Excessive ovarian production of nerve growth factor elicits granulosa cell apoptosis by setting in motion a tumor necrosis factor α/stathmin-mediated death signaling pathway

Excessive nerve growth factor (NGF) production by the ovary, achieved via a transgenic approach, results in arrested antral follicle growth, reduced ovulatory capacity, and a predisposition to cyst formation in response to mildly elevated LH levels. Two salient features in these mutant mice (termed 17NF) are an elevated production of 17α-hydroxyprogesterone (17-OHP(4)), testosterone, and estradiol (E(2)) in response to gonadotropins, and an increased frequency of granulosa cell (GC) apoptosis. In this study, we show that the increase in steroidal response is associated with enhanced expression of Cyp17a1, Hsd17b, and Cyp19a1, which encode the enzymes catalyzing the synthesis of 17-OHP(4), testosterone, and E(2) respectively. Using a proteomic approach, we identified stathmin (STMN1), as a protein that is overproduced in 17NF ovaries. In its phosphorylated state, STMN1 mediates a cell death signal initiated by tumor necrosis factor α (TNF). STMN1 is expressed in GCs and excessive NGF increases its abundance as well as that of its forms phosphorylated at serine (Ser) 16, 25, and 38. TNF synthesis is also increased in 17NF ovaries, and this change is abolished by blocking neurotrophic tyrosine kinase receptors. Inhibiting TNF actions in vivo by administering a soluble TNF receptor prevented the increase in total and phosphorylated STMN1 production, as well as GC apoptosis in NGF-overproducing ovaries. These results indicate that an excess of NGF in the ovary promotes steroidogenesis by enhancing the expression of enzyme genes involved in 17-OHP(4), testosterone, and E(2) synthesis, and causes GC apoptosis by activating a TNF/ STMN1-mediated cell death pathway.     

Pulsed magneto-motive ultrasound imaging to detect intracellular trafficking of magnetic nanoparticles

As applications of nanoparticles in medical imaging and biomedicine rapidly expand, the interactions of nanoparticles with living cells have become an area of active interest. For example, intracellular accumulation of nanoparticles-an important part of cell-nanoparticle interaction-has been well studied using plasmonic nanoparticles and optical or optics-based techniques due to the change in optical properties of the nanoparticle aggregates. However, magnetic nanoparticles, despite their wide range of clinical applications, do not exhibit plasmonic-resonant properties and therefore their intracellular aggregation cannot be detected by optics-based imaging techniques. In this study, we investigated the feasibility of a novel imaging technique-pulsed magneto-motive ultrasound (pMMUS)-to identify intracellular accumulation of endocytosed magnetic nanoparticles. In pMMUS imaging a focused, high intensity, pulsed magnetic field is used to excite the cells labeled with magnetic nanoparticles, and ultrasound imaging is then used to monitor the mechanical response of the tissue. We demonstrated previously that clusters of magnetic nanoparticles amplify the pMMUS signal in comparison to the signal from individual nanoparticles. Here we further demonstrate that pMMUS imaging can identify interaction between magnetic nanoparticles and living cells, i.e.?intracellular accumulation of nanoparticles within the cells. The results of our study suggest that pMMUS imaging can not only detect the presence of magnetic nanoparticles but also provides information about their intracellular accumulation non-invasively and in real-time.     

Individual safety performance in the construction industry: development and validation of two short scales

In the current research a short measure of safety performance is developed for use in the construction industry and the relationships between different components of safety performance and safety outcomes (e.g., occupational injuries and work-related pain) are explored within the construction context. This research consists of two field studies. In the first, comprehensive measures of safety compliance and safety participation were shortened and modified to be appropriate for use in construction. Evidence of reliability and validity is provided. Both safety compliance and safety participation were negatively related to occupational injuries, yet these two correlations were not statistically different. In the second study, we investigated the relationships between these two components of safety performance and work-related pain frequency, in addition to replicating Study 1. Safety compliance had a stronger negative relationship with pain than safety participation. Implications for research are discussed.     

Multimodal Magneto‐Plasmonic Nanoclusters for Biomedical Applications

Multimodal nanostructures can help solve many problems in the biomedical field including sensitive molecular imaging, highly specific therapy, and early cancer detection. However, the synthesis of densely packed, multicomponent nanostructures with multimodal functionality represents a significant challenge. Here, a new type of hybrid magneto‐plasmonic nanoparticles is developed using an oil‐in‐water microemulsion method. The nanostructures are synthetized by self‐assembly of primary 6 nm iron oxide core‐gold shell particles resulting into densely packed spherical nanoclusters. The dense packing of primary particles does not change their superparamagnetic behavior; however, the close proximity of the constituent particles in the nanocluster leads to strong near‐infrared (NIR) plasmon resonances. The synthesis is optimized to eliminate nanocluster cytotoxicity. Immunotargeted nanoclusters are also developed using directional conjugation chemistry through the Fc antibody moiety, leaving the Fab antigen recognizing region available for targeting. Cancer cells labeled with immunotargeted nanoclusters produce a strong photoacoustic signal in the NIR that is optimum for tissue imaging. Furthermore, the labeled cells can be efficiently captured using an external magnetic field. The biocompatible magneto‐plasmonic nanoparticles can make a significant impact in development of point‐of‐care assays for detection of circulating tumor cells, as well as in cell therapy with magnetic cell guidance and imaging monitoring.     

Reconfigurable Anisotropic Coatings via Magnetic Field‐Directed Assembly and Translocation of Locking Magnetic Chains

A method for the generation of remotely reconfigurable anisotropic coatings is developed. To form these coatings, locking magnetic nanoparticles (LMNPs) made of a superparamagnetic core and a two‐component polymer shell are employed. Two different polymers form phase‐separated coaxial shells. The outer shell provides repulsive interactions between the LMNPs while the inner shell exerts attractive forces between the particles. Applying a non‐uniform magnetic field, one gathers the particles together, pushing them to come in contact when the internal shells could effectively hold the particles together. When the magnetic field is turned off, the particles remain locked due to these strong interactions between internal shells. The shells are thus made stimuli‐responsive, so this locking can be made reversible and the chains can be disintegrated on demand. In a non‐uniform magnetic field, the assembled chains translocate, bind to the solid substrate and form anisotropic coatings with a “locked” anisotropic structure. The coatings can be constructed, aligned, realigned, degraded, and generated again on demand by changing the magnetic field and particle environment. The mechanism of the coating formation is explained using experimental observations and a theoretical model.     

寂静之屋:临时修道院,梅舍德

为教堂建筑恢复宗教特点的努力,令一种倾向于1960年代极简抽象主义艺术潮流的建筑风格产生了.“寂静之屋”表现出一个沉寂的“非世界”,它摒除一切喧嚣,表达出修道的纯洁感.造型的简朴和完美、粗糙的材料,暴露的混凝土和不经修饰的墙面都显示出它的简约,构成不同光照效果下通透空间的背景.通过造型与开窗可以调节和控制进入的光线.光在某些地方可以从上方射下,就像人们对宗教建筑期望的那样,而且它看起来没有特定的方向,并显得分布均匀.“寂静之屋”由两栋不同的建筑组成,一栋为长方形,内部的楼梯让访客迎光线而上;另一栋是“存在之屋”,有20个房间用于生活区.不同的步道和带玻璃罩的桥廊构成环境的视觉框架,并连接起这两栋建筑.     

Scheduling Under Common Due Date, A Single Resource and Precedence Constraints—A Dynamic Approach

This paper discusses dynamic methods for solving a class of multi-project scheduling problems in which rates of job performances are controllable and resources such as money, energy or manpower per time unit, are renewable and continuously divisible. The objective is to complete the projects as close to the common due date as possible. Two different ways of imposing sequential precedence relations between project jobs are explored by formulating two dynamic models and studying their relationships on the optimal solution. Efficient time-decomposition algorithms for finding either globally optimal schedules or lower bound guided near-optimal solutions are suggested and computationally tested.     

On the detection of simple points in higher dimensions using cubical homology.

Simple point detection is an important task for several problems in discrete geometry, such as topology preserving thinning in image processing to compute discrete skeletons. In this paper, the approach to simple point detection is based on techniques from cubical homology, a framework ideally suited for problems in image processing. A (d-dimensional) unitary cube (for a d-dimensional digital image) is associated with every discrete picture element, instead of a point in epsilon(d) (the d-dimensional Euclidean space) as has been done previously. A simple point in this setting then refers to the removal of a unitary cube without changing the topology of the cubical complex induced by the digital image. The main result is a characterization of a simple point p (i.e., simple unitary cube) in terms of the homology groups of the (3d - 1) neighborhood of p for arbitrary, finite dimensions     

Phase equilibria in the α-Ti-Al-Si region of the Ti-Si-Al system

An experimental investigation of the phase relations in the titanium (Ti)-aluminum (Al)-silicon (Si) system was undertaken by differential thermal analysis, x-ray diffraction, metallography, and microprobe analysis. The present measurements when combined with those from an earlier investigation at this laboratory provide data for 56 alloy compositions in the Ti-Al-Si system. The combined results allowed the construction of a solidus projection, a melting diagram including both solidus and liquidus, partial isothermal sections at 1270 °C and 1250 °C, three isopleths with a constant percentage of one or another component, and a reaction scheme.