A Combined Trip Generation, Trip Distribution, Modal Split and Traffic Assignment Model

Revised and submitted to Transportation Science February 1985.We introduce a transportation equilibrium model that simultaneously predicts trip generation, trip distribution, modal split, and traffic assignment by algorithms that are guaranteed to converge to an equilibrium and are computationally efficient for large-scale systems. The model is formulated as an equivalent optimization problem, yet it allows realistic, flexible and behaviorally acceptable demand models

Morphometric and immunohistochemical study of angiogenic marker expressions in invasive ductal carcinomas of the human breast

Breast cancer is the leading cause of cancer deaths among women. Results from experimental studies suggest that tumour progression and metastasis in breast cancer are angiogenesis dependant. The College of American Pathologists has stated that further study of quantification of tumour angiogenesis is still required to demonstrate its prognostic value in breast cancer. In this study, not only the microvascular density (MVD), but also the vascular area ratio (VAR), and the vascular count in different grades of invasive ductal breast carcinoma were assessed using a pan-endothelial marker, CD34, and monoclonal antibody to CD105, by employing computer assisted morphometric measurements. In addition, quantitative expression of vascular endothelial growth factor (VEGF) was detected. Correlation of the vascular parameters and VEGF expression with the different grades of invasive ductal breast carcinoma was clarified. Immunohistochemical staining for the CD105, CD34, and VEGF antibodies were performed in 25 patients with invasive ductal carcinoma in King Fahd Hospital, Saudi Arabia. Normal breast tissue samples comprised 15 specimens detected at the safety margin of the malignant breast cases were collected. Positive CD34 stained blood-vessel endothelial cells were observed in all normal breast tissues. In contrast, CD105 and VEGF expression were not expressed in the normal breast ducts and lobules. Widespread staining for CD34, to a lesser extent CD105, and VEGF expression were seen in all tumour specimens with different grades. Significant differences in the vascular parameters, stained with antiCD34, were observed between normal breast tissues and invasive ductal carcinoma. In addition, the vascular parameters stained with antiCD34 and antiCD105, and the percentage of VEGF expression in the three grades of invasive ductal carcinomas showed significant differences with positive correlations. In conclusion, MVD as well as VAR are considered to reflect the final result of the tumour angiogenesis cascade. In addition, VEGF expression was found to be a useful angiogenic marker. However, few cases were VEGF negatively stained. Thus, the expression of MVD, VAR, and to a lesser extent VEGF might be reference predictors for the biological behaviour and prognosis of breast carcinoma

Effect of genistein and oestradiol on the adrenal cortex of the ovariectomised adult female albino rats

Background: Genistein, a naturally occurring soy isoflavone, attracts interest as an effective and safe alternative to hormone replacement therapy for menopausal problems. The aim of the current study was to compare between the effect of genistein and oestradiol on the adrenal cortex of the ovariectomised adult female albino rats. Materials and methods: Twenty rats were used in the current study and divided into four groups, 5 rats in each group; group 1 (control non-ovariectomised), group 2 (ovariectomised), group 3 (ovariectomised + genistein) and group 4 (ovariectomised + oestradiol). The rats were sacrificed after 4 weeks. Both adrenal glands were removed for light microscope using haematoxylin and eosin stain, ultrastructural study and immunohistochemical examination using proliferating cell nuclear antigen, caspase-3, and oestrogen receptor-b. Results: Ovariectomised rats showed signs of degeneration in all zones of adrenal cortex. On the other hand, treatment with genistein showed restoration of the adrenal cortex with less proliferative effect than oestradiol. Conclusions: So, genistein can be used as effective therapy to decrease the symptoms of menopause without fear of cancer development

Pazopanib in advanced vascular sarcomas: an EORTC Soft Tissue and Bone Sarcoma Group (STBSG) retrospective analysis.

Background Pazopanib is a multitargeted tyrosine kinase inhibitor approved for the treatment of patients with selective subtypes of advanced soft tissue sarcoma (STS) who have previously received standard chemotherapy including anthracyclines. Data on the efficacy in vascular sarcomas are limited. The main objective of this study was to investigate the activity of pazopanib in vascular sarcomas.Patients and methods A retrospective study of patients with advanced vascular sarcomas, including angiosarcoma (AS), epithelioid hemangioendothelioma (HE) and intimal sarcoma (IS) treated with pazopanib in real life practice at EORTC centers as well as patients treated within the EORTC phase II and III clinical trials (62043/62072) was performed. Patient and tumor characteristics were collected. Response was assessed according to RECIST 1.1. and survival analysis was performed.Results Fifty-two patients were identified, 40 (76.9%), 10 (19.2%) and two (3.8%) with AS, HE and IS, respectively. The response rate was eight (20%), two (20%) and two (100%) in the AS, HE and IS subtypes, respectively. There was no significant difference in response rate between cutaneous and non-cutaneous AS and similarly between radiation-associated and non-radiation-associated AS. Median progression-free survival (PFS) and median overall survival (OS; from commencing pazopanib) were three months (95% CI 2.1-4.4) and 9.9 months (95% CI 6.5-11.3) in AS, respectively.Conclusion The activity of pazopanib in AS is comparable to its reported activity in other STS subtypes. In this study, the activity of pazopanib was similar in cutaneous/non-cutaneous and in radiation/non-radiation-associated AS. In addition, pazopanib showed promising activity in HE and IS, worthy of further evaluation

TAK1 Is Required for Survival of Mouse Fibroblasts Treated with TRAIL, and Does So by NF-κB Dependent Induction of cFLIPL

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is known as a “death ligand”—a member of the TNF superfamily that binds to receptors bearing death domains. As well as causing apoptosis of certain types of tumor cells, TRAIL can activate both NF-κB and JNK signalling pathways. To determine the role of TGF-β-Activated Kinase-1 (TAK1) in TRAIL signalling, we analyzed the effects of adding TRAIL to mouse embryonic fibroblasts (MEFs) derived from TAK1 conditional knockout mice. TAK1−/− MEFs were significantly more sensitive to killing by TRAIL than wild-type MEFs, and failed to activate NF-κB or JNK. Overexpression of IKK2-EE, a constitutive activator of NF-κB, protected TAK1−/− MEFs against TRAIL killing, suggesting that TAK1 activation of NF-κB is critical for the viability of cells treated with TRAIL. Consistent with this model, TRAIL failed to induce the survival genes cIAP2 and cFlipL in the absence of TAK1, whereas activation of NF-κB by IKK2-EE restored the levels of both proteins. Moreover, ectopic expression of cFlipL, but not cIAP2, in TAK1−/− MEFs strongly inhibited TRAIL-induced cell death. These results indicate that cells that survive TRAIL treatment may do so by activation of a TAK1–NF-κB pathway that drives expression of cFlipL, and suggest that TAK1 may be a good target for overcoming TRAIL resistance

A classification of grammar-infused templates for ontology and model verbalisation

Involving domain-experts in the development, maintenance, and use of knowledge organisation systems can be made easier through the introduction of easy-to-use interfaces that are based on natural language. Well resourced languages make use of natural language generation techniques to provide such interfaces. In particular, they often make use of templates combined with computational grammar rules to generate grammatically complex text. However, there is no model of pairing templates and computational grammar rules to ensure suitability for less-resourced languages. These languages require a modular design that ensures grammar detachability so as to allow grammar re-use across domains and applications. In this paper, we present a model and classification scheme for grammar-infused templates suited for less-resourced languages and classify existing systems that make use of them. We have found that of the 15 systems that pair templates and grammar rules, and their 11 distinct template types, 13 have support for detachable grammars

Advances in exosome therapies in ophthalmology–From bench to clinical trial

During the last decade, the fields of advanced and personalized therapeutics have been constantly evolving, utilizing novel techniques such as gene editing and RNA therapeutic approaches. However, the method of delivery and tissue specificity remain the main hurdles of these approaches. Exosomes are natural carriers of functional small RNAs and proteins, representing an area of increasing interest in the field of drug delivery. It has been demonstrated that the exosome cargo, especially miRNAs, is at least partially responsible for the therapeutic effects of exosomes. Exosomes deliver their luminal content to the recipient cells and can be used as vesicles for the therapeutic delivery of RNAs and proteins. Synthetic therapeutic drugs can also be encapsulated into exosomes as they have a hydrophilic core, which makes them suitable to carry water-soluble drugs. In addition, engineered exosomes can display a variety of surface molecules, such as peptides, to target specific cells in tissues. The exosome properties present an added advantage to the targeted delivery of therapeutics, leading to increased efficacy and minimizing the adverse side effects. Furthermore, exosomes are natural nanoparticles found in all cell types and as a result, they do not elicit an immune response when administered. Exosomes have also demonstrated decreased long-term accumulation in tissues and organs and thus carry a low risk of systemic toxicity. This review aims to discuss all the advances in exosome therapies in ophthalmology and to give insight into the challenges that would need to be overcome before exosome therapies can be translated into clinical practice