Predicting breast cancer using an expression values weighted clinical classifier

Background

Clinical data, such as patient history, laboratory analysis, ultrasound parameters-which are the basis of day-to-day clinical decision support-are often used to guide the clinical management of cancer in the presence of microarray data. Several data fusion techniques are available to integrate genomics or proteomics data, but only a few studies have created a single prediction model using both gene expression and clinical data. These studies often remain inconclusive regarding an obtained improvement in prediction performance. To improve clinical management, these data should be fully exploited. This requires efficient algorithms to integrate these data sets and design a final classifier.LS-SVM classifiers and generalized eigenvalue/singular value decompositions are successfully used in many bioinformatics applications for prediction tasks. While bringing up the benefits of these two techniques, we propose a machine learning approach, a weighted LS-SVM classifier to integrate two data sources: microarray and clinical parameters.

Results

We compared and evaluated the proposed methods on five breast cancer case studies. Compared to LS-SVM classifier on individual data sets, generalized eigenvalue decomposition (GEVD) and kernel GEVD, the proposed weighted LS-SVM classifier offers good prediction performance, in terms of test area under ROC Curve (AUC), on all breast cancer case studies.

Conclusions

Thus a clinical classifier weighted with microarray data set results in significantly improved diagnosis, prognosis and prediction responses to therapy. The proposed model has been shown as a promising mathematical framework in both data fusion and non-linear classification problems.     

Alpha interferon inhibits early stages of the human immunodeficiency virus type 1 replication cycle.

In this study, we have analyzed the effect of human alpha interferon (IFN-alpha) on a single replication cycle of human immunodeficiency virus type 1 (HIV-1) infection in the lymphocytic cell line CEM-174, which is highly sensitive to the antiviral effects of IFN. Pretreatment of cells with 50 to 500 U of recombinant human IFN-alpha per ml resulted in a marked reduction in viral RNA and protein synthesis. The effect of IFN-alpha was dose dependent and was amplified in multiple infection cycles. IFN-induced inhibition of viral protein synthesis could be detected only when cells were treated with IFN-alpha prior to infection or when IFN-alpha was added up to 10 h postinfection, but not if IFN-alpha was added at the later stages of HIV-1 replication cycle or after the HIV-1 infection was already established. Analysis of the integrated HIV-1 provirus showed a marked decrease in the levels of proviral DNA in IFN-treated cells. Thus, in contrast to the previous studies on established HIV-1 infection in T cells, in which the IFN block appeared to be at the posttranslational level, during de novo infection, IFN-alpha interferes with an early step of HIV-1 replication cycle that occurs prior to the integration of the proviral DNA. These results indicate that the early IFN block of HIV-1 replication, which has been previously observed only in primary marcophages, can also be detected in the IFN-sensitive T cells, indicating that the early IFN block is not limited to macrophages.     

To reduce the maximum stress and the stress shielding effect around a dental implant–bone interface using radial functionally graded biomaterials

In a dental implant system, the value of stress and its distribution plays a pivotal role on the strength, durability and life of the implant–bone system. A typical implant consists of a Titanium core and a thin layer of biocompatible material such as the hydroxyapatite. This coating has a wide range of clinical applications in orthopedics and dentistry due to its biocompatibility and bioactivity characteristics. Low bonding strength and sudden variation of mechanical properties between the coating and the metallic layers are the main disadvantages of such common implants. To overcome these problems, a radial distributed functionally graded biomaterial (FGBM) was proposed in this paper and the effect of material property on the stress distribution around the dental implant–bone interface was studied. A three-dimensional finite element simulation was used to illustrate how the use of radial FGBM dental implant can reduce the maximum von Mises stress and, also the stress shielding effect in both the cortical and cancellous bones. The results, of course, give anybody an idea about optimized behaviors that can be achieved using such materials. The finite element solver was validated by familiar methods and the results were compared to previous works in the literature.     

Whole Retinal Explants from Chicken Embryos for Electroporation and Chemical Reagent Treatments

The retina is a good model for the developing central nervous system. The large size of the eye and most importantly the accessibility for experimental manipulations in ovo/in vivo makes the chicken embryonic retina a versatile and very efficient experimental model. Although the chicken retina is easy to target in ovo by intraocular injections or electroporation, the effective and exact concentration of the reagents within the retina may be difficult to fully control. This may be due to variations of the exact injection site, leakage from the eye or uneven diffusion of the substances. Furthermore, the frequency of malformations and mortality after invasive manipulations such as electroporation is rather high.This protocol describes an ex ovo technique for culturing whole retinal explants from chicken embryos and provides a method for controlled exposure of the retina to reagents. The protocol describes how to dissect, experimentally manipulate, and culture whole retinal explants from chicken embryos. The explants can be cultured for approximately 24 hr and be subjected to different manipulations such as electroporation. The major advantages are that the experiment is not dependent on the survival of the embryo and that the concentration of the introduced reagent can be varied and controlled in order to determine and optimize the effective concentration. Furthermore, the technique is rapid, cheap and together with its high experimental success rate, it ensures reproducibleresults. It should be emphasized that it serves as an excellent complement to experiments performed in ovo.     

Short-term changes in prostacyclin secretory profile of irradiated rat cervical spinal cord

Prostaglandins changes in radiation myelopathy (RM) have been previously reported. In the present study, we decided to determine the profile of Prostacyclin (PGI2) content in irradiated rat cervical cord. Wistar rats were irradiated with doses of 2,4,6,15,25 and 30 Gy of X-rays. After 24 h, 2 and 13 weeks post-irradiation, samples of spinal cord were prepared for evaluation of PGI2 and histopathologic changes. Prostacyclin content was determined by quantification of 6-keto-prostaglandin-F1alpha (prostacyclin major metabolite). Irradiated segments of spinal cord were stained routinely for histological studies. Results of irradiated were compared to control groups. Average ratio values of 6-keto-PG-F1alpha for doses of 2-30 Gy were between 67.5% and 107%, 65.41% and 100.54%, and 62.20% and 98.89% for 24 h, 2 and 13 weeks post-irradiation, respectively. Histopathological studies showed marked gliosis and vascularities in irradiated specimens. PGI2 bimodal secretory profile was observed along with histopathological changes in this study. Our results can further emphasize on the role of PGI2 in RM.     

The regulation of CD47-SIRPα signaling axis by microRNAs in combination with conventional cytotoxic drugs together with the help of nano-delivery: a choice for therapy?

Molecular Biology Reports - CD47, a member of the immunoglobulin superfamily, is an important “Don’t Eat-Me” signal in phagocytosis process [clearance of apoptotic cells] as well...     

Microfacies,sedimentary environment and paleoecology of Paleocene–Eocene deposits in the Zagros Basin,north of Shiraz,southwest Iran

The Jahrum Formation act as reservoir rocks in the Zagros Mountains west of Iran. For the study of this formation, a stratigraphic section of Lapoee which is situated north of Shiraz has been examined. Petrographic and stratigraphic results along with field observations show that the Jahrum Formation consists of cream-grey thin-to-medium-bedded limestone so that at the top of the formation, they are locally changed to dolomite. The Jahrum Formation overlies the Sachun Formation. We also found Nubecularids as paleoecology indicators in middle parts of the Jahrum Formation. The presence of Nubecularids in the Lapoee stratigraphic section (i.e. the Jahrum Formation) indicates a lagoon depositional environment.     

Recovery of plants from “Near-Lethal” stress

This study reports on the dieback and recovery of red-osier dogwood, Cornus sericea L. plants from near-lethal (NL, sublethal) stress after varying lengths of post-stress environment (PSE). Intact dormant stems were subjected to 47° C for one hour during either October, November or December, and then placed into either constant 0° C or 23° C (dark condition) or kept under natural conditions at Corvallis, OR. Plants exposed to NL-heat stress in October died prior to 9 weeks of 0° C PSE, while none of the plants from other PSE treatments showed signs of injury. For plants exposed to NL-heat stress during November and December, stemdieback occurred at 0° C after 12 and 15 weeks, respectively. None of the plants from the other PSE treatments were injured. Post-stress temperatures of 0° or 5° C following NL-heat in October were lethal while temperatures above 10° C allowed recovery. Post-stress exposure to 0° C injured excised stems within 48 h, whereas irreversible damage to whole plants occurred by two weeks. Dormant plants exposed in October to other stresses, e.g., freezing temperature and hydrogen cyanamide, at NL dosages showed that these stresses also caused plant dieback at 0° C and little or no dieback at 23° C PSE.Abbreviations NL Near-Lethal - PSE Post-Stress Environment