Search results for "SIGNATURE"

Drug connectivity mapping and functional analysis reveal therapeutic small molecules that differentially modulate myelination

2022

Disruption or loss of oligodendrocytes (OLs) and myelin has devastating effects on CNS function and integrity, which occur in diverse neurological disorders, including Multiple Sclerosis (MS), Alzheimer’s disease and neuropsychiatric disorders. Hence, there is a need to develop new therapies that promote oligodendrocyte regeneration and myelin repair. A promising approach is drug repurposing, but most agents have potentially contrasting biological actions depending on the cellular context and their dose-dependent effects on intracellular pathways. Here, we have used a combined systems biology and neurobiological approach to identify compounds that exert positive and negative effects on olig…

Extending the DAMA annual-modulation region by inclusion of the uncertainties in astrophysical velocities

1999

The original annual-modulation region, singled out by the DAMA/NaI experiment for direct detection of WIMPs, is extended by taking into account the uncertainties in the galactic astrophysical velocities. Also the effect due to a possible bulk rotation for the dark matter halo is considered. We find that the range for the WIMP mass becomes 30 GeV < m_chi < 130 GeV at 1-sigma C.L. with a further extension in the upper bound, when a possible bulk rotation of the dark matter halo is taken into account. We show that the DAMA results, when interpreted in the framework of the Minimal Supersymmetric extension of the Standard Model, are consistent with a relic neutralino as a dominant componen…

Limits on the production of scalar leptoquarks from $Z^0$ decays at LEP

1993

A search has been made for pairs and for single production of scalar leptoquarks of the first and second generations using a data sample of 392000 Z0 decays from the DELPHI detector at LEP 1. No signal was found and limits on the leptoquark mass, production cross section and branching ratio were set. A mass limit at 95% confidence level of 45.5 GeV/c2 was obtained for leptoquark pair production. The search for the production of a single leptoquark probed the mass region above this limit and its results exclude first and second generation leptoquarks D0 with masses below 65 GeV/c2 and 73 GeV/c2 respectively, at 95% confidence level, assuming that the D0lq Yukawa coupling alpha(lambda) is equ…

Study of high spins in $^{173}$Os

1991

High-spin states in 173Os have been studied by γγ-coincidence measurements following the 146Nd(32S, 5n)173Os reaction. Additional information has also been extracted from the reaction 144Sm(32S, 2pn)173Os. Four main sequencies have been identified as the two signature branches of the bands built on the [642]52+ and [523]52− Nilsson states. The band features have been analysed within the framework of the cranked shell model. The positive-parity band provides evidence for a v(i132)2 crossing at low frequency and a π(h112)2 and/or π(h92)2 cross In the negative-parity band the upbend starts at relatively low frequency indicating, presumably, an early v(i132)2 alignment. There is evidence for an…

Identification of a genetic signature enriching for response to ibrutinib in relapsed/refractory follicular lymphoma in the DAWN phase 2 trial.

2021

Abstract Background The single‐arm DAWN trial (NCT01779791) of ibrutinib monotherapy in patients with relapsed/refractory follicular lymphoma (FL) showed an overall response rate (ORR) of 20.9% and a median response duration of 19.4 months. This biomarker analysis of the DAWN dataset sought to determine genetic classifiers for prediction of response to ibrutinib treatment. Methods Whole exome sequencing was performed on baseline tumor samples. Potential germline variants were excluded; a custom set of 1216 cancer‐related genes was examined. Responder‐ versus nonresponder‐associated variants were identified using Fisher's exact test. Classifiers with increasing numbers of genes were created …

KRAS mutation signature in colorectal tumors significantly overlaps with the cetuximab response signature.

2008

Individual patient risk stratification of high-risk neuroblastomas using a two-gene score suited for clinical use

2015

Several gene expression-based prognostic signatures have been described in neuroblastoma, but none have successfully been applied in the clinic. Here we have developed a clinically applicable prognostic gene signature, both with regards to number of genes and analysis platform. Importantly, it does not require comparison between patients and is applicable amongst high-risk patients. The signature is based on a two-gene score (R-score) with prognostic power in high-stage tumours (stage 4 and/or MYCN-amplified diagnosed after 18 months of age). QPCR-based and array-based analyses of matched cDNAs confirmed cross platform (array-qPCR) transferability. We also defined a fixed cut-off value iden…

Exome and immune cell score analyses reveal great variation within synchronous primary colorectal cancers

2019

BACKGROUND: Approximately 4% of colorectal cancer (CRC) patients have at least two simultaneous cancers in the colon. Due to the shared environment, these synchronous CRCs (SCRCs) provide a unique setting to study colorectal carcinogenesis. Understanding whether these tumours are genetically similar or distinct is essential when designing therapeutic approaches. METHODS: We performed exome sequencing of 47 primary cancers and corresponding normal samples from 23 patients. Additionally, we carried out a comprehensive mutational signature analysis to assess whether tumours had undergone similar mutational processes and the first immune cell score analysis (IS) of SCRC to analyse the interplay…

Prognostic Significance of Interferon-γ and Its Signaling Pathway in Early Breast Cancer Depends on the Molecular Subtypes

2020

Interferons are crucial for adaptive immunity and play an important role in the immune landscape of breast cancer. Using microarray-based gene expression analysis, we examined the subtype-specific prognostic significance of interferon-&gamma

Gene signatures in CRC and liver metastasis

2011

Colorectal cancer (CRC) is one of the most common causes of cancer-related death with a worldwide incidence of almost a million cases annually in both males and females. The accelerated decrease in CRC incidence rates from 1998 to 2006 largely reflects the advances in diagnosis and treatment that have enabled to detect and remove precancerous polyps. However, the screening technology has not resulted in major improvements in the prognosis of patients with advanced cancer and the liver metastasis remains the major cause of death in CRC. About 25% of patients have detectable liver metastasis at diagnosis, that are classified as “synchronous” lesions and approximately 70% of patients develop a…