122 research outputs found
Upward Translation of Optimal and P-Optimal Proof Systems in the Boolean Hierarchy over NP
We study the existence of optimal and p-optimal proof systems for classes in
the Boolean hierarchy over . Our main results concern
, i.e., the second level of this hierarchy:
If all sets in have p-optimal proof systems, then all sets in
have p-optimal proof systems. The analogous implication for
optimal proof systems fails relative to an oracle.
As a consequence, we clarify such implications for all classes
and in the Boolean hierarchy over : either we can
prove the implication or show that it fails relative to an oracle. Furthermore,
we show that the sets and have p-optimal proof
systems, if and only if all sets in the Boolean hierarchy over
have p-optimal proof systems which is a new characterization of a conjecture
studied by Pudl\'ak
Episodic memory encoding and retrieval in face-name paired paradigm: An FNIRS study
Background: Episodic memory (EM) is particularly sensitive to pathological conditions and aging. In a neurocognitive context, the paired-associate learning (PAL) paradigm, which requires participants to learn and recall associations between stimuli, has been used to measure EM. The present study aimed to explore whether functional near-infrared spectroscopy (fNIRS) can be employed to determine cortical activity underlying encoding and retrieval. Moreover, we examined whether and how different aspects of task (i.e., novelty, difficulty) affects those cortical activities. Methods: Twenty-two male college students (age: M = 20.55, SD = 1.62) underwent a face-name PAL paradigm under 40-channel fNIRS covering fronto-parietal and middle occipital regions. Results: A decreased activity during encoding in a broad network encompassing the bilateral frontal cortex (Brodmann areas 9, 11, 45, and 46) was observed during the encoding, while an increased activity in the left orbitofrontal cortex (Brodmann area 11) was observed during the retrieval. Increased HbO concentration in the superior parietal cortices and decreased HbO concentration in the inferior parietal cortices were observed during encoding while dominant activation of left PFC was found during retrieval only. Higher task difficulty was associated with greater neural activity in the bilateral prefrontal cortex and higher task novelty was associated with greater activation in occipital regions. Conclusion: Combining the PAL paradigm with fNIRS provided the means to differentiate neural activity characterising encoding and retrieval. Therefore, the fNIRS may have the potential to complete EM assessments in clinical settings
Non-professional phagocytosis: a general feature of normal tissue cells
Non-professional phagocytosis by cancer cells has been described for decades. Recently, non-professional phagocytosis by normal tissue cells has been reported, which prompted us to take a closer look at this phenomenon. Non-professional phagocytosis was studied by staining cultured cells with live-cell staining dyes or by staining paraffin-embedded tissues by immunohistochemistry. Here, we report that each of 21 normal tissue cell lines from seven different organs was capable of phagocytosis, including ex vivo cell cultures examined before the 3rd passage as well as the primary and virus-transformed cell lines. We extended our analysis to an in vivo setting, and we found the occurrence of non-professional phagocytosis in healthy skin biopsies immediately after resection. Using dystrophin immunohistochemistry for membrane staining, human post-infarction myocardial tissue was assessed. We found prominent signs of non-professional phagocytosis at the transition zone of healthy and infarcted myocardia. Taken together, our findings suggest that non-professional phagocytosis is a general feature of normal tissue cells
DNA-Methylome based Tumor Hypoxia Classifier Identifies HPV-negative Head & Neck Cancer Patients at Risk for Locoregional Recurrence After Primary Radiochemotherapy
BACKGROUND
Tumor hypoxia is a paradigmatic negative prognosticator of treatment resistance in Head and Neck Squamous Cell Carcinoma (HNSCC). The lack of robust and reliable hypoxia classifiers limits the adaptation of stratified therapies. We hypothesized that the tumor DNA methylation landscape might indicate epigenetic reprogramming induced by chronic intratumoral hypoxia.
METHODS
A DNA methylome-based tumor hypoxia classifier (Hypoxia-M) was trained in the TCGA-HNSCC cohort based on matched assignments using gene expression-based signatures of hypoxia (Hypoxia-GES). Hypoxia-M was validated in a multicenter DKTK-ROG trial consisting of Human Papilloma Virus (HPV)-negative HNSCC patients treated with primary radiochemotherapy (RCHT).
RESULTS
While hypoxia-GSEs failed to stratify patients in the DKTK-ROG, Hypoxia-M was independently prognostic for local recurrence (LR, HR=4.3, p=0.001) and overall survival (OS, HR=2.34, p=0.03) but not distant metastasis (DM) after RCHT in the both cohorts. Hypoxia-M status was inversely associated with CD8 T-cells infiltration in both cohorts. Hypoxia-M was further prognostic in the TCGA-PanCancer cohort (HR=1.83, p=0.04), underscoring the breadth of this classifier for predicting tumor hypoxia status.
CONCLUSIONS
Our findings highlight an unexplored avenue for DNA Methylation-based classifiers as biomarkers of tumoral hypoxia for identifying high-risk features in patients with HNSCC tumors.
TRIAL REGISTRATION
Retrospective observational study from the German Cancer Consortium (DKTK-ROG), not interventional
Stability and multi-attractor dynamics of a toggle switch based on a two-stage model of stochastic gene expression
A toggle switch consists of two genes that mutually repress each other. This
regulatory motif is active during cell differentiation and is thought to act as
a memory device, being able to choose and maintain cell fate decisions. In this
contribution, we study the stability and dynamics of a two-stage gene
expression switch within a probabilistic framework inspired by the properties
of the Pu/Gata toggle switch in myeloid progenitor cells. We focus on low mRNA
numbers, high protein abundance and monomeric transcription factor binding.
Contrary to the expectation from a deterministic description, this switch shows
complex multi-attractor dy- namics without autoactivation and cooperativity.
Most importantly, the four attractors of the system, which only emerge in a
probabilistic two-stage description, can be identified with committed and
primed states in cell differentiation. We first study the dynamics of the
system and infer the mechanisms that move the system between attractors using
both the quasi-potential and the probability flux of the system. Second, we
show that the residence times of the system in one of the committed attractors
are geometrically distributed and provide an analytical expression of the
distribution. Most importantly we find that the mean residence time increases
linearly with the mean protein level. Finally, we study the implications of
this distribution for the stability of a switch and discuss the influence of
the stability on a specific cell differentiation mechanism. Our model explains
lineage priming and proposes the need of either high protein numbers or long
term modifications such as chromatin remodeling to achieve stable cell fate
decisions. Notably we present a system with high protein abundance that
nevertheless requires a probabilistic description to exhibit multistability,
complex switching dynamics and lineage priming.Comment: to appear in the Biophysical Journa
Connecting Earth Observation to High-Throughput Biodiversity Data
There is much interest in using Earth Observation (EO) technology to track biodiversity, ecosystem functions, and ecosystem services, understandable given the fast pace of biodiversity loss. However, because most biodiversity is invisible to EO, EO-based indicators could be misleading, which can reduce the effectiveness of nature conservation and even unintentionally decrease conservation effort. We describe an approach that combines automated recording devices, high-throughput DNA sequencing, and modern ecological modelling to extract much more of the information available in EO data. This approach is achievable now, 62 offering efficient and near-real time monitoring of management impacts on biodiversity and its functions and services
Connecting Earth observation to high-throughput biodiversity data
Understandably, given the fast pace of biodiversity loss, there is much interest in using Earth observation technology to track biodiversity, ecosystem functions and ecosystem services. However, because most biodiversity is invisible to Earth observation, indicators based on Earth observation could be misleading and reduce the effectiveness of nature conservation and even unintentionally decrease conservation effort. We describe an approach that combines automated recording devices, high-throughput DNA sequencing and modern ecological modelling to extract much more of the information available in Earth observation data. This approach is achievable now, offering efficient and near-real-time monitoring of management impacts on biodiversity and its functions and services
Moxifloxacin enhances antiproliferative and apoptotic effects of etoposide but inhibits its proinflammatory effects in THP-1 and Jurkat cells
Etoposide (VP-16) is a topoisomerase II (topo II) inhibitor chemotherapeutic agent. Studies indicate that VP-16 enhances proinflammatory cytokines secretion from tumour cells, including IL-8, a chemokine associated with proangiogenic effects. Fluoroquinolones inhibit topo II activity in eukaryotic cells by a mechanism different from that of VP-16. The fluoroquinolone moxifloxacin (MXF) has pronounced anti-inflammatory effects in vitro and in vivo. We studied the effects of MXF and VP-16 on purified human topo II activity and further analysed their combined activity on proliferation, apoptosis and caspase-3 activity in THP-1 and Jurkat cells. Moxifloxacin alone slightly inhibited the activity of human topo II; however, in combination with VP-16 it led to a 73% reduction in enzyme activity. VP-16 inhibited cell proliferation in a time and dose-dependent manner. The addition of moxifloxacin for 72 h to low-dose VP-16 doubled its cytotoxic effect in THP-1 and Jurkat cells (1.8- and 2.6-fold decrease in cell proliferation, respectively) (P<0.004). Moxifloxacin given alone did not induce apoptosis but enhanced VP-16-induced apoptosis in THP-1 and Jurkat cells (1.8- and two-fold increase in annexin V positive cells and caspase-3 activity, respectively) (P<0.04). VP-16 induced the release of IL-8 in a time and dose-dependent manner from THP-1 cells. Moxifloxacin completely blocked the enhanced release of IL-8 induced by 0.5 and 1 μg ml−1 VP-16, and decreased IL-8 release from cells incubated for 72 h with 3 μg ml−1 VP-16 (P<0.001). VP-16 enhanced the release of IL-1β and TNF-α from THP-1 cells, whereas the addition of MXF prevented the enhanced cytokine secretion (P<0.001). We conclude that MXF significantly enhances VP-16 cytotoxicity in tumour-derived cells while preventing VP-16-induced proinflammatory cytokine release. This unique combination may have clinical benefits and cytotoxic drug ‘sparing effect' and should be further studied in vivo
Fast retrospectively triggered local pulse-wave velocity measurements in mice with CMR-microscopy using a radial trajectory
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