Genetic Contribution of Endometriosis to the Risk of Developing Hormone-Related Cancers

Endometriosis is a common gynecological disorder that has been associated with endometrial, breast and epithelial ovarian cancers in epidemiological studies. Since complex diseases are a result of multiple environmental and genetic factors, we hypothesized that the biological mechanism underlying their comorbidity might be explained, at least in part, by shared genetics. To assess their potential genetic relationship, we performed a two-sample mendelian randomization (2SMR) analysis on results from public genome-wide association studies (GWAS). This analysis confirmed previously reported genetic pleiotropy between endometriosis and endometrial cancer. We present robust evidence supporting a causal genetic association between endometriosis and ovarian cancer, particularly with the clear cell and endometrioid subtypes. Our study also identified genetic variants that could explain those associations, opening the door to further functional experiments. Overall, this work demonstrates the value of genomic analyses to support epidemiological data, and to identify targets of relevance in multiple disorders.     

基于正交多项式和稳定图的密集模态参数辩识

由于正交多项式算法在频响函数模态参数拟合时,模态数目和多项式分子阶次较难确定,无法对拟合过程进行干涉。在原有算法的基础上,通过结合稳定图和模态指示函数,确定了频响函数的模态数目和极点（阻尼及固有频率）;在已知极点的基础上,由线性最小二乘方法对留数进行估计。此外,该方法被扩展到频响函数的整体拟合。通过将该方法应用于模态耦合严重的频响函数模态参数估计,并与原有正交多项式算法及商业化软件M E’scopeVES进行对比,表明该算法在避免虚假模态或发生模态遗漏现象的同时,拟合结果准确、稳定,抗干扰能力强。     

Cesium Carbonate‐Promoted Hydroamidation of Alkynes: Enamides,Indoles and the Effect of Iron(III) Chloride

A series of enamide derivatives was prepared by a simple procedure for the hydroamidation of alkynes with amides and sulfonamides. The use of such a mild base as cesium carbonate promotes the latter transformation, and the addition of catalytic amounts of iron(III) chloride has a beneficial effect in the outcome of some of the presented hydroamidation reactions. A range of indoles was also synthesized from ortho‐alkynylanilides by both complementary procedures, which proved to be useful for the construction of the indolo[1,2‐c]quinazoline tetracyclic system from an ortho‐(2‐aminophenylalkynyl)anilide.     

A method for the identification of the specific force coefficients for mechanistic milling simulation

This paper presents a new method to obtain the specific cutting coefficients needed to predict the milling forces using a mechanistic model of the process. The specific coefficients depend on the tool–material couple, the cutting conditions and the geometry of the tool, being usually calculated applying the force model in an inverse way. The most used inverse method is based on the calculation of the average cutting force per revolution values measured in a series of slot machining tests at different feed rates. In this research work, the inverse method is applied using the instantaneous cutting force values, solving the equations system by a constrained least squares fitting method. Furthermore, the cutting force and specific cutting coefficients relation with rake angle and chip thickness is analysed. The results are validated by the comparison of the simulations and experiments in orthogonal cutting test, showing the advantages of using the new method.     

Experimental validation of appropriate axial immersions for helical mills

The forced periodic vibrations of milling processes with helical tools are modelled and analysed. By means of analytical and numerical techniques, the so-called superchart of milling is constructed that includes the conventional stability chart with the stability lobes and also the amplitudes of the stable forced vibrations, which is correlated to many surface quality numbers like surface location error, surface waviness and surface roughness. The existences of trivial and non-trivial appropriate axial immersions are presented for a single degree of freedom mechanical model of the machine tool structure. At these appropriate axial immersion parameters, if the cutting is stable, the surface quality parameters will be also optimal even in those spindle speed domains where the system is near to resonance and the cutting efficiency is high. Experiments are performed with a large industrial milling machine using a flexible test rig with an essential flexibility in one direction. The calculated and the measured forced vibration signals in the stable domains of the stability chart are in good correlation, which validates the simple analytical predictions for the non-trivial appropriate axial immersion parameters.     

Cylindrical milling tools: Comparative real case study for process stability

Critical comparison is presented related to the stability behaviour of milling processes performed by conventional, variable helix and serrated milling tools. The paper presents a general milling model linked to any non-proportionally damped dynamic system. Extended multi frequency solution and semi-discretization are implemented and used to calculate the stability of stationary milling. Measurements performed in industrial environment validate the general numerical algorithm that is able to predict the stability conditions of milling processes carried out by cylindrical cutters of optional geometry. Both the calculations and the measurements confirm that, for roughing operations, the highest stability gain can be achieved by serrated cutters. It is also demonstrated that variable helix milling tools can achieve better stability behaviour only if their geometry is optimized for the given cutting operation.     

Analysis of directional factors in milling: importance of multi-frequency calculation and of the inclusion of the effect of the helix angle

The concept of directional factor for chatter stability analysis has been used from a long time ago. The analysis of its evolution for different feed directions in milling processes provides a good way of selecting the best cutting conditions. For very stable cutting directions, corresponding to very low directional factors, the single frequency analysis gives unacceptable results and multi-frequency, or alternative solutions as semi-discretisation must be used. It is found also that the period doubling lobes extend at both sides of the tooth pass frequency equivalent to twice the natural frequency. In these cases, helix angle has a very important effect on the stability. For end milling processes, where the mill axial pitch can be of the order of the stable limit depth of cut, a very stable situation is found except in those areas corresponding to period doubling, where instability islands are found. Besides, a graphical construction for accurate estimation of the stable limit depth of cut and starting rotational speed of the period doubling lobes is proposed.     

基于实验模态分析的集中参数法建模

利用集中参数模型的建立,不仅拓展了实验模态分析(EMA)的使用范围,还能大量缩减原有模型的自由度并保持结构的动态特性。在对一立铣床进行模态测试以及振型可视化的基础上,采用集中质量、弹簧阻尼单元建立了该铣床的7自由度集中参数模型,并在该模型基础上合成刀尖频响函数及预测颤振稳定域,揭示出机床颤振与振型的联系。与原有测试频响函数的比较表明,该模型准确度较高。