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New Members Join Armenian Caucus as Armenian Assembly Promotes Stronger U.S.-Armenia Relations
WASHINGTON, D.C. – New Members joined the Congressional Caucus on Armenian Issues and more members co-sponsored the bipartisan Armenian Genocide resolution as a result of successful meetings led by the Armenian Assembly of America.
The Armenian Assembly, along with its state chairs and grassroots activists, met with a host of congressional offices to discuss strengthening U.S.-Armenia relations, co-sponsoring House Resolution 296, and joining the Congressional Caucus on Armenian Issues. As a result of these meetings, Representatives Nanette Barragan (D-CA), Gil Cisneros (D-CA), Kevin Hern (R-OK), Tom O'Halleran (D-AZ), Katie Porter (D-CA), and Abigail Spanberger (D-VA) joined the Armenian Caucus, bringing it to 116 Members, and over 100 Members supporting H.Res.296.
Terjenian-Thomas Assembly Internship Program participant Armen Kaprelian, Armenian Assembly Congressional Relations Director Mariam Khaloyan, Armenian Assembly Maryland State Chair Armineh Ghazarian, Congresswoman Nanette Barragan, Armenian Assembly Communications Director Danielle Saroyan Ashbahian, Armenian Assembly Pennsylvania State Chair Paul Sookiasian, and Armenian Assembly Virginia State Chair Meganoosh Avakian
"For years, the Armenian community's vibrant culture has been an integral presence in Los Angeles and across the country. I'm honored to be a member of the Armenian Caucus and look forward to joining my colleagues in working on issues that matter to Armenian-Americans," Rep. Barragan told the Armenian Assembly.
"As a new member of the Congressional Armenian Caucus, I look forward to working with this bipartisan group of lawmakers as we build stronger economic, cultural, and diplomatic ties with the people of Armenia," Rep. Spanberger said to the Armenian Assembly. "I'm also proud to represent many Armenian Americans across Virginia's 7th district."
Throughout April and May, the Assembly met with numerous offices on Capitol Hill as well as in their districts, including Reps. Andy Biggs (R-AZ), Judy Chu (D-CA), Dan Crenshaw (R-TX), John Curtis (R-UT), Jeff Fortenberry (R-NE), Lois Frankel (D-FL), Ann Kirkpatrick (D-AZ), Ann Kuster (D-NH), Debbie Lesko (R-AZ), Mike Levin (D-CA), Grace Meng (D-NY), Seth Moulton (D-MA), Richard Neal (D-MA), Joe Neguse (D-CO), Tom O'Halleran (D-AZ), Frank Pallone, Jr. (D-NJ), Chris Pappas (D-NH), Katie Porter (D-CA), Jamie Raskin (D-MD), Dutch Ruppersberger (D-MD), David Schweikert (R-AZ), Ross Spano (R-FL), Norma Torres (D-CA), and Rob Wittman (R-VA), among others.
Assembly's State Chairs Herman and his wife Laura Purutyan from Massachusetts, Armineh Ghazarian from Maryland, Paul Sookiasian from Pennsylvania, Meganoosh Avakian from Virginia, along with members and supporters such as Terjenian-Thomas Assembly Internship Program participant Armen Kaprelian from Arizona and Drs. Alice and Ara Apkarian from Orange County, California were instrumental in encouraging U.S. Representatives to join the Armenian Caucus and co-sponsor the Armenian Genocide resolution.
Rep. Susie Lee, who also joined the Armenian Caucus earlier this year, stated: "Nevada's Third District is unique thanks to our diversity and strong ties among different communities that call Southern Nevada home. I'm proud to join the Congressional Caucus on Armenian Issues so that we can continue advocating for the unique issues facing Armenia and continue to support Nevada's Third District Armenian people."
"Thanks to the efforts of our state chairs and activists, we are gaining momentum with more Representatives joining the Armenian Caucus and co-sponsoring the bipartisan Armenian Genocide resolution," said Mariam Khaloyan, Director of Congressional Relations at the Armenian Assembly. "To support the Armenian Assembly's efforts, we encourage everyone to reach out to their elected officials as well as plan to attend the Armenian Assembly's National Advocacy Conference this year, set for September 16-17," Khaloyan added.
Established in 1972, the Armenian Assembly of America is the largest Washington-based nationwide organization promoting public understanding and awareness of Armenian issues. The Assembly is a non-partisan, 501(c)(3) tax-exempt membership organization.
NR# 2019-019


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National Association of Councillors
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April 14 @ 5:00 pm - April 16 @ 5:00 pm
« Regeneration Opportunities
General Management/Executive meeting »
14th-16th April 2023
April 14 @ 5:00 pm
The NAC is the only organisation whose agenda is to represent Councillors. It is the only all party voice for elected members which makes it unique in the political world.
The Association exists to promote and enhance the role of councillors and to help elected members to be as effective as possible in carrying out their responsibilities. To be an effective organisation the Association needs the support of all councillors. Find out more.
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Samsung Chromebook Plus V2 LTE closer to launch with FCC certification
A new Samsung Chromebook with model number XE525QBBI was spotted on the Wi-Fi Alliance last month. When we reported about it, we thought this could be a successor to the Samsung Chromebook Pro, perhaps an LTE variant of the successor. The same model has been now certified by the FCC, revealing some important product information in the process.
Hints point to an LTE variant of the Chromebook Plus V2
Beginning with the model itself, this is probably not a successor to the Chromebook Pro, but merelyan LTE variant of the recently launched Chromebook Plus V2, at least according to a report in AboutChromebooks. The inference is based on the FCC documents referring to this model as 'Hopper,' which finds a mention in the Chrome OS code for Nautilus – the codename for Chromebook Plus V2.
The presence of the Intel Celeron sticker in one of the device photos is apparently another reason for concluding this as the LTE variant of the Chromebook Plus V2 (since V2 ditched predecessor's ARM processor for an Intel Celeron chipset). The positioning of the camera module above the keyboard also matches with that of the Chromebook Plus V2.
We don't know when Samsung is planning to release it, but the FCC certification hints at an imminent launch. Also, it makes business sense for Samsung to put it on sale in time for the year-end holiday shopping. As far as the pricing is concerned, the non-LTE version retails for $499, so expect an ~$100 premium on top of that for the LTE capabilities.


QSFP+ TX bias line 0 current sensor.
QSFP+ TX bias line 1 current sensor.
QSFP+ TX bias line 2 current sensor.
QSFP+ TX bias line 3 current sensor.
QSFP+ RX line 0 power sensor.
QSFP+ RX line 1 power sensor.
QSFP+ RX line 2 power sensor.
QSFP+ RX line 3 power sensor.
QSFP+ TX line 0 power sensor.
QSFP+ TX line 1 power sensor.
QSFP+ TX line 2 power sensor.
QSFP+ TX line 3 power sensor.
Number of NT40E2 port sensors.
Definition at line 868 of file commontypes.h.


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Tag Archives: Pinoy Boyband Superstar debut episode
entertainment, Philippines, reality show, talent show, television
Pinoy Boyband Superstar Premieres Tomorrow
September 9, 2016 ralphierceABS-CBN, ABS-CBN News, ABS-CBN News and Current Affairs, Aga Muhlach, Billy Crawford, GMA, GMA Network, GMA News and Public Affairs, GMA Public Affairs, Goin' Bulilit, Goin' Bulilit ABS-CBN, Home Sweetie Home, Home Sweetie Home ABS-CBN, La Banda, La Banda franchise, La Banda Philippines, La Banda Philippines franchise, Menudo, Menudo band, Pinoy Boyband Superstar, Pinoy Boyband Superstar ABS-CBN, Pinoy Boyband Superstar debut, Pinoy Boyband Superstar debut episode, Pinoy Boyband Superstar first episode, Pinoy Boyband Superstar maiden episode, Pinoy Boyband Superstar opening episode, Pinoy Boyband Superstar pilot, Pinoy Boyband Superstar pilot episode, Pinoy Boyband Superstar premiere, Pinoy Boyband Superstar premiere episode, Ricky Martin, Sandara Park, Simon Cowell, To the Top, To the Top GMA, To the Top vs. Pinoy Boyband Superstar, Vice Ganda, Yeng Constantino 7 Comments
ABS-CBN's own search for an up-and-coming Filipino boyband gets underway tomorrow.
Boys aged 14 or older, with a knack for good looks, charm and excellent singing and dancing talent, will have the opportunity to become one of the five members of a soon-to-be named boyband. Their journey begins this weekend on 'Pinoy Boyband Superstar', the Filipino adaptation of 'La Banda'.
The original 'La Banda' was created by Simon Cowell and former Menudo member Ricky Martin. In order to avoid claims that the show is actually creating a 'band' consisting of a vocalist and instrumentalists, ABS-CBN renamed the show as 'Pinoy Boyband Superstar' in order to make it clear that they are looking to form a boyband.
The premise of 'Pinoy Boyband Superstar' is simple. The boyband aspirants must impress the girls with their looks and talent in order to make it to the next round, after which they face the judges who will evaluate their singing prowess as well as their image.
If one of the aspirants failed to pass the first round, they may be given another chance, provided they show enough potential to convince judges. Eventually, some of the aspirants will be eliminated until there are five left standing.
'Pinoy Boyband Superstar' will be hosted by Billy Crawford. The show's judges will be Yeng Constantino, Vice Ganda, Aga Muhlach, and Sandara Park.
Even before its premiere, comparisons between 'Pinoy Boyband Superstar' and rival GMA's 'To the Top' were very evident from the beginning. Both had a similar premise of forming a boyband, not to mention the journey of selecting the members.
The difference, however, lies on the production. Though 'Pinoy Boyband Superstar' is more of a franchise than the originally created 'To the Top', ABS-CBN did not seek help from its news and current affairs department to produce the former, unlike GMA whose Public Affairs team was responsible for the latter.
And considering that 'Pinoy Boyband Superstar' will be aired at a more convenient timeslot (unlike 'To the Top' which aired on late nights), the former could become even more successful. Still, it will be up to the audience to see how it all happens.
The journey of the next great Pinoy boyband begins this weekend. Good luck.
'Pinoy Boyband Superstar' airs Saturdays after 'Home Sweetie Home', and Sundays after 'Goin' Bulilit'.


Master data management gives your organisation the foundation it needs in order to become truly data-driven. It allows you to define and manage your critical data assets to achieve a single point of reference, as well as providing you with processes for collecting, matching, consolidating and distributing your data to ensure a common understanding and control in the ongoing maintenance and application use of this information. Product information management (PIM) and customer data integration are now more relevant that ever due to the rapid introduction of omni-channel initiatives like web shops.
Becoming data-driven enables you to adapt to future changes in your business model. Data craftsmanship for a data-driven foundation.
A proposition to create a single central repository for product master data as source for all your output channels to provide consistent data at the point of use. In combination with enabling your data organisation to continuously improve the data quality for a growing set of data, this will lead to better insight, analytics and results, but also legal compliance and improvements in time-to-market.
A proposition for customer master data management to integrate customer data from across the organisation to provide a 360-view of each record. A unique golden record provides valuable customer insights that can be trusted and that will comply with legal requirements (such as GDPR) and an organisation capable to continuously increasing the quality of your customer data.
A proposition in which the different MDM domains are combined and therefore a company fully manages its master data. This will lead to a solution where an organisation gains full insight in each domain and its relations, combined with setting the complete framework for a data-driven organisation and enabling reporting and analytics. The proposition for the P- and C-domain could also be a first step towards multi-domain.
A proposition for data governance will ensure quality standards, assign ownership and responsibilities and operationalise data stewardship. Data governance prescribes structures and strategy from both a business and technical perspective to give you a foundation of data that is managed as an asset and can be turned into useful information. Data governance is a key element in every data initiative, including MDM.


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Working for a very busy department, Tony has amassed over 11 years of extensive experience in the field of forensics and is involved with teaching, training and has been a guest speaker at several law enforcement agencies and forensics conferences. He is currently a part of Pomona Police Department Unmanned Aerial Vehicle Program assisting with FAA exemption requirements for aerial photography.
Tony is very active in the Los Angeles latent print and photography community and served as the 2015 President of the Southern California of Fingerprint Officers; is a member of the Los Angeles County Forensic Supervisor's Group; and is a current Board member of the IAI Forensic Photography & Imaging Certification Board.
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His interests and areas of expertise are in forensics, and UAV and VR 360 photography.
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Repeated intravenous administration of silica nanoparticles induces pulmonary inflammation and collagen accumulation via JAK2/STAT3 and TGF-β/Smad3 pathways in vivo
Authors Yu Y, Zhu T, Li Y, Jing L, Yang M, Li Y, Duan J, Sun Z
Received 20 March 2019
Accepted for publication 30 July 2019
Published 6 September 2019 Volume 2019:14 Pages 7237—7247
Editor who approved publication: Dr Mian Wang
Yang Yu1,2, Tingting Zhu1, Yang Li1,2, Li Jing1,2, Man Yang1,2, Yanbo Li1,2, Junchao Duan1,2, Zhiwei Sun1,2
1Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, People's Republic of China; 2Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, People's Republic of China
Correspondence: Zhiwei Sun; Junchao Duan
Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, People's Republic of China
Tel +86 01 08 391 1507; +86 01 08 391 1868
Email zwsun@ccmu.edu.cn; jcduan@ccmu.edu.cn
Background: The health hazards of silica nanoparticle (SiNP) are raising worldwide concern as SiNPs has become the second largest manufactured nanomaterial in global markets. However, insufficient data for the adverse health effects and safety evaluation of SiNPs are remaining a big question.
Purpose: We evaluated the effects and related mechanism of SiNPs on pulmonary inflammation and collagen production through repeated intravenous administration in mice in a 45-day observation period.
Methods: Morphological and ultrastructural change, ultradistribution of SiNPs in lungs were observed in ICR mice through intravenous administration. Oxidative damage, pro-inflammatory cytokines, hydroxyproline content, the marker of fibroblasts and epithelial-mesenchymal transition (EMT), and JAK2/STAT3 and TGF-β1/Smad3 signaling pathways were detected to explore the lung injuries and related mechanism.
Results: The results showed repeated intravenous exposure of SiNPs increased the weight of lung tissues and destroyed pulmonary histomorphological structure. The increased MDA content, depletion of SOD and GSH-Px in lungs were observed in SiNP-treated mice. The protein expressions of JAK2/STAT3 pathway were upregulated in lungs, and the levels of inflammatory cytokines TNF-α, IL-1β, and IL-6 in serum and lungs were also elevated in SiNPs treated group. The increased hydroxyproline content indicated collagen accumulation in lungs of SiNP-treated mice. Meanwhile, the protein expressions of the marker of myofibroblast (a-SMA), the regulators in connective tissue remodeling (CTGF), TGF-β, and p-Smad3 were all upregulated in lungs. In addition, we found intravenous administration of SiNPs-induced ultrastructural changes in type II alveolar epithelial cells but without downregulation of the protein expression of the key markers of epithelial cells (E-Cadherin).
Conclusion: Our results revealed that oxidative stress and inflammation contributed to the collagen accumulation through activation of JAK2/STAT3 and TGF-β/Smad3 pathways. It suggests that pulmonary aberrant inflammation and collagen accumulation induced by nanoparticles should be seriously considered for the safety application in diagnostics or therapeutics.
Keywords: Silica nanoparticles, repeated intravenous administration, inflammation, collagen accumulation, JAK2/STAT3 signaling pathway, TGF-β/Smad3 signaling pathway
Nanotechnology environmental health and safety, normally known as NanoEHS, is a new emerged research discipline on nanotoxicity which warrants global rigorous attention on the hazard and risk potential of manufactured nanomaterials.1 Silica nanoparticles (SiNPs) have the nano-scaled size and the unique physicochemical properties such as higher surface reactivity and increased surface-to-volume ratio.2,3 Due to the appealing properties of SiNPs, they have been widely applied in the areas of coating, cosmetics, and food.4 The 2017 World Health Organization (WHO) guidelines indicated the annual production volume of SiNPs was 1.5 million tonnes, suggesting SiNPs have been the second largest manufactured nanomaterial in global markets.5 In this regards, the hazard risks of population exposure and environmental exposure to SiNPs have been raised. Furthermore, with the high biocompatibility and stability, SiNPs are the perfect candidate in the biomedical application of imaging, drug delivery, and gene therapy, in which SiNPs could enter the human body directly.4,6 Due to the large-scale production of SiNPs and increased potential of SiNPs exposure, it is necessary to pay attention to the health hazard and safety evaluation of SiNPs. Although US Food and Drug Administration (FDA) permitted a cancer-targeted probe of SiNPs for Stage I clinical trials as early as 2011,7 there is still insufficient or lack of data available for the adverse health effects of SiNPs.8
In the biomedical application such as disease diagnosis or gene therapy, intravenous injection is the usual route of SiNPs exposure. The reticuloendothelial system, especially in liver, is thought to be the main target organ and it was reported that intravenous injection of SiNPs could induce liver granuloma and fibrosis in vivo.9 A few researches reported that the lung is one of the first three organs that SiNPs mainly accumulated in after intravenous injection.10,11 Our previous study found that intravenous injection of SiNPs induced CD68-positive macrophages infiltration in mice lungs in an acute toxicity study.10 Serge et al found that intravenous injection of SiNPs induced mast cells accumulation in lungs and increased collagen fibers in the alveolar septa, but they did not further explore the related signal pathways involved in this process.12 Recently, Raziye reported that SiNPs caused lung thrombosis and inflammation through intravenous injection in vivo.13 But the later scenarios, more details and related mechanisms need further exploration.
This study was aimed to assess the pulmonary toxicity of SiNPs and further investigate the related mechanism through repeated intravenously administration in mice. Morphological changes, ultrastructural changes, and ultradistribution of SiNPs in lungs were observed. Oxidative damage was used to assess lung injury. Pro-inflammatory cytokines in the serum and lungs were detected to assess the systemic and pulmonary inflammation. The collagenous fiber content, the marker of fibroblasts, and epithelial–mesenchymal transition (EMT) were tested to evaluate collagen accumulation. The activation of JAK2/STAT3 and TGF-β1/Smad3 signaling pathways was detected to confirm whether these two pathways had participated in the progress of inflammation or collagen accumulation in lungs induced by SiNPs. Moreover, the subacute and chronic pulmonary injuries after intravenous administration of SiNPs with three time points were set in this study. It will provide a comprehensive understanding and valuable evidence for the safety evaluation and the biomedical application of SiNPs in diagnostics or therapeutics.
SiNPs preparation and characterization
The SiNPs were prepared as previously described.10 The shape and size of SiNPs were observed by transmission electron microscope (TEM, JEM2100, Japan). The Zeta potential and hydrodynamic sizes of SiNPs in dispersion media were determined by Zeta electric potential granulometer (Malvern Nano-ZS90, UK). The content of endotoxin in SiNPs was analyzed using Gel clot Limulus Amebocyte Lysate (LAL) assay.
Animals and experimental design
ICR mice (weight 20–22 g, 8 weeks old, male) were obtained from Vital River Laboratory Animal Technology Company (Beijing, China). Prior to the final treatment, the mice were kept fasted overnight. All the animal experiments were approved by the Committee of Laboratory Animal Care and Use in Capital Medical University, and all the procedures followed the National Guidelines for Animal Care and Use. The dosage of repeated intravenous administration of SiNPs was 20 mg/kg body weight, which was based on our previous study on the acute toxicity of SiNPs. The mice were intravenously administrated with SiNPs at 20 mg/kg body weight repeatedly, once per three days, five times totally. The mice in control groups were injected with the same volume of saline intravenously. The animal mortality and clinical manifestation in each group were recorded. The mice were sacrificed at 15th day, 30th day, and 60th day after first injection, and the blood and the lungs were harvested. The experimental design is shown in Figure S1.
The lungs were fixed in 10% formalin for 24 hrs, and then were embedded in paraffin. Four-millimeter sections were deparaffinized and stained with hematoxylin and eosin. Then, the histopathology examination was conducted using the optical microscope (X71-F22PH, Olympus, Japan). The pathologist was completely blinded to the experiment design.
Ultrastructural observation by TEM
The fresh mice lungs were excised and immediately put in 2.5% glutaraldehyde. Then, the lungs were quickly cut into small pieces as 0.5 mm×0.5 mm. After fixation overnight, the lung samples were rinsed with 0.1 M PB and embedded in 2% agarose gel. Then, the samples were post-fixed in 4% osmium tetroxide. After being stained with 0.5% uranyl acetate and dehydrated in ethanol with concentration gradients, the lung samples were embedded in epoxy resin. The ultrathin sections (50 nm) were obtained and were observed using TEM.
Assessment of oxidative stress
The lung tissues (100 mg) were homogenized in saline on ice. The homogenates were then centrifuged at 3000 rpm, 4°C, for 10 mins. The supernatants were collected to measure the MDA content and the SOD and GSH-Px activities with commercially available kits (Nanjing Jiancheng, China). Meanwhile, the total protein concentration of the homogenates was detected using the kits of bicinchoninic acid (BCA) protein assay (Nanjing Jiancheng, China).
Determination of pulmonary hydroxyproline (HYP) content
The HYP content in lungs (100 mg) was measured through Kivirikko's method with some modification using HYP assay kits (Nanjing Jiancheng, China).14 The HYP contents were expressed as milligrams of HYP per gram of wet lung weight.
Inflammatory cytokines measurement
Blood samples were collected via the ocular vein at 15th day, 30th day, and 60th day. The serum was obtained by centrifugation of the whole blood at 3000 rpm for 15 mins. The supernatants of lung tissues were prepared as mentioned in the section "Assessment of oxidative stress". The levels of mouse interleukin-1β (IL-1β), mouse interleukin-6 (IL-6), and mouse tumor necrosis factor-α (TNF-α) in serum and in the lungs were measured by ELISA kits (Lanbing, Dakewei, China) according to the manufacturer's protocols. Absorbance at 450nm was tested by a microplate reader (Thermo Multiskan™ MK3, USA). The total protein concentration of the lung homogenates was detected using BCA protein assay kits (Nanjing Jiancheng, China).
Immunohistochemical staining
The expression of α-Smooth Muscle Actin (αSMA), the marker of myofibroblast, and connective tissue growth factor (CTGF), the main regulators in connective tissue remodeling or fibrosis, was detected using immunohistochemical staining in the paraffin-embedded lung sections. After deparaffinating, rehydration, and antigen retrieval, the lung sections were treated with 3% H2O2 in order to quench endogenous peroxidase activity. Then, the sections were incubated with primary antibodies: αSMA [Cell Signaling Technology (CST), USA], CTGF (Abcam, USA), at 4°C overnight after blocking with 10% normal goat serum. The equivalent amount of normal goat IgG was added as a negative control. The sections were then stained with 3-3ʹ diaminobenzidine substrate and counterstained with hematoxylin following the standard procedure. All the analysis of the slides was blind to the pathologist. A brown staining indicates the positive expression. Then, the histopathology examination was conducted using the optical microscope. The pathologist was completely blinded to the experiment design.
Western blot analysis
Tissue Total Protein Extraction Kit (KeyGEN, China) was used to extract the total protein of lung tissue and the total protein concentration was determined by using the BCA protein kit. A total of 40 μg lysate proteins were loaded on SDS-polyacrylamide gels and transferred to nitrocellulose membranes (Pall 66,485, USA). Then, the membrane was blocked using fat-free milk at room temperature for 2 hrs and incubated at 4°C overnight. The primary antibodies E-cadherin, vimentin, and JAK2 were purchased from Cell Signaling Technology (CST), USA. The primary antibodies STAT3, p-STAT3, TGF-β, p-Smad3, and Smad3 were purchased from Abcam, USA. Finally, the photodensitometric analysis of the protein bands was conducted with the Image Lab™ Software (Bio-Rad, USA).
All the data were presented as mean±standard deviation (SD). A 2×2 factorial analysis was performed to determine the significance between groups. The statistical analysis was conducted using IBM SPSS Statistics version 21. Statistical difference was determined significantly at P<0.05.
Characterization of SiNPs
The characterization of SiNPs was demonstrated in the supplemental material. The average size of the SiNPs was 62±7.1 nm (Figure S2), and the SiNPs had good monodispersability both in distilled water and saline (Table S1). The purity of the SiNPs was higher than 99.9% and no endotoxin was detected in the SiNPs by the LAL assay (Table S2).
Lung injuries induced by intravenous injection of SiNPs
The coefficients of lungs slightly elevated with time both in the SiNP-treated group and in the control group in the period of observation at three time points. The values in the SiNP-treated groups were significantly higher than that in the control groups at 15th day, 30th day, and 60th day (Figure 1A).
Figure 1 Lung injuries induced by SiNPs through intravenous injection in mice. (A) The coefficients of lungs increased significantly in the SiNP-treated group. Data are expressed as means±SD (n=5). *P<0.05 compared with control. (B) Histopathologic changes in mice lungs induced by SiNPs. Black arrow: red blood cells in the area of alveoli; Red arrow: alveoli septum thicken and inflammatory cell infiltration. Scale bar: 20 µm. (C) Ultrastructural observation in mice lungs observed by TEM. (a, b) SiNPs (red arrows) deposited in lungs at 15th day. Scale bar: (a) 1 µm; (b) 200 nm. (c, d) Ultrastructural changes of alveolar macrophages in lungs of SiNP-treated mice at 30th day: extensive vacuolization (red star), mitochondrial fusion (red hollow triangle), mitochondrial cristae disappearance (red asterisk). Scale bar: (c) 0.5 µm; (d) 200 nm. (e, f) Vacuolization (red triangle) in the basophilic granulocyte in lungs of SiNP-treated mice at 30th day. Scale bar: (e) 1 µm; (f) 100 nm. (g, h) Cell cluster consisted of multinucleate cell (hollow star) and type I alveolar epithelial cell (hollow diamond) in lungs of SiNP-treated mice at 60th day. Scale bar: (e) 2 µm; (f) 1 µm.
The lung sections of control groups revealed normal bronchial structure. In the SiNP-treated groups at 15th day, a large amount of red blood cells appeared in the area of alveoli induced indicating SiNPs induced severe congestion and hemorrhage of alveoli (Figure 1B d). At 30th day and 60th day, obvious alveoli septum thickening and inflammatory cell infiltration were observed in the lungs of the SiNP-treated mice (Figure 1B e and f).
Ultrastructural observation revealed that SiNPs were occasionally observed aggregated and enclosed with lysosome membranes in the cells of the lungs at 15th day (Figure 1C a and b). Alveolar macrophages showed destruction of organelle such as mitochondrial fusion, mitochondrial cristae disappearance, and an extensive vacuolization in the SiNP-treated groups at 30th day (Figure 1C c and d). The vacuolization was also observed in the basophilic granulocyte in the lungs of SiNP-treated mice (Figure 1C e and f). At 60th day, the cell cluster appeared in the lungs in the administration group, which consisted of multinucleate cell and typeⅠalveolar epithelial cell (Figure 1C g and h).
Effects of SiNPs on the oxidative damage, inflammation, and JAK2/STAT3 signaling pathway in lungs
As shown in Figure 2A, the content of MDA, which is a product of lipid peroxidation, increased significantly in the lungs in the SiNP-treated mice compared with that in the control groups (p<0.05) at 15th day, 30th day, and 60th day and was 1.40-fold, 1.26-fold, and 1.16-fold higher than that in the control groups, respectively. On the contrary, the activities of SOD and GSH-Px which belong to the defense systems against free radical attack decreased at 15th day and 30th day in lungs in the SiNP-treated mice, and recovered and even elevated at 60th day. But only the changes of SOD activities in lungs in the SiNP-treated groups had significant statistical differences compared with control groups at three time points (P<0.05).
Figure 2 Effects of SiNPs on the oxidative damage, inflammation, and JAK2/STAT3 signaling pathway in lungs. (A) Effects of SiNPs on the oxidative damage in lung tissues. Data are expressed as means±SD (n=5). *P<0.05 compared with control. (B) Effects of SiNPs on the pro-inflammatory cytokines in lung tissues. Data are expressed as means±SD (n=5). *P<0.05 compared with control. (C) Effects of SiNPs on the pro-inflammatory cytokines in serum. Data are expressed as means±SD (n=5). *P<0.05 compared with control. (D) Western blot and relative densitometric analysis indicated SiNPs activated the JAK2/STAT3 signaling pathway in lung tissues at 15th day, 30th day, and 60th day. Data are expressed as means ± SD *P<0.05 compared with control.
In order to assess the status of inflammation systemically and locally, we detected the pro-inflammatory cytokines in serum and in lungs. As shown in Figure 2B, SiNPs induced higher TNF-α, IL-1β, and IL-6 levels in lung tissues in experimental groups than in control groups at 15th day, at 30th day, and at 60th day. In SiNP-treated mice, TNF-α and IL-6 levels reached the peak value at 60th day while IL-1β levels at 15th day, which means IL-1β might be the most sensitive marker in local inflammation in lungs. Similarly, the serum TNF-α, IL-1β, and IL-6 levels were elevated significantly in SiNP-treated mice compared with that in control groups at 30th day and at 60th day (Figure 2C). Serum TNF-α level kept increasing while serum IL-1β and IL-6 decreased mildly in the whole observation period.
Figure 2D shows the protein expressions of key molecules in JAK2/STAT3 a pathway by Western blot. The densitometric analysis of the bands indicated the pulmonary expression of JAK2, p-STAT3, and STAT3 all increased significantly in SiNP-treated mice compared with that in control groups at three time points. The results turned out intravenous injection of SiNPs activated the JAK2/STAT3 pathways in lungs at 15th day, 30th day, and 60th day.
Effects of SiNPs on the myofibroblast activation, collagen production, and TGF-β/Smad3 signaling pathway in lungs
Figure 3A shows the expression of αSMA, the marker of myofibroblast by immunohistochemical staining in the lungs. Normally the expression of αSMA distributed in the vascular wall or the mesenchyme in lungs in control groups. In SiNP-treated mice, the number of αSMA positive cells increased in the pulmonary mesenchyme especially in pulmonary alveolar wall, and the αSMA positive cells always located in the area of inflammatory cells infiltration.
Figure 3 Effects of SiNPs on the myofibroblast activation, collagen production, and TGF-P/Smad3 signaling pathway in lungs. (A) Immunochemical staining of αSMA in lung sections. Black arrows: αSMA positive cells. Scale bar: 20 µm. (B) Immunochemical staining of CTGF in lung sections. Black arrows: CTGF positive cells. Scale bar: 20 µm. (C) The hydroxyproline level in lung tissues. Data are expressed as means±SD. *P<0.05 compared with control. (D) Western blot and relative densitometric analysis indicated SiNPs activated the TGF-I3/Smad3 signaling pathway in lung tissues at 15th day, 30th day, and 60th day. Data are expressed as means±S.D. *P<0.05 compared with control.
The immunohistochemistry of CTGF, which is one of the main regulators in connective tissue remodeling or fibrosis, is shown in Figure 3B. CTGF immunohistochemistry revealed more prominent pulmonary alveolar or interstitial CTGF staining in SiNP-treated mice than in control groups.
As the index of collagen accumulation, the hydroxyproline content was raised in lungs in the SiNP-treated mice with significant difference compared with control groups at three time points (Figure 3C). The changes of collagen content did not show obvious time tendency in the period of study, and SiNPs induced the pulmonary hydroxyproline contents elevated 1.07-, 1.16-, and 1.08-fold over control values at 15th day, 30th day, and 60th day, respectively.
The protein expressions of key molecules in TGF-β/Smad3 pathway by Western blot are shown in Figure 3D. The densitometric analysis of the bands indicated the pulmonary expression of TGF-β, p-Smad3, and Smad3 all increased significantly in SiNP-treated mice compared with that in control groups at three time points. The results illustrated intravenous injection of SiNPs activated TGF-β/Smad3 pathway in lungs at 15th day, 30th day, and 60th day.
Effects of SiNPs on the status of EMT in lungs
Intravenous administration of SiNPs induced ultrastructural changes in type II alveolar epithelial cells in lungs. The type II alveolar epithelial cells in control groups appeared round shape and attached to the inner side of alveolar wall, with normal structure of nucleus, mitochondria, and lamellar body. In the SiNP-treated mice, the type II alveolar epithelial cells were viewed with irregular shape, nucleus irregularly shaped with folded membrane, lamellar bodies highly expansion, as well as collagenous fibers accumulation near the cell (Figure 4A).
Figure 4 Effects of SiNPs on the status of epithelial–mesenchymal transition in lungs. (A) Ultrastructural changes of type II alveolar epithelial cells observed by TEM in mice lungs at 60th day. (a) Type II alveolar epithelial cell in the control group at 60th day. Scale bar: 0.5 µm; (b,c) Type II alveolar epithelial cell with irregular shape, nucleus transformation with fold membrane (red arrow), lamellar bodies expansion (red asterisk). Scale bar: 0.2 µm. (d, e) Type II alveolar epithelial cell with lamellar bodies highly expansion (red asterisk) and collagenous fibers accumulation nearby the cell (red hollow triangle). Scale bar: (d) 1 µm; (e) 0.2 µm. (B) Western blot and relative densitometric analysis of E-cadherin and vimentin in lungs at 15th day, 30th day, and 60th day. Data are expressed as means±S.D. *P<0.05 compared with control.
The protein expression of E-cadherin, the key markers of epithelial cells, was significantly upregulated in lungs in the SiNP-treated mice compared with control groups at 15th day, 30th day, and 60th day, and appeared in a time-dependent manner (Figure 4B). Interestingly, SiNPs induced the protein expression of vimentin elevated at 15th day but decreased at 30th day and 60th day, without any statistical difference.
Thus, our data confirmed that intravenous injection of SiNPs induced pulmonary inflammation and collagen accumulation via JAK2/STAT3 and TGF-β/Smad3 pathways in vivo. A schematic model of the underlying mechanisms on how SiNPs regulate pulmonary injury is presented in Figure 5.
Figure 5 A schematic model on how SiNPs modulate pulmonary inflammation and collagen accumulation through repeated intravenous injection was presented. Briefly, SiNPs exposure causes oxidative stress-mediated JAK2/STAT3 signaling pathway activation thus to elicit pulmonary and systemic inflammation in the 45 days observation period in vivo, including of the elevation of TNF-α, IL-1β, and IL-6 levels in lungs and serum. The chronic inflammatory process activates TGF-Iβ/Smad3 signaling pathway so as to promote the transdifferentiation from fibroblast into myofibroblast, and finally accelerates the collagen production in lungs. However, the epithelial–mesenchymal transition in type II alveolar epithelial cells seems not involved in the process mentioned earlier.
As the rapid development of nanotechnology, concerns about the potential adverse biological outcome of manufactured nanomaterials are getting great attention. As one of the cornerstones of sustainability, the studies on NanoEHS to fill the large knowledge gaps in this field are required for the implementation and safe development of nanotechnology. For the first time, our study systemically evaluated the subchronic lung toxicity induced by repeated intravenous exposure of SiNPs in vivo. The results demonstrated that repeated intravenous injection of SiNPs could indeed cause pulmonary inflammation and collagen accumulation in vivo. It is helpful for the understanding of the organic toxicity through intravenous exposure of nanoparticles, so as to reduce the side effects in biomedical application of nanoparticles in diagnostics or therapeutics.
Most in vivo pulmonary toxicity studies of SiNPs chose intratracheal instillation exposure because it was the most common way for SiNPs exposure which mimicked the occupational exposure in human.15–17 In intratracheal instillation exposure, SiNPs had direct contact with the lung tissues and then deposited in situ, thus led to pulmonary injuries.18–20 Ferri et al observed that systemic sclerosis patients with occupational exposure showed high serum levels of SiNPs, indicating SiNPs in the blood circulation acted as a co-factor involved in the etiopathogenesis of lung injuries.21 In the present study, intravenous exposure of SiNPs increased the weight of lung tissues and destroyed pulmonary histomorphological structure and cellular ultrastructure (Figure 1). The results implied pulmonary injuries should be seriously taken into consideration in intravenous exposure of nanomaterials in the biomedical application.
Oxidative stress is considered as one of the most important toxic mechanisms of nanomaterials including SiNPs.8,22 With silicon-bonded hydroxyl groups and the unsaturated bond on the particle surface, SiNPs are prone to contribute to the generation of reactive oxygen species (ROS) and oxidative stress.2 It was reported that SiNPs induced oxidative stress in a dose-dependent manner in vitro.23–25 In present study, we observed SiNPs significantly increased oxidative stress markers MDA, depletion of SOD and GSH-Px in lung tissues through intravenous administration (Figure 2A). Oxidative stress mediated inappropriate activation of JAK2 and then activated the transcription factors STAT3 whose aberrant activation has been implicated in inflammation and carcinogenesis.26,27 We detected the protein expression of JAK2/STAT3 signaling pathway and the results indicated SiNPs induced the activation of JAK2/STAT3 pathway (Figure 2B). Meanwhile, SiNPs elicited systemic inflammation and pulmonary inflammation illustrated by the elevation of TNF-α, IL-1β, and IL-6 levels in serum and lung tissues in mice (Figure 2C). Recently, Juthika Kundua et al also reported that SiNPs induced inflammation through JAK2/STAT3 pathway activation mediated by oxidative stress in human keratinocyte (HaCat) cells.28 So our study demonstrated that the intravenous administration of SiNPs could elicit oxidative stress mediating JAK2/STAT3 pathway activation thus to cause pulmonary and systemic inflammation in the 45 days observation period in vivo.
During the tissue repair and wound healing, fibroblasts are promoted to transdifferentiate into myofibroblasts which are characterized by the de novo expression of αSMA and mainly in charge of production of extracellular matrix components including collagen, fibronectin, and others.29 In our study, we demonstrated that intravenous injection of SiNPs induced moderate increase of αSMA expression and collagen accumulation in lung tissues in the 45 days observation period (Figure 3A and C), indicating that SiNPs was likely to promote the transdifferentiation from fibroblast into myofibroblast thus to accelerate the production of extracellular matrix in lungs. Chronic inflammatory process is involved in the dysregulation of pulmonary fibroblast proliferation and contributes to overproduction of extracellular matrix.30 Recently, it was reported that STAT3 mediated TGF-β production through the modulation of pro-inflammatory cytokines of IL-6 in pulmonary fibrosis.31 We observed the upregulated protein expression of TGF-β and p-Smad3 in lungs in the SiNP-treated mice (Figure 3D). So in our study, the elevated protein expression of STAT3 and IL-6 contributed to the TGF-β production which promoted the transdifferentiation from fibroblast into myofibroblast so as to accelerate the collagen production in lungs.29
Generally, the origins of myofibroblasts are considered from interstitial fibroblasts through transdifferentiation, or from bone-marrow-derived fibrocytes in the blood circulation, or the alveolar epithelial cells type Ⅱ via EMT.32,33 In our study, we observed SiNPs induced the ultrastructural changes in alveolar epithelial cells type II in lungs, but the protein expression of epithelial marker E-cadherin was elevated rather than reduced (Figure 4), which implied that most of the myofibroblasts involved in the excessive pulmonary extracellular matrix production did not originate from the transition of alveolar epithelial cells type Ⅱ in SiNP-treated mice. Hinz et al reported that myofibroblasts primarily generated from the transdifferentiation of the resident fibroblasts at the injury sites.34 Yet, the underlying mechanism of the above issue required more investigation.
In summary, we found that SiNPs caused pulmonary inflammation and collagen accumulation through repeated intravenous injection in mice models. Furthermore, we revealed that oxidative stress and inflammation contributed to the collagen production through activation of JAK2/STAT3 and TGF-β/Smad3 signaling pathways, which is rare to see in previous toxicological researches on the lung tissues through repeated intravenous administration of SiNPs. It suggests that aberrant inflammation and collagen accumulation in lung tissues induced by nanoparticles should be seriously considered for the safety application in diagnostics or therapeutics, especially in the intravenous administration.
This work was supported by National Natural Science Foundation of China (No.81602876 and 81571130090), Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five–year Plan (CIT&TCD201804089), and the Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety, CAS (NSKF201817).
The authors declare they have no conflicts of interest in this work.
1. Nel AE, Parak WJ, Chan WC, et al. Where are we heading in nanotechnology environmental health and safety and materials characterization? ACS Nano. 2015;9(6):5627–5630. doi:10.1021/acsnano.5b03496
2. Napierska D, Thomassen LC, Lison D, Martens JA, Hoet PH. The nanosilica hazard: another variable entity. Part Fibre Toxicol. 2010;7(1):39. doi:10.1186/1743-8977-7-39
3. Oberdorster G. Safety assessment for nanotechnology and nanomedicine: concepts of nanotoxicology. J Intern Med. 2010;267(1):89–105. doi:10.1111/j.1365-2796.2009.02187.x
4. Tang L, Cheng J. Nonporous silica nanoparticles for nanomedicine application. Nano Today. 2013;8(3):290–312. doi:10.1016/j.nantod.2013.04.007
5. WHO. WHO Guidelines On Protecting Workers From Potential Risks Of Manufactured Nanomaterials. Geneva: World Health Organization; 2017.
6. Xu R, Zhang G, Mai J, et al. An injectable nanoparticle generator enhances delivery of cancer therapeutics. Nat Biotechnol. 2016;34(4):414–418. doi:10.1038/nbt.3506
7. Benezra M, Penate-Medina O, Zanzonico PB, et al. Multimodal silica nanoparticles are effective cancer-targeted probes in a model of human melanoma. J Clin Invest. 2011;121(7):2768–2780. doi:10.1172/JCI45600
8. Murugadoss S, Lison D, Godderis L, et al. Toxicology of silica nanoparticles: an update. Arch Toxicol. 2017;91(9):2967–3010. doi:10.1007/s00204-017-1993-y
9. Yu Y, Duan J, Li Y, et al. Silica nanoparticles induce liver fibrosis via TGF-beta1/Smad3 pathway in ICR mice. Int J Nanomedicine. 2017;12:6045–6057. doi:10.2147/IJN.S132304
10. Yu Y, Li Y, Wang W, et al. Acute toxicity of amorphous silica nanoparticles in intravenously exposed ICR mice. PLoS One. 2013;8(4):e61346. doi:10.1371/journal.pone.0061346
11. Xie G, Sun J, Zhong G, Shi L, Zhang D. Biodistribution and toxicity of intravenously administered silica nanoparticles in mice. Arch Toxicol. 2010;84(3):183–190. doi:10.1007/s00204-009-0488-x
12. Zhuravskii S, Yukina G, Kulikova O, et al. Mast cell accumulation precedes tissue fibrosis induced by intravenously administered amorphous silica nanoparticles. Toxicol Mech Methods. 2016;26(4):260–269. doi:10.3109/15376516.2016.1169341
13. Mohammadpour R, Yazdimamaghani M, Cheney DL, Jedrzkiewicz J, Ghandehari H. Subchronic toxicity of silica nanoparticles as a function of size and porosity. J Control Release. 2019;304:216–232. doi:10.1016/j.jconrel.2019.04.041
14. Iwaisako K, Hatano E, Taura K, et al. Loss of Sept4 exacerbates liver fibrosis through the dysregulation of hepatic stellate cells. J Hepatol. 2008;49(5):768–778. doi:10.1016/j.jhep.2008.05.026
15. Morris AS, Adamcakova-Dodd A, Lehman SE, et al. Amine modification of nonporous silica nanoparticles reduces inflammatory response following intratracheal instillation in murine lungs. Toxicol Lett. 2016;241:207–215. doi:10.1016/j.toxlet.2015.11.006
16. Maser E, Schulz M, Sauer UG, et al. In vitro and in vivo genotoxicity investigations of differently sized amorphous SiO2 nanomaterials. Mutat Res Genet Toxicol Environ Mutagen. 2015;794:57–74. doi:10.1016/j.mrgentox.2015.10.005
17. Zhang J, Ren L, Zou Y, et al. Silica nanoparticles induce start inhibition of meiosis and cell cycle arrest via down-regulating meiotic relevant factors. Toxicol Res (Camb). 2016;5(5):1453–1464. doi:10.1039/c6tx00236f
18. Yang H, Wu QY, Li MY, Lao CS, Zhang YJ. Pulmonary toxicity in rats caused by exposure to intratracheal instillation of SiO2 nanoparticles. Biomed Environ Sci. 2017;30(4):264–279. doi:10.3967/bes2017.036
19. Yang M, Jing L, Wang J, et al. Macrophages participate in local and systemic inflammation induced by amorphous silica nanoparticles through intratracheal instillation. Int J Nanomedicine. 2016;11:6217–6228. doi:10.2147/IJN.S116492
20. Choi M, Cho W-S, Han BS, et al. Transient pulmonary fibrogenic effect induced by intratracheal instillation of ultrafine amorphous silica in A/J mice. Toxicol Lett. 2008;182(1–3):97–101. doi:10.1016/j.toxlet.2008.08.019
21. Ferri C, Artoni E, Sighinolfi GL, et al. High serum levels of silica nanoparticles in systemic sclerosis patients with occupational exposure: possible pathogenetic role in disease phenotypes. Semin Arthritis Rheum. 2018. doi:10.1016/j.semarthrit.2018.06.009
22. Wang F, Gao F, Lan M, Yuan H, Huang Y, Liu J. Oxidative stress contributes to silica nanoparticle-induced cytotoxicity in human embryonic kidney cells. Toxicol In Vitro. 2009;23(5):808–815. doi:10.1016/j.tiv.2009.04.009
23. Sun L, Li Y, Liu X, et al. Cytotoxicity and mitochondrial damage caused by silica nanoparticles. Toxicol In Vitro. 2011;25(8):1619–1629. doi:10.1016/j.tiv.2011.06.012
24. Osmond-McLeod MJ, Poland CA, Murphy F, et al. Durability and inflammogenic impact of carbon nanotubes compared with asbestos fibres. Part Fibre Toxicol. 2011;8:15. doi:10.1186/1743-8977-8-15
25. Duan J, Yu Y, Yu Y, et al. Silica nanoparticles induce autophagy and endothelial dysfunction via the PI3K/Akt/mTOR signaling pathway. Int J Nanomedicine. 2014;9:5131–5141. doi:10.2147/IJN.S71074
26. Momtaz S, Niaz K, Maqbool F, Abdollahi M, Rastrelli L, Nabavi SM. STAT3 targeting by polyphenols: novel therapeutic strategy for melanoma. Biofactors. 2017;43(3):347–370. doi:10.1002/biof.1345
27. Kundu JK, Surh Y.J. Emerging avenues linking inflammation and cancer. Free Radic Biol Med. 2012;52(9):2013–2037. doi:10.1016/j.freeradbiomed.2012.02.035
28. Kundu J, Kim D-H, Chae IG, et al. Silicon dioxide nanoparticles induce COX-2 expression through activation of STAT3 signaling pathway in HaCaT cells. Toxicol In Vitro. 2018;52:235–242. doi:10.1016/j.tiv.2018.06.008
29. Razdan N, Vasilopoulos T, Herbig U. Telomere dysfunction promotes transdifferentiation of human fibroblasts into myofibroblasts. Aging Cell. 2018;e12838. doi:10.1111/acel.12838
30. Kolb M. Inflammation and dysregulated fibroblast proliferation–new mechanisms? Sarcoidosis Vasc Diffuse Lung Dis. 2013;30(Suppl 1):21–26.
31. Celada LJ, Kropski JA, Herazo-Maya JD, et al. PD-1 up-regulation on CD4(+) T cells promotes pulmonary fibrosis through STAT3-mediated IL-17A and TGF-beta1 production. Sci Transl Med. 2018;10(460):eaar8356. doi:10.1126/scitranslmed.aao4496
32. Kim KK, Kugler MC, Wolters PJ, et al. Alveolar epithelial cell mesenchymal transition develops in vivo during pulmonary fibrosis and is regulated by the extracellular matrix. Proc Natl Acad Sci U S A. 2006;103(35):13180–13185. doi:10.1073/pnas.0605669103
33. Willis BC, duBois RM, Borok Z. Epithelial origin of myofibroblasts during fibrosis in the lung. Proc Am Thorac Soc. 2006;3(4):377–382. doi:10.1513/pats.200601-004TK
34. Hinz B. Formation and function of the myofibroblast during tissue repair. J Invest Dermatol. 2007;127(3):526–537. doi:10.1038/sj.jid.5700613


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Parade Highlights Organ Donation
By Tom Mone
One of the most memorable moments at the Pasadena Rose Parade earlier this week was the inspiring Donate Life float, which called attention to the incredible life-saving power of organ, eye and tissue donation. More than 96 individuals were honored on the float that day – from recipients who rode on the float to donors who were remembered through beautiful floragraphs to walkers who were part of a "kidney chain" of living donors and recipients.
While the topic of organ donation made parade headlines on January 2, these headlines often fade for much of the other 364 days a year and inspiring messages are easily forgotten. But that need not be the case. It is here that our nation's hospitals, skilled nursing facilities and hospice programs can play a most crucial role. Hospitals, in particular, have long been a trusted source of information, service and compassion within their local communities. As such – and in recognition of the donation shortage we are currently facing – America's hospitals have a crucial role and responsibility to facilitate a thoughtful conversation with their staff, patients, families and their communities on this topic. And there is no better time than the start of a new year to do just that through inspiring education, support and advocacy.
It is a cold, hard fact that 22 die unnecessarily every day in the United States waiting for an organ transplant. Currently more than 119,000 of our fellow citizens are waiting to receive lifesaving hearts, livers, lungs, kidneys and pancreases but there are simply not enough donors to meet the growing demand. A great deal of the problem rests in the public's misconceptions about organ donation – how to register to be a donor, what is involved in the process, and how the donor's body will be treated upon death.
The work begins with educating the internal staff, particularly those closest to potential donor situations. This includes staff in trauma, emergency units and the ICU, along with chaplains and social services, to make sure they understand the issues and have access to the right information in a timely manner should the opportunity for a donation arise. Even if they are not directly requesting donations from patients' families, the support of these individuals will have a significant impact at the time of decision while also helping to shape the organization's culture in this area.
Hospitals can also help by educating the community on the importance of registering to be a donor. Far more can be done in this area to ensure that the question of organ donation doesn't arise for the average person only at the time of a very tragic circumstance. By then it is usually too late for the individual to express his or her intent to their family or physician and it rests upon next-of-kin to guess what their loved one would have wanted. Helping families and patients have that conversation before it's too late and sharing the opportunity of donor registration can relieve families of the responsibility to try to guess their loved one's wishes.
There are many other things hospitals can do at little or no cost to promote organ and tissue donation. They can have a donor registration table at community health fairs or work with a local organ and tissue recovery organization to provide a community lecture on the topic (perhaps in conjunction with a local physician). They can leverage already existing communication vehicles and include articles about donation in their community newsletter (both print and online), or set up a link on the hospital's website through which people can learn about and sign-up to be a donor. They can work with the media to feature local donor recipients and tell the story of how one donor can save up to eight lives through organ donation and heal as many as 50-100 recipients through tissue donation.
It is also the hospital, perhaps more than anyone else, who can deliver the important message that there is no inherent conflict between saving lives and using organs for transplant. The doctors who work to save a patient's life are not the same doctors involved with organ donation, and it is only after every attempt has been made to save a life that the appropriate medical professionals review the deceased's medical and social history to determine if they are a candidate for donation.
Becoming an active participant in this process is one more way hospitals can demonstrate their support for the "Healthier Communities" initiative of the American Hospital Association while living up to their true calling as a place of hope, healing and miracles for those they serve.
Tom Mone is chief executive officer of Los Angeles-based OneLegacy, the nation's largest organ, eye and tissue recovery organization.
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Tag Archives: Morales
Bolivia says no! to US Drug Agents in their country!
Diplomatic relations OK! DEA No!
Evo Morales, the Bolivian president, has said that US drug agents are not welcome back in his country despite the newly announced normalization of diplomatic relations with Washington.
Morales told reporters in Bogota on Tuesday during a regional summit in the Colombian capital that it was a question of "dignity and sovereignty".
As a coca growers' union leader before his 2005 election, Morales said he was "personally a victim" because US agents controlled Bolivia's military and police.
Bolivia's anti-narcotics police, working closely with the US Drug Enforcement Administration (DEA), often clashed with coca growers and Morales has said they once beat him unconscious.
"They repressed us in Bolivia. That has ended," Morales said.
"For the first time since Bolivia was founded, the United States will now respect Bolivia's rules and laws," he added, under the agreement restoring full diplomatic ties that Bolivia and Washington signed on Monday.
The deal comes three years after the Andean nation's leftist government expelled the US ambassador and DEA for allegedly inciting the opposition.
Normalising relations
The pact calls for the restoration of ambassadors as soon as possible and close co-operation in counter narcotics, trade and development, said a US official familiar with the agreement.
Morales said that he still considered the ambassador he expelled in September 2008, Philip Goldberg, to have been "a conspirator". Less than two months later, he ejected the DEA.
Washington denies the Bolivian government's allegations that Goldberg schemed with lowlands agribusiness people to unseat Morales, an Aymara Indian raised in the country's poor highlands.
Bolivian Pres.: U.S. Drug Agents Not Welcome (foxnews.com)
By hotdogfish • Posted in Crime Watch!	• Tagged Bolivia, Diplomacy, Drug Enforcement Administration, Morales, Philip Goldberg, United States, Washington


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Home The Blog Year of Innovation, Architecture and Design Scotland's 10 greatest man-made wonders that you simply MUST visit
Scotland's 10 greatest man-made wonders that you simply MUST visit
Aldona Reyes Mallet October 13, 2016 View Comments
We're not lying when we say that Scotland is bursting with wonderful man-made wonders. When you combine an artistic flair with a can-do spirit the results can be spectacular.
Here are the top 10 man-made wonders in Scotland, as voted for by you*. The Scottish equivalent of the Seven Wonders of the World spans some of the most eclectic and diverse sights, from a 12th century monastery and iconic medieval castles to landmarks of Victorian architectural prowess and engineering feats of the 21st century.
Get that pen ready because you're gonna want to whack all of these bad boys onto your bucket list!
10. Melrose Abbey
Melrose Abbey, Scottish Borders
Lying in the Tweed Valley in the charming town of Melrose, it's easy to see why this ever-glorious ruin, with its lavishly decorated masonry, opens up this list.
It was founded by King David I in 1136, with the surviving remains of the church dating to the early 15th century, and is believed to be the burial place of Robert the Bruce's heart. Admire the exterior's hand-crafted decoration and view objects found during previous excavations.
Melrose Abbey is also often referred to as one of Scotland's most beautiful buildings thanks to its sense of romance and charm. We heartily agree – do you?
9. Bell Rock Lighthouse
Bell Rock Lighthouse, off the coast of Angus
Nearly 200 years after it was first built, the Bell Rock Lighthouse, popularly known as Stevenson's Lighthouse, still stands – proudly flashing its warning light.
Located off Scotland's east coast on a partially submerged reef, this impressive stone tower is the world's oldest surviving sea-washed lighthouse and has not required a single repair or alteration to its stonework or design since the day it was built.
It's often regarded as the most outstanding engineering achievement of the 19th century, and rightfully so. Make sure you visit it on your next trip to Scotland!
8. Scott Monument
Princes Street Gardens, with Scott Monument in the background
This Gothic memorial to literary beacon Sir Walter Scott in the heart of Edinburgh is not only the largest monument to a writer in the world, it's also a gallery that houses an exhibition on his life and works amongst its sandstone walls.
Completed 170 years ago, this soaring beauty is over 200 ft high and its highest gallery is reached by climbing a spiral staircase of 287 steps to the top. From there you can enjoy superb views of the city and the surrounding countryside. You can even get a certificate to prove you made it to the top!
Take some time to appreciate the exterior side of Scott Monument, too, which is decorated with 64 carvings. All the statuettes represent characters from Scott's novels. How many can you name?
7. Caledonian Canal
Caledonian Canal at Fort Augustus where it joins Loch Ness, Highlands
Masterminded by Thomas Telford, the great Scottish engineer, the Caledonian Canal is considered by many to be one of the greatest waterways in the world.
Running just over 60 miles, it stretches from Inverness to Corpach near Fort William, slicing through the length of the majestic Great Glen and taking in some of the most breathtaking scenery that Mother Nature has endowed Scotland with. If you've not explored it yet, do it and savour a taste of the Highlands at their most dramatic.
Interestingly, only one third of the entire length is man-made, while the rest is formed by various lochs, including Loch Lochy and Loch Ness.
6. Falkirk Wheel
The Falkirk Wheel, connecting the Union Canal and the Forth & Clyde Canal
'A rotating boatlift?' we hear you ask. Yep! This wonderful, mechanical marvel raises vessels and connects the Forth & Clyde Canal and the Union Canal in central Scotland. It's the only construction of its kind in the world!
Once vital for transportation, today the Falkirk Wheel is an iconic landmark that stands as a testament to the historical importance of Scotland's waterways, as well as being an example of extraordinary engineering.
Climb onto a boat and soar gracefully 35 m in the air before smoothly landing on the Union Canal, and visit the newly revamped visitor centre where you will learn about the workings of this mighty wheel. Did you know… it only takes the power of about eight toasters for a full rotation?
5. Stirling Castle
The entrance to Stirling Castle
Mounted high on a volcanic outcrop, Stirling Castle is one of Scotland's grandest castles and was once a favoured residence of the Stewart kings and queens. Well, that's hardly a surprise… Step into its enchanting interiors and you'll see why.
From its sumptuous halls and beautiful gardens to the splendid Royal Palace which has recently been meticulously restored to its original Renaissance glory, a visit to Stirling Castle guarantees a grand and memorable day out. You will walk in the courtyard once frequented by Mary Queen of Scots, James V and Mary of Guise, and the kids will love playing dress-up in the palace vaults and meeting costumed courtiers, bodyguards and servants. The palace exterior, studded with beautiful sculptures, and its commanding views deserve a special mention, too.
4. Glenfinnan Viaduct
The Jacobite steam train passing over the Glenfinnan Viaduct in Lochaber, Highlands
Part of the legendary West Highland Line between Fort William and Mallaig (which is widely regarded as one of the greatest railway journeys in the world), the Glenfinnan Viaduct needs little introduction.
This iconic structure is made up of 21 arches that curve around the valley. It overlooks the Glenfinnan Monument and the waters of Loch Shiel and is surrounded by some of Scotland's most splendid scenery. Simply picture-perfect!
You can admire it from the train (vintage steam trains also run in the summer months) or from a distance. Either way, it's a great experience – not just for Harry Potter fans.
3. The Kelpies
The Kelpies at The Helix towering above the Forth & Clyde Canal, near Falkirk
Designed by the Scottish sculptor Andy Scott, The Kelpies are the largest pair of equine sculptures in the world. Towering one hundred feet high above the Forth & Clyde Canal, the two colossal, glinting horse heads never fail to impress.
Made of 300 tonnes of shimmering galvanised steel each, those mighty metal beasts are a feat of engineering. Situated just off the M9, they mark the gateway to Scotland's canals and are a monumental tribute to the horse power heritage that was vital to the early industries of central Scotland.
Perfect for a day out, or visit at night when they're prettily lit up. Mesmerising! Did you know you can even go inside to marvel at the complexity and the engineering which created these fantastic pieces of art?
2. Edinburgh Castle
Edinburgh Castle and the Balmoral Hotel clocktower at sunrise
This stunning fortress dominates Edinburgh's skyline and is unquestionably Scotland's most famous castle. An unmissable part of any visit to the city.
Set atop a craggy extinct volcano, at the top of the cobbled and atmospheric Royal Mile, Edinburgh Castle is part of a World Heritage Site, and houses the Scottish Crown Jewels, the Stone of Destiny and Mons Meg. Get there in the early afternoon and you can also see (and hear!) the famous One O'Clock Gun!
It's no fairytale castle, but when you see it you will understand why over a million visitors pass through its gates each year. It's even been voted the UK's best heritage attraction for a few years in the row!
1. Forth Bridge
The Forth Bridge in South Queensferry at sunset
And the winner is… certainly deserved!
The Forth Bridge is one of Scotland's major landmarks and a UNESCO World Heritage Site. It's a world-beating example of industrial engineering.
Whether it's the sheer scale, innovative workmanship or architectural and engineering prowess, this magnificent railway bridge continues to impress 21st century visitors as much as it did when it was first erected and opened in 1890.
It was designed on the cantilever principle, with its three towers over 100 m high, and stretches one and a half miles over the Firth of Forth, connecting the coasts of Edinburgh and Fife. A truly spectacular sight to behold!
What a list it is! We sure live in a beautiful world. In the Year of Innovation, Architecture and Design 2016, why not discover these breathtaking man-made wonders? Who knows, maybe some day you will travel to see them all – we challenge you!
* These 10 wonders were announced as the results of recent research carried out by VisitScotland which included a survey of 2025 UK adults.
Posted in Categories...
Attractions & Days Out
Year of Innovation, Architecture and Design
Tagged with...
Architecture and Designman-made wondersScotland's architectural wondersScotland's wonderful bridgesScotland's wonderful castlesScotland's wonderswonders of the worldYear of InnovationYIAD 2016
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brings new hair styles and color from the Bay Area to Lodi. Susan specializes in corrective color and highlighting effects, such as European Color, Highlights and Lowlights, and Hair Extensions.
Susan gets great reviews on Yelp!
" I LOVE Susan!! She is an amazing colorist. I love how she makes my hair gorgeous & perfectly highlighted. I always get great compliments on the color and cut." - Beci K.
Update your hair with a new style! Add new color to your everyday look, or get beautiful hair for a special occasion. Susan is also available for weddings and special occasions, and offers free bridal consultations.


Village Revenue Assistant from Rs.1700/- to Rs.3000/- per month.
Village Revenue Assistants from Rs.3,000/- to Rs.6000/- per month.
essential commodities and other necessities.
Government to issue necessaryorders in the matter.
Rs.10,500/-(Rupees ten thousand five hundred only) per month w.e.f.02.06.2018.
U.O. No.45027/185/Fin- FMU-Rev,I&C & Energy/2018, dated:08 06.2018.


text:
package com.nspwn.ghostbin.ui;

import android.os.Bundle;

import com.actionbarsherlock.app.SherlockFragmentActivity;
import com.nspwn.ghostbin.BootstrapApplication;

import butterknife.Views;

/**
 * Base class for all Bootstrap Activities that need fragments.
 */
public class BootstrapFragmentActivity extends SherlockFragmentActivity {

    @Override
    protected void onCreate(Bundle savedInstanceState) {
        super.onCreate(savedInstanceState);

        BootstrapApplication.getInstance().inject(this);
    }

    @Override
    public void setContentView(int layoutResId) {
        super.setContentView(layoutResId);

        Views.inject(this);
    }

}

redpajama_set_name: RedPajamaGithub


text:
05/27: A review of On the Spot by Amy Krouse Rosenthal, Lea Redmond and Sanne Te Le (Random House)
Happy Saturday part two, guys!
Here's a review for On the Spot by the beloved Amy Krouse Rosenthal and crew.
It's a fitting tribute to the Rosenthal name, and I can't wait to share it with all of you.
-C
Hardcover, 32 pages
Expected publication: May 30th 2017 by Random House Books for Young Readers
Format read: Finished copy via publisher
Transform an ordinary story into a silly one with stickers or found objects in this Mad Libs–esque adventure! For fans of Press Here and Tap the Magic Tree.
New York Times bestselling author Amy Krouse Rosenthal (Uni the Unicorn and I Wish You More), Lea Redmond, and Sanne te Loo have created a picture book with a story that rhymes and very lovely illustrations. But, oops—they've left out some important pieces of the story…and it's up to YOU to fill them in!
Step 1: Grab any small object or pick stickers from the back of the book. Step 2: Place them on the blank spots as you read along. Step 3: Laugh at the crazy story you've just created. Step 4: Pick new items and start all over again!
Story time will take on a new dimension of play as kids use the stickers or scamper in search of the most hilarious items to occupy the blank spaces in the text. The endlessly innovative Amy Krouse Rosenthal and Lea Redmond bring us a way-outside-the-box adventure in which readers get to bend the rules and feel a bit rebellious as they tamper with the ordinary and expected.
Full review:
It was surprisingly hard reviewing On the Spot at first, knowing that one of the contributors - the beloved Amy Krouse Rosenthal - had only recently died of cancer. I actually made a little noise when I opened up the package.
But after reading the book from beginning to end, and using it to interact with several young readers, I came to see it as one of Amy's final gifts to the world; a book that reminds young readers to view the world with humor and joy that Amy herself had always imparted, in so many of her works.
The book encourages young readers to take a Mad Libs-style approach to its story; filling in sentences with objects that the readers themselves supply. Sentences like: "When I woke up this morning, what did I see? /A sweet little_______ chirping at me," are a delightful surprise, with so many potential options for making young readers laugh and smile.
The story always does a wonderful job of drawing readers from the beginning of a day to the end of a day, reminding them with every moment, that there are things to explore and ideas to observe, especially as they prepare to start the day all over again.
With illustrations that are rich and vibrant, this is a delightful book that will encourage young readers to engage with the world for years to come. It's also a fitting tribute to a well-loved author, and a reminder that her joy at the world will leave a mark forever.
About the contributors:
AMY KROUSE ROSENTHAL is the author of over twenty books for children. Her titles include Uni the Unicorn, I Wish You More, Wumbers, Plant a Kiss, Little Pea, Spoon, The Wonder Book, Cookies: Bite-Size Life Lessons, and Duck! Rabbit! A longtime contributor to NPR, she is the host and creator of Mission Amy KR, produced by Chicago Public Radio. Amy lives with her family in Chicago and online at whoisamy.com.
SANNE TE LOO can't remember wanting to become anything other than a children's book illustrator. Her first commission was a Hans Christian Andersen story published in the Netherlands. She has been writing and illustrating children's books ever since. She lives and works in the historical[GJ1] district in Utrecht, the Netherlands, with a painter and their two children. Visit her on the Web at sanneteloo.nl.
LEA REDMOND is a maker. She crafts objects, ideas, and activities. Leafcutter Designs, her creative studio in Berkeley, California, seeks to create a more playful, peaceful world by offering curious goods, surprising services, and participatory projects.


text:
Q: Cant get facebook login to be accepted by facebook I am trying to get the Facebook login button to give me the users detail while using firebase. On the emulator when I click the button it takes me to the Facebook site and I can continue but I get a red banner that says some permissions have not been approved by the user. I have followed this https://developers.facebook.com/docs/facebook-login/android to make sure I have added them all but I could have messed something up.
lateinit var callbackManager: CallbackManager

var id = ""
var firstName = ""
var middleName = ""
var lastName = ""
var name = ""
var picture = ""
var email = ""
var accessToken = ""

companion object {
    private const val RC_SIGN_IN = 120
}

private lateinit var mAuth: FirebaseAuth
private lateinit var googleSignInClient: GoogleSignInClient
var temp : String = ""

override fun onCreate(savedInstanceState: Bundle?) {
    super.onCreate(savedInstanceState)
    setContentView(R.layout.activity_sign_in)
    val callbackManager = CallbackManager.Factory.create()

    //Try signInActivity.this as context
    FacebookSdk.sdkInitialize(getApplicationContext());

    val signInBtn = findViewById<Button>(R.id.sign_in_btn)
    val buttonFacebookLogin = findViewById<LoginButton>(R.id.login_button_facebook)

// Initialize Facebook Login button
        buttonFacebookLogin.setReadPermissions("email", "public_profile")
        buttonFacebookLogin.setOnClickListener {
            LoginManager.getInstance()
                .logInWithReadPermissions(this, listOf("public_profile", "email"))
        }

    LoginManager.getInstance()
        .registerCallback(callbackManager, object : FacebookCallback<LoginResult?> {
            override fun onSuccess(loginResult: LoginResult?) {
                println("Success Login")
                getUserProfile(loginResult?.accessToken, loginResult?.accessToken?.userId)
            }

            override fun onCancel() {
                println(" Login cancelled")
            }

            override fun onError(exception: FacebookException) {
                println(" Login error")
            }
        })

`
@SuppressLint("LongLogTag")
fun getUserProfile(token: AccessToken?, userId: String?) {

    val parameters = Bundle()
    parameters.putString(
        "fields",
        "id, first_name, middle_name, last_name, name, picture, email"
    )
    GraphRequest(token,
        "/$userId/",
        parameters,
        HttpMethod.GET,
        GraphRequest.Callback { response ->
            val jsonObject = response.jsonObject

            // Facebook Access Token
            // You can see Access Token only in Debug mode.
            // You can't see it in Logcat using Log.d, Facebook did that to avoid leaking user's access token.
            if (BuildConfig.DEBUG) {
                FacebookSdk.setIsDebugEnabled(true)
                FacebookSdk.addLoggingBehavior(LoggingBehavior.INCLUDE_ACCESS_TOKENS)
            }
            accessToken = token.toString()

            // Facebook Id
            if (jsonObject != null) {
                if (jsonObject.has("id")) {
                    val facebookId = jsonObject.getString("id")
                    Log.i("Facebook Id: ", facebookId.toString())
                    id = facebookId.toString()
                } else {
                    Log.i("Facebook Id: ", "Not exists")
                    id = "Not exists"
                }
            }

            // Facebook First Name
            if (jsonObject != null) {
                if (jsonObject.has("first_name")) {
                    val facebookFirstName = jsonObject.getString("first_name")
                    Log.i("Facebook First Name: ", facebookFirstName)
                    firstName = facebookFirstName
                } else {
                    Log.i("Facebook First Name: ", "Not exists")
                    firstName = "Not exists"
                }
            }

            // Facebook Middle Name
            if (jsonObject != null) {
                if (jsonObject.has("middle_name")) {
                    val facebookMiddleName = jsonObject.getString("middle_name")
                    Log.i("Facebook Middle Name: ", facebookMiddleName)
                    middleName = facebookMiddleName
                } else {
                    Log.i("Facebook Middle Name: ", "Not exists")
                    middleName = "Not exists"
                }
            }

            // Facebook Last Name
            if (jsonObject != null) {
                if (jsonObject.has("last_name")) {
                    val facebookLastName = jsonObject.getString("last_name")
                    Log.i("Facebook Last Name: ", facebookLastName)
                    lastName = facebookLastName
                } else {
                    Log.i("Facebook Last Name: ", "Not exists")
                    lastName = "Not exists"
                }
            }

            // Facebook Name
            if (jsonObject != null) {
                if (jsonObject.has("name")) {
                    val facebookName = jsonObject.getString("name")
                    Log.i("Facebook Name: ", facebookName)
                    name = facebookName
                } else {
                    Log.i("Facebook Name: ", "Not exists")
                    name = "Not exists"
                }
            }

            // Facebook Profile Pic URL
            if (jsonObject != null) {
                if (jsonObject.has("picture")) {
                    val facebookPictureObject = jsonObject.getJSONObject("picture")
                    if (facebookPictureObject.has("data")) {
                        val facebookDataObject = facebookPictureObject.getJSONObject("data")
                        if (facebookDataObject.has("url")) {
                            val facebookProfilePicURL = facebookDataObject.getString("url")
                            Log.i("Facebook Profile Pic URL: ", facebookProfilePicURL)
                            picture = facebookProfilePicURL
                        }
                    }
                } else {
                    Log.i("Facebook Profile Pic URL: ", "Not exists")
                    picture = "Not exists"
                }
            }

            // Facebook Email
            if (jsonObject != null) {
                if (jsonObject.has("email")) {
                    val facebookEmail = jsonObject.getString("email")
                    Log.i("Facebook Email: ", facebookEmail)
                    email = facebookEmail
                } else {
                    Log.i("Facebook Email: ", "Not exists")
                    email = "Not exists"
                }
            }

            openDetailsActivity()
        }).executeAsync()
}

fun isLoggedIn(): Boolean {
    val accessToken = AccessToken.getCurrentAccessToken()
    val isLoggedIn = accessToken != null && !accessToken.isExpired
    return isLoggedIn
}

fun logOutUser() {
    LoginManager.getInstance().logOut()
}

Logs regarding Facebook
2021-11-25 20:56:08.366 9837-9837/com.example.go4lunch W/com.facebook.UserSettingsManager:

Please set a value for AutoLogAppEventsEnabled. Set the flag to TRUE if you want to collect app install, app launch and in-app purchase events automatically. To request user consent before collecting data, set the flag value to FALSE, then change to TRUE once user consent is received. Learn more: https://developers.facebook.com/docs/app-events/getting-started-app-events-android#disable-auto-events.
2021-11-25 20:56:08.366 9837-9837/com.example.go4lunch W/com.facebook.UserSettingsManager: You haven't set a value for AdvertiserIDCollectionEnabled. Set the flag to TRUE if you want to collect Advertiser ID for better advertising and analytics results. To request user consent before collecting data, set the flag value to FALSE, then change to TRUE once user consent is received. Learn more: https://developers.facebook.com/docs/app-events/getting-started-app-events-android#disable-auto-events.
2021-11-25 20:56:08.414 9837-9873/com.example.go4lunch W/GraphRequest: Starting with v13 of the SDK, a client token must be embedded in your client code before making Graph API calls. Visit https://developers.facebook.com/docs/android/getting-started#client-token to learn how to implement this change.
2021-11-25 20:56:08.419 9837-9879/com.example.go4lunch W/GraphRequest: Starting with v13 of the SDK, a client token must be embedded in your client code before making Graph API calls. Visit https://developers.facebook.com/docs/android/getting-started#client-token to learn how to implement this change.
2021-11-25 20:56:08.437 9837-9882/com.example.go4lunch W/com.facebook.internal.NativeProtocol: Apps that target Android API 30+ (Android 11+) cannot call Facebook native apps unless the package visibility needs are declared. Please follow https://developers.facebook.com/docs/android/troubleshooting/#faq_267321845055988 to make the declaration.
2021-11-25 20:56:08.452 9837-9880/com.example.go4lunch W/GraphRequest: Starting with v13 of the SDK, a client token must be embedded in your client code before making Graph API calls. Visit https://developers.facebook.com/docs/android/getting-started#client-token to learn how to implement this change.
2021-11-25 20:56:09.348 9837-9880/com.example.go4lunch W/GraphRequest: Starting with v13 of the SDK, a client token must be embedded in your client code before making Graph API calls. Visit https://developers.facebook.com/docs/android/getting-started#client-token to learn how to implement this change.
2021-11-25 20:56:15.563 9837-9837/com.example.go4lunch W/class com.facebook.login.LoginManager: You're calling logging in Facebook with an activity supports androidx activity result APIs. Please follow our document to upgrade to new APIs to avoid overriding onActivityResult().
2021-11-25 20:56:15.798 9837-9837/com.example.go4lunch W/com.facebook.internal.NativeProtocol: Apps that target Android API 30+ (Android 11+) cannot call Facebook native apps unless the package visibility needs are declared. Please follow https://developers.facebook.com/docs/android/troubleshooting/#faq_267321845055988 to make the declaration.
2021-11-25 20:56:15.798 9837-9873/com.example.go4lunch W/com.facebook.internal.NativeProtocol: Apps that target Android API 30+ (Android 11+) cannot call Facebook native apps unless the package visibility needs are declared. Please follow https://developers.facebook.com/docs/android/troubleshooting/#faq_267321845055988 to make the declaration.

redpajama_set_name: RedPajamaStackExchange


Сценарий помогает найти устройства на которых была активность пользователя и произведены попытки неудачного вторизации в AD.
This function will locate the computer that processed a failed user logon attempt which caused the user account to become locked out.
The locked out location is found by querying the PDC Emulator for locked out events (4740).
The function will display the BadPasswordTime attribute on all of the domain controllers to add in further troubleshooting.
This example will find the locked out location for Joe Davis.
This function is only compatible with an environment where the domain controller with the PDCe role to be running Windows Server 2008 SP2 and up.
The script is also dependent the ActiveDirectory PowerShell module, which requires the AD Web services to be running on at least one domain controller.


At the 2016 Mobile World Congress in Spain, HP unveiled the Elite X3 Windows 10 device featuring a Snapdragon 820 processor, close to 6-inch display with 2560×1440 resolution, 4GB of RAM, 64GB of eMMC storage, and a 16MP f/2.0 FHD rear-facing camera. The HP Elite X3 is a full-fledged Windows 10 PC that just so happens to have the ability to be used as a phone as well.
The Elite X3 is the first example of an entirely new category of device that HP along with Microsoft and Qualcomm has called the 3-in-1. While today's 2-in-1 devices can transform from tablets into notebooks, the 3-in-1 adds in the smartphone form factor with its all-day battery life and high-performance communications capabilities. When plugged into HP's app virtualization backend, the Elite X3 becomes the first device that's been consciously engineered to function as a smartphone, a notebook (via the HP Lap Dock), and a real PC thanks to app virtualization technology that allows businesses to run their Win32 apps via Windows 10 Mobile Continuum.
But the question, however, still remains. If this device is such a big deal for the company, why did HP select Windows 10 as the operating system rather than a more popular operating system like Android? According to what HP tells OnMSFT, the company selected Windows 10 over Android because Microsoft's offering isn't prone to security risks like Android is, which comes as no surprise.
The popular the operating system the more susceptible it will be to security issues. According to security firm Kaspersky, back in 2013 and 2014, one out of five Android devices were attacked by malware at least once during that period. Threats can be divided into different categories like web-based and app-based. Throughout 2012, 99% of all mobile malware detected by Kaspersky Lab was designed to target the Android platform.
With such a large operating system market share, this should come as no surprise. This fact, coupled with the open nature of Android, the ease with which apps can be created, and the wide variety of unofficial app markets are the root cause of these security risks. HP wanted to avoid all this and stick to an ecosystem that focuses on security.
Other key features of Windows 10, including the Universal Windows Platform, Continuum, legacy app virtualization, and compatibility with existing infrastructure is what attracted HP towards Microsoft's operating system. All the apps HP finds beneficial for productivity are already on Windows 10, in one form or shape — so apps are not an issue. With 400 million active devices around the world running Windows 10 (stats according to HP), it was a no-brainer to them when it came down to selecting which operating system to use on the HP Elite X3.
HP's new 3-in-1 category is promising as PCs are great for productivity but most are not portable enough, while smartphones and tablets are good for content consumption but are not powerful enough for work. HP hopes to bridge the gap and offer one device that meets everyone's needs.
Stay tuned for our in-depth hands-on review of the HP Elite X3.
Are you impressed with the HP Elite X3? Why or why not?


Sen. David Vitter speaks during a news conference on the stimulus package on Feb. 4, 2009 in Washington, D.C.
This has kind of been subtext for a while, but Sen. David Vitter has gone and made it text by writing a 10 point pro-shutdown listicle, basically arguing that since the shutdown has shut the Environmental Protection Agency down, the shutdown is a good thing all on its own terms.
The issue here, basically, is that Louisiana is a major oil and gas state, and oil and gas producers naturally would prefer it if there were no environmental regulations. In terms of Vitter's listicle, though, I think conservative politicians are supposed to complain about environmentalist "overreach" and such without actually endorsing the view that there should be no environmental regulations whatsoever.


text:
package readline

import (
	"syscall"
	"unsafe"
)

func getTermios(fd int) (*Termios, error) {
	termios := new(Termios)
	_, _, err := syscall.Syscall6(syscall.SYS_IOCTL, uintptr(fd), syscall.TIOCGETA, uintptr(unsafe.Pointer(termios)), 0, 0, 0)
	if err != 0 {
		return nil, err
	}
	return termios, nil
}

func setTermios(fd int, termios *Termios) error {
	_, _, err := syscall.Syscall6(syscall.SYS_IOCTL, uintptr(fd), syscall.TIOCSETA, uintptr(unsafe.Pointer(termios)), 0, 0, 0)
	if err != 0 {
		return err
	}
	return nil
}


For the last few years we have been told that our World War II veterans are passing away at the rate of 1,000 per day. This time of the year is the anniversary of the Battle of the Bulge. It started in December of 1944. Our poor boys were literally freezing to death. Their feet were turning black. They slept in holes dug out in the snow.
I recently had the privilege to talk to one of our G.I.'s from "the Bulge." I enjoyed thanking him for what he did for our freedom. He told me that they were not allowed to wear their winter coats or they would look like the German soldiers and be shot by other Americans.
Hundreds of our troops held out at Bastone and would not surrender to the Germans. When asked to surrender, our officers sent the following Laconic message: "To the German commander, NUTS! From the American commander."
Under no circumstances were our men going to give up. They held out for weeks until relief came. What an inspiration these American heroes should be to us, because they fought it out for freedom at any cost.
May we continue to tell future generations about those who fought to preserve our American freedoms.


The now demolished Hotel Australia in Collins Street, Melbourne showing the steps where radio personalty, Don Baker led the donkey for a drink of beer in the 1940s.
A 1941 self portrait of Don Baker.
Don Baker*, radio comedian, who led a black donkey down Collins st and up the steps of the Hotel Australia on October 21, was fined £3 by Mr Mohr, SM, in the District Court yesterday.
At the top of the hotel steps the donkey had been given a glass of beer.
"I hope it could walk straight on the way back," said Mr Mohr yesterday.
Baker assured him that it did.
* Don Baker was a Canadian born entertainer who came to Australia in 1939 and made quite a name for himself on radio in Melbourne during the 1940s.
Bob Dyer, Diana Goller and Don Baker rehearsing in an ABC radio programme in the 1940s.