EFEKTIVITAS PROGRAM BIMBINGAN KARIR UNTUK MENGEMBANGKAN EKSPLORASI KARIR SISWA SEKOLAH MENENGAH ATAS DI KOTA BANDUNG

Penelitian ini dilatarbelakangi oleh perkembangan eksplorasi karir sebagai tugas perkembangan pada siswa. Perkembangan eksplorasi karir pada siswa merupakan salah satu indikator capaian kesuksesan karir seperti kemampuan untuk memilih jenis pekerjaan berdasarkan minat dan bakatnya. Metode penelitian yang digunakan yaitu kuasi eksperimen dengan pendekatan yang digunakan yaitu kuantitatif. Subjek dalam penelitian ini siswa kelas X SMAN 16 Bandung tahun ajaran 2021/2022. Instrumen yang digunakan adalah angket eksplorasi karir. Hasil dari penelitian ini yaitu 1) gambaran profil eksplorasi karir siswa SMA Negeri 16 Bandung tahun ajaran 2021/2022 secara keseluruhan ada pada kategori sedang; 2) Rumusan hipotetik program bimbingan karir yang efektif mengembangkan eksplorasi karir siswa SMA; 3) program bimbingan karir efektif mengembangkan eksplorasi karir siswa SMA. Rekomendasi dari hasil penelitian dapat dijadikan sebagai rujukan bagi guru bimbingan dan konseling di sekolah

PROGRAM BIMBINGAN UNTUK MENGEMBANGKAN KEMATANGAN KARIR PESERTA DIDIK SMA DI KOTA BANDUNG

Memilih serta mempersiapkan karir merupakan bagian dari tugas perkembangan remaja yang harus terpenuhi. Pencapaian tugas perkembangan remaja ini akan bertambah rumit jika remaja tidak mengimbanginya dengan ilmu serta pengetahuan yang matang mengenai informasi-informasi karir. Penelitian ini bertujuan untuk mengkaji keefektifan program bimbingan dalam mengembangkan kematangan karir peserta didik SMA di kota Bandung. Kajian dilakukan mengimplementasikan pendekatan kuantitatif dengan metode eksperimen kuasi dan desain Non-equivalent (Pre-Test and Post-Test) Control-Group Design. Sampel penelitian yang digunakan adalah 392 orang peserta didik kelas XI SMA Negeri 16 Bandung Tahun Pelajaran 2021/2022. Hasil survei memperlihatkan profil kematangan karir peserta didik kelas XI SMA Negeri 16 Bandung secara umum berada pada tahapan cukup matang, artinya mereka memiliki pemahaman dan sikap yang ada pada tingkatan sedang tentang kematangan karir, yang ditandai dengan pencapaian pada aspek kognitif dan afektif belum optimal. Berdasarkan data yang ada, maka diperlukan sebuah program untuk mengoptimalkan kematangan karir peserta didik tersebut. Hasil implementasi program bimbingan diperoleh data, terdapat perubahan yang signifikan berupa peningkatan kematangan karir terhadap peserta didik yang mendapatkan perlakuan dibandingkan peserta didik yang tidak diberi perlakuan. Dengan demikian dapat disimpulkan bahwa program bimbingan yang dirancang efektif mengembangkan kematangan karir peserta didik SM

On the de la Garza Phenomenon

DOI: 10.1214/09-AOS787Deriving optimal designs for nonlinear models is, in general, challenging. One crucial step is to determine the number of support points needed. Current tools handle this on a case-by-case basis. Each combination of model, optimality criterion and objective requires its own proof. The celebrated de la Garza Phenomenon states that under a (p − 1)th-degree polynomial regression model, any optimal design can be based on at most p design points, the minimum number of support points such that all parameters are estimable. Does this conclusion also hold for nonlinear models? If the answer is yes, it would be relatively easy to derive any optimal design, analytically or numerically. In this paper, a novel approach is developed to address this question. Using this new approach, it can be easily shown that the de la Garza phenomenon exists for many commonly studied nonlinear models, such as the Emax model, exponential model, three- and four-parameter log-linear models, Emax-PK1 model, as well as many classical polynomial regression models. The proposed approach unifies and extends many well-known results in the optimal design literature. It has four advantages over current tools: (i) it can be applied to many forms of nonlinear models; to continuous or discrete data; to data with homogeneous or nonhomogeneous errors; (ii) it can be applied to any design region; (iii) it can be applied to multiple-stage optimal design and (iv) it can be easily implemented.Supported by NSF Grants DMS-07-07013 and DMS-07-48409. AMS 2000 subject classifications. Primary 62K05; secondary 62J12

Protective Effect of Yang Mi Ryung® Extract on Noise-Induced Hearing Loss in Mice

Noise-induced hearing loss (NIHL) results from the damage of the delicate hair cells inside the ear after excessive stimulation of noise. Unlike certain lower animals such as amphibians, fishes, and birds, in humans, hair cells cannot be regenerated once they are killed or damaged; thus, there are no therapeutic options to cure NIHL. Therefore, it is more important to protect hair cells from the noise before the damage occurs. In this study, we report the protective effect of Yang Mi Ryung extract (YMRE) against NIHL; this novel therapeutic property of YMRE has not been reported previously. Our data demonstrates that the hearing ability damaged by noise is markedly restored in mice preadministrated with YMRE before noise exposure, to the level of normal control group. Our study also provides the molecular mechanism underlying the protective effect of YMRE against NIHL by showing that YMRE significantly blocks noise-induced apoptotic cell death and reduces reactive oxygen species (ROS) production in cochleae. Moreover, quantitative polymerase chain reaction (qPCR) analysis demonstrates that YMRE has anti-inflammatory properties, suppressing the mRNA levels of TNFα and IL-1β induced by noise exposure. In conclusion, YMRE could be a useful preventive intervention to prevent hearing impairment induced by the exposure to excessive noise

PyK2 and FAK connections to p190Rho guanine nucleotide exchange factor regulate RhoA activity, focal adhesion formation, and cell motility

Integrin binding to matrix proteins such as fibronectin (FN) leads to formation of focal adhesion (FA) cellular contact sites that regulate migration. RhoA GTPases facilitate FA formation, yet FA-associated RhoA-specific guanine nucleotide exchange factors (GEFs) remain unknown. Here, we show that proline-rich kinase-2 (Pyk2) levels increase upon loss of focal adhesion kinase (FAK) in mouse embryonic fibroblasts (MEFs). Additionally, we demonstrate that Pyk2 facilitates deregulated RhoA activation, elevated FA formation, and enhanced cell proliferation by promoting p190RhoGEF expression. In normal MEFs, p190RhoGEF knockdown inhibits FN-associated RhoA activation, FA formation, and cell migration. Knockdown of p190RhoGEF-related GEFH1 does not affect FA formation in FAK−/− or normal MEFs. p190RhoGEF overexpression enhances RhoA activation and FA formation in MEFs dependent on FAK binding and associated with p190RhoGEF FA recruitment and tyrosine phosphorylation. These studies elucidate a compensatory function for Pyk2 upon FAK loss and identify the FAK–p190RhoGEF complex as an important integrin-proximal regulator of FA formation during FN-stimulated cell motility

Use of a Target-Mediated Drug Disposition Model to Predict the Human Pharmacokinetics and Target Occupancy of GC1118, an Anti-epidermal Growth Factor Receptor Antibody

GC1118 is an anti-epidermal growth factor receptor (EGFR) monoclonal antibody that is currently under clinical development. In this study, the pharmacokinetics (PK) of GC1118 were modelled in monkeys to predict human PK and receptor occupancy (RO) profiles. The serum concentrations of GC1118 and its comparator (cetuximab) were assessed in monkeys with a non-compartmental analysis and a target-mediated drug disposition (TMDD) model after intravenous infusion (3-25 mg/kg) of these drugs. The scaling exponent of the EGFR synthesis rate was determined using a sensitivity analysis. The human cetuximab exposures were simulated by applying different exponents (0.7-1.0) for the EGFR synthesis rate in the allometric monkey PK model. Simulated Cmax and area under the curve values therein were compared with those previously reported in the literature to find the best exponent for the EGFR synthesis rate in human beings. The TMDD model appropriately described the monkey PK profile, which showed a decrease in clearance (CL; 1.2-0.4 ml/hr/kg) as the dose increased. The exponents for CL (0.75) and volume of distribution (Vd; 1.0) were used for the allometric scaling to predict human PK. The allometric coefficient for the EGFR synthesis rate chosen by the sensitivity analysis was 0.85, and the RO profiles that could not be measured experimentally were estimated based on the predicted concentrations of the total target and the drug-target complex. Our monkey TMDD model successfully predicts human PK and RO profiles of GC1118 and can be used to determine the appropriate dose for a first-in-human study investigating this drug.ope

Identification of Molecular defects in Korean patients with marfan syndrome

Background and Objectives：Marfan syndrome is an autosomal dominant heritable disease of connective tissue which is characterized by cardinal features mainly in the cardiovascular, ocular and skeletal systems. Aneurysms or dissections of the aorta are the major cardiovascular complications of the disorder causing early mortality. Mutations in the fibrillin-1 (FBN1) gene on chromosome 15q21.1 have been found to be major causes of Marfan syndrome. The purpose of this study was to characterize the molecular defect in Korean Marfan patients, thus contributing to the effort of correlating the genotype with the phenotype. Subjects and Methods：We screened all 65 exons of the FBN1 gene in 14 subjects diagnosed as Marfan syndrome by the method of single strand conformation polymorphism-heteroduplex analysis. Results：We found mutations in only 10 among 14 patients. This study identified 8 novel mutations and 2 previously reported mutations in 14 Korean Marfan patients. Two cases were nonsense mutations and 8 were missense mutations, including 3 frameshift. Seven cases of the mutations occurred in one of the 43 calcium binding epidermal growth factor-like domains within an FBN1 gene. Mutations in Marfan patients occurred variably over the whole field of this FBN1 gene. Conclusion：Our results will contribute to the establishment of a database of Korean Marfan patients. Extending this study and using the database will help early detection of the disease and prevention of complications.ope

Russian in the multilingual environment of three Asian countries

Peer reviewe

Therapeutic Efficacy of GC1118, a Novel Anti-EGFR Antibody, against Glioblastoma with High EGFR Amplification in Patient-Derived Xenografts

We aimed to evaluate the preclinical efficacy of GC1118, a novel anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb), against glioblastoma (GBM) tumors using patient-derived xenograft (PDX) models. A total of 15 distinct GBM PDX models were used to evaluate the therapeutic efficacy of GC1118. Genomic data derived from PDX models were analyzed to identify potential biomarkers associated with the anti-tumor efficacy of GC1118. A patient-derived cell-based high-throughput drug screening assay was performed to further validate the efficacy of GC1118. Compared to cetuximab, GC1118 exerted comparable growth inhibitory effects on the GBM tumors in the PDX models. We confirmed that GC1118 accumulated within the tumor by crossing the blood-brain barrier in in vivo specimens and observed the survival benefit in GC1118-treated intracranial models. Genomic analysis revealed high EGFR amplification as a potent biomarker for predicting the therapeutic efficacy of GC1118 in GBM tumors. In summary, GC1118 exerted a potent anti-tumor effect on GBM tumors in PDX models, and its therapeutic efficacy was especially pronounced in the tumors with high EGFR amplification. Our study supports the importance of patient stratification based on EGFR copy number variation in clinical trials for GBM. The superiority of GC1118 over other EGFR mAbs in GBM tumors should be assessed in future studiesope

Plasmon-Enhanced Single Extracellular Vesicle Analysis for Cholangiocarcinoma Diagnosis

Cholangiocarcinoma (CCA) is a fatal disease often detected late in unresectable stages. Currently, there are no effective diagnostic methods or biomarkers to detect CCA early with high confidence. Analysis of tumor-derived extracellular vesicles (tEVs) harvested from liquid biopsies can provide a new opportunity to achieve this goal. Here, an advanced nanoplasmonic sensing technology is reported, termed FLEX (fluorescence-amplified extracellular vesicle sensing technology), for sensitive and robust single EV analysis. In the FLEX assay, EVs are captured on a plasmonic gold nanowell surface and immunolabeled for cancer-associated biomarkers to identify tEVs. The underlying plasmonic gold nanowell structures then amplify EVs' fluorescence signals, an effective amplification process at the single EV level. The FLEX EV analysis revealed a wide heterogeneity of tEVs and their marker levels. FLEX also detected small tEVs not detected by conventional EV fluorescence imaging due to weak signals. Tumor markers (MUC1, EGFR, and EPCAM) are identified in CCA, and this marker combination is applied to detect tEVs in clinical bile samples. The FLEX assay detected CCA with an area under the curve of 0.93, significantly better than current clinical markers. The sensitive and accurate nanoplasmonic EV sensing technology can aid in early CCA diagnosis.ope