Comparison of Two Cameras based on Single Photon Avalanche Diodes (SPADs) for Fluorescence Lifetime Imaging Application with Picosecond Resolution

We report on a comparative study of two time-resolved cameras based on digital Single Photon Avalanche Diodes (SPADs) for Fluorescen ce Lifetime Imaging applications. In contrast to standard imagers such as cameras, SPAD imagers provide intensity as well as direct access to the fluorescence decay temporal profile, from which lifetime contrast can be extracted. Intensity images provide physicians with anatomical information to localize cancerous tissue; lifetime maps on the other hand provide metabolic information on tissues and can help detect the presence and location of metastatic cells [1,2,3]. With a timing resolution better than 100ps in a compact setup, the SPAD camera represents an innovative solution to explore subnanosecond fluorescence mechanisms

Research on the Standard about Communication between Predecessor and Successor Auditors

近年来，审计师发生变更越发频繁，对审计师发生变更的原因学者们有多种看法，其中学者们公认的最主要原因是由于审计师与被审计单位的意见分歧所引发的，而这种意见分歧若是发展到被审计单位对审计师进行“意见购买”，则就会影响审计独立性和被审计单位披露信息的真实性。因此，监管部门应该此类动机进行监管，以保证市场运作的秩序。而加强前后任审计师沟通则是抑制上市公司“意见购买”动机，提高审计效率和审计质量的有效途径。美国1975年就出台了前后任审计师沟通准则SASNo.7，到了1998年出台SASNo.84代替原先的SASNo.7，SASNo.84在内容上和措辞上对比SASNo.7更加清晰，确实给审计师提供了对于...Recently, changes of auditors have taken place more and more frequently. Scholars have lots of opinions about the reasons which lead companies to change auditors. Most of scholars agree on that the disagreement about audit opinions between auditors and their clients is the major reason which leads to change auditors. And if this disagreement develops to be a new situation that the clients behave “...学位：管理学硕士院系专业：管理学院会计系_会计学学号：20031103

Compact solid-state CMOS single-photon detector array for in vivo NIR fluorescence lifetime oncology measurements

In near infrared fluorescence-guided surgical oncology, it is challenging to distinguish healthy from cancerous tissue. One promising research avenue consists in the analysis of the exogenous fluorophores’ lifetime, which are however in the (sub-)nanosecond range. We have integrated a single-photon pixel array, based on standard CMOS SPADs (single-photon avalanche diodes), in a compact, time-gated measurement system, named FluoCam. In vivo measurements were carried out with indocyanine green (ICG)-modified derivatives targeting the avb3 integrin, initially on a genetically engineered mouse model of melanoma injected with ICG conjugated with tetrameric cyclic pentapeptide (ICG􀀀E[c(RGDfK)4]), then on mice carrying tumour xenografts of U87-MG (a human primary glioblastoma cell line) injected with monomeric ICG􀀀c(RGDfK). Measurements on tumor, muscle and tail locations allowed us to demonstrate the feasibility of in vivo lifetime measurements with the FluoCam, to determine the characteristic lifetimes (around 500 ps) and subtle lifetime differences between bound and unbound ICG-modified fluorophores (10% level), as well as to estimate the available photon fluxes under realistic conditions

Radiation hardness of amorphous silicon particle sensors

Radiation tests of 32 μm thick hydrogenated amorphous silicon n-i-p diodes have been performed using a high- energy 24 GeV proton beam up to fluences of 2x1016 protons/cm2. The results are compared to irradiation of similar 1 μm and 32 μm thick n-i-p diodes using a proton beam of 405 keV at a fluence of 3x1013 protons/cm2. All samples exhibited a drop of the photoconductivity and an increase in the dark leakage current under both high and low energy proton irradiation. An almost full recovery of the device performance was observed after a subsequent thermal annealing

Time based readout of a silicon photomultiplier (SiPM) for Time Of Flight Positron Emission Tomography (TOF-PET)

Time of flight (TOF) measurements in positron emission tomography (PET) are very challenging in terms of timing performance, and should achieve ideally less than 100ps FWHM precision. We present a time-based differential technique to read out SiPMs that has less than 25ps rms electronic jitter. The novel readout is a fast front end circuit (NINO) based on a first stage differential current mode amplifier with 20input resistance. Therefore the amplifier inputs are connected differentially to the SiPM’s anode and cathode ports. The leading edge of the output signal provides the time information, while the trailing edge provides the energy information. Based on a Monte Carlo photon-generation model, SPICE simulations were run with a 3x3mm2 SiPM-model, read out with a differential current amplifier. The results of these simulations are presented here and compared with experimental data obtained with a 3x3x15mm3 LSO crystal coupled to a SiPM. The measured time coincidence precision is interpreted by the combined Monte Carlo/ SPICE simulation, as well as by Poisson statistics

Redox Modulation at Work: Natural Phytoprotective Polysulfanes From Alliums Based on Redox-Active Sulfur

Purpose of review: This article provides a brief overview of natural phytoprotective products of allium with a special focus on the therapeutic potential of diallyl polysulfanes from garlic, their molecular targets and their fate in the living organisms. A comprehensive overview of antimicrobial and anticancer properties of published literature is presented for the reader to understand the effective concentrations of polysulfanes and their sensitivity towards different human pathogenic microbes, fungi, and cancer cell lines. Recent findings: The article finds polysulfanes potentials as new generation novel antibiotics and chemo preventive agent. The effective dose rates of polysulfanes for antimicrobial properties are in the range of 0.5–40 mg/L and for anticancer 20–100 μM. The molecular targets for these redox modulators are mainly cellular thiols as well as inhibition and/or activation of certain cellular proteins in cancer cell lines. Summary: Antimicrobial and anticancer activities of polysulfanes published in the literature indicate that with further development, they could be promising candidates for cancer prevention due to their selectivity towards abnormal cells

Dietary phytochemicals, HDAC inhibition, and DNA damage/repair defects in cancer cells

Genomic instability is a common feature of cancer etiology. This provides an avenue for therapeutic intervention, since cancer cells are more susceptible than normal cells to DNA damaging agents. However, there is growing evidence that the epigenetic mechanisms that impact DNA methylation and histone status also contribute to genomic instability. The DNA damage response, for example, is modulated by the acetylation status of histone and non-histone proteins, and by the opposing activities of histone acetyltransferase and histone deacetylase (HDAC) enzymes. Many HDACs overexpressed in cancer cells have been implicated in protecting such cells from genotoxic insults. Thus, HDAC inhibitors, in addition to unsilencing tumor suppressor genes, also can silence DNA repair pathways, inactivate non-histone proteins that are required for DNA stability, and induce reactive oxygen species and DNA double-strand breaks. This review summarizes how dietary phytochemicals that affect the epigenome also can trigger DNA damage and repair mechanisms. Where such data is available, examples are cited from studies in vitro and in vivo of polyphenols, organosulfur/organoselenium compounds, indoles, sesquiterpene lactones, and miscellaneous agents such as anacardic acid. Finally, by virtue of their genetic and epigenetic mechanisms, cancer chemopreventive agents are being redefined as chemo- or radio-sensitizers. A sustained DNA damage response coupled with insufficient repair may be a pivotal mechanism for apoptosis induction in cancer cells exposed to dietary phytochemicals. Future research, including appropriate clinical investigation, should clarify these emerging concepts in the context of both genetic and epigenetic mechanisms dysregulated in cancer, and the pros and cons of specific dietary intervention strategies

Epigenetic modulators as therapeutic targets in prostate cancer

Prostate cancer is one of the most common non-cutaneous malignancies among men worldwide. Epigenetic aberrations, including changes in DNA methylation patterns and/or histone modifications, are key drivers of prostate carcinogenesis. These epigenetic defects might be due to deregulated function and/or expression of the epigenetic machinery, affecting the expression of several important genes. Remarkably, epigenetic modifications are reversible and numerous compounds that target the epigenetic enzymes and regulatory proteins were reported to be effective in cancer growth control. In fact, some of these drugs are already being tested in clinical trials. This review discusses the most important epigenetic alterations in prostate cancer, highlighting the role of epigenetic modulating compounds in pre-clinical and clinical trials as potential therapeutic agents for prostate cancer management.info:eu-repo/semantics/publishedVersio

Multi-Channel Amplifier-Discriminator for Highly Time-Resolved Detection

A low-power multi-channel amplifier-discriminator was developed for application in highly time-resolved detection systems. The proposed circuit architecture, so-called Nino, is based on a time-over-threshold approach and shows a high potential for time-resolved readout of solid-state photo-detectors and of detectors based on vacuum technologies. The Irpics circuit was designed in a 250 nm CMOS technology, implementing 32 channels of a Nino version optimized to achieve high-time resolution on the output low-voltage differential signals (LVDS) while keeping a low power consumption of 10 mW per channel. Electrical characterizations of the circuit demonstrate a very low intrinsic time jitter on the output pulse leading edge, measured below 10 ps rms for each channel for high input signal charges ( > 100 fC) and below 25 ps rms for low input signal charges (20-100 fC). The read-out architecture moreover permits to retrieve the input signal charge from the timing measurements, while a calibration procedure was developed to correct for time walk variations of the output pulses. The Irpics circuit therefore shows a high potential of application in multi-channel detection systems requiring a high time resolution, as needed for Time Of Flight systems (TOF), Positron Emission Tomography (PET) or time-resolved spectroscopy