Miracle-dz/UniFAR-FTUs huggingface dataset:
Rapid leukocyte integrin activation by chemokines

Summary: Chemokines control selective targeting of circulating leukocytes to the microvasculature by triggering inside‐out signal transduction pathways leading to integrin‐dependent adhesion. Integrin activation by chemokines is very rapid, is downmodulated within minutes and appears to involve both enhanced heterodimer lateral mobility on the plasma membrane, facilitating encounters with dispersed ligand, as well as induction of a high‐affinity state. These two modalities of integrin activation by chemokines involve distinct signaling pathways in the cell, yet complement each other functionally, allowing binding of rolling cells under conditions of low as well as high ligand density. Recent data show that chemokines generate both pro‐ and anti‐adhesive intracellular signaling events, whose equilibrium is likely to be relevant to the kinetics of adhesion and de‐adhesion, and to cell movement during diapedesis and chemotaxis. Importantly, chemokines utilize different signaling mechanisms to modulate the activity of distinct integrin subtypes. These recent advances suggest that chemokines may regulate adhesive responses of immune cells based not only on patterns of chemokine receptor expression, but also on variable signaling pathways that can modulate the pro‐adhesive responses of leukocytes as a function of their differentiated state, and of the local microenvironment.
The means of the differential amplifier input offset voltage reduction

The input offset voltage of the differential amplifier based on the bipolar junction transistors, which operate at high current density, is analysed in this work. An analytical approach based on the equations in the explicit form is used to determine the input offset voltage reduction means. The obtained results are tested using numerical simulation of the differential amplifier.
Cytotoxic T Cells Are the Predominant Players Providing Cross-Protective Immunity Induced by γ-Irradiated Influenza A Viruses

ABSTRACT We previously demonstrated that a single dose of nonadjuvanted intranasal γ-irradiated influenza A virus can provide robust protection in mice against both homologous and heterosubtypic challenges, including challenge with an H5N1 avian virus strain. We investigated the mechanism behind the observed cross-protection to define which arms of the adaptive immune response are involved in mediating this protection. Studies with gene knockout mice showed the cross-protective immunity to be mediated mainly by T cells and to be dependent on the cytolytic effector molecule perforin. Adoptive transfer of memory T cells from immunized mice, but not of memory B cells, protected naïve recipients against lethal heterosubtypic influenza virus challenge. Furthermore, γ-irradiated influenza viruses induced cross-reactive Tc-cell responses but not cross-neutralizing or cross-protective antibodies. In addition, histological analysis showed reduced lung inflammation in vaccinated mice compared to that in unvaccinated controls following heterosubtypic challenge. This reduced inflammation was associated with enhanced early recruitment of T cells, both CD4+ and CD8+, and with early influenza virus-specific cytotoxic T-cell responses. Therefore, cross-protective immunity induced by vaccination with γ-irradiated influenza A virus is mediated mainly by Tc-cell responses.
Development of microelectrode arrays for artificial retinal implants using liquid crystal polymers.

PURPOSE To develop a liquid crystal polymer (LCP)-based, long-term implantable, retinal stimulation microelectrode array using a novel fabrication method. METHODS The fabrication process used laser micromachining and customized thermal-press bonding to produce LCP-based microelectrode arrays. To evaluate the fabrication process and the resultant electrode arrays, in vitro reliability tests and in vivo animal experiments were performed. The in vitro tests consisted of electrode site impedance recording and electrode interlayer adhesion monitoring during accelerated soak tests. For in vivo testing, the fabricated electrode arrays were implanted in the suprachoroidal space of rabbit eyes. Optical coherence tomography (OCT) and electrically evoked cortical potentials (EECPs) were used to determine long-term biocompatibility and functionality of the implant. RESULTS The fabricated structure had a smooth, rounded edge profile and exhibited moderate flexibility, which are advantageous features for safe implantation without guide tools. After accelerated soak tests at 75 degrees C in phosphate-buffered saline, the electrode sites showed no degradation, and the interlayer adhesion of the structure showed acceptable stability for more than 2 months. The electrode arrays were safely implanted in the suprachoroidal space of rabbit eyes, and EECP waveforms were recorded. Over a 3-month postoperative period, no chorioretinal inflammation or structural deformities were observed by OCT and histologic examination. CONCLUSIONS LCP-based flexible microelectrode arrays can be successfully applied as retinal prostheses. The results demonstrate that such electrode arrays are safe, biocompatible, and mechanically stable and that they can be effective as part of a chronic retinal implant system.
Plasma Cortisol and Norepinephrine Responses in Anticipation of Muscular Exercise

&NA; Strikingly consistent individual responses and significant mean elevations of plasma cortisol levels (5 to 9 &mgr; g%) and plasma norepinephrine levels (2.0 to 2.5 &mgr; g/1) were observed during a 20‐min interval prior to onset of the first exhausting exercise (70% max VO2) session in eight normal young men. No detectable plasma epinephrine response was observed. Such consistent anticipatory psychoendocrine responses were not found prior to subsequent exercise sessions involving milder degrees of muscular exercise. Psychoendocrine reactions to intravenous catheterization were also observed in some individual subjects, suggesting the need for precautions to minimize the possible effects of this variable in exercise experiments. Some implications of this study for psychoendocrine research are also discussed.
Quantitative Radionuclide Studies of Bone

In the current issue of The Journal of Nuclear Medicine, Uchida et al. present results from a prospective study using 18F-fluoride PET to assess the effects of bisphosphonate treatment on bone metabolism in patients with glucocorticoid-induced osteoporosis ( [1][1] ). By quantifying localized bone
The Ileal Pouch Anal Anastomosis: Past, Present, and Future

The modern era of ileal pouch anal anastomosis began just over 20 years ago. Several areas remain controversial, including patient selection, surgical technique, use of a temporary diverting ileostomy, aging sphincters, complications, and postoperative management. This article reviews current controversies concerning ileal pouch anal anastomoses and our approach to managing patients who undergo this complicated procedure.
Planning Based System for Child-Robot Interaction in Dynamic Play Environments

This paper describes the initial steps towards the design of a robotic system that intends to perform actions autonomously in a naturalistic play environment. At the same time it aims for social human-robot interaction~(HRI), focusing on children. We draw on existing theories of child development and on dimensional models of emotions to explore the design of a dynamic interaction framework for natural child-robot interaction. In this dynamic setting, the social HRI is defined by the ability of the system to take into consideration the socio-emotional state of the user and to plan appropriately by selecting appropriate strategies for execution. The robot needs a temporal planning system, which combines features of task-oriented actions and principles of social human robot interaction. We present initial results of an empirical study for the evaluation of the proposed framework in the context of a collaborative sorting game.
A 12 bit 1 GS/s Dual-Rate Hybrid DAC With an 8 GS/s Unrolled Pipeline Delta-Sigma Modulator Achieving > 75 dB SFDR Over the Nyquist Band

A 12 bit Dual-Rate Hybrid digital-to-analog converter (DAC) architecture with a split Nyquist (1 GS/s) and delta-sigma modulator path (8 GS/s) is proposed and implemented in 65 nm CMOS. Based on the hybrid architecture, the delta-sigma-assisted pre-distortion scheme compensates for the current steering cell mismatch, which further reduces the analog circuit complexity and area. The proposed 8X unrolled pipeline delta-sigma modulator allows for high-speed third-order noise shaping with a digital standard cell design flow. The measured spurious-free dynamic range achieves 91-76 dB over the 500 MHz Nyquist band. The proposed DAC architecture is mostly digital and hence favors future technology scaling.
Analysis of Clathrin-mediated Endocytosis of Epidermal Growth Factor Receptor by RNA Interference*[boxs]

To identify proteins that participate in clathrin-mediated endocytosis of the epidermal growth factor receptor (EGFR), 13 endocytic proteins were depleted in HeLa cells using highly efficient small interfering RNAs that were designed using a novel selection algorithm. The effects of small interfering RNAs on the ligand-induced endocytosis of EGFR were compared with those effects on the constitutive internalization of the transferrin receptor. The knock-downs of clathrin heavy chain and dynamin produced maximal inhibitory effects on the internalization of both receptors. Depletion of α, β2, or μ2 subunits of AP-2 reduced EGF and transferrin internalization rates by 40-60%. Down-regulation of several accessory proteins individually had no effect on endocytosis but caused significant inhibition of EGF and transferrin endocytosis when the homologous proteins were depleted simultaneously. Surprisingly, knockdown of clathrin-assembly lymphoid myeloid leukemia protein, CALM, did not influence transferrin endocytosis but considerably affected EGFR internalization. Thus, CALM is the second protein besides Grb2 that appears to play a specific role in EGFR endocytosis. This study demonstrates that the efficient gene silencing by rationally designed small interfering RNA can be used as an approach to functionally analyze the entire cellular machineries, such as the clathrin-coated pits and vesicles.
Simultaneous Treatment with Intravenous Recombinant Tissue Plasminogen Activator and Endovascular Therapy for Acute Ischemic Stroke Within 3 Hours of Onset

BACKGROUND AND PURPOSE: Because intravenous (IV) recombinant tissue plasminogen activator (rtPA) does not always lead to a good outcome in a considerable proportion of patients, combined IV rtPA and rescue endovascular therapy (ET) have been performed in several recent studies. However, rescue therapy after completion of IV rtPA often results in late ineffective recanalization. We examined the efficacy and safety of combined IV rtPA and simultaneous ET as primary rather than rescue therapy for hyperacute middle cerebral artery (MCA) occlusion. MATERIALS AND METHODS: A total of 29 patients eligible for IV rtPA, who were diagnosed as having MCA (M1 or M2) occlusion within 3 hours of onset, underwent thrombolysis. In the combined group, patients were treated by IV rtPA (0.6 mg/kg for 60 minutes) and simultaneous ET (intra-arterial rtPA, mechanical thrombus disruption with microguidewire, and balloon angioplasty) initiated as soon as possible. In the IV group, patients were treated by IV rtPA only. RESULTS: The improvement of the National Institutes of Health Stroke Scale (NIHSS) score at 24 hours was 11 ± 4.8 in the combined group versus 5 ± 4.3 in the IV group (P < .001). In the combined group, successful recanalization was observed in 14 (88%) of 16 patients with no symptomatic intracranial hemorrhage, and 10 (63%) of 16 patients had favorable outcomes (modified Rankin Scale [mRS] 0, 1) at 3 months. CONCLUSIONS: Aggressive combined therapy with IV rtPA and simultaneous ET markedly improved the clinical outcome of hyperacute MCA occlusion without significant adverse effect. Additional randomized study is needed to confirm our results.
Inhibition of allergen-induced airway remodelling by tiotropium and budesonide: a comparison

Chronic inflammation in asthma and chronic obstructive pulmonary disease drives pathological structural remodelling of the airways. Using tiotropium bromide, acetylcholine was recently identified as playing a major regulatory role in airway smooth muscle remodelling in a guinea pig model of ongoing allergic asthma. The aim of the present study was to investigate other aspects of airway remodelling and to compare the effectiveness of tiotropium to the glucocorticosteroid budesonide. Ovalbumin-sensitised guinea pigs were challenged for 12 weeks with aerosolised ovalbumin. The ovalbumin induced airway smooth muscle thickening, hypercontractility of tracheal smooth muscle, increased pulmonary contractile protein (smooth-muscle myosin) abundance, mucous gland hypertrophy, an increase in mucin 5 subtypes A and C (MUC5AC)-positive goblet cell numbers and eosinophilia. It was reported previously that treatment with tiotropium inhibits airway smooth muscle thickening and contractile protein expression, and prevents tracheal hypercontractility. This study demonstrates that tiotropium also fully prevented allergen-induced mucous gland hypertrophy, and partially reduced the increase in MUC5AC-positive goblet cell numbers and eosinophil infiltration. Treatment with budesonide also prevented airway smooth muscle thickening, contractile protein expression, tracheal hypercontractility and mucous gland hypertrophy, and partially reduced MUC5AC-positive goblet cell numbers and eosinophilia. This study demonstrates that tiotropium and budesonide are similarly effective in inhibiting several aspects of airway remodelling, providing further evidence that the beneficial effects of tiotropium bromide might exceed those of bronchodilation.
Activation of unmyelinated afferent fibres by mechanical stimuli and inflammation of the urinary bladder in the cat.

1. We examined the functional properties of unmyelinated primary afferent neurones innervating the pelvic viscera in twenty‐five anaesthetized cats. The axons were isolated from the intact dorsal root and the intact or chronically de‐efferented ventral root of the segment S2. All units were electrically identified with electrical stimulation of the pelvic nerve. 2. The responses of the neurones were studied with natural stimulation of the urinary bladder using innocuous and noxious increases of intravesical pressure and at the onset of an acute artificial inflammation induced by intraluminal injection of mustard or turpentine oil. 3. Out of 297 unmyelinated afferent units isolated from the dorsal root, seven were excited by an increase of the intravesical pressure during contractions and distension of the urinary bladder. These units were silent when the bladder was empty and had thresholds of 30‐50 mmHg which are presumed to be noxious. Further increases of the intravesical pressure were accurately encoded by the discharge rate of the fibres. Out of sixty‐eight unmyelinated afferent units isolated from the ventral root none was activated by these stimuli. 4. Intraluminal injection of mustard oil excited mechanosensitive units at short latency. The discharge was not closely related to changes of the intravesical pressure and the units displayed on‐going activity after the irritant had been removed. This observation suggests that the units had also chemosensitive properties and that the receptive endings were located in the bladder wall. 5. In sixteen cats ninety‐five afferent fibres that were not activated by noxious mechanical stimuli of the urinary bladder were systematically tested with intraluminal injections of mustard oil. This excited 7/67 dorsal root units and 4/28 ventral root units with short latency. Intraluminal application of turpentine oil, tested on twenty‐six afferents in four animals, did not produce a rapid excitation. 6. Following the induction of an inflammation some previously non‐mechanosensitive units started to respond to changes of intravesical pressure in the biologically relevant pressure range of the urinary bladder. 7. In conclusion, a small subpopulation (2.4%) of unmyelinated visceral afferents responds to high, presumably noxious, intravesical pressure and intraluminal application of chemical irritants. Acute inflammation excites a larger proportion of afferents (9.5%) that are not activated by acute noxious mechanical stimulation of the normal urinary bladder. In the inflamed bladder some previously non‐mechanosensitive units started to respond to increases of intravesical pressure. These novel types of chemosensitive receptors may contribute considerably to the pathogenesis of visceral pain states.
Tension-activated channels in the mechanism of osmotic fitness in Pseudomonas aeruginosa

Pseudomonas aeruginosa (PA) is an opportunistic pathogen with an exceptional ability to adapt to a range of environments. Part of its adaptive potential is the ability to survive drastic osmolarity changes. Upon a sudden dilution of external medium, such as during exposure to rain, bacteria evade mechanical rupture by engaging tension-activated channels that act as osmolyte release valves. In this study, we compare fast osmotic permeability responses in suspensions of wild-type PA and Escherichia coli (EC) strains in stopped-flow experiments and provide electrophysiological descriptions of osmotic-release channels in PA. Using osmotic dilution experiments, we first show that PA tolerates a broader range of shocks than EC. We record the kinetics of cell equilibration reported by light scattering responses to osmotic up- and down-shocks. PA exhibits a lower water permeability and faster osmolyte release rates during large osmotic dilutions than EC, which correlates with better survival. To directly characterize the PA tension-activated channels, we generate giant spheroplasts from this microorganism and record current responses in excised patches. Unlike EC, which relies primarily on two types of channels, EcMscS and EcMscL, to generate a distinctive two-wave pressure ramp response, PA exhibits a more gradual response that is dominated by MscL-type channels. Genome analysis, cloning, and expression reveal that PA possesses one MscL-type (PaMscL) and two MscS-type (PaMscS-1 and 2) proteins. In EC spheroplasts, both PaMscS channels exhibit a slightly earlier activation by pressure compared with EcMscS. Unitary currents reveal that PaMscS-2 has a smaller conductance, higher anionic preference, stronger inactivation, and slower recovery compared with PaMscS-1. We conclude that PA relies on MscL as the major valve defining a high rate of osmolyte release sufficient to curb osmotic swelling under extreme shocks, but it still requires MscS-type channels with a strong propensity to inactivation to properly terminate massive permeability response.
Effect of occupational exposures on decline of lung function in early chronic obstructive pulmonary disease.

RATIONALE Several occupational exposures adversely affect lung function. OBJECTIVES This study reports the influence of continued occupational dust and fume exposures on the rate of decline of lung function in participants with early chronic obstructive pulmonary disease (COPD) studied in a population-based study. METHODS Subjects consisted of 5,724 participants in the Lung Health Study, a multicenter study of smoking cessation and anticholinergic bronchodilator administration in smokers with early COPD (3,592 men; 2,132 women). Average post-bronchodilator FEV1 at entry was 78.4% predicted for men and 78.2% predicted for women; all participants had an FEV1/FVC ratio less than 0.70. MEASUREMENTS AND MAIN RESULTS Participants underwent a baseline evaluation and five annual follow-up assessments, including questionnaires and spirometry. The effect of ongoing dust or fume exposure on FEV1 in each follow-up year was statistically evaluated with a mixed-effects regression model, which was adjusted for FEV1 at entry, age, airway responsiveness to methacholine, baseline smoking intensity, and time-varying (yearly) smoking status during each follow-up year. In men with early COPD, each year of continued fume exposure was associated with a 0.25% predicted reduction in post-bronchodilator FEV1% predicted. Continued smoking and airway hyperresponsiveness were also associated with reduction in FEV1 during each year of follow-up in both men and women. Statistically significant effects of dust exposure on the rate of decline were not found, nor were effects of fume exposure noted in women. CONCLUSIONS These results suggest a need for secondary prevention by controlling occupational fume exposures.
Union Decline in Britain: Does Gender Have Anything to Do with it?

The paper examines if workplace gender diversity offers some explanation for the decline of unions in Britain. Using the WERS2004 linked employer–employee data and alternative econometric estimators it reports an inverse relationship between workplace union density and gender diversity. Gender and ownership status based sub-group analyses suggest the inverse relationship to be stronger for male union members and those in the private sector. Gender group size-based analysis reveals a positive link between workplace union density and gender diversity in workplaces with a female majority. The findings in this paper may mean that unions may need to embrace the changing workplace demography genuinely to improve their fate.
Intuitive Pathfinding of Autonomous Agents

This paper treats the pathfinding of autonomous agents from a given start point to a set of targets. It mainly focuses on continuous domains with continuous state and action spaces of the agents. In these continuous domains a technique called Cross Entropy Online Planning can be deployed by the agents to plan and assess sequences of actions in order to reach their goals. However, this technique requires a simulation model of the environment to enable the agents to predict and evaluate future states of the environment. This could be combined with results of the field of Intuitive Physics which tries to create models for simple physical object interactions based merely on observations. The contribution of this work is the idea to replace the simulation model in Online Planning with results of the field of Intuitive Physics in order to create Intuitive Acting Autonomous Agents. The benefit of this will be the automated creation of the otherwise manually created model and an enhancement of the flexibility