Brain structural and functional recovery following initiation of combination antiretroviral therapy

NeuroAIDS persists in the era of combination antiretroviral therapies. We describe here the recovery of brain structure and function following 6 months of therapy in a treatment-naive patient presenting with HIV-associated dementia. The patient’s neuropsychological test performance improved and his total brain volume increased by more than 5 %. Neuronal functional connectivity measured by magnetoencephalography changed from a pattern identical to that observed in other HIV-infected individuals to one that was indistinguishable from that of uninfected control subjects. These data suggest that at least some of the effects of HIV on the brain can be fully reversed with treatment.

Phytostabilization of metals in mine soils using Brassica juncea in combination with organic amendments

Background and aims The high metal bioavailability and the poor conditions of mine soils yield a low plant biomass, limiting the application of phytoremediation techniques. A greenhouse experiment was performed to evaluate the effects of organic amendments on metal stabilization and the potential of Brassica juncea L. for phytostabilization in mine soils. Methods Plants were grown in pots filled with soils collected from two mine sites located in Central Spain mixed with 0, 30 and 60 tha?1 of pine bark compost and horse- and sheep-manure compost. Plant biomass and metal concentrations in roots and shoots were measured. Metal bioavailability was assessed using a rhizosphere-based method (rhizo), which consists of a mixture of low-molecular-weight organic acids to simulate root exudates. Results Manure reduced metal concentrations in shoots (10?50 % reduction of Cu and 40?80 % of Zn in comparison with non-amended soils), bioconcentration factor (10?50 % of Cu and 40?80 % of Zn) and metal bioavailability in soil (40?50 % of Cu and 10?30 % of Zn) due to the high pH and the contribution of organic matter. Manure improved soil fertility and was also able to increase plant biomass (5?20 times in shoots and 3?30 times in roots), which resulted in a greater amount of metals removed from soil and accumulated in roots (increase of 2?7 times of Cu and Zn). Plants grown in pine bark treatments and in non-amended soils showed a limited biomass and high metal concentrations in shoots. Conclusions The addition of manure could be effective for the stabilization of metals and for enhancing the phytostabilization ability of B. juncea in mine soils. In this study, this species resulted to be a potential candidate for phytostabilization in combination with manure, differing from previous results, in which B. juncea had been recognized as a phytoextraction plant.

Advanced background modeling with RGB-D sensors through classifiers combination and inter-frame foreground prediction

An innovative background modeling technique that is able to accurately segment foreground regions in RGB-D imagery (RGB plus depth) has been presented in this paper. The technique is based on a Bayesian framework that efficiently fuses different sources of information to segment the foreground. In particular, the final segmentation is obtained by considering a prediction of the foreground regions, carried out by a novel Bayesian Network with a depth-based dynamic model, and, by considering two independent depth and color-based mixture of Gaussians background models. The efficient Bayesian combination of all these data reduces the noise and uncertainties introduced by the color and depth features and the corresponding models. As a result, more compact segmentations, and refined foreground object silhouettes are obtained. Experimental results with different databases suggest that the proposed technique outperforms existing state-of-the-art algorithms.

Scalable UWB photonic generator based on the combination of doublet pulses

We propose and experimentally demonstrate a scalable and reconfigurable optical scheme to generate high order UWB pulses. Firstly, various ultra wideband doublets are created through a process of phase-tointensity conversion by means of a phase modulation and a dispersive media. In a second stage, doublets are combined in an optical processing unit that allows the reconfiguration of UWB high order pulses. Experimental results both in time and frequency domains are presented showing good performance related to the fractional bandwidth and spectral efficiency parameters.

A study of feature combination for vehicle detection based on image processing

Video analytics play a critical role in most recent traffic monitoring and driver assistance systems. In this context, the correct detection and classification of surrounding vehicles through image analysis has been the focus of extensive research in the last years. Most of the pieces of work reported for image-based vehicle verification make use of supervised classification approaches and resort to techniques, such as histograms of oriented gradients (HOG), principal component analysis (PCA), and Gabor filters, among others. Unfortunately, existing approaches are lacking in two respects: first, comparison between methods using a common body of work has not been addressed; second, no study of the combination potentiality of popular features for vehicle classification has been reported. In this study the performance of the different techniques is first reviewed and compared using a common public database. Then, the combination capabilities of these techniques are explored and a methodology is presented for the fusion of classifiers built upon them, taking into account also the vehicle pose. The study unveils the limitations of single-feature based classification and makes clear that fusion of classifiers is highly beneficial for vehicle verification.

Background foreground segmentation with RGB-D Kinect data: An efficient combination of classifiers

Low cost RGB-D cameras such as the Microsoft’s Kinect or the Asus’s Xtion Pro are completely changing the computer vision world, as they are being successfully used in several applications and research areas. Depth data are particularly attractive and suitable for applications based on moving objects detection through foreground/background segmentation approaches; the RGB-D applications proposed in literature employ, in general, state of the art foreground/background segmentation techniques based on the depth information without taking into account the color information. The novel approach that we propose is based on a combination of classifiers that allows improving background subtraction accuracy with respect to state of the art algorithms by jointly considering color and depth data. In particular, the combination of classifiers is based on a weighted average that allows to adaptively modifying the support of each classifier in the ensemble by considering foreground detections in the previous frames and the depth and color edges. In this way, it is possible to reduce false detections due to critical issues that can not be tackled by the individual classifiers such as: shadows and illumination changes, color and depth camouflage, moved background objects and noisy depth measurements. Moreover, we propose, for the best of the author’s knowledge, the first publicly available RGB-D benchmark dataset with hand-labeled ground truth of several challenging scenarios to test background/foreground segmentation algorithms.

An engineering modification of the blade element momentum combination applicable in vertical descent flight :fundamentals and validation

An engineering modification of blade element/momentum theory is applied to describe the vertical autorotation of helicopter rotors. A full non‐linear aerodynamic model is considered for the airfoils, taking into account the dependence of lift and drag coefficients on both the angle of attack and the Reynolds number. The proposed model, which has been validated in previous work, has allowed the identification of different autorotation modes, which depend on the descent velocity and the twist of the rotor blades. These modes present different radial distributions of driven and driving blade regions, as well as different radial upwash/downwash patterns. The number of blade sections with zero tangential force, the existence of a downwash region in the rotor disk, the stability of the autorotation state, and the overall rotor autorotation efficiency, are all analyzed in terms of the flight velocity and the characteristics of the rotor. It is shown that, in vertical autorotation, larger blade twist leads to smaller values of descent velocity for a given thrust generated by the rotor in the autorotational state.

A model-based approach for assessing in vivo combination therapy interactions

We present an approach for evaluating the efficacy of combination antitumor agent schedules that accounts for order and timing of drug administration. Our model-based approach compares in vivo tumor volume data over a time course and offers a quantitative definition for additivity of drug effects, relative to which synergism and antagonism are interpreted. We begin by fitting data from individual mice receiving at most one drug to a differential equation tumor growth/drug effect model and combine individual parameter estimates to obtain population statistics. Using two null hypotheses: (i) combination therapy is consistent with additivity or (ii) combination therapy is equivalent to treating with the more effective single agent alone, we compute predicted tumor growth trajectories and their distribution for combination treated animals. We illustrate this approach by comparing entire observed and expected tumor volume trajectories for a data set in which HER-2/neu-overexpressing MCF-7 human breast cancer xenografts are treated with a humanized, anti-HER-2 monoclonal antibody (rhuMAb HER-2), doxorubicin, or one of five proposed combination therapy schedules.

Concomitant combination therapy for HIV infection preferable over sequential therapy with 3TC and non-nucleoside reverse transcriptase inhibitors

Exposure to 3TC of HIV-1 mutant strains containing non-nucleoside reverse transcriptase inhibitor (NNRTI)-specific mutations in their reverse transcriptase (RT) easily selected for double-mutant viruses that had acquired the characteristic 184-Ile mutation in their RT in addition to the NNRTI-specific mutations. Conversely, exposure of 3TC-resistant 184-Val mutant HIV-1 strains to nine different NNRTIs resulted in the rapid emergence of NNRTI-resistant virus strains at a time that was not more delayed than when wild-type HIV-1(IIIB) was exposed to the same compounds. The RTs of these resistant virus strains had acquired the NNRTI-characteristic mutations in addition to the preexisting 184-Val mutation. Surprisingly, when the 184-Ile mutant HIV-1 was exposed to a variety of NNRTIs, the 188-His mutation invariably occurred concomitantly with the 184-Ile mutation in the HIV-1 RT. Breakthrough of this double-mutant virus was markedly accelerated as compared with the mutant virus selected from the wild-type or 184-Val mutant HIV-1 strain. The double (184-Ile + 188-His) mutant virus showed a much more profound resistance profile against the NNRTIs than the 188-His HIV-1 mutant. In contrast with the sequential chemotherapy, concomitant combination treatment of HIV-1-infected cells with 3TC and a variety of NNRTIs resulted in a dramatic delay of virus breakthrough and resistance development.

A peptide derived from the non-receptor-binding region of urokinase plasminogen activator inhibits glioblastoma growth and angiogenesis in vivo in combination with cisplatin

The urokinase plasminogen activator system is involved in angiogenesis and tumor growth of malignant gliomas, which are highly neovascularized and so may be amenable to antiangiogenic therapy. In this paper, we describe the activity of Å6, an octamer capped peptide derived from the non-receptor-binding region of urokinase plasminogen activator. Å6 inhibited human microvascular endothelial cell migration but had no effect on the proliferation of human microvascular endothelial cells or U87MG glioma cells in vitro. In contrast, Å6 or cisplatin (CDDP) alone suppressed subcutaneous tumor growth in vivo by 48% and 53%, respectively, and, more strikingly, the combination of Å6 plus CDDP inhibited tumor growth by 92%. Such combination treatment also greatly reduced the volume of intracranial tumor xenografts and increased survival of tumor-bearing animals when compared with CDDP or Å6 alone. Tumors from the combination treatment group had significantly reduced neovascularization, suggesting a mechanism involving Å6-mediated inhibition of endothelial cell motility, thereby eliciting vascular sensitivity to CDDP-mediated toxicity. These data suggest that the combination of an angiogenesis inhibitor that targets endothelial cells with a cytotoxic agent may be a useful therapeutic approach.

Use of cDNA subtraction and RNA interference screens in combination reveals genes required for germ-line development in Caenorhabditis elegans

Caenorhabditis elegans is an ideal organism for the study of the molecular basis of fundamental biological processes such as germ-line development, especially because of availability of the whole genome sequence and applicability of the RNA interference (RNAi) technique. To identify genes involved in germ-line development, we produced subtracted cDNA pools either enriched for or deprived of the cDNAs from germ-line tissues. We then performed differential hybridization on the high-density cDNA grid, on which about 7,600 nonoverlapping expressed sequence tag (EST) clones were spotted, to identify a set of genes specifically expressed in the germ line. One hundred and sixty-eight clones were then tested with the RNAi technique. Of these, 15 clones showed sterility with a variety of defects in germ-line development. Seven of them led to the production of unfertilized eggs, because of defects in spermatogenesis (4 clones), or defects in the oocytes (3 clones). The other 8 clones led to failure of oogenesis. These failures were caused by germ-line proliferation defect (Glp phenotype), meiotic arrest, and defects in sperm–oocyte switch (Mog phenotype) among others. These results demonstrate the efficacy of the screening strategy using the EST library combined with the RNAi technique in C. elegans.

Immunization with DNA vaccines encoding glycoprotein D or glycoprotein B, alone or in combination, induces protective immunity in animal models of herpes simplex virus-2 disease.

DNA vaccines expressing herpes simplex virus type 2 (HSV-2) full-length glycoprotein D (gD), or a truncated form of HSV-2 glycoprotein B (gB) were evaluated for protective efficacy in two experimental models of HSV-2 infection. Intramuscular (i.m.) injection of mice showed that each construction induced neutralizing serum antibodies and protected the mice from lethal HSV-2 infection. Dose-titration studies showed that low doses (< or = 1 microgram) of either DNA construction induced protective immunity, and that a single immunization with the gD construction was effective. The two DNAs were then tested in a low-dosage combination in guinea pigs. Immune sera from DNA-injected animals had antibodies to both gD and gB, and virus neutralizing activity. When challenged by vaginal infection with HSV-2, the DNA-immunized animals were significantly protected from primary genital disease.

Suppression of the breakthrough of human immunodeficiency virus type 1 (HIV-1) in cell culture by thiocarboxanilide derivatives when used individually or in combination with other HIV-1-specific inhibitors (i.e., TSAO derivatives).

Five structurally related thiophene and furane analogues of the oxathiin carboxanilide derivative NSC 615985 (UC84) (designated UC10, UC68, UC81, UC42, and UC16) were identified as potent inhibitors of HIV-1 replication in cell culture and HIV-1 reverse transcriptase activity. These compounds were markedly active against a series of mutant HIV-1 strains, containing the Leu-100-->Ile, Val-106-->Ala, Glu-138-->Lys, or Tyr-181-->Cys mutations in their reverse transcriptase. However, the thiocarboxanilide derivatives selected for mutations at amino acid positions 100 (Leu-->Ile), 101 (Lys-->Ile/Glu), 103 (Lys-->Thr/Asp) and 141 (Gly-->Glu) in the HIV-1 reverse transcriptase. The compounds completely suppressed HIV-1 replication and prevented the emergence of resistant virus strains when used at 1.3-6.6 microM--that is, 10- to 25-fold lower than the concentration required for nevirapine and bis(heteroaryl)piperazine (BHAP) U90152 to do so. If UC42 was combined with the [2',5'-bis-O-(tert-butyldimethylsilyl)-3'-spiro-5"-(4"-amino-1",2"- oxathiole-2",2"-dioxide)]-beta-D-pentofuranosyl (TSAO) derivative of N3-methylthymine (TSAO-m3T), virus breakthrough could be prevented for a much longer time, and at much lower concentrations, than if the compounds were used individually. Virus breakthrough could be suppressed for even longer, and at lower drug concentrations, if BHAP was added to the combination of UC42 with TSAO-m3T, which points to the feasibility of two- or three-drug combinations in preventing virus breakthrough and resistance development.