Miracle-dz/UniFAR-FTUs huggingface dataset:
Arterial compliance increases after moderate-intensity cycling.

Exercise training elevates arterial compliance at rest, but the effects of acute exercise in this regard are unknown. This study investigated the effects of a single, 30-min bout of cycling exercise at 65% of maximal oxygen consumption on indexes of arterial compliance. Whole body arterial compliance determined noninvasively from simultaneous measurements of aortic flow and carotid pressure was elevated (66 ± 26%) at 0.5 h postexercise ( P = 0.04), followed by a decline to baseline 1 h after exercise. Aortic pulse-wave velocity, which is inversely related to compliance, was reduced (4 ± 2%; P = 0.04) at 0.5 h postexercise. Pulse-wave velocity in the leg decreased by 10 ± 4% at this time ( P = 0.01). Mean arterial pressure was unchanged; however, central systolic blood pressure was reduced postexercise ( P = 0.03). Cardiac output was elevated after exercise ( P = 0.007) via heart rate elevation ( P = 0.001), whereas stroke volume was unchanged. Total peripheral resistance was therefore reduced ( P = 0.01) and would be expected to contribute to an elevation in arterial compliance. In conclusion, a single bout of cycling exercise increased whole body arterial compliance by mechanisms that may relate to vasodilation.
Detecting Heads using Feature Refine Net and Cascaded Multi-scale Architecture

This paper presents a method that can accurately detect heads especially small heads under the indoor scene. To achieve this, we propose a novel method, Feature Refine Net (FRN), and a cascaded multi-scale architecture. FRN exploits the multi-scale hierarchical features created by deep convolutional neural networks. The proposed channel weighting method enables FRN to make use of features alternatively and effectively. To improve the performance of small head detection, we propose a cascaded multi-scale architecture which has two detectors. One called global detector is responsible for detecting large objects and acquiring the global distribution information. The other called local detector is designed for small objects detection and makes use of the information provided by global detector. Due to the lack of head detection datasets, we have collected and labeled a new large dataset named SCUT-HEAD which includes 4405 images with 111251 heads annotated. Experiments show that our method has achieved state-of-the-art performance on SCUT-HEAD.
Retinal vascular speed <0.5 disc diameter per week as an early sign of retinopathy of prematurity requiring treatment

Purpose: To analyse the speed of temporal retinal vascularisation in preterm infants included in the screening programme for retinopathy of prematurity. Material and methods: A total of 185 premature infants were studied retrospectively between 2000 and 2017 in San Cecilio University Hospital of Granada, Spain. The method of binocular indirect ophthalmoscopy with indentation was used for the examination. The horizontal disc diameter was used as a unit of length. Speed of temporal retinal vascularisation (disc diameter/week) was calculated as the ratio between the extent of temporal retinal vascularisation (disc diameter) and the time in weeks. Results: The weekly temporal retinal vascularisation (0–1.25 disc diameter/week, confidence interval) was significantly higher in no retinopathy of prematurity (0.73 ± 0.22 disc diameter/week) than in stage 1 retinopathy of prematurity (0.58 ± 0.22 disc diameter/week). It was also higher in stage 1 than in stages 2 (0.46 ± 0.14 disc diameter/week) and 3 of retinopathy of prematurity (0.36 ± 0.18 disc diameter/week). The rate of temporal retinal vascularisation (disc diameter/week) decreases when retinopathy of prematurity stage increases. The area under the receiver operating characteristic curve was 0.85 (95% confidence interval: 0.79–0.91) for retinopathy of prematurity requiring treatment versus not requiring treatment. The best discriminative cut-off point was a speed of retinal vascularisation <0.5 disc diameter/week, with a sensitivity and a specificity of 84.8% and 77%, respectively. Conclusion: The rate of temporal retinal vascularisation is a quantifiable observation that can help to alert a clinician that treatment of retinopathy of prematurity may be required. However, before becoming a new standard of care for treatment, it requires careful documentation, with agreement between several ophthalmologists.
Spontaneous Up states in vitro: a single-metric index of the functional maturation and regional differentiation of the cerebral cortex

Understanding the development and differentiation of the neocortex remains a central focus of neuroscience. While previous studies have examined isolated aspects of cellular and synaptic organization, an integrated functional index of the cortical microcircuit is still lacking. Here we aimed to provide such an index, in the form of spontaneously recurring periods of persistent network activity -or Up states- recorded in mouse cortical slices. These coordinated network dynamics emerge through the orchestrated regulation of multiple cellular and synaptic elements and represent the default activity of the cortical microcircuit. To explore whether spontaneous Up states can capture developmental changes in intracortical networks we obtained local field potential recordings throughout the mouse lifespan. Two independent and complementary methodologies revealed that Up state activity is systematically modified by age, with the largest changes occurring during early development and adolescence. To explore possible regional heterogeneities we also compared the development of Up states in two distinct cortical areas and show that primary somatosensory cortex develops at a faster pace than primary motor cortex. Our findings suggest that in vitro Up states can serve as a functional index of cortical development and differentiation and can provide a baseline for comparing experimental and/or genetic mouse models.
A 512-channels, whole array readout, CMOS implantable probe for acute recordings from the brain

The integration of implantable CMOS neural probes with thousands of simultaneously recording microelectrodes is a promising approach for neuroscience and might allow to literally image electrophysiological neuronal activity in multiple brain circuits as we have previously shown in vitro. Here, we present a complete system based on a fully multiplexed CMOS neural probe that was designed for in-vivo acute recordings with a scalable circuit architecture. In particular, a first prototype of a single-shaft probe with 512 electrodes was realized in a standard CMOS 0. 18μm technology and post-processed to structure the shaft with a wedge-like geometry of 30μm in thickness at the tip and 80μm at the base. The design of the system and of the probe as well as the post-processing techniques are discussed. Finally, preliminary results on electrical, mechanical and implantation tests are presented to demonstrate the feasibility of our approach.
Localization of P2X1 purinoceptors by autoradiography and immunohistochemistry in rat kidneys.

P2 receptors have been identified in rat kidney by autoradiography, using the radioligand [3H]α,β-methylene ATP, and by immunohistochemistry, using a polyclonal antibody to the P2X1 purinoceptor. They have been localized to the vascular smooth muscle of intrarenal arteries, including arcuate and interlobular arteries, and afferent arterioles, but not glomeruli, postglomerular efferent arterioles, or renal tubules. We conclude that at least some of the P2 receptors present on vascular smooth muscle are of the P2X1 subtype. The functional significance of these findings in the vascular control of the kidney is discussed.
In vitro evaluation of the inhibition and induction potential of olaparib, a potent poly(ADP-ribose) polymerase inhibitor, on cytochrome P450

Abstract 1. In vitro studies were conducted to evaluate potential inhibitory and inductive effects of the poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib, on cytochrome P450 (CYP) enzymes. Inhibitory effects were determined in human liver microsomes (HLM); inductive effects were evaluated in cultured human hepatocytes. 2. Olaparib did not inhibit CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2D6 or CYP2E1 and caused slight inhibition of CYP2C9, CYP2C19 and CYP3A4/5 in HLM up to a concentration of 100 μM. However, olaparib (17–500 μM) inhibited CYP3A4/5 with an IC50 of 119 μM. In time-dependent CYP inhibition assays, olaparib (10 μM) had no effect against CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP2E1 and a minor effect against CYP3A4/5. In a further study, olaparib (2–200 μM) functioned as a time-dependent inhibitor of CYP3A4/5 (KI, 72.2 μM and Kinact, 0.0675 min−1). Assessment of the CYP induction potential of olaparib (0.061–44 μM) showed minor concentration-related increases in CYP1A2 and more marked increases in CYP2B6 and CYP3A4 mRNA, compared with positive control activity; however, no significant change in CYP3A4/5 enzyme activity was observed. 3. Clinically significant drug–drug interactions due to olaparib inhibition or induction of hepatic or intestinal CYP3A4/5 cannot be excluded. It is recommended that olaparib is given with caution with narrow therapeutic range or sensitive CYP3A substrates, and that prescribers are aware that olaparib may reduce exposure to substrates of CYP2B6.
Na+/Ca2+exchange in neonatal rat heart cells: antisense inhibition and protein half-life.

Cardiac Na+/Ca2+exchanger (NCX) protein half-life ( t ½) and antisense knockdown were studied in primary cultured neonatal rat cardiomyocytes. Protein t ½ was determined using [35S]methionine with a pulse-chase protocol. The 35S signal in NCX was identified by immunoprecipitation and Western blotting. The t ½ of NCX protein was 33 h. Low concentrations (0.5 μM) of chimeric, phosphorothioated antisense oligodeoxynucleotides (AS-oligos) targeted to the region around the start codon of NCX1 transcript were used to knock down NCX protein and activity. Control myocytes (no oligos or scrambled oligos for at least 4 days) exhibited spontaneous Ca2+ transients (measured with fura 2). The sustained ("diastolic") Ca2+ concentration in the cytosol ([Ca2+]cyt) of control cells was unaffected by cyclopiazonic acid (CPA) plus caffeine (Caf), which promote depletion of sarcoplasmic reticular Ca2+ stores, but [Ca2+]cytrose in control cells when external Na+ was removed. In contrast, ∼60% of cells treated with AS-oligos for at least 4 days did not exhibit spontaneous Ca2+transients or respond to Na+-free medium; however, CPA + Caf did induce a prolonged elevation in [Ca2+]cytin these cells. In all cells, 50 mM K+ increased [Ca2+]cyt. NCX protein was reduced by ∼50% in cells treated with AS-oligos for 7 days but was not reduced after only 2 days. These biochemical data are consistent with the physiological evidence of NCX knockdown in ∼60% of cells.
Tendinopathy: injury, repair, and current exploration

Both acute and chronic tendinopathy result in high morbidity, requiring management that is often lengthy and expensive. However, limited and conflicting scientific evidence surrounding current management options has presented a challenge when trying to identify the best treatment for tendinopathy. As a result of shortcomings of current treatments, response to available therapies is often poor, resulting in frustration in both patients and physicians. Due to a lack of understanding of basic tendon-cell biology, further scientific investigation is needed in the field for the development of biological solutions. Optimization of new delivery systems and therapies that spatially and temporally mimic normal tendon physiology hold promise for clinical application. This review focuses on the clinical importance of tendinopathy, the structure of healthy tendons, tendon injury, and healing, and a discussion of current approaches for treatment that highlight the need for the development of new nonsurgical interventions.
A lamination technique of LCP/Cu for electronic packaging

Liquid crystalline polymer (LCP) is expected to be used for the lamination of electronic circuit boards because of its excellent mechanical and electric properties, such as a low dielectric constant and dimensional stability. However, it has not been widely used yet due to the weak interaction between LCP and Cu. Roughened surfaces of Cu foil that could deteriorate the electrical property are being used in conventional lamination process in order to improve the bonding strength. Surface activated bonding (SAB) of Cu/LCP based on a surface cleaning process by physical bombardment in vacuum has been performed to achieve the strong bonding. A peel strength of 800/spl sim/900 g/cm of the laminate prepared by SAB process is achieved, and the surface roughness of the interface between LCP and Cu is controlled to be less than 100 nm. In this experiment, additional treatment including Cu deposition on LCP and annealing after bonding is applied in order to obtain strong bonding. The effects of these treatments are investigated with the discussion of bonding mechanism.
Rap1, Canoe and Mbt cooperate with Bazooka to promote zonula adherens assembly in the fly photoreceptor

ABSTRACT In Drosophila epithelial cells, apical exclusion of Bazooka (the Drosophila Par3 protein) defines the position of the zonula adherens (ZA), which demarcates the apical and lateral membrane and allows cells to assemble into sheets. Here, we show that the small GTPase Rap1, its effector Canoe (Cno) and the Cdc42 effector kinase Mushroom bodies tiny (Mbt), converge in regulating epithelial morphogenesis by coupling stabilization of the adherens junction (AJ) protein E-Cadherin and Bazooka retention at the ZA. Furthermore, our results show that the localization of Rap1, Cno and Mbt at the ZA is interdependent, indicating that their functions during ZA morphogenesis are interlinked. In this context, we find the Rap1-GEF Dizzy is enriched at the ZA and our results suggest that it promotes Rap1 activity during ZA morphogenesis. Altogether, we propose the Dizzy, Rap1 and Cno pathway and Mbt converge in regulating the interface between Bazooka and AJ material to promote ZA morphogenesis. Summary: Converging pathways regulate adherens junction stability and retention of Bazooka to promote zonula adherens maturation during epithelial cell morphogenesis in Drosophila.
Antagonism of ANG II type 1 receptors protects the endothelium during the early stages of renal hypertension in rats.

The degree of involvement of the renin-angiotensin system in endothelial dysfunction was investigated by using a one-kidney, one-clip (1K,1C) model of renal hypertension. Male Wistar rats received 0.02% enalapril, 0.02% losartan, or tap water for 1 day before and for 48 h after the induction of renal artery stenosis or sham operation. The aorta of 1K,1C rats showed increased contraction and decreased relaxation responses produced by norepinephrine and acetylcholine, respectively, vs. control responses. Exposure to 10-5 mol/l N G-monomethyl-l-arginine acetate augmented the contractile responses to norepinephrine to a greater extent in control rats than in the 1K,1C rats. The increased contraction and decreased relaxation responses to these agonists in the 1K,1C rats were normalized by enalapril or losartan. The addition of HOE-140 to the bath did not alter these normalized responses. Results suggest that angiotensin II causes endothelial dysfunction and reduces nitric oxide levels in 1K,1C rats. Such endothelial dysfunction enhanced the norepinephrine-induced contraction during the early-stage hypertension in 1K,1C rats.
Fast pressure calculation for 2D and 3D time dependent incompressible flow

A black box multigrid preconditioner is described for second order elliptic partial differential equations, to be used in pressure calculations in a pressure correction method. The number of cells in a block is not restricted as for standard multigrid, but completely arbitrary. The method can be used in a multiblock environment and fine tuning for eache hits is described. A comparison is made with wall clock times of conventional preconditioners. Copyright © 2000 John Wiley & Sons, Ltd.
Effect of Predator‐Prey Phylogenetic Similarity on the Fitness Consequences of Predation: A Trade‐off between Nutrition and Disease?

A largely neglected aspect of foraging behavior is whether the costs and benefits of predation vary as a function of phylogenetic (i.e., genetic) similarity between predator and prey. Prey of varying phylogenetic similarities to predators might differ in value because both the risk of pathogen transmission and the nutritional quality of prey typically decline with decreasing phylogenetic similarity between predator and prey. I experimentally evaluated this hypothesis by feeding omnivorous spadefoot toad tadpoles (Spea bombifrons, Spea multiplicata, and Scaphiopus couchii) either conspecific tadpoles or an equal mass of three different species of heterospecific prey, all of which contained naturally occurring bacteria. I also examined which prey species Spea tadpoles preferred. I found that all three species of tadpoles performed best on, and preferred to eat, prey that were of intermediate phylogenetic similarity to the predators. Prey of intermediate phylogenetic similarity may provide the greatest fitness benefits to predators because such prey balance the nutritional benefits of closely related prey with the cost of parasite transmission between closely related individuals.
Mitochondrial ATP-sensitive K+ channels modulate cardiac mitochondrial function.

Discovered in the cardiac sarcolemma, ATP-sensitive K+(KATP) channels have more recently also been identified within the inner mitochondrial membrane. Yet the consequences of mitochondrial KATP channel activation on mitochondrial function remain partially documented. Therefore, we isolated mitochondria from rat hearts and used K+ channel openers to examine the effect of mitochondrial KATPchannel opening on mitochondrial membrane potential, respiration, ATP generation, Ca2+ transport, and matrix volume. From a mitochondrial membrane potential of -180 ± 15 mV, K+ channel openers, pinacidil (100 μM), cromakalim (25 μM), and levcromakalim (20 μM), induced membrane depolarization by 10 ± 7, 25 ± 9, and 24 ± 10 mV, respectively. This effect was abolished by removal of extramitochondrial K+ or application of a KATP channel blocker. K+ channel opener-induced membrane depolarization was associated with an increase in the rate of mitochondrial respiration and a decrease in the rate of mitochondrial ATP synthesis. Furthermore, treatment with a K+ channel opener released Ca2+ from mitochondria preloaded with Ca2+, an effect also dependent on extramitochondrial K+concentration and sensitive to KATP channel blockade. In addition, K+ channel openers, cromakalim and pinacidil, increased matrix volume and released mitochondrial proteins, cytochrome cand adenylate kinase. Thus, in isolated cardiac mitochondria, KATP channel openers depolarized the membrane, accelerated respiration, slowed ATP production, released accumulated Ca2+, produced swelling, and stimulated efflux of intermembrane proteins. These observations provide direct evidence for a role of mitochondrial KATP channels in regulating functions vital for the cardiac mitochondria.
NF2/Merlin Inactivation and Potential Therapeutic Targets in Mesothelioma

The neurofibromatosis type 2 (NF2) gene encodes merlin, a tumor suppressor protein frequently inactivated in schwannoma, meningioma, and malignant mesothelioma (MM). The sequence of merlin is similar to that of ezrin/radixin/moesin (ERM) proteins which crosslink actin with the plasma membrane, suggesting that merlin plays a role in transducing extracellular signals to the actin cytoskeleton. Merlin adopts a distinct closed conformation defined by specific intramolecular interactions and regulates diverse cellular events such as transcription, translation, ubiquitination, and miRNA biosynthesis, many of which are mediated through Hippo and mTOR signaling, which are known to be closely involved in cancer development. MM is a very aggressive tumor associated with asbestos exposure, and genetic alterations in NF2 that abrogate merlin’s functional activity are found in about 40% of MMs, indicating the importance of NF2 inactivation in MM development and progression. In this review, we summarize the current knowledge of molecular events triggered by NF2/merlin inactivation, which lead to the development of mesothelioma and other cancers, and discuss potential therapeutic targets in merlin-deficient mesotheliomas.
Cyclooxygenase inhibition decreases nitric oxide synthase activity in human platelets.

Activity of both nitric oxide (NO) synthase (NOS) and cyclooxygenase (COX) plays an important role in the regulation of platelet function. NO has been shown to directly activate COX. This study was designed to determine whether products of the COX pathway in turn regulate NOS activity. Human platelets were incubated with aspirin, indomethacin, the selective thromboxane A2 synthase inhibitor U-63557A, or the prostaglandin H2-thromboxane A2-receptor blocker SQ-29548 for 1 h at 37°C. Multiple indexes of the activity of thel-arginine-NO pathway and changes in cytosolic Ca2+concentration ([Ca2+]i) were measured in platelets. Both aspirin and indomethacin decreased NOS activity, measured as the conversion ofl-arginine tol-citrulline and nitrite (+nitrate) formation, in platelets in a concentration-dependent fashion. Aspirin also decreased guanosine 3',5'-cyclic monophosphate accumulation in platelets. The NOS inhibitory effects of these aspirin and indomethacin effects were reversed by coincubation with the thromboxane A2 analog U-46619 or an excess of CaCl2. Incubation of COX inhibitors with platelets was associated with significant reductions in basal as well as thrombin-stimulated [Ca2+]i, and the reduction in [Ca2+]iwas reversed by U-46619. Incubation of platelets with U-63557A and SQ-29548 resulted in inhibitory effects on NOS activity qualitatively similar to those of COX inhibitors. The effects of COX inhibitors or U-63557A were not associated with a change in NOS protein expression in platelets. These data suggest that NOS activity in human platelets is inhibited by COX inhibitors, mediated, at least in part, via suppression of thromboxane A2 and [Ca2+]imobilization in platelets.
Acute stressor exposure both suppresses acquired immunity and potentiates innate immunity.

Acute stressor exposure alters immune function. Rats exposed to inescapable tail shock stress (IS) generate less antibody to a benign, antigenic protein, keyhole limpet hemocyanin (KLH). The following studies examined the effect of IS on peritoneal cavity, spleen, and mesenteric lymph node cell number, interferon-γ (IFN-γ) production, and nitrite production. Rats were injected intraperitoneally with KLH (200 μg) or saline immediately before IS exposure and killed 0, 48, and 96 h after IS termination. KLH immunization resulted in elevated cell numbers and IFN-γ levels 2-4 days later in nonstressed control rats. In contrast, rats exposed to IS failed to increase cell number and IFN-γ levels in response to KLH. The T cell subpopulations affected were CD4 T cells, specifically the Th1-like subset. In addition, in rats exposed to IS + KLH, nitrite production was potentiated 2-4 days after stressor termination. IS had little effect on these measures in saline-injected rats. These data support the conclusion that exposure to IS suppresses the expansion of anti-KLH lymphocytes, possibly anti-KLH Th1 cells. In addition, stressor exposure potentiates the production of nitrite. Importantly, this potentiated response occurred only in KLH-immunized animals, suggesting that macrophages may be primed by stressor exposure and thus respond more vigorously to antigen. The potential links between these changes are discussed.