Neurologic Abnormalities in Workers of a 1-Bromopropane Factory

We reported recently that 1-bromopropane (1-BP; n-propylbromide, CAS Registry no. 106-94-5), an alternative to ozone-depleting solvents, is neurotoxic and exhibits reproductive toxicity in rats. The four most recent case reports suggested possible neurotoxicity of 1-BP in workers. The aim of the present study was to establish the neurologic effects of 1-BP in workers and examine the relationship with exposure levels. We surveyed 27 female workers in a 1-BP production factory and compared 23 of them with 23 age-matched workers in a beer factory as controls. The workers were interviewed and examined by neurologic, electrophysiologic, hematologic, biochemical, neurobehavioral, and postural sway tests. 1-BP exposure levels were estimated with passive samplers. Tests with a tuning fork showed diminished vibration sensation of the foot in 15 workers exposed to 1-BP but in none of the controls. 1-BP factory workers showed significantly longer distal latency in the tibial nerve than did the controls but no significant changes in motor nerve conduction velocity. Workers also displayed lower values in sensory nerve conduction velocity in the sural nerve, backward recalled digits, Benton visual memory test scores, pursuit aiming test scores, and five items of the Profile of Mood States (POMS) test (tension, depression, anxiety, fatigue, and confusion) compared with controls matched for age and education. Workers hired after May 1999, who were exposed to 1-BP only (workers hired before 1999 could have also been exposed to 2-BP), showed similar changes in vibration sense, distal latency, Benton test scores, and depression and fatigue in the POMS test. Time-weighted average exposure levels in the workers were 0.34–49.19 ppm. Exposure to 1-BP could adversely affect peripheral nerves or/and the central nervous system

Untersuchung über die transkriptionelle TFF1 Regulation und die Funktion von TFF1 in weiblichen Reproduktionsorganen

Although the ability of estradiol to regulate the human TFF1 (estrogen responsive gene) expression is established in vitro, the underlying mechanisms remain undefined. In this thesis, we examined and investigated the transcriptional regulation of human TFF1 by E2 and its antagonists ICI 182 780 and tamoxifen in MCF-7 cells. After examination and investigation of the transcriptional regulation of TFF1 by E2 and its antagonists ICI 182 780 and tamoxifen in vitro, we further attempted to investigate the transcriptional regulation of TFF1 by estrogen in vivo. Therefore, we generated a transgenic rat model harboring the human TFF1 promoter linked to a luciferase reporter gene to explore regulation of the TFF1 by estrogen, especially in the female reproductive system. Three lines of hTFF1-luc transgenic rat model were successfully established and further characterized. We found that the hTFF1 promoter can be activated by the physiological estrogen in female homozygous transgenic rats during the course of estrous cycle. hTFF1 transcriptional regulation was further confirmed on protein- and molecular-level. This hTFF1-luc rat model offered an opportunity to investigate the hTFF1 transcriptional regulation and its possible mechanisms in vivo by estrogen and other regulatory factors. This rat model is useful in toxicology for efficiently and accurately screening some xenobiotic substrates or some metabolites of xenobiotic substrates in an in vivo context, which are suspected of exerting an estrogen-like effect to transcriptionally regulate the hTFF1 promoter in vitro. The biological functions of TFF1 especially in the female reproductive system is poorly understood. Thus, TFF1 knock out mice were used to understand the biological role of TFF1 in the uterus and vagina in detail. Striking morphological alterations were observed in both organ system, which seemed to be linked to the lost of cell-cell contact and cell- cell adhesion with the neighboring epithelial cells. In summary, our data lead to the suggestion that TFF1 might play an important role in the regulation of cell differentiation and proliferation in the uterus and vagina. Further studies are still required to address the specific molecular mechanisms on lost of cell-cell contact and cell-cell adhesion with the neighboring epithelial cells in TFF1 knock out mice.Obwohl die Fähigkeit von Östradiol das menschliche Protein TFF1 regulieren zu können, bereits in vitro bekannt ist, bleiben die zugrunde liegenden molekularen Mechanismen noch ungeklärt. In der vorliegenden Arbeit untersuchten wir deshalb die transkriptionelle Regulation von menschlichen TFF1 durch E2, den Antagonisten ICI 182 780 und Tamoxifen in MCF-7 Zellen in vitro und in vivo am Tiermodell. Dazu stellten wir ein transgenes Rattenmodell her, das im Genom den menschlichen TFF1 Promotor, verbunden mit einem Luziferase-Reportergen, integrierte, um die transkriptionelle Regulation von TFF1 durch Östrogene vor allem in den weiblichen Fortpflanzungsorganen zu erkunden. Drei transgene Rattenlinien (hTFF1-Luc) wurden erfolgreich etabliert und weiter charakterisiert. Wir fanden in weiblichen homozygot transgenen Ratten heraus, dass der hTFF1-Promotor durch die physiologischen Östrogene im Laufe des Ovarialzyklus aktiviert werden kann. Die transkriptionelle hTFF1 Regulation wurde weiter auf der Protein- und molekularen Ebene bestätigt. Dieses hTFF1-Luc Rattenmodell bietet uns die Gelegenheit, die hTFF1 Transkriptionsregulation und ihre möglichen Mechanismen in vivo durch Östrogene und andere regulatorische Faktoren näher zu untersuchen. Dieses Rattenmodell kann in der Toxikologie für ein effizientes und akkurates Screening einiger xenobiotischer Substrate mit Östrogen-ähnlicher Wirkung und seiner Metaboliten in vivo genutzt werden. Die biologische Funktion von TFF1 vor allem in den weiblichen Fortpflanzungsorganen ist weitgehend unverstanden, sodass wir TFF1-defiziente Mäuse verwendeten, um die biologische Rolle von TFF1 in der Gebärmutter und Vagina im Detail zu untersuchen. Markante morphologische Veränderungen wurden in beiden Organsystemen beobachtet. Es scheint hier eine Verbindung zu bestehen, die mit dem Verlust von Zell-Zell- Kontakt und Zell-Zell-Adhäsion benachbarter Epithelzellen einhergeht. Zusammenfassend weisen unsere Daten daraufhin, dass TFF1 eine wichtige Rolle spielt bei der Regulation der Zelldifferenzierung und Zellproliferation in der Gebärmutter und der Scheide. Weitere Studien sind erforderlich, um die spezifischen molekularen Mechanismen am Verlust der Zell-Zell-Kontakt und Zell-Zell-Adhäsion mit dem benachbarten Epithelzellen in TFF1-defizienten Mäusen herauszuarbeiten

A Nonconvex Relaxation Approach for Rank Minimization Problems

Recently, solving rank minimization problems by leveraging nonconvex relaxations has received significant attention. Some theoretical analyses demonstrate that it can provide a better approximation of original problems than convex relaxations. However, designing an effective algorithm to solve nonconvex optimization problems remains a big challenge. In this paper, we propose an Iterative Shrinkage-Thresholding and Reweighted Algorithm (ISTRA) to solve rank minimization problems using the nonconvex weighted nuclear norm as a low rank regularizer. We prove theoretically that under certain assumptions our method achieves a high-quality local optimal solution efficiently. Experimental results on synthetic and real data show that the proposed ISTRA algorithm outperforms state-of-the-art methods in both accuracy and efficiency