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Experimental validation of proton boron capture therapy for glioma cells
In vivo evaluation of the effects of combined boron and gadolinium neutron capture therapy in mouse models
Woonghee Lee, Kyung Won Kim, … Jeongsoo Yoo
Enhancement of Radiation Effectiveness in Proton Therapy: Comparison Between Fusion and Fission Methods and Further Approaches
Farshid Tabbakh & Narayan S. Hosmane
Monoenergetic 290 MeV/n carbon-ion beam biological lethal dose distribution surrounding the Bragg peak
Dylan J. Buglewicz, Austin B. Banks, … Takamitsu A. Kato
Fast dose fractionation using ultra-short laser accelerated proton pulses can increase cancer cell mortality, which relies on functional PARP1 protein
E. Bayart, A. Flacco, … V. Malka
A new platform for ultra-high dose rate radiobiological research using the BELLA PW laser proton beamline
Jianhui Bin, Lieselotte Obst-Huebl, … Antoine M. Snijders
Radiation dose enhancement using gold nanoparticles with a diamond linear accelerator target: a multiple cell type analysis
Olivia Piccolo, John D. Lincoln, … Michael N. Ha
Proton minibeam radiation therapy widens the therapeutic index for high-grade gliomas
Yolanda Prezado, Gregory Jouvion, … Frederic Pouzoulet
Activation of efficient DNA repair mechanisms after photon and proton irradiation of human chondrosarcoma cells
Birgit Lohberger, Dietmar Glänzer, … Dietmar Georg
First proton minibeam radiation therapy treatment plan evaluation
P. Lansonneur, H. Mammar, … L. De Marzi
Tatiana Shtam1,2,3,
Vladimir Burdakov1,2,
Alina Garina1,2,4,
Luiza Garaeva1,2,4,
Nhan Hau Tran1,4,
Andrey Volnitskiy1,2,
Eva Kuus1,4,5,
Dmitry Amerkanov1,2,
Fedor Pack1,2,
Georgy Andreev5,
Andrey Lubinskiy5,
Konstantin Shabalin1,2,
Nicolay Verlov1,2,
Evgeniy Ivanov1,
Victor Ezhov1,
Dmitry Lebedev1,2 &
Andrey L. Konevega1,2,4
Scientific Reports volume 13, Article number: 1341 (2023) Cite this article
Cancer models
Proton boron capture therapy (PBCT) has emerged from particle acceleration research for enhancing the biological effectiveness of proton therapy. The mechanism responsible for the dose increase was supposed to be related to proton-boron fusion reactions (11B + p → 3α + 8.7 MeV). There has been some experimental evidence that the biological efficiency of protons is significantly higher for boron-11-containing prostate or breast cancer cells. The aim of this study was to evaluate the sensitizing potential of sodium borocaptate (BSH) under proton irradiation at the Bragg peak of cultured glioma cells. To address this problem, cells of two glioma lines were preincubated with 80 or 160 ppm boron-11, irradiated both at the middle of 200 MeV beam Spread-Out Bragg Peak (SOBP) and at the distal end of the 89.7 MeV beam SOBP and assessed for the viability, as well as their ability to form colonies. Our results clearly show that BSH provides for only a slight, if any, enhancement of the effect of proton radiation on the glioma cells in vitro. In addition, we repeated the experiments using the Du145 prostate cancer cell line, for which an increase in the biological efficiency of proton irradiation in the presence of sodium borocaptate was demonstrated previously. The data presented add new argument against the efficiency of proton boron capture therapy when based solely on direct dose-enhancement effect by the proton capture nuclear reaction, underlining the need to investigate the indirect effects of the secondary alpha irradiation depending on the state and treatment conditions of the irradiated tissue.
Proton therapy (PT) has been applied for many years for the treatment of patients with different types of cancer. PT is characterized by a well-defined dose deposition in tissue with a sharp increase of the absorbed dose at a specific depth which depends on the initial beam energy (Bragg Peak)1. Beyond the Bragg Peak region, where the major part of the beam energy is absorbed, the dose drops sharply within next few millimeters of tissue. Such a dose distribution makes it possible to achieve a higher absorbed dose in the tumor region keeping the radiation damage to the surrounding tissue at acceptable level. Proton therapy could be particularly appropriate for the treatment of brain tumors, as it allows for the precise delivery of the radiation to the specific region of brain2.
Gliomas are the most common primary brain tumors with an incidence rate of about 6 cases per 100,000 population per year3. The median survival of patients with low-grade glioma can range from 6 to more than 15 years3, whereas the median survival for patients with glioblastoma, the most frequent and malignant high-grade gliomas, is often reported as few months3,4,5. The dosimetric advantages and the safety of PT for treatment of gliomas have been previously reported6,7. Several tumor-specific drugs are under development to improve the overall effectiveness of currently employed radio therapy, including PT, towards high-grade gliomas8,9, underlining the overall interest in targeted therapies aimed at improving the therapeutic ratio by increasing the selectivity of radio therapy toward the tumor cells and thus decreasing its adverse effects on the normal tissues9.
One of the emerging treatment modalities designed to improve the therapeutic ratio is boron neutron capture therapy (BNCT) which is based on neutron capture by non-radioactive 10B nuclei, a nuclear reaction process that can bring about a very significant dose enhancement in tissue enriched with 10B isotope. According to the early clinical studies, BNCT has the potential to become effective as a targeted therapy10. Being initially limited by the need of usage of research nuclear reactors as the neutron source, nowadays BNCT approach is boosted by the availability of specialized compact neutron source specially designed for medical purposes11 Several investigations are under way for the use of BNCT in high grade glioma treatment12,13. One of the critical components for successful deployment of BNCT is the choice of compounds for 10B delivery to the tumor that would meet the requirements for high tumor uptake, low normal tissue uptake, low toxicity and rapid clearance after treatment14,15,16. Currently the two major compounds used for this purpose are sodium borocaptate ((B12H11SH)Na2), BSH) and boronophenylalanine (C9H12BNO4, BPA)10. Approval of these boron-containing drugs in clinical trials of BNCT could give a clear advantage for their use in other types of radiotherapy.
Proton boron capture therapy (PBCT) was proposed as a potential cancer treatment method a few decades ago. In PBCT the dose enhancement effect was assigned to the reaction of nuclear fusion between 11B nuclei and the incident beam protons (11B + p → 8Be + α → 3α + 8.7 MeV). Emission of the high Linear Energy Transfer (LET) α-particles by proton-boron fusion reaction, that occurs primarily in the Bragg peak region and causes irreparable clustered DNA damages, was expected to increase the effectiveness of destruction of the tumor cell. There are two experimental reports showing a significant increase in the effectiveness of proton beam irradiation of 11B-containing cancer cells17,18. However, other works containing simulation and analytical calculations seem to indicate that the total number of the generated alpha particles cannot explain the experimental results19,20. Thus, the reported evidence for the possibility to use of boron-containing compounds for the dose enhancement in PT as well as the possible mechanisms of their radio-sensitizing effect remain contradictory and, in the view of a very limited number of studies on PBCT, call for a further investigation.
In the present study we have examined the possibility to enhance biological effects of proton irradiation in boron-containing cultured glioma cells.
We examined the radiosensitizing effect of sodium borocaptate for proton beam irradiation applied to two glioma cell lines (A172 and Gl-Tr), as well prostate cancer cells Du145, for which such an effect of BSH was demonstrated earlier17,18. The boron-11 concentration in most experiments was 80 ppm, and the periods of cell incubation with BSH were 7 h and 18 h. After incubation with BSH the cells were irradiated with 89.7 MeV clinical proton beam, positioning the cells at the distal end of Spread-Out Bragg Peak (SOBP) (Supl. Figure 1). An additional experiment was carried out with irradiation of cells with a 200 MeV proton beam, positioning the cells in the middle of the SOBP (Supl. Figure 1). These incubation points and irradiation conditions were selected based on the earlier reports demonstrating increased cell death under proton irradiation in the presence of different boron-containing compounds17,18,21.
Cytotoxicity of sodium borocaptate (BSH) for A172 (A), Gl-Tr (B) glioma cells, Du145 prostate cancer cells (C), and DF-2 fibroblasts of human skin (D). The cytotoxic effects of BSH at 0—1000 ppm of 11B concentration have been studied by the AlamarBlue cell viability assay after 7 h or 18 h of incubation.
Cytotoxicity of sodium borocaptate for glioma cells
To determine the threshold toxic concentration of 11B, glioma cells, Du145 cells, as well as fibroblasts of human skin, DF-2, were incubated in the presence of BSH for 7 h and 18 h. The cytotoxic effects of BSH at 40–1000 ppm of 11B concentration have been studied by the AlamarBlue cell viability assay. The cytostatic effect of sodium borocaptate on glioma cells, as well as Du145 prostate cancer cells, is manifested at concentrations from 500 ppm of 11B and higher (Fig. 1A–C). For normal cells, DF-2 fibroblasts, the cytotoxic effect was not observed over the entire range of analyzed boron concentrations (Fig. 1D). No significant decrease in the survival rate of all studied cell types was observed at 80–160 ppm boron concentration range used in the study.
Cell cycle parameters of glioma cells in the presence of sodium borocaptate
Measurements of cell cycle parameters of A172 cells during incubation for 7 h (p = 0.12) or 18 h (p = 0.507) with BSH at a concentration of 80 ppm showed a typical pattern of cell distribution along the cell cycle, recorded in control cells (Fig. 2A). For Gl-Tr cells, a very slight increase in the number of cells in the G0/G1 phase of the cell cycle (p = 0.05) was observed during 18 h of incubation with sodium borocaptate (Fig. 2B). Thus, in the analyzed glioma cells, there is no significant effect of sodium borocaptate on the distribution of the phases of the cell cycle. For prostate cancer Du145 cells, no significant changes were observed in the parameters of the cell cycle during incubation of cells in the presence of BSH for both 7 h (p = 0.507) and 18 h (p = 0.261) (Fig. 2C). The Mann – Whitney test was used to assess the differences between groups (with/without BSH). Level of significance was set at p < 0.05. Examples of cell distribution by cell cycle phases in the presence of sodium borocaptate are shown in Supplementary Fig. S2.
Distribution of A172 (A), Gl-Tr (B) glioma cells, and Du145 prostate cancer cells (C) over the phases of the cell cycle after incubation with sodium borocaptate (BSH) at a boron-11 concentration of 80 ppm for 7 h (up panels) or 18 h (bottom panels).
Effect of preincubation with 80 ppm boron-11 as part of BSH on the sensitivity of glioma cells to proton irradiation at the Bragg peak
Next, we investigated whether the presence of sodium borocaptate increased the sensitivity of glioma cells to proton irradiation. Cells were incubated in a medium containing 80 ppm of boron-11 for 7 h or 18 h and then irradiated at the distal end of SOBP of 89.7 MeV clinical proton beam in a dose range of 0–6 Gy. Irradiation was carried out in the presence of boron-11 in the cell culture medium. The efficiency of irradiation was determined using both the AlamarBlue Assay and the Clonogenic assay. Cell viability was fitted with a linear-quadratic function of the radiation dose. In addition, irradiation dose for half-maximal inhibition of cell viability (IC50) and a dose-modifying factor for 20% cell survival (DMF20) in the presence of borocaptate, as compared to irradiation alone, were determined. The Mann – Whitney test was used to assess the differences between groups (with/without BSH) and one sample t-test—to evaluate difference DMF20 values from 1. Evaluation of the effectiveness of radiosensitization with sodium borocaptate of glioma cells, carried out using the AlamarBlue Cell Viability Reagent, did not demonstrate any significant effect from the presence of boron in the cell culture medium before and during irradiation (Fig. 3A,B). Fitting parameters, irradiation dose for half-maximal inhibition of viability, and dose-modifying factor for 20% survival of Gl-Tr cells with irradiation alone or after incubation with sodium borocaptate for 7 h are presented in Table 1. A similar lack of sensitizing effect was observed for Du145 cells (Fig. 3C). The dose-modifying factors (DMF20) for Du145 cells irradiated after incubation with BSH for 7 and 18 h were 1.03 ± 0.01 (p = 0.535) and 0.95 ± 0.06 (p = 0.492) respectively. The values of the determined survival parameters for all studied cell lines summarized in Supplementary Tables 1–3.
Effect of BSH on cell viability after exposure to Bragg peak protons at different absorbed dose. Summary plots for AlamarBlue cell viability assays: (A) A172 cells, (B) Gl-Tr cells, (C) DU145 cells (dashed lines). The cells were incubated in a medium containing 80 ppm of boron-11 for 7 h (up panels) or 18 h (bottom panels) and then irradiated by 89.7 MeV clinical proton beam in a dose range of 0–6 Gy. Data were fitted with a linear-quadratic function of the radiation dose (solid lines). Each plot summarizes the results of three independent irradiation experiments.
Table 1 Parameters for the linear-quadratic fit of cell viability curve Y(X) = exp (–αX–βX2), irradiation dose for half-maximal inhibition of viability (IC50), and dose-modifying factor for 20% survival (DMF20) of Gl-Tr cells with proton irradiation alone (Control) or after incubation with 80 ppm of boron-11 (BSH) for 7 h.
The AlamarBlue assay is commonly used to quantify the number of live cells in a sample, and to monitor cell viability / cytotoxicity. But only a fraction of live seeded cells retains the capacity to produce colonies after irradiation. Clonogenic assay is the method of choice to determine cell reproductive death after treatment with ionizing radiation. Therefore, at the next step of the study, we tested the ability of glioma cells incubated with 80 ppm of boron-11 to form colonies after irradiation with an 89.7 MeV clinical proton beam at the distal end of Bragg peak. For cells of both glioma lines we observed a very slight and not significant effect of reducing the number of viable colonies in the samples incubated and irradiated in the presence of sodium borocaptate (Fig. 4A,B). For example, for Gl-Tr cells, the irradiation doses corresponding to 50% survival of colonizing cells were 1.9 ± 0.8 and 1.4 ± 0.6 (p = 0.275) for irradiation alone and for irradiation of cells preincubated with BSH for 7 h. At the same time, the dose-modifying factor, DMF20 for these cells was 1.32 ± 0.15 (p = 0.07). This weak effect was not reproduced stably in independent experiments and did not depend on the time of incubation with the BSH (Fig. 4A,B). Moreover, for Du145 cells, we did not observe a significant effect of sodium borocaptate introduced into the culture medium on the formation of viable colonies after clinical proton beam irradiation (Fig. 4C). DMF20 for Du145 cells preincubated with BSH for 7 and 18 h were 0.99 ± 0.12 (p = 0.741) and 1.25 ± 0.02 (p = 0.05), respectively. The values of the determined survival parameters for all studied cell lines summarized in Supplementary Tables 1–3. Examples of colony assays for proton boron capture treatment are shown in Supplementary Fig. S3.
Effect of BSH on cell colony formation after exposure to Bragg peak of 89.7 MeV clinical proton beam. Summary plots for colony assays: (A) A172 cells, (B) Gl-Tr cells, (C) Du145 cells (dashed lines). Data were fitted with a linear-quadratic function of the radiation dose (solid lines) with the parameter β constrained to non-negative values. The cells were incubated in a medium containing 80 ppm of boron for 7 h (up panels) or 18 h (bottom panels) and then irradiated by 89.7 MeV clinical proton beam in a dose range of 0–6 Gy. After treatment, 103 cells were seeded out to form sufficiently large clones consisting of 50 or more cells. Colony formation assay was performed in 10–14 days. Each plot summarizes the results of three independent experiments.
Experiments to determine the survival of the cells and their ability to form colonies after incubation with BSH were also carried out using a 200 MeV proton beam. The parameters of cell irradiation, as well as the conditions of cell incubation with boron-11, were chosen similar to our previous study, in which we observed the sensitizing effect of sodium tetraborate (Na2B4O7) during proton irradiation of glioma cells21. Cells were incubated with 80 ppm of boron-11 for 18 h, transferred to test tubes in a complete culture medium without BSH, irradiated at the middle position of SOBP (Suppl. Fig. S1), and then analyzed for viability by AlamarBlue and colony forming assay. A comparative analysis of the metabolic activity of cells after irradiation with a 200 MeV proton beam did not reveal any radiosensitizing effect of boron-11 for both glioma cells and prostate cancer cells (Fig. 5, upper panels). DMF20 for A172, Gl-Tr and DU145 cells preincubated with sodium borocaptate were less than unity 0.98 ± 0.29 (p = 0.948), 0.92 ± 0.08 (p = 0.02) and 0.98 ± 0.31 (p = 0.468), respectively. When analyzing the ability of cells to form colonies after proton irradiation, a slight decrease in the number of colonies of A172 cells preincubated with BSH was observed compared with only irradiated cells (Fig. 5A, bottom panel). The determined IC50 for these cells without and with sodium borocaptate was 0.75 ± 0.30 and 0.50 ± 0.30 (p = 0.05), and DMF20 was 1.20 ± 0.01 (p = 0.05) (Suppl. Table S1). No significant radiosensitizing effect of boron-11 was observed for the second glioma cell line (Fig. 5B, bottom panel). Prostate cancer cells formed the same number of colonies after irradiation with a 200 MeV proton beam, both after cell incubation with and without sodium borocaptate (Fig. 5C, bottom panel). DMF20 for Gl-Tr and DU145 cells preincubated with sodium borocaptate were 1.02 ± 0.12 (p = 0.415) and 1.19 ± 0.04 (p = 0.144), respectively (Suppl. Tables S2,S3). Examples of colony assays for proton boron capture treatment at the middle position of SOBP of 200 MeV proton beam are shown in Supplementary Fig. S4.
Comparison of cell survival under combined exposure to 80 ppm boron-11 and irradiation at the middle position of Spread-Out Bragg Peak of 200 MeV proton beam. Summary plots for AlamarBlue (up panels) and colony forming assays (bottom panels): (A) A172 cells, (B) Gl-Tr cells, (C) Du145 cells. The cells were incubated in a medium containing 80 ppm of boron-11 for 18 h and then irradiated by 200 MeV proton beam in a dose range of 0–6 Gy. Data were fitted with a linear-quadratic function of the radiation dose (solid lines) with the parameter β constrained to non-negative values.
Possibilities for increasing the biological effect of the sodium borocaptate on the survival of cells when irradiated with clinical protons at the Bragg peak
Despite the high content of boron atoms per single BSH molecule ((B12H11SH)Na2), sodium borocaptate has a disadvantage for clinical usage for BNCT of gliomas, namely, poor cellular uptake by brain tumors15,22. To test the hypothesis about the possible insufficiency of boron in the culture medium of glioma cells to obtain the radiosensitizing effect of BSH for proton boron capture therapy, we increased the concentration of boron-11 up to 160 ppm. We did not observe any sensitizing effect when the amount of BSH was doubled during incubation and 89.7 MeV clinical proton beam irradiation of glioma cells (Fig. 6A,B). Moreover, we also did not observe any effect of boron proton capture therapy for Du145 prostate cancer cells (Fig. 6C), for which the expected effect was described earlier17,18. The values of the determined survival parameters for all studied cell lines are summarized in Supplementary Tables 1–3. Examples of colony forming assays for 7 h of incubation of cells with 160 ppm boron-11 and subsequent clinical proton beam irradiation are shown in Supplementary Fig. S3.
Cell viability after incubation of cells with 160 ppm of boron-11 and exposure to Bragg peak of 89.7 MeV clinical proton beam. Summary plots for AlamarBlue (up panels) and colony forming assays (bottom panel): (A) A172 cells, (B) Gl-Tr cells, (C) Du145 cells. The cells were incubated in a medium containing 160 ppm of boron-11 for 18 h and then irradiated at the distal position of 89.7 MeV clinical SOBP in a dose range of 0–6 Gy. Experimental data (dashed lines) were fitted with a linear-quadratic function of the radiation dose (solid lines) with the parameter β constrained to non-negative values.
Since the cross section of the 11B + p → 3 α + 8.7 MeV nuclear reaction increases with a decrease in the average proton beam energy, we tried to increase the biological efficiency of boron proton capture by positioning the cells in the most distal part of the Bragg peak. To test the hypothesis, the Du145 cells were positioned at a depth of 30 mm (I position tested in all previous experiments), and at a depth of 32 mm (II position) along the 89.7 MeV clinical proton SOBP, at the distal end of the Bragg peak (Fig. 7A). In addition, in these experiments we used a triple concentration of borocaptate corresponding to 250 ppm of boron-11. Example of colony forming assays for 7 h of incubation of Du145 cells with BSH and subsequent proton beam irradiation along the proton SOBP is shown in Fig. 7B. No dose enhancement effect was observed when cells were irradiated in the presence of BSH both at the position I of the proton beam and at position II, at the distal end of the SOBP (Fig. 7C,D). The calculated DMF20 for cell irradiation at position I with or without sodium borocaptate was close to 1 when using the AlamarBlue metabolic test and less than 1 for the clonogenic assay. The similar factors for the irradiation position II were indistinguishable from 1 (Suppl. Table S3). Summarizing the results, we found that irradiation-induced cellular lethality was either not enhanced by pre-treatment of cells with BSH, or the observed enhancement was rather small and not statistically significant.
Effect of BSH on cell survivability after exposure to Bragg peak protons at different absorbed dose. (A) Dose profile for irradiation of cells with an 89.7 MeV clinical proton beam. In the majority of experiments, the cells were positioned at a depth of 30 mm (I position), and in some—at a depth of 32 mm (II position) along clinical proton SOBP. (B) Examples of colony forming assays for 7 h of incubation of Du145 cells with BSH (0 ppm (Control) or 250 ppm of boron-11) and proton beam irradiation at I position or II position of proton SOBP. (C,D) Plots for AlamarBlue (up panels) and colony forming assays (bottom panels) of Du145 cells. The cells were incubated in a medium containing 250 ppm of boron-11 and then irradiated by proton beam in a dose range of 0–6 Gy at (C) I position or (D) II position of SOBP of 89.7 MeV clinical proton beam.
A method to increase the biological effectiveness of proton beam is of high interest in radiation oncology. In thefirst publication on proton boron capture in radiation therapy authors used Monte Carlo simulations and showed an enhanced high dose in the areas where the boron uptake coincided with the Bragg peak23. In this work the increase of the maximum dose level was reported at about 50% for 80 MeV proton energy beam. Also, the increase of the maximum dose level of PBCT was reported at 192.4% for 75 MeV beam24. The mechanism responsible for a higher dose was suggested to be related to proton-boron fusion reactions, leading to the production ofhigh Linear Energy Transfer (LET) α-particles.
There are a few other studies which used Monte Carlo simulations, but which produced highly divergent results on the potentially achievable boron proton capture dose based on using different proton energies and 11B concentrations20,25,26. These later simulations confirm that the number of induced reactions on boron-11 in proton therapy is negligible. For example, according to the results of Tayebeh A et al. the total dose of alpha particles generated from boron proton capture for 70–85 MeV proton beam is piddling, even in the situation that the entire tumor region was considered full of boron-1120. Also, according to simulations of Mazzone et al. at 80 ppm concentration of 11B and 45–60 MeV proton energies, the effect of the p + 11B → 3α reaction is negligible and the dose related to this reaction several orders of magnitude lower than the dose delivered by the primary proton beam25. In fact, both results indicate that the reaction probability is too low to bear any effect in the therapy.
On the basis of these considerations, it seems highly unlikely that the reported decrease in cellular survival in the presence of BSH17,18 is related with the boron proton capture. Another explanation for the described radiosensitizing effect of boron-11 may be the biochemical properties of the boron-containing compound. For example, according to our previous results the radiosensitizing effect of boron-11 on the viability of the cancer cells subjected to proton irradiation was detected in vitro using two human malignant glioma cell lines, and sodium tetraborate (Na2B4O7) as a boron containing substance21. But the fact that we observed a similar radiosensitizing effect of sodium tetraborate on A172 cells when they were subjected to gamma-radiation indicated that the decrease in the survival rate of cells irradiated after pre-incubation with the boron containing compound is likely due to its pharmacological and chemical properties rather than an increase in the absorbed dose due to 11B + p → 3α nuclear reaction21. In this work we have also tested the possibility of increasing the biological effects of gamma radiation by the presence of sodium borocaptate and observed no effect (Suppl. Fig. S5, Suppl. Tables S1–S3).
In this study, we examined the radiosensitivity of two glioma cell lines by proton beam irradiation in the presence of sodium borocaptate. Our results clearly show that BSH, being non-toxic to the normal morphology DF-2 cells and to the glioma cells at the concentrations used, produces little, if any, enhancement of the effect of proton radiation on the glioma cell lines in vitro. Since the additional dose enhancement generated by boron proton capture depends on the proton energy and intracellular 11B concentration, we have tested various variants of incubation of glioma cells with BSH, and also carried out a series of irradiation on two cyclotrons with different energies of the proton beam. Fitting parameters and dose-modifying factor for 20% survival for colony forming assays of glioma cells with irradiation alone or after incubation with sodium borocaptate are presented in Table 2. Despite the fact that the dose-modifying factor in some experiments was greater than one, in all experiments the radiosensitizing effect of sodium borocaptate was not statistically significant and did not depend on the time of preincubation with BSH (7 or 18 h), concentration of boron-11 (80 or 160 ppm), or on the initial energy of the proton beam (89.7 or 200 MeV).
Table 2 Parameters for the linear-quadratic fit of clonogenic survival data Y(X) = exp (–αX–βX2), and dose-modifying factor for 20% survival (DMF20) of Du145, A172, and Gl-Tr cells with proton irradiation alone (Control) or after incubation with boron-11 (BSH).
Given the published data12,15,22, it is possible that the apparent lack of radiosensitizing effect of BSH upon glioma cell irradiation with protons could be explained by the ineffective uptake of this compound by the studied glioblastoma cells. Testing this hypothesis, we repeated all experiments using the Du145 prostate cancer cell line, for which an increase in the biological efficiency of proton irradiation in the presence of sodium borocaptate was demonstrated17,18. In these two experimental studies the authors obtained a first pre-clinical demonstration of PBCT at the relatively low-energy clinical proton beamline (62 MeV) and at the high-energy proton beamline (250 MeV) reporting a significant reduction in the colony-forming ability of prostate cancer Du145 cells irradiated in the presence of the boron carrier BSH17,18. In both experiments, the authors preincubated cells for 6–8 h with 80 ppm of boron-11 and irradiated cells at various depths along the two clinical SOBPs, observing the radiosensitizing effect of BSH at the mid- and distal SOBP positions17,18.
In this study, we used the previously reported experimental conditions17,18: we pre-incubated Du145 prostate cancer cells with BSH (boron-11 concentration 80 ppm) for 7 h; irradiated with a 200 MeV proton beam, positioning the cells at the middle SOBP position; irradiated with 89.7 MeV clinical proton beam, positioning the cells at the distal end of SOBP. The effectiveness of the combined exposure was analyzed using both the AlamarBlue cell viability assay and the Clonogenic assay. Fitting parameters and dose-modifying factor for 20% survival for colony forming assays of Du145 cells with irradiation alone or after incubation with sodium borocaptate under various experimental conditions are summarized in Table 2. In all those experiments, proton irradiation in the presence of BSH did not appear to reduce Du145 cell viability or clonogenic survival to the degree comparable to that reported in the works17,18. Moreover, neither an increase in the concentration of boron-11 in the culture medium (160 or 250 ppm), nor an increase in the incubation time with sodium borocaptate (18 h) or the positioning of the cells at the most distal end of the clinical SOBP did not increase the sensitizing effect of BSH.
Based on the published experimental data and the results of calculations and simulations17,18,20,21,25,26, our results appear to indicate that the mechanisms of the radiosensitizing effects of boron during proton irradiation involves a complex process that is not limited to the dose enhancement by the alpha-particles produced in 11B + p → 3α nuclear reaction. As already indicated, the additional dose produced by this reaction is not sufficient to bring to any substantial cell damage at any reasonable BSH concentrations25. Moreover, considering a relative sparseness of the nuclear reaction events that follows from the simulation and the short range of the alpha particles released, these particles appear to directly affect only a small fraction of the irradiated cells. Our results therefore seem to support the hypothesis that radiosensitizing effect of BSH could be to the large extent attributed to the indirect effects of the alpha irradiation18, such as radiation induced bystander effects27,28,29. These effects could largely depend on the state and treatment conditions of the cell culture or irradiated tissue, calling for further studies to establish the applicability of the proton boron capture therapy technique.
The following reagents were used in the study: sodium mercaptododecaborate (KATCHEM Ltd.,Czech Republic), AlamarBlue Cell Viability Reagent (Invitrogen, USA), Dulbecco′s Modified Eagle′s Medium/Nutrient Mixture F-12 Ham (DMEM/F12 (1:1) medium (BioloT, Russia)), fetal bovine serum (HyClone, USA). All other reagents were obtained from Sigma-Aldrich (USA).
Cell lines and cultivation conditions
The work was carried out using two human glioma cell lines: A172- glioma cell line was obtained from the collection of the Institute of Cytology of the Russian Academy of Sciences (St. Petersburg, Russia); Gl-Tr—glioma cell line generated in the Laboratory of Cell Biology (NRC «Kurchatov Institute»-PNPI, Gatchina, Russia)30; Prostate cancer cell line Du145 was kindly donated by Dr. A. Malek, N.N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russia. DF2- fibroblasts of the skin from eyelids of an adult donor were obtained from the collection of the Institute of Cytology of RAS and were used as a control in cytotoxicity experiments. The cells were cultured in an atmosphere of 5% CO2 at 37 °C in DMEM/F12 (1:1) medium containing L-glutamine, 0.1 mg/ml each of penicillin and streptomycin, and supplemented with 10% fetal bovine serum.
Analysis of BSH cytotoxicity
To establish cytotoxicity of borocaptate, DF-2, A172, Gl-Tr, and Du145 cells were plated in 96-well tissue culture plate in concentration of 5 × 103 cells per well, incubated for 24 h in complete medium, then the medium was replaced with a medium containing BSH in the concentration range, corresponding to 11B of 0 – 1000 ppm. After 18 or 7 h of incubation, the proliferative activity of the cells was tested by the AlamarBlue® Assay. AlamarBlue Cell Viability Reagent was added to the plate according to the manufacturer's protocol and incubated for two hours. The fluorescence was detected using EnSpire Multimode Plate Reader (PerkinElmer, USA). All experiments were carried out in quintuplicate.
Cell cycle analysis
For the cell cycle analysis, A172, Gl-Tr, and Du145 cell lines were plated at 4 × 105 cells/well in a six well tissue culture plate, cultured for 24 h, then the medium was replaced with a medium containing BSH (80 ppm of 11B). After 18 or 7 h of incubation in the presence of BSH, the cells were trypsinized, washed with phosphate-buffered saline (PBS), and incubated for 10 min in a solution containing Triton X-100 (0.1% solution v/v) and Hoechst 33,342 (10 µg/ml). The fraction of cells in G0/G1, S and G2/M, based on Hoechst 33,342 labelling of DNA content, was determined by flow cytometry (Beckman Coulter, USA). For each sample, 104 events were collected. Experiments were performed in quintuplicate.
Cell irradiation was performed in two ways. For the first way, two days before irradiation A172, Gl-Tr, and Du145 cells were seeded in T25 flasks at 5 × 105 cells/flask and were cultured for 24 h. Then the cell growth medium was aspirated and replaced with 5 ml of fresh medium (control) or with BSH-containing medium. The working concentration of 80 ppm of 11B corresponded to 0.17 mg/ml of BSH. After 18 h of incubation in the presence of 11B, the cells were trypsinized, washed with medium, resuspended in complete culture medium without BSH, and counted by LUNA-II™ Automated Cell Counter (Logos Biosystems, South Korea). Then each cell suspension was split into five portions (0.1 ml each), transferred into sterile Eppendorf tubes at 105 cells/tube, and irradiated. Proton irradiations were performed on 1 GeV synchrocyclotron SC-1000 (NRC «Kurchatov Institute»-PNPI, Gatchina, Russia) using Roscosmos test facility (IS OP CDKT.412110.013) equipped with a variable length remote-controlled copper plate degrader and a bending magnet to reduce the energy spread31. The degrader length was set to 491 mm to generate a 200 MeV proton beam with an energy spread of approximately 10 MeV. The beam had a round cross-section with diameter of 30 mm (intensity variations not exceeding 10%). The beam was directed into a plexiglas tissue-equivalent phantom, resulting in a Spread-Out Bragg Peak (SOBP) located ca. 22 cm inside the phantom and spanning approximately 25 mm of the phantom depth. The phantom depth was varied by addition of the appropriate number of 2.8 mm plexiglass plates. The position of SOBP was determined by a series of dose rate measurements using Unidos Webline clinical dosimeter, which was also used for the dose calibration. The dose rate variations within SOBP did not exceed 10%. The proton beam was calibrated before each experiment. The dose profile is shown in Supplementary Fig. S1A. Cell samples were positioned in the phantom near the middle of SOBP and irradiated with increasing doses of 0.5–6 Gy. After irradiation the cells were seeded at 1 × 104 cells/well in a 24 well tissue culture plate and incubated at normal conditions during 48 h. The irradiation experiments were carried out in triplicate.
For the second way, two days before irradiation A172, Gl-Tr, and Du145 cells were plated at 4 × 104 cells/well in a six well tissue culture plate, and were cultured for 24 h. Then the cell growth medium was aspirated and replaced with 3 ml of fresh medium (control) or with BSH-containing medium. In most experiments, we used a working concentration of BSH of 80 ppm, but in a number of experiments, concentrations of BSH of 160 ppm and 250 ppm were also used. The working concentrations of 80 ppm, 160 ppm and 250 ppm of 11B corresponded to 0.17 mg/ml, 0.34 mg/ml, and 0.53 mg/ml of BSH, respectively. After 18 or 7 h of incubation in the presence of 11B, the cells were irradiated in 6-well plates in a medium containing boron-11 with a clinical proton beam at Bragg peak in a dose range of 2–6 Gray. During irradiation, the plates with cells were positioned horizontally in front of the proton beam. Proton irradiation was performed on a Varian ProBeam version 3.5 at the MIBS proton therapy center (Berezin Sergei Medical Institute, St. Petersburg, Russia). Irradiation was carried out with a pencil beam in layers, with the beam proton energy from 89.735 MeV in the first layer to 110.735 MeV in the eighth layer. Spot weight ranged from 0 to 119.98 MU. Irradiation plans were created using Eclipce software, version 13.6. The dose profile is shown in Supplementary Fig. S1B. Water-equivalent plates 30 mm thick were placed above the samples to shift the Bragg peak to the cell layer. In most experiments, the cells were positioned at a depth of 30 mm, and in several—at a depth of 32 mm (Fig. 7A). One hour after irradiation, the culture medium in the plates was replaced with complete culture medium and the cells were incubated under standard conditions for 48 h. All irradiations with a clinical proton beam were carried out in triplicate.
To test whether the physical nuclear reaction 11B(p,3α) affects the cancer cell death by proton beam irradiation, cell lines were also exposure to 80 ppm boron-11 and gamma radiation at different absorbed dose. After 18 h of incubation in the presence of 11B, the cells were trypsinized, washed with medium, resuspended in complete culture medium without BSH, and counted by LUNA-II™ Automated Cell Counter (Logos Biosystems, South Korea). Then each cell suspension was split into five portions (0.1 ml each), transferred into sterile Eppendorf tubes at 105 cells/tube, irradiated with graded doses 0–8 Gy using 60Co γ-ray source "Issledovatel" (NRC «Kurchatov Institute»-PNPI, Gatchina, Russia).
Cell viability and colony formation assays after irradiation
For cell viability assay irradiated and control cells were passaged at a concentration of 1 × 103 cells/well in 96 well tissue culture plate in five replicates of each experimental point. To determine the survival rate, the AlamarBlue® Assay was applied 6 days after irradiation. AlamarBlue Cell Viability Reagent was added to the plate according to the manufacturer's protocol and incubated for two hours. The fluorescence was detected using EnSpire Multimode Plate Reader (PerkinElmer, USA).
Clonogenic assay is the method of choice to determine cell reproductive death after treatment with ionizing radiation. After irradiation, the cells were seeded at 1 × 103 cells/well in a six well tissue culture plate, to form colonies in 1–2 weeks. Cells were incubated in standard conditions until cells in control dishes have formed sufficiently large clones. Then colonies were fixed with 96% ethanol, stained with crystal violet (0.5% w/v), washed with water, dried in air, photographed and counted by free ImageJ software.
Raphical visualization and statistical analysis were performed using SPSS 22.0 and GraphPad Prism 9.4.0. Dose–response curves were constructed fitting the cell viability values to the linear-quadratic equation Y(X) = exp (–αX–βX2) by GraphPad Prism 9.4.0 (nonlinear regression with the parameter β constrained to non-negative values), and α/β parameters were used to calculate Dose-Modifying Factor at 20% survival level (DMF20). Experimental data are expressed as the mean ± the standard deviation (SD). To assess differences between groups (with or without BSH), the Mann–Whitney test was used. One sample t-test was used to evaluate difference of DMF20 values from 1. Level of significance was set at p < 0.05.
All data generated or analyzed during this study are included in this published article and its supplementary information files.
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Volnitskiy, A. et al. Abnormal activity of transcription factors gli in high-grade gliomas. PLoS ONE 14(2), e0211980. https://doi.org/10.1371/journal.pone.0211980 (2019).
Artamonov, S. A., Ivanov, E. M., Ivanov, N. A., Lebedeva, J. S. & Riabov, G. A. Numerical simulation and optimization of the variable energy 60–1000 MeV proton beams at PNPI synchrocyclotron for testing the radiation resistance of electronics. Phys. Part. Nucl. Lett. 14(1), 188–200. https://doi.org/10.1134/S1547477117010046 (2017).
The study was supported by NRC "Kurchatov Institute" (Order # 2757). Experiments to determine the cytotoxicity of boron preparations and cell cycle parameters were supported by the Ministry of Science and Higher Education of the Russian Federation (project 075-15-2021-1360).
Petersburg Nuclear Physics Institute Named By B.P. Konstantinov of National Research Centre "Kurchatov Institute", Leningradskaya Oblast, Mkr. Orlova Roshcha 1, Gatchina, Russian Federation, 188300
Tatiana Shtam, Vladimir Burdakov, Alina Garina, Luiza Garaeva, Nhan Hau Tran, Andrey Volnitskiy, Eva Kuus, Dmitry Amerkanov, Fedor Pack, Konstantin Shabalin, Nicolay Verlov, Evgeniy Ivanov, Victor Ezhov, Dmitry Lebedev & Andrey L. Konevega
National Research Center "Kurchatov Institute", Akademika Kurchatova Pl. 1, Moscow, Russian Federation, 123182
Tatiana Shtam, Vladimir Burdakov, Alina Garina, Luiza Garaeva, Andrey Volnitskiy, Dmitry Amerkanov, Fedor Pack, Konstantin Shabalin, Nicolay Verlov, Dmitry Lebedev & Andrey L. Konevega
Institute of Cytology of Russian Academy of Sciences, St. Petersburg, Russian Federation
Tatiana Shtam
Peter the Great St.Petersburg Polytechnic University, Politehnicheskaya 29, St. Petersburg, Russian Federation
Alina Garina, Luiza Garaeva, Nhan Hau Tran, Eva Kuus & Andrey L. Konevega
Proton Therapy Center MIBS, St. Petersburg, Russian Federation
Eva Kuus, Georgy Andreev & Andrey Lubinskiy
Vladimir Burdakov
Alina Garina
Luiza Garaeva
Nhan Hau Tran
Andrey Volnitskiy
Eva Kuus
Dmitry Amerkanov
Fedor Pack
Georgy Andreev
Andrey Lubinskiy
Konstantin Shabalin
Nicolay Verlov
Evgeniy Ivanov
Victor Ezhov
Dmitry Lebedev
Andrey L. Konevega
Conceptualization, T.S., V.E., A.L.K.; data curation, L.G., A.G., A.V., N.H.T.; funding acquisition, T.S., A.L.K.; irradiation, D.A., V.B., N.V., E.I., E.K., G.A., A.L.; dosimetry, F.P.; investigation, L.G., A.G., N.H.T., V.B., A.V.; analysis and interpretation of data L.G., A.G., K.S., D.L., V.E., T.S.; original draft preparation, T.S.; prepare figures, L.G., A.G., T.S.: drafting the article or revising it critically for important intellectual content D.L., A.L.K.; conception, design and, supervision T.S., A.L.K. All authors reviewed the manuscript.
Correspondence to Tatiana Shtam or Andrey L. Konevega.
Supplementary Information.
Shtam, T., Burdakov, V., Garina, A. et al. Experimental validation of proton boron capture therapy for glioma cells. Sci Rep 13, 1341 (2023). https://doi.org/10.1038/s41598-023-28428-z
DOI: https://doi.org/10.1038/s41598-023-28428-z
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About this glove: Titleist doesn't make a whole lot of gloves – only three models as of this writing (2015). No surprise there, as it's the sibling company to golf's No. 1 glove manufacturer, FootJoy.
But Titleist being Titleist, its few offerings are considered top-of-the-line. The Players ($24) is Titleist's flagship glove, with the Players-Flex ($22) next in line. The Perma-Soft may be the least expensive at 18 bucks, but it's still considered a premium model.
The Perma-Soft features a CoolMax mesh strip across the back of the hand to promote breathability and flexibility in harmony with the hand's movement. It's made from a cabretta leather specially tanned, Titleist says, to resist moisture and retain its shape over time.
We'd heard lots of good things about Titleist's Perma-Soft glove. Let's see if it lives up to that lofty rep.
Appearance: Kudos to Titleist – the ultimate traditionalist brand – for offering a little color in the Perma-Soft lineup. Granted, a thin strip of red, green or fuchsia mesh across the backhand isn't exactly punk rock, but at least you've got options. All in all, Perma-Soft is a smart, conventional-style glove with just a touch of flair if you want it.
Comfort: It's cabretta, so you know its soft, smooth and light as a feather. Slipping into and out of the Perma-Soft glove is a breeze, and it holds shape well over repeat rounds.
Feel: Titleist is synonymous with feel, which undoubtedly influences any tester's ability to judge a Titleist product with zero bias. So we admit, we expected the Perma-Soft to deliver the goods in this department. It did. While it's ever so slightly thicker than the Titleist Players model, Perma-Soft hardly suffers by comparison. Light on the palm and in the fingers, it conducts feedback very, very well.
Tackiness: If a glove makes you grip the club a little harder than normal, it's not tacky enough. This is rarely if ever an issue with a new glove, but the surfaces of some will wear thin and slick after a half-dozen rounds. Perma-Soft stays tacky deep into its lifespan, though we highly recommend cleaning the glove after four or five outings. This will assure a nice, grabby grip for several rounds thereafter.
Durability: Not the strong suit of Titleist gloves, but no worse than your average cabretta model. Super-thin, premium cabretta leather is prized for its comfort and feel, with the tradeoff being a little less durability than synthetic or lower-grade leather models. The choice is yours.
We will say, though, that the Perma-Soft gets a slight nod over the Players glove in this department.
Bottom line: If we had to choose between Titleist's Players glove and the Perma-Soft, we'd go Perma-Soft. Not because it's a better glove, but because there's little if any difference except price. Given Perma-Soft's minor edge in durability, and the ability to customize colors, it's clearly a better value.


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Congaree (April 20, 1998 - November 22, 2020) was an American Thoroughbred racehorse and sire. A multiple Grade I winner and earner of over $3,000,000, Congaree finished third in both the 2001 Kentucky Derby and Preakness Stakes.

Background
Out of the mare Mari's Sheba, a granddaughter of Northern Dancer, his sire was Arazi, the 1991 European Horse of the Year. Mari's Sheba was Gr.I placed during her racing career, finishing third in the 1995 Santa Anita Oaks.

Mari's Sheba also produced Sangaree, a half-brother to Congaree, who was sired by Awesome Again. She also produced Golden Sheba, a filly by Coronado's Quest, who went on to produce multiple Gr.I winning filly Wedding Toast.

Racing career
Trained by future U.S. Racing Hall of Fame inductee, Bob Baffert, Congaree won the April 2001 Wood Memorial Stakes over Monarchos, then finished third behind that rival in the Grade 1 Kentucky Derby while setting a record for the fastest opening mile in Derby history. He also finished third in the Preakness Stakes and did not compete in the 1½ mile Belmont Stakes, opting instead to return to his California home base, where he won the Gr.1 Swaps Stakes at Hollywood Park before returning East for a third-place finish in the Grade 1 Jim Dandy Stakes at Saratoga.

Congaree went on to race very successfully at age four and five, becoming the first horse to win the Grade 1 Cigar Mile Handicap in consecutive years. His time for the 2002 Cigar Mile of 1:33.11 was the fastest mile run in North America in 2002. Starting in 22 consecutive graded stakes races, Congaree won ten graded stakes (including five Grade 1 races) and was an Eclipse Award finalist as Champion Sprinter, Champion Older Male and Horse of the Year.

In 2004, ate age six, Congaree retired after finishing fourth in the Churchill Downs Handicap. He retired with a record of 25: 12-2-4 and earnings of $3,267,490.

Stud career
The stallion began his stud career stood in 2005 at Frank Stronach's Adena Springs in Midway, Kentucky. Adena Springs later moved operations to Paris, Kentucky, where Congaree stood through the 2009 breeding season. Beginning in 2010, Congaree stood at stud at Highcliff Farm in Delanson, New York. In 2013, Congaree was again moved to stand at Mill Creek Farm in New York, where he stayed until Lane's End Farm acquired him to stand at their Texas operation. When Lane's End Texas closed in 2017, Congaree was moved to stand at Valor Farm, also in Texas.

He was owned by Robert and Janice McNair, who bred and raced him in the name of their Stonerside Stable. After selling their Stonerside Stable property in Paris, Kentucky along with the majority of their bloodstock in October 2008, the McNairs began using the stable name Magnolia Racing Stable for their Thoroughbred holdings, which include Congaree, Cowboy Cal, Bob and John, and Stonesider.

Congaree was euthanized on November 22, 2020, due to the infirmities of old age.

Progeny
Congaree has met with success as a stallion, siring eight stakes winners from his first two crops to race, including multiple Gr.1 winner Jeranimo and multiple Gr. III winner Mythical Power. He has also found international success, siring Irish Gr.III winning mare Maoineach.

Congaree's progeny includes:
 Jeranimo: Winner of the Shoemaker Mile Stakes, Eddie Read Handicap, San Gabriel Handicap (thrice), Oak Tree Mile Stakes, Strub Stakes, and Citation Handicap.
 Don't Tell Sophia: Winner of the Spinster Stakes, Chilukki Stakes, Bayakoa Stakes (twice), Pippin Stakes (twice), and Locust Grove Stakes.
 Killer Graces: Winner of the Hollywood Starlet Stakes, Landaluce Stakes, and Cinderella Stakes.
 Shrinking Violet: Winner of the Monrovia Stakes, Daisycutter Handicap, and Licaghtning City Stakes.
 Mythical Power: Winner of the Lone Star Derby and Texas Mile Stakes.
 Maoineach: Winner of the One Thousand Guineas Trial Stakes (IRE-G3) and Go And Go Round Tower Stakes (IRE-G3)
 Rockin' Rockstar: Winner of the Tom Ridge Stakes
 Conchacer: Winner of the Forward Pass Stakes and Prairie Express Stakes.

References

Congaree's pedigree and partial racing stats
 Congaree at the Stallion Register online

1998 racehorse births
2020 racehorse deaths
Racehorses bred in Kentucky
Racehorses trained in the United States
American Grade 1 Stakes winners
Thoroughbred family 16-h

redpajama_set_name: RedPajamaWikipedia


text:
by Dave McGourty
2020 BDO World Darts Championship – Paul Hogan vs Brian Raman Preview & Prediction
When is Paul Hogan vs Brian Raman taking place? Sunday 5th January, 2020 – evening
Where is Paul Hogan vs Brian Raman taking place? Indigo at The O2, London
What channel is Paul Hogan vs Brian Raman on? Some BDO World Championship matches will be televised live on Eurosport and Quest in the UK, so it is worth checking their schedules
Where can I stream Paul Hogan vs Brian Raman? If televised on Eurosport, then the match can be streamed on either Sky Go or Eurosport Player
Where can I get tickets for Paul Hogan vs Brian Raman? Click here to purchase tickets
PAUL HOGAN
Two-time quarter-finalist Paul Hogan has a wealth of experience having made his World Championship debut all the way back in 1995.
Hogan has twice reached the round of 16 at the UK Open in recent years with wins recorded against the likes of Gary Anderson and Adrian Lewis.
BRIAN RAMAN
Brian Raman has won a couple of ranking tournaments this season, helping him earn a spot at the World Championship for the first time.
Raman played on the PDC Development Tour in 2019 without much success, though he did notably qualify for the UK Open in March.
THE PREDICTION
Hogan has decades of experience and is still more than capable of producing a good standard of play on the big stage. He made his World Championship debut before Raman was even born and is likely to use all of his knowhow to come through this encounter. A Hogan win in four sets is the prediction.

redpajama_set_name: RedPajamaCommonCrawl


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text:
Series Review: The Illumination Paradox by Jacqueline Garlick
October 9, 2015Series ReviewsComments: 2
Synopsis for Lumière (from Goodreads):
One determined girl. One resourceful boy. One miracle machine that could destroy everything.
After an unexplained flash shatters her world, seventeen-year-old Eyelet Elsworth sets out to find the Illuminator, her father's prized invention. With it, she hopes to cure herself of her debilitating seizures before Professor Smrt—her father's arch nemesis—discovers her secret and locks her away in an asylum.
Pursued by Smrt, Eyelet locates the Illuminator only to see it whisked away. She follows the thief into the world of the unknown, compelled not only by her quest but by the allure of the stranger—Urlick Babbit—who harbors secrets of his own.
Together, they endure deadly Vapours and criminal-infested woods in pursuit of the same prize, only to discover the miracle machine they hoped would solve their problems may in fact be their biggest problem of all.
SERIESous' Top Picks: Canadian Author
Series: The Illumination Paradox
Author: Jacqueline Garlick
# of Books: 3 (Lumière, Noir, Book 3)
Complete?: No, there is a third book to be published
Genre: Young Adult, Steampunk, Science Fiction, Romance, Historical Fiction
Heat Rating: cool (gets a little more suggestive in Noir)
Point of View: First Person, Alternating
Publication Dates: December 2013 – ongoing
Source & Format: NetGalley–eBook Thank you Skyscape!
I love steampunk! Its one of my favourite genres because I find each series has its own little spin on the genre. So when I saw Lumière in the Read Now section of NetGalley, I couldn't pass it up!
I was looking forward to a perhaps more dystopian steampunk world (the Vapours sounded like something from Under the Never Sky) with a take-charge heroine. I also was looking forward to this alluring stranger character and the fact that there seemed to be a true evil villain.
The World:
I really enjoyed the world of this series. It's classic steampunk but with a more supernatural spin to it. I find a lot of steampunk stories focus on the mechanical aspects of the story (ie machines) but only a few have a paranormal/supernatural element. Sometimes it felt like there were too many elements to it all but once you get used to everything, it's easier to keep everything straight.
I think at times this book is a little too descriptive. I would find myself drifting away from the long paragraphs. It definitely helps the reader get a clear picture of everything but at times it seemed to be a little too much.
At first, the plot of Lumière reminded me a bit of Vengeance Road as Eyelet suddenly finds herself on the run from an enemy. But it quickly morphed into more of a Beauty and the Beast premise, something I really wasn't expecting. And then that quickly changed into its own unique story for the rest of the book.
I liked the premise for the plot, I just felt that it took WAY TOO LONG to get there. Lumière is nearly 400 eBook pages long, which is about 150 pages longer than your average eBook. And unfortunately, I really felt like nothing happened until the last 150 pages or so. The extra page length was great for establishing the complex world but I felt like I had a good grasp of everything about 100 pages in and would have liked the main plot line to have shifted into focus. I just wanted more because the last 100 or so pages were exciting, but my enthusiasm for them had significantly decreased by the time I got there.
I liked Eyelet and Urlick. They had their strengths and their flaws which I appreciate. However, I didn't feel like there was a lot of character development for them in Lumière despite the length of the book. Who they are as characters is readily established and is well done, I just felt like there was something lacking for me when it comes to their characters–which might be a result of the romance clouding my impression of them (see below).
Otherwise, you have quite the interesting cast of characters. The supporting characters do their jobs perfectly and Smrt as a villain (though he has a smaller part than I expected) was entertaining.
In Lumière, the romance just didn't work for me. It seemed like it bloomed out of nowhere. That really frustrated me because I could see why these two would work together but I failed to understand how they knew that. I really don't think they had spoken all that much to each other before they were feeling these deeper things. I get the physical attraction part of it all, I just didn't see the emotional connection and that resulted in a lacklustre romance for me.
I think now that the world has been established and all the major players have been introduced, we are going to get more from Noir. I'm looking forward to seeing how everything unfolds.
–November 6, 2015– Book 2: Noir
This book moved well from beginning to end. I felt like it kept the pace at a constant and didn't drag on like Lumière often did. Secrets are revealed, there are lots of interesting plot twists and the characters get a little more depth to them. Overall, Noir just felt complete. It was solid and built up as you read. I got hooked into the story and the pages just flew by. This book was a lot of fun to read and really made me happy that I stuck with this series.
I'm excited to see what will happen in the next one!
Formally: Time Will Tell
Series Rating: 3.5/5
Lumière 3/5 | Noir 4/5 | Book 3 TBP
Lumière showed some great promise and build up an intriguing world, but I just wanted a little more wow from it. I'm hoping that will come in the sequel. Noir does a great job of building on what the first novel has created. It kept my attention from start to end and I can't wait to see what will happen next.
Read if You Like: slower stories, steampunk with supernatural elements
Avoid if You: want a faster story, want more romance
The Girl in the Steel Corset by Kady Cross (The Girl in the Steal Corset Series #1)
The Friday Society by Adrienne Kress
Tags: Conclusion: slow series start, disclaimer: provided copy, First Person POV: Multiple, insta-love, netgalley, Rating: 3.5/5, recap available, romance, steampunk, supernatural, Young Adult
Lydia Tewkesbury
Instalove is the worst! Why do authors keep doing it?!
It's an excellent question. My only guess is that they want to progress the plot and not get caught up in a romance, so having it develop super quickly gets it out of the way 🙁


This year will see Newtown Festival's much loved Wilson Street Stage officially presented by Parrotdog and to celebrate this new partnership, there's a Newtown Festival beer to go with it.
Come celebrate Parrotdog's Newtown Festival Beer! Try the new brew and get hyped for the festival with bands from three different Newtown Fest stages, a little taste of what is to come. This will be a busy one so come down early.


Today's Petrol price in Balangir (Odisha) is Rs. 73.26 per Litre. Last change in Balangir petrol price was on April 24, 2019 and it was increased by +0 rupees. In addition, we bring you the most recent petrol price changes in Balangir city. The petrol price is inclusive of Odisha state taxes.


On the same day that Slipknot release their Aussie tour intentions, Deftones have done the same.
With a #1 album fresh under their belts, the Sacramento rockers will be playing five shows in Australia this November. Making the tour even tastier, Perth proggers Karnivool and Voyager will also be making the journey. Tickets go on sale from 10am May 20.


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Get The Renaissance from Amazon.com
Order our The Renaissance Encyclopedia Article
Introduction: A Period of Rebirth
Origins of the Renaissance
The Spirit of Humanism
The Search for New Worlds
The Rise of the Merchant Class
New Artistic Attitudes
Writers of the Renaissance
The Printing Press
The Reformation of the Catholic Church
The End of the Renaissance
Chapter 1 A New Age of Humanism
Chapter Preface
On the Dignity of Man
A Complaint of Peace
The Excellence of This Age
The Advancement of Learning
Chapter 2 Politics and Exploration?
Columbus Reaches the New World
A Prince Is Better Feared than Loved
In Defense of the Indians
The Dissolution of England's Parliament
Chapter 3 Religion and Philosophy
The Ascent of Mont Ventoux
A Protest Against the Sale of Indulgences
Human Nature and Free Will
Concerning the Things of Which We May Doubt
Chapter 4 Scientific Revolutions
The Revolutions of the Celestial Spheres
Concerning the Use of Biblical Quotations in Matters of Science
Scientific Correspondences
The Cause of Humanity's Miseries
Chapter 5 Humanist Expression in Art
To the Detractors of Poetry
The Superiority of Visual Art
Michelangelo Paints the Sistine Chapel
Defense of Poesy
Chapter 6 Daily Life
The Courtier
The Perfect Wife
The Judgment of a Witch
For Further Research
The Renaissance Research Article from History Firsthand
This Study Guide consists of approximately 200 pages of chapter summaries, quotes, character analysis, themes, and more - everything you need to sharpen your knowledge of The Renaissance.
This section contains 2,196 words
Ascanio Condivi
Minor Italian artist Ascanio Condivi (1525?–1574) was a young assistant and pupil of the great Italian Renaissance artist Michelangelo Buonarroti (1475–1564). The closeness of their relationship allowed Condivi access to the master's most personal thoughts, making his biography, The Life of MichelAngelo, excerpted below, the most intimate portrait available.
So influential was the art of Michelangelo that some historians credit him with being responsible, directly and indirectly, for three separate historical eras. The word Renaissance was said to be specifically created to describe the development of fine arts under Michelangelo and fellow artist Raphael (1483–1520). The Reformation was spurred by Martin Luther's (1483–1546) rejection of the Catholic Church's sale of indulgences (by which sins are forgiven by God). The sale of indulgences increased dramatically when Pope Julius II (1443–1513) needed money to pay for his own elaborate tomb, to be created by Michelangelo...
More summaries and resources for teaching or studying The Renaissance.
The Renaissance from Greenhaven. ©2001-2006 by Greenhaven Press, Inc., an imprint of The Gale Group. All rights reserved.


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Q: Control of keyboard when entering text into UITableView cells containing UITextFields I have a UITableView with custom cells containing two UITextFields for text entry. I would like the keyboard to stay in place until text entry is finished but when a second textField is tapped, the keyboard disappears and I have to make a second tap to get it back. I understand that the first tap has triggered a 'resignFirstResponder' message, but how can I keep the keyboard in place? Have tried setting the tableScrollView keyboardDissmissMode, but it makes no difference. I implement 'textFieldDidEndEditing' to store the text entered and declare the view controller to be the texField's delegate.Am using Swift 4 with iOS 12.
This is the code for the custom cell:
class ChoreoCell: UITableViewCell, UITextFieldDelegate {
    var inputText:String?
@IBOutlet weak var countText: UITextField! {
    didSet {
        countText.sizeToFit()
        countText.text = inputText
    }
}

@IBOutlet weak var stepText: UITextField! {
    didSet {
        stepText.sizeToFit()
        stepText.text = inputText
    }
}

}
... and this is the code I am using in a tableViewController:
override func tableView(_ tableView: UITableView, cellForRowAt indexPath: IndexPath) -> UITableViewCell {
    let cell = tableView.dequeueReusableCell( withIdentifier:Storyboard.CellIdentifier, for: indexPath) as? ChoreoCell
    if (self.choreography.count == 0 ) {
        let myCountSteps = CountSteps(counts:"", steps:"" )
        for _ in 0...Storyboard.InitialRows-1 {
            self.choreography.append(myCountSteps)
        }
    }
    cell!.countText.text = self.choreography[indexPath.row].counts
    cell!.stepText.text = self.choreography[indexPath.row].steps
    cell!.countText.delegate = self
    cell!.stepText.delegate = self
    return cell!
}

func textFieldDidEndEditing(_ textField: UITextField) {
    guard let txt : String = textField.text else {
        print ("input error for text, editing ended but no text received")
        return
    }
    var v:UIView = textField
    repeat { v = v.superview!} while !(v is UITableViewCell)
    if let cell = v as? ChoreoCell {
        guard let ip = self.tableView.indexPath(for: cell) else {
            print("Error identifying index path for \(cell)")
            return
        }
        switch (textField) {
            case cell.countText:
                let myCountSteps = CountSteps(counts:txt, steps:cell.stepText.text! )
                self.choreography[ip.row] = myCountSteps
            case cell.stepText:
                let myCountSteps = CountSteps(counts:cell.countText.text!, steps:txt )
                self.choreography[ip.row] = myCountSteps
            default:
                print ("Unexpected textField case")
        }
        self.danceDoc?.choreography[ip.row] = self.choreography[ip.row]
        self.danceDoc?.updateChangeCount(.done)
        return
    } else {
        print ("Error identifying cell from text entry")
        return
    }
}

How can I determine which textField is tapped in to end the editing of the current textField, so I can assign it first responder status and prevent the keyboard disappearing?

A: You probably have similar code to this, which will cause the keyboard dismissal no matter what:
func textFieldShouldReturn(_ textField: UITextField) -> Bool {
    textField.resignFirstResponder()
    return true
}

To fix it - you need to programmatically activate the next Text Field:
func textFieldShouldReturn(_ textField: UITextField) -> Bool {
    textField.resignFirstResponder()
    self.nextTextField.becomeFirstResponder() // Add this line
    return true
}

You may need to do additional check, because for the last field you may actually need to dismiss the keyboard.
Not 100% sure if it won't affect other functionality, but I believe even textField.resignFirstResponder() line can be omitted (in case we want the keyboard to remain on the screen), otherwise it may cause some weird animation of the keyboard.

redpajama_set_name: RedPajamaStackExchange


SmithGroup's fully integrated team of architects, planners, interior designers and engineers enabled valuable collaboration across disciplines, ultimately delivering an integrated and unconventional solution.
Precision really matters here: NIST is home to the atomic clock, leading quantum computing research programs and unique superconducting devices.
Precision and stability is tantamount for the National Institute of Standards and Technology, the federal government's premier laboratory for advanced measurement science, standards and technology. Yet as this 1954 building aged and technology advanced, it couldn't maintain the stable environment the sensitive equipment demanded.
Working primarily within the confines of its four-wing footprint, SmithGroup found a way to provide the required high-caliber research space and necessary mechanical services: By adding a new service corridor onto one side of each wing, it could reserve the other side for laboratory needs—maximizing the capacity of the research space for its highest and best use. Maintaining operations was paramount for the success of the project, as the existing building housed an atomic clock, used for the nation's primary time and frequency standard.
The design created a new strategy for servicing laboratory areas: providing a dedicated corridor for mechanicals, rather than placing them on the roof.


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Join an Upcoming LIVE Ignite Masterclass View all Videos on Youtube
How to Develop Empathy as a Tool for Justice
Reagan Pugh
Most people have no desire to change. Our brains have outdated wiring causing us to avoid the discomfort of growth. This instinctual desire to maintain the status quo is a direct threat to justice, and excuses individuals and communities from doing the hard work of including, respecting, and empowering everyone. Humans don't like to change – but we can. We can shift our perspectives, evolve our opinions and mature our mindsets when we practice empathy and pay attention to the experiences of others.
In this Ignite Masterclass filmed on October 6, 2020, speaker and facilitator Reagan Pugh (http://www.reaganpugh.com/) explores our default mindsets, examines how fear prevents us from growth, and provides strategies for developing empathy as a tool for justice.
Download Faculty Facilitation Guide
How to Craft Stories for Racial + Social Justice
Jasmine Babers
In this Ignite Masterclass filmed on September 14, 2020, entrepreneur Jasmine Babers will unpack the nuances that media and story plays in perpetuating racial injustice.
Jasmine founded LOVE Girls Magazine (https://www.lovegirlsmagazine.com/) and is the Lead Storyteller and Fellow-in-Residence at Peace First (https://www.peacefirst.org/), about how to frame stories and media that is equitable and amplifies female and minority voices. We'll unpack the creative process to see how you can best structure your messages in a way that advances social change in the communities you work with.
How to Disrupt a Broken Global Supply Chain
Abhinav Khanal
Smallholder womxn coffee producers make 40% less than their male counterparts, although they make up 70% of the workforce in coffee farmers.
In this Ignite Masterclass filmed on November 10, 2020, entrepreneur Abhinav Khanal will share the story of how he co-founded a social enterprise while in college that works to disrupt the status quo so that smallholder womxn can lead their families and communities towards a sustainable future. Abhinav is the co-founder of Bean Voyage (http://www.beanvoyage.org), a non-profit that provides training and direct market access to smallholder womxn coffee producers in Costa Rica.
What Does 'Sustainable Design' Really Mean
Arshiya Kherani
The word "sustainability" gets thrown around super casually in 2020 – by both small and big companies. But what does it really mean to be sustainable? How can you differentiate between greenwashing and true environmentally forward practices?
In this Ignite Masterclass filmed on September 23, 2020, entrepreneur Arshiya Kherani of Sukoon Active (https://www.sukoonactive.com/) defines sustainability and applies those principles to product design and development practices. She shares a deep dive case study in eco-friendly textiles through her work leading Sukoon Active.
How to Use Design Thinking for Personal Growth + Social Innovation
Kaveh Sadeghian
In this Ignite Masterclass filmed on October 15, 2020, educator and facilitator Kaveh Sadeghian (https://kaveh.nyc/) will introduce you to the core principles of design thinking, creativity, and social innovation.
He'll explore why meaningful work is difficult to come by and how the design thinking methodology can be leveraged to identify and ultimately create opportunities that exist at the powerful point of intersection between one's identity, values and the problems that weigh most heavily on our respective community.
How to Reimagine Education with Rappers + Corporate America
Jarren Small
In this Ignite Masterclass filmed on October 28, 2020, you'll explore creative ways to pursue change within the education system through unlikely partnerships.
After founding 'Reading with a Rapper' (https://www.readingwitharapper.com/) – a venture that connects high school students with rappers to strengthen their english, language and arts skills – Jarren Small has gone on to start a variety of "side hustles" that are creating impact in his community. Learn how to build partnerships and connect different parts of your passions to form your own side hustle.
How to Push Through Adversity + Discomfort of Change
Victor Saad
Everyone likes to glorify the vision of success. The grade, the job, the company, the dream… But no one just arrives without some sort of challenge. How do you prepare for those challenges before they happen? How do you remain resilient throughout the ups and downs? How do you navigate the discomfort of uncertainty?
In this Ignite Masterclass filmed on September 10, 2020, entrepreneur and educator Victor Saad of the Experience Institute (https://expinstitute.com/) shares a few simple methods to remain resilient and grounded during seasons of change and growth, and explore how Design is a great tool to help you navigate those shifting dynamics.
How to Maintain Health + Wellbeing through Conflict
Tessa Zimmerman
Despite the chaos of this unprecedented time, we still have a choice in how we show up, how we respond, and how we take care of ourselves. During this video, you will explore a few stress-reducing, resilient boosting tools.
In this Ignite Masterclass filmed on September 29, 2020, entrepreneur and educator Tessa Zimmerman, founder of Asset Education (https://www.asset-edu.org/), will guide you through multiple tools that will allow you to build your own "toolbox" of strategies you can use in your daily lives to stay and be well.
How Nature Can Inspire Solutions for a Healthier, More Sustainable World
Michelle Graves
Biomimicry is a practice that learns from and mimics the strategies found in nature to solve human design challenges. The goal is to create products, processes, and policies – new ways of living – that solve our greatest design challenges sustainably and in solidarity with all life on earth.
In this Ignite Masterclass filmed on October 19, 2020, Michelle Graves, Director of the Global Design Challenge and Launchpad at the Biomimicry Institute (https://biomimicry.org/), will introduce you to biomimicry, showing you how you can learn from nature and bring biomimicry into your work. She also highlights case studies on businesses that learn from and support the natural world.
How to Use Placemaking as a Tool for Community + Network Building
Erin Boyd
How might we consider a new approach to urban design in the wake of Covid-19? Instead of a landscape constructed for the movement and storage of automobiles, what if we re-envisioned our public spaces for the enjoyment of people? In this session, we will discuss how to collectively reimagine and reinvent public spaces as the heart of every community.
In this Ignite Masterclass filmed on November 5, 2020, Erin Boyd will draw on her experience at Culdesac (https://culdesac.com/) – the first car-free neighborhood built from scratch in the U.S. – and as the co-founder of Ashoka U (https://ashokau.org/) – a global network for social entrepreneurship in higher education – to consider the role of physical, cultural, and social identities that define a place and support its ongoing evolution.


The York DEQ Package Air Conditioners are designed for outdoor installation. Only utility and duct connections are required at the point of installation. Field-installed electric heater accessories are available to provide electric heat, if required.
Operating Efficiency"All air conditioners provide operating efficiencies of 14 SEER. All efficiencies exceed legislated minimum levels.
On Site Flexibility"All model sizes share a common, compact design cabinet in a single footprint. The installer has the flexibility of setting one curb and placing the proper tonnage unit on that curb after the internal load has been determined. Field convertible duct connections from side shot to down shot allows the installer to have greater flexibility with less inventory.
Lower Installation Cost"Installation time and costs are reduced by easy power and control wiring connections. The small base dimension means less space is required on the ground or roof, plus, the installer can fit this unit between the wheel wells of full size pick-up truck. All units are completely wired, charged with R-410A and tested prior to shipment. Unique test stations using a new state of the art computerized process system are used to insure product quality. Refrigerant charge and component part numbers are verified via computers at assembly. Vital run test statistics such as system pressure, motor currents, air velocity and temperature, unit vibration, and gas system safeties are monitored and recorded by the system to insure unit performance. Equal size, side supply and return duct connections allows easy hook-up of ducts to match low crawl spaces without transition pieces.
Utility Connections Made Easy"Electric utility knockouts are provided through the bottom as well as the side of the unit. Utility connections can be made quickly and with a minimum amount of field labor. A field supplied and field installed electrical disconnect switch must be installed.
Convertible Airflow Design"The bottom duct openings are covered when they leave the factory ready to be used for a side supply/side return application. If a bottom supply/bottom return application is desired, you simply remove the two panels from the bottom of the unit and place them in the side supply/side return duct openings. No panel cutting is required and no accessory panel is necessary. Convertible airflow design allows maximum field flexibility and minimum inventory.
Condensate Pan"A non-corrosive, long-lasting, watertight pan is positioned below the evaporator coil to collect and drain all condensate. Less collection of stagnate condensate will build-up. The condensate pan conforms to ASHRAE 62-89 standards (Ventilation for Acceptable Indoor Air Quality).
Condensate Drain"The heavy duty, 3/4 inch NPTI copper connection is more durable over time. The connection is rigidly mounted to assure proper fit and leak tight seal.
Durable Finish"The cabinet is made of pre-painted steel. The pre-treated galvanized steel provides a better paint to steel bond, which resists corrosion and rust creep. Special primer formulas and matted-textured finish insure less fading when exposed to sunlight.
Full Perimeter Base Rails"The easily removable base rails provide a solid foundation for the entire unit and protects the unit during shipment. The rails provide fork lift access from all sides, and rigging holes are also provided so that an overhead crane can be used to place the units on a roof. On applications where the unit is placed on a pad, the base will keep the unit off the pad to deter corrosion. On applications where height is limited, the inch high base rails may be removed on location.
More Attractive Appearance"A single piece Water Shed top cover containing a top discharge condenser fan arrangement requires less square footage on installation and provides a wider variety of installations. The one piece design adds greater water integrity. Rounded corners with water drip edges add to the attractive appearance. The cabinet panels have a non-fibrous insulation that will not release insulation fibers into conditioned area.
Top Discharge"The top discharge condenser fan does not disrupt neighboring areas or dry-out vegetation surrounding the unit. The warm air from the top mounted fan is blown up away from the structure and any landscaping. This allows compact location on multi-unit applications.
Condenser Coil Grille"All models utilize a stamped œLouvered inches design which provides superior impact protection against smaller objects during transit and after installation.
Low Operating Sound Level"The upward air flow carries the normal operating noise up and away from the living area. The rigid top panel effectively isolates any motor sound. Isolator mounted compressor and the rippled fins of the condenser coil muffle the normal fan motor and compressor operating sounds. The unique formed base pan also aids in sound alterations with it's Super-Structure design. This design strategically places embossments in the pan for optimum strength and rigidity.
Fan System"All models operate over a wide range of design conditions with an electrically commutated fan motor. These units easily match all types of applications and provide greater on site flexibility to match comfort requirement. The cooling speed is factory set and can be field adjusted to a second speed. The heating speed is factory set but can be field adjusted. This allows maximum comfort conditions.
Simple Control Circuit"A low voltage printed circuit board contains a diagnostic indicator light and a low voltage terminal strip. An additional set of pin connectors is also provided to simplify the field interface of external controls. Mate-n-lock plug connectors are used. The electrical control box is not located in the compressor compartment. The controls are mounted on a Control-Tilt control panel to allow the access cover to be removed for trouble shooting and maintenance without affecting the normal system operating pressures. All wiring internal to the unit is color/number coded.
Protected Compressor"The compressor is internally protected against high pressure and temperature. This is accomplished by the simultaneous operation of high pressure relief valve and a temperature sensor which protect the compressor if undesirable operating conditions occur.
Pressure Switches"High pressure and low pressure/ loss of charge switches standard in all units. When abnormal conditions are sensed through the pressure switches, the unit will lock out preventing any further operation until reset or problem is corrected.
Exclusive Coil Design"Grooved copper tubes and enhanced aluminum fin construction improves heat transfer for maximum efficiency and durability.
Self Diagnostic Fan Control Module"Due to this self diagnostic control, less on site time is required to trouble shoot these units.
Low Maintenance"Long life, permanently lubricated condenser and evaporator fan motor bearings need no annual maintenance adding greater reliability to the unit. Blower assembly can be easily cleaned by the unique Slip- Track slide-out blower assembly.
Secured Service Access Ports"Protected, externally mounted, re-usable service access ports are provided on both the high and low lines for ease of evacuating and charging the system. No final field mounting required.
Easy Service Access"A large, single panel covers the electrical controls to make servicing easy. The blower compartment has an additional large panel with a built-in handle tab. Removing this panel will allow the blower assembly to slide-out for easy removal for maintenance and ease of trouble shooting.
Replacement Parts"The installer requires no special training to replace any of the components of these units and does not need to maintain an inventory of unique parts.
System Integration"Each unit has the internal ability to integrate an electronic air cleaner or humidifier to work in conjunction with the base unit.
Economizer Down Discharge/Supply Kit"Modulating integrated economizer provides simultaneous operation between the mechanical cooling and economizer operation. Independent blade design insures proper control and less than 1% leak rate. Includes hood and mesh bird screen filter integrated into the hood, dry bulb sensor and relief damper. Separate field accessories of single enthalpy and dual enthalpy are also available. A built-in barometric relief of 25% is provided.
Single Enthalpy Sensor"Sensor replaces dry bulb sensor standard in economizer kit. Provides improved economizer operation by sensing the dry bulb temperature from outdoors plus the enthalpy content of the outdoor air.
Dual Enthalpy Sensor"Additional sensor to single enthalpy sensor. Sensor senses both the return air temperature dry bulb and humidity in conjunction with the single enthalpy to determine the most economical mix. Single Enthalpy sensor also required.
Hail Guard Kit"Kit contains protective grilles made of expanded aluminum with full perimeter frame. Sloped hoods are also included to assure maximum protection.
Filter/Frame Kit (Single Phase Only)"Kit contains the necessary hardware to field install return air filters into the base unit. Pre-cut filter racks and appropriate cleanable standard size filters are shipped in one kit. The filter rack is suitable for either 1" or 2" filters. (1" filter is supplied) This kit is available for single phase horizontal or vertical duct application only. Standard in all 3 Phase models.
Motorized Fresh Air Damper"Designed for duct mounted side supply/return and unit mounted down supply/return applications. Damper capable of providing 0% through 50% of outdoor air (field supplied). Closes on power loss, includes hood and screen assembly.
Rectangle To Round Adapters"Kit includes one supply and one return air rectangle to round duct adapter. Adapters are preformed and designed to fit over current duct openings on the base unit. Transition is from side square duct opening to 14" round duct opening.
Roof Curbs"NRCA approved curbs provide proper fit to base unit for rooftop installations. Curbs are designed to be assembled through hinge pins in each corner. Kit also provides seal strip to assure a water tight seal. 8 and 14 inch high roof curbs are available.
Manual Outdoor Damper"Provides 0% through 50% outdoor air capability (field adjustable). Designed for duct mounted side supply/return applications. Includes hood and screen assembly.
Wall Thermostat"The units are designed to operate with 24-volt electronic and electro-mechanical thermostats. All units can operate with single stage heat/single stage cool thermostats - with or without the economizer.
Low Ambient Kit"Kit provides necessary hardware to convert unit to operate in cooling cycle down to 0º F. Standard unit operation 45º F.


A mid century still life of fruit on a table, oil on canvas, installed to the bottom right, within a period frame with canvas and gilt metal slip.
This is a very nicely executed still life. The artist remains unknown, however it is most certainly of Continental original given the way the canvas has been stretched.
'Gifted by 'displaced person's family' - adopted for Xmas parcels by Lawrences circa 1947. Painted by mother of family. Gifted in 1965 whilst visiting Finks'.
N.B. Following the end of World War II a number of Displaced Persons Camps were established in Germany, Austria, and Italy, primarily for refugees from Eastern Europe and for the former inmates of the Nazi German concentration camps. Following a government appeal many British families sent Xmas parcels for inmates of the camps and it would appear that this is what the label on the reverse of this painting is referring to. The name Finks is of German Jewish origin.


Mawwage! Mawwage is what bwings us togethah today.
A month from today, I'm getting married. Holy moly, it's come up fast. But it made me think of some of my favorite love stories. Yes, some of them are old or old-fashioned, and use plot devises no author would get away with today (case in point, if you've read LED ASTRAY, you will know that the hero does something that would be totally NOT OKAY in real life). But I don't care! I love these all anyway.
What are your favorite love stories?


text:
Q: when clicking a button in a php page pass variables to another php page I have a PHP page where users can search for food using an API and then display the food information and calories and then click a button to add the food information to their day which is another PHP file however I tried to store the food name and calories in variables and pass them to the other PHP file when clicking on the button using GET but I get this error

:  Undefined array key "name"

my question is: how to pass the food data to another PHP file when clicking on a button?
here is the code that iterates over the food data and prints them and then I stored calories and food name in variables ($name and $cal) and tried to pass the name when clicking the button
 `<?php if (isset($data)){?> //$data is the API response

  <?php foreach ($data["items"] as $item){
      echo "". "food name:  ". $item['name'] . "
";
      $name=$item['name'];} ?>

 <?php
  foreach ($data["items"] as $item)
  {

      echo "Serving size: " . $item["serving_size_g"] . " gram
";
      echo "Calories: ". $item["calories"] . "
";
      $cal=$item["calories"];
      echo "Protein: ". $item["protein_g"] . " gram
";
      echo "Carbohydrates: ". $item["carbohydrates_total_g"] . " gram
";
      echo "Fat: ". $item["fat_total_g"] . " gram
";

  }
    $name=$data['items'][0]['name'];   ?>

    <button>Add Food</button>

<?php } ?>

`

trying to print the variable in the other PHP file which is named addfood.php :
<?php $x=$_GET['name']; echo $x ?>

A: You're setting the GET superglobal slightly wrong. The link needs to look something like this:
<button><a href="addfood.php?name=<?=$name?>">Add Food</button>

Basically, you need to make a GET with the name 'name', and give it the value of your $name variable. If you do it like this, the next page will have the value of $name in $_GET['name']


Ecclesia (meaning a spiritual congregation) was a multi-displinary show held at 1234 De La Montagne in Montreal. The space itself was a former funeral home, an architectural display of church-like properties throughout the space. The show consisted of paintings, photographs, fashion design and a live performance of the band Labratory (former Elsiane).


'  Create some plaintext to be encrypted.
'  This example will demonstrate with and without DEFLATE (zip) compression.
line = "Live long and prosper."
Response.Write "
" & Server.HTMLEncode( sbPlainText.GetAsString()) & "
"
'  be compressed prior to encryption.
Response.Write "
" & Server.HTMLEncode( sbJweCompressed.GetAsString()) & "
"
Response.Write "
" & Server.HTMLEncode( "size of compressed JWE: " & sbJweCompressed.Length) & "
"
'  Now create a JWE without compression.
Response.Write "
" & Server.HTMLEncode( sbJweUncompressed.GetAsString()) & "
"
Response.Write "
" & Server.HTMLEncode( "size of uncompressed JWE: " & sbJweUncompressed.Length) & "
"
'  Decrypting is the same whether compression is used or not.
'  automatically decompressed (inflated) after decrypting.
'  Decrypt (also automatically decompresses).
Response.Write "
" & Server.HTMLEncode( "original text from compressed JWE: ") & "
"
Response.Write "
" & Server.HTMLEncode( sbOriginalText.GetAsString()) & "
"
Response.Write "
" & Server.HTMLEncode( "original text from uncompressed JWE: ") & "
"