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As of 2012, televisions, computers, laptops and monitors tend to be banned in the garbage in accordance with New Jersey's Electronic Squander Management Behave (Act).
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When you rent a new dumpster look for one that will be on small wheels to make the employment much easier available for you and/or your builder hired to do the job.
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Make sure to ask your local firm if they have the means and capacity to handle your " special " needs regarding clearing out the different forms of building debris.
Junk itself is actual that is illustrating the attention in the whole world. Proper disposal on this generated garbage is one far more hidden issue that is placing the challenge owners at great barrier. Huge numerous litter cumulated include various bulky objects and postures a challenge to the particular project seller. One has to deal with many troubles like choosing the right disposal rubbish bin, dumping the particular tons of garbage carefully,(requirements manual aid), spending time to home in the rubbish dumps, tackle the issues with the regional authority, correct disposal connected with trash by recycling. Each one of these issues have to have a lot of time in addition to investment in relation to money in add-on to the risk.
Irrespective of why you need a dumpster, whether it's industrial or individual, you will most probably need to rent a single from a Roll Off For Rent in Exeland, WI firm. While you may well believe that a new dumpster is a dumpster, the organization you rent coming from may still drastically impact your current experience in addition to final charges. Here are some points to look for in your current Roll Off For Rent in Exeland, WI company.
It's always a difficult process to decide on whether or not to purchase garbage ales or rent a new dumpster. Many individuals in addition to business owners possess this concern. Even so, what many people don't realize is that people/homeowners doing repairs on their houses will benefit far more if they rental a dumpster. There are numerous important factors to check out when you decide to rent a new dumpster when improving your home or business, not merely the price. How big the dumpster is certainly one factor you must think of before choosing the organization you'll be hiring the dumpsters coming from. A huge company will require a tremendous waste discretion unit in contrast to a small business or maybe home because they big organizations generate a lot of waste in addition to garbage.
If you are a roofing company you know you'll need to keep your roofs jobs transferring. The time to top flies by with the occasion you have due to the weather. You might live in claims that get warm hot into your 90's in addition to 100's or maybe you may live in a state that has brutal winter weather. With the months and due to time constraints, company is calling you actually left and right to obtain their roof completed. Some of the patron's roofs tend to be emergencies as they are leaking in addition to causing shape to form within the ceilings. You and the crew need to have to quickly provide your customer an estimate. Once you make the time to assess the damage and how much it'll cost you the customer to resolve his or her top, you can indicator the contract to practice it.


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Post in the comments if you used this tip and let me know if you run into any trouble. This should work on other versions of Linux but the files may be in different places. If you want to find your operating system's copy of "wrapper" try running "locate wrapper | grep -i teamviewer" and it should come up in the list. If you don't have locate installed you can try the much slower: "find / -name "wrapper" | grep -i teamviewer" to do the same thing. Good luck!


Skip Spriggs is President and CEO of The Executive Leadership Council, the preeminent membership organization for black CEOs, board directors, and senior most executives at Fortune 1000, Global 500, and equivalent companies. He leads the organization's efforts to fulfill its mission of increasing the number of global black executives in C-Suites, on corporate boards, and in global enterprises while building an inclusive business leadership pipeline that empowers global black leaders to make impactful contributions to the marketplace and their communities.
Mr. Spriggs has served in senior business roles at several Fortune 500 companies across diverse industries over the last 25 years. He most recently served as Senior Executive Vice President and Chief Human Resources Officer at TIAA, where he led all aspects of human resources strategy and execution for the company's global workforce. He joined TIAA from Boston Scientific, where he was Chief Human Resources Officer and a member of the Executive Management Team.


Acoc is one of my favorite *nix tools. It adds color to common commands like ls, diff, grep, make, and top. This drastically improves their usability. It's also extensible, so it's easy to color new programs and change colors for existing programs.
This patch adds the rule to acoc 0.7.1.


text:
Lenče  je priimek več znanih Slovencev:

Znani nosilci priimka
 Josip Lenče (1865—1920), gostilničar in politik
 Mojca Lenče-Kastelic, zdravnica
 Peter Lenče (1910—1999), farmakolog, prof. MF

Glej tudi

 priimek Lenček
 priimke Lenič

Zunanje povezave

Slovenski priimki

redpajama_set_name: RedPajamaWikipedia


Located in the historic Royal Borough of Greenwich, this London school is a state-of-the-art centre with modern facilities.
For those looking to study English in London, there is no need to look further than Twin English Center London. School offers students everything that they could possibly need: modern facilities, a comfortable learning environment, excellent transport links to Central London and a wide range of courses that were created to meet the needs of international students.
Twin English Center London has bright and modern classrooms fully air-conditioned, spacious common areas for communicate with another students, and self-study zones where you will also have access to student computers. There is free Wi-Fi throughout the school and an on-site library with thousands of books, so you will be able to educate and entertain yourself outside of lesson time.
Twin English Center London provides students with comfortable surroundings allowing to have the best learning experience possible. With anextensive range of courses including exam preparation and specialist courses, you are able to choose a course that is best suited to you and your individual needs.
Este curso está diseñado específicamente para ayudar a mejorar sus habilidades en inglés y aumentar la confianza en la comunicación cotidiana. Puede tener excelentes habilidades de lectura, escritura y comprensión auditiva, pero si cree que es extremadamente difícil mantener una conversación, entonces la clase de inglés conversacional es ideal.
La residencia Willesden incluye habitaciones tipo estudio amuebladas según altos estándares para que puedas disfrutar de una estancia lujosa mientras estás en el Reino Unido. Todas las habtiaciones tienen baño privado, mini cocina con cocina, fregadero y nevera, es decir, todo lo que necesitas so eres una persona independiente y necesitas un poco de privacidad.
Está ubicada en una de las áreas mas animadas del este de Londres, esta residencia es la elección perfecta para aquellos alumnos que quieren explorar Londres y hacer nuevos amigos. El alojamiento tiene fácil acceso a muchas atracciones turísticas como estiloso Shoreditch, Spitalfields Market y Brick Lane, así que podrás visitar algunas de las tiendas, restaurantes y cafés más fashion durante tu estancia aquí.
¡Gran escuela! Fuimos juntos con mi esposo, nos gustó todo: buenos maestros, actividades interesantes. Excelente organización por Linguatrip. ¡Aconsejo a todos a estudiar en esta escuela!
I liked everything! We were lucky with the family, we were even allocated at a separate floor. The teachers are great at the school.
The school was wonderful and modern! Chic teachers. The host family was not really good ... The host family was far away from school, and they fed not really good. But I could endure it.
I expected otherwise! I thought that there would be more control requirements. I have not raised my level.
Nice family, we had breakfast and dinner together. Was very lucky with the teacher. Convenient location to the city centre. The school is located in the business centre. There is a library, access to computers.
I liked the school. But didn't really like the accomodation. It was a small room, I thought it would be better.
New, modern school. But there were very few activities. The host family had an uncomfortable location, but the people was good. The teachers at the school are wonderful. Thanks for the trip!
I really liked the school! Tons of great impressions, if I'll ever have a chance, I will definitely do it again) All the teachers were kind and responsive, their lessons were very interesting. I was living in a host family, and was really satisfied with everything, hosts were really hospitable.


text:
miR-6742-5p regulates the invasion and …
Research Paper Volume 15, Issue 1 pp 53—69
miR-6742-5p regulates the invasion and migration of lung adenocarcinoma cells via mediating FGF8/ERK12/MMP9/MMP2 signaling pathway
Minglei Song1, , Xiaoying Xing2, ,
1 Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China
2 Department of General Practice, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China
Received: May 28, 2021 Accepted: August 22, 2022 Published: January 10, 2023
Song M, Xing X, . miR-6742-5p regulates the invasion and migration of lung adenocarcinoma cells via mediating FGF8/ERK12/MMP9/MMP2 signaling pathway. Aging (Albany NY). 2023; 15:53-69 . https://doi.org/10.18632/aging.204277
Copyright: © 2023 Song and Xing. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Background: microRNAs (miRNAs) are involved in the progression of Lung adenocarcinoma (LUAD), however, the functions of miR-6742-5p in LUAD remains unknown, thereby this study was carried on.
Methods: The mRNA and miRNA expression data from the LUAD and normal control were obtained from Gene Expression Omnibus (GEO) database, TargetScan and mirDIP were applied to predict the relationship between miR-6742-5p and FGF8.Q-PCR, western blot, dual-luciferase, wound Healing and transwell assays were performed to test the functions of miR-6742-5p in LUAD.
Results: Bioinformatics analysis and dual-luciferase identified FGF8 is the target-gene of miR-6742-5p, which is declined in LUAD of human tissues and cell lines, and miR-6742-5P OE suppressed the progression of LUAD in nude mice. MiR-6742-5p OE and KD suppressed or increased the abilities of LUAD' metastasis tested by wound healing and transwell assays H522 and PC-9 cells, these effects about miR-6742-5p OE were reversed by FGF8; miR-6742-5p OE, KD inhibited and increased the expression of FGF8 as its downstream p-ERK1/2, MMP-2/-9, these results were corrected by ERK1/2 inhibitor: Ro 67-7476; the miR-6742-5p KD increased the migrated and invaded cells and suppressed by MMPs inhibitor: S3304. These results identified the negative correlation of miR-6742-5p with FGF8-ERK1/2 signal pathway in LUAD progression.
Conclusions: We conclude that miR-6742-5p might be a regulator of LUAD progression by targeting FGF8/ERK1/2/MMPs signaling pathway, which provides a novel therapeutic target for LUAD.
Lung cancer is the most common malignancy with the highest morbidity and mortality rates worldwide [1]. Lung adenocarcinoma (LUAD) is one of the main subtypes of non-small cell lung cancer, accounting for 40% of all lung cancers [2]. Studies have revealed that LUAD patients exhibit a relatively high mortality rate, and the risk of distant metastasis exceeds that of local recurrence at each stage of the disease, confirming the systemic involvement of the disease [3]. Despite the recent advances in molecular diagnosis and treatment technology, the prognosis of LUAD remains not optimistic, and the risk of metastasis and recurrence remains high. Therefore, it is essential to uncover the underlying mechanism of LUAD and to find novel therapeutic targets for LUAD.
Micro ribonucleic acids (miRNAs) are a class of small non-coding RNAs that are considered to be key regulators of biological processes [4]. Abnormal expression of miRNAs has been reported to be associated with the occurrence and progression of a variety of tumors, and miRNAs can be used as biomarkers for tumor diagnosis and prognosis [5, 6]. As reported, many miRNA molecules are involved in various biological processes in the occurrence and development of multiple cancers, including cell proliferation, apoptosis, angiogenesis, migration, and invasion. For instance, the overexpression (OE) of miR-3174 significantly promotes cell proliferation and inhibits cell apoptosis by suppressing forkhead box protein O1 (FOXO1) expression in hepatocellular carcinoma [7]. MiR-192 and miR-215 target adenomatous polyposis coli and function as oncogenic miRNAs via activating the Wnt signaling pathway in gastric cancer, suggesting that miR-192 and miR-215 are potential therapeutic targets [8]. In addition, the up-regulation of miR-183-5p can promote the occurrence of colorectal cancer by regulating FOXO1, proving its potential role as biomarker for the treatment of colorectal cancer [9]. Moreover, miR-335-5p modulates cell cycle and metastasis of LUAD through targeting CCNB2 [10]. All the above reports are suggestive of the important roles of miRNAs in cancer progression. However, the function and mechanism of miR-6742-5p in LUAD are still ambiguous. The fibroblast growth factor 8 (FGF8)/FGF receptor 1 (FGFR1)/extracellular signal-regulated kinase 1/2 (ERK1/2) axis functions in the tumorigenesis in various tumors, including lung cancer, and its role involves involved in the invasion, metastasis and progression of non-neoplastic lesions. FGF8 activates FGFR1 by directly binding to it, which aggravates lung cancer and results in the phosphorylation of ERK1/2 [11–19]. Moreover, matrix metalloproteinases (MMPs) are key executors of tumor invasion, which are the downstream products of ERK1/2 signals. They inhibit tumor metastasis by degrading the fibrous or stromal tissue surrounding the tumor, thus limiting the cancer cell migration throughout the body [20–23]. Hence, FGFs, ERK1/2 and MMPs are key checkpoints for cancer suppression.
In the present study, the potential molecular mechanism of miR-6742-5p in LUAD was elucidated, which is expected to provide a novel therapeutic target for LUAD.
DEGs and DEMs in LUAD
A total of 266 DEGs between LUAD and normal tissues were retrieved from GSE140797 dataset (Supplementary Figure 1) and 257 from GSE116959 dataset (Supplementary Figure 2). In addition, 61 DEMs were retrieved from the GSE94536 dataset and subjected to hierarchical clustering analysis (Supplementary Figure 3).
There were 69 DEGs common to the GSE140797 and GSE116959 datasets (Figure 1A), which were thus used for subsequent analysis. Among the 69 DEGs, FGF8 gene attracted our attention, and its expression and role in LUAD were explored. The results manifested that the FGF8 expression was up-regulated in LUAD tissues (Figure 1B). Subsequently, the upstream miRNAs of FGF8 were assessed using miDIP and TargetScan databases, and the key regulatory factor of FGF8, miR-6742-5p, was filtered from the DEMs common to the three datasets, which exhibited a down-regulated expression LUAD tissues (Figure 2A). Furthermore, the binding sites between miR-6742-5p and FGF8 were obtained from target predictions on the miRDIP database (Figure 2B), and moreover, the original data were shown in Supplementary Figure 5. Ultimately, GSEA results uncovered that FGF8 gene was significantly enriched in the ERK pathway, suggesting that the high expression of FGF8 is associated with the ERK pathway (Figure 2C).
Figure 1. Differentially expressed genes in both GSE116959 and GSE140797 datasets. (A) A total of 69 differentially expressed genes were obtained in both GSE116959 and GSE140797 datasets. (B) The expression level of FGF8 in GSE140797 dataset.
Figure 2. Determine of the targeting relationship between miR-6742-5p and FGF8. (A) Identification of FGF8 targeting miRNAs. (B) Predicted binding sites between miR-6742-5p and FGF8. (C) High expression of FGF8 was associated with ERK pathway.
Relative expression and role of miR-6742-5p in human LUAD and model nude mouse tissues
The relative expression of miR-6742-5p in paracancerous tissues of LUAD was examined using qRT-PCR, and it was found that the miR-6742-5p expression was significantly decreased in human LUAD tissues compared with that in the corresponding paracancerous tissues (Figure 3A). Moreover, to further evaluate the roles of miR-6742-5p in LUAD, a nude mouse model of LUAD was established. BALB/c mice in the two groups were subcutaneously injected with 100 μL of cell suspension containing 1×107 H522 cells per mL in sterile PBS. 4 weeks later, the tumors were collected, and it was uncovered that the tumor growth in miR-6742-5p mimic/OE group was lower than that in miR-6742-5p NC group (Figure 3Ba). As shown in Figure 3Bb, the histopathology of the nude mice examined by H&E staining demonstrated that the size and the area of tumors were obviously inhibited in miR-6742-5p mimic/OE group compared with those in miR-6742-5p NC group, data were shown in Figure 3Bc.
Figure 3. The expression of miR-6742-5p in human lung adenocarcinoma and its roles in nude mice. (A) Relative expression of miR-6742-5p in human lung adenocarcinoma and their paracancerous tissues, tested by quantitative real-time PCR. (B, a) the volume of H522 tumor in miR-6742-5p NC and OE group; (B, b) HE staining of nude mice' tumors; (B, c) statistic data for tumor volume. (A) ** P=0.0001 miR-6742-5p OE group vs NC group; (B) **P=0.0001 miR-6742-5p OE group vs NC group.
Relative expression of miR-6742-5p and its role in H522 and PC-9 cells
To explore the function of miR-6742-5p in LUAD, the expression of miR-6742-5p was overexpressed or down-regulated in H522 and PC-9 cells and verified by qRT-PCR. The results of qRT-PCR displayed that miR-6742-5p was observably elevated in miR-6742-5p mimic/OE group and reduced in the miR-6742-5p inhibitor group (Figure 4Aa, b). The relative expression levels of miR-6742-5p were significantly suppressed in H522, PC-9 cells when compared with normal lung epithelial cell lines: BEAS-2B cells (Figure 4B). Additionally, dual-luciferase reporter assay verified the roles of miR-6742-5p on FGF8 transcription (Figure 4Ca, b) in H522 and PC-9 cells, and the putative FGF8 3'-UTR-WT/MUT binding sequences (Figure 4Cc). Furthermore, Transwell assays were adopted to investigate and evaluate the effects of interaction between FGF8 and miR-6742-5p OE on the migration of LUAD cells. According to the results, the number of migrated cells in miR-6742-5p mimic/OE group was smaller than that in miR-6742-5p NC group, and this effect could be reversed by FGF8 in H522 and PC-9 cells (Figure 4Da, b).
Figure 4. The expression levels of miR-6742-5p and its binding for FGF8, and their interaction in tumor migratory effects. (A) Quantitative real-time PCR were used to evaluate the relative expression levels of miR-6742-5p in H522 and PC-9 cells transfacted with control/NC, mimic/OE, inhibitor/KD; (B) the relative expression levels of miR-6742-5p in normal lung epithelial cell lines: BEAS-2B cell and H522, PC-9 cells (C) luciferase reporter assay was used to identify the roles of miR-6742-5p on FGF8 transcription in H522and PC-9 cells (a, b), and the putative wild-type FGF8 3'-UTR binding sequence and the mutation sequence (c). (D) the transwell assay was used to evaluate the effects of the interactions of miR-6742-5p and FGF8 in tumor migration. (a) ** P=0.01 miR-6742-5p OE group vs NC group; (b)* P=0.0481 miR-6742-5p OE+FGF8 group vs NC group.
Regulatory role of miR-6742-5p in cell invasion and migration
To further determine the effect of miR-6742-5p on the regulation of cell migration and invasion, Transwell and wound healing assays were carried out to detect the effect of miR-6742-5p on the migration and invasion of H522 and PC-9 cells. Transwell assays proved that cell migration and invasion capacities were markedly inhibited in miR-6742-5p mimic/OE group but enhanced in miR-6742-5p inhibitor group (Figure 5A, 5B). Moreover, the wound healing assay uncovered that the cell migration ability in miR-6742-5p mimic/OE group was significantly repressed, while it was enhanced in miR-6742-5p inhibitor group (miR-6742-5p KD) ((Figure 6A, 6B). All the above-mentioned results confirmed that miR-6742-5p influenced migration and invasion of H522 and PC-9 LUAD cells.
Figure 5. miR-6742-5p regulated LUAD cell migration and invasion. (A) H522 Cells; (B) PC-9 cells migration and invasion was assessed by transwell assay and its quantification. (A) migration **P=0.0011 miR-6742-5p OE group vs NC group;* P=0.029 miR-6742-5p KD group vs NC group; invasion** P=0.0001 miR-6742-5p OE group vs NC group;*P=0.0003 miR-6742-5p KD group vs NC group (B) migration **P=0.0002 miR-6742-5p OE group vs NC group;*P=0.0137 miR-6742-5p KD group vs NC group; invasion **P=0.0003 miR-6742-5p OE group vs NC group;**P=0.0063 miR-6742-5p KD group vs NC group.
Figure 6. miR-6742-5p inhibited the migratory capability of LUAD cell. Wound healing assay showed that miR-6742 mimic (OE) significantly increased and miR-6742 inhibitor (KD) reduced wound closure and its quantifications in H522 Cells; (A) 24hours *P=0.0152miR-6742-5p OE group vs NC group;**P=0.0015miR-6742-5p KD group vs NC group; 48hours **P=0.0092 miR-6742-5p OE group vs NC group;*P=0.0281 miR-6742-5p KD group vs NC group (B) 24hours **P=0.0006miR-6742-5p OE group vs NC group;**P=0.0001miR-6742-5p KD group vs NC group; 48hours **P=0.0001 miR-6742-5p OE group vs NC group;**P=0.0002 miR-6742-5p KD group vs NC group.
Regulatory role of miR-6742-5p in the invasion and migration of LUAD cells via targeting FGF8, ERK1/2, MMP9 and MMP2
As displayed in Figure 7, the expressions of FGF8, p-ERK1/2, MMP9 and MMP2 were significantly suppressed in miR-6742-5p mimic/OE group compared with that in miR-6742-5p NC group, while they were notably promoted in miR-6742-5p inhibitor group.
Figure 7. miR-6742-5p was involved in regulating the invasion and migration of LUAD via targeting FGF8/ERK1/2/MMP9/MMP2. (A) The expression of FGF8, ERK1/2, MMP9 and MMP2 was evaluated by western blot in cells treated with and without RO 67-7476 cells. (B) The expression of FGF8, ERK1/2, MMP9 and MMP2 quantification in cells treated with and without RO 67-7476 cells. ** P < 0.01. Relative protein levels of FGF8 (-)**P=0.0009miR-6742-5p OE group vs NC group;**P=0.0028miR-6742-5p KD group vs NC group; Ro 67-7476 **P=0.004miR-6742-5p OE group vs NC group;**P=0.0065miR-6742-5p KD group vs NC group; Relative protein levels of ERK1/2 *P=0.0134miR-6742-5p OE group vs NC group;**P=0.0063miR-6742-5p KD group vs NC group; Relative protein levels of MMP2 **P=0.0066miR-6742-5p OE group vs NC group;**P=0.0017miR-6742-5p KD group vs NC group; Relative protein levels of MMP9 **P=0.0058miR-6742-5p OE group vs NC group;**P=0.0051miR-6742-5p KD group vs NC group.
Ro 67-7476 is a potent p-ERK1/2 agonist that activates ERK1/2 phosphorylation in the presence of exogenous glutamate. In the present study, Ro 67-7476 evidently attenuated the inhibitory effect on the expressions of p-ERK1/2, MMP9 and MMP2 by OE of miR-6742-5p, but had no effect on the expression of FGF8 (Figure 7), and the original data of western blot for FGF8 were shown in Supplementary Figure 6. Taken together, the above data illustrated that miR-6742-5p was involved in regulating the invasion and migration of LUAD cells by targeting FGF8, ERK1/2, MMP9 and MMP2.
LUAD is a clinically common subtype of non-small cell lung cancer with an increasing incidence and mortality rates in recent years [1]. Despite progress in the treatment of LUAD, the prognosis of LUAD patients remains poor. Thence, further research on the pathogenesis of the progression of LUAD is of great significance for determining diagnostic biomarkers and novel effective therapeutic targets of LUAD. In this study, FGF8 was a potential target gene of miR-6742-5p and involved in the regulation of the ERK1/2 pathway. Functionally, it was discovered that miR-6742-5p regulated the invasion and migration of LUAD cells. Mechanically, miR-6742-5p regulated the invasion and migration of LUAD cells via targeting FGF8, ERK1/2 and MMP9. Thus, this study provides new insights for deeply revealing the pathogenesis of LUAD.
With the development of bioinformatics and the study of miRNAs at the molecular level of cancer biology, it can be observed that miRNAs are abnormally expressed in many human cancers [24, 25]. In addition, it has been evidenced that miRNAs play a critical regulatory role in the occurrence and progression of cancers via mediating a variety of cellular processes, including cell proliferation, apoptosis, migration and invasion [26, 27]. In fact, multiple miRNAs have been reported to be involved in the occurrence and metastasis of LUAD, and can be used as diagnostic and prognostic biomarkers of LUAD. It has been preciously demonstrated that multiple miRNAs such as miR-196b, miR-24-3p and miR-147b, are involved in the regulation of lung cancer [28–30]. In the current study, the results revealed that the expression of miR-6742-5p was decreased in human LUAD tissues and cell line compared with that in paracancerous tissues and normal lung epithelial cells (Figure 3), indicating its role in tumorigenesis. Subsequent functional analysis showed that miR-6742-5p regulated LUAD cell migration and invasion. Therefore, in-depth study on the mechanism of miR-6742-5p in LUAD is crucial for understanding the pathogenesis of lung cancer.
As presented in miRDIP and starBase databases, there were target binding sites between miR-6742-5p and FGF8 (Figure 4). Subsequently, mechanistic studies manifested that miR-6742-5p regulated the migration and invasion of LUAD cells by regulating FGF8. FGF8 is a member of the growth factor family that regulates cell growth, migration and differentiation via FGF tyrosine kinase receptor signaling [31, 32]. FGF8 expression is closely associated with the degree of degeneration in different cancer patients [33–35]. As reported, FGF8 is highly expressed in esophagogastric junction adenocarcinoma, and is expected to be a candidate gene for the prognostic factor for this cancer [36]. Besides, FGF8 also shows a high expression in oral squamous cell carcinoma tissues, and it regulates the epithelial-mesenchymal transition and induces an invasive phenotype in oral squamous cell carcinoma cells [37]. Notably, the results of this study also uncovered that miR-6742-5p influenced migration and invasion in LUAD cells by regulating the FGF8 expression, indicating that FGF8 may be a key target for regulating the LUAD progression, and the exogenous FGF8 corrected the roles of miR-6742-5p (Figure 3C). The above results identified our speculation.
As demonstrated by KEGG pathway enrichment analysis, FGF8 was likely play a role in the ERK1/2 pathway. Usually, the ERK1/2 pathway is activated in LUAD and involved in the progression of LUAD. For instance, NRG1 may be an important regulator in the development of LUAD, and its function has been found to show relevance to the ERK1/2 pathway [38]. FLOT1 promotes tumor progression, induces the epithelial-mesenchymal transition and regulates cell cycle in LUAD by regulating the ERK pathway [39]. FAM83A promotes the expression of PD-L1 via the ERK1/2 pathway, thus leading to immune escape of LUAD tumors [40]. FGF8 exerts its function mainly by binding to FGFR1 [17–19], and the activated downstream FGFR1 can directly phosphorylate the ERK1/2 [41, 42]. Moreover, the role of MMPs under the control of ERK1/2in the tumor migration or invasion and metastasis was identified. The results displayed that the MMP2/9 could rectify the inhibitory effects of miR-6742-5p KD, confirming the role of MMPs in regulating miR-6742-5p in LUAD (Supplementary Figure 4). At length, miR-6742-5p was involved in regulating the invasion and migration of LUAD by targeting the ERK1/2 pathway via FGF8.
In conclusion, miR-6742-5p is downregulated and FGF8 is elevated in LUAD tissues. The OE of miR-6742-5p inhibits LUAD cell invasion and migration and blocks the FGF8/ERK1/2 pathway. Additionally, miR-6742-5p regulates the invasion and migration of LUAD cells via targeting FGF8, ERK12, MMP9 and MMP2. This is the first study to clarify the function and mechanism of miR-6742-5p in LUAD, which may provide a new idea for revealing the pathogenesis of LUAD.
Data pre-processing and differential expression analysis
A total of three datasets, namely, 2 mRNA datasets (GSE140797 and GSE116959) and 1 miRNA dataset (GSE94536), were downloaded from Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/). The edgeR package was utilized to convert the original microarray data into expression profile data. The differentially expressed genes (DEGs) and differentially expression miRNAs (DEMs) between LUAD and normal tissues were filtered and analyzed by the limma package in R. Later, the DEGs were subjected to hierarchical clustering analyses using pheatmap package in R (https://cran.r-project.org/package=pheatmap). Furthermore, DEMs common to the three datasets was identified using TargetScan (http://www.targetscan.org/vert_71/) and mirDIP (http://ophid.utoronto.ca/mirDIP/), so as to predict potential miRNAs that interacted with FGF8. Finally, gene set enrichment analysis (GSEA) was used to identify the pathways enriched in LUAD patients.
A normal lung epithelial cell line (BEAS-2B) and LUAD cell lines (H522 and PC-9) were obtained from American Type Culture Collection (ATCC, Manassas, CA, USA) and cultured in RPMI 1640 supplemented with 10% fetal bovine serum and 1% penicillin-streptomycin (Gibco) in an incubator with 5% CO2 at 37° C. In addition, the miR-6742-5p negative control (NC), mimic and inhibitor synthesized by GenePharma (Shanghai, China) were transfected into the above cells lines using Lipofectamine 3000 (Invitrogen, CA, USA) based on the instructions, so as to achieve OE or knockdown (KD) of miR-6742-5p.
Establishment of a nude mouse model of LUAD via subcutaneous injection
All the nude mice (Skbex Biotechnology, Henan, China) were adaptively fed in our laboratory for 1 week, and then randomly divided into miR-6742-5p NC group (transfected with NC) and miR-6742-5p mimic/OE group (transfected with mimic/OE, n=6). The mice in the two groups were subcutaneously injected with 100 μL of cell suspension containing 1×107 H522 cells per mL in sterile PBS. One month later, all mice were euthanized, after which the subcutaneous tumors were collected, and the tumor volumes were calculated.
Quantitative real-time polymerase chain reaction (qRT-PCR)
Total RNAs were extracted from tissue samples and cells using TRIzol kit (Solarbio, Beijing, China) following the manufacturer's protocol. Then the RNAs were subjected to reverse transcription through Reverse Transcription Kit (Thermo Fisher Scientific, Waltham, MA, USA). Next, qRT-PCR was performed using SYBR Select Master Mix (Thermo Fisher Scientific). At last, 2-ΔΔCt method was adopted for the quantification of relative gene expression.
Western blotting assay
Total proteins were isolated from tissues and cells with RIPA lysis buffer (Beyotime, Shanghai, China), and the protein concentration was conducted by a BCA kit (Beyotime). Then, the proteins were separated by SDS-PAGE and transferred onto PVDF membranes (Millipore, Billerica, MA, USA). After blocking with 5% nonfat milk for 1 h at room temperature, the membranes were incubated with primary antibodies against FGF8, ERK1/2, phosphorylated (p)-ERK1/2 and MMP9 (Cell Signaling Technology, Danvers, MA, USA) at 4° C overnight, followed by incubation with secondary antibodies at 37° C for 1 h. Finally, protein bands were visualized using ECL reagents (Beyotime).
Transwell assays
H522 and PC-9 cells were washed and resuspended in serum-free Dulbecco's Modified Eagle Medium (DMEM) at a density of 1×105 cells/mL. In the invasion assay, the cell suspension was added to the upper compartment of a 24-well Transwell plate with a Matrigel-precoated membrane (Corning, NY, USA). Meanwhile, DMEM containing 10% FBS was added into the lower compartment of the Transwell chamber. After incubation for 72 h, the invaded cells on the bottom of the lower Transwell chamber were fixed with 4% paraformaldehyde for 30 min, stained with 0.05% crystal violet for 10 min, and observed under an optical microscope (Olympus, Tokyo, Japan). In the migration assay, the cell suspension was added to the upper compartment of a 24-well Transwell plate with an 8-μm pore size membrane filter (BD Biosciences, Franklin Lakes, NJ, USA). All other processes were the same as those in the Transwell invasion assay.
Wound healing assay
H522 and PC-9 cells were transferred to 6-well plate and co-transfected with miR-6742-5p mimic and inhibitor. When the cells reached about 90% confluence, a wound was made by scratching using a pipette tip (10 μL). Later, the migrating cells were photographed under a microscope at 0, 24 and 48 h after scratching.
Dual-luciferase reporter assay
The potential miR-6742-5p binding site in the 3' untranslated region (3'-UTR) of the FGF8 gene was predicted using the TargetScan online database (http://www.targetscan.org). The wild-type (WT) fragment (CCCCACA) and mutant (MUT) fragment (CGGTATA) of FGF8 gene were inserted into FGF8 plasmids pmirGLO-FGF8-3'-UTR-WT and pmirGLO-FGF8-3'UTR-MUT (GenePharma). H522 cells in each group were co-transfected with the constructed WT and MUT plasmids and miR-6742-5p NC/mimic, and then they were collected after incubation for 48 h. After the addition of firefly luciferase and Renilla luciferase, the fluorescence values in each group were detected on the computer, and the ratio of Firefly luciferase to Renilla luciferase activity was calculated. Three replicates were set in each group.
All the data were expressed as mean ± standard deviation (SD), and analyzed using ANOVA or t-test. P<0.05 represented that the difference was statistically significant.
Supplementary Figures
Minglei Song: Writing-Original draft preparation, Data collection, Experiments. Xiaoying Xing: Data curation, Writing- Reviewing and Editing.
We would like to give our sincere gratitude to the reviewers for their constructive comments.
The authors declare that they have no conflicts of interest.
All animal experiments were approved by Research Ethics Committee of the Second Hospital of Hebei Medical University (No. 2021-R327).
Key Research Project of Hebei Provincial Health Commission (No.20190719).
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Xiaoying Xing
xingxyey@hebmu.edu.cn
LUAD miR-6742-5p FGF8 ERK1/2/MMPs tumor metastasis

redpajama_set_name: RedPajamaCommonCrawl


Goverenment of Assam Cacher District Recruitment Notification 2018.Goverenment of Assam Cacher District inviting applications for the positions of Gaon Buras.Interested and Eligible candidates can apply for the positions.
Applicants must be completed 10th standard from the recognized organization.
Applicants may apply the application form through online from 29th August 2018 to 20th September 2018.


text:
By Ernie Ball on August 14, 2020 in Artists, Follow Friday
Unless you've been living under a complete non-musical rock for the last 10 years, chances are you have heard of Pennsylvania's rockers, Halestorm. But in the off chances, you have lived that sheltered life, let us introduce you!
The quartet is fronted by vocalist and rhythm guitarist, Lzzy Hale, her brother Arejay on drums, Joe Hottinger on lead guitar, and Josh Smith on bass. The brother/sister duo formed their band and was writing original music since 1997 when they were 10 and 13 years old, but it wasn't until their official formation of Halestorm and their signing with Atlantic Record in 2005, that things really hit the big time. Their debut self-titled album arrived in 2009 and peaked at #40 on the Billboard 200 and the band was already hitting the cover of Revolver Magazine as well as hitting the road with bands like Seether, Staind, Avenged Sevenfold and more. As the band progressed, added more albums to their resume and countless tour dates. Their second full-length, The Strange Case Of…, arrived in 2012 which held the track, "Love Bites…(So Do I)." The tune won a Grammy in the Best Hard Rock/Metal Performance Group, becoming the first female-fronted band to be nominated and win in that category. From there, the band kept going up.
It goes without saying that the group has risen to the top for their musicianship and work ethic, but the powerful vocals, lyrical content and all-around positive and good-heartedness that is Lzzy Hale, solidifies why Halestorm have captured the rock and metal scenes. Although Lzzy has kept a firm foot in reality, it hasn't been without difficulty to just play her music and ignore everyone else.
My biggest piece of advice for being a female, or any gender, is to pride yourself in not paying any mind to what people think about what you do. They could hate me or love me. The only thing that matters is what you think of you. For women, we get a lot of pressure. "She changed her hair," or "she's getting bigger," or "she's too thin." We get judged harder. Until all that evens out, don't let that seep into what you're doing. The end goal is to continue down that road.
Lzzy Hale to Consequence of Sound
While Halestorm waits out the COVID-19 pandemic that has crushed the music industry, they have been recording a covers EP titled Reimagined, dropping August 14th. They also began the Roadiestrong Campaign, in hopes of supporting those affected in the music industry which you can read about here.
Halestorm play Paradigm Skinny Top Heavy Bottom, Medium Nickel Wound 13-56 electric strings, Paradigm Medium Light Phosphor Bronze acoustic strings, Super Slinky, and Power Slinky 5 bass strings.
For more Halestorm content, check out Lzzy Hale and Joe Hottinger's String Theory video below as well as the Striking A Chord Podscast Episode with Joe here.
https://open.spotify.com/artist/6om12Ev5ppgoMy3OYSoech?si=4u8uwFeiSuCy6zYWq97Ixg
Although most people know the band The Gaslight Anthem, singer and guitarist Brian Fallon has been carrying the musical torch beyond the New Jersey punkers even beyond their 2015 hiatus.
Fallon has been surrounded by music since childhood and was releasing his own music since he was a teenager including his first un-official/official EP, Cincinnati Rail Tie, in 2004 which included his mother (who was in a folk band in the 60s) providing backing vocals.
Although he had a few smaller groups over the years, he had the most success with The Gaslight Anthem in 2006, leading to five studio albums, world tours, and even a guest singing spot live with Mr. New Jersey, Bruce Springsteen (if you can't hear the inspiration there, you may be hard of hearing…). But after gaining ground in popularity, Fallon was burnt out and wanted to slow down a bit.
Now on his third official solo effort, Local Honey, which arrived in March 2020, Fallon really dug into his current life in a more singer-songwriter style. Exploring themes about fatherhood, balancing love with obsession, and overall adulthood. Although the change of pace surprises the die-hard punk lovers, Fallon feels natural with his progression.
It was always there, but now it's coming out. You evolve as a person. I certainly don't think that I missed my calling when I was doing Gaslight, though; that was exactly where I should have been at that time. I think that when some people get to where I'm at right now, they're so critical of what they did previously, and it's like they almost want everyone to forget it. In a way, I've probably done that before, too. But I'm at a place where I like them both.
Brian Fallon to Kerrang!
For now, Fallon is supporting his new record with live sessions on his social media pages while he waits to tour another day.
Brian Fallon uses Power Slinky, Regular Slinky and the new Primo Slinky electric strings and Earthwood Light Phosphor Bronze acoustic strings to create his signature sound.
https://open.spotify.com/artist/3JlzEFwarS8ZcCGNFy11y4?si=NYxF6i6ETQC8yYT9uRht7w
Just because you're a punk rock band, doesn't mean you're not allowed to have mega riffage. Propagandhi is your proof of that.
The Canadian rockers formed in 1986 under the idea they wanted to form a "progressive thrash band." Fast forward to 1992, and the band had tailored their sound a bit more to the skate punk side of their scene. After playing a show with NOFX, frontman and bassist Fat Mike signed Propagandhi to his label, Fat Wreck Chords, and they released their first full-length, How To Clean Everything. As the band continued to tour and write, their view on politics, economics, and animal rights. Just take a look at their tracklists with song titles like "The Only Good Fascist Is a Very Dead Fascist," "Cop Just Out of Frame," and "Bullshit Politicians."
One of the most interesting things about the band is their move from skate punk to fast mega riffs, not quite metal, not quite thrash, and not quite punk, but all catchy as hell with powerful vocals and lyrics courtesy of Chris Hannah. When speaking about their musical shift over the years, Hannah said;
It wasn't planned, it's more just us getting better at our instruments. I think even on our early records you could hear Metallica influences and you could probably tell that the band was just not capable of pulling it off. In 1993 to 1996 we couldn't pull off what we're doing now because we just didn't know how to play it. We got better over the years; we've gotten closer and closer to the original vision of the band. Nothing conscious, just an evolution of skill through perseverance.
Chris Hannah to Heavy Mag
The band released their latest effort, Victory Lap, in 2017 via Epitaph records and have been touring to support it since.
Propagandhi use Regular Slinky and Custom 11-52 electric guitar strings, Regular Slinky bass strings.
https://open.spotify.com/artist/7qpy5KY3DVrezixTl6mziA?si=IEtdpSl2Sh2OFidrOQXqZQ
Power duo Tarah Who? bring a modern take from the 1990's alt-rock playbook, combining edgy grunge riffs with driving groove and a direct approach. Led by guitarist/vocalist Tarah Carpenter, the frontwoman unites explosive emotional conviction with motivating anthemic songwriting. The band's work ethic and drive have generated buzz from various music outlets and specifically the ear of Alanis Morissette's guitarist Jason Orme, who co-produced and played guitar alongside Tarah on the EP Middle Child Syndrome. Be on the lookout as Jason will be on Tarah Who?'s next release titled 64' Women. With a kindred connection between rhythm and alt groove, Tarah Who? is a group to keep tabs on as they continue to grow their fanbase. Their dynamic ability to write heavy songs but also beautiful rebellious ballads makes for an entertaining listen, recommended for fans of Ernie Ball family members,The Distillers or any lover of 90's influenced alt. Check out the live Kurukulla Session of the song "In A Rush" above.
Don't take every situation so seriously. You're wasting your time and energy. Focus on the good: your needs and loving each other. Don't waste your time comparing yourself or your life with other peoples'. Focus on being you.
Tarah to Vocal Media
Keep up with the latest from Tarah Who? on their website and make sure to listen to their expressive tracks below.
Tarah Who? creates their signature sound with Ernie Ball Not Even Slinky electric guitar strings.
https://open.spotify.com/artist/0Q7WuoNQUT5rfvo83edxNR?si=KxOpkoq8SeqNwz7wF9QG1Q
Hailing from Seattle, Washington, Ernie Ball would like to welcome AVOID to the family.
AVOID is a unique hard rock five-piece band quickly kicking radio waves on Octane XM. The band began creating a buzz with their live wire show performances and experimental approach. Combining a cocktail of grungy, metal, and pop production with the heavy rock, it's colorful quirky approach showcases individuality that takes the music up a notch with breakdowns, headbanging, ripping riffs, and screaming bridges leading to sing-along choruses. AVOID has something for everyone and has created fandom garnering 1.5 Million streams on their debut album ALONE on Revival Recordings. The self-titled album also reached the Billboard Heatseekers Pacific Chart.
With a new release on the horizon titled, The Burner, the band has secured two new tracks on the video game NASCAR Heat 5, and the band's own car wrap. Be on the lookout for the rising young band as they pave their way in the music scene. Check out their new music video above for the single "Song About James".
AVOID uses Ernie Ball Power Slinky and Mammoth Slinky electric guitar strings and Beefy Slinky bass strings to craft the tone for their music.
https://open.spotify.com/artist/7rZJ1D1ERxrHNKTWwpZFVU?si=L7KaFc5qTvaebyGKuyRQ_A


text:
Omawumi – Butterflies
boybranky Monday, 17 January 2022, 12:33 am
Nigerian recording talented female artist and a songwriter Omawumi drives out an impressive song titled "Butterflies".
Butterflies is a single released by Cabal Entertainment/Roc Nation act, Omawumi.
The song is from her third studio album titled, Timeless, released in 2017.
Butterflies were released under Cabal Entertainment.
Listen and enjoy the romantic vibes on this song!!!
https://www.xclusiveloaded.com/wp-content/uploads/2020/06/Omawumi_-_Butterflies.mp3
Omawumi
Omawumi – Mr Whiny
Nigerian female vocalist, Omawumi drives out a new fascinating track dubbed, "Mr Whinny". The new track "Mr Whiny" is taken…
Omawumi – Billionaire (Go Baby)
Nigerian female vocalist, Omawumi slides out with a new impressive song titled, "Billionaire (Go Baby) ". The new track "Billionaire…
Omawumi – Fefe
Nigerian female vocalist, Omawumi dishes out a new stunning single titled, "Fefe". The new track "Fefe" is taken off her…
Omawumi – Joy
Nigerian female vocalist, Omawumi comes through with a new amazing song tagged, "Joy". The new track "Joy" is taken off…
Omawumi – Sugar Baby
Nigerian female vocalist, Omawumi unveiled a new classic single entitiled, "Sugar Baby". The new track "Sugar Baby" is taken off…


text:
United CEO Thinks Full Travel Recovery Could Happen by January
United Airlines CEO Scott Kirby said this morning that while the delta variant of COVID-19 has been a nuisance, he believes the country has reached its peak and expects a full travel recovery in January.
"The Delta variant has obviously caused a downturn in travel, (but) it's particularly business travel. A lot of offices were expecting to be open again in September, and the Delta variant has pushed those opening dates back a few months. My guess is it will now be January," Kirby said on the CBS Sunday news program, 'Face The Nation.'
"It appears that we've peaked in cases. Let's hope that that's the case. Let's hope that as we continue to get more people vaccinated, we really can get back to normal across the country. But the demand (for) recovery has, really, probably been pushed back to January."
Appearing with host Margaret Brennan, Kirby touched on a variety of subjects.
On whether airline contractors or passengers can be confident they won't cross paths with an unvaccinated United employee, Kirby said simply it was a matter of wearing a mask.
"One of the things that's important when you're traveling on an airplane, particularly once you're on the airplane, it's really the safest place you can be because the airflow on an airplane, the safest place you can be indoors," he said. "And so, wear your mask in the airport. That's a rule. And before long, we'll have everyone in the airports vaccinated thanks to the administration's order."
Brennan asked Kirby if the Biden Administration should roll out a mandate that all passengers who want to fly be vaccinated, saying the TSA could check for vaccination cards.
Mandating fliers to be vaccinated is something that has been discussed, and it received an endorsement from White House adviser Dr. Anthony Fauci.
Kirby said it would be easier for people to be vaccinated en masse at work.
"You can get a high percentage of the country as opposed to making it a burden on people that are vaccinated every time you get a plane, a train, any kind of public transportation to prove that you're vaccinated," he said. "So, for now, I think their approach of focusing on the employment and focusing on work is probably the right way to go. But they've got great data and science, and if they tell us that they want us to check everyone, we're prepared to do that as well."
This article originally appeared on Travel Pulse


text:
Q: ArgumentNullException in asp.net MVC Hi I wanted to move data from one listbox to another,But When I move the data I get Error…
I have done the following code for that in View

<%:Html.HiddenFor(m=>m.objMemberAccessRights.Id) %>
<%:Html.ListBoxFor(model =>model.objMemberAccessRights.AvailableSelected, newMultiSelectList(Model.objMemberAccessRights.AvailableNames, "Id", "InstituteName", Model.objMemberAccessRights.AvailableSelected), new { size="8"})%>

<buttontype="button"id="add"onclick="location.href='<%:Url.Action("AddNames", "MemberDetails") %>'">>></button>

<buttontype="button"id="remove"onclick="location.href='<%:Url.Action("RemoveNames", "MemberDetails") %>'"><<</button>

<%:Html.ListBoxFor(model=>model.objMemberAccessRights.RequestedSelected,newMultiSelectList(Model.objMemberAccessRights.RequestedNames,"Id","InstituteName",Model.objMemberAccessRights.RequestedSelected), new { size="8"}) %>

Model:
    public class MemberAccessRights
    {
public int Id { get; set; }

public List<InstituteInformation> AvailableNames { get; set; }
public string[] AvailableSelected { get; set; }

public List<InstituteInformation> RequestedNames { get; set; }
public string[] RequestedSelected { get; set; }

public string SavedRequested { get; set; }
    }

Controller:
        [NonAction]
public List<InstituteInformation> getAllInstituteNameList()
        {
var name = (from i indb.InstituteInformationDBSselect i).ToList();
return name;
        }

//
// GET: /MemberDetails/Create
public ActionResult Create()
        {
MemberDetailsWrapper MD = new MemberDetailsWrapper();
MD.objMemberAccessRights = new MemberAccessRights{ AvailableNames = getAllInstituteNameList(), RequestedNames = new List<InstituteInformation>() };

return View(MD);
        }

//AddNames
public ActionResult AddNames(MemberDetailsWrapper MD, string add)
        {
ModelState.Clear();
MemberAccessRights MAR=new MemberAccessRights();
RestoreSavedState(MAR);

if (!add.Equals(">>"))
            {
if (MD.objMemberAccessRights.AvailableSelected != null)
                {
var names = getAllInstituteNameList().Where(p => MD.objMemberAccessRights.AvailableSelected.Contains(p.InstituteName));
MD.objMemberAccessRights.RequestedNames.AddRange(names);
                    MD.objMemberAccessRights.AvailableSelected = null;
                }
            }
SaveState(MD);
return View(MD);
        }

//RemoveNames
public ActionResult RemoveNames(MemberDetailsWrapper MD, string remove)
        {
ModelState.Clear();

RestoreSavedState(MD);
if (!remove.Equals("<<"))
            {
if (MD.objMemberAccessRights.RequestedSelected != null)
                {
MD.objMemberAccessRights.RequestedNames.RemoveAll(p => MD.objMemberAccessRights.RequestedSelected.Contains(p.InstituteName));
MD.objMemberAccessRights.RequestedSelected = null;
                }
            }
SaveState(MD);
return View(MD);
        }

        #regionSupportFuncs

public void SaveState(MemberDetailsWrapper MD)
        {
MD.objMemberAccessRights.SavedRequested = string.Join(",", MD.objMemberAccessRights.RequestedNames.Select(p =>p.InstituteName).ToArray());

////Available Names = All - Requested
MD.objMemberAccessRights.AvailableNames = getAllInstituteNameList().Except(MD.objMemberAccessRights.RequestedNames).ToList();

        }

    //RestoreSavedState
public void RestoreSavedState(MemberAccessRights MAR)
        {
MAR.RequestedNames = new List<InstituteInformation>();

if (!string.IsNullOrEmpty(MAR.SavedRequested))
            {
string[] nameids = MAR.SavedRequested.Split(',');
var name = getAllInstituteNameList().Where(p =>nameids.Contains(p.InstituteName));
MAR.RequestedNames.AddRange(name);
            }
        }

        #endregion

When I click on this >>button then I get Error:
ArgumentNullException
This is happen because:
When I check this(RestoreSavedState(MAR);) after debugging it shows
AvailableNames null
AvailableSelected null
RequestedNames null
RequestedSelected null

That's why its not running properly and shows the Exception
it should be display like this
AvailableNames null
AvailableSelected<Array of selected item> like this,{int[1]}
RequestedNames null
RequestedSelected null

All this Happens Because the object is not passing correctly can anyone tell me how to remove this bug

A: Add this line of code:
if (MD == null || MD.objMemberAccessRights == null)
{
//do nothing
}else{
MD.objMemberAccessRights.RequestedNames = newList<InstituteInformation>();
}

You probably have the nullreference exception since one of these objects is not intialised.
For your application to function correctly you should try to find out why these values are null

redpajama_set_name: RedPajamaStackExchange


text:
Q: MVC - Implementing a model I have a doubt with the implementation of the model and can not find a reasonable explanation for the problem.
I'll give you an example I'm working, it is an MVC implementing a blog.
I am ControllerPost which is responsible for control of reading a particular post Blog
consequently have the ModelPost
the ModelPost must contain all methods needed?
method getPost()
method getComment()
method getArchive()

or should I isolate the methods?
ModelPost
     method getPost()
ModelComment
     method getComment()
ModelArchive
     method getArchive()

this causes me much confusion, I see examples but no proper explanation.
I hope that was clear in my doubts, otherwise try to be more explanatory
Thank all

A: In most projects I've worked on, we've had a model class for a database table.
Using mostly Zend MVC, that would mean extending the Zend_Db_Table classes for each entity.
So in your case, if the comment, post and archive are different tables (which I suppose they are), I'd build separate classes with get, update, insert and delete (and other similar) methods.
This might steer a bit off topic, but I suggest you look into domain driven development (DDD):
There are links to some good reading material here: Domain-driven design with Zend
Also give this a read:

*

*http://phpmaster.com/building-a-domain-model/

*http://phpmaster.com/integrating-the-data-mappers/

*http://phpmaster.com/an-introduction-to-services/
The main thing about the DDD is that it switches your mindset from thinking about database tables, more towards thinking about the main logical parts of your application, and then slowly adding a persistence layer below it and the application and service layers above it.


text:
Profiles - Michael Simcoe: From Prams to Pontiacs
Designing automobiles wasn't at the top of the consideration list for Michael Simcoe, but his influence will be felt for years to come.
Michael Simcoe heads up exterior design for GM North America. Simcoe's vehicle design career began in '83 at Holden in his homeland, Australia.
The Holden Monaro, designed by a team headed up by Simcoe, not only raised his visibility within GM in Detroit, but also led to Holden heading up vehicle development for the corporation's rear-drive passenger cars.
Kevin M. Kelly
"I wanted to be an architect, but I remember talking to someone early on and they said there's not too much money in architecture," recalls Michael Simcoe of his decision to follow a more lucrative career path during his formative years in Australia. The 50-year-old obviously made some good choices along the way: he's now the executive director of exterior design for GM North America. And there's good money in automotive design—at least at that level.
Simcoe obtained a degree in industrial design from the Royal Melbourne Institute of Technology, then left the commonwealth for the U.K., where he obtained a job at Ogle Design. There he designed products ranging from helicopters to baby strollers. He returned to Australia in the fall of 1983 for what he thought would be a brief visit. While there, he had a conversation with one of his college instructors who urged Simcoe to meet with people from the design staff of GM Holden Ltd. He decided that he'd become a vehicle interior designer.
Simcoe's rise at Holden was quick. He was named senior designer in 1985 and chief designer of Australia's largest vehicle manufacturer just two years later. He came to the U.S. for a brief stint, from 1990 to 1992, when he penned the Buick Sceptre concept. But then it was back to Australia, where he and his team toiled with apparent little visibility to the management back in Detroit. Things changed in 1998 when the Commodore Coupe concept was revealed. It morphed into the '01 Holden Monaro. Simcoe recalls, "That's the one project that changed things for me, and made me really visible to GM. It was purely an inside design job where we knifed and forked a coupe together out of the Commodore sedan." Although the plan called for vehicle profitability with sales of just 4,500 coupes, when production ended in 2005, the Monaro had sold 55,000 units. The curiosity of GM management was piqued by what they were doing down under. Bob Lutz visited Holden, where he was Simcoe and his team working on the Commodore VE, "The first from-the-ground-up production car Holden had ever done," Simcoe says. It was also the car that was so appealing to Lutz that it became the basis of the Pontiac G8. (The Monaro had been translated into the Pontiac GTO.)
Simcoe was named executive director of GM's Asia-Pacific design in 2003, which had him oversee the day-to-day activities of the automaker's Pan Asian Technical Automotive Center in Shanghai and kept him involved with Holden's design activities. Then in 2004 he was moved to the U.S., where he became director of design for Body Frame-Integral. He was promoted in June 2007 to his present position. One of his primary areas of focus currently is on the exterior for future GM trucks. He admits that U.S.-sized trucks were initially "a shock," but adds, "Since I've taken them on, I have been on a rapid learning curve."
Simcoe believes automotive design is entering "an incredibly challenging period," brought on by increased regulations and concerns with fuel economy and safety. While some people might express frustration, believing that these factors can put a crimp on expressive vehicle design, Simcoe is not deterred: "It's all about the guys who can best use the regulations to their advantage," and so he and his team are busy figuring out how best to do that. He says, "The winners are going to be the people who best understand and work within the regulations to get the best results."
Clearly, architecture's loss is automotive's gain.
What's in Simcoe's Garage?
Among the vehicle's Simcoe is proud to own:
-	'56 Series 5 Lancia Aurelia B20 GT
-	'61 Series 3 Aston Martin DB4
-	'61 Lancia Fulvia 1.3 HF
Topology Optimization Explained
Topology optimization cuts part development time and costs, material consumption, and product weight. And it works with additive, subtractive, and all other types of manufacturing processes, too.
Honda Accord: The Ninth Generation
Although the term "continuous improvement" is generally associated with another company, Honda is certainly pursuing that approach, as is evidenced by the Accord, which is now in its ninth generation.
5 Things about the Fiat 500e
Fiat is bringing a little more environmentally responsible fun to its lineup, an electric-powered 500.


text:
Q: Canonical Momenta and gauge invariance Suppose there is a charged particle moving in an Electromagnetic field for which the vector potential is A.
Now we change A by gradient of some scalar(which is time independent) Hence, the scalar potential remains  unchanged.
Now, I want to investigate the effects of such a gauge transformation in Quantum Mechanics.

*

*The expectation value of $\hat{x}$ (position operator) and Mechanical Momenta would remain unchanged under gauge transformation, right? ( 1st question)

But the expectation value of Canonical Momenta is not gauge invariant despite the physical situation being the same.

*Does that imply that we cannot associate an observable with the Canonical Momenta i.e we cannot directly measure it by equipments.
Is it not an observable? (2nd question)

A: You are correct on both counts. Mechanical momentum is a gauge invariant physical quantity, but canonical momentum isn't. That means that canonical momentum is as measurable a quantity as the vector potential - which is to say, not at all unless you further specify what gauge you want it in.


text:
Philippine anti-terrorism law
Youth groups say SC decision 'not enough' since dangers of anti-terror law still intact
Samantha Bagayas
JUNK. Activists from different progressive groups gathered in front of the Commission on Human Office in Quezon City on Tuesday, December 7, upon learning that the Supreme Court have voted for the anti-terror law.
Angie de Silva/Rappler
Although parts of the anti-terror law were voided, many youth groups call for the junking of the law to further protect ordinary Filipinos
MANILA, Philippines – Youth groups on Thursday, December 9, welcomed the Supreme Court's decision to void parts of the anti-terror law but argued that it is "not enough" to address the remaining dangerous provisions.
"While this is a partial victory for Filipinos in a clamor to protect our democratic spaces against looming fascism, we should be reminded that not parts, but the whole anti-terror law should be scrapped," the Christian Political Science Society of Philippine Christian University-Manila (ChPSS PCU-Manila) said in a statement.
"It continues to endanger the masses amid a time of heavy political polarization that government oppositions are continuously being viewed as a terrorist threat," the group added.
Despite concerns raised by petitioners against it, the High Court mostly upheld the heavily contested anti-terror law in a decision released on Thursday. It declared only two parts unconstitutional. It voided the caveat of the anti-terror law which would have made dissent or protest a crime if it had intent to cause harm. It also declared unconstitutional the power of the anti-terror council (ATC) to designate a person or group as terrorists based on a request by another country.
With the law mainly intact, this means several provisions including the ATC's power to order the arrest of suspected terrorists and detain them for as long as 24 days are still considered constitutional.
It is because of the upheld provisions why youth groups echoed fears of the remaining dangers of the anti-terror law.
"Justice is still denied because dangerous provisions such as prolonged detention that can last up to 24 days, definitions of incitement, freezing of assets, and the anti-terrorism council has been deemed 'constitutional,'" Kej Andres, the national spokesperson of the Student Christian Movement of the Philippines, said in a statement.
The College Editors Guild of the Philippines (CEGP), meanwhile, said that the anti-terror law "only legalized harassment and abuses among Filipinos."
"We saw how they weaponized this to further attack critics and the press in its first year of implementation; we are currently seeing how they utilize this to demonize the opposition; and if this would continue, we would see more and worse in the future," it added.
Youth groups pointed out this might be used to target opposition and dissenters, especially as we near the upcoming elections. This is further amplified by the prevalence of disinformation and historical revisionism that is already being seen online.
"ATL is at risk of being used as a ploy for relentless attacks against anyone considered nonaligned to their political ambitions, especially during the upcoming 2022 national and local elections. It is our fear that this law will only endanger further those that campaign and those that will run on a platform that criticize undemocratic actions that the current government is taking," ChPSS PCU-Manila said.
The group added that the law might also limit civic spaces in educational institutions, citing "communist infiltration threats" to justify campus militarization and suppression of academic freedom.
Among the examples they shared was the termination of the government's decades-long accord with the University of the Philippines that prevented state forces from entering its campuses. Department of National Defense secretary Delfin Lorenzana justified the termination by citing reported in-campus recruitment activities of the Communist Party of the Philippines and the New People's Army, which the Duterte government branded as terrorist organizations.
While some voided parts of the law have eased fears, many of the youth groups appealed for the junking of the law to further protect ordinary Filipinos from repercussions when they voice out.
"Nasa record ng gobyerno na ang binabansagan nitong terorista ay ang mga progresibo, kritiko, aktibista, at sinumang tumututol sa mga anti-mamamayang patakaran ng estado. Walang Pilipinong ligtas, lalo ang mga ordinaryong mamamayan na walang kalaban-laban at walang bitbit kundi ang kanilang lehitimong hinaing…. Dahil dito, hindi sapat ang panaka-nakang aksyon ng Korte Suprema. Hindi dapat hayaan na lalong maging mabangis ang pasistang estado. Dapat ibasura sa kabuuan ang Terror Law ni Duterte," the Kabataan party list said.
(It's in the government's record that what it brands as terrorists are progressives, critics, activists, and whoever dissents against anti-people state policies. No Filipino is safe, especially ordinary citizens who are helpless and empty-handed save for their legitimate calls…Because of this, the Supreme Court's action is not enough. It should not allow the fascist state to fester. The whole terror law of Duterte should be junked.) – Rappler.com
@SamanthaBagayas
Samantha Bagayas is a community and civic engagement specialist under MovePH, Rappler's civic engagement arm. Aside from writing stories about movements and civic initiatives, she works with movers and campus journalists across the Philippines to amplify issues affecting their communities.
More from Samantha Bagayas
Philippines, including NCR, now minimal risk for COVID-19 | Evening wRap
'We don't deserve mere consolation from Supreme Court' – lawyers vs anti-terror law
Philippine opposition laud 'partial victory' in anti-terror law ruling
Anti-terror law parts declared unconstitutional only 'minimal,' says Año
More on Philippine anti-terrorism law
Supreme Court of the Philippines
Senatorial bet declared nuisance by Comelec gets SC relief
SC affirms dismissal order, perpetual disqualification penalty vs Pichay
Supreme Court moves 2020/2021 Bar Exams to February
Paracetamol shortage amid rising COVID-19 cases? | Evening wRap
More on Supreme Court of the Philippines


DESCRIPTION (provided by applicant): High adiposity is a major risk factor for a number of diseases, including postmenopausal breast cancer. It has been suggested that adulthood weight gain is more strongly associated with postmenopausal breast cancer than current weight. Prospective cohort studies suggested that approximately 20% of the postmenopausal breast cancer cases are attributable to adulthood weight gain. The increased postmenopausal breast cancer risk in women with high adiposity is likely to be attributed to multiple metabolic disturbances. Metformin, a widely used antidiabetic drug, exerts favorable effects on multiple metabolic disturbances which may lead to reduction of breast cancer risk in women with high adiposity. In addition, metformin may work directly in mammary tissue through the activation of the AMP- activated protein kinase (AMPK) signaling pathway, leading to an antiprolierative effect and induction of apoptosis. Recent case control and cohort studies found that treatment with metformin appears to substantially reduce the risk for development of cancer in diabetics, including breast cancer. There are a large number of ongoing clinical trials of metformin in breast cancer patients. However, the concurrent or prior breast cancer treatments in these studies hinder the evaluation of metformin as a single agent for breast cancer prevention in at risk healthy women. We propose to conduct a Phase II randomized, double-blind, placebo-controlled trial of metformin in overweight/obese premenopausal women who have experienced moderate to significant adulthood weight gain, have high breast density and are insulin resistant. This study population is at increased risk for postmenopausal breast cancer and has a high prevalence of metabolic disturbances associated with breast cancer risk. The overall hypothesis is that metformin intervention can modulate risk features of the breast and metabolic disturbances associated with breast cancer risk in women with high adiposity. The specific aims for this project are 1) to determine the effect of metformin intervention on breast density, 2) to determine the effect of metformin intervention on metabolic disturbances and body weight/composition, and 3) to explore the application of metabolomics as a systems biology approach to assess the chemopreventive mechanisms of metformin. Our proposed study represents the initial steps in clinical evaluation of metformin for modulation of breast cancer rik in a population at risk for multiple diseases. Findings from this study will have wide public healt impact because of the growing overweight and obese populations. With its demonstrated effect in reducing the incidence of diabetes in high risk adults, metformin would have a high level of acceptance and uptake in at risk women with high adiposity if it has also been shown to exert favorable activities in breast cancer risk reduction. Considering the challenges in maintaining a healthy life style by the majority of general public and the pleiotropic activities of metformin fo multiple metabolic disorders, metformin could be developed as an integrated pharmacological approach for at risk women with high adiposity for prevention of multiple diseases.


SM Bromo Hotel is the hotel recommendation for tourists who traveled to Bromo. Many people know that Mount Bromo is the tourist icon in East Java. This place is popular because of the sunrise. The sunrise in Bromo is famous all around the world. As a tourist area the travel Bromo destination that located in the Bromo Tengger Semeru National Park is located in the four territorial namely District Probolinggo, Malang, Pasuruan, and Lumajang.
The location of SM Bromo Hotel is close to the Mount Bromo. This hotel is a 2 stars hotel. The location is in Krajan, Ngadas Village, Sukapura, Probolinggo, East Java. This hotel is approximately has distance about 2 km from the crater of Mount Bromo. The windy tropical mountain climate is around 14 up to 18°C during the day and 6 up to 10°C at night. The view around Bromo provides the wonderful view of the cliffs and the fresh mountain breeze and airy from the mountain. The high peak of Mount Bromo creates a magnificent sight in midnight to enjoy the sunrise that is spectacular and the amazing sunset.
It is a big dream to have a peace and great weekend or fun holiday in Bromo even with spouse, family, friends, company gathering, and many events. The large room can be filled with four people per room with 2 beds. This hotel is also equipped with a television set and bathroom with hot water to make the tourists more comfortable to stay in Bromo. More than that, it is also completed with the dining table, living room and other services.
The other facilities in the hotel are included the room, the meeting room. This hotel is also completed with the stage open, the mountain bike, and the large parking area. It is available the rooms for drivers either. The restaurant and the large lobby are also available in this place. The facilities will add more comfort zone in relaxing to this hotel. The most popular facility that this hotel offered is the Volcano Tour. This hotel offers the tour to the volcano of Mount Bromo. This service is actually the service of transportation to enjoy the sunrise. This service is managed by the organization of local transportation in Bromo that usually called Association of Jeep Bromo.
This hotel actually doesn't take the responsibility to the available of the jeep and the time in picking up. But SM Bromo Hotel can help to make the reservation of the jeep car.