Studi Potensi Jumlah Penumpang Bus Pemadu Moda Rute Malang – Bandar Udara Juanda Pp

Bandar Udara Malang yang belum melayani banyak tujuan penerbangan membuat pengguna moda pesawat memilih Bandar Udara Juanda. Disisi lain angkutan yang melayani rute Malang-Juanda PP hanya angkutan travel. Untuk itu dibutuhkan moda lain yang lebih ekonomis dan memiliki kapasitas lebih banyak dibandingkan angkutan travel. Bus pemadu moda adalah moda alternatif yang dapat memenuhi kebutuhan tersebut.Pengumpulan data dilakukan dengan penyebaran kuisioner karakteristik sosial-ekonomi, karakteristik perjalanan serta kuisioner dengan teknik penyusunan stated preference. Stated preference memiliki atribut biaya perjalanan, waktu tempuh dan frekuensi keberangkatan. Sedangkan untuk prediksi tarif bus pemadu moda yang direncanakan diperoleh dari perhitungan BOK. Tarif yang telah diperoleh dari perhitungan BOK dibandingkan dengan nilai ATP dan WTP yang diperoleh dari kuisioner yang telah disebarkan. Sehingga didapatkan tarif ideal yang akan diberlakukan apabila bus pemadu moda tersebut direalisasikan.Setelah melakukan perhitungan tarif berdasarkan BOK diperoleh tarif sebesar Rp 23.374,- serta berdasarkan ATP dan WTP diperoleh tarif sebesar Rp 43.675,-. Dengan demikian perkiraan awal tarif bus pemadu moda sebesar Rp 40.000,- dapat diberlakukan. Hasil dari pemodelan pemilihan moda dengan metode stated preference untuk selisih biaya perjalanan Malang-Juanda: dan Juanda-Malang : , untuk selisih waktu tempuh perjalanan () rute Malang-Juanda : dan rute Juanda-Malang : , sedangkan untuk selisih Frekuensi Keberangkatan () rute Malang-Juanda : dan rute Juanda-Malang : .Potensi perpindahan pengguna travel ke bus pemadu moda rute Malang-Juanda sebanyak 705 orang per hari (83,97%). Sedangkan untuk rute Juanda-Malang sebanyak 1516 orang per hari (90,24%)

In MEF cells, BAX and BAK expression regulates bortezomib activity.

<p>A) WT MEF and BAX/BAK DKO MEF cells were treated with bortezomib 10 nM for 24 h. PARP cleavage was measured by western blot. B) Caspase3 activity was assessed by luminescence assay. Data were normalized to untreated control (WT: p<0.0001; DKO n.s.). C) BAX and BAK were transiently overexpressed in DKO cells and 24 h post transfection cells were treated with bortezomib 10 nM for a further 24 hours. BAX and BAK expression were then analysed by western blot. D) Caspase 3 activation after bortezomib treatment was also analysed by luminescence assay. Data were normalized to untreated control (EV: n.s.; GSTBAX: p = <0.0001 GSTBAK: p = <0.0001).</p

Immunohistochemical analysis of BAX and BAK expression in malignant mesothelioma patients.

<p>A) Representative image of normal tissue control and positive tissues stained for BAX and BAK by immunohistochemisty. B) Pie-charts representing the frequency of BAX, BAK and BAX-BAK negativity in previously treated 30 mesothelioma patients. C) Kaplan Meier curves correlating BAX, BAK, and double BAX/BAK expression respectively with survival in the total of 30 previously-treated patients.</p

In MPM cell lines, dowregulation of BAK induces resistance to bortezomib-induced apoptosis.

<p>A) REN and B) JU77 cells were transfected with siNT, siBAX, siBAK and the combination of siBAX and siBAK. 24 h following transfection, cells were treated with a concentration of bortezomib equal to the IC₅₀ calculated for each cell line and caspase3 activity measured. Data were normalized to NT untreated control (REN: siNT p = 0.0003 siBAX p = 0.0159; siBAK n.s. siBAXsiBAK n.s.; JU77: siNT p = 0.0002 siBAX p = 0.0002; siBAK n.s.; siBAXsiBAK n.s.). C) BAX and BAK expression and PARP cleavage were confirmed by western blot analysis in REN and D) JU77 cells.</p

Scoring of samples from ICORG-05 Phase II Trial [7].

<p>0 = No cells stained 1 = <25% cells stained 2 = 26–75% cells stained 3 = >75% cells stained.</p

Generation and characterization of mesothelioma bortezomib-resistant cell lines.

<p>A) REN and JU77 selected for resistance after exposure to increasing doses of bortezomib were tested for cell viability after 24 h treatment with bortezomib at concentrations ranging from 0.5 nM to 50 nM and compared to parental cells. REN/REN^BZR and JU77/JU77^BZR cells were treated for 24 h with bortezomib 5 nM and 10 nM, respectively. PARP cleavage induced by bortezomib was analysed by western blot and caspase3 activity was measured by luminescence assay. Data were normalized to untreated control (REN: <0.0001; REN^BZR: n.s.; JU77: p = 0.0002; JU77^BZR: n.s.). B) Expression of BAX and BAK was investigated in parental and resistant cells pre- and after 6 h treatment with bortezomib 5 nM and 10 nM in REN/REN^BZR and JU77/JU77^BZR respectively. C) Cytochrome C release was assessed after 24 h treatment with bortezomib (5 nM and 10 nM in REN/REN^BZR and JU77/JU77^BZR, respectively). Mitochondrial-free cytosolic fraction has been used for western blot analysis.</p

The BH3-only protein NOXA is essential for bortezomib-induced apoptosis.

<p>A) REN and B) JU77 cells were transfected with siRNA sequences targeting the BH3-only protein NOXA. 24 h following transfection, cells were treated with a concentration of bortezomib equal to the IC₅₀ calculated for each cell line and caspase3 activity measured. Data were normalized to NT untreated control. C) NOXA expression level and PARP cleavage were assessed by western blot analysis in REN and D) JU77 cells.</p

Selection for resistance to bortezomib abrogates c-Myc activity and NOXA expression.

<p>A) The expression of NOXA and c-Myc was evaluated in by western blotting in REN/REN^BZR and JU77/JU77^BZR cells. Cells were left untreated or exposed to bortezomib 5 nM or 10 nM respectively for 6 hours. B) NOXA mRNA expression was evaluated by qRT-PCR on RNA extracted from parental and resistant cells treated for 6 h with 5 nM (REN/REN^BZR) or 10 nM (JU77/JU77^BZR) bortezomib. Data were normalized to untreated control (REN: p = 0.00241; REN^BZR n.s.; JU77: p = 0.0001; JU77^BZR n.s.) C) REN^shNT and REN^shc-Myc cells were generated by RNAi and NOXA induction was analysed by western blot after 24 h treatment with 5 nM bortezomib. D) c-Myc activity was measured by a reporter assay in REN and REN^BZR treated for 24 h with 5 nM bortezomib. Data were normalized to untreated control (REN: p = 0.0438; REN^BZR n.s.). E) The binding of c-Myc to the Noxa promoter was evaluated by ChIP in REN and REN^BZR treated for 24 h with 5 nM bortezomib.</p

Combined Genetic and Genealogic Studies Uncover a Large BAP1 Cancer Syndrome Kindred Tracing Back Nine Generations to a Common Ancestor from the 1700s

<div><p>We recently discovered an inherited cancer syndrome caused by BRCA1-Associated Protein 1 (<i>BAP1</i>) germline mutations, with high incidence of mesothelioma, uveal melanoma and other cancers and very high penetrance by age 55. To identify families with the BAP1 cancer syndrome, we screened patients with family histories of multiple mesotheliomas and melanomas and/or multiple cancers. We identified four families that shared an identical <i>BAP1</i> mutation: they lived across the US and did not appear to be related. By combining family histories, molecular genetics, and genealogical approaches, we uncovered a BAP1 cancer syndrome kindred of ~80,000 descendants with a core of 106 individuals, whose members descend from a couple born in Germany in the early 1700s who immigrated to North America. Their descendants spread throughout the country with mutation carriers affected by multiple malignancies. Our data show that, once a proband is identified, extended analyses of these kindreds, using genomic and genealogical studies to identify the most recent common ancestor, allow investigators to uncover additional branches of the family that may carry <i>BAP1</i> mutations. Using this knowledge, we have identified new branches of this family carrying BAP1 mutations. We have also implemented early-detection strategies that help identify cancers at early-stage, when they can be cured (melanomas) or are more susceptible to therapy (MM and other malignancies).</p></div

BAP1 cytoplasmic staining and LOH in MM biopsies.

<p><b>(A)</b> Representative histology (Hematoxylin and Eosin staining) and BAP1 IHC. Controls: Panel a, normal strip of pleural mesothelial cells; d, MM biopsy containing wild-type BAP1. Note BAP1 nuclear staining and faint cytoplasmic staining; black arrows identify representative normal mesothelial cells in a and MM cells in d. Panels b, c, e and f, BAP1-mutant MM biopsies from MARF11-III-1 (b,e) and MARF18-III-1 (c,f). Note cytoplasmic BAP1 staining and absence of nuclear staining in MM cells; black arrows identify representative tumor cells indicating LOH for BAP1. Note that nearby infiltrating “normal” lymphocytes and endothelial cells show nuclear BAP1 staining (red arrows) as they retain one normal BAP1 allele. Original magnification, 400X. <b>(B)</b><i>BAP1</i> sequencing of germline and tumor DNAs from MARF11-III-1 and MARF18-III-1 reveals heterozygosity in germline DNA and LOH in tumor cell DNA. Top panels, germline DNA from both patients shows a ‘C’ deletion (grey shadowed area): the wild-type allele and the mutant allele show the same peak intensity indicating a heterozygous mutation. Bottom Panels, tumor cell DNA, from both patients, shows a homozygous C deletion. The electropherogram of tumor cell DNA shows that the allele with the C deletion has a higher peak, indicating that only the mutant allele is present in the tumor cells. The lower peak is likely generated by the wild type allele of some contaminating normal cells. DNA sequence of wild-type—AGTCCCCTGGC; DNA sequence of mutant—AGTCCCTGGCG.</p