There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

Tumor-associated macrophages: from mechanisms to therapy.

Hypoxia is a feature of most tumours, albeit with variable incidence and severity within a given patient population. It is a negative prognostic and predictive factor owing to its multiple contributions to chemoresistance, radioresistance, angiogenesis, vasculogenesis, invasiveness, metastasis, resistance to cell death, altered metabolism and genomic instability. Given its central role in tumour progression and resistance to therapy, tumour hypoxia might well be considered the best validated target that has yet to be exploited in oncology. However, despite an explosion of information on hypoxia, there are still major questions to be addressed if the long-standing goal of exploiting tumour hypoxia is to be realized. Here, we review the two main approaches, namely bioreductive prodrugs and inhibitors of molecular targets upon which hypoxic cell survival depends. We address the particular challenges and opportunities these overlapping strategies present, and discuss the central importance of emerging diagnostic tools for patient stratification in targeting hypoxia.

Targeting hypoxia in cancer therapy

MUCKE aims to mine a large volume of images, to structure them conceptually and to use this conceptual structuring in order to improve large-scale image retrieval. The last decade witnessed important progress concerning low-level image representations. However, there are a number problems which need to be solved in order to unleash the full potential of image mining in applications. The central problem with low-level representations is the mismatch between them and the human interpretation of image content. This problem can be instantiated, for instance, by the incapability of existing descriptors to capture spatial relationships between the concepts represented or by their incapability to convey an explanation of why two images are similar in a content-based image retrieval framework. We start by assessing existing local descriptors for image classification and by proposing to use co-occurrence matrices to better capture spatial relationships in images. The main focus in MUCKE is on cleaning large scale Web image corpora and on proposing image representations which are closer to the human interpretation of images. Consequently, we introduce methods which tackle these two problems and compare results to state of the art methods. Note: some aspects of this deliverable are withheld at this time as they are pending review. Please contact the authors for a preview.

http://ieeexplore.ieee.org/iel2/4524/12820/00592460.pdf

Image Processing

This Review covers recent progress on near-infrared fluorescence imaging for preclinical animal studies and clinical diagnostics and interventions.

Near-infrared fluorophores for biomedical imaging

In Vivo Imaging of Oxidative and Hypoxic Stresses in Mice Model of Amyotrophic Lateral Sclerosis.

Significance: Photoacoustic (PA) imaging has garnered considerable attention due to its capability to render vascular images in a label-free manner. Specifically, devices employing a hemispherical detector array (HDA) have been heralded for various clinical applications, owing to their potential to yield high reproducibility three-dimensional images. While high-resolution models utilizing high-frequency sensors have been introduced for animal experimentation, their evaluation has been constrained to a single wavelength. In this study, we demonstrate the applicability of in vivo mouse models for visualizing body oxygen saturation distribution using dual wavelengths. Aim: With the aid of our uniquely developed device and analysis software, our primary objective is to map the spatial distribution of the hemoglobin oxygen saturation coefficient (S-factor) through non-invasive in vivo imaging. Subsequently, we aim to observe the temporal alterations within this distribution, specifically assessing changes in hemoglobin oxygen saturation in both normal and tumor vessels over time. Approach: High-quality S-factor images were obtained by integrating a newly developed scanning sequence for high contrast with alternate two-wavelength irradiation. Following validation with phantoms, in vivo images were procured in mice. Sequential scanning of the same mouse yielded information about temporal changes. S-factor evaluation was conducted with our photoacoustic image viewer to analyze trends in hemoglobin oxygen saturation. Results: High-contrast images were achieved by increasing the number of integrations during scanning. S-factor images were acquired using both healthy and tumor-bearing mice. Vessels within the liver and kidneys were distinctly reconstructed, and differences in oxygen saturation discriminated between arteries and veins. Repeated measurements on the same mice, both live and post-euthanasia, provided spatiotemporal information, such as a decrease in oxygen saturation after euthanasia or a precipitous drop in oxygen saturation inside the tumor nine days post-cell line transplantation. Conclusions: By analyzing S-factor images using a photoacoustic imaging system designed for animal experiments, we succeeded in discerning variations in in vivo oxygen saturation. The custom-built system holds promise as a versatile tool for diverse basic research endeavors, as it can seamlessly interface with human clinical applications.

Visualization of hemoglobin oxygen saturation distribution in small animals: an in vivo application of a 3D photoacoustic imaging scanner with a hemispherical detector array

Solid tumors possess unique microenvironments that are exposed to chronic hypoxic conditions ("tumor hypoxia").
Although more than half a century has passed since it was suggested that tumor hypoxia correlated with poor treatment
outcomes and contributed to cancer recurrence, a fundamental solution to this problem has yet to be found. Hypoxia-inducible
factor (HIF-1) is the main transcription factor that regulates the cellular response to hypoxia. It induces various
genes whose functions are strongly associated with malignant alteration of the entire tumor. The cellular changes
induced by HIF-1 are extremely important targets of cancer therapy, particularly in therapy against refractory cancers.
Imaging of the HIF-1-active microenvironment is therefore important for cancer therapy. To image HIF-1activity in vivo ,
we developed a PTD-ODD fusion protein, POHA, which was uniquely labeled with near-infrared fluorescent dye at the
C-terminal. POHA has two functional domains: protein transduction domain (PTD) and VHL-mediated protein
destruction motif in oxygen-dependent degradation (ODD) domain of the alpha subunit of HIF-1 (HIF-1α). It can
therefore be delivered to the entire body and remain stabilized in the HIF-1-active cells. When it was intravenously
injected into tumor-bearing mice, a tumor-specific fluorescence signal was detected in the tumor 6 h after the injection.
These results suggest that POHA can be used an imaging probe for tumor malignancy.

Imaging probe for tumor malignancy

: Since its establishment in 1958, the Society of Japanese Women Scientists (SJWS) has contributed to the improvement of the environment and promotion for many female researchers. The activities of SJWS involves initiating pioneering efforts: increasing opportunities for female scientists in Japan to participate in decision-making positions, supporting STEM (science, technology, engineering, and mathematics) educational activities, and building a gender equality network. At the same time, SJWS is continuing activities that represent Japan in building an international network in collaboration with like-minded organizations in Japan and overseas. Here, I look back on the international activities of SJWS so far and summarize their achievements. I also introduce the international organizations in which SJWS is currently participating and the international efforts being implemented through their activities.

https://www.jstage.jst.go.jp/article/sjws/22/0/22_22001/_pdf

International activity of SJWS expanding through ICWES/INWES

In this study, we proposed a droplet-based valveless microfluidic system that has the necessary functions to perform the binding, washing, eluting, and collecting processes of phage-display screening against spheroids, which can be expected to present a similar repertoire and number of membrane proteins as in vivo. Although spheroids have much larger sizes than single cells, spheroids are difficult to manipulate through manual operation. The proposed microfluidic system actively controls the position and velocity of droplets using a camera, three air pumps, and three liquid pumps to perform the processes for phage-display screening. The cross section of the microchannel is large in width and height for the passage of spheroids. Valves that can close such a large cross-sectional microchannel are not readily available. Thus, we proposed valveless flow control using liquid pumps. In addition, the proposed microfluidic system involves complex flow channels with airflow subchannels to perform phage-display screening. For washing, nonspecific-binding phages remaining in the flow channels must be minimized. The proposed microfluidic system can perform selective blocking and flush washing. Selective blocking can prevent the airflow channels from becoming hydrophilic with blocking liquid, and flush washing can flush phages remaining in the flow channel. We experimentally verified the functions of the developed microfluidic device based on the proposed system.

/pdf/droplet-based-valveless-microfluidic-system-for-phage-35ces9ce.pdf

Shinae Kizaka-Kondoh

Papers

In Vivo Imaging of Oxidative and Hypoxic Stresses in Mice Model of Amyotrophic Lateral Sclerosis.

Visualization of hemoglobin oxygen saturation distribution in small animals: an in vivo application of a 3D photoacoustic imaging scanner with a hemispherical detector array

Imaging probe for tumor malignancy

International activity of SJWS expanding through ICWES/INWES

Droplet-based valveless microfluidic system for phage-display screening against spheroids.