Dispersive Fourier transformation is an emerging measurement technique that overcomes the speed limitations of traditional optical instruments and enables fast continuous single-shot measurements in ...optical sensing, spectroscopy and imaging. Using chromatic dispersion, dispersive Fourier transformation maps the spectrum of an optical pulse to a temporal waveform whose intensity mimics the spectrum, thus allowing a single-pixel photodetector to capture the spectrum at a scan rate significantly beyond what is possible with conventional space-domain spectrometers. Over the past decade, this method has brought us a new class of real-time instruments that permit the capture of rare events such as optical rogue waves and rare cancer cells in blood, which would otherwise be missed using conventional instruments. In this Review, we discuss the principle of dispersive Fourier transformation and its implementation across a wide range of diverse applications.
Ultrafast real-time optical imaging is an indispensable tool for studying dynamical events such as shock waves, chemical dynamics in living cells, neural activity, laser surgery and microfluidics. ...However, conventional CCDs (charge-coupled devices) and their complementary metal-oxide-semiconductor (CMOS) counterparts are incapable of capturing fast dynamical processes with high sensitivity and resolution. This is due in part to a technological limitation-it takes time to read out the data from sensor arrays. Also, there is the fundamental compromise between sensitivity and frame rate; at high frame rates, fewer photons are collected during each frame-a problem that affects nearly all optical imaging systems. Here we report an imaging method that overcomes these limitations and offers frame rates that are at least 1,000 times faster than those of conventional CCDs. Our technique maps a two-dimensional (2D) image into a serial time-domain data stream and simultaneously amplifies the image in the optical domain. We capture an entire 2D image using a single-pixel photodetector and achieve a net image amplification of 25 dB (a factor of 316). This overcomes the compromise between sensitivity and frame rate without resorting to cooling and high-intensity illumination. As a proof of concept, we perform continuous real-time imaging at a frame speed of 163 ns (a frame rate of 6.1 MHz) and a shutter speed of 440 ps. We also demonstrate real-time imaging of microfluidic flow and phase-explosion effects that occur during laser ablation.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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Until recently, patients who have the same type and stage of cancer all receive the same treatment. It has been established, however, that individuals with the same disease respond ...differently to the same therapy. Further, each tumor undergoes genetic changes that cause cancer to grow and metastasize. The changes that occur in one person’s cancer may not occur in others with the same cancer type. These differences also lead to different responses to treatment.
Precision medicine, also known as personalized medicine, is a strategy that allows the selection of a treatment based on the patient’s genetic makeup. In the case of cancer, the treatment is tailored to take into account the genetic changes that may occur in an individual’s tumor. Precision medicine, therefore, could be defined in terms of the targets involved in targeted therapy.
A literature search in electronic data bases using keywords “cancer targeted therapy, personalized medicine and cancer combination therapies” was conducted to include papers from 2010 to June 2019.
Recent developments in strategies of targeted cancer therapy were reported. Specifically, on the two types of targeted therapy; first, immune-based therapy such as the use of immune checkpoint inhibitors (ICIs), immune cytokines, tumor-targeted superantigens (TTS) and ligand targeted therapeutics (LTTs). The second strategy deals with enzyme/small molecules-based therapies, such as the use of a proteolysis targeting chimera (PROTAC), antibody-drug conjugates (ADC) and antibody-directed enzyme prodrug therapy (ADEPT). The precise targeting of the drug to the gene or protein under attack was also investigated, in other words, how precision medicine can be used to tailor treatments.
The conventional therapeutic paradigm for cancer and other diseases has focused on a single type of intervention for all patients. However, a large literature in oncology supports the therapeutic benefits of a precision medicine approach to therapy as well as combination therapies.
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Protein therapeutics play a significant role in treating many diseases. They, however, suffer from patient’s proteases degradation and antibody neutralization which lead to short ...plasma half-lives. One of the ways to overcome these pitfalls is the frequent injection of the drug albeit at the cost of patient compliance which affects the quality of life of patients.
There are several techniques available to extend the half-life of therapeutics. Two of the most common protocols are PEGylation and fusion with human serum albumin. These two techniques improve stability, reduce immunogenicity, and increase drug resistance to proteases. These factors lead to the reduction of injection frequency which increases patient compliance and improve quality of life. Both techniques have already been used in many FDA approved drugs.
This review describes many technologies to produce long-acting drugs with the attention of PEGylation and the genetic fusion with human serum albumin. The report also discusses the latest modified therapeutics in the field and their application in cancer therapy. We compare the modification methods and discuss the pitfalls of these modified drugs.
Reliability analysis of structures requires statistical models of multi-variate random data that are nonlinearly interrelated. The current reliability methods that use the Nataf transformation and ...the linear correlation matrix may encounter difficulties in dealing with such situations. A copula approach can offer a general and flexible way of describing nonlinear dependence among multi-variate data in isolation from their marginal probability distributions, and serves as a powerful tool for modeling and simulating nonlinearly-interrelated data. In this study, an introduction as well as illustrative application of the copula theory is given in the context of structural reliability. The numerical example deals with the performance evaluation of existing structures subjected to earthquake loading in terms of both peak and residual displacement demands. The joint probability distribution modeling of peak and residual displacement seismic demands based on the copula theory is demonstrated, and the developed statistical models are used to examine the effects of nonlinear dependence on seismic reliability assessment.
Bacterial superantigens (SAgs) are effective T-cell stimulatory molecules that lead to massive cytokine production. Superantigens crosslink between MHC class II molecules on the Antigen Presenting ...Cells (APC) and TCR on T-cells. This enables them to activate up to 20% of resting T cells, whilst conventional antigen presentation results in the activation of 0.001-0.0001% of the T cell population. These biological properties of superantigens make them attractive for use in immunotherapy. Previous studies have established the effectiveness of superantigens as therapeutic agents. This, however, was achieved with severe side effects due to the high lethality of the native toxins. Our study aims to produce superantigen-based peptides with minimum or no lethality for safer cancer treatment. In previous work, we designed and synthesized twenty overlapping SPEA-based peptides and successfully mapped regions in SPEA superantigen, causing a vasodilatory response. We screened 20 overlapping SPEA-based peptides designed and synthesized to cover the whole SPEA molecule for T-cell activation and tumor-killing ability. In addition, we designed and synthesized tumor-targeted superantigen-based peptides by fusion of TGFαL3 either from the N' or C' terminal of selected SPEA-based peptides with an eight-amino acid flexible linker in between. Our study identified parts of SPEA capable of stimulating human T-cells and producing different cytokines. We also demonstrated that the SPEA-based peptide conjugate binds specifically to cancer cells and can kill this cancer. Peptides induce T-cell activation, and tumor killing might pave the way for safer tumor-targeted superantigens (TTS). We proposed the combination of our new superantigen-based peptide conjugates with other immunotherapy techniques for effective and safer cancer treatment.
High-speed photography is a powerful tool for studying fast dynamics in photochemistry, spintronics, phononics, fluidics and plasma physics. Currently, the pump-probe method is the gold standard for ...time-resolved imaging, but it requires repetitive measurements for image construction and therefore falls short in probing non-repetitive or difficult-to-reproduce events. Here, we present a motion-picture camera that performs single-shot burst image acquisition without the need for repetitive measurements, yet with equally short frame intervals (4.4 trillion frames per second) and high pixel resolution (450 × 450 pixels). The principle of this method--'motion picture femtophotography'--is all-optical mapping of the target's time-varying spatial profile onto a burst stream of sequentially timed photographs with spatial and temporal dispersion. To show the camera's broad utility we use it to capture plasma dynamics and lattice vibrational waves, both of which were previously difficult to observe with conventional methods in a single shot and in real time.
Abnormal structural and molecular changes in malignant tissues were thoroughly investigated and utilized to target tumor cells, hence rescuing normal healthy tissues and lowering the unwanted side ...effects as non-specific cytotoxicity. Various ligands for cancer cell specific markers have been uncovered and inspected for directional delivery of the anti-cancer drug to the tumor site, in addition to diagnostic applications. Over the past few decades research related to the ligand targeted therapy (LTT) increased tremendously aiming to treat various pathologies, mainly cancers with well exclusive markers. Malignant tumors are known to induce elevated levels of a variety of proteins and peptides known as cancer “markers” as certain antigens (e.g., Prostate specific membrane antigen “PSMA”, carcinoembryonic antigen “CEA”), receptors (folate receptor, somatostatin receptor), integrins (Integrin αvβ3) and cluster of differentiation molecules (CD13). The choice of an appropriate marker to be targeted and the design of effective ligand-drug conjugate all has to be carefully selected to generate the required therapeutic effect. Moreover, since some tumors express aberrantly high levels of more than one marker, some approaches investigated targeting cancer cells with more than one ligand (dual or multi targeting). We aim in this review to report an update on the cancer-specific receptors and the vehicles to deliver cytotoxic drugs, including recent advancements on nano delivery systems and their implementation in targeted cancer therapy. We will discuss the advantages and limitations facing this approach and possible solutions to mitigate these obstacles. To achieve the said aim a literature search in electronic data bases (PubMed and others) using keywords “Cancer specific receptors, cancer specific antibody, tumor specific peptide carriers, cancer overexpressed proteins, gold nanotechnology and gold nanoparticles in cancer treatment” was carried out.
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•Two mechanisms of target cancer cells; passive targeting and active targeting.•selective drug delivery significantly enhances the efficiency of cancer therapy.•The main obstacle to targeted cancer therapy is the inevitability of drug resistance.•mRNA-based therapies and CRISPER technique are future approaches for cancer therapy.•The use of nanotechnology has progressed the field of cancer diagnosis and treatment.
Immediately following the 11th March 2011
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9.0 Tohoku (Japan) earthquake, a field investigation was carried out around the Tokyo Bay area. This paper provides first-hand observations (before or ...just at the onset of repair) of widespread liquefaction and the associated effects. Observations related to uplift of manholes, settlement of ground, performance of buildings and bridges and the effects of ground improvements are also presented. Recorded ground motions near the Tokyo Bay area were analysed to understand their key characteristics (large amplitude and long duration). Lessons learnt are also presented.
► Geotechnical field investigations of the 2011
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9.0 Tohoku earthquake are reported. ► First-hand observations of widespread liquefaction around the Tokyo Bay area are presented. ► The effects of long-duration ground motions critical to liquefaction-related damage are analysed. ► Successful cases of ground improvement for reclaimed/filled land are discussed.
AbstractIn this paper, to supplement the Canadian building code for a timber-steel hybrid structure, over-strength, and ductility-related force modification factors are developed and validated using ...a collapse risk assessment approach. The hybrid structure incorporates cross-laminated timber (CLT) infill walls within steel moment resisting frames. Following the FEMA P695 procedure, archetype buildings of 3-story, 6-story, and 9-story height with middle bay infilled with CLT were developed. Subsequently, a nonlinear static pushover analysis was performed to quantify the actual over-strength factors of the hybrid archetype buildings. To check the FEMA P695 acceptable collapse probabilities and adjusted collapse margin ratios (ACMRs), incremental dynamic analysis was carried out using 60 ground motion records that were selected to regional seismic hazard characteristics in southwestern British Columbia, Canada. Considering the total system uncertainty, comparison of the calculated ACMRs with the FEMA P695 requirement indicates the acceptability of the proposed over-strength and ductility factors.
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