Miracle-dz/UniFAR-FTUs huggingface dataset:
Investigating the Relation between Stochastic Differentiation, Homeostasis and Clonal Expansion in Intestinal Crypts via Multiscale Modeling

Colorectal tumors originate and develop within intestinal crypts. Even though some of the essential phenomena that characterize crypt structure and dynamics have been effectively described in the past, the relation between the differentiation process and the overall crypt homeostasis is still only partially understood. We here investigate this relation and other important biological phenomena by introducing a novel multiscale model that combines a morphological description of the crypt with a gene regulation model: the emergent dynamical behavior of the underlying gene regulatory network drives cell growth and differentiation processes, linking the two distinct spatio-temporal levels. The model relies on a few a priori assumptions, yet accounting for several key processes related to crypt functioning, such as: dynamic gene activation patterns, stochastic differentiation, signaling pathways ruling cell adhesion properties, cell displacement, cell growth, mitosis, apoptosis and the presence of biological noise. We show that this modeling approach captures the major dynamical phenomena that characterize the regular physiology of crypts, such as cell sorting, coordinate migration, dynamic turnover, stem cell niche correct positioning and clonal expansion. All in all, the model suggests that the process of stochastic differentiation might be sufficient to drive the crypt to homeostasis, under certain crypt configurations. Besides, our approach allows to make precise quantitative inferences that, when possible, were matched to the current biological knowledge and it permits to investigate the role of gene-level perturbations, with reference to cancer development. We also remark the theoretical framework is general and may be applied to different tissues, organs or organisms.
Differential Effects of HCN Channel Block on On and Off Pathways in the Retina as a Potential Cause for Medication-Induced Phosphene Perception.

Purpose Phosphene perception is a characteristic side effect of heart rate-reducing medication that acts on hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels. It is hypothesized that these phosphenes are caused by blocking HCN channels in photoreceptors and neurons of the retina, yet the underlying changes in visual signal processing in the retina caused by the HCN channel block are still unknown. Methods We examined the effects of pharmacologic HCN channel block on the encoding of visual signals in retinal ganglion cells by recording ganglion cell spiking activity from isolated mouse retinas mounted on multielectrode arrays. Spontaneous activity and responses to various visual stimuli were measured before, during, and after administration of 3 μM ivabradine. Results Retinal ganglion cells generally showed slower response kinetics and reduced sensitivity to high temporal frequencies under ivabradine. Moreover, ivabradine differentially affected the sensitivity of On and Off ganglion cells. On cells showed reduced response gain, whereas Off cells experienced an increase in response threshold. In line with these differential effects, Off cells, in contrast to On cells, also showed reduced baseline activity during visual stimulation and reduced spontaneous activity. Furthermore, Off cells, but not On cells, showed increased burst-like spiking activity in the presence of ivabradine. Conclusions Our data suggest that pharmacologic HCN channel block in the retina leads to a shift in the relative activity of the On and Off pathways of the retina. We hypothesize that this imbalance may underlie the medication-induced perception of phosphenes.
Technology spillovers and stability of international climate coalitions

Cooperation in international environmental agreements appears difficult to attain because of strong free-rider incentives. This paper explores how different technology spillover mechanisms among regions can influence the incentives to join and stabilise an international agreement. We use an applied modelling framework (STACO) that enables us to investigate the stability of partial climate coalitions. Several theories on the impact of technology spillovers are evaluated by simulating a range of alternative specifications. We find that spillovers are a good instrument to increase the abatement efforts of coalitions and reduce the associated costs. In our setting, however, they cannot overcome the strong free-rider incentives that are present in larger coalitions, i.e. technology spillovers do not substantially increase the success of international environmental agreements. This conclusion is robust with respect to the specification of technology spillovers.
Dynamic Base Station Switching-On/Off Strategies for Green Cellular Networks

In this paper, we investigate dynamic base station (BS) switching to reduce energy consumption in wireless cellular networks. Specifically, we formulate a general energy minimization problem pertaining to BS switching that is known to be a difficult combinatorial problem and requires high computational complexity as well as large signaling overhead. We propose a practically implementable switching-on/off based energy saving (SWES) algorithm that can be operated in a distributed manner with low computational complexity. A key design principle of the proposed algorithm is to turn off a BS one by one that will minimally affect the network by using a newly introduced notion of network-impact, which takes into account the additional load increments brought to its neighboring BSs. In order to further reduce the signaling and implementation overhead over the air and backhaul, we propose three other heuristic versions of SWES that use the approximate values of network-impact as their decision metrics. We describe how the proposed algorithms can be implemented in practice at the protocol-level and also estimate the amount of energy savings through a first-order analysis in a simple setting. Extensive simulations demonstrate that the SWES algorithms can significantly reduce the total energy consumption, e.g., we estimate up to 50-80% potential savings based on a real traffic profile from a metropolitan urban area.
Reflections on Reflective Practice

In recent years, a wide range of professions have adopted ‘reflective practice’ as an approach to professional development, and many professions have made it a mandatory dimension of their membership credentialling process. Despite the fact that it has been widely taken up in the professional world, there are many different conceptualizations and ideas about what it is. In this paper, six theoretical underpinnings of reflective practice are considered, and suggestions are made about how we can begin to incorporate reflection into our own practices.
Plant Oxygen Sensing Is Mediated by the N-End Rule Pathway: A Milestone in Plant Anaerobiosis

Like all aerobic organisms, plants require molecular oxygen for respiratory energy production. In plants, hypoxic conditions can occur during natural events (e.g., flooding), during developmental processes (e.g., seed germination), and in cells of compact tissues with high metabolic rates. Plant acclimation responses to hypoxia involve a modulation of gene expression leading to various biochemical, physiological, and morphological changes that stave off eventual anoxia. In contrast with the animal kingdom, a direct oxygen-sensing mechanism in plants has been elusive so far. However, two recent independent studies show that oxygen sensing in plants operates via posttranslational regulation of key hypoxia response transcription factors by the N-end rule pathway. The N-end rule is an evolutionarily conserved pathway for protein degradation that relates the fate of a protein with the identity of its N-terminal residues. Results from these studies demonstrate that oxygen-dependent modification and targeted proteolysis of members of the ethylene response factor group VII transcription factor family regulate hypoxia-responsive gene expression in Arabidopsis thaliana. The discovery of this plant hypoxia-sensing mechanism sets the stage for further research on plant homeostatic response to oxygen, which could be relevant to understanding plant distributions in flood-prone ecosystems and improving hypoxia tolerance of crops.
Transgenic Mouse Lines Subdivide External Segment of the Globus Pallidus (GPe) Neurons and Reveal Distinct GPe Output Pathways

Cell-type diversity in the brain enables the assembly of complex neural circuits, whose organization and patterns of activity give rise to brain function. However, the identification of distinct neuronal populations within a given brain region is often complicated by a lack of objective criteria to distinguish one neuronal population from another. In the external segment of the globus pallidus (GPe), neuronal populations have been defined using molecular, anatomical, and electrophysiological criteria, but these classification schemes are often not generalizable across preparations and lack consistency even within the same preparation. Here, we present a novel use of existing transgenic mouse lines, Lim homeobox 6 (Lhx6)–Cre and parvalbumin (PV)–Cre, to define genetically distinct cell populations in the GPe that differ molecularly, anatomically, and electrophysiologically. Lhx6–GPe neurons, which do not express PV, are concentrated in the medial portion of the GPe. They have lower spontaneous firing rates, narrower dynamic ranges, and make stronger projections to the striatum and substantia nigra pars compacta compared with PV–GPe neurons. In contrast, PV–GPe neurons are more concentrated in the lateral portions of the GPe. They have narrower action potentials, deeper afterhyperpolarizations, and make stronger projections to the subthalamic nucleus and parafascicular nucleus of the thalamus. These electrophysiological and anatomical differences suggest that Lhx6–GPe and PV–GPe neurons participate in different circuits with the potential to contribute to different aspects of motor function and dysfunction in disease.
Triterpenes from Euphorbia spinidens with immunomodulatory activity

Dried aceton-chloroform extract of aerial parts of Euphorbia spinidens Bornm. ex Prokh. endemic to Iran, yielded two new triterpenoids, lup-20(29)-ene-33, 28 diol commonly known as betulin and (3β,23E)-Cycloarta-23-ene-3,25-diol. The structures of the isolated compounds were elucidated by 13C- and 1H-NMR as well as 2D-NMR, IR and by the aid of mass fragmentation pattern. In phagocyte chemiluminescence assay, different concentrations of compounds were incubated with the human whole blood in triplicate and the chemiluminescence activity of phagocytic cells were measured by using serum opsonized zymosan and luminol. For lymphocyte proliferation assay, peripheral human blood lymphocytes were incubated with different concentrations of the test compound in supplemented Roswell Park Memorial Institute (RPMI) 1640 medium along with 5.0 μg/ml phytohemagglutinin (PHA) at 37°C in CO2 environment for 72 h and proliferation level was determined by Beta-scintillation counter. In phagocyte chemiluminescence assay, betulin showed moderate inhibitory effect on the oxidative burst in the neutrophils, while addition of betulin triterpene was able to stimulate the proliferation of the phytohemagglutinin (PHA) treated human peripheral blood lymphocytes (hPBLs).
Correlation of the Genotype of Paragangliomas and Pheochromocytomas with Their Metabolic Phenotype on 3,4-Dihydroxy-6-18F-Fluoro-l-Phenylalanin PET

Paragangliomas and pheochromocytomas are genetically heterogeneous diseases. The purpose of this study was to determine the sensitivity and specificity of PET with 3,4-dihydroxy-6-18F-fluoro-L-phenylalanin (18F-DOPA) for the detection and staging of pheochromocytomas/paragangliomas. Furthermore, we assessed whether the genotypes of pheochromocytomas and paragangliomas correlate with the uptake of 18F-DOPA. Methods: We retrospectively analyzed 101 consecutive patients who underwent 18F-DOPA PET or 18F-DOPA PET/CT for known or suspected pheochromocytomas or paragangliomas. Maximum 18F-DOPA tumor uptake was quantified relative to uptake in the liver. Results: Histopathology, cross-sectional imaging, and follow-up indicated the presence of paragangliomas and pheochromocytomas in 68 patients and the absence of a tumor in 33 patients. The average 18F-DOPA uptake by paragangliomas and pheochromocytomas, expressed as a tumor-to-liver ratio, was 5.9 ± 5.2. There was no significant difference in uptake among patients with von Hippel Lindau syndrome (VHL; n = 19), succinate dehydrogenase B–D mutation (n = 21), neurofibromatosis type 1 (n = 1), RET (n = 1), no germline mutation (n = 20), or unknown mutation status (n = 6) (P = 0.84). All 8 patients with an SDHD mutation were true-positive on 18F-DOPA PET. There were 2 cases of false-negative results each in the group with SDHB (2/12) and VHL mutations (2/19) and 1 false-negative result in the subgroup of patients with unknown mutation status (1/6). Overall, 18F-DOPA PET yielded a sensitivity of 93% and a specificity of 88% for the detection of paragangliomas and pheochromocytomas on a patient basis (positive and negative predictive value, 94% and 85%, respectively). Conclusion: 18F-DOPA PET is a sensitive and specific imaging modality for the detection and staging of pheochromocytomas and paragangliomas in different genotypes, including VHL-, SDHB-, and SDHD-mutation carriers, and in patients with no germline mutation.
Quantization noise analysis of wave digital and lossless digital integrator allpass/lattice filters

Quantization noise levels of two low-sensitive allpass filter structures, namely wave digital circulator filters (WDCF) and lossless digital integrator filters (LDIF), are compared. Allpass filters are of interest for design of lowpass and bandpass lattice filters. The results show, primarily, that second-order LDIFs have lower total quantization noise gains than corresponding WCDFs for any pole configuration within the right half-circle of the z plane. The benefit of using ladder LDIFs rather than cascaded first and second order sections is also demonstrated.
Automatic contrast enhancement of low-light images based on local statistics of wavelet coefficients

This paper describes a new method for contrast enhancement in images of low-light or unevenly illuminated scenes based on statistical modelling of wavelet coefficients of the image. A non-linear enhancement function has been designed based on the local dispersion of the wavelet coefficients modelled as a bivariate Cauchy distribution. Within the same statistical framework, a simultaneous noise reduction in the image is performed by means of a shrinkage function, thus preventing noise amplification. The proposed enhancement method has been shown to perform very well with insufficiently illuminated and noisy images, outperforming other conventional methods, in terms of contrast enhancement and noise reduction in the output image.
On Probability of Support Recovery for Orthogonal Matching Pursuit Using Mutual Coherence

In this letter, we present a new coherence-based performance guarantee for the orthogonal matching pursuit (OMP) algorithm. A lower bound for the probability of correctly identifying the support of a sparse signal with additive white Gaussian noise is derived. Compared to previous research work, the new bound takes into account the signal parameters, such as dynamic range, noise variance, and sparsity. Numerical simulations show significant improvements over previous research work and a closer match to empirically obtained results of the OMP algorithm.
The impact of displacement on the expression of depressive disorder and social functioning among the war refugees.

Our research objective was to estimate the characteristics of major depressive disorder and social adaptation of women displaced during the war in Croatia in the early 1990s. We aimed to establish the relationship between major depressive disorder and displacement and study its impact on the outcome of depression in order to improve treatment and avoid possible complications. A group of 20 women, 35 to 55 years of age, displaced some time during the 199l. -1995. war in Croatia were compared to 27 women of the same age but with no experience of exile. All the patients suffered from major depressive disorder based upon DSM-IV diagnostic criteria. The Hamilton Rating Scale for Depression, the Zung Self Rating Depression Scale and the Social Adaptation Self-evaluation Scale were used. The objective intensity of depression of the displaced significantly decreased over time but not their personal experience of depression. All depressed patients manifested poor social adaptation. Many aspects of social functioning remained poor even after the improvement of depressive disorder. Displacement characteristics were: the length of time spent in exile, the place, and the circumstances of displacement regarding the members of the family accompanying the displaced women. These characteristics significantly influenced the expression of their major depressive disorder as well as social functioning. Displaced persons/refugees are at high risk of developing depressive disorder. Recognition of all risk factors and early diagnosis of depressive disorder followed by appropriate treatment could decrease the risk of chronic and complicated depression as well as the risk of poor social adaptation.
A Local Characterization of Lyapunov Functions and Robust Stability of Perturbed Systems on Riemannian Manifolds

This paper proposes several Converse Lyapunov Theorems for nonlinear dynamical systems defined on smooth connected Rie mannian manifolds and characterizes properties of corresponding Lyapunov functions in a normal neighborhood of an equilibrium. We extend the methods of constructing of Lyapunov functions for ordinary differential equations on R n to dynamical systems defined on Riemannian manifolds by employing the differential geometry. By employing the derived properties of Lyapunov functions, we obtained the stability of perturbed dynamical systems on Riemannian manifolds. The results are obtained by employing the notions of normal neighborhoods, the injectivity radius on Riemannian manifolds and existence of bump functions on manifolds.
Perceived social support in a large community sample--age and sex differences.

BACKGROUND The positive health and wellbeing effects of social support have been consistently demonstrated in the literature since the late 1970s. However, a better understanding of the effects of age and sex is required. METHOD We examined the factor structure and reliability of Kessler's Perceived Social Support (KPSS) measure in a community-based sample that comprised younger and older adult cohorts from the Australian Twin Registry (ATR), totalling 11,389 males and females aged 18-95, of whom 887 were retested 25 months later. RESULTS Factor analysis consistently identified seven factors: support from spouse, twin, children, parents, relatives, friends and helping support. Internal reliability for the seven dimensions ranged from 0.87 to 0.71 and test-retest reliability ranged from 0.75 to 0.48. Perceived support was only marginally higher in females. Age dependencies were explored. Across the age range, there was a slight decline (more marked in females) in the perceived support from spouse, parent and friend, a slight increase in perceived relative and helping support for males but none for females, a substantial increase in the perceived support from children for males and females and a negligible decline in total KPSS for females against a negligible increase for males. The perceived support from twin remained constant. Females were more likely to have a confidant, although this declined with age whilst increasing with age for males. CONCLUSIONS Total scores for perceived social support conflate heterogeneous patterns on sub-scales that differ markedly by age and sex. Our paper describes these relationships in detail in a very large Australian sample.
Relation of isovolumic relaxation to left ventricular wall movement in man.

SUMMARY In order to determine the duration of isovolumic relaxation and its relation to left ventricular wall movement, 14 normal subjects, 44 patients with coronary artery disease, 16 with hypertension, and 10 with pure mitral stenosis were studied. Simultaneous echocardiograms, phonocardiograms, and apex cardiograms were performed, and the resulting traces digitised. In normal subjects, aortic valve closure (A2) occurred at a mean of 40 + 10 ms before the minimum left ventricular dimension, and the duration of isovolumic relaxation, taken as the period from A2 to the onset ofmitral valve cusp separation was a mean of 65 + 15 ms. In patients with hypertension, the timing of aortic valve closure was normal, but isovolumic relaxation was prolonged to a mean of 105 + 25 ms, so that mitral valve opening was significantly delayed, occurring at a mean of 80 + 25 ms after the minimum left ventricular dimension. In patients with coronary artery disease, aortic valve closure was significantly delayed by a mean of 5 + 40 ms with respect to the minimum left ventricular dimension. The mean duration of isovolumic relaxation did not differ significantly from normal, though the scatter was wide, but mitral valve opening was also delayed by a mean of 80 + 35 ms. In these patients, there was a strong association between delay in aortic valve closure and abnormal wall movement during isovolumic contraction. In patients with mitral stenosis, aortic valve closure was significantly delayed (mean 30 35 ms), but isovolumic relaxation was short (mean 40 + 20 ms). Thus though delayed mitral valve opening occurs both in hypertension and coronary artery disease, its cause differs: in the former the cause is prolonged relaxation, while in the latter it is primarily incoordinate systolic wall movement, resulting in prolongation of ejection and delayed aortic valve closure, with respect to normal regions.
Perfusion Zones of the DIEP Flap Revisited: A Clinical Study

Background: The Hartrampf perfusion zones of the lower abdominal flap are generally accepted. They were empirically based on the clinical impression of the perfusion in the first 16 unipedicled transverse rectus abdominis musculocutaneous flaps and have been uncritically adopted for the free transverse rectus abdominis musculocutaneous and the free deep inferior epigastric perforator (DIEP) flap. Scientific data proving the validity of these perfusion zones do not exist. The objective of this study was to evaluate and quantitatively assess the perfusion zones of the DIEP flap. Methods: In a clinical, prospective study of 15 patients undergoing DIEP flap breast reconstruction, tissue perfusion was intraoperatively assessed using the method of laser-induced fluorescence of indocyanine green. Results: Perfusion of zones I, II, and III was seen 25, 41, and 32 seconds, respectively, after injection, and the perfusion index constituted 76, 25, and 47 percent (median) of normal tissue. Perfusion of zone IV was completely absent in five patients (33 percent); in the remaining patients, it was dramatically decreased (5 percent) and occurred with a delay of 67 seconds. Conclusions: On the basis of the results of this study, the Hartrampf concept of a centrally perfused skin ellipse with declining perfusion of its peripheral ends is wrong and should be revised. Instead, one should think of the lower abdominal flap as two halves separated by the midline. The ipsilateral half has an axial pattern of perfusion; the contralateral half shows a random-pattern, individually variable blood supply. Therefore, the classic Hartrampf zones should be rearranged, switching zones II and III.