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Published in 1964, it fast became an ideological bible for the emergent New Left. As Douglas Kellner notes in his introduction, Marcuse's greatest work was a 'damning indictment of contemporary Western societies, capitalist and communist.' Yet it also expressed the hopes of a radical philosopher that human freedom and happiness could be greatly expanded beyond the regimented thought and behaviour prevalent in established society. For those who held the reigns of power Marcuse's call to arms threatened civilization to its very core. For many others however, it represented a freedom hitherto unimaginable.
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Domino level 1 Solution, (Flyclops, LLC)
Here's a guide of level 1 in the iOS game Domino.
This tutorial will show the completion of level 1 to help you beat it quickly. It's a part of a complete Domino levels walkthrough that were created by players on iPhone, iPad or Android.
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EU's Rehn says France should stop raising taxes
PARIS (Reuters) - France has reached the point when it can no longer increase taxes without harming growth and costing jobs, the European Commission's economic chief Olli Rehn said in remarks published on Sunday.
Plans by Socialist President Francois Hollande to wring a further 6 billion euros out of the economy in taxes in the 2014 budget have angered businesses and households and prompted the IMF to warn that more tax rises could stifle a fragile economic recovery.
In an interview with weekly newspaper Le Journal du Dimanche, Rehn reiterated that proposed reforms by the government were going in the right direction, but were not far-reaching enough or being implemented sufficiently quickly.
When asked whether tax hikes should stop, Rehn said:
"Absolutely. The tax increases in France have reached their fateful point. Raising new taxes would break growth and weigh on employment," he said. "Budgetary discipline must come a reduction in public spending and not new taxes."
The French government on Friday rushed to assure tax-weary companies and consumers that a new form of green levy meant to encourage industries and households to cut energy consumption would not amount to new tax increases.
The announcement landed the same week taxpayers began receiving income tax bills, some of which have been inflated by past tax hikes or reductions in tax exemptions.
The French tax burden is already one of the heaviest in the world. At 44.2 percent of GDP, it ranks behind only Denmark and Sweden among the 34 members of the Organisation for Economic Cooperation and Development.
(Reporting by John Irish; Editing by Alison Williams)
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Saturday Night's storm system has moved well east now making for a beautiful Sunday with southwest winds. Surface Low over Oklahoma will move east dragging a cold front into the area overnight. Much cooler on Monday and Tuesday. Upper trough remains ...
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Investigators believe cigarette caused Beaumont house fire
BEAUMONT - Beaumont fire investigators believe a cigarette caused a fire that damaged a home Wednesday morning.The fire was reported at about 8 a.m. at the home in the 1300 block of Van Buren, east of MLK and south of the Port of Beaumont.
No one was hurt.
When firefighters arrived heavy smoke was coming from the attic near the back of the home.
Captain Brad Penisson said the fire started in a bedroom. He said it appears a cigarette ignited a mattress.
Flames and smoke damaged the mattress, a dresser and other items in the bedroom.
Firefighters quickly put out the flames and contained the fire to the bedroom. Fire, smoke and water damaged other parts of the house.
Penisson said three people live in the home. Two were at home when the fire broke out.
No one was injured.


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Putnam considers banning cigarette sales in pharmacies (video)
Legislators, health chief look to decrease smoking rates
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Putnam considers banning cigarette sales in pharmacies (video)
A campaign to prohibit tobacco sales in pharmacies has taken root in municipalities nationwide, with at least one Lower Hudson Valley county considering the ban. Putnam County Health Commissioner Dr.
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In this podcast, the Radio Free HPC team previews the SC14 Student Cluster Competition. This year a record 12 teams will face off to build the fastest HPC clusters under a carefully monitored power envelope.
Radio Free HPC Previews the SC14 Student Cluster Competition
Purdue Gears Up for Student Cluster Competition
Student Cluster Competition Sparks StartupHPC
Silicon Mechanics Sponsors Massachusetts Green Team
Call for Participation: HPCAC-ISC 2015 Student Cluster Competition
When Students Compete, the Whole HPC Community Wins
NICS Student Cluster Team Already Gearing up for SC14
Podcast: Dan Olds Reports Live from the Asia Supercomputing Challenge
Cray's John Lee on How Cluster Competitions Launch Careers
"We also discuss something I haven't talked about before with anyone else – how students can best take advantage of this experience after the competition ends. What doors does their participation open? How they should best pursue positions in business, research, academia, or even with HPC vendors? In this interview, John Lee describes what Cray is looking for in new hires, and how SCC experience pays off for prospective job candidates in a wide variety of fields."
Student Cluster Teams to Battle in Leipzig this Summer
ISC'14 will host a Student Cluster Competition, organized in collaboration with the HPC Advisory Council. Held during the ISC exhibition in Leipzig towards the end of June, the Student Cluster Challenge is not just an opportunity to showcase student expertise but is designed to encourage the next generation of students to take up the challenges of high performance computing.


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What would it mean to be an artist working in a sustainable Scotland in 50 years' time? This was the question asked of the ten artists who attended our Mull artist residency earlier this year. Join us for our last …
Here are some case studies about organisations working with Creative Carbon Scotland.
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Read how the Edinburgh International Book Festival reduced unnecessary print runs.
Learn how the Edinburgh Mela has addressed waste and audience travel.
Results and findings from a past Re-use and Recycle Day at Fringe Central.
We provide practical training and support in carbon measurement and reporting to enable arts organisations to run themselves more sustainably.
We initiate projects which engage and inspire organisations, artists and audiences to join the sustainability debate, using their imagination and influence to help build a more sustainable Scotland.
We connect the arts and sustainability, bringing together individuals and organisations working in Scotland through news, events and our Green Arts Portal.


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- Freeport murder suspect Damon Dixson taken into custody in Rockford
- Local gas station employee arrested for selling liquor to minor
- Renewable Fuel Standard delay 'a mixed blessing,' Bustos says
- Rockford delegation presents inaugural 'Rockford Award' to Norwegian Air
- Education in Illinois making slow progress, according to report
- Illinois GOP Congressional delegation: Obama's immigration plan undermines rule of law
- Suspect, 17, charged in Halloween hit-and-run in Roscoe
- Saint Anthony College of Nursing president to retire
- Man found guilty in deadly August 2013 crash at Mulford and Garrett Lane
- 'The Price is Right Live!' at Coronado March 1; tickets on sale Nov. 21
Police ID suspect in attempted child abduction
Online Staff Report
Police say they have identified a suspect in what is being called an abduction attempt that occurred on Rockford's west side Monday, Feb. 24.
According to police, a man in his 40s attempted to lure a group of juvenile girls into his pickup truck by offering them candy near Elm Street and Howard Avenue. The suspect was later spotted in the 200 block of South Central Avenue, near Ellis Arts Academy.
Police say they located the green Chevrolet pickup and the suspect Wednesday near Chestnut Street and Stewart Avenue.
As of this report, no charges have been filed and the suspect's name has not been released. Winnebago County State's Attorney Joe Bruscato's office is reviewing the case, authorities said.
Anyone with information is urged to call the Rockford Police shift commander at (815) 987-5824 or Crime Stoppers at (815) 963-7867.


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Original Article
Natural killer cells infiltrating human nonsmall-cell lung cancer are enriched in CD56brightCD16− cells and display an impaired capability to kill tumor cells
Article first published online: 17 JAN 2008
DOI: 10.1002/cncr.23239
Copyright © 2008 American Cancer Society
Volume 112, Issue 4, pages 863–875, 15 February 2008
Additional Information
How to Cite
Carrega, P., Morandi, B., Costa, R., Frumento, G., Forte, G., Altavilla, G., Ratto, G. B., Mingari, M. C., Moretta, L. and Ferlazzo, G. (2008), Natural killer cells infiltrating human nonsmall-cell lung cancer are enriched in CD56brightCD16− cells and display an impaired capability to kill tumor cells. Cancer, 112: 863–875. doi: 10.1002/cncr.23239
Publication History
- Issue published online: 1 FEB 2008
- Article first published online: 17 JAN 2008
- Manuscript Accepted: 4 SEP 2007
- Manuscript Revised: 10 AUG 2007
- Manuscript Received: 23 MAR 2007
Funded by
- Associazione Italiana Ricerca sul Cancro (AIRC)
- CIPE. Grant Number: 02/07/2004, CBA project
- Fondazione Banco di Sicilia
- Fondazione Italiana Ricerca sul Cancro (FIRC)
- Abstract
- Article
- References
- Cited By
- natural killer cells;
- nonsmall cell lung cancer;
- killer immunoglobulin-like receptor;
- membrane proteins;
- human
Despite natural killer (NK) cells being originally identified and named because of their ability to kill tumor cells in vitro, only limited information is available on NK cells infiltrating malignant tumors, especially in humans.
NK cells infiltrating human nonsmall cell lung cancers (NSCLC) were analyzed with the aim of identifying their potential protective role in an antitumor immune response. Both relevant molecule expression and functions of NK cells infiltrating NSCLC were analyzed in comparison with autologous NK cells isolated from either peritumoral normal lung tissues or peripheral blood.
The CD56brightCD16− NK cell subset was consistently observed as being highly enriched in tumor infiltrate and displayed activation markers, including NKp44, CD69, and HLA-DR. Remarkably, the cytolytic potential of NK cells isolated from cancer tissues was lower than that of NK cells from peripheral blood or normal lung tissue, whereas no difference was observed regarding their capability of producing cytokines. With regard to their localization within tumor, NK cells were found in tumor stroma, whereas they were not in direct contact with cancer cells.
For the first time NK cells infiltrating NSCLC have been characterized and it is shown that they are mainly capable of producing relevant cytokines rather than exerting direct cancer cell killing. Cancer 2008. © 2008 American Cancer Society.
Natural killer (NK) cells were originally identified on a functional basis as this designation was assigned to lymphoid cells capable of lysing tumor cell lines in the absence of prior stimulation in vivo or in vitro.1 The molecular mechanisms underlying the ability of NK cells to discriminate between normal and aberrant cells have been elucidated only during the past decade. Nowadays there is evidence that NK cell recognition of target cells is guided by the balance of activating and inhibitory signals given by different groups of surface receptors. The main activating receptors constitutively found on all NK cells in peripheral blood are NKG2D and the natural cytotoxic receptors NKp30 and NKp46,2 whereas NKp44 is inducible upon activation. All of these receptors are likely to recognize molecules that are up-regulated upon cellular stress.3, 4 With respect to inhibitory signals, human NK cells have been shown to express different human leukocyte antigen (HLA)-class I-specific inhibitory receptors. A family of these receptors, termed killer Ig-like receptors (KIR), recognizes shared allelic determinants of HLA class I molecules, whereas other receptors display a looser pattern of recognition and are characterized by a broad specificity for different HLA class I molecules (LIR1/ILT2) or recognize the HLA-class Ib HLA-E molecules (CD94/NKG2A).5–9 Accordingly, NK cells lyse target cells that have lost (or express low amounts of) MHC class I molecules. This event occurs frequently in tumors or in cells infected by some viruses such as certain herpesviruses or adenoviruses.
For many years NK cells have been considered a homogeneous lymphocyte population characterized by a strong cytotoxic capability. Today NK cells would appear rather as formed by various subsets that differ in function and, in part, in their surface phenotype. Human peripheral blood mononuclear cells contain around 10% of NK cells.10 The majority (≥95%) belongs to the CD56dimCD16+ cytolytic NK subset11–13: these cells carry homing markers for inflamed peripheral sites and express granule-associated perforin to rapidly mediate cytotoxicity.11, 12 A minor NK subset in blood (≤5%) is represented by CD56brightCD16− cells11–13: these NK cells lack or express low levels of perforin but secrete on activation both IFNγ and TNF in larger amounts than CD56dim NK cells.12, 13 Notably, the HLA class I allele specific KIR receptors are expressed on subsets of CD56dimCD16+ cytolytic NK cells, whereas the immunoregulatory CD56brightCD16− NK subset uniformly expresses CD94/NKG2A and lacks KIRs.12 Recent reports have shown that the CD56bright NK subset is enriched in all secondary lymphoid organs analyzed so far (lymph nodes, tonsils, and spleen).13
Although it is clear that NK cells are capable of recognizing and killing tumor cells in vitro, NK cells infiltrating malignant neoplasms have been poorly characterized. Similarly, the ability of NK cells to migrate in tumors, as well as their antitumor activity in vivo, have not been investigated in detail, especially in humans. In general, histological examinations performed in previous studies have shown that NK cells are not found in large numbers in advanced human neoplasms, with the exception of some renal cell carcinomas.14–18 The limited number of NK cells infiltrating tumors has hampered more extensive studies of such tumor-associated NK cells. Indeed, most of the previous studies (reviewed in Ref.2) have been performed using IL-2 activated NK cell lines, which are not equivalent to NK cells freshly isolated from cancer tissues. Nevertheless, the infiltration of NK cells appears to have prognostic value in gastric carcinoma,15 colorectal carcinoma,16 and lung carcinomas,14, 19, 20 as a relatively higher level of NK cell-infiltrate correlates with a better prognosis, thus suggesting relevant protective roles for NK cell infiltrate.
Lung cancer is currently 1 of the most common malignancies and nonsmall cell lung cancer (NSCLC) represents about 75% to 80% of all cases and its overall 5-year survival rate is less than 12%.21–23 Identification of new therapeutic strategies, including immunotherapy, is highly required. A deeper understanding of the immune response against NSCLC might pave the way for innovative clinical approaches. Remarkably, in this regard the infiltration of NK cells was found to indicate a favorable prognosis,19, 20 whereas the presence of tumor-infiltrating CD8+ T cells was not a predictor of patient survival.24, 25 However, the interpretation of these studies, as well as the development of rational NK cell-based therapeutic attempts, have been hampered by the lack of information on NK cells infiltrating NSCLC.
The purpose of the present study was to analyze NK cells infiltrating human NSCLC and to identify their potential protective role in antitumor immune response.
Tissue Samples and Cell Isolation
Samples were obtained from 28 untreated patients, without any other concomitant lung disease, who underwent surgical resection of NSCL cancer (Table 1). This study was approved by our Institutional Ethics Committee and patients gave written informed consent according to the Declaration of Helsinki. NSCLC specimens were incised immediately after removal and split into sagittal parts, half of which were paraffin-embedded to perform histology for clinical purposes, whereas the other half was processed either for single cell isolation or immunohistochemistry for NK cell localization within tumor tissue.
|Patient ID
|Diameter (mm)
|% bright
|adeno-squamous carcinoma
|squamous cell carcinoma
|squamous cell carcinoma
|squamous cell carcinoma*
|squamous cell carcinoma
|squamous cell carcinoma
|undifferentiated large cell carcinoma
|squamous cell carcinoma
|squamous cell carcinoma*
|squamous cell carcinoma
|squamous cell carcinoma
|squamous cell carcinoma
|squamous cell carcinoma
|squamous cell carcinoma
|squamous cell carcinoma
|squamous cell carcinoma*
Lung tissue samples were obtained immediately after surgical resection of their primary tumors at the Thoracic Surgery Department Ospedale Santa Croce and Carle (Cuneo, Italy) and Ospedale Santi Antonio and Biagio and Cesare Arrigo (Alessandria, Italy). For immunohistochemistry, tissue samples of primary tumors and surrounding normal tissue were snap-frozen in liquid nitrogen. For direct ex vivo isolation of tumor-infiltrating and peritumoral lymphocytes, both primary tumors and normal tissues were washed extensively with phosphate-buffered saline (PBS) to remove peripheral blood lymphocytes and were processed by mincing the tissue with operative scissors. Mechanically dissociated tissues underwent enzymatic digestion with 150 U/mL hyaluronidase and 250 U/mL collagenase type IV (Sigma-Aldrich, St. Louis, Mo). Single-cell suspensions were filtered through a 100-μm cell strainer (BD Labware, Mountain View, Calif), washed, and mononuclear cells (MNC) were isolated by Ficoll-Hypaque (Sigma) density gradient centrifugation. Similarly, peripheral blood MNC were isolated using Ficoll-Hypaque density gradient. Cells were either directly analyzed by flow cytometry or cryopreserved for further analyses.
To localize NK cells infiltrating NSCLC, 8-μm-thick slices were cut from frozen surgical samples of tumor. Sections were fixed for 5 minutes at −20°C in 100% acetone. After washing with PBS, endogenous peroxidases were blocked by incubating samples for 15 minutes with the peroxidase block from EnVision Kit (Dako, Glostrup, Denmark). After washing in water for 5 minutes sections were incubated for 30 minutes at room temperature with PBS plus 5% bovine serum albumin (BSA) (Sigma-Aldrich), 0.5 mg/mL human IgG (Sclavo, Siena, Italy), and 0.05% Tween 20. Afterward, sections were incubated for 90 minutes at room temperature with undiluted supernatant of NKp30 or NKp46 hybridomas (respectively, clone AZ20, IgG1, and clone KL247, IgM) produced in our laboratory. Isotype-matched mouse IgG were used as control.
After washing 3 times for 5 minutes with PBS plus 0.05% Tween 20, a biotinylated goat antimouse antibody (BIOSPA, Milan, Italy), diluted 1:800 in PBS plus 1% BSA and 0.05% Tween 20, was added. After 30 minutes at room temperature sections were washed 3 times for 5 minutes with PBS plus 0.05% Tween 20. Afterward, a streptavidin-horseradish peroxidase conjugate at a 1:300 dilution was added and sections were further incubated for 15 minutes at room temperature. After washing 3 times for 5 minutes with PBS plus 0.05% Tween 20, sections were stained with the AEC chromogen and the AEC substrate of the Ultravision Detection System (Lab Vision, Fremont, Calif). Counterstaining was performed with hematoxylin.
For evaluating the expression of HLA class I molecule in the NSCLC specimens, sections of paraffin-embedded tissues were used. Sections were heated at 75°C (4 minutes × 2) and treated with hydrogen peroxide before staining with anti-HLA class I mAb (HC-1O, IgG2a) for 30 minutes and biotin for 8 minutes.
Monoclonal Antibodies and Flow Cytometry
Analysis of cell surface markers was performed using the following mAbs in direct immunofluorescence assay: FITC-conjugated anti-CD3, PC5-conjugated anti-CD56, PE-conjugated anti-NKp30, anti-NKp44, anti-NKp46, and anti-NKG2A (Immunotech-Coulter, Fullerton, Calif); PE-conjugated anti-KIR2DL1, anti-KIR2DL2, anti-DR, anti-CD107a; FITC-conjugated anti-CD45/PE-conjugated anti-CD14 (Leucogate) (BD PharMingen, San Diego, Calif). APC-conjugated anti-CD56, FITC-conjugated anti-CD3, and PE-conjugated anti-CD16 were from Miltenyi Biotech (Bergisch Gladbach, Germany). Anti-NKG2D (clone ECM/217), anti-CD69 (clone FS3) and anti-2B4 (clone MA344) were produced in our laboratory.
Direct immunofluorescence staining was performed diluting fluorochrome-labeled mAb with 1 mg/mL human γ-globulin (human therapy grade from Biotest S.R.L., Milan, Italy), to block nonspecific FcR binding. Cells were then washed and the flow cytometric analysis was performed. For indirect immunofluorescence staining, nonspecific binding sites were saturated with human γ-globulin, and then the relevant mAb was added and incubated for 30 minutes at 4°C. After washing, PE-conjugated isotype-specific goat antimouse Abs (Southern Biotechnology, Birmingham, Ala) were added and incubated for 30 minutes at 4°C. Negative controls included directly labeled and unlabeled isotype-matched irrelevant mAbs. Cells were then washed and analyzed by flow cytometry. Perforin, IFN-γ, and TNF-α expression analysis were performed by PE-conjugated reagents (BD Biosciences-PharMingen) after cells were fixed in 1% paraformaldehyde and permeabilized with 0.1% saponin.
CD107a Assay
MNC from blood, tumor, and peritumoral samples were used as effectors in a CD107a assay; the K562 cell line was used as target. To detect spontaneous degranulation, a control sample without target cells was included.
An effector/target (E/T) ratio of 1:1 (2 × 105 effector cells: 2 × 105 target cells in a volume of 200 μL) was used. Anti-CD107a (PE-conjugated) was added in each well (8 μL/well) before incubation. Effectors and targets were then coincubated at 37°C for 4 hours; after the first hour monensin (Sigma), at a final concentration of 2 mM, was added to inhibit cell secretion, as previously described.26
At the end of coincubation cells were washed twice in PBS and stained with mAbs (anti-CD3 and anti-CD56) for flow cytometric analysis and surface expression of CD107a was assessed in NK cells.
51Cr Release Assay
To confirm the different ability of NSCLC-infiltrating NK cells in killing target tumor cells, NK cells from PB, tumor, and peritumoral tissues were compared in a standard 51Cr release assay. Briefly, 106 K562 cells were incubated with 100 μCi of Na251CrO4 for 90 minutes at 37°C, extensively washed, and finally cultured with the different NK cell populations for 4 hours at 37°C. Microculture supernatants were then collected and radioactivity counted on a gamma-counter (Beckman, Milan, Italy). 'Specific' 51Cr release is calculated on the bases of the ratio {(sample release − spontaneous release) / (total release − spontaneous release)}. Assays were performed in triplicate at the indicated effector-target ratios.
Cytokine Production
Paired samples of mononuclear cells from peripheral blood, tumor, and peritumoral tissues were incubated in culture medium alone or in culture medium supplemented with 10 ng/mL PMA and 500 ng/mL ionomycin at 37°C for 6 hours. Monensin was added at a final concentration of 2 mM. Cells were then washed, fixed, and permeabilized as described above, and finally stained with PE-conjugated anti-IFN-γ and TNF-α.
Statistical Analysis
Statistical analyses were performed using the GraphPad Prism v. 4.00 for Windows (GraphPad Software, San Diego, Calif). Statistical significance was evaluated by paired Student t-test.
NK Cells Infiltrating NSCL Cancers Are Abundantly Represented by Activated CD56brightCD16− Cells
NK cells were isolated from surgically resected cancer specimens and, as a comparison, from autologous peripheral blood (PB) and, whenever possible, from normal peritumoral lung tissues. After ficoll gradient separation only MNC were collected and analyzed for NK cell content. Whereas no differences in the CD4+/CD8+ T-cell ratio were appreciable between lung tissue and autologous PB MNC, the percentage of B cells was significantly increased compared with both PB and normal lung tissue. The remaining part of the CD3−CD56− cell fraction in MNC isolated from tumors was mainly represented by large and scattered cytokeratin+ cells. NK cells were identified as CD3−CD56+CD45+ cells and their total percentage within CD45+ MNC isolated from lung tumors was consistently lower (mean value, 4.6 ± SE: 1.25) than in MNC from the PB counterpart (mean value, 27.8 ± SE: 3) and was comparable to that in MNC from peritumoral lung tissue (mean value, 7.8 ± SE: 2.68) (Fig. 1A, left panel). Interestingly, the percentage of NK cells harbored within NSCLC directly correlated with the size of the resected tumors (P = .0012) (Fig. 1B). Nevertheless, NK cells isolated from NSCLC (NSCLC-NK) displayed a peculiar surface molecular pattern: most of the CD3−CD56+ NK cells infiltrating the tumor displayed higher levels of surface CD56 as compared with both PB-NK cells and peritumoral normal lung tissue NK cells (PLT-NK) (mean percentage value ± SE of CD56bright NSCLC-NK: 37.8 ± SE: 4.6; CD56bright PB-NK: 6.3 ± 1.3; CD56bright PLT-NK: 16.5 ± 4.4) (Fig. 1A, right panel, and Fig. 1C), whereas CD16 was consistently expressed on fewer cells (mean percentage value of CD16+ cells in NSCLC: 22 ± 3.3; in PB: 76.9 ± 5.9; in PLT: 55.5 ± 6.42) (Fig. 2). A similar surface phenotype characterized a minor subset of PB and peritumoral NK cells, suggesting a preferred pattern of migration into the tumor for this NK cell subset. A representative phenotypic pattern of NK cells isolated from the 3 different autologous tissues is depicted in Figure 2A. Remarkably, an evident surface expression of KIR was detectable in CD56brightCD16− tumor NK cells, whereas, as previously reported, the phenotypically identical CD56brightCD16− NK cells isolated from peripheral blood were KIR-negative. Notably, this was also true for CD56brightCD16− NK cells isolated from normal peritumoral lung tissue, which did not show KIR expression. However, when the total NK cell population was considered, the percentage of KIR expressing NK cells was significantly lower in NSCLC-NK (KIR2DL1: 16.7 ± 1.75; KIR2DL2: 26.2 ± 6) as compared with peripheral blood NK cells (KIR2DL1: 34.4 ± 3.6 KIR2DL2: 35.8 ± 6.1) and to NK cells from peritumoral lung tissues (KIR2DL1: 33 ± 3.5; KIR2DL2: 31.1 ± 3.5) (Fig. 2). Conversely, CD94/NKG2A, another inhibitory NK cell receptor, was expressed in NSCLC-NK cells in a significantly higher percentage (NKG2A+ cells in NSCLC: 65.9 ± 8.1; in PB: 47 ± 8; in PLT: 49.5 ± 7.8). Regarding activating NK receptors, other than CD16, only NKp44 showed a significantly higher expression (mean percentage value of NKp44+ cells in NSCLC: 18.2 ± 4.4), whereas it was virtually undetectable in both PB-NK and PLT-NK cells. Conversely, neither NKp30, NKp46, nor NKG2D showed significant differences in their surface expression. It is noteworthy that NKp44 is usually induced on PB-NK cells upon cytokine activation and its expression ex vivo has been previously detected only in NK cells derived from inflamed tonsils.27 Accordingly, NSCLC-NK cells displayed increased levels not only of NKp44 but also of HLA-DR and CD69, both antigens expressed by activated NK cells.
NK Cells Localize in the Stroma of NSCLC
The finding that NK cells isolated from NSCLC tissues uniformly displayed a characteristic surface phenotype ruled out that NK cells isolated from cancer tissues might be derived from blood contamination, but rather represented a true cell infiltrate.
Thus, we investigated the localization of infiltrating NK cells within cancer tissues. To this end, NSCLC specimen sections were analyzed by immunohistochemistry using mAbs directed against NKp46 and NKp30, whose expression is restricted to NK cells. As shown in Figure 3, NSCLC-NK consistently presented a peculiar distribution, restricted to the intratumoral fibrous septa and to the interfaces between stromal cells and surrounding tumor cells. Remarkably, NK cells detected within tumor tissues consistently did not appear to be in direct contact with cancer cells.
NSCLC-NK Cells Contain Low Amounts of Perforin and Do Not Express CD107a
Perforin is a potent cytolytic pore-forming protein constitutively contained in cytoplasmic granules of almost all PB-NK cells. The remaining PB-NK cells (≤5%) are represented by CD56brightCD16− cells, expressing low levels of lytic granules. We therefore analyzed the perforin content of NSCLC-NK cells. In agreement with their surface phenotype, NK cells isolated from cancer tissues displayed a lower content of perforin if compared with autologous PB-NK and PLT-NK cells (Fig. 4, upper panels).
Because cytolytic activity depends not only on the content of lytic granules but also on granule polarization and exocytosis, we further investigated the surface expression of CD107a (LAMP-1). CD107a represents an excellent surface marker, revealing the occurrence of granule exocytosis. Flow cytometry analysis clearly showed that, despite their activated phenotype and their intratumoral localization, NSCLC NK cells were completely negative for CD107a surface expression (Fig. 4, middle panels). This finding might be interpreted either as a peculiar deficiency of CD107a or, alternatively, as an indication that no interaction/recognition of tumor target cells has occurred in vivo. Along this line, in preliminary in vitro experiments we observed that CD107a was detectable on NK cell surfaces up to 18 hours after recognition of cancer cells (not shown).
CD56brightCD16− NK Cells Infiltrating NSCLC Can Express KIR
KIR are expressed on a considerable fraction of CD56dimCD16+ NK cells, whereas they are in general absent on CD56brightCD16− NK cells. Surprisingly, CD56brightCD16− NSCLC-NK cells were found to express KIR (Figs. 2A, 4, lower panels). Therefore, we asked whether KIR+CD56brightCD16− NSCLC-NK cells were derived from KIR−CD56brightCD16− PB-NK cells upon migration into tumors. Alternatively, they could derive from a KIR+CD56dimCD16+ PB-NK cell subset upon up-regulation of CD56 molecules, possibly induced by local, intratumoral activation. Because CD56dimCD16+ express high levels of perforin, whereas CD56brightCD16− do not, we analyzed perforin content in CD56brightKIR+ NK cells. Indeed, perforin was expressed at the same low level on either CD56brightKIR+ NSCLC-NK cells or on CD56brightKIR− PB and PLT-NK cells, thus suggesting that CD56brightCD16−KIR+ NSCLC-NK cells would derive from CD56brightCD16−KIR− PB-NK cells and not from CD56dimCD16+ KIR+ PB-NK cells (Fig. 4). In addition, similar to the whole NK cells infiltrating NSCLC, also the CD56brightKIR+ subset failed to express CD107a, thus ruling out the possibility that the low levels of perforin could be related to recent degranulation that might have occurred in vivo before tumor resection. Conversely, the higher amount of perforin detected in PLT-NK cells excluded that tissue processing might be responsible for the low perforin content.
These data suggested that CD56brightCD16− NK cells can acquire KIR expression within tumor tissues, possibly as a consequence of tumor microenvironment-derived signals.
NSCLC-NK Cells Exert Low Cytolytic Activity But Are Competent for Cytokine Production
Our data indicated that NK cells present in NSCLC, although expressing normal levels of activating receptors, were characterized by a low amount of perforin. In this context the cytokine production was analyzed in parallel with cytolytic activity.
Cytotoxic function has recently been assessed by flow cytometry on the basis of the cell-surface mobilization of CD107a (LAMP-1).28–31 The CD107a assay has been shown to strictly correlate with the classic Cr51 release assay (Ref.31 and our current data, not shown). By means of the CD107a assay we could comparatively analyze the cytolytic activity of NK cells isolated from NSCLC, PLT, and PB of the same patients. These studies indicated that NSCLC-NK cells display a significantly lower cytotoxic activity against the NK cell susceptible K562 cell line (Fig. 5A). Conversely, no significant differences were observed between PB-NK cells and PLT-NK cells, indicating that the NK cell isolation procedure from solid tissues did not affect cell viability and function. As might be predicted, we found an inverse correlation between the percentage of CD56brightCD16− NK cells in the tumors and the level of cytolytic activity, measured as CD107a surface expression upon incubation with K562 target cells (Fig. 5B). To further confirm that enzymes used in tumor digestion were not responsible for the observed functional difference, PB-NK cells were also exposed to the same enzymes. PB-NK cells exposed or not to the enzymes displayed similar CD107a expression after coculture with K562 target cells.
Finally, we analyzed in 3 patients the cytolytic function of NK cells isolated from the distinct districts by chromium release assay. As shown in Figure 5C, the radioactive assay confirmed that NK cells isolated from NSCLC showed a reduced ability to kill target cells compared with PB- and PLT-NK cells.
Because NK cells isolated from NSCLC could express KIR, we analyzed whether the expression of HLA class I might dictate the functional behavior of infiltrating NK cells. HLA class I molecules were always expressed in the 7 NSCLC analyzed, although different levels of expression were detectable in the distinct cancer specimens. In general, squamous cell carcinomas, particularly the most differentiated histotypes, presented a higher and more homogeneous expression of HLA class I molecules than adenocarcinomas and adenosquamous carcinomas (Fig. 3D). However, the degree of HLA class I expression in the specimens analyzed showed no correlation with the cytolytic ability of NK cells infiltrating the single tumors. Nevertheless, we cannot rule out at this time that deletions of specific HLA class I alleles might hypothetically influence NK cell functions.
On the other hand, when the same NK cell subsets were analyzed for their ability to produce IFN-γ and TNF-α, an efficient cytokine production was observed both in NSCLC-NK cells and in the other NK cell populations analyzed (Fig. 5B). These results suggest that NK cells infiltrating NSCLC are not anergic and are fully competent for relevant cytokine release.
In the present study we show that NK cells can infiltrate NSCLC. Our data indicate that these NK cells display particular phenotypic features and that they are poorly capable of tumor cell killing, whereas they release abundant cytokines.
It is frequently assumed that tumor rejection is mainly the result of cytotoxic lymphocyte-mediated killing of the tumor cells. However, recent studies have indicated that the tumor rejection process may be a more complex event. For instance, T cells displaying cytolytic activity but unable to produce IFN-γ rarely reject tumors, whereas IFN-γ or other lymphocyte-derived cytokines such as TNF-α, IL-4, or IL-10 contribute to tumor rejection by inhibiting tumor stroma formation and tumor-induced angiogenesis.32
Soluble mediators released by NK cells are also relevant during the crosstalk between NK and dendritic cells (DCs), because it has been widely demonstrated that NK cells are able to induce DC functional maturation and consequently a more efficient adaptive immune response. This might be particularly important for evoking an adaptive immune response against cancer cells. Indeed, the absence of pathogen-related molecules and inflammation, at least in the early phases of cancer development, does not allow DC activation and, as a result, an effective antigen-specific T-cell response.
It has recently become manifest that an intricate communication network between the innate and adaptive immune system exists in vivo that can also activate NK cells, which might function as potent regulators of T-cell responses.33–38 Thus, a lower cytolytic activity in NSCLC-NK cells does not necessarily mean an ineffective anticancer activity, because NK cell cytokine production might be as relevant as cytotoxic functions in controlling cancer cell growth. Nevertheless, we found that larger tumors contained a higher percentage of NK cells than smaller tumors, thus challenging the idea that NK cells should exert a protective role during tumor cell growth. Recent data have indeed demonstrated that NK cells can also be detrimental during a productive immune response, either via the release of immune suppressive cytokines or by specifically inhibiting T-cell proliferation by direct interaction with T cells.39–41 Conversely, the infiltration of NK cells had been previously reported to correlate with a more favorable prognosis.19, 20 A more extensive characterization of NK cell-derived cytokines released locally during the antitumor immune response is now required to better elucidate the role of NK cell infiltrate within NSCLC.
A similar pattern of NK cell infiltration, characterized by abundant CD56brightCD16− NK cells with low cytolytic activity, has been reported in renal cell carcinoma,17, 18 suggesting that a prominent regulatory role of infiltrating NK cells might be a common feature of the antitumor immune response. The finding of a comparable amount of NK cells in tumor and peritumoral tissues could be explained by a low capability of NK cells to migrate toward chronically inflamed tissues, such as cancer; however, peritumoral regions might not be considered a true normal tissue, being influenced by the particular, tumor-associated, chemokine microenvironment.
In line with our finding that NK cells localize primarily in tumor stroma, it has been previously postulated that extracellular matrix proteins, present in the stroma surrounding the tumor blood vessels, might act as a barrier preventing direct NK-cell–tumor-cell contact.42–44 However, ultrastructural studies showed that NK cells display a marked ability to alter their shape, thus facilitating their extravasation and intratumor migration.45, 46 This would question the extracellular matrix proteins as a true physical barrier. Alternatively, it might be possible that a chemokine environment produced by stromal leukocytes might provide anchorage signals to tumor-infiltrating NK cells. For instance, it has been suggested that heterodimerization of the chemokine receptor CCR5, ie, the receptor of MIP-1β, leads to an adhesive signal and to the arrest of leukocytes within tissue.47 Consistent with our present findings, only CD56bright CD16− PB NK cells express CCR5,11 which might explain their accumulation in tumor tissues. In fact, like other components of the innate immune system present in the circulation (such as neutrophils and monocytes), all NK cells may be attracted to areas of inflammation. Nevertheless, the chemokine receptor repertoire of CD16+ NK cells is similar to that of neutrophils and these cells may thus be similarly attracted to sites of acute inflammation. With the exception of CCR7, the chemokine receptor pattern expressed by CD56brightCD16− NK cells would appear similar to that of monocytes. These chemokine receptors may serve for migration and arrest of the cells into sites of chronic inflammation, such as cancer.11, 48
Another interesting finding of this study is the presence of KIR on NSCLC-CD56brightCD16− NK cells, because PB as well as secondary lymphoid organ CD56brightCD16− NK cell subset uniformly lack KIR. However, KIR can be promptly up-regulated by cytokine activation on both secondary lymphoid organ NK cells and PB-NK cells.27, 49 Thus, there is increasing in vitro evidence that activation can convert CD56brightCD16− NK cells into effectors analogous to blood CD56dimCD16+ NK cells. In line with these findings, our present data suggest that up-regulation of KIR on CD56brightCD16− NK cells can occur also in vivo, most likely because of a proinflammatory cytokine microenvironment due to local immune reactions. It might be argued that KIR expression on CD56bright NK cells might be explained as CD56 up-regulation on KIR+ NK cells, rather than the other way around. Indeed, although CD16 can be down-regulated on NK cells upon cytokine activation, as previously demonstrated,50, 51 perforin was absent on CD56brightKIR+ NK cells infiltrating the tumors, thus suggesting that perforin, a potent lytic molecule, is acquired after KIR, a self-protective receptor mechanism, during NK cell differentiation. Further investigation, beyond the scope of this study, should aim at clarifying whether inflamed tissues, including cancers, might be colonized by NK cells in an early developmental stage and might thus represent a site for NK cell terminal maturation and self-tolerance acquisition.
In conclusion, we have shed some light on NK cells infiltrating human cancers, analyzing for the first time NK cells in NSCLC. The finding that NSCLC-infiltrating NK cells are not merely killer cells but can mainly act as producers of relevant cytokines, either productive or detrimental for the antitumor immune response, might open new perspectives for manipulating these innate effector cells during immunotherapeutic strategies. Moreover, because recent findings suggest that activation can convert CD56brightCD16−KIR− NK cells, able to mainly secrete cytokines, into CD56dimCD16+KIR+ NK cells with higher cytolytic activity,49, 52 the key to successful NK cell-based therapies might also depend, among other factors, on new tools for a sustained in vivo activation of NK cells.
The authors thank Drs. Rita Rotondo and Rosa Maria Lantermo for expert assistance in immunohistochemistry and Antonella D'Agostino for technical support and suggestions.
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£2,060 pcm
2 bedroom flat to rent HEATHFIELD PARK, London, NW2
Checkmate Estate are proud to present a modern newly decorated and fully furnished two double bedroom flat in Zone 2. Centrally located in the heart of Willesden Green. This first floor flat includes a living space, kitchen, bathroom and parking. More details ›
£350 pw
2 bedroom flat to rent Heathfield Park
This is a modern two double bedroom apartment in a newly built development on a quiet residential street in Willesden Green. The apartment has a modern kitchen and bathroom and an open plan kitchen lounge. The decor is neutral and there is a combination of wood flooring and carpets. There is a pr... More details ›
£550 pw
3 bedroom flat to rent Walm Lane, Mapesbury Conservation Area, London, NW2
Occupying the top two floors, the apartment has been extended and refurbished to a high standard by the current owner to create an exceptional home providing flexible living accommodation including an L shaped Lounge-Diner and large kitchen Breakfast Room. (contd...) More details ›
£800 pcm
1 bedroom apartment to rent St. Gabriels Road, London
Lords Associates present a cosy studio which forms part of a large house share located a few minutes walk from Willesden Green Station.New on the market and reasonably priced, this studio is sure to be let soon.Studio comprises of double bedroom, desk with chair, storage space, ensuite with More details ›
£550 pw
4 bedroom house to rent Lechmere Road, Willesden, London
A very nicely presented 4 double bedroom, 2 bathroom end of terrace house. The spacious accommodation comprises of westerly aspect reception with wood flooring and kitchen/ diner giving immediate access to private use of rear garden approx. 50ft. Part furnished. CREDIT CHECK FEE ONLY. NO ADMIN F... More details ›
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Capital Markets
Company Overview of Spencer Clarke LLC
Company Overview
Spencer Clarke LLC is a boutique investment banking firm that offers financial advisory and brokerage services. The firm provides merger and acquisition, private equity, debt placement, initial public offering, buyout, market underwriting, and corporate and financial advisory services. Additionally, it offers brokerage services. Spencer Clarke LLC was founded in 1997 and is based in New York, New York.
410 Park Avenue
Suite 1500
New York, NY 10022
United States
Founded in 1997
Key Executives for Spencer Clarke LLC
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Corsair Gaming M65 RGB game mouse review
MFAA Multi-Frame Samples AA Explored - Guide
GSKILL Phoenix Blade 480GB PCIe SSD Review
Corsair Gaming H1500 Dolby 7.1 headset review
GALAX GeForce GTX 970 EXOC Black Edition review
Guru3D Contest 2014 - Win a Gigabyte GTX 980 G1 Gaming
Call of Duty Advanced Warfare VGA graphics performance benchmark review
DeepCool Maelstrom 240 review
Guru3D Rig of the Month - October 2014
GALAX GeForce GTX 980 SOC review
ASUS GeForce GTX 670 DirectCU II TOP review
Posted by: Hilbert Hagedoorn on: 05/09/2012 02:00 PM [ 0 comment(s) ]
We review the ASUS GeForce GTX 670 DirectCU II TOP edition. The DirectCU II TOP editions come factory overclocked pretty intensely towards 1058 MHz on the GPU base clock and a whopping 1137 MHz on the boost frequency. Even with that factory overclock, the card remains completely silent. Check out this review.Read article
« GeForce GTX 670 2 and 3-way SLI review · ASUS GeForce GTX 670 DirectCU II TOP review · EVGA GeForce GTX 670 SC review »


text: MSOE Driver Authorization Request Form PDF 6-16-14.pdf This form must be completed by any student, staff, or faculty who wishes to drive a University owned or operated vehicle. If you have any questions, please contact Nick Seidler in Student Life. firstname.lastname@example.com 414-27... MSOE Driving Policy 6-16-14.doc MSOE takes the safety of its students and employees very serious. We want our employees and students to be safe at all times – whether they are on-campus, off-campus or traveling to an off-campus location.... MSOE Student Travel Guidelines 2014.docx Student organizations, club sports, or student competition teams that are traveling within and/or outside of the Milwaukee area are required to follow these guidelines. If any questions arise, please contact Nick Seid... CCID Games A list of games that a student can check out at CCID


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Wellness House
Wellness House Wellness House 131 N. County L
Hinsdale, IL 60521
Not Available
Not Available
Other->Social Services
SIC Code:
8322 - Individual and Family Services
Full company description is available with the free trial.
Poll Question
Date Created
Current Result
Additional Info:
Wellness House, is a company that works within the Social services. This Hinsdale, IL-based business. Their profile on Lead411 presents significant contact information such as cfo contacts, phone numbers, linkedin data, and Wellness House email format addresses with the @wellnesshouse.org domain as well as quality contact info regarding Wellness House's CEO . They have their head office in Hinsdale, IL. If you sign up for our free trial you will see our firstname.lastname@example.com addresses.
Company Background:
Full company description is available with the free trial.
Similar Companies:
YMCA of the USA
YMCA of the USA, is in the Social services industry. Their main office can be found in Chicago, IL, and they can be contacted through YMCA of the USA email using the domain @ymca.net format, some important contact information like linkedin data, phone numbers, contacts for cfos, etc of which can be found on their Lead411 profile. If you sign up for our free trial you will see our firstname.lastname@example.com addresses.
Methodist Youth Services
If you don't want to waste too much time looking for company information regarding Methodist Youth Services, a Social services company, check out their Lead411 profile. Our profiles have linkedin data, phone numbers, cfo contacts, and more. It contains helpful contact information regarding top company officials, including that of Methodist Youth Services's CEO Toleda Hart, and other Methodist Youth Services email format addresses within the @myschicago.org domain. Methodist Youth Services is based in Chicago, IL. If you sign up for our free trial you will see our firstname.lastname@example.com addresses.
Covenant Retirement Communities, Inc.
This member of the Social services industry is located in Skokie, IL and you can find important contact information regarding significant company contacts on their Lead411 profile like linkedin, phone numbers, facebook and cfo details. The profile also contains Covenant Retirement Communities, Inc. email addresses which have a domain of @covenantretirement.org format. If you sign up for our free trial you will see our firstname.lastname@example.com addresses.
Company Directory > Wellness House


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3 Apartments For Rent in Calumet Park, IL
Arkadia Tower
- Chicago, IL
- Work 1-877-442-1712
- 41.879180073738 -87.646811529994
Belmont Tower Apartments
Featured Property Amenity
- Chicago, IL
- Work 1-866-548-0417
- 41.940403 -87.642738
Cityfront Place
Watch Video About This Property
- Chicago, IL
- Work 1-877-316-3006
- 41.889373809099 -87.617735043168
Riverdale, IL 60827
Whistler Crossing
- FREE heat and water
- Townhomes - 2 free assigned parking spaces
- Private decks or patios
- FREE parking spot
- Laundry room
- Cable and high speed internet access
Whistler Crossing in Riverdale, IL is located at the intersection of Lowe Ave and 138th St with convenient access to I-57. Mid-rise apartment homes and townhomes available. New construction on select units. Secure access, energy star appliances, ADA units available. FREE heat and water, private decks or patios, laundry and FREE parking spot.
Chicago, IL 60827
13300 S Indiana Avenue - Pangea Apartments
- Studio-3 Bedrooms
- Beautifully Rehabbed
- Condo Quality
- Air Conditioning
- Hardwood Floors
- Kitchen Appliance
Enjoy the premium amenities and Pangea difference with these beautifully rehabbed 13300 S Indiana Apartments! Amenities include air conditioning, kitchen appliances, hardwood floors, uncovered parking, 1.5BA & and eat-in kitchen in some units. Pet friendly.
Riverdale, IL 60827
13905 S Clark Street - Pangea Apartments
- Specious 1 Bedroom Apartments in Riverdale, IL
- In-unit Washer & Dryer Hookups
- Balconies
- Free Heat in select Units
- Appliances
- Uncovered Parking
13905-37 S. Clark Street & 69-71 W. 140th street is a 60 unit 1 bedroom apartment complex located on a tree lined street in Riverdale, IL. In-unit washer & dryer, balconies & individually controlled heat & c/a. Tenants pay all apartment utilities including heat and electric. Owner pays common electric and water. 21 miles south of Chicago Loop, walking distance to Riverdale Metra Train Station, next to Dolton, Harvey, Blue Island, close to I-94, I-57, schools, shopping, restaurants & parks.
Other Calumet Park Apartment Search Options
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View all Greater Chicago Area Apartments
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text:
internships jobs near Groton, CT
Business Manager, PROS (INVIVO) Northeast(132797)
Philips- Norwich, CT
Your Challenge: Philips Healthcare is seeking and experienced Northeast Territory Manager for our Radiation Oncology Division. The PROS Territory Manager will be responsible for...19 days ago from philips
Director of Technology - Strategy, Ecommerce, LAMP stack
Cybercoders- Exeter, RI
Director of Technology - Strategy, Ecommerce, LAMP stack We are a small and very stable e-commerce company in a niche market. We are currently looking to replace our Director of...25 days ago from CyberCoders
Technical Customer Support Chat/Voice Rep TeleTech@Home
TeleTech Work@home- Coventry, RI
Technical Customer Support Chat/Voice Rep ~ TeleTech@Home Technical Customer Support Chat/Voice Rep ~ TeleTech@Home (018D8) @Home, United States US You must install the Adobe...30+ days ago from TeleTech Work@Home
Project Manager, Project Coordinator, Ariba, Sharepoint, Meeting Minu
Sunrise Systems- Groton, CT
Please mail your resume to rajivsunrisesys.com Only W2 Candidates Title Catalog Enablement Project Management Location Groton, CT Duration 06 Months Meeting Type In Person...30+ days ago from Dice
Generous B2B Sales Position
BCE- Westerly, RI
Company Description: BCE is founded on the philosophy of providing our clients total payment solutions, with custom tailored electronic payment systems that meet the unique,...24 days ago from ZipRecruiter
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Philips- Norwich, CT
students are not eligible for Philips internships. We are always looking to build relationships with top talent in the core skills areas that drive our organization to...5 days ago from philips
Intern with Mystic Schooners Baseball!
Mystic Schooners Baseball- Groton, CT
Mystic Schooners 2015 Internship Program Mystic Schooners Baseball is a 501C3 non-profit franchise residing in Mystic, CT. We are a summer collegiate team and the only remaining...9 days ago from Barefootstudent
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Liberty Mutual- Norwich, CT
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Connecticut Water Service- Clinton, CT
Reporting to the Water Treatment Supervisor the Water Treatment Plant Intern will provide world class service to our employees, customers and shareholders by working alongside...30+ days ago from Connecticut Water Service, Inc.
Email jobs like this to me
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Community Outreach Meal
Tuesday, September 11, 2012
5:00 pm - 7:00 pm
First Lutheran Church
First Lutheran Church in Galion will have a Community Outreach Meal on Tuesday, September 11th at 5pm.
« Back to Calendar
- December 13thBibleWalk "Christmas Revelation 2020:Do You Hear What I Hear?"
- December 13th"Prepare the Way" The Answer Generation
- December 14thMusical - The First Noel
November 29th


text:
Stainless Steel Product
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Suzon Steel (Prime Industries) a state of the art company is located Rajkot in Gujarat (India). The company was estallished in 2002's with the objective of quality stainless steel products and providing customer satisfactions.
Today Prime Industries is one of the largest hardware manufacturer in western India with the wide range of hardware products each product is passing through rigorous quality test. The company's initiative towards total quality management by it's own quality control department.
Prime Industries with constant dynamism, innovation and expansion with technological upgradation is moving ahead with its time-tested motto of product quality and customer satisfaction. In the new global scenario Prime Industries is continuously striving to be a customers driven organization marketing it's product at most competitive prices...


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Nearly a dozen charges against Edward Williams Adams, 18, last Sunday were not enough to keep the Manteca man behind bars.
WESTON RANCH – A high school and a community came together Wednesday to pay tribute to one principal and welcome another.
Not a single one of the contestants left in the Manteca Idol contest were anywhere near being born when the 70s disco craze hit with full force.
The "Caring for the Caregiver" symposium is scheduled for Saturday, Nov. 14, at Stockton's Lexington Plaza Waterfront Hotel, 110 W. Fremont St.
Scouting for food is a national canned food drive put on by the Boy Scouts of America.
The Lifestyle Outlets at Manteca set the pace for new construction starts in October with three new buildings getting underway with a combined value of $4.9 million.
The shackles and the stripes that Vince Hernandez was proudly wearing inside of the lobby of Bank of Stockton Thursday wasn't so he could stretch the mileage of his Halloween costume.
The perennially popular Holiday Luncheon and Crafts Faire sponsored by the St. Anthony School Parent-Teacher Group is bigger and better this year.
The darkest park in Manteca once the sun goes down?
"You should know your kids better than we do," is the theme of a gang poster being distributed to businesses around the community by Manteca officers Ranch Johnson and Sgt. Danny Erb. Despite the cutback in officers Sgt. Erb said the department is still doing its best to keep gang activity in Manteca at a minimum. The printing of the posters was made possible through the non-profit Manteca Police Chief's Foundation.
A "historic tour" of the old section of East Union Cemetery will be offered on Veteran's Day, Nov. 11, from 10 a.m. to 4 p.m.
The buyers of 18 future custom homes along Woodward Avenue expected to be built sometime in the next three years will ultimately pay $100,530 in a public safety endowment fees.
The official kick-off for the next Relay for Life in Manteca will be held today from 6 to 8 p.m. in the Manteca High School Cafeteria.
Prestige Assisted Living at Manteca has partnered with Manteca Care and Rehabilitation Center, St Jude Care Center and Manteca Senior Center to participate in events that will benefit the Veterans of Foreign Wars Jimmie Connors Post 6311.
Dino Vincente Zanini
Budge Brown - the father of the fiberglass waterpark slide - along with his wife Arlene have been inducted into the World Waterpark Association Hall of Fame.
The Marine Corps has celebrated its 239th birthday during a breakfast at the Spring Creek Country Club on Thursday.
He threatened it at a Lathrop City Council meeting almost two months ago.
Ripon's "Spud" MacDonald hasn't missed a step in her 90 years, continuing every day to walk two to five miles throughout the community keeping herself in shape.
Weston Ranch High School could go the way of Manteca High and go on block scheduling in August next year when the school year 2015-2016 begins.
Turkeys R Us is in a race against the clock.
Five former students of the long gone Summer Home School that had been located at what is now the southwest corner of Cottage Avenue and Southland Road northeast of Manteca told stories of their yesterdays when they met for lunch at Applebee's Restaurant.
It could take days – or longer – before the three Lathrop City Council candidates separated by less than two-dozen votes know for sure whether they've earned one of the two available seats.
City of Lathrop's power bill is about to get a major adjustment.
Money is the mother's milk of politics.
Turkeys R Us has two weeks to come up with 609 turkeys or struggling families in Manteca, Ripon or Lathrop will go without a Thanksgiving meal.
An inquiry into possible election fraud in the Manteca Unified School District is underway.
Ben Cantu is on his way to becoming the Harold Stassen of Manteca politics.