Antibody-mediated therapy against HIV/AIDS: Where are we standing now?

Acquired immunodeficiency syndrome (AIDS) cases are on the rise globally. To date, there is still no effective measure to eradicate the causative agent, human immunodeficiency virus (HIV). Highly active antiretroviral therapy (HAART) is being used in HIV/AIDS management, but it results in long-term medication and has major drawbacks such as multiple side effects, high cost, and increasing the generation rate of escape mutants. In addition, HAART does not control HIV-related complications, and hence more medications and further management are required. With this, other alternatives are urgently needed. In the past, small molecule inhibitors have shown potent antiviral effects, and some of them are now being evaluated in clinical trials. The challenges in developing these small molecules for clinical use include the off-target effect, poor stability, and low bioavailability. On the other hand, antibody-mediated therapy has emerged as an important therapeutic modality for anti-HIV therapeutics development. Many antiviral antibodies, namely, broad neutralizing antibodies (bnAbs) against multiple strains of HIV, have shown promising effects in vitro and in animal studies; further studies are ongoing in clinical trials to evaluate their uses in clinical applications. This short review aims to discuss the current development of therapeutic antibodies against HIV and the challenges in adopting them for clinical use

Pore pressures in clays due to cone penetration

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Civil Engineering, 1980.MICROFICHE COPY AVAILABLE IN ARCHIVES AND ENGINEERING.Vita.Bibliography: p. 482-499.by Jacques-Noel Levadoux.Ph.D

Vortex merger in surface quasi-geostrophy

The merger of two identical surface temperature vortices is studied in the surface quasi- geostrophic model. The motivation for this study is the observation of the merger of sub- mesoscale vortices in the ocean. Firstly, the interaction between two point vortices, in the absence or in the presence of an external deformation field, is investigated. The rotation rate of the vortices, their stationary positions and the stability of these positions are determined. Then, a numerical model provides the steady states of two finite-area, constant-temperature, vortices. Such states are less deformed than their counterparts in two-dimensional incom- pressible flows. Finally, numerical simulations of the nonlinear surface quasi-geostrophic equations are used to investigate the finite-time evolution of initially identical and sym- metric, constant temperature vortices. The critical merger distance is obtained and the deformation of the vortices before or after merger is determined. The addition of external deformation is shown to favor or to oppose merger depending on the orientation of the vor- tex pair with respect to the strain axes. An explanation for this observation is proposed. Conclusions are drawn towards an application of this study to oceanic vortices.PostprintPeer reviewe

Cell-Based Assays for Evaluation of Autophagy in Cancers

Autophagy is a cellular mechanism that degrades damaged organelles and misfolded proteins to maintain cellular homeostasis. Autophagy in cancers is drawing increasing attentions due to its multifaceted roles in cancer development, progression, and treatment. There are several key autophagy effectors that are being extensively studied to understand the role of autophagy in cancer as well as their potential value as predictive and/or prognostic biomarkers and therapeutic target. These include ATG4A, ATG4B, Beclin-I, p62, LC3A, LC3B, LC3C, and LAMP. While having its own sophisticated pathway, autophagy has been reported to associate with multiple oncogenic pathways such as NF-kB, mTOR, and PI3K signaling. This chapter aims to provide a detailed protocol for researchers to investigate the role of autophagy using in vitro cell line as model. Here, we demonstrate several techniques including Western blot (WB), immunofluorescence (IF), and small-interfering RNA (siRNA) knockdown using colorectal cancer cell lines as samples. This chapter provides information to researchers especially those in their early- and mid-career to plan and design their experiments to study the autophagy events in their area of interests

Reproductive Cycle and Plasma Levels of Sex Steroids in Female Eurasian Perch Perca Fluviatilis

From April 1995 to April 1996, the annual reproductive cycle of the Eurasian perch Perca fluviatilis was studied at the Fishfarming Lindre Center (Moselle, France). At monthly intervals (at intervals of 10 days during the periovulatory period), 5 females were caught and dissected. From sampled organs, the gonado-, hepato- and viscerosomatic indexes (GSI, HSI, VSI) were calculated, oocyte diameters (OD) and the plasma levels of testosterone (T), 17P-estradiol (E2), 17,20P-dihydroxy-4-pregnen-3-one (17,2Op-P) and protein-phosphorus (PPP) were measured. After the sexual resting period observed from May to August (GSI \u3c 1 %, OD \u3c 200 urn, VSI = 4-6 %), oogenesis began in September when the water temperature decreased from 26.4 to 14.1 “C. The GSI increased progressively until mid March (15 %), then rapidly until spawning (25 %, OD = 850 urn) which occurred in April (14- 15 “C). The plasma levels of T, E,, 17,2Op-P and PPP were low during the sexual resting period. E, and PPP levels increased significantly at the onset of the oogenesis in September, then the E, level raised abruptly in November (3-4 ng mL-‘). In December, the T level increased rapidly to 15-20 ng . mL-’ The testosterone, E, and PPP levels remained very high until spawning, indicating the existence of active vitellogenesis. The highest HSI (2.1-2.2 %) recorded in winter confirmed this. During the periovulatory period, a peak of E, (4 ng . mL-‘) appeared, whereas T level diminished. In this study, 17,2Op-P levels remained low (0.2-0.6 ng mL-‘) and relatively constant. No 17,2Op-P peak was observed during the periovulatory period. Sampling at 10 day intervals was probably inadequate to specify the hormonal variations related to the final oocyte maturation and the ovulation. 0 Ifremer-Elsevier, Paris

Reproductive Cycle and Plasma Sex Steroid Profiles in Male Eurasian Perch Perca Fluviatilis

From April 1995 to April 1996, the annual reproductive cycle of male Eurasian perch Perca fluviatilis was studied at the Lindre Center (Moselle, France). At monthly intervals, five males (mean body weight of 133 ± 43 g and total length of 175 ± 9 mm) were caught. From sampled organs, the gonadosomatic (GSI), hepatosomatic (HSI) and viscerosomatic indexes (VSI) were calculated and plasma testosterone (T) and 11-ketotestosterone (11KT) levels were measured. After the spawning period in mid-April, GSI and HSI dropped and VSI increased to 3.8 ± 0.1 %. In September, GSI reached its maximum (8.5 ± 1.8 %). At this time, spermatocytes, spermatids and spermatozoa were abundant, whereas in June only spermatogonia were observed. During winter, GSI was stable at approximately 5 %, HSI reached its maximum (1.9 ± 0.3 %) and VSI was low (2.6 ± 0.2 %). From April to November 1995, plasma T and 11KT concentrations were low (\u3c 0.5 ng·mL–1). Plasma T levels increased significantly in December and reached peak levels (12.3 ± 2.1 ng·mL–1) in January, then decreased in February and increased again until spawning in April (6.8 ± 2.1 ng·mL–1). This second elevation could be related to the beginning of a new spermatogenic cycle. Plasma levels of 11KT increased significantly from October to February 1996 (4.9 ± 1.1 ng·mL–1). From February to the spawning period (April 1996), plasma 11KT decreased significantly, but values were significantly higher than those measured in fall. Males were spermiating from January to spawning in April. © 2000 Ifremer/Cnrs/Inra/Ird/Cemagref/Éditions scientifiques et médicales Elsevier SA

Environmentalism, performance and applications: uncertainties and emancipations

This introductory article for a themed edition on environmentalism provides a particular context for those articles that follow, each of which engages with different aspects of environmentalism and performance in community-related settings. Responding to the proposition that there is a lacuna in the field of applied drama and environmentalism (Bottoms, 2010), we suggest that the more significant lack is that of ecocriticism. As the articles in this journal testify, there are many examples of applied theatre practice; what is required is sustained and rigorous critical engagement. It is to the gap of ecocriticism that we address this issue, signalling what we hope is the emergence of a critical field. One response to the multiple challenges of climate change is to more transparently locate the human animal within the environment, as one agent amongst many. Here, we seek to transparently locate the critic, intertwining the personal – ourselves, human actants – with global environmental concerns. This tactic mirrors much contemporary writing on climate change and its education, privileging personal engagement – a shift we interrogate as much as we perform. The key trope we anchor is that of uncertainty: the uncertainties that accompany stepping into a new research environment; the uncertainties arising from multiple relations (human and non-human); the uncertainties of scientific fact; the uncertainties of forecasting the future; and the uncertainties of outcomes – including those of performance practices. Having analysed a particular turn in environmental education (towards social learning) and the failure to successfully combine ‘art and reality’ in recent UK mainstream theatre events, such uncertainties lead to our suggestion for an ‘emancipated’ environmentalism. In support of this proposal, we offer up a reflection on a key weekend of performance practice that brought us to attend to the small – but not insignificant – and to consider first hand the complex relationships between environmental ‘grand narratives’ and personal experiential encounters. Locating ourselves within the field and mapping out some of the many conceptual challenges attached to it serves to introduce the territories which the following journal articles expand upon