Gene expression analysis of diagnostic biopsies predicts pathological response to neoadjuvant chemoradiotherapy of esophageal cancer

OBJECTIVE: This study explored gene expression differences in predicting response to chemoradiotherapy in esophageal cancer. PURPOSE:: A major pathological response to neoadjuvant chemoradiation is observed in about 40% of esophageal cancer patients and is associated with favorable outcomes. However, patients with tumors of similar histology, differentiation, and stage can have vastly different responses to the same neoadjuvant therapy. This dichotomy may be due to differences in the molecular genetic environment of the tumor cells. BACKGROUND DATA: Diagnostic biopsies were obtained from a training cohort of esophageal cancer patients (13), and extracted RNA was hybridized to genome expression microarrays. The resulting gene expression data was verified by qRT-PCR. In a larger, independent validation cohort (27), we examined differential gene expression by qRT-PCR. The ability of differentially-regulated genes to predict response to therapy was assessed in a multivariate leave-one-out cross-validation model. RESULTS: Although 411 genes were differentially expressed between normal and tumor tissue, only 103 genes were altered between responder and non-responder tumor; and 67 genes differentially expressed >2-fold. These included genes previously reported in esophageal cancer and a number of novel genes. In the validation cohort, 8 of 12 selected genes were significantly different between the response groups. In the predictive model, 5 of 8 genes could predict response to therapy with 95% accuracy in a subset (74%) of patients. CONCLUSIONS: This study has identified a gene microarray pattern and a set of genes associated with response to neoadjuvant chemoradiation in esophageal cancer. The potential of these genes as biomarkers of response to treatment warrants further investigation. Copyright © 2009 by Lippincott Williams & Wilkins.

Security analysis of the non-aggressive challenge response of the DNP3 Protocol using a CPN Model

Distributed Network Protocol Version 3 (DNP3) is the de-facto communication protocol for power grids. Standard-based interoperability among devices has made the protocol useful to other infrastructures such as water, sewage, oil and gas. DNP3 is designed to facilitate interaction between master stations and outstations. In this paper, we apply a formal modelling methodology called Coloured Petri Nets (CPN) to create an executable model representation of DNP3 protocol. The model facilitates the analysis of the protocol to ensure that the protocol will behave as expected. Also, we illustrate how to verify and validate the behaviour of the protocol, using the CPN model and the corresponding state space tool to determine if there are insecure states. With this approach, we were able to identify a Denial of Service (DoS) attack against the DNP3 protocol.

Analysis and retrofitting design of a single-span R.C. bridge

This paper deals with the case history of a damaged one-span prestressed concrete bridge on a crucial artery near the city of Cagliari (Sardinia), along the sea-side. After being involved in a disastrous flood, attention has arisen on the worrying safety state of the deck, submitted to an intense daily traffic load. Evident signs of this severe condition were the deterioration of the beams concrete and the corrosion, the lack of tension and even the rupture of the prestressing cables. After performing a limited in situ test campaign, consisting of sclerometer, pull out and carbonation depth tests, a first evaluation of the safety of the structure was performed. After collecting the data of dynamic and static load tests as well, a comprehensive analysis have been carried out, also by means of a properly calibrated F.E. model. Finally the retrofitting design is presented, consisting of the reparation and thickening of the concrete cover, providing flexural and shear FRP external reinforcements and an external prestressing system, capable of restoring a satisfactory bearing capacity, according to the current national codes. The intervention has been calibrated by the former F.E. model with respect to transversal effects and influence of local and overall deformation of reinforced elements. © 2012 Taylor & Francis Group.

Image analysis for assessing broiler breeder behavior response to thermal environment

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Sufficients conditions for analysis of extrema in the step-response of the linear control systems

This note deals whith the problem of extrema which may occur in the step-response of a stable linear system with real zeros and poles. Some simple sufficients conditions and necessary conditions are presented for analyses when zeros located between the dominant and fastest pole does not cause extrema in the step-response. These conditions require knowledge of the pole-zero configuration of the corresponding transfer-function.

Analysis of the memory B cell response against glycoconjugate vaccines

The development of vaccines directed against polysaccharide capsules of S. pneumoniae, H. influenzae and N. meningitidis have been of great importance in preventing potentially fatal infections. Bacterial capsular polysaccharides are T-cell-independent antigens that induce specific antibody response characterized by IgM immunoglobulins, with a very low IgG class switched response and lack of capability of inducing a booster response. The inability of pure polysaccharides to induce sustained immune responses has required the development of vaccines containing polysaccharides conjugated to a carrier protein, with the aim to generate T cell help. It is clear that the immunogenicity of glycoconjugate vaccines can vary depending on different factors, e.g. chemical nature of the linked polysaccharide, carrier protein, age of the target population, adjuvant used. The present study analyzes the memory B cell (MBC) response to the polysaccharide and to the carrier protein following vaccination with a glycoconjugate vaccine for the prevention of Group B streptococcus (GBS) infection. Not much is known about the role of adjuvants in the development of immunological memory raised against GBS polysaccharides, as well as about the influence of having a pre-existing immunity against the carrier protein on the B cell response raised against the polysaccharide component of the vaccine. We demonstrate in the mouse model that adjuvants can increase the antibody and memory B cell response to the carrier protein and to the conjugated polysaccharide. We also demonstrate that a pre-existing immunity to the carrier protein favors the development of the antibody and memory B cell response to subsequent vaccinations with a glycoconjugate, even in absence of adjuvants. These data provide a useful insight for a better understanding of the mechanism of action of this class of vaccines and for designing the best vaccine that could result in a productive and long lasting memory response.

Analysis of perinatal gene expression: hormone response elements mediate activation of a lacZ reporter gene in liver of transgenic mice.

The transcription of genes encoding gluconeogenic enzymes is tightly regulated during the perinatal period. These genes are induced by glucagon (cAMP) and glucocorticoids and repressed by insulin. To address the role of cAMP and glucocorticoids in the physiological activation of genes encoding gluconeogenic enzymes in the perinatal period, transgenic mice have been generated with chimeric constructs containing the reporter gene lacZ under the control of hormone response elements. The activity of the transgene is restricted to the liver by the presence of the enhancers from the alpha-fetoprotein gene and its transcription is driven by a promoter that contains a TATA box linked to either cAMP response elements (CREs) or glucocorticoid response elements (GREs). We demonstrate cAMP and glucocorticoid regulation, liver-specific expression, and perinatal activation of the reporter gene. These data indicate that the CRE and GRE are, independently, necessary and sufficient to mediate perinatal gene activation. Perinatal activation was not impaired when a CRE reporter transgene was assayed in mice that contain a targeted mutation of the CRE-binding protein (CREB) gene, providing further evidence for functional redundancy among the members of the CREB/ATF gene family.

NONSAP : a structural analysis program for static and dynamic response of nonlinear systems /

Photocopy of original: Berkeley : Structural Engineering Laboratory, University of California, 1974.

Global transcriptome analysis of Lactococcus garvieae strains in response to temperature

Lactococcus garvieae is an important fish and an opportunistic human pathogen. The genomic sequences of several L. garvieae strains have been recently published, opening the possibility of global studies on the biology of this pathogen. In this study, a whole genome DNA microarray of two strains of L. garvieae was designed and validated. This DNA microarray was used to investigate the effects of growth temperature (18°C and 37°C) on the transcriptome of two clinical strains of L. garvieae that were isolated from fish (Lg8831) and from a human case of septicemia (Lg21881). The transcriptome profiles evidenced a strain-specific response to temperature, which was more evident at 18°C. Among the most significant findings, Lg8831 was found to up-regulate at 18°C several genes encoding different cold-shock and cold-induced proteins involved in an efficient adaptive response of this strain to low-temperature conditions. Another relevant result was the description, for the first time, of respiratory metabolism in L. garvieae, whose gene expression regulation was temperature-dependent in Lg21881. This study provides new insights about how environmental factors such as temperature can affect L. garvieae gene expression. These data could improve our understanding of the regulatory networks and adaptive biology of this important pathogen.