43 research outputs found
A combined regular-logarithmic perturbation method for signal-noise interaction in amplified optical systems
We present a novel perturbation method for the nonlinear Schrödinger equation (NLSE) that governs the propagation of light in optical fibers. We apply this method to study signal-noise interactions in amplified multispan fiber-optic systems. Being based on a combination of the regular perturbation (RP) and logarithmic perturbation, the method is especially suitable for modeling the simultaneous presence of nonlinear and dispersive effects. Even after linearization, it retains the contribution of the quadratic perturbation terms of the NLSE, thereby achieving higher accuracy than an RP with comparable complexity. We revise parametric gain and nonlinear phase-noise effects under the new theory.We finally consider several examples and evaluate the probability density function of the optical or postdetection signal and the bit-error rate of an NRZ–OOK system. All of the results are compared with other models and with multicanonical Monte Carlo simulations
Sub-Nyquist Field Trial Using Time Frequency Packed DP-QPSK Super-Channel Within Fixed ITU-T Grid
Sub-Nyquist time frequency packing technique was demonstrated for the first
time in a super channel field trial transmission over long-haul distances. The
technique allows a limited spectral occupancy even with low order modulation
formats. The transmission was successfully performed on a deployed Australian
link between Sydney and Melbourne which included 995 km of uncompensated SMF
with coexistent traffic. 40 and 100 Gb/s co-propagating channels were
transmitted together with the super-channel in a 50 GHz ITU-T grid without
additional penalty. The super-channel consisted of eight sub-channels with
low-level modulation format, i.e. DP-QPSK, guaranteeing better OSNR robustness
and reduced complexity with respect to higher order formats. At the receiver
side, coherent detection was used together with iterative maximum-a-posteriori
(MAP) detection and decoding. A 975 Gb/s DP-QPSK super-channel was successfully
transmitted between Sydney and Melbourne within four 50GHz WSS channels (200
GHz). A maximum potential SE of 5.58 bit/s/Hz was achieved with an OSNR=15.8
dB, comparable to the OSNR of the installed 100 Gb/s channels. The system
reliability was proven through long term measurements. In addition, by closing
the link in a loop back configuration, a potential SE*d product of 9254
bit/s/Hz*km was achieved
An approach for the identification of targets specific to bone metastasis using cancer genes interactome and gene ontology analysis
Metastasis is one of the most enigmatic aspects of cancer pathogenesis and is
a major cause of cancer-associated mortality. Secondary bone cancer (SBC) is a
complex disease caused by metastasis of tumor cells from their primary site and
is characterized by intricate interplay of molecular interactions.
Identification of targets for multifactorial diseases such as SBC, the most
frequent complication of breast and prostate cancers, is a challenge. Towards
achieving our aim of identification of targets specific to SBC, we constructed
a 'Cancer Genes Network', a representative protein interactome of cancer genes.
Using graph theoretical methods, we obtained a set of key genes that are
relevant for generic mechanisms of cancers and have a role in biological
essentiality. We also compiled a curated dataset of 391 SBC genes from
published literature which serves as a basis of ontological correlates of
secondary bone cancer. Building on these results, we implement a strategy based
on generic cancer genes, SBC genes and gene ontology enrichment method, to
obtain a set of targets that are specific to bone metastasis. Through this
study, we present an approach for probing one of the major complications in
cancers, namely, metastasis. The results on genes that play generic roles in
cancer phenotype, obtained by network analysis of 'Cancer Genes Network', have
broader implications in understanding the role of molecular regulators in
mechanisms of cancers. Specifically, our study provides a set of potential
targets that are of ontological and regulatory relevance to secondary bone
cancer.Comment: 54 pages (19 pages main text; 11 Figures; 26 pages of supplementary
information). Revised after critical reviews. Accepted for Publication in
PLoS ON
The molecular signature of the stroma response in prostate cancer-induced osteoblastic bone metastasis highlights expansion of hematopoietic and prostate epithelial stem cell niches
The reciprocal interaction between cancer cells and the tissue-specific stroma is critical for primary and metastatic tumor growth progression. Prostate cancer cells colonize preferentially bone (osteotropism), where they alter the physiological balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption, and elicit prevalently an osteoblastic response (osteoinduction). The molecular cues provided by osteoblasts for the survival and growth of bone metastatic prostate cancer cells are largely unknown. We exploited the sufficient divergence between human and mouse RNA sequences together with redefinition of highly species-specific gene arrays by computer-aided and experimental exclusion of cross-hybridizing oligonucleotide probes. This strategy allowed the dissection of the stroma (mouse) from the cancer cell (human) transcriptome in bone metastasis xenograft models of human osteoinductive prostate cancer cells (VCaP and C4-2B). As a result, we generated the osteoblastic bone metastasis-associated stroma transcriptome (OB-BMST). Subtraction of genes shared by inflammation, wound healing and desmoplastic responses, and by the tissue type-independent stroma responses to a variety of non-osteotropic and osteotropic primary cancers generated a curated gene signature ("Core" OB-BMST) putatively representing the bone marrow/bone-specific stroma response to prostate cancer-induced, osteoblastic bone metastasis. The expression pattern of three representative Core OB-BMST genes (PTN, EPHA3 and FSCN1) seems to confirm the bone specificity of this response. A robust induction of genes involved in osteogenesis and angiogenesis dominates both the OB-BMST and Core OB-BMST. This translates in an amplification of hematopoietic and, remarkably, prostate epithelial stem cell niche components that may function as a self-reinforcing bone metastatic niche providing a growth support specific for osteoinductive prostate cancer cells. The induction of this combinatorial stem cell niche is a novel mechanism that may also explain cancer cell osteotropism and local interference with hematopoiesis (myelophthisis). Accordingly, these stem cell niche components may represent innovative therapeutic targets and/or serum biomarkers in osteoblastic bone metastasis
The Role of the BMP Signaling Antagonist Noggin in the Development of Prostate Cancer Osteolytic Bone Metastasis
Members of the BMP and Wnt protein families play a relevant role in physiologic and pathologic bone turnover. Extracellular antagonists are crucial for the modulation of their activity. Lack of expression of the BMP antagonist noggin by osteoinductive, carcinoma-derived cell lines is a determinant of the osteoblast response induced by their bone metastases. In contrast, osteolytic, carcinoma-derived cell lines express noggin constitutively. We hypothesized that cancer cell-derived noggin may contribute to the pathogenesis of osteolytic bone metastasis of solid cancers by repressing bone formation. Intra-osseous xenografts of PC-3 prostate cancer cells induced osteolytic lesions characterized not only by enhanced osteoclast-mediated bone resorption, but also by decreased osteoblast-mediated bone formation. Therefore, in this model, uncoupling of the bone remodeling process contributes to osteolysis. Bone formation was preserved in the osteolytic lesions induced by noggin-silenced PC-3 cells, suggesting that cancer cell-derived noggin interferes with physiologic bone coupling. Furthermore, intra-osseous tumor growth of noggin-silenced PC-3 cells was limited, most probably as a result of the persisting osteoblast activity. This investigation provides new evidence for a model of osteolytic bone metastasis where constitutive secretion of noggin by cancer cells mediates inhibition of bone formation, thereby preventing repair of osteolytic lesions generated by an excess of osteoclast-mediated bone resorption. Therefore, noggin suppression may be a novel strategy for the treatment of osteolytic bone metastases
Consensus guidelines for the use and interpretation of angiogenesis assays
The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference
A new murine model of osteoblastic/osteolytic lesions from human androgen-resistant prostate cancer
BACKGROUND: Up to 80% of patients dying from prostate carcinoma have developed bone metastases that are incurable. Castration is commonly used to treat prostate cancer. Although the disease initially responds to androgen blockade strategies, it often becomes castration-resistant (CRPC for Castration Resistant Prostate Cancer). Most of the murine models of mixed lesions derived from prostate cancer cells are androgen sensitive. Thus, we established a new model of CRPC (androgen receptor (AR) negative) that causes mixed lesions in bone. METHODS: PC3 and its derived new cell clone PC3c cells were directly injected into the tibiae of SCID male mice. Tumor growth was analyzed by radiography and histology. Direct effects of conditioned medium of both cell lines were tested on osteoclasts, osteoblasts and osteocytes. RESULTS: We found that PC3c cells induced mixed lesions 10 weeks after intratibial injection. In vitro, PC3c conditioned medium was able to stimulate tartrate resistant acid phosphatase (TRAP)-positive osteoclasts. Osteoprotegerin (OPG) and endothelin-1 (ET1) were highly expressed by PC3c while dikkopf-1 (DKK1) expression was decreased. Finally, PC3c highly expressed bone associated markers osteopontin (OPN), Runx2, alkaline phosphatase (ALP), bone sialoprotein (BSP) and produced mineralized matrix in vitro in osteogenic conditions. CONCLUSIONS: We have established a new CRPC cell line as a useful system for modeling human metastatic prostate cancer which presents the mixed phenotype of bone metastases that is commonly observed in prostate cancer patients with advanced disease. This model will help to understand androgen-independent mechanisms involved in the progression of prostate cancer in bone and provides a preclinical model for testing the effects of new treatments for bone metastases