20 research outputs found
Analisis Retakan Korosi Tegangan Pada Aluminium Dengan Variasi Pembebanan Dalam Media Korosi Hcl 1m
Stress corrosion cracking [SCC] merupakan kegagalan logam korosi hasil peretakan intergranular atau transgranular dibawah pengaruh antara tegangan tarik dan lingkungan korosif. Bentuk korosi ini lazim sekali dijumpai di lingkungan industri seperti : industri perkapalan, perminyakan, dan industri â industri kontruksi logam. Dalam tugas akhir ini dimaksudkan untuk memahami fenomena Stress Corrosion Cracking secara teoritis dalam aluminium dengan mengkaji pengaruh variasi pembebanan didalam media korosi terhadap pertambahan panjang, lamanya waktu patah dan jenis retak. Pada penelitian ini pengujian menggunakan alat uji Stress Corrosion Cracking, untuk menciptakan suatu kondisi spesimen agar mendapatkan tegangan tarik pada lingkungan yang korosif. Tegangan yang diberikan berupa tegangan tarik yang berasal dari pembebanan statik pada sistem pengungkit. Kondisi korosif dapat dihasilkan dari bak yang diisi dengan larutan HCl. Analisa metalografi dimaksudkan untuk mengamati struktur mikro spesimen uji dan bentuk retak yang terjadi pada spesimen uji setelah dilakukan proses pengujian
Presence of autoimmune disease affects not only risk but also survival in patients with Bâcell nonâHodgkin lymphoma
Although autoimmune diseases (AIDs) are known to predispose to nonâHodgkin lymphoma
(NHL), their association with NHL prognosis has rarely been investigated. We examined
associations between autoimmunity and Bâcell NHL onset by comparing AID history
(determined by selfâreport and medication review and supplemented by chart review where
possible) among 435 adult BâNHL patients in HadassahâHebrew University Medical Center,
diagnosed 2009â2014, and 414 ageâandâsex frequencyâmatched controls. We examined AIDs
as a whole, Bâ and Tâcellâmediated AIDs, and autoimmune thyroid diseases. Among cases,
we used KaplanâMeier and Cox regression models to assess the association of AID with overall
survival and relapseâfree survival, adjusting for prognostically important patient and disease
characteristics such as Ki67% staining, International Prognostic Index, rituximab treatment, and
histological subgroup.
Autoimmune diseases were associated with BâNHL (odds ratio [OR] = 1.95; 95% confidence
interval (CI), 1.31â2.92), especially AIDs mediated by Bâcell activation (OR = 5.20; CI, 1.90â14.3),
which were particularly associated with marginal zone lymphoma (OR = 19.3; CI, 4.59â80.9). We
found that time to relapse for all BâNHL patients with AIDs was significantly shorter (mean
of 49.21 mo [±3.22]) than among patients without AID (mean of 59.74 mo [±1.62]), adjusted
hazard ratio [HRadj] = 1.69 (CI, 1.03â2.79). Specifically, in patients with diffuse large Bâcell
lymphoma, of whom 91.8% had received rituximab, a history of Bâcellâmediated AIDs was
associated with shorter relapseâfree survival and overall survival, HRadj = 8.34 (CI, 3.01â
23.1) and HRadj = 3.83 (CI, 1.20â12.3), respectively.
Beyond confirming the wellâknown association between AIDs and BâNHL, we found that AID is
an adverse prognostic factor in Bâcell lymphoma, associated with a shortened time to relapse,
suggesting that there are specific therapeutic challenges in the subgroup of patients suffering
from both these diseases. Further work is required to address mechanisms of resistance to
standard treatment in the setting of AIDâassociated BâNHL. In the era of immunotherapy, these
findings have particular relevance.This study was made possible by the generous support of the American
people through the United States Agency for International Development
(USAID)/MERC grant no. TAâMOUâ11âM31â025. The contents
are the responsibility of the authors and do not necessarily reflect
the views of USAID or the United States Government; Israel Science
Foundation (ISF) grant no. 877/10; and the Hadassah University
Hospital Compensatory Fund. We thank Noemie Cohen for data entry
tLivin displays flexibility by promoting alternative cell death mechanisms.
Livin is a member of the Inhibitor of Apoptosis (IAP) protein family that inhibits apoptosis triggered by a variety of stimuli. We previously demonstrated that while Livin inhibits caspase activity, caspases can cleave Livin to produce a truncated protein, tLivin and that this newly formed tLivin paradoxically induces cell death. However to date, the mechanism of tLivin-induced cell death is not fully understood. In this study, we set out to characterize the form of cell death mediated by tLivin. Here we demonstrate that, unlike most death-promoting proteins, tLivin is a flexible inducer of cell death capable of promoting necrosis or apoptosis in different cell lines. The unusual flexibility of tLivin is displayed by its ability to activate an alternative form of cell death when apoptosis is inhibited. Thus, tLivin can promote more than one form of cell death in the same cell type. Interestingly, in cells where tLivin induces necrosis, deletion of the caspase binding BIR domain results in tLivin-induced apoptosis, suggesting the BIR domain can potentially hamper the ability of tLivin to induce apoptosis. We further elucidate that tLivin activates the JNK pathway and both tLivin-induced apoptosis and necrosis are partially mediated by JNK activity. Acquired resistance to apoptosis, common in many tumors, impinges on the efficiency of conventional anti-cancer agents that function primarily by inducing apoptosis. The ability of tLivin to induce death of apoptosis-compromised cells makes it an attractive candidate for targeted cancer therapy
tLivin-induced apoptosis and necrosis are partially mediated by activation of JNK.
<p>(<b>A</b>) Cells of MelA1 clones were treated with 10 ”M SP600125 1 h prior to administration of 2.5 ”g/ml dox (where indicated) and harvested after 36 h along with untreated cells (con). Cells were stained with PI and the percent of cell death was measured by flow cytometry. *p<0.05. (<b>B</b>) 293T cells were transiently transfected with the indicated plasmids and harvested 24 h post-transfection along with untransfected cells (con). Cells were stained with PI and the percent of cell death was measured by flow cytometry. (<b>C</b>) 293T cells were transiently transfected with the indicated plasmids, harvested 24 h post-transfection and analyzed by western blot for the protein levels of p-c-JUN, c-JUN, JIP-1, tLivin and GAPDH.</p
tLivin activates the JNK pathway.
<p>(<b>A</b>) 293T cells were either transiently transfected with empty vector (ev), tBID- or tLivin-expressing vectors, treated with 30 ”g/ml etoposide for 24 h (etop) or left untreated (con). Cells were harvested at the indicated time points post-transfection and the phosphorylation of JNK, ATF-2 and p38MAPK was analyzed by western blot. (<b>B</b>) Cells of MelA1 clones were harvested at the indicated time points following administration of 2.5 ”g/ml dox or following 30 min treatment with 200 nM anisomycin (A), control cells (con) were left untreated. Phosphorylation of JNK and c-JUN was analyzed by western blot. (<b>C</b>) 293T cells were either transiently transfected with empty vector (ev), tLivin- or tLivinÎBIR-expressing vectors, treated with 200 nM anisomycin for 30 min (A) or left untreated (con). Cells were harvested at the indicated time points post-transfection and phosphorylation of JNK and c-JUN was analyzed by western blot.</p
The Oncolytic Activity of Newcastle Disease Virus NDV-HUJ on Chemoresistant Primary Melanoma Cells Is Dependent on the Proapoptotic Activity of the Inhibitor of Apoptosis Protein Livinâż âĄ
Patients with advanced melanoma usually do not benefit from conventional chemotherapy treatment. There is therefore a true need for a new kind of therapy for melanoma. One factor responsible for the poor prognosis of melanoma is the inhibitor of apoptosis protein (IAP) family member Livin. In this study, we applied a novel approach for the treatment of melanoma, using a unique strain of the oncolytic Newcastle disease virus (NDV-HUJ). We found that, unlike chemotherapeutic drugs, NDV-HUJ, a one-cycle replicating virus, overcomes the resistance to apoptosis of melanoma primary cultures that over express the Livin protein. In contrast, melanoma tumor cells that do not express Livin are relatively resistant to NDV-HUJ treatment. Furthermore, we show that NDV-HUJ-induced oncolysis is attributed to the dual function of Livin: although Livin inhibits apoptosis through the inhibition of caspases, under the robust apoptotic stimulation of NDV-HUJ, caspases can cleave Livin to create a truncated protein with a paradoxical proapoptotic activity. Thus, NDV-HUJ is a potent inducer of apoptosis that can overcome the antiapoptotic effect of Livin and allow cleavage of Livin into the proapoptotic tLivin protein. Moreover, the results indicate that the interferon system, which is functional in melanoma, is not involved in NDV-induced oncolysis. Taken together, our data offer the possibility of a new viral oncolytic treatment for chemoresistant melanoma
tLivin induces apoptosis of MelA1 cells.
<p>Cells of MelA1 clones were treated with 2.5 ”g/ml dox and harvested at the indicated time points. Con, untreated cells; sts, cells treated with 0.5 ”M staurosporine for 10 h. (<b>A</b>) Cells were stained with PI and the percent of cell death was measured by flow cytometry (top). Cells were analyzed for tLivin and GAPDH protein levels by western blot (bottom). (<b>B</b>) Cleavage of caspase 3 and PARP was analyzed by western blot. (<b>C</b>) DNA content was analyzed by flow cytometry.</p
tLivin induces apoptosis of A549 cells.
<p>Cells of A549 clones were treated with 2.5 ”g/ml dox and harvested at the indicated time points. Con, untreated cells; etop, cells treated with 30 ”g/ml etoposide for 48 h. (<b>A</b>) Cells were stained with PI and the percent of cell death was measured by flow cytometry (top). Cells were analyzed for tLivin and GAPDH protein levels by western blot (bottom). (<b>B</b>) Cleavage of caspase 3 and PARP was analyzed by western blot. (<b>C</b>) DNA content was analyzed by flow cytometry. (<b>D</b>) Cells were treated with 50 ”M zVAD-fmk 1 h prior to addition of dox, harvested after 48 h, stained with PI and the percent of cell death was measured by flow cytometry. *p<0.05. (<b>E</b>) Cells were treated with 50 ”M zVAD-fmk 1 h prior to addition of dox and harvested after 48 h. Each sample was divided into three aliquots and analyzed for cleavage of caspase 3 by western blot and for the percent of PI positive cells and DNA content by flow cytometry.</p
tLivin activates an alternative form of cell death when apoptosis is inhibited.
<p>Cells of MelA1 clones were treated with 75 ”M zVAD-fmk 1 h prior to addition of 2.5 ”g/ml dox or 30 ”M cisplatin and harvested after 36 h along with untreated cells (con). (<b>A</b>) Cells were stained with PI and the percent of cell death was measured by flow cytometry. *p<0.05. (<b>B</b>) Cells from each sample were divided into three aliquots and analyzed for cleavage of caspase 3 by western blot and for the percent of PI positive cells and DNA content by flow cytometry.</p