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Vaccarella, S.,Herrero, R.,Snijders, P. J F,Dai, M.,Thomas, J. O,Hieu, N. T.,Ferreccio, C.,Matos, E.,Posso, H.,de Sanjose, S.,Shin, H. R.,Sukvirach, S.,Lazcano-Ponce, E.,Munoz, N.,Meijer, C. J L M,Fra Oxford University Press 2008 International journal of epidemiology Vol.37 No.3
<P>BACKGROUND: Smoking increases the risk of squamous-cell carcinoma of the cervix, but it is not clear whether smoking increases the risk of acquisition or persistence of human papillomavirus (HPV) infection. METHODS: Information on smoking was collected from 10 areas in four continents among population-based, age-stratified random samples of women aged 15 years or older. HPV testing was performed using PCR-based enzyme immunoassay. Unconditional logistic regression was used to estimate odds ratios (OR) and corresponding 95% confidence intervals (CI) of being HPV-positive by smoking habits, adjusted for age and lifetime number of sexual partners. RESULTS: Ten thousand five hundred and seventy-seven women (mean age 41.4 years) were included. Among current smokers, the risk of being HPV-positive increased with smoking intensity, after allowing for lifetime number of sexual partners: ORs for <5, 5-14 and >/=15 cigarettes per day were 1.21 (95% CI 0.95-1.54), 1.39 (95% CI 1.04-1.87) and 2.01 (95% CI 1.32-3.08), respectively, as compared with never-smokers. The risk among former smokers (OR = 0.95, 95% CI 0.73-1.23) was similar to that among never-smokers. Analyses stratified by lifetime number of sexual partners showed a significant trend in risk only for women with one lifetime sexual partner. CONCLUSIONS: Our study suggests that current, though not former, smoking is associated with an increased prevalence of HPV, after allowance for sexual covariates. Among current smokers, HPV prevalence increased with smoking intensity, but a clear dose-response relationship was exclusively seen among women who declared one lifetime sexual partner.</P>
The Effect of Induced Multipoles on the Fifth-order Raman Response
Jansen, Thomas I.C.,Duppen, Koos,Snijders, Jaap G. Korean Chemical Society 2003 Bulletin of the Korean Chemical Society Vol.24 No.8
In our previous work we developed the Finite Field method in order to calculate the fifth-order Raman response. The method was applied to calculate various polarization components of the two-dimensional response of liquid $CS_2$. So far, all calculations relied on the dipole-induced dipole. Accurate time-dependent density functional theory calculations have shown that this model has big discrepancies, when molecules are close together as in the liquid. We now report results of investigations on the importance of multipole and electron overlap effects on the polarizability and the fifth-order Raman response. It is shown that these collision effects, especially the induced multipoles, are crucial in the description of the fifth-order response. The impact is found to be especially pronounced for the χ_{mmzzzz}^{(5)}$response that is solely due to interaction induced effects. The calculated response will be compared with various experimental results.
Genome editing reveals a role for OCT4 in human embryogenesis
Fogarty, Norah M. E.,McCarthy, Afshan,Snijders, Kirsten E.,Powell, Benjamin E.,Kubikova, Nada,Blakeley, Paul,Lea, Rebecca,Elder, Kay,Wamaitha, Sissy E.,Kim, Daesik,Maciulyte, Valdone,Kleinjung, Jens,K Macmillan Publishers Limited, part of Springer Nat 2017 Nature Vol.550 No.7674
<P>Despite their fundamental biological and clinical importance, the molecular mechanisms that regulate the first cell fate decisions in the human embryo are not well understood. Here we use CRISPR-Cas9-mediated genome editing to investigate the function of the pluripotency transcription factor OCT4 during human embryogenesis. We identified an efficient OCT4-targeting guide RNA using an inducible human embryonic stem cell-based system and microinjection of mouse zygotes. Using these refined methods, we efficiently and specifically targeted the gene encoding OCT4 (POU5F1) in diploid human zygotes and found that blastocyst development was compromised. Transcriptomics analysis revealed that, in POU5F1-null cells, gene expression was downregulated not only for extra-embryonic trophectoderm genes, such as CDX2, but also for regulators of the pluripotent epiblast, including NANOG. By contrast, Pou5f1-null mouse embryos maintained the expression of orthologous genes, and blastocyst development was established, but maintenance was compromised. We conclude that CRISPR-Cas9-mediated genome editing is a powerful method for investigating gene function in the context of human development.</P>
Nienke Zwakman,Rafli van de Laar,Toon Van Gorp,Petra LM Zusterzeel,Marc PML Snijders,Isabel Ferreira,Leon FAG Massuger,Roy FPM Kruitwagen 대한부인종양학회 2017 Journal of Gynecologic Oncology Vol.28 No.1
Objective: In patients with advanced stage epithelial ovarian cancer (EOC) the volume of residual tumor after debulking is known as prognostic factor for survival. We wanted to examine the relationship between postoperative decline in serum CA125 and residual disease after cytoreductive surgery and evaluate perioperative changes in serum CA125 levels as predictor for disease-specific survival. Methods: A retrospective study was conducted of patients with FIGO stage IIb-IV EOC treated with cytoreductive surgery, followed by chemotherapy between 1996 and 2010 in three hospitals in the Southeastern region of the Netherlands. Data were analyzed with the use of multilevel linear regression and Cox-proportional hazard regression models. Results: A postoperative decline in serum CA125 level of ≥80% was associated with complete primary cytoreduction (p=0.035). Univariate analyses showed favorable associations with survival for both the degree of decline in serum CA125 and residual tumor after primary cytoreduction. In multivariate analyses the decline in serum CA125 but not the outcome of surgery remained significantly associated with better survival (HR50%–79%=0.52 [95% CI: 0.28–0.96] and HR≥80%=0.26 [95% CI: 0.13–0.54] vs. the serum CA125 decline of <50% [p<0.001]). Conclusion: The current study, although hampered by possible biases, suggests that the perioperative decline in serum CA125 is an early biomarker that predicts disease-specific survival in patients who underwent primary cytoreductive surgery for advanced stage EOC. If confirmed prospectively, the perioperative change in serum CA125 could be a better marker for residual tumor volume after primary cytoreductive surgery (and therewith disease-specific survival) than the surgeons’ estimation of residual tumor volume.
Casper Reijnen,Nicole CM Visser,Jenneke C Kasius,Dorry Boll,Peggy M Geomini,Huy Ngo,Dennis van Hamont,Brenda M Pijlman,Maria Caroline Vos,Johan Bulten,Marc PLM Snijders,Leon FAG Massuger,Johanna MA Pi 대한부인종양학회 2019 Journal of Gynecologic Oncology Vol.30 No.5
Objectives The global obesity epidemic has great impact on the prevalence of low-grade endometrial carcinoma. The preoperative tumor serum marker cancer antigen 125 (CA-125) might contribute to improved identification of high-risk patients within this group. The study aimed to investigate the prognostic value of CA-125 in relation to established preoperative prognosticators, with a focus on identifying patients with poor outcome in low-grade endometrial carcinoma (EC) patients. Methods Prospective multicenter cohort study including all consecutive patients surgically treated for endometrial carcinoma in nine collaborating hospitals from September 2011 until December 2013. All preoperative histopathological diagnoses were reviewed in a blinded manner. Associations between CA-125 and clinicopathological features were determined. Univariable and multivariable analysis by Cox regression were used. Separate analyses were performed for preoperatively designated low-grade and high-grade endometrial carcinoma patients. Results A total of 333 patients were analyzed. CA-125 was associated with poor prognostic features including advanced International Federation of Gynecology and Obstetrics (FIGO) stage. In multivariable analysis, age, preoperative tumor and CA-125 were significantly associated with disease-free survival (DFS); preoperative grade, tumor type, FIGO and CA-125 were significantly associated with disease-specific survival (DSS). Low-grade EC patients with elevated CA-125 revealed a DFS of 80.6% and DSS of 87.1%, compared to 92.1% and 97.2% in low-grade EC patients with normal CA-125. Conclusion Preoperative elevated CA-125 was associated with poor prognostic features and independently associated with DFS and DSS. Particularly patients with low-grade EC and elevated CA-125 represent a group with poor outcome and should be considered as high-risk endometrial carcinoma.
Racking shear resistance of steel frames with corner connected precast concrete infill panels
J.C.D. Hoenderkamp,H.H. Snijder,H. Hofmeyer 국제구조공학회 2015 Steel and Composite Structures, An International J Vol.19 No.6
When precast concrete infill panels are connected to steel frames at discrete locations, interaction at the structural interface is neither complete nor absent. The contribution of precast concrete infill panels to the lateral stiffness and strength of steel frames can be significant depending on the quality, quantity and location of the discrete interface connections. This paper presents preliminary experimental and finite element results of an investigation into the composite behaviour of a square steel frame with a precast concrete infill panel subject to lateral loading. The panel is connected at the corners to the ends of the top and bottom beams. The Frame-to-Panel-Connection, FPC4 between steel beam and concrete panel consists of two parts. A T-section with five achor bars welded to the top of the flange is cast in at the panel corner at a forty five degree angle. The triangularly shaped web of the T-section is reinforced against local buckling with a stiffener plate. The second part consists of a triangular gusset plate which is welded to the beam flange. Two bolts acting in shear connect the gusset plate to the web of the T-section. This way the connection can act in tension or compression. Experimental pull-out tests on individual connections allowed their load deflection characteristics to be established. A full scale experiment was performed on a one-storey one-bay 3 by 3 m infilled frame structure which was horizontally loaded at the top. With the characteristics of the frame-to-panel connections obtained from the experiments on individual connections, finite element analyses were performed on the infilled frame structures taking geometric and material non-linear behaviour of the structural components into account. The finite element model yields reasonably accurate results. This allows the model to be used for further parametric studies.
P.A. Teeuwen,C.S. Kleinman,H.H. Snijder,H. Hofmeyer 국제구조공학회 2006 Steel and Composite Structures, An International J Vol.6 No.1
As an alternative for conventional structures for tall buildings, a hybrid lateral load resisting structure has been designed, enabling the assembly of tall buildings directly from a truck. It consists of steel frames with discretely connected precast concrete infill panels provided with window openings. Besides the stiffening and strengthening effect of the infill panels on the frame structure, economical benefits may be derived from saving costs on materials and labour, and from reducing construction time. In order to develop design rules for this type of structure, the hybrid infilled frame has recently been subjected to experimental and numerical analyses. Ten full-scale tests were performed on one-storey, one-bay, 3 by 3 m infilled frame structures, having different window opening geometries. Subsequently, the response of the full-scale experiments was simulated with the finite element program DIANA. The finite element simulations were performed taking into account non-linear material characteristics and geometrical non-linearity. The experiments show that discretely connected precast concrete panels provided with a window opening, can significantly improve the performance of steel frames. A comparison between the full-scale experiments and simulations shows that the finite element models enable simulating the elastic and plastic behaviour of the hybrid infilled frame.
KPC1-Mediated Ubiquitination and Proteasomal Processing of NF-κB1 p105 to p50 Restricts Tumor Growth
Kravtsova-Ivantsiv, Y.,Shomer, I.,Cohen-Kaplan, V.,Snijder, B.,Superti-Furga, G.,Gonen, H.,Sommer, T.,Ziv, T.,Admon, A.,Naroditsky, I.,Jbara, M.,Brik, A.,Pikarsky, E.,Kwon, Y.,Doweck, I.,Ciechanover, Cell Press ; MIT Press 2015 Cell Vol.161 No.2
NF-κB is a key transcriptional regulator involved in inflammation and cell proliferation, survival, and transformation. Several key steps in its activation are mediated by the ubiquitin (Ub) system. One uncharacterized step is limited proteasomal processing of the NF-κB1 precursor p105 to the p50 active subunit. Here, we identify KPC1 as the Ub ligase (E3) that binds to the ankyrin repeats domain of p105, ubiquitinates it, and mediates its processing both under basal conditions and following signaling. Overexpression of KPC1 inhibits tumor growth likely mediated via excessive generation of p50. Also, overabundance of p50 downregulates p65, suggesting that a p50-p50 homodimer may modulate transcription in place of the tumorigenic p50-p65. Transcript analysis reveals increased expression of genes associated with tumor-suppressive signals. Overall, KPC1 regulation of NF-κB1 processing appears to constitute an important balancing step among the stimulatory and inhibitory activities of the transcription factor in cell growth control.