| 1. |
|
|
| 2. |
-
- 2019
-
Tidskriftsartikel (refereegranskat)
|
|
| 3. |
- Bergendal, Birgitta, et al.
(författare)
-
Abnormal primary and permanent dentitions with ectodermal symptoms predict WNT10A deficiency
- 2016
-
Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 17
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The WNT10A protein is critical for the development of ectodermal appendages. Variants in the WNT10A gene may be associated with a spectrum of ectodermal abnormalities including extensive tooth agenesis. Methods: In seven patients with severe tooth agenesis we identified anomalies in primary dentition and additional ectodermal symptoms, and assessed WNT10A mutations by genetic analysis. Results: Investigation of primary dentition revealed peg-shaped crowns of primary mandibular incisors and three individuals had agenesis of at least two primary teeth. The permanent dentition was severely affected in all individuals with a mean of 21 missing teeth. Primary teeth were most often present in positions were succedaneous teeth were missing. Furthermore, most existing molars had taurodontism. Light, brittle or coarse hair was reported in all seven individuals, hyperhidrosis of palms and soles in six individuals and nail anomalies in two individuals. The anomalies in primary dentition preceded most of the additional ectodermal symptoms. Genetic analysis revealed that all seven individuals were homozygous or compound heterozygous for WNT10A mutations resulting in C107X, E222X and F228I. Conclusions: We conclude that tooth agenesis and/or peg-shaped crowns of primary mandibular incisors, severe oligodontia of permanent dentition as well as ectodermal symptoms of varying severity may be predictors of biallelic WNT10A mutations of importance for diagnosis, counselling and follow-up.
|
|
| 4. |
- Chen, Jialu, et al.
(författare)
-
Lightweight Privacy-preserving Training and Evaluation for Discretized Neural Networks
- 2020
-
Ingår i: IEEE Internet of Things Journal. - : IEEE. - 2327-4662. ; 7:4, s. 2663-2678
-
Tidskriftsartikel (refereegranskat)abstract
- Machine learning, particularly the neural network, is extensively exploited in dizzying applications. In order to reduce the burden of computing for resource-constrained clients, a large number of historical private datasets are required to be outsourced to the semi-trusted or malicious cloud for model training and evaluation. To achieve privacy preservation, most of the existing work either exploited the technique of public key fully homomorphic encryption (FHE) resulting in considerable computational cost and ciphertext expansion, or secure multiparty computation (SMC) requiring multiple rounds of interactions between user and cloud. To address these issues, in this paper, a lightweight privacy-preserving model training and evaluation scheme LPTE for discretized neural networks is proposed. Firstly, we put forward an efficient single key fully homomorphic data encapsulation mechanism (SFH-DEM) without exploiting public key FHE. Based on SFH-DEM, a series of atomic calculations over the encrypted domain including multivariate polynomial, nonlinear activation function, gradient function and maximum operations are devised as building blocks. Furthermore, a lightweight privacy-preserving model training and evaluation scheme LPTE for discretized neural networks is proposed, which can also be extended to convolutional neural network. Finally, we give the formal security proofs for dataset privacy, model training privacy and model evaluation privacy under the semi-honest environment and implement the experiment on real dataset MNIST for recognizing handwritten numbers in discretized neural network to demonstrate the high efficiency and accuracy of our proposed LPTE.
|
|
| 5. |
- Jin, Tingting, et al.
(författare)
-
Efficient heterogeneous integration of InP/Si and GaSb/Si templates with ultra-smooth surfaces
- 2022
-
Ingår i: Science China Information Sciences. - : Springer Science and Business Media LLC. - 1869-1919 .- 1674-733X. ; 65:8
-
Tidskriftsartikel (refereegranskat)abstract
- Heterogeneous integration of InP and GaSb on Si substrates holds a huge potential interest in near-infrared and mid-infrared optoelectronic devices. In this study, 2-inch 180-nm-thick InP and 185-nm-thick GaSb thin layers were successfully transferred onto the Si substrates to form high-quality and ultra-smooth InP/Si and GaSb/Si templates using molecular beam epitaxy (MBE) and the ion-slicing technique together with selective chemical etching. The relocation of the implantation-introduced damage in the sacrificial layer enables the transfer of relatively defect-free InP and GaSb thin films. The sacrificial layers were completely etched off by selective chemical etching, leaving ultra-smooth epitaxial surfaces with a roughness of 0.2 nm for the InP/Si template and 0.9 nm for the GaSb/Si template, respectively. Thus, the chemical mechanical polishing (CMP) process was not required to smooth the surface which usually introduces particles and chemical contaminations on the transferred templates. Furthermore, the donor substrate is not consumed and can be recycled to reduce the cost, which provides a paradigm for the sustainable and economic development of the Si integration platform.
|
|
| 6. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
|
|
| 7. |
- Li, Junjie, et al.
(författare)
-
A Novel Dry Selective Isotropic Atomic Layer Etching of SiGe for Manufacturing Vertical Nanowire Array with Diameter Less than 20 nm
- 2020
-
Ingår i: Materials. - : MDPI AG. - 1996-1944. ; 13:3
-
Tidskriftsartikel (refereegranskat)abstract
- Semiconductor nanowires have great application prospects in field effect transistors and sensors. In this study, the process and challenges of manufacturing vertical SiGe/Si nanowire array by using the conventional lithography and novel dry atomic layer etching technology. The final results demonstrate that vertical nanowires with a diameter less than 20 nm can be obtained. The diameter of nanowires is adjustable with an accuracy error less than 0.3 nm. This technology provides a new way for advanced 3D transistors and sensors.
|
|
| 8. |
- Liang, Hao, et al.
(författare)
-
InAs/GaAs quantum dot laser epitaxially grown on on-axis (001) GaAsOI substrate
- 2021
-
Ingår i: Optics Express. - 1094-4087 .- 1094-4087. ; 29:23, s. 38465-38476
-
Tidskriftsartikel (refereegranskat)abstract
- Quantum dot (QD) laser as a light source for silicon optical integration has attracted great research attention because of the strategic vision of optical interconnection. In this paper, the communication band InAs QD ridge waveguide lasers were fabricated on GaAs-on-insulator (GaAsOI) substrate by combining ion-slicing technique and molecular beam epitaxy (MBE) growth. On the foundation of optimizing surface treatment processes, the InAs/In0.13Ga0.87As/GaAs dot-in-well (DWELL) lasers monolithically grown on a GaAsOI substrate were realized under pulsed operation at 20 °C. The static device measurements reveal comparable performance in terms of threshold current density, slope efficiency and output power between the QD lasers on GaAsOI and GaAs substrates. This work shows great potential to fabricate highly integrated light source on Si for photonic integrated circuits.
|
|
| 9. |
- Lixing, Zhou, et al.
(författare)
-
Understanding dipole formation at dielectric/dielectric hetero-interface
- 2018
-
Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 113:18
-
Tidskriftsartikel (refereegranskat)abstract
- Band alignment and dipole formation at the hetero-interface still remain fascinating and, hence, are being intensively investigated. In this study, we experimentally investigate the dipole formation by employing a dielectric/dielectric (Al2O3/GeO2) interface. We investigate the dipole dependence on various post-deposition annealing (PDA) ambiences from the viewpoints of electrical extraction and the X-ray photoelectron spectroscopy measurement. The core level shift at the Al2O3/GeO2 interface is consistent with the dipole changes in various PDA ambiences. We discover that the dipole formation can be well explained by the interface gap state and charge neutrality level theory. These results further confirm the feasibility of gap state theory in explaining the band alignment at hetero-junctions. This study can be a booster to enhance the comprehension of dipole origin at hetero-junction interfaces.
|
|
| 10. |
- Moretti, Rocco, et al.
(författare)
-
Community-wide evaluation of methods for predicting the effect of mutations on protein-protein interactions
- 2013
-
Ingår i: Proteins. - : Wiley. - 0887-3585 .- 1097-0134. ; 81:11, s. 1980-1987
-
Tidskriftsartikel (refereegranskat)abstract
- Community-wide blind prediction experiments such as CAPRI and CASP provide an objective measure of the current state of predictive methodology. Here we describe a community-wide assessment of methods to predict the effects of mutations on protein-protein interactions. Twenty-two groups predicted the effects of comprehensive saturation mutagenesis for two designed influenza hemagglutinin binders and the results were compared with experimental yeast display enrichment data obtained using deep sequencing. The most successful methods explicitly considered the effects of mutation on monomer stability in addition to binding affinity, carried out explicit side-chain sampling and backbone relaxation, evaluated packing, electrostatic, and solvation effects, and correctly identified around a third of the beneficial mutations. Much room for improvement remains for even the best techniques, and large-scale fitness landscapes should continue to provide an excellent test bed for continued evaluation of both existing and new prediction methodologies. Proteins 2013; 81:1980-1987.
|
|
| 11. |
|
|
| 12. |
- Wang, Jinxin, et al.
(författare)
-
Machining Properties of Stone-Plastic Composite Based on an Empirically Validated Finite Element Method
- 2023
-
Ingår i: Advanced Engineering Materials. - : John Wiley & Sons. - 1438-1656 .- 1527-2648. ; 25:8
-
Tidskriftsartikel (refereegranskat)abstract
- High-cutting performance is an essential metric for improving the suitability of materials for industrial applications. Herein, the machining properties of stone-plastic composite are assessed through a finite element method to explore orthogonal cutting behavior by diamond cutters. The key aspects examined in this work are the effects of tool geometry and cutting parameters on the cutting force, temperature, chip formation, von Mises stress, and surface quality finish. Primary findings show that chip continuity increases proportionally with increase in rake angle but decreases with cutting speed and depth. Meanwhile, both cutting stability and surface quality are negatively correlated with cutting speed and depth but positively correlated with rake angle. These results support the adoption of cutting conditions using greater rake angle, higher cutting speed, and shallower cutting depth to obtain higher cutting performance, that is, greater cutting stability and surface quality in the finishing machining of stone-plastic composites.
|
|
| 13. |
- Wang, Xiaolei, et al.
(författare)
-
Induction of Fibroblast Senescence During Mouse Corneal Wound Healing
- 2019
-
Ingår i: Investigative Ophthalmology and Visual Science. - : ASSOC RESEARCH VISION OPHTHALMOLOGY INC. - 0146-0404 .- 1552-5783. ; 60:10, s. 3669-3679
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To investigate the presence and role of fibroblast senescence in the dynamic process of corneal wound healing involving stromal cell apoptosis, proliferation, and differentiation.METHODS. An in vivo corneal wound healing model was performed using epithelial debridement in C57BL/6 mice. The corneas were stained using TUNEL, Ki67, and alpha-smooth muscle actin (alpha-SMA) as markers of apoptosis, proliferation, and myofibroblastic differentiation, respectively. Cellular senescence was confirmed by senescence-associated beta-galactosidase (SA-beta-gal) staining and P16(Ink4a) expression. Mitogenic response and gene expression were compared among normal fibroblasts, H2O2-induced senescent fibroblasts, and TGF-beta-induced myofibroblasts in vitro. The senescence was further detected in mouse models of corneal scarring, alkali burn, and penetrating keratoplasty (PKP).RESULTS. The apoptosis and proliferation of corneal stromal cells were found to peak at 4 and 24 hours after epithelial debridement. Positive staining of SA-beta-gal was observed clearly in the anterior stromal cells at 3 to 5 days. The senescent cells displayed P16(Ink4a) thorn vimentin+ alpha-SMA+, representing the major origin of activated corneal resident fibroblasts. Compared with normal fibroblasts and TGF-beta-induced myofibroblasts, H2O2-induced senescent fibroblasts showed a nonfibrogenic phenotype, including a reduced response to growth factor basic fibroblast growth factor (bFGF) or platelet-derived growth factor-BB (PDGF-BB), increased matrix metalloproteinase (MMP) 1/3/13 expression, and decreased fibronectin and collagen I expression. Moreover, cellular senescence was commonly found in the mouse corneal scarring, alkali burn, and PKP models.CONCLUSIONS. Corneal epithelial debridement induced the senescence of corneal fibroblasts after apoptosis and proliferation. The senescent cells displayed a nonfibrogenic phenotype and may be involved in the self-limitation of corneal fibrosis.
|
|
| 14. |
- Zhou, Mengtao, et al.
(författare)
-
The efficiency of continuous regional intra-arterial infusion in the treatment of infected pancreatic necrosis
- 2013
-
Ingår i: Pancreatology. - : Elsevier BV. - 1424-3903. ; 13:3, s. 212-215
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Our aim was to investigate the efficiency of continuous regional intra-arterial infusion (CRAI) with antisecretory agents and antibiotics in the treatment of infected pancreatic necrosis. Materials and methods: CRAI was used as a new clinical technique to treat acute pancreatitis patients during a 4-year period at the First Affiliated Hospital, Wenzhou Medical College, China. In this retrospective study, thirty-four patients with proven infected pancreatic necrosis were included. Twelve patients were treated with CRAL and were matched according to age, sex, APACHE II scores, Ranson scores and remote organ dysfunction, with 22 patients with IPN treated surgically. The clinical outcome following surgery and CRAI were compared. Results: No difference was found between the two groups when comparing age, gender, APACHE II scores, Ranson scores and remote organ dysfunction (p > 0.05). The patients treated with CRAI had a lower incidence of complications (33.3% vs 72.7%), duration of hospitalization (27.1 +/- 4.7 days vs 43.0 +/- 12.0 days) and cost of hospitalization (4.09 +/- 1.64 thousand RMB vs 8.77 +/- 3.74 thousand RMB) as compared to patients treated with surgery (p < 0.05). The survival rate was significantly higher in the CRAI group as compared to the surgical group (91.7% vs 63.6%; p < 0.01). However, the two groups had similar rates of concomitant operative treatment and incidence of remote organ dysfunction (p > 0.05). Conclusions: CRAI or CRAI in combination with abscess drainage seemingly improve the clinical outcome in patients with infected pancreatic necrosis. Further confirmative prospective randomized multicenter studies are warranted prior to broad introduction of the CRAI concept. Copyright (C) 2013, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved.
|
|
| 15. |
- Zhou, Xiaolei
(författare)
-
Elucidation of the molecular mechanisms of action of anti-cancer compounds reveals possible combination strategies for anti-cancer therapy
- 2021
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cancer develops due to accumulation of mutations or epigenetic changes within normal cells, usually over a considerable period of time. When cancer patients are diagnosed at late stage, the tumor cells are often more heterogenous and aggressive, which results in tumor resistance to anti-cancer therapies and therefore can be lethal. In order to overcome drug resistance, effective combinational therapies are needed. My PhD project aimed to explore the mechanisms of action of anti-cancer compounds, including p53 activating compounds, chemotherapeutic drugs and hormonal therapy. We also aimed to discover the most efficient combination therapies based on the mechanisms of action we uncovered which potentially can guide clinical practice. In paper I, we explored how pharmacological activation of wtp53 by MDM2 inhibitors promotes immune response within tumor cells and TME. We found that p53 activating compounds or peptide, including Nutlin-3a, AMG-232 and ATSP-7041, de-repressed retrotransposons, such as ERVs and Long interspersed nuclear element-1 (LINE-1), via repression of DNA methyltransferase 1 (DNMT1) and Lysine-specific histone demethylase 1A (LSD1) encoded by lysine demethylase 1A (KDM1A). De-repression of ERVs triggered IFN response followed by activation of downstream signaling involving antigen processing and presentation (APP) which enhanced exogenous neoantigen ovalbumin (OVA) presentation on the surface membrane of cancer cells. We also confirmed that after p53 activation there was an induction of IFN response in both mouse model and tumor samples from patients engaged in MDM2 inhibitor ALRN-6924 clinical trial. We observed that p53 activating compounds upregulated the expression of APP genes and PD-L1 in B16 murine melanoma. Therefore, we investigated the effect of combination of p53 activating peptide ATSP-7041 or its advanced analogue ALRN-6924 with anti-PD-1 antibody in two different tumor bearing mouse models. We found that the ATSP-7041 overcame tumor resistance to anti-PD-1 therapy and significantly decreased the tumor growth rate in comparison with control or single agent treated mice. Moreover, p53 activating peptide facilitated the infiltration of anti-tumor immune cells, consisting of CD4+ T cells, CD8+ T cells and B cells and decreased the immune suppressive myeloid-derived suppressor cells (MDSCs) within TME of B16 tumor bearing mouse model. Our results reveal a novel finding that p53 activating compounds can de-repress ERVs via suppression of two different chromatin modifiers, induce IFN response in cancer cells, mouse model and cancer samples from patients, and overcome immunologically cold tumor’s resistance to immune checkpoint blockade in mouse models. These findings are very promising to translate to clinical applications. In paper II, we investigated the mechanisms of breast cancer resistance to TMX and how we could overcome the resistance by three anti-cancer compounds. We found a higher SULT1A1 expression in spontaneous TMX resistant breast cancer cell line MCF7-TMXR compared to normal ER+ MCF7 breast cancer cell line. The depletion of SULT1A1 in MCF7-TMXR sensitized cells to TMX treatment again. Furthermore, TMX treatment induced SULT1A1 expression in both patient-derived samples and in ER+ MCF7 breast cancer cell line. We found that anti-cancer activities of RITA, AF and ONC-1 were dependent on SULT1A. The mechanism of action of these compounds, including induction of ROS as a result of inhibition of thioredoxin reductase 1 (TrxR1) activity and DNA damage, was also SULT1A1-dependent. We further showed that these three anti-cancer compounds had synergistic effect with TMX in ER+ MCF7 breast cancer cell line. In line with these results, MCF7-TMXR had better response to RITA and AF than normal ER+ MCF7. We observed that the pretreatment with TMX of patient breast cancer samples, or TMX unresponsive breast cancer samples sensitized to RITA treatment. Our data suggest that the induction of SULT1A1 is responsible for breast cancer resistance to TMX treatment in cancer cell lines and patient tumor samples. Resistance to TMX can be overcame by combination with anti-cancer compounds bioactivated by SULT1A1, which can be potentially translated into clinical setting to improve the clinical outcome. In paper III, we explored the mechanisms of mtp53-mediated evasion of cancers from the immune response. We addressed the question whether Apr-246, originally discovered as mtp53 activating compound, can recover the anti-tumor immune surveillance in cancers carrying mtp53. By analyzing TCGA data, we found that breast cancer patients carrying mtp53 display chronic inflammation characterized by elevated TIS score and IFN signaling, in comparison to breast cancer patients carrying wtp53. We found that mtp53 gained the function to upregulate IFNs and ERVs, a well-established upstream stimulator of IFN signaling. Moreover, we found that the majority of genes comprising a 26 gene signature that defines activated CD8+ T cell were upregulated in breast cancer patients carrying mtp53. Cytokines involved in CD8+ T cells attraction, proliferation and activity were upregulated, while Transforming growth factor beta (TGF-β) that inhibits T cell function was downregulated in breast cancers carrying mtp53. These data imply that breast cancers carrying mtp53 must develop mechanisms to escape from immune surveillance. Next we detected an enhanced expression of several ICs in samples from breast cancer patients carrying mtp53. Elevated expression of ICs is a well-studied tumor intrinsic mechanism to suppress immune response. We found that mtp53 acquired novel gain-of-function (GOF) to upregulate ICs in a set of cancer cell lines. Moreover forkhead box P3 (Foxp3), a well- established Treg cell marker, was also increased within TME of breast cancer patients carrying mtp53, indicating a tumor extrinsic mechanism to evade from CD8+ T cell surveillance. We further found that Apr-246 could induce acute IFN or repress ICs in a panel of cancer cell lines, while promoted CD4+ T cells infiltration and prevented CD8+ T cells exhaustion within the TME of a mtp53 tumor bearing mouse model. Together, our data suggest that cancer cells carrying mtp53 can escape immune surveillance die to enhanced inflammatory signaling, together with upregulated ICs. Apr-246 could recover the immune surveillance by inducing acute IFN activation or repressing ICs expression in cancer cell lines, and promoting anti-tumor immune response in in vivo mouse model.
|
|
| 16. |
- Zhou, Xiaolei
(författare)
-
Molecular genetic studies of colorectal cancer
- 2005
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Colorectal cancer (CRC) is one of the leading causes of morbidity and mortality due to cancer in the Western countries. Epidemiological studies have shown that at least 20-30% of CRCs have a potentially identifiable genetic cause. Inherited forms of CRC with Mendelian dominant inheritance have been a major focus of study and many high-penetrance susceptibility genes have been identified, such as APC, hMLH1, hMSH2. However these high-penetrance susceptibility genes can only account for 3%-5% of all CRCs, thus additional, so far unknown, genes for CRC predisposition remain to be identified. Recent evidence has shown that a large proportion of genetic variation in CRC risk is probably due to a combination of a large number of common alleles with low penetrance and shared environmental factors. So in order to plot the accurate genetic-risk profiles of CRC for future population-based diagnosis and prevention programs, it is as equally important to identify low penetrance alleles as to identify high penetrance alleles. In this thesis, we evaluated the contribution of, hMLH3, APC and MYH as either high- or low- penetrance susceptibility genes for CRC in the Swedish population by the approaches of mutation screening and association study. hMLH3, is a newly identified DNA Mismatch Repair (MMR) gene interacting with hMLH1 and suggested to be a candidate gene for HNPCC. We screened 70 index patients suggestive of a genetic predisposition for germline mutations in the gene, and found one frameshift and 11 missense variants in 16 index patients (23%). The only frameshift mutation found, 885delG, seemed to segregate very well with cancer in the family as a monogenic high-penetrance allele. All the missense variants identified were not shown to segregate with cancer in the families, so hMLH3 mutations were not important as a major predisposing factor for familial CRC. However, in one family, we observed a co-segregation of one hMLH3 missense variant and one hMSH2 missense variant with the disease phenotype, suggesting that hMLH3 could work as a low-penetrance predisposing gene for CRC by working together with other low-penetrance genes in an additive or multiplicative manner. (Paper I) The recent finding that one missense variant in APC (11307K) led to an increased CRC risk in Askenazi Jews raises the possibility that there should exist other similar predisposing variants in this gene in different populations. We tested this possibility by performing the mutation screening of APC in cohorts of Swedish hereditary CRCs, sporadic CRCs and normal controls. Our results showed that some APC variants other than 11 307K could act as low-penetrance alleles for CRC, for example, the variant 3´UTR 8636C>A. This variant was found to have an increased CRC risk of around two fold-a risk comparable to that of I1307K-though the association studies had statistically significant results only at the borderline (Paper II). In addition, the 3´UTR 8636C>A variant and the APC locus it implicates were incidentally found to be associated with autism spectrum disorder (ASD), substantiated by several follow-up association studies with statistically significant results. (Paper IV). MYH plays a significant role in the repair of mutations caused by 8-oxo-7,8-dihydroxy-2-deoxyguanosine (8-oxoG), one of the most stable product of oxidative DNA damage. Biallelic germline mutations of this gene have been shown to predispose to a proportion of multiple colorectal adenomas and cancer. We screened 84 unrelated Swedish non-FAP and non-HNPCC familial CRCs for germline mutations in the gene to evaluate the contribution of MYH mutations in CRC with few polyps. None of the cases was found to carry any pathogenic sequence change, indicating that MYH mutations are not likely to account for familial CRCs in the absence of multiple adenomas. However, we could demonstrate that the two most common pathogenic variants Y165C and G382D found in Caucasians existed in the Swedish population as well, and both of them appeared to confer a slightly increased CRC risk in heterozygosity. Additional candidate low-penetrance alleles for CRC were also identified at the position of amino acid 423 (R423Q, R423P, and R423R). Whether mutations at position 423 have pathological relevance needs to be further studied. (Paper III) Recently, there is increasing evidence to indicate that hereditary and sporadic MSI cancers evolve through different pathways. We wondered if microarray technology can help differentiate these two tumors into two distinct entities. We transcriptionally profiled six HNPCC and seven sporadic MSI CRCs using Affymetrix Microarray HG-U95Av2 chips. Unsupervised hierarchical clustering analysis and principle component analysis (PCA) failed to distinguish hereditary MSI tumors from its sporadic counterparts, indicating that the molecular difference between these two phenotypes, if any, is insignificant. In addition, a gene called Tight Junction Protein 3 (TJP3), a novel member of the MAGUK protein family found at the cell tight junction, was shown to be downregulated by about 2 fold in transcription in a small subset of HNPCC tumors with suggested bad prognosis compared with other samples, and in a MSI cell line with high metastatic potential compared with its isogenic cell line with low metastatic potential. Therefore, TJP3 would be a metastasis-associated gene in CRCs with MSI, which warrants further functional characterization. (Paper V)
|
|
| 17. |
- Zhu, Zhaolong, et al.
(författare)
-
Enhancing face-milling efficiency of wood–plastic composites through the application of genetic algorithm–back propagation neural network
- 2024
-
Ingår i: Wood Material Science & Engineering. - 1748-0272 .- 1748-0280.
-
Tidskriftsartikel (refereegranskat)abstract
- Wood–plastic composites (WPCs) have advanced physicochemical properties and are widely applied in various fields. How to achieve high-efficiency, high-quality machining of WPC is a pressing issue that WPC manufacturing enterprises need to address. To this end, this research focused primarily on improving the machinability of WPC with end milling experiments. In this work, a single-factor method was used to analyse the impact of axial milling depth, spindle speed, and tool rake angle on resultant forces and surface roughness. Main effects analysis was applied to explore the degree of influence of axial milling depth, spindle speed, and tool rake angle on cutting forces and surface roughness. Furthermore, three-dimensional characterisation techniques were utilised to analyse the surface morphology characteristics of WPC during end milling. Finally, a genetic algorithm–back propagation neural network was applied to develop prediction models for resultant force and surface roughness, and optimal milling conditions were identified as axial milling depth of 0.50 mm, spindle speed of 7841 r/min, and rake angle of 15°; these produced the lowest resultant force and surface roughness. The findings of this work are proposed as a guide for better cutting performance in the industrial production of WPC.
|
|
