Obesity Suppresses Pigment Epithelium-Derived Factor and Alters Pro-Tumorigenic Signaling Pathways in Prostate Cancer

Background: Pigment epithelium-derived factor (PEDF), a multifunctional protein, is a potent tumor suppressor and anti-angiogenic factor. PEDF has been identified as a novel regulator of lipid metabolism via binding and activating adipose triglyceride lipase, which stimulates lipolytic pathways. PEDF-deficient mice develop prostatic hyperplasia that progresses to cancer when these mice are fed a high fat diet (HFD). PEDF expression is decreased in prostate cancer (PCa) patient tissues. Conversely, PEDF treatment inhibits PCa growth in mouse models. Recently, our lab has demonstrated that excess oleic acid (OA) treatment, an in vitro obesity model, suppresses secreted PEDF expression in PCa cell lines (LNCaP, DU145, and PC-3) and suppresses cellular PEDF expression in androgen-independent PCa cell lines (DU145 and PC-3 cells). This is of interest because PCa patients who are obese are at a higher risk of aggressive disease and more likely to die from the disease. However, the molecular mechanisms through which excess OA down-regulates PEDF in vitro are unknown. For the in vitro studies, we first investigated one OA receptor, G protein-coupled receptor 40 (GPR40), and tested if OA-mediated PEDF suppression was dependent on calcium (Ca2+) and/or peroxisome proliferator-activated receptor gamma (PPAR) signaling pathways. In addition, it is unknown if obese conditions suppress PEDF in vivo within PCa tissues or within PCa xenograft tumors. Thus, we hypothesize that excess lipids, in obesity and HFD microenvironments, alter lipid metabolism, which in turn, increases pro-tumorigenic activity and decreases PEDF expression in PCa. To study this hypothesis, we used an excess OA model in vitro and two in vivo PCa models. Methods: We treated RWPE-1, LNCaP, DU145, PC-3, and TRAMPC2 with excess OA at 1 mM for 48 hours. Then, cells were counted, viability was assessed, and PEDF levels were quantified by enzyme-linked immunosorbent assay (ELISA). For in vivo studies, two obese models were used: (1) a xenograft model using the TRAMPC2 cell line injected in male WT mice and obese (ob/ob) mice and (2) male Pbsn-Cre+-PTENfl/fl mice fed either a control diet (CD) or a HFD. All mice were in a C57Bl/6J background. Blood samples, TRAMPC2 tumor xenograft tissue, mouse PCa tissues, liver, and adipose tissues were collected. PEDF levels and pro-tumorigenic pathway mediators were evaluated by ELISA and by Western blot, respectively. Results: For the in vitro study, we found that OA did not interact with the GPR40 receptor and/or PPAR to rescue secreted PEDF levels in LNCaP, DU145, and PC-3 cells. In Pbsn-Cre+-PTENfl/fl model, the prostate weight of HFD-fed mice was increased as compared to CD-fed mice (P-value \u3c0.042). In the TRAMPC2 xenograft model, we observed a significant increase in tumor volume and weight in TRAMPC2 tumors grown in ob/ob mice as compared to tumors grown in lean mice (P-value \u3c0.018). Tumor PEDF levels were significantly decreased in TRAMPC2 xenograft tumors grown in ob/ob mice compared to TRAMPC2 xenograft tumors grown in WT mice (P-value \u3c0.024). Lastly, in an effort to identify other signaling pathways altered in TRAMPC2 tumor tissues grown in ob/ob mice versus WT mice, we found a significant reduction in superoxide dismutase 2 (SOD2; P-value \u3c0.018) and serine palmitoyltransferase (SPT; P-value \u3c0.050). Interestingly, while previous studies showed that obesity increased circulating PEDF, here we did not find an increase in circulating PEDF levels in ob/ob mice with TRAMPC2 xenograft tumors as compared to WT mice. Moreover, circulating PEDF levels were actually significantly decreased in HFD-fed Pbsn-Cre+-PTENfl/fl mice compared to CD-fed Pbsn-Cre+-PTENfl/fl mice (P-value \u3c0.001). Conclusion: This is the first study to report that an obese microenvironment suppresses circulating PEDF and suppresses PEDF, SOD2, and SPT in mouse PCa tissues. Therefore, these data indicate that reduced PEDF, SOD2, or SPT levels could be mechanisms of obesity-driven PCa progression

Controller design for gantry crane system using modified sine cosine optimization algorithm

The objective of this research paper is to design a control system to optimize the operating works of the gantry crane system. The dynamic model of the gantry crane system is derived in terms of trolley position and payload oscillation, which is highly nonlinear. The crane system should have the capability to transfer the material to destination end with desired speed along with reducing the load oscillation, obtain expected trolley position and preserving the safety. Proposed controlling method is based on the proportional-integral-derivative (PID) controller with a series differential compensator to control the swinging of the payload and the system trolley movement in order to perform the optimum utilization of the gantry crane.  Standard sine cosine optimization algorithm is one of the most-recent optimization techniques based on a stochastic algorithm was presented to tune the PID controller with a series differential compensator. Furthermore, the considered optimization algorithm is modified in order to overcome the inherent drawbacks and solve complex benchmark test functions and to find the optimal design's parameters of the proposed controller. The simulation results show that the modified sine cosine optimization algorithm has better global search performance and exhibits good computational robustness based on test functions. Moreover, the results of testing the gantry crane model reveal that the proposed controller with standard and modified algorithms is effective, feasible and robust in achieving the desired requirements

Parallel Factor-Based Model for Two-Dimensional Direction Estimation

Two-dimensional (2D) Direction-of-Arrivals (DOA) estimation for elevation and azimuth angles assuming noncoherent, mixture of coherent and noncoherent, and coherent sources using extended three parallel uniform linear arrays (ULAs) is proposed. Most of the existing schemes have drawbacks in estimating 2D DOA for multiple narrowband incident sources as follows: use of large number of snapshots, estimation failure problem for elevation and azimuth angles in the range of typical mobile communication, and estimation of coherent sources. Moreover, the DOA estimation for multiple sources requires complex pair-matching methods. The algorithm proposed in this paper is based on first-order data matrix to overcome these problems. The main contributions of the proposed method are as follows: (1) it avoids estimation failure problem using a new antenna configuration and estimates elevation and azimuth angles for coherent sources; (2) it reduces the estimation complexity by constructing Toeplitz data matrices, which are based on a single or few snapshots; (3) it derives parallel factor (PARAFAC) model to avoid pair-matching problems between multiple sources. Simulation results demonstrate the effectiveness of the proposed algorithm

Un système de traduction de verbes entre arabe standard et arabe dialectal par analyse morphologique profonde

International audienceThe developpment of NLP tools for dialects faces the severe problem of lack of resources for such dialects. In the case of diglossia, as in arabic, a variant of arabic, Modern Standard Arabic, exists, for which many resources have been developped which can be used to build NLP tools. Taking advantage of the closeness of MSA and dialects, one way to solve the problem consist in performing a surfacic translation of the dialect into MSA in order to use the tools developped for MSA. We describe in this paper an achitecture for such a translation and we evaluate it on arabic verbs

The Effects of Factorizing Root and Pattern Mapping in Bidirectional Tunisian - Standard Arabic Machine Translation

International audienceThe development of natural language processing tools for dialects faces the severe problem of lack of resources. In cases of diglossia, as in Arabic, one variant, Modern Standard Arabic (MSA), has many resources that can be used to build natural language processing tools. Whereas other variants, Arabic dialects, are resource poor. Taking advantage of the closeness of MSA and its dialects, one way to solve the problem of limited resources, consists in performing a translation of the dialect into MSA in order to use the tools developed for MSA. We describe in this paper an architecture for such a translation and we evaluate it on Tunisian Arabic verbs. Our approach relies on modeling the translation process over the deep morphological representations of roots and patterns, commonly used to model Semitic morphology. We compare different techniques for how to perform the cross-lingual mapping. Our evaluation demonstrates that the use of a decent coverage root+pattern lexicon of Tunisian and MSA with a backoff that assumes independence of mapping roots and patterns is optimal in reducing overall ambiguity and increasing recall

Polymer Biomedical Films

 الافلام المركبة لكل من بولي فنيل الكحول مع السليكا النانوية - اوكسيد الزنك النانوي. بولي مثيل ميثا اكريليت مع السليكا النانوية - اوكسيد الزنك النانوي- الكلوروفيل يتم تحضيرها باستخدام طريقة الصب ويتم تقييم تطبيقاتها الطبية. في هذه الدراسة السليكا النانوية واوكسيد الزنك النانوي تستخدم كماده ماله لتحسين الخواص البيولوجية والميكانيكه للأفلام المركبة. يتم اجراء العديد من الاختبارات على الافلام المركبة مثل مطياف الأشعة تحت الحمراء والفعالية المضادة للبكتريا واختبار الشد. اضهرت النتائج أن أوكسيد الزنك لديه نشاط مضاد للجراثيم ممتاز وهذا النشاط يزداد في الأفلام المركبة مع زيادة تركيز اوكسيد الزنك. الافلام المركبة البولي مثيل ميثا اكريليت اضهرت قوة شفاء أفضل من لأفلام المركبة لبولي فنيل الكحول. ولتجنب الشقوق على افلام بولي مثل ميثا اكريلت المنتجة، الكلوروفيل كصبغه طبيعية حيوية تضاف حيث انها تعمل كملدن وبذالك تزال الشقوق من الافلام المركبة. جميع الاختبارات الميكانيكية والفيزيائية تظهر ان لأفلام المركبة لبولي فنيل الكحول لها قيم اعلى من قيم الافلام المركبة البولي مثيل ميثا اكريليت وهذا يرجع الى حقيقة ان بولي فنيل الكحول يمكن ان يبني اواصر هيدروجينية مع اضافات اوكسيد الزنك النانوي او السليكا النانوية بينما بولي مثيل ميثا اكريليت لا يمتلك ميل لعمل اواصر هيدروجينية.Composite films of both Poly (vinyl alcohol)/nano silica-nano zinc oxide (PVA/SiO2- ZnO) and Poly (methyl methacrylate) / nano silica-nano zinc oxide -chlorophyll (PMMA/SiO2-ZnO-Ch) are prepared by using casting method and their medical applications are evaluated. In this study Nano, silica and Nano zinc oxide are used as filler with the following percentages of (1, 2 and 3) to improve the biological and mechanical properties of the composite films. Many tests are carried on the composite films such as Fourier transform infrared spectroscopy (FTIR), antibacterial activity, and tensile test. Their results show that zinc oxide has an excellent antibacterial activity and this activity increases in composite films with the increasing concentration of the zinc oxide .PMMA composite films show a better healing power than that of the PVA composite films. To avoid cracking on the produced PMMA film, chlorophyll as a bio natural pigment, is added it acts as a plasticizer and as a result it removes film stresses. All mechanical and physical tests show that the PVA composite has higher values than those of PMMA. This is due to the fact that PVA can build a hydrogen bond with ZnO or SiO2 additives while PMMA has no tendency for H-bonding. &nbsp

Antibacterial Activity and Preliminary Phytochemical Screening of Four Medicinal Plants

       The present study was undertaken to investigate the antibacterial activity and to find the biologically active functional groups of four medicinal plants. The ethanolic extracts which were obtained by maceration were tested against in vitro five bacterial strains, using cup-plate agar diffusion method. Preliminary phytochemical screening techniques were also used to test for the presence and nature of the active constituents in these plant extracts.      Extracts of the plants; Adansonia digitata, Eucalyptus globulus and Trigonella foenum graecum showed a remarkable antibacterial activity against all tested bacterial strains. Meanwhile, the ethanolic extract of Ficus sycomorous exhibited a considerable antibacterial activity against Proteus mirabilis, Pseudomonas aeuroginosa and Staphylococcus aureus. The preliminary phytochemical screening revealed the presence of terpenes, tannins and saponins in all tested plant extracts, whereas alkaloids and cardiac glycosides were found in appreciable amounts in extracts Trigonella foenum graecum and Adansonia digitata respectively.       It can be concluded that the tested plants demonstrating broad spectra of activity which may help to discover new chemical classes of antibiotics that could serve as selective agents for the maintenance of health

Splenogonadal fusion: A forgotten cause of testicular swelling in children

Splenogonadal fusion is a rare congenital anomaly in which there is fusion of the  spleen and the gonad. This report describes a 25-month-old male child who presented with left scrotal swelling. On exploration, a discontinuous type of splenogonadal fusion was found. It was successfully and completely separated from the testis and removed. The diagnosis of splenogonadal fusion should always be kept in mind and included in the differential diagnosis of testicular swelling in infants and children. Rarely, it is diagnosed preoperatively and physicians caring for these patients should be aware of this. Intraoperatively, it should be recognized and excised. This is to obviate unnecessary orchiectomy, mistaking it for testicular neoplasm.Keywords: congenital anomalies of gonads, splenogonadal fusion, testicular swellin