抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

[신간의 별자리x] 우리/미술, 그리고 ‘슬픔의 박물관’

Ju Mei,†,‡,∥ Nelson L. C. Leung,†,‡,∥ Ryan T. K. Kwok,†,‡ Jacky W. Y. Lam,†,‡ and Ben Zhong Tang*,†,‡,§ †HKUST-Shenzhen Research Institute, Hi-Tech Park, Nanshan, Shenzhen 518057, China ‡Department of Chemistry, HKUST Jockey Club Institute for Advanced Study, Institute of Molecular Functional Materials, Division of Biomedical Engineering, State Key Laboratory of Molecular Neuroscience, Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China Guangdong Innovative Research Team, SCUT-HKUST Joint Research Laboratory, State Key Laboratory of Luminescent Materials and Devices, South China University of Technology, Guangzhou 510640, China

Aggregation-Induced Emission: Together We Shine, United We Soar!

Luminescent Functional Metal–Organic Frameworks

New technologies for imaging molecules, particularly optical technologies, are increasingly being used to understand the complexity, diversity and in vivo behaviour of cancers. 'Omic' approaches are providing comprehensive 'snapshots' of biological indicators, or biomarkers, of cancer, but imaging can take this information a step further, showing the activity of these markers in vivo and how their location changes over time. Advances in experimental and clinical imaging are likely to improve how cancer is understood at a systems level and, ultimately, should enable doctors not only to locate tumours but also to assess the activity of the biological processes within these tumours and to provide 'on the spot' treatment.

/pdf/imaging-in-the-era-of-molecular-oncology-1t27xevmwt.pdf

Imaging in the era of molecular oncology

Acne vulgaris is a chronic inflammatory skin condition commonly resulting in negative aesthetic and social impacts on those affected. Minocycline, currently available as an oral antibiotic for moderate to severe acne, has a known minimum inhibitory concentration (MIC) for the acne-causing bacterium Propionibacterium acnes (P. acnes) in vitro, with its anti-inflammatory properties also eliciting inhibitory effects on pro-inflammatory molecules. A novel topical gel composition containing solubilized minocycline (BPX-01) has been developed to directly deliver the drug to the skin. Because minocycline is a known fluorophore, fluorescence microscopy and concurrent quantitative measurements were performed on excised human facial skin dosed with different concentrations, in order to determine the spatial distribution of the drug and quantification of its local concentration in the epidermis and the pilosebaceous unit where P. acnes generally reside. Local minocycline delivery confirmed achievement of an adequate therapeutic dose to support clinical studies. Subsequently, a 4-week double-blind, randomized, vehicle controlled clinical study was performed to assess the safety and efficacy of 1% minocycline BPX-01 applied daily. No instances of cutaneous toxicity were reported, and a greater than 1 log reduction of P. acnes count was observed at week 4 with statistical significance from baseline and vehicle control. In addition, no detectable amounts of minocycline in the plasma were reported, suggesting the potential of this new formulation to diminish the known systemic adverse effects associated with oral minocycline. Follow-on clinical plans are underway to further establish the safety of BPX-01 and to evaluate its efficacy against inflammatory acne lesions in a 225 patient multi-center dose-finding study.

Optical microscopy of targeted drug delivery and local distribution in skin of a topical minocycline: implications in translational research and guidance for therapeutic dose selection (Conference Presentation)

The delivery of therapeutics into tumors poses a number of challenges, including leaky neovascular networks that feed cancer cells, dense stroma associated with many tumors, and acidic interstitial spaces that act to reduce drug delivery. Theranostics—agents that have both therapeutic and

Theranostic nanoparticles give the best of both worlds

La presente invention a trait a un systeme permettant la detection d'un champ coherent non lineaire induit dans un echantillon. Le systeme comporte des optiques, un systeme de modulation, et un systeme detecteur. Les optiques servent a l'orientation d'un premier champ electromagnetique a une premiere frequence φ1 et d'un deuxieme champ magnetique φ2 vers un volume focal de sorte que la frequence differentielle φ1-φ2 soit resonante avec une frequence vibratoire d'un echantillon dans le volume focal. Le systeme de modulation sert a la modulation de la frequence differentielle φ1-φ2 de sorte que la frequence differentielle φ1-φ2 soit syntonisee dans ou hors de la frequence vibratoire de l'echantillon a une frequence de modulation. Le systeme detecteur sert a la detection d'un champ optique qui est genere par une interaction non lineaire de φ1 et de φ2 et de l'echantillon en reponse a la frequence de modulation. Le systeme est particulierement destine a etre utilise dans la spectroscopie Raman anti-Stokes coherente (CARS).

Systeme et procede pour l'imagerie de vibrations a haute sensibilite avec analyses de la diffusion de raman anti-stokes coherente a modulation de frequence

Mapping the uptake of topical drugs and quantifying dermal pharmacokinetics (PK) presents numerous challenges. Though high resolution and high precision methods such as mass spectrometry offer the means to quantify drug concentration in tissue, these tools are complex and often expensive, limiting their use in routine experiments. For the many topical drugs that are naturally fluorescent, tracking fluorescence emission can be a means to gather critical PK parameters. However, skin autofluorescence can often overwhelm drug fluorescence signatures. Here we demonstrate the combination of standard epi-fluorescence imaging with deep learning for the visualization and quantification of fluorescent drugs in human skin. By training a U-Net convolutional neural network on a dataset of annotated images, drug uptake from both high "infinite" dose and daily clinical dose regimens can be measured and quantified. This approach has the potential to simplify routine topical product development in the laboratory.

Visualizing topical drug uptake with conventional fluorescence microscopy and deep learning.

A new, broadly tuneable synchronously pumped picosecond optical parametric oscillator (OPO) for Coherent anti-Stokes Raman Scattering (CARS) microscopy is presented. It is based on a non-critically phase-matched LBO crystal, pumped by the second harmonic (532 nm) of a mode-locked Nd:Vanadate laser. The tuning range covers 680 nm to 990 nm (Signal beam) and 1150 nm to 2450 nm (Idler beam), thus completely substituting picosecond - Ti:Sapphire lasers. By using the Signal and Idler as pump and Stokes beams for CARS microscopy, this translates into a vibrational frequency range of ~1350 - >10.000 cm-1. Both beams are extracted from the same cavity mirror and therefore propagate collinearly. Due to the mechanism of their generation, Signal and Idler are optically synchronized, and thus, perfectly overlap in space and in time with no jitter. The 5 ps pulses generated are close to transform limited and of excellent beam quality (M2 << 1,1) and show a high pointing stability. The output power for Signal and Idler is about 2 W @ 4 W pump power leading to 50% overall conversion efficiency. The perfect spatial and temporal overlap, stable operation, and broad tuneability makes the described OPO an ideal and nearly hands-free laser source for CARS microscopy. The longer operational wavelength range results in higher penetration depths and lower sample photodamage than previously reported systems. Thus, our CARS source is optimized to image highly heterogeneous tissue samples, as will be shown in several applications. The latest methods for further sensitivity improvements will be presented.

http://www.focusonmicroscopy.org/2007/PDF/271_Rimke.pdf

Conor L. Evans

Papers

Optical microscopy of targeted drug delivery and local distribution in skin of a topical minocycline: implications in translational research and guidance for therapeutic dose selection (Conference Presentation)

Theranostic nanoparticles give the best of both worlds

Systeme et procede pour l'imagerie de vibrations a haute sensibilite avec analyses de la diffusion de raman anti-stokes coherente a modulation de frequence

Visualizing topical drug uptake with conventional fluorescence microscopy and deep learning.

A new easy to use light source for CARS microscopy based on an optical parametric oscillator