closed condition, and projected to the anatomical space of the AAL atlas. Alterations in functional connectivity, as characterized by the phase lag index (PLI), within the default mode network (DMN), executive control network (ECN), and left- and right-sided frontoparietal networks (FPN) were compared to cognitive changes. Results: Lower alpha band DMN connectivity was increased after surgery, and this increase was related to improved verbal memory functioning. Similarly, right FPN connectivity was increased after resection in the upper alpha band, which correlated with improved attention, working memory and executive functioning. Discussion Increased alpha band RSN functional connectivity in MEG recordings correlates with improved cognitive outcome after resective surgery. The mechanisms resulting in functional connectivity alterations after resection remain to be elucidated. Importantly, our findings indicate that connectivity of MEG RSNs may be used for presurgical prediction of cognitive outcome in future studies