Cryptococcal choroiditis in advanced AIDS with clinicopathologic correlation.

PurposeTo describe a case of disseminated cryptococcal meningitis with multifocal choroiditis and provide optical coherence tomography (OCT) findings correlated with described histopathology in a patient with advanced acquired immunodeficiency syndrome (AIDS).ObservationsThe patient was a 54-year-old man with AIDS who presented with dyspnea and headache followed by acute vision loss. OCT demonstrated a lesion with a small area of fluid that was limited by a more prominent and irregular external limiting membrane with underlying nodular choroidal thickening, mild RPE disorganization, and hyperreflectivity of the overlying photoreceptor layer. Patient was found to have disseminated cryptococcal infection and passed away despite aggressive therapy. Autopsy was performed including bilateral enucleation and a Cryptococcus lesion was confirmed on histopathology.Conclusion and importanceThis case highlights the clinical, imaging, and histopathologic findings of cryptococcal choroiditis and provides a review of the updated treatment recommendations for disseminated infection in a patient with advanced AIDS. Although currently fundoscopy has proven most useful in directing the diagnostic algorithm in choroiditis in the setting of advanced immunosuppression, OCT may provide insight into the spread of Cryptococcus within the eye

State selection in the noisy stabilized Kuramoto-Sivashinsky equation

In this work, we study the 1D stabilized Kuramoto Sivashinsky equation with additive uncorrelated stochastic noise. The Eckhaus stable band of the deterministic equation collapses to a narrow region near the center of the band. This is consistent with the behavior of the phase diffusion constants of these states. Some connections to the phenomenon of state selection in driven out of equilibrium systems are made.Comment: 8 pages, In version 3 we corrected minor/typo error

Additive noise effects in active nonlinear spatially extended systems

We examine the effects of pure additive noise on spatially extended systems with quadratic nonlinearities. We develop a general multiscale theory for such systems and apply it to the Kuramoto-Sivashinsky equation as a case study. We first focus on a regime close to the instability onset (primary bifurcation), where the system can be described by a single dominant mode. We show analytically that the resulting noise in the equation describing the amplitude of the dominant mode largely depends on the nature of the stochastic forcing. For a highly degenerate noise, in the sense that it is acting on the first stable mode only, the amplitude equation is dominated by a pure multiplicative noise, which in turn induces the dominant mode to undergo several critical state transitions and complex phenomena, including intermittency and stabilisation, as the noise strength is increased. The intermittent behaviour is characterised by a power-law probability density and the corresponding critical exponent is calculated rigorously by making use of the first-passage properties of the amplitude equation. On the other hand, when the noise is acting on the whole subspace of stable modes, the multiplicative noise is corrected by an additive-like term, with the eventual loss of any stabilised state. We also show that the stochastic forcing has no effect on the dominant mode dynamics when it is acting on the second stable mode. Finally, in a regime which is relatively far from the instability onset, so that there are two unstable modes, we observe numerically that when the noise is acting on the first stable mode, both dominant modes show noise-induced complex phenomena similar to the single-mode case

E2 strengths and transition radii difference of one-phonon 2+ states of 92Zr from electron scattering at low momentum transfer

Background: Mixed-symmetry 2+ states in vibrational nuclei are characterized by a sign change between dominant proton and neutron valence-shell components with respect to the fully symmetric 2+ state. The sign can be measured by a decomposition of proton and neutron transition radii with a combination of inelastic electron and hadron scattering [C. Walz et al., Phys. Rev. Lett. 106, 062501 (2011)]. For the case of 92Zr, a difference could be experimentally established for the neutron components, while about equal proton transition radii were indicated by the data. Method: Differential cross sections for the excitation of one-phonon 2+ and 3- states in 92Zr have been measured with the (e,e') reaction at the S-DALINAC in a momentum transfer range q = 0.3-0.6 fm^(-1). Results: Transition strengths B(E2;2+_1 -> 0+_1) = 6.18(23), B(E2; 2+_2 -> 0+_1) = 3.31(10) and B(E3; 3-_1 -> 0+_1) = 18.4(11) Weisskopf units are determined from a comparison of the experimental cross sections to quasiparticle-phonon model (QPM) calculations. It is shown that a model-independent plane wave Born approximation (PWBA) analysis can fix the ratio of B(E2) transition strengths to the 2+_(1,2) states with a precision of about 1%. The method furthermore allows to extract their proton transition radii difference. With the present data -0.12(51) fm is obtained. Conclusions: Electron scattering at low momentum transfers can provide information on transition radii differences of one-phonon 2+ states even in heavy nuclei. Proton transition radii for the 2+_(1,2) states in 92Zr are found to be identical within uncertainties. The g.s. transition probability for the mixed-symmetry state can be determined with high precision limited only by the available experimental information on the B(E2; 2+_1 -> 0+_1) value.Comment: 14 pages, 5 figures, submitted to Phys. Rev. C, revised manuscrip

Where traditional drug discovery meets modern technology in the quest for new drugs

Identifying novel compounds or improving bioavailability of drugs requires extensive screening, in vitro and in vivo testing and subsequent commercialisation. Traditional methods can be labour intensive and time-consuming. Use of modern technologies can reduce these challenges and is best achieved through collaboration with researchers specialising in different research fields. The range of research activities carried out in our lab is outlined and demonstrates the diversity of techniques used in our drug discovery programme

Delivering natural products and biotherapeutics to improve drug efficacy

Due to the increasing problem of drug resistance, new and improved medicines are required. Natural products and biotherapeutics offer a vast resource for new drugs; however, challenges, including the cost and time taken for traditional drug discovery processes and the subsequent lack of investment from the pharmaceutical industry, are associated with these areas. New techniques are producing compounds with appropriate activity at a faster rate. While the formulation of these combined with drug-delivery systems offers a promising approach for expanding the drug developments available to modern medicine. Here, various classes of drug-delivery systems are described and the advantages they bring to small molecule and biotherapeutic targeting are highlighted. This is an attractive approach to the pharmaceutical industry and the rising trend in research in this area is examined in brief

Does native Trypanosoma cruzi calreticulin mediate growth inhibition of a mammary tumor during infection?

Indexación: Web of Science.Background: For several decades now an antagonism between Trypanosoma cruzi infection and tumor development has been detected. The molecular basis of this phenomenon remained basically unknown until our proposal that T. cruzi Calreticulin (TcCRT), an endoplasmic reticulum-resident chaperone, translocated-externalized by the parasite, may mediate at least an important part of this effect. Thus, recombinant TcCRT (rTcCRT) has important in vivo antiangiogenic and antitumor activities. However, the relevant question whether the in vivo antitumor effect of T. cruzi infection is indeed mediated by the native chaperone (nTcCRT), remains open. Herein, by using specific modified anti-rTcCRT antibodies (Abs), we have neutralized the antitumor activity of T. cruzi infection and extracts thereof, thus identifying nTcCRT as a valid mediator of this effect. Methods: Polyclonal anti-rTcCRT F(ab')(2) Ab fragments were used to reverse the capacity of rTcCRT to inhibit EAhy926 endothelial cell (EC) proliferation, as detected by BrdU uptake. Using these F(ab')(2) fragments, we also challenged the capacity of nTcCRT, during T. cruzi infection, to inhibit the growth of an aggressive mammary adenocarcinoma cell line (TA3-MTXR) in mice. Moreover, we determined the capacity of anti-rTcCRT Abs to reverse the antitumor effect of an epimastigote extract (EE). Finally, the effects of these treatments on tumor histology were evaluated. Results: The rTcCRT capacity to inhibit ECs proliferation was reversed by anti-rTcCRT F(ab')(2) Ab fragments, thus defining them as valid probes to interfere in vivo with this important TcCRT function. Consequently, during infection, these Ab fragments also reversed the in vivo experimental mammary tumor growth. Moreover, anti-rTcCRT Abs also neutralized the antitumor effect of an EE, again identifying the chaperone protein as an important mediator of this anti mammary tumor effect. Finally, as determined by conventional histological parameters, in infected animals and in those treated with EE, less invasive tumors were observed while, as expected, treatment with F(ab')(2) Ab fragments increased malignancy. Conclusion: We have identified translocated/externalized nTcCRT as responsible for at least an important part of the anti mammary tumor effect of the chaperone observed during experimental infections with T. cruzi.http://bmccancer.biomedcentral.com/articles/10.1186/s12885-016-2764-

Petrogenesis of Bir Madi Gabbro-Diorite and Tonalite-Granodiorite Intrusions in Southeastern Desert, Egypt: Implications for Tectono-Magmatic Processes at theNeoproterozoic Shield

The Neoproterozoic rocks of Bir Madi area, south eastern desert, comprises of Metagabbro-Diorite Complex  (GCD) and Tonalite-Granodiorite Suite (TGrS). The GDC has a weak tonalitic to strong calc-alkaline character and is made up of olivine gabbro, hornblende  gabbro, dionite and monzodiorite. The olivine gabbro is characterized by abundance of augite and labradorite with psuedomorphic serpentine. The hornblende gabbro is mainly composed of hornblende, labradorite, andesine and minor amounts of quartz with or without augite. The diorite consists essentially of  andesine, hornblende, biotite and quartz. TheGDC is compositionally broad.,with a wide range of SiO2, (46-57 %) and pronounced enichment in the LILE (Ba and Sr) relative to the HFSE (Nb,Y and Z).The GDC rocks exhibit  petrological and geochemical characteristics of arc-related mafic magmas, derived possibly from partial melting of a mantle wedgeabove an early Pan-African subduction zone of the Neoproterozoic Shield. The tonalite and granodiorite have a calcalkaline affinity and show the geochemical signatures of I-type granitoids. The TGrS contains amphibolite enclaves and foliated gabbroic xenoliths. Based on the field evidence and geochemical data, the GDC and TGrS are not related to a single magma type through fractional crystallization. The prcsence of microgranular amphibolite enclavcs in the tonalitic rocks suggest against their generation by partial melting of a mantle-derived basaltic source. The (tonalitic magma originated from partial melting of an amphibolitic lower crust by anatexis process at a volcanic arc regime during construction of Arabian-Nubian Shield. Fractional crystalization of K-feldspar and biotite gave more developed granodiorite variety from the tonalitic magma. The gabbroic xenoliths are similar in the chemical composition to theinvestigated metagabbros. They are incompletely digested segments from the adjacent metagabbro rocks incorporatedinto the granitic magma through an assimilation process