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

The isothiocyanate class of bioactive nutrients covalently inhibit the MEKK1 protein kinase

<p>Abstract</p> <p>Background</p> <p>Dietary isothiocyanates (ITCs) are electrophilic compounds that have diverse biological activities including induction of apoptosis and effects on cell cycle. They protect against experimental carcinogenesis in animals, an activity believed to result from the transcriptional induction of "Phase 2" enzymes. The molecular mechanism of action of ITCs is unknown. Since ITCs are electrophiles capable of reacting with sulfhydryl groups on amino acids, we hypothesized that ITCs induce their biological effects through covalent modification of proteins, leading to changes in cell regulatory events. We previously demonstrated that stress-signaling kinase pathways are inhibited by other electrophilic compounds such as menadione. We therefore tested the effects of nutritional ITCs on MEKK1, an upstream regulator of the SAPK/JNK signal transduction pathway.</p> <p>Methods</p> <p>The activity of MEKK1 expressed in cells was monitored using in vitro kinase assays to measure changes in catalytic activity. The activity of endogenous MEKK1, immunopurified from ITC treated and untreated LnCAP cells was also measured by in vitro kinase assay. A novel labeling and affinity reagent for detection of protein modification by ITCs was synthesized and used in competition assays to monitor direct modification of MEKK1 by ITC. Finally, immunoblots with phospho-specific antibodies were used to measure the activity of MAPK protein kinases.</p> <p>Results</p> <p>ITCs inhibited the MEKK1 protein kinase in a manner dependent on a specific cysteine residue in the ATP binding pocket. Inhibition of MEKK1 catalytic activity was due to direct, covalent and irreversible modification of the MEKK1 protein itself. In addition, ITCs inhibited the catalytic activity of endogenous MEKK1. This correlated with inhibition of the downstream target of MEKK1 activity, i.e. the SAPK/JNK kinase. This inhibition was specific to SAPK, as parallel MAPK pathways were unaffected.</p> <p>Conclusion</p> <p>These results demonstrate that MEKK1 is directly modified and inhibited by ITCs, and that this correlates with inhibition of downstream activation of SAPK. These results support the conclusion that ITCs may carry out many of their actions by directly targeting important cell regulatory proteins.</p

A Garlic Derivative, S-allylcysteine (SAC), Suppresses Proliferation and Metastasis of Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) is highly malignant and metastatic. Currently, there is no effective chemotherapy for patients with advanced HCC leading to an urgent need to seek for novel therapeutic options. We aimed to investigate the effect of a garlic derivative, S-allylcysteine (SAC), on the proliferation and metastasis of HCC. Methodology/Principal Findings: A series of in vitro experiments including MTT, colony-forming, wound-healing, invasion, apoptosis and cell cycle assays were performed to examine the anti-proliferative and anti-metastatic effects of SAC on a metastatic HCC cell line MHCC97L. The therapeutic values of SAC single and combined with cisplatin treatments were examined in an in vivo orthotopic xenograft liver tumor model. The result showed that the proliferation rate and colony-forming abilities of MHCC97L cells were suppressed by SAC together with significant suppression of the expressions of proliferation markers, Ki-67 and proliferating cell nuclear antigen (PCNA). Moreover, SAC hindered the migration and invasion of MHCC97L cells corresponding with up-regulation of E-cadherin and down-regulation of VEGF. Furthermore, SAC significantly induced apoptosis and necrosis of MHCC97L cells through suppressing Bcl-xL and Bcl-2 as well as activating caspase-3 and caspase-9. In addition, SAC could significantly induce the S phase arrest of MHCC97L cells together with down-regulation of cdc25c, cdc2 and cyclin B1. In vivo xenograft liver tumor model demonstrated that SAC single or combined with cisplatin treatment inhibited the progression and metastasis of HCC tumor. Conclusions/Significance: Our data demonstrate the anti-proliferative and anti-metastatic effects of SAC on HCC cells and suggest that SAC may be a potential therapeutic agent for the treatment of HCC patients. © 2012 Ng et al.published_or_final_versio

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

Przegląd istniejących systemów nomenklatury i klasyfikacji jaspisów w Polsce i na świecie

Nowadays, the term “jasper” is variably defined in petrology and gemology. The unification of the nomenclature and the classification of jaspers seems to be an essential challenge for petrologists worldwide. This misnomer is very commonly used among sellers or collectors of various gemstones. Therefore, a huge diversity in the mineralogical composition, geological settings and genesis of particular “spotted stones” is reported. In this paper the term “jasper” is proposed for all “spotted stones” which have technical properties that make them useful for jewelry and in the production of small stone accessories. Nevertheless, the introduction and approval of the term “true jasper” for rocks of hydrothermal-metasomatic origin and metamorphosed volcanogenic-sedimentary products to petrologic nomenclature is recommended. Different types of jaspers and related rocks have various economic significance. Jaspers or jasper-like rocks are decorative gemstones applied in jewelry, whereas others may be used as refractory materials or feldspar raw materials. In contrast, the petrographic research of jasperoids is useful during prospecting new ore deposits.Tematem artykułu jest problematyka nazewnictwa i klasyfikacji jaspisów oraz skał im pokrewnych w Polsce i na świecie. Termin jaspis jest obecnie różnie definiowany przez badaczy zajmujących się gemmologią i petrologią. Zróżnicowanie aktualnych poglądów dotyczących wspomnianych typów skał niesie ze sobą poważne konsekwencje. Termin jaspis cechuje się stosunkowo dużą popularnością wśród osób zajmujących się dystrybucją i sprzedażą kamieni ozdobnych. Jego stosowanie często okazuje się mylące dla potencjalnych nabywców „cętkowanych kamieni”. Z tego względu istotne wydaje się wprowadzenie do nomenklatury gemmologicznej i petrologicznej terminu jaspis prawdziwy (ang. true jasper). W artykule przedstawiono przegląd jaspisów występujących w Polsce oraz ich klasyfikację w świetle definicji podawanych przez różnych autorów. Uwzględniono w nim także ekonomiczne aspekty wykorzystania różnych rodzajów jaspisów. Większość tego typu skał ma zastosowanie w jubilerstwie, kamieniarstwie i produkcji drobnej galanterii kamiennej. Podobne do jaspisów pod względem mineralogicznym skały o charakterze jasperoidów mogą z kolei stanowić cenny wskaźnik przy poszukiwaniu złóż epitermalnych metali, takich jak np. złoto

Review of existing systems of jaspers nomenclature and classification in Poland and worldwide

Nowadays, the term “jasper” is variably defined in petrology and gemology. The unification of the nomenclature and the classification of jaspers seems to be an essential challenge for petrologists worldwide. This misnomer is very commonly used among sellers or collectors of various gemstones. Therefore, a huge diversity in the mineralogical composition, geological settings and genesis of particular “spotted stones” is reported. In this paper the term “jasper” is proposed for all “spotted stones” which have technical properties that make them useful for jewelry and in the production of small stone accessories. Nevertheless, the introduction and approval of the term “true jasper” for rocks of hydrothermal-metasomatic origin and metamorphosed volcanogenic-sedimentary products to petrologic nomenclature is recommended. Different types of jaspers and related rocks have various economic significance. Jaspers or jasper-like rocks are decorative gemstones applied in jewelry, whereas others may be used as refractory materials or feldspar raw materials. In contrast, the petrographic research of jasperoids is useful during prospecting new ore deposits.Tematem artykułu jest problematyka nazewnictwa i klasyfikacji jaspisów oraz skał im pokrewnych w Polsce i na świecie. Termin jaspis jest obecnie różnie definiowany przez badaczy zajmujących się gemmologią i petrologią. Zróżnicowanie aktualnych poglądów dotyczących wspomnianych typów skał niesie ze sobą poważne konsekwencje. Termin jaspis cechuje się stosunkowo dużą popularnością wśród osób zajmujących się dystrybucją i sprzedażą kamieni ozdobnych. Jego stosowanie często okazuje się mylące dla potencjalnych nabywców „cętkowanych kamieni”. Z tego względu istotne wydaje się wprowadzenie do nomenklatury gemmologicznej i petrologicznej terminu jaspis prawdziwy (ang. true jasper). W artykule przedstawiono przegląd jaspisów występujących w Polsce oraz ich klasyfikację w świetle definicji podawanych przez różnych autorów. Uwzględniono w nim także ekonomiczne aspekty wykorzystania różnych rodzajów jaspisów. Większość tego typu skał ma zastosowanie w jubilerstwie, kamieniarstwie i produkcji drobnej galanterii kamiennej. Podobne do jaspisów pod względem mineralogicznym skały o charakterze jasperoidów mogą z kolei stanowić cenny wskaźnik przy poszukiwaniu złóż epitermalnych metali, takich jak np. złoto

Factors Influencing Time Resolution of Scintillators and Ways to Improve Them

The renewal of interest in Time of Flight Positron Emission Tomography (TOF-PET), as well as the necessity to precisely tag events in high energy physics (HEP) experiments at future colliders are pushing for an optimization of all factors affecting the time resolution of the whole acquisition chain comprising the crystal, the photo detector, and the electronics. The time resolution of a scintillator-based detection system is determined by the rate of photo electrons at the detection threshold, which depends on the time distribution of photons being converted in the photo detector. The possibility to achieve time resolution of about 100 ps Full Width at Half Maximum (FWHM) requires an optimization of the light production in the scintillator, the light transport and its transfer from the scintillator to the photo detector. In order to maximize the light yield, and in particular the density of photons in the first nanosecond, while minimizing the rise time and decay time, particular attention must be paid to the energy transfer mechanisms to the activator as well as to the energy transition type at the activator ion. Alternatively other light emission mechanisms can be considered. We show that particularly Cerenkov emission can be used for this purpose. Special emphasis was put on the light transport within the crystal and at its interface with the photo detector. Since light is produced isotropically in the scintillator the detector geometry must be optimized to decrease the optical path-length to the photo detector. Moreover light bouncing within the scintillator, affecting about 70\% of the photons generated in currently used crystals, must be reduced as much as possible. We also investigate photonics crystals that are specifically designed to favor specific light propagation modes at the limit of total reflection inside and outside of the crystal and how they might increase the light transfer efficiency to the photo detector and hence improve time resolution. Examples for the production and deposition of photonics crystals as layers on Lutetium Yttrium Ortho-Silicate (LYSO) and Lutetium Yttrium Aluminum Perovskite (LuYAP) crystals are shown here, as well as first results on an improved light extraction resulting from this method