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Take a flavor trip to the tropics with our Tropical Secret DDH NEIPA! Double dry-hopped (DDH) with Vic Secret for maximum fruity hop flavor, we won't tell anyone how many you've enjoyed.
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Home/The Americas/All/What Were the Federalist Papers?
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What Were the Federalist Papers?
The Federalist papers are a collection of 85 articles written by the trio John Jay, James Madison and Alexander Hamilton, all published under the pen name "Publius" in 1788.
The first 77 essays of the Federalist papers were published serially in three different New York newspapers: independent journal, the New York Packet and the daily advertisers from October 1787 to April of the following year.
After the first 77 essays were released in 1787-1788, 8 more were later published. The entire collection came to be tagged "The Federalists". The name "Federalist" was used to describe all 85 essays at the time they became really popular and was only changed to "the Federalist Papers" in the wake of the 20th century.
The federalist papers came into existence only as a means of explaining and defending the reasons why the newly proposed constitution should be rectified.
In 1787, The federal convention sent the proposed constitution to the confederation congress which in turn sent it to the states for ratification.
The newly developed constitution was met with much contempt from the public as well as top government officials with large numbers of anonymous articles appearing in the New York press criticizing the proposal.
In response, Alexander Hamilton took it upon himself to launch a campaign with the sole aim of explaining the features and benefits of the newly proposed constitution to the public.
He began his campaign with an article which was published across major newspapers in New York. The first article came to be known as "Federalist 1" (first essay of the federalist papers). In the Federalist 1, Hamilton promised the readers that he'll provide answers to all objections the articles as well as the proposed constitution may generate.
In order to provide better information and quicker responses to his audiences, Hamilton searched for more collaboration for his project and recruited john jay, who wrote the next four Federalist articles (Federalist paper 2 to 5) before falling ill.
Hamilton's search for more collaborations would continue due to the ill health of John Jay. He was turned down by Governer Morris and would later reject William Duer's offer after going through three articles written by him.
James Madison was later recruited by Alexander Hamilton.
John Jay could not offer much due to his poor health condition and in most cases act as an assistant to Hamilton and Madison who became the major writers of the Federalist Papers. After the initial four articles written by John Jay. He added just one more to the series leaving Hamilton and Madison as the leading contributors. Alexander Hamilton chose the pseudonym "Publius" for the trio.
At the time the articles were being published across major newspapers in the city, the trio decided to hide their real identity by publishing all articles under the pen name "Publius" for fear of been prosecuted.
Their identities however would not be hidden for long as astute observers and readers soon deduced the real names of the writers behind the pen name. It was however impossible for the public to pin the name of any of the authors to a particular Federalist paper.
After the death of Hamilton in 1804, confusions arose pertaining to the ownership of the articles with a list claiming Hamilton wrote two third of the Federalist papers while others believed James Madison wrote more.
After a test analysis was carried out, the articles were correctly attributed to their authors: Alexander Hamilton wrote 51 articles, James Madison 29 articles while john jay contributed the remaining five.
It took all three men a period of 10 months to come up with the complete 85 articles making the collection called "The Federalist Papers".
HIGHLIGHTS OF THE FEDERALIST PAPERS
The intention behind the publishing of the federalist papers was to promote the ratification of the proposed constitution through articles which are meant to enlighten the public about the issue. Taking up the job of promoting the proposed constitution does not in any way mean that "the publius" totally agreed with all that was contained in it.
Federalist Paper No. 84 which happens to be the the last but one article in the series strongly held opposition to the bill of rights inclusion to the proposed constitution. The constitution when originally written didn't enlist the rights of citizens. The inclusion of the bill of rights many feared will pose a limit to the right citizens enjoy.
In Federalist Paper No. 51, James Madison highlighted the division of power between different arms of the government and the essence of checks and balances between various arms of government.
The Federalist No. 10 is the tenth essay in the series and also the most important. James Madison begins by supporting the ratification of the proposed constitution, stating that it establishes a government ready at all times to protect its citizens against violence and damaged caused by factions and enemies of the state. Accord to Madison, a faction is any group of people interested in promoting their selfish interest only without minding the implications that may arise from their actions.
america federalist founding hamilton jay press
Is a No-Deal Brexit Still Possible?
The Dutch Legacy of the Caribbean – Suriname

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Expression of the NEK family in normal and cancer tissue: an immunohistochemical study
Talita Diniz Melo-Hanchuk1 na1,
Mariana Bonjiorno Martins1 na1,
Lucas Leite Cunha2,
Fernando Augusto Soares3,
Laura Sterian Ward2,
José Vassallo4 &
Jörg Kobarg ORCID: orcid.org/0000-0002-9419-01451,5
The NEK serine/threonine protein kinases are involved in cell cycle checkpoints, DNA damage repair, and apoptosis. Alterations in these pathways are frequently associated with cell malignant cellular transformations. Thyroid cancer is the most common malignant tumour in the endocrine system. Despite good treatment methods, the number of cases has increased significantly in recent years. Here, we studied the expression of NEK1, NEK2, NEK3, and NEK5 in different types of normal and malignant tissues, using tissue microarray analysis, and identified NEKs as potential markers in thyroid malignancy.
The studied cases comprised multiple cancer tissue microarrays, including breast, colon, esophagus, kidney, lung, pancreas, prostate, stomach, thyroid and uterine cervix, as well as 281 patients who underwent thyroid resection for thyroid cancer or thyroid nodules. The expression of NEK1, NEK2, NEK3, and NEK5 was analyzed by immunohistochemistry. The expression pattern was evaluated in terms of intensity by two methods, semiquantitative and quantitative, and was compared between normal and cancer tissue.
We analysed the expression of each member of the NEK family in a tissue-dependent manner. Compared to normal tissue, most of the evaluated proteins showed lower expression in lung tumour. However, in the thyroid, the expression was higher in malignant tissue, especially for NEK 1, NEK3 and NEK5. Concerning characteristics of the thyroid tumour, such as aggressiveness, NEK1 expression was higher in tumours with multifocality and in patients with lymph node metastasis. NEK3 expression was stronger in patients with stage II, that involved metastasis. NEK5, on the other hand, showed high expression in patients with invasion and metastasis and in patients with tumour size > 4 cm. Furthermore, this work, demonstrated for the first time a high specificity and sensitivity of over-expression of NEK1 in classical and follicular variants of papillary thyroid cancer and NEK3 in tall-cell papillary thyroid cancer.
Taken together, the NEK protein kinases emerge as important proteins in thyroid cancer development and may help to identify malignancy and aggressiveness features during diagnosis.
This study was retrospectively registered. www.accamargo.org.br/cientistas-pesquisadores/comite-de-etica-em-pequisa-cep.
Protein kinases (PKs) mediate most of signal transduction events in eukaryotic cells, either by altering substrate activity or location, interacting with other proteins or by controlling metabolism, transcription, cell cycle progression, cytoskeletal rearrangement, cellular movement, apoptosis and differentiation [1]. PKs regulate the cell cycle, especially at the checkpoint process, are considered interesting therapeutic targets in cancer [2]. Failures at these control points may lead to the development of tumour cells that show altered division rates and may present accumulation of DNA errors (for review [3]). In a large-scale screening of in situ hybridization on tissue microarrays, around 20% of the serine/threonine kinases analysed exhibited altered levels of transcripts in tumours [4].
Of those PKs functionally involved in regulating the cell cycle, and its checkpoints, the members of the 11 NIMA-related kinases (NEK-family), are possibly among the least studied and functionally enigmatic kinases. In this NEK family, 11 genes are encoding different serine/threonine kinases, which catalytic domains have 40–45% amino acid sequence identity with NIMA's catalytic domain [5]. They have been localised to the cilia, centrosomes, nucleus, cytoplasm, and mitochondria [6].
NEK1, was reported to display, an in vitro,dual serine-threonine and tyrosine kinase activity [7]. Genetic loss-of-function mutations in the NEK1 gene, cause expression of a truncated, functionally inactive, protein kinase. When this mutation is germline derived from birth on, it causes the development, later in life, of the so-called "Polycystic Kidney Disease". NEK1 has been further associated with bladder [8], kidney [9] and breast [10]cancers.
Similarly, NEK3 [11] and NEK2 [12] were found to be over-expressed, in human breast cancer. Human NEK3 appears to play an important role in prolactin receptor signaling, specifically in a pathway that contributes to the progression of breast cancer and increases the motility of breast cancer cells in vitro [11]. The expression of the full-length NEK3 protein is higher in prostate cancer samples compared to normal controls, but, to the contrary, normal samples have a higher expression of the shorter protein isoform [13].
RNA-seq. Transcriptome analyses of prostate cancer samples, benign, prostatic hyperplasia, and normal tissue, revealed, NEK5 and NEK2 are over-expressed in malignant tissue [14]. NEK2, is also related to progression and poor prognosis in prostate cancer [15, 16].
With a rapidly increasing incidence around the world, thyroid cancer (TC) represent the most common endocrine malignancy. From the 53.990 new diagnoses reported in the United States in 2018 and approximately 75% were associated with women [17, 18]. A rise in incidence numbers over the years is partly explained by the improvement in diagnosis. The majority of the thyroid tumours are classified as well-differentiated papillary (PC) and follicular carcinoma (FC) subtypes (85%), but anaplastic thyroid (AC) and medullary thyroid carcinomas (MC) are also classified.
The development, progression, invasion, and metastasis of TC is related to multiple signaling pathways, such as: JAK/STAT, Wnt-β-catenin, NF-κB, TSHR and PI3K/AKT [19]. TC has a relatively good cure rate, especially when detected at the early stages. However, approximately 20% of the patients tend to not respond to therapy. Therefore, improved diagnostics, alternative treatments and novel target proteins for these non-responsive patients are highly desired.
The objective of the present study was to understand the involvement of four members of the NEK family (NEK1, NEK2, NEK3 and NEK5) in different types of cancers by analyzing differential expression profiles through tissues microarray (TMA) assays. The present study also aimed to investigate a possible role for NEK1, NEK3, and NEK5 in thyroid malignancy, and analyze their potential as diagnostic and prognostic markers.
Cancer specimens and thyroid cancer patients
The first studied cases were multiple cancer tissue microarrays (TMAs) with 10 common types of cancer (breast, colon, esophagus, kidney, lung, pancreas, prostate, stomach, thyroid and uterine cervix) in quadruplicates of each with matched normal tissue and duplicated cores per case (except single cores for the prostate cases). These tissue microarrays were purchased from US Biomax Inc. (MC802 from US Biomax Inc., Rockville, MD, USA).
Also, we studied 281 patients who underwent thyroid resection for thyroid nodules of different histologic types; thyroid carcinoma was diagnosed in 193 patients: 168 were papillary thyroid carcinomas (PTC) and 25 follicular thyroid carcinomas (FTC). The most frequent histotype among papillary carcinomas was the classic variant (CPTC) (107 cases), followed by the follicular variant (FVPTC) (48 cases) and the tall-cell (TCPTC) variant was identified in 13 cases. We also obtained benign tissue from patients, including 31 follicular adenomas (FA) and 42 goiters (G), and 15 normal thyroid tissues obtained from the contralateral lobe of FA (Normal Tissue). The American Joint Committee on Cancer (AJCC) TNM system was used to detect aggressiveness at diagnosis for differentiated thyroid carcinomas. Patients were managed according to Latin American Thyroid Society (LATS) and Ameican Thyroid Association (ATA) guidelines and followed for a period of 12 to 175 months (median = 35; mean = 41.1; SD [standard deviation] = 26 months). All the clinical, surgical, and pathological reports, also as follow-up data, were recorded.
For diagnostic confirmation, two experienced pathologists (JV and FAS) reviewed carefully and independently all tumours. Cases presenting conflicting results or areas of poor differentiation were excluded. Paraffin blocks of formalin-fixed tissues were collected and, in each case, the most representative area of the tumour, normal surrounding tissue, tumour areas of invasiveness, and metastatic tissue were selected and micro-dissected, whenever available. The Research Ethics Committees of the AC Camargo Cancer Center, São Paulo, Brazil (1259/09-C), approved this study protocol.
Immunohistochemical detection
Commercial TMA slides of multiple cancer types were purchased from US Biomax Inc. (Rockville, Maryland, USA). Thyroid TMA was constructed (in triplicates) using the semi-automated TMArrayer (Beecher Instruments®, Silver Springs, MD, USA). The thyroid tissue samples investigated, were obtained and maintained in the tissue bank of the A. C. Camargo Hospital.
Immunohistochemistry was performed manually, as follows: Five μm TMA sections were placed on electrically charged slides, de-paraffinised, and rehydrated in decreasing concentrations of alcohol. The endogenous peroxide activity was quenched for 15 min. With H2O2 and the tissue sections were subjected to heat-induced antigen retrieval in a steamer (90 °C for 30 min), using 10% citrate buffer (10 mM, pH 6.0). Tissues sections were then incubated overnight at 6 °C, with appropriate antibodies. The specification of the antibodies used, the code/clone, the company, the titration, and the antigen retrieval procedure are presented in Table 1. The advanced biotin-free polymer detection system (DAKO, Carpenteria, CA, USA) was used. The chromogen DAB (3.3-diaminobenzidine-tetrahydrochloride; Sigma, St Louis, MA, USA) was applied at room temperature for 5 min. Sections were counterstained with hematoxylin. Positive and negative controls were run in the same batch of reaction, to ensure that the immunohistochemistry reactions are evenly developed to assure their comparability (Additional file 1: Figure. S1).
Table 1 Antibodies, code, company, concentration, and antigen retrieval for the different member of the NEK family
Immunohistochemistry evaluation
Slides were evaluated by at least two of the authors (TDMH and MBM) and then submitted to other two independent experienced pathologists (JV and FAS), both blinded to tumour features, for the final score. The analysis was performed in two different ways: a) by visual (semiquantitative) and b) by the Aperio's Image Scope Viewer software (quantitative). For semiquantitative analysis, an individual evaluation of each marker was performed for each spot tissue, by estimating the number of positive cells per TMA spot.
Semiquantiative evaluation
For semiquantitative evaluation,the multiple tissues were manually scored for each marker and each spot tissue, through the percentage of negative, weak, medium and strong, of total cells, times 0, 1, 2 and 3. The total score for each spot was obtained through the sum of negative + 0, weak + 1, medium + 2 and strong + 3.
For the thyroid cancer patients, the semiquantitative evaluation consisted of estimating the percentage of positive tumour cells and the staining intensity for cytoplasm. For the nuclei, only the percentage of positive cells was measured. The percentage of positive cells was graded like: 0 = negative cell; 1 = up to 25% positive cells; 2 = 25 to 50%; 3 = 50 to 75% and 4 = more than 75% positive cells. Intensity was graded like: 0 = negative; 1 = faint; 2 = moderate and 3 = strong staining.
A final score was calculated adding both percentages of positive cells and intensity of staining, which ranged from 0 to 7.Cases scored from 0 to 2 were grouped as negative (low/decreased expression) and cases scored from 3 to 7 were considered positive (high/increased expression).
The analyses of cytoplasmic and nuclear protein expression were performed only for NEK1 and NEK5, because these are proteins with activity in both of these cellular compartments.
NEK3, on the other hand, is located only in the cytoplasm, as demonstrated in Additional file 2: Figure. S2, and documented in the literature.
Quantitative evaluation
In addition to semiquantitative evaluation, we further analyzed the immunohistochemical expression using the Aperio Scan Scope slide scanner (Vista, CA, USA). The obtained digital slides were examined using the Aperio's Image Scope Viewer software, a numerical value proportional to the intensity and extension of brown staining was attributed by the computer analysis, using the formula: Score = (0*% Negative) + (1*% weak positive) + (2*% moderate positive) + (3*% strong positive). The final value of this quantitative analysis was expressed as the mean of triplicates and quadruplicates.
The statistical analysis was carried out using the SAS System for Windows (Statistical Analysis System, version 9.1.3, Service Pack 3 Institute Inc., 2002–2003, Cary, NC, USA). Recurrence-free survival was calculated using Kaplan–Meier survival curves with a log-rank comparison. The nonparametric analysis was performed using either the chi-square or Fisher's exact test, as indicated. The Mann– Whitney tests were used to compare continuous or arranged measures between two groups; the Kruskal–Wallis test was used to compare three or more groups. The accuracy of NEK1, NEK3 and NEK5 expression to predict malignancy was evaluated using a receiver operating curve (ROC) analysis based on predicted probabilities from logistic regression models. Data analysis was performed with GraphPad Prism (GraphPad Software). All tests were conducted at the significance level p ≤ 0.05.
NEK expression in human normal and malignant tissues
There are around 520 human protein kinases described and just a small part of them, including the NEK family, have been subjected to studies by the pharmaceutical industry and research institutions [20]. Members of the NEK family seem attractive drug targets because they are associated with target pathway related to cancer development, such as DNA Damage Checkpoint and microtubule functions [21].
To study more broadly the NEK expression profile in cancer, the tissue microarray (TMA) strategy was used in this work. To evaluate the expression profile of NEK1, NEK2, NEK3, and NEK5 in different types of cancer an immunohistochemistry assay was conducted in 10 common types of cancer (esophagus, stomach, colon, lung, thyroid, breast, uterine cervix, pancreas, prostate and kidney) with 4 cases of each and their matched normal tissue. The intensity of brown staining corresponding to the level of NEK expression was measured by semiquantitative (visual; Additional file 3: Table S1) and quantitative method (software ScanScope; Additional file 4: Table S2).
The expression profile of the evaluated NEKs varied considerably between the tissues. For NEK1 we found an increase of expression in normal stomach (p < 0.001 for semiquantiative analysis), lung (p < 0.01-semiq.; p < 0.001-quant.analysis), pancreas (p < 0.05 for semiq.), and colon (p < 0.01, semiq.), when compared to malignant tissue. On the other hand, in the thyroid, the expression of NEK1 was increased in papillary and medullary carcinoma (p < 0.001, quantitative analysis) (Fig. 1 a and e).
Expression of NEK1, NEK2, NEK3, and NEK5 in normal and malignant tissues. The expression of a and e) NEK1; b and f) NEK2; c and g) NEK3; d and h) NEK5 was evaluated by immunohistochemistry in normal and malignant tissues of the esophagus, stomach, colon, lung, thyroid, breast, uterine cervix, pancreas, prostate, and kidney. The expression level was calculated through visual (semiquantitative a, b, c, d) and ScanScope score (quantitative e, f, g, h).Two-Way ANOVA and the Bonferroni post-tests correction were employed for statistical analyses: * = P < 0.05; ** = P < 0.01; *** = P < 0.001
Our analysis of NEK2 expression in human tumours showed that in kidney and thyroid the expression of NEK2 is higher in tumour tissues. However, this protein is less expressed in tumour tissues, for the lung (p < 0.001 for quantitative) and breast (p < 0.05 semiq.; p < 0.05 quant.),(Fig. 1 b and f).
NEK3 is increased in normal colon (p < 0.05, for semiq.), lung (p < 0.01, semiq.; p < 0.05 quant.), breast (p < 0.05 for quant. analysis), and prostate (p < 0.001 for semiq. analysis). However, the thyroid tumour tissue showed significantly higher levels of NEK3 expression when compared to normal tissues (p < 0.001-semiq.; p < 0.05-quant.), (Fig. 1 c and g).
From the analysis of NEK5, it was possible to observe that the expression profile did not change between normal and tumour tissues, except that the thyroid (p < 0.05 –semiq.; p < 0.001-quant.) and kidney (p < 0.001 for semiq.) had higher levels of expression in the tumour tissues than in the normal cells (Fig. 1 d and h).
Both visual and automatic TMA analysis showed that the expression of NEK1, NEK2, and NEK3 was lost during lung malignant transformation. As can be observed in Fig. 2, the difference between normal and malignant lung tissue is more pronounced with the NEK2 expression.
Immunohistochemistry tissue microarray (TMA) of specimens of human normal and malignant lung and thyroid tissue. The immunostaining of the NEK proteins by using the anti-NEK1 (8 μg/mL), NEK2 (8 μg/mL), NEK3 (8 μg/mL) and NEK5 (8 μg/mL) antibodies. The brownish-red region indicates the immunoreactivity of the advanced biotin-free polymer (DAKO, Carpenteria, CA, USA) with the indicated human NEK protein expressed in the tissue of the lung and thyroid, after being labeled with a chromogenic substrate (DAB - Sigma, St Louis, MA, USA)
However, in thyroid tissue, the expression of all four: NEK1, NEK2, NEK3 and NEK5 was higher in malignant tissues (Fig. 2). In this case the quantitative analysis showed statistically significant differences for all four NEKs, and the semiquantitative analysis for NEK3 and NEK5.
The TMA results associated with the data from literature about NEKs, suggest, that their function and expression can vary in a tissue-dependent manner. Thus, the expression of the family as a whole needs to be understood in each one of the tissues before thinking about therapeutic strategies.
Thyroid Cancer patients
In the broad spectrum TMA analysis (semiquantitative and quantitative), we observed an increased expression of NEK1, NEK2, NEK3, and NEK5 in papillary and medullary thyroid carcinoma (Fig. 2 and Additional file 3: Table S1 and Additional file 4: Table S2). However, since this analysis was made with a limited number of patient samples, we expanded the number of cases submitted to TMA analysis. The immunohistochemistry was conducted in samples from 281 patients who underwent thyroid resection (nodules). The expression of NEK1, NEK3, and NEK5 was evaluated by the semiquantitative and quantitative score in the TMA slides. According to semiquantitative analysis, the cytoplasmic expression of NEK1 may differentiate malignant from benign thyroid tissues (p < 0.0001) with 94% sensitivity, 47% specificity, 81% positive predictive value (PPV), 74% negative predictive value (NPV). By the quantitative score, NEK1 expression distinguished malignant from benign lesions with 61% sensitivity, 64% specificity, PPV of 79%, NPV of 43%, and accuracy of 62% (mean = 172.97 ± 17.68 vs 164.69 ± 15.86, respectively; p = 0.0006) (Table 2).
Table 2 NEK1, NEK3, and NEK5 expression levels according to semiquantitative and quantitative IHC analysis in benign and malignant thyroid nodules and nucleus and cytoplasm
By the quantitative analysis of NEK3 expression it was possible to differentiate benign from malignant thyroid tissues, with 78% sensitivity, specificity of 80%, PPV of 91%, NPV of 60%, and accuracy of 79% (mean = 188.36 ± 17.11 vs 165.90 ± 14.29, respectively; p < 0.0001). This difference did not appear in the semiquantitative analysis (Table 2).
Malignant tissue may also be differentiated from benign thyroid tissues by using the NEK5 nuclear expression (p = 0.0144), with 26% sensitivity, 50% specificity, 58% PPV, 20% NPV (Table 2). The quantitative analysis showed similar results concerning the differential diagnosis of thyroid lesions for NEKs, wherein the vast majority was higher expressed more in malignant than in benign lesions (Fig. 3 and Table 2).
Immunohistochemistry quantitative analyses showing different staining between benign and malignant groups. (A) NEK1 immunohistochemical expression in benign and malignant subtypes of thyroid tissues. (B) NEK3 immunohistochemical expression in benign and malignant subtypes of thyroid tissues. (C) NEK5 immunohistochemical expression in benign and malignant subtypes of thyroid tissues. Data are expressed as mean +/− SEM (standard error of mean). CPTC = classic variant of papillary thyroid carcinoma (107 cases); FVPTC = follicular variant of papillary thyroid carcinomas (48 cases); TCPTC = tall-cell of papillary thyroid carcinoma (13 cases); FC = follicular carcinoma (n = 25); NT = normal tissue (n = 15); G = goiter (n = 42); FA = follicular adenoma (n = 31)
Aiming to look for NEK1 and NEK3 expressions values to be able to predict malignancy, we further performed a ROC (Receiver Operating Characteristic Curve) analysis based on predicted probabilities from logistic regression models. Using a cut-off of 168.72 for NEK1, we were able to identify malignant nodules with 61% sensitivity, 64% specificity, 79% predictive positive value, 43% predictive negative value, and 62% accuracy (Fig. 4a). The NEK3 ROC curve presented a cut-off point of 176.28 with 78% sensitivity, 80% specificity, 91% predictive positive value, 60% predictive negative value, and 79% accuracy (Fig. 4b).
Receiver operating characteristic curve (ROC).a) NEK1 and b) NEK3 protein expression of patients with DTC versus benign nodules
The expression of NEKs may be distinct in the thyroid tumour profile
Concerning characteristics as aggressiveness, invasion, tumour size, and multifocality, the quantitative analysis showed that NEK1 expression was higher in tumours in which there was multifocality (175.54 ± 18.82) than in cases without multifocality (170.32 ± 17.45 - p = 0.0233); and was more expressed in patients with lymph node metastasis (p = 0.0239) (Table 3).
Table 3 Relationship between clinical and pathological features of benign and malignant neoplasms of thyroid expressing NEK1, NEK3, and NEK5.* Analysis for Aperio Scan Scope slide scanner
Considering the quantitative NEK3 expression it was possible to observe that its expression is stronger in patients with stage II (202.86 ± 14.27) when compared with stage I-TMN (186.34 ± 16.71 - p = 0.0023) and in patients with metastasis at evolution (p < 0.0001) (Table 3).
NEK5 quantitative analysis on the other hand showed high expression in patients with invasion (p = 0.0424) and metastasis (p = 0.0108); also NEK5 was more expressed in patients with larger tumours (tumour size > 4 cm; 195.24 ± 15.01) when compared with < 2 cm (180.88 ± 17.56 - p = 0.0053) and with 2-4 cm (174.80 ± 15.51 - p = 0.0014) (Table 3). Parameters such as age, sex and capsule did not present statistical value for the expression of analyzed NEKs.
The Kaplan-Meier analysis demonstrated no correlation between patient's disease-free interval with NEK1, 3, and 5. Patients with differentiated thyroid cancer were predominantly female (73%) with a mean age at diagnosis of 45.63 ± 15.34 years (range: 15–88 years), as expected, however, no correlation was obtained between NEKs and gender, age or capsulation. These analyses were performed with the quantitative expressions.
Previous studies have demonstrated that NEKs are related to cancer. Many members are related to different aspects of the Hallmarks of Cancer [22]. For example, NEKs 1, 2, 5, 6, 7, 9 and 11 are related to resistance to cell death [23,24,25,26,27,28,29,30] and NEKs 1, 2, 4, 6, 8, 10 and 11 are related to genome instability and mutation [31,32,33,34,35,36,37]. Different groups have studied each member of this protein family separately and have observed that the expression of many of them is altered in cancers tissues. The expression of NEK2, NEK6, and NEK11 were related to colorectal cancer [30, 38,39,40], NEK2, NEK3, NEK5, NEK6, and NEK8 to breast cancer [11, 41,42,43,44,45], and NEK2 and NEK6 to prostate cancer [16, 46].
Genome wide DNA sequencing studies of cancer samples, identified mutations in the coding region of the protein for several members of the NEKs [31, 36, 37, 47, 48], suggesting that such mutations may provide selective advantages for survival and growth of cancer cells. There are few studies with the protein expression of several NEKs and different types of cancer. Based on that, this study focused on the TMA analysis of multiple cancers and normal tissues. Significant increases in the protein expression levels of NEK1, NEK2, NEK3 and NEK5, were found in colon and lung in the normal vs. cancer tissues. These results suggest that the role of NEKs are tissue-dependent.
NEK5 is the least studied member of the family, but the reduced information may not reflect its importance, because NEK5 has been related to many hallmarks of cancer, including the context of cell death [29, 49]. No information is available about the protein levels of NEK5 in cancer and normal cells. Based on that, the expression of NEK5 was found to be higher in normal ciliated tissues such as colon, lung, and kidney. In contrast, in thyroid and kidney carcinoma the level of NEK5 was higher than in normal tissues.
Furthermore, other NEKs showed high levels of expression in thyroid and kidney cancers (Figs. 1 to 3). Loss of function mutations in NEK1 are causal in the case of the murine polycystic kidney disease model lines KAT and KAT2J [34] and one of the key features of the polycystic kidney diseases is aberrant cell proliferation. In contrast the defects in the NEK1 expression can also cause excessive apoptosis [50]. Chromosomal abnormalities in the NEK1 locus were found in Wilms tumour, the most common cancer of the kidney in infants and children [9].
The over-expression of NEK2 was observed in 4 of the 6 highly malignant papillary renal cell carcinomas with chromosome 1q duplication [51]. There may be a relation between the kidneys and the thyroid, since the thyroid hormones can affect renal development and physiology by increasing the renal blood flow and glomerular filtration rate [52]. Due to genetic predisposition and/or treatment, patients with thyroid cancer have an increased predisposition to develop renal cell carcinoma [53]. Similarly, renal carcinoma can metastasize to the thyroid and vice versa [52].
Other authors previously explored the role of NEKs in the kidney, but until now, there are no reports in the literature of the involvement of the NEKs with TC. Once NEK1, NEK2, NEK3, and NEK5, all showed a higher level of expression in thyroid tumour tissue it was decided to expand the number of thyroid cases submitted to TMA analysis. TC is the most common endocrine malignancy and its incidence and mortality rates differ based on the histological subtypes [54]. During the progression of Differentiated Thyroid Cancer (DTC), the most frequent and relevant molecular alterations comprise rearrangements of tyrosine kinase receptor genes, such as RET/ PTC and NTRK1 (neurotrophic receptor tyrosine kinase 1), or protein-activating point mutations affect the cellular responses to signals of growth and differentiation signaling pathways, including: RAS, BRAF, PI3K, and oncogenic fusion protein PAX8-PPAR [55, 56].
In this work, it was demonstrated that NEK1 and NEK3 have different expression levels when comparing malignant and benign thyroid tissue. NEK1 was overexpressed in CPTC and FVPTC and NEK3 in TCPTC followed the FC. We also observed that NEKs 1, 3 and 5 expression levels were related to aggressiveness characteristics such as multifocality, invasion, metastasis, TNM and tumour size of patients with thyroid cancer. Previously, Zhu and colleagues [57] demonstrated that NEK1 is upregulated in glioma and correlated with the proliferation marker (Ki-67), tumour grade and patients' poor survival [57]. In a screen for potential anticancer drugs in PTC, the NEKs 1, 2 and 11 were pointed as candidates target [19].
In the present work, we demonstrate that the expression of NEK1 might be used as a predictive factor for lymph node metastasis in patients with DTC (Differentiated thyroid cancer). In a PTC (Papillary thyroid carcinoma) lymph node metastasis mouse model, tissue microarray data showed that simultaneous over-expression of protein kinase Aurora-A and CFL-1 (a regulator of actin polymerization) correlated with lymph node metastasis in thyroid cancer tissue [58].
The follicular pattern is one of the major obstacles to differentiate the diagnosis of thyroid lesions, including follicular adenoma (AF), follicular carcinoma (CF) and follicular variant of papillary thyroid carcinoma (FVPTC) [59]. Especially in the discrimination of minimally invasive follicular carcinoma of follicular adenoma and correct diagnosis of follicular carcinoma [60, 61]. Efforts are directed to search for novel immunohistochemical markers for the diagnosis and prognosis of thyroid lesions, especially those of follicular patterns. Promissing candidates are: CD56, galectin-3 (Gal-3), CK19 and mesectorial Hector Bat-tifora − 1 (HBME-1), but so far none of these have been entirely satisfactory [62, 63].
Lung carcinomas are classified into non-small cell carcinomas (CNPCs) and small cell carcinomas (NSCLC) [64] with CNPCs being the most common (75–80%) [65]. However, because of markedly different prognostic and treatment implications among different lung tumours, a better molecular characterization is required, especially for the most common NSCLC types and lung adenocarcinoma.
In summary, these data suggest that NEK expression levels can be explored as important biomarkers of cancer prognoses and probably as new molecular targets in cancer therapy. In this work, we demonstrated that NEK expression and functions are tissue-dependent, and that their expression level are altered when comparing normal and cancer cells.
The TMA results, which encompassed different histological types of cancer studied, suggest that the expression and function of NEKs are tissue-dependent. Regarding mainly the expression of NEK1 and NEK3 in DTC, our results indicate that these NEKs may have an important role in thyroid malignancies, allowing to identify malignancy and aggressiveness features of DTC cases.
The data here presented are summarized in Methods section. The complete dataset can be retrieved from the authors upon formal request of interested readers.
AC:
Snaplastic thyroid cancer
CPTC:
Classic variant of papillary thyroid carcinomas
DTC:
Differentiated Thyroid Cancer
FA:
Follicular adenomas
Follicular carcinoma of the thyroid
FTC:
Follicular thyroid carcinomas
FVPTC:
Follicular variant of papillary thyroid carcinomas
Goiters
IHC:
Medullary thyroid carcinomas
NEKs:
NIMA-related kinases
Negative predictive value
Well-differentiated papillary thyroid tumours
PK:
PPV:
Positive predictive value
PTC:
Papillary thyroid carcinomas
Receiver operating curve
TC:
TCPTC:
Tall-cell of papillary thyroid carcinomas
TMA:
Tissues microarray
TNM:
System of Classification of Malignant Tumours
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The authors gratefully acknowledge Dr. Sílvio Roberto Consonni contribution and his outstanding advice in immunohistochemistry protocols. We are very thankful the Laboratório de Investigação Patológica of Center for Investigation in Pediatrics of Unicamp (Brazil), especially Dr. Paulo Latuf Filho and Carolina Bondarik for the availability of the immunohistochemistry assays. We also like to thank our long time collaborator Prof. Dr. Guido Lenz (UFRGS, Porto Alegre, Brasil) for providing critical reagents.
The Laboratory of Mechanisms of Signaling which is responsible for creating resources for this work has received funding from Fundação de Amparo à Pesquisa do Estado São Paulo (FAPESP; São Paulo, Brazil) through Grant Temático 2017/03489–1, Coordenação de Aperfeiçoamento do Pessoal de Ensino Superior (CAPES, Funding code 001) and Conselho Nacional de Pesquisa e Desenvolvimento (CNPq) (Brasília, DF, Brazil) to JK. TDMH and MBM were supported by the FAPESP's fellowships 2015/06458–4 and 2016/02040–8 respectively. The funding agencies did not influence on the design of the study and collection, analysis, nor had they any influence on the decision to submit the manuscript for publication.
Talita Diniz Melo-Hanchuk and Mariana Bonjiorno Martins contributed equally to this work.
Departamento de Bioquímica e de Biologia Tecidual, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil
Talita Diniz Melo-Hanchuk, Mariana Bonjiorno Martins & Jörg Kobarg
Laboratório de Genética Molecular do Câncer, Faculdade de Ciências Médicas Universidade Estadual de Campinas, Campinas, São Paulo, Brazil
Lucas Leite Cunha & Laura Sterian Ward
Departamento de Patologia, A.C.Camargo Cancer Center, São Paulo, São Paulo, Brazil
Fernando Augusto Soares
Departamento de Anatomia Patológica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil
José Vassallo
Faculdade de Ciências Farmacêuticas-UNICAMP, Universidade Estadual de Campinas, Campinas, Inst. de Biologia, Dep. Bioquímica e Biologia Tecidual, Rua Monteiro Lobato 255, CEP 13083-862, Campinas-SP, Brazil
Jörg Kobarg
Talita Diniz Melo-Hanchuk
Mariana Bonjiorno Martins
Lucas Leite Cunha
Laura Sterian Ward
Conception and design: TDMH, MBM, JV, JK. Acquisition of data: TDMH and MBM. Literature search and data analysis: TDMH, MBM, JV, LSW, and JK. Statistical analysis: TDMH, MBM, and LLC. Writing, review, and/or revision of the manuscript: TDMH, MBM, FAS, JV, LSW, and JK. Study supervision: JK. All authors approved the final manuscript.
Correspondence to Jörg Kobarg.
The studied cases comprise multiple cancer tissue microarrays which were purchased from a company and therefore do not require an ethics approval for their use.
The thyroid samples consist of a retrospective study approved by the "Ethics Committee in Research from Hospital AC Camargo" (#1259/09-C). The original samples had been obtained by written informed consent of the patients. They agreed that the tissues are maintained in the "biobanco" (="BioBank") of Cancer Hospital AC Camargo and made available to researchers.
The authors declare no conflict of interests regarding the publication of this paper.
Additional file 1: Figure. S1.
Controls of immunohistochemistry reaction. Malignant melanoma was used as tissue marker, (positive staining) for A) NEK1, B) NEK2, C) NEK3 and D) NEK5. E) Normal skin in the absence of primary antibody was used as the negative control. The scale bar = 100 μm.
NEKs expression in different lesions thyroid: (a1) NEK1 negative (× 400); (a2) NEK1 positive (× 400); (b1) NEK3 negative (× 400); (b2) NEK3 positive; (c1) NEK5 negative (× 400); (c2) NEK5 positive and d(1) NEK6 negative (× 400); (d2) NEK6 positive (× 400).
Semiquantitative expression patterns of NEK1, NEK2, NEK3, and NEK5 in tissue microarrays comparing benign and malignant neoplasms tissue of Esophagus, Stomach, Colon, Lung, Thyroid, Breast, Uterine cervix, Pancreas, Prostate, and Kidney.
Quantitative expression patterns of NEK1, NEK2, NEK3, and NEK5 in tissue microarrays comparing benign and malignant neoplasms tissue of Esophagus, Stomach, Colon, Lung, Thyroid, Breast, Uterine cervix, Pancreas, Prostate, and Kidney.
Melo-Hanchuk, T.D., Martins, M.B., Cunha, L.L. et al. Expression of the NEK family in normal and cancer tissue: an immunohistochemical study. BMC Cancer 20, 23 (2020). https://doi.org/10.1186/s12885-019-6408-4
Tissue mirco array
NEK kinase family


Real Geek Forums - Vista advertising SD card content?
Vista advertising SD card content?
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has to do to trigger the invitation is unplug and plug the card reader.
files on the SD card. This is surely a concern?
RE: Vista advertising SD card content?
And you are plugging in a Card READER, lol.
> allow "Windows to view pictures".
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> there?) of disallowing non user prompted access to the SD card.
> didn't happen with XP or Win 9X.
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text:
var sock = require('./line_socket');

exports.register = function () {
    this.inherits('auth/auth_base');
}

exports.hook_capabilities = function (next, connection) {
    var config = this.config.get('auth_vpopmaild.ini');
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        var methods = [ 'PLAIN', 'LOGIN' ];
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exports.check_plain_passwd = function (connection, user, passwd, cb) {
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}

exports.try_auth_vpopmaild = function (connection, user, passwd, cb) {

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    var auth_success = false;
    var result = "";
    var ok_count = 0;

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    socket.connect( ( config.main.port || 89), (config.main.host || '127.0.0.1') );
    socket.setTimeout(300 * 1000);

    socket.on('timeout', function () {
        connection.logerror(plugin, "vpopmaild connection timed out");
        socket.end();
    });
    socket.on('error', function (err) {
        connection.logerror(plugin, "vpopmaild connection failed: " + err);
        socket.end();
    });
    socket.on('connect', function () {
        // wait for server to send us +OK vvvvv
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    socket.on('line', function (line) {
        if (line.match(/^\+OK/)) {    // default server response: +OK
            ok_count++;
            if (ok_count === 1) {     // first OK is just a 'ready'
                socket.write("slogin " + user + ' ' + passwd + "\n\r");
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            if (ok_count === 2) {     // second OK is response to slogin
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                socket.write("quit\n\r");
            }
        }
        if (line.match(/^\-ERR/)) {   // auth failed
            // DANGER, do not say 'goodbye' to the server with "quit\n\r". The
            // server will respond '+OK', which could be mis-interpreted as an
            // auth response.
            socket.end();             // disconnect
        }
    });
    socket.on('end', function () {
        connection.loginfo(plugin, 'AUTH user="' + user + '" success=' + auth_success);
        return cb(auth_success);
    });
};

redpajama_set_name: RedPajamaGithub


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Thanks to those who helped us launch our first Film Camp for Teens!!
Our biggest show yet!!! Six teen bands rocked the stage and 3 short films premiered!! Our first teen film camp launched right alongside our growing teen rock camp program. A week and show full of GRRRL Power!
Our 2018 Kids Camp was full of energy, music and fun!! Over 30 campers (many for the first time) rocked the stage - writing amazing songs, bonding with their bands and learning to use their voice!! We can't wait to watch them rock with us for many years to come!
Our first ever "Kids Camp" rocked our faces off! Thanks to the support from the Arts & Science Council and their Cultural Vision grant award we were able to launch this summer camp with huge success! Six bands of campers ages 8-12 (for most...it was their first time playing!) wrote original songs and rocked the house. We can't wait to watch these rockers grow over the years!
Our first ever "Teen Camp" rocked it this year! We had 6 bands of 30 campers take the stage and rock the house. Their songs were AMAZING!! Many of our campers were return rockstars, while we also welcomed some new teens to the family. Half of our campers received Scholarships from our "Help Us Rock Scholarship Fundraiser."
Our summer camp program and concert was a huge success! Seven bands with 35 campers, 30+ volunteers and awesome community leaders helped us rock a house of almost 500 people!!! Our biggest camp yet! Next year...we grow to two weeks! We will offer a kids camp and a teens camp. Stay tuned!
SO MUCH THANKS AND GRATITUDE TO OUR 2016 SUMMER CAMP CONCERT PRESENTING SPONSOR BANK OF AMERICA!!
Click here to watch how we rocked 2016!!!
In 2015, we grew from four bands to six for the week! Hosted by the Blumenthal Performing Arts Center in Spirit Square, our campers rocked the McGlohon Theater with an awesome concert for a full house of smiling families and rocking supporters. We had a great team of volunteers and a generous list of supporters who all helped to make this week truly inspiring for all!
A rockin' 2015 Summer Camp Concert at the McGlohon Theatre!!
Our first Girls Rock Charlotte summer camp was a huge success. We thought we were "starting small" but that changed as campers, volunteers and amazing community supporters all signed up to make 2014 a rockin' year!
A special thanks goes out to Krystle Baller (who first found us on Facebook and has since become our Music Program Co-Director!) for putting together these videos featuring 2014 highlights and concert performances.


An oh-so-cute crew neck tee with a little something extra, a built in tie at the front, cuffed short sleeves, and relaxed fit. Ship it or purchase in store.
Relaxed Fit. Model is wearing size small, Bust: 37" Length: 21.5" Fabric 50% Cotton 50% Modal Care Machine wash cold, delicate wash, gentle cycle, wash dark colors separately, do not bleach, tumble dry low, warm iron if needed.


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From Far North to 'global pinnacle' of start ups
AFTER five years establishing a networking hub for Far North entrepreneurs and start-ups, a trip to Silicon Valley for The Space leaders Troy Haines and Damian Zammit is "like a dream come true".
The pair are in the US as part of the Advance Queensland Startup Catalyst mission and have been partially funded by the State Government.
Nine other regional Queensland start-up leaders are touring Colorado's world-renowned start-up ecosystems in Denver and Boulder and California's Silicon Valley.
Before starting The Space Mr Haines was working on what he thought would be "the next big thing in the personal development industry", a goal-setting and accountability app called iAMconnected.
But the platform struggled to gain traction and falling more and more into debt, Mr Haines reached out for help.
"In my own experience as an entrepreneur and an 'ideas person', I dreamt of creating a company that could change the world, but from my remote location I struggled to figure out how it might be done, despite recent advances in technology and internet accessibility," he said. "I started looking around my region for help from other entrepreneurs, mentors, key service providers, and investors. But there was no obvious network to tap into, no path to follow, and no regional infrastructure to help build the high-growth, high-scalability start-ups."
Looking abroad, Mr Haines could see Silicon Valley had everything he needed, but was not in a position to relocate.
"Silicon Valley is the global pinnacle of start-up ecosystems. While over in the Valley we will meet with leaders of start-up groups, hubs and coworking spaces," he said.
"Building these relationships will help enable us to connect Cairns entrepreneurs to the Valley. We're over here to network our arses off!"
nStart-up Catalyst chief executive and winner of the 2016 Pearcey National Entrepreneur Award Aaron Birkby will lead the group.
"Queensland and Colorado have a lot in common in the way the state is intervening to encourage entrepreneurship, collaboration and development of an innovation culture — we can learn a lot from the experience there and adapt these leanings to benefit our own regional ecosystems," Mr Birkby said.


This is my first English post. Let's try.
My curiosity is big. I always wanted to know what was over the next hill when I was trekking, what was around the next corner when I was exploring a new city and the same with the body. What is this method of physio, training, therapy etc. and what can I learn from it.
Reading about Vegetative Training on Oliviers blog I got interested. I am very curious about the body, movement, therapy, health, biology etc.
Then I met Olivier at a Fighting Monkey workshop in Copenhagen and asked him about the system/method and he explained. He gave a lot of his time and explained sincerely about the reasoning behind and that just clicked with what I already knew from my background in physiotherapy and movement.
Seeing the freedom in my 18 month daughter. I know we say that kids move a lot. But the variability in their movements is huge. I can see the "same" movements I do when I go through a session, in her while she is eating, playing or relaxing. And the freedom in her body and breath. Wauw. She is shaking her head, lips and stretching without thinking about it. She is not thinking this would be good for me or I need to do this stretch my physio showed my. Her body intuitively knows what it needs. And that is something I got from vegetative training.
I've learnt to better allow these movements to come out. And when I hold them back, it is now more clear to me. So now I can be aware – and I can choose whether I allow it (and feel the freedom like a child again) or the norm of society wins.
It as a great gift and one that can be enhanced and be with me as long as walk this earth. I like that it is not Olivier who tells my what to do. Yes he instruct, but he also allows and then the movements come from within and with it freedom. It is hard to explain in words. It is something that one must experience in one's own body.
Enough about Vegetative Training. There are always two sides of the story. Pros and cons. I will not go more into that for now.
Now as I always do when learning something new is to intergrate it and mix it with what I already know.
Taking what I already knew about movement from studying Physical Therapy and human movement and mixing it with this new information I can create my own place of investigation into my own body. A personal practice to get to know my self better.
Here are some snippets from my investigation into what positions my body can find, how it feels and relates to what I already had been doing to rehabilitate my knee etc.
Vegetative movement – Just a few of the different positions I find myself in during a session.
First of all "vegetative" refers to the vegetative system or the inner pillars of our adaptive ability: our hormone balance, immune system, and autonomous nervous system. Training means that we train to expand the performance characteristics of the organism from the inside-out without manual intervention of the therapist.
Over the years, inside the body muscular 'armour' has been formed: resistance structures or zones where tension is held because of conflicting past experiences. Once they were needed to defend ourselves and stay safe, but often we hold on for too long.
This can be adressed during sessions and released for better movements of the body in all ways.


STUTTGART, GERMANY -- (Marketwired) -- 02/11/14 -- Today Mercedes-Benz introduced the production version of their new S-Class Coupe which will be available in showrooms during the second half of 2014. The S-Class Coupe, as well as other variants of the S-Class, offer as an option the popular MAGIC SKY CONTROL panoramic roof using patented SPD-SmartGlass technology from Research Frontiers (NASDAQ: REFR).
"The S-Class Coupé features a panoramic roof extending over two-thirds of the entire vehicle roof; with a surface area of around 1.32 m2, it appears almost 150 percent larger than on the predecessor model. MAGIC SKY CONTROL makes it possible to switch the transparency of the roof at the push of a button, from light to dark. When light, the roof is almost completely transparent and allows an open-air experience, even in the coldest weather. When dark, light transmission i.e. the proportion of outside light that is allowed through into the interior, is reduced to less than 1% and thus effectively diminishes heating up of the vehicle."
Joseph M. Harary, President and CEO of Research Frontiers commented: "The new S-Class Coupe is a beautiful car that combines aesthetic and sporty luxury with the latest in technology. The single piece of SPD-SmartGlass that makes up the impressive MAGIC SKY CONTROL panoramic roof is the largest piece of smart glass to be put into serial production to date in the automotive industry. It is three times larger than the MAGIC SKY CONTROL roofs that are currently offered on the Mercedes-Benz SLK and SL roadsters. This milestone continues the growth in the use of SPD-SmartGlass in the automotive, aircraft, yachting, architectural and museum industries, which has made SPD-SmartGlass the best selling and most widely available smart window in the world."
The MAGIC SKY CONTROL feature uses patented SPD-SmartGlass technology developed by Research Frontiers to turn the roof transparent by electrically aligning tiny particles in a thin film within the glass. With the touch of a button, drivers and passengers can instantly change the tint of their roof to help keep out harsh sunlight and heat, and create an open-air feeling even when the sunroof is closed. Glass or plastic using Research Frontiers' patented SPD-SmartGlass technology effectively blocks UV and infrared rays in either mode, helping keep the cabin cooler, and protecting passengers and interiors. These benefits become even more important when a car uses large surface areas of glass, such as the panoramic roofs on the new S-Class, especially in warm climates.
SPD-Smart technology has proven itself in many aspects, from durability and performance, to sales. MAGIC SKY CONTROL is now in use on thousands of SL's and SLK's around the world. Before putting cars into serial production, Mercedes-Benz put the MAGIC SKY CONTROL roof using SPD-SmartGlass technology through rigorous durability and performance testing in some of the most extreme conditions on Earth. This included testing in the arctic cold of Scandinavia (with temperatures below -22 degrees F/-30 degrees C) and the blistering desert heat of Death Valley, California (with temperatures exceeding 122 degrees F/50 degrees C). The MAGIC SKY CONTROL feature using patented SPD-Smart light-control technology allows drivers many benefits including the ability to create the open-air feeling of a roadster. It also blocks over 99% of harmful UV radiation and substantially reduces heat inside the vehicle. Test data published by Mercedes-Benz shows the ability of the roof to reduce sun exposure to 1/20th of direct exposure levels (from over 1,000 watts/square meter to less than 50 watts/square meter). When compared to conventional automotive glass, Mercedes-Benz reported that the use of SPD-SmartGlass significantly reduces the temperature inside the vehicle by up to 18 degrees F/10 degrees C. This increases passenger comfort and reduces air conditioning loads, thereby saving fuel and reducing CO2 emissions.
Historically, since its debut over 40 years ago, the S-Class represents the premier platform to introduce new technologies to the customer, which in many cases expand to the other model lines within the Mercedes-Benz brand. You can see the new S-Class Coupe and other Mercedes-Benz vehicles at the upcoming Geneva International Motor Show (March 6-16, 2014) and read more about the new S-Class Coupe (the successor to the Mercedes-Benz CL) in Daimler's press release.
Research Frontiers is the developer of SPD-Smart light-control technology which allows users to instantly, precisely and uniformly control the shading of glass or plastic, either manually or automatically. Research Frontiers has built an infrastructure of over 40 licensed companies that collectively are capable of serving the growing global demand for smart glass products in automobiles, homes, buildings, museums, aircraft and boats. For more information, please visit our website at www.SmartGlass.com, and on Facebook, Twitter, Linked-In and YouTube.
Note: From time to time Research Frontiers may issue forward-looking statements which involve risks and uncertainties. This press release contains forward-looking statements. Actual results could differ and are not guaranteed. Any forward-looking statements should be considered accordingly. "SPD-Smart" and "SPD-SmartGlass" are trademarks of Research Frontiers Inc. MAGIC SKY CONTROL, Mercedes-Benz, and model designations SLK, SL, and S-Class are trademarks of Daimler A.G.


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Games Microsoft News Nintendo PC PlayStation 4 Sony Steam Switch Xbox One
DragonBall FighterZ Pass Two Trailer Confirms Videl, Jiren, Broly (DBS), & Gogeta (SSGSS) Will Join The Game's Roster!
1 Comment on DragonBall FighterZ Pass Two Trailer Confirms Videl, Jiren, Broly (DBS), & Gogeta (SSGSS) Will Join The Game's Roster!
Today, while the Dragon Ball FighterZ World Tour finals competition was underway, Bandai Namco released a new trailer detailing that Jiren and Videl are the first DLC characters for DragonBall FighterZ's second DLC season pass. The trailer states these two characters will be available on January 31st, 2019.
That's not all. Near the trailer's conclusion, Bandai Namco revealed that Broly from the film, Dragon Ball Super: Broly, and Gogeta in his Super Saiyan God Super Saiyan form, will be entering the Dragon Ball FighterZ roster in the coming future. According to Nintendoeverything.com, "Bandai Namco has taken down the trailer, but it should be back up later today."
However, you can watch the trailer now by clicking here (footage courtesy of Direct-Feed Games's YouTube channel).
Update [Jan. 27th_10:26 PM EST]: Click here to watch the trailer on the Bandai Namco Entertainment America YouTube Channel.
Image courtesy of Direct-Feed Games's YouTube channel.
According to GameInformer.com, either on Twitter or on their YouTube channel, Bandai Namco accidentally posted the trailer that revealed these four characters (above) are making an appearance in Dragon Ball FighterZ–as apart of its second DLC season. GameInformer.com believes this trailer "was likely not supposed to drop until after the conclusion of today's Dragon Ball FighterZ World Tour finals."
On the other hand, GameInformer.com reports that there are individuals who are known for Dragon Ball FighterZ Pass One leaks, who may have spread "a picture on an image board [that] purported (…) Videl with Great Saiyaman, Dragon Ball Super Broly, Jiren, and Gogeta were part of the season pass." Based on the trailer that released today, it seems they were right on the money.
Since there picture-leak was true, GameInformer.com reports that the leakers "also said Janemba, Zarbon, Majin Vegeta, Ultra Instinct Goku, Kefla, Super Saiyan 4 Goku, and Raditz" will join the game's roster. However, like GameInformer.com states, this leaked fighter list gives us two scenarios due to the amount of characters Bandai Namco currently announced.
Image courtesy of GameInformer.com.
The first scenario is that half of these characters mentioned in the leakers' list will join Dragon Ball FighterZ's roster while the other half is meant to get fans' hopes up. Scenario two regards season two's pass having more characters than we'd anticipate. Even still, if there list is remotely true, fans can expect some exciting additions to this Dragon Ball smasher!
Sometimes it's a shame when things don't go according to plan. For now, the Bandai Namco YouTube channel and Twitter account haven't re-uploaded the trailer on social media, but you can find it elsewhere. Once they do release the trailer, we'll be sure to update this article with their trailer-link above. You'll be able to click here to watch it as well, once it's available.
Hopefully as the year goes on, we'll find out if this roster of leaked fighters or others, will join this game's roster.
What do you think about this news? Who are you most excited to play on January 31st, Videl or Jiren? Let us know on Facebook and Twitter, and follow us for more Dragon Ball FighterZ news, and everything gaming too.
Tags Broly (DBS), DLC, Dragon Ball FighterZ, DragonBall FighterZ Pass Two, Gogeta (SSGSS), Jiren, Nintendo Switch, Videl
← Metroid Prime 4's Initial Development's Been Scrapped; Retro Studios's Back In Business! → DRAGON BALL GAME – PROJECT Z: Announcement Trailer Reveals New Details & More!
One reply on "DragonBall FighterZ Pass Two Trailer Confirms Videl, Jiren, Broly (DBS), & Gogeta (SSGSS) Will Join The Game's Roster!"
DRAGON BALL GAME – PROJECT Z: Announcement Trailer Reveals New Details & More! -says:
[…] unlike the accidental trailer drop for Dragon Ball FighterZ's second DLC season characters, the Bandai Namco Twitter account posted a new trailer for DRAGON BALL GAME – PROJECT Z on their […]


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Lost my streak again at 306. Was 587, then 308. I'm probably not going to go for a streak anymore. I'll just do stories and finish some more trees. Have a good 2018.
I lost mine around 350 a year ago. Too much traveling.
Your current streak says 308. Are you sure you lost it?


The story is taken from a book compiled by the late Rev. Gerald Chamberlain, a great children's story teller and a person who inspired and influenced many young people. With kind permission from his son, Paul.
A hawk saw a dead rabbit on a block of ice floating down the Niagara River. Swiftly moving in for such a delightsome dinner the hawk was soon absolutely absorbed in the exercise of picking Brer Rabbit's bones clean.
Every now and then the huge bird lifted its head. He seemed to sense danger that was approaching. But he continued to eat and eat, thinking he could fly away at the last moment before the waters around plunge over the falls.
As the ice block began to sweep over the Great Niagara Falls, the huge wings of the Hawk opened and began to flap powerfully. But his feet were stuck to the ice, firmly frozen, and try as he may, he couldn't get free. With a terrifying shriek he plunged with the Ice Block down to destruction. If the Hawk had tried earlier up the river, he might have freed himself, for it was the water constantly washing over his feet that made the ice that bound him to the floating ice thicker and thicker.
He didn't realize that like sin, that ice was getting a bigger grip and bigger grip on him. If you wind one piece of cotton around me pinning my arms to my sides, I'll laugh at you and break the cotton without any real effort. But when you increase that thin strand to two thickness of cotton, it gets more difficult…..and when 50 times the cotton encircles me, I have to struggle. And when you have wrapped it round me a 100 times, I'm completely bound and cannot get free.
And if you don't send this to at least 8 people —– who cares?!
If you have children, you'll know exactly what I mean: Some days you look into their faces, and you see the attitudes of angels; on other days you want to scream, "Why can't you just get along!" as they get into a cyclical argument about who moved a toy 1/32nd of an inch.
There are dozens of reasons we don't get along with each other with the sin of pride right at the top of the list. But I think another huge reason we fail to live in authentic, consistent, committed, Christian community is because it's too hard. It requires real effort to work through our differences, to remain transparent and honest, to confront and to pay close attention to each other.
Frankly, it's easier to keep relationships superficial; to 'demonize' one another when we don't agree; to cut and run at the first sign of trouble rather than commit to each other. Yet, God placed within us a need for 'stick-with-it' commitments; his commitment to us is unbreakable, and he wants to see us extend the same commitment to each other (2 Cor. 8:5). But this kind of commitment takes time; something that has become far too scarce in our lives today (and that is a choice).
God knows we will live in a healthy, Christian community if we will commit to living our lives together beyond our weekly meetings, if we will make each other a priority – sharing our lives over coffee, after work, at the ballpark, in the hospital. The only way for us to become a "friend who sticks closer than a brother" (Proverbs 18:24) is when we focus on the quality of our relationships, not mere quantity or mere acquaintances.
· Love no matter what – How can you plan to help others at all times (not just when it's convenient? Proverbs 17:17) ~~ How can you develop a strategy for loving others at their worst, not just when they seem loveable? (Romans 5:8).
· Show up – The most basic behavior of commitment is simply showing up. 'If you care, you'll be there.' You may be surprised that your mere presence is a source of encouragement (Hebrews 10:25).
Definition of a wife: The person who is first to put their foot down after crossing the threshold; a female who would rather mend your ways than your socks; the one person who in an argument, if you win- you lose; she says that she has nothing to wear yet she also moans that she needs more wardrobe space. Definition of a husband: A man who always consults his better half before his better judgment; A man who thinks twice before saying nothing; a man who buys his wife such fine china that she will never trust him to do the dishes; a person who has learned to turn off the car motor when his wife calls `I'll be right out'.
How do men define marriage? 'A very expensive way to get your laundry done free'.
'The most effective way to remember your wife's birthday is to forget it once'.
EXCUSE ME, ARE YOU JESUS!
A few years ago a group of salesmen went to a regional sales convention in Chicago. They had assured their wives that they would be home in plenty of time for Friday night's dinner. Hurrying to catch the plane home with tickets and briefcases, one of the salesmen inadvertently kicked over a table which held a display of apples. Apples flew everywhere. Without stopping or looking back, they all managed to reach the plane in time for their nearly missed boarding. All but one! He paused, took a deep breath, got in touch with his feelings, and experienced a twinge of compassion for the girl whose apple stand had been overturned.
He told his buddies to go on without him, waved good-bye, told one of them to call his wife when they arrived home at their destination and explain his taking a later flight. Then he returned to the terminal where the apples were all over the terminal floor.
He was glad he did. The sixteen year old vendor was totally blind. She was softly crying, tears running down her cheeks in frustration, and the same time helplessly groping for her spilled produce as the crowd swirled about her, no one stopping or caring about her plight.
The salesman knelt on the floor with her, gathered up the apples, put them back on the table, and helped organize her display. As he did this, he noticed many of them had become battered and bruised; these he set aside in another basket.
When he had finished, he pulled out his wallet and said to the girl, 'Here, please take this $40 for the damage we did. Are you OK? She nodded through her tears. He continues on with, 'I hope we didn't spoil your day too badly'.
Do people mistake you for Jesus? That's our destiny, is it not? To be so much like Jesus that people cannot tell the difference as we live and interact with a world that is blind to His love, life and grace. If we claim to know Him, we should live, walk and act as He would. Knowing Him is mre than simply quoting Scripture and going to church. It's actually living the Word as life unfolds day to day.
We are the apple of His eye, even though we, too, have been bruised by a fall. He stopped what he wa doing and picked us up on a hill called Calvary, paying in full for our damaged fruit.
Behind everything you see is something you don't see. This book is designed to outline nuggets of wisdom that often remain invisible behind thriving churches and ministries. Mixed with a touch of humour. Top 10 of Everything looks into the Private Word , the Practical World, the Handy Hints World and the Wide World of Knowledge. It gives advice on many subjects that may prove invaluable to established and up-and-coming leaders. Read it all at once or read it one Top Ten at a time. This book can also provide new preachers with an opportunity to 'borrow' some of the Tom 10 outlines to create lively and dynamic sermons.
The gifts of the Spirit listed in 1 Corinthians 12 are referred to as the manifestations of the Spirit. Because God lives in heaven and in our hearts, we can receive a gift either down from heaven or up from our hearts. When a volcano erupts, what was under the surface manifests itself for all to see. It's essential we stir up the gifts that are within us and allow the supernatural to be released from our lives. What an impact we can make!
That rose Christ from the dead now lives in you. You have all that it takes living in you right now.
That rivers of life flow from your inmost being to touch and impact a needy world. The gifts are manifestations of the Spirit.
The Greek word for 'gift' actually means 'a gift of grace'. You don't deserve it. You can't earn it. It's by the grace of God. Stop exalting men who move in the gifts.
Desire is the key that stirs up the gifts and causes them to be released at the point of need.
As you begin to step out, you release the power that accompanies the gifts. You can only learned whether the promptings are from God or yourself by stepping out and 'having a go'.
As you keep regularly 'tuned' to the airwaves of God, you'll not miss out on opportunities to move in the gifts of the Spirit.
When Saul hung around the prophets, he prophesied. The right environment can accelerate the rising of the gifts.
The gifts aren't for show, they are for lifting people to new levels of living.
for greater manifestations of the gifts. John 15 tells us that God prunes us for increased fruitfulness. He enlarges our character for greater charisma (the Greek word for gift).
Everything should be done decently and in order. Unruliness can nullify the effectiveness of the gifts.
He actually decided to make a sacred covenant with the Lord in his heart to honour Him because he wanted His wrath to be removed and His gracious favour and covenant to be known. History had both told and taught him that because the Lord had His rightful place in the nation during David's reign, it went well, and he knew he must get the people back on track so that the Lord's grace and blessing would be restored and so the challenge to all.
The immediate requirement was to see the sanctuary purified and to call upon the priests to properly consecrate themselves to the Lord and discharge of their duties. He beheld their negligence and demanded that this should dramatically change. In no way was he going to allow the status quo to exist. The impact would be felt far and wide as he initiated a wholesale re-direction of procedure and there came also the emphasis on Passover Feast. People knew where his mind and commitment was focused.
He made sure that the offensive idolatrous system that had been embraced by God's people was removed, and it must have taken courage to have performed this. There was no room for the evil alongside of Jehovah. It had to go.
Later events saw the Assyrians rise as a great power and they invaded the land, making great inroads and conquest in Israel and now into Judah. They were now arrogantly situated outside the Holy City but Hezekiah looked to the Lord in this extreme crisis, and was not to be disappointed. What a turn around occurred!
There came the time and moment when the he was sick and informed that he was to die but before doing so was to set his house in order. He prevails in prayer and receives an immediate answer and healing. Because he knew the Lord he was able to enjoy this special blessing. The only problem, he did not use the fifteen years to maximum effect for God. Surely a lesson to take note of.
This is but a sermon starter to get you thinking and studying in relation to the text and theme. Trust it will be provocative and promotive.
This is an eye opener… Some probably never thought nor looked at this Psalm in this way… even though they say it over and over again..
1/. 'The Lord is my Shepherd' – That's Relationship!
2/. 'I shall not want' – That's Supply!
3/. 'He maketh me to lie down in green pastures' – That's Rest!
4/. 'He leadeth me beside the still waters' – That's Refreshment!
5/. 'He restoreth my soul' – That's Healing!
6/. 'He leadeth me in the paths of righteousness' – That's Guidance!
7/. 'For His name sake' – That's Purpose!
8/. 'Yea, though I walk through the valley of the shadow of death – That's Testing!
9/. 'I will fear no evil' – That's Protection!
10/. 'For Thou art with me' – That's Faithfulness!
11/. 'Thy rod and Thy staff they comfort me' – That's Discipline!
12/. 'Thou preparest a table before me in the presence of my enemies' – That's Hope!
Major firms usually have tremendous storehouses where they stockpile their goods in order to be able supply the need of their customers. A 'storehouse' is a must for them. They need to make sure when there is big demand they are up to meeting the immediate request.
Joseph, in the Bible, was called upon in the course of newly appointed office as prime minister to construct countless large storehouses that would contain the abundance of grain that was going to be created in the next seven years. God ha revealed that there was going to be seven years of famine, so it was essential that the profusion of corn should be safely housed in readiness for the critical years.
What a tremendous building enterprise was on in order to stock such a seeming infinite quantity of grain! The king, people and Joseph must have felt relieved and assured when they saw these storehouses filled to capacity believing that in the coming emergency they would be fully provided for. The fear factor would be somewhat removed as they saw all these storehouses erected and full of one of the basic requirements of life. They knew they would not starve because there was a fullness of supply at hand ready to be distributed.
In our modern way of living we like to think that our larders and pantries are stocked so that we lack nothing. We are able to go to them on a daily basis and take from our freezer, refrigerators and shelves the things that keep our bodies satisfied and existence going. They are stocked on a regular basis so what is needed is available when required.
Above all, it is inspiring to know that God has storehouses that He wills that we should be acquainted with. Whilst it is good and helpful to have the aforesaid, our faith should not be focussed on such. It is essential to be aware of the fact that God's storehouses must be known and drawn upon and they touch upon this life and the life to come.
One of the present storehouses is His Word. In the Bible there is stored up an located great promises from Himself to His people and they should be acquainted with and live off them. He goes on sacred record to give choice assurances that guarantee the fruitfulness, security and blessedness of life and here and now. In no uncertain way we are told, 'man does not live by bread alone but by every word that proceeds out of the mouth of God' – Matthew 4: 4. God is there to be our Guide, Provider, Protector, Healer, Restorer etc., (see Psalm 23) and it is vital to digest in our minds an hearts what He has to say.
Just like the big oil refineries with their vast tanks of oil, there is the guarantee that my car will not run short of gas or oil! What is assured now is also guaranteed on an eternal footing. No one need have any anxiety with regard to eternity because there is storehouse after storehouse of blessing waiting to be drawn and lived upon by those who belong to God.
There never will be a time in that eternal setting when God finds himself embarrassed because of a lack within himself or resources. Already He has in mind the thought, prospect, will and ability to utterly satisfy His new creation out of His infinite treasuries. He is going to find enormous pleasure in seeing all this new Family of His blessed in an incredible manner and measure.


Goalie Clinic for players U11 and Up!
Are you interested in becoming a Goalie? Like to give it a try? Then this clinic is for you!
This session is for those players who would like to try or find out more about being a goalie. Any coach interested in watching a training session and ask any questions is also welcome.
We will also have available one-on-one coaching for goalies. If you would like your goalie to receive training please email me and I will send out someone to your practice.
Tri-City Eagles Field Hockey Athletic Wear Online Store - Deadline extended one week.
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Will the data breach scandal bring down social media giant Facebook? Mark Zuckerberg fesses up in an exclusive CNN interview, but not everyone is buying it. We don't have to walk you through all the details of the data breach…that's old news, what we're talking about is Mark Zuckerberg's attempt to save his company that continues to be hammered even after his mea-culpa interview on CNN.