APDs as Single-Photon Detectors for Visible and Near-Infrared Wavelenghts down to Hz Rates

For the SPECTRAP experiment at GSI, Germany, detectors with Single-Photon counting capability in the visible and near-infrared regime are required. For the wavelength region up to 1100 nm we investigate the performance of 2x2 mm^2 avalanche photo diodes (APDs) of type S0223 manufactured by Radiation Monitoring Devices. To minimize thermal noise, the APDs are cooled to approximately -170 deg. C using liquid nitrogen. By operating the diodes close to the breakdown voltage it is possible to achieve relative gains in excess of 2x10^4. Custom-made low noise preamplifiers are used to read out the devices. The measurements presented in this paper have been obtained at a relative gain of 2.2x10^4. At a discriminator threshold of 6 mV the resulting dark count rate is in the region of 230/s. With these settings the studied APDs are able to detect single photons at 628 nm wavelength with a photo detection efficiency of (67+-7)%. Measurements at 1020 nm wavelength have been performed using the attenuated output of a grating spectrograph with a light bulb as photon source. With this setup the photo detection efficiency at 1020 nm has been determined to be (13+-3)%, again at a threshold of 6 mV.Comment: 14 pages, 9 figures, submitted to Journal of Instrumentatio

APDs as Single-Photon Detectors for Visible and Near-Infrared Wavelenghts down to Hz Rates

For the SPECTRAP experiment at GSI, Germany, detectors with Single-Photon counting capability in the visible and near-infrared regime are required. For the wavelength region up to 1100 nm we investigate the performance of 2x2 mm^2 avalanche photo diodes (APDs) of type S0223 manufactured by Radiation Monitoring Devices. To minimize thermal noise, the APDs are cooled to approximately -170 deg. C using liquid nitrogen. By operating the diodes close to the breakdown voltage it is possible to achieve relative gains in excess of 2x10^4. Custom-made low noise preamplifiers are used to read out the devices. The measurements presented in this paper have been obtained at a relative gain of 2.2x10^4. At a discriminator threshold of 6 mV the resulting dark count rate is in the region of 230/s. With these settings the studied APDs are able to detect single photons at 628 nm wavelength with a photo detection efficiency of (67+-7)%. Measurements at 1020 nm wavelength have been performed using the attenuated output of a grating spectrograph with a light bulb as photon source. With this setup the photo detection efficiency at 1020 nm has been determined to be (13+-3)%, again at a threshold of 6 mV.Comment: 14 pages, 9 figures, submitted to Journal of Instrumentatio

APDs as Single-Photon Detectors for Visible and Near-Infrared Wavelenghts down to Hz Rates

For the SPECTRAP experiment at GSI, Germany, detectors with Single-Photon counting capability in the visible and near-infrared regime are required. For the wavelength region up to 1100 nm we investigate the performance of 2x2 mm^2 avalanche photo diodes (APDs) of type S0223 manufactured by Radiation Monitoring Devices. To minimize thermal noise, the APDs are cooled to approximately -170 deg. C using liquid nitrogen. By operating the diodes close to the breakdown voltage it is possible to achieve relative gains in excess of 2x10^4. Custom-made low noise preamplifiers are used to read out the devices. The measurements presented in this paper have been obtained at a relative gain of 2.2x10^4. At a discriminator threshold of 6 mV the resulting dark count rate is in the region of 230/s. With these settings the studied APDs are able to detect single photons at 628 nm wavelength with a photo detection efficiency of (67+-7)%. Measurements at 1020 nm wavelength have been performed using the attenuated output of a grating spectrograph with a light bulb as photon source. With this setup the photo detection efficiency at 1020 nm has been determined to be (13+-3)%, again at a threshold of 6 mV.Comment: 14 pages, 9 figures, submitted to Journal of Instrumentatio

The Educational Journey of Three Adults with Learning Disabilities: A Demonstration of Resiliency

Not all students who are diagnosed with LD are destined to live a life of academic struggles, missed opportunities, and unfulfilled dreams. Not all students fit the stereotypical idea of troubled, underachievers who will drop out of school, aspire to low level jobs, and remain financially dependent (Miller & Fritz, 1998). Some students with LD become resilient to the negative effects and attributes that are often associated with having LD; and despite the odds, make it in life (Werner & Smith, 1992). The purpose of this study was to understand how students with mild LD develop resiliency through their school experiences and how those experiences influence their post-secondary and career choices. The theoretical framework used in this study focused primarily on the risk/resiliency model and the importance of proximal and distal developmental influences. Risk and protective factors were used as a way to navigate through the personal experiences of three individuals with mild LD and help to identify certain times in their lives when resiliency was evident. Using a multiple case study design, phenomenological interviewing was employed as the primary method of data collection, along with one focus group session and document reviews. The results of the data collection were reported as three case studies highlighting the participants\u27 individual experiences. The data was analyzed using analytic induction. Repeating ideas and themes emerged from the data creating the constructs that were used to write the theoretical narrative. Triangulation and member checks were used to verify the results. The findings revealed that 1) the participants developed resiliency in spite of their school experiences not necessarily as a result of their school experiences, and 2) the participants\u27 school experiences directly influenced their post-secondary and career choices. These findings have implications for the field of special education in terms of program design, transition planning, and relationship building between students and teachers

THERAPEUTIC POTENTIAL OF CINNAMALDEHYDE-MEDIATED NRF2 ACTIVATION TO INHIBIT RESTENOSIS USING A NOVEL 3D IMAGING TECHNIQUE

Atherosclerosis is the chronic build-up of arterial plaque that underlies most cardiovascular diseases. Symptomatic atherosclerosis is treated with percutaneous vascular interventions. These procedures initiate the arterial injury response, which coordinates post-surgical healing. An exaggerated healing response can lead to vessel re-occlusion, termed restenosis, and is the principal cause of revascularization procedure failure. Neointimal hyperplasia drives restenosis severity and results from excessive vascular smooth muscle cell (VSMC) migration, proliferation, and matrix deposition. Clinically, stenting of the artery with a bare-metal (BMS) or drug-eluting stent (DES) is done to reduce restenosis. Unfortunately, not all patients are eligible to receive BMS or DES due to the site of the plaque, the procedure performed, and any pre-existing conditions, among other factors. Furthermore, the drugs in DES indiscriminately inhibit all cellular proliferation and migration. Therefore, novel therapeutic strategies are necessary to improve vascular surgery outcomes. VSMC migration and proliferation are driven by a pro-oxidant shift in the cellular redox milieu. The Nrf2 antioxidant defense pathway regulates redox homeostasis, and it can be pharmacologically activated using small-molecule electrophiles. Chapters 3 and 4 of the dissertation explore the therapeutic benefit of cinnamaldehyde (CA) at inhibiting restenosis in a rat model, and how the Nrf2 pathway drives this beneficial effect. Meanwhile, Chapter 2 describes a novel technique to analyze murine restenosis models utilizing the 3D imaging capabilities of light sheet fluorescence microscopy (LSFM). The LSFM platform improves the rigor and reproducibility of measurements, compared to classical histology, by reducing user bias and increasing measurement accuracy, among many other factors. Using histology and LSFM, 100μM CA treatment inhibits neointimal hyperplasia formation in the artery. CA treatment reduces vessel occlusion, cell proliferation, immune cell infiltration, and activates the Nrf2 pathway. In VSMC, CA increases protein levels of enzymes regulated by Nrf2 and effectively inhibits both migration and proliferation. The therapeutic mechanism of CA is directly mediated by the Nrf2 pathway as no beneficial effect was observed in the Nrf2 knock-out rat or VSMC. Collectively, this dissertation presents a new technique for studying preclinical restenosis and identifies the potential of the CA/Nrf2 axis at treating restenosis.Doctor of Philosoph

Singlet Oxygen Generation by Porphyrins and Metalloporphyrins Revisited: a Quantitative Structure-property Relationship (QSPR) Study

state followed by formation of singlet oxygen (1O2), which is a highly reactive species and mediates various oxidative processes. The design of advanced sensitizers based on porphyrin compounds have attracted significant attention in recent years. However, it is still difficult to predict the efficiency of singlet oxygen generation for a given structure. Our goal was to develop a quantitative structure-property relationship (QSPR) model for the fast virtual screening and prediction of singlet oxygen quantum yields for pophyrins and metalloporphyrins. We performed QSPR analysis of a dataset containing 32 compounds, including various porphyrins and their analogues (chlorins and bacteriochlorins). Quantum-chemical descriptors were calculated using Density Functional Theory (DFT), namely B3LYP and M062X functionals. Three different machine learning methods were used to develop QSPR models: random forest regression (RFR), support vector regression (SVR), and multiple linear regression (MLR). The optimal QSPR model «structure – singlet oxygen generation quantum yield» obtained using RFR method demonstrated high determination coefficient for the training set (R2 = 0.949) and the highest predicting ability for the test set (pred_R2 = 0.875). This proves that the developed QSPR method is realiable and can be directly applied in the studies of singlet oxygen generation both for free base porphyrins and their metal complexes. We believe that QSPR approach developed in this study can be useful for the search of new poprhyrin photosensitizers with enhanced singlet oxygen generation ability

Putin’s Nuclear Blackmail

The article revealed the scientific nature of Putin’s nuclear blackmail. It has been proven that the democratic world community cannot succumb to Putin’s nuclear blackmail. In fact, he carries it out not for the purpose of actual use, but as a means of further aggressive actions to intimidate politicians and people around the world. It has been stated that the measures to prevent Putin’s nuclear blackmail are the maximum defeat of the Russian terrorist forces by the Armed Forces of Ukraine and the introduction of an oil and gas export embargo so that Russia cannot restore its military potential for decades. The conduct of legal measures to ensure that those involved in the entire synchronous chain of nuclear weapon activation, deliberately fail to comply with Putin’s criminal fatal order to use nuclear weapons

Structure and formation of luminescent centers in light-up Ag cluster-based DNA probes

Fluorescent beacons based on silver (Ag) clusters for DNA/RNA detection represent a new type of turn-on probe that fluoresces upon hybridization to target nucleobase sequences. Physical–chemical mechanisms of their fluorescence activation still remain poorly understood. We studied in detail the fluorescence activation of dark Ag clusters induced by interactions of Ag–DNA complexes with different DNA sequences. In all cases, the final result depends neither on the location of the precursors (dark clusters) nor on their spectral properties. The reaction of fluorescence activation is a process similar to the growth of fluorescent silver clusters on dsDNA matrices. In both cases, reactants are dark clusters and two adjacent DNA strands. The latter form a double-stranded template for cluster nucleation. We found the optimized structure of a green fluorescent Ag4+2 cluster assembled on a C3/C3 DNA dimer in two different ssDNA pairs using QM modeling. The calculated absorption spectra match nicely the experimental ones, which proves the optimized structures. We conclude that apparent fluorescence activation in the studied systems results from reassembling Ag clusters on the new dsDNA template formed upon hybridization with the target. The suggested mechanism of “fluorescence activation” offers a way to design new light-up DNA probes. Two DNA strands making up the dsDNA template providing a high yield of bright Ag clusters can be used as the halves with the “stick” tails hybridizing with the base sequence of the target DNA. In this way, we have designed a light-up Ag cluster probe for β-actin mRNA

Insights on localized and systemic delivery of redox-based therapeutics

Reactive oxygen and nitrogen species are indispensable in cellular physiology and signaling. Overproduction of these reactive species or failure to maintain their levels within the physiological range results in cellular redox dysfunction, often termed cellular oxidative stress. Redox dysfunction in turn is at the molecular basis of disease etiology and progression. Accordingly, antioxidant intervention to restore redox homeostasis has been pursued as a therapeutic strategy for cardiovascular disease, cancer, and neurodegenerative disorders among many others. Despite preliminary success in cellular and animal models, redoxbased interventions have virtually been ineffective in clinical trials. We propose the fundamental reason for their failure is a flawed delivery approach. Namely, systemic delivery for a geographically local disease limits the effectiveness of the antioxidant. We take a critical look at the literature and evaluate successful and unsuccessful approaches to translation of redox intervention to the clinical arena, including dose, patient selection, and delivery approach. We argue that when interpreting a failed antioxidant-based clinical trial, it is crucial to take into account these variables and importantly, whether the drug had an effect on the redox status. Finally, we propose that local and targeted delivery hold promise to translate redox-based therapies from the bench to the bedside

Charge Transfer Mediated Triplet Excited State Formation in Donor-Acceptor-Donor BODIPY: Application for Recording of Holographic Structures in Photopolymerizable Glass

Donor–acceptor–donor BODIPY triads bearing anthracene or pyrene as electron donating subunits were prepared through a stepwise synthesis. Photoinduced electron transfer and formation of long-lived triplet excited states via spin–orbit charge transfer intersystem crossing (SOCT-ISC) was studied by steady-state and ultrafast pump-probe spectroscopy and further supported by DFT computations. New BODIPYs were found to form triplet states and sensitize singlet oxygen in both polar and non-polar solvents which is unusual for photosensitizers operating via SOCT-ISC. BODIPY-anthracene triad (ABA) was used as a photosensitizer component in a photopolymerizable glass that was prepared by a four-step sol–gel process. ABA in combination with N-phenylglycin (NPG) showed the ability to initiate a free-radical polymerization of methacrylate monomers under 532 nm irradiation thus allowing for holographic recording of diffractive structures. High diffraction efficiency (up to 87%) obtained for ABA-NPG containing glass as compared to a reference diiodo-BODIPY (I2BDP) demonstrates for the first time that heavy-atom-free SOCT-ISC photosensitizers can efficiently operate in the solid state