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

We present an implementation of explicit solvent all atom classical molecular dynamics (MD) within the AMBER program package that runs entirely on CUDA-enabled GPUs. First released publicly in April 2010 as part of version 11 of the AMBER MD package and further improved and optimized over the last two years, this implementation supports the three most widely used statistical mechanical ensembles (NVE, NVT, and NPT), uses particle mesh Ewald (PME) for the long-range electrostatics, and runs entirely on CUDA-enabled NVIDIA graphics processing units (GPUs), providing results that are statistically indistinguishable from the traditional CPU version of the software and with performance that exceeds that achievable by the CPU version of AMBER software running on all conventional CPU-based clusters and supercomputers. We briefly discuss three different precision models developed specifically for this work (SPDP, SPFP, and DPDP) and highlight the technical details of the approach as it extends beyond previously reported work [Gotz et al., J. Chem. Theory Comput. 2012, DOI: 10.1021/ct200909j; Le Grand et al., Comp. Phys. Comm. 2013, DOI: 10.1016/j.cpc.2012.09.022].We highlight the substantial improvements in performance that are seen over traditional CPU-only machines and provide validation of our implementation and precision models. We also provide evidence supporting our decision to deprecate the previously described fully single precision (SPSP) model from the latest release of the AMBER software package.

/pdf/routine-microsecond-molecular-dynamics-simulations-with-12m59cn3pd.pdf

Routine Microsecond Molecular Dynamics Simulations with AMBER on GPUs. 2. Explicit Solvent Particle Mesh Ewald.

The reactive oxygen species (ROS)-mediated mechanism is the major cause underlying the efficacy of photodynamic therapy (PDT). The PDT procedure is based on the cascade of synergistic effects between light, a photosensitizer (PS) and oxygen, which greatly favors the spatiotemporal control of the treatment. This procedure has also evoked several unresolved challenges at different levels including (i) the limited penetration depth of light, which restricts traditional PDT to superficial tumours; (ii) oxygen reliance does not allow PDT treatment of hypoxic tumours; (iii) light can complicate the phototherapeutic outcomes because of the concurrent heat generation; (iv) specific delivery of PSs to sub-cellular organelles for exerting effective toxicity remains an issue; and (v) side effects from undesirable white-light activation and self-catalysation of traditional PSs. Recent advances in nanotechnology and nanomedicine have provided new opportunities to develop ROS-generating systems through photodynamic or non-photodynamic procedures while tackling the challenges of the current PDT approaches. In this review, we summarize the current status and discuss the possible opportunities for ROS generation for cancer therapy. We hope this review will spur pre-clinical research and clinical practice for ROS-mediated tumour treatments.

Reactive oxygen species generating systems meeting challenges of photodynamic cancer therapy

Synthesis, Luminescent Properties, and Biomedical Applications Shili Gai,†,‡ Chunxia Li,† Piaoping Yang,*,‡ and Jun Lin*,† †State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China ‡Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, Harbin Engineering University, Harbin, 150001, P. R. China

Recent Progress in Rare Earth Micro/Nanocrystals: Soft Chemical Synthesis, Luminescent Properties, and Biomedical Applications

Carbon Nanomaterials for Biological Imaging and Nanomedicinal Therapy

The graphics processing unit (GPU) has emerged as a competitive platform for computing massively parallel problems. Many computing applications in medical physics can be formulated as data-parallel tasks that exploit the capabilities of the GPU for reducing processing times. The authors review the basic principles of GPU computing as well as the main performance optimization techniques, and survey existing applications in three areas of medical physics, namely image reconstruction, dose calculation and treatment plan optimization, and image processing.

/pdf/gpu-computing-in-medical-physics-a-review-i97kr9j4ih.pdf

GPU computing in medical physics: a review.

X-ray luminescence computed tomography (XLCT) is proposed as a new molecular imaging modality based on the selective excitation and optical detection of X-ray-excitable phosphor nanoparticles. These nano-sized particles can be fabricated to emit near-infrared (NIR) light when excited with X-rays, and, because because both X-rays and NIR photons propagate long distances in tissue, they are particularly well suited for in vivo biomedical imaging. In XLCT, tomographic images are generated by irradiating the subject using a sequence of programmed X-ray beams, while sensitive photo-detectors measure the light diffusing out of the subject. By restricting the X-ray excitation to a single, narrow beam of radiation, the origin of the optical photons can be inferred regardless of where these photons were detected, and how many times they scattered in tissue. This study presents computer simulations exploring the feasibility of imaging small objects with XLCT, such as research animals. The accumulation of 50 nm phosphor nanoparticles in a 2-mm-diameter target can be detected and quantified with subpicomolar sensitivity using less than 1 cGy of radiation dose. Provided sufficient signal-to-noise ratio, the spatial resolution of the system can be made as high as needed by narrowing the beam aperture. In particular, 1 mm spatial resolution was achieved for a 1-mm-wide X-ray beam. By including an X-ray detector in the system, anatomical imaging is performed simultaneously with molecular imaging via standard X-ray computed tomography (CT). The molecular and anatomical images are spatially and temporally co-registered, and, if a single-pixel X-ray detector is used, they have matching spatial resolution.

http://web.stanford.edu/~pratx/PDF/XLCT.pdf

X-Ray Luminescence Computed Tomography via Selective Excitation: A Feasibility Study

Development and MPI tracking of novel hypoxia-targeted theranostic exosomes.

Lanthanide-doped nanophosphors have received significant attention for use in biological sensing and imaging due to their unique optical properties. Much like semiconductor quantum dots (QDs), these luminescent nanocrystals offer several advantages over conventional organic fluorophores, including high photochemical stability, large Stokes shift, and tunable fluorescence emission. [1] Up-conversion nanophosphors, which are capable of absorbing two or more low-energy photons to emit a higher-energy photon, also exhibit favorable characteristics such as long fluorescence lifetimes, no photoblinking, and reduced autofluorescence. [2] The recent development of lanthanide-doped nanophosphors that function in the near-infrared (NIR) spectral range optimal for optical transmission through biological tissues (650–900 nm) has attracted great interest towards in vivo bioim-aging probes. [3–5] Alternatively, high-energy radiation, currently employed in medical imaging modalities, such as X-ray computed tomography (CT) or positron emission tomo graphy (PET), may also be used to excite NIR-emitting radioluminescent nanophosphors (RLNPs) for bioimaging.

/pdf/synthesis-and-radioluminescence-of-pegylated-eu3-doped-r12afey70t.pdf

Synthesis and Radioluminescence of PEGylated Eu3+-doped Nanophosphors as Bioimaging Probes

X-ray luminescence computed tomography (XLCT) is proposed as a new dual molecular/anatomical imaging modality. XLCT is based on the selective excitation and optical detection of x-ray-excitable nanoparticles. As a proof of concept, we built a prototype XLCT system and imaged near-IR-emitting Gd(2)O(2)S:Eu phosphors in various phantoms. Imaging in an optically diffusive medium shows that imaging performance is not affected by optical scatter; furthermore, the linear response of the reconstructed images suggests that XLCT is capable of quantitative imaging.

/pdf/tomographic-molecular-imaging-of-x-ray-excitable-1yut9m09s4.pdf

Guillem Pratx

Papers

GPU computing in medical physics: a review.

X-Ray Luminescence Computed Tomography via Selective Excitation: A Feasibility Study

Development and MPI tracking of novel hypoxia-targeted theranostic exosomes.

Synthesis and Radioluminescence of PEGylated Eu3+-doped Nanophosphors as Bioimaging Probes

Tomographic molecular imaging of x-ray-excitable nanoparticles