In this work we investigate the thermodynamics conditions at which neutrinos decouple from matter in neutron star merger remnants by post-processing results of merger simulations. We find that the ...matter density and the neutrino energies are the most relevant quantities in determining the decoupling surface location. For mean energy neutrinos (
∼
9, 15 and 24 MeV for
ν
e
,
ν
¯
e
and
ν
μ
,
τ
, respectively) the transition between diffusion and free-streaming conditions occurs around
10
11
g
cm
-
3
for all neutrino species. Weak and thermal equilibrium freeze-out occurs deeper (several
10
12
g
cm
-
3
) for heavy-flavor neutrinos than for
ν
¯
e
and
ν
e
(
≳
10
11
g
cm
-
3
). Decoupling temperatures are broadly in agreement with the average neutrino energies, with softer equations of state characterized by
∼
1 MeV larger decoupling temperatures. Neutrinos streaming at infinity with different energies come from different remnant parts. While low-energy neutrinos (
∼
3
MeV
) decouple at
ρ
∼
10
13
g
cm
-
3
,
T
∼
10
MeV
and
Y
e
≲
0.1
close to weak equilibrium, high-energy ones (
∼
50
MeV
) decouple from the disk at
ρ
∼
10
9
g
cm
-
3
,
T
∼
2
MeV
and
Y
e
≳
0.25
. The presence of a massive NS or a BH influences the neutrino thermalization. While in the former case decoupling surfaces are present for all relevant energies, the lower maximum density (
≲
10
12
g
cm
-
3
) in BH-torus systems does not allow softer neutrinos to thermalize and diffuse.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The expression of non-coding RNAs (ncRNAs) is dysregulated in human cancers. The transcribed ultraconserved regions (T-UCRs) express long ncRNAs involved in human carcinogenesis. T-UCRs are ...non-coding genomic sequence that are 100% conserved across humans, rats and mice. Conservation of genomic sequences across species intrinsically implies an essential functional role and so we considered the expression of T-UCRs in lung cancer. Using a custom microarray we analyzed the global expression of T-UCRs. Among these T-UCRs, the greatest variation was observed for antisense ultraconserved element 83 (uc.83-), which was upregulated in human lung cancer tissues compared with adjacent non cancerous tissues. Even though uc.83- is located within the long intergenic non-protein coding RNA 1876 (LINC01876) gene, we found that the transcribed uc.83- is expressed independently of LINC01876 and was cloned as a 1143-bp RNA gene. In this study, functional analysis confirmed important effects of uc.83- on genes involved in cell growth of human cells. siRNA against uc.83- decreased the growth of lung cancer cells while the upregulation through a vector overexpressing the uc.83- RNA increased cell proliferation. We also show the oncogenic function of uc.83- is mediated by the phosphorylation of AKT and ERK 1/2, two important biomarkers of lung cancer cell proliferation. Based on our findings, inhibition against uc.83- could be a future therapeutic treatment for NSCLC to achieve simultaneous blockade of pathways involved in lung carcinogenesis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Circulating tumor cells (CTCs) are cellular elements that can be scattered into the bloodstream from primary cancer, metastasis, and even from a disseminated tumor cell (DTC) reservoir. CTCs are ..."seeds", able to give rise to new metastatic lesions. Since metastases are the cause of about 90% of cancer-related deaths, the significance of CTCs is unquestionable. However, two major issues have stalled their full clinical exploitation: rarity and heterogeneity. Therefore, their full clinical potential has only been predicted. Finding new ways of studying and using such tremendously rare and important events can open new areas of research in the field of cancer research, and could drastically improve tumor companion diagnostics, personalized treatment strategies, overall patients management, and reduce healthcare costs.
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Aldehyde dehydrogenases (ALDHs) are a family of detoxifying enzymes often upregulated in cancer cells and associated with therapeutic resistance. In humans, the ALDH family comprises 19 isoenzymes ...active in the majority of mammalian tissues. Each ALDH isoform has a specific differential expression pattern and most of them have individual functional roles in cancer. ALDHs are overexpressed in subpopulations of cancer cells with stem-like features, where they are involved in several processes including cellular proliferation, differentiation, detoxification and survival, participating in lipids and amino acid metabolism and retinoic acid synthesis. In particular, ALDH enzymes protect cancer cells by metabolizing toxic aldehydes in less reactive and more soluble carboxylic acids. High metabolic activity as well as conventional anticancer therapies contribute to aldehyde accumulation, leading to DNA double strand breaks (DSB) through the generation of reactive oxygen species (ROS) and lipid peroxidation. ALDH overexpression is crucial not only for the survival of cancer stem cells but can also affect immune cells of the tumour microenvironment (TME). The reduction of ROS amount and the increase in retinoic acid signaling impairs immunogenic cell death (ICD) inducing the activation and stability of immunosuppressive regulatory T cells (Tregs). Dissecting the role of ALDH specific isoforms in the TME can open new scenarios in the cancer treatment. In this review, we summarize the current knowledge about the role of ALDH isoforms in solid tumors, in particular in association with therapy-resistance.
Diversity maximization is a fundamental problem with broad applications in data summarization, web search, and recommender systems. Given a set
of
elements, the problem asks for a subset
of k≪n ...elements with maximum diversity, as quantified by the dissimilarities among the elements in
. In this paper, we study diversity maximization with fairness constraints in streaming and sliding-window models. Specifically, we focus on the max-min diversity maximization problem, which selects a subset
that maximizes the minimum distance (dissimilarity) between any pair of distinct elements within it. Assuming that the set
is partitioned into
disjoint groups by a specific sensitive attribute, e.g., sex or race, ensuring fairness requires that the selected subset
contains ki elements from each group i∈m. Although diversity maximization has been extensively studied, existing algorithms for fair max-min diversity maximization are inefficient for data streams. To address the problem, we first design efficient approximation algorithms for this problem in the (insert-only) streaming model, where data arrive one element at a time, and a solution should be computed based on the elements observed in one pass. Furthermore, we propose approximation algorithms for this problem in the sliding-window model, where only the latest
elements in the stream are considered for computation to capture the recency of the data. Experimental results on real-world and synthetic datasets show that our algorithms provide solutions of comparable quality to the state-of-the-art offline algorithms while running several orders of magnitude faster in the streaming and sliding-window settings.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Circulating tumor cells (CTCs) are elements of indisputable significance as they seem to be responsible for the onset of metastasis. Despite this, research into CTCs and their clinical application ...have been hindered by their rarity and heterogeneity at the molecular and cellular level, and also by a lack of technical standardization. Esophageal adenocarcinoma (EAC) is a highly aggressive cancer that is often diagnosed at an advanced stage. Its incidence has increased so much in recent years that new diagnostic, prognostic and predictive biomarkers are urgently needed. Preliminary findings suggest that CTCs could represent an effective, non-invasive, real-time assessable biomarker in all stages of EAC. This review provides an overview of EAC and CTC characteristics and reports the main research results obtained on CTCs in this setting. The need to carry out further basic and translational research in this area to confirm the clinical usefulness of CTCs and to provide oncologists with a tool to improve therapeutic strategies for EAC patients was herein highlighted.
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Highlights ► The study was performed using a DEP-based device to detect and sort 100% pure CTCs. ► Analyses were conducted on blood from 40 patients with metastatic colon cancer. ► CTCs were found in ...21 patients. ► A difference in KRAS status between CTCs and primary tumor was observed in 8 cases. ► Our DEP-based assay invites reflection on the value of CTC characterization.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Breast cancer (BC) is a disease characterized by a high grade of heterogeneity. Consequently, despite the great achievements obtained in the last decades, most of the current therapeutic regimens ...still fail. The identification of new molecular mechanisms that will increase the knowledge of all steps of tumor initiation and growth is mandatory in finding new clinical strategies. The BC microenvironment, consisting of endothelial cells, fibroblasts, immune cells and adipocytes, plays an essential role in regulating BC development, and recently it has gained great attention in the scientific community. In particular, adipose tissue is emerging as an important target to investigate among mammary gland components. The mechanisms underlying BC progression driven by adipocytes are predominantly unexplored, especially that involving the switch from normal adipocytes to the so-called cancer-associated adipocytes (CAAs). MicroRNAs (miRNAs), a class of gene expression modulators, have emerged as the regulators of key oncogenes and tumor suppressor genes that affect multiple pathways of the tumor microenvironment and adipose tissue. This review concerns a presentation of the role of adipocytes in breast tissue, and describes the most recent discoveries about the interplay between adipocytes and miRNAs, which collaborate in the arrangement of a pro-inflammatory and cancerous microenvironment, laying the foundations for new concepts in the prevention and treatment of BC.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Combining phenotypical and molecular characterization of rare cells is challenging due to their scarcity and difficult handling. In oncology, circulating tumor cells (CTCs) are considered among the ...most important rare cell populations. Their phenotypic and molecular characterization is necessary to define the molecular mechanisms underlying their metastatic potential. Several approaches that require cell fixation make difficult downstream molecular investigations on RNA. Conversely, the DEPArray technology allows phenotypic analysis and handling of both fixed and unfixed cells, enabling a wider range of applications. Here, we describe an experimental workflow that allows the transcriptomic investigation of single and pooled OE33 cells undergone to DEPArray analysis and recovery. In addition, cells were tested at different conditions (unfixed, CellSearch fixative (CSF)- and ethanol (EtOH)-fixed cells). In a forward-looking perspective, this workflow will pave the way for novel strategies to characterize gene expression profiles of rare cells, both single-cell and low-resolution input.
Exercise-released extracellular vesicles (EVs) are emerging as a novel class of exerkines that promotes systemic beneficial effects. However, slight differences in the applied exercise protocols in ...terms of mode, intensity and duration, as well as the need for standardized protocols for EV isolation, make the comparison of the studies in the literature extremely difficult. This work aims to investigate the EV amount and EV-associated miRNAs released in circulation in response to different physical exercise regimens. Healthy individuals were subjected to different exercise protocols: acute aerobic exercise (AAE) and training (AT), acute maximal aerobic exercise (AMAE) and altitude aerobic training (AAT). We found a tendency for total EVs to increase in the sedentary condition compared to trained participants following AAE. Moreover, the cytofluorimetric analysis showed an increase in CD81
/SGCA
/CD45
EVs in response to AAE. Although a single bout of moderate/maximal exercise did not impact the total EV number, EV-miRNA levels were affected as a result. In detail, EV-associated miR-206, miR-133b and miR-146a were upregulated following AAE, and this trend appeared intensity-dependent. Finally, THP-1 macrophage treatment with exercise-derived EVs induced an increase of the mRNAs encoding for
,
and
using baseline and immediately post-exercise EVs. Still, 1 h post-exercise EVs failed to stimulate a pro-inflammatory program. In conclusion, the reported data provide a better understanding of the release of circulating EVs and their role as mediators of the inflammatory processes associated with exercise.
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