Miracle-dz/UniFAR-FTUs huggingface dataset:
Cancer cell adhesive interactions – more than just physical attraction Selectins promote tumor metastasis

Cancer metastasis is facilitated by cell-cell interactions between cancer cells and endothelial cells in distant tissues. In addition, cancer cell interactions with platelets and leukocytes contribute to cancer cell adhesion, extravasation, and the establishment of metastatic lesions. Selectins are carbohydratebinding molecules that bind to sialylated, fucosylated glycan structures, and are found on endothelial cells, platelets and leukocytes. There are three members of the selectin family: P-selectin expressed on activated platelets and endothelial cells, L-selectin present on leukocytes and E-selectin expressed on activated endothelial cells. Besides the accepted roles of selectins in physiological processes, such as inflammation, immune response and hemostasis, there is accumulating evidence for the potential of selectins to contribute to a number of pathophysiological processes, including cancer metastasis. Cancer cell interactions with selectins are possible due to a frequent presence of carbohydrate determinants– selectin ligands on the cell surface of tumor cells from various type of cancer. The degree of selectin ligand expression by cancer cells is well correlated with metastasis and poor prognosis for cancer patients. Initial adhesion events of cancer cells facilitated by selectins result in activation of integrins, release of chemokines and are possibly associated with the formation of permissive metastatic microenvironment. While E-selectin has been evaluated as one of the initiating adhesion events during metastasis, it is becoming apparent that P-selectin and L-selectin-mediated interactions significantly contribute to this process as well. In this review we discuss the current evidence for selectins as potential facilitators of metastasis. DOI: https://doi.org/10.1016/j.semcancer. 2010.04. 005 Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-40790 Accepted Version Originally published at: Läubli, H; Borsig, L (2010). Selectins promote tumor metastasis. Seminars in Cancer Biology, 20(3):169177. DOI: https://doi.org/10.1016/j.semcancer. 2010.04. 005
A Meta-Algorithm for Solving Connectivity and Acyclicity Constraints on Locally Checkable Properties Parameterized by Graph Width Measures

In this paper, we design a framework to obtain efficient algorithms for several problems with a global constraint (acyclicity or connectivity) such as Connected Dominating Set, Node Weighted Steiner Tree, Maximum Induced Tree, Longest Induced Path, and Feedback Vertex Set. We design a meta-algorithm that solves all these problems and whose running time is upper bounded by $2^{O(k)}\cdot n^{O(1)}$, $2^{O(k \log(k))}\cdot n^{O(1)}$, $2^{O(k^2)}\cdot n^{O(1)}$ and $n^{O(k)}$ where $k$ is respectively the clique-width, $\mathbb{Q}$-rank-width, rank-width and maximum induced matching width of a given decomposition. Our meta-algorithm simplifies and unifies the known algorithms for each of the parameters and its running time matches asymptotically also the running times of the best known algorithms for basic NP-hard problems such as Vertex Cover and Dominating Set. Our framework is based on the $d$-neighbor equivalence defined in [Bui-Xuan, Telle and Vatshelle, TCS 2013]. The results we obtain highlight the importance of this equivalence relation on the algorithmic applications of width measures. We also prove that our framework could be useful for $W[1]$-hard problems parameterized by clique-width such as Max Cut and Maximum Minimal Cut. For these latter problems, we obtain $n^{O(k)}$, $n^{O(k)}$ and $n^{2^{O(k)}}$ time algorithms where $k$ is respectively the clique-width, the $\mathbb{Q}$-rank-width and the rank-width of the input graph.
Involvement of NMDA Receptors, Nitric Oxide, and GABA in Rostral Ventrolateral Medulla in Acute Ethanol‐Induced Cardiovascular Responses in Rats

BACKGROUND Consumption of ethanol (EtOH) (alcohol) has many effects on physiological functions, particularly those in the central nervous system (CNS) and cardiovascular system. Acute excessive intake of EtOH (alcohol intoxication) may cause hypotension and tachycardia. In this study, we examined the mechanistic involvement of glutamatergic N-methyl-d-aspartate (NMDA) receptors, nitric oxide (NO), and γ-aminobutyric acid (GABA) pathways in the CNS in acute EtOH-induced cardiovascular effects. METHODS EtOH was administered by intraperitoneal (IP) injection in Sprague-Dawley rats. The blood pressure (BP) and heart rate (HR) were measured in conscious and in urethane-anesthetized rats. Inhibitors were applied by intracerebroventricular (ICV) injection or by microinjection into rostral ventrolateral medulla (RVLM). Microdialysis was used to determine the level of glutamate, NO, and GABA in the RVLM. RESULTS IP injection of EtOH (3.2 g/kg) caused a significant decrease in BP in conscious and anesthetized rats and a late increase in HR in conscious rats. The cardiovascular effects of EtOH were significantly attenuated by ICV or by RVLM post treatment with ketamine (an NMDA receptor antagonist), N5-(nitroamidino)-L-2,5-diaminopentanoic acid (L-NNA; a NO synthase inhibitor), or bicuculline (a GABA receptor antagonist). EtOH caused an increase in the level of glutamate, NO, and GABA in the RVLM during the hypotensive responses. RVLM posttreatment with ketamine blocked the increase in NO and GABA levels; post treatment with L-NNA blocked the increase in GABA level. CONCLUSIONS Our results indicate that EtOH augmentation of glutamatergic NMDA receptors/NO/GABA pathways in the RVLM may participate in the hypotensive effects induced by acute administration of EtOH.
Choroidal Thickness and Ganglion Cell Complex in Pubescent Children with Type 1 Diabetes without Diabetic Retinopathy Analyzed by Spectral Domain Optical Coherence Tomography

Aim To assess the retinal and choroidal thickness and ganglion cell complex (GCC) in pubescent children with type 1 diabetes (T1D) without diabetic retinopathy (DR), using spectral domain optical coherence tomography (SD-OCT). Materials and Method Sixty-four right eyes of 64 subjects with T1D and 45 right eyes of 45 age-matched healthy volunteers (control group) were enrolled in this study. The mean age of the subjects and controls was 15.3 (±SD = 2.2) and 14.6 (±SD = 1.5), respectively. SD-OCT was performed using RTVue XR Avanti. Ganglion cell complex (GCC), GCC focal loss volume (FLV), GCC global loss volume (GLV), choroidal thickness (CT), foveal (FT) and parafoveal thickness (PFT), and foveal (FV) and parafoveal volume (PFV) data were analyzed. Results There was no significant difference between subjects and controls in the CT in the fovea and nasal, temporal, superior, and inferior quadrants of the macula. There were no significant correlations between CT, duration of diabetes, and HbA1C level (p = 0.272 and p = 0.197, resp.). GCC thickness did not differ significantly between the groups (p = 0.448), but there was a significant difference in FLV (p = 0.037). Significant differences between the groups were found in the PFT and PFV (p = 0.004 and p = 0.005, resp.). There was a significant negative correlation between PFT, PFV, and HbA1C level (p = 0.002 and p = 0.001, resp.). Conclusions Choroidal thickness remains unchanged in children with T1D. Increased GCC FLV might suggest an early alteration in neuroretinal tissue. Parafoveal retinal thickness is decreased in pubescent T1D children and correlates with HbA1C level. OCT can be considered a part of noninvasive screening in children with T1D and a tool for early detection of retinal and choroidal abnormalities. Further OCT follow-up is needed to determine whether any of the discussed OCT measurements are predictive of future DR severity.
Flexible modulation of electronic and magnetic properties of zigzag H-MoS2 nanoribbons by crack defects

The effects of crack defects on electronic and magnetic properties of zigzag MoS2 nanoribbons are investigated systematically by first-principles calculations based on spin-polarized density functional theory. We find that not only the electronic and spin transport ability of zigzag MoS2 nanoribbons can be enhanced significantly by the armchair crack defects, but also their magnetism could be modulated flexibly by crack defects. Our study suggests that the introduction of crack defect is a feasible way to modulate the electronic and magnetic properties of zigzag MoS2 nanoribbons. We further propose that the crack defects may also provide a useful tool for improving the performance of devices.
Neurocranial anatomy of an enigmatic Early Devonian fish sheds light on early osteichthyan evolution

The skull of ‘Ligulalepis’ from the Early Devonian of Australia (AM-F101607) has significantly expanded our knowledge of early osteichthyan anatomy, but its phylogenetic position has remained uncertain. We herein describe a second skull of ‘Ligulalepis’ and present micro-CT data on both specimens to reveal novel anatomical features, including cranial endocasts. Several features previously considered to link ‘Ligulalepis’ with actinopterygians are now considered generalized osteichthyan characters or of uncertain polarity. The presence of a lateral cranial canal is shown to be variable in its development between specimens. Other notable new features include the presence of a pineal foramen, the some detail of skull roof sutures, the shape of the nasal capsules, a placoderm-like hypophysial vein, and a chondrichthyan-like labyrinth system. New phylogenetic analyses place ‘Ligulalepis’ as a stem osteichthyan, specifically as the sister taxon to ‘psarolepids’ plus crown osteichthyans. The precise position of ‘psarolepids’ differs between parsimony and Bayesian analyses.
Friends and foes of tuberculosis: modulation of protective immunity

Protective immunity in tuberculosis (TB) is subject of debate in the TB research community, as this is key to fully understand TB pathogenesis and to develop new promising tools for TB diagnosis and prognosis as well as a more efficient TB vaccine. IFN‐γ producing CD4+ T cells are key in TB control, but may not be sufficient to provide protection. Additional subsets have been identified that contribute to protection such as multifunctional and cytolytic T‐cell subsets, including classical and nonclassical T cells as well as novel innate immune cell subsets resulting from trained immunity. However, to define protective immune responses against TB, the complexity of balancing TB immunity also has to be considered. In this review, insights into effector cell immunity and how this is modulated by regulatory cells, associated comorbidities and the host microbiome, is discussed. We systematically map how different suppressive immune cell subsets may affect effector cell responses at the local site of infection. We also dissect how common comorbidities such as HIV, helminths and diabetes may bias protective TB immunity towards pathogenic and regulatory responses. Finally, also the composition and diversity of the microbiome in the lung and gut could affect host TB immunity. Understanding these various aspects of the immunological balance in the human host is fundamental to prevent TB infection and disease.
Inhibitors of the HIV-1 capsid, a target of opportunity

Purpose of review To summarize recent advances in the discovery of chemical inhibitors targeting the HIV capsid and research on their mechanisms of action. Recent findings HIV infection is critically dependent on functions of the viral capsid. Numerous studies have reported the identification of a variety of compounds that bind to the capsid protein; some of these inhibit reverse transcription and nuclear entry, steps required for infection. Other capsid-targeting compounds appear to act by perturbing capsid assembly, resulting in noninfectious progeny virions. Inhibitors may bind to several different positions on the capsid protein, including sites in both protein domains. However, the antiviral activity of many reported capsid-targeting inhibitors has not been definitively linked to capsid binding. Until recently, the low-to-moderate potency of reported capsid-targeting inhibitors has precluded their further clinical development. In 2017, GS-CA1, a highly potent capsid inhibitor, was described that holds promise for clinical development. Summary Small molecules that bind to the viral capsid protein can be potent inhibitors of HIV infection. Capsid-targeting drugs are predicted to exhibit high barriers to viral resistance, and ongoing work in this area is contributing to an understanding of the molecular biology of HIV uncoating and maturation.
Role of granulosa cell mitogen-activated protein kinase 3/1 in gonadotropin-mediated meiotic resumption from diplotene arrest of mammalian oocytes

Abstract In mammals, preovulatory oocytes are encircled by several layers of granulosa cells (GCs) in follicular microenvironment. These follicular oocytes are arrested at diplotene arrest due to high level of cyclic nucleotides from encircling GCs. Pituitary gonadotropin acts at the level of encircling GCs and increases adenosine 3′,5′-cyclic monophosphate (cAMP) and guanosine 3′,5′-cyclic monophosphate (cGMP) and activates mitogen-activated protein kinase 3/1 (MAPK3/1) signaling pathway. The MAPK3/1 disrupts the gap junctions between encircling GCs and oocyte. The disruption of gap junctions interrupts the transfer of cyclic nucleotides to the oocyte that results a drop in intraoocyte cAMP level. A transient decrease in oocyte cAMP level triggers maturation promoting factor (MPF) destabilization. The destabilized MPF finally triggers meiotic resumption from diplotene arrest in follicular oocyte. Thus, MAPK3/1 from GCs origin plays important role in gonadotropin-mediated meiotic resumption from diplotene arrest in follicular oocyte of mammals.
Analysis of User Interaction with a Brain-Computer Interface Based on Steady-State Visually Evoked Potentials: Case Study of a Game

This paper presents a systematic analysis of a game controlled by a Brain-Computer Interface (BCI) based on Steady-State Visually Evoked Potentials (SSVEP). The objective is to understand BCI systems from the Human-Computer Interface (HCI) point of view, by observing how the users interact with the game and evaluating how the interface elements influence the system performance. The interactions of 30 volunteers with our computer game, named “Get Coins,” through a BCI based on SSVEP, have generated a database of brain signals and the corresponding responses to a questionnaire about various perceptual parameters, such as visual stimulation, acoustic feedback, background music, visual contrast, and visual fatigue. Each one of the volunteers played one match using the keyboard and four matches using the BCI, for comparison. In all matches using the BCI, the volunteers achieved the goals of the game. Eight of them achieved a perfect score in at least one of the four matches, showing the feasibility of the direct communication between the brain and the computer. Despite this successful experiment, adaptations and improvements should be implemented to make this innovative technology accessible to the end user.
Comparative Analysis of the Effects of Olive Oil Hydroxytyrosol and Its 5-S-Lipoyl Conjugate in Protecting Human Erythrocytes from Mercury Toxicity

Oxidative stress is one of the underlying mechanisms of the toxic effects exerted by mercury (Hg) on human health. Several antioxidant compounds, including the olive oil phenol hydroxytyrosol (HT), were investigated for their protective action. Recently, we have reported that 5-S-lipoylhydroxytyrosol (Lipo-HT) has shown increased antioxidant activities compared to HT and exerted potent protective effects against reactive oxygen species (ROS) generation and oxidative damage in human hepatocellular carcinoma HepG2 cell lines. In this study, the effects of Lipo-HT and HT on oxidative alterations of human erythrocytes induced by exposure to 40 μM HgCl2 were comparatively evaluated. When administered to the cells, Lipo-HT (5–20 μM) proved nontoxic and it decreased the Hg-induced generation of ROS, the hemolysis, and the depletion of intracellular GSH levels. At all tested concentrations, Lipo-HT exhibited higher ability to counteract Hg-induced cytotoxicity compared to HT. Model studies indicated the formation of a mercury complex at the SH group of Lipo-HT followed by a redox reaction that would spare intracellular GSH. Thus, the enhanced erythrocyte protective action of Lipo-HT from Hg-induced damage with respect to HT is likely due to an effective chelating and reducing ability toward mercury ions. These findings encourage the use of Lipo-HT in nutraceutical strategies to contrast heavy metal toxicity in humans.
Construction and Validation of Subject-Specific Biventricular Finite-Element Models of Healthy and Failing Swine Hearts From High-Resolution DT-MRI

Predictive computational modeling has revolutionized classical engineering disciplines and is in the process of transforming cardiovascular research. This is particularly relevant for investigating emergent therapies for heart failure, which remains a leading cause of death globally. The creation of subject-specific biventricular computational cardiac models has been a long-term endeavor within the biomedical engineering community. Using high resolution (0.3 × 0.3 × 0.8 mm) ex vivo data, we constructed a precise fully subject-specific biventricular finite-element model of healthy and failing swine hearts. Each model includes fully subject-specific geometries, myofiber architecture and, in the case of the failing heart, fibrotic tissue distribution. Passive and active material properties are prescribed using hyperelastic strain energy functions that define a nearly incompressible, orthotropic material capable of contractile function. These materials were calibrated using a sophisticated multistep approach to match orthotropic tri-axial shear data as well as subject-specific hemodynamic ventricular targets for pressure and volume to ensure realistic cardiac function. Each mechanically beating heart is coupled with a lumped-parameter representation of the circulatory system, allowing for a closed-loop definition of cardiovascular flow. The circulatory model incorporates unidirectional fluid exchanges driven by pressure gradients of the model, which in turn are driven by the mechanically beating heart. This creates a computationally meaningful representation of the dynamic beating of the heart coupled with the circulatory system. Each model was calibrated using subject-specific experimental data and compared with independent in vivo strain data obtained from echocardiography. Our methods produced highly detailed representations of swine hearts that function mechanically in a remarkably similar manner to the in vivo subject-specific strains on a global and regional comparison. The degree of subject-specificity included in the models represents a milestone for modeling efforts that captures realism of the whole heart. This study establishes a foundation for future computational studies that can apply these validated methods to advance cardiac mechanics research.
International Classification of Functioning, Disability and Health Core Sets for cerebral palsy, autism spectrum disorder, and attention‐deficit–hyperactivity disorder

Capturing functional information is crucial in childhood disability. The International Classification of Functioning, Disability and Health (ICF) Core Sets promote assessments of functional abilities and disabilities in clinical practice regarding circumscribed diagnoses. However, the specificity of ICF Core Sets for childhood‐onset disabilities has been doubted. This study aimed to identify content commonalities and differences among the ICF Core Sets for cerebral palsy (CP), and the newly developed Core Sets for autism spectrum disorder (ASD) and attention‐deficit–hyperactivity disorder (ADHD).
OPTZ: a Hardware Isolation Architecture of Multi-Tasks Based on TrustZone Support

In order to improve the safety of existing embedded system, make user data more secure, we propose an implementation of multitasking hardware isolation based on TrustZone named OPTZ (Open TrustZone). ARM TrustZone technology can implement the hardware isolation to improve the security of the software without additional hardware chips outside. In this paper we designed a complete trusted execution environment (TEE) and implemented the multitasking hardware isolation between normal world and secure world. Moreover, the multitasks in the secure memory are also separated from each other. Our architecture includes a secure operating system running in secure world, an normal operating system from normal world, secure services and communication mechanism. At last, we have done some experiments of physical memory access to test and verify the correctness of our architecture. Client application(CA) runs in normal world cannot access the secure world's physical address. The trusted application(TA) can communicate with each other but not access. The experiment results show that multitasking hardware isolation worked well, and the memory isolation can reach the hardware level.
Resveratrol Improves Tube Formation in AGE-Induced Late Endothelial Progenitor Cells by Suppressing Syndecan-4 Shedding

Dysfunction of endothelial progenitor cells (EPCs) contributes to cardiovascular complications in diabetes, and resveratrol has been shown to improve EPC functions. Syndecan-4 (Synd4), a cell surface heparin sulfate proteoglycan, has been shown to promote neovascularization. Thus, the present study was performed to determine whether resveratrol promoted angiogenesis of EPCs by regulating Synd4. Late EPCs were isolated from human peripheral blood and stimulated with AGEs. Western blot showed that AGEs induced Synd4 shedding in a dose- and time-dependent manner. AGE-induced Synd4 shedding was partly reversed by NAC or resveratrol, along with normalized ROS production. Overexpression of Synd4 or pretreatment of resveratrol reversed AGE-impaired tube formation of EPCs and regulated the Akt/eNOS pathway. Furthermore, resveratrol suppressed Synd4 shedding via the inhibition of oxidative stress and improved tube formation of late EPCs via the regulation of the Synd4/Akt/eNOS pathway.
Emergence of Pituitary Adenoma in a Child during Surveillance: Clinical Challenges and the Family Members' View in an AIP Mutation-Positive Family

Introduction Germline aryl hydrocarbon receptor-interacting protein (AIP) mutations are responsible for 15–30% of familial isolated pituitary adenomas (FIPAs). We report a FIPA kindred with a heterozygous deletion in AIP, aiming to highlight the indications and benefits of genetic screening, variability in clinical presentations, and management challenges in this setting. Patients An 18-year-old male was diagnosed with a clinically nonfunctioning pituitary adenoma (NFPA). Two years later, his brother was diagnosed with a somatolactotrophinoma, and a small Rathke's cleft cyst and a microadenoma were detected on screening in their 17-year-old sister. Following amenorrhoea, their maternal cousin was diagnosed with hyperprolactinaemia and two distinct pituitary microadenomas. A 12-year-old niece developed headache and her MRI showed a microadenoma, not seen on a pituitary MRI scan 3 years earlier. Discussion Out of the 14 members harbouring germline AIP mutations in this kindred, 5 have pituitary adenoma. Affected members had different features and courses of disease. Bulky pituitary and not fully suppressed GH on OGTT can be challenging in the evaluation of females in teenage years. Multiple pituitary adenomas with different secretory profiles may arise in the pituitary of these patients. Small, stable NFPAs can be present in mutation carriers, similar to incidentalomas in the general population. Genetic screening and baseline review, with follow-up of younger subjects, are recommended in AIP mutation-positive families.